Kinetic analysis of the placental microsomal 3 beta-hydroxysteroid dehydrogenase activity.

A sensitive accurate assay for the placental microsomal 3 beta-hydroxysteroid dehydrogenase (E.C.1.1.1.51) has been developed using tritiated substrates. Kinetic analysis of the enzyme with 3 beta-hydroxy-5-androsten-17-one and 3 beta-hydroxy-5-pregnen-20-one indicates that the apparent Km values for these substrates are orders of magnitude less than previously described. Analyses were carried out with microsomal preparations from two different placentas. For placenta 1 the apparent Km value for 3 beta-hydroxy-5-androsten-17-one was 14 nM and for 3 beta-hydroxy-5-pregnen-20-one was 36 nM; for placental 2 apparent Km values were 19 nM and 42 nM respectively. The analyses were performed over wide ranges of substrate concentration (about 200 fold), both above and below the Km values and no deviation from linearity of Eadie-Hoftsee plots was observed.


Visual acuity at home and in eye clinics.

Most elderly visually disabled people have lower levels of visual acuity for both reading and getting about in their homes than would be inferred from clinic measurements. Even with optimum optical correction, performance can be much improved by simple modifications to existing facilities, individual advice, and in most cases the addition of a simple adjustable reading lamp.


Cyclosporin A: an immunosuppressive agent preferentially active against proliferating T cells.

The in vitro action of the immunosuppressive agent Cyclospirin A has been investigated using porcine cells. Lymphocyte proliferation induced in response to transplantation antigens and phytohaemagglutinin (PHA), was inhibited by this agent at doses that failed to inhibit mitogenisis in response to sheep anti-pig IgM, growth of kidney cell monolayers, and leukocyte migration.


Human skin grafts from mixed lymphocyte culture-positive donors provide help for the rapid rejection of simultaneously transplanted skin grafts from mixed lymphocyte culture-negative donors.

The influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood.


Partial characterization of cytotoxic cells infiltrating sponge matrix allografts.

Adapting the Roberts and Hayry sponge allograft model, we have demonstrated the presence of an enriched, specifically cytotoxic population of cells which infiltrate rejecting sponge allografts. The number of cells infiltrating a rejecting sponge allograft peaks on day 14 after transplantation. Utilizing a short-term 51chromium cytotoxicity assay, peak antiallogeneic killing was demonstrable on day 14 also. Only T cell killing was apparent for the first 15 days after transplantation. After day 20, specific cytolysis was present which was not sensitive to anti-theta serum and complement. The infiltrating cytotoxic cells are large, specifically cytotoxic, do not proliferate in culture, do not respond to mitogen, and do not respond in mixed lymphocyte culture even to the same alloantigen to which the animal had been sensitized. In contrast, spleens from sponge-bearing animals kill poorly, respond to mitogen, and respond vigorously in mixed lymphocyte culture to specific and nonspecific alloantigens. The following hypotheses are set forth with regard to the cytotoxic lymphocytes (1) Such cells may be end stage and cannot proliferate. (2) The cytotoxic cells may kill the stimulator cells more rapidly than they can be stimulated to proliferate. (3) The sponge cell population may be enriched for nonspecific supressor cells. (4) The sponge cells may be devoid of helper T cells.


Minimum length of time required for alloantigen recognition.

The minimum length of time required for lymph node lymphocytes to recognize alloantigens in vitro was examined in mixed skin cell-lymphocyte culture reactions. Responding lymphocytes in the mixture were successfully separated from stimulating skin cells by Ficoll-Hypaque gradient sedimentation. Lymphocyte activation by allogeneic skin cells took place within 15 min of contact. The amount of measured stimulation was approximately 30% of that produced by an equal concentration of antigen present continuously in culture. The presence of alloantigen was no longer needed after 24 hr. Several control experiments were made in order to exclude the effects of contamination and culture conditions. Identical results were obtained with allogeneic hepatocytes. These data indicate that the recognition of alloantigen leading to lymphocyte proliferation may occur during the early period of contact.


Evaluation of a computer programme for interpretation of 12-lead electrocardiograms.

A 12-lead electrocardiogram (ECG) interpretation programme (Cardionics, Brussels) was treated for computer diagnosis of ECG. The computer performance was evaluated on an ECG population from hospital patients by a method giving results which will allow the clinician to judge the usefulness of the computer diagnosis in clinical practice. Diagnoses made by experienced ECG readers were in essential agreement with the computer diagnoses in 83.5%, of 493 ECGs. Clinically significant disagreements due to differences in criteria occurred in 6.0% of the tracings, whereas such disagreements due to programme errors were found in 10.5%.


Experience with a newly developed automatic uroflowmeter.

An automatic cabin uroflowmeter was developed in order to guarantee the privacy of the patient, to simplify the measurement, and in particular, for screening. The meter is based on the method of von Garrelts, and the registration is performed with a music cassette. After an extensive calibration, 76 measurements from 22 persons without urologic complaints and 42 measurements from patients were analyzed. The obtained values of the control group, as well as those of the patient group were comparable to the data mentioned in literature. A normogram is presented correlating maximum flow rate and voided volume.


[Types of urination in men according to urodynamic flow measurement data].

The work is grounded on the analysis of the urination parameters, obtained from the examination of 195 men with various urological pathologies and of 100 healthy individuals, through urodynamofluometry--a new method of the express-diagnosis of the urination disorders. 5 types of the urination according to its volume have been distinguished. The devised system of the quantitative-qualitative evaluation of the urination is an attempt to differentiate various conditions of the urodynamics of the lower urinary passages versus the peculiarities of their anatomo-functional state in men.


[Phage relationships of coagulase-positive staphylococci isolated from raw and pasteurized cow's milk].

Studied is the behaviour to phages of 136 strains of coagulase positive cstaphylococci, isolated from raw (82), pasteurized milk stored in tanks (30) and pasteurized milk in bottles (24). The Staphylococcus aureus strains investigated are sensitive to bovine phages and, above all, to those of the 4th group (102, 107, 117 and 42D) or in combination with them. No lyses are established in the 1st and 3rd phage groups. The 107/117 and 107/117/42D are the phage types most frequently identified. The same phage types are found in both raw and pasteurized cow milk. It is established that 82 per cent of the Staphylococcus aureus strains studied with the rystal-violet test belong to types A and B after Meyer.


Argyrophil pituitary tumors showing TSH cells or small granule cells.

Among 74 histochemically and ultrastructurally studied pituitary adenomas, 12 apparently chromophobe tumors were characterized by the presence of numerous argyrophil cells. All these argyrophil adenomas failed to reveal presence of GH, prolactin or ACTH cells. Two tumors were found to consist of well granulated cells reacting intensely with anti-TSH antibodies and resembling TSH cells of the normal pituitary. The remaining argyrophil adenomas did not show TSH immunostaining and, with one exception, failed to react with an anti-HCG serum staining gonadotroph cells of human pituitary. They were composed of small, closely apposed cells with small compact or vesicular granules. These tumor cells seem to correspond to some small argyrophil cells found in non-neoplastic pituitary, which differ from TSH cells and from all other types of functionally identified adenohypophyseal cells.


Glomerulonephritis induced by high doses of ovalbumin. Studies by electron microscopy, immunofluorescence and immuno-electron microscopy.

Experimental glomerulonephritis was produced in 16 rabbits by intravenous injections of ovalbumin in high doses (0.1 g/day during the first week, 0.2 g x 6/day during the second). The animals were killed on day 14. At that time all animals had 2--4+ proteinuria and a serum C3 level reduced to about 50% of the control level; 11 animals had a significantly raised blood urea level. In all rabbits the antigen had induced severe proliferative glomerulonephritis. Electron microscopy showed that many of the cells accounting for the hypercellularity were monocytes. Surprisingly, electron dense deposits were few and small, mainly on the subendothelial and subepithelial aspects of the glomerular basement membrane. In all the animals ultrastructural immunoperoxidase technique revealed deposits containing ovalbumin, rabbit IgG and C3. With immunofluorescence sparse deposits were occasionally seen. It is concluded that a severe experimental glomerulonephritis can be produced in a state of antigen excess, with the deposition of immune complexes being minimal. Immuno-electron microscopy is essential, however, in detecting even the smallest animals of deposited immune reactants.


[On the pathology of acute heart failure in bronchial asthma (author's transl)].

In cases dying with asthma, heart muscle stained by the Haematoxylin-basic-Fuchsin-Pikric acid-method showed multiple areas of focal ischaemic injury of single or small groups of muscle fibres. The localisation of these changes in the inner layers of the wall and septum of the ventricle and the pattern of the changes produced, suggest poor coronary perfusion. The changes are explained as the result of combined damage due to hypoxic circulatory disturbances of the heart muscle and the effects of catecholamines. The appearances may provide the morphological basis for accurate diagnosis.


Intrauterine wound healing in a 20 week human fetus.

Limb amputations, probably caused by amniotic constriction bands, were examined histologically in a 20 week human fetus to assess the degree of intrauterine healing. No acute inflammatory process, no removal of necrotic material, and no granulation tissue formation were seen at any of the amputation sites. A recent ulcer, probably caused by friction of an exposed piece of bone in the stump of the right leg, also showed no inflammatory response. Healing was by coagulation of exposed tissue and by a minor degree of mesenchymal proliferation without repair. Similar changes have been described in experimental intrauterine wound healing in rats, lambs, opossums and baboons. Conversion from a non-specific to a classical postnatal inflammatory response occurs sometime before term. It is not known at what point this change takes place in man; examination of this infant suggests that it occurs after the twentieth week of gestation.


[Severe diphtheria with acute myocardial infarction (author's transl)].

Report on a female patient with severe diphtheria and electrocardiographic changes of acute myocardial infarction. Cases of such a kind seem to be seldom, as a review of international literature shows.


Histochemical observations on the taste buds of the marmosets (Callithrix jacchus and Callithrix penicillata).

The epithelial cells in the taste buds of C. jacchus and C.  penicillata show a moderate amount of ribonucleic acid an a concentration of a PAS-positive diastase-resistant material at their apical part. These cells are devoid of UDPG-GT, phosphorylases, G-6-PA, alanyl aminopeptidase, leucine aminopeptidase, cholinesterase and MAO; they present a weak reaction of F-1, 6-P Ald, LDH, SDH, MDH, cytochrome oxidase, beta-OHBDH, nonspecific esterase and acid phosphatase and a stronger reaction to ADH, NADPH2-TR, ATPases, alpha-GPDH, alkaline  phosphatase, 5-nucleotidase and GDH. Although some enzymes (alkaline phosphatase, 5-nucleotidase and ATPases) have an almost uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller uniform reactivity by the several taste buds, the other ones react with a lesser intensity in the smaller taste buds of the fungiform papillae. As a rule the apical part of the cells shows a stronger enzymatic reactivity. The taste buds of the marmosets are penetrated by acetylcholinesterase positive nerve fibers whereas the autonomic ganglia in the connective tissue contain both-acetyl and butyrylcholinesterase.


