[Urate transport in erythrocytes: possible role of a transport membrane]. Urate transport seems dependant of ATP. So, we studied urate behaviour in relation with the isolated membrane: we observed a linkage between urate and a membrane protein of which molecular weight was estimated to twenty thousand. The exact role of this protein remains to be clarify.


[Ventrobulbular hypotensive action of muscimol]. Muscimol, a rigid analogue of GABA has been injected in the CNS of urethane anesthetized, normotensive cats. Injected either intracisternally (1 or 2 microgram/kg, 0.05 ml) or directly by microinjection in a restricted ventrolateral region of the brain stem (0.5 or 1 microgram/kg, 0.5 microliter), muscimol induced hypotension and bradycardia. These central cardiovascular effects of muscimol were antagonized by bicuculline, a "specific" GABA antagonist agent. These data emphasize the involvement of gabergic mechanisms in the central cardiovascular control, at least in the ventrolateral part of the medulla oblongata.


[Intestinal tolerance in mice after low dose rate 60CO irradiation. Implications for radiotherapy]. Influence of absorbed dose rate has been studied in BALB/c mice for early intestinal tolerance. After selective abdominal irradiation, LD50 at 5.5 days increases from 12.36 to 20.22 and 21.79 Gy when dose rate decreases from 0.61 to 0.054 and 0.026 Gy/mn. LD50 at 6.5 days increases from 12.05 to 19.22 and 21.58 Gy respectively. The LD50 ratios are then 1.6 and 1.8 for both endpoints. After total body irradiation. LD50 at 5.5 days increases from 9.92 to 15.20and 16.83 Gy when dose rate decreases from 0.56 to 0.049 and 0.024 Gy/mn. The corresponding LD50 ratios, i.e. 1.5 and 1.7, are then similar to the former ones. Increase of LD50 when decreasing dose rate is in agreement with that expected taking into account only repair of sublethal lesions, for the generally accepted cellular models.


[RBE/absorbed dose relationship of d(50)-Be neutrons determine for early intestinal tolerance in mice]. RBE/absorbed dose realtionship of d(50)-Be neutrons (ref.: 60Co) was determined using intestinal tolerance in mice (LD50) after single and fractionated irradiation. RBE is 1.8 for a single fraction (about 1000 rad 60Co dose); it increases when decreasing dose and reaches the plateau value of 2.8 for a 60Co dose of about 200 rad. This RBE value is used for the clinical applications with the cyclotron "Cyclone" at Louvain-la-Neuve.


[Organ cultures of mammalian testes. I. Adult mouse testis]. Organ cultures of adult normal mice testes have shown that the tubular structure is best preserved at 31 degrees C. With the simple anhormonal conditions we have used, the germ cells actively involved in meiosis disappear in ten days, following a stereotyped pattern. During the same time, Sertoli cells become enlarged, with a marked cytoplasmic vacuolisation. After 2 weeks in vitro, the seminiferous tubules are completely filled up with Sertoli cells and no more spermatocytes are recognized.


[Centromere staining in ten species of ruminants by C and R banding techniques]. The centromeric regions of acrocentric or telocentric chromosomes of 10 species of the order Artiodactyla, suborder Ruminantia, have shown to be equally deeply stained either with the C-banding or the R-banding technique. These unusual staining properties could be linked with the presence of a particular type of chromatin. The importance of centromeric fusions linked with speciation in the Bovoidea is recalled.


[Peritoneal resorption of ethidium bromide, free or linked to DNA in rodents]. Ethidium bromide, either free (EB) or bound to DNA (EB-DNA), is injected into the peritoneal cavity of adult rats or mice. EB is then detected by fluorescence microscopy in peritoneal cells and by spectrophotometry in the peritoneal fluid. EB-DNA persists for a longer period of time in the peritoneal cavity than free EB does.


[Different types of virus inhibitory factors in interferon produced by different organs]. Fragments of organs from mice inoculated with Newcastle disease virus were incubated at 30 degrees C. Lungs and liver produced thermolabile virus-inhibiting factor (IF) or interferon at earlier stages. The spleen, lymph nodes and thymus produced thermolabile IF at earlier stages and thermostable IF at later stages.


[Hyper- and hypo-reactivity in mice with regard to the induction of virus inhibitory factor or interferon]. 1. IF induction in mice with Newcastle disease virus produced hyperreactivity on subsequent induction with certain doses of poly I:C. 2. Laparotomy or intraperitoneal injection with air caused temporary hyporeactivity of spleen and lungs on IF induction with endotoxin. Laparotomy in splenectomised mice did not affect IF formation in lungs.


Subcellular effects of some anesthetic agents on rat myocardium. The effects of ether, chloroform, and halothane on calcium accumulation and ATPase activity of rat heart microsomes and mitochondria as well as on myofibrillar ATPase activity were investigated. Chloroform and halothane depressed microsomal and mitochondrial calcium uptake and binding in a parallel fashion. Ether decreased microsomal calcium binding and mitochondrial calcium uptake to varying degrees, while mitochondrial calcium binding was slightly enhanced. Whereas ether had no effect, chloroform depressed microsomal and mitochondrial total APTase activities and halothane decreased microsomsl ATPase and slightly stimulated mitochondrial total ATPase activities. Halothane was found to depress myofibrillar Mg2+-ATPase and ether was capable of decreasing myofibrillar Ca2+-ATPase. Chloroform was seen to inhibit both myofibrillar enzymes. These results suggest that the cardiodepressant actions of volatile anesthetic agents may be due to alterations in the calcium accumulating abilities of microsomal and mitochondrial membranes while direct myofibrillar effects may contribute to the depression seen with relatively higher concentrations of anesthetics.


Parathyroid adenomas following irradiation. Parathyroid adenomas have been demonstrated to occur following external head and neck irradiation. The median latency interval is 30 years. In a series of 74 consecutive patients with histologically diagnosed parathyroid adenomas, 25% gave a history of prior radiation exposure. When compared to a matched control incidence of 7.9%, statistical significance is reached at p less than 0.01. Thyroid abnormalities were present in 68% of the irradiated patients, and 30% of these were malignant. Tumor of skin, breast, and parotid gland also occurrred more frequently than expected. Forty-seven percent of the irradiated group had malignant neoplasms within the radiation field. The histopathology of the radiation-associated parathyroid adenomas is similar to that seen experimentally.


Inhibition of spontaneous breast cancer formation in female C3H(Avy/a) mice by long-term treatment with dehydroepiandrosterone. Long-term p.o. treatment with dehydroepiandrosterone, an adrenal steroid found in subnormal plasma concentrations in women predisposed to develop breast cancer, inhibits the formation of spontaneous mammary cancer in female C3H(Avy/a) mice.


Mutation induction by 5-fluorodeoxyuridine in synchronous Chinese hamster cells. Chinese hamster ovary cells synchronized by mitotic detachment were treated with 5-fluorodeoxyuridine (FdUrd), 0.2 micrograms/ml, at various times in the cell cycle. FdUrd treatment in the early S period induced resistance to 6-thioguanine. Treatment of asynchronous cells with FdUrd caused little increase in 6-thioguanine resistance over the spontaneous frequency. Mitotic selection thus enhances the probability of a cell being in the portion of S period receptive to mutation. These observations suggest that FdUrd treatment leads to mutagenesis at the growing points of DNA replication.


Mediated mutagenesis of dimethylnitrosamine in Neurospora crassa by various metabolic activation systems. Four metabolic activation systems (growth mediated mycelium extract mediated, host mediated, and organ homogenate mediated) were used to study the mutagenic activity of dimethylnitrosamine (DMN) in both forward and reverse mutation systems in the ad-3 (adenine-3) region of Neurospora crassa. DMN was not mutagenic in Neurospora if conidia alone were treated. It was highly mutagenic, however, if conidia were treated with this compound under any of the four activation systems. Quantitative differences in DMN-induced mutation frequencies were observed between in vivo (growth and host mediated) and in vitro (mycelium extract and organ homogenate mediated) activations. The efficiency of the conversion of DMN to a mutagenic metabolite by the organs of rats and mice appeared to be in a reversed order between the host-mediated (liver greater than kidney greater than lung) and the in vitro organ homogenate-mediated (lung greater than kidney greater than liver) assays. Inductions of reverse mutations in strain N23 indicated that DMN induces base-pair substitution in N. crassa.


Enhancement by caffeine of neocarzinostatin cytotoxicity in murine leukemia L1210 cells. Posttreatment incubation with nontoxic doses of caffeine resulted in enhancement of cell lethality and inhibition of cell growth in L1210 mouse leukemia cells which had been exposed to a protein antibiotic, neocarzinostatin. In addition, caffeine treatment appeared to inhibit the eventual maturation of newly synthesized DNA in L1210 cells following exposure to this antibiotic. These results, indicating the existence of caffeine-sensitive repair in L1210 leukemia cells treated with neocarzinostatin, provide further evidence for DNA damage as a mechanism of the cytocidal action of the antibiotic.


The role of left ventricular conduction in the electrogenesis of left ventricular hypertrophy. An electrophysiologic study in man. Various electrocardiographic and vectorcardiographic (ECG-VCG) patterns of ventricular conduction disturbances are inducible by premature right atrial stimulation (PRAS). These patterns are a consequence of different degrees of refractoriness in the specialized ventricular conduction system. We observed that the intermediate phase of left bundle branch block (LBBB) induced by PRAS in 20 subjects with normal basal QRS (complexes) were similar to those of left ventricular hypertrophy (LVH). In 18 patients with basal ECG-VCG signs of LVH, right bundle branch block (RBBB) induced by PRAS produced a progressive disappearance of these signs and the "normalization" of the tracings. The initial maximum QRS vector decreased, disappeared or remained absent in the patients with LBBB induced by PRAS, and appeared (when absent in the basal VCG) and remained unchanged (when present) in patients with RBBB induced by PRAS. In this paper we discuss the electrogenetic implications of these data. The ECG-VCG sings of LVH are probably dependent on a slowed conduction in the left bundle branch system, while anatomical hypertrophy per se probably plays a less important role.


