A calcium-sensitive preparation from Physarum polycephalum. Differential ultracentrifugation of an extract of the plasmodium of Physarum polycephalum yields a high-speed fraction which exhibits calcium-sensitive adenosine triphosphate activity at low ionic strength. The rate of inorganic phosphate production increased from 2- to 25-fold in different preparations when the calcium concentration was increased from about 10(-8) to 10(-5) M. Complement fixation using specific antibody to Physarum myosin showed the fraction to contain 3% myosin. By electron microscopy, actin-like microfilaments 50--150 nm long were present. Addition of pure rabbit F-actin or myosin to this fraction activated the ATPase measured in EGTA and so partially reversed the calcium sensitivity. If muscle myosin was added to the supernatant from which the fraction was centrifuged, a "hybrid complex" was obtained which included actin and additional protein from the plasmodium, and this hybrid was also calcium sensitive. Over 85% of the calcium-sensitive, magnesium-activated ATPase could be precipitated by sequential "hybrid" formation. The calcium sensitivity of the hybrid was maximal when formed at the lowest ratios of added myosin to Physarum proteins. It is concluded that the results do not allow a simple interpretation along the lines of either actin-linked or myosin-linked sensitivity. Evidence consistent with both a form of actin-linked and myosin-linked sensitivity is present in our results.


Role of the intramitochondrial adenine nucleotides as intermediates in the uncoupler-induced hydrolysis of extramitochondrial ATP. 1. A formula is given that describes the appearance of [14C]ATPADP outside the mitochondria after the addition of [14C] 1atp during the steady-state uncoupler-induced hydrolysis of extramitochondrial ATP. If the transported adenine nucleotides equilibrate with the intramitochondrial pool, [14C]ADP0 would be expected to appear with a lag phase that corresponds with the time needed for the radioactive labelling of the intramitochondrial adenine nucleotide pool. 2. The rates of formation of [14C]ADP outside the mitochondria after addition of [14C]ATP during the steady-state uncoupler-induced ATP hydrolysis catalysed by rat-liver mitochondria at 0 degree C were measured. 3. In the presence of carbonyl cyanide m-chlorophenylhydrazone the time course  of the [14]ADPo formation  was the same as that predicted on the basis of the above assumption. 4. In the presence of the less effective uncoupler, 2,4-dinitrophenol, the time course of [14C]ADPo formation was not consistent with the theoretical predictions: no lag phase was present and the measured rate was higher than the maximal calculated rate. These results can be explained by assuming a functional interaction between the adenine nucleotide translocator and the mitochondrial ATPase (F1). 5. It is concluded that under phosphorylating as well as dephosphorylating conditions, the adenine nucleotide translocator and the mitochondrial ATPase can be functionally linked to catalyse phosphorylation or dephosphorylation of extramitochondrial ADP or ATP, without participation of the intramitochondrial adenine nucleotides.


The (Na + K+)-dependent ATPase. Mode of inhibition of ADP/ATP exchange activity by MgC12. Na+-dependent ADP/ATP exchange activity, of a (Na++K+)-dependent ATPase preparation from eel electric organ, was measured in terms of the incorporation of 14C into ATP during incubations with labeled ATP and [14C]ADP. Estimates of initial rates of exchange were possible by keeping changes in nucleotide concentrations, from both exchange and extraneous hydrolytic processes, to less than 10%. Under these conditions, increases in MgC12 concentration, from 0.2 to 3 mM, generally inhibited this exchange activity. The concentrations of free Mg2+, Mg-ATP, and Mg-adp present, with a range of MgC12, ATP, and ADP concentrations, were calculated from measured dissociation constants. Inhibition was associated with Mg-ATP as well as with Mg2+, at concentrations from 0.4 to 1 mM (Mg-ADP, in the same concentration range, probably inhibited also). The affinity of the enzyme for these inhibitors is in fair correspondence with demonstrated affinties for Mg2+, Mg-atp, and Mg-ADP at low affinity substrate sites, measured kinetically. These observations are considered in terms of a dimeric enzyme with high and low affinity substrates sites: ADP/ATP exchange being catalyzed at the high affinity sites, with inhibition occurring through occupancy by Mg2+, Mg-ATP, or Mg-ADP, of the low affinity sites, thereby pulling the reaction process away from those steps involved in exchange.


Aspects of the mechanism of action of local anesthetics on the sarcoplasmic reticulum of skeletal muscle. 1. The effect was studied of local anesthetics (tetracaine, dibucaine, procaine and xylocaine) on the forward and the backward reactions of the calcium pump of skeletal muscle sarcoplasmic reticulum. 2. The inhibition of the rate of calcium uptake, the rate of calcium-dependent ATP splitting and the rate of calcium-dependent ATP-ADP phosphate exchange by sarcoplasmic reticulum in the presence of the above drugs is at least partially due to the inhibition of the phosphoprotein formation from ATP. 3. The rate of the ADP-induced calcium release from sarcoplasmic reticulum and the rate of ATP synthesis driven by the calcium efflux are inhibited on account of a reduction of the phosphoprotein formation by orthophosphate. 4. The phosphorylation of calcium transport ATPase by either ATP or orthophosphate is diminished by the local anesthetics owing to a reduction in the apparent calcium affinity of sarcoplasmic reticulum emmbranes on the outside and on the inside, respectively. 5. The drug-induced calcium efflux from calcium-preloaded sarcoplasmic reticulum vesicles, a reaction not requiring ADP, is probably not mediated by calcium transport ATPase.


On the amount of (Na+ + K+)-ATPase available for transepithelial sodium ion transport in the amphibian skin. Pretreatment of frog skin epithelium homogenates with sodium dodecyl sulphate in the presence of ATP reveals levels of ouabain-sensitive ATPase activity usually higher and occasionally far higher than those required to sustain maximum rates of Na+ transport. This supports the view that Na+ transport involves only a fraction of the epithelial cells.


Fibrinolysis in normal plasma and blood: evidence for significant mechanisms independent of the plasminogen-plasmin system. Fibrinolytic activity of normal plasma and blood has been measured by 125l-fibrin solid phase assay. Activity of plasma is not affected by removal of plasminogenplasmin by affinity chromatography. Activities of euglobulin and pseudoglobulin fractions are approximately equal. epsilon-aminocaproic acid (EACA) (10 mM), tranexamic acid (10 mM), diisopropylfluorophosphate (DFP, 50 mM), and soybean and lima bean trypsin inhibitors (100 mug/ml) do not inhibit plasma activity at concentrations that inhibit pure plasmin and urokinase-activated plasma. Activity is not affected by glass contact and is not inhibited by inhibitors of contact or enzymatic activation of Hageman factor (hexadimethrine bromide, 100 mug/ml; cytochrome C, 250 mug/ml; spermidine, 2 mM; phenylmethylsulfonylfluoride, 1 mM). It is inhibited partially (30%-40%) by heating (56 degrees C, 30 min) and by zymosan (2.5 mg/ml; 40%-90% inhibition), and is increased by hydrazine (20 mM), salicylaldoxime (20 mM), DFP (50 mM), and tosyl-L-arginine methyl ester (TAMe, 10 mM)-the latter two at concentrations known to inhibit Cls of the classic, and factor D of the alternate complement pathways. Increase fibrinolytic activity with TAMe is associated with reciprocal decrease in classic and alternate complement pathway activity. It is concluded that normal plasma fibrinolytic activity is relatively independent of plasmin as the ultimate fibrinolytic enzyme, that Hageman factor-dependent pathways are of minor importance, and that significant heat-stable and heat-labile nonplasmin fibrinolytic activities are operative. These may include proteinases involved in complement activation, and in common control of classic and alternate complement pathways, as well as other nonplasmin proteinases.


[T-cell leukemias of adulthood].

[T-cell leukemias of adulthood]. 9 adult patients suffering from different forms of T-cell-malignancies were investigated: 4 patients with T-ALL; 1-T-ALL-CLL mixed form (prolymphocytic); 2 T-CLL; 2 Sézary-syndrome. The clinical peculiarities of the different forms of leukemias were compared: involvement of lymph nodes and spleen, of the central nervous system and the skin was frequent; in contrast to the findings in Sézary-syndrome, bone marrow infiltration was prominent. Light and electron microscopic morphology of the malignant cells are described. In all cases a strong activity of acid phosphatase was demonstrated, in one patient prominent deposits of glycogen. The T-cell-quality of the respective malignant cell population as well as the B-T-cell distribution of the remaining "normal" lymphocytes were shown by the following cell markers: demonstration of T-cell-antigen, resp. membrane immunoglobulins with the aid of specific heterologous antisera conjugated with peroxidase, 125iodine or fluoresceine; complement consumtion or cytotoxicity with such antisera; spontaneous rosette formation with sheep red cells or with acrylic acid beads. Usually, there was a good coincidence in results obtained with the different markers. In two patients, however, T-cells demonstrated by anti-T-globulin were not able to form T-rosettes. Responsiveness of the malignant T-cells and also of the remaining "normal" blood lymphocytes to different mitogens usually was depressed, immunoglobulin levels in the blood mostly were normal. Taking all findings into consideration, T-cell-leukemias of the adult represent a special group of hematological malignancies; the different subgroups show similarities; transitional forms occur.


Starting procedures for the isolation and purification of granulocyte chalone activities. Several starting materials and procedures for the extraction and purification of granulocyte chalone activities were tested and evaluated. Among others, leuko-adhesion of bovine blood granulocytes on nylon and cotton wool and direct extraction with polar organic solvents were found suitable. Following PVP-leukapheresis ascites fluids were collected from rats, purified by ultrafiltration and Sephadex G 25 chromatography to yield 2 inhibitors at Ve/Vo = 2.1 and 2.6 and one stimulator at 2.0 by the in vitro 3H-thymidine test. Fraction 2.1, which has met the criteria of a granulocyte chalone by the diffusion chamber and agar colony test, was found thermostabile and to contain several peptides. Yet evidence for the peptide nature of the inhibitor is not conclusive. Extracts from bovine blood granulocytes contained only the inhibitor at 2.1. Problems related to the in vitro test for chalone activity were discussed.


