[Neurogenic urethra. Urethrogram and pathophysiological aspects].

In the analysis of neurogenic urinary voiding disturbances, too much attention has been paid to the bladder, too little to the muscular tubing of the posterior urethra and to the pelvic floor. Contrast radiography of the urethra in injection and micturition, combined with urodynamic investigations, seemed suitable for comprehension of neurogenic functional disturbances of the posterior urethra and the pelvic floor. A cross section of 143 predominantly traumatic patients and 69 patients with myelomeningocele were investigated radiologically. In addition, in a number of patients urinary flow was determined by uroflowmetry and micturition studies with simultaneous recording of intravesical and intrarectal pressure, of the EMG-activity of the pelvic floor and urinary flow were performed by a special method. The radiologic section shows that the urinary picture of various neurogenic bladder types are characterized by specific changes in form of the posterior urethra. With the help of systematic investigations of a number of cases it was demonstrated that in automatic bladder the roentgen contour of the urethra changes with duration of illness and that primarily secondary, morphologic changes--recognizable at the same time from the increasing number of radiologically demonstrable changes of the prostate and the seminal vesicles--are responsible. Simultaneously a typical deformation of the posterior urethra in passive urinary voiding is described, and attention directed to the fact that the urinary pictures of children with neurogenic impaired urethra sometimes cannot be distinguished from those with urethral values. Urinary flow measurements show that the flow rates from a cross section of patients with lesions of the upper and lower neurons are significantly lower in comparison to normals. With the help of combined urodynamic investigations it was demonstrated that a functional obstruction was present in the neurogenic bladder at the level of spastic and of paretic pelvic floors. It was proved that the roentgenologically visible deformation of the posterior urethra plays a quite decisive role in neurogenically disturbed urinary voiding. It is the main reason why, despite sufficient bladder pressure values, urinary voiding remains unsatisfactory and urinary performance low. Hence the therapeutic consequence follows: an improvement in urinary performance in neurogenic bladder is generally only possible through a decrease in the expulsion resistance. Various operative procedures for the release of bladder outlet obstruction and their uses are discussed.


[Acute abdomen in immune complex vasculitis].

The case of a 51 year old male with 6 months history of loss of weight and abdominal pain is discussed. Laparotomy revealed gangrene of the gall bladder and perforation of the small intestine with consecutive peritonitis. Postmortem examination showed hypertensive intracerebral bleeding and disseminated infarctions of the abdominal organs and the kidneys. Histological findings including immune-fluorescence methods revealed the final diagnosis of immune complex vasculitis.


Comparative in vivo mutagenicity testing by SCE and micronucleus induction in mouse bone marrow.

The treatment of mice with repeated injections of BUdR and FUdR allows for the demonstration  of differentially stained metaphases from bone marrow after FPG (fluorescence plus Giemsa; Perry and Wolff, 1974) treatment. Thus, it is possible to determine the number of SCE's under in vivo conditions, which appears as a very promising system for mutagenicity testing. We studied the response of this system in comparison to the micronucleus test using six mutagenic agents: triaziquone, cyclophosphamide (CP),  dimethylphenyltriazene  (PDMT), methylnitronitrosoguandine (MNNG), dimethylnitrosamine (DMNA), and diethylnitrosamine (DENA). With the exception of MNNG and DENA, all these agents induce both, SCE and micronuclei, MNNG and and DENA being ineffective in both systems. The most potent SCE-inducing agent was triaziquone, followed by PDMT, CP, and DMNA. The quantitative comparison indicates that SCE are induced at  1/10-1/100 of the concentrations which are required for the detection of micronuclei.


Plasma cholinesterase polymorphism in Down's syndrome.

The plasma cholinesterase variants in 80 patients having Down's syndrome have been examined and compared with a random control sample of individuals domiciled in the same area. Neither a change in frequency of known C5+ variant nor any new variant has been found in the electrophoretic studies. A highly significant increase in frequency of the fluoride resistant gene as well as a significant decrease in frequency of the atypical gene has been found in the Down's syndrome individuals. This altered distribution of the rare phenotype of plasma cholinesterase in mental illness may lead to a useful diagnostic acid in genetic counselling.


Immunologically mediated macrophage aggregation in monolayers of peritoneal cells from BCG-sensitized mice.

Aggregation of cultured macrophage monolayers derived from BCG-sensitized mice was produced if nonadherent cells and specific antigen (tuberculin) were present, particularly if the antigen was renewed in the form of tubercle bacilli. The evidence indicated that antigen-stimulated BCG-sensitized lymphocytes in these cultures produced a soluble factor, which in the presence of the renewed supply of antigen caused the aggregation. The phenomenon was irreversible and followed by death of the macrophages. The 'overlays' of aggregated monolayers would aggregate normal macrophages, provided that the recipient cultures contain-d their own (normal) lymphocytes as well as antigen; this suggested that cultures of BCG-sensitized peritoneal cells produced a factor able to effect aggregation via the activity of normal lymphocytes. Overlays from aggregated monolayers were able also to inhibit the migration of normal mouse macrophages; this and other evidence suggested a similar origin for the inhibition factor, but the latter's identity with the aggregation factor remains undecided. We conclude that the aggregation factor depends upon the presence of specific antigen both for its formation and its expression.


T-and B-lymphocyte chimerism in the marmoset.

Marmosets are natural blood chimeras, this condition resulting from the high frequency of fraternal twinning and the consistent development of placental vasular anastomoses between the two embryos. Identification of chimerism by sex-chromosome analysis of cultured blood lymphocytes provided a means of determining the proportion of chimerism among T and B lymphocytes. Peripheral blood lymphocytes were enriched for T or B cells by filtration through a nylon column (yields greater than 95 per cent T-cells) or inactivation of T lymphocytes by treatment with a goat anti-marmoset thymocyte antiserum in the presence of complement (yeilds greater than 95 per cent B cells). Mitogenic stimulation of these separated, enriched cell populations yielded metaphase plates which could be scored for percentage male and female cells. Tests on five different blood chimeras showed the T- and B-lymphocyte chimerism to be the same. Stimulation of blood lymphocytes with cells from another species of marmoset in a mixed lymphocyte culture test revealed the chimeric T-cell response (i.e., host and co-twin cells) to be similar to that obtained with a mitogenic lectin. The demonstration of equivalent T- and B-cell chimerism in these animals suggests derivation of these cells from a common stem cell pool and the response of both T-cell populations to an antigenic stimulus in proportions similar to their percentage chimerism suggests complete immunologic tolerance exists in this species for co-twin histocompatibility antigens.


Human mixed lymphocyte culture using separated lymphocyte populations.

The ability of human blood lymphocyte populations enriched with T or B cells to act as responder and stimulator populations in the one-way mixed lymphocyte reaction (MLR) was investigated. T- and B-cell-enriched populations were obtained by separation of rosette-forming and non rosette-forming cells and T-cell-enriched populations were also obtained by nylon-fibre column filtration. Using cells prepared by rosette sedimentation, control unseparated and T-cell-enriched populations responded well when stimulated by mitomycin C-treated unseparated cells from a second individual; and stimulation by T- and B-enriched populations generally produced some response, although the magnitude was variable. B-cell-enriched populations gave virtually no response regardless of the composition of the stimulating populations. Nylon-column-enriched T-cell populations responded to stimulation by control unseparated cells but not to T cells purified by the same procedure. T-cell enriched populations prepared by the two methods thus had different activities in the MLR despite containing similar numbers of T cells suggesting that other factors, such as the presence of small numbers of accessory cells, are important in determining the magnitude of the MLR.


The application of economic analysis to evaluation of alcoholism rehabilitation programs.

We have presented an algorithm designed to facilitate the application of economic analysis to the evaluation of individual alcoholism rehabilitation programs. In doing so we have attempted to delineate the limitations of such analyses as well as the type and value of information they provide. After a brief review of the basic principles of cost-benefit analysis and a listing of the economic costs of alcoholism, a case study was developed as an heuristic device to illustrate the algorithm and the potential utility of cost-benefit analysis, particularly when used in conjunction with sensitivity analysis, as a logical framework for the evaluation effort.


Altered immune responsiveness associated with Encephalitozoon cuniculi infection in rabbits.

The variation in immune response of two unrelated colonies of laboratory rabbits to high doses of heat-killed Brucella abortus strain 19 was investigated. One was a mixed-breed, multicolored colony in which a high prevalence of encephalitozoonosis had been recorded, whereas the other rabbits were derived from a colony of Dutch-marked specific-pathogen-free rabits. Although considerable variation in the immune response between individual rabbits was noticed at all bleeds, rabbits infected with Encephalitozoon cuniculi showed, on comparison with uninfected rabbits from either colony, a depressed immunoglobulin G response from week 5 of the antigen injection schedule and, from week 8, an elevated immunoglobulin M response.


Cell-mediated and humoral immune responses in mice. I. Necessary conditions for the detection of delayed-type hypersensitivity.

Footpad assay of delayed-type hypersensitivity to bovine serum albumin (BSA) was studied. Injection of saline solution of BSA (S-BSA) into footpads of sensitized mice resulted in the development of only the local Arthus-type reaction. Injection of alumprecipitated BSA (AP-BSA), however, was effective in generating both Arthus- and delayed-type reactions. The difference between S-BSA and AP-BSA in the ability of elicitation of delayed-type reaction may be attributable to the difference in the retention of these two forms of antigen in the footpad, since S-BSA was found to be eliminated much more rapidly from footpads than AP-BSA.


Tissue culture of lens epithelial cells from normal and Nakano mice.

Lens epithelial cells from normal and Nakano adult mice have been cultured for over 1 year, and the cells have retained certain differentiated characteristics. Fluorescent antibody to mouse gamma crystallin reacted with the spherical lentoid bodies which appeared approximately 2 weeks after the start of the culture. The lentoid bodies also contained cells which had few cell organelles and homogenous cytoplasms. Both gamma crystallin production and loss of cellular organelles are characteristics of differentiated fiber cells rather than epithelial cells. An inhibitor of the Na-K ATPase is responsible for the hydration and subsequent cataract formation in the Nakamo mouse. The inhibitor of the Na-K ATPase was demonstrated in the lens in culture from the Nakamo mice, but no inhibitory activity was detected in the cultures from normal mice.


A comparative histochemical study of the masseter muscle of the cattle, sheep, swine, dog, guinea pig, and rat.

