Myocardial blood flow in congestive and hypertrophic cardiomyopathy: relationship to peak wall stress and mean velocity of circumferential fiber shortening.

Myocardial blood flow/unit mass (MBF) and the determinants of myocardial oxygen consumption were measured in seven control subjects (group I) and 15 patients (pts) with cardiomyopathy (CM), group II (group IIa-congestive CM: 10 pts; group IIb-hypertrophic CM: 5 pts). In group I left ventricular (LV) MBF was 64 +/- 8 (SD) ml/100g-min; it was significantly lower in IIa (45 +/- 15 ml/100g-min, P less than 0.01) and IIb (39 +/- 7 ml/100g-min, P less than 0.01). However, calculated total LV flow (LV mass X MBF) was increased in the two CM groups. In nine CM pts, LV MBF increased in response to atrial pacing from 41 +/- 7 to 63 +/- 13 ml/100g-min. In group IIa, calculated peak wall stress was normal (4.39 +/hortening (MVcf) was significantly reduced (0.53 +/- 0;18 vs 1.26 +/- 0.12 circum/sec, P less than 0.01). In IIb, MVcf was normal but peak stress was significantly reduced (2.80 +/- 0.75 vs 4.51 +/- 1.10 dynes/cm2 X 10(5), P less than 0.05). Multiple regression analysis based on all pts yielded, MBF - 16.9 MVcf + 9.30 Stress + 0.26 Heart Rate - 26.4 (r=0.79). The data indicate that MBF is reduced in CM patients and the regression analysis suggests that MBF in these 22 pts with normal coronary arteriograms was determined largely by heart rate, peak stress, and ventricular performance.


Hyaluronate-binding by proteoglycans. Comparison of mildly and severely osteoarthritic regions of human femoral cartilage.

The ability of proteoglycans from hip cartilage of a patient with osteoarthritis to bind hyaluronic acid was examined. Proteoglycans from areas showing severe morphologic changes of the disease showed no interaction with hyaluronic acid in vitro. Moreover, fractions which normally contain aggregated proteoglycans were no larger in hydrodynamic size than disaggregated proteoglycans, suggesting that the proteoglycans from these regions were not aggregated in vivo. Proteoglycans from less extensively diseased areas, in contrast, underwent aggregation in vitro and appeared to have been aggregated by tissue hyaluronic acid in vivo. The results suggest that the progressive morphologic changes of osteorthritis are associated with progressive defects in proteoglycan aggregation due, at least in part, to impaired ability of the proteoglycans to interact with hyaluronic acid.


A semiautomated method for the determination of 11-deoxy-17-oxo-steroids in urine.

A semiautomated method is described for the determination of total 11-deoxy-17-oxo-steroids (11-DOOS: androsterone, etiocholanolone plus dehydroepiandrosterone) in urine. Urinary conjugates are manually extracted on a XAD-2 resin, hydrolysed by beta-glucuronidase and "solvolysed" in acid ethyl-acetate according to Burnstein-Lieberman. The free 11-DOOS are extracted automatically with iso-octane and estimated colorimetrically by the Zimmerman reaction in an Auto-Analyzer II system. The method was evaluated by investigation of its precision, accuracy, sensitivity and specificity. It was found to be satisfactory for the rapid and reliable screening of large numbers of urine samples.


A method for the quantitative determination of urinary glycosaminoglycans.

A method is presented by which the urinary glycosaminoglycans can be isolated in a macromolecular fraction with complete recovery by preparative gel filtration. The urinary glycosaminoglycans can be quantitated by determinations of uronic acid and sulfaminohexose in the macromolecular fraction. Using untreated, random urine specimens of less than 5 ml volume, clinical mucopolysaccharidoses types I, II, and III could be readily distinguished.


Role of adenosine deaminase in lymphocyte proliferation.

Activity of adenosine deaminase (ADA), an enzyme known to be deficient in some patients with severe combined immunodeficiency, increased three-fold within a 24-hour exposure of human peripheral blood lymphocytes to phytohaemagglutinin (PHA) in culture. This increase took place before the onset of DNA synthesis. Increased levels of ADA activity were also observed in lymphocytes incubated with pokeweed mitogen (PWM) for 60 hr. DNA synthesis induced by PHA, PWM or mixed lymphocyte cultures (MLC) was strongly inhibited by adenosine at concentrations of 10(-4) M or higher when human peripheral blood lymphocytes were cultured in a medium supplemented with horse serum, which lacks ADA. 10(-6)-10(-8) M coformycin, a potent inhibitor of ADA, inhibited PHA-, PWM- and MLC-induced DNA synthesis to a variable extent, whereas thymidine incorporation induced by Salmonella lipopolysaccharide (LPS) in mouse spleen cell cultures was strongly inhibited (by 75% or more) by 10(-6) M coformycin. Combination of 10(-7)-10(-8) M coformycin and 10(-4)-10(-5) M adenosine synergistically inhibited mitogen- or MLC-induced DNA synthesis in human and mouse lymphocyte cultures. These results, together with observations on children with ADA deficiency, provide evidence that adenosine deaminase is highly important for lymphocyte proliferation. Human peripheral blood lymphocytes incubated with PHA, 10(-5) M adenosine and 10(-7) M coformycin showed some cytotoxicity whereas the rate of 51Cr release from normal lymphocytes was not modified by the drugs. These findings suggest that in vivo clones of lymphocytes responding to specific antigens might be eliminated by coformycin, which may prove to be useful as a specific immunosuppressive agent.


Hyperactive T-cell function in young NZB mice; increased proliferative responses to allogenic cells.

The one-way mixed lymphocyte reaction was employed to study proliferative responses to antigens by mature, immunocompetent T cells from NZB mice 3 weeks to 4 months old. Compared to cells from control mice of the same H-2 type, thymus, spleen and lymph node cells from NZB mice were hyperactive in this response. The results are discussed in relation to possible effects of chronic stimulation by endogenous type C leukaemia virus upon differentiation of functional T cells or upon regulation by T cells of other T-cell functions, including augmentation of antibody responses.


Leucocyte migration inhibition factor (LIF) production by lymphocytes of normal children, newborns, and children with immune deficiency.

The reproducibility of a simplified, sensitive and rapid agarose-cell droplet assay for leucocyte migration inhibition factor (LIF) activity was studied. Removal of T cells with anti-T-cell serum eliminated LIF activity, indicating that in humans it is probably the T cell that produces LIF. Cord blood lymphocytes produce LIF, although spontaneous migration of leucocytes is less than in older children. The cause of this apparently does not reside in the PMN leucocytes. Studies of children with immunodeficiency suggest that the T-cell population in humans is heterogenous. B-cell deficiencies such as hypogammaglobulinaemia, have normal PPD and PHA induced LIF production, whilst some patients with ataxia-telangiectasia have defective PPD LIF activity, their PHA LIF activity being only minimally depressed. On the other hand, Down's syndrome patients with reduced blood T cells have remarkably deficient LIF activity to PHA and relatively good activity to PPD. Children receiving steroid therapy lose much of their ability to produce LIF to the specific antigen PPD, but not to the non-specific mitogen PHA.


Immunologic mechanisms responsible for adverse reactions to routine immunizations in children.

The principal licensed biologicals for human use in the United States have been listed with special emphasis given to antiviral vaccines. Possible adverse reactions of an immunologic nature which may be encountered in the use of these agents in routine immunization programs are described, while at the same time, their relative rarity is emphasized. The special problems one may encounter in immunizing the atopic child, the immunodeficient child, the child with active tuberculosis and the pregnant woman are considered separately, as are the undesirable consequences of hyperimmunization are mentioned.


[Nerve-root damage from local injections (author's transl)].

Paravertebral injections of local anaesthetics (procaine hydrochloride, frequencly in combination with other substances) may damage cervical or lumbosacral nerve roots, depending on the site of injection. Five such iatrogenic lesions are described. Paravertebral injections of local anaesthetics also carry the risk of irreversible paraplegia and such treatment should therefore not be given in the cervical and lumbar segments.


Enzymic unwinding of DNA. 1. Purification and characterization of a DNA-dependent ATPase from Escherichia coli.

Evidence from various sources in the literature suggests that, in connection with DNA, ATP dephosphorylation can be used to provide energy for mechanical effects. Starting from this concept we have studied a novel DNA-dependent ATPase purified to 90% homogeneity from Escherichia coli. The enzyme has a peptide weight near 180 000 and, in high salt, is a monomeric, probably highly anisometric molecule. In salt-free buffer, where the ATPase activity is highest, the enzyme forms aggregates. ATP is the preferred substrate (Km 0.27 mM) and dephosphorylated at the gamma-position at a maximal rate near 10(4) molecules per enzyme monomer per min at 35 degrees C. A requirement for divalent cation is best satisfied by Mg2+ or Ca2+ and the requirement for DNA best by the single-stranded, circular DNA of phages phiX174 (Km 62 nM nucleotide) and fd indicating that the enzyme recognizes internal DNA regions. When saturated with E. coli DNA unwinding protein phiX DNA is not accepted but, once in contact with the DNA, the enzyme is little inhibited by unwinding protein. Apparently the unwinding protein interferes preferentially with the recognition of DNA. The enzyme does not detectably cleave DNA, and for this and genetic reasons is not identical with the recBC ATPase or the K12 restriction ATPase of the extracted cells. The enzyme is probably not identical either with the dnaB-product-associated ATPase or the ATPase activity found in DNA polymerase III holoenzyme under appropriate conditions, and it is certainly not identical with a DNA-dependent ATPase of molecular weight 69 000 from E. coli which has recently been purified. Attempts to ascribe the enzyme to other genes, including recA, lex and rep, have failed.


Enzymic unwinding of DNA. 2. Chain separation by an ATP-dependent DNA unwinding enzyme.

The DNA-stimulated ATPase characterized in the accompanying paper is shown to be a DNA unwinding enzyme. Substrates employed were DNA, RNA hybrid duplexes and DNA-DNA partial duplexes prepared by polymerization on fd phage single-stranded DNA template. The enzyme was found to denature these duplexes in an ATP-dependent reaction, without detectably degrading. EDTA, an inhibitor of the Mg2+-requiring ATPase, was found to prevent denaturation suggesting that dephosphorylation of the ATP and not only its presence is required. These results together with those from enzyme-DNA binding studies lead to ideas regarding the mode of enzymic action. It is proposed that the enzyme binds, in an initial step, to a single-stranded part of the DNA substrate molecule and that from here, energetically supported by ATP dephosphorylation, it invades double-stranded parts separating base-paired strands by processive, zipper-like action. It is further proposed that chain separation results from the combined action of several enzyme molecules and that a tendency of the enzyme to aggregate with itself reflects a tendency of the molecules to cooperate. Various functions are conceivable for the enzyme.


A comparative study of reactive--SH groups of cardiac and skeletal muscle myosins.