Unusually high occurrence of drug reactions with nafcillin.

Five patients seen during a two-month period who developed untoward systemic reactions following high dose intravenous administration of nafcillin are described. Recovery was complete upon discontinuation of the drug. The clustering of these cases and the high incidence (5 of 5) of side effects are highly unusual, and suggest that the frequency of nafcillin reactions might be higher than previously suspected.


Cultured lung cells: interplay effects of beta-mimetics, prostaglandins and corticosteroids in the biosynthesis of dipalmitoyl lecithin.

Cell lines derived from type II lung cells were used to study interplays of substances affecting incorporation of labeled precursors [1(-14)C]palmitate and [methyl-3H]choline into phosphatidyl choline. Ethanol stimulated markedly biosynthesis of dipalmitoyl phosphatidyl choline in cloned rabbit lung cells; the stimulating action of ethanol was reduced very much by cortisol and less by ritodrine. In the presence of 0.1 microM isoproterenol, two prostaglandins, E2 and F2alpha, caused marked depressions in the incorporation of both precursors by cell line A 549 derived from human lung adenocarcinoma. One concluded that among the agents studied, ethanol and cortisol are potent antagonists, and so were also the prostaglandins and isoproterenol.


[The in vitro and in vivo stability of the entrapment of methotrexate in negatively charged liposomes after sterile filtration (author's transl)].

The preparation of sterile artificial liposomes (phosphatidylcholine:cholesterol:dicethylphosphate=5:5:1) by Millipore filtration is described. Conditions for storing liposome entrapped Methotrexate have been found which allow storage of the drug in the entrapped form over a period of at least 4 months. It is shown that intravenously injected liposome entrapped Methotrexate is retained for at least 15 hours in the particulate form. During this time no free Methotrexate is detectable in the blood.


Enhanced melanization of Harding-Passey mouse melanoma cells following treatment with exogenous melanosomes in monolayer culture.

Purified melanosomes isolated from subcutaneously growting Harding-Passey melanomas of NMRI-mice were labeled either in vitro with [14C]tyrosine or [14C]DOPA in the melanin portion, or in vivo in the melanin and protein portion following i. p. injection of [14C]tyrosine. Treatment of monolayer cultures of Harding-Passey melanoma cells (HPM-73 line) with such labeled melanosomes resulted in rapid uptake of label during the first 4 h which leveled off thereafter. A portion of the "incorporated" label could be removed by a 15 min chase with unlabeled melanosomes. Uptake of labeled melanosomes by HPM-73 cells was followed by increased cellular melanization which was not only due to melanin derived from incorporated melanosomes but primarily to newly formed melanin. Tyrosinase activity was elevated in melanosome-treated cells. Tyrosinase activity of control cells was significantly reduced following a 24 h exposure to actinomycin D or cycloheximide. On the other side, the same inhibitor treatment of melanosome-pretreated cells resulted in less inhibition of tyrosinase activity. The present findings suggest "melanophagic" properties of cultured melanoma cells resulting in enhanced melanogenesis after phagocytotic uptake of functionally active exogenous melanosomes.


Osmotic sensitivity and tolerance and proteinase production in a strain of Saccharomyces.

A brewing yeast strain, NCYC 1085, unusual in that it sporulated freely and produced diploid spores, was sensitive to the degree of osmotic tension induced by the addition of 1.5 M KC1 or 2.5 M ethylene glycol to yeast extract-peptone glucose medium, but its progeny, obtained on sporulation and dissection of the resulting asci, included a number of osmotic-tolerant strains, the percentage of which increased as these strains were also sporulated and dissected. In addition, after repeated isolation of single-spore clones for three or four generations, clones producing zones of liquefaction of gelatin ranging in size from zero to large (approximately 1.5 cm) appeared, with the intensity of hydrolysis increasing in clones obtained from the later generations. The isolation of erythromycin-resistant mutants by manganese treatment was also accompanied by the appearance of osmotic-tolerant and gelatin-liquefying clones.


Phenylalanyl-tRNA synthetase from baker's yeast: structural organization of the enzyme and its complex with tRNAPhe as determined by X-ray small-angle scattering.

The quaternary structure of the phenylalanyl-tRNA synthetase and its complex with tRNAPhe was studied in dilute solutions by small angle X-ray scattering. For the free synthetase the radius of gyration was determined as 5.5 nm, the volume 523 nm3, the maximum diameter 17.5 nm and the molecular weight as 260,000 using an isopotential specific volume of 0.735. The overall shape could be best approximated by a flat cylinder with dimensions 18.2 nmx11.5 nmx4nm; the loose structure was approximated by building up the cylinder by spheres (diameter 4.2 nm). The corresponding parameters of the enzyme tRNA complex were the following: radius of gyration 5.9 nm, volume 543 nm3, maximum diameter 21 nm and molecular weight 290,000. These parameters suggest an 1:1 complex, whereby it must be assumed that the tRNA molecule is attached in the extension of the longer axis. From the difference in the distance distribution functions of the free enzyme and the complex it is evident that we have to assume a change of conformation (contraction) of the enzyme upon the binding of the specific tRNA.


[The acetylcholinesterase of Bungarus multicinctus venom. Purification and properties (author's transl)].

Acetylcholinesterase from Banded krait (Bungarus multicinctus) venom has been purified by CM-Sephadex chromatography and affinity chromatography to a specific activity of 4290 U/mg. The purified enzyme is a glycoprotein. It is free of electrophoretically detectable contaminating proteins. A molecular weight of 140,000 +/- 5,000 has been determined by gradient gel electrophoresis for the native enzyme. It is split into two equal-sized subunits (Mr 70,000 +/- 2,000) by SDS treatment. The N-terminal amino acid analysis gave glycine and serine. The purified acetylcholinesterase can be resolved by disc gel electrophoresis into four and by isoelectric focusing into six isozymes. The pI value of the main isozyme has been found to be 5.98 +/- 0.05.


Stained native collagen: interpretation of the small angle X-ray scattering and electron microscopic pictures in terms of the primary structure.

The average axial electron-density distribution of stained collagen fibers derived from X-ray small angle pattern, is shown to be substantially related to the projection of the polar amino acid residues onto the axis of the microfibril taking into consideration the staggering of neighbouring molecules. In order to arrive ultimately at a quantitative representation of the experimental data, an additional periodic fluctuation of the density in direction of the fibril axis is required. The necessity of this regular microphase structure for an understanding of known physical properties of collagen fibers will be indicated.


Assimilatory nitrate reductase of Rhodopseudomonas capsulata AD2: a molybdo-hemeprotein.

The assimilatory nitrate reductase of the phototrophic bacterium Rhodopseudomonas capsulata strain AD2 was purified to homogeneity by a combination of ammonium sulfate fractionation, chromatography on DEAE-cellulose and isoelectric focusing (isoelectric point of 4.8). The purified enzyme was active only with reduced viologen dyes or reduced flavin as electron donors. Contrary to other bacterial assimilatory nitrate reductases, the enzyme was not inhibited by chlorate, but rather accepted this substance as an alternate substrate. The molecular weight of the enzyme was 185,000 dalton as determined by gelfiltration. Subunit analysis by sodium dodecyl sulfate (SDS) gel electrophoresis yielded a single protein band with a molecular weight of 85,000 dalton,, suggesting that the enzyme was composed of two identical subunits. The nitrate reductase contained 0.8 g-atoms molybdenum per 1.85 x 10(5) g protein and exhibited absorption maxima at 418, 523 and 552 nm in the reduced state (dithionite as reductant). The nitrate reductase of Rps. capsulata AD2 is the first prokaryotic enzyme of the assimilatory type that has been shown to contain heme.


Purification, subunit structure, and kinetics of the chloroform-released F1ATPase complex from Rhodospirillum rubrum and its comparison with F1ATPase forms isolated by other methods.

A stable and homogeneous adenosine-5'-triphosphatase (ATPase, EC 3.6.1.3) has been solubilized from Rhodospirillum rubrum (R. rubrum) chromatophores by chloroform extraction. Purification of the Ca2+-dependent ATPase activity was 200-fold. Ca2+ can be replaced by Mg2+, Cd2+, and Mn2+. The Km for Ca-ATP (0.17 mM) is increased about 5-fold during solubilization of the enzyme, whereas the Km values for Mg-ATP (0.029 mM) and Cd-ATP (0.014 mM) are not affected. The chloroform-released ATPase has a molecular weight of 400,000 +/- 30,000 and consists of the following subunits (molecular weights in parenthesis): alpha(58,000), beta(53,500), gamma(39,000), delta(18,500), and epsilon(14,000). The amino acid composition and the fluorescence spectra are presented. Besides the chloroform-released ATPase complex three other Ca2+-dependent ATPase forms have been isolated from R. rubrum chromatophores by other methods for comparison. Ultrasonication of the membranes leads to the release of an ATPase complex which is mainly composed of alpha, beta, and gamma-subunits. From an acetone powder extract an ATPase complex could be purified by affinity chromatography which is composed of four kinds of subunits (alpha, beta, gamma, delta). The same acetone powder yields an ATPase consisting of only three different types of subunits (alpha, beta, gamma) if the final purification step is preparative disc electrophoresis on 6% polyacrylamide gels instead of affinity chromatography.


Methylmercury-induced sedimentation heterogeneity of T7 bacteriophage DNA.

Single-stranded and methylmercurated T7 DNA is composed of two species as evidenced from the sedimentation pattern displayed during band-sedimentation in self-generating density gradients as well as during equilibrium-sedimentation in CS2SO4 density gradients. Under the given experimental conditions, viz., at pH 9.18 and in presence of 0.1 mM CH3HgOH, the two species band in CS2SO4 with a density difference of 0.008 g/ml. The ratio of the sedimentation coefficients of the two species is sw, 20 (fast)/sw, 20 (slow) = 1.63 at pH 9.18 and in presence of 1.6 mM CH3HgOH. Both native and denatured T7 DNA behave as monodisperse systems in the absence of CH3HgOH.


Evidence for the existence of meta and para directing O-methyltransferases in tobacco cell cultures.

