Products of dehydroepiandrosterone metabolism by human mammary tumors and their influence on estradiol receptor binding.

The high concentrations of dehydroepiandrosterone and its 3beta-sulfate in the blood are potential preocursors for further metabolism by normal and tumorous human mammary tissue. In vitro metabolism of 7n-3H- and 1,2,6,7(n)-3H-dehydroepiandrosterone by fifteen mammary tumors was examined. Some 10--50% of the radioactivity recovered was in the form of 7-oxygenated derivatives: the major metabolite being 7alpha-hydroxydehydroepiandrosterone accompanied by lesser amounts of the 7beta-epimer. 5-Androstene-3beta,17beta-diol was formed in all but one case. Evidence showed that the high yield of 7alpha-hydroxy derivative resulted from direct action of a 7alpha-hydroxylase capable of using both dehydroepiandrosterone and 5-androstene-3beta,17beta-diol as substrates. Although 5-androstene-3beta,17beta-diol competed with estradiol-17beta for the estrogen receptor, this property was considerably reduced as a consequence of the introduction of a 7alpha-hydroxyl or 16alpha-hydroxyl group. Dehydroepiandrosterone, which competed less effectively for the estrogen receptor site, showed almost no affinity for the site upon the introduction of a 7alhpa-hydrocyl group. A regulatory role for the 7alpha-hydroxylase is outlined.


[Influence of detergents and inhibition of Na+,K+-ATPase and Mg2+ATPase on erythrocyte membrane SH-groups].

The article deals with the influence of sodium dodensylsulfate, lubrol and also of inhibition of Na+,K+-ATPase and Mg2+-ATPase activities by N-ethyl malemid on the form of curves of erythrocyte membranes amperometric titration by Ag+. It is shown that changes in a conformational structure of proteins membranes under the influence of detergents results in the transformation of SH-group of type I to SH-groups of type II. A 70% fall of Na+,K+-ATPase activity has the same result. So, the form of the curves for titration of erythrocyte membranes sulphydryl groups may serve as an indicator to the morpholocial and functional state of the membranes protein part.


[Effect of muscular relaxants and anesthetic fluothane on activity of Ca2+-dependent ATPase of skeletal muscle sarcolemma].

Ca2+-ATPase of rats and rabbits skeletal muscle sarcolemma was studied as affected by relaxants: tubocurarine, myorelaxin and dioxonium, and by anesthetic fluothane in experiments in vitro and in vivo with lung artificial ventilation during curarization. The musclular relaxant, myorelaxin and anesthetic fluothane both in the experiments in vitro and in vivo inhibited the activity of the enzyme, dioxonium under these conditions caused no significant changes. Tubocurarin in vitro activated the enzyme and in vivo, vice versa, induced inhibition of the enzymic activity. The latter evidences for a many-sided character of the tubocurarine metabolic effect in the living organism. Combination of tubocurarine with fluothane had a less pronounced inhibitory effect on the activity of Ca2+-ATPase than the components used separately.


[ATPase activity in neuronal and glial enriched fractions of cerebral cortex in normal conditions and with hyperoxia].

The ATP-hydrolyzing activity was studied without addition of the exogenic cations and in the presence of Ca2+, Mg2+, Na+, K+ in myelin of rat brain cortex fractions enriched with neurons and glia. In the variant without addition of the exogenic cations the fraction enriched with neurons possesses the highest specific activity of ATPase and the myelin fraction possesses the lowest one. Addition of Ca2+, Mg2+, Na+, K+, triton X-100 activates ATPase in the nerve tissue cell fractions, ouabain inhibits the Mg2+, Na+, K+-ATPase activity. Action of oxygen under high pressure changes the percentage of transport ATPases distribution in neuropile and decreases the share of Na+, K+-ATPase sensitive to ouabain in myelin of the nerve tissue fractions enriched with neurons and glia.


Long-term ureteral replacement prosthesis.

A silicone rubber tube with bonded Dacron felt cuffs have been implanted in dogs as a ureteral replacement prosthesis. A one-way valve has also been developed to prevent reflux so the prosthesis may be put into the bladder. The prosthesis has been implanted for periods up to nine months. Although there are some problems associated with the prosthesis, most animals have maintained a normal serum creatinine, sterile urine, and a normal excretory urogram.


[Nicotinamide inhibition of 2-14C acetate incorporation into free fatty acids and lipids of rat tissues].

The synthesis of fatty acids and lipids in the rat tissues is inhibited to a considerable extent during fasting and is activated when feeding highly carobhydrate ration to rats after fasting. Nicotinamide (50 mg/100 g of weight) causes a decrease in intensity of 14C incorporation into free fatty acids and lipids of blood, liver, epididimal and perienal fatty tissues. The degree of nicotinamide inhibition of fatty acids and lipids sythesis is in direct dependence on lipogenesis intensity.


The efficacy of in-feed medication with fenbendazole against gastrointestinal nematodes of sheep, with particular reference to inhibited larvae.

Anthelmintic activity of fenbendazole in a feed formulation was tested against nematode parasites of sheep. Dose rates ranging from 1.4 mg per kg for four days to 0.4 mg per kg for 14 days removed 98 to 100 per cent of the total gastrointestinal worm burden, including large numbers of inhibited fourth stage larvae of Ostertagia circumcincta. One hundred per cent effectiveness against adult Dictyocaulus filaria was also recorded.


Cytomegalic adrenal hypoplasia with pituitary cytomegaly.

A case of cytomegalic congenital adrenal hypoplasia (C.C.A.H.) is reported with similar cytomegalic changes in the hypophysis. In this case the pituitary gland was small as were the thyroid and testes. The various groups of patients with C.A.H. are presented. Associated pituitary cytomegaly does not appear to have been previously described, and this association between the adrenal and pituitary changes is discussed. It is suggested that the adrenal cytomegaly is the result of overstimulation by the pituitary and the similar change in the latter may be the result of overstimulation of a hypoplastic organ.


The bivalence of juxtaglomerular cells in the maturing rat kidney. A comparative study of secretory and contractile potential.

A comparative immunofluorescence and light microscopical study of the three cell types of the juxtaglomerular apparatus (pure muscle cells, pure granular cells and mixed cells) was performed on the growing and maturing kidney of the rat. Mixed cells, containing contractile protein and secretory granules, are detectable on the first postnatal day in about one third of the JGAs. From the third week, the number of bivalent cells increases, while the proportion of pure muscle or pure granular cells decreases. Morphological and functional maturation, achieved by 3 to 4 weeks, is associated with increasing numbers of bivalent cells and a shift in the main site of renin production from the inner to the outer cortical zone. The divergent internal structure of JGA cell types expresses the range of varied differentiation expressed by one cell line. Pure muscle or granular cells are at the extremes of the range and mixed cells take up an intermediate position.


[An osseus tumor in the skull of a precolumbian indian from Peru (author's transl)].

A walnut-sized, stalked, osseus tumor in the region of the protuberantia occipitalis externa of the skull of a precolumbian indian from Peru is described. Radiological and histological examinations grouped this neoplasm with the fibro-osseus tumors. Cytologically, it is one of the rarely seen nearly compact forms of the large, mostly spongy osteomas of the skull roof.


Schwannian origin of neurinoma. Electron-microscopic examinations of 10 cases (author's transl).

In benign tumours of the nerve sheath, the neurinoma clearly originates from the Schwann's cell. This can be said, because there are neurinoma cells with the typical tendency to cytoplasmic processes out of which peculiar myelin sheaths are built; these peculiar myelin sheaths wrap themselves around parts of their own neurinoma cell.


[Aortic amyloidosis in adult life (author's transl)].

Aortic amyloid deposits were found in 53% of adult subjects (mean age 47.5 years). They appeared to be localized mainly in the mediaintimal border zone and the internal third of the aortic media, and were not usually related to atherosclerotic lesions. The thoracic aorta was more extensively and frequently involved than the abdominal. It was concluded that aortic amyloidosis: 1. is progressive in its extent and distribution 2. does not seem to be related to atherosclerosis 3. should not be considered to be a form of senile amyloidosis, but rather a peculiar microfocal amyloidosis of the aorta.


Extraskeletal Ewing's sarcoma.

Clinicopathologic study of five cases of soft tissue tumors revealed distinct differences from skeletal Ewing's sarcoma in preferential localisation and mean age. The cases examined here are similar to cases described earlier as "extraskeletal Ewing's sarcomas". They show light- and electronmicroscopical features analogous to skeletal Ewing's sarcoma. The term extraskeletal Ewing's sarcoma appears to be appropriate for this type of soft tissue tumor.


Epidermal chalones and squamous cell carcinomas. The growth inhibitory effects of aqueous epidermal extracts (G1 and G2 chalones) on the epidermis and on a transplantable keratinizing carcinoman in nude mice.

Balb/c/nu nude mice that had been transplanted with a moderately differentiated squamous cell carcinoma were injected i.p. with different doses of epidermal chalone, and control animals were injected with saline. The labelling indices (H3TdR) and the mitotic rate (stathmokinetic method with vinblastine sulphate) were determined. In the untreated animals, both the labelling index and the mitotic rate of the tumor were considerably higher than in the epidermis, and the rate of cell birth was almost twice that of the epidermis. Higher doses of chalone were needed to reduce the labelling index for the tumour than for the epidermis, and there was generally a less pronounced dose/response relationship in the tumours than in the epidermis. The same was true of the mitotic rate but here the results were not as obvious as for the labelling index.  A possible explanation of the results may be that the tumour cells are less sensitive than epidermal cells to the injected chalones, or that reduced vascularization of the transplanted tumour may lead to reduced access of chalone, or that tumour necrosis may pay a role. However, it is evident that the tumour cells react less than the epidermis to both the G1 and the G2 chalone, and thus the findings of this study do not provide any evidence against the theory that epidermoid transplanted tumours are less sensitive to epidermal chalones than normal tissue of the same histogenetic origin.


[Comparative study of the changes in the ATPase activity of actomyosin and in the activity of skeletal muscle glycolytic enzymes in the early postnatal period of development].

ATPase activity of actomyosin and activity of glycogenolytic enzymes were distinctly increased during postnatal period of development. Direct correlation was observed between the actomyosin ATPase and phosphofructokinase, phosphohexoisomerase, enolase, pyruvate kinase, lactate dehydrogenase and "bound" fraction of aldolase. Kinetic patterns of phosphofructokinase (Km and Hill's coefficient) were not altered at the postnatal period. Formation of complexes between the contractile proteins and glycolytic enzymes appears to be important in development of contractile function.


[Importance of the fibrinogen-heparin complex in the fibrinolytic activity of the blood euglobulin fraction after the intravenous administration of thrombin or plasmin].