Stereospecific actions of 2,5-dimethoxy-4-methylamphetamine (DOM) on colonic temperature in the rat at various ambient temperatures. The R(-) and S(+)-isomers of 2,5-dimethoxy-4-methylamphetamine (DOM) produce a dose-dependent hypothermia in rats kept in the cold (6 degrees C). 2 This hypothermia was linearly dependent upon ambient temperature and the R(-)-isomer was considerably more potent than the S(+)-isomer. 3 A statistically significant tachyphylaxis was observed when R(-)-DOM was administered on two successive days. The response seven days after the second injection was similar to that on the first day of injection. 4 The hypothermia induced by R(-) and S(+)-DOM was antagonized by methysergide but not by p-chlorophenylalanine (PCPA) or pimozide. Methysergide, PCPA or pimozide alone did not elicit hypothermia at the doses used. The results indicate that R(-) and S(+)-DOM act at post-synaptic 5-hydroxytryptamine receptors.


The possible involvement of Na+ ions in corticosterone-induced hypercontractility in the rat anococcygeus muscle. The possibility that corticosterone-induced hypercontractility in the rat anococcygeus muscle might be due to an intramuscular redistribution of Na+ was investigated. 2 The contractility of the isolated muscle to noradrenaline (NA) was directly dependent on the Na+ concentration of the Krebs solution. 3 There was a linear relationship between the maximum contractile response of the muscle to NA and the Na+ concentration of the Krebs solution. 4 Muscle contractility was also increased by the presence of ouabain (10(-4)M) in the bathing medium. 5 Muscles from rats treated with corticosterone exhibited increases in both total and ouabain-sensitive ATPase activity. 6 The relationship between corticosterone, Na+ distribution, and muscle contractility is discussed.


[Influence of L-leucine overloading on the level of free amino acids in the diabetic rat]. Alloxan injection in the rat results in a large increase of branched free amino acids (leucine, isoleucine, valine) in the blood, liver and muscle; it decreases most of the non essential free amino acids in liver. L-leucine administration in the diabetic rat results in a large decrease of plasma corticosterone. It increases free leucine but decreases free isoleucine and valine in blood and muscle. It decreases most of the essential free amino acids in liver.


[Afferent projections to the locus coeruleus nucleus in the cat. Study by the horseradish peroxidase technic]. Using a retrograde tracer technique with horseradish peroxidase, we have revealed some afferent projections to the locus coeruleus complex from the contralateral pontine tegmentum, raphe nuclei, substantia nigra, nucleus of the solitory tract, dorsal motor nucleus of the vagus and other regions of the ponto-bulbar reticular formation as well as from hypothalamic and preoptic areas.


[Asymmetry of the cerebral hemispheres in man: a bridge binding the 1st and the 2d temporal gyri, superior face of the 2d temporal gyrus, and fusiform gyrus]. The autors study 76 human brains, 36 of which are dissected. They observe a "T1 T2 bridge" over the first temporal and second temporal gyri more often on the left side than on the right. They find the maximal width of the superior face of the second temporal gyrus predominant on the right side in 70% of cases, on the left side in 15% and equivalent on both sides in 15%. The fusiform gyrus is found wider on the left side in 53% of cases, on the right in 22% and equivalent on both sides in 25%.


[Turnover of free adenine nucleotides of the isolated and perfused rabbit heart]. The turnover of free adenine nucleotides was studied in the perfused rabbit heart by the decline in radioactivity 3 h 30 after administration of a single pulse of tritiated adenine. The radioactivity of the perfusate was followed during the experiments. About 7% of the labelled adenine nucleotides were renewed by hour and 1,5% of the radioactivity was lossed by hour in the perfusion fluid.


[Motricity of the female genital apparatus in mammals. Hormonal correlations]. The motility and the pharmacological reactivity of the uterine tract of mammals are linked with the ovarian cycle and the gestation. In the birds, the study of general scheme of the hormonal mechanism and the uterine motility involued in the ovulation, the egg formation and the uterine dilatation can be used as an experimental model of the mammalian gestation.


[Release of antidiuretic hormone (ADH) under the influence of gastric distention in the rabbit. Demonstration by radioimmunoassay]. In this investigation, are studied in rabbits, the effects of gastric distention upon plasma concentration of vasopressin; the arginine-vasopressine is determined by a very sensitive radio-immunologic method. Increases of intragastric ballonet pressure up to 10-20 cmH2O induce significant rise in plasma vasopressin concentrations averaging 21 +/- 3,7 muU/ml (base line 6,25 +/- 2,3 muU/ml). Increase of vasopressin is associated with significantly lowered diuresis. Intravenous injections of nicotine induce similar decrease in urine flow and increase of plasma AVP concentrations up to 12,01 +/- 1,7 muU/ml.


[Kinetic study of the accumulation of anaphasic abnormalities in a synchronized population of meristematic root cells of Allium sativum L]. A population of meristematic root cells of Allium sativum L. is previously synchronized thanks to Hydroxyurea. When it reaches mitosis, this population undergoes the action of different antimetabolic drugs which slightly check the normal operating of the mitotic spindle without preventing chromosomic separation. In such conditions we can obtain from 30 to 50 slightly altered anaphasic cells out of 1000 cells. This is enough to allow us to contemplate the electronic microscope study of these abnormalities.


[Accumulation of Fe, Cu, Zn, Mg, Mn and Co in the ovary of Carcinus maenas L. during ovogenesis]. During ovogenesis the ovary of Carcinus maenas shows a continuous accumulation of Fe, Cu, Mg, Mn and Co. For Zn the accumulation seems to stop for gonad indexes near 6.5. The goal of this accumulation is not determined. Nevertheless we suppose that it is in relation with the role of organic reserves that possess the female sexual cells in decapods and with the synthesis of enzymes and hemocyanin.


[Metabolism of the Fe, Cu, Zn, Mg, MN and Co in the ovum of Cancer irroratus (decapod crustacean)]. The concentrations of Fe, Cu, Zn, Mn and Co in the eggs of Cancer irroratus show variations in relation with time running out after laying, that is to say with embryogenesis. The increase of the rates of Fe, Mn and Mg is independant of the variations of the water content. Inversely, the decrease of Cu and Zn concentrations is in close relation with the increase of water content during the same period. The increase of Fe, Mn and Mg concentrations seems to be essentially under the dependance of physico-chemical, rather than biochemical, process in connection with the chitinous nature of the membranes surrounding the egg.


[Study of adenine mononucleotides of the adductor muscle of the oyster by fractionation on a PEI cellulose column]. Adenine mononucleotides of transulucent and white parts in the adductor muscle of Japanese oyster are identified and measured after the separation on PEI-cellulose column. The studies are performed on oysters kept in aerated sea water aquarium. Results obtained for both tissues are compared each other and with the literature data.


[Study of a further case of bisalbuminemia in Brittany]. A rapidly migrating variant of albumin has been discovered in a 28-year-old breton woman. At least eight relatives also bear the trait. This new variant is described in terms of its electrophoretic mobilities, immunological properties and heat- and storage stability. Two other reports of the slow type are presented, but no family study was performed in these cases. It is suggested that bisalbuminaemia could be a relatively common inherited condition in Brittany.


[Demonstration of a critical period of ovarian activity in the control of early receptivity induced by estrogen in the female rat with 4-day cycles]. A significant decrease in early receptivity during the night from dioestrus II to prooestrus was observed in estrogen-treated 4-day cyclic rats following bilateral ovariectomy on dioestrus II at 4-5 p.m. Early receptivity appeared then to be dependent on the presence of ovary at this stage of the cycle. The mechanism whereby the adrenals may compensate for the ovaries when removed on dioestrus I, at 10-11 a. m. (Roos et al. 1973), was not observed in the present experimental conditions.


[Mechanisms operating in the action of pheromones on the estrous cycle of the guinea-pig]. An increase in follicular growth was observed on the 6th and 8th days of the period of vaginal closure (PVC) in adult cyclic female guinea-pigs exposed to the odor of male urine from the beginning of this period. No statistically significant decrease in peripheral blood progesterone level occured on the same days of the PVC following exposure to the odor of male urine.


[Modality of the antimitotic acitivity of the diamine cis-dichloroplatinum (II) studied on the plant cell]. In the order of decreasing doses, cis-platinum (II) diamine dichloride acting on root meristem of Allium sativum produces first an irreversible metostatic effect quickly followed by lethal effect, then a variable mitodepression accompanied by important chromosomal alterations: numerous disruptions and stickiness. This chromatoclasic effect persists at very low concentrations but stathmodieretic effect is not observed. The chromatoclasic activity of the compound is compared to that of other antitumoral drugs.


[Histochemical study of the adrenal cortex of the rat after epiphysectomy]. The authors investigate the effects of pinealectomy on male rat's adrenal cortex. Fat material accumulates in the fascicular and reticular zones; different enzyme activities show light variations in operated animals. The frequent presence of mitochondrial multilamellar structures in pinealectomized rats is discussed.


[Presence of conjugated noradrenaline in the walls of the nest of Vespula germanica Linné]. Conjugated noradrenaline (NA) has been identified as a constituant of the walls of a Vespid wasp: Vespula germanica Linne. Concentrations range between 1,8 mug/g (external wall) and 18 mug/g (internal structure). Probably NA originates from the saliva of the Hymenoptera.