The O-methyltransferase of tobacco cell culture was resolved to its meta and para directing forms by chromatography on DEAE-cellulose. Despite similarities in molecular weights and pI values of the two forms, however, evidence from pH optima, SH-group inhibitors, methylation ratios, SDS-acrylamide gels and mixed substrate experiments indicates the existence of two discrete enzymes acting at the meta and para positions of caffeic acid and quercetin, respectively; though the latter enzyme was less substrate specific than its meta counterpart.


Search for millimeter microwave effects on enzyme or protein functions.

Recent observations of nonthermal, resonant biological responses to weak millimeter microwave irradiation have led us to investigate whether similar influences exist on enzymatic functions in vitro. We chose (i) the reduction of ethanol in the presence of alcohol dehydrogenase and (ii) the cooperative binding of oxygen on hemoglobin. Using an irradiation intensity near 10 mW/cm2 the frequency was continuously varied from 40 to 115 GHz with a resolution of a few MHz. No microwave influences were detectable within our experimental sensitivity of about 0.1% of the reaction rate in (i), or of the amount of bound oxygen at half saturation in (ii).


In vitro action of gastric mucosal lysosomal enzymes on intracellular gastric glycoproteins.

The results show that incubation of gastric mucosal cells from rat at pH approximately 4.5 or in the presence of aspirin is associated with a specific increase in the activity of some acid-hydrolases. Intracellular glycoproteins, isolated by non-degrative techniques from rat or dog fundic mucosal cells, were found to be potential bio-substrates for these acid-hydrolyses. This may suggest that cleavage of the carbohydrate moieties of the intracellular and mucosal cell wall glycoproteins is a fundamental step in the development of gastric ulceration. A model for gastric lesions is proposed and discussed in the light of the results obtained.


Characterization of an endogenous transcription inhibitor from Physarum polycephalum.

A substance has been purified from isolated nuclei of Physarum polycephalum by equilibrium and velocity gradient centrifugations, ion exchange chromatography and gel filtration which has a high molecular weight, can be labeled in vivo with 32P, is heat stable and resistant to amylases, proteases, nucleases and phosphodiesterase but is sensitive to phosphatases or hydrolysis. This material consists of phosphate and glycerol. It selectively inhibits in vitro transcription of RNA polymerases, predominantly the homologous enzyme A by binding to the enzyme. In the presence of this inhibitor of transcription a stable RNA polymerase-template complex cannot be formed. Binding to and inactivation of RNA polymerase is reversible at high ionic strength.


The role of acidic proteins from cytoplasmic fractions of Krebs II ascites cells for efficient translation.

Acidic proteins with affinity to RNA from cytoplasmic fraction of Krebs II Ascites cells were isolated by means of affinity chromatography on RNA-Sepharose CN-Br-columns. Stepwise elution with 350 mM [K+] and 1000 mM [K+] removed two fractions of proteins both of which are required for the formation of 40S- or 80S-initiation complexes and for efficient translation.


[Primary chronic polyarthritis with kidney involvement (mesangiocapillary glomerulonephritis)].

A 34 year old white male patient suffering from seropositive "probable" rheumatoid arthritis developed a severe hypocomplementemic mesangiocapillary glomerulo-nephritis. Rheumatoid factors (Latex test, Waaler-Rose titer) and IgM were markedly elevated in the serum. The third component of complement (C3) was markedly depressed, while the fourth component (C4) was within normal range. The rapid progression of the disease forced us to start an immunosuppressive drug therapy using azathioprine and steroids. Despite marked clinical improvement, e.g. normalisation of complement components, renal function, the disappearance of rheumatoid factor and proteinuria, the second biopsy taken two years later showed unchanged histological and immuno-histological changes of the glomerula.


[Enterococcal flora of some species of synanthropic flies].

The study of enterococcal species present in 16 species of synanthropic flies revealed the predominance of Str. faecalis and its variants, a high percentage of fly populations being infected. The spectrum of enterococci was proved to depend on the living conditions of the flies. The percentage of Musca domestica with the infected digestive tract was found to vary with changes in the age composition of the fly population.


[Dynamics of the types of carrier state and their relationship to the phage group characteristics of pathogenic staphylococci].

A total of 305 persons belonging to the medical staff of a hospital surgery unit were subjected to multiple examinations during period of up to 8 years. 2,354 staphylococcal strains isolated from these subjects were studied, and the following types of carrier state were determined: constant (23.6 +/- 2.43%), intermittent (57.4 +/- 2.83%), resident (7.9 +/- 1.54%), and the stable absence of carrier state (11.1 +/- 1.60%). An increase in the number of examinations and the terms of observation resulted in a regular increase in the number of intermittent carriers at the expense of constant carriers and persons not identified as carriers. Against this background resident carriers constituted a relatively more stable group. Carrier states of the resident type were connected with staphyloccci belonging to various phage groups without pronounced differences in the frequency with which any of the phage groups occurred.


Assessment of left ventricular filling by echocardiography in normal subjects and in subjects with coronary artery disease and with asymmetric septal hypertrophy.

To examine the time course of left ventricular filling, a computerized analysis of echocardiograms was performed in 16 normal subjects, 10 patients with coronary artery disease (CAD) but no cardiac enlargement and 7 patients with asymmetric septal hypertrophy (ASH). After hand-controlled digitization of the echocardiogram, a plot of the left ventricular diameter time-curve demonstrated separate phases of rapid filling, slow filling and atrial contribution. The left ventricular diameter at end-systole and at the end of the three diastolic phases was determined by pattern analysis of the diameter-time curve. On analysis of successive beats in the normals, the coefficient of variation for each of these four values of the left ventricular diameter was less than +/- 5%. Between CAD, ASH and normals there was no significant difference in left ventricular end-diastolic diameter, nor in the extent and percentage of diameter shortening during systole. In contrast, abnormalities of the filling pattern were found in CAD and ASH. The maximal rate of diameter lengthening was not different in CAD (13.0 vs 13.7 cm/sec in normals, N.S.) but decreased in ASH (9.3 cm/sec, p less than .01). The percentage of diameter lengthening occurring in the rapid filling phase was decreased in both patient groups (55% in CAD and ASH vs 73% in normals, p less than .001). The slow filling phase did not contribute to more diameter lengthening (13% in CAD and 17% in ASH vs 12% in normals, N.S.). In CAD and ASH, the atrial contribution was markedly increased (33% in CAD and 28% in ASH, vs 15% in normals, p less than .001), and there was a higher rate of diameter lengthening during the atrial contraction (7.6 cm/sec in CAD, p less than .001 and 5.7 cm/sec in ASH, p less than .01, vs 3.1 cm/sec in normals). In conclusion, after computer processing, noninvasive measurements of the left ventricular diameter allows to identify a typical filling pattern in patients with CAD and ASH, consistent with an abnormal compliance of the left ventricle and a compensatory increased atrial contribution.


Double trisomy as a mosaic. Case history (48, XYY, + 21/47,XY, +21) and survey of the literature of mixed autosomal-gonosomal trisomies.

The case of a boy is reported showing the typical symptoms of Down's syndrome, in whom the chromosome analysis revealed a mosaic karyotype: 50% 48,XYY,+21/50% 47,XY,+21. Findings of 92 cases from the literature are summarized to show the frequencies of double gonosome-autosome aneuploidies compared with single trisomies. Referring to the different chromosomes involved, the aneuploid cell formation, the frequencies of combinations, as well as the tendency to mosaic formation are analyzed. The age of parents at the time of birth and the life expectancy are described as well as the clinical symptoms. Theories concerning the origin of double aneuploidies are discussed.


Evidence for a rat granulocyte chalone effect on the proliferation of normal human bone marrow and of myeloid leukemias.

Evidence is presented that rat ascites cell extracts, acting as granulocyte chalone, temporarily inhibit the cell doubling of granulocytopoietic precursors in suspension cultures of human bone marrow. The extracts do not affect the proliferation of erythroblasts and do not show any cytotoxicity. In addition, a relative increase of granulocytic precursors capable of proliferation was found, suggesting an increase in the resting population of the granulocytopoietic proliferation pool due to extract treatment. However, the extract capable of depressing the proliferation of the normal granulocytopoiesis did not affect the granulocytopoiesis of 7 chronic myeloid and 2 chronic myelomonocytic leukemias at the same dose level. In contrast to these chronic leukemias, blast proliferation of 4 acute myeloid and monocytic leukemias was greatly depressed not only for 6 h but for the whole culture period of 48 h.


Method for continuous measurement of carbon dioxide output during anesthesia. An assessment.

Employing the Mapleson D circuit, a modified closed-circuit flow-through technique for the continuous measurement of carbon dioxide production (VCO2) was tested for accuracy and precision in a lung model. The recovery of carbon dioxide production was found to be between 90 and 110%, the maximized errors for a single estimate of carbon dioxide production were between +/- 4 and +/- 28%, with the highest errors at high gas flows and low carbon dioxide inputs. Accepting arbitrarily chosen limits of maximized errors of +/- 10%, it could be shown that the system did not work acceptably when the mean carbon dioxide concentration was below 1.5 vol.% within the fresh gas flow rates (2.2--7.7 1 min-1) and the range of minute ventilation (4--10 1 min-1) employed. The half-life of carbon dioxide washout varied between 41 and 138 s, thus limiting the suitability of the system for detecting changes in carbon dioxide output. The method may be used as an approximate monitor of VCO2 in anaesthetized patients, but cannot be regarded as sufficient for research purposes.


Monitoring ventilation during anesthesia.

In patients under anesthesia, ventilation is often monitored less adequately than circulation. A simple method, neglected in adults, is the use of a precordial or oesophageal stethoscope. Respiratory volumes may be measured directly, or inferred from flowrates or pressure changes. A rough measurement of inspired volumes may be made using a nonrebreathing valve, and controlling fresh gas input to maintain a constant underfilled reservoir bag. Spirometry of expired volumes is difficult and requires sophisticated apparatus. Respiratory volumes are easily inferred from flowrates using the Wright or Dräger respirometers. Flowrates may also be inferred from pressure changes, which are easy to record, as in the pneumotachorgraph. Accurate measurements require attention to many details, such as linearity of the transducer response over the flowrates measured. Calibration should be with the anesthetic gases used, at controlled temperature and humidity. Positive pressure ventilation peaks give a high flow artefact, and electronic drift requires regular recalibration. Electrical impedance changes may also be used to infer and record respiratory volumes, with reasonable accuracy if individual calibration is carried out. Anesthesia offers excellent opportunities to measure compliance and resistance, but itself changes these values, so that relation to normal values or changes due to pathology is difficult. Occlusion pressure is also readily measured during anesthesia, as an indication of respiratory drive, but rigid control of all other factors affecting respiratory muscle tensions is necessary.