Intravenous administration of plasmin as distinct from thrombin inhibited or did not provide a secretion of endogenous heparin into circulation. In these conditions non-enzymatic fibrinolysis was not observed both in fraction of euglobulins and in fibrinogen-heparin complex, isolated from euglobulins, due to insufficiency of heparin. Exogenous heparin, injected into circulation or added to corresponding fractions, enabled to produce the active heparin complexes. About 70% of total fibrinolytic activity was due to fibrinogen-heparin complex in euglobulin fraction of blood plasma, isolated from blood of animals intravenously administered with thrombin.


[Metabolism of myocardial poly A+-containing mRNA normally and in compensatory cardiac hyperfunction].

Two fractions of mRNA--polyA+ and polyA- containing mRNA--were found in rat heart muscle by affinity chromatography using polyU cellulose. These fractions constituted 30% and 70% of total mRNA, respectively. The ratio of polyA+/polyA- mRNA was not altered in myocardium under heart hyperfunction and in physiological ageing. Duration of life of polyA+ containing mRNA was 4 hrs in normal heart. A; the beginning of myocardium hyperfunction the period of mRNA life was decreased down to 2-3 hrs; this pattern of mRNA life alteration did not differ from control one in prolonged heart hypertrophy within 6 months. The rate of polyA+ containing mRNA synthesis was increased by 70% at the early steps of heart hyperfunction as compared with normal state; it decreased below the normal state in long-term hypertrophy of myocardium. In development of heart hyperfunction acceleration of polyA+ containing mRNA synthesis was more distinct than an increase in rRNA synthesis.


[Phosphofructokinase activity of the plague bacterium].

Synthesis of phosphofructokinase was decreased in pestilential microbe if cultivation temperature was increased from 28 degrees to 37 degrees. Aeration of cultural fluid effected slightly on the enzyme production. Glucose, added to cultural fluid, decreased synthesis of phosphofructokinase in virulent strain and increased it in avirulent one. Phosphofructokinase activity from pestilential microbe was inhibited by ATP, citrate, 3-phosphoglycerate, by Ca2+ and Mn2+. AMP and lesser ADP reduced the effect of ATP and citrate on the enzyme, but when ATP was maintained in reaction mixture at non-inhibitory concentration these substances decreased phosphofructokinase activity.


[Liver metabolism during massive hemorrhage and subsequent blood transfusion].

Content of lactate, pyruvate as well as activity of hexokinase, phosphorylases, ATPase and transaminases were studied in dog and rat liver tissues under conditions of acute profuse hemorrhage and after its complete compensation by autogenic, isogenic blood and by sodium chloride 0.9% solution. Distinct inhibition of the hexokinase activity in the hemorrhage led to impairment of glucose utilization in liver tissue and to development of hyperglycemia. Alterations in arterial blood pressure correlated with the activity of tissue enzymes. Tissue metabolism was improved after compensation of blood losses by adequate amounts of blood at early period of hemorrhagic shock.


[Mechanisms of interaction of vitamins B1 and PP during absorption in rat intestine].

Interrelation between vitamins B1 and PP during absorption in rat intestinum tenue depended on the quantitative ratio of vitamins in luminal contents. Large doses of one of vitamins decreased absorption of physiologic doses of another drug affecting vitamin metabolism in intestinal wall. Excess of nicotinic acid (40-10(-3)M) inhibited thiamine pyrophosphatase activity in intestinal mucosa if thiamine was used at concentration 3-1-10(-6) M). Use of low amount of 14C-nicotinic acid (40-10(-6) M) caused an occurrence of 14C-nicotinamide in intestinal mucosa; content of nicotinamide was distinctly decreased, when 14C-nicotinic acid was administered simultaneously with 3-1-10(-3) M thiamine. tat the same time, thiamine did not effect on 14C-nicotinic acid accumulation in segments of rat intestinum tenue in vitro.


[Endoscopic studies in determining the stage of lung cancer].

An associated simultaneous mediastino- and laparoscopy allows the detection of lung cancer metastases in lymph nodes of the anterior mediastinum and liver and thereby the precise determination of the tumor process stage. The procedure is tolerated by patients well. 100 examinations showed metastases in mediastinal lymph nodes in 27 cases, in the liver- in 7. No complications were noted. Metastases were most frequently found in patients with undifferentiated lung cancer. Hepatic scanning by means of radioactive gold was performed in 30 patients. Laparoscopic data correlated well with scannographic findings.


[State of the glycolytic system in the hypertrophied heart].

A turnover of glycogen was distinctly increased in hypertrophic rat heart within 2 months after coarctation of aorta; this was corroborated by increased 4.5-fold incorporation of 14C-glucose into glycogen and by removing of label from glycogen in heart perfusion using Langendorf preparation. Due to stationary activation of glycolysis secretion of lactate from isolated hypertrophic heart was twice more than that from intact one in aerobic contitions. Activities of glycolytic enzymes, extracted from intact and hypertrophic heart muscles in optimal conditions of incubation, were approximately of the same value; this suggests the distinct potential activity of glycolytic system in myocardium in vivo. Decrease in oxygen utilization is apparently the reason of glycolytic system activation in development of heart hypertrophy.


[Effect of vitamins PP and B1 on pentosephosphate pathway enzymatic activity in the kidneys of adrenalectomized rats].

The activity of glucose-6-phosphate dehydrogenase (EC 1.1.1.44), transketolase (EC 1.1.1.44), transketolase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 2.2.1.1.) and also the thiaminediphosphate (TDP) content were investigated on the 8th day after adrenalectomy. With compensated sodium dysbalance the removal of suprarenals is shown not to change the activity of dehydrogenases, but it does lower the transketolase activity and the TDP level. A seven-fold administration to adrenalectomized animals of nicotinic acid, thiamine or a simple injection of nicotinamide normalize the transketolase activity through raising the TDP level. The fact of the reduced transketolase activity in the kidneys in hypocorticotism being due to deficiency of the co-enzyme is also proved by the presence of the TDP-effect in vitro.


[Endo-osseous isotope therapy of malignant skeletal disease (author's transl)].

The intravenous application of 89-strontium for the relief of pain in 43 patients with breast cancer, bronchogenic cancer, carcinoma of the prostate, hypernephroma and lymphoma with generalized bone metastases is reported. A remarkable clinical improvement was achieved in 33 (76.7%) patients. In four patients a transient analgesic effect was observed. In six cases no response could be achieved. The therapeutic effect usually was long-lasting. At the same time, an increase of alkaline phosphatase was observed, which was interpreted as an indication for the stimulation of osteoblasts and osteoid peripheral zones owing to beta-emission of the radioisotope in the affected areas. There was a significant correlation between the concentration of 85Sr in the bone scan and the therapeutic result of 89Sr-therapy. The indication for such therapy and possible late adverse effects of bone-seeking isotopes are discussed.


In vivo DNA repair after N-methyl-N-nitrosourea administration to rats of different ages.

DNA repair time-course was studied after injury by N-methyl-N-nitrosourea (MNU) in rat liver cells of animals of different ages and in fetuses using hydroxyurea (HU) as inhibitor of scheduled DNA synthesis. DNA repair was a rapid phenomenon, more so in young adults than in newborns, and was not detectable in fetuses. A correlation seems to exist among organ sensitivity to carcinogen, age of animal and DNA repair.


[On the occurrence of so-called clear cells in salivary gland tumors. Ultrastructure and differential diagnosis (author's transl)].

Clear cell tumors of the salivary glands are monomorphic clear cell adenomas, clear cell carcinomas, clear cell variants of acinic cell and mucoepidermoid tumours, sebaceous cell tumors, salivary duct carcinomas and pleomorphic adenomas with clear cell sectors. At the light microscopical level the descriptive term of the clear cell comprises cell types of different origin and functional importance which can be differentiated by cytochemistry and electron microscopy. The following cell types were analysed precisely: indifferent duct cells (small formation of organelles, desmosomes), storing striated duct cells (glycogen granules, multiple mitochondrias, basal labyrinth), myoepithelial cells (myofilaments, pinocytosis vesicles, lipofuscin granules, hemidesmosomes), goblet cells (mucous vacuoles, basal endoplasmatic reticulum), sebaceous cells (lipid droplets, microvilli, desmosomes) and clear acinic cells (electron pale secretory granules, small mitochondrias, small golgi apparatus). Clear cell tumor types of the salivary gland region which primarely do not derive from the salivary gland tissue must also be included in the differential diagnoses. These are metastases of hypernephroid renal carcinomas, paragangliomas, glomus tumors of Masson, granular cell tumor and alveolar soft-part sarcomas.


Induction of gastric tumors in BD-VI rats by single application of N-methyl-N'-nitro-N-nitrosoguanidine in dimethylsulfoxide (DMSO).

The oral acute LD50 of N-Methyl-N'-Nitro-N-Nitrosoguanidine (MNNG) in a 10% aqueous solution of dimethylsulfoxide (DMSO) amounted to approximately 90 mg/kg. After single oral application of 50 mg/kg (group I), 75 mg/kg (group II) and 100 mg/kg (group III) of MNNG in a 10% aqueous solution of DMSO, generalized papillomatoses of the forestomach were found in all BD-VI rats after a test period of 500 days. Squamous cell carcinomas could be detected in 7/24 (21%) rats in group I, in 12/26 (46%) in group II and in 7/23 (30%) in group III). Benign adenomatous dysplasia of the glandular stomach was diagnosed in 2 rats (8%) of group I, in 1 animal (4%) of group II and in 12 rats (52%) of group III. Adenocarcinomas of the glandular stomach were induced in 1 animal (4%) of both group I and II and in 8 rats (35%) of group III. 20--30% of the animals treated with MNNG also showed degenerative cystic alterations in the liver with bile-duct proliferation.


Ultrastructural studies on hydantoin induced lymphomas in mice.

Ultrastructural studies were done on cells from original tumors and from short time cultures of mouse thymic lymphomas experimentally induced by chronic exposure to diphenyl-hydantoin. The tumors appeared in mouse strains with low (C57Bl) and high (SJL/J) susceptibility to spontaneous lymphoma development and were not observed in a resistant strain (C3Hf). Thymic lymphoma development was usually preceded by increasing lymphoreticular atrophy followed by progressive reticulohistiocytic hyperplasia, and subsequently spread to other tissues. Morphologically the tumor was characterized as a lymphoblastic lymphoma. Abnormal cell changes in the original tumors and cultured cells, and the presence of murine C-type particles in the cultured cells but not in the original tumors, are discussed in relation with the disturbance of immune system and the lymphoma enhancement produced by diphenyl-hydantoin.


Carcinogenicity of acetoxymethyl-methyl-nitrosamine after subcutaneous, intravenous and intrarectal applications in rats.