Prevalence of arrhythmias during 24-hour electrocardiographic monitoring and exercise testing in patients with obstructive and nonobstructive hypertrophic cardiomyopathy. Many patients with hypertrophic cardiomyopathy die suddenly and unexpectedly, a significant number perhaps due to arrhythmia. Of 100 patients initially evaluated for signs or symptoms suggestive of heart disease or a family history of hypertrophic cardiomyopathy, 51 were selected solely because they met the echocardiographic criteria for the disease, and 49 patients were selected primarily because they had: 1) normal sinus rhythm despite left atrial enlargement, 2) a history of syncope, 3) a family history of premature death, or 4) a history of paroxysmal atrial fibrillation. All 100 patients were studied by 24-hour ambulatory electrocardiographic monitoring and 74 of them also underwent treadmill exercise testing. More than 50% of patients in repetitive ventricular premature depolarizations, including 19% who had ventricular tachycardia. Monitoring was superior to exercise testing for exposing these arrhythmias. Two patients experienced cardiac arrest within 2 months of monitoring; in each, monitoring had revealed ventricular tachycardia. Two patients with paroxysms of supraventricular tachycardia during monitoring developed fixed atrial fibrillation within 1 year. These preliminary observations suggest that monitoring may help identify patients at increased risk for significant arrhythmic events.


Suppression of lymphoproliferative responses to alloantigens by autologous AML cells. Autologous acute myeloid leukaemia (AML), cells caused the suppression of incorporation of 3H-thymidine (3H-Tdr) by remission lymphocytes stimulated with allogeneic cells. In five patients, autologous AML cells suppressed 3H-Tdr uptake by lymphocytes stimulated with up to three different allogeneic cells. Responses to allogeneic AML cells were more strongly suppressed than responses to pooled allogeneic lymphocytes. Suppression was abolished by ultrasonic disintegration of the autologous AML cells, suggesting that a soluble factor was not involved. Suppression was absent from autologous AML cells exposed to ultraviolet light, or when untreated autologous AML cells were present in ratios of less than 1:1 to lymphocytes, or when added 24 or more hours after stimulation of remission lymphocytes with allogeneic cells. It is suggested that suppression is a property of the differentiative level of AML cells, rather than of their malignant properties, although malignant-transformation may bring AML cells into contact with circulating T cells in vivo. Autologous AML cells seem to interfere with the recognition phase of T cell function.


Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus. Peripheral blood mononuclear cells (PBM) obtained from patients with active untreated systemic lupus erythematosus (SLE) were evaluated both for the number of cells spontaneously secreting immunoglobulin (Ig) as well as for their capacity to generate immunoglobulin-secreting cells (ISC) in vitro in response to pokeweed mitogen (PWM). ISC were enumerated by a reverse haemolytic plaque assay designed to quantify the number of cells secreting IgG, IgM and IgA. PBM obtained from eight patients with active untreated SLE contained markedly increased numbers of ISC compared to age-, sex-, and race-matched normal control PBM. SLE PBM contained a mean of 13,805 +/- 3266 ISC per 10(6) cells, of which 74% secreted IgG, 10% IgM and 22% IgA, while normal PBM contained a mean of 779 +/- 143 ISC per 10(6) cells, with 57% secreting IgG, 25% IgM and 33% IgA. PBM obtained from SLE patients were also examined for their ability to generate ISC in vitro in response to PWM. SLE PBM were markedly deficient in their capacity to respond to PWM with the differentiation of ISC. This diminished responsiveness could not be ascribed to serum factors, the presence of increased numbers of cells with suppressive capacity or the absence of potentially responsive B cells. Rather, a deficiency of helper T cell activity appeared to be responsible. This was indicated by the observation that PWM responsiveness could be restored to SLE PBM by co-culturing them with purified mitomycin C-treated normal T cells.


Differences in the constitution and distribution of acidic glycosaminoglycans in the intimal and adventitial layers of bovine aorta. Differences in the constitution of acidic glycosaminoglycans (AGAG) in the intimal layer and in the adventitia of bovine aorta were demonstrated by means of enzymatic assay and electrophoretic characterization after fractionation by ion-exchange chromatography and by gel filtration. The data obtained after ion-exchange chromatography indicated that chondroitin 4-sulfate and chondroitin 6-sulfate were the predominant constituents in the intima, whereas hyaluronic acid, dermatan sulfate, oversulfated dermatan sulfate, and heparan sulfates and a related glucosaminoglycan were the predominant constituents in the adventitia. The molecular weight dependent distribution of the aortic AGAG by gel filtration indicated that hyaluronic acid was prevalent in the high molecular weight fractions from both layers whereas chondroitin, heparan sulfates and the related glucosaminoglycan were present in the low molecular weight fraction, especially in adventitial AGAG. Chondroitin sulfate isomers, dermatan sulfate and oversulfated dermatan sulfate were distributed almost equally in all fractions, but the proportions were different in the two layers.


A comparative study of two isolation procedures for elastin and contaminating substances in fetal and adult rabbit aortas. A quantitative study of the individual steps in the isolation of elastin from mature and fetal aortas of rabbits was carried out. The proportions of insoluble residue and acetone- and ether-soluble substances were determined. The yields of elastin and other associated components of connective tissue derived from the aortas by two different isolation procedures were compared, i.e. the classical Lansing treatment with hot alkali and the less drastic procedure described by Rasmussen et al. Results were found to be strongly influenced by the method used. The purity of the elastin preparations was evaluated by means of amino acid analyses for relative contents of desmosines and dicarboxylic amino acids. The possible reasons for the differences found are discussed.


Dependence of collagen synthesis by embryonic chick tendon cells on the extracellular concentrations of glutamine. An agent in rheumatoid synovial fluid which stimulates collagen synthesis by embryonic chick tendon cells was identified as glutamine. The stimulating effect was observed only at a subnormal concentration of proline (0.02 mM). The concentration of glutamine in rheumatoid synovial fluid is about 2.5 mM but it falls rapidly during storage even at -20 degrees C. Collagen synthesis is shown to depend on the extracellular concentrations of glutamine and proline in addition to any connective tissue activating factors.


Influence of maturation and age on mechanical and biochemical parameters of connective tissue of various organs in the rat. The mechanical and biochemical parameters of connective tissue components of several organs in rats, e.g. skin, tail tendons and aorta, have been compared. Organ samples have been analyzed at various ages allowing investigation of the changes during maturation and senescence. The age dependent changes in the various organs were quite similar. The parameters indicating strength and elasticity, e.g. ultimate load, ultimate strength, ultimate strain, modulus of elasticity and rate of load increase, rose sharply during the maturation process and decreased during senescence. These values correlated with changes in insoluble collagen but not with those in elastin or glycosaminoglycans as shown in earlier experiments. The relevance of mechanical models to explain age-dependent changes as compared to descriptive correlations between mechanical and biochemical data is discussed.


Explant culture of human and rabbit articular chondrocytes. Copious outgrowth of chondrocytes was obtained by explantation from each of three rabbit and one surgically-resected human articular cartilages pretreated briefly with trypsin. In lapine explants, ascorbate (40 micrograms/ml) increased DNA three-fold over control values and resulted in deposition of a chondroid matrix. It doubled radiosulfate incorporation by the outgrowths. Up to 56% of the sulfated glycosaminoglycan synthesized was located in the trypsin-digestible pericellular coat compared with about 15% in previous monolayer cultures. The collagens synthesized were characterized partially. In rabbit cell cultures, the alpha 1:alpha 2 ratio varied from 2.9 to 3.8. In human cultures, an unusual post-alpha 2 peak was observed. The findings suggest an uncoupling of the phenotypic expression of the major cartilaginous macromolecules in the cultures. There were no distinctive differences between chondrocytes derived from normal and fibrillated human cartilage of the same individual.


Generation of Hall voltage in bone.

Generation of Hall voltage in bone. Hall type voltage has been observed in bone and its two major components (collagen and apatite) in the region of moderately high electric and magnetic fields. The configuration of the sample placement and the experimental set up was the same as that adopted in standard Hall measurements. The resistivity of the sample has been related to the Hall Coefficients through the standard relationship and an estimate of Hall mobility was made. The Hall Coefficients were found to be of the order of 10(6) cm3 col-1 while the Hall mobility generally was in the region of less than 1 cm2/volt sec. A comparison with drift mobility suggests that the latter is at least two to three orders of magnitude less than the former. A possible mechanism underlying the said transport phenomena is discussed.


Proteogylcan heterogeneity in embryonic chick articular and epiphyseal cartilages. Proteoglycans from two regions of the chick limb rudiment (articular and epiphyseal) were examined for chemical microheterogeneity. These cartilages are composed of at least two series of proteoglycan variants whose glycosaminoglycan side chains display microheterogeneity with respect to the proportions of 4- and 6-linked ester sulfate. Other differences are noted which are consonant with the hypothesis that extracellular matrix components may be structurally adapted to a tissue's developmental fate or function.


Functional differentiation of various types of cardiomyopathies by echocardiography. Echocardiography was used to compare the left ventricular function in 35 cases of congestive cardiomyopathy (COCM), 16 cases of obstructive and 28 cases of non-obstructive asymmetric septal hypertrophy, 43 cases of scleroderma heart disease, 21 cases of ischaemic cardiomyopathy (ICM), 2 cases of restrictive cardiomyopathy, and one case of cardiac amyloidosis. COCM was characterized by left ventricular dilatation, decreased contractility and signs of elevated end-diastolic pressure. In asymmetric septal hypertrophy there was a decreased distensibility of the obstructed left ventricle, both in early and end-diastole, but the pump function remained normal. In scleroderma and amyloid heart disease both the contractility and distensibility of the small, stiff heart were reduced. In restrictive cardiomyopathy the only abnormality was the impaired end-diastolic distensibility. Reduced contractility confined primarily to the interventricular septum and impaired early diastolic distensibility are the characteristic features distinguishing ischaemic cardiomyopathy from COCM. However, echocardiography is not suitable for individual differentiation of ICM and COCM. The COCM can be differentiated from left ventricular aneurysm by M-mode sector scanning technique.


Kyrle's disease.

Kyrle's disease. A fifty-nine year old man is reported herein with a hyperkeratotic papular eruption that clinically and histologically was compatible with Kyrle's disease (hyperkeratosis follicularis et parafollicularis in cutem penetrans). Treatment with tretinoin (topical vitamine A acid) resulted in a severe inflammatory reactions in the lesions which persisted for four monthes and did not prevent a mild recurrence of the disease. The clinical and histologic differential diagnosis is reviewed perforating folliculitis, reactive perforating collagenosis, and elastosis perforans serpiginosa. The close similarity between Kyrle's disease and perforating folliculitis often makes absolute diagnosis very difficult.


Adverse effects of corticosteroids.