The Coffin-Siris syndrome.

A 14-month-old female with the Coffin-Siris syndrome is described. Typical features included underweight at birth, growth retardation, microcephaly, profound mental retardation, severe hypotonia with lax joints, feeding difficulties and frequent respiratory tract infections; sparce scalp hair, small nose, epicanthic folds, a prominent philtrum and full lips; a congenital heart defect; hypoplasia or aplasia of the distal phalanges of digits 2--5 and the corresponding nails, especially of the fifth fingers and toes, and aplasia of the middle phalanges of the little fingers and the second and fifth toes; severe delay in bone maturation. The proposita also showed hypoplasia of the lateral portions of both clavicles. Inheritance of the Coffin-Siris syndrome is possibly autosomal recessive.


Mechanism of cell dissociation with trypsin and EDTA.

The mechanism of cell dissociation with trypsin and EDTA was examined. Cell dissociation was possible when trypsin and EDTA were given simultaneously, when trypsin was given after EDTA treatment, but not when trypsin was given before EDTA treatment.


Heterotransplantation of human leukemic B-cell, T-cell and null-cell lines in hamsters.

Human leukemic B-cell (BALL-1), T-cell (TALL-1) and null-cell (NALL-1) lines have been established from three patients with acute lymphoblastic leukemia (ALL). To study the heterotransplantability and in vivo growth characteristics, attempts were made to transplant these ALL cell lines into newborn Syrian hamsters treated with rabbit anti-hamster thymocyte serum. Intraperitoneal implantation of 1.8-3.5 x 10(7) cells gave rise to invasive tumors in all recipients after 15 to 41 days. In addition to a common in vivo feature of mesenteric and retroperitoneal tumors, BALL-1 line was characterized by infiltration of the skin, massive ascites and bone marrow invasion. TALL-1 cells infiltrated various organs including the lymph nodes, liver, gallbladder, spleen, bone marrow, central nervous system and eyes. NALL-1 line grew slowly, producing the least tumors, although there were distant metastases in the lungs. Tumor cells were detected in the blood of 2 of 3 BALL-1-bearing hamsters and in the blood of 4 of 5 TALL-1-bearing hamsters. Thus, these three ALL cell lines were found to exhibit a characteristic biological behavior in hamsters, which might be related to the different cell lineage.


Chronic non-allergic hypertrophic rhinitis. A histochemical study.

The enzymatic changes in chronic hypertrophic rhinitis were studied in 14 patients. The cholinesterase content was increased in the subepithelium and stroma, denoting parasympathetic hyperactivity. Acid phosphatase was increased in the epithelium, subepithelium and around the glands, indicating increased shedding and phagocytic activity. Succinic dehydrogenase, alkaline phosphatase and alpha-esterase were increased in the mucous glands, denoting increase secretory activity, hence increased natural defence mechanism of the nasal mucosa.


Immunotherapy of gastrointestinal cancer patients with levamisole.

Levamisole was administered to 177 patients with gastrointestinal cancer (88 curative resection, 58 noncurative resection and 31 without resection). It was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started, as a rule, 3 days before operation. This medication was repeated as frequently as possible at least for one month. The cellular immunity and 18-month survival rate of treated and control groups were compared. Levamisole effectively improved peripheral lymphocyte blastformation against phytohemagglutinin and increased the numbers of peripheral blood lymphocytes. Levamisole caused extremely high blastformation rates, in general, enhanced PPD reactions in non-curative resection cases 7 months after operation and showed no influence upon the number of peripheral blood lymphocyte. The effect of levamisole on the 6-month survival rate was most marked in patients without resection. Increased 12-month survival rate was marked in non-curative resection cases and, to a lesser extent, curative resection cases. Patients without resection had a slightly improved 12-month survival rate. Levamisole improved the 18-month survival rate in resectable cases; however, there were no significant differences in 18-month survival between levamisole and control groups of patients not undergoing resection. The results suggest that levamisole is effective in the patients whose tumor cells have been decreased by any method.


Recurrent transient thyrotoxicosis with painless thyroiditis--a case report.

A case of a 40-year-old woman who was suffering from painless thyroiditis with recurrent transient thyrotoxicosis is reported. Acute exacerbations occurred four times during the past ten years, two after delivery and two after catching a cold. Serum thyroid hormones increased, though radioiodine uptake by the thyroid was very low and no inflammatory signs were observed. The histological findings of the thyroid were of atypical thyroiditis and not consistent with either chronic lymphocytic thyroiditis or subacute thyroiditis. Tanned sheep red cell hemagglutination titers for anti-thyroglobulin antibodies (TRC) and for anti-microsomal antibodies (MHA) were negative or low. The disease seems to be rare and the pathophysiology and etiology are discussed.


Three cases of myxofibroma.

Myxofibroma is a rare tumor. Three cases of myxofibroma, each of which developed at the right mandibular ramus, mandibular anterior tooth region, are presented. Myxofibroma developing in the mandibular ramus region is rare, and there has been only one case reported so far in Japan.


Technical considerations in the evaluation of pediatric motor scales.

Guidelines are suggested for evaluating the validity and reliability of fine and gross motor scales. In the process of examining three types of validity (domain, construct, discriminant) and two types of reliability (interobserver, decision-making), it was found that there were marked deficiencies in most of the instruments currently available, particularly in the areas of discriminant validity and decision-making reliability. Each psychometric property of the scales was addressed from both scale-developer and user perspectives. An evaluative checklist is generated to assist occupational therapists who need to decide on the quality and appropriateness of a motor behavior scale for specific decision applications.


Clinical evaluation of automated processing of electrocardiograms by the Veterans Administration program (AVA 3.4).

Automated processing of electrocardiograms by the Veterans Administration program was evaluated for both agreement with physician interpretation and interpretative accuracy as assessed with nonelectrocardiographic criteria. One thousand unselected electrocardiograms were analyzed by two reviewer groups, one familiar and the other unfamiliar with the computer program. A significant number of measurement errors involving repolarization changes and left axis deviation occurred; however, interpretative disagreements related to statistical decision were largely language-related. Use of a printout with a more traditional format resulted in agreement with physician interpretation by both reviewer groups in more than 80 percent of cases. Overall sensitivity based on agreement with nonelectrocardiographic criteria was significantly greater with use of the computer program than with use of the conventional criteria utilized by the reviewers. This difference was particularly evident in the subgroup analysis of myocardial infarction and left ventricular hypertrophy. The degree of overdiagnosis of left ventricular hypertrophy and posteroinferior infarction was initially unacceptable, but this difficulty was corrected by adjustment of probabilities. Clinical acceptability of the Veterans Administration program appears to require greater physician education than that needed for other computer programs of electrocardiographic analysis; the flexibility of interpretation by statistical decision offers the potential for better diagnostic accuracy.


Left ventricular radius to wall thickness ratio.

Left ventricular relative wall thickness, expressed as the ratio of end-diastolic radius to wall thickness (R/Th ratio), has a constant relation with left ventricular systolic pressure in children and adults with a normal heart, subjects with physiologic forms of cardiac hypertrophy (athletes) and patients with compensated chronic left ventricular volume overload (chronic aortic regurgitation). Greatly increased values for the radius/thickness ratio, suggesting inadequate hypertrophy, indicate a poor prognosis in patients with chronic aortic regurgitation and in those with congestive cardiomyopathy; decreased values for this ratio are found in patients with hypertrophic cardiomyopathy (inappropriate hypertrophy) and in patients with compensated aortic stenosis (appropriate hypertrophy). In patients with compensated aortic stenosis, echocardiographic measurement of the left ventricular end-diastolic radius/wall thickness ratio has been used to estimate left ventricular systolic pressure. Measurement of left ventricular relative wall thickness appears to provide diagnostic and prognostic data in patients with a broad variety of cardiac disorders.


Fibrinolysis in familial pulmonary hypertension.

Although an autosomal dominant mode of inheritance has been documented for many cases of primary pulmonary hypertension, the pathogenesis of the disease remains unclear. A report of abnormal fibrinolysis in familial pulmonary hypertension has raised the possibility that the pathogenesis may be related to an impaired ability to lyse recurrent pulmonary microemboli. Primary pulmonary hypertension was diagnosed in three of ten members of a kindred. The pattern of inheritance was compatible with an autosomal dominant gene. Eight members of the kindred were available for study, one of whom has primary pulmonary hypertension. The results of coagulation studies, caseinolytic determinations of plasminogen and antiplasmin, and fibrinolytic titers of antiurokinase did not differ significantly from those of the control group. These findings suggest that a deficient fibrinolytic system is not the cause of primary pulmonary hypertension, although differences in methodology may explain our inability to demonstrate abnormal circulating fibrinolysis in this kindred.


Tetralogy of Fallot in adults. A report on 147 patients.

Presented here is the clinical and hemodynamic profile of 147 patients, above the age of 18 with tetralogy of Fallot. Cardiac catheterization and selective cineangiocardiography were performed in all. Infundibular pulmonary stenosis, a subaortic large infracristal ventricular septal defect, mitral-aortic fibrous continuity and equal pressures in both the ventricles and aorta were considered mandatory for the diagnosis of tetralogy of Fallot. Cardiac enlargement was seen in 25.8 per cent of the patients, and 15.6 per cent were in congestive cardiac failure; 9.5 per cent had systemic hypertension, and aortic regurgitation was present in 6.7 per cent. A reticular pattern in the lung fields due to bronchial collaterals was seen in 23.1 per cent. The incidence of right aortic arch (19.9 per cent), absent left pulmonary artery (2.8 per cent), absent right pulmonary artery (0.7 per cent) and dextrocardia (1.4 per cent) is brought out. The right atrial mean pressure was increased in 4.8 per cent and a prominent "a" wave greater than 10 mm Hg was present in 10.9 per cent. The right ventricular end-diastolic pressure was increased in 23.8 per cent and the left ventricular end-diastolic pressure in 25.9 per cent of the patients.


Parental speech to young Down's syndrome children: an intervention study.

Parents with Down's syndrome children who were at the one-two word stage of expressive language development were given a language objective to work towards with their child, but no instructions on how to attain this goal. The parents spontaneously altered their language strategies in their attempts. Some parents were more successful and differed in their strategies, using more target words in shorter "statement" utterances. Parents who used a questioning or imitating strategy were less successful. The less successful parents were then shown how to alter their language strategies more appropriately to produce a greater improvement in their child's use of the target words.


Use of laparoscopy to determine the microbiologic etiology of acute salpingitis.