The masseter muscles of different mammals were studied by means of hisotchemical reactions: NADH: Nitro BT oxidoreductase (NADHOX), 3-hydroxybutyrate: NAD+ oxidoreductase (HBOX), glycerol-3-phosphate: menadione oxidoreductase (GPOX), and acid-stable and alkali-stable myosin adenosine triphosphatase (ATPase). The masseter mucles of cattle and sheep consisted only of the fibres that reacted moderately for GPOX and strongly for NADHOX, HBOX, and the acid-stable ATPase. The masseter fibres of rats and guinea pigs reacted uniformly and strongly for GPOX and the alkali-stable ATPase. The fibres of the rats showed a weak to strong reaction for NADHOX and mostly a negative reaction for HBOX, whereas those of the guinea pigs reacted uniformly and strongly for NADHOX and HBOX.The masseter fibres of swine and dogs showed a weak or strong reaction for the alkali-stable and a negative or weak reation for HBOX. The fibres of the swine were weak to strong in NADHOX activity and those of the dogs uniformly strong; the fibres of the two species gave a moderate to strong reaction for GPOX. The masseter fibres of the ruminant differed from those of the other species in histochemical properties, and appeared to have the histochemical characteristics that meed functional demands for slow, long-term exercise.


Metabolic evaluation of sexual dimorphism. V. Action of testosterone on the phosphofructokinase of mice submaxillary gland cells in vitro.

1) The kinetics of phosphofructokinase and growth rate of submaxillary gland cells of C3H mice of both sexes in presence and in absence of testosterone have been studied. 2) Both enzymes show sigmoidal kinetics, with Hill's coefficient higher for the females. 3) The maximal activity is remarkably more elevated for the males. 4) The testosterone modifies the growth rate and the kinetic properties of the phosphofructokinase and these modifications depend on the sex.


Depressed lymphocyte responsiveness in autistic children.

Although there are associations linking autism with prenatal rubella, cytomegalovirus, syphilis, and varicella, the etiology of the autistic state remains obscure. Host defense against the etiologic agents postulated to be responsible for the autism-associated syndromes is believed to be primarily of the cell-mediated type. In this preliminary study, cellular immune function was assessed in vitro by phytohemagglutinin (PHA) stimulation of lymphocyte cultures. Twelve autistic children and 13 control subjects were compared. The autistic group exhibited a depressed lymphocyte transformation response to PHA when compared to the control subjects (p less than .01).


Adenosine 5'-triphosphate-linked transhydrogenase in cytoplasmic membranes of colicin-treated and untreated Escherichia coli.

The adenosine 5'-triphosphate (ATP)-linked transhydrogenase reaction, present in the particulate fractions of Escherichia coli, was previously shown to be inhibited in these fractions when the bacteria were treated with colicins K or El. The purpose of this study was to characterized the ATP-linked transhydrogenase reaction and the colicin-caused inhibition of the reaction in purified cytoplasmic membranes. Particulate fractions from bacteria treated or untreated with colicins were separated on sucrose gradients into cell wall membrane and cytoplasmic membrane fractions. The ATP-linked transhydrogenase reaction was found to be exclusively associated with the cytoplasmic membrane fractions. The reaction was inhibited by carbonylcyanide m-chlorophenlhdrazone, dinitrophenol, N,N'-dicyclohexylcarbodiimide, and trypsin. Although the cytoplasmic membrane fractions were purified from the majoriy of the cell wall membrane and its bound colicins, they showed the inhibitory effects of colicins K and El on the ATP-linked transhydrogenase reaction. The inhibition of ATP-linked transhydrogenase reaction induced by the colicin could not be reversed by subjection the isolated membranes to a variety of physical and chemical treatments. Cytoplasmic membranes depleted of energy-transducing adenosine triphosphatase ATPase) complex (coupling factor) lost the ATP-linked transhydrogenase activity. The ATPase complexes isolated from membranes of bacteria treated or untreated with colicins El or K reconstituted high levels of ATP-linded transhydrogenase activity to depleted membranes of untreated bacteria. The same ATPase complexes reconstituted low levels of activity to depleted membranes of the treated bacteria.


Genetic and kinetic analysis of Neurospora crassa mtr mutants.

Allelic complementation occurs at the mtr (methyltryptophan resistance) locus. Kinetic properties of neutral amino acid transport are altered for mtr mutants.


Uptake of calcium ions into microsomes isolated from Physarum polycephalum.

Membranous vesicles (microsomes) were isolated from plasmodia of the acellular slime mold, Physarum polycephalum. The microsomes were about 0.2 about 0.2 micronM in diameter, and about 10 nm thick. The main protein component of the vesicles had a molecular weight of 100,000 daltons. Calcium ions were taken up by the microsomes only in the presence of Mg2+- ATP. The maximum amount of Ca2+ ions accumulated in the microsomes was 0.24 micronmole/mg protein. The Ca2+ uptake was not accelerated by oxalate. The ATPase [EC 3.6.1.3] activity required Ca2+ ions for full activation. The concentration of Ca2+ ions required for half-maximum activation was about 1 micronM. The Km and Vm values were 53 micronM and 1.6 micronmole/(mg-min), respectively. About 0.2 mole of Ca2+ ions was taken up by the microsomes, coupled with the hydrolysis of 1 mole of ATP. THE ATPase activity and Ca2+ uptake of the microsomes were not inhibited by sodium azide. Furthermore, electron microscopic examination showed that mitochondrial contamination was slight. These results suggest that a vesicular calcium transport system, analogous to the sacroplasmic reticulum in skeletal muscle, is involved in regulation of the Ca2+ concentration in plasmodia of Physarum.


Essential factor of gizzard "troponin" fraction. A new type of regulatory protein.

The physiological activity of gizzard "troponin" fraction ((1975) J. Biochem. 78, 859) was shown to be due to the 80,000 dalton component.


Temperature induced analog reaction of adenylyl imidodiphosphate to an intermediate step of heavy meromyosin adenosine triphosphatase.

The UV absorption difference spectrum of heavy meromyosin induced by adenylyl imidodiphosphate (AMP-PNP) was found to be changed by temperature. At higher temperatures, the shape of the difference spectrum resembled the ATP-form of difference spectrum induced by ATP. At lower temperatures, a different shape was observed, resembling that induced by ADP. This temperature transition was found in the presence of both MgCl2 and MnCl2. The transition temperatures, were 21 degrees and 9 degrees in the presence of MnCl2 and MgCl2, respectively. A similar temperature dependence was observed with the difference spectrum induced by ATP at the steady state. The transition temperatures in this case were 11 degrees and 4.5 degrees in the presence of MnCl2 and MgCl2, respectively. The similarity of the effects of the two kinds of divalent cation on both transitions indicates that the temperature induced transition between two species of heavy meromyosin-AMP-PNP complex mimics the step in APTase [EC 3.6.1.3] reaction in which the intermediate complex showing the ATP-form of difference spectrum changes to that showing the ADP-form. The equilibrium constant of the decay step of the ATP-form of difference spectrum to the ADP-form in ATPase is, therefore, thought to be highly temperature dependent. Thermodynamic parameters were calculated for the transition between the two species of heavy meromyosin AMP-PNP complex. Large decreases in enthalpy and entropy were observed, while the standard free energy change was small. The results suggest that the intermediate showing the ATP-form of difference spectrum hardly changes to the forward direction in the ATPase reaction at higher temperature. The complex appears to be so stable in the steady state that almost all the myosin is present as this complex. The decay step in ATPase of the difference spectrum from the ATP-form to to the ADP-form may be coupled to muscular contraction. The temperature induced transition of heavy meromyosin AMP-PNP complex may, therefore, provide information concerning the state of myosin in active muscles.


Distribution of keratan sulfate in cartilage proteoglycans.

After chondroitinase digestion of bovine nasal and tracheal cartilage proteoglycans, subsequent treatment with trypsin or trypsin followed by chymotrypsin yielded two major types of polypeptide-glycosaminoglycan fragments which could be separated by Sepharose 6B chromatography. One fragment, located close to the hyaluronic acid-binding region of the protein core, had a high relative keratan sulfate content. This fragment contained about 60% of the total keratan sulfate, but less than 10% of the total chondroitin sulfate present in the original proteoglycan preparation. The weight average molecular weight of the keratan sulfate-enriched fragment was 122,000, as determined by sedimentation equilibrium centrifugation. The chemical and physical data indicate that this fragment contains an average of 10 to 15 keratan sulfate chains, if the average molecular weight of individual chains is assumed to be about 8,000, and about 5 chondroitin sulfate chains attached to a peptide of about 20,000 daltons. The other population of fragments was derived from the other end of the proteoglycan molecule, the chondroitin sulfate-enriched region, and contained mainly chondroitin sulfate chains. About 90% of the total chondroitin sulfate, but only 20 to 30% of the total keratan sulfate was recovered in these fragments. On the average, approximately 5 chondroitin sulfate chains and 1 keratan sulfate chain could be linked to the same peptide. Another 10 to 20% of the total keratan sulfate, originally found in or near the hyaluronic acid-binding region, was not separated from the chondroitin sulfate-enriched fragments. Hydroxylamine could be used to liberate a large molecular size, chondroitin sulfate-enriched fragment (Kav 0.54 on Sepharose 2B) from the proteoglycan aggregates. The remainder of the protein core, containing the keratan sulfate-enriched region, was bound to hyaluronic acid with the link proteins and recovered in the void volume on the Sepharose 2B column.


Purification and some properties of the Glu- and Lys-human plasmin heavy chains.

The heavy polypeptide chains of human Glu-plasmin and human Lys-plasmin have been isolated in native solvents, after partial reduction and carboxymethylation of the corresponding plasmins. Two major forms of each heavy chain can be eluted, after adsorption to Sepharose/lysine, utilizing a gradient of epsilon-aminocaproic acid as the eluant. The elution profile of these heavy chains is practically identical to the elution behavior previously observed for human Glu- and Lys-plasminogen, and human Glu- and Lys-plasmin adsorbed to these columns. Sedimentation velocity analysis of the heavy chain of human Glu-plasmin, in the presence of epsilon-aminocaproic acid, demonstrated that a gross conformational alteration occurs in this peptide accompanying binding of this amino acid. A much smaller conformational alteration occurs under similar circumstances with the human Lys-plasmin heavy chain. We find that the NH2-terminal peptide released in the Glu-plasminogen to Lys-plasminogen and Glu-plasmin to Lys-plasmin conversions is also released in the Glu-plasmin heavy chain to Lys-plasmin heavy chain conversion. This reaction is catalyzed at a significant rate only by plasmin and not by urokinase. Finally, no strong interaction between streptokinase and the isolated plasmin heavy chains is observed.


