[Problems of the clinical diagnosis of myocarditis]. Anamnesis, clinical findings, changes of the ECG, findings of X-ray examinations and biological reactions in 39 patients with myocarditis are discussed. For the diagnosis of myocarditis are discussed. For the diagnosis of myocarditis changes of the ECG, enlargement of the heart, cardiac insufficiency and disturbances of rhythm are of greatest importance. Changes in the ST-T-segment are non-specific. An exact anamnesis and a comparison with previous findings (X-ray serial examination, ECG) may give decisive hints. Biological reactions are often unreliable in making the diagnosis. There are no typical symptoms and findings for the diagnosis of the inflammatory disease of the myocardium. In the individual case the diagnosis of a myocarditis may be a tentative or excluded diagnosis.


[Cardiomypathies].

[Cardiomypathies]. Heart insufficiency, cardiomegaly and pathological changes of the ECG after exclusion of coronary heart disease, congenital or acquired vitia cordis and hypertension of the greater or lesser circulatory system result in the diagnosis cardiomyopathy with the liability of further differential-diagnostic demarcation. If causes of a secondary cardiomyopathy can be detected, a causal therapy is often possible, as to the remaining group of the idiopathic cardiomyopathies one must for the time being limit to an exclusively symptomatic treatment (protective therapy, limitation of the fluid supply, glycosides, diuretics, medicamentous and electric therapy of disturbances of the rhythm).


[Treatment of bradycardia with an atropine ester]. In view of the unsatisfying drug treatment of bradycardias in most cases, clinical studies with new compounds seem to be urgent. A report is given on experiences with a derivative of atropine (gen. Ipratropiumpromid) in 34 cases suffering from various types of bradycardias. Comparing heart rate following intravenous injections of 0.5 to 1.0 mg, the new drug proved to be definitely more effective than atropine sulfate. Side effects were limited to diminution of salivary glands function.


[Clinical-pathological findings in a case of obstructive myocardiopathy]. Extensive description of familial obstructive myocardiopathy by means of clinical observations and autopsy findings from a 26 year old made suffering from sudden unexpected death. Striking was the rare fact, that clinical and morphological findings were precisely corresponding and independently lead to the correct diagnosis. By means of Ecg, Pcg, carotid-sphygmogram and radiological findings, pathogenesis, pathophysiology as well as the morphological basis of this disease is illustrated. 3 siblings of the patient have similar symptoms, which progressing slowly suggest analogous disease.


Identifying Reiters disease in Papau New Guinea. Seven cases of non-supportive polyarthritis are reported from the Madang General Hospital over a 12 month period from June 1972. The distribution of diagnostic categories is similar to that reported by Maddocks in Port Moresby, with Reiter's disease featuring prominently. One case of Reiter's disease was associated with a haemolytic anaemia, considered to be auto-immune in origin.


[General factors in the pathogenesis of parodontosis and chronic recurring aphthous stomatitis]. Parodontosis and aphthous stomatitis form a nosological entity which may be considered to be due to a pathological condition of exchange functions within the matrix of the connective tissue. As final products of the catabolism of collagen, there may be found peptid fragments containing both oxyproline and free amino acids. A large number of series of tests were made on a total of 164 patients in order to determine the various products of decomposition of collagen in the urine and their accumulation in the plasma.


[Comparative studies on the shape of the interproximal surfaces]. Studies on the shape of interproximal contact in the lower side teeth region were performed in 203 persons and 73 models. In 74,9% of cases a spheric-plane and in 25,1% a more punctuous-plane contact was registered. These findings are compared with observations of the interproximal abrasion of the lower premolars and molars in roe.


[The behavior of the lower front teeth after systematic extraction of the upper premolars]. Narrowly spaced frontal teeth in the lower jaw have been the object of repeated discussions in the orthodontic literature. There are a number of factors which either directly or indirectly cause the space between frontal teeth in the lower jaw to become narrower and narrower in the course of life. The purpose of the present work was to find out whether orthodontically indicated extraction of premolare in the upper jaw may, in the case of distal occlusion, result in the space between front teeth in the lower jaw becoming narrower and narrower.


[Participation of the serotoninergic system of the brain in regulation of emotional reactivity]. Vocalization and aggressiveness reactions were evoked in experiments on male Wistar rats by means of electric shock stimulation. The influence of serotonin- and dopaminergic drugs was studied in parallel on emotional reactivity and serotonin metabolism. It has been found that l-tryptophane depresses while l-Dopa intensifies emotional reactivity and aggressiveness, the latter lowering the level of endogenous serotonin and enhancing its catabolism. L-Dopa, dl-amphetamine, alpha-methyl-Dopa, parachlorophenylalanine and serotonino-blockators--deseryl and lysergide--eliminate the tranquilizing action of tryptophane on emotional reactivity, decreasing serotonin accumulation and intensifying the formation of 5-oxyindolacetic acid.


An unusual side effect on the skin under high dose D-penicillamin treatment. An unusual side effect on the skin after one year's high dosage (3,0 g/die) of D-Penicillamin-treatment is reported. The skin showed double-pin-sized vesicles and laceration after minor injuries. After reduction of the dosage to 1,8 g/die and bathing the hands three times/day for 2 minutes in 1% Tannin solution the skin lesions and wounds healed eventually.


[The width and longitudinal development of the deciduous dentition in children with unilateral total cleft lip and palate]. This paper recommends that the development of deciduous teeth in patients with extensive unilateral clefts should be studied by reference to jaw models and compared with results obtained by Heckmann in a series of investigations of regular sets of deciduous teeth and that such studies should be made on the model of those which were conducted, in recent years, by workers at the Rostock Department of Orthopedic Stomatology and which were concerned with questions associated with the normal development of dentures.


Phenylbutazone in treatment of acute lumbago-sciatica. In a double-bind investigation of the effect phenylbutazone (initially injected + Butazolidin Alka p.o.) was compared with that of placebo in 36 patients with acute lumbago-sciatica without root involvement in the form of paresis. The investigation showed that the effect of phenylbutazone was significantly better than that of placebo. The side-effects of the drug were mild.


[Results of therapy of lip neoplasms from a radiotherapeutic point of view]. The increasing use, in recent years, of surgical methods for the treatment of labial carcinomata caused us to review the results of treatment by means of irradiation. The different methods of radiotherapy are described, and a comparison is made between the results of radiotherapy and surgical treatment. Also, cases are described in which it is indicated to use either surgical treatment or radiotherapy or a combination of the two methods.


[Characterization and determination of residual monomer content of implantation materials from polymethacrylic acid methylester]. Cold polymerizates "Kallocryl K" and "Palacos" were characterized by means of physico-chemical methods of examination. The residual monomer content of the polymerizates, which is of major toxicological interest, was also determined quantitatively. It was possible to show that the residual monomer content decreases exponentially as a function of the duration of polymerization. "Palacos" polymerizates had much higher residual monomer contents than "Kallocryl K" polymerizates when the same time of polymerization was used. Also discussed in this paper are possible methods of reducing the residual monomer content prior to implantation of the plastic materials.


[Studies on the diffusion of the remaining monomers from implantation plastics of polymethacylic acid methylester]. Positive clinical results were obtained using implanted cold polymerizates, and these were compared with the negative results of experiments made on animals. The observed local pathophysiological processes are considered to be due to the effects produced by the methacrylic methyl ester. The absolute content of residual monomers in the implants does not allow to make any definite conclusions as to the rate of diffusion into the organism. Therefore, the diffusion of residual monomers into an aqueous medium was titrimetrically measured for three weeks by the pyridine sulfate dibromide method. After a description of the method of titration and the results obtained, a discussion is given of the causes of the different rates of diffusion of residual monomers from Kallokryl K and Palacos samples, which are dependent upon the duration of polymerization in air.


[Neoplastic degeneration of odontogenic cysts. A contribution to the problem of early diagnosis]. This report is dealing with 3 cases of odontogenic cysts which developed carcinomatous changes. It is recommendable to look always carefully for epithelial atypias and to keep marsupialised cysts in control by clinical, radiological and cytological examinations. The excision and histological examination of tissue proliferations in cysts is to advise in any case.


[Sensitivity to polyvalent therapeutic staphylococcal bacteriophage as a supplementary criterion of staphylococcal pathogenicity]. It is recommended to use the capacity of pathogenic staphylococci to be lysed by polyvalent therapeutic staphylococcal bacteriophage in the capacity of an additional simple and accessible criterion of staphylococcus pathogenicity. Of 147 strains of the pathogenic plasmacoagulating staphylococci 101 were lysed by the phage and of 166 nonplasmocoagulating nonpathogenic strains--only 6. This test correlated with the other signs of staphylococcus (lecithinase and hemolytic activity). The simplicity and sufficient specificity of this test permits to use it in any practical laboratory. Polyvalent diagnostic phage can be used on the basis of therapeutic bacteriophage by its additional adaptation to the pathogenic strains of staphylococcus.


[Study of the functional activity of the macrophages of animals immunized with staphylococcal alpha-anatoxin]. A study was made by histochemical methods of the activity of the enzymatic systems of macrophages from normal rabbits and those immunized with staphylococcus alpha-toxoid per se and infected with the strains of staphylococcus--producers of alpha-toxin or leukocydin. Immunization of rabbits was accompanied by a reduction in macrophages of the activity of the group of lysosomal enzymes and by an increase in the activity of the redox enzymes. In infection of "immune" macrophages with the living culture of the alpha-toxigenic strains the mentioned changes were more pronounced; no such changes were found after the infection with the leukocydin-active strain. The data obtained suggested that the lysosomal enzymes played a definite role in the process of phagocytosis.


[Differential traits and antigenic properties of the S- and R-forms of Neisseria meningitidis]. The authors demonstrated a marked dissociation of the Neisseria meningitis cultures and the capacity to their rapid change from S- to R-forms. Differential signs of the S- and R-forms are described. Differences in the degree of dissociation of the cultures depending on their origin were shown: strains isolated from the cerebrospinal fluid and the blood of patients with meningitis proved to be less dissociated, and those isolated from carriers--more dissociated. Transfers from media to media and adaptation of cultures to artificial nutrient media produced the greatest influence on dissociation of the freshly isolated strains.


[Clinical characteristics of the mosaic variant of Down's disease]. The authors studied the clinical features in 19 patients with the mosaic variety of Down's disease and 63 patients with trisomia in relation to the 21st chromosome. It was demonstrated that mild forms of mental retardation are mainly seen in mosaicism rather than in the trisome variety, although severe forms of retardation may be seen in the first group as well. A full correlation between the severity of mental retardation and the % of the aneuploid cell content in the peripheral blood was not always observed.