Adverse effects of corticosteroids. The introduction of corticosteroids has constitutded the most revolutionary event in dermatologic therapy in the last twenty-five years. The effectiveness of topical therapy in well diagnosed and obscure dermatoses led to wide applications by specialists and general practitioners, and resulted in the development of more potent topical steroid preparations. Their enthusiastic acceptance, and often indiscriminante use, has been followed by occasional reports of adverse effects. After the introduction of occlusive topical steroid therapy under plastic wrap, more dramatic therapeutic effects were achieved, but the adverse effects also increased. There is presently an abundance of reports elaborating on systemic and local adverse reactions resulting from topically applied or intralesionally injected steroids. This report summarizes the local side effects of these steroids.


Healing of recalcitrant acne by resting the skin. A rest treatment for recalcitrant acne in a patient with acne of ten years' duration is presented herein.


Idiopathic portal hypertension and chronic arsenic poisoning. Report of a case. We report a case of idiopathic portal hypertension which is related to chronic arsenic poisoning. Only 7 cases have been reported previously. The patient presented with bleeding esophageal varices. Splenomegaly and hyperkeratosis of palms and soles were later noted and led to the discovery of chronic arsenic poisoning. The hemodynamic studies revealed a gradient between the splenic pulp pressure and hepatic wedge pressure which is consistent with presinusoidal hypertension. The liver histology revealed only mild portal fibrosis. Arsenic poisoning is one cause of idiopathic protal hypertension.


Laparoscopic diagnosis of peritoneal mesothelioma. Report of a case and review of the diagnostic approach. This is the second report of a malignant peritoneal mesothelioma diagnosed by laparoscopy and guided needle biopsy and the first with photographic documentation of the lesion. The case illustrates the following points: (1) diagnosis of peritoneal mesothelioma should be considered in the evaluation of exudative ascites; (2) the only definitive diagnostic procedure is to obtain tissue for histology; and (3) laparoscopy with biopsies under direct vision is an accurate and safe technique which is underutilized and should be considered as the diagnostic procedure of choice when peritoneal disease is suspected.


[Attempt of a definite statement on dental care for the handicapped]. A survey made in cooperation with various institutions for the handicapped ascertained the dental coverage and care of the handicapped. Participating in the survey were 634 institutions for the handicapped. The study included 98,737 handicapped individuals treated on both an in-patient and an out-patient basis in these institutions. The results of the survey tend to indicate that dental care for the handicapped is in need of improvement.


Impairment of olfactory perception in male rats by treatment with p-chlorophenylalanine and hydrocortisone. p-Chlorophenylalanine treatment eliminated the normal male rat preference for the female preputial gland odor. Oral administration of hydrocortisone had a similar effect on dimethyl sulfite preference, which slowly reappeared after the discontinuance of the treatment. These changes of behavior are discussed in relation to possible serotonin alterations resulting from the treatments.


Adrenarche: a survey of rodents, domestic animals, and primates. The concentrations of the adrenal steroids dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and delta 4-androstenedione (delta 4-A) have been measured by RIA before and after sexual maturation in plasma of rodents, domestic animals, and primates to determine whether these species exhibit and adrenarchal process comparable to man. The average concentrations of DHA and DHAS were less than 60 ng/dl and 5 microgram/dl, respectively, in plasma of sexually mature rodents and domestic animals, and a significant increase in the plasma DHA level after sexual maturation was seen only in the rabbit and dog. The concentrations of DHA, DHAS, and delta 4-A in 21 rhesus monekeys from 0-3 yr of age were 2021 +/- 235 ng/dl (mean +/- SE), 357 +/- 60 microgram/dl, and 107 +/- 9 ng/dl, respectively, and did not increase during sexual maturation. By contrast, DHA, DHAS, and delta 4-A levels in plasma of chimpanzees were 5.9-fold, 3.3-fold, and 4.8-fold greater, respectively, in 7- to 22-compared to 0- to 3-yr-old animals. Temporally, the increase in DHA levels in the chimpanzee is apparent at 5 yr and this precedes the increase in gonadal steroids, as is characteristic of human adrenarche. It is apparent that adrenal androgen levels and their developmental patterns differ markedly among species, and that among the species examined, only the chimpanzee exhibits an adrenarche comparable to that of man.


Formation of steroids by the pregnant mare. VI. Metabolism of [14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone injected into the fetus. A mixture of [4,8,12-14C]farnesyl pyrophosphate and [3H]dehydroepiandrosterone was injected into a horse fetus im during laparotomy, after which maternal urine was collected for 6 days. Steroid conjugates in the urine were extracted with Amberlite XAD-2 resin, hydrolyzed, and separated into phenolic and neutral fractions. Estrone, 17 alpha-estradiol, equilin [3-hydroxy-1,3,5(10),7-estratetraen-17-one], and 17 alpha-dihydroequilin [1,3,4(10),7-estratetraene-3,17 alpha-diol] were isolated from the phenolic fraction and their radiochemical purities were established. Only estrone and 17 alpha-estradiol contained both 3H and 14C, while the B ring unsaturated estrogens, equilin and 17 alpha-dihydroequilin, contained only 14C. From the neutral fraction, 14C-labeled 3 beta-hydroxy-5 alpha-pregnan-20-one, 5 alpha-pregnane-3 beta-20 beta-diol, and 5 alpha-pregnane-3 beta, 20 alpha-diol were isolated. These results together with our previous findings demonstrate that the route of biosynthesis of both the ring B saturated and unsaturated estrogens is the same up to the stage of farnesyl pyrophosphate. Thus, the bifurcation in the classical pathway of steroid biosynthesis is occurring at a point after the formation of farnesyl pyrophosphate and before the formation of squalene and cholesterol.


Systolic time intervals and echocardiographic findings in borderline hypertension. Systolic time intervals, echocardiographic dimensions and hemodynamic parameters were determined in 42 borderline hypertensive patients with high cardiac output and 33 normal subjects. In borderline hypertensive patients, the preejection period was significantly reduced (P less than 0.001) and was negatively correlated to cardiac index (P less than 0.001). The interventricular septum thickness (IVS) was significantly increased (P less than 0.001) while the posterior wall thickness (PW) was within normal values. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). These findings suggest that (i) myocardial hypertrophy and increased left ventricular performance exist in borderline hypertension, (ii) myocardial contractility is reduced as myocardial hypertrophy increases.


[Rearing of germfree rabbits and establishment of an SPF rabbit colony]. Baby rabbits hysterectomy-derived from conventional Japanese white rabbits were reared under aseptic condition by feeding with 4 types of artificial diets. Rabbit milk for the artificial diet was obtained from conventional dams at 7--25 days after delivery. The artificial diets was given by stomach tube twice a day. The total volumes of diet given (ml per day) were Y = 2.3X + a (1 to approximately 14 days of age), Y = 32.2 + a (l5 to approximately 25 days of age), or Y = (32.2 + a) - 37.5 (X - 25) (26 to approximately 34 days of age), (X = age in days, a = volumes fed at 0 day of age). After 14 days of age young animals were also fed freely sterilized commercial pellets and weaned at 35 days of age. Out of 155 rabbits, 130 were aseptically reared till 36 approximately 40 days of age, and no difference on weaning rate was seen between the 4 groups of rabbits. Thereafter, they were exposed to a barriered room of SPF rabbitry outside the isolators. The best growth was seen in animals given by artificial diet containing rabbit milk at 40%. The SPF breeding colony of rabbits was found to be free of Pasteurella pneumotropica, Bordetella bronchiseptica, Salmonella spp., Eimeria spp., Encephalitozoon cuniculi and Acaritic otistis.


[Rearing of germfree guinea pigs and establishment of an SPF guinea pig colony]. New born guinea pigs of Hartley strain derived by hysterectomy were fed commercial pellets, cow's milk, egg yolk and vitamin mixture since 0 days of age, when they were kept at 31 +/- 1 degrees C. Out of 33 animals, 30 were reared for 40 days under aseptic state and they were transfered to a barrierred facility to establish an SPF colony free from Bordetella bronchiseptica, Streptococcus zooepidemicus (Animal C), Salmonella spp., Tyzzer's organisms, Mycoplasma spp., Reo 3 virus, Sendai virus, Eimeria spp., Chirodiscoides caviae and Gliriocola porcelli.


Reduced T cell reactivity in vasectomized rhesus monkeys: association with histocompatibility type. The capacity of peripheral lymphocytes from rhesus monkeys which had been vasectomized for 7 or 11 years to stimulate and respond to normal rhesus lymphocytes in mixed lymphocyte cultures (MLC) was tested to determine whether vasectomy affects immunologic reactivity. The ability to respond in MLC, a T cell function, was significantly reduced in the 11-year vasectomized animals and in two 7-year vasectomized animals. The ability to stimulate in MLC, a B cell function, was significantly increased in the 11-year vasectomized group. MLC reactivity of normal lymphocytes cultured in plasma from vasectomized animals and lymphocytes from vasectomized animals cultured in normal plasma was not altered, ruling out serum effects in the reduction of MLC responsiveness in these vasectomized animals. Seventy-five per cent of the vasectomized animals with markedly reduced MLC reactivity had the RhL-A determinates 19 and 24, indicating an association between the tendency toward reduced MLC reactivity after vasectomy and histocompatibility type.


Is palmoplantar keratoderma of Greither's type a separate nosologic entity? 17 patients with palmoplantar keratoderma (PPK) were detected among 48 investigated members of the clan O. 5 of these 17 patients had a well-expressed hyperkeratosis on their knees. In one family hyperkeratosis of the knees was inherited as a dominant feature, but in two other families it was not. The observation was made that the expressivity of the disease was fading: while there were 15 PPK patients among the 25 investigated members in the generations II and III, there were only 2 patients among 22 members in the generations IV and V. In addition to PPK incontinentia pigmenti was diagnosed in two instances and pollex duplex in one. The question of the identity of PPK of Greither's type is shortly discussed.


Antibiotic sensitivity of gonococcal strains isolated from patients in Basel and environs. During the first 4 months of 1977, 95 different strains of gonococcus were isolated in the out-patient department of the Dermatology Clinic of the University of Basel. These were systemically tested for sensitivity to penicillin G, spectinomycin, thiamphenicol, doxycycline and rifampicin. The MIC values and the diameter of the zones of inhibition were determined. Tests for beta-lactamase production were made. A correlation in the degree of sensitivity was observed between the following antibiotics: penicillin G/rifampicin; penicillin G/thiamphenicol; penicillin G/doxycycline; thiamphenicol/doxycycline; thiamphenicol/rifampicin; doxycycline/rifampicin. The size of the inoculum had little influence on the activity of the substances, except for that of penicillin G against the beta-lactamase-positive reference strains. No beta-lactamase-producing strains were detected amongst the clinical isolates. In the case of penicillin G, there was a correlation between the minimum inhibitory concentration and the inhibition-zone diameter.