[Urinary clearance of noradrenaline in the dog]. Glomerular filtration rate (GFR) and noradrenaline clearance are highly correlated in anesthetized dogs (ratio CNA-3H/GFR approximately 1).


[Influence of the nutritional state on exercise induced hyperlactacidemia]. In normal man, food ingested two hours before the beginning of physical exercise increases the lactacidemia (+ 27%).


[Histological study of the voluntary traumatic inclusion of a foreign body in the gingival mucosa]. First histological features of traditional tattooing of gingival mucosae using smoke-black are reported. They show the complete tolerance of connective tissue. The microscopic examination occurs several weeks or months after the tattoo was done. Thus, one can notice that carbon particles localize particularly around blood vessels (small arteries), and that never arises inflammatory reaction of any type.


[Presence of a membrane system associated with the nucleus in the gamete of Pomacentrus leucostictus (teleostean fish)]. In the course of spermiogenesis of Pomacentrus leucostictus, a membraneous formation in the shape of a stack of saccules is applied to the nuclear envelope of the spermatid and persists into the spermatozoon stage. This formation occurs at the time the nuclear envelope of the spermatid forms, just at the end of the last maturation division.


[Ultrastructure of the spermatozoid of Centrorhynchus milvus Ward 1956 (Paleacanthocephala, Polymorphidae)]. The Centrorhynchus milvus spermatozoon is a filiform cell. The free part of the flagellum measure 2 mu and is situated in front of the gamete. The centriole is no more visible but an axial tubule formation is found at the anterior extremity of the flagellum. This Polymorphidae spermatozoon shows a reversed anatomy like the one we described for the first time with an acanthocephala wich belongs to the Rhadinorhynchidae family.


[Phosphlipids and neutral lipids of the testis of the monkey as a function of sexual maturity]. Biochemicals analysis of lipid parameters of testicular extracts of 14 monkeys (Cercopithecide) was found to confirm prior observations made with the same species by histochemical and histoenzymatic methods. Total lipids decrease with sexual activity; contrariwise total cholesterol increase; both parameters, however, showing higher levels in the absence of sexual activity. Phospholipids increase with sexual maturity after puberty but revert to normal with the cessation of spermatogenesis. Chromatographic separation reveals the specific variations of triglycerides the total being higher during pre-puberty and in animals lacking sexual potency. Phospholipid constituents are constant and may be classified in order of their concentration with lecithin being the major constituent. These observations though somewhat fragmentary and representing a rather small population will stimulate new studies and at the present time, agree with similar work done on other species of animals.


[Prenatal development of monoamine neurons in the rat]. The histofluorescence method allows the study of the prenatal development of monoamines neurons in the foetal rat brain. Certain patterns of this development can be defined: the locus niger and the raphe appears fluorescent on the 14th day, the locus coeruleus on the 15th day. These systems differentiate independently in various areas of the neural axis. Their maturation are progressive: first for the DA system, then for the NA and the 5 HT systems. The mechanisms for synthesis and storage of amines precede the complete development of the effector structures.


[Modifications by BCG of the mortality of the irradiated mouse]. Freeze-dried Bacillus Calmette Guerin (B.C.G.) of Institut Pasteur was given by intravenous route to mice at 1,2 and 4 mg/kg before and after gamma irradiation of animals by 1 000 rad. B.C.G. 1 mg/kg injected the day or the day after irradiation has a protective effect (mortality reduced from 77% for controls to 58% and 50% for treated mice). B.C.G. given before irradiation in single or double doses increased mortality.


[Effects of different metabolites of vitamin D3 and of calcium concentration on the intestinal absorption of strontium]. The effect of calcium concentration and vitamin B3 25 OHD3 and 1.25 diOHD3 upon intestinal strontium transport was studied in vitamin D deficient rats with duodenal perfusion in situ. When the calcium concentration was increased, the strontium passive absorption was decreased. The vitamin D3 and its derivatives increased intestinal strontium transport significantly and this increment was not modified by calcium. In our experiment, calcium is competitive with strontium only in passive absorption.


[Study of the threshold dose of penicillin which induces an epileptogenic focus during ontogenesis in the rabbit]. A local application on the cortex surface of a very small drop of Ringer solution containing Penicillin was performed to establish the threshold dose required to elicit and epileptogenic focus and consequently the occuring latency of it. Threshold doses are small (20 - 60 International Units) and show a significant decrease during the maturation of the C.N.S. On the other hand latencies, whatever the animal's age, decrease fairly. The results are confronted to the various supposed modes of action of penicillin, modes which involve a dysfonctioning of the Na+ and K+ ionic pump.


[Biosynthesis of thyroglobulin in an adult lamprey, Lampetra planeri (Bloch)]. Thyroglobuline (Tg) biosynthesis has been studied in an adult fresh water lamprey Lampetra planeri (Bloch), by injection in coelomic cavity or by in vitro incorporation in follicles of branchial region of various radioactive labels: 125I-, 3H-leucine, 3H-mannose, 3H-galactose, N-acetyl mannosamine and 3H-N-acetylglucosamine. Labelling by all theses substances, present in Tg of mammals, proceeds efficiently in two hours. It has been demonstrated that the cyclostome studied synthetizes a 18 S iodinated glycoprotein analogous to Tg of higher vertebrates by its molecular size. It contains all the same hexose and N-acetyl derivatives of these in its sugar moiety and the same iodinated aminoacids. Purified 18 S Tg of the lamprey has been prepared; it is very poor in iodine (127I) and has a very low T3 and T4 content.


[Effect of phascoline and phascolosomine, new natural guanide derivatives, on cultured rat cardiac cells]. Two new biological guanido compounds from sipunculid worms, phascocoline [N-(3-guanidinopropionyl)-2-hydroxy-n-heptylamine] and phascolosomine [N-(3-guanidinoisobutyryl)-2-methoxy-n-heptylamine], have been tested for their effect on cultured rat heart cells. Both compounds were found to stop the beating of the cells at concentrations greater than or equal 10(-3) M, the effect being observed after 30 minutes for phascolosomine and after 24 hours for phascoline. At 10(-4) M concentration, the same compounds did not stop the beats but slowed the rhythm after 24 hours of contact. Assays performed with the hydrolysis products of phascoline and phascolosomine, beta-guanidinopropionic acid and 2-hydroxyheptylamine for the former, and beta-guanidinoisobutyric acid and 2-methoxy-n-heptylamine for the latter, have shown that the biological activity is located in the aminoalcool or aminoether moiety of the molelcule. It has been found that the effect on cultured rat heart cells was reversible at concentrations less than or equal 10(-3) M.


[Cyto-immunological study of the anterior pituitary somatotropin cells of male and female adult Peking, Barbary and hybrid (from crossing male Peking X female Barbary) ducks and of male ducklings of the 3 races)]. The anti-human-STH immunserum applied on hypophysis sections of adults males and females Peking (Anas platyrhynchos L.) Barbary (Cairina moschata L.) and Hybrid (from the mating male Peking X female Barbary) ducks, marks orangeophils, oval- or round shaped, PAS negative cells exclusively localized in the caudal lobe of the pars distalis. In the males ducklings of the three races this immunserum reveals numerous and partially exhausted cells. The authors conclude that the acidophils alpha cells observed in the caudal lobe of the duck are somatotrophic cells.


[Comparative study in the guinea pig, cat and dog of hypothalamo-infundibular nervous fibers immunoreactive to an anti-LH-RH immune serum]. In the median eminence of guinea pig, cat and dog some axons of the hypothalamo-infundibular tract are immunoreactive with anti LH-RH. In these three species, the axons have a similar topography and area of peripheric terminations. These one occur at the capillaries of Mantelplexus. It was also shown, in the cat, that these areas of termination exhibit a strong monoamine fluorescence.


[Study on a synchronized population of the antimitotic effect of cycloheximide at various phases of the cell cycle in Allium sativum L]. The effect on the entry in mitosis, induced in synchronized meristematic cells of Allium sativum L. by a treatment with cycloheximide (10 mug/ml-30 min) at different phases of the cell cycle has been investigated. In all cases cells enter mitosis after a long delay but it appears that the delay induced on G1 cells is longer. Incorporation of 3H leucine is immediately inhibited at any stage of the cell cycle.


[Study of the role or weaning and of androgens in the determinism of adrenal sexual dimorphism at the moment of puberty in the guinea pig]. Sexual dimorphism of the adrenal, which appears at puberty in guinea-pig, is not the fact of weaning. This dimorphism is suppressed by castration in male or injection of testosterone in female. Testis androgens are the cause of the lower values of plasma and adrenal cortisol concentrations and of adrenal weight noticed in male compared with female between days 20 and 90 of postnatal life.


[Neurophysins of Mammals: evolution and biological signification]. Neurohypophysial hormone-Neurophysin complexes have been prepared from posterior pituitary glands of Artiodactyla (ox, sheep, pig), Perissodactyla (horse) and Cetacea (whale), by fractionated salt precipitation. The components have been separated by molecular sieving in 0.2 M acetic acid and neurophysins have been purified by ion-exchange chromatography on DEAE-Sephadex A-50. Two types of neurophysins, MSEL-neurophysins and VLDV-neurophysins, can be distinguished according to the amino acid residues in positions 2, 3, 6 and 7. MSEL-neurophysins of sheep, ox and pig have been characterized by the amino acid sequence. Ovine and bovine MSEL-neurophysins are nearly identical (one substitution out of 95 residues) and porcine MSEL-neurophysin is very similar (four substitutions and an apparent 3-residue C-terminal deletion). The biological function of neurophysins might be the carriage of neurohypophysial hormones but in this respect, each type of neurophysin is not clearly specific for a given hormone. On the other hand, each neurophysin might share a common precursor with a neurohypophysial hormone, the two parts remaining associated after cleavage. However, in the sheep posterior pituitary gland, the molar proportions of the two types of neurophysins, oxytocin and arginine vasopressin, are not equal, MSEL-neurophysin being more abundant than the other components. If a common precursor exists, neurophysins and neurohypophysial hormones are not merely produced by a simple cleavage mechanism.