Molecular organization of subunits of electroplax (sodium plus potassium)--activated adenosine triphosphatase.

Antisera against each of the two major subunits of detergent-solubilized electroplax (sodium plus potassium)-activated adenosine triphosphatase from Electrophorus electricus were prepared. Antiserum against the small subunit (a glycoprotein, Mr = 58,000) partially inhibits [3H]ouabain binding to the enzyme, but does not interfere with the phosphorylation of enzyme. Conversely, antiserum against the large subunit (the catalytic subunit Mr = 96,000) partially inhibits phosphorylation of the enzyme, but does not interfere with the binding of [3H]ouabain to the enzyme. Since ouabain only interacts with enzyme from the outer surface of the membrane and phosphorylation of enzyme takes place on the inner surface of the membrane, the results suggest that the small subunits are exposed on the outer surface of the membrane, whereas the large subunits are oriented predominantely facing the cytoplasmic side.


Mechanism of action of choleragen. Evidence for ADP-ribosyltransferase activity with arginine as an acceptor.

Choleragen catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide; nicotinamide production was dramatically increased by L-arginine methyl ester and to a lesser extent by D- or L-arginine, but not by other basic amino acids. Guanidine was also effective. Nicotinamide formation in the presence of L-arginine methyl ester was greatest under conditions previously shown to accelerate the hydrolysis of NAD by choleragen (Moss, J., Manganiello, V. C., and Vaughan, M. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 4424-4427). After incubation of [adenine-U14C]NAD and L[3H]arginine with coleragen, a product was isolated by thin layer chromatography that contained adenine and arginine in a 1:1 ratio and has been tentatively identified as ADP-ribose-L-arginine. Parallel experiments with [carbonyl-14C]NAD have demonstrated that formation of the ADP-ribosyl-L-arginine derivative was associated with the production of [carbonyl-14C]nicotinamide. As guanidine itself was active and D- and L-arginine was equally effective in promoting nicotinamide production, whereas citrulline, which possesses a ureido rather than a guanidino function, was inactive, it seems probable that the guanidino group rather than the alpha-amino moiety participated in the linkage to ADP-ribose. Based on the assumption that the ADP-ribosylation of L-arginine by choleragen is a model for the NAD-dependent activation of adenylate cyclase by choleragen, it is proposed that the active A protomer of choleragen catalyzes the ADP-ribosylation of an arginine, or related amino acid residue in a protein, which is the cyclase itself or is critical to its activation by choleragen.


Surface characteristics of the cardiac prostheses in vivo.

The pseudoneointima (PNI) deposited onto a cardiac prosthesis surface reflects many factors of biocompatibility, surface morphology, flow distribution, design, animal's physiological condition, and duration. In the evaluation of any prosthesis, the PNI is one of the prime considerations from both material and functional standpoints. Historically, Dacron fabric has been used as an internal lining for cardiac prostheses. However, we have observed cracks on the Dacron fibers, fiber fracture, fiber protrusion, and poor attachment to the diaphragm, which can cause potentially disastrous complications. In addition, there are basic differences in the PNI formation on aldehyde-treated pericardium and natural aortic valves as compared to the Dacron fabric. 1) Minimal degeneration takes place on the chemically treated natural tissue compared with the fabtic surface. Intact cells on the tissue suggest a greater compatibility. In later specimens (13 and 24 days), there is active cell infiltration onto the pericardium structure with capillary formation. 2) The deposits on natural tissue are mostly fibrin, with minimum cellular involvement and a trend toward reduction in thickness. 3) Fibroblast cells are found on the natural tissue as early as 7 days but were not observed on the Dacron fabrics. Based on these findings, the Dacron fabric-covered diaphragm studied was not favorable for use in long-term implantation of cardiac prostheses.


Chemonucleolysis.

A prospective study of 480 patients who underwent enzymatic dissolution of the nucleus pulposus with chymopapain is reported. Seventy per cent of patients with the clincial criteria for a disc herniation had a favourable response to chemonucleolysis. The commonest cause of failure was persistent back pain. In patients with sequestered discs or lateral recess stenosis surgical intervention was not made more difficult by chemonucleolysis. Those with a previous operation, spinal stenosis or psychogenic components to the disability had very poor results. Complications were few and easily managed.


Origin of urinary 16 beta-hydroxydehydroepiandrosterone in essential hypertension.

The excretion rates and precursors of the 3-sulfate and glucuronide conjugates of 16 beta-hydroxydehydroepiandrosterone (16 beta-OH DHEA) were measured in normotensive controls and in patients with normal and low renin essential hypertension. The hypertensive subjects, and to the greatest degree those of the low renin subgroup, excreted increased amounts of 16 beta-OH DHEA sulfate and glucuronide and lesser amounts of DHEA sulfate and glucuronide than the controls. The major precursor of the urinary 16 beta-OH DHEA sulfate in the hypertensives was circulating DHEA sulfate, whereas the major precursors of 16 beta-OH DHEA glucuronide were DHEA, DHEA sulfate and 17-OH pregnenolone, as determined from their specific activities. Furthermore, both subgroups of hypertensives had similarly elevated DHEA and DHEA sulfate secretory rates compared to the controls. The stimulus to this increased peripheral conversion of circulating 17-OH pregnenolone, DHEA and DHEA sulfate into 16 beta-OH DHEA conjugates in essential hypertension, especially of the low renin type, is unknown.


Effect of prolactin on adrenocortical and gonadal function in normal men.

Dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (A), testosterone (T), estrone (E1), estradiol (E2) and gonadotropins were measured in 3 normal adult men before and after administration of 50 mg ovine prolactin for 5 days. No significant change as a result of ovine prolactin administration was observed in any of the parameters examined.


Wheel chair transfer techniques for the dental office.

With the use of these three techniques and variations when necessary, the immobile or partially immobile patient may be moved relatively easily in the dental office. The dentist and his auxiliaries should be able to make the wheel chair transfer a routine and uneventful procedure that will increase the chances of the patient's return in the future.


A community-based continuing care program for the elderly disabled: an evaluation of planned intermittent hospital readmission.

Fifty of 217 patients on the Continuing Care Program of a Department of Geriatric Medicine have been studied in detail. All patients had sufficient disability to justify permanent admission to a traditional long stay or chronic unit. Utilizing flexible community-supporting services integrated with a hospital-based program of planned intermittent relief of the patients' supporters, patients were maintained in the community at an average cost of 79.5 hospital bed days per patient per annum. Within the near future, unprecedented numbers of persons over 75 years of age, with a high prevalence of chronic disability, will become the financial responsibility of health care systems of Western countries. The Continuing Care Program described may help contain the increasing demand for permanent admission to hospital and allow the disabled elderly citizen an alternative to institutionalization.


Thrombolysis of palmar and digital arterial thrombosis by intra-arterial Thrombolysin.

In nine patients, one with bilateral findings, impending gangrene of the hand due to thrombosis of the palmar arch or digital arteries did not respond to current surgical methods or to common nonsurgical measures and was treated by intra-arterial thrombolysin. The author's recommended diagnostic arteriography, direct surgical treatment, if indicated, and specific coagulation studies. Thrombolysin was given by perfusion at a rate of 100,000 U. per hour. Careful monitoring of the clotting process prevented any significant bleeding and excellent recovery occurred in eight hands and there was a good result in two.


Immunogenicity of human B cell antigens solubilized from cultured human lymphoid cells.

Antigens solubilized from culured human lymphoid cells WI-L2 and RPMI 1788 were partially purified by ultracentrifugation on a KBr gradient. These antigens injected into rabbits produced xenoantibodies which after absorption with melanoma cells became specific to B cell antigens. Three such xenoantisera were submitted to the Second Histocompatibility Workshop of the Americas and reacted much like alloantisera to B cell antigens against a large panel of B peripheral lymphocytes and cells from patients with chronic lymphocytic leukemia. Xenoantisera to B cell antigens inhibited the mixed lymphocyte reaction, but did not affect the mitogenic activity of phytohemagglutinin or the functional properties of C3 receptors, monkey red blood cell receptors, or T cell receptors.


Quantitative studies on the precursors of cytotoxic lymphocytes. I. Characterization of a clonal assay and determination of the size of clones derived from single precursors.

A microculture system for estimating the frequency of cytotoxic lymphocyte precursors (CLP) to alloantigens is described. Cytotoxic T lymphocytes (CL) were generated by culturing limiting numbers of RNC (H-2k)-nu/+lymph node (LN) cells with irradiated C3D2F1 (H-2k/d) spleen cells in the presence of RNC-nu/nu spleen cells for 7 days in microtiter trays. At the end of the culture period, individual wells were assayed for cytotoxic effector cells directed against 51CrP815 (H-2d) target cells. The effector cells generated under these conditions are sensitive to killing by rabbit anti-mouse brain serum and guinea pig complement. The process of differentiation from precursors to CL is radiation sensitive (Do approximately 180 rads). The frequency of precursors for H-2d was calculated by fitting the proportion of nonresponding cultures to the zero order term of the Poisson distribution, Po = e-vn, where Po = per cent nonresponders, v = precursor frequency, and N = number of LN cells cultured per well. The frequency of precursors in the RNC-nu/+LN population responding to the H-2d haplotype was found to be 1 in 776. Under conditions where no backstimulation is possible, the frequency of precursors responding to the H-2d haplotype is 1 in 885 for B6-nu/+LN and 1 in 2550 for B6-nu/+ spleen, respectively. In combination with a visual assay for individual CL, it was found that the average clone size per precursor after 7 days in culture is about 1040. Our assay could detect clones with as few as 40 CL/well. Since the average clone size in 26 times the detection limit, we conclude that the assay for CLP is highly sensitive and does not represent a minimum estimate.


Human immunodeficiency disease: impairment of cellular interactions leading to abnormal mediator production in mixed lymphocyte culture reaction.