[Morphohistochemical changes in cerebral vascular plexi in connective tissue diseases]. The vascular brain plexi were studied in 40 cases of rheumatism, 18 cases of systemic lupus vulgaris, 12 cases of nodus periarthritis and 5 cases of sclerodermia. In all cases there were phenomena of a desorganization of the connective tissue in the stroma and vascular walls accompanied by a significant accumulation of acid mucopolysaccharides, panvasculitis, thrombovasculitis, necrobiotic changes of the chorioid epithelium and nervous filaments. The authors report of special traits of structural changes inherent in each disease.


Subcellular localization of (Na+ + K+)-activated ATPase in the brush border membrane of the mucosal cell of the rat small intestine. The localization of (Na+ + K+)-activated ATPase was investigated in isolated brush borders of rat small intestinal mucosa. The purity of the fractions has been checked by morphological and enzymatic criteria. The brush borders were found to contain a significant quantity of (Na+ + K+)-activated ATPase. Separation of isolated brush borders into their substructures suggests that (Na+ + K+)-activated ATPase is localized deeper within the brush border region than invertase. These findings are discussed in relation to active monosaccharide transport in the intestine.


Reactive hyperaemia in the hind limbs of the rabbits. III. The effect of hypervolemia and venous congestion. The effect of increased circulatory fluid volume and local venous congestion on reactive hyperaemia was studied in the hind limbs of rabbits. Compared with controls, hypervolemia reduced maximal flow significantly after all occlusion times. Percentual repayment decreased after 10 second occlusions, increased above control level after 60 second occlusions, and otherwise was similar to controls. Hypervolemia increased recovery time significantly after occlusions longer than 10 seconds. It is possible that decreased oxygen carrying capacity of the blood due to decreased haematocrit after infusion can explain the increased repayment observed during hypervolemia. Furthermore, oedema formation may to some extent prolong the wash-out of metabolites in the postischaemic period. During venous congestion, maximal flow, percentual repayment as well as recovery time were significantly reduced after all occlusion times. Venous congestion may represent an increased resistance against blood arriving from the arterial side after release of the arterial occlusion, thereby reducing the initial part of reactive hyperaemia and perhaps a major part of the hyperaemia after short occlusions. In addition the congested blood may represent an increased amount of oxygen made available for the tissue, and finally venoarterial reflexes may contribute to the reduction of reactive hyperaemia during venous congestion. These results show that factors such as circulatory blood volume and venous pressure and blood volume of the local vascular bed affect reactive hyperaemia significantly.


Studies on the pattern of circulating steroids in the normal menstrual cycle. I. Simultaneous assays of progesterone, pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone, androstenedione, oestradiol and oestrone. In an attempt to analyze the multiple changes and interactions in circulating steroid levels in the peri-ovulatory and peri-menstrual periods, the plasma levels of immunoreactive luteinizing hormone (LH), progesterone and unconjugated pregnenolone, dehydroepiandrosterone, testosterone, oestradiol and oestrone were assayed daily during a complete cycle in 17 normally menstruating women. In 14 of the 17 subjects studied androstenedione and unconjugated dihydrotestosterone were also estimated. The day of the LH-peak and the first day of menstruation, respectively, were used to synchronize the peri-ovulatory and peri-menstrual plasma levels of the various steroids. With the exception of dehydroepiandrosterone and dihydrotestosterone, the plasma levels of all steroids exhibited significant, but different changes during the cycle. Testosterone levels showed a slight but significant increase around the LH-peak, whereas the levels of pregnenolone and androstenedione were higher in the post-ovulatory than in the pre-ovulation periods. The levels of oestradiol and oestrone, as well as the ratios of oestradiol to oestrone gradually increased from the low values observed in the early proliferative phase to pre-ovulatory peak values. The relationship between peaks of oestradiol and oestrone and that of LH exhibited great individual variation. The same was true for the individual oestradiol to oestrone ratios. The combination of several steroidal signals did not improve the predictive value of the analyses. However, an increase of individual progesterone values by at least 0.35 ng/ml from the day preceding the LH-peak to the day of the LH-peak was observed in 13 of the 17 subjects. It is suggested that for the early detection of the LH surge and prediction of the subsequent ovulation daily assays of plasma progesterone are of more value than the assay of the other steroids investigated.


Pathways of testosterone synthesis in decapsulated testes of mice. In order to study the temporal relations in the biogenesis of testosterone, decapsulated testes of adult mice were incubated with carbon-14-labelled sodium acetate and attempts were made to isolate the most likely intermediates. Considerable quantities of radiochemically homogeneous squalene, lanosterol, cholesterol, testosterone and androstenedione, but no pregnenolone, progesterone, 17-hydroxypregnenoline, 17-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone sulphate or dehydroepiandrosterone sulphate were isolated. The same pattern of incorporation was found when gradually increasing amounts of non-labelled pregnenolone, progesterone, 17-hydroxypregenenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate or testosterone were added to the system as "trapping agents" or when Leydig cell preparations rather than decapsulated testes were used. The presence of 10 mIU of HCG greatly enhanced the de novo formation of testosterone, androstenedione and 5alpha-dihydrotestosterone but did not change the pattern of acetate incorporation. Radioimmunoassays of the incubation medium with or without added HCG, and carried out at different periods of time indicated the presence of gradually increasing amounts of testosterone and androstenedione together with some 5alpha-dihydrotestosterone, whereas only trace amounts of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone and dehydroepiandrosterone were present. An analysis of the incubated testes revealed that the addition of HCG significantly enhanced the content of testosterone, androstenedione and 5alpha-dihydrotestosterone. Little or no increase was observed as far as pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone or dehydroepiandrosterone were concerned. It is concluded that decapsulated testes of mice synthesize de novo testosterone from sodium acetate under conditions in which the formation of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone sulphate and 17-hydroxypregnenolone sulphate cannot be demonstrated.


Tubal sterilization via laparoscopy and hysteroscopy. The combination of a growing need for improved contraceptive technology, plus the new advances in endoscopic equipment, have resulted in widespread use of laparoscopic sterilization throughout the world. Recent developments have succeeded in making hysteroscopy a reliable technique and it too has been quickly evaluated for a new, simpler female sterilization method. This work is still in progress and no reliable clinical method is yet available. However, the use of a chemical, such as methyl cyanoacrylate, delivered by hysteroscope, or possibily by a blind method, does seem to be most promising as a new clinical technique shortly.


Studies on the integument of cestodes. VI. Histochemical studies on the fate of structural polysaccharide in the integument of gravid proglottides of Taenia hydatigena. Histochemical study of the structural polysaccharide in the integument of gravid proglottides revealed that the main cuticle is only feebly positive to PAS reaction when compared with that of other regions of the cestode body. The significance of such change in the PAS reaction has been discussed. It was observed that there is no change in the acid mucopolysaccharide of the outer layer of the integument.


Histochemical studies on the mucosubstances in the ovotestis of a hermaphrodite land pulmonate Semperula maculata in seasonal breeding-aestivation cycle. With a view to augment the cytochemical localization characterization and, probable functional significance of mucosubstances in the ovotestis in the reproductive physiology of land pulmonates, the mucosubstances were investigated in the ovotestis of a land snail, Semperula maculata (Stylommatophora) in the seasonal breeding-aestivation cycle. Widely accepted, recent and well-established histochemical techniques were emoloyed. The results showed that the cells in the germinal epithelium of the follicular wall, were endowed with a capacity of synthesis of neutral muco-substances. They also contained glycogen. The nurse cells contained neutral mucosubstances and glycogen in them, while maturing ovum contained hyaluronic acid and protein. Among all the male germ cell stages, only matured sperms showed sialoglycoprotein in their heads and glycogen in the tails. The seasonal variations in the mucosubstances showed that the synthesis of the mucosubstances in the male germ cells of the ovotestis was initiated at the end of the breeding season and attained a maximum in the post-breeding season. Most strikingly the presence of the sperm in the follicular cavity was a permanent feature throughout the seasonal breeding-aestivation cycle of the snails. The synthesis of the mucosubstances in the ovum and the nurse cells was initiated somewhat earlier in the post-breeding season and attained a peak prior to the active breeding season. The importance of the mucosubstances synthesised by the different cells of the ovotestis, is discussed with reference to the reproductive physiology of the snails.


Studies on the mucosubstances elaborated by female duct of a land pulmonate Semperula maculata in seasonal breeding-aestivation cycle. With a view to augmenting the understanding of the mucosubstances elaborated by the epithelial gland cells in the female duct of stylommatophoran pulmonate snail in general and finding out the seasonal variations in them during the breeding seasonal cycle of the snails in particular, the female duct mucosubstances were investigated in detail employing recent well-established histochemical techniques. The results showed that the gland cells in the female duct elaborated mucosubstances consisting of neutral mucins, glycogen, weakly sulfated sulfomucins, strongly sulfated sulfomucins and sialomucins. The study of cellular sites of mucosubstance elaboration showed that there are five different types of cells, the first type elaborated neutral mucins, the second weakly sulfated sulfomucins, the third strongly sulfated sulfomucins, the fourth sialomucins and the fifth glycogen. The seasonal variations in the mucosubstances showed that the acidic mucosubstance elaboration begins just before the post-breeding period and reaches a maximum in the pre-breeding season. Cyclic variations not only in the amount of the different mucosubstances but also in the number of cells elaborating them were witnessed in seasonal breeding-aestivation cycle. Since the results appear to indicate that the stages in the maturation of female sex cells in the ovotestis and uterus are closely related to the secretory process of the glandular cells in the female duct in the seasonal reproductive cycle of these snails, the importance of the mucosubstances secreted by the gland cells in the female duct is discussed with reference to the reproductive physiology of the snails.


Demonstration of adenosine triphosphate hydrolysis in the enamel organ of the mouse incisor. The hydrolysis of adenosine triphosphate in the mandibular enamel organ demonstrated that the Mg++-activated ATPase was destroyed by pre-treatment with either heat or alcohol, substrate specific for ATP, stimulated by the addition of glutathione or dinitrophenol, and inhibited by oligomycin. The distribution of reaction product was the same with Mg++, Mn++ or Zn++ as the activating cation. Omission of Mg++ from the incubation medium, or replacement with Ca++ or Sr++ resulted in marked hydrolysis of ATP in the cells associated with enamel matrix formation, with loss of enzyme activity in the cells of the zone of enamel matrix maturation. Hydrolysis of ATP by the cells of the stratum intermedium, stellate reticulum and papillary layer was dependent upon Mg++, Mn++, or Zn++.