[Uptake and storage of indolamines in the ultimobranchial body of the fetal murine thyroid. 1-Autoradiographic histological study]. Incorporation of 3H-5 HTP is studied in ultimobranchial cells and thyroid cells of the mouse foetus from the 13th day to the 18th day of gestation. The APUD characteristics of these cells are first observed on the 14th day when the U.B. bodies are included in the thyroid anlage. The silver granules are then localized on the parafollicular cell cords from which C cells of the adult thyroid arize.


[Electrophoretic analysis of intestinal acid phosphatase and N-acetyl-beta-glucosaminidase in the Discoglossus tadpole treated by thyroxine]. Polyacrylamide gel electrophoresis has been used to separate the two isoenzymes of intestional acid phosphatase (PI and P2) and N-acetyl-beta-glucosaminidase (G1 and G2) in Discoglossus pictus tadpoles treated by thyroxine. When the isoenzyme activities of each pair are expressed as percentages, the activity of the slower form (P2 or G2) increases significantly when the tadpoles are treated by the hormone.


[Polychromatism of the egg shell in the domestic quail (Coturnix coturnix japonica). 5. Augmentation of the incidence of phenodeviants through consanguinity]. An observation of interest is that brother-sister inbreeding appears to have increased the size of protoporphyrin spots of wild type egg-shells in japanese quail. Phenodeviant theory can explain the modalities of trait segregation.


[Polychromatism of the egg shell in the domestic quail (Coturnix coturnix japonica). 6. Comparison with polychromatism in related species]. Polychromatism and pigments of five Phasianides egg-shells others than japanese quail are studied. Polychromatism modalities and pigments repartitions are species specific.


[Variations of triglycerides and of plasma free fatty acids in the rat as a function of the duration of cold maintenance]. During the first day of rat exposure to cold (4 degrees C), there was a rapid and regular decrease in plasmatic triglyceride levels and an increase in the free fatty acid ones. These levels remained constant for one week then, untill the third week, they changed slowly and reached the typical levels found in cold acclimated animals. After six weeks of cold exposure, triglycerides were 2.5 fold lesser than in controls and free fatty acids were increased by 50%.


[In-situ intestinal loop study of the carbohydrate and phosphate modulation of calcium absorption]. Absorption of 45Ca from a 10 or 20 mM CaCl2 solution given into rat by injection in jejunal or ileal loops in situ is lowered by sodium phosphate and enhanced by L-xylose. Curves relative to the magnitude of absorption depending of doses of phosphate (5 to 50 mM) or carbohydrate (10 to 150 mM) are similar to those which account for the effect of activators or inhibitors upon the activity of enzymes.


[Effect of frequency on the loudness of short sounds: comparison between 2 near frequencies, 500 and 1000 Hz]. Loudness egalizations between short tone (1 to 400 ms) and a long reference tone (800 ms) were made. Two frequencies, 500 and 1000 Hz, were employed. Loudness comparisons were made at 20, 40 and 80 dB SL. Results show a frequency effect on the loudness of short tones. Some partial recuperation of loudness appears, it is greater for the high level.


[Pharmacological analysis of the inhibition of peristalsis of the isolated guinea-pig ileum by tetramethylammonium]. Tetramethylammonium in small concentrations contracted the longitudinal muscle of the guinea-pig isolated ileum, but had no effect on the peristaltic reflex. However, in high concentrations, it contracted the longitudinal muscle and blocked the peristaltic reflex. Acetylcholine, methacholine, carbachol, eserine and neostigmine antagonized the peristaltic block previously produced by tetramethylammonium. On the other hand, propionylcholine, butyrylcholine, nicotine, pilocarpine, arecoline, histamine and 5-hydroxytryptamine did not remove the peristaltic block. From these experiments, it is concluded that the predominant sites of the depressive effect of tetramethylammonium on the peristalsis are the cholinoceptive ganglia of myenteric plexus subserving the peristaltic reflex of guinea-pig isolated ileum.


[Influence of a lathyric agent and of hypercholesterolemic serum on cell cultures of fetal rabbit aorta]. Cell cultures of foetal rabbit aorta are cultivated with a lathyric agent (beta-amino-propio-nitrile) or with an hypercholesterolemic serum; if morphological features, in these two cases, correspond with modifications observed, in vivo, when adult rabbits are respectively submitted to the same treatment, enzymatic activities of collagen metabolism vary in opposite way. Therefore, the influence of different parameters to be studied on vascular cell functions become easier.


[Demonstration of antibodies during experimental toxocarosis using antigenic extract prepared from the adult parasit]. The detection of antibodies in subjects with visceral larva migrans syndrome caused by Toxocara canis is usually carried out with antigenic larvae, whose preparation presents some difficulties. Results obtained using extracts prepared from adult parasites show that such antigens are quite suitable for the detection of antibodies present in visceral larva migrans syndrome. This phenomenon is easily understood when one considers that there are numerous antigenic points in common between the different stages of the evolution of this parasite.


[Conditions and limits of serum LH radioimmunoassay in normal, hypophysectomized or castred rats]. Serum LH was measured by radioimmunoassay (NIAMD Kits) free and linked hormones were separated by double antibodies method. Influence of concentration on antibody-hormone complex is studied. Hypophysectomised rats serum does not modify results. The standard (rat LH-RP1) has the same action as serum LH. Rat serum LH contents are measured in normal or castred rats.


[Influence of microflora on the metabolism of L-threonine at the level of the rat digestive tract]. Intestinal tissues are found to incorporate L threonine 14CU at faster rate in the absence of microflora. Most of the radioactivity of the digestive contents occurs in the TCA soluble compounds, except in the coecum and large intestine of the conventional rats where the microflora synthetized its own proteins from the labelled digestive material. Free threonine is the main labelled soluble compound in the conventional rats digestive contents. In the other hand, in the germfree rats digestive contents, radioactivity of the other compounds is found in higher concentration than free threonine.


[Variations of various enzymatic activities of the Krebs cycle (malate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase) during experimental ischemic shock in the rat. Influence of adenosine 5' triphosphoric acid]. During the ischemic shock caused by the removal of tourniquets placed on the hind paws of the rat, a marked decrease in the enzyme activities of Krebs cycle yielding ATP (malate dehydrogenase, isocitrate dehydrogenase, succinate dehydrogenase) at the level of the gastrocnemius muscle and the liver, was observed together with a plasma increase of these enzymes. The intraperitoneal injection of ATP diminishes significantly the variations observed.


[Influence of an hypolipemic agent on the incorporation of 14C-labelled precursors in hepatic and serous lipids of the rat]. The action of a new hypolipidemic agent, the calcium diacetone-(ceto 2)-gulonate (D.C.G.Ca), on cholesterol and other lipid compounds biosynthesis has been studied in rats. The incorporation of 14C labelled acetate and mevalonate in liver and serum lipids of control rats has been compared with that of rats previously treated with D.C.G.Ca. No action of this compound has been noted on cholesterol biosynthesis after the mevalonate stage, which is an important result in consideration of therapeutic risks. Otherwise, a significant decrease of 14C-acetate incorporation in triglycerides has been observed in treated rats.


[Influence of lead on the microflora of the soil]. In the soil, bacteria are not inhibited by lead. In vitro great sensibility of bacteria and resistance phenomena of gram plus bacteria are showed. Lead is attracted by clay-humic complexes and becomes unavailable for microorganisms.


[Modifications of motility and respiratory activity of human spermatozoa following congelation in liquid nitrogen]. By using a polarographic technique it has been noticed that the respiratory activity of human sperms was increased after addition of cryoprotector medium to semen. But this activity was markedly reduced after freezing in liquid nitrogen. We suppose that freezing causes a damage of some metabolic structures of cells which affects more severely their respiratory activity than their motility.


[Exploration of digestive electrophysiology using a new technic : electrointraperitoneography (EIG)]. A new and simple method, the electrointraperitoneography (E.I.G.) is described and used for the recording of the digestive motility in conscious dogs and in anesthetized rabbits and rats. With the E.I.G. method, we have found the two types of potentials which characterise the electrical activity of the small intestine : the basic electrical rhythm (B.E.R.) and the action potentials (spikes).


[Influence of captivity on the pituitary gonadotropic area and correlative modifications of the sexual cycle in Serranus cabrilla Linné (Teleosts, Serrinidae)]. In Serranus cabrilla, ventral pars distalis contains characteristic gonadotropic cells which present morphological and functional variations in relation with sexual cycle and captivity. Their secretory activity, particularly marked when confinement begins before spawning, and gonads evolution are examined within various experimental conditions.


[Resistance and facilitation gradient in synchronized cardiac stimulation in the dog]. Electrical stimulation synchronized on spontaneous or paced cardiac rhythms demonstrates, in dogs : 1) phenomena of intermittent capture (I.C.), and intermittent loss (I.L.) of control, at all moments in the idastole ; 2) constant lowering of Excitability Threshold (E.T.) and Pacing Threshold (P.T.). These experiments confirm the existence of Resistance Gradients (including I.C. and I.L. phenomena) and Facilitation Gradients (measuring E.T. and P.T. lowerings). These gradients -- that we previously described in human pacing -- are parameters of the cardiac excitability.