Cardiac and skeletal muscle myosins have been treated by N-ethylmaleimide in presence or absence of Mg-ADP. The variations of Ca2+ and K+-ATPase activities and the incorporation of N-[14C]ethylmaleimide into the whole myosin molecule and into its separated subunits (heavy and light chains) have been measured with N-ethylmaleimide treatment for different lengths of time. The results reported here show the following: 1. The Ca2+-ATPase activity of cardiac myosin is activated by N-ethylmaleimide treatment to a lesser extent than that of skeletal myosin. 2. The K+-ATPase activity of both myosins is inhibited in the same quantitative way. 3. The cardiac light chain L1 contains one highly reactive thiol group which is absent from the skeletal light chains. 4. The labelling of three SH-groups localized in the heavy subunits of both myosins induced the same degree of inactivation. 5. The difference observed between the degree of inhibition of the Ca2+-ATPase activity for the two types of myosin with longer treatments appears to be due to differences in the reactivity of the fourth--SH group labelled on the heavy chains.


The use of several energy-coupling reactions in characterizing mutants of Escherichia coli K12 defective in oxidative phosphorylation.

Oxidative phosphorylation, ATP-32Pi exchange, ATP-dependent quenching of acridine-dye fluorescence, ATP-dependent transhydrogenase and ATP-dependent transport of thiomethyl beta-D-galactoside are shown to be experimentally equivalent tools to study the functional state of the ATPase complex in Escherichia coli wild-type and mutant strains defective in oxidative phosphorylation. According to these criteria ten mutants in the ATPase complex were classified having lesions in the unc A,B region of the chromosome. The first mutant type lacks ATPase activity, but the membrane-integrated part of the complex remains functional (class I). The second mutant type lacks a functional membrane-integrated part, but retains ATPase activity (class II). The third mutant type is shown to be defective in both parts of the ATPase complex (class III).


Benign intracranial hypertension due to A-hypervitaminosis in adults and adolescents.

Three new cases of chronic vitamin A intoxication are reported and a review of the literature with special reference to chronic intoxication in adolescents and adults is presented. The most prominent features are intracranial hypertension, skin and hair deviations, pain in the musculoskeletal system, and fatigue. Intracranial hypertension occurs in 50% of chronic intoxications, but is not invariably linked with the other symptoms. Young women are the major age group represented. There seems to be no relation between the severity of the clinical picture and the vitamin A serum level. Discontinuance of vitamin A intake is sufficient for cure.


Pyrogen fever in rabbits pretreated with p-chlorophenylalanine or 5, 6-dihydroxytryptamine.

The hyperthermic effect of a bacterial pyrogen has been studied in rabbits pretreated or not with p-chlorophenylalanine or 5, 6-dihydroxytryptamine. The results obtained indicate that a selective reduction of cerebral 5-hydroxytryptamine levels by these drugs do not significantly affect pyrogen hypertermia.


Speculations on the evolution of ion transport mechanisms.

Primate cells evolved a plasma membrane to restrict the loss of important molecules. The osmotic problems that then arose were solved in one of several ways. Of major importance was the evolution of specific ion pumps, to actively extrude those salts whose inward diffusion would have led to swelling and lysis. In addition, these pumps allowed the cell to store energy in the form of ion gradients across the membrane. Thus, even in the earliest stages, the evolution of ion transport systems coincided with the development of mechanisms which catalyzes the energy transformations. It is postulated that an "ATP"-driven proton pump was one of the  first ion transport systems. Such a proton pump would extrude hydrogen ions from the cell, establishing both a transmembrane pH gradient (alkaline inside) and a membrane potential (negative inside). This difference in electrochemical potential for protons (the proton-motive force) could then drive a variety of essential membrane functions, such as the active transport of ions and nutrients. A second major advance was the evolution of an ion transport system that converted light energy into a form which could be used by the cell. The modern model for this is the "purple membrane" of Halobacterium halobium, which catalyzes the extrusion of protons after the capture of light. The protonmotive force generated by such a light-driven proton pump could then power net synthesis of ATP by a reversal of the ATP-driven proton pump. A third important evolutionary step associated with ion transport was the development of a system to harness energy released by biological oxidations. Again, the solution of this problem was to conserve energy as a protonmotive force by coupling the activity of a respiratory chain to the extrusion of protons. Finally, with the development of animal cells a more careful regulation of internal and external pH was required. Thus, an ATP-driven Na+-K+ pump replaced the proton-translocating ATPase as the major ion pump found in plasma membranes.


Pipillon-Lefèvre syndrome: report of two familial cases.

Two cases with Papillon-Lefèvre Syndrome (PLS) are reported. They are two brothers belonging to a family which there is strong consanguinity. An autosomal recessive pattern of inheritance is suggested. Some pathological findings as congenital bronchiectasis observed in one of the patients as well as the PLS features are discussed and considered to be fortuitous defects. These observations are compared with those described in the literature.


Bullous fixed drug eruption presumably due to erythromycin.

A case of bullous fixed drug eruption involving upper lip, tongue and foot, presumably due to erythromycin, is reported. It is perhaps the first report of erythromycin to be very likely the cause of fixed drug eruption.


Child health and paediatrics in the U.S.S.R.

Observations on child health and paediatrics made during a three weeks' visit to the USSR are recorded. There are separate health services for children and their organization is outlined, as are the training and career structure of the many thousands of paediatricians employed. Provision for handicapped children is briefly discussed and a few comments are made on social aspects of child care.


Studies of tryptophan and albumin metabolism in a patient with carcinoid syndrome, pellagra, and hypoproteinemia.

Detailed studies of protein metabolism were undertaken in a patient with pellagra and hypoproteinemia associated with the carcinoid syndrome both before and after treatment. The synthesis of albumin improved from 82 mg per kg per day to 135 mg per kg per day with little change in the daily excretion of 5-hydroxyindole acetic acid. After treatment with nicotinamide the patient made good progress with a complete resolution of the signs of pellagra and protein malnutrition. These results support the hypothesis that a reduced availability of the essential amino acid L-tryptophan may limit the synthesis of albumin and nicotinic acid in patients with the carcinoid syndrome who become anoretic.


Effect of long-term isolation of the rat on in vitro biosynthesis of gonadal steroids from dehydroepiandrosterone.

In vitro biosynthesis of gonadal steroids from dehydroepiandrosterone was studied in isolated and in socially reared male and female rats. Acetone-dried powder of gonadal tissue incubated with dehydroepiandrosterone-4-14C yielded androstenedione, androst-5-ene-3beta, 17beta-diol, 11beta-hydroxyandrostenedione and testosterone. In the male, conversion to androstenedione was significantly increased after isolation and conversion to androst-5-ene-3beta, 17beta-diol was significantly lowered. In the female, conversion to androstenedione and androstenediol was significantly lowered by isolation. Testosterone and 11beta-hydroxyandrostenedione were not affected by isolation. Gonadal tissue of isolated and of socially reared male and female rats metabolizes dehydroepiandrosterone in a different way. These findings support the view that the conditions of housing affect the production of sex steroids.


21 ring chromosome in a girl with stigmata of Down's and G deletion I syndromes.

An 11-year-old girl with severe psychomotor retardation and other congenital anomalies characteristic of Down's and G deletion I syndromes, was confirmed to be a chromosome 21 ring carrier by R- and G-banding techniques. The dynamics of the ring evolution resulting in a population of complex unstable rings, as in our index case, and the effects of the consequent ring mosaicism are briefly discussed.


Keratosis palmo-plantaris cum degeneratione granulosa.

Two cases of keratosis palmo-plantaris cum degeneratione granulosa Voerner are reported. A brief description of the characteristics of the clinical and histologic aspects of the disease is given and the mode of inheritance within the family affected is discussed.


Mutant forms of erythrocyte glucose 6-phosphate dehydrogenase in Ashkenazi. Description of two new variants: G6PD Kirovograd and G6PD Zhitomir.

Two new variants of erythrocyte glucose 6-phosphate dehydrogenase are discovered in 3 unrelated Ashkenazi Jew patients with severe deficiency of enzyme. Both variants have a resemblance to 2 other variants in Ashkenazi: G6PD Boston and G6PD Kilgore, but have a significantly higher affinity for substrates and their analogues and are not associated with chronic hemolytic disease. Probably, all 4 variants arise from two ancestral mutations.


On the origin of the supernumerary chromosome in autosomal trisomies--with special reference to Down's syndrome. A bias in tracing nondisjunction by chromosomal and biochemical polymorphisms.

The differential staining methods for chromosomes have led to the demonstration of more chromosomal polymorphisms. Not rarely, these polymorphisms allow in autosomal trisomies the detection of parental origin of the supernumerary chromosome. In addition, the malsegregation may be ascribed to 1st or 2nd meiotic division in informative families. This approach of analyzing possible causes of trisomies is subject to a considerable bias. Trisomic phenotypes are twice as frequent for 2nd meiotic errors than for 1st meiotic errors. Also, rare chromosome variants seldom occur in matings where malsegregation in 1st meiotic division can be detected. In the present paper this bias is analyzed mathematically on the family as well as on the population level. From this mathematical analysis and from the data in the literature we conclude that Down's syndrome as a whole is caused about 5-10 times more often by a malsegregation in 1st meiotic than by an error in 2nd meiotic division. Mainly from experimental studies in rodents, causes for errors in 1st and 2nd meiotic division are becoming apparent. They are summarized in the context of the results of the present paper.


Adjuvant and mitogenic properties of a supernatant fraction of sonically treated Myobacterium bovis (BCG).

A water-soluble, oil-free supernatant fraction of sonically treated BCG (BCG-SS) was shown to be an immunological adjuvant and a mitogen. When BCG-SS and sheep erythrocytes (SRBC) were injected intravenously into mice, the plaque-forming cell (PFC) response was 10 times greater than that induced by injection of SRBC alone. Circulating antibody responses to SRBC and to bovine serum albumin were also enhanced by BCG-SS. The in vitro enhancement of PFC and circulating antibody responses did not require mineral oil or exogenous lipids. In vitro PFC responses by normal mouse spleen cells were also greatly increased in the presence of BCG-SS. Anti-theta serum-treated spleen cells from mice that had been lethally irradiated and reconstituted with normal bone marrow cells also gave a higher PFC response to SRBC in the presence of BCG-SS. This suggests that BCG-SS can stimulate B lymphocytes to develop an immune response when T lymphocytes are severely depleted or absent. BCG-SS also stimulated the uptake of 125IUdR by normal spleen cell cultures, indicating that it is a mitogen.


A venous pulse Doppler catheter-tip flowmeter for measuring arterial blood velocity, flow, and diameter in deep arteries.