[Histotopochemical investigations on elastic membranes of blood vessels with special regard to diabetes mellitus. I. Proteins (author's transl)]. Histochemical investigations on elastic membranes of vessels under normally and diabetic conditions have been accomplished. These studies were made on man (diabetic and non-diabetic subjects) and on rats with streptozotocin-diabetes. The results are comparable among one another. The amino acids histidine, tyrosine and tryptophan were not demonstrable. The detection of primary NH2-groups (ninhydrin-Schiff-method and o-diacetylbenzen-reaction) was positive however. The results of the reactions in healthy men and animals were more distinct than in diabetic human subjects and animals. In healthy children the intensities of the histochemically reactions were higher than in adults.


A histochemical study on the respiratory epithelium of an eel fish - Amphipnous cuchia (Ham). The respiratory epithelium of the air sac and that of the buccal cavity resemble each other in having high vascularization, very small air/blood pathway (below 1 mum), phospholipid, ascorbic acid content and having two morphologically distinct mucous cells. The larger mucous cells appear to secrete strongly acidic sulfated mucopolysaccharides while the smaller ones are responsible for secreting sialic acid containing glycoproteins. Elongated mucous cells with foamy cytoplasm and tapering apex of the vascularised buccal epithelium are similar in histochemical properties to the same type of mucous cells reported in the epidermis of the skin. These cells secrete weakly acid mucopolysaccharides. Negligible number of mucous cells are present along the margin of the fused gill filaments of the gill. Presence of large amount of scattered phospholipid globules in the respiratory epithelium appears to be true of all the air breathing fishes utilising oxygen from air. Foreceful water or air breathing for nearly 5 1/2 h by the fish does not indicate change of phospholipid content of the respiratory epithelium but prevention of surfacing a continuous flow of water system resulted in 35% increase in blood ascorbic acid and more concentration of vitamin C granules along the respiratory epithelium.


The cytology of the testaceous rhizopod Lesquereusia spiralis (Ehrenberg) Penard. I. Cytochemistry. The cytology of the testaceous ameba, Lesquereusia spiralis (EHRENBERG) PENARD, has been described using a broad spectrum of cytochemical methods. Most cytological characteristics lie within the range of variability reported for free living non-shelled amebas. The shell of L. spiralis is complex, being composed of siliceous platelets positioned in an organic matrix. This interplatelet matrix is composed of sulfomucin complexed with basic protein. The matrix contains a complex of pore-like structures. The structure and possible origins and function of this matrix complex are discussed.


Metabolic changes in the cerebral cortex of the rat induced by intravenous pentothalsodium. The effects of thiopental on cerebral metabolism were evaluated by means of measurements of cerebral metabolic rate for oxygen (CMRO2) and of tissue levels of organic phosphates, glycolytic substrates, citric acid cycle intermediated and selected amino acids. Shortly after the beginning of thiopental administration, CMRO2 was reduced to half the normal value, and there were signs of retardation of glycolytic flux at the phosphofructokinase step. Inhibition at this regulatory enzymatic step could be related to an increase in phosphocreatine and a fall in inorganic phosphate concentration. The rise in phosphocreatine, and the unchanged levels of ATP, ADP and AMP demonstrate that induction of anaesthesia with thiopental is unrelated to energy failure. Changes in citric acid intermediated included a fall in malate, and probably also in citrate, alpha-ketoglutarate and fumarate, with a tendency towards reduction in the pool of citric acid cycle intermediates; and the amino acid changes were dominated by a progressive rise in aspartate. It is suggested that these changes are secondary to a reduced rate of pyruvate delivery, and to a decrease in malate/oxaloacetate ratio.


[Ultrastructural reaction of the multipotential glia in the cerebellum of the rat after treatment with 6-aminonicotinamide]. 6-Aminonicotinamide (6-AN), an antimetabolite of nicotinamide, damages the astrocytes and oligodendrocytes through a blockade of the pentose phosphate pathway. Both types of glia cells become hydropic. A third type of glia cell, described by VAUGHN and PETERS, the multipotential glia, is affected to a lesser extent. These cells phagocytize and form pseudopodia after treatment with 6-AN. Thus the multipotential glia cells are 'marked' by the action of 6-AN, since they are obviously less dependent on the pentose phosphate pathway in the carbohydrate metabolism.


Autoradiographic study of chick limb cartilage in vivo and in vitro and its response to mitomycin C (MMC). Effect of mitomycin C on mucopolysaccharide synthesis by the cartilage cells of chick limb bud (5-9 days old) was investigated both in vivo and in vitro by the uptake study of 35S. Control specimens (both in vivo and in vitro) showed higher concentration of silver grains, mostly intercellular, in the initial stages. Hypertrophy of cartilage cells at later stages reduced the matrix, leading to a corresponding decrease in the accumulation of silver grains. In the treated groups, both in vivo and in vitro, the silver grains were found to be less in number during the initial stage of growth than in the corresponding controls, due to the suppressive effect of the mitomycin C. However, during the later period of growth, uptake of 35S was more in the matrix of treated specimens, which was apparently not reduced due to lack of hypertrophy of cartilage cells. The mechanism of the suppressive effect of mitomycin C seems similar in vivo and in vitro.


[Animal experiment histological-histochemical studies on the development of hearing disorders related to hypothyroidism]. It has been known for a long time that hearing deficits may coexist in patients with thyroid disease, but without definite morphologic evidence present to correlate gland dysfunction with hearing disturbances. To clarify this relationship between thyroid dysfunction and hearing disturbances, the guinea pig was employed as an experimental model. 70 animals were thyroidectomized, and maintained in a hypothyroid state for varying periods of time. The animals were then sacrificed, and various histochemical studies then performed. These studies included analysis for glycosidase (beta-galactosidase, beta-glucuronidase, n-acetyl-beta-glucosamide), non-specific esterases, sulfatases, sulghydryl groups as well as mucous substances within the cochlea and saccus endolymphaticus of the experimental animals. Results indicated that hyaluronidase-sensitive mucous substances were increased in the scala of the inner ear. As a consequence of increased deposition of acid mucopolysaccharides, the relationship of potassium to sodium in endolymph and perilymph was found markedly altered. Marked swelling of the chambers of the inner ear was noted, and believed to represent hydropic induction by acid mucopolysaccharide-with consequent alteration of electrolyte relationships ("Electrochemical Theory").


On the possible involvement of sulphomucopolysaccharides in the storage of catecholamines within the central nervous system. Rats treated at birth with 6-OH DA were sacrificed in adult age 24 h after an injection of 3H-NA. Synaptosomes were isolated from the cerebral cortex, the hypothalamus, the pons-medulla region and the cerebellum. The similar distribution pattern of 3H-NA and 35S on gradient centrifugation of the synaptosome preparations, the similar effect of 6-OHDA on the uptake of 3H-NA into slices of brain tissue in vitro and on their 35S content as well as the identification of chondroitin and heparan sulphate in the synaptosome fractions are observations which indicate a possible function of SMPSs in the storage of NA in adrenergic terminals.


Comparison of the effects of physical exercise, cold acclimation  and repeated injections of isoprenaline on rat muscle enzymes. The metabolic effects on rat cardiac and skeletal muscle of a strenous program of swimming, of cold acclimation and of isoprenaline treatment (0.3 mg/kg daily for 5 five-day weeks) were compared. Exercised and cold-exposed rats gained less body weight than did controls or isoprenaline-treated rats. In all treated groups the heart and the intercapular brown adipose tissue hypertrophied. The size of the adrenals increased only in isoprenaline-treated animals. Cold-acclimation and physical training increased and isoprenaline treatment reduced or did not affect the activities of succinate dehydrogenase, malate dehydrogenase and citrate synthase of cardiac muscle. In the skeletal muscle all treatments resulted in increased activities of these enzymes. Of the anaerobic enzymes analysed, only the activity of hexokinase increased in response to the treatements used. This increase was the same in cardiac as in skeletal muscle, but it was significantly greater with isoprenaline-treatment than with training or with cold-acclimation. The activities of lactate dehydrogenase and phosphofructokinase did not differ significantly. All treatments improved cold resistance, but only swimming exercise and cold acclimation significantly increased tolerance to exercise. It is concluded that prolonged stimulation of adrenergic beta-receptors by catecholamines is responsible for the metabolic changes observed.


Studies on the metabolism of beta-hydroxy- aspartic acid. The content of beta-hydroxyaspartic acid was measured in the urine of man and several species of animals. The configuration of urinary beta-hydroxyaspartic acid was deduced to be L-erythro in form by chromatographic comparisons with authentic samples. An increased excretion of urinary beta-hydroxyaspartic acid was observed in cats when serine or thiamine was administered with glycine. Glycine-1-14C administered to rats was incorporated into the urinary beta-hydroxyaspartic acid. The formation of beta-hydroxyaspartic acid in pig-liver homogenate increased in the presence of glutamate and thiamine pyrophosphate. These results were discussed in relation to the author's working hypothesis on the biosynthesis of beta-hydroxyaspartic acid.


Electrical and mechanical activities of longitudinal muscle contraction elicited by transmural electric stimulation. Intracellular electrical and mechanical activities were simultaneously recorded from the longitudinal muscle of isolated guinea-pig jejunum when the preparation was stimulated transmurally by square pulses of 1 msec, 10 Hz, 10-40 V. Transmural stimulation of more than 30 V induced co-ordinated peristaltic waves under intraluminal pressure at levels subthreshold for the peristaltic reflex. Transmural stimulation of less than 30 V induced various types of mechanical responses. After termination of stimulation, rebound excitation was observed. Electrical activities of the longitudinal muscle were compared with various mechanical responses. Slow depolarization without spike potential was recorded when the longitudinal muscle contracted without circular muscle contraction. However, spike potential was recorded from the longitudinal muscle when circular muscle contraction was present as a response. Hyperpolarization was observed soon after the beginning of stimulation. This hyperpolarization was persistent to atropine at 10(-6) g/ml. These electrical and mechanical responses to transmural stimulation disappeared when the preparation was treated with tetrodotoxin at 2 X 10(-7) g/ml.