[Reactivity of the somesthesic cortex (S1) during the wakefulness-sleep cycle in the rat]. The changes in amplitude of the activities evoked in the S1 cortex by stimulation of the specific radiations have been studied during the sleep-waking cycle. The recovery mode of these activities after a short or long delay has been tested by the paired stimuli method. Results are in general agreement with those described in the cat.


[Synchronous electric activity with inspiration in the vastus lateralis muscle of the anesthesied dog breathing spontaneously]. In the dog, under chloralose or pentobarbitone anesthesia and breathing spontaneously, a muscular electrical activity of low voltage synchronous with respiration was observed in m. vastus lateralis. The mean maximum amplitude of this activity is inversely linked with respiratory rate. When the respiratory frequency is equal or exceeds 25 cycles per minute this activity disappears. Such a phenomenon seems to be related to the activity of the respiratory centre.


[Genetic study on the intersexuality of males with female genital apertures in the oniscoid Armadillidium vulgare Latr.: interpretation and modalities of hereditary transmission]. The males with female genital apertures of the Niort population of A. vulgare are genetic males that have been made intersexual by two factors which are probably epigenetic : one is feminizing, the other masculinizing. The transmission of the masculinizing factor seems to be controlled by a genetic mechanism which, in the crossing of an intersexe with a genetic female, makes half the female issue turn into neo-males and intersexes.


[Bioecological consequences of an accidental hydrocarbon discharge on the rocky shore of the high Normandy coast. Results one year after the oil pollution on the november 26th 1974]. We have followed, during one year, the ecological consequences of an accidental oil pollution on four rocky shores of the norman coast. In the shores where the detergents have not been used, the mussels have progressively excreted the hydrocarbons accumulated in their organism ; the other fixed animals have not been changed. In the shores where the detergents have been used their spreading had not only noxious demoecological consequences, but also synecological consequences with modifications of the fixed species which have colonized the rocks. These observations prove that the use of detergents to clean the polluted shores is not without care.


[Hemodynamic study of postural regulation in the dog treated or not treated with levomepromazine]. Analysis of hemodynamic parameters in untreated and treated dogs (levomepromazine 5 mg/kg i.v.) during supine and erect position showed, 1) that the regulation of cerebral blood flow remained in the anaesthetized (pentobarbital 25 mg/kg i.v.) dogs ; 2) that the sympathetic reaction induced different effects in various vascular regions ; 3) that levomepromazine induced an impairement of the mechanisms involved in the regulation of the encephalic irrigation.


[Period of sensitivity of the rabbit fetus to the embryopathic and lethal action of D-glucose in intraovular injection]. We studied the effect of injection of D-glucose in rabbit foetus ovulary liquid at the 14th, 16th and 18th day of pregnancy. Injection of 14th and 16th day determined a high percentage of foetal death and limb necrosis. On and after the 18th day of pregnancy, the foetus is insensible to the treatment. The 18th day is, in the rabbit, the period of a new hormonal equilibre establishment.


[Chronologic and quantitative modalities of luteinization and ovulation in the female rat exposed to FSH action at the beginning of 4-day cycles]. Female Wistar rats were injected with two successive doses of 150 mug FSH on dioestrus I (5 p. m.) and dioestrus II (9 a.m.) of 4-day cycles. Superovulation and formation of an increased number of corpora lutea with included oocytes occurred in these animals. Meprobamate or pentobarbitone injections at 11.30 a.m. et 1.30 p.m. respectively completely blocked ovulation and luteinization phenomena in FSH-treated females. Ovulation normally occurred in FSH-treated females injected with meprobamate at 5.30 p.m. It was concluded that no modification of timing of the 'critical period' resulted from FSH treatment.


[Recovery after fasting in the rat placed either on spontaneous diet choice or on imposed diet conditions]. During recovery from a five days' fasting, rats fed with separately presented glucids, proteins and lipids, show a 22 days' increase of the total caloric intake, and thus the fasting caloric lack is exactly compensated. On the contrary, rats fed with choice between proteins or glucids-lipids mixture (with various ratios) do not show such an increase, and thus do not compensate. The conclusion is, that the alimentary conditions are determinant in these kinds of experimentations.


[Chromosome modifications induced in mouse spermatogonia through exposure to high-energy neutrons]. The incidence of reciprocal translocations induced in mouse spermatogonia has been studied in CBA mice given X-ray or neutron exposure. Analysis of dividing spermatocytes at diakinesis-first metaphase stage of meiosis shows that in X-irradiated mice there is a linear dose-response relationship. After exposure to fast neutrons the yield of translocations follows a humped curve with a maximum of chromosome exchanges after exposure to 100 rad.


[Study of chromosome characteristics of artificially-induced ascite tumors]. Some ascite tumours have been induced in rat by intraperitoneal injection of RadLV and in mouse by intraperitoneal injection of RadLV, or of protozoa such as Trypanosoma brucei and Toxoplasma gondii. Cytological examination of the resulting ascite tumours has shown that chromosome aberrations were associated with the presence of C and A viral particles.


[Endogenous prostaglandins and decrease of sensitivity to noradrenaline in the rat]. In the Rat, desensitization to noradrenaline induced by perfusion of large doses of noradrenaline (0.5 to 0.75 mug/mn/100 g), is not suppressed by indomethacine (1 to 5 mg/100 g). Synthesis and release of endogenous prostaglandins of the PGE group are not the cause of the desensitization.


[Relative biological efficiency of neutrons (2 MeV) and X-rays for mastocytoma cell division capacity]. The effects of 2 MeV neutrons were compared with those of 200 kV X-rays for the criterion of lethality in mastocytoma cells of ascites type. The cells prepared as suspension were exposed to the radiations in vitro under aerobic condition and transplanted in the abdominal cavity of mice. Their viability was estimated according to the growing speed of the excreted amount of urinary 5-HIAA in the host animal. The RBE varied between a value of 3.1 at the 10 per cent level of cell survival to 1.8 for the mean lethal dose (Do).


[Characteristics of a mastocytoma cell line adapted to in-vitro culture]. A cell line adapted to in vitro culture was obtained starting from ascites type mastocytoma cells which were maintained by successive transplantation in mice. The cells make colonies in liquid culture medium as well as on agar plate. In comparison under microscope and of behaviour in abdominal cavity of mice, no difference was detected between cells of this cell line and those of original one.


[Distribution of terminal intragenicular depolarization of visual afferences during reserpine PGO activity]. The distribution during reserpine-induced PGO spikes of terminal depolarization among the visual afferents in cat lateral geniculate nucleus was studied. The terminal depolarization was found to be distributed rather evenly among the crossed and uncrossed retinal afferents of different conduction velocities.


[Characteristics of unitary afferent discharges of neuromuscular spindles in man]. The primary ending of muscle spindle in man shows a dynamic and static sensitivity to stretch, but the dynamic and vibratory sensitivities as well as conduction velocity of the afferent fibres seem to be relatively low in comparison to those described in the cat.


[Effect of therapy using the "receptor-destroying enzyme" of T and B cells on antibody production]. Being interested in knowing if there is any relation between the sialic acid present on the surface of the immunocyte and the antibody formation by the latter, an attempt was made to treat immunocytes, T and B, by RDE before their inoculation into irradiated mice. C57Bl mice of more than 8 weeks of age were used throughout. Cells derived from thymus and those from bone marrow were used as T- and B-cells, respectively. On intravenous injection into irradiated mice of syngeneic T and B cells associated with SRBC, if the T cells were treated by RDE beforehand, the antibody production, as expressed in number of PFC/spleen, was remarkably suppressed when compared with that of mice inoculated with normal cells. It was not the case with the B cells. These facts would permit us to suppose that the sialic acid present on the surface of T cell has an intimate relation with the recognition of antigen by this cell, or else, with the mechanism of transmission of antigenic informations from T cell to B cell.


Reproducibility of vitamin assays with mutants of Neurospora crassa maintained by freeze-drying. Three mutant strains (ATCC 9277, ATCC 9278, ATCC 9683) of Neurospora crassa requiring choline, inositol, and p-aminobenzoic acid respectively for normal growth were deposited at the ATCC by G.W. Beadle 30 years ago and were preserved at various time intervals by freeze-drying. Each preservation batch yielded cultures that, when used for biological assays, exhibited the same biochemical properties as they originally possessed. The freeze-drying technique is shown to be applicable to preserving biological properties of sporulating fungi for bioassay over prolonged periods of time.


Influence of long-term treatment with dipyridamole on the aorta-stenosed rabbit heart: morphometric and functional investigations. The well-known effects of dipyridamole on the increase of the coronary vessel system and on cardiac metabolism suggest that dipyridamole may have a favourable influence on the chronic pressure loaded heart. In the model of the aorta-stenosed growing rabbit the cardiomegaly was diminished after a 3-month treatment using high doses of dipyridamole. Histometrically a marked decrease of the enlargement of the cross-sectional area of muscle fibres was found. It is assumed that dipyridamole retards myocardial hypertrophy and stimulates hyperplasia. Simultaneously the impairment of distinct parameters of cardiac contractility in the aorta-stenosed heart was prevented in growing rabbits by long-term dipyridamole treatment.


Rickettsioses studies. 1. Natural foci of rickettsioses in the Armenian Soviet Socialist Republic. Ixodid ticks collected in the Armenian SSR during 1971 and 1974 were positive for rickettsiae of the spotted fever group, as confirmed by haemocyte tests and by isolation experiments. Serum specimens collected from human beings and from domestic and wild animals in the same areas contained antibodies against such rickettsiae and against Coxiella burnetii. These results indicate the existence of mixed natural foci of rickettsioses of the spotted fever group and of Q fever in the Armenian SSR.