Numerous schemes have been used for measuring hemodynamic properties of deeply lying arteries; however, all have their limitations. This paper describes a new relatively nontraumatic intravenous approach that uses a catheter in connection with a pulsed ultrasonic Doppler velocity meter (PUDVM) and an echo track. The catheter was initially tested in a hydraulic model system for calibration of velocity and flow parameters. Lately, the catheter has permittted measurements of local instantaneous blood velocity, flow, and wall motion characteristics in adult Beagle dogs in the abdominal aorta and iliac artery. Evaluation studies have been conducted to compare the catheter-tip recordings with an independent method for measuring blood flow and wall motion. Coupling of this catheter-tip device with the PUDVM and echo track provides chronic measurements of hemodynamic parameters in these deep vessels which were virtually impossible to obtain previously. This technique may prove useful in monitoring vessel pathology longitudinally as well as in basic experimental situations requiring flow and arterial wall mechanical properties.


Intrafusal fibre types in rat limb muscle spindles: morphological and histochemical characteristics.

Morphological, histochemical and ultrastructural characteristics of intrafusal fibre types were studied in rat muscle spindles. The existence of three intrafusal fibre types, namely the typical bag, the intermediate bag and the chain fibres was confirmed. Intrafusal fibres differ in diameter, length and number of nuclei in the equatorial zone. Histochemically, typical bag fibres exhibit both alkali- and acid-stable ATPase activity and low SDH activity. Intermediate bag fibres possess low alkali-stable ATPase activity; after acid-preincubation, however, they have low activity only in the juxtaequatorial region, whereas in the polar zones they exhibit high acid-stable ATPase activity. The SDH activity varies from moderate to high. The chain fibres exhibit high alkali-stable and low acid-stable ATPase and high SDH activity in the extensor digitorum longus muscle, whereas in the soleus muscle the acid-stable ATPase activity varies from a low one to a high one, either among individual chain fibres in one spindle, and/or repeatedly along the fibre length. Since there are regional differences in morphological characteristics and in staining properties of intrafusal fibres, a reliable identification of intrafusal fibre types can only be achieved by an analysis of serial sections.


Carnitine biosynthesis in Neurospora crassa: enzymatic conversion of lysine to epsilon-N-trimethyllysine.

The enzymatic conversion of L-lysine, epsilon-N-trimethyl-L-lysine the first series of reactions in the biosynthesis of carnitine in Neurospora crassa, proceeds via sequential methylation of free L-lysine, epsilon-N-methyl-L-lysine, and epsilon -N-dimethyl-L-lysine. The latter two compounds have been shown to be intermediates in the biosynthesis of carnitine by radioisotope dilution and incorporation experiments in growing cultures of N. crassa 33933 (lys-) and 38706 (met-). Methionine but not choline, has been recognized as an effective methyl donor in vivo. Inclusion of choline in the growth medium of strain 33933 does, however, enhance incorporation of the methyl groups of L-[methyl-3H]methionine into carnitine in an apparent "sparing" effect on methionine synthesis. Studies in cell-free extracts of the lysine auxotroph strain 33933 of N. crassa have established that lysine and epsilon-N-methyl and epsilon-N-dimethyllysine are enzymatically methylated, with S-adenosyl-L-methionine as the methyl group donor. The enzyme system appears to have no essential cofactors. Lysine does not induce synthesis of the enzyme system in the wild-type strain 262, whereas both carnitine and epsilon-N-trimethyllysine repress its synthesis in strain 33933.


Metabolic rate of acidic complex saccharides in rabbit uterus under estrogenic condition.

Uterine slices obtained from estrogen-treated rabbits were incubated in vitro with N-acetyl-D-[1-3H]glucosamine together with D-[U-14C]glucose. The isotope-labelled acidic complex saccharides were then isolated by pronase digestion, Dowex 1 column chromatography and preparative electrophoresis on cellulose acetate membrane, in succession. In this way, individual acidic complex saccharides (hyaluronic acid, heparan sulfate, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, sulfated glycopeptide, and sialoglycopeptide) were separated into 2-5 subfractions. The specific radioactivity of hexosamine in the subfractions indicated that the metabolic rate of the uterine complex saccharides as follows: hyaluronic acid greater than sulfated glycopeptide greater than heparan sulfate greater than chondroitin sulfate C greater than dermatan sulfate. In addition, metabolic heterogeneity of heparan sulfate, chondroitin sulfate A, chondroitin sulfate C, and dermatan sulfate was suggested.


Proteochondroitin sulfate A in the euglobulin fraction of human plasma.

Euglobulin fraction of human plasma was extracted with 0.01 M phosphate buffer (pH 7.3) (PB) containing 1 M NaCl. The substances in the extract were separated by DEAE-cellulose column chromatography into two uronic acid-containing fractions (0.5 Fr and 0.75 Fr). The major fraction (0.75 Fr) was eluted at the void volume in gel filtration on Sephadex G-200, yielding 0.75-G Fr. 0.5 Fr and 0.75 Fr and their pronase digestion products (0.5-P Fr and 0.75-P Fr) together with 0.75-G Fr were examined by electrophoresis on cellulose acetate membrane. The results of electrophoresis and the digestibility with mucopolysaccharidases of these fractions indicated that 0.5 Fr and 0.75 Fr contained proteochondroitin sulfate A. It is suggested that chondroitin sulfate A in 0.5 Fr might be less sulfated than that in 0.75 Fr. Furthermore, analytical data and the infrared spectrum of 0.75-G Fr supported the above view.


A mathematical analysis of the substrate effect observed in 3beta-hydroxysteroid dehydrogenase reactions of rat testicular microsomes.

The substrate effect in enzyme reactions has been explained mostly in terms of an additional substrate binding site on the enzyme other than the catalytic site. A rate equation for the reaction is introduced according to the steady state mechanism as follows: v = (Ps3+Qs2+Rs)/(s3+Ls2+Ms+N), were the six parameters, L,M,N,P,Q, and R, can be determined by the least-squares method from the experimental points. The v vs. s curve has an asymptote parallel to the s abscissa, and can be classified into one of four types. The type A curve has an intersection with the asymptote and an apparent maximum velocity; the curve descends toward the asymptote. Type B has no intersection and no stationary point; the curve ascends toward the asymptote. Type C has two intersections and two stationary points, an apparent maximum velocity and a minimum velocity; the curve ascends toward the asymptote. Type D has no intersection and two stationary points; the curve ascends toward the asymptote. The equation was applied to the 3beta-hydroxysteroid dehydrogenase [EC 1.1.1.145] reaction of rat testicular microsomes. The conversion of 3beta-hydroxyandrost-5-ene-17-one was represented by type C, with an apparent maximum velocity of 0.338 nmole/min/mg protein at 0.912 muM of the substrate concentration, minimum velocity of 0.108 nmole/min at 16.6 muM, and saturating velocity of 0.169 nmole/min at infinite concentration of the substrate. The converson of 3beta-hydroxypregn-5-ene-20-one was of type B, having two inflexion points, 0.320 nmole/min at 2.735 muM and 0.814 nmole/min at 12.39 muM, and a saturating velocity of 3.80 nmoles/min at infinite concentration of the substrate.


Reaction intermediates of H-meromyosin-ATPase and ultraviolet difference spectrum of H-meromyosin induced by ATP.

UV Difference spectra of H-meromyosin (HMM) during the steady state of the myosin-ATPase reaction [EC 3.6.1.3] were measured in 1.5 and 0.05M KC1 in the presence of 5mM MgC1(2) and 20mM Tris-HC1 at pH 8.0 and 24 degrees, using pyruvate kinase [EC 2.7.1.40] and phosphoenolpyruvate to regenerate ATP. It was found that the difference spectrum and its dependence on ATP concentration were the same in 1.5M KC1 as in 0.05M KC1. On the bases of these and other results, the nature of the intermediates of HMM ATPase in the steady-state reaction of HMM ATPase was discussed.


Characterization of cytoplasmic actin isolated from Acanthamoeba castellanii by a new method.

Cytoplasmic actin has been isolated from Acanthamoeba castellanii by a new method, employing chromatography on DEAE-cellulose, that improves the yield by more than 20-fold over the previously reported method. This procedure should be particularly useful for isolating actin from cells in which it is present in relatively low concentration because the method does not depend initially on the polymerization of actin or its interaction with myosin. Systematic comparison of the properties of purified Acanthamoeba actin and rabbit skeletal muscle actin shows them to be similar in many ways: viscosity of F-actin, stoichiometry of bound nucleotide, stoichiometry of binding of muscle heavy meromyosin and myosin subfragment 1 in the absence of ATP, and ability to inhibit the KATPase activity of heavy meromyosin. The amino acid compositions of Acanthamoeba and muscle actin are also quite similar, but significant differences, especially the presence of epsilon-N-methyllysines in Acanthamoeba actin, have been confirmed. In addition to this structural difference, we find that Acanthamoeba actin is only one-third as effective as muscle actin as an activator of the MgATPase of muscle heavy meromyosin and subfragment 1. For Acanthamoeba actin, as for muscle actin, this activation exhibits hyperbolic dependence on actin concentration; i.e. the double reciprocal plot of ATPase activation versus actin concentration is linear. From these plots we find that the two actins give the same extrapolated ATPase activity at infinite actin concentration (Vmax) but differ by a factor of three in the concentration of actin needed to produce half-maximal activation (Kapp).


Specific sodium-22 binding to a purified sodium + potassium adenosine triphosphatase. Inhibition by ouabain.

Analysis of sodium-22 binding to purified sodium + potassium ion-activated adenosine triphosphatase (Na+, K+)-ATPase reveals the presence of two classes of binding sites. The higher affinity site (Kd = 0.2 mM) binds 6 to 7 nmol of sodium per mg of protein. Pretreatment of (Na+, K+)-ATPase with ouabain blocks the binding of sodium to this higher affinity site. Neither heat-denatured enzyme nor phospholipids extracted from the (Na+, K+)-ATPase contain a ouabain-inhibitable, higher affinity sodium binding site. The ouabain enzyme complex therefore appears to contain altered binding sites for cations.


Craniofacial contour defect reconstruction with a dacron/urethane composite: an alloplastic tray for bone induction fabrication and application.

An alloplastic tray made of poly(ethylene terephthalate) cloth mesh and poly(ether urethane) used in conjunction with cancellous bone-chip grafts is the basis for this new method of reconstructing facial osseous contour defects. The tray can be prefabricated in quantity and at low cost for standard defects, such as discontinuity defects of the mandible or for chin augmentation. It can be custom-fabricated for specific defects in individual patients as, for example, gunshot wounds to the forehead. The materials were chosen because of their known histocompatibility, the ease of fabrication, and because the materials can be molded to form esthetic contours. The can be easily modified at the time of surgery. Sterilization is by autoclaving. Initial studied were undertaken in mongrel dogs where mandibular discontinuity defects in the range of 2-4 cm were reconstructed. In man, the technique has been used to reconstruct discontinuity defects of the mandible ranging in size from 1.5-12 cm in 16 patients. Atrophic mandibular alveolar ridges have been augmented using this technique in 7 patients, thus providing an adequate alveolar ridge for dentures. Two patients with defects of the skull secondary to gunshot wounds have had frontal bone restoration using this method. Reconstructions of the ear, the chin, and the orbital floor are currently being evaluated. This technique overcomes many problems of esthetic contour reconstruction and combines the use of autogenous cancellous particulate bone and a tissue-compatible synthetic composite material.