Comedo formation following cobalt irradiation. After cobalt-60 therapy 3 patients developed open and closed comedones in the face corresponding to the treatment fields. Biopsies showed extensive dermal elastotic material. It is suggested that the elastotic fibres may contribute to a change in the supporting function of the dermis and a secondary sebum retention and comedo formation.


Laparoscopic finding of the gallbladder in a case of intramural gallstones. In this 42-year-old-man with suspected cholelithiasis the following finding of the serosal surface of the gallbladder was discovered by laparoscopic examination: Smooth serosal elevation, dark-greenish in color in a size of the small bean; No hypervascularity in the surrounding serosa. This finding was confirmed to be due to intramural gallstones. This is the first description of the laparoscopic finding of the intramural stones of the gallbladder, which may assist in establishing the clinical characteristics of the intramural gallstones.


Fibrinolytic activity in gastric venous blood. A comparison between normal and diseased stomachs. The fibrinolytic activity of blood draining from the stomachs of patients with gastroduodenal disease has been compared with the fibrinolytic activity of blood in the systemic venous circulation and with the blood draining from normal stomachs. Gastric venous blood from normal and diseased stomachs contains greater amounts of plasminogen activator than simultaneously sampled systemic venous blood. However, gastric venous fibrinolytic activity does not differ between the normal and diseased stomachs and thus indicates that increased gastric venous fibrinolysis is not just a characteristic of the diseased stomach. The studies suggest that stress may cause activation of the fibrinolytic system in gastric venous blood with the release of small amounts of free plasmin. It is postulated that local fibrinolysis may play a part in potentiating gastric hemorrhage.


Origin of the extra chromosome in trisomy 21. Of 61 families of children with trisomy 21, polymorphism of chromosome 21 elucidating the origin of the extra chromosome was found in 42. Nondisjunction was of paternal origin in 8 cases (19.04%) and the anomaly occurred with equal frequency during the first and second meiotic divisions. Maternal nondisjunction was demonstrated in 34 cases (80.95%), in which nondisjunction occurred by far the most often during the first meiotic division (29 cases). These results are in agreement with data from the literature, and suggest the existence of at least two different causes for chromosomal nondisjunction, the first being the same in both sexes and occurring in both meiotic divisions and the second specifically limited to the first meiotic division in the mother.


[Physical education for spina bifida children in special schools for the physically handicapped (primary school)]. With a rate of 0.5-1/1,000 of the total number of births in West Germany, spina bifida is next to cerebral paresis one of the most frequent congenital defects. Altogether, fifty places in special schools are needed per one million of inhabitants for spina bifida children. The loss of physical unctions is comparable to that in the case of paraplegia. The variety of medical and psychological problems makes the cooperation of highly different branches of study indispensible in a rehabilitation team (neurosurgeon, neuropediatrician, urologist, orthopaedist, pediatrician, educator, social worker, physical therapist). Each team member must be informed about the complete rehabilitation plan. These children's shortage of environmental experience is mainly due to their backwardness as regards motoric development, which cannot be recovered by means of individual physical therapy alone. On the other hand, additional, specifically selected and organised physical education makes possible the necessary mobility and social experiences. By giving the children exercises suitable for their ages it is hoped to achieve a late maturation and stabilization of the personality. In choosing the exercises it is first of all necessary to go back to the so-called fundamental activities like climbing, hanging by one's hands, sliding, pushing oneself up off the ground, swinging or throwing and catching, before going on to wheel-chair sports. Wheel-chair sport promises a varied selection for group exercises (games) and for everyday use. Using the wheel-chair as sports equipment, it is possible for persons with other types of locomotive handicaps to be integrated into the group. For physical education in special schools the pupils whould be arranged into groups according to their ability in order to keep the groups as homogenous and the children's chances as equal as possible. The most important teaching criteria are in this case: the creation of a happy atmosphere, a high degree of clarity, the fulfilment of individual inclinations, the encouragement of independence, the development of community life and the fulfilment of everyday tasks. In swimming, the spina bifida child differs from the normal child in his greater initial fear and in the existence of contractions, a scoliosis, hyperlordosis or -kyphosis due to the resultant instability of the water. Because of this, specifically oriented swim- and work-aids must be used. The didactic procedure is then the same as in the case of normal children. After the child's familiarity with and safety in the water is assured, one can proceed to individual swimming techniques and in a few cases to sport swimming. Bacteriological examination of the water did not yield any results which could cause objection on the grounds of hygiene.


Impact of chronic illness on child and family: an overview based on five surveys with implications for management. For the past eight years the Rochester Child Health Group has systematically investigated chronic illness in childhood with the goal of minimizing the psychosocial sequelae of chronic illness through more optimal management. This overview examines the impact of chronic illness on 404 children and their families in five separate studies: 1) 209 children in a follow-up of all children with chronic symptoms in a previous random sampling of children; 2) 42 children with juvenile arthritis; 3) 44 nephrotic children; 4) 54 asthmatic children; 5) 55 chronically ill children living in rural areas of Western New York. Information was obtained through parental interviews, school reports, and psychological testing of the child. The percentage of parents reporting impact of the child's illness on family differed according to study population. The percentage reporting areas of impact according to severity of the illness is as follows: worry, 75--97; financial, 46--60; fatigue of parent, 31--65; change in sleep arrangements, 17--31; change in furnishings, 15--40; less social life for parents, 12--35; restrictions on travel, 13--40; parental friction, 9--20; sibling neglect, 10--20; sibling resentment, 10--25; embarrassment, 12--20; interference from relatives, 5--17. Over half the parents felt their child's future education, job chances, and social life would be affected. One third reported activity limitations. Compared to a control group of children, a significantly greater percentage of parents of the chronically ill reported teacher concern about their child's effort and behavior, and showed concern about the child having too few friends. Two of the three studies in which psychological appraisals were obtained suggested that more of the ill children than controls showed indices of maladjustment. School information from two studies showed more of the ill children than controls underachieving and being referred to a school psychologist. Work by the Rochester Child Health Group has pointed up several ways in which providers of care can more optimally assist families in order to minimize these problems: 1) identifying families at risk at the onset to find which families may require special support; 2) Assuring that family and all care providers know who is orchestrating care, and that all areas of care are being provided; 3) Assuring that where necessary, an outreach person is meeting the needs of the family and child on an intensive, sustained, caring and creative basis.


The influence of calcium on lens ATPase activity. The activities of ouabain-sensitive (Na-5-) and ouabain-insensitive ATPases were determined in 3.6 mM calcium-containing and calcium-free media. Three lens tissue segments were studied: the epithelium/capsule segment, the anterior cortical segment and the posterior cortical segment. In the presence of calcium, the Na-K-ATPase activity in each segment was reduced, whereas the ouabain-insensitive ATPase activity in each segment was increased.


Chalones and stroma as possible growth-limiting factors in the rat ventral prostate. In an attempt to determine the mechanism that limits the growth of the rat ventral prostate, atrophied ventral prostates from orchiectomized inbred rats were implanted into the ventral prostate of other inbred rats. Under the influence of endogenous or exogenous androgen the DNA content of the ventral prostates was increased above normal. This indicates that there is no soluble growth inhibitor diffused in the normal prostate in a concentration sufficient to block cell divisions of the epithelial cells. In other experiments pieces of plastic sponge were implanted into the rat ventral prostate. Orchiectomy and subsequent androgen treatment led to an increased cell number in the prostate. Histologic examination revealed an ingrowth of loose connective tissue and also of normal-looking prostatic tissue in the sponge. The results suggest that implantation of pieces of sponge induced increased growth of the fibromuscular stroma and a secondary proliferation of the epithelial cells. A growth control of the prostatic epithelial cells by the fibromuscular stroma is suggested.


[Comparative study of the effect of Adona on the plasma volume]. The perfusion of a physiological sodium chloride (Ringer) solution, with the addition of 200 mg/l of Adona, yields a volumetrical effect which lasts for 4 h. After 4 h, the plasma volume shows an average increase of +13%. Perfusions of a physiological NaCl-solution by itself, or of a gelatine solution do not display any volumetrical effect 4 h after the beginning of the perfusion. In the majority of surgical interventions, the surgeon may replace the solution of gelatine and of Dextran which are expansive to store and not devoid of side effects, by a physiological sodium chloride (Ringer) solution to which have been added 2 ampouls of 100 mg/l each (20 ml/l) of Adona.


Benign hereditary (dominant) chorea of early onset. Two siblings (one girl 7 1/2 and one boy 6 1/2) are described with a choreic syndrome dating from early childhood without other neurological abnormalities. The father was similarly affected but has markedly improved. Extensive neurological work-up and family history permitted to rule out numerous conditions known to cause abnormal movements in childhood. The clinical entity corresponds to the recently described syndrome of hereditary benign non progressive chorea. To our knowledge it is the first described family with this entity in Switzerland. The relevant literature is reviewed particularly as it pertains to the genetic unity of the syndrome. Its importance lies in its differentiation from the other more severe hereditary abnormal movements of childhood, its non progression and tendency to improve with time. The possible reasons for the only very recent recognition of this purely clinical syndrome are also discussed.


Intraocular lens fixation with dacron.

Intraocular lens fixation with dacron. To overcome the problem of postoperative lens dislocation, we evaluated a new means of lens fixation. Our experimental studies in rabbits and primates demonstrated that Dacron polyethylene terephtalate induced a cellular reaction from either the anterior or posterior iris surface when placed in contact with the iris, thereby establishing a bond between the Dacron fibers and the iris. Dacron mesh can be attached to the distal portion of either the anterior or posterior loops of a Binkhorst iris clip (4-loop) lens. In the rabbit eye, lens fixation occurred within five days; in the primate eye, 30 days. When combined with silk, Dacron produced tissue ingrowth in the primate eye within 14 days. No unwanted reaction occurred in any animal with the Dacron and silk combination. Being biodegradable, the silk induced faster cellular ingrowth than the Dacron. However, Dacron, which is not biodegradable, provided a permanent means of fixation.


Depolymerization of brain microtubules by skeletal muscle myosin. Brain microtubules are found to disperse rods of skeletal muscle myosin and become decorated with amorphous aggregates of myosin. Then microtubules are partially depolymerized by myosin. Myosin shows high Mg2+-GTPase activity which is not influenced by microtubules, and induces the partial depolymerization of microtubules by exhaustion of GTP in the solution. H-meromyosin depolymerizes microtubules like myosin does. H-meromyosin is, however, contaminated with a trace amount of trypsin, which irreversibly depolymerizes microtubules.