A method for microdetermination of major neutral lipids and an application of the procedure to tissue lipids. Cholesterol, cholesteryl esters, triglycerides and fatty acids as major neutral lipids and phospholipids were examined in quantitative analysis. The method consisted of three steps: (1) separation of lipids by one-dimensional thin-layer chromatography on silica gel plates; (2) elution of neutral lipids from scraped silica gel with chloroform-methanol (4:1); and (3) colorimetric determination of individual neutral lipids in eluates and phospholipids in silica gel. The conditions were modified for chromotropic acid reaction for determining triglycerides. Laurell's method for determining fatty acids was also modified to apply to quantitative thin-layer chromatography. The accuracy of the modified methods was well-defined as the absorbance values were on a linear curve. A quantitative study was made of the recovery of triglycerides and fatty acids after chromatography. Combining these modified methods and colorimetry for determination of cholesterol cholesteryl esters and phospholipids, the author established a micromethod for determining the major neutral lipids and phospholipids by thin-layer  chromatography. Lipids from HeLa, S-3 cells were analyzed to examine the applicability of this method to tissues. The results indicated that the new method permitted a reliable estimation of the major neutral lipids and phospholipids from small amounts of tissues.


The maturation of reticulocytes. I. Following introduction of reticulocytes into polycythemic and normocythemic animals. Investigations were conducted on the life-span of "stress" reticulocytes and the fate of the early denucleated large-sized reticulocytes in  circulating blood. Reticulocyte disappearance was examined after reticulocyte introduction into the vein and into the peritoneal cavity of polycythemic and normocythemic animals. The results indicated that these introduced reticulocytes matured to red cells by about 36 hours after injection under both the polycythemic and normocytehmic conditions. The large-sized reticulocytes disappeared by about 4 to 12 hours after introduction. The maturation of reticulocytes was largely arrested when the cells were introduced into the peritoneal cavity.


The maturation of reticulocytes. II. Life-span of red cells originating from stress reticulocytes. Life-spans of macroreticuloytes and macrocytic red cells were studied. Rabbits were made anemic by injecting phenylhydrazine. Peripheral blood rich in reticulocytes was drawn, labeled with 3H-amino acids, and injected back into the anemic animal. Autoradiographic observation on circulating red cells revealed that macroreticulocytes matured at nearly the same time as normal-sized reticulocytes but that the macrocytic red cells had a short life-span compared to normal-sized red cells.


Large round cell granulomas induced by murine sarcoma virus (Moloney) in mouse brains. The effect of murine sarcoma virus of Moloney strain on central nervous system was examined morphologically in Swiss mice of different age. A single intracranial inoculation of cell-free virus solution resulted in the induction of characteristic intracerebral granulomas in 82.8% of the newborn to 5 day-old group, in 71.4% of the 6 to 10 day-old group, and in 68.0% of the 11 to 20 day-old group. The mean latency periods to tumor recognition were 16.5, 21.1, and 33.5 days, respectively. The granuloma consisted of inflammatory cell infilrations, reactive gliosis, and richly developed blood vessels. The lesions consistently contained numerous characteristic large round cells. In cases of long-survival, the findings included reparative changes, such as extensive gliosis, withdrawal of inflammation, and a decrease in the numbers of large round cells and blood vessels. These lesions were tentatively designated as "large round cell granuloma." The early foci of the granoloma were composed of proliferating glial cells and large round cells at the subependymal regions. Electron microscopically these large round cells had abundant intracytoplasmic fibrils quite similar to gliofibrils. Numerous C-type virus particles were present in the intercellular nad perivascular spaces, and occasionally budded from cell membranes of the large round cells and vascular endothelia. The large round cells were considered to be reactive astrocytes activated by biral infection. It was conclided that MSV-M was not a sarcomogenic but a granulomogenic virus in mice. Control animals showed no pathological changes.


Cyanotic congenital heart disease.

Cyanotic congenital heart disease. This review describes the evolving concepts of diagnosis and management of patients with cyanotic congenital heart disease. Early palliative surgical procedures were followed by reparative operations and are now to a large extent replaced by these operations which are designed to relieve the problem. Collaboration of the team of cardiologists, surgeons, radiologists, anesthesiologists and nurses has made the many developments possible. The teamwork has not only widened the scope of what can be accomplished but has also extended the opportunities for beneficial reparative surgery down to the first weeks and months of life. Precise diagnosis and meticulous operative and perioperative care by the team are essential elements of success. Long-term follow-up and regular analyses of results have led to continuing improvements. Although these patients were born to be blue, their color and their outlook have been changed during these last 3 decades to something close to rosy.


Differentiation of normal human mammary epithelial cells in culture: an ultrastructural study. An ultrastructural and cytochemical study of normal human mammary epithelial cells cultured from post-weaning breast fluids is described. Cells were examined at the time of plating and at intervals up to 28 days in culture. Three different stages in the morphological differentiation of these cells in vitro were observed: (1) the first stage was the formation of a monolayer of single cells, which occurred between days 1 and 10 in culture. The cells in this stage were not interconnected by junctional complexes and lacked Mg++- dependent ATPase activity in the plasma membranes, but did contain a large quantity of lipid and exhibited some secretory characteristics. (2) The second stage, occurring at 10 to 16 days in culture, was characterized by the formation of junctional complexes, the appearance of Mg++-dependent ATPase in the plasma membrane and a decrease in the number of dense bodies with peroxidase activity. (3) The third stage, occurring at 16 to 28 days in culture, was characterized by the formation of stratified layers of epithelial cells, which were interconnected by a larger number of desmosomes with numerous pleomorphic microfilaments. The Mg++-dependent ATPase activity in the plasma membrane was retained and the dense bodies with peroxidase activity were rarely observed at this stage. During the last seven days were prominent in the cells of the stratified layer. After 28 days in the culture, the cells began to round up and slough off the culture plate.


Epidemiology of hepatitis B virus in an institution for mentally retarded persons. Sera from patients and employees of the Lynchburg Training School and Hospital were tested for Hepatitis B surface antigen by complement fixation test and antibody against Hepatitis B surface antigen by radioimmunoprecipitation test. Hepatitis B surface antigen was detected in 20% of the Down's syndrome patients and 7 percent of the matched other retarded patients. Antibody against Hepatitis B surface antigen was detected in 40% of the Down's syndrome and 57% of the matched other retarded patients. Hepatitis B virus infection as measured by presence of either Hepatitis B surface antigen or antibody was similar in the Down's syndrome patients (59%) and the matched other retarded patients (63%). Male patients had a higher frequency of Hepatitis B surface antigen chronic carriers and a lower frequency of antibodies to Hepatitis B surface antigen than the female patients. No relationship between age at time of first institutionalization and prevalence of Hepatitis B virus infection was demonstrated. However, it was observed that patients institutionalized at an earlier age were more likely to be housed in wards with a high frequency of Hepatitis B surface antigen. Increased length of institutionalization was associated with increased prevalence of Hepatitis B virus infection. Antibody to Hepatitis B surface antigen was detected in 33% of the employees. Employees who worked on wards with a high frequency of Hepatitis B virus infection had a high frequency of Hepatitis B surface antibody (50%) whereas those working on wards with a low frequency of infection had a low frequency of Hepatitis B surface antibody (9%).


Hepatitis and Down's syndrome.

Hepatitis and Down's syndrome. Data obtained concerning Hepatitis B as a possible couse of Down's syndrome, neonatal hepatitis, and the occurrence of Hepatitis A and B in institutionalized Down's syndrome and matched non-Down's syndrome retarded patients was summarized. The results of our studies indicated that Hepatitis B infection during pregnancy was not related to the genetic changes associated with Down's syndrome. It was further indicated that in institutionalized patients the incidence of Hepatitis B infection in both Down's syndrome and other mentally retarded patients was similar. Within the institition we studied, the incidence of Hepatitis B varied among wards. This ward variation seemed to be related to age at time of institutionalization and degree of mental retardation. Those patients with most retardation and those institutionalized at an early age were placed on wards with highest incidence of Hepatitis B antigenemia.


Mental retardation and stress on the parents: a contrast between Down's syndrome and childhood autism. Mothers of autistic, Down's syndrome, and outpatient psychiatric clinic children completed a questionnaire about their attitudes toward the identified child and the effects of the child on themselves and their families. A canonical correlation between the 15 questionnaire scales and three groups revealed a general retardation/social dependency factor separating the mothers of the two retarded groups from the clinic sample. The autism group was differentiated from the Down's syndrome group by scales measuring severity of the child's handicap and family integration problems more than by scales measuring stress on the mother. The hypothesis that mothers of autistic children would report more problems than both other groups was supported; the hypothesis that mothers of Down's syndrome children would report more problems than mothers of outpatient clinic children was not.


Long-term treatment of hyperkinetic heart syndrome with propranolol. Twelve men suffering from the primary hyperkinetic heart syndrome (PHHS) displayed palpitation, rapid and forceful heart action, increased pulsations of the large arteries, cardiac systolic murmur, and the following circulatory values (averages): systolic arterial pressure (SAP) =154 mm Hg; heart rate (HR)=91 b/min; cardiac index (Ci) =5494 ml/min/m2; left ventricular mean systolic ejection rate index (SMEJR) =227 ml/min/m2; left ventricular mean pre-ejection delta P/delta t (delta P/delta t) = 1.32 mm Hg/msec. A two-year followup during which propranolol was administered (80-160 mg/day) revealed good subjective improvement and disappearance of signs of circulatory hyperkinesis. At the end of this period the hemodynamic functions were as follows: SAP=134; HR=69; Cl=3489; MSEJR=171; delta P/delta t=0.89. Substitution of placebo for the active drug caused prompt reappearance of symptoms of cardiac overactivity in each patient, and brought the circulatory functions back to these levels: SAP=157; HR=96; Cl=5530; MSEJR=245; delta P/delta t=1.33. These findings lend further credence to the concept that the PHHS is, indeed, a definable disease entity; they also document that propranolol ameliorates the symptoms of the disease but is ineffective for the underlying disorder.


Heart in Friedreich's ataxia.

Heart in Friedreich's ataxia. Most articles on Friedreich's ataxia report that cardiac complications are almost universal in patients with this disease. However, the present study of 30 cases, observed for two to ten years, seems to belie the experience of other writers in the field. Only six (20 per cent) of these patients showed electrocardiographic abnormalities. Only one patient had cardiac enlargement and congestive heart failure. One other patient had paroxysmal tachycardia. Seventy-four family members were also studied and the results were similar. It is suggested that this impressive difference may be a racial one and indeed very few reports on Friedreich's ataxia have come from India. Further study of this group of patients is in progress. The author also includes a review of the literature of neuromyopathic diseases and their relationship to myocardial involvement.