In comparison to the known carcinogenic properties of Acetoxymethyl-Methyl-Nitrosamine (AMMN) after oral or intraperitoneal application the dimethylnitrosamine derivative was tested by subcutaneous, intravenous and intrarectal route in male Sprague-Dawley or Wistar rats. AMMN proved to be primarily a locally acting carcinogen. However, a second mode of action is indicated by systemic carcinogenic properties found after i.v. and s.c. applications. The lung and heart, and to a less extent the kidney and earduct were found as target organs of distant carcinogenic response.


On the distributive patterns of ATPase activity and its functional significance in retinae of certain birds.

The present study incorporates the details of distribution of adenosine triphosphatase amongst the various constituents of retinae of Passer, Psittacula, Streptopelia and Athene. The outer segments in all the cases are intensely positive for the enzyme. This is the part where the light strikes first and initiates the visual processes. The nuclear layers are also positive for the enzyme activity. It is interesting to note that inner plexiform layers show clear-out demarcations of various sub-synaptic layers in all the birds except Psittacula. The ganglion cells and optic nerve fibres are also positive for the enzyme.


Nonthermal effects of millimeter microwaves on yeast growth.

Weak microwave irradiation of aqueous yeast cultures was found to affect their growth rate in a frequency-selective manner. Depending on frequency (near 42 GHz), both increases and decreases of the growth rate were observed. The resonance bandwidths are of the order of 0.01 GHz. Simple thermal effects can be excluded. These findings support theoretical predictions of coherent molecular oscillations activating metabolic processes.


Electromagnetically induced fluid streaming as a possible mechanism of the biomagnetic orientation of organisms.

The results show that both the direction and the intensity of the geomagnetic field can be sensed within the chamber of a Zeiss Cytopherometer. This suggests that electromagnetically induced fluid streaming might play a role in the perception of the geomagnetic field by organisms, although it is not clear at present in which organ the perception occurs. A basic requirement for such an organ would be an anisotropy of cells or cellular structures. The nervous system with its parallel axons, or specific cells associated with the nervous system, could thus be possible locations of the sensitivity towards magnetic fields.


[Investigation of crystalline structures in fats of animals by x-ray scattering (author's transl)].

Fat-praeparates of cow and pork have been investigated by small-angle X-ray scattering methods. Dependent on the temperature these fats show distinct X-ray interference patterns in the small-angle region. Hence complete phasediagrams of the fats in the temperature region between -20 degrees C and 55 degrees C could be estimated. Using the intensity distribution of the X-ray scattering the electron-density distribution along one direction of the ground-cells of the fat crystals were calculated.


Inhibition of Mg, Ca-ATPase from E. coli by ruthenium red.

The membrane-bound, solubilized, and trypsin-treated forms of Mg, Ca-ATPase from E. coli are inhibited by ruthenium red [RR]. The inhibition is noncompetitive and is reduced at higher substrate concentrations. n-Butanol-extracted ATPase is not inhibited by ruthenium red and is not activated by KCl.


Effect of cortisone on aspartate and alanine aminotransferases in a desert lizard.

1. Liver and serum aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) activities were measured in a hibernating desert lizard, Uromastix hardwickii. The levels of both enzymes were found to be lower in hibernation than during the active period, particularly in the liver. 2. After intramuscular injection of 2 mg of cortisone acetate there was a rapid rise in the levels of these enzymes with a peak of 18 hours (GOT) and 12 hours (GPT). 3. The response of both enzymes to cortisone was much greater during the active period than during hibernation. 4. GOT showed a much more rapid and greater response to cortisone than GPT. This is in contrast to the response of rat liver where GPT is more responsive to this hormone. 5. These studies indicate that the transferase enzymes of this lizard differ from those of the rat in their sensitivity and time of response to cortisone.


Psoralen photosensitization of L 1210 leukaemia cells: an approach to a new combined therapy.

Psoralen photosensitization of L 1210 cells has a strong effect on DNA and RNA syntheses and this result appears connected with the psoralen photobinding to DNA. Protein synthesis is less sensitive and its inhibition seems due to a different photochemical interaction, very likely to the psoralen photobinding to RNA. A combined therapy using cyclophosphamide and L 1210 cells psoralen-photoinactivated was performed after the leukaemia transplant, showing a significant decrease in mortality, even in comparison with the simple treatment with the alkilating drug.


Cesium determination in physiological fluids and tissues by field desorption mass spectrometry.

Quantitative ultratrace analysis (10 nmol to 10 mumol/l) of cesium in biological samples such as human body fluids and animal tissues is performed without any prior purification or concentration steps. The normal level of cesium ions in heart cells was determined. After poisoning these cells with high concentrations of the alkali cation much higher levels were found inside the cells then had been suggested previously. It is demonstrated that field desorption mass spectrometry is a unique tool for the qualitative and quantitative investigations of metal cations in biological material.


Determination of the electron density profile of the nerve myelin membrane in different states taking paracrystalline lattice distortions into account.

Recent investigations point to the presence of paracrystalline lattice disorder in the nerve myelin in the swollen, fixed and to some extent also in the native state. This leads to the distortion of the Q-function of the membrane stack and the Q0-function of the unit cell, which can be experimentally isolated through swelling. Representing the distance statistics between neighbouring membranes and the electron density distribution of the single membrane with Gaussian functions, the Q-function can be expressed analytically as a convolution polynomial of the electron density, its mirror image and the distance statistics functions. Fitting this model Q-function to the experimental Q-function obtained by the inverse Fourier transformation of the scattered intensity, one can determine the optimal parameters of the electron density distribution and the distance statistics functions. The elimination of the distance fluctuations between neighbouring membranes permits the calculation of the undistorted Q-function or the Q0-function. The Fourier Analytical Deconvolution of the undistorted Q0-function enables a unique determination of the double membrane profile, thus a unique phase determination.


[Radiation-induced aggregation of proteins: binding of amino acids to myoglobin (author's transl)].

When myoglobin is irradiated in the presence of amino acids, the most radiation-reactive species, like the aromatic and sulfur-containing amino acids, will bind preferentially to the protein. The radiation-induced binding is strongly dependent on the concentration of protein and amino acid. Subsequent to irradiation of myoglobin in the presence of radioactively labelled tryptophan followed by tryptic hydrolysis, only a single radioactive spot was detected on the fingerprint. The binding of amino acids is thus not randomly distributed over the protein molecule but occurs at specific reactive sites.


ATP dependent uptake of zinc by human erythrocyte ghosts.

The energy dependence of Zn2+ accumulation by human erythrocytes was studied by preparing resealed ghosts loaded with ATP or AMP. Uptake of Zn2+ was followed by radioactivity or atomic absorption spectroscopy measurements. Zn2+ taken up is not adsorbed by the membrane but transported into the ghosts. Ghosts containing ATP took up more Zn2+ than those containing AMP. The effect is not specific for ATP, however, GTP and CTP showing the same increased uptake. Zn2+ uptake by ATP ghosts can be further drastically enhanced by addition of Cu2+. Therefore, in spite of the enhancement of Zn2+ uptake by ATP, Zn2+ seems to be accumulated by a passive mechanism even when the ghosts contain ATP. The accumulation is probably brought about by binding of Zn2+ to substances inside the ghosts.


Isopycnic equilibrium of mouse liver [131I]albumin digesting particles in sucrose gradients.

The isopycnic equilibrium of [131J]albumin digesting particles from mouse liver homogenates occurs, in a sucrose gradient, at a density 1.25, and it does not change with time after albumin injection (5 to 300 minutes).


[Studies on the specific effects of serum and cytoplasm of the liver on the [3H]TTP-incorporation of isolated liver nuclei (author's transl)].

Previous authors have described that liver cytoplasm and serum from partially hepatectomized rats stimulate the DNA synthesis of isolated nuclei of liver cells. The aim of our investigation was to prove whether such stimulating effects are part of a specific regulation of growth. The sera and the cytoplasm supernatant 105000 x g) were isolated at several intervals after partial hepatectomy and laparotomy and were tested on isolated nuclei of liver cells from adult rats partially hepatectomized 20 hours before. The supernatants isolated at 8 and 16 hours after both partial hepatectomy and laparotomy have a significant stimulatory effect on the [3H]TTP-uptake by nuclei. The presence of serum (10%) causes a general elevation (75%) of the [3H]TTP-uptake by isolated nuclei. The sera isolated 4 to 12 hours after operation from both partially hepatectomized and laparotomized rats have an additional stimulatory effect on the [3H]TTP-uptake synthes of nuclei. In no case did the sera and liver cytoplasm of partially hepatectomized rats have a significantly different and therefore "specific" effect on the nuclear DNA synthesis. Additional experiments showed that frozen and thawed nuclei of liver cells respond only to the nutritive power but not to the stimulatory effects of the sera. Thus, thawed nuclei cannot be used for growth investigations.


Further evidence for period lengthening effect of Li+ on circadian rhythms.

The period length of the activity rhythm of the cockroach Leucophaea maderae is increased by a LiCl solution of 100 mol m-3 offered as drinking water by about 1%.


Differentiation of Rhizobium japonicum, I. enzymatic comparison of nitrogenase repressed and derepressed free living cells and of bacteroids.

Derepressed free living cells of Rhizobium japonicum strain 61-A-101 with leucine as single nitrogen source develop a maximum nitrogenase activity of 180 nmol C2H4.mg protein -1.H-1 in liquid culture under 2% 2% O2 in the gas phase. Only 10% of this activity is found with no oxygen in the gas phase during a 90 min incubation period. The maximum activity under 2% oxygen in the gas phase is unaffected by addition of 1-100 mM NH+4 and by addition of low concentrations of glutamine (0.36-1.44 mM). Specific activities of alanine dehydrogenase (E.C. 1.4.1.1.) asparatate aminotransferase (E.C. 2.6.1.1.) and, with much lower activities, of GOGAT (E.C. 1.4.1.13) in nitrogenase active free living cells are more similar to bacteroids than to nitrogenase repressed free living cells from liquid culture. The activities in nitrogenase repressed cells were about 50% lower. Glutamine synthetase (E.C. 6.3.1.2.) activity in bacteroids and in nitrogenase active cells were also similar, but only about 25-30% of that found in nitrogenase repressed Rhizobium japonicum cells.


Effects of Ecdysterone and the juvenile hormone analogue methoprene on protein, RNA and DNA synthesis in wing discs of Calliphora vicina.

The protein, RNA and DNA content of wing discs increase exponentially during the last larval instar. Biosynthesis of protein, RNA and DNA was studied by injecting labelled precursors into larvae or white prepupae and measuring the incorporation in the wing discs dissected out after an appropriate time. Protein synthesis is stimulated by ecdysterone, methoprene has no effect. Biosynthesis of rRNA is increased in wing discs of white prepupae after ecdysterone or methoprene injection. Methoprene inhibits the synthesis of mRNA, while ecdysterone has no clear-cut effect within the limits of our method (gel electrophoretic analysis). Ecdysterone and methoprene have no detectable influence on incorporation of thymidine into DNA, but the incorporation label from uridine into DNA is diminished; this effect may be due to changes in the precursor pool.