Oxidized orlon as a blood interface.

Polyacrylonitrile fabric (Orlon) may by oxidized by heating in air, when it becomes black and carbonized. During the heat treatment, the fibers shrink; this shrinkage allows components such as diaphrams to be shaped around molds. Oxidation reduces the tensile strength by about 25% and also reduces the stiffness of the material. The oxidized Orlons was screened in tissue culture for possible cytotoxic effects. Finding none, patches of the material were sutured into the right atrium of dogs and examined after 48 hr. Because of encouraging results, 10 atrial patches, consisting of Dacron velour and oxidized Orlon side-by-side, were implanted into the right atrium of dogs. Five patches were backed with Silastic to render them impervious, and five with segmented polyurethane. The atrial patches were examined after 48 hr, and in all instances the oxidized Orlon part of the patch was coated with a thinner and smoother fibrin layer than was the Dacron velour half. a left ventricular bypass pump was fabricated from oxidized Orlon and spray-coated on the nonblood surface with segmented polyurethane. After 48 hr implantation in the chest cavity of a calf, pumping without systemic anticoagulation, the pump was found covered by a thin, smooth, firmly attached layer of fibrin.


Placental sulfatase deficiency: a case study.

A pregnancy with placental sulfatase deficiency was suspected when a 36-year-old patient at 41 weeks of gestation was found to have extremely low urinary estriol excretion and an otherwise normal prenatal course. The maternal plasma levels of estriol and estradiol 17-beta (E2) were extremely low and estetrol (E4) was undetectable (less than 40 pg/ml), whereas dehydroepiandrosterone sulfate (DS) was normal. THE AMNIOTIC Fluid DS concentration was 22-fold higher than the mean of normal pregnancy, while that of dehydroepiandrosterone (D) and androstenedione (A) was normal. Following intravenous infusion of 50 mg DS, no rise of plasma E2 was noted and plasma E4 levels remained undetectable. At 42 weeks of pregnancy, after induction of labor failed, a healthy male infant was delivered by cesarean section. The umbilical vein (UV) and umbilical artery (UA) levels of DS were extremely high, and those of E2 and E4 were subnormal. The UA level of A was normal and the levels of D and testosterone were slightly elevated. In vitro studies of placental microsomes and the 10,000 x g supernantant confirmed the diagnosis of placental sulfatase deficiency. The infant at 6 months of age had normal growth and development and normal peripheral plasma DS concentration.


Failure of endogenous plasmin to convert human growth hormone to its "activated" isohormones.

Human growth hormone B can be converted to its more acidic isohormones C, D, and E by limited enzymatic cleavage with purified plasmin in vitro. This process is accompanied by an increase of biological activity in the rat tibia line assay. A possible role of endogenous circulating plasmin in the in vivo formation of these isohormones was investigated. Human plasma, serum, glass-contact-activated serum, and serum extracts after the removal of protease inhibitors were incubated with ratioiodinated hGH-B and C for up to 24 h. Aliquots were analyzed at frequent intervals by polyacrylamide gel electrophoresis, followed by autoradiography and counting of radioactive bands. No evidence for interconversion or transformation to hGH-D and E was found. It is concluded that endogenous circulating plasmin does not play a major role in the conversion of hGH to its "activated" isohormones.


Sex hormone binding globulin: the carrier protein for d-norgestrel.

The binding of different synthetic steroids, used in hormonal contraception, to Sex Hormone Binding Globulin (SHBG) was studied by measuring their ability to displace tritiated testosterone from SHBG in a competitive protein binding system. Only 19-nortestosterone derivates had any significant ability to displace testosterone from SHBG, d-norgestrel (d-Ng) being the strongest displacer. Increasing the SHBG levels in women with previous constant plasma d-Ng levels increased these levels two- to sixfold. It is concluded that SHBG is the main carrier protein for d-Ng. The strong testosterone displacing activity of d-Ng might also explain androgenic side effects observed with d-Ng containig oral contraceptives.


A new method for measuring venous blood flow with the aid of an electromagnetic flowmeter.

Using a silicone elastometer sheath, wrapped around the portal vein, with an external probe for electromagnetic flowmetry, and with the aid of an outside depression, the authors succeeded in measuring portal vein blood flow with great precision, both under normal conditions and during vasoconstriction induced by drug administration. The above system allows variations synchronous with respiration and cardiac contractions to be seen. The reproducibility of a "no flow" point further enables registrations to be continued for hours for physiological and pharmacological studies. The sheath probe system described for the registration of portal vein blood flow is applicable to all other veins.


Effect of 7beta, 17alpha-dimethyltestosterone (calusterone) on cortisol metabolism in women with advanced breast cancer.

It was demonstrated that oral administration of 7beta, 17alpha-dimethyltestosterone (Calusterone) reversibly alters cortisol production and metabolism in women with advanced breast cancer. There was a 30% decrease in cortisol production  rate, a 50% decrease in transformation to tetrahydrocortisone (THE) glucuronide, a 50% prolongation of plasma cortisol half-life and decreased conversion to C-19 metabolites. The plasma cortisol concentrations (means and 24-hour profiles) remained unchanged by Calusterone despite the reduction in adrenocortical function. We have concluded that the beneficial effect of Calusterone in breast cancer is probably not due to its effects on cortisol production.


The effect of thyroid hormone on bile salt-independent bile flow and Na+, K+ -ATPase activity in liver plasma membranes enriched in bile canaliculi.

The relationship between bile salt-independent canalicular flow and ATPase activity in liver plasma membranes (LPM) enriched in bile canaliculi, was studied in control, hyperthyroid, and hypothyroid rats. Canalicular bile production was significantly increased in hyperthyroid rats (3.19 +/- 0.23 mul/min per g liver) compared to controls (2.27 +/- 0.24 mul/min per g liver), while it diminished in hypothyroid animals (1.58 +/- 0.17 mul/min per g liver). Although bile salt excretion was also increased in hyperthyroid animals (62.4 +/- 13.3 vs. 41.2 +/- 8.4 nmol/min per g liver), the stimulation in canalicular secretion was primarily related to enhancement of the bile salt-independent fraction of flow (2.47 mul/min per g liver in hyperthyroid rats vs. 1.67 mul/min per g liver in controls). LPM Na+, K+-ATPase activity doubled in hyperthyroid animals (21.5 +/- 5.8 vs. 10.7 +/- 3.1 mumol Pi/mg protein per h) while Mg++-ATPase activity remained unchanged and 5'-nucleotidase activity increased to a small but significant extent. In hypothyroid rats, bile salt excretion remained unchanged from control values so that the reduced secretion was entirely secondary to an inhibition of bile salt-independent secretion (1.19 mul/min per g liver). Na+, K+-ATPase activity in the LPMs from hypothyroid animals decreased by nearly 50% (5.4 +/- 1.6 mumol Pi/mg protein per h), although comparable reductions in the specific activity of Mg++-ATPase and 5'-nucleotidase were also observed. Administration of L-thyroxine to hypothyroid animals restored both bile salt-independent canalicular secretion and membrane enzymes to control values within 2 and 4 days, respectively. Sodium dodecyl sulfate gel electrophoresis demonstrated no significant changes in LPM protein fractions from any of the treatment groups. These studies indicate that thyroid hormone has a parallel effect on bile salt-independent canalicular secretion and LPM Na+, K+-ATPase activity, supporting the hypothesis that Na+ transport and Na+, K+-ATPase may be determinants of bile salt-independent canalicular flow.


Retention and degradation of 125I-insulin by perfused livers from diabetic rats.

The retention of degradation of insulin by isolated perfused liver have been examined. Noncyclically perfused livers from streptozotocin-diabetic rats retained 25% and degraded 10% of 125I-insulin administered as a 1-min pulse. On gel filtration (Sephadex G50F), the degradation products released into the vascular effluent eluted in the salt peak. During the 45-min interval after the end of the 125I-insulin infusion, 0.19% of the total dose was excreted in the bile. 60-90% of this material consisted of iodinated, low-molecular-weight degradation products. Inclusion of native insulin with the 125I-insulin in the pulse depressed both the retention and degradation of iodinated material; however, this reflected increased retention and degradation of the total insulin dose (125I-insulin plus native hormone). The log of the total amounts of insulin retained and degraded were linearly related to the log of the total amount of insulin infused at concentrations between 12.7 nM and 2.84 muM. Increasing the amount of native insulin in the infused pulse also depressed the total amount of iodinated material found in the bile and led to the appearance in the bile of intermediate-sized degradation products that did not simultaneously appear in the vascular effluent. Addition of high concentrations of glucagon to the infused 125I-insulin had no effect on the retention or degradation of the labeled hormone, or on the apparent size and amount of iodinated degradation products found in the vascular effluent or in the bile. Preinfusion of concanavalin A inhibited both 125I-insulin retention and degradation. A greater depression by concanavalin A of degradation than binding was also observed with isolated hepatocytes. In contrast to 125I-insulin, the retention and degradation of two iodinated insulin analogues of relative low biological potency, proinsulin and desalanyl-desasparaginyl insulin, were small. The amount of radioactivity appearing in the bile after infusion of these analogues was almost negligible. However, degradation products of these analogues that appeared in the bile and in the vascular effluent was qualitatively similar to those found after the infusion of 125I-insulin. Our findings suggest that the rapid initial uptake of 125I-insulin after its infusion into noncyclically perfused liver, as well as its subsequent degradation, behaves in a qualitatively similar fashion to the binding of 125I-insulin and its degradation by isolated rat hepatocytes. This uptake and the subsequent phase of degradation may be attributable to binding of insulin at specific recognition sites, preliminary to its transfer to a degradative site(s) presumed to be located inside the cell.


Interactions of actin, myosin, and an actin-binding protein of chronic myelogenous leukemia leukocytes.