Effects of various concentrations of MgATP on the superprecipitation and ATPase activity of scallop striated muscle myosin B1. 1. The superprecipitation and ATPase activity of scallop striated muscle myosin B showed essentially the same biphasic pattern as that of vertebrate skeletal muscle myosin B in its responses to changes in the MgATP concentration. Ca2+ had no effect at MgATP concentrations less than 10(-5) M. 2. The superprecipitation of gizzard myosin B showed a weak biphasic pattern, but its ATPase activity showed no sign of a biphasic pattern up to 3 x10(-3) M MgATP, in accord with the result of Bremel (1974). 3. Thus scallop striated muscle is classified into the same group as vertebrate skeletal muscle as far as its response to changes in MgATP concentration is concerned. Gizzard is distinct from the other two kinds of muscle.


'Freezing' of the calcium-regulated structures of gizzard thin filaments by glutaraldehyde. Reconstituted thin filaments (the actin-tropomyosin-leiotonin complex) of chicken gizzard were cross-linked with glutaraldehyde either in the presence or absence of Ca2+. The ability of resultant thin filaments to activate myosin ATPase was 'frozen' in the activated or inactivated state, respectively. This result clearly indicates the existence of actin-linked regulation in smooth muscle.


The mechanism of the irreversible inhibition ofrat liver phenylalanine hydroxylase due to treatment with p-chlorophenylalanine. The lack of effect on turnover of phenylalanine hydroxylase. The administration of a single dose of p-chlorophenylalanine (360 mg/kg) to rats leads to the irreversible loss of 90% of hepatic phenylalanine hydroxylase activity after 24 h. This loss of activity is not the result of either an alteration in the overall structure of the enzyme, as determined by its antigenicity, or in the total immunologically reactive protein in the liver, as tested with a specific antiserum prepared against native phenylalanine hydroxylase. Neither the rate of synthesis nor the rate of degradation of phenylalanine hydroxylase is changed by p-chlorophenylalanine (pClPhe) treatment. The half-life for the enzyme is about 2 days in control and in pClPhe-treated rats. In addition, there is no detectable incorporation of pClPhe into the phenylalanine hydroxylase molecule itself.


Purification and reconstitution of the N,N'-dicyclohexylcarbodiimide-sensitive ATPase complex from spinach chloroplasts. The dicyclohexylcarbodiimide-sensitive ATPase from spinach chloroplast has been isolated. On sodium dodecyl sulfate gels, seven different polypeptides were seen. Five of these polypeptides coincided with the CF1 subunits, a 7,500-dalton peptide was identified as the proteolipid which interacts with [14C]dicyclohexylcarbodiimide, and there was a 15,500-dalton hydrophobic polypeptide with unknown function. In two-dimentional gels, two additional peptides were resolved, one 17,500 daltons (co-migrating in sodium dodecyl sulfate gels with subunit delta) and one 13,500 daltons (co-migrating with subunit epsilon). Reconstitution was obtained by freezing and thawing the complex with a crude mixture of phospholipids. After reconstitution the complex catalyzed 32P1-ATP exchange (rates of 200 to 400 nmoles x mg-1 x min-1) and ATP formation during acid-to-base transition. These reactions were inhibited by dicyclohexylcarbodiimide and uncouplers. Uncouplers at low concentrations stimulated and at high concentrations inhibited the Mg2+-ATPase activity. ATP hydrolysis and 32P1-ATP exchange were catalyzed by the complex in the presence of either Mg2+ or Mn2+ but not with Ca2+ or Co2+. ATP and GTP were substrates for the exchange reaction but not ADP or CTP.


The action of trypsin on the gastric (H+ + K+)-ATPase. The effect of trypsin on gastric (H+ + K+)-ATPase and K+-phosphatase was studied. Loss of both enzymic activities was biphasic, consisting of a fast and slow phase. Several peptides were produced from the original 105,000-dalton region of the sodium dodecyl sulfate electrophoretic separation, but only two, 87,000 and 47,000 daltons, were labeled following incubation with [gamma-33P]ATP. After a 30-min hydrolysis, 35% of the original peptide remained unaltered and appeared to be a glycoprotein. ATP and ADP abolished the second phase of tryptic inactivation of both activities and only two peptides, of 78,000 and 30,000 daltons, were found on the acrylamide gel in addition to the original 105,000-dalton region, neither of which was labeled by [gamma-33P]ATP. The protection was specific for these nucleotides, AMP, beta, gamma-methylene ATP, TTP, and pNPP being ineffective. Na+ and K+ at high concentrations reduced the rate of loss of activity but no change in the peptides produced was found. The level of phosphoenzyme was increased 2-fold by trypsin treatment, whereas the quantity of K+-sensitive phosphoenzyme remained relatively constant. Thus, the 105,000-dalton region is heterogeneous, consisting of a catalytic subunit (the active site is on a 47,000-dalton fragment), a glycoprotein, and another 105,000-dalton peptide. The action of trypsin is initially to prevent interconversion of a K+-insensitive to a K+-sensitive form of the phosphoenzyme, thus inhibiting hydrolysis.


The use of arylazido-beta-alanyl-ATP as a photoaffinity label for the isolated and membrane-bound mitochondrial ATPase complex. The effects of a photoaffinity derivate of ATP, arylazido-beta-alanyl-ATP, 3'-O-(3-[N-(4-azido-2-nitrophenyl)amino]propionyl) adenosine 5'-triphosphate, on submitochondrial particles and the partially purified ATPase complex of beef heart mitochondria have been investigated. In the absence of light the ATP analogue has been found to be a substrate for the E132PA1P1-ATP exchange reaction of submitochondrial particles. When photoirradiated in the presence of arylazido-beta-alanyl-ATP, the ATPase activity and the the the [32P]Pi-ATP exchange reaction are inhibited maximally 80%. Arylazido-beta-alanyl-ATP following photolysis is a noncompetitive inhibitor with respect to ATP while arylazido-beta-alanine, the azido-containing adjunct of the ATP analogue, has no inhibitory effect under the same conditions. The inactivating effect of arylazido-beta-alanyl-ATP is prevented in part by the presence of ATP, or ADP and pyrophosphate. Photolabeling produces a covalent binding of the derivative with the F1ATPase being the major protein labeled. The binding of 0.22 mumol of arylazido-beta-alanyl-ATP/mg of mitochondrial protein is associated with a maximal inhibitory effect. The ATPase activity of the partially purified ATPase complex is also sensitive to photoirradiation in the presence of arylazido-beta-alanyl-ATP. When the ATPase complex is associated with liposomes there is an increase in the specific ATPase activity with a 10-fold increase in Vmax and a 4-fold decrease in KmATP associated with a parallel increase in the apparent affinity and maximal inhibitory effect of the arylazido-beta-alanyl-ATP. The photoinhibition of the ATPase complex in the presence of arylazido-beta-alanyl-ATP results in covalent binding of 1.6 mumol of arylazido-beta-alanyl-ATP/mg of protein. The alpha and beta subunits are the only components of the ATPase complex labeled by the [3H]arylazido-beta-alanyl-ATP. The relationship between the arylazido-beta-alanyl-ATP-labeled sites and the nucleotide binding sites on the mitochondrial ATPase is discussed.


Thyroid hormone stimulates synthesis of a cardiac myosin isozyme. Comparison of the two-two-dimensional electrophoretic patterns of the cyanogen bromide peptides of cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits. The CNBr peptides of [14C]carboxymethylated cardiac myosin heavy chains from euthyroid and thyrotoxic rabbits have been compared using a two-dimensional electrophoretic system. The results indicated that there were extensive differences in the peptide "maps" of these heavy chains, which included differences in the distribution of radiolabeled thiol peptides. Also, the patterns of heavy chain peptides from the cardiac myosins have been compared with those produced by the heavy chain myosin isozymes from skeletal muscles. Peptide maps of heavy chains from red skeletal muscle myosin closely resembled the pattern of peptides found with cardiac myosin heavy chains from euthyroid rabbits. However, peptide maps of heavy chains from white skeletal muscle myosin were dissimilar to those of the cardiac myosin isozymes. We conclude that thyroxine administration stimulates the synthesis of a cardiac myosin isozyme with a heavy chain primary structure which is different from either of the skeletal muscle myosin isozymes.


The mechanism of the skeletal muscle myosin ATPase. I. Identity of the myosin active sites. In the present study, the question of whether the two myosin active sites are identical with respect to ATP binding and hydrolysis was reinvestigated. The stoichiometry of ATP binding to myosin, heavy meromyosin, and subfragment-1 was determined by measuring the fluorescence enhancement caused by the binding of MgATP. The amount of irreversible ATP binding and the magnitude of the initial ATP hydrolysis (initial Pi burst) was determined by measuring [gamma-32P]ATP hydrolysis with and without a cold ATP chase in a three-syringe quenched flow apparatus. The results show that, under a wide variety of experimental conditions: 1) the stoichiometry of ATP binding ranges from 0.8 to 1 mol of ATP/myosin active site for myosin, heavy meromyosin, and subfragment-1, 2) 80 to 100% of this ATP binding is irreversible, 3) 70 to 90% of the irreversibly bound ATP is hydrolyzed in the initial Pi burst, 4) the first order rate constant for the rate-limiting step in ATP hydrolysis by heavy meromyosin is equal to the steady state heavy meromyosin ATPase rate only if the latter is calculated on the basis of two active sites per heavy meromyosin molecule. It is concluded that the two active sites of myosin are identical with respect to ATP binding and hydrolysis.


The mechanism of the skeletal muscle myosin ATPase. II. Relationship between the fluorescence enhancement induced by ATP and the initial Pi burst. A major question about the mechanism of the myosin ATPase is how much of the fluorescence change which accompanies the binding of ATP to myosin is due to the conformational change induced by ATP and how much is due to the subsequent hydrolysis of ATP in the initial Pi burst. Several laboratories have suggested that the maximal rate of the fluorescence change represents the rate of the irreversible conformational change induced by ATP. In the present study, the rate of irreversible ATP binding, the rate of the initial Pi burst, and the rate of the fluorescence enhancement were compared under varied conditions. The results show that: 1) the fluorescence enhancement is mainly due to the hydrolysis of ATP in the initial Pi burst rather than to the conformational change induced by the binding of ATP; 2) the rate of the initial Pi burst is considerably slower than the rate of irreversible ATP binding at high ATP concentration; 3) the rate of the initial Pi burst is almost the same as the rate of the fluorescence enhancement. Therefore, the maximum rate of the fluorescence enhancement represents the rate of the initial Pi burst rather than the rate of the conformational change induced by ATP binding.