Birth weight of children with Down's syndrome. The difference in birth weight between children with Down's syndrome and their siblings was estimated to be in the interval from .18 to .37 kg with 90 percent confidence, the Down's syndrome infants having the smaller mean birth weights. When we adjusted their birth weight, using a multiple linear regression analysis, to take into account several factors known to affect it, the difference in birth weight was only slightly less than the unadjusted difference. The data support the hypothesis that an extra chromosome No. 21 results in a smaller than expected birth weight.


The metabolic clearance rate of dehydroisoandrosterone sulfate. IV. Acute effects of induced hypertension, hypotension, and naturesis in normal and hypertensive pregnancies. In the present study, the metabolic clearance rate of dehydroisoandrosterone sulfate (MCRDS) decreased in normotensive gravidas during short-term studies utilizing angiotensin II-induced elevation of blood pressure. Therapy with hydralazine hydrochloride in chronic hypertensive gravidas resulted in a decrease in blood pressure and an accompanying decrease in the MCRDS. A variable response was observed in the apparent volume of distribution of DS (AVDDS) during therapy with hydralazine hydrochloride. Decreases in MCRDS also occurred in chronic hypertensive gravidas following therapy with 40 mg. of intravenously administered furosemide despite a failure of blood pressure to be altered. The AVDDS increased in four of five patients receiving furosemide, suggesting a possible direct action of furosemide upon vascular smooth muscle.


Maternal mortality rates in eclampsia.

Maternal mortality rates in eclampsia. This study evaluates the dominant factors that influence the course of eclampsia toward a lethal outcome by means of statistical analysis of various clinical, laboratory, and morphologic data of 365 cases of toxemia with convulsions, that included 49 deaths and 33 autopsies, registered during a 9 year period. This communication suggests that the death of eclamptic patients resulted from a combination of several factors that showed a very wide individual variation. Since advancing age of the mother was associated with a high incidence of coincidental renal and vascular diseases, this was the most clearly influential factor. The presence of twins, delay in hospitalization, under haste in deciding upon cesarean delivery, and underestimation of the initial clinical condition were all influential factors, although without statistical significance. Cesarean section, performed in 141 instances of ante- and intrapartum eclasmpsia (40.4 per cent), was not associated with a higher maternal mortality rate.


Cardiac output in the fetal lamb: the effects of spontaneous and induced changes of heart rate on right and left ventricular output. Right and left ventricular outputs were measured continuously in fetal lambs in utero for 2 to 21 days after implantation of electromagnetic flow tranducers around the main pulmonary trunk and ascending aorta. Surface pacing electrodes were implanted on the left and right atria. The intact cervical vagus nerve was stimulated by electrodes implanted around the nerve. Spontaneous increased in fetal heart rate were associated with increases in both right and left ventricular outputs and spontaneous falls in heart rate with reduction in both  outputs. There was a linear relationship between fetal heart rate and ventricular outputs. Vagal stimulation reduced fetal heart rate with a consistent and linear fall in ventricular output. Left atrial pacing increased right ventricular output by 15 to 20 per cent but produced a variable response, ususally a fall, in left ventricular output. Right atrial pacing resulted in increases in both outputs but the increase in right ventricular output was less than during left atrial pacing at the same rate. The difference in response of ventricular outputs to induced as compared to spontaneous heart rate changes relates to the effects on left and right atrial phasic pressure relationships. These changes probably alter blood flow patterns across the foramen ovale.


Thiocyanate inhibition of ATPase and its relationship to anion transport. Adenosine triphosphatase activity not dependent on sodium or potassium but inhibited by thiocyanate is present in broken-cell homogenates of eel gill and rat kidney. This enzymatic property is predominantly associated with mitochondria, although thiocyanate-inhibited ATPase can also be detected in microsomes with little or no mitochondrial contamination as measured by the activity of the mitochondrial marker enzyme succinic dehydrogenase. When eels are transferred from fresh to salf water, thus increasing active outward transport of chloride across the gill, the thiocyanate-inhibited ATPase of gill microsomes does not change, though the activities of succinic dehydrogenase and Na-K-ATPase in gill homogenates are augmented. The thiocyanate-inhibited ATPase of homogenates of outer renal medulla does not differ from that of renal cortex, in contrast to Na-k-atpase which is higher in renal medulla than in cortex. The data do not support a role for thiocyanate-inhibited ATPase in active chloride transport by epithelial tissues.


Myocardial transcapillary exchange in the hypertrophied heart of the dog. Myocardial transcapillary exchange was investigated in control hearts and in two types of hypertrophied hearts: exercise hypertrophy and pathological hypertrophy due to tricuspid insufficiency. Using the single-injection indicator diffusion method (6, 28), myocardial extractions (E), capillary clearances (C), and permeability surface area products (PS) of urea, sucrose, and inulin were measured in intact, pump-perfused, working hearts of anesthetized dogs. Both types of cardiac hypertrophy were associated with a decreased coronary vascular resistance. Myocardial E, C, and PS values from the exercised group were not significantly different from control. Dogs with pathological hypertrophy exhibited increased central venous pressures, RVEDP's, and heart rates which were greater than control values. The E, C, and PS values from the pathologically hypertrophied hearts were significantly greater than control. These increases in myocardial transcapillary exchange can be explained either by increasing the equivalent pore radius of myocardial capillary membranes from a control value of 70 to 100 A or by assuming that pathologically hypertrophied hearts have a myocardial capillary surface area available for exchange which is twice that of control hearts.


Potassium adaptation and Na-K-ATPase activity in mucosa of colon. The specific activity of sodium-potassium-activated adenosine triphosphatase in the mucosa of the colon rises when the dietary load of potassium is increased. The change in enzymatic activity depends on the presence of intact adrenal glands, since adrenalectomy abolishes the response of Na-K-ATPase to potassium loading. The increased secretory rate of aldosterone normally evoked by potassium loading appears to mediate at least in part of the effect of potassium loading, since aldosterone induces a discernible increase in the specific activity of Na-K-ATPase in the colon of adrenalectomized rats.


Embryo transfer in pigs: a method for introducing genetic material into primary specific-pathogen-free herds. Fifty-five embryos were transferred from 4 Duroc donor sows into 4 crossbred recipient gilts. The embryo survival rate was 66%; 53% of eggs ovulated by donors were represented by live pigs at term. Three of the litters were obtained by hysterectomy of the recipients and introduced into a primary specific-pathogen-free herd, thereby saving the donor sows for subsequent use. Embryo transfer provided a method for exploiting the genetic potential of superior females.


Some gas machine hazards and their elimination. Constant improvement in anesthetic gas machines has been the objective mutually of anesthesiologists, manufacturers, and engineers. Yet the literature continues to report mishaps, sometimes fatal to the patient, due to machine design or function or to "human error." The author reviews some of these hazards and describes proposals for their elimination. He points out that initiative on the part of anesthesiologists is vital in spurring needed changes by manufacturers.


A gentamycin resistance plasmid in Staphylococcus aureus. Drug resistance in Staphylococcus aureus is frequently mediated by non-chromosomal DNA molecules referred to as R plasmids. So far, resistance to aminosidic antibiotics was observed with streptomycin [8] and kanamycin-neomycin [3]. Resistance to gentamycin has not been reported in a recent survey by Lacey [7]. In this paper, we describe a strain of S. aureus resistant to gentamycin-kanamycin-tobramycin-sisomycin, and experiments which suggest that the genetic determinant of these resistance characters is plasmid borne.


[Skin pigmentation after amiodarone administration. Histogenetic problems]. The authors present a pathological study of the skin in a 62 year-old man with facial pigmentation due to amiodarone. They found under the light microscope, cells resembling histiocytes filled with pigment. They were less numerous than usually reported, but were found associated with a pericapillary and periglandular lymphocytic infiltration, which raises the problem of iatrogenic lupus or Jessner-Kanoff's disease. Examination under the electron microscope, permitted identification of 5 groups of granulations, three of which had already been observed by Mrs. Fagola. These pigments correspond to lipofuscins, melanin, but also yet unidentified substances, may be metabolites of amiodarone.


Pathogenesis of subacute spongiform encephalopathies. The subacute spongiform encephalopathies include scrapie of sheep, transmissible mink encephalopathy, and kuru and Creutzfeldt-Jakob disease of man. These diseases are caused by filterable infectious agents with unique physical properties. The usual sources of infection in nature are not completely known. Epidemiological evidence suggests that the agents may enter the body through breaks in the skin and mucous membranes. Experimental studies of scrapie after subcutaneous inoculation demonstrated early replication of the agent in lymphoid tissues and later appearance in other organs; as the amount of agent in the central nervous system (CNS) increased, it decreased in or disappeared from lymphoid tissues. In preliminary studies of kuru and Creutzfeldt-Jakob disease, the infectious agents were regularly recovered from the brains of clinically-ill patients and experimental animals but only occasionally from organs outside the CNS. It remains to be seen if early events in the pathogenesis of the two human diseases, before the appearance of clinical signs, are similar to those in scrapie.


[Comparative study of the biological activity of tetracycline hydrochloride and morphocycline by using reverse turbidimetry]. The method of back turbidimetry was used for determination of the biological activity of the antibiotics, since high turbidity of the nutrient medium with Staph. aureus as the testculture prevented from direct measurements. Broth containing phosphate buffer, Staph. aureus and definite concentrations of the antibiotic was used as the reference solution. The experiments showed that the differences in the biological activities of tetracycline hydrochloride and morphocycline may be found with the method of back turbidimetry 6-8 hours after the microbe cultivation on media with the antibiotics.


Results of treatment of incisional hernias with extractable prostheses. A series of 80 patients with an incisional ventral hernia were treated with an extractable prosthesis in the period 1 January 1965--1 January 1974. The results are discussed. After a description of the advantages of an extractable prosthesis, attention is given to a number of factors which are possibly of importance in the development of such a hernia. This is most probably a multifactorial process, in which suturing technique, wound infection, obesity and postoperative rise of intra-abdominal pressure may play a part. The technique of inserting the extractable prosthesis is accurately described and illustrated with drawings and photographs. Success was ultimately obtained in 86.25% of the cases. The failure rate was 13.75%. In comparison with the data from the literature, this is a low percentage, the more so because the author's series consisted mainly of large incisional hernias. Recurrences can be treated successfully several times with an extractable prosthesis. This is, in general, easy in view of the smaller dimensions of the hernial orifices. The extractable prosthesis is recommended both for the treatment and prevention of incisional ventral hernia.