Actin, myosin, and a high molecular weight actin-binding protein were purified from chronic myelogenous leukemia (CML) leukocytes. CML leukocyte actin resembled skeletal muscle and other cytoplasmic actins by its subunit molecular weight, by its ability to polymerize in the presence of salts, and to activate the Mg2+-ATPase activity of rabbit skeletal muscle myosin. CML leukocyte myosin was similar to other vertebrate cytoplasmic myosins in having heavy chains and two light subunits. However, its apparent heavy-chain molecular weight and Stokes radius suggested that it was variably degraded during purification. Purified CML leukocyte myosin had average specific EDTA- AND Ca2+-activated ATPase activities of 125 and 151 nmol Pi released/mg protein per min, respectively and low specific Mg2+-ATPase activity. The Mg2+-ATPase activity of CML myosin was increased 200-fold by rabbit skeletal muscle F-actin, but the specific activity relative to that of actin-activated rabbit skeletal muscle myosin was low. CML leukocyte myosin, like other vertebrate cytoplasmic myosins, formed filaments in 0.1 M KCl solutions. Reduced and denatured CML leukocyte-actin-binding protein had a single high molecular weight subunit like a recently described actin-binding protein of rabbit pulmonary macrophages which promotes the polymerization and gelation of actin. Cytoplasmic extracts of CML leukocytes prepared with ice-cold 0.34-M sucrose solutions containing Mg2+-ATP, dithiothreitol, and EDTA at pH 7.0 underwent rapid gelation when warmed to 25 degrees C. Initially, the gel could be liquified by cooling to ice-bath temperature. With time, warmed cytoplasmic extract gels shrunk ("contracted") into aggregates. The following findings indicated that CML leukocyte actin-binding protein promoted the temperature-dependent gelation of actin in the cytoplasmic extracts and that CML leukocyte myosin was involved in the contraction of the actin gels: (a) Cytoplasmic extract gels initially contained actin as their major polypeptide component and consistent of tangled thin filaments; (b) Contracted aggregates of cytoplasmic extract gels contained by large quantities of myosin as well as actin; (c) Purified actin-binding protein underwent a temperature-dependent, reversible aggregation and caused low concentrations of purified muscle or CML leukocyte actins to gel in sucrose solutions; (d) The gels formed from purified actin plus purified actin-binding protein slowly contracted in the presence but not in the absence of purified CML leukocyte myosin; (e) Rabbit antiserum against purified CML leukocyte actin-binding protein but not against purified CML leukocyte myosin inhibited the gelation of warmed CML leukocyte extracts. Antiserum against CML leukocyte myosin had no effect on the gelation of CML leukocyte extracts but partially curtailed the contraction of the CML leukocyte extract gels and of gels formed from purified CML leukocyte actin-binding protein plus rabbit skeletal muscle actin.


Pulsed Doppler ultrasound detection of flow disturbances in arteriosclerosis.

Pulsed Doppler ultrasound blood flow detection has been used in a noninvasive manner to detect arterial abnormalities associated with arteriosclerosis. Sound spectrograms of ultrasound signals obtained from in vitro and animal studies in which flow was disturbed by obstacles placed in the flow stream showed a different distribution of energy over frequency than signals obtained from studies with no flow disturbances. Similar findings were seen clinically. A technique has been developed which can detect disturbed flow patterns resulting from partial occlusion in important superficial arteries (e.g. femoral and carotid) up to 15 cm distal to localized arterial wall abnormalities. Thirty-five arterial examinations of normal and arteriographically abnormal arteries in 12 patients revealed a sensitivity of 83 percent and a specificity of 61 percent. This study suggests that pulsed Doppler ultrasound may be useful as a screening technique for detection of arteriosclerotic lesions in major superficial arteries.


Diagnostic echocardiography in the adult.

The purpose of this paper is to review basic and practical adult echocardiography. The commonly used techniques are briefly described. Normal valve characteristics, common valvular abnormalities, evaluation of cardiac chamber dimensions, pericardial space and left ventricular function are discussed. Newer aspects of echocardiography, two-dimensional scanning and pulsed Doppler techniques, are briefly reviewed. Finally, a discussion of problems and new directions in the field are presented.


Dietary adequacy, feeding practices, and eating behavior of children with Down's syndrome.

The dietary adequacy, eating behavior, and feeding practices of children with Down's syndrome were studied. Half of the children obtained from their food less than the recommended allowances for food energy, calcium, iron, vitamin A, and thiamin; children under six were vulnerable to iron inadequacies. Three-fourths of the children exceeded the allowances for protein and ascorbic acid. Contrary to the belief that parents of handicapped children are permissive, parents seemed to control the food consumption patterns of their children by appropriate techniques. Weight status appeared to be compatible with height in the majority of the participants.


Generation of cytolytic T lymphocytes in vitro. VIII. failure of anti-RS antisera to inhibit the generation of cytolytic T lymphocytes or cytolytic T lymphocyte activity.

Antibody reactive with "recognition structures" (RS) of mouse lymphoid cells for alloantigens (anti-RS) was prepared by immunization of F1 hybrid mice with parentalstrain lymphoid cells or with antibody produced in one parental strain against alloantigens of the other parental strain. Such antisera prevented generation of the "product of antigenic recognition" (PAR) that is produced within a few hours in cultures prepared with a mixture of lymphoid cells from genetically disparate mice. However, treatment of responding lymphoid cells with anti-RS sera and complement did not inhibit generation of cytolytic T lymphocytes (CTL) in mixed lymphocyte cultures (MLC). Treatment of cells obtained from MLC with anti-RS sera and complement failed to inhibit cytolytic activity of such cells for specific alloantigens.


Specificity of allogeneic and xenogeneic cell recognition in the fetal lamb.

Cells prepared from liver, thymus, and spleen of fetal lambs at different stages if gestation were confronted with allogeneic and xenogeneic cells in MLC. Specific elimination of the responding cells with BUdR and UV light together with a subsequent restimulation was used to study the specificity of the reaction. The response of fetal liver cells was not based on the existence of specifically recognizing cellular subpopulations; the response was concluded to be due either to stimulatory products released by the stimulating cells or to the multipotentiality of the responding cells. Specifically recognizing cells first appeared in the thymus at 58 days postconception and in the spleen at 70 days. In the response of sheep lymphocytes against allogeneic and xenogeneic (mouse, human) cells, a cross-reactivity occurred. Fetal lamb lymphocytes were also capable of recognizing intraspecies differences on the xenogeneic cells. This capacity developed simultaneously with the specific recognition of allogeneic cells. No clear difference was observed in the reactivity of fetal thymus cells and spleen cells when compared to that of adult peripheral blood lymphocytes. These findings indicate that immunologically specific recognition of foreign cells is created in the sheep during the early intrauterine development.


Altered lymphocyte functions in rats bearing syngeneic Moloney sarcoma tumors. I. Mitogen responses, mixed lymphocyte reactions (MLR) and mixed lymphocyte-tumor reactions (MLTR).

Impairment of mitogen responses to Con A and LPS and of MLR and MLTR was detected in the spleens of rats bearing syngeneic Moloney sarcoma tumors. Depressed responses of both T cell and Ig+ cell populations were observed. During the observation period of 6 to 10 days post-tumor inoculation when maximal T cell-mediated cytotoxicity was observed in spleen and draining lymph node cells, spleen cells showed marked impairment in response to stimuli mentioned above. By contrast, draining lymph node cell activity was either unaltered or somewhat elevated above the level of activity measured in normal control populations. Data presented in this and an accompanying paper strongly indicate that macrophages are activated as immunosuppressor cells in tumor-bearing rats.


A search for mycoplasmas and chlamydiae in acne lesions.

No mycoplasmas and no chlamydiae were found in cultures of 75 uninflamed comedones, 72 papulopustular lesions, and 7 cystic lesions from 14 subjects with acne. Chlamydial serologic tests were negative for 11 subjects and showed antibodies in 3 subjects to 3 different antigenic types of trachoma agent. These results are viewed as substantial evidence against the possibility that either mycoplasmas or chlamydiae play an important part in the pathogenesis of acne.


The penetration of local anesthetics into phosphatidylcholine monolayers.

The penetration of tetracaine into monolayers of phosphatidylcholine and trioctanoin at different surface pressures, and the penetration of dibucaine, tetracaine, butacaine, lidocaine, and procaine into monolayers of didecanoylphosphatidylcholine at II = 10 mN/m was determined by the use of a modified Gibbs adsorption equation. These data were shown to fit a geometric model and compared favorably with data determined by a method based on the geometric model. The penetration of tetracaine into phosphatidylcholine monolayers was pressure dependent. At II = 10 mN/m, the local anesthetics penetrate into a phosphatidycholine monolayer in the order: dibucaine greater than tetracaine greater than butacaine greater than lidocaine greater than procaine. This correlates with their potencies in blocking nerve conduction and inhibiting phospholipase A2.


Local anesthetic inhibition of pancreatic phospholipase A2 action on lecithin monolayers.

Using quantitative data previously reported for the penetration of local anesthetics into lecithin monolayers, the effects of surface and subphase concentrations of anesthetics on the inhibition of pancreatic phospholipase A2 action on didecanoyl phosphatidylcholine monolayers was investigated. Inhibition as a function of subphase concentration of anesthetic was in the order: dibucaine greater than tetracaine greater than butacaine greater than lidocaine = procaine. Inhibition as a function of surface concentration showed no obvious correlation; procaine inhibited at a very low surface concentration, followed by lidocaine at a somewhat higher concentration, and tetracaine, butacaine and dibucaine only at rather high concentrations. Ultraviolet difference spectroscopy indicated an interaction between lidocaine and enzyme in the subphase. Fluorescence studies showed that lidocaine is a competitive inhibitor of enzyme-lipid interface interaction. It is proposed that the more surface-active anesthetics inhibit by surface effects while the less surface-active anesthetics (lidocaine and procaine) inhibit by interaction with the enzyme in the subphase, which prevents enzyme penetration at the monolayer interface.


Comparison of the electrocardiogram and vectorcardiogram for the diagnosis of left atrial enlargement.

Standard 12 lead electrocardiograms (ECG) and Frank vectorcardiograms (VCG) were recorded in 21 consecutive patients with mitral valvular disease and angiographically documented left atrial enlargement. Comparative sensitivities for the detection of left atrial enlargement were: diagnostic, ECG = 6/21 (29%), VCG = 14/21 (67%); suggestive, ECG = 3/21 (14%), VCG = 2/21 (9%); non-diagnostic, ECG = 12/21 (57%), VCG = 5/21 (24%). It is concluded that the Frank atrial vectorcardiogram is superior to the standard electrocardiogram for the diagnosis of left atrial enlargement.


Postnatal cytochemical development of muscle fibers in segmental tail muscles of the rat.

Postnatal development of extrafusal and intrafusal muscle fibers was examined histochemically in segmental tail muscles of the rat. At birth all fibers show a strong reaction for myosin ATPase, uniformity in diameter, and homogeneity in staining intensity. During the first postnatal week, the muscle fibers undergo gradual hypertrophy and hyperplasia but they all maintain the same intense homogeneous staining pattern for the enzyme. By day 9, further differentiation of the muscle fibers results in the formation of a second intrafusal fiber type while the extrafusal fibers are still relatively homogeneous. Finally, two kinds of extrafusal fiber and a third type of intrafusal fiber can be distinguished by day 21. This histochemical fiber pattern is essentially maintained in the adult. These findings show that fiber type development in rat tail muscles lags behind the usual time course of myogenesis known to occur in more rostral regions of the animal. It also indicates that histochemical differentiation of intrafusal fibers in these muscles does not parallel that which occurs in extrafusal fibers. It is likely that arrival and initial contact of sensory nerve terminals on developing intrafusal fibers at day 7 directly influences their relatively early histochemical heterogeneity.