Leukocyte migration inhibitory factor (LMIF) production in mixed lymphocyte culture (MLC) reactions is the result of cellular interactions based on two separate phenomena: the capacity of lymphocytes to stimulate in MLC, and the capacity of lymphocytes to respond in MLC. Puromycin-treated lymphocytes are capable of stimulating allogeneic cells for LMIF production, but are unable to respond with synthesis of LMIF (one-way MLC-LMIF test). We have studied the stimulating and responding capacity of lymphocytes from patients with different immunodeficiency syndromes in a one-way MLC-LMIF assay. Lymphocytes from patients known to have qualitative and quantitative defects of T cell or B cell functions (Hodgkin's disease, mycosis fungoides, thymoma, chronic lymphatic leukemia) were found to respond poorly as measured by mediator production although their stimulating fuction was frequently retained. Patients with advanced solid tumors often had both MLC-stimulating and responding functions depressed. There was no apparent correlation between mitogen response and MLC-induced LMIF responses or between MLC proliferative response (as measured by thymidine incorporation) and mediator production. Studying of stimulatory and responding capacity of lymphocytes in the MLC-LMIF assay provides a new tool for assessing immunocompetence and allows for in vitro evaluation of cellular interactions that may play an important role in vivo.


Immunoregulatory properties of fractions from human pregnancy urine: evidence that human chorionic gonadotropin is not responsible.

The immunologically privileged position of the histoin-compatible fetus and placenta is a striking example of a physiologic immunoregulatory mechanism. This study was designed to examine the effects of human chorionic gonadotropin (HCG) on the recognitive proliferative phase and the cytotoxic effector phase of in vitro cell-mediated immune responsiveness, since HCG has previously been reported to be immunosuppressive in vitro and in vivo. Commercial preparations of HCG were found to be potent inhibitors of lymphocyte proliferative responses to nonspecific mitogens like phytohemagglutinin (PHA), specific antigens such as streptolysin-O (SLO), and allogeneic cells as measured in the one-way mixed leukocyte response. Cytotoxic effector function of lymphocytes as measured by antibody-dependent cellular cytotoxicity (ADCC) and mitogen-induced cellular cytotoxicity were also markedly inhibited by these preparations. However, the 50% inhibitory concentration varied widely from lot to lot of these commercial materials. After dialysis, a portion of the inhibitory activity was lost from some but not all HCG lots. The dialysate from those lots with diminished activity was found to be immunosuppressive in vitro but contained no HCG detectable by radioimmunoassay. Following dialysis, the immunosuppressive activity of the various HCG lots remained variable and correlated poorly with values for HCG obtained by a double antibody radioimmunoassay. HCG preparations purified to a homogeneity sufficient for amino acid sequence were found to be only minimally immunosuppressive to the in vitro PHA response and had almost no effect on proliferative responses to antigens and allogeneic cells. These data do not support the concept of a primary immunoregulatory role for HCG, but they suggest that other uncharacterized compounds partially co-purified from pregnant urine along with HCG may have such immunoregulatory activity. Further characterization and identification of this immunoregulatory material(s) is essential, since it appears to have many of the properties of an ideal immunosuppressive compound: a) nontoxicity, b) ready reversibility, c) activity at very low concentration, and d) activity on a broad range of cellular immune functions.


Effects of lymphocytes from Marek's disease-infected chickens on mitogen responses of syngeneic normal chicken spleen cells.

PHA responses have been measured in lymphoid cell cultures prepared by mixing normal chicken spleen cells with spleen or thymus cells from syngeneic chickens infected with the oncogenic herpesvirus MDV. Results of these studies may be summarized as follows: 1) spleen cells from MDV-infected chickens with visceral lymphomas inhibit the PHA response of normal spleen cells possibly by release of soluble inhibitory factors in response to the mitogen; 2) lymphoid cells from asymptomatic MDV-infected chickens, although hyporeactive themselves to PHA, can have a stimulatory effect on PHA responses of normal spleen cells in mixed cultures; 3) spleen cells from MDV-infected chickens, effectively protected from viral oncogenesis by HVT vaccination, show normal reactivity to PHA in spearate cultures and may react in mixed cultures like normal lymphocytes, with neither a pronounced stimulatory nor inhibitory effect on the PHA response of normal spleen cells.


Interaction with homologous erythrocytes of rat T cells which act as aggressors in the mixed lymphocyte reaction.

Substantial percentages of T-enriched spleen lymphocytes or thymocytes of inbred rats were found to form rosettes with the RBC of homologous strains. When an excess of RBC was used, essentially all of the rosette-forming subpopulation of lymphocytes was removed when the rosettes were separated by centrifugation. After depletion of the lymphocytes, reactive with RBC of one strain, most of the lymphocytes reactive with RBC of other strains could be recovered in the supernatant. A very large percentage of lymphocytes of the BN strain formed rosettes when a mixture of the RBC of five other strains was tested; the percentage was, however, somewhat lower than that predicted on the basis of complete additivity. Rosettes dissociated when warmed to 37 degrees C. The lymphocytes recovered were unable to form rosettes again. In nearly all instances, the subpopulation that formed rosettes with RBC of a given strain included essentially all of the lymphocytes that acted as aggressors against peripheral leukocytes or mytomycin C-treated thymocytes of that strain; the lymphocytes in the supernatant always retained activity as aggressors against the leukocytes of one or more other strains and retained their responsiveness to PHA. Lymphocytes recovered from rosettes, by warming to 37 degrees C, were highly reactive as aggressors in the MLR against the strain providing the RBC. Varying degrees of reactivity were noted against leukocytes of other strains.


Fractionation of lymphocyte subpopulations which regulate mixed lymphocyte reactions.

Four days after injection of allogeneic lymphocytes BALB/c splenic T cells suppress proliferation of syngeneic cells in mixed lymphocyte reactions (MLR). Conversely, lymph node cells from the same mice amplify MLR responses. To further characterize these functional subpopulations, alloantigen-primed lymphocyte suspensions from both organs were fractionated by velocity sedimentation at unit-gravity. After fractionation MLR suppressor cells from spleens localized exclusively in rapidlly sedimenting fractions of large cells. MLR suppressor activity of cells from these fractions, as well as that of unfractionated spleen cell suspensions, was abolished by treatment with anti-Thy-1.2 serum and complement. Spleen cell fractions of similar sedimentation velocity also secreted a soluble MLR suppressor into culture supernatants. Although inhibitory of MLR, spleen cells of rapid sedimentation velocity did not suppress responses to T cell mitogens. In marked contrast with the effects of spleen cells, large 4-day-alloantigen-primed lymph node cells had no suppressive activity in MLR. MLR amplifier cells of uncertain derivation were found in fractions of medium sedimentation velocity from both spleens and lymph nodes. Fractionation of alloantigen-primed lymph node cell suspensions did reveal, however, a subpopulation of small cells with MLR suppressor acitivty which was unaffected by treatment with anti-Thy-1 serum and complement. The data thus indicate that large alloantigen-activated lymphocytes are not intrinsically suppressive nor are cells which suppress MLR necessarily large. We consequently conclude that regulation of MLR responses by alloantigen-primed lymphocytes involves a complex interaction between distinct functional subpopulations of cells which are separable both by physical and biologic properties.


5-ene-3beta-hydroxysteroid dehydrogenase of human and bovine adrenocortical endoplasmic reticulum: solubilization and fractionation.

Protein moieties of various molecular sizes and possessing 5-ene-3beta-hydroxysteroid dehydrogenase activity have been successfully solubilized from the microsomal membranes of both bovine and human adrenal glands using a combination of Triton X-100 and sonication. These moieties have been studied by gel filtration, sucrose density gradient centrifugation and isoelectric focusing, and were shown to possess a minimum molecular weight of about 118 000, with an isoelectric point between 7-2 and 7-4. The molecular weight was dependent upon the concentration of Triton X-100 used during fractionation. No separation of dehydrogenase activities toward the three steroid substrates, pregnenolone, 17alpha-hydroxy-pregnenolone and dehydroisoandrosterone, was observed. Changes in the relative activities for the steroid substrates during fractionation were observed, but have been attributed to the formation of allotypes rather than to the existence of separate dehydrogenases with restricted substrated specificity.


Ouabain inhibition of gill Na-K-ATPase: relationship to active chloride transport.

Ouabain circulating in blood inhibits Na-K-ATPase in the gills of seawater eels at a concentration similar to that necessary for inhibition in vitro. By contrast, a much higher concentration is required when ouabain is applied to the exterior of the gill. Inhibition by external ouabain occurs only when the drug gains access to the circulation of the fish, as evidenced by simultaneous inhibition of Na-K-ATPase in the kidney. These results suggest that the Na-K-ATPase of gill chloride cells faces inward, lining intracytoplasmic tubular channels continuous with the extracellular fluid. Inhibition of gill Na-K-ATPase by ouabain in intact salt water eels results in almost complete inhibition of the efflux of both Na+ and Cl-. The efflux is tritiated water was much less  reduced, to 60% of normal. Since chloride is actively transported outward across the gill of seawater teleosts, it is suggested that active chloride transport is coupled to Na-K-ATPase. A neutral sodium chloride carrier is postulated that is energized by the movement of sodium from extracellular fluid down its electrochemical gradient into the chloride cell.


Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process.

Two genes in Drosophila, rdgA and rdgB, which when defective cause retinal degeneration, were discovered by Hotta and Benzer (Hotta, Y., and S. Benzer. 1970. Proc. Natl, Acad. Sci. U. S, A. 67:1156-1163). These mutants have photoreceptor cells that are histologically normal upon eclosion but subsequently degenerate. The defects in the rdgA and rdgB mutants were localized by the study of genetic mosaics to the photoreceptor cells. In rdgB mutants retinal degeneration is light induced. It can be prevented by rearing the flies in the dark or by blocking the receptor potential with a no-receptor-potential mutation, norpA. Vitamin A deprivation and genetic elimination of the lysosomal enzyme acid phosphatase alsoprotect the photoreceptors of rdgB flies against light-induced damage. The photopigment kinetics of dark-reared rdgB flies appear normal in vitro by spectrophotometric measurements, and in vivo by measurements of the M potential. In normal Drosophila, a 1-s exposure to intense 470-nm light produces a prolonged depolarizing afterpotential (PDA) which can last for several hours. In dark-reared rdgB mutants the PDA lasts less than 2 min;; it appears to initiate the degeneration process, since the photoreceptors become permanently unresponsive after a single such exposure. Another mutant was isolated which prevents degeneration in rdgB flies but which has a normal receptor potential. This suppressor of degeneration is an allele of norpA. It is proposed that the normal norpA gene codes for a product which, when activated, leads to the receptor potential, and which is inactivated by the product of the normal rdgB gene.