Shed preconceived ideas...look, listen... A response to Sheridan's position on the spontaneous play of handicapped children. Sheridan's article concerning the importance of spontaneous play for learning in handicapped children reflects both a historical and a contemporary negative valuation of 'handicapment'. Specifically, the authors suggest that contemporary views of handicapment fail to take into consideration the social and cultural concomitants of handicapment and in fact create an atmosphere wherein learned helplessness and self-fulfilling prophesies thrive. This state of affairs can only serve to perpetuate contemporary negative valuations of those individuals culturally labelled as 'handicapped'.


Parent's meetings in a hospital day centre. This paper is an attempt to describe a project of parent meetings in a day centre for young handicapped children. It tries to reconcile social worker activity with sociological theory of disability and deviance and to weigh the relative balance of parent and professional contributions to care.


Children with a handicap and their families. The mothers' perceptions of the emotional and social stresses experienced by families who have children suffering from spina bifida, cerebral palsy or a limb deficiency, and the mothers' suggestions for easing situations that were causing them concern are recorded in this study. One hundred and sixteen mothers were interviewed. The children were between the ages of five and ten years at the time of the interview and were patients at the Royal Children's Hospital, Melbourne. The study investigates the problems of attending a public hospital and draws attention to the difficulties in communication between the hospital staff and parents. It emphasizes the physical demands made on the parents, particularly the mothers, in caring for a handicapped child and indicates the lack of supporting services in the home, such as home help and child minding services. The effect on the parental relationship and on brothers and sisters is studied and attention is drawn to the need for ongoing social work support to the parents, and that brothers and sisters should be included in the counselling services. Some of the difficulties encountered by the child with a handicap are recorded, in particular the problems of socialization and leisure time occupation. The parents' difficulties in rearing a handicapped child are discussed including their problem in talking to the child about his handicap. The mothers' comments about community attitudes to their child, and ways of alleviating these are also mentioned.


Left atrial enlargement. Echocardiographic assessment of electrocardiographic criteria. A comparison of electrocardiographic manifestations of left atrial enlargement (LAE) and left atrial size by echocardiography was made in 307 patients in sinus rhythm. Electrocardiographic criteria used were L:P wave duration in lead II equal to or greater than 0.12 sec; Va: the ratio of the duration of negative terminal P in V1 to the P-R segment equal to or greater than 1.0; Vb: a negative P terminal force in V1 less than -0.03 mm sec. The echocardiographic diagnosis of left atrial enlargement was based on 1) transverse dimension greater than 4.0 cm; or 2) a ratio of transverse atrial to transverse aortic root dimension greater than 1.17. In the presence of left atrial enlargement, a combination of criteria occurred more often than a single criterion. The overall predictive index of the electrocardiogram for left atrial enlargement was 63% (excluding criterion Vb raised probability to 80%); and that for absence of left atrial enlargement was 78%. The index of coarse versus fine fibrillary waves was unreliable in predicting left atrial enlargement. Changes in P wave morphology may be used as a reasonably specific but less sensitive indicator of left atrial enlargement.


Retina, tear and serum beta-N-acetylglucosaminidase activities in diabetic patients. In previous studies, beta-N-acetyglucosaminidase activities were found to be markedly decreased in streptozotocin diabetic rat kidney, while that of the liver, spleen and intestine remained unchanged. The decrease in total kidney enzyme activity was in parallel with a decrease in the enzyme activity of the main isozyme of beta-N-acetylglucosaminidase, of which little or none was contained in the other three tissues. The present paper reports that the retina, also sensitive to diabetic microangiopathy, showed a similar isozyme pattern to that of kidney, composed of mainly type II isoenzyme of beta-N-acetylglucosaminidase. Type II isoenzyme was not detectable in any of the other materials tested including human and rat erythrocytes, lymphocytes and platelets, and human buccal epithelia and saliva, except human tear. The physiologic significance of the human tear beta-N-acetylglucosaminidase is unknown, but this enzyme was found to contain a considerable amount of Type II isoenzyme, and the enzyme activities were decreased in poorly controlled diabetic patients. Patients with retinopathy also showed markedly lowered tear enzyme activity. The diabetic patients were followed up for several months with occasional ophthalmoscopic examination and determination of serum beta-N-acetylglucosaminidase activity. As a result, changes in the latter were found to be useful as an indicator of the development of microangiopathy.


Some glycolytic enzymes in normal cerebrospinal fluid, brain tissue and blood plasma of infants. The activities of several glycolytic enzymes (hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase) as well as glycerol-1-phosphate dehydrogenase and (Mg2+)ATPase in normal cerebrospinal fluid (CSF) and blood plasma samples, from 12 healthy infants, aged 2-18 months, and in supernatants from brain tissue slices, taken during neurosurgical operations from infants of the same range of age were estimated. The values obtained confirm the high activity of the above enzymes found in animal brains, and indicate an independence of these activities in blood plasma and CSF. The origin of the activities of the investigated enzymes in CSF seems to be mainly, if not, exclusively, from brain tissue. This might be useful for detection of brain tissue damage as was earlier proven with LDH activity in CSF.


Children abandoned in long-stay hospitals. This study, financed by the Buttle Trust, investigates some aspects of the problems of abandonment of children in hospital, employing a sample of sixty-eight children from six selected hospitals, who meet a given definition of abandonment. Almost a fifth of the total population of children in the hospitals studied meet this definition; about a third of the sample are abandoned early in their lives, and for the remainder, admission itself appears to be a factor in abandonment.


Mechanisms of the acquired erythrocyte enzyme deficiencies in blood diseases. Acquired enzymatic activity defects of erythrocyte pyruvate kinase, glucose phosphate isomerase and phosphofructokinase have been studied in patients with acute myeloid leukemias, sideroblastic refractory anemias and unclassified acquired dyserythropoiesis. 6 patients with acute myeloid leukemia had a lowered erythrocyte pyruvate kinase activity; in 5 of them the concentration of the "pyruvate kinase"-antigen was parallely decreased, in such a manner that the ratio enzyme activity/immunologic reactivity (i.e. the molecular specific activity) was normal. In 1 patient with acute leukemia, 4 with refractory anemia and 1 with acquired dyserythropoiesis the defect of the pyruvate kinase activity was associated with a normal antigen concentration (and, therefore, the molecular specific activity in whole hemolysate was lowered). The enzyme activity was restored by incubation with SH reagents in two cases and by partial purification as often as it was performed. The electrofocusing pattern of erythrocyte pyruvate kinase was normal in both these types of defects. In two patients with so-called "acquired dyserythropoiesis" an erythrocyte glucose phosphate isomerase deficiency has been detected; in both the cases it was associated with a parallel decrease of the antigen concentration. The residual enzyme had a normal electrofocusing and electrophoretic pattern and a normal heat stability; the enzyme activity could not be restored by any treatment. In 1 patient with erythroleukemia and in 1 other with acquired dyserythropoiesis the erythrocyte phosphofructokinase activity was lowered. The enzyme activity was not restored by cross incubation in isologous plasma or by the SH reagents. In one case immunologic study could be performed, indicating that the enzyme defect was mainly due to the decreased ratio of the muscle type subunit of the erythrocyte phosphofructokinase. The electrofocusing pattern of deficient phosphofructokinases was normal. Finally, we point out the probable existence of several direct mechanisms, genetic and post translational, accounting for the acquired enzyme defects of red blood cells in various blood disorders.


A comparison of the dermatogram with other indices for the diagnosis of Down's syndrome. The Dermatogram, a dermatoglyphic nomogram based upon four pattern areas, was compared with three other indices for the diagnosis of Down's syndrome (D.S.). The measure of diagnostic accuracy used was the percentage of patients scoring outside reported overlap scores between normal and D.S. The Dermatogram correctly diagnosed 79% of 119 D.S. patients. Two other indices, using more pattern areas and requiring calculations, correctly diagnosed more patients (81 and 87%), but one had several incorrect diagnoses and the other was less efficient when scored on a small sample of normal, karyotyped, non-D.S. retardates. The Dermatogram is suggested for use as a rapid diagnostic screen. For patients in the Dermatogram overlap, added discrimination may be obtained from secondary scoring on other indices.


In vitro monitoring of cadaver kidney donor pretreatment by lymphocyte culture. Fourteen cadaver kidney donors were pretreated with a rapid infusion of 5 g of cyclophosphamide and 5 g of methylprednisolone in an attempt to reduce graft immunogenicity by altering immunogenic "passenger" leucocytes. The effects of this drug infusion on peripheral lymphocytes were monitored by measuring the ability of donor lymphocytes to respond and to stimulate recipient cells in mixed lymphocyte culture and by measuring their ability to respond to phytohaemagglutinin stimulation before and after infusion of the drugs. Pretreatment severely decreased the ability of donor cells to function in these tests, but the maximum effect was not seen until several hours after completion of the infusion. The results of this study suggest that donor nephrectomy should be delayed for at least 4 hr after pretreatment to obtain maximum lymphocyte effect using this regimen. This type of in vitro testing may provide means of monitoring donor pretreatment and comparing different pretreatment protocols in human cadaveric allotransplantation.