Morphometric studies of the neuropathological changes in choreatic diseases.

The striatum, pallidum and subthalamic nucleus were studied by combined morphometric methods in serial sections of 13 brains of normal adults and of 15 patients with choreatic diseases. In addition the volume of the hemispheres and of the cortex were measured. All data obtained were corrected by the shrinkage factor to represent fresh brain values. In Huntington's chorea the pallidum was more severely affected than is commonly appreciated. The average volume reduction was of the same degree (lateral-57%, medial-50%) as that of the striatum (-56%). The absolute number of nerve cells of the pallidum decreased in both segments by about 40%. The reduction of the volume and of the number of nerve cells was not reduced in the three subcortical nuclei studied. For the first time it has been shown that there is no increase in the absolute number of glial cells in the striatum. The increased  numerical density of glial cells is caused by shrinkage. The loss of nerve cells of the pallidum and subthalamic nucleus is caused mainly by a primary process. Huntington's chorea is a multifocal process. Morphometric data do not suggest that subchorea is a variant of Huntington's chorea. Chorea minor is regarded as a multifocal process with varying affliction of the striatum, pallidum and subthalamic nucleus. An increase in the number of glial cells and, as a rule, a moderate loss of nerve cells were found in this disease.


Muscle pathology of myotonia congenita.

We have investigated the muscle biopsies of 8 patients with myotonia congenita. There were 2 families with autosomal recessive inheritance (5 cases), 1 with autosomal dominant inheritance, and 2 sporadic cases. Mild abnormalities were seen with routine pathological preparations which were nondiagnostic. Histochemical studies of fiber subtypes demonstrated a complete absence of Type 2B muscle fibers in all of our patients regardless of the type of inheritance. this is the first reporot of an entity in which there is a consistent absence of a muscle fiber type, and some speculation has been made as to the possible causes.


The pathology of the muscle spindle in Duchenne muscular dystrophy.

Muscle spindles have been studied in 7 autopsied cases of Duchenne muscular dystrophy. The autopsies of 2 boys of similar age who died without known neuromuscular disease were used as controls. The abnormalities found consisted of degenerative changes, atrophy and loss of intrafusal muscle fibres, thickening of the spindle capsule and widening of the periaxial space. In some very severely affected muscles there was evidence that spindles were destroyed in the course of the disease. Statistical comparison of these observations was made between the pathological and normal material. The muscle spindle innervation appeared normal in sectioned material. Teased preparations were not available for study.


Morphogenesis of rat muscle spindles after nerve lesion during early postnatal development.

The influence of innervation on muscle spindle morphogenesis has been investigated in rat hind-limb muscles by sectioning the sciatic nerve, with suture of the stumps, at various postnatal stages. After nerve section at 4 or 7 days of age a proportion of spindles survived during the denervation phase and developed, during the subsequent reinnervation phase, into atypical structures. The reinnervated spindles were recognized by the presence of a limiting capsule but lacked the characteristic distinction of equatorial and polar regions. The intrafusal fibres were fewer than normal and were indistinguishable in size and fine structure from extrafusal fibres; they had a single motor endplate and lacked sensory nerve terminals. In reinnervated muscles of animals operated at 13 and 22 days of age there was a progressive tendency towards a restoration of normal spindle structure and innervation. These findings indicate that muscle spindle morphogenesis is profoundly altered by nerve lesion at early development stages, apparently as a result of inadequate sensory reinnervation. This study also shows that the differentiation of intrafusal fibres is dictated by their specific pattern of innervation and is not intrinsically predetermined.


Responses of cortical neurons (areas 3a and 4) to ramp stretch of hindlimb muscles in the baboon.

1. A study was made of the response of single cortical units in areas 3a and 4 to electrical stimulation of hindlimb muscle nerves and to ramp stretch of hindlimb muscles in baboons anesthetized with chloralose.2. Stimulation of hindlimb muscle nerves revealed a group I projection primarily to area 3a but with some input into adjacent area. 4. A major group II projection was found in area 4 adjacent to area 3a. A small number of area 3a neurons receive convergence from both group I and group II muscle afferents.3a. On the basis of their response pattern to ramp stretch, units were classified into one of six categories and their cytoarchitectonic location was determined. Units in area 3a had hynamic sensitivities equivalent to that of the primary spindle afferents. Although the discharge of some area 3a neurons also reflected differences in muscle length, most area 3a neurons had low position sensitivities. One unit type in area 3a did not respond to maintained muscle stretch and signaled only velocity of stretch.4. Units in area 4 had position sensitivities equivalent to that of primary and secondary spindle afferents. Although the discharge of some area 4 units reflected different velocities of muscle stretch, these units had dynamic sensitivities similar to those of secondary spindle afferents rather than those of primary afferents. One type of unit in area 4 had no dynamic component to muscle stretch and signaled only muscle length.5. The results demonstrate that there is a transfer of dynamic and position sensitivity from spindle afferents to cortical neurons. Furthermore, data processing has occurred because some units respond only to the steady-state length of muscle, while other units encode only the dynamic phase of stretch. This behavior is different from the responses to ramp stretch of either group I or group II muscle afferents in the baboon.6. The results demonstrate that single units in cerebral cortex can encode the information transmitted to the central nervous system by muscle spindle afferents. The purpose for which this information is used remains undetermined.


Clindamycin: an evaluation of its role in dental patients.

A review of the etiology of orofacial infections, of the pharmacology and spectrum of clindamycin and its associated complications, and a treatment plan for orofacial infections have been presented. On the basis of the data presented, it would seem that except for proved B fragilis infections, clindamycin is not a first-line drug for infections of the orofacial region. There are, however, indications for its use that have been presented. The serious complications associated with its use have also been presented. A high index of suspicion must be maintained regarding the development of these complications if clindaymcin is to be used.


Aortic aneurysm in childhood: report of six instances.

Six instances of aortic aneurysm in children have been observed in the past 15 years. Four children with aortic stenosis and coarctation of the aorta had aneurysmal dilatation of the ascending aorta, and two children with coarctation of the aorta had ruptured post-stenotic dilatation of the descending aorta. Our observations suggest that aortic aneurysm can be the result of hemodynamic stress, although developmental anomaly of the aorta associated with aortic stenosis or coarctation could be responsible for the development of the aneurysm.


Servo action in the human thumb.

1. The servo-like properties of muscle in healthy human subjects have been studied by interfering unexpectedly with flexion movements of the top joint of the thumb. This movement is carried out by the flexor pollicis longus muscle only. 2. The movements were standardized in rate by giving the subject a tracking task. They started off against a constant torque load offered by an electric motor. 3. In some movements the load remained constant, but in others, in mid-course, perturbations were introduced at random. Either the movement was halted, or released and allowed to accelerate by reducing the load, or reversed by suddenly increasing the current in the motor, so stretching the muscle. 4. Usually eight or sixteen responses to each kind of perturbation and a similar number of controls against a constant load were averaged. 5. Muscle activity was recorded as the electromyogram from surface electrodes over the belly of the long flexor in the lower forearm. Action potentials were usually full-wave rectified and integrated. 6. About 50 msec after a perturbation the muscle's activity alters in such a sense as to tend to compensate for the perturbation, i.e. it increases after a halt or a stretch and decreases after a release. The latency is similar in each case. 7. These responses are interpreted as manifestations of automatic servo action based on the stretch reflex. They are considered to be too early to be voluntary. 8. This interpretation was supported by measuring voluntary reaction times to perturbations under tracking conditions. They were found to be 90 msec or longer. 9. When the initial load was increased by a factor of 10, the servo responses were all scaled up likewise. Thus to a first approximation the gain of the servo is proportional to initial load. 10. It follows that in relaxed muscle the gain should be zero. This was confirmed by showing that stretching a relaxed muscle gives no reflex, or only a small one. 11. Gain appears to be determined by the level of muscle activation as determined by the effort made by the subject, rather than by the actual pressure exerted by the thumb. 12. Thus in fatigued muscle gain is boosted as the muscle has to be activated more strongly to keep up the same force output. The net effect is to compensate for fatigue and maintain the performance of the servo. 13. The Discussion centres on the implications of gain control in the servo. For a start, if the gain of the stretch reflex arc is zero in relaxed muscle, contractions cannot be initiated via the stretch reflex by simply causing the spindles to contract, as proposed on the original 'follow-up' servo theory.


Correlation analysis of muscle spindle responses to single motor unit contractions.

1. Cross-correlation techniques have been used to study the responses of muscle spindle afferents from the soleus muscle of the cat to twitch contractions of single motor units. 2. Cross-correlograms (post-stimulus time histograms) were used to give the frequency of occurrence of a receptor spike at various times following the initiation of a motor unit contraction together with a display of the average twitch tension wave form. 3. The cross-correlograms revealed that the contraction of a single motor unit can be an effective stimulus to a spindle receptor and may induce afferent firing pattern alterations similar to those observed with whole muscle contraction. 4. The cross-correlograms also revealed  quantitative differences in the response of a receptor to contraction of different motor units and to contraction of the same motor unit at different lengths. These differences reflect subtle changes in receptor deformation developed by the twitch of a motor unit under different conditions and by the twitches of different motor units. The results are consistent with anatomical data on the number and distribution of motor units and receptor organs in cat soleus. 5. These findings emphasize that rather than simply acting as generalized force or length sensors for the muscle as a whole, each receptor's spike train carries information about the state of a particular set of motor units.


Alkyl streptozotocin analogues with improved biological activities.

Alkyl 16alpha- and -beta-glycosides of a series of N3-alkyl homologues of streptozotocin were synthesized from glucosamine hydrochloride. These compounds, when tested against ascites Sarcoma 180, Ehrlich ascites carcinoma, or leukemia L1210, exhibited potent antitumor activities, and antibacterial and diabetogenic activities were eliminated. Furthermore, the acute toxicities of these compounds were lower than that of streptozotocin. The methyl, ethyl, n-propyl, and n-butyl glycosides of streptozotocin, whether alpha- or beta-anomers, all showed higher antitumor activities than streptozotocin itself. The most active compound was found to be the methyl beta-streptozotocin.


Karyotypic analysis of 150 cases of Down's Syndrome in Iraq.

This study represents a cytological survey of 150 cases of Down's syndrome to find the proportion of the different types of chromosomal aberrations and how they compare with other studies.


The chronic and acute effects of ethanol on adenosine triphosphatase activity in cultured astroblast and neuroblastoma cells.