To determine the microbiologic etiology of acute salpingitis, laparoscopy was used in 26 patients to obtain specimens for a variety of microorganisms directly from the fallopian tube. Simultaneous culdocentesis was performed to obtain peritoneal fluid for microbiologic analysis. A variety of microorganisms were isolated from the fallopian tubes and cul-de-sac aspirate. However, the organisms isolated from the fallopian tube were not consistent with the cul-de-sac isolates. It appears that direct culture from the fallopian tube may be necessary to determine the microbiologic etiology and pathogenesis of acute salpingitis. N. gonorrhoeae was isolated from the cul-de-sac in 32 per cent of cases and the fallopian tube in 19 per cent. In patients with endocervical gonorrhea, the gonococcus was isolated from the fallopian tube in 38.5 per cent of cases. Aerobic and/or anaerobic bacteria were present in the cul-de-sac aspirate in 46 per cent of patients and in the fallopian tube in 38 per cent.


Cow red blood cells. I. Effect of purines, pyrimidines, and nucleosides in bovine red cell glycolysis.

Cow red cells, under in vitro incubation conditions, exhibit a comparatively low glycolytic rate of 0.56 +/- 0.05 micromol/(ml cells.h), with a ratio of lactate formed to glucose consumed of 1.58. It has been found that this low glycolytic rate can be stimulated 50--60% above the basal level in the presence of a variety of purine and pyrimidine compounds including adenosine, inosine, adenine, hypoxanthine, xanthine, and uracil. In contrast, calf red cells, which have a much higher glycolytic rate, display no discernible response to these agents. In attempts to elucidate the mechanism by which this stimulation takes place, both glucose transport and glycolytic enzyme activities were determined in the presence of these stimulators. Glucose influx in cow red cells, measured using the glucose analog 3-O-methyl-glucose, exhibits both a low Km of 117 microM and a Vmax of 0.38 micromol/(ml cells.min), and is unaltered in the presence of adenosine. On the other hand, hexokinase, which in normal hemolysates of cow red cells has an activity of 0.49 +/- 0.03 micromol/(g Hb.min). was found to be stimulated to 0.73 micromol/(g Hb.min) in the presence of adenine. Both pyruvate kinase and phosphofructokinase were unaffected by this compound. These data suggest that certain purines and pyrimidine compounds may exert their stimulatory effect on hexokinase activity, resulting in an augmentation of cow red cell glycolysis.


Cardiac changes during behavioral stress in dogs.

Alterations in heart rate (HR), left ventricular systolic pressure (LVP), and maximum rate of left ventricular pressure development (LV dP/dtmax) during a Sidman avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a nonstressed control group. In the experimental group, in addition to phasic increases in HR, LVP, and LV dP/dtmax during the avoidance period of each day, tonic increases in these measures were also observed over the 13 days of the experiment. Left ventricular systolic pressure was found to be least sensitive to the stress procedure inasmuch as the phasic changes were no longer present after the 10th day and tonic levels were within base-line values by the 13th day. When alterations in cardiac activity were observed in the nonstressed animals, there were decreases in function. It was concluded that controlled behavioral stress produces increased cardiac performance without increased bodily activity. It was also hypothesized that preavoidance increases in heart rate in experimental animals were the result of vagal influences on the heart, whereas avoidance increases in HR, LV dP/dtmax, and LVP were functions of increased beta-sympathetic activity on the heart and adaptive peripheral vascular changes.


Effect of brain 5-hydroxytryptamine alterations on reflex bradycardia in rats.

The vasopressor and bradycardia responses to an intravenous dose of epinephrine were assessed in saline-controlled, 5-hydroxytryptamine-(5-HT) depleted, and 5-HT-potentiated rats. Regardless of the previous treatment epinephrine produced an insignificant change in the basal levels of mean arterial pressure and heart rate. However, brain serotonin alteration did produce some influences on the reflex bradycardia in response to an elevation in arterial pressure. Elevating 5-HT contents in brain with 5-hydroxytryptophan (5-HTP) after peripheral decarboxylase inhibition with Ro 4-4602 produced a significant reduction in reflex bradycardia compared to the controls. In contrast, depleting 5-HT contents in brain with either p-chlorophenylalanine (PCPA) or 5,7-dihydroxytryptamine (5,7-DHT) led to an enhancement of epinephrine-induced bradycardia. Moreover, the enhanced reflex bradycardia induced by PCPA treatment was readily blocked by the replacement of the depleted brain 5-HT with 5-HTP and Ro 4-4602. The results suggest that serotoninergic systems play a role in the elaboration or modulation of reflex bradycardia. Specifically, 5-HT appears to inhibit reflex bradycardia since its depletion facilitated and its elevation inhibited reflex bradycardia.


Diabetes, dietary tryptophan, and protein intake regulation in weanling rats.

The effects of streptozotocin-induced diabetes and tryptophan content of the protein fed on protein intake regulation by weanling rats selecting from 10 and 60% casein diets were evaluated. In uncompensated diabetes the ratio of tryptophan to other selected neutral amino acids in plasma and brain tryptophan were reduced, protein intake per unit of body weight was increased, and serotonin, 5-hydroxyindoleacetic acid, and norepinephrine were unaffected. Enrichment of the tryptophan content of the ingested protein caused a decrease in protein, but not energy consumption of both diabetic and nondiabetic rats. The reduction in protein intake correlated inversely with increases in the tryptophan content relative to the neutral amino acids in plasma and with increases in brain tryptophan and serotonin levels in both diabetic and nondiabetic rats. The data suggest that protein-feeding behavior is regulated by a mechanism that includes brain serotonergic activity with insulin, through its influence on circulating amino acids, determining the quantity of protein consumed in relation to body weight.


Post-weaning heart development and dietary lipid level in the male rat: evolution of lipoprotein lipase activity.

The wet weight evolution and specific and total lipoprotein lipase (LPL) activities of the heart were studied in male rats fed with diets containing 4, 12 or 21 p. 100 lipids from 50 g (3 weeks age) to 400 g body weight (13 weeks of age). The animals were compared at 100, 150, 200 and 400 g. The main results show that:--a lipid-rich diet caused some cardiac hypertrophy beginning at 100 g body weight:--specific LPL activity (activity/g of wet tissue) in the 50-400 g interval was higher when the diet contained more lipids;--when the diet contained 4 p. 100 and 12 p. 100 lipids, specific LPL activity decreased from weaning until a plateau was reached at 200 g body weight. On the other hand, when the diet contained 21 p. 100 lipids, specific LPL activity increased to a maximum in the 150-200 g interval; it then declined rapidly so that at 400 g there were no longer significant differences between the specific LPL cardiac activities of the three groups of animals. The activities thus became independant of the dietary lipid level;--total LPL cardiac activity was higher when the diet contained more lipids, at least up to the 400 g stage. When the diet contained 4 and 12 p. 100 lipids, the activity increased linearly in the 100-400 g interval. When the diet contained 21 p. 100 lipids, it increased very rapidly in the 50-200 g interval then decreased in the 200-400 g interval. In the latter interval, the differences between LPL activities of the three groups were less so that at 400 g there was only significant difference between the extreme high and low lipid groups. Thus, as specific activity, total LPL cardiac activity tended to become independent of dietary lipid level when the animals became adult.


Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia.

A brief description is given of neurofibrillary changes of the paired helical filament type in a variety of chronic neurological diseases. These include subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis, Down syndrome, Hallervorden-Spatz disease, and lipofuscinosis. In these conditions, with the exception of Hallervorden-Spatz disease neurofibrillary changes were previously recognized but paired helical filaments were identified only in some cases. Moreover, in the present series, the age of patients at death was often younger than in previously recorded cases.


[Experimental study of the effectiveness of antibacterial preparations in treating dysentery].

It was found that for successful elaboration of effective schemes for the use of antibacterial drugs in treatment of dysentery it was necessary to exploit various experimental models providing consideration of the drug toxicity and effect on the extra- and intracellular growth of the bacteria in addition to the other factors. The administration of enteroceptol for 3 days followed by furazolidon showed the best therapeutic effect in the treatment of guinea pigs with Shigella keratoconjunctivitis and Syrian hamsters with dysentery. The above drugs had low toxicity which was shown in the experiments with Hep-2 cell cultures. It was concluded that the use of the drugs with different modes of action was advisable in treatment of dysentery.


[Effects of prolactin on nucleo-proteic metabolism in gill epithelium of two euryhalin mullets, Chelon labrosus and Liza ramada during fresh-water adaptation (author's transL)].

Prolactin (PRL) treatment induced a decrease in DNA content in SW, -- an increase in FW 8 days, -- and no effect in FW 20 days fish. In "nuclear", "microsomal" and "supernatant" centrifugation fractions, RNA content was increased in SW, -- decreased in FW 8 days, by PRL treatment while a little increase was observed in FW 20 days fish with an increase of 14C leucine and 3H uridine incorporation. These results are discussed with reference to existence of two chloride-cell-types.


An acne grading method using photographic standards.

A grading system for following the clinical course of acne was devised in which overall severity of acne is evaluated on a zero to eight scale anchored to photographic standards that illustrate grades 0, 2, 4, 6, and 8. Experience with use of this system in large-scale clinical trials has shown it to be useful and reliable. Photographs taken at each visit create a permanent and regradable record of each subject's clinical status throughout the course of treatment.


Complicated intestinal atresias.

In this group of 45 intestinal atresia patients (duodenum, 16; jejunum, 24; ileum five) at the University of Mississippi Medical Center, individual hospitalizations ranged up to 245 days. Twelve patients required multiple operations, and the overall mortality rate was 22% (ten patients). While the patients with duodenal atresia had the greatest incidence of other congenital anomalies, including Down's syndrome, the patients with jejunal atresia presented with the most challenging surgical problems. Of the 24 jejunal atresia patients, only three had a single, simple area of obstruction. The remainder were complicated by other gastrointestinal lesions (five patients), by multiple areas of atresia (seven patients) including those in one surviving patient with 22 separate atretic segments, and by the Christmas tree deformity (nine patients). Intraoperative management of the complicated atresia should include: 1) grouping of multiple atresias during resection, 2) adequate resection of the dilated proximal atonic loop, 3) end-to-end anastomoses, 4) avoidance of intraluminal catheters, 5) additional resection of a segment of the distal loop in the Christmas tree deformity and 6) consideration of the shish kebab technique for multiple atretic webs. Postoperative management should involve early intravenous nutrition and repeated exploration for continued obstruction.


[Gastroschisis: study of a series of 50 cases from 1960 to 1976 and therapeutic indications].