Immediate and delayed hypersensitivity in chronic dermatophytosis. Delayed hypersensitivity (DH) to seven common antigens was examined in 38 men with chronic dermatophyte infections and in 20 controls. A similar percentage of the infected and the control groups reacted to four antigens. In addition to showing a low frequency of DH to trichophytin, the infected group also showed a significant reduction in their reactions to intradermal mumps skin test antigen and to a Rhus oleoresin patch test. Two members (5%) of the infected group were anergic to all tests. Patients with chronic dermatophytosis appear to have a relatively specific defect in DH to trichophytin, but their cell-mediated responses to other antigens may also be somewhat decreased. The subjects studied did not appear to suffer excessive morbidity from infectious diseases, other than dermatophytosis.


The safety of long-term clindamycin therapy for acne. Sixty patients with severe pustular and cystic acne were treated for prolonged periods with clindamycin (150 mg to 300 mg daily). The average duration of therapy was five months, with 18 patients being treated for more than six months. Only two (3.4%) patients developed mild diarrhea, which was rapidly reversible on discontinuance of the drug. No other adverse reactions were observed. These data suggest that long-term, low-dose clindamycin therapy may be safe for severe pustular of cystic acne.


Topically applied niacinamide in isoniazid-induced pellagra. A patient with tuberculous meningitis developed a pellagra-like skin eruption after treatment with isoniazid. Administration of the drug was continued, and a topical preparation of niacinamide (nico-tinamide) was applied to one half of the face and the back of one hand. The areas treated responded rapidly, and subsequently all affected areas of the patient were treated, with almost complete resolution of the rash. At the same time, there was noticeable improvement in the patient's depression and apathy. We suggest that all of these changes could be due to percutaneous absorption of niacinamide.


Generalized seborrhoeic dermatitis. Clinical and therapeutic data of 25 patients. Twenty-five infants with generalized seborrhoeic dermatitis have been studied with reference to the provision of optimum treatment. Leucocyte counts and chest x-ray examination are recommended in every case. Irrespective of clinical findings, antibiotics should be given to patients with overt bacterial infection and those with leucocytosis, shift to the left, and toxic granulation. One group of infants was treated with vitamin B complex plus biotin given slowly intravenously over 24 hours; a second group was given only biotin intravenously over 2-3 hours; and a third group only biotin over 1-2 minutes. A fourth group was treated with both biotin and antibiotics for confirmed or suspected superimposed bacterial infection. The results were excellent in all groups. Skin lesions improved within 4-8 days and cleared completely within 15-30 days. Intravenous administration of biotin is recommended as less painful and less dangerous than multiple intramuscular injections.


Comedo formation in acne.

Comedo formation in acne. Comedones contain a considerable quantity of water. In some cases a water content of more than 40% can be detected. The comedo consists of two parts, an inner nucleus built up to unorganized materials and a capsule with concentrically arranged shells. The material of the nucleus contains small scales produced by normal keratinization. The materials of the capsule consists of larger scales, which result from hyperkeratosis. The nucleus of the comedo seems to be identical with the early comedo. A similar structure can be formed in vitro by adding water to sebum. Microorganisms have optimal growth conditions in the early comedo.


[Electrocardiography of the hypertensive patient: correlations with hemodynamic parameters]. A comparative study between electrocardiographic signs of left ventricular hypertrophy and haemodynamic parameters is performed in 184 permanent hypertensive patients. They are divided into 3 groups taking into account the level of electrocardiographic changes. Patients with a normal electrocardiogram have a slight increase in arterial pressure, an increase in cardiac index (P is less than 0.01) and total peripheral resistances (P is less than 0.001) and a reduction of plasma volume (P is less than 0.001). Patients with a moderate change in their electrocardiogram have normal cardiac output, high peripheral resistances (P is less than 0.001) and a slight decrease in plasma volume (P is less than 0.05). Patients with a left major ventricular hypertrophy have a reduced cardiac output (P is less than 0.01), increased peripheral resistances (P is less than 0.001) and a normal plasma volume. The significance of such facts, especially concerning the hemodynamic response in upright position, is discussed.


Laparoscopic ovarian biopsy in seventy-one amenorrhoeic patients. During laparoscopy we performed 132 ovarian punch biopsies in seventy one amenorrhoeic patients. With increasing experience, laparoscopic ovarian biopsy is a valuable element in the examination of amenorrhoeic patients. Biopsy specimens with an edge length of 4-5 mm for surface and depth can be obtained during laparoscopy under general anaesthesia without any great risk or difficulty. When performed bilaterally, it provides a representative picture of the cellular structure and function of the ovaries and thus makes a contribution to the prognosis of a disturbance in the endocrine regulating-circuit of ovarian function. In addition, the ovarian biopsy provides information about the basic gonadotrophic situation of the patient as a longitudinal section. It should be included in the synopsis of all endocrine and genetic parameters of a patient, particularly in clinic in which the morphological substrate of disturbed functions and apparent diseases is still examined.


Investigation of 17-ketosteriod excretion in mastopathia and premenopausal breast cancer. Measurement of the excretion of total 17-ketosteroids, androsterone, etiocholanolone, and dehydroepiandrosterone demonstrate in contrast to the well known age dependency of normal women in cases of both mastopathia and breast cancer the following results: 1. the age dependence of the 17-ketosteriod excretion is not marked; 2. the total 17-ketosteroid excretion is lower than that of normal controls, 3. the values of the etiocholanolone excretions and that of the dehydroepiandrosterone excretions are similarly lower.


Urinary excretion of 17-ketosteroids in patients suffering from mammary cancer. 1. The excretion of dehydroepiandrosterone is lower in patients suffering from mammary cancer than in healthy women. 2. There doesn't exist any relation between the 17-ketosteroid excretion and the age of postmenopausal women. 3. Patients with mammary tumors in stages III and IV are characterized by a lower excretion of dehydroepiandrosterone in percental parts than patients in stages I and II. 4. In patients with mammary tumors in stages III and IV and in patients with recurrences independently from the tumor stages we find higher extrem values for aetiocholanolone and smaller ones for dehydroepiandrosterone than in the other stages. 5. The quotient of percental parts of excreted aetiocholanolone to dehydroepiandrosterone shows significantly higher values for patients with recurrences than without them. 6. The quotient of aetiocholanolone to dehydroepiandrosterone is not a valid factor for a postoperative control of recurrences of the disease.


Content analysis of verbal communication between spinal cord injured and nondisabled male college students. Does the interaction between a disabled person and a nondisabled person differ in content and climate from the interaction between two nondisabled persons? The purpose of this study was to compare dyadic interaction behavior of traumatically disabled and nondisabled men paired in homogeneous or mixed dyads. Forty-five disabled and 45 nondisabled men, assigned to dyads consisting either of two disabled students, two nondisabled students, or one disabled and one nondisabled student, discussed a low, medium and high intimacy topic. A group of trials analysis of variance was used to assess the effects of dyad composition and topic intimacy on self-disclosure. Dyads consisting of two nondisabled partners exhibited the least self-disclosure at all levels of topic intimacy. Dyads in which both partners were disabled exhibited the most self-disclosure on low and medium intimacy topics and had the greatest frequency of disability related responses. The mixed dyads exhibited the most self-disclosure on the high intimacy topic. Disabled subjects in homogeneous dyads exhibited greater depth of self-disclosure than nondisabled subjects in homogeneous dyads. The implications of the results are discussed in terms of facilitating the acquisition of interaction skills for traumatically disabled persons, evaluating patient-staff communication and the role of peer counseling in rehabilitation settings.


[Vessels of the heart and lung in some experimental defects]. Under study were changes of intraorganic blood vessels of the heart and lungs in some experimental defects (open arterial defect, coarctation of the aorta, simultaneous existence of these two defects, stenosis of the pulmonary trunk, defect of the interatrial septum, triad of Fallot, syndrom of Lutembachet). Morphological data correlated with blood pressure in the pulmonary circulation and cardiac chambers. The complex of compensatory-adaptational mechanisms consisting of comparatively active and passive zones is formed in the heart and lungs. In most cases the changes develop in the vessels already existing. In hypertrophy of the myocardium when there is hypertension and hypervolemia in coronary vessels, sinusoids perform the function of blood reservoir, to a certain degree balancing the blood pressure, and luminar ducts relieve the muscle from excessive blood. The changes in the vascular system of the lung are directly dependent upon the pressure in the pulmonary circulation and the duration of observation. The closing arteries are the most active link in the chain of compensatory-adaptational mechanisms.


[Secretion of the intercalated cells of the fibrillar epithelium of the mucous membrane of the maxillary sinus]. Cytological and histochemical methods were used in order to establish that the intercalated cells of the ciliated epithelium of the rabbit's maxillary sinus mucosa performed gland function giving secretion formed in the shape of granules and represented by neutral mucopolysaccharides. Analysis of the morphology of intercalated cells, the amount of secretion in them, the shape and disposition of the Golgi apparatus and the nucleus allowed establishing 4 successive phases in their secretory cycle: the phase of synthesis, accumulation, aquosity and sectering. Under normal conditions of life the secretory activity of intercalated cells was asynchronous. In experiments with synchronization of the secretory activity by administration of pilocarpine it was established that the duration of the intercalated cells secretory cycle was 16-18 hours. Active participation of alkali phosphatase in the synthesis of secretion in the ciliated epithelium was noted.


Dental treatment for handicapped patients. 1. The efficacy of a preventive programme for children. 11. Economics of dental treatment-a cost benefit analysis. A comprehensive programme of treatment and home care was shown to be effective in greatly reducing dental caries, improving oral cleanliness and controlling gingivitis in handicapped patients. Maintenance required less than half the time and approximately one-third of the cost of initial restoration.


[Occupational skin allergy to alerc (Fitzroya cupressoides)]. The authors report a case of skin allergy to Fitzroya cupressoides (Alerce), and describe the phytochemical classification of that tropical tree. The method of detection of this skin allergy is detailed.