Mg2+ATPase and (Na+ + K+)ATPase activities were measured in clonal line NN hamster astroblasts and in clonal lines M1 and N1E-115 mouse neuroblastoma cells after the cells had been subjected to the acute and chronic actions of 100 mM ethanol. Exposure of the astroblasts to ethanol for periods as long as 68 days produced an increase in total cellular Mg2+ ATPase activity, as measured in cell homogenates; however, activity reverted to control levels upon withdrawal of ethanol. Chronic exposure of clonal line N1E-115 neuroblastoma cells to ethanol produced an increase in Mg2+ATPase and (Na+ +K+)ATPase activities. In contrast, the activities of both ATPases of clonal line M1 neuroblasts were unaffected by chronic exposure to ethanol. Acute exposure of cell homogenates to 100 mM ethanol inhibited Mg2+ ATPase and (Na+ + K+)ATPase of astroblasts but not that of neublastoma cells. These findings suggest that neural cells in culture may serve as useful models for studying the effects of ethanol on specific cell types.


Echocardiographic study on hypertrophic cardiomyopathy.

Echocardiographic study was performed on 21 cases with hypertrophic cardiomyopathy (HCM), 10 obstructive and 11 nonobstructive. Asymmetric septal hypertrophy was demonstrated in both obstructive and nonobstructive HCM. In all cases of HCM studied, the thickness of the interventricular septum was 1.4 cm or more (1.4-3.7 cm) and the ratio of septal to left ventricular posterior wall thickness was 1.4 or more (1.4-3.2). A systolic anterior movement of the mitral valve (SAM) was observed in obstructive cases only and characterized by a large backward component in late systole and an extreme approximation to the interventricular septum at its peak. Patients with HCM also showed abnormal echocardiographic indices of the left ventricular diastolic properties, such as the rate of diastolic descent of the mitral valve (DDR), mean diastolic posterior wall velocity (mPWVd), D/S ratio and mean rapid filling rate (mRFR). DDR correlated well with the ratio of rapid filling to total filling volume, rapid filling fraction, (r = 0.79, p less than 0.001), suggesting that reduced DDR in HCM was related with an abnormal left atrio-ventricular flow pattern. A significant correlation was also observed between mRFR and negative maximum dp/dt derived from the first derivative curve of the left ventricular pressure (r = o.68, p less than 0.005). Thus echocardiography was proved to be a valuable means for investigation of the left ventricular properties during early diastole.


Functionally atrialized parchment-like right ventricle with extensive myocardial fibrosis of left ventricle.

A 18-year-old female with unusual type of parchment-like right ventricle died of intractable congestive heart failure was reported. A catheter study revealed the absence of systolic contraction of the right ventricle. The pressure tracing curve in the right ventricle was virtually the same as in the right atrium. At autopsy, there was an extensive myocardial fibrosis of the left ventricle in addition to the almost total absence of the myocardium of the right ventricle. The case was considered to be a unique type of idiopathic cardiomyopathy.


Intrarenal distribution and ATPase inhibiting activity of ouabain in dogs.

Experiments were undertaken to substantiate the hypothesis that the mechanism of the direct effect of ouabain on the renal excretion of electrolytes is the result of inhibition of the transport enzyme, (Na, K)-ATPase. In dogs hydrated with saline, an injection of 3H-ouabain into the unilateral renal artery produced a continuing marked increase in excretion of water and sodium from the kidney, but not from the counter kidney. At maximal diuresis--90 min after ouabain injection, both kidneys were removed to assay microsomal ATPase activity and determine radioactivity distributed in subcellular structures. It was demonstrated that 3H-ouabain was deposited in the microsome fraction obtained from the injected kidney in concentrations ranging from 10(-7) to 10(-6) M/kg wet weight, and (Na, K)-ATPase activity of this fraction was inhibited as compared with that of the microsomal fraction obtained from control kidneys. Since (Na, K)-ATPase activity of renal microsomes was significantly inhibited in vitro by more than 10(-7) M of ouabain, ouabain concentration in microsomes obtained from the injected kidney was considered to be sufficient to inhibit ATPase activity. These findings indicate that ouabain diuresis under the present condition is closely related to direct inhibitory effect of ouabain on (Na, K)-ATPase activity of microsomes in tubular cells.


[Experimental basis of a new method of determination of coronary blood flow with the aid of electromagnetic flowmeter].

Canine experiments have demonstrated the high precision of measurements performed with the aid of modern electromagnetic flowmeters (1-2%). Under such conditions, cuff transducers of a large diameter permit to record low volume flow rates. Proceeding from this observations, the authors have introduced and experimentally substantiated a new method of measuring the coronary blood flow that consists in the determination of the minute volume gradient between the pulmonary artery trunk and the ascending aorta. In contrast to the existing techniques of coronary flow measurements, the introduced method has several advantages (it takes into account the total coronary flow, permits high precision and an unlimited number of repeated measurements in a dynamic observation), but it can be employed only in the course of surgical interventions on the heart after the ascending aorta has been separated from the trunk of the pulmonary artery.


Acute effect of nephrotoxic serum on renal sodium transport in the dog.

In order to study the tubular mechanism for salt retention in acute proliferative glomerulonephritis, clearance and micropuncture experiments were performed on nine volume-expanded dogs before and after injection of sheep anti-dog glomerular basement membrane (GBM) antibodies (nephrotoxic sera [NTS]). Histologic sections obtained two hours after NTS injection following completion of the functional studies demonstrated infiltration of glomerular tufts by polymorphonuclear leukocytes, swelling of both glomerular endothelial and mesangial cells and the mesangial matrix, and linear anti-GBM antibody deposits along the glomerular capillaries. There was an almost immediate reduction in glomerular filtration rate (GFR), filtration fraction, urine flow and absolute and fractional sodium excretion; arterial blood pressure and renal plasma flow were not significantly altered. Micropuncture studies revealed no change in fractional sodium reabsorption in the proximal tubule despite a fall in single nephron GFR. A proportional reduction in single nephron and kidney GFR coupled with an unchanged intrarenal distribution of blood flow following NTS suggests a relatively uniform effect on both superficial and deep nephrons. In contrast to the well-preserved glomerulotubular balance in the proximal tubule, fractional distal sodium reabsorption was significantly increased as reflected by the decreased fractional urinary sodium excretion. We conclude that salt retention and low fractional urinary sodium excretion observed in acute glomerulonephritis could be primarily due to reduced distal delivery of sodium which leads to increased fractional sodium reabsorption in the nephron segments distal to the proximal convoluted tubule.


Immunologic mechanisms in systemic vasculitis.

Thirty-four patients with systemic vasculitis were studied to determine the possible type and frequency of associated immunologic abnormalities. The patients were divided into three clinical groups--those with systemic vasculitis without respiratory tract involvement, those with systemic vasculitis with respiratory tract involvement (particularly Churg-Strauss vasculitis and Wegener's granulomatosis), and those with limited vasculitis without visceral involvement. A diminished level of serum complement was found in half the patients with systemic vasculitis without respiratory tract involvement. These patients usually had diffuse skin disease that often was associated with the presence of rheumatoid factor and cryoglobulinemia and most likely represented an immune-complex induced disease. The serum IgE often was elevated in patients who had systemic vasculitis with respiratory tract involvement, particularly those with Churg-Strauss vasculitis and Wegener's granulomatosis, and may be a clue to the pathogenesis in this group of patients.


Alcohol intake in the rat after lowering brain 5-hydroxtryptamine content by electrolytic midbrain raphé lesions, 5, 6-dihydroxytryptamine or p-chlorophenylalanine.

Voluntary alcohol consumption was measured in male albino rats after selectively lowering their brain 5-hydroxytryptamine concentration (an AA strain of rats was used, selectively outbred for its high alcohol consumption). The brain 5-hydroxytryptamine concentration was reduced using three different techniques: electrocoagulation of the dorsal and median raphé nuclei of the midbrain; injection of 75 mug of 5,6-dihydroxytryptamine into the lateral cerebral ventricle; and oral administration of 300 mg/kg/day p-chlorophenylalanine as a 0.5 per cent carboxymethylcellulose suspension, for 12 days. The first two methods did not markedly affect alcohol consumption despite a sizable decrease in the brain 5-hydroxytryptamine level: 69 per cent in the raphé-lesioned group and 31 per cent in the 5,6-dihydroxytryptamine-treated group. Intraperitoneal injection of 50 mg/kg L-5-hydroxytryptophan on five successive days resulted in a non-significant decrease in alcohol consumption by the 5,6-dihydroxytryptamine-treated rats. p-Chlorophenylalanine did reduce significantly alcohol drinking but it had a greater effect in increasing water intake, producing a net rise in total fluid consumption. The reduction in alcohol consumption, therefore, was probably an indirect result of the treatment. These findings raise doubts about the previously suggested relationships between brain serotonin depletion and alcohol drinking.


Ageing of Neurospora crassa. III. Induction of cellular death and clonal senescence of an inositol-less mutant by inositol starvation and the protective effect of dietary antioxidants.

Clonal growth rate and cellular viability of an inositol-less mutant of Neurospora crassa decline rapidly during deprivation of dietary inositol. Dietary antioxidants, either nordihydroguaiaretic acid, vitamin E or 3,5-ditert.-butyl-4-hydroxybenzyl alcohol, protected cells and clones of the mutant from death and senescence. Membrane deterioration with associated lipid autoxidation and consequent deleterious free radical reactions appear to be, in part at least, the causes of the mutant's death and senescence.


Acne vulgaris.

A theory concerning the pathogenesis of acne vulgaris is offered and, based on the theory, a rationale for treatment is presented. Acne vulgaris should be regarded as a cosmetically unacceptable biological variation in most cases, a syndrome rather than a disease. One must not lose sight of the occasional case in which it is the marker of an endocrine disorder.


Comparison of ultraviolet and blacklight for the induction of nutritional independence at two loci in Neurospora crassa.

The inactivating effects of both near ultraviolet (blacklight) and shortwave ultraviolet (UV) have been investigated for two auxotrophic strains of Neurospora crassa. The two strain were indistinguishable with respect to their sensitivity to inactivation by blacklight, but differed in their sensitivity to UV (DEF congruent to 1.3-1.6 at 0.1 survival). The strains each carried an allele of different genes previously demonstrated as being capable of mutation in response to UV. The results confirm the mutability of these alleles, but reveal that within the population densities investigated mutations to nutritional independence by blacklight were undetectable.


Clonidine antinociceptive activity: effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat.

Clonidine is able to increase the threshold for vocalisation during stimulation and the threshold for vocalisation after withdrawal of stimulus (vocalisation afterdischarge). These effects of clonidine were investigated after treatment of rats with drugs influencing central monoaminergic and cholinergic mechanisms. Chlorpromazine, atropine and p-chlorophenylalanine increased the activity of clonidine at both thresholds while phenoxybenzamine and reserpine pretreatment increased the activity at the thresholds for vocalisation only. Yohimbine decreased clonidine activity at both thresholds while 5-HTP and alpha-methyl-p-tyrosine decreased the effects at the threshold for vocalisation  afterdischarge. Naloxone did not change the activity of clonidine at either pain response studied. It is concluded from the present findings that influence from several neuronal systems modulate the antinociceptive action of clonidine. The inhibition of the medullary nociceptive response after clonidine might be connected to a decreased activity of noradrenergic neurons. Endogenous noradrenaline seems to be of minor importance in mediating this effect. It is moreover shown that decreased cholinergic receptor activity enhances clonidine antinociceptive action on both medullary and diencephalic-rhinencephalic pain responses. The possible involvement of serotonin these functional responses after clonidine is also discussed.