Fifty cases of gastroschisis were treated at the Hôpital des Enfants Malades from 1960 to 1976. Up to 1973, 90% of the babies died. From 1974-1976, 17 infants were treated and 10 (59%) were cured. The authors emphasise the importance of intravenous feeding, the prevention of infections and intensive respiratory care. Complete intestinal ileus for more than one month is associated with a bad prognosis. The use of drugs and further surgery in this situation in discussed.


[Development of neuromuscular spindles in the muscles of the floor of the human oral cavity during intrauterine development].

By means of histological, neurohistological, histochemical and morphometrical techniques the development, number and histotopography of neuromuscular spindles have been studied in 860 muscles of the mouth cavity fundus obtained from 108 human embryos, fetuses and newborns. In genioglossal and in geniohyoid muscles, the spindles are layed down at the 7th week of gestation. Their differentiation starts at the 9th week -- with forming the first sensitive endings, nuclear bursa and cellular elements of the spindle capsule. By the 14th week, the subcapsular space becomes evident, and by the 20th week of embryogenesis neuromuscular spindles resemble definitive structures. In the anterior belly of the digastric muscle, the foundation and initial differentiation of the spindles is retarded. The mylohyoid muscle has no spindles. Morphogenesis of neuromuscular spindles has been studied with special reference to the beginning of functional activity of the fundal muscles in the mouth cavity during embryogenesis in view of the theory of systemogenesis.


[Comparative characteristics of villous chorionic polysaccharides during the first 3 months of human uterine and tubal pregnancy].

Qualitative composition of polysaccharides has been studied in 100 chorions of human fetuses, 3.5--12 weeks of embryonic development, 40 of them have been obtained from tubal pregnansies. It has been stated that in villous stroma of the tubal pregnancy at the 4--5th week of gestation, sulphate polysaccharides appear that demonstrates an earlier maturation of villi at this type of pregnancy. It is possible that in the formation of intracellular substance of the villous stroma together with fibroblasts Kastschenko -- Hoffbauer's cells also participate. A characteristic feature for the tubal pregnancy is the appearance of distrophically changed villi beginning from the 4th week of gestation. In plasmodiotrophoblast of such villi the amount of Hale-positive and PAS-positive substances is sharply decreasing, and neutral polysaccharides, chondroitin-4-sulfate, chondroitin-6-sulfate and dermatan-sulfate (small amount) are intensively accumulating in the stroma.


Studies of antithyroid antibodies in Down's syndrome.

The presence of antithyroid antibodies (antithyroglobulin and antimicrosomal) in serum of patients with Down's syndrome and their respective mothers were studied based on data from the literature, showing a possible correlation between the presence of these antibodies in the serum of mothers and the birth of mongoloid children. Antithyroid antibodies were studied in 40 patients with Down's syndrome, with ages ranging from 5 months to 21 years old, 24 males and 16 females and in the respective mothers whose ages varied from 22 to 66 years. In none of the analyzed sera of the mongoloids as well of their mothers, the authors were able to detect the antithyroid antibodies studied.


Modifications of the local immune response to Vibrio cholerate attributed to the intestinal microbial flora of the mouse.

Oral immunisation studies in germfree, specific pathogen-free (SPF) and conventionalised mice illustrated that the autochthonous gut flora can have a suppressive effect on the induction of a local intestinal immune response to Vibrio cholerae. Temporary colonisation of the small bowel by viable vibrios occurred only in the germfree animal. The lack of colonisation in SPF and conventionalised mice was presumably a cause of their lower coproantibody responses. Prevention of colonisation was probably due to bacterial antagonism rather than to cross-reaction antibodies. This conclusion was reinforced by studies involving oral immunisation of SPF mice maintained on streptomycin, and of conventionalised ex germfree mice. In addition to the increased protective coporantibody response of animals with reduced gut flora, there were increased levels of non-complement-fixing protective antibodies in their serum, which were probably derived from the guy lamina propria.


Purification and properties of the adenosine triphosphatase released from the liver mitochondrial membrane by chloroform.

1. Soluble ATPase (adenosine triphosphatase) activity is released when rat liver submitochondrial particles are shaken with chloroform, provided that ATP or glycerol is present in the suspending medium. The extraction is very rapid and appears to be complete. 2. The ATPase of the chloroform extract is about 50% pure and can be readily purified to a specific activity of 60-70mumol/min per mg of protein by (NH(4))(2)SO(4) fractionation and column chromatography on Sephadex G-200. 3. The particulate and soluble ATPases have many similar properties, including their K(m) values for ATP, activation by various metal ions, hydrolytic activity with other nucleotides and stimulation by bicarbonate ions. 4. Unlike the particulate enzyme, the soluble enzyme is cold-labile and insensitive to oligomycin. 5. The molecular weight indicated by the mobility of the soluble ATPase on Sepharose 6B is 360000. 6. The soluble ATPase combines very readily with liver submitochondrial particles depleted of ATPase by salt extraction, and oligomycin-sensitivity is restored. Very little recombination of the enzyme occurs with chloroform-extracted particles. 7. The soluble enzyme contains orcinol-reactive material, suggesting that it may be a glycoprotein. The carbohydrate content was estimated to be 1-2% by weight. 8. It is concluded that the liver ATPase obtained by the chloroform extraction method of Beechey, Hubbard, Linnett, Mitchell & Munn [(1975) Biochem. J.148, 533-537] is similar to other preparations described previously and that this method is superior in simplicity and speed.


Mixed anhydrides of nucleotides and mesitylenecarboxylic acid as new specific inhibitors of mitochondrial adenosien triphosphatase.

Mixed anhydrides of nucleoside triphosphates and mesitylenecarboxylic acid inhibit soluble mitochondrial ATPase (adenosine triphosphatase), but do not inhibit ATPase of submitochondrial particles. Inhibition of soluble mitochondrial ATPase by the mixed anhydride of epsilon-ATP and mesitylenecarboxylic acid is followed by the covalent binding of one nucleotide residue to a molecule of the protein. It is suggested that this covalent binding occurs in the catalytic site of the mitochondrial ATPase. The mixed anhydride of ADP and mesitylenecarboxylic acid inhibits the ATPase activity of submitochondrial particles and has no effect on the activity of soluble mitochondrial ATPase. After separation of the submitochondrial particles from the mixed anhydride of ADP and mesitylenecarboxylic acid, their ATPase activity is restored to its original value (half-time of reactivation 3--4 min). Incubation of submitochondrial particles or soluble mitochondrial ATPase with the mixed anhydride of ADP and mesitylenecarboxylic acid results in AMP formation.


Long term chrysotherapy: incidence of toxicity and efficacy during sequential time periods.

The frequency and incidence of certain forms of toxicity in patients receiving long term chrysotherapy for rheumatoid arthritis have been reliably calculated for defined, sequential time periods. Ninety-four patients who received 100 courses of gold therapy for a total treatment period of 134.4 patient-years were followed at one gold therapy clinic. For the period of 0--3 months, the incidences of rash, mouth ulcer, and proteinuria were 9.8, 4.0, and 1.8 episodes per 10,000 patients/month, respectively. However, the incidence of these forms of toxicity decreased progressively in subsequent time periods of continued chrysotherapy. No similar decrease was noted in the incidence of thrombocytopenia, but it would appear that the methodology used in monitoring significantly affects the incidence of clinically important thrombocytopenia. No predictive correlates could be determined for patients who had gone into sustained remission. However, the data strongly suggest that patients who improve within 6 months may continue chrysotherapy for at least up to 3 years with an increasing margin of safety for mucocutaneous and renal toxicity.


[Pharmacokinetics of fominoben-HCl in the dog and the rabbit (author's transl)].

The pharmacokinetics of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)-methyl]-aminomethyl)benzanilide-hydrochloride (P-B 89 Cl, fominoben-HCl, Noleptan) was studied in dog and rabbit following a dose of 3 mg/kg on i.v. and p.o. administration of the 44C-labelled compound. Absorption: The compound is absorbed fast in the dog and very fast in the rabbit. Practically the entire dose is absorbed by the two species. Maximum levels in blood: dog 0.5 microgram/ml, rabbit 0.8 microgram/ml, in the plasma: dog 0.6 microgram/ml, rabbit 1.2 microgram/ml at 1--2 h p.a. and 15--30 min p.a. Elimination: The elimination from blood and plasma proceeds biphasically. 1st half-life: 1--2 h, 2nd half-life: 19--27 h (higher values for the rabbit). The dog eliminates preponderantly via the bile with the faeces, the rabbit via the kidneys: Dog: 19% in urine and 63% in faeces, rabbit 79% in urine and 16% in faeces, measured up to 96 h p.a. One rabbit excreted 70% via the urine up to 7 h p.a. The half-lives of urinary elimination are very well comparable with the figures for plasma. Biotransformation: Plasma (maximum level): Dog: Visible amounts of parent compound (M0), Rabbit: Traces M0, much M2. Urine (0--24 h p.a.): Dog: Traces: M0, Rabbit: Traces M0, much M2.


[Measurement of global diffusion capacity for CO, membrane diffusion capacity for CO and capillary blood volume in patients with bronchial emphysema after fominoben HCl. Short- and long-time trials (author's transl)].

The effect of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)-benzanilide hydrochloride (fominoben HCl, P-B 89 Cl, Noleptan) on the global and membrane diffusion capacities and on the capillary blood volume in patients with emphysematous bronchitis is described. All 3 parameters, independent of the severity of the emphysema and the resulting respiratory insufficiency, are increased. It can thus be concluded that fominoben by improving the ventilation-perfusion ratio leads to an enlargement of the active diffusion surface (capillary surface), from which the increase in the global diffusion capacity results. The site of action of fominoben for its positive effect on respiration is thus established as being in the alveoli.


Plasminogen activation transforms the morphology of quiescent 3T3 cell monolayers and initiates growth.

Plasminogen activator of cell origin converts the plasma protein plasminogen to the proteolytic enzyme plasmin. Recently, high levels of activator have been observed to be particularly associated with tumours and transformed cells, and a functional relationship between plasminogen activation and malignancy has been proposed. In this paper we have attempted to induce transformation-like morphology and growth in a population of confluent quiescent cells in tissue culture, by inducing plasminogen activation. Untransformed 3T3 cells grown to confluence in plasminogen-free medium were subjected to plasminogen activation by the addition of urokinase and plasminogen or plasminogen-containing acid-treated serum, or plasmin. Under these conditions, the previously well ordered monolayers became disrupted, with multilayering, and discontinuities in the cell sheet, and the cells simultaneously grew to significantly higher densities. Removal of the plasmin-containing medium supplements effected some restoration of normal morphology. Thus, lhen plasmin was present 3T3 cells did not become transformed, but expresses transformation-like features. Well ordered monolayer morphology and quiescence in 3T3 cells at confluence are therefore dependent upon the absence of plasminogen activation.