Comparison of heart sarcolemmal enzyme activities in normal and cardiomyopathic (UM-X7.1) hamsters. 1. The activities of some membrane-bound enzymes such as adenylate cyclase, Na+ + K+-stimulated adenosine triphosphatase (Na+ + K+-ATPase), Ca2+-stimulated ATPase and Mg2+-stimulated ATPase were examined in heart sarcolemmal fractions from control and cardiomyopathic hamsters at different stages of heart failure. 2. The basal adenylate cyclase activity in sarcolemma from cardiomyopathic animals with early, moderate and late stages of heart failure was not different from the control values whereas the sodium fluoride- and catecholamine-stimulated adenylate cyclase activities were depressed in cardiomyopathic sarcolemma at moderate and late stages. 3. The sarcolemmal Na+ + K+-ATPase activity was decreased and the non-specific phosphatase activity was increased at early, moderate and late stages of heart failure. 4. The sarcolemmal Ca2+-ATPase activity was decreased at moderate and late stages whereas the Mg2+-ATPase activity was decreased at the late stages of heart failure only. 5. A marked decrease was found in calcium binding by heart sarcolemma from cardiomyopathic hamsters at late stages of failure. 6. These results suggest that dramatic sarcolemmal changes are associated with heart failure, and support the view that membrane abnormalities play a crucial role in the development of myocardial dysfunction, cyclase, calcium binding, heart failure, heart membranes, sarcolemmal enzymes.


Glucocorticoid and starvation effect on glycosaminoglycans in vascular connective tissue. Biochemical studies on repair processes in rabbit aorta. Male rabbits were injured by a single mechanical dilatation injury of aorta and then injected with prednisone 2 mg/kg or saline for 14 days or subjected to starvation. The biosynthesis of the sulfated glycosaminoglycans as evaluated by the uptake of 35S-sulfate and the content of the glycosaminoglycans were measured on the intima-media layer of the descending thoracic aorta. The results indicate that prednisone may inhibit the biosynthesis of heparan and/or dermatan sulfate while starvation increases the biosynthesis of all the sulfated glycosaminoglycans. No alterations were observed in the total amount of glycosaminoglycans in aorta following glucocorticoid injection or starvation. The metabolism of aortic glycosaminoglycans during repair is less sensitive to the action of prednisone than in undamaged aorta. This contrasts with the effect of prednisone on the metabolism of aortic collagen.


Site of hydrolysis of collagen by hot trichloroacetic acid. When calfskin collagen is treated with trichloroacetic acid at 90 degrees C, it is hydrolyzed to a mixture of peptides, some of which are quite small. Cleavage of collagen by acid seems to occur at bonds between proline (or hydroxyproline) and other amino acids, with only a limited specificity for which amino acid donates its amino group to the susceptible peptide bond.


A sensitive automated procedure for the determination of glucuronic acid. A newly automated method for the detection of uronic acids, particularly glucuronic acid is described. Data showing the limitations of this method are also presented. The advantages of the method are: (1) greatly increased sensitivity compared to the carbazole methods and increased range; (2) lowered interference from other sugars, proteins and salts; (3) variability to allow small sample volumes and/or continuous flow; (4) a more stable color reagent solution.


Measurement of some viscoelastic properties of rat skin following repeated load. The influence of age and of corticosteroid treatment on viscoelastic properties of skin samples has been studied in rats. Hysteresis curves were evaluated with increased extension for each cycle. Maximum stress and modulus of elasticity were increased by age and by 10 days' prednisolone treatment. However, hysteresis indicating viscous properties measured by the ratio of energy dissipation versus energy input was only slightly decreased by age and almost unchanged by prednisolone treatment. The same holds true for the residual extension, another parameter of viscosity. In another experimental series the effects of repeated loading were studied. Again the parameters indicating elasticity were increased by age and prednisolone treatment but the parameters of viscosity were only slightly decreased by age.


RNA biosynthesis in the chick embryo during development and its relation to collagen synthesis. A study of RNA synthesis in the legs and wings of chick embryos suggests synthesis of specific RNA's as a function of development. An increase in RNA at day 10 was followed by an increase in collagen synthesis. That RNA had a sedimentation coefficient of 23S and several of the characteristics of mRNA. Thus it appeared to contain a poly A sequence since it was retained on poly U coated-filters, it was not methylated, and its synthesis was not inhibited by low doses of actinomycin D. That RNA was found able to direct protein synthesis in a cell-free system derived from wheat germ. In the presence of that RNA, a small amount of protein was synthesized that migrated in acrylamide gel electrophoresis with the alpha chains of collagen and was partially digested by bacterial collagenase.


Effect of hydrophobic elastin ligands on the stress-strain properties of elastin fibers. Alkyl sodium sulfates as well as sodium oleate previously shown to bind to insoluble elastin markedly decrease the tensile strength of fibers of ligament elastin. This effect correlates with the increasing number of carbon atoms in the detergent molecules. These data support previously proposed models which emphasize the importance of hydrophobic bonding to the elastic properties of this connective tissue protein.


The physical properties of elastic fibers and elastolysis. The effects of two forms of elastase on the Young's Modulus of elastic tissue have been studied. The monomeric, calcium poor form of the enzyme lowers the value of the Young's Modulus before an appreciable amount of protein is taken into solution. The polymeric, calcium rich enzyme on the other hand degrades the protein before reduction in Young's Modulus occurs. On the basis of these observations, it is confirmed that the enzyme/substrate complex in elastolysis is formed by interaction through a co-ordinately bound calcium atom and that this atom can be derived either from the substrate, where it stabilises the molecule, or from the enzyme.


A stabilised tris(hydroxymethyl)aminomethane adduct in reduced collagen. The reduction of collagen with sodium [3H] borohydride in the presence of Tris buffer results in the stabilization of a Schiff base adduct which is formed between allysine residues and tris(hydroxymethyl)aminomethane. The reduced, radioactive derivative of this adduct has been identified in hydrolyzates or reduced collagen. It elutes before hydroxylysine on an amino acid analyzer column close to the position of dihydroxylysinonorleucine. Similar artifacts may occur when aldehydes present in or added to proteins react with Tris or other amines prior to reduction.


A convenient method for the identification and estimation of soluble elastin synthesis in vitro. A method is described by which newly synthesized soluble elastin can be routinely and conveniently identified and estimated in vitro without the need for unlabelled carrier tropoelastin. Aortic tissue from 11 day old chick embryos is incubated in the presence of [14C] L-proline and [3H] L-valine and the distributions of [14C] proline-, [14C] hydroxyproline-and [3H] valine-labelled proteins on SDS-polyacrylamide gels are determined. Soluble elastin is identified as a [14C] hydroxyproline-labelled peak of molecular weight approximately 70,000 daltons which also incorporates large quantities of [3H] valine and has a [14C] hydroxyproline/[14C] proline ratio of about 0.2. Whereas the hydroxyproline label can be used to estimate newly synthesized soluble elastin even after several hours of incubation, similar use of the [3H] valine label is limited to short incubation times. Paradoxically, the quantity of [14C] hydroxyproline-labelled soluble elastin detected by the assay decreases with increased incubation time. This fall-off in labelled soluble elastin is not due to an increase in the rate of crosslinking of the protein over the course of the incubation. Soluble elastin is detectable both in tissue extract and medium fractions. The presence of hydroxyproline-labelled protein fragments in the medium fraction is evidence of proteolytic breakdown of collagen or elastin or both proteins. This proteolytic activity is augmented by the inclusion of serum in the incubation medium and is not inhibited by phenylmethylsulfonylfluoride. The method provides a convenient assay by which factors affecting the synthesis and secretion of soluble elastin may be studied.


Significance of peritoneoscopic examination, direct cholangiography and cytological examination of aspirated bile in the diagnosis of biliary and pancreatic malignancies. The roles played by peritoneoscopic examination, direct cholangiography and cytological examination of aspirated bile at the time of direct cholangiography were studied in 140 patients with various biliary and pancreatic diseases. Both peritoneoscopic and cholangiographic examinations were important in detecting the lesion, and cytological examination was effective in deciding the nature of the lesion. The detection rate of the cancer cells in aspirated bile depended upon the location of aspiration in relation to that of the lesion. The closer the distance the better was the detection rate. The combined use of these three diagnostic methods contributed to correct diagnosis.


The lipid-chemical features of the biopsied human liver tissues of patients with malignant neoplastic diseases. In order to clarify the differences in lipid metabolism between malignant neoplastic and benign cases, livers of patients were biopsied under peritoneoscopy. One half of each sample was subjected to histologic examination and the other half to lipid analyses by means of thin layer chromatography and gas lipid chromatography. Histologic examination was necessary to confirm whether the lipid metabolism in the liver of patients would be influenced by hepatic disease or not. The most significant differences between malignant and benign cases were observed when the ratio of fatty acid content of the phospholipid fraction to that of triglyceride was calculated for each patient. These ratios were over 2.20 in 40 cases out of 47 malignant neoplastic cases without benign hepatic diseases and in 3 out of 4 malignant neoplastic cases combined with benign hepatic diseases, but were under 2.19 in 35 benign cases. Moreover, 4 cases of early gastric cancer and a case of relatively early pancreatic cancer included in the malignant cases mentioned above also showed the ratios over 3.00. This finding would be applicable for the clinical diagnosis of the malignant neoplastic diseases.


Hydrocephalus in Down's syndrome.

Hydrocephalus in Down's syndrome. An infant with hydrocephalus, aqueductal stenosis and partial agenesis of the corpus callosum in association with Down's syndrome is reported. Review of the literature reveals that hydrocephalus is infrequent in Down's syndrome. Of special interest is the occurrence of agenesis of the corpus callosum in our patient, a lesion often reported with other chromosomal abnormalities, but not previously observed in Down's syndrome.


[Problem of biological tolerance of vessel prostheses from dacron and synthetic fibre material]. In human beings there have been no observations of heterogenous sarcoma after application of macromolecular artificial implants although such materials have been applied for the last 25 years. Only benign granulomas and inflammatory processes have been described. This paper describes the appearance of double-refraction artificial particles in macrophages and in granulomas encapsulated in the neighborhood of Dacron arterial prosthesis and synthetic suture materials. These processes are possibly an expression of a biological discharge of the implants.