Inhibition of glucose phosphorylation in rat brain by thiopental.

The purpose of the present investigation was to shed some light on the suppression of the glycolytic pathway by anesthetics. The antimetabolite 6-aminonicotinamide (6-AN) was used to discriminate between the key enzymes hexokinase and phosphofructokinase which are suggested to be involved in the effect of anesthetics on glycolysis. The cerebral energy metabolism was studied in the isolated perfused rat brain after the addition of thiopental (0.15 mM) to the perfusion medium, after the administration of 6-AN (35mg/kg i.p.) to the intact animals 15 h before perfusion was started, as well as in brain preparations treated in the same manner with both 6-AN and thiopental. After a perfusion period of 30 min brain levels of the following substrates and metabolites were determined: phosphocreatine, ATP, ADP, AMP, glycogen, glucose, glucose 6-phosphate, fructose 6-phosphate, pyruvate, lactate, alpha-ketoglutarate, blutamate, ammonia, and 6-phosphogluconate. The metabolic alterations in the isolated rat brain caused by 6-AN or thiopental were such as reported in the literature. When the isolated brains of the 6-AN pretreated rats were perfused with thiopental we found as the most interesting result that the concentration of glucose 6-phosphate was reduced in comparison to that in brains only treated with 6-AN but still significantly higher than that in controls. The glucose concentration was significantly elevated and the lactate concentration decreased considerably. The effect of thiopental on cerebral glycolysis was interpreted as an inhibition of hexokinase activity.


Leucocidin from Pseudomonas aeruginosa and membrane functions.

Leucocidin from Pseudomonas aeruginosa (strain 158) induced loss of potassium from isolated hepatocytes. The (Na+-K+) stimulated ATPase activity of isolated rat liver plasma membranes showed dose-dependent activation up to 56%. Electron-spin-resonance (ESR) measurements gave no indication of toxin-induced changes in membrane fluidity. On isolated guinea pig heart auricles the toxin produced an increase in frequency from 180/min to about 300/min, with arrhythmia and transitory flutter. On isolated nerve-diaphragm preparations the toxin caused a contracture and  a decline in twitch tension, with a loss of potassium into the bathing solution. The action potential of the electrically stimulated N. ischiadicus of rat or frog was not affected when leucocidin was added to the bathing solution up to a concentration of 10 micrograms/ml.


[The effect of hypertonic solutions on the electrical activity of isolated frog muscle spindles].

Electrical activity of an isolated frog muscle spindle was investigated in hypertonic solutions obtained by adding 400 mM of sucrose, glucose or glycerine to the Ringer solution. In sucrose and glucose hypermedia the frequency of background impulse activity first increased and then decreased up to zero; receptor potentials and evoked impulse activity simultaneously decreased and disappeared. In the glycerine hypermedia impulse activity after some increase returned to normal and then a second rise of frequency to a constant supernormal level was observed. After returning to the Ringer solution from sucrose or glucose the background and evoked impulse activity progressively returned to normal. But after glycerine hypermedia a significant growth in the background impulse activity and a small change in frequency of evoked impulse activity were observed. The observed changes of electrical activity of the muscle spindle in hypermedia are discussed in terms of deformation of sensory endings and intrafusal muscles fibres leading to depolarization of the receptor membrane.


[Responses of the muscle spindles of tenotomized and hypertrophied muscles to stretch and vibration].

Responses of primary and secondary endings of muscle spindles were studied after tenotomy and hypertrophy in the cat soleus muscles. Under constant load (100 g) background activity of primary endings in a control muscle was 17 +/- 1.5 imp/s. It did not change in hypertrophic muscle and increased after tenotomy to 26 +/- 1.5 imp/s. Responses of secondary endings did not change under the same conditions. The frequency of a response from primary and secondary endings of tenotomized and hypertrophic muscles were higher during dynamic and static phase of stretching as compared to response of normal muscle spindles. Primary endings of tenotomized and hypertrophic muscles were able to repeat vibration up to 200 Hz, while secondary endings responded only with some increase in the discharge frequency.


Cerebrospinal fluid gamma-aminobutyric acid in neurologic disease.

Cerebrospinal fluid gamma-aminobutyric acid (CSF GABA) was analyzed in 151 patients who underwent evaluation for central nervous system disease. CSF GABA was not detected in 19 of these patients, who had no evidence of neurologic disease and who served as controls. GABA was most frequently detected in patients with cerebrovascular disease, and was detected only in Parkinson's syndrome of atherosclerotic origin and dementia of multi-infarct type. CSF GABA was not detected in Alzheimer's disease or Huntington's disease. Patients with grand mal seizures exhibited CSF GABA elevation within 24 hours of the ictus. In patients with multiple sclerosis GABA detection was related to the presence or exacerbation of spinal cord lesions. Further study is necessary to evaluate the significance of elevated CSF GABA in central nervous system disease.


Brain serotonin after experimental vascular occlusion.

Unilateral ligation of a common carotid artery in gerbils causes a decreased rate of serotonin synthesis and degradation but an increased release of this monoamine. In the brain, reduction of cerebral serotonin content during ischemia is followed by accumulation of its main metabolite, 5-hydroxyindolacetic acid. These data support the contention that serotonin plays an important role in the progression of cerebral infarction.


Suppression of decerebrate rigidity by phenytoin and chlorpromazine.

In cats decerebrated by a midcollicular section, decerebrate rigidity developed that was not alleviated by phenytoin even in doses as great as 60 mg per kilogram. Chlorpromazine that depresses decerebrate rigidity in a dose-related fashion requires 1.5 to 2.0 mg per kilogram to exhibit an appreciable effect. In the presence of 20 mg per kilogram phenytoin, however, as little as 0.1 mg per kilogram chlorpromazine markedly reduces decerebrate rigidity. This drug combination did not impair neuromuscular transmission nor did it severely impair motor coordination in cats. Although phenytoin depressed muscle spindle discharges, this peripheral suppression was insufficient to abolish the rigidity. Phenytoin with or without chlorpromazine may be of value in suppressing muscle rigidity in some disorders of upper motor neuron lesions.


Starch granuloma syndrome. Starch peritonitis as an iatrogenic disease.

A report of a patient with granulomatous peritonitis following general surgery is presented. Laparoscopy was performed as the final diagnostic procedure. Prevention is the remedy for this iatrogenic problem.


47,XXX karyotype obtained by amniocentesis.

A 29-year-old pregnant patient, gravida 4, para 3, sought genetic counseling because of a daughter who had Down's syndrome. Amniotic fluid obtained by amniocentesis indicated the fetal karyotype to be 47,XXX. The pregnancy was terminated and the karyotype was confirmed by typing venous blood from the fetus and the finding of double Barr bodies in the histologic sections of fetal tissue.


Ovarian and adrenal contributions to peripheral steroid levels in postmenopausal women.

Serum levels of cortisol (F), pregnenolone (delta5-P), 17-hydroxypregnenolone (17-delta5-P), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), progesterone (P), 17-hydroxyprogesterone (17-P), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), androst-5-ene-3beta, 17beta-diol (delta5-diol), estrone (E1), and estradiol-17beta (E2) were measured in 10 postmenopausal and 5 premenopausal women before (control) and after 7 days of Dexamethasone (post-dex). Control and post-dex levels of delta5-P, P, DHT, T, and F were not different (P greater than 0.05) in premenopausal versus postmenopausal women, while the control levels of 17-P, DHEA, DHEA-S, A, delta5-diol, and E2 were lower in the postmenopausal women (P less than 0.05). Assuming post-dex levels equal ovarian contribution, the ovarian contribution of 17-delta5-P, 17-P, DHEA, delta5-diol, A, E1, and E2 and the adrenal contribution (control-post-dex) to DHEA, DHEA-S, 17-P, A, and delta5-diol was significantly lower (P less than 0.05) in postmenopausal subjects.


Prenatal genetic diagnosis in 350 amniocenteses.

Three hundred and fifty second trimester amniocenteses performed for prenatal diagnosis of genetic disorders are reported. One hundred and ninety-three of these were performed because maternal age was greater than 35 years, and 6 fetuses with unbalanced chromosomal abnormalities (3%) were identified. Thirteen procedures were performed because a previous child had had a neural tube defect; 1 anencephalic fetus was identified. Ninety-six percent of the initial taps were cultured successfully; we failed to obtain amniotic fluid in 3% of patients. The risk of a spontaneous abortion occurring at some time after the amniocentesis was 0.85%, and no cases of fetal injury were identified.


[New cestode, Fimbriarioides tadornae sp. n. from the sheldrake, Tadorna tadorna, and its development in the intermediate host].

A new species of cestodes, Fimbriarioides tadornae sp. n., is described from Tadorna tadorna from the Lake Tengiz (Central Kazakhstan). Artemia salina is an intermediate host of the above cestode. The development of F. tadornae from the oncosphere to the invasional cysticercoid under conditions prevailing in the Lake Tengiz (water salinity of 65% 0, average temperature of 22 degrees C) lasts 12 to 13 days.


[Paraiotonchium osiris (Iontonchiinae : Tylenchida), a new species of nematode of the zoophilic fly, Musca osiris Wd].

The description and figures are given to the nematode Paraiotonchium osiris sp. n. parasitic in the body cavity of Musca osiris and in the genital organs of the host females from Turkmenia. Two morphologically different generations of nematodes, gamagenetic and parthenogenetic ones, develop in the body cavity of the insects. Juvenile females of the gamagenetic generation: n=11; L=474.6 to 587.6; a=15.02 to 22.1; c=5.23 to 6.97; V=(71.5 to 77.7); St=13.0 to 16.1. Mature parasitic females of the gamagenetic generation: n=14; L=1028.3 to 2695.1; a=8.79 to 18.04; c=8.51 to 15.9; V=(76.2 to 84.6); St=21.0 to 27.0. Parasitic females of the parthenogenetic generation: n=7; L=813.6 to 1412.5; a=8.24 to 13.15; c=9.94 to 17.92; V=(88.2 to 91.9); St=14.0 to 16.5. Males: n=30; L=469.2 to 803.8; a=17.0 to 29.12; c=4.5 to 6.99; St=7.5 to 14.0; Sp (d)=18.4 to 23.0; Sp (pr)=34.5 to 41.4; T=(62.41 to 83.57). The new species differs from two other members of the genus Paraiotonchium in the structure of the spicules (a longer distal portion) and a larger bursa in males. A key to the species of the genus Paraiotonchium is given.