Effects of vitamin B6 deficiency on liver, kidney, and adipose tissue enzymes associated with carbohydrate and lipid metabolism, and on glucose uptake by rat epididymal adipose tissue.

Adipose tissue and liver from vitamin B6-deficient rats have an increased lipogenic capacity. Whether this phenomenon is accompanied by changes in the activities of certain enzymes involved in the metabolism of carbohydrate and lipid, or by altered transport of glucose into adipocytes, has been studied. Five glycolytic enzymes (hexokinase, phosphoglucose isomerase, phosphofructokinase, aldolase, and pyruvate kinase), two pentose phosphate pathway enzymes (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), malic enzyme, and ATP citrate lyase were measured in the epididymal adipose tissue, livers and kidneys of vitamin B6-deficient and control rats. Vitamin B6 deficiency did not significantly affect the glycolytic enzyme levels in the tissues studied, or the dehydrogenases measured in adipose tissue and kidneys. Liver glucose-6-phosphate dehydrogenase, and adipose tissue and liver malic enzyme were significantly lowered in deficient rats compared to ad libitum and pair-fed controls. Adipose tissue and liver ATP citrate lyase activities were also significantly decreased by vitamin B6 deficiency. In the presence of insulin, the uptake of glucose and 3-O-methyl glucose, a non-metabolizable sugar, by fat pads from deficient rats was greater than uptake by fat pads from control rats. These observations suggest that the increased glucose utilization by adipose tissue and liver of vitamin B6-deficient rats is not directly related to changes in the enzymes studied, but in the case of adipose tissue, may be explained, at least in part, by enhanced glucose uptake.


Effects of high sucrose or starch-bran diets on glucose and lipid metabolism of normal and diabetic rats.

Normal and streptozotocin-diabetic rats were fed a low carbohydrate diet or one of two high carbohydrate diets (sucrose or starch-bran). High carbohydrate diets were associated with slightly higher plasma glucose levels in both control and diabetic rats. However, glucose tolerance tests were not altered by the diets in either the control or diabetic rats. Plasma and liver triglyceride values for control and diabetic rats fed the high sucrose diet were similar to those of rats fed the low carbohydrate diet. The starch-bran diet was associated with lower plasma and liver triglyceride values in both control and diabetic rats. Plasma triglyceride values of diabetic rats fed the high sucrose diet or the low carbohydrate diet were significantly higher than values of control rats fed the same diets. On the other hand, plasma triglyceride values of diabetic rats fed the starch-bran diet were similar to values for control rats fed the same diet. These studies suggest that a high carbohydrate diet containing starch and wheat bran is associated with a reduction in plasma triglyceride values in both normal and diabetic rats. Liver glycolytic enzyme activities were significantly lower in diabetic rats than in control rats in all three dietary groups.


Inhibition of renal adenosine triphosphatase by cadmium.

The effects of CdCl2 on adenosine triphosphatase (ATPase) were studied microsomal fractions or tissue homogenates of outer cortex, inner cortex and outer medulla of dog kidney. Cd was found to be an inhibitor of Na+ +K+ Atpase with 150 value of 2.1 to 3.2 X 10(-4) M regardless of type or source of the enzyme preparation tested. Mg++ ATPase was about 10-fold less sensitive to inhibition by Cd than Na+ +K+ ATPase. The inhibition of microsomal NA+ +K+ ATPase from outer medulla was characterized by irreversible kinetics. The inhibitory effect was not altered by varying Na+ or K+ concentrations, but was decreased by disodium ethylenediaminetetracetic acid (EDTA). EDTA was more effective in preventing than in reversing the inhibition. Na+ +K+ ATPase from kidneys of several other mammalian species showed a similar sensitivity to Cd.


Digitalis toxicity: lack of marked effect on brain na+,k+-adenosine triphosphatase in the cat.

Effect of digitalis on central sympathetic neurons have been proposed to alter sympathetic influences on the heart and to contribute to the induction of arrhythmias. Recently, however, we have presented evidence which indicates that the involvement of a direct central action of digitalis is negligible in the alteration of sympathetic nerve activity after i.v. administration of the drug. Thus, a group of experiments were designed to determine if central drug concentrations or biochemical events in the brain would suggest a central action of the drug. Tritiated digoxin (20 microng/kg) was injected i.v. into cats every 15 minutes until ventricular fibrillation occurred. The concentrations of digoxin in cerebrospinal fluid and serum increased linearly with time as the cumulative dose of digoxin was increased. At the mean arrhythmic dose, 140 microng/kg, cerebrospinal fluid contained approximately 10 nM digoxin whereas free digoxin concentration in serum was approximately 30 nM and total digoxin concentration in serum was approximately 120 nM. Since inhibition of Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) is often associated with the pharmacological effects of digitalis, effects of nanomolar concentrations of digoxin on Na+,K+-ATPase activity were determined in vitro. The concentration of digoxin faund in cerebrospinal fluid at arrhythmia inhibited Na+,K+-ATPase only slightly (5-10%). Activity of Na+,K+-ATP-ase was also examined in brains of cats which had died in ventricular arrhythmias due to treatment with lethal dose of digitoxin. After ventricular fibrillation, the cat brains were removed and Na+,K+-ATPase activity and ouabain binding were determined in eight areas. No reduction in Na+,K+-ATPase activity or [3H]ouabain binding was observed in any area. Thus, it appeared that toxic doses of digitalis did not cause sail to provide evidence for central effects of toxic doses of digoxin or digitoxin.


Effect of gentamicin on p - aminohippurate metabolism and transport in rat kidney slices.

The mechanism by which gentamicin augments the uptake of p-aminohippurate (PAH) by rat renal cortical slices was investigated. In all experiments, gentamicin was administered as gentamicin sulfate at 100 mg/kg b.wt. per day for 2 days; control rats were injected with saline. The effect of gentamicin on the metabolism of PAH to p-aminobenzoic acid (PABA), acetyl-PABA and acetyl-PAH was studied by high performance liquid chromatography. No metabolites of PAH were detected in renal slices of gentamicin-injected or control rats incubated in medium containing PAH. Efflux of 14C-PAH was measured after incubating renal cortical slices for 2 hours in medium containing 8 X 10(-5) M 14C-PAH. The efflux rate constant was 0.080 +/- 0.003/min in control slices and 0.059 +/- 0.003/min in gentamicin slices, P less than .001. No significant difference in the diffusible pool of PAH was found between the two groups which supports an argument against increased tissue-binding of PAH as the explanation for the augmented uptake of PAH by slices of gentamicin-injected rats. Active PAH transport was assessed in terms of Michaelis-Menten kinetics. Vmax was 0.93 +/- 0.08 micronmol/g/15 min in control slices and 1.37 +/- 0.10 micronmol/g/15 min in gentamicin slices (P less than .005). The apparent reaction rate constant (Km) was not different; Km was 0.25 +/- 0.03 and 0.29 +/- 0.04 mM in control and gentamicin slices, respectively (P less than .4). In contrast to PAH, gentamicin did not alter uptake of N'-methynicotinamide, an organic base; nor did it alter the efflux rate constant or diffusible pool of N'-methylnicotinamide. Increased PAH uptake was still evident when slices of gentamicin-injected rats were incubated in medium without acetate. These studies indicate that gentamicin stimulates active PAH transport and decreases PAH efflux in rat renal cortical slices. Both changes implicate an effect of gentamicin at the antiluminal membrane of proximal tubular cells. The finding of an increase in Vmax without a change in Km raises the possibility that gentamicin increases the amount or availability of carrier protein-mediating PAH transport.


Frog muscle spindles with unbranched myelinated afferent axons: the response to stretch and the length of the first myelinated segment.

1. Twenty-five muscle spindles innervated by unbranched myelinated axons in the capsule were isolated from sartorius muscle in young frogs (2-2--9-5 g in weight, 28-47 mm in rostro-caudal length). 2. The lengths and the diameters of the first myelinated segments varied from 30 to 170 mum and from 9 to 20 mum respectively. There was no relationship between the lengths and the diameters. 3. Dynamic and static components were analysed from discharge rates of the muscle spindles during ramp-and-hold stretches of 0-8 mm from different initial lengths. The values of the dynamic components to a certain stretch stimulation increased with shortening in the length of the first myelinated segment. The values of the static components were independent in length. 4. The amplitudes of action potentials recorded from the spindle terminal decreased during the dynamic phase of the stretch. The ratio of amplitude decrease at the end of the dynamic phase versus the initial length depended upon the length of the first myelinated segment. 5. These results suggest that the discharges during stretch may arise at the first node, though the spontaneous discharges may be generated at the terminal.


Control of dynamic and static nuclear bag fibres and nuclear chain fibres by gamma and beta axons in isolated cat muscle spindels.

1. The behaviour of nuclear bag and nuclear chain intrafusal fibres in isolated cat muscle spindles with a blood supply, during stimulation of dynamic gamma axons, dynamic beta axons, or static gamma axons in ventral root filaments was observed and recorded on still and moving film. 2. Most spindles were controlled by one dynamic gamma axon (sometimes a beta axon) and three static gamma axons, one of which was often non-selective in distribution. A large majority of fusimotor axons controlled one pole of the spindle only. 3. Dynamic gamma and beta axons produced focal contraction in only one of the two nuclear bag fibres in any spindle and this fibre was never activated by static gamma axons. Maximal tetanic contraction was attained slowly and the primary sensory spiral on this fibre was stretched by a small amount only. This fibre has been named the 'dynamic nuclear bag fibre'. 4. Static gamma axons produced either: (a) focal contraction in the second of the two nuclear bag fibres only; (b) local contraction in the bundle of nuclear chain fibres only; or (c) contraction in one nuclear bag fibre and the nuclear chain fibres together. Maximum tetanic contraction of this nuclear bag fibre stretched its primary sensory spiral considerably and the time to plateau was relatively short. This fibre has been named the 'static nuclear bag fibre'. 5. 'Driving' of the Ia afferent discharge could always be produced by non-selective static gamma axons, frequently by static gamma axons controlling nuclear chain fibres alone, and was probably due to mechanical oscillation in nuclear chain fibres. It was never produced by dynamic gamma axons and on one occasion only by a static gamma axon controlling a nuclear bag fibre alone. 6. The conduction velocities of dynamic gamma and static gamma axons overlapped extensively, though dynamic gamma axons were absent from the lower end, and static gamma axons innervating nuclear chain fibres only were absent from the upper end, of the range of velocities. 7. The observations are correlated with spindle structure and histochemistry. Dynamic and static nuclear bag fibres are shown to correspond with 'bag1 fibres' and 'bag2 fibres', respectively (Ovalle & Smith, 1972). 8. The possible origin of the dynamic and static actions of fusimotor axons and the role of the dynamic and static intrafusal systems in motor control are discussed.