Isolation of plasma membrane vesicles, derived from transverse tubules, by selective homogenization of subcellular fractions of frog skeletal muscle in isotonic media.

A new technique for isolating fragmented plasma membranes from skeletal muscle has been developed that is based on gentle mechanical disruption of selected homogenate fractions. (Na+ + K+)-stimulated, Mg2+-dependent ATPase was used as an enzymatic marker for the plasma membrane, Ca2+-stimulated, Mg2+-dependent ATPase as a marker for sarcoplasmic reticulum, and succinate dehydrogenase for mitochondria. Cell segments in an amber low-speed (800 x g) pellet of a frog muscle homogenate were disrupted by repeated gentle shearing with a Polytron homogenizer. Sarcoplasmic reticulum was released into the low-speed supernatant, whereas most of the plasma membrane marker remained in a white, fluffy layer of the sediment, which contained sarcolemma and myofibrils. Additional gentle shearing of the white low-speed sediment extracted plasma membranes in a form that required centrifugation at 100,000 x g for pelleting. This pellet, the fragmented plasma membrane fraction, had a relatively high specific activity of (Na+ + K+)-stimulated ATPase compared with the other fractions, but it had essentially no Ca2+-stimulated ATPase activity and only a small percentage of the succinate dehydrogenase activity of the homogenate. Experimental evidence suggests that the fragmented plasma membrane fraction is derived from delicate transverse tubules rather than from the thicker, basement membrane-coated sarcolemmal sheath of muscle cells. Electron microscopy showed small vesicles lined bu a single thin membrane. Hydroxyproline, a characteristic constituent of collagen and basememt membrane, could not be detected in this fraction.


(Ca2+ + Mg2+)-ATPase activator: its presence in human red blood cells and rabbit skeletal muscle.

We find that both human red blood cells and rabbit skeletal muscle contain a soluble activator which can stimulate (Ca2+ + Mg2+)-ATPase activity. The activator protein from either source can enhance the (Ca2+ + Mg2+)-ATPase of both the red blood cell membrane and the microsomal fraction from skeletal muscle. The data suggest that they are members of the class of Ca2+-binding modulator proteins. A possible physiological role for the skeletal muscle activator protein in the contractile process is discussed.


Purification and partial characterization of different forms of phosphofructokinase in man.

Phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) from human muscle, brain, heart and granulocytes has been purified using a two or three step purification procedure. The main step is Blue Dextran-Sepharose 4B chromatography with selective elution of phosphofructokinase by formation of the ternary complex ADP or ATP-fructose-6-P-enzyme. Muscle and heart contain only enzyme subunits with a molecular weight of 85,000. This type of subunit is predominnant in brain, where it co-exists with subunits of about 80,000 daltons. A single type of subunits is found in the granulocytes, with a molecular weight of 80,000. Anti-muscle phosphofructokinase antiserum reacts only with M-type enzyme. Anti-granulocyte enzyme antiserum, absorbed by pure brain phosphofructokinase, exhibits a narrow specificity against the so-called L-type enzyme. Anti-brain antiserum, absorbed by pure muscle phosphofructokinase and partly purified red cell enzyme, exhibits a narrow specificity against a phosphofructokinase form predominant in fibroblasts and present in brain (F-type).


Vocalization and looking behaviour of Down's syndrome infants.

The effect of contingent and non-contingent vocal stimulation on vocalization and looking behaviour was investigated for 10 Down's syndrome infants. There were two experimental sessions consisting of four stages, namely 1 min base-line, 1 min experimental condition, a further 1 min base-line and a final 2 min experimental condition. Maternal vocal stimulation was contingent upon infant vocalization for the experimental conditions of one session and was presented every 10 s independent of infant vocalization for the experimental conditions of the other session. Neither condition increased infant vocalization but there was a significant decrease in looking at mother during the base-line stages which followed maternal vocalization (F = 5.07, d.f. = 4, 28, P less than 0.01). It is suggested that looking behaviour may be an important indication of competence in pre-linguistic social communication for developmentally delayed infants.


A radiological approach to infertility--hysterosalpingography.

The hysterosalpingograms of 98 patients with infertility were reviewed with reference to technical problems, radiological features of each pathology and accuracy of reporting. Findings were confirmed by review of the reports of laparotomy or laparoscopy on all patients. Of the total number of fallopian tubes investigated (196), 70 hydrosalpinges were correctly diagnosed from a total of 77. Agreement between HSG and operation was achieved in 123 of 127 fallopian tubes with peritubal adhesions, in all six of those with cornual spasm and in eight with cornual occlusion. In 16 of 20 fallopian tubes with partial distal occlusion, reporting was correct. With the potential accuracy of HSG diagnosis, we contend that it should be a preliminary procedure in every case, and in many may be the only investigation of tubal patency required prior to surgery or conservative management.


Fissuring of the posterior annulus fibrosus in the lumbar spine.

Severe back-ache in young adults may present a difficult clinical problem when the absence of neurological signs results in delayed diagnosis. Fourteen patients, with discographic evidence of posterior annular fissuring are reported. The discrepancy between painful disability and negative radiographic examination including radiculography is stressed. Discography has proved to be the investigation of choice in these patients. This will demonstrate the morphology of the lesion and reproduce the symptomatology in the majority of cases. The clinical implications are discussed.


Prevalence of facial acne vulgaris in late adolescence and in adults.

A survey of 1066 healthy women and 1089 healthy men aged 18-70 years, performed to determine the prevalence of facial acne, showed that clinical acne was not confined to adolescents. Though it was more prevalent among men than women at 18, beyond the age of 23 clinical acne was more prevalent among women as the prevalence in men gradually declined. At 40-49 years 3% of men and 5% of women still had definite, albeit mild, clinical acne, and at 50-59 years 6% of men and 8% of women had physiological acne. The surprisingly high prevalence of acne in adults may be related to antibiotic treatment or, in women, to the use of oral contraceptives or cosmetics, though this survey did not study their influence. Further studies in different populations are needed to establish the prevalence of acne in the community, and its distribution.


Bicarbonate-activated ATPase activity in renal cortex of chronically acidotic rats.

The effect of chronic NH4Cl-induced acidosis on the activity of a bicarbonate-activated component of ATPase was studied in homogenates of renal tissue from Wistar rats. This particular component of ATPase, which is maximally stimulated by 50 mM bicarbonate, and is insensitive to the action of ouabain, has been implicated in the active transport of bicarbonate in various tissues. The activity of this enzyme in cortical homogenates from an acidotic group of animals was 4.3 +/- 0.4 mumol Pi/mg protein per hour compared with 5.8 +/- 0.3 mumol Pi/mg protein per hour in a control group (p less than 0.02). No significant change in bicarbonate ATPase activity was observed in medullary homogenates, and NaK-ATPase activity remained the same in cortex and medulla of both groups. Subcellular fractionation of the cortical tissue homogenates revealed that bicarbonate ATPase activity in a microsomal fraction from acidotic animals was 6.5 +/- 1.1 mumol Pi/mg protein per hour compared with 9.4 +/- 1.2 mumol Pi/mg protein per hour in control animals (p less than 0.02). Bicarbonate ATPase activity in other subcellular fractions was not different in the two groups of animals. These findings are compatible with the hypothesis that a certain percentage of bicarbonate reabsorption in the nephron is mediated by a bicarbonate-activated component of ATPase.


Action of oxytocin on mammary gland: influence of hypotonicity.

The enhancement of the response of an isolated strip of lactating mouse mammary gland to oxytocin, resulting from dilution of the Tyrode solution in which oxytocin is administered, is due to the effects of hypotonicity per se and not to changes in concentration of any of the ions in the bathing solution. Inhibition of membrane ATPase also causes an enhancement, which is probably due to activation of a secondary facilitating mechanism, rather than to enhancement of the entire train of oxytocin-induced reactions. A variety of conditions which alter the response to oxytocin have the same effect on the response to acetylcholine. Hypotonicity can therefore increase the sensitivity of this bioassay for oxytocin, but not its selectivity.


Treatment of aortoiliac disease by axillofemoral artery bypass.

Between July 1, 1971 and June 30, 1977, 45 axillofemoral artery bypass procedures were performed on 39 men and 5 women whose average age was 67.7 years. Twenty-four patients received 25 unilateral axillofemoral bypasses; the remaining 20 patients underwent axillobifemoral artery procedures. The indication for surgery in 42 patients was limb salvage; the other 2 had infected aortic prostheses. All patients in the former group had serious associated disorders which would have made a conventional intra-abdominal procedure hazardous. The early mortality was 2.3% and the late mortality 29.6%. Of these 45 grafts 20 became occluded; however, 8 of the occluded grafts were successfully revised and have remained patent. For the 25 unilateral grafts at risk the 5-year cumulative patency rate determined by life-table methods was 50.6% and for the 20 bilateral grafts it was 89.7%. Our experience indicates that axillobifemoral bypass has a significantly (P less than 0.02) higher patency rate than unilateral axillofemoral bypass and is an acceptable alternative to conventional intra-abdominal procedures in elderly and poor-risk patients with aortoiliac disease.


Pyogenic infections of the adult spine.

A retrospective analysis of 61 patients forms the basis for this paper's comment on three major types of pyogenic spinal disease. The first group consists of 22 patients with vertebral osteomyelitis and intervertebral discitis. The second group comprises 22 patients in whom the diagnosis of pyogenic spinal disease was made only after failure of discectomy. In retrospect they were shown to have atypical degenerative disc disease and were similar to the first group. The third group of 17 patients, while demonstrating some similarities to the second group, represents true postdiscectomy wound infection. An understanding of the clinical presentation and pathophysiology of pyogenic disease of the spine allows it to be distinguished preoperatively from degenerative disc disease which superficially it resembles. Further, true postdiscectomy wound infection can be distinguished from pyogenic spinal disease misdiagnosed preoperatively. The differences in the results of treatment of these three groups warrant such distinctions.


Extragenital adenomatoid tumor: Evidence for the mesothelial theory of origin.

The histogenesis of so-called adenomatoid tumors has been contested. Doubts as to a mesothelial derivation often have been based on the belief that adenomatoid tumors originate exclusively in or nearby genital tract organs. This report documents a histologically typical adenomatoid tumor which developed in the mesentery of the small intestine. Extensive clinical investigations and an uneventful 3-year postoperative follow-up interval confirmed that the tumor was not a metastatic adenocarcinoma or malignant mesothelioma. The extragenital site of origin of this neoplasm provides additional corroborative evidence for the mesothelial origin of adenomatoid tumors. Regardless of their anatomic location, these distinctive neoplasms should be classified as benign adenomatoid mesotheliomas.