13C nuclear magnetic resonance spectra of fungal melanins.

The 13C resonance spectra of fungal melanins from Aspergillus niger, Eurotium echinolatum, and Stachybotrys chartarum are reported. The spectra were taken in 5% W/W solution of the substances in 0.1 N NaOD in D2O using the Fourier-transform-technique. The spectra and possible assignments of the bands are discussed. The similarities of these spectra to those of soil humic acids are unexpectedly small.


[Role of various diseases of the upper respiratory tract in the epidemiological process of streptococcal infections].

Investigations conducted with the use of a specially elaborated method revealed a specific association of some (15--24%) of diseases diagnosed clinically as "acute respiratory affection" (ARA) with streptococcus infection. This was also confirmed by detection of an epidemiological association of ARA with scarlet fever revealed in some child collective bodies. The data obtained pointed to the definite role played by such diseases in the epidemic process in streptococcus infections.


[Exploration of natural foci of tularemia and plague in Armenia using the serological examination of bird droppings and excrements of predatory mammals].

Forty strains of tularemia and 619 of plague microbes were isolated in 1974 in bacteriological examination of natural plague and tularemia foci from a great number of small mammals and their ectoparasites. At the same time in serological examination (in the antibody neutralization test) of bird pellets, 52 mummified cadavers, and 34 excretion samples of mammalian beasts of prey collected in Armenia (its central and North-Western part) in 1973 the antigen of tularemia microbe was revealed in 73, 8, and 3, and of plagye--in 42, 5, and 1 cases, respectively. In one of the sites examined the number of positive findings failed to exceed 10--17%, this indicating a low intensity of the epizootic in the majority of the places. Judging by the mean titres of the serological test, which varied from 1:12 to 1:1428 in examination for tularemia and from 1:12 to 1428 in examination for plague, it was possible to detect both epizootics coursing during the examination, and those which occurred several monts ago. Tularemia and plague foci were not infrequently present at the same territories, and these diseases could involve the same individual animals of Microtus arvalis (Pall.). The data obtained pointed to the greater effectiveness of examination of bird's pellets and excretions of mammalian beasts of prey for the reconnaisance investigation of the natural foci of plague and tularemia in comparison with the bacteriological methods applied usually.


[Prevention of toxoplasmoses].

Prophylaxis of toxoplasmosis consists of a complex of general medical and veterinary measures. Of importance is detection of latent forms of toxoplasmosis in pregnant women and their timely treatment. Thorough clinical and immunological examination of persons with prolonged diseases of obscure etiology is necessary. Suggestions are given for dispensary observation of persons who sustained the disease and had positive immunological reactions for toxoplasmosis. Materials on prophylaxis of hemotransfusion transmission of the infection are presented for the first time. A number of recommendations concerns measures of general organization and also planned prophylactic examination with the use of immunological methods of some groups of population with increased risk of infection.


[Evaluation of the results of animal studies with a scheme of serologic reactions according to a table of standards].

The authors suggest a method of processing of the data of examination of the animals in the system of serological reactions for the purpose of diagnosis of epizootic situations in the natural plague foci. Positive results are recorded in a table in the form of a grid whose cells correspond to all possible variants of the two reaction titres. The table is divided into 6 sections into which the results differing by the correlation and the absolute reaction titres (the standard grid) are placed. The frequency of reactions is determined by the grid sections in the regions in which the character of the epizootic development in nature was studied by bacteriological examination of the animals. The diagnostic scale is drawn by the results of such standard observations. The trial of the suggested method was carried out in the regions of plague epizootics among the Rhombomys optimus Licht. in the Lowland Kara-Kum; it was possible to differentiate the signs of epizootic situations there in greater detail than by the methods suggested earlier.


[Data on a study of the nature of secondary immunodeficient states. I. An immunophysiological analysis of the mechanisms of allergic reaction suppression in experimental lesion of the structures of the dorsal hippocampus].

Experiments on rabbits demonstrated that local electrocoagulation of the dorsal hyppocampus portions by means of the implanted electrodes caused reduction of the complementary and lysozyme activity of the blood serum, inhibited the development of Arthus' skin allergic-reaction, decreased the intensity of systemic anaphylaxis to the blood serum antigens, this being accompanied by a relative fall of the precipitating antibodies titres and a reduction of the vagus response of the heart to adrenaline.


[Comparative study of the immunoglobulin content in persons from leptospirosis foci in different geographical zones of the RSFSR].

The authors carried out a comparative study of the content of serum immunoglobulins in persons from the leptospirosis foci of various geographical zones of the RSFSR: European part--the Centre (Moscow and Ryazan regions), the South (Checheno-Ingush ASSR and Krasnodar Territory), and Western Siberia (Altai territory), Leptospira of serological group Pomona, Grippotyphosa, and Hbedomadis served as the causative agents of the diseases. It appeared that the annual course of the climatic factors acted equally (inhibitory action) on the immuno-globulin metabolism in the residents of temperate and southern zones of the RSFSR at the warm period of the year (May-September), and in the Western Siberia- in winter. However, irrespective of the time of the year, the level of immunoglobulins G and A was greater in the residents of Western Siberia than in the native population of the European part. There proved to be no correlation between the levels of leptospirosis seropositivity in the foci of infection under study and the serum immunoglobulins in local residents of various geographical zones.


[Patterns in the change in the number of carriers and epizootic activity in a floodplain local natural focus of tularemia in Voronezh Province].

Prolonged study of the population of Arvicola terrestris L. in connection with tularemia epizootic among these animals showed this animal to serve as the principal carrier of tularemia infection in the Povorinsk natural focus. Epizootics proved to originate with a definite threshold count of Arvicola terrestris L.; this threshold constituted about 30% of the trapped animals. Dynamics of the epizootic activity was characterized by alterations of cycles of various duration, coursing by waves, with 2--3-year periods. Reduction of the epizootic intensity coursed during a decade in 2 waves with 3-year periods, and during a 7-year period--in one 3-year wave. During the epizootics with the character of a 2-year wave the population of the principal carrier diminished, and with a 3-year wave the count of Arvicola terrestris L. decreased during the first year, and began to increase during the second year, despite the persistence of the epizootic. Detection of regularities attending the changes in the population of the principal carrier of the infection and its connection with the epizootics permitted to make long-period prognoses of the epizootic activity and to plan antiepidemic measures in the focus.


[Study data on ornithosis infection in the Azerbaijan SSR].

Data are presented on the study of epizootology and epidemiology of ornithosis. There were revealed natural foci of ornithosis in the Kyzyl-Agach preserve, at the Sary-Su lakes and at the Glinyany island; these foci were dihostal and polyhostal, as well as conjointed (ornithosis, arboviruses, Q-fever, Asian tick-borne typhus, leptospirosis). Anthropurgic foci were found in 12 populated localities, semi-wild dove serving as the main component. Fowl was found to be infected in 12 poultry-farms; occupational ornithosis was present among the bird-rearers. Immunological structure of the population in respect to ornithosis was studied. Patients with various diagnoses showed positive serological reactions retrospectively; there were 155 cases of ornithosis among them.


Adverse reactions with methyldopa--a decade's reports.

During 1966-75 the Swedish Adverse Drug Reaction Committee received some 300 reports of reactions to methyldopa. As the Swedish rules for reporting adverse reactions emphasize the importance of severe and unexpected reactions, the relative incidence of various adverse effects differs greatly from what would be found in an intensive study. The three most commonly reported reactions are fever, hemolysis and hepatic effects. Two-thirds of these patients were women. The median age of the groups differed, from 57 years (hepatic effects) to 69 years (hemolysis). The clinical picture of the different reactions was consistent, in the main, with what has been described previously. Between 70 and 85% of the patients in these groups were admitted to hospital because of the adverse reaction.


ECG aberrations, latent coronary heart disease and cardiopulmonary fitness in various age groups of Norwegian cross-country skiers.

To assess the prevalence of possible, latent coronary heart disease (CHD) among physically active men, 149 elite cross-country skiers in three age groups (26-33, 43-50 and 58-64 years) were invited for an examination which included clinical examination, Vitalogram, resting ECG, and a near maximal bicycle test. Of the invited men, 122 participated, i.e. 81.8%. The following findings were made: Normal clinical findings in all except 2, low resting heart rate, lung function parameters of about normal mean; voltage signs of left ventricular hypertrophy in resting ECG in 61/122, incomplete right bundle branch block in 14/122, codable Q waves (Minnesota Code, MC) in 5/87 from the highest age groups, ischaemic exercise ECG changes of MC 4.1 or 4.2 types in 11/87 vs. 1/35 in the two oldest vs. the youngest age group. Physical performance was very high in all age groups, but regular training did not seem to inhibit the normal age-dependent decline in physical performance. The resting and exercise ECG data in the two oldest age groups did not differ favourably from similar data obtained in sedentary men of the same age from approximately the same geophraphic area. Thus, it is possible that regular strenuous exercise and training may not protect against the development of CHD. The implications of such a view are briefly discussed.


The immunopharmacologic and anti-inflammatory properties of RMI 9563 with special reference to its effect on the complement system.

The immunopharmacology of RMI 9563 - bis[3-(diethylamino)propyl]fluoranthene-3,9-dicarboxylate dihydrochloride--has been described. The compound, when given parenterally, inhibited several cell-mediated immune responses (EAE, tuberculin skin reaction, adjuvant arthritis) in rats, enhanced IgM and IgG antibody-producing cells in mice, and displayed anti-inflammatory activity in several models (carrageenan paw edema, adjuvant arthritis, direct passive Arthus reaction--a model of inflammation that is immunologically induced and complement-dependent). RMI 9563 suppressed the activation of complement in vitro by the selective inhibition of C1 esterase.


"Malignant" hypertrophic cardiomyopathy: identification of a subgroup of families with unusually frequent premature death.

Eight families were identified in which premature cardiac death due to hypertrophic cardiomyopathy occurred with unusual frequency. A total of 69 first degree relatives in the eight families were studied; 41 relatives had evidence of hypertrophic cardiomyopathy and 31 (75 per cent) died of their heart disease. Eighteen of these 31 patients were less than 25 years of age at the time of death. Death was sudden and unexpected in 23 of the 31 patients; in 15 of these 23 patients sudden death was the initial manifestation of cardiac disease. The remaining eight patients (seven were from two families) died after a chronic cardiac illness characterized by congestive heart failure, atrial fibrillation or thromboembolic events. Hence, premature cardiac death occurs frequently in certain families with hypertrophic cardiomyopathy. Such deaths are usually sudden, often occur in previously asymptomatic subjects and are common in children and young adults. These findings suggest that some families may manifest an unusually virulent expression of hypertrophic cardiomyopathy. Although this study cannot establish the precise prevalence with which "malignant" hypertrophic cardiomyopathy occurs, such families appear to be uncommon.