27 Years of occupational dermatology in Finland. A survey is given of the actual causes of occupational dermatoses and the variation in their incidence in a series of 4,529 patients seen at the out-patient clinic for skin diseases in the Institute of Occupational Health, Helsinki, and its precursor, during the 27-year period from 1946 to 1972. The overall incidence was highest for alkalis and detergents, cement, oil of turpentine and other solvents. Due to the increased use of synthetic resins in recent years a rise was seen in the frequency of eczema caused by these substances. Nevertheless, eczema due to rubber chemicals has also increased. The decreased incidence of turpentine eczema reflects its reduced use. In 45% of the cases the diagnosis was verified by positive epicutaneous tests. Of the 8,057 patients admitted because of a suspected occupational skin disorder, a non-occupational skin disease was diagnosed or the occupational origin remained unproved in 3,528 cases. The most important differential diagnoses and the differences in the location of the skin changes in the non-occupational as compared with the occupational group are discussed.


[Double blind test with a protective ointment (Ivosin) on the hands of cement workers]. 56 builder's labourers manipulating lime cement applied a protective cream on their hands and 57 used a placebo in a double blind test of two months' duration. The labourers, the doctors who surveyed the condition of their hands, and the statistician who analyzed the results knew only that one cream had a blue label, and the other a green one. Before and after the test, the presence or the absence of certain symptoms on the hands were objectively examined, while the subjective opinion of the labourers was registered at the end of the test. As usual in tests of that kind, the great majority of the labourers (more than 75%) were satisfied, 62% of them acknowledged an improvement. That percentage justified a comparative double-blind study that revealed a much higher quota (86% of the test persons) of satisfaction among the labourers treated with Ivosin than in the placebo group (66%). That difference was statistically significant. On the other hand, no objective difference could be revealed between the two groups. It was impossible to discover among the symptoms studied, any objective cause of that subjective difference.


Basolateral plasma membranes of intestinal epithelial cells. Identification by lactoperoxidase-catalysed iodination and isolation after density perturbation with digitonin. Lactoperoxidase-catalysed iodination was used to label intestinal epithelial cell sheets with 125I. The iodination was carried out under conditions that allowed little penetration of lactoperoxidase into the cells and membrane-bound 125I therefore provided an effective marker for following plasma-membrane fragments through subcellular-fractionation procedures. 2. After homogenization and isopycnic zonal centrifugation through sucrose gradients two peaks of membrane-bound 125I were detected. One coincided with brush border enzymes such as alkaline phosphatase, disaccharidases and L-leucine B-naphthylamidase, whereas the other was coincident with the major peak of (Na++K+)-stimulated ATPase (adenosine triphosphatase), which has been thought to be concentrated in the basolateral plasma membranes of these cells. Neither peak of 125I reflected the distribution of any marker for an intracellular organelle. 3. A larger proportion of the (Na++K+)-stimulated ATPase, and thus of the basolateral plasma-membrane material, was found in a crude 'mitochondrial' fraction. It was not readiily separated from mitochondria by conventional techniques of subcellular fractionation. 4. Treatment of the 'mitochondrial' fraction with digitonin increased the density of basolateral plasma membrane but had little effect on mitochondrial density. A purified preparation of digitonin-loaded basolateral plasma membranes was isolated at a density of 1.20-1.22 by isopycnic centrifugation. 5. The enzymic composition of this preparation of basolateral plasma membranes is compared with previous preparations isolated from intestinal mucosal 'scrape' materials and from isolated cells.


Characterization of sulfhydryl groups on chloroplast coupling factor 1 exposed by heat activation. Two sulfhydryl groups in the gamma subunit of solubilized chloroplast coupling factor 1 (CF1) are exposed by heat activating the enzyme. These two groups have been selectively labeled with [3H]-N-ethylmaleimide, N-[p-(2-benzoxazolyl)phenyl]maleimide (NBPM), and N-(4-dimethylamino-3,5-dinitrophenyl)maleimide (DDPM). Modifying these groups did not appreciably effect Ca2+-ATPase activity, the ability of the enzyme to bind quercetin and 1,N6-ethenoadenosine diphosphate (epsilonADP), or the ability of the enzyme to react with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1). Fluorescence resonance energy transfer was used to measure the distance from the sulfhydryl groups on the gamma subunit to the quercetin sites, the NBD-C1 reactive sites, and the tight nucleotide sites on CF1 using the donor-acceptor pairs NBPM-quercetin, NBPM-NBD, and epsilonADP-DDPM, respectively. The distance from the sulfhydryl groups to the quercetin sites was found to be less than 30 A, the distance to the NBD-C1 reactive was 34-41 A, and the distance to the tight nucleotide sites as greater than 40 A. A three-dimensional symmetrical model is proposed for the relative positions of sites on CF1.


The isolation and partial characterization of diphosphoglycerate mutase from human erythrocytes. Diphosphoglycerate mutase has been purified to homogeneity from outdated human erythrocytes. The native enzyme has a molecular weight of 57 000 as determined by equilibrium centrifugation and exclusion chromatography. Disc gel electrophoresis in the presence of sodium dodecyl sulfate yields a single protein band with a molecular weight of about 26 500, indicating that diphosphoglycerate mutase is comprised of two subunits of similar mass. The enzyme exhibits the following intrinsic activities: diphosphoglyceratemutase, monophosphoglycerate mutase, and 2,3-diphosphoglycerate phosphatase. The latter activity is enhanced in the presence of either organic or inorganic anions. Glycolate-2-P, particularly, has a profound activating effect. Nonspecific phosphatase and enolase activities are absent. The enzyme has an extinction coefficient at 280 nm of 1.65 cm2/mg. The amino acid composition of the homogeneous protein has been determined.


A kinetic study of the subunit dissociation and reassembly of rabbit muscle phosphofructokinase. The kinetics of dissociation and reassembly of rabbit skeletal muscle phosphofructokinase has been studied using fluorescence, stopped-flow fluorescence and enzyme activity measurements. The dissociation of the fully active tetramer in 0.8 M guanidine hydrochloride (0.1 M potassium phosphate, pH 8.0) occurs in three kinetic phases as measured by changes in the protein fluorescence emission intensity: dissociation of tetramer to dimer with a relaxation time of a few milliseconds; dissociation of dimer to monomer with a relaxation time of a few seconds; and a conformational change of the monomer with a relaxation time of a few minutes. All three phases exhibit first-order kinetics; ATP (0.05 mM) retards the second step but does not influence the rate of the other two processes. The rate of the second process increases with decreasing temperature; this may be due to the involvement of hydrophobic interactions in the stabilization of the dimeric enzyme. A further unfolding of the monomer polypeptide chain occurs at higher guanidine concentrations, and the relaxation time associated with this process was found to be 83 ms in 2.5 M guanidine, 0.1 M potassium phosphate (pH 8.0) at 23 degrees C. The phosphofructokinase monomers were reassembled from 0.8 M guanidine chloride by 1:10 dilution of the guanidine hydrochloride concentration and yielded a protein with 70-94% of the original activity, depending on the protein concentration. The reactivation process follows second-order kinetics; ATP (5 mM) increases the rate of reactivation without altering the reaction order, while fructose 6-phosphate does not influence the rate of reaction. The rate-determining step is probably the association of monomers to form the dimer.


Changes in (Na+ + K+)-ATPase activity of Ehrlich ascites tumor cells produced by alteration of membrane fatty acid composition. The fatty acid composition of plasma membrane derived from Ehrlich ascites tumor cells was altered in vivo by changing the dietary lipid of the tumor-bearing mice. The activity of (sodium + potassium)-adenosinetriphosphatase ((Na+ + K+ATPase), in partially purified plasma membranes, was measured ass a function of temperature. Arrhenius plots of the data were biphasic. Striking differences, dependent on the membrane fatty acid composition, were observed in the transition temperature and in the energies of activation below the transition temperature. The transition temperatures for the (Na+ + K+)-ATPase of plasma membrane derived from tumor cells grown in mice fed a regular chow diet containing a mixture of fatty acids (PMC), a 16% sunflower oil diet (PMSU), or a 4% tristearin diet (PMTS) were 20, 21, and 13.5 degrees C, respectively...


Biochemical characterization of density-separated human erythrocytes. A simple, reproducible method for the separation of human erythrocytes, described recently (Murphy, J. R. (1973) J. Lab. Clin. Med. 82, 334-341) has been utilized for the purpose of obtaining a wide range of biochemical data on these cells. Using phthalate ester density centrifugation of the fractions obtained by Murphy's method, we established that the cells were separated exclusively on the basis of their densities. Data on a wide range of biochemical and hematological parameters, when compared with previously reported density separation procedures showed that this simple technique can be used to fractionate the cells according to their densities (age) in their own plasma. Cells of increasing density consistently and reproducibly exhibited an increase in hemoglobin concentration, a moderate elevation in Na+ and a decrease in the following: K+, acetylcholinesterase, sialic acid, membrane protein, 2,3-diphosphoglycerate, ATP, cholesterol, phospholipid, mean corpuscular volume and critical hemolytic volume, However, no change in mean corpuscular hemoglobin was evident. The observed differences were not artifacts of the centrifugation process. This was determined in recentrifuged top fractions from which new top and bottom cells were obtained. The latter cells resembled the top fraction from which they were obtained, rather than the original bottom fraction. Whereas the parameters mentioned above exhibited consistency and reproducibility, such was not the case with the ATPase values. Depending on the cell density group examined and/or buffer as well as other conditions, significant variability in the activity levels of the ouabain sensitive, as well as the Ca2+ -stimulated ATPase, was observed. Use of these enzyme activities as indicators of cell age must be viewed with caution.


Effects of 4-acetamido-4'-isothiocyano-2,2-disulfonic stilbene on ion transport in turtle bladders. The disulfonic stilbene (4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene) is found to be more potent than acetazolamide as an anion transport inhibitor in the turtle bladder, but less potent than acetazolamide as a carbonic anhydrase inhibitor. The anion-dependent (HCO-3,Cl-) moiety of the short-circuiting current is eliminated by 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene, but only after its addition to the serosal bathing fluid. Whereas 4-acetamido-4'-isothiocyano-2,2'-disulfonic stilbene has no effect on Na+ transport across the bladder, it is more potent than ouabain as an inhibitor of microsomal (Na+ + K+)-ATPase of both turtle bladder and eel electric organ.