[Parasitic calcifications: elements for diagnostic (author's transl)].

Among the radiologic calcifications, those of parasitic etiology are rather commonly found. They are heterotopic dystrophic calcifications, their late apparition in the evolution of the parasitic disease is not subordinate to any metabolic dysfunction. The authors describe the morphologic and the topographic criteria of different parasitic calcifications except the fungic ones and protozoaire. Moreover they state for each parasite some epidemiological, biological and clinical facts which can be helpful for the diagnosis.


Studies on anticoccidial agents. 11. Synthesis and anticoccidial activity of nitropyridinecarboxamides and derivatives.

Of the nine nitropyridinecarboxamides, which are isomers of 5-nitronicotinamide, a potent anticoccidial agent, 2-nitropyridine-3, -4, -5-, or 6-carboxamides and 3-nitropyridine-4- or 6-carboxamides were prepared from the corresponding acids via the esters of the acid chlorides. 3-Nitropyridine-2-carboxamide was obtained from 2-methyl-3-nitropyridine by oxidation with SeO2, oximation, dehydration with Ac2O, and hydrolysis with H2SO4. 4-Nitropyridine-2-carboxamide was prepared from 2-cyano-4-nitropyridine by hydrolysis, and the 3-carboxamide analogue was obtained from 4-amino-3-cyanopyridine by oxidation with H2O2 and fuming H2SO4. Of these compounds 2-nitro- and 3-nitro- but not 4-nitropyridinecarboxamides were found to be active against Eimeria tenella. N-Substituted analogues of 2-nitro- and 3-nitropyridine carboxamides were also prepared in a conventional manner and optimal anticoccidial activity was attained with 2-nitroisonicotinamide and its N-alkanoyl, N-aromatic, and N-heterocyclic acyl derivatives.


Histological and histochemical studies on the nervous influence on minced muscle regeneration of triceps surae of the rat.

The degree of minced rat muscle regeneration in the absence of nerve fibers was compared with that of normal regenerates between one and 270 days postoperatively. Up to around 30 days, the number of muscle fibers and their morphology were comparable in both normal innervated and denervated regenerates; both showed clear cross striations and peripherally located nuclei. Histochemically, SDH and myofibrillar ATPase (pH=9.4) reactions were positive, but there were no typical signs of fiber types in either case of regeneration. The only consistent difference in the early period was the smaller fiber cross sectional areas in denervated regenerates than in innervated ones. Starting about 40 days, the muscle fibers in innervated regenerates became differentiated into different fiber types (fast-twitch-oxidative-glycolytic, FOG., fast-twitch-glycolytic, FG., slow-twitch-oxidative, SO.) but there were no such activities in denervated regenerates, although their SDH and myofibrillar ATPase reactions remained positive for a long time. Degenerating muscle fibers could no longer be identified in innervated regenerates. In the denervated regenerates, however, muscle fibers underwent atrophic or degenerative changes and were replaced by connective tissue. The complete disappearance of muscle fibers varied with individual regenerates. In some cases, it occurred about 90 days and in others, traces of muscle fibers could still be seen as late as 150 days postoperatively. Thus, nerves seem to be important primarily in the late phase of regeneration; namely, differentiation of fiber types and maintenance of the structural integrity of muscle fibers.


Antibody to hepatitis A antigen in institutionalized mentally retarded patients.

Institutionalized patients with Down syndrome and matched controls with other causes of mental retardation were tested by immune adherence hemagglutination for the presence of antibody to hepatitis A antigen (anti-HA). Altogether 75.1% (175 of 233) exhibited presence of anti-HA, with no differences by sex or age. Patients reactive for hepatitis B surface antigen (HBsAg) or its antibody (anti-HBs) were reactive for anti-HA significantly more frequently than those with a negative reaction for these markers. In contrast to serologic markers of hepatitis type B, prevalence of anti-HA does not depend on the cause of mental retardation or on the age at primary infection. The rate of anti-HA positivity was found to be closely correlated with duration of institutionalization. The study confirmed that many closed institutions for the mentally retarded are hyperendemic for hepatitis type A and that formation of anti-HA is not greatly affected by either immune deficiency or immune immaturity.


Studies on the low back pain among electric construction workers. Report 2. Workers' attitude to the prevention and the treatment of their low back pain.

In the previous report, the author demonstrated that the electric construction workers were exposed to the high risk of low back pain, and discussed on the ways to prevent and to treat their occupational disorders. He concluded that the improvement of their working conditions, especially lessening of the working load, was necessary to prevent occupational low back pain, and that it was the most helpful effect on their low back pain to take a rest on an after the attack of the disorder, while most of the medical treatment without a rest were almost helpless. In this report, the author studied and discussed on the workers' opinions on the ways to prevent and to treat their low back pain, by means of questionnaire-method. The workers examined were classified by whether they had the disorder or not and also by the grades of their working load. The results are as follow: 1. As for preventive measures, it is the most popular opinion that they should take care not to hurt their low back; nevertheless, as a matter of fact, their low back pain has been mainly resulted from overwork. 2. As for necessary means on the attack of low back pain, many workers believe that medical treatment is the most helpful to the disorder. Fewer workers recognize the low back pain as an occupational disorder and have opinion that they should take a rest on the attack of the disorder. 3. There is much discrepancy between the workers' opinions mentioned above and the occupational health doctors' recommendations that it is most desirable to improve the working conditions and to let the workers take a rest. 4. The more seriously they suffer from the disorder, the more practical and reasonable are the contents of their opinions. 5. In order to let these workers take a rest from labour more easily, the employers should recognize their low back pain as an occupational disorder, including offjob-payment.


[Characteristics of the course of pregnancy in women with heart defects].

In 33 patients with different forms of the cardiac valves lesion the specificity marking the course of atriomegalia was studied on the ground of clinical, roentgenological and functional findings. Unlike non-pregnant women with similar forms of the malady here intercurrent pulmonary hypertension during gestation was ascertained, this increasing the hazard of developing edema of the lungs. The authors give preference to delivery in these patients via natural maternal passages by employing the operation with application of obstetrical forceps.


[State of the cardiovascular system in patients with decompensated mitral valve defect under conditions of high altitude].

A clinical study was conducted in 236 patients with decompensated mitral valve disease--permanent residents of the areas located at various altitudes in the Pamirs and Tien Shan (760 to 4,200 m above the sea level). The main parameters of haemodynamics were studied by means of the dye dilution method in 158 of them, as well as the indices of cardiodynamics by way of polycardiography. The data obtained in 120 normal individuals living in foothills (760 m) served as control. It was demonstrated that with the same stages of cardiac insufficiency, the most striking changes in the haemo- and cardiodynamics were noted among the residents of the high altitude areas. Among those living at medium altitudes (1,650 to 2,020 m), the cardiac output and the left ventricular function appeared to be reduced most distinctly. These patients also exhibited a clear relationship between the main variables of the cardiovascular functions and the severity of cardiac insufficiency. The revealed clinical and functional peculiarities of the decompensated mitral valve disease in mountaneers are atrributable to the effect of hypoxic  hyposy upon the regulation of the respiration and the pulmonary circulation.


[Blood flow in the transplant after aorto-coronary bypass].

With the help of an electromagnetic flowmeter the authors measured the blood flow in the graft during aorto-coronary bypass procedures. The flow was measured in 74 patients with 88 bypass grafts, along them--in 43 grafts to the right coronary artery, in 31 grafts to the anterior interventricular artery, and in 14 cases of double aoroto-coronary bypass grafts. In 21 cases the flow was measured in the coronary artery graft after endarterectomy. The analysis has demonstrated that the flow in the graft depends on many factors, the leading among which is the severity of the coronary lesion, the state of its distal portion and of the cardiac muscle in the zone of the diseased coronary artery. A direct relationship was established between the degree of the narrowing of the proximal coronaries and the flow values in the graft connected with the artery in question. The greater the stenosis in the proximal portion of the coronary artery, the higher the blood flow in the bypass. The highest blood flow was registered in cases of complete coronary occlusions. Blood flow measurements in the bypass grafts during surgery help to determine the amount of blld supplied to the revascularized myocardium and, hence, to assess the direct efficacy of the aorto-coronary bypass procedures in the management of the ischaemic heart disease.


[Mechanism of increasing the functional capacity of the cardiac muscle after adaptation to physical exertion].

The main parameters of contraction and relaxation of papillary muscle strips taken from the left ventricle of control and exercise-adapted rats were measured. The contractile velocity and amplitude of thin and thick strips of the cardiac muscle of adapted rats were found to be 2--3 times higher than in the controls. This fact can be explained by an elevation of myosine ATP-ase activity. The developed tension was higher than in the controls only in thick strips of adapted rats. This increase depends on the adaptive augmentation of the functional power of systems responsible for the transport of oxygen and substrates to the mitochondria. The myocardium of adapted rats differed from that of the controls in that the relaxation velocity and compliance were significantly elevated. These facts suggested an increase in the funcitonal power of the ionic transport system that is responsible for Ca++ elimination from the myofibrils. In general, the results suggest that an elevation of maximal myocardial performance after adaptation to exercises may be due to a coordinative increase in the power of three basic systems of the myocardial cells--ion transport system, myosine ATPase and resynthesis ATP system.


[Bilateral dendritic pseudokeratitis (Richner-Hanhart syndrome)].

A Turkish baby was treated several times for bilateral "recurrent dendritic keratitis" before a diagnosis of Richner-Hanhart syndrome could be made (recessively inherited keratosis palmaris et plantaris with pathognomonic corneal dystrophy). No effective conservative treatment has been reported in the literature for the recurrent eye pain. Highly hydrophilic contact lenses gave prompt and absolute symptomatic relief.


[Kinetics and regulation of granulocytopoiesis (author's transl)].

The present survey of the development of the granulocytes consists of two parts. In the first section the different stages of granulopoiesis are discussed with special regard to the stem cells. In the second one the regulation of the granulopoiesis and the different factors taking part in the homeostasis of the granulocytes are examined. Emphasis is placed upon the colony stimulating activity" (CSA) previously tested in different situations of stress in relationship to the granulopoietic system. In a separate chapter some marked clinical syndromes are discussed which accompany disorders of granulocyte-homeostasis. The pathogenesis of leukaemia is reviewed.