Primary intimal fibroplasia in a child with Down's syndrome.

A 14-year-old girl known to have trisomy 21 and who came to us with weight loss followed by hypertension proved to have diffuse arterial dysplasia involving the intimal layer (primary intimal fibroplasia). This is a rare cause of elevated blood pressure in children and has not been previously reported in a child with Down's syndrome. Unusual features of this case also include the widespread distribution of the lesions limited to the large muscular distributing arteries, the rapidly progressive course, and the predominance of abdominal signs and symptoms.


Endocrinology in preadolescents and adolescents. I. Hormonal changes during normal puberty.

Hormonal changes during puberty have been well described: rise of gonadotropins followed by the rise of gonadal secretions at ages 10 to 16 years. The most striking new data are in fact concerning events that occur before puberty, first during the first months of life, second at age 7 years. The first event consists of a rise of gonadal steroids, which gives a hormonal impring that might be important for the future of the child. The second event concerns the prepubertal maturation of the androgenic zone of the adrenal cortex and the increasing secretion with age of the adrenal androgens. The mechanism of onset of both events is poorly explained. What causes the rise of gonadal steroids during infancy is unknown. Which pituitary factor, in addition to ACTH, stimulates the corticoadrenal androgenic zone, and which mechanism regulates its secretion remain unknown.


Laparoscopic Falope Ring sterilization. Two years of experience.

The most commonly utilized method of tubal sterilization via laparoscopy currently is electrocautery. Because this procedure has led to disastrous consequences in a small percentage of cases, a method of nonelectric sterilization has been sought by several investigators. The Falope-Ring sterilization technique was introduced in 1973 and a preliminary report appeared in 1974. The procedure was begun at Michael Reese Hospital in 1975 and over a 2 year period 241 cases were accumulated. The procedure was found to be a relatively simple operative technique which required decreased operating time and less pneumoperitoneum at laparoscopy. It was also found to be easily teachable. It was found to be free of immediate disastrous complications and, in a rather early evaluation, it was found to be effective. There are clear indications that this technique is a viable alternative to female tubal electrocautery.


Androgen, estrogen, and progesterone by a lipid cell tumor of theovary.

In a 64-year-old woman with a virilizing lipid-cell tumor of the left ovary, serum progesterons, androgens, estrogens, and cortisol levels in the peripheral and ovarian veins were measured. Although virilization was the only symptom of hormone production by the tumor in this patient, endocrine studies showed that several steroids were secreted by this neoplasm. Of the steroids measured, androstenedione was the principal secretory product. Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, and testosterone were also secreted, but in quantities which were one third to one sixth the amount of androstenedione. The tumor's pattern of hormone secretion was similar to patterns of steroid production by ovarian stromal cells found in previously reported in vitro studies. This case and a review of the literature demonstrate that androstenedione appears to be the predominant secretory product of lipid cell tumors, whereas testosterone is the predominant secretory product of hilus cell tumors.


Minilaparotomy tubal sterilization.

Two hundred and twenty-six minilaparotomy Pomeroy tubal ligations performed between January, 1976, and July, 1977, are compared to 226 laparoscopic tubal sterilization operations. Operating time, length of hospital stay, and complications were similar for the two groups. Postoperative discomfort was greater in the minilaparotomy group but did not significantly increase the duration of hospitalization and was effectively relieved with oral administration of medication for pain. It is the author's belief that the minilaparotomy procedure provides the best current method of tubal sterilization in the patient who is not massively obese. The slight increase in postoperative discomfort is a small price to pay for freedom from the rare major complications of visceral, vascular, and thermal injuries. In addition the author recently has decreased the postoperative discomfort experienced by carefully expressing the room air from the peritoneal cavity just prior to tying the peritoneal suture.


Adverse reactions to co-trimoxazole in hospitalized medical patients.

Of 29,524 hospitalized medical patients monitored in a drug surveillance program, 649 (2.2%) received the fixed dose combination of trimethoprim-sulfamethoxazole, co-trimoxazole. Adverse effects of this drug occurred in 8% of recipients, the most frequent being skin rashes which occurred in 23 patients (3.5%) and upper gastrointestinal upsets which occurred in 22 (3.4%). Reactions frequently occurred within 72 hours of starting the drug and promptly resolved on stopping it. No patient experienced severe or life-threatening adverse effects. Adverse effects were unrelated to age, weight, duration of hospitalization or presenting blood urea nitrogen concentration, but were significantly commoner in female recipients.


Irradiation-induced polyglandular neoplasia of the head and neck.

Eighteen patients are presented with twenty-one tumors of the head and neck, which include ten salivary gland tumors and eight parathyroid adenomas. Eight of the patients also had thyroid neoplasms. All patients had a history of prior irradiation to the head and neck. Seventy per cent of the salivary gland tumors and 37 per cent of the thyroid tumors were malignant. Recommendations are made for detection and treatment.


[Necessity to control endexpiratory CO2-concentration during laparoscopic sterilisation under general anaesthesia with controlled ventilation (author's transl)].

During laparoscopy and intraabdominal insufflation of CO2 cardio-respiratory accidents following increased PaCO2 are possible. The continuous measurement of endexpiratory CO2-concentration by infrared absorption spectrometry is a simple method for controlling the level of ventilation. Respiratory acidosis under controlled artificial ventilation during laparoscopy can thus be avoided.


The lipid-protein interaction in the membrane-bound Na+, K+-ATPase: a spin label study.

The interrelated temperature induced structural changes in the protein and lipid fractions of the Na+, K+-ATPase preparations were studied. A spin-labelled analog of ATP (ATP) was used, where the paramagnetic fragment was attached to the 2' (3')-OH ribose group. It is shown that the rotational mobility of ATP changes with the temperature in a discontinuous way. This correlates with the behaviour of the enzymatic activity of Na+, K+-ATPase and with the state of lipids in the enzyme preparations, both being characterized by a break in the 20-23 degrees C temperature region. When the Mn2+ ions were substituted by Mn2+ a strong magnetic dipolar interaction between the spin label in ATP and the Mn2+ ion was observed, which proves that the complex E-ATP--Mn2+ is formed before the hydrolysis of ATP. The structural changes which occur near 20 degrees C were also observed in the neighbourhood of the SH-groups modified by spin label X, an analog of maleimide. The structural changes observed support the idea that the protein-lipid interactions in the Na+, K+-ATPase provide the relaxation of the system from the unstable state during hydrolysis of ATP and cation transport.


Regression of a T-cell lymphoma after administration of antithymocyte globulin.

A patient with Sézary syndrome developed a diffuse undifferentiated lymphoma of T-cell origin. After becoming resistant to multiple chemotherapeutic agents, the patient was treated with antithymocyte globulin. A 75% reduction in adenopathy and complete resolution of skin erythema was observed during an 8-day period. In addition the percent of circulating T cells and the ability of those cells to respond to phytohemagglutinin and concanavalin A were reduced after antithymocyte globulin therapy. The patient died of an intracerebral hemorrhage secondary to profound thrombocytopenia. The study suggests that tumor lysis may be achieved by passive antibody therapy in certain advanced lymphomas.


Studies of fragmented sarcoplasmic reticulum from human skeletal muscle.

Sarcoplasmic reticulum (SR) vesicles were isolated from muscle biopsies of 4 normal volunteers, a patient with McArdle disease (before and during contracture), and a patient with normokalemic periodic paralysis. Fractions were analyzed for purity by electron microscopy and biochemical analysis of specific marker enzymes. Adenosine triphosphate (ATP)-dependent calcium ion uptake was measured kinetically by the absorbence changes of murexide, a metallochromic indicator of ionized Ca++ concentrations, in the absence of oxalate or other calcium-complexing anions. In these experiments, time resolution of the Ca++ transport rate was limited by the manual mixing of reagents, which occurred in 1 to 3 seconds. In 1 case the "true" initial velocity of Ca++ uptake was measured by rapid mixing of ATP in a stopped-flow apparatus and by following the change in absorbence of murexide in a storage oscilloscope. In SR from normal human muscle the ATP-dependent Ca++ uptake was 3.5 nmoles per second per milligram of protein for the first 5 seconds after ATP mixing. Fast kinetic experiments showed that Ca++ uptake proceeded linearly for the first 500 msec at a rate of 9 nmoles per second per milligram of protein (at 25 degrees C) and then progressively declined to reach steady-state levels in 40 to 50 seconds. No abnormality of Ca++ transport was found in SR vesicles from the patient with McArdle disease and the patient with normokalemic periodic paralysis.


Effect of N'-methylnicotinamide on the renal accumulation and reabsorption of gentamicin in rats.

N'-methylnicotinamide, a substrate of the organic base transport system, reduced renal accumulation of [(14)C]gentamicin in rats by 15% and increased clearance by 25%, suggesting that gentamicin is not secreted by this mechanism.


[Hypertensive cardiopathy. Study of cardiac performance].

Twenty-two hypertensive patients with normal coronary arteriograms underwent a complete study of left ventricular performance. The patients were classified into three groups according to the findings on X-ray and ECG investigation: group I--ECG normal, X-ray normal (6 cases); group II--ECG showed left atrial hypertrophy, X-ray normal (7 cases); group III-ECG showed left ventricular hypertrophy, X-ray showed cardiac dilatation (9 cases). The results of this study were as follows:--cardiac ouptut was lowered in groups II and III;--end-diastolic volume was lowered in group II and raised in group III;--LVEDP was raised in groups II and III;--V max and VEC max were lower in groups II and III than in group I;--left ventricular compliance was diminished in groups I and II. Myocardial rigidity of the left ventricle was similar in the three groups. Hypertensive heart disease is therefore characterised by early changes in compliance of the left ventricle. These are associated with geometrical changes in the ventricle: disturbance of the volume/mass ratio of the left ventricle. These findings have therapeutic implications for the importance of beta-blockers.


[The myocardiopathies of glycogenosis].

Thirty-three patients with glycogen abnormalities and myocardial disease were studied. 27 of them has type II glycogen disorders (Pompe's disease, with an intralysozymal deficit of acid maltase) and 6 with type III glycogen disorders Forbes disease, with a deficit in amylo-1-6-glucosidase). The picture of a type II abnormality in the infant is very standard: early onset, often neonatally; the association with asystole and muscular hypotonia and a characteristics clinical picture; invariable cardiomegaly and typical ECG findings (short PR interval, high voltage complexes). Death occurs before one year of age, treatment has limited effect, and attention is centred on the early discovery of heterozygotes and of diagnosis antenatally. The possibility of an obstructive type (4 out of 24) and a type with endocardial fibroelastosis (3 out of 24) must be emphasised. In the late onset myopathic form of type II disorder (3 cases), involvement of the myocardium is always found, but is of secondary importance in determining the clinical picture and natural history. The same can be said of type III disorders in which, despite the infrequency of asystole or significant cardiomegaly, a hypertrophic cardiomyopathy which may be obstructive can lead to sudden death in infancy (2 cases out of 6).