Differential inhibition of branching enzyme in a morphological mutant and in wild type Neurospora. Influence of carbon source in the growth medium. 1. A morphological mutant of Neurospora crassa, smco 9, (R2508) that exhibits colonial morphology when grown on sucrose or on maltose, showed a partial reversal of this morphology toward that of the wild type when it was grown on potato starch or on isomaltose. 2. A common feature of both potato starch and isomaltose is the presence of alpha-1, 6 glucosidic linkages. This suggested that these morphological effects might be due to differences in alpha-1,4 glucan: alpha-1,4 glucan 6 glycosyltransferase, (EC 2.4.1.18) commonly known as "the branching enzyme". 3. The branching enzyme was purified from wild type, Neurospora crassa, and from the semicolonial mutant, R2508, both grown on sucrose or on potato starch. It has a molecular weight of 140,000 as estimated by gel filtration on a Bio Gel A 1.5 m column. This enzyme plus phosphorylase a in an unprimed reaction catalyzes the synthesis of a branched polysaccharide in vitro. 4. No branching enzyme activity was apparent in extracts of the mutant R2508, grown on potato starch until a thermolabile inhibitor was removed by fractionation on a DEAE column. 5. This inhibitor has a molecular weight greater than 100,000 as estimated on a P-100 polyacrylamide gel column. The specificity of the inhibitor is not absolute in that it inhibits glycogen synthetase in addition to the branching enzyme in Neurospora.


Accelerated turnover of blood glucose in pertussis-sensitized rats due to combined actions of endogenous insulin and adrenergic beta-stimulation. 1. Epinephrine-induced hyperglycemia was attenuated by the treatment of rats with pertussis vaccine, but this attenuation was abolished when endogenous insulin was suppressed by streptozotocin or anti-insulin serum. It was concluded that epinephrine-induced hyperglycemia was counterbalanced by the hypoglycemic action of insulin, the secretion of which was markedly potentiated in pertussis-sensitized rats. 2. Without epinephrine, no hypoglycemia developed in pertussis-sensitized rats despite the higher blood level of insulin. Tracer experiments with [14C,3H] glucose or [14C]bicarbaonate showed that, in pertussis-sensitized rats, more glucose was liberated into the blood from hepatic gluconeogenesis at the expense of hepatic glycogenesis, thereby accelerating the turnover of blood glucose. 3. Since this activation of hepatic glucose production was reduced by propranolol, a beta-adrenergic blocking agent, it is very likely that adrenergic beta-stimulation is, at least partly, responsible for the metabolic alterations observed in pertussis-sensitized rats.


Inhibition of axoneme and dynein ATPase from sea urchin sperm by free ATP. Sea urchin sperm flagellar ATPase (EC 3.6.1.3) has magnesium-ATP as an effective substrate and is inhibited by free ATP. The inhibition is prevented by high concentration of KCl or NaCl. 0.4 M KCl extracts 48% of ATPase activity from axoneme. The 0.4 M KCl extract and 0.4 M KCl-treated axoneme are also inhibited by free ATP and this inhibition is reversed by KCl. Dynein purified twice by sucrose density gradient centrifugation is also inhibited by free ATP; this inhibition is also reversed by KCl.


Increase of enzyme activities in Neurospora crassa during incubation at low temperatures. The effect of lowering the incubation temperature of sucrose-grown cultures of Neurospora crassa on the level of various enzyme activities was investigated. Of twelve inducible/derepressible activities studied, three, in addition to glycerol kinase, were found to increase during 48 h of incubation at 4-6 degrees C: trehalase (increase in specific activity of 3-10-fold), beta-glucosidase (6-12-fold) and beta-N-acetylglucosaminidase (4 to 6-fold). The maximum increases occurred at 6 degrees C and no increases took place in mycelia incubated at 0 degrees C. The kinetics of the changes in activity were markedly different from those observed previously with glycerol kinase. The increases were inhibited by cycloheximide. Trehalase, beta-glucosidase and beta-N-acetylglucosaminidase activities were not rapidly lost when cultures incubated at 6 degrees C were returned to 26 degrees C.


Binding of antibody to the active site of the adenosine triphosphatase of sarcoplasmic reticulum. 1. The thiol group of fragmented sarcoplasmic reticulum that is protected from reaction with N-ethylmaleimide by 1 mM ATP was labelled with N-ethyl-[2,3-14C2] maleimide. Autoradiography after electrophoresis of this material on dodecylsulphate/polyacrylamide gels showed that this group is located on the polypeptide chain of the ATPase. 2. The ATP-protected thiol group of fragmented sarcoplasmic reticulum has been labelled by treatment with either 1-(2,4,-dinitrophenylamino), 6-(N-maleimido) hexane or N, N'-bis(2,4-dinitrophenyl)-L-cystine. The total dinitrophenyl contents of the dinitrophenyl-vesicle conjugates found by spectrophotometry were in good agreement with the ATP-protected thiol content, especially in the case of the N,N'-bis(2,4-dinitrophenyl)-L-cystine-treated vesicles. Fluorescence-quenching titrations of anti-dinitrophenyl-antibody tryptophyl fluorescence with the dinitrophenyl-vesicle conjugates showed that not all the dinitrophenyl groups were available for combination with antibody. 3. Phospholipase C(EC 3.1.4.3) digestion of ATP-protected, N-ethylmaleimide-treated vesicles, labelled with dinitrophenyl groups using N,N'-bis(2,4-dinitrophenyl)-L-cystine, caused the dinitrophenyl groups to become completely inaccessible to anti-dinitrophenyl-antibody, although no dinitrophenyl groups were lost during the incubation. This indicates a possible crowding together of the ATPase molecules as the effective membrane area was reduced.


Ouabain-binding and phosphorylation of (Na+ + K+) ATPase treated with N-ethylmaleimide or oligomycin. Ouabain-binding and phosphorylation of (Na+ mk+)-ATPase (EC 3.6.1.3) of the plasma membranes from kidney were investigated after treatment with N-ethylmaleimide or oligomycin. Either of these inhibitors brought about the following changes: the phosphoenzyme, formed in the presence of Na+, Mg2+ and ATP became essentially insensitive to splitting by K+ but was split by ADP. One mole of this ADP-sensitive phosphoenzyme bound one mole of ouabain but the enzyme-ouabain complex was less stable than in the native enzyme primarily because the rate of its dissociation increased. Ouabain was bound to the ADP-sensitive phosphoenzyme in the presence of Mg2+ alone and addition of inorganic phosphate enhanced both the rate of formation and the steady-state level of the enzyme-ouabain complex. The inhibitors did not affect the properties of this second type of complex. Both in the native enzyme and in the enzyme treated with the two inhibitors inorganic phosphate enhanced ouabain binding by phosphorylating the active center of the enzyme as shown (a) by mapping the labeled peptides from the enzyme after peptic digestion, (b) by inhibition of this phosphorylation with Na+ and (c) by the 1:1 stoichiometric relation between this phosphorylation and the amount of bound ouabain. Unlike the phosphoenzyme, the binding of ouabain remained sensitive to K+ in the enzyme treated with the inhibitors. K+ slowed ouabain-binding either in the presence of Na+, Mg2+ and ATP or of Mg2+ and inorganic phosphate. A higher concentration of K+ was needed to slow ouabain-binding either in the presence of Na+, Mg2+ and ATP or of Mg2+ and inorganic phosphate. A higher concentration of K+ was needed to slow ouabain-binding than to stimulate dephosphorylation. This finding is interpreted as being an indication of separate sites for K+ on the enzyme: a site(s) with high K+-affinity which stimulates dephosphorylation, another site(s) with moderate K+-affinity which inhibits ouabain-binding. Inhibitors may enhance formation of the ADP-sensitive phosphoenzyme by blocking interaction between K+ and the site(s) with high affinity.


On the nature of the energised state of submitochondrial particles; investigations with N-aryl naphthalene sulphonate probes. 1. A further investigation has been made of the way in which the fluorescent probes 1-anilino-naphthalene-8-sulphonate and 2-(N-methyl-anilino) naphthalene-6-sulphonate report on the energised state of bovine heart submitochondrial particles. 2. A comparison of the probe responses to energisation with ATP or to a potassium diffusion potential has been made. The fluorescence enhancements seen in these two cases have different characteristics, and in view of this it is questioned whether a substrate generated energised state of a submitochondrial particle can be equated with a trans-membrane potassium diffusion potential. 3. Substitution of ITP for ATP reduces the rate at which either of the probes respond to energisation. In contrast reducing the ATPase activity of the particles by treatment with the covalent ATPase inhibitors 4-chloro-7-nitrobenzofurazan or N,N'-dicyclohexyl-carbodiimide has no effect on this rate. This finding that the rate of the fluorescence changes is directly sensitive to events at the level of the ATPase, but not to the total ATPase activity, suggests that this rate may not be controlled by a delocalised energised state. Reduction of ATPase activity decreases the extent of the fluorescence enhancement and a relationship between the change in probe fluorescence and ATPase activity is given. 4. The results in this paper are discussed in the context of the mechanisms which have been proposed to account for the fluorescence enhancements of N-aryl naphthalene sulphonate probes upon energisation of submitochondrial particles.


[Several features of the oligomycin effect on phosphorylating oxidation of mitochondria at various states]. Effect of oligomycin on the oxygen uptake at the 4th state of the respiration chain in mitochondria with the stable coupling of respiration and phosphorylation is studied. Oligomycin is shown to inhibit the respiration in the absence of exogenous phosphorylation substrate. The inhibition curve at the 4th state is hyperbolic, at the 3d state-it is S-form. The antibiotic inhibited the oxidation of beta-hydroxybutric acid at the 4th state more intensively, than succinate oxidation. It is suggested that ATP-synthetase acts for the expense of endogenous ADP at the 4th state of the respiration chain.


[Effect of acetylcholine on Na, K-ATPase of synaptasomes]. Effect of acetylcholine (ACh) on Na, K-ATPase system has a complex character. ACh concentration, as well as the type of membrane are responsible for the increase or decrease of Na, K-ATPase activity. The inhibition and activation capacity is not constant in different subcellular fractions. The maximal effect is observed in subcellular fractions rich in junctional complexes, whereas minimal effect is in microsomes. There is no effect in mitochondria and myelin at all. EGTA and EDTA removes the inhibition, but the activation remains unchanged. ACh is supposed to release from membrane structure Ca2+, which subsequently inhibits Na, K-ATPase. On the other hand, activation by ACh is the result of its direct effect. The inhibition prevails over the activation at high (2-10 mM) concentration of ACh, whereas at low (2mM) concentration it might be vice versa. Thus the effect of ACh on Na K-ATPase is the result of two different processes having opposite effects.