[Transformation of a poststreptococcal type glomerulonephritis into a rapidly progessive glomerulonephritis (author's transl)].

In the morphological course of a poststreptococcal type glomerulonephritis in a 37-year old patient without evidence of streptococcal infection crescents of Bowman's capsule developed after 4 months. The clinical course was rapidly progessive (the patient was uremic 5 months after onset) in contrast to the normal fair prognosis of the poststreptococcal type glomerulonephritis. Two renal biopsies were examined at an interval of 4 months. Both showed closely packed immunecomplex deposits (humps) on the glomerular immunecomplex deposits in the poststreptococcal type glomerulonephritis is a prognostically unfavourable sign.


Measurement of airflow in speech.

It has been shown previously that a mask-type wire screen pneumotachograph can be constructed with a time resolution of 1/2 msec. In this paper it is shown that with careful design a resolution of about 1/4 msec can be achieved. The various factors involved in optimizing such a mask are described. A major practical limitation in the design has been the need for a fast-responding differential pressure transducer to measure mask pressure; however, a simple electrical compensating network is described that allows the use of a nondifferential transducer. Also determined are the conditions under which breath moisture condensing on the wire screen affects the performance of the mask. An example is given of how a high-speed pneumotachograph can be used, with a measure of the pressure across a constriction in the vocal tract, to derive the time variation of the flow conductance and resistance at that constriction. The advantages of a high-speed pneumotachograph in laryngeal frequency extraction are also considered.


Suppression of stimulating cell activity by microtubule-disrupting alkaloids.

Microtubule-disrupting alkaloids and protein fixatives were used to investigate the nature of an active process that must occur within stimulator cells in order for them to initiate a unidirectional mixed lymphocyte response (MLR). Brief treatment of the stimulator cells (SC) with glutaraldehyde (0.15%), formalin (0.6%), or lanthanum chloride (10-3 M) abolished their capacity to activate responder cells (RC). Pretreatment of SC with microtubule-disrupting alkaloids, colchicine (c) (10-4 to 10-6 M) or colchicine + vincristine (c+v) (10-4 to 10-6 M) also abrogated their stimulating capacity. This capacity was not restored by the addition of supernates from untreated cultures, thereby excluding the possibility that the alkaloids acted by decreasing the release of soluble stimulatory factors from SC. The introduction of alkaloid-inactivated, mitomycin-treated RC as drug carriers did not affect the mitogenic response of untreated RC to concanavalin A. This excluded a significant leakage of alkaloids from the treated SC and uptake by RC during culture. Lumicolchicine produced no decrease in the stimulating capacity of SC. This suggested that the suppression induced by low concentrations of colchicine resulted from its specific disruption of microtubules. None of the above treatments quantitatively reduced the antigenicity of SC, as evaluated by humoral and cell-mediated lysis of the treated cells. Also, these treatments produced no significant changes in the specific binding of concanavalin A by SC. These results indicate there is a functional interaction of microtubular structures with cell surface antigens that appears to regulate either the capacity of SC to associate with RC, or the ability of SC to form and stabilize stimulatory antigenic configurations on the cell surface.


Orthoterminal correction of coexisting d-transposition of the great arteries, subpulmonary stenosis, and a complete form of atrioventricular canal.

This report outlines orthoterminal correction in an 8-year-old boy with coexisting d-transposition of the great arteries (d-TGA), subpulmonary stenosis, and a complete form of atrioventricular canal (CAVC). The repair consisted of covering the tricuspid valve and atrial part of the atrioventricular canal with a Dacron patch and inserting a valve-containing conduit between the then isolated right atrium and the pulmonary artery to create a venous outlet. The patient's exercise tolerance has improved remarkably. The arterial oxygen saturation has risen from 86 to 90 per cent. A plea is made to expand the indications for orthoterminal correction to patients in whom the severity of the heart malformation precludes application of well-established methods of surgical repair.


[Computertomography of the parotid gland (author's transl)].

In the first computer-tomographic investigations of the parotis epithelial and mesenchymal tumours histologically ascertained were examined as well as a sialadenitis. For the first time the non invasive computer-tomography allows to demonstrate directly the glandular body morphologically-quantitatively in the macroscopic area and topographically clear in the transverse tomogram. In the face of tumours of the lateral part of the gland, easily to access from the clinical diagnostic point of view, the computer-tomogram can improve pretherapeutically the differential diagnosis to a great extent by additional morphological-quantitative information about the macroscopic possibility to palpate the borders of a tumour, depth of expansion, and tissue structure, the mixed tumour, in particular, seems to have an absorption pattern relatively appropriate to computer-tomography as a result of its different tissue formation, calciferous histopathologic in part, often sealed off macroscopicly. The case observed displays a well-developed annular capsule structure with massive deposits of calciferous substance as a prominent computer-tomographic feature (histological: fibrohyaline capsule). The degree of correlation between the histopathologic and computer-tomographic appearance and its differential diagnostic value is to be checked by further investigation. The hidden tumours of the deep tissue parts, of the processus parapharyngeus, in particular, will be realized earlier by computer-tomography than by conventional diagnostic methods. In order to exclude deficiency symptoms of the nervus facialis a computer-tomography of the parotis is indicated in neurological and otological cases of doubt for a direct demonstration of the deep tissue part with processus parapharyngeus. By means of computer-tomography a growth of parotid tumours affecting other organs can be realized directly in the macroscopic area, and even in good time in the direction of the spatium parapharyngeum. In view of parotid tumour diagnosis orientated topographically and based on the TNM system computer-tomography makes a more exact realization of the T categories possible; therefore, a further subordination of the key of localisation for clinical trials is suggested.


[Determination of the impaired ear's frequency selectivity using psychoacoustical tuning curves (author's transl)].

An apparatus for clinical use is described by which simplified psychoacoustical tuning curves can be measured near 500 Hz and near 4 kHz. Data produced by four groups (normal hearing, conductive hearing loss, noise induced hearing loss and degenerative hearing loss) are separately averaged and compared. The first mentioned two groups as well as the third in the low frequency range show good frequency resolution, the others, however, show largely decreased frequency resolution.


[Recurrent infantile laryngeal papillomas and antuitary insufficiency (author's transl)].

The report at issue discusses the relationship between laryngeal papillomatosis and the endocrine system. It is referred to the clinical course of a 19-years-old patient suffering infantil laryngeal papillomatosis and antuitary insufficiency since childhood. The cause of hormonal insufficiency was the destruction of the hypophysis by a craniopharyngeoma. As a result of this insufficiency the total metabolic process of the patient was reduced to a "vita-minima"-function for years. Despite this metabolic depression the laryngeal papillomas have grown excessively. The number of recurrent papillomas could not even be reduced by exstirpation of the craniopharyngeom although the secundary insufficiency of the adrenal cortex and the secundary hypothyreosis have been compensated by cortisone and thyroxine. A hormonal influence on the laryngeal papillomas by the adrenocorticotrophic hormone and the thyroid hormone could be excluded. An inhibitory effect on the papillomas by the somatotrophic hormone seems unlikely. Furthermore the effect of the sexual hormones remains doubtful. The regression of laryngeal papillomas frequently observed by the end of puberty supports a hormonal influence by gonadotrophic hormone.


[Long-term observation in juvenile papillomas of the larynx after surgical removal and ultra-sound treatment (author's transl)].

The paper cover 17 juveniles suffering from papillomas of the larynx. They were treated mainly surgically and with ultrasound. In most cases repeated interventions were necessary over an extended period of time. Because of the -- frequently considerable -- extension of the papillomas, a double spoon was used to remove larger tissue parts before the ultrasound treatment. In six children a tracheotomy was inevitable, in four of those children it was necessary to preserve it over several years. In the course of the treatment a lengthening of the intervals was generally noted. Related to an observation period of up to 10 years, out of 16 patients 13 were in the end permanently without any relapse, the remaining can be expected to be cured definitely because of the significant improvement of the local evidence. No malignant improvement of the local evidence. No malignant degeneration has been observed so far. All the methods of treatment used to date, including ultrasound and cryoscopic probes, are not entirely satisfactory, at least they do not constitute any causal therapy.


[Electron microscopy of human nasal mucosa in disturbances of the autonomic nervous system. I. Sympathetic denervation (author's transl)].

The fine structure of the human nasal mucosa is described shortly after unilateral stellate gang-lion blockage as well as in a case of sympathetic denervation of four weeks duration. For the clinical picture, corresponding to vasomotor rhinitis, there is a characteristic fine structural correlation consisting of dilatation and increased permeability of the vessels as well as stimulation of the nasal glands. In the glands, both increased activity and degenerative changes suggesting "secretory exhaustion" are observed. The findings differ from those seen in acute and chornic allergic rhinitis, but correspond to those in experimental animals following the administration of parasympathicomimetic drugs.


[Rhinosinusitis polyposa as the only symptom of aspirin intolerance -- a rhinorheomanometric diagnosis (author's transl)].

Chronic rhinosinusitis with nasal polyposis may be a symptom of aspirin-intolerance. If the other symptoms of aspirin intolerance -- above all urticaria and asthma -- are absent, the rhinologist and not the pulmologist or dermatologist has to do the etiological diagnosis. In doubtful cases rhinorheomanometry is to use.


[Eustachian tube function and middle ear pressure with adhesive tympanic membrane (author's transl)].

The function of the Eustachian tube and the corresponding middle ear pressure are significant factors in the etiology of adhesive ear drums as well as in the prognosis of a possible tympanoplasty. In 58 patients with adhesive tympanic membrane tubal function and middle ear pressure were determined by means of the air pressure equalization technique respectively by direct punction. Normal or only slightly impaired tubal function as well as the middle ear pressure was found in one third of the cases, whereas in the majority of the patients an impaired tubal function and underpressure in the middle ear was registrated. As a precondition for a successful tympanoplasty the ventilation of the middle ear must be improved in these cases. At present this is achieved by a polyethylene tube inserted in the tympanic membrane during the operation.


[The treatment of sudden deafness and Menière's disease with papaverin and low molecular weight dextran (author's transl)].