[The mutual transmission of Staphylococcus aureus between humans and cattle and the environmental adaptation of hemolysin and fibrinolysin formation].

In an ecological investigation in 20 dairy herds of cattle we compared the characteristics of strains isolated from nasal swabs of milkers, from the udder of cows and from cases of mastitis in cows. In 7 herds we found definite strains in the nasal flora of the milkers and in the udder-flora of the cows which only differ in the formation of hemolysin and of fibrinolysin. In the other checked characteristics strains from man and strains from cattle show identical patterns. In 5 herds these strains correspond to the host-specific variety hominis, in 2 herds to the hostspecific--variety bovis. These results refer to an environmental adaptation of the phenotypically detectable formation of hemolysins and fibrinolysin. From the ecological point of view an exchange of strains between man and cattle is likely. The origin of strains which can not be alloted to one ot the known host-specific varieties can be explained by an environmental adaptation. Besides the facts that strains of the host-specific variety bovis occur only very rarely in man and that strains of the host-specific variety hominis occur occasionally in cattle the clinical significance of the reported results has to be clarified by further investigations.


Cardiomyopathy produced by cigarette smoke. Ultrastructural observations in guinea pigs.

Guinea pigs were restrained in a smoking machine and were exposed to the smoke of eight cigarettes a day, five days a week for 12 to 15 weeks. One group of animals inhaled filtered smoke from which most of the tar and nicotine had been removed. Heart weight of the smoking animals was found to be significantly increased in both the filtered and unfiltered groups. Toxic changes were evident in myocardial mitochondria that were associated with edema, increased lipid and enhanced autophagolysosomal activity. The observed cardiomyopathy is probably caused by carbon monoxide and resembles the changes of chronic intermittent hypoxia.


Psychological adjustment to physical disability: trends in theories.

Explanations of psychological reactions to physical disability have recently tended to ascribe maladjustment to environmental rather than to personal causes. Historically, common-sense theories were first replaced by metalistic doctrines. These, in turn, were later supplemented by theories that integrated mentalism with environmentalism and by approaches that recognized only environmental causes of behavior. Each theory makes a unique contribution to rehabilitation. Consequently, unification rather than elimination should be the goal of future theoretical development.


Lyssavirus infection of muscle spindles and motor end plates in striated muscle of hamsters.

Immunofluorescent, light, and electron microscopy were used to document lyssavirus infection of muscle spindles and motor end plates. Virus particles were seen in the narrow intercellular space between sensory nerve endings and intrafusal muscle fibers; they were also observed budding from intracellular and plasma membranes of the latter. Involvement of motor nerves and motor end plates could only be demonstrated by electron microscopy. In nature, rabies virus invasion of the peripheral nervous system must involve centripetal spread across these junctions.


Autoreactivity between lymphocytes and thymus cells in myasthenia gravis.

Thymus cell preparations from four of five myasthenia gravis patients with thymic hyperplasia and from one additional patient with thymic involution stimulated autologous peripheral blood lymphocytes. No autostimulation was observed in two patients with thymoma. Autostimulation as associated with an increase in the fraction of B lymphocytes in the thymus.


Seizures of axial structures. Presumptive evidence for brain stem origin.

Scattered reports, both clinical and experimental, have been accumulating in the past 20 years indicating that true seizures may, indeed, originate from the brain stem and its immediate connections. Four cases are reported that give further strong presumptive evidence that this is so. All the seizures were confined to axial structures (face, tongue, palate, pharynx, diaphragm, and abdomen), and in one case each seizure had an identical "Jacksonian march." The phenomena were documented by 16-mm motion pictures, brain stem signs, and electroencephalography. The EEG consisted of periods of burst activity followed by relative interictal electrocerebral silence.


Long chain fatty acid inhibition of sodium plus potassium-activated adenosine triphosphatase from rat heart.

Long chain fatty acids were found to inhibit (Na+ + K+)-ATPase prepared from rat heart. Unsaturated and polyunsaturated fatty acids were more inhibitory than saturated fatty acids with myristic acid being the most inhibitory saturated fatty acid tested and linoleic the most inhibitory unsaturated fatty acid. As an example of fatty acid modification of the enzyme, inhibition of (Na+ + K+)-ATPase by oleate was examined. When compared to ouabain, inhibition of (Na+ + K+)-ATPase by oleate was found to be similar in that both were dependent on K+ concentration, but, in contrast to the almost instantaneous inhibition by ouabain, oleate inhibition was a slow process requiring over 20 min incubation at 37 degrees to produce maximum inhibition. Inhibition of rat heart (Na+ + K+)-ATPase by oleate was found to be readily reversible by washout. In the presence of albumin an oleate/albumin molar ratio greater than 7.5 was required for inhibition to occur. The activity of rat heart (Na+ + K+)-ATPase had a temperature optimum above 40 degrees and a discontinuous Arrhenius' plot with a transition temperature of 25 degrees. In the presence of oleate, however, the enzyme's optimum temperature decreased to below 40 degrees, the activation energy of the reaction at temperatures below 25 degrees was lowered from 24.7 kcal/mol to 12.6 kcal/mol and the enzyme had a linear Arrhenius' plot. The possibility of in vivo inhibition of cardiac (Na+ + K+)-ATPase under conditions of elevated fatty acids is discussed.


[Alteration of the ATP-ase Mg++ and Mg++ Na+ K+ activities of the central nervous system of Periplaneta americana L. after sonification. (author's transl].

A prolonged ultrasonic homogenization of a Periplaneta americana L. suspension of ganglia in a buffer solution pH 7,6 when compared with a Potter Elvehjem homogenization shows a marked reduction of Mg++ and (Mg++ + Na+ + K+) ATPase activities. Mg++ ATPase was not modified while the (Mg++ + Na+ + K+) ATPase was completely inhibited after 30 second ultrasonic homogenization. This probably results from an enzyme structure alteration caused by the ultrasonic treatment.


Hereditary C2 deficiency associated with immune complex disease.

A patient presenting with a syndrome probably due to immune complex deposition was investigated and found to possess an inherited C2 complement deficiency. Family studies indicated that the deficiency was transmitted as an autosomal recessive trait. HLA typing for the HLA-A and HLA-B specificities and HLA-D specificities indicated a close linkage between the HLA and C2 genes, as has been described elsewhere. The HLA-A and B locus specificities HLA-AW25 and HLA-B18 were coded for by each of the two chromosomes carrying the C2(0) gene. However, the two chromosomes differed at the HLA-D locus, as one coded for HLA-DW2 whilst the other did not. This case, therefore, provides a unique haplotype and may be of importance in mapping the C2(0) locus, as it suggests that the gene order on chromosome 6 is HLA-D, C2(0), HLA-B, HLA-A. Extensive complement component assays indicated that utilization of complement in the patient was occurring via the alternate complement pathway. It is suggested that, as a result of the C2 deficiency, infections with viruses and other agents could lead to an immune complex disease due to an impaired capacity to effectively eliminate circulating complexes.


Chronic low back pain: evaluation and therapy.

Chronic low back pain is a common complaint afflicting a large percentage of the population. More interest is required in solving this problem, which is of large economic proportions. This paper reports some procedures by which this may be achieved.


Swine kidney worm disease in Cuba (Stephanurus dentatus Diesing, 1839).

The results of a two-year study on swine stephanuriasis in Cuba indicate the high economic importance of this parasitosis in view of its pattern of local distribution and pathological changes occurring during the endogeneous phase of its life cycle. Under the present conditions of pig breeding in Cuba, it appears to be most economic to base control measures on a strict observance of general zoohygienic rules and on several specific measures suggested in the paper. The administration of expensive drugs is uneconomic because none of them is universally effective in any phase of the life cycle of S. dentatus. It is suggested to direct research work to suitable preventive measures and the choice of drugs to be administered during the most critical period in the spread of infection covering the time from birth to weaning.


A calcium ion-dependent adenosine triphosphate pyrophosphohydrolase in plasma membrane from rat liver. Demonstration that the adenosine triphosphate analogues adenosine 5'-[betagamma-imido]triphosphate and adenosine 5'-[betagamma-methylene]-triphosphate are substrates for the enzyme.

An ATP pyrophosphohydrolase in a rat liver plasma-membrane subfraction was studied with respect to specific Ca2+ activation of the beta-phosphate bond hydrolysis. ATP and, in addition, adenosine 5'-[betagamma-imido]triphosphate and adenosine 5'-[betagamma-methlylene]triphosphate were substrates for Ca2+-stimulated enzymic hydrolysis of the beta-phosphate bond. A 15-fold activation was observed by raising the free Ca2+ concentration from 10(-7) to 10(-5) M. Mg2+ had little effect. Solubilization in 1% deoxycholate and partial purification on a sucrose density gradient resulted in a 5-fold increase in specific activity with unaltered Ca2+-stimulation pattern. The possible importance of the enzyme in Ca2+ transport is discussed.


The properties of adenosine triphosphatase from exponential and synchronous cultures of Alcaligenes eutrophus H16.

The properties of Alcaligenes eutrophus ATPase (adenosine triphosphatase) were investigated by using subcellular fractions prepared from cells growing in exponential and synchronous cultures. Both the soluble and membrane-bound forms of the ATPase were inhibited non-competitively (K(i) 142mum) by Nbf-Cl (4-chloro-7-nitrobenzofurazan), whereas only the membrane-bound enzyme was inhibited (non-competitive; K(i) 750mum) by NN'-dicyclohexylcarbodi-imide. Neither the activity of the ATPase nor its sensitivity to these two inhibitors varied during exponential growth. However, marked variations in ATPase activity were observed during synchronous growth, which were characterized by maxima at approx. 0.4 and 0.9 of a cell cycle and minima at approx. 0.1 and 0.6 of a cycle. Sensitivity to Nbf-Cl and NN'-dicyclohexylcarbodi-imide also varied during the cell cycle; maximum inhibition by the former occurred at approx. 0.4 and 0.9 of a cell cycle, whereas maximum inhibition by the latter was located at approx. 0.1 and 0.6 of a cell cycle. Proton conductance by whole cells was also periodic during the cell cycle, the lowest rates occurring at approx. 0.15 and 0.55 of a cycle and the highest rates at approx. 0.4 and 0.9 of a cycle, but -->H(+)/O quotients for the oxidation of endogenous substrates remained relatively constant and indicated the presence of four proton-translocating respiratory segments throughout the cell cycle. These results are discussed in terms of ATPase and respiratory-chain structure and function during the cell cycle of Alcaligenes eutrophus.


A new mouthpiece for the Wright peak flow meter.