Stimulation of human chorionic gonadotropin by JAr line choriocarcinoma after inhibition of DNA synthesis.

Treatment of choriocarcinoma cells (JAr line) for 24 hr with methotrexate, fluorodeoxyuridine, 1-beta-D-arabinofuranosylcytosine, or hydroxyurea, in doses that inhibit DNA synthesis, results in a 2.5- to 12-fold increase in human chorionic gonadotropin (HCG) synthesis. Under the conditions of use, these agents do not significantly depress RNA or protein synthesis. Simultaneous addition of thymidine with methotrexate or fluorodeoxyuridine and of deoxycytidine with 1-beta-D-arabinofuranosylcytosine blocks the HCG stimulation. Despite a rapid inhibition of DNA synthesis, HCG stimulation is gradual and reaches a peak after drug removal. Decline in HCG synthesis is coincident with recovery of DNA synthesis, and there is a positive correlation between the duration of inhibition of DNA synthesis and the amount of HCG increase. Although most of the methotrexate-induced stimulation of HCG synthesis occurs after methotrexate removal, preventing protein synthesis during the exposure to methotrexate abrogates the increase. The stimulation of HCG synthesis by methotrexate is more sensitive to protein synthesis inhibition during the first 12 hr of a 24-hr exposure than it is during the second 12 hr. Thus, in accord with the kinetics, specificity, dose dependence, and protein synthesis requirement, HCG synthesis seems to be stimulated as a direct consequence of inhibition of DNA synthesis, with a requirement for some other protein synthesis-dependent event(s) preceding the stimulation.


Experimental and clinical studies on the formation of antibodies to neocarzinostatin, a new protein antibiotic.

The injection of clinical doses of neocarzinostatin (NCS) in guinea pigs did not result in antibody formation as judged by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, fluorescence polarization, and passive cutaneous anaphylaxis reaction. This confirmed previous work on passive hemagglutination and passive cutaneous anaphylaxis reaction in a heterocytotropic system in guinea pigs. Forty-eight serum samples from 28 patients who were previously treated with NCS alone (8--161 mg) for a period of 8-85 days did not show any sign of antibody formation as revealed by immunoelectrosyneresis, micro-Ouchterlony agar diffusion, and fluorescence polarization techniques. In a homocytotropic system, the passive cutaneous anaphylaxis reaction was carried out with sera of sensitized guinea pigs and test guinea pigs which revealed that no IgE and IgA antibody to NCS was present in the sensitized sera. Those patients with bladder cancer who did not respond to NCS therapy or exhibit any side effects even after 21 mg were found to have proteolytic activity in their sera which degraded NCS very rapidly as revealed by the fluorescence polarization technique.


Phase I study of neocarzinostatin in children with cancer.

Twenty-three children with advanced cancer refractory to conventional therapy received weekly iv doses of neocarzinostatin for 5 weeks. Doses were escalated from 500 to 6750 units/m2/week. Four types of toxic manifestations occurred: acute reactions consisting of shaking chills with or without fever and cyanosis (rigor), hypersensitivity, vomiting, and marrow depression. Evidence of oncolytic activity was limited to patients with acute leukemia in whom phase II trials at doses between 3000 and 4500 units/m2 appear warranted.


Preliminary evaluation of 15 chemotherapeutic agents applied topically in the treatment of mycosis fungoides.

This is an interim report of a double-blind multi-institutional study to examine the effect of chemotherapeutic agents applied topically to patients with mycosis fungoides. To date, 41 patch tests have been completed using 15 drugs. Five of the drugs produced some improvement, four were highly irritating, and six had no effect. This patch-testing study is a prelude to more extensive therapy trials.


Plasma norepinephrine concentration in the coronary sinus in cardiomyopathies.

In order to evaluate the cardiac sympathetic nerve tone in cardiomyopathies, plasma norepinephrine concentration in the coronary sinus (NE(CS)) and artery (NE(A)) was measured by THI method in five patients with the hypertrophic type (HCM) and in seven with the congestive type (CCM); six patients with functional murmur served as controls. NE(CS) was 182 +/- 39 ng/liter (SEM) in HCM, 288 +/- 47 in CCM, and 306 +/- 65 in controls. The NE(CS) - NE(A) difference (delta NE) was 9 +/- 22 ng/liter in HCM, -57 +/- 34 in CCM, and 81 +/- 29 in controls. Norepinephrine overflow into the coronary sinus,which was calculated by multiplying coronary sinus plasma flow by delta NE, was 0.54 +/- 0.86 ng/min/100gm, -2.81 +/- 1.47, and 3.73 +/- 1.77, respectively. Norepinephrine overflow and delta NE were significantly lower in CCM than in controls. The results suggest than an excessive sympathetic discharge does not exist in HCM and that cardiac sympathetic activity is reduced in CCM.


Inhibition of pyrimidine incorporation without inhibition of DNA synthesis.

A putative lymphocytic chalone was tested measuring the incorporation of purine and pyrimidine nucleosides and by cytophotometry. The pyrimidine precursors were inhibited but not the purines. Thymidine and deoxycytidine incorporation even performed simultaneously with cytophotometry can be misleading in the analysis of the inhibition of cell division.


Cardiac contractile proteins. Adenosine triphosphatase activity and physiological function.

This review has pointed out the good correlation frequently observed between ATPase activity of various contractile protein preparations and contractile function of various muscles including the myocardium. Some of the variables in the measurement of the various ATPases and the relationship of these measurements to physiological ATPase in the intact myofibril have been mentioned. The possible roles of changes in the light chains of sulfhydryl groups in the control of ATPase activity have been outlined. The possibility that phosphorylating reactions might exert control over physiological activity remains to be clarified. It is evident that, despite the large amount of research  that has been done, our understanding of how the biochemistry of contractile proteins relates to physiological function is in its infancy, and only with a more complete elucidation of the underlying biochemistry of the components of contractile proteins of physiological and pathophysiological adaptations become evident.


Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog.

Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), which assesses arteriolar-capillary recruitment of perfusing radius and measures a more distal pulmonary vascular response to changing flows, also was calculated. Twelve control dogs were studied and had mean Qpa (pulmonary blood flow) = 2.02 +/- 0.15 liters/min, Zo = 193 +/- 20 dyne sec cm-5 and PVR = 416 +/- 32 dyne sec cm-5. Ten dogs were studied awake 20 weeks after creation of bilateral arteriovenous fistulae. Five of these shunted dogs, designated group A, developed Qpa = 3-4 liters/min (mean = 3.80 +/- 0.09, P less than 0.001 different from control group); the other five dogs (group B) developed Qpa = 4-8 liters/min (mean = 5.87 +/- 0.16, P less than 0.001). In group A, Zo = 143 +/- 8 (P less than 0.05) and PVR = 249 +/- 6 (P less than 0.10). In group B, Zo = 90 +/- 5 (P less than 0.005) and PVR = 126 +/- 14 (P less than 0.01). The total input power (potential and kinetic) was 125% above the controls for group A (P less than 0.001) and 264% for group B (P less than 0.001), but the mean energy components increased significantly more than did the pulsatile components. These data demonstrate a lower impedance to pulsatile flow during chronically elevated total flow which effects a reduction in both the work load of the right ventricle and the transmission of energy to the precapillary bed. Analysis of the alterations in characteristic impedance suggests a distinct proximal pulmonary vascular mechanism of decreased vessel stiffness (decreased elastic moduli) for adaptation to chronically elevated flow loads which is in addition to the two geometric alterations of proximal arterial dilation and distal vascular channel recruitment.


Left axis deviation: a reassessment.

This report deals with the ramifications of the concept of left axis deviation. In early life, the leftward shift of the frontal plane QRS axis is determined chiefly, if not solely, by the relative weights of the ventricles. Once adult ventricular weight ratios are reached, there is a long period of axis stability, then a gradual leftward drift of the QRS, governed principally by left anterior fascicular conduction. Thus, the normal QRS axis is age-dependent, and left axis deviation must be considered accordingly.


Influence of aortic insufficiency on the hemodynamic significance of a coronary artery narrowing.

The coronary hemodynamic effects of controlled aortic insufficiency (AI) were studied in 10 dogs. Coronary blood flow (CBF), before and during reactive hyperemia (RH) with graded coronary diameter narrowings (CN), aortic (Ao) and left ventricular (LV) pressures (P), and aortic blood flow (AoF) were recorded. Opening an adjustable basket catheter, positioned across the aortic valve, created reversible AI quantitated from phasic AoF. AI was regulated so that mean CBF was similar with or without AI. During AI, heart rate and systolic AoP were unchanged, but diastolic AoP declined 14 mm Hg (mean) and end-diastolic LVP increased 8 mm Hg, both p less than 0.05. With CN greater than or equal to 85%, mean CBF decreased with or without AI. Coronary resistance was similar with or without AI. During AI with no CN, peak RH CBF declined significantly and was similar to peak RH with 70% CN without AI. Furthermore, AI with 60% CN caused additional reduction in peak RH and was similar to peak RH with 80% CN without AI. These data suggest that CBF reserve, exposed during RH, is decreased during AI. With AI, a given CN has coronary hemodynamic properties similar to higher degrees of CN without AI. These results may relate to clinical findings of ischemia in patients with AI and no or moderate CN.


A comparison of simultaneous measurements of systolic function in the baboon by electromagnetic flowmeter and high frame rate ECG-gated blood pool scintigraphy.

Left ventricular (LV) systolic timing and relative volume variations were simultaneously measured by electromagnetic flowmeter (EMF) and high frame rate ECG-gated blood pool scintigraphy in five baboons. No significant differences (p greater than 0.1, paired t test) were observed in the time (from R wave) to peak aortic flow (maximum LV ejection rate), time to cessation of aortic flow (end-systole) or in the duration of aortic flow (LV ejection time). A small (approximately 15 msec) but significant systematic difference (p less than 0.02) was noted in the time to onset of aortic flow. The shape of each scintigraphic time-activity curve during systole was compared to an equivalent curve synthesized from 10 EMF flow profiles obtained in the same baboon. Comparison of these paired curves over systolic ejection yielded an average correlation or r = 0.95 (range 0.90--0.99). The ratio of peak flow to stroke volume determined from these data did not differ significantly (p greater than 0.05). In the baboon, quantitative high temporal resolution ECG-gated scintigraphy appears to reflect closely the detailed timing and relative magnitude variation of LV volume during the entire period of systolic ejection. We conclude that the assumptions underlying the scintigraphic method are valid in the baboon during the ejection interval.