Characterization of the plasma membrane Mg2+-ATPase from the yeast, Saccharomyces cerevisiae. The plasma membrane of Saccharomyces cerevisiae has a Mg2+-dependent ATPase which is distinct from the mitochondrial Mg2+-ATPase and at the pH optimum of 5.5 has a Km for ATP of 1.7 mM and a Vmax of 0.42 mumol of ATP hydrolyzed/mg/min. At least three protein components of the crude membrane (Mr = 210,000, 160,000 and 115,000) are labeled with [gamma"32P]ATP at pH 5.5. These phosphoproteins form rapidly in the presence of Mg2+, rapidly turn over the bound phosphate when unlabeled ATP is added, and dephosphorylate after incubation in the presence of hydroxylamine. Vanadate, an inhibitor of the Mg2+-ATPase activity, blocks the phosphorylation of the 210,000- and 115,000-dalton proteins. At pH 7.0, only the 210,000- and 160,000-dalton proteins are phosphorylated. While these three phosphorylated intermediates have not been unambiguously identified as components of the Mg2+-ATPase, the finding of such phosphorylated components in association with that activity implies that this enzyme differs in mechanism from the mitochondrial proton pump and that it is similar in mechanism to the metal ion pumps ((Na+-K+)-ATPase and Ca2+-ATPase) of the mammalian plasma membrane.


A protein inhibitor of the mitochondrial adenosine triphosphatase complex of rat liver. Purification and characterization. A heat-stable protein has been purified from rat liver mitochondria which inhibits the ATP hydrolytic activity of both the soluble and membrane-bound mitochondrial F1-ATPase. The overall purification is about 2400-fold with the major purification step consisting of Sephadex "affinity" chromatography. The purified rat liver inhibitor is homogeneous as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 12,300. Amino acid analysis reveals a high content of glutamic acid, lysine, and arginine and the absence of cysteine, proline and methionine. Whether tested with the rat liver or bovine heart ATPase, the liver inhibitor is equally as potent and specific as the heart inhibitor preparation of Pullman and Monroy (Pullman, M.E., and Monroy, G.C. (1963) J. Biol. Chem. 238, 3762-3769). Although the results presented show that the rat liver ATPase inhibitor resembles closely the ATPase inhibitors from other tissues with respect to specific activity and reaction specificity, it is important to note that the rat liver inhibitor is almost 2000 daltons larger than the bovine heart inhibitor, about 5000 daltons larger than ATPase inhibitors of yeast, and contains significantly more lysine residues than both the bovine heart and yeast inhibitors.


Arterio-venous shunt with percutaneous leads in calves for long-term in vivo testing of blood-contact materials. In six calves an extracorporeal arteriovenous shunt in combination with a successful type of percutaneous lead has been implanted. Flow chambers with various test materials can be inserted. Preliminary results show that this shunt can be used for long term tests for evaluation of blood contact material and studies about thrombus formation in an ex vivo setting as well as for permanent blood access for the purpose of various measurements, drug application and for hemodialysis.


[Unusual procedures in the cure of aneurisms of the subrenal aorta (author's transl)]. From 1959 to 1977, out of 419 aneurisms of the subrenal aorta operated on, 84 were by unusual procedures: --25 restoratory endo-aneurismorraphies with thrombo-endarterectomy were carried out for small aneurisms in young subjects; --4 were enveloped in dacron (in particular for a risk of distal acute post-operative thrombosis); --in 55 cases, these were high risk surgical subjects where conventional treatment by removal of the aneurism and graft appeared to have a bad prognosis: 43 were treated by axillo-femoral by pass with ligature of the aorta just above the aneurism either for acute arterial obstruction with sensory and motor ischemia, or for embolism or for subjacent obstruction; 12 large advanced aneurisms with fissures of tears were treated by axillo-bifemoral by pass and exclusion. Depending on the results obtained, are deduced the operative indications for these procedures.


[Treatment of post-operative ventral hernia: elementary biomechanical basis. Report of 51 cases treated by mersilene mesh (author's transl)]. Elementary functional anatomy of the normal abdominal wall and following incisional hernia are described. The treatment of postoperative hernia should be based on this: its object is to restore the morphology and functions of the abdominal wall, in particular its respiratory function. It may be necessary to carry out gradual pneumo-peritoneum before parietal repair. A mersilene mesh was used by the authors in 51 cases. Certain rules should be observed when this prosthesis is placed in position so that the abdominal muscles find the conditions closest to their normal function.


Endocrine features of an adrenal-like tumor of the ovary. Detailed in vivo endocrine studies of a virilizing adrenal-like tumor of the ovary are reported. A nonspecific steroidogenic baseline profile was observed in the face of clearcut histological adrenal-like features. Dynamic testing disclosed incomplete dexamethasone-related steroidogenic suppression suggestive of partial tumoral autonomy. At the same time, the observation of sizable dexamethasone-related steroidogenic decrements, unaccounted for by normal adrenal contribution, may be interpreted to suggest a direct, pharmacological, inhibitory effect of dexamethasone on tumoral and/or ovarian stromal steroidogenesis. These observations confirm the limited role of baseline steroid profiling and dynamic testing in the preoperative localization of androgen-secreting tumors. Reversible dysfunction of hypothalamic gonadotropic feedback mechanisms was suggested by combined single dose LRH-clomiphene testing. Complete resolution followed tumor removal.


Mechanism of the hypocalcemic effect of mithramycin. Mithramycin is effective in the treatment of hypercalcemia. The mechanism of its hypocalcemic effect was studied in six patients with hypercalcemia by serum 85Sr or 45Ca kinetic techniques. Mithramycin was given at two dosage levels (25 or 50 microgram/kg iv). Mithramycin at the low dosage had little effect on the rate of bone accretion. However, at both dosage levels, mithramycin caused an upward shift of the slope of the specific activity curve, indicating an inhibitory effect on bone resorption. This effect started 6-12 h after a 25-microgram/kg dose of mithramycin and lasted from 4-6 days. It appears that mithramycin has a preferential effect on bone resorption.


Changes in lymphocyte activity after thermal injury. The role of suppressor cells. The high incidence of fatal septicemia associated with severe thermal injury is believed to result from a loss of immunocompetence. To detect burn-mediated immune defects, lymphocyte function in peripheral blood leukocytes from 18 individuals sustaining 20-80% full thickness thermal burns was investigated. We examined the kinetics of the mitogen responses, the development of suppressive activity, and the correlation of mononuclear cell functional abnormalities with the incidence of sepsis. Patients were divided into three groups corresponding to their clinical course. The phytohemagglutinin responses of Ficoll-Hypaque purified leukocytes from eight of these patients (group III) were normal at day 1-2 after injury, but were significantly depressed (mean 16% of normal) at days 5-10 after injury. All of these group III patients experienced multiple, severe, septic episodes, and septic mortality was 75%. The other 10 burned individuals showed either augmented (group II) or unaltered (group I) mitogen responsiveness. Concomitant with evaluation of their mitogen responses, the cells of burn patients were assessed for development of suppressive activity by addition to on-going normal mixed leukocyte reactions (MLR). Only the addition of mononuclear cells with depressed phytohemagglutinin responsiveness (group III) significantly decreased MLR proliferation (mean 80% reduction) by the previously highly responsive, normal MLR combinations. Addition of cells from group III burn patients collected immediately after injury had no suppressive effect. Addition of cells from patients in group I or II or of normal individual's cells had no suppressive effect. These experimental results strongly suggest that a suppressive mononuclear cell is at least partially responsible for the decreased immunocompetence of burn patients.


Human C4-binding protein. Association with immune complexes in vitro and in vivo. C4-binding protein (bp), a glycoprotein with specific binding affinity for the activated form of C4 (C4b), has recently been isolated from human serum and partially characterized. This report demonstrates that C4-bp is incorporated into soluble immune complexes after complement activation in vitro. The reaction requires Ca++ ions and the presence of C4 in serum. Immunopathological studies of various forms of glomerulonephritis revealed intense C4-bp deposition in glomeruli from patients with immune-complex type of pathogenesis. C4-bp deposition was in close correlation with that of C4. These observations, together with the in vitro association of C4-bp to immune complexes, support the notion that the deposits in glomeruli represent the local accumulation of immune complexes.


Trend analysis of jaw jerk action potential-amplitude data. The amplitude of the jaw jerk action potential (MSP) is a parameter with potential diagnostic value. It has apparently a large and irregular variation which has not yet been subjected to a thorough analysis. It is important to know if samples of MSP contain trends. The occurrence of trends indicates that the average value is influenced in a principally different way by changes in the number of observations per sample than if trends do not occur. If, for instance, there is a positive linear trend in the data, this means that the average value is larger if the number of observations is small. Samples of MSPs therefore were recorded, using surface EMG electrodes in the masseter and the anterior temporal muscles of young and elderly subjects, and subjected to trend analysis. Trends of the 1--4th grade occurred in 51% of the samples. Both positive and negative linear trends were found and had about the same frequency. The trend components were, however, randomly distributed. Comparisons between groups may therefore be made without the claim of trend-free samples. This significantly facilitates the use of the parameter MSP-amplitude, since it is difficult to obtain samples which have a normal and identical distribution.


Standard values of the amplitude of jaw jerk action potential and differences due to age, sex and L-dopa treatment. The amplitude of the jaw jerk action potential (MSP) is a parameter with possible diagnostic value. Standard values have, however, not yet been established. MSPs were recorded using surface EMG electrodes in the masseter and the anterior temporal muscles of young and elderly healthy males and females. The group means ranged from 0.26 to 2.11 mV in the masseter and from 0.17 to 0.81 mV in the anterior temporalis. The amplitude of MSP was higher in females than in males, decreased in elderly subjects and lower in the temporalis than in the masseter. The jaw jerk action potentials also were recorded in four subjects before and after L-Dopa administration. The amplitude increased by about 90%. It is concluded that the parameter MSP amplitude can be useful in the studies of muscle spindle sensitivity and the influence of various physiological, pathophysiological and pharmacological factors on the nervous regulation and muscle function in the masticatory system.


Reasonable expectations in geriatric rehabilitation. Rehabilitation and traditional medical treatment have different primary orientations within philosophic, operational and time frameworks. As a result, traditionally trained physicians often do not understand the possible benefits of energetic rehabilitation efforts in the elderly. Accurate assessment includes differentiating the irreversible handicaps of normal aging from the disabilities of remediable disease. Such assessment is the essential prerequisite of effective rehabilitation; together with positive attitudes and continuous reevaluation, the likelihood of a successful outcome is greatly enhanced.