When tested against artificially produced peak flows, the Wright peak flow meter is found to be an accurate instrument. A factor contributing to the variation seen when the meter is in clinical use in the design of the mouthpiece. This paper reports the results obtained using a new mouthpiece designed specifically to reduce this variation.


Inhibition of plasmin by antithrombin-heparin complex. II. During thrombolytic therapy in man.

The role of antithrombin as an inhibitor of plasmin in the presence and absence of heparin was studied during thrombolytic therapy in 12 patients with vascular occlusive disease. The extent of plasmin-antithrombin-(heparin) complex formation was studied by intravenous injection of iodine-labelled antithrombin (5-20 muCi) and quantitation of the amount of antithrombin bound to plasmin. In the absence of heparin, less than 0.8% of the labelled antithrombin was recovered in the plasmin-antithrombin complex but between 1.2 and 4.8% following injection of 5000 iu of heparin. Thus only between 3 and 11% of the in vivo formed plasmin is neutralized by antithrombin-heparin complex. Repeated activation of the fibrinolytic system resulted in a shortening of the plasma radioactivity half-life of labelled antithrombin from 2.45 to 2.03 d in the absence of heparin (three patients), and from 3.13 to 2.35 d following heparin administration (two patients). This increased turnover does not result in a decrease of the plasma antithrombin level.


Ultrastructural identification of acid complex carbohydrate in cytoplasmic granules of normal and leukaemic human monocytes.

Complex carbohydrate in granules of monocytes was compared with that in granules of neutrophils by ultrastructural cytochemical methods. The acid mucosubstance in granules of both cell types stained with dialysed iron after brief fixation with dilute glutaraldehyde, but that in monocyte granules differed in failing to stain after stronger fixation. Approximately 10% granules in normal blood monocytes stained with this method, whereas more than 90% of granules in leukaemic monocytes from two of seven patients with acute myelomonocytic leukaemia stained intensely. This difference presumably results from unmasking of acid groups in immature granules or increased synthesis of granule mucosubstance in some leukaemic monocytes. Granules of monocytes differed further from those of neutrophils in failing after either type of fixation to stain with a high iron diamine technique for for demonstration of sulphated mucosubstance. The absence of high iron diamine staining could reflect a lack of sulphate esters in monocyte granule mucosubstance, masking of the sulphate groups by other components, or extraction of the sulphated mucosubstance during specimen processing.


The effect of sodium on inorganic phosphate- and p-nitrophenyl phosphate-facilitated ouabain binding to (Na+ + K+)-activated ATPase.

The effect of the hydrolysis product Pi and the artificial substrate p-nitrophenyl phosphate (p-nitrophenyl-P) on ouabain binding to (Na+ + K+)-activated ATPase was investigated. The hypothesis that (Mg2+ + p-nitrophenyl-P)-supported ouabain binding might be due to Pi release and thus (Mg2+ + Pi)-supported could not be confirmed. The enzyme . ouabain complexes obtained with different substrates were characterized according to their dissociation rates after removal of the ligands facilitating binding. The character of the enzyme . ouabain complex is determined primarily by the monovalent ion present during ouabain binding, but, qualitatively at least, it is immaterial whether binding was obtained with p-nitrophenyl phosphate or Pi. The presence or absence of Na+ during binding has a special influence upon the character of the enzyme . ouabian complex. Without Na+ and in the presence of Tris ions the complex obtained with (Mg2+ + Pi) and that obtained with (Mg2+ + p-nitrophenyl-P) behaved in a nearly identical manner, both exhibiting a slow decay. High Na+ concentration diminished the level of Pi-supported ouabain binding, having almost no effect on p-nitrophenyl phosphate-supported binding. Both enzyme . ouabain complexes, however, now resembled the form obtained with (Na+ + ATP), as judged from their dissociation rates and the K+ sensitivity of their decay. The complexes obtained at a high Na+ concentration underwent a very fast decay which could be slowed considerably after adding a low concentration of K+ to the resuspension medium. The most stable enzyme . ouabain complex was obtained in the presence of Tris ions only, irrespective of whether p-nitrophenyl phosphate of Pi facilitated complex formation. The presence of K+ gave rise to a complex whose dissociation rate was intermediate between those of the complexes obtained in the presence of Tris and a high Na+ concentration. It is proposed that the different ouabain dissociation rates reflect different reactive states of the enzyme. The resemblance between the observations obtained in phosphorylation and ouabain binding experiments is pointed out.


Stability of messenger RNA for nitrate reductase in Neurospora crassa.

A method has been developed to study the synthesis and decay of the messenger RNA for nitrate reductase in Neurospora crassa. Glutamine prevents the synthesis of the mRNA which appears to have a half-life of approximately 8.5 min.


The effect of mechanical stretching of the myosin rod component (fragment LMMMM S-2) on the ATPase activity of myosin.

The binding of myosin to nylon fiber gives immobilized myosin with a considerable ATPase activity. Treatment of immobilized enzyme with papain results in the entire ATPase activity (known to be concentrated in myosin heads, (fragment HMM S-1)) being replaced from the fiber into the solution; this means that myosin is chemically bound to the fiber via its rod part (fragment LMM+HMM S-2). When nylon fiber is mechanically stretched, the ATPase activity of myosin attached to it sharply decreases; after relaxation of the fiber the enzymatic activity returns to the initial level. The detailed study of this phenomenon has shown that reversible inactivation of myosin upon fiber stretching is not the result of an altered microenvironment of the enzyme. The discovered regulatory effect is ascribed to deformation of myosin molecules induced by support stretching. Thus deformation of the myosin tail (not indispensable for ATPase since its cleaving-off does not alter the enzymatic activity) leads to decrease in the ATPase activity of the enzyme. The possible role of the above phenomenon in the mechanism of muscle contraction is discussed.


Purification and characterization of epsilon-N-trimethyllysine L-amino oxidase from Neurospora crassa.

epsilon-N-Trimethyllysine L-amino oxidase from Neurospora crassa has been purified to electrophoretic homogeneity. A 1500-fold purification was obtained by centrifugation and successive column chromatography on ion-exchange and gel filtration supports. The enzyme has an estimated molecular weight of 160 000. It transforms epsilon-N-trimethyllysine into alpha-keto, epsilon-N-trimethylhexanoic acid by oxidative deamination. Kinetic studies of this new enzyme are reported and its probable physiological role is discussed.


Inhibition of gill (Na+ + K+)-ATPase in rainbow trout (Salmo gairdneri) by a purinedisulfide analog of adenosine triphosphate.

The effect of the adenosine triphosphate analog, 6,6'-dithiobis(inosinyl imidodiphosphate), (sIMP-PNP)2, was tested on the ouabain-sensitive (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and the ouabain-insensitive Mg2+ - ATPase in microsomes prepared from gill tissue of sea water-adapted rainbow trout, Salmo gairdneri. The (Na+ + K+)-ATPase was completely inhibited by low concentrations of (sIMP-PNP)2 (6 micrometer) but the Mg2+ - ATPase was unaffected by the inhibitor at concentrations as high as 28 micrometer, supporting the suggestion that the two activities represent separate enzymes. The specificity of inactivation could be demonstrated both at a physiological temperature (13 degrees C) and at 37 degrees C. The rates of inactivation were similar at both temperatures. Inactivation of the (Na+ + K+)-ATPase by (sIMP-PNP)2 was reversed by dithiothreitol, suggesting that the inhibitor forms a mixed disulfide with sulfhydryl groups on the enzyme. The inability of substrate (either ATP or its analog, adenyl-5'-yl imidodiphosphate) to protect against inactivation suggests that (sIMP-PNP)2 is reacting with sulfhydryl groups which are not associated with the active site.


Hormone action at the membrane level. VIII. Adrenergic receptors in rat heart and adipocytes and their modulation by thyroxine.

The regulation of adrenergic receptors in rat heart was measured in rats made hyperthyroid by injection with thyroxine and made hypothyroid by addition of propylthiouracil to the drinking water. Hyperthyroid rats display cardiac hypertrophy and a decrease in epididymal fat pad weight. The maximal beta-receptor level of ventricular membranes, as determined by (-)-[3H]dihydroalprenolol binding, was increased 60% by thyroxine treatment and decreased about 30% by propylthiouracil treatment. The affinity of the beta receptor was unchanged after thyroxine or propylthiouracil treatment. The maximal activity of the isoproterenol-stimulated adenylate cyclase (EC 4.6.1.1) varied with thyroid state in a manner parallel to the increase in beta-adrenergic binding sites. Thyroxine treatment also increases by 2-fold the beta receptors in isolated rat fat cells. Propylthiouracil treatment lowered the level of alpha receptors in heart by 30% as measured by [3H]dihydroergocryptine binding, but increased the affinity about 2.5-fold. The highest level of alpha receptors was seen in control hearts. These studies indicate that thyroxine may control the turnover of beta-adrenergic receptors in heart and fat cells and regulate physiological responses in these tissues via a hormone-hormone interplay system. Thyroxine treatment reduced the activity of the membrane-bound Mg2+-ATPase (EC 3.6.1.3) and 5'-mononucleotidase (EC 3.1.3.5) but appears to increase the activity of the (Na+ + K+)ATPase (EC 3.6.1.4).


Purification and characterization of myosin from bovine retina.

Myosin has been isolated from bovine retinae and characterised by its ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity, its mobility in sodium dodecyl sulphate polyacrylamide gels and by electron microscopy. The purified myosin shows high ATPase activity in the presence of EDTA or Ca2+ and a low activity in the presence of Mg2+. The Mg2+-dependent ATPase activity is stimulated by rabbit skeletal muscle actin. The presumptive retinal myosin possesses a major component which has a mobility in sodium dodecyl sulphate polyacrylamide gel electrophoresis similar to that of the heavy chain of bovine skeletal muscle myosin. Electron microscopy showed retinal myosin to form bipolar filaments in 0.1 M KCl. It is concluded that the retina possesses a protein with enzymic and structural properties similar to those of muscle myosin.


[Changes in ATPase activity of dog kidney nuclear membrane under the effect of polyenic antibiotics].

Effect of amphotericin B and nistatin on ATPase activity of dog kidney nuclear membranes is studied in vivo and in vitro. Long-term intravenous injections of the antibiotics do not change the ATPase activity of kidney nuclear membranes. However, short-term injections of polyenic antibiotics have some effect on ATPase activity on nuclear membranes: amphotericin B, considerably activates the enzyme . In vitro incubation of isolated dog kidney nuclei with amphotericin and nistatin at concentrations of 1 and 10 mcg/ml does not affect the activity of nuclear membrane ATPase, while increased concentrations of polyenic antibiotics, (up to 200 mcg/ml) results in a slight inhibition of the enzyme activity. The role of the data obtained for solving molecular basis of the toxic effect of polyenic antibiotics.


[Effect of SH-reagents on ATPase systems of rabbit skeletal muscle nuclei].