This study is concerned with the mean hearing gain in 50 cases of sudden deafness and 40 cases of Menière's disease treated with different drugs and treated with Papaverin and low molecular weight dextran. The treatment of sudden deafness with Papaverin and low molecular dextran was more effective than different drugs. In cases of Menière's disease the treatment with different drugs was not effective, but Papaverin and low molecular dextran was significantly successful. Finally, it is concluded that treatment according to Spoendlin (1969) with Papaverin and low molecular dextran is superior to different drugs.


[New methods in ear drum photography (author's transl)].

A new optic system, developed in collaboration with Fa. Wolf is introduced. This new optic facilitates diagnostic and demonstration of eardrum findings. The 6.8 mm Lumina-optic has an air channel for avoiding efflorescence of the optic. By adapting the optic system with a camera good, large and easy reproducible pictures were got.


[The Gellé-Test in Practice (author's transl)].

For diagnosis of otosclerosis the Gellé-test is useful although the measurement of impedance is more effective and correct. It's not imperative to pursue the test with the display of the pneumophone, but the simplest method by merely using Politzer-balloon into the external meatus is not acceptable. It ought to be arranged that a connecting tube is placed between the ballon and the closing-piece. The examination occurs with the b.c. receiver placed on the processus mastoideus. Frequency 500 cycles and intensity above the threshold 10-20 dB are recommended. Combining the Gellé-test with white noise produces interesting subjective phenomena.


[The possibilities of Electric Response Audiometry in Medical Legal Assessment (author's transl)?].

A case of nonorganic hearing loss combined with noise-induced hearing loss and the necessity of differentiating them by Electric Response Audiometry in legal assessment is described. A second example deals with monaural functional hearing loss induced by ill-treatment. Finally is reported on a bilateral neurinoma of the acoustical nerve with an extrem auditory fatique and the impossibility to detect evoked potentials.


[Discrimination and critical signal to noise ratio of normal and pathological hearing (author's transl)].

With reference to the cocktail party situation the selective hearing of normal and pathological hearing  was examined during a period of monaural or binaural noise representation. To describe the physiological situation we modified the physical definition of the signal to noise ratio adding the word "critical". Procedure of examination: Hearing level and speech intensity for maximum discrimination of numbers, monosyllables and sentences was evaluated. The speech intensity level defined by these measurements was fixed while the noise level was raised till speech discrimination was reduced to 35-45%. This value is characteristic for the critical signal to noise ratio. A second measurement examined the change of the critical signal to noise ratio by representing the same noise to the contralateral ear. Thus noise is lateralized in the middle of the head and speech discrimination is better in normal hearing compared to the monaural situation. Results of normal and pathological hearing are discussed and dependences between selective hearing and critical signal to noise ratio are shown.


Noxious effects upon cochlear metabolism.

The influence of various toxic substances and of drugs with ototoxic side effects upon energy generation, energy utilization, and membrane processes of the cochlea were studied. None of the drugs tested interfered with energy generation to as great an extent as did anoxia or cyanide and 2,4-dinitrophenol. Ouabain produced a pronounced interference with energy utilization of the stria vascularis. The "loop" diuretics ethacrynic acid and furosemide produced a reduction of energy utilization of a lesser degree than did ouabain. The "loop" diuretics do not seem to exert their toxic action upon strial Na+K+-ATPase, but may act by interfering with strial adenylate cyclase. Aminoglycoside antibiotics and diuretic and nondiuretic mercurials seem to exert their primary noxious action upon cochlear function by interfering with membrane processes of the structures bounding the cochlear duct.


Physiological principles of therapy in head and neck cutaneous wounds.

It is essential that surgeons treating soft tissue wounds about the head and neck have a basic understanding of skin anatomy and physiology. The quality as well as the rate of healing is usually dependent on the type and extent of the original injury. Having a practical working knowledge of the pathophysiology of the various types of head and neck soft tissue injuries allows an intelligent choice of the most appropriate approach to a particular wound. The best functional and cosmetic results routinely are achieved by the wound's undergoing primary healing. Skin tapes and various sutures each exhibit certain benefits and disadvantages in primary closure of wounds. Skin tapes cause less inflammatory reaction but fail to close the subepithelial wound spaces. The inflammatory reaction and subsequent scarring caused by the various sutures depends upon the size of the suture needle, the diameter of the suture material and whether it is a monofilament or a woven suture. The essential nutrition of the wound must be maintained with the body providing adequate amounts of carbohydrates, proteins, trace elements and vitamins. The lack of adequate wound tissue perfusion by a normal or reversed oxygen gradient will lead to tissue necrosis and infection. The size of the inoculum of micro-organisms, the virulence of the organisms and host antimicrobial defense mechanisms determine if an infection will develop. The pharmacological action of each antibiotic must be understood in order to choose the proper antibiotic, its route of administration and to avoid unwanted side effects. Crushing tissue injuries, high velocity projectile tissue injuries and major burns of tissue may require several days to exhibit the true scope of the original injury. Most of these injuries must be treated by the open delayed method of wound treatment until the proper tissue conditions exist for healing. The proper timing and correct choice of autografts and tissue flaps from the surgeon's personal experience, study and conferring with other qualified surgeons. Upon gaining insight into the cellular and humoral antimicrobial defense system, the surgeon is able to provide the best conditions to allow these systems to function properly. Studies in the ultrastructures of skin along with the recently developed microbioassay techniques will allow a closer monitoring during the process of wound healing that will provide the basis for future techniques in the beneficial manipulation of wound healing.


Clearance of chylomicron triacylglycerol and cholesteryl ester from the plasma of streptozotocin-induced diabetic and hypercholesterolemic hypothyroid rats.

Labeled chylomicrons in thoracic duct lymph were collected after test meals containing 14C cholesterol and 2-3H glyceryl trioleate and were given by intravenous injection to groups of control rats, rats made diabetic by treatment with streptozotocin, and rats made hypothyroid and hypercholesterolemic by a diet containing cholesterol, peanut oil, cholic acid, and thiouracil. In the diabetic rats clearances from the plasma of chylomicron triacylglycerol and cholesteryl ester were impaired. A large variability in triacylglycerol clearance in diabetic rats was ascribed to variability in plasma triacylglycerol concentrations. Adipose tissue lipoprotein lipase activity was not impaired in the female diabetic rats used in this study. In the hypothyroid hypercholesterolemic rats chylomicron cholesteryl ester clearance from the plasma was impaired but chylomicron triacylglycerol was cleared efficiently, and adipose tissue lipoprotein lipase activity was similar to or greater than activity in controls. Ten minutes after intravenous injection most plasma radioactivity was recovered in lipoproteins of density less than 1.006 g/ml in all groups of rats, but relatively more was recovered at this density in both treatment groups. We suggest that chylomicron remnants accumulate in the plasma and contribute to the development of hyperlipemia in both treatment groups, but that the remnants formed in the diabetic rat are less depleted of triacylglycerol than the remnants formed in the hypothyroid hypercholesterolemic rat. It is suggested that factors other than measured lipoprotein lipase activities of adipose tissues may be important in determining the initial extent of hydrolysis of chylomicron triacyglycerol. We propose that the hypercholesterolemic hypothyroid rat is a useful model for the experimental production of the remnants of triacylglycerol-rich primary lipoproteins.


Genetic and metabolic regulation of purine base transport in Neurospora crassa.

Neurospora crassa can utilize various purine bases such as xanthine or uric acid and their catabolic products as a nitrogen source. The early purine catabolic enzymes in this organism are regulated by induction and by ammonium repression. Studies were undertaken to investigate purine base transport and its regulation in Neurospora. The results of competition experiments with uric acid and xanthine transport strongly suggest that uric acid and xanthine share a common transport system. It was also shown that the common transport system for uric acid and xanthine is distinct from a second transport system shared by hypoxanthine, adenine and guanine, and apparently also distinct from the transport system(s) for adenosine, cytosine and uracil. Regulation of the uric acid-xanthine transport system and the hypoxanthine-adenine-guanine transport system was studied. The results reveal that the uric acid-xanthine transport system is regulated by ammonium repression, but does not require uric acid induction. Neither ammonium repression nor uric acid induction controls the hypoxanthine-adenine-guanine transport system. A gene, designated amr, which is believed to be a positive regulatory gene for nitrogen metabolism of Neurospora crassa, was found to dramatically affect both the uric acid-xanthine transport system and the hypoxanthine-adenine-guanine transport system. A model for the action of the amr locus as a positive regulatory gene and for the interaction between the amr gene product and its recognition sites will be discussed.


Spectinomycin versus tetracycline for the treatment of gonorrhea.

Spectinomycin and tetracycline are alternative drugs to penicillin in the treatment of gonorrhea. To compare the efficacy of these agents and their propensity to select resistant gonococci, we treated 4043 patients randomly with either 2 or 4 g of spectinomycin once or 9 g of oral tetracycline for four days. Minimum cure rate for anogenital gonorrhea was 94 per cent with either drug. Oropharyngeal infection responded poorly to spectinomycin in men, with failure of therapy in six of 11. Postgonococcal urethritis in men was less common after tetracycline than after spectinomycin (P less than 0.005). Spectinomycin failure was not related to drug resistance. Tetracycline failure correlated with resistance (P less than 0.0002); one fifth of the isolates resistant to 1.0 mug per milliter of tetracycline were not eradicated. For several reasons, including the appearance of beta-lactamase-producing gonococci, it is no longer clear that penicillin G is the "drug of choice" for gonorrhea. Spectinomycin and tetracycline are equally acceptable alternatives, each with distinct advantages and disadvantages.


Renal transplantation between HLA identical siblings. Comparison with transplants from HLA semi-identical related donors.

We compared 26 HLA-A, B identical sibling kidney-transplant recipients followed for one to 10 years, with 104 HLA-A, B semi-identical kidney recipients from living, related donors to determine clinical differences. Graft-survival rates were significantly better in the HLA identical group at two years (85 per cent identical versus 53 per cent in semi-identical, P less than 0.005); patient-survival rates were high for both (96 per cent in identical and 87 per cent in semi-identical at two years, P less than 0.005). The incidence of complications was similar in HLA identical and semi-identical recipients. Nine of the 26 grafts in HLA identical recipients failed one week to eight years after transplantation. Rejection caused most of the graft failures. Recipients of HLA identical-sibling kidney transplants have a high patient and graft survival, but they also encounter many complications. Immunologic rejection occurs, even with negative mixed lymphocyte culture, suggesting the importance of donor determinants other than the HLAA, B and D other than the HLA-A, B and D.