[The effects of intraocular irrigating solutions on the human corneal endothelium (author's transl)]. Human corneas from enucleated eyes get thicker during perfusion with B.S.S. On the contrary, their thickness decreases when perfused with T.C. Earle solution. Addition of reduced glutathion and adenosine does not change the results obtained with T.C. Earle. Histological study of the endothelium after a 24 hours perfusion demonstrates a better conservation of the cells with T.C. Earle and T.C. Earle glutathion--adenosine than with B.S.S.


[Drainage of subretinal fluid: technic and results]. The drainage of subretinal fluid (S.R.F.) after choroidal diathermy offers a distinct advantage: important reduction of massive haemorrhages from the drainage site (4% vs 48% in the non diathermy group in our series). According to us it is not a decisive factor for the anatomical prognosis because complications of drainage in themselves seem to be a quite infrequent cause of anatomical failure. On the other hand we think that visual outcome is better in the diathermy group because of a diminution of macular haemorrhages.


[Massive bilateral orbito-palpebral hematoma complicating acute myeloblastic leukemia]. The authors present a case of acute mieloblastic leucemia, having as an unique symptom a massive bilateral orbito-palpebral hematoma, but having not other symptoms of the hemoragipar syndroms common in acute leucemiae. After a short period of retreat of the disease, the goeson, leading to death.


[A new lacrimal intubation set (author's transl)]. The authors report a new lacrimal intubation set made with two very malleable metal probes and with a silicone tube. The system can be used during the repair of the nasolacrimal duct injuries, during dacryorhinocystostomy, and also for the repair of canaliculus injuries with the little set.


[A criticism of Lancaster's test and its variations (its inadequacies during the study of oculomotor paralyses) (author's transl)]. Lancaster's test has many technical inconveniences : Its interpretation is sometimes difficult or impossible. The information it gives is often incomplete. It is of no value in cases with binocular motor lesions. It should always be combined with other oculomotor examinations.


[Is the Fadenoperation easy or difficult? (author's transl)]. The operative indications are more or less difficult according to the clinical type ; some of them belong to a very high specialization. The operative technique is not very difficult if the operator is accustomed with the surgery of the posterior segment. On the contrary, the operator who is only accustomed with the surgery of the anterior segment or the classical techniques for strabismus, will find real difficulties.


[Experimental studies with timolol: a new ocular hypotensive agent (author's transl)]. The present report reviews the animal pharmacology supporting the clinical use of timolol maleate ophthalmic solution in the therapy of glaucoma and elevated intraocular pressure (IOP). The studies have included the effects of timolol upon normal IOP of rabbits and upon elevated IOP in two models of experimental ocular hypertension. Comparisons are made between the latter actions of timolol and those of the reference adrenergic antiglaucoma agent, epinephrine. The interaction of timolol and the beta-adrenergic stimulant, isoproterenol, was also studied to assess the ability of timolol to block beta-adrenergic receptors in the eye. Additionally, the penetration and distribution of timolol in ocular and extraocular tissues and fluids following local application to the eyes of rabbits is described and a resume of the toxicological studies with timolol are presented.


[A new beta-blocking agent in the treatment of chronic open-angle glaucoma: timolol maleate. Effect of instillation of 1 drop on the intraocular pressure]. A total of 45 patients with chronic open-angle glaucoma were divided randomly into three groups of fifteen. Each patient in each group was given one drop into one eye (the other eye serving as a control), of either placebo, timolol 0,5%, or timolol 1,5%. The patients were observed for a period of seven hours, and results showed that timolol was effective in reducing ocular tension when compared to placebo. It was also rapid in action (one to two hours after instillation), and no side-effects were noted. Timolol 0,5% appears to be as equally effective as the 1,5% strength.


[Results of a double-blind medium-term study comparing effects of timolol maleate and epinephrine in 120 patients with chronic open-angle glaucoma]. A double-blind medium term study of the activity of timolol in chronic open-angle glaucoma was conducted in four French ophthalmological centers, using the same protocol. A total of 119 patients were treated: --60 with timolol; --59 with épinéphrine, for comparison. Results showed a significantly superior efficacy for timolol over épinéphrine, after in weeks of treatment. Good tonometric control was obtained in 81.6% of the patients treated with timolol, against 52.5% of those receiving épinéphrine. In 68% of the glaucomatons patients treated with timolol, good tonometric control was obtained with the lowest dose preparation containing 0.1%. No side-effects were noted during the study, either locally or generally (particularly blood pressure changes).


[Results of a double-blind study comparing the effects of timolol and pilocarpine in 110 patients with chronic open-angle glaucoma]. Following a seventeen weeks study including 110 patients with open-angle glaucoma, 81,8% of the patients treated by timolol, administered twice a day, had a satisfactory control of their intraocular pressure, against only 41,8% of those patients treated by pilocarpine, administered four times a day. The side effects liable to timolol are clinically reduced, in a osit with pilocarpine which is followed by a series of well-known subjective and objective signs often causing discomfort to the patients.


[Effect of daily instillations of timolol on the nycthemeral tension in subjects with chronic open-angle glaucoma (author's transl)]. This study included 22 patients with chronic open-angle glaucoma who were treated with either 0.25% or 0.5% timolol. The results showed that a single daily instillation of 0.25% or 0.5% timolol was effective, without producing any side-effects. It was interesting to note that timolol caused the tension peaks to disappear, the nycthemeral graph curve becoming plateau-shaped.


[Timolol maleate: results of its long-term action in the treatment of chronic primary open-angle glaucoma]. Three groups of patients with chronic open-angle glaucoma, who had ineluded in the previous study, had been treated with timolol twice daily for more than a year. The long-term results confirm the efficacity noted in the medium-term survey, and the absence of side-effects, especially those related to the pulse rate and blood pressure in some of the patients. Drug associations had been necessary:--pilocarpin,--acetazolamid, seem to have the best synergic action with timolol.


[A single dose of maleate of timolol given orally: the effect on the ocular pressure (author's transl)]. A single dose of 5 mg of maleate of timolol given orally to glaucomatous patients, considerably lowers their I.O.P. during a period of time of at least 6 hours. It causes only a slight decrease in blood pressure and pulse rate.


[Hypoplasia of the optic nerve head].

[Hypoplasia of the optic nerve head]. Optic nerve hypoplasia is not a rare eventuality in children. This report discusses the clinical features of 10 new cases on a multiple point of view including optic canal tomography, fluorescein angiography and cat's examination. Optic nerve hypoplasia is not always accompanied by decreased visual acuity: sector fields are often identified in these cases.


[Primary malignant melanoma of the cornea (author's transl)]. In this communication, we present a case of malignant melanoma of the cornea, in an 80-year old female. The tumor, covering 3/4 of the cornea, had a lobulated appearance, pinkish colour with vascularization and pigment granules, in a few places. The limbal area was free of tumor. Histologic examination indicated that the melanoma was primary, of the epithelioid type, with a few areas of spindle type cells.


[Menkes' disease: apropos of a recent case]. The authors describes a case of Menkes' disease, sex-linked recessive hereditary disease characterized by early progressive psychomotor deterioration, failure to gain weight, seizures, hypothermie and characteristic Kinky hair (Pilitorti). This boy is a blind child, unable to fix and follow light. Fundus examination shows optic nerve atrophy with tortuosity of the retinal blood vessels. The case is discussed in the light of similar and others reports in the literature. The disease is believed to be cause by a generalized copper deficiency in the body by defect in copper intestinal absorbtion. The pathologic changes in the retina are similar to those seen in the brain which shows diffuse neuronal degeneration lose of nerve filers and optic atrophy. Retinal changes should be reversible by short term systemic copper administration.


[Fluorescence angiography: personal technics of automatized development of films and printing]. The film of an angiography by fluorescence presents specific particular characteristics. Treatment of the film has to be adapted to these particularities, and the chemical products used have to be specially chosen. In this way, the results obtained can be greatly improved. The procedure can be automatized by the use of a simple apparatus, and printing on paper causes no particular difficulty.


[A case of cavernous hemangioma of the retina]. A case of hemangioma of the retina is reported. Its typical ophtalmoscopic and fluorescein angiographic aspects are studied. The benign evolution is stressed in spite of a possible macular risk checked by argon laser therapy.


[Painful ophthalmoplegia and cavernous sinus syndrome of inflammatory origin (discussion of 2 cases)]. Two patients with unilateral painful ophthalmoplegia are presented, a woman of 26 and a man of 28. In both cases the phlebography of the orbit shows an alteration of the orbital veinous blood flow, specially of the third segment of the superior orbital vein. Another characteristic feature of this syndrom is efficiency of corticotherapy and heparinotherapy, which may suggest an inflammatory and thrombophlebitic origin.


[Surgical management of divergent strabismus (author's transl)]. This study, about 111 cases of exodeviations, establishes a guideline for surgical management of divergent strabismus. First the main points of the clinical examination, and the different classifications of the exodeviations are exposed. Then the technics of surgical treatment are defined, with or without pre or post surgical orthoptic treatment. The conclusions are as following: -- some clinical elements guide our treatment: the refraction, the age at onset, the study of the deviation after constant use of prisms, the existence of A or V syndrome. -- The main points of the surgical management are: the age of surgery, the choice of technic (symmetrical or not), the usefulness of a transient overcorrection, and above all the quantative rules for the surgical treatment. So it as been possible to stress the functional result is quite depending on the clinical type of exodeviation.


[Future of coelioscopy tappings of ovarien cysts (author's transl)]. In a study of 136 tapping of ovarien cysts carried out in the surgical departement of Broca Hospital from 1968 to 1971, the authors point out the diagnostic interest of such a practice, which is harmeless if the contra-indications are respected and often easily carried out (tapping needle by Mintz). The macroscopic and cytological aspect of the liquid tapped enable one to make a precise diagnostic in almost all cases and to lead the therapy in the proper direction.


[Meadows syndrome. A case history (author's transl)]. The authors, having studied a case of Meadows syndrome, confirm that this cardiomyopathy is a specific entity in pregnancy and the puerperium. They point out the difficulties in diagnosis, as Meadows syndrome seems to be diagnosis of elimination. They point out that a paraclinical balance has to be drawn up very fully on the biological and haemodynamic planes to confirm this condition. Finally, after a short discussion about the therapy, they tackle the problem of the prognosis for life and for future childbearing in these patients, which is determined by the persistence or absence of cardiac enlargement.