The influence of sulfhydryl reagents on ATPase systems of rabbit sceletal muscles nuclei was studied. It is found that p-ChMB at low concentration similarly inhibits both Mg2+- and Mg2+, Ca2+-ATPases. p-ChMB at higher concentrations inhibits completely Mg2+, Ca2+-ATPase, while Mg2+- ATPase--only by 60%. N-EM is lesser specific inhibitor of SH-groups, than p-ChMB. The degree of nuclear ATPases inhibition by N-EM is practically identical. Using inhibitory analysis, two hypes of skeletal muscles nuclei SH-groups are found: easily reacting with N-EM, and those reacting with N-EM at more high concentrations, which are essential for ATPase ATP-hydrolysing activity. ATP defends Mg2+, Ca2+-ATPase, but not the Mg2+-ATPase from N-EM inhibitory action. Cysteine completely eliminates the inhibitory effect of p-ChMB on Mg2+-ATPase but only 40% on MG2+, Ca2+-ATPase. Mg2+, Ca2+-ATPase of nuclei is more sensitive to the sulfhydryl venoms action than Mg2+-ATPase.


[Purification and characterization of epidermal G2- and G1-chalones].

Highly purified epidermal G1- and G2-chalones from rat skin inhibit the entering of epidermocytes to S and M phases of cell cycle respectively. Their biological activity is characterized by tissue-specificity and not by species-specificity. Both of them are tissue-specific glycoproteins as for their antigenic properties. Molecular weight of G1-chlone is 21 000, G2-chalone--34 000, isoelectric point (pH) 5.55 and 5.85 respectively. G2-chalone is the fastest as compared to G1-chalone in 5% acrylamide gel electrophoresis, pH 8.3. When injected in rabbits, G2-chalone produced monospecific antibodies which have no cross-reactivity with G1-chalone. The amino acid composition of both chalones and immunofluorescent localization of G2-chalone in epidermal tisues are given.


[Effect of para-chlorophenylalanine and 5-hydroxytryptophan on the caudate nucleus in cats].

In unrestrained cats parachlorophenylalanine, an inhibitor of serotonin synthesis, increased the thresholds of the contraversive reaction and arrest reaction accompanied by spindle-waves in the sensory-motor cortex in the stimulation of the rostro-ventral areas of the caudate nucleus. The reactions evoked from the dorso-medial areas of the head and the body of the nucleus changed differently. On the contrary, 5-hydroxytryptophane, serotonin precursor, increased most of the indices of the caudate activity independently of the site of stimulation. It is suggested that the serotoninergic mechanisms (antagonistic to the dophaminergic system) existing in the ventral part of the caudate nucleus may trigger some caudate functions.


[Change in the activity of epidermal chalones during skin reaction to the effect of a carcinogen and epilation].

The biological activity of an epidermal G2-chalone extracted from the rat back skin was found to decrease 1 to 2 days after the treatment with methylnitrosourea (a carcinogen), and one day after the epilation. Results of quantitative recording and morphological analysis of the skin serving as the source of chalones, pointed to different mechanisms which underlay this effect.


[Effect of blockers of serotonin and noradrenaline synthesis on learning with emotionally different reinforcement in rats].

The effect of inhibitor of serotonin and norepinephrine synthesis in the brain on learning was investigated in rats with emotionally different reinforcement. Parachlorphenylalanine (320 mg/kg) was shown to inhibit learning with food reinforcement, but facilitated learning with pain reinforcement. Disulfiram (100 mg/kg) inhibited learning with pain reinforcement considerably, but failed to influence learning with food reinforcement. Alpha-methyl-m-thyrosine inhibited both forms of learning. These new facts are in line with our previous data on mediating role of the brain monoaminergic systems between emotions and memory.


[Role of membrane-bound calcium in changes in the ATPase activity, permeability and structural state of human erythrocyte membranes].

A study was conducted on the reconstituted erythrocytes obtained by the method of fast reversible hemolysis. The concentration of free Ca2+ ions in the reconstituted erythrocytes was supported by Ca-EGTA and Ca-nitrate buffers. Oubain-uninhibited ATPase component with a high affinity for Ca2+ (K0.5=4 micron) and alteration of passive and active K+-permeability in the region of free Ca2+ concentration up to 10 micron could be determined only when the content of membrane-bound Ca+ varied. Depletion of the inner side of the membrane of reconstituted erythrocyte is accompanied by alteration of hydrophobic character of the hydrocarbon region of the membrane. It is suggested that Ca+-induced alterations in the structure of the erythrocyte membrane may be a direct cause of the alterations in ATPase activity with a high Ca2+ affinity and permeability for univalent cations.


[Quantitative histoenzymologic characteristics of the submaxillary salivary glands of white rats during an ovarian cycle].

Ovarian cycle in albino rats was applied to ascertain the problem of the relationship between the salivary and endocrine glands, and also of the extent of participation of individual components of the salivary glands with different functional orientation in the endocrine regulation of individual components of the salivary glands. The content of protein, mucopolysaccharides, DNA, and RNA, the activity of NAD- and NADP-diaphorase, alkaline phosphatase, malate and isocitrate dehydrogenase, alpha-leucine-aminopeptidase was studied. Cytospectrophotometric analysis showed that synchronous changes in the activity of the enzymes under study occurred in all the portions of the salivary glands, depending on the ovarian cycle phases. Of the four successive phases of the cycle the greatest activity of the enzymes and of the protein and mucopolysaccharide content was noted during the proestrus and metaestrus. Different metabolic processes were observed in the salivary ducts in comparison with other parts of the gland; this was apparently connected with peculiarities of the secretion and hormone production.


Molecular weight and some chemical properties of the granulocytic chalone.

Granulocytic Chalone (GCh) has been highly purified from culture medium conditioned by human peripheral leukocytes. Purification was performed by column chromatography on Sephadex G-25 and G-10, rechromatography on G-10, preparative paper chromatography and thin-layer-chromatography. The inhibitory activity and specificity of GCh was monitored by agar colony formation and 3H-thymidine incorporation into bone marrow and thymic cells. The gelchromatographic behavior of GCh is discussed in detail with regard to its molecular weight. The results obtained indicate that GCh may be a small (MW 500--600), acidic and highly polar peptide containing aspartic and glutamic acid among others. The N-terminal aminogroup seems to be blocked.


Vein surgery during defibrinogenation.

The effect of defibrinogenation on thrombosis after thrombectomy and on the patency of Dacron femoral vein grafts has been studied in dogs. In all experiments the defibrinogenation significantly reduced thrombosis. Bleeding from suture lines and through the Dacron prostheses was not increased.


Response to transient disturbances during intentional forearm flexion in man.

Steps of torque were applied to the human forearm during intentional flexion movements with peak velocities of 40-500 degrees/sec and during ballistically initiated flexion movements. The question asked was whether or not the motor ouput to both agonist and antagonist muscles is independent of sensory input data or is accessible and influenced by these inputs. The data obtained demonstrate unequivocally that the applied perturbation affects the motor output, irrespective of the speed of the movement. The time of onset of the reflex changes in motor output and their maxima are related to the movement's parameters. Data are presented which indicate that the source for the reflex changes observed are the muscle spindles.


Blockage of depolarization-induced mitogenesis in CNS neurons by 5-fluoro-2'-deoxyuridine.

Experiments designed to provide further evidence, at the basic metabolic level, that true mitogenesis and mitotic activity are being induced in CNS neurons in response to sustained ionic depolarization were conducted. The ability of 5-fluoro-2'-deoxyuridine (FUdR), a well-studied inhibitor of normal mitogenesis in naturally proliferating cells, to block induction of DNA synthesis (and subsequent nuclear division) in culture-matured neurons depolarized with ouabain was ascertained, as well as the ability of exogenously supplied thymidine to permit effective bypass of such blockage. Observations of the sequence of intracellular morphological changes induced by ouabain were also made, along with a determination of the alterations in this sequence introduced by FUdR. The results indicate that ouabain mediated depolarization rapidly induces and/or activates the key mitogenic enzyme thymidylate synthetase in the mitotically quiescent neurons, along with all other mitogenesis-specific enzymes required for DNA synthesis and nuclear division. A probable mechanism by which such mitogenic induction may proceed is elaborated. The early morphological changes observed correlate well with the early time-sequence of mitogenic metabolic events, while development of the later changes appears to be dependent upon the progress of mitogenesis activity. The results support the possibility that CNS neurons of adult origin may also be induced to initiate normal mitogenesis by appropriately imposed depolarization treatments.


Effect of dichloromethylene diphosphonate on morphology, enzyme activity, and ash content of bones of thyroparathyroidectomized rats.

Dichloromethylene diphosphonate (Cl2MDP) was given at doses of 4 mg/kg and 10 mg/kg daily for 7 days to adult thyroparathyroidectomized rats fed a low calcium diet. Primary metaphyseal trabeculae in Cl2MDP-treated rats were more numerous and longer than in controls. The light and electron microscopic appearance of osteoblasts, osteocytes and osteoclasts were unaltered by Cl2MDP. Bone alkaline phosphatase was significantly elevated in rats given Cl2MDP but adenosine triphosphatase activity was unchanged. Bone fat-free weight, fat-free minus ash weight, and bone calcium and phosphorus concentration were reduced significantly in rats given 10 mg/kg Cl2MDP compared to controls. Bone magnesium concentration was significantly elevated in rats given 10 mg/kg Cl2MDP. Serum calcium and phosphorus concentration were lower in Cl2MDP-treated rats. These results suggest that Cl2MDP is capable of altering bone remodeling, enzyme activity and mineral content, without significantly altering bone cell morphology, independent of the effects of parathyroid hormone, calcitonin, and dietary calcium.


Neurospora endoexonuclease and its inactive (precursor?) form.

Two nuclease activities which were shown previously to copurify from extracts of log-phase Neurospora mycleia, a single-strand specific endonuclease activity (with DNA and RNA), and a strand nonspecific exonuclease activity (with DNA only) have been found to be associated with a single polypeptide. The enzyme has therefore been classified as an endoexonuclease. In logphase extracts, about 75% of this enzyme was found to exist in an inactive form which was activated in vitro either by endogenous phenylmethylsulfonyl fluoride sensitive proteinase(s) or by exogenous trypsin. The inactive form of endoexonuclease has been purified 45-fold in 15% yield free of the active enzyme. On electrophoresis in 6 M urea--polyacrylamide gels, it migrated at a much slower rate than the active enzyme, indicating that it is a less acidic and(or) larger protein than the active nuclease. The strong adsorption of this inactive enzyme on octyl-Sepharose suggests that the protein may have a relatively large hydrophobic domain. The protein may be a precursor of the active enzyme (a pronuclease) or a strong complex of enzyme with a proteinaceous inhibitor that is not dissociated in 6 M urea or during a variety of chromatographic procedures.