Evidences for the existence of glycoproteins and mucopolysaccharides metabolic cycles in the cerebellum of birds and mammals. Cerebellum glycoproteins of rats and ducks are studied using sugar-specific agglutinins. It is used the Con A-Peroxidase-DAB technique described by Bernhard and Avrameas (1971). Other agglutinins (Tetragonolobus Purpureus Lectin, Wheat Germ Agglutinin and Soybean Agglutinin) fixed to Peroxidase according to the technique of Gonatas and Avrameas (1973) are also used. The techniques for mucopolysaccharides as described Martínez-Rodriguez et al., (1976) are carried out as well. By means of all these techniques, results that suggest the existence of metabolic cycles in Purkinje cells are obtained.


Effects of potassium para-aminobenzoate on growth and macromolecule synthesis in fibroblasts cultured from normal and sclerodermatous human skin, and rheumatoid synovial cells. Potassium para-aminobenzoate was tested for its ability to affect growth and macromolecule synthesis in vitro using fibroblasts from normal human skin, from affected skin of patients with scleroderma, and rheumatoid synovial cells. The proliferation of all 3 cell types showed dose-dependent inhibition beginning at about 3000 microgram/ml. Acid mucopolysaccharide secretion by rheumatoid synovial cells and scleroderma fibroblasts was inhibited even at 100 microgram/ml, which is within the therapeutic range, and there was over 50% inhibition at 5000 microgram/ml. Collagen synthesis by several different strains, was not affected, despite the use of a range of concentrations and treatment times.


Glomerulopathy in rats with streptozotocin diabetes. Accumulation of glomerular basement membrane analogous to human diabetic nephropathy. Glomeruli from streptozotocin-diabetic and age-matched nondiabetic rats were quantitatively isolated by a differential sieving technique. The insoluble glomerular basement membranes were purified following sonic disruption in the presence of proteolytic inhibitors. The yield of glomeruli and of glomerular basement membrane relative to the amount of renal cortex and the body weight of the animals, as well as the calculated amount of basement membrane per glomerulus, were all significantly greater in diabetic rats when compared to non-diabetic controls. Glomerular basement membranes from normal and diabetic rats were solubilized by reduction and denaturation in the presence of SDS and subjected to agarose gel analysis. About 65% of both normal and diabetic basement membrane was solubilized by this procedure, and the elution profiles of non-diabetic and diabetic preparations were similar. These results suggest that rat renal basement membrane is qualitatively similar but quantitatively increased in streptozotocin-diabetes. Since glomerular enlargement and accumulation of basement membrane are characteristic of human diabetic nephropathy, the findings also suggest that the streptozotocin-diabetic rat is an appropriate animal model for studies relating to the pathogenesis of this complication of diabetes.


Antigens of human trophoblast. Effects of heterologous anti-trophoblast sera on lymphocyte responses in vitro. This report describes the inhibition of human mixed lymphocyte culture (MLC) reactions by rabbit antisera to intact and detergent solubilized, fractionated, human trophoblast membranes. Heat-inactivated antisera were passed through solid-phase immunoabsorption columns of normal human serum and extensively absorbed with human erythrocytes, lymphocytes and liver powder. Immunohistological experiments with these absorbed antisera showed that they reacted brilliantly with syncytiotrophoblast in cryostat sections of human but not baboon or monkey placentae, and not with other normal adult tissues including peripheral blood lymphocytes (PBL). Addition of these antisera to MLC reactions produced significant and reproducible suppression of responses without affecting cell viability. Absorption studies demonstrated complete removal of MLC inhibition and trophoblast membranes but not with PBL or suspensions of HEp-2 cells. Timed experiments showed that optimal inhibition occurred when the antisera were added between 2 and 6 h after culture initiation, and that little suppression was achieved after 18 h. Lymphocytes harvested from MLC reactions after 2 h showed that 3--5% of the cells reacted with PBL/liver-absorbed anti-trophoblast sera, and that unstimulated PBL were negative. Cultures of subhuman primate lymphocytes in the presence of heterologous antisera to human trophoblast membranes showed total inhibition of rhesus:human and human:rhesus MLC, and no suppression of baboon:human or human:baboon reactions, whereas human lymphocytes responded in an exagerated manner when stimulated by baboon cells. Modulated MLC responses to human, rhesus, or baboon lymphocytes, in the presence of anti-trophoblast sera indicate that the antisera recognize trophoblast cross-reactive lymphocytes antigens. We propose that these antigens are reaction products of cell-cell interactions, and that the nature of the antigens is determined by the specificity of the recognition signals which initiate the reaction.


Functional disability of geriatric patients in a family medicine program: implications for patient care, education, and research. While the elderly comprise a large proportion of patients seen in ambulatory care settings, characteristics of these patients have not been well documented. This paper summarizes results of a survey of functional impairment of elderly patients seen in a family medicine center. Assessments were performed in the areas of social and economic resources, mental health, physical health, and the ability to perform routine activities needed for independent living. Results of the survey suggest that family physicians need to know how to perform a multidimensional functional assessment in order to formulate a comprehensive treatment plan for elderly patients.


Histoenzymatic and permeability changes in human brain adjacent to meningioma. Cerebral specimens were removed from ten patients with meningioma. Vascular permeability was tested with sodium fluorescein and a correlative study of the oxidative and hydrolytic enzyme activity was performed. Vascular permeability change was observed in half of the specimens of cortex taken from the region of the tumor. Labeled tracer diffusion was found to be either perivascular or involved microscopic ischemic areas. Fluorescein diffusion of the edematous white matter was observed in only two specimens. Enzyme activity in walls of the blood vessels was modified in the fluorescent specimens. Alkaline phosphatase and oxidoreductase activities were decreased. Experimental results have shown a relationship between increased vascular permeability and metabolic disorder of both vascular walls and cerebral cortex. Our findings agree with Zülch's hypothesis regarding a "hemodynamic" mechanism in the formation of edema by extraneural compression.


The utilization of ornithine and citrulline by the growing kitten. Previous experiments have demonstrated that cats fed an arginine free purified amino acid diet (-Arg) could be protected from hyperammonemia by the inclusion of ornithine in the diet. Experiments reported here show that diets containing ornithine added at an equimolar (+Orn) or five times equimolar (+5 Orn) to replace arginine in the +Arg basal diet (2.0% Arg . HCl), were incapable of maintenance of body weight. Growing kittens fed a -Arg +Orn and -Arg +5 Orn diets had a daily rate of body weight loss of 6.5 +/- 0.6 and 7.9 +/- 2.2 g, respectively, which is somewhat less than the mean rate of weight loss of kittens fed diets devoid of most of the other amino acids indispensable for the kitten. When citrulline was added to a -Arg diet at an equimolar level to the arginine in the +Arg basal diet, growth rates were equivalent. The mean plasma free ornithine concentration of kittens receiving the -Arg +5 Orn diet was about 33 times higher than when they were fed the +Arg diet. For kittens fed the -Arg + Orn and -Arg +5 Orn diets the mean plasma free arginine was less (but significant only for the -Arg + Orn diet) than that observed for the basal diet. When the -Arg + Cit diet was fed, plasma free arginine concentration was similar and plasma free citrulline was about 18 times higher than when these cats were fed the basal diet.


Hyperkeratosis palmoplantaris with periodontosis (Papillon-Lefevre syndrome): report of three cases, two occurring in siblings. Three cases of palmar-plantar hyperkeratosis with periodontosis, two cases of which occurred in siblings, are reported. The parents were unaffected, and parental consanguinity was present in all three cases. All essential features of the syndrome were present in these cases.


Voluntary activation of spindle endings in human muscles temporarily paralysed by nerve pressure. 1. In normal human subjects, the afferent activity from muscle spindle endings in the pretibial muscles was recorded while a pressure block was applied to the peroneal nerve proximally in the popliteal fossa. 2. In five of ten blocks, spindle activity increased in attempted isometric voluntary contractions when the receptor-bearing muscles were completely paralysed. In the remaining five blocks, voluntary effort still increased spindle activity when maximum voluntary power was reduced by more than 90%, but the ability to activate spindles voluntarily was lost with or slightly before block of the last motor units. When the ability to activate spindle endings in an attempted voluntary contraction was lost sympathetic efferent fibres remained unblocked. 3. It is concluded that the fusimotor effects seen during a voluntary contraction are mediated by myelinated fibres of small calibre which probably innervate intrafusal structures exclusively (gamma fusimotor fibres). There is no necessity to postulate that skeleto-fusimotor (beta) fibres are responsible for the tight 'alpha-gamma co-activation' seen in man during voluntary contractions.


Histochemical reactions of fibres in a fast twitch muscle of the cat. 1. Serial sections of flexor digitorum longus muscle (f.d.l.) of the cat were examined histochemically for four enzyme systems: adenosine triphosphatase (ATPase) with alkaline and acid pre-incubation, phosphorylase and succinic dehydrogenase (SDHase).2. The number of types into which fibres should be divided was assessed by estimating enzyme reaction intensity from measurements of light transmission through photomicrographs. It was concluded that in general the enzyme reaction intensities of fibres were distributed continuously. However, the distribution histograms showed two (phosphorylase and SDHase) or three (acid and alkaline ATPase) clear peaks. Eighteen combinations of reaction intensities (profiles) were seen of which eight were very rare. The distribution of profiles differed between individuals but were similar in right and left muscles.3. Areas of fibres were measured from muscles which had been fixed at the length at which twitch tension was maximal. The variance in fibre area with any one profile was significantly less than the variance in fibre area of all fibres within a muscle. There were significant differences between the mean areas of fibres with different profiles.4. If only three enzyme reactions are considered (acid and alkaline ATPase and phosphorylase) the majority of fibres fall into one of the three classes commonly accepted for other muscles. The remainder would fit into this classification with the minimal assumption of only one error of fibre typing resulting from the continuous distributions of enzyme reaction intensities. The SDHase reaction was not strongly correlated with the three classes and could be used to divide the fibres further into six groups. Differences between means of fibre areas were significant for all pairs out of these six groups except one.5. The grouping may be considered to reflect a dual system of enzymes, the two systems being (a) ATPases and phosphorylase, (b) SDHase. A possible role of nervous activity in determining this dual system is discussed. The hypothesis involves two partly independent characteristics of motoneuronal activity: (a) the frequency of impulses, and (b) the total number of impulses.6. The measurements are correlated with other physiological variables in the individual animals. The mean areas of fibres in all groups increased with body weight. There were changes in the proportions of light and dark SDHase fibres related to weight. The total area contributed by dark alkaline ATPase fibres decreased and that by intermediate alkaline ATPase fibres increased with increasing twitch time to peak.7. Specific tension of the group of slower muscle fibres in f.d.l. was estimated to be 0.29 N.mm(-2) compared with 0.39 N.mm(-2) for the faster fibres.