Acne vulgaris: new concepts in pathogenesis and treatment. The successful management of acne involves a careful detailing of the factors involved in pathogenesis to ensure confidence and co-operation with the now quite successful therapeutic measures available.


Lipid ordering and enzymic activities in chromaffin granule membranes. 1. The interaction of a variety of fluorescent probes with the membranes of adrenal medullary chromaffin granules is described. 2. Changes in the motional properties of the bound probes with temperature were investigated and evidence is presented which indicates that ordering of the membrane lipids occurs below 33 degrees C. 3. The ordering is characteristics of the membrane lipids and is retained by sonicated aqueous dispersions of the total lipid extracted from chromaffin granule membranes. 4. The ATPase and NADH:acceptor oxidoreductase activities of the chromaffin granule membrane have discontinuous Arrhenius temperature versus activity relationships with 'transitions' at 33 degrees C. 5. The ATPase has a second transition at 36.5 degrees C. 6. The 33 degrees C 'transition' for the NADH:acceptor oxidoreductase is removed by treatment with the detergent Triton X-100. 7. The correlation between the onset of lipid ordering and the change in activation energy of the membrane-bound enzyme activities is discussed in terms of the co-operative interactions of the different membrane components. The possible role of lipid ordering in exocytosis is discussed.


Nicotinamide-dependent one-electron and two-electron (flavin) oxidoreduction: thermodynamics, kinetics, and mechanism. 1. Biological nicotinamide-dependent oxidoreduction consists of reversible 2e- oxidoreduction of substrates. A mechanism involving subsequent 1e- steps is shown to be very unfavourable due to the high energy of the nicotinamide radical. 2. Free energy relationships provide a convenient tool, allowing one to differentiate between hydride transfer and hydrogen atom transfer. It is concluded that biological nicotinamide-dependent, as well as flavin-nicotinamide oxidoreduction, proceed via hydride transfer but not via hydrogen atom transfer. 3. In flavin-nicotinamide oxidoreduction, flavin-nicotinamide charge transfer complexes are very likely the catalytic intermediates, preceding transfer of hydride ion. The energy of the long-wavelength charge transfer transition of zwitterionic oxidized-nicotinamide/reduced-flavin complexes is strongly dependent on polarity. It is maximal in a highly polar environment. 4. 5-Deazaflavins show the high thermodynamic radical instability of nicotinamides. They have to be considered as nicotinamide analog 2e- oxidoreductants rather than flavin analogs, therefore, lacking the ability to catalyze reversible 1e- oxidoreduction, essential for many flavoenzymes.


Localization and possible role of an adenosine triphosphatase in Chlorobium thiosulfatophilum. 1. Evidence is presented that the ATPase activity detected in cell extracts of Chlorobium thiosulfatophilum is bound to the cytoplasmic membrane rather than to the chlorobium vesicles. 2. The activity of this ATPase is inhibited in vitro by various carbodiimides, phloridzin and sodium azide. 3. The apparent Km for ATP is approximately 0.2 mM and the enzyme shows product inhibition by ADP. 4. Photophosphorylation, characterized in vivo, is inhibited by many of the compounds that inhibit the ATPase.


Membrane-bound F1 ATPase from Micrococcus Sp. ATCC 398E. Purificationa and characterization ny affinity chromatography. A chemically reactive ATP analogue, 6-[(3-carboxy-4-nitrophenyl)thio]-9-beta-D-ribofuranosylpurine 5'-triphosphate (Nbs6ITP) has been synthesized. It has the ability to form stable thioether bonds between the 6-position of the purine ring and aliphatic mercapto groups. The nucleotide moiety of the reagent has been covalently bound to agarose, via iminobispropylamine and N-acetyl-homocysteine as space with the purpose of producing an affinity chromatography material. The affinity matrix binds solubilized F1 ATPase from a crude extract of Micrococcus sp. membranes. Afterwards the enzyme can be selectively eluted from the column at a defined ATP concentration. This method is superior to the conventional purification with respect to speed and convenince of the preparation. The affinity chromatography leads in a one-step process to the same purity to enzyme, substituting several steps of the conventional method. In addition, the affinity matrix was used for binding studies. Although the presence of Mg2+ ions is a prerequisite for the hydrolysis of nucleoside 5'-triphosphates, evidence is presented indicating that the binding of the nucleoside triphosphates to highly purified F1 ATPase from Micrococcus sp. appears not to be influenced by Mg2+ ion concentrations so far examined.


Localization on mitochondrial DNA of mutations leading to a loss of rutamycin-sensitive adenosine triphosphatase. Four cytoplasmic mutants of Saccharomyces cerevisiae showing loss of mitochondrial rutamycin-sensitive ATPase activity but having significant cytochrome oxidase and NADH-cytochrome c reductase have been isolated. Genetic studies indicate the mutations to be closely linked to each other and have been assigned to a new locus, PHO1. The mutations show a low frequency of recombination with the OL12 locus, suggesting a linkage to this marker. They are not, however, linked to the OLI1 locus. Linkage of the ATPase mutations to the OLI2 locus is also indicated by restoration of wild-type diploids by sigma- clones that retain the segment of mitochondrial DNA carrying OLI2. Based on the recombinants issued from crosses of the mutants with a triple drug-resistant strain and an analysis of the resistance markers present in sigma- clones that are effective in restoring a wild-type phenotype, the PHO1 locus has been placed in the segment of DNA located between PAR1 and OLI2.


A low-molecular-weight ATPase from wheat-seedling mitochondria. An ATPase which strikingly differed from the mitochondrial ATPases of yeast and of animal tissues was obtained when wheat seedling mitochondria, or electron transport particles derived from them, were subjected to ultrasonication and treated with ammonium sulphate. The enzyme which was purified by chromatography on Sephadex G-100 and DEAE-Sephadex (A50) failed to be inactivated as low as 43 000. The enzyme preparation was capable of hydrolysing ADP, in addition to ATP, and several other nucleoside diphosphates and triphosphates. In contrast to the ATPase of animal mitochondria, the activity of the wheat enzyme was almost as insensitive to oligomycin in intact mitochondria as it was after isolation from the organelles.


The subunits of rabbit-muscle phosphofructokinase. A search for sequence repetition. Rabbit muscle phosphofructokinase uniformly carboxymethylated with iodo[2-14C]acetate consists of subunits with a molecular weight of 80 000 +/- 5000. The subunit polypeptide chain contains 16 and 52 residues respectively of cysteine and arginine and, contrary to previous results, peptide mapping experiments gave no indication that phosphofructokinase chains yield fewer than the expected numbers of cysteine and arginine containing peptides. To test further for the possible occurrence of repeat sequences within a single subunit chain, cysteine-containing peptides were isolated and sequenced from tryptic and thermolytic digests of s-[2-14C]carboxymethylated phosphofructokinase. In all, 15 different cysteine sequences (comprising a total of 104 residues) were identified, showing that not more than one of an expected 16 cysteine-containing sequences is repeated, and that the subunits of phosphofructokinase are of unique sequence along their entire length. The near quantitative isolation of several cysteine-containing peptides shows further that all subunits are of similar if not identical sequence.


Symphysiotomy or transpubic approach to traumatic strictures of the posterior urethra. The trans-symphyseal or transpubic approach is a useful technique which gives a very good exposure of the prostatic and membraneous urethra. We have used it on seven patients, for repair of post-traumatic strictures of the posterior urethra, complementary to the transperineal route in most difficult cases. This technique has allowed a correct anastomosis between the distal and the prostatic urethra in all these cases. The short-term results are good and no lasting orthopaedic sequelae have been observed.


Modern trends of surgical treatment in male infertility: alloplastic spermatocele in cases of excretory azoospermia. It is demonstrated in 30 rats that implantation of a cup-shaped silicone prothesis upon the head and the tail of the epididymis can serve as an alloplastic spermatocele. The implantation of six similar protheses upon the epididymis in bulls confirms the results obtained in rats. Spermatozoa aspirated from this prothesis up to 4 months after operation showed good morphology and motility which improved: (1) the earlier they were obtained after surgery, and (2) the nearer the tail of the epididymis, the prothesis was implanted.


Long-term treatment with beta-blockers after myocardial infarction. 162 patients discharged from hospital after mycardial infarction were randomly allocated to two groups, one received alprenolol 400 mg daily and the other served as the control. The period of follow-up was two years and all other treatment given was standardized. The two groups did not differ with respect to risk factors for myocardial infarction, the course of the acute infarct or treatment during follow-up. After two years one patient in the group treated with alprenolol had died suddenly as compared to nine in the control group. During the same period four fresh infarcts had occurred in the alprenolol group compared to 15 in the control group. Both these differences were statistically significant. Only four patients were obliged to discontinue beta-blocker treatment because of suspected side-effects. Long-term post-infarction treatment with beta-blockers appears to be an effective form of secondary therapy without serious side-effects.


A comparison between amantadine and bromocriptine using the stereotyped behaviour response test (SBR) in the rat. Amantadine (100 mg/kg), apomorphine (2.5-10 mg/kg) and bromocriptine (10-50 mg/kg) all produced stereotyped behaviour in the rat. Apomorphine was rapid in onset and of short duration, amantadine was slower to reach a maximum and bromocriptine had a delayed onset of 50 min and a prolonged action. Amantadine and bromocriptine were antagonised by pimozide (1 mg/kg for 30 min) suggesting an action on dopamine receptors, and by D,L-alpha-methyl-p-tyrosine (150 mg/kg for 3 h) suggesting an indirect action. Amantadine, though not bromocriptine, antagonised apomorphine and amantadine also reversed the SBR due to bromocriptine. Pretreatment of rats with p-chlorophenylalanine (100 mg/kg twice daily for 2 days) had no effect on bromocriptine. The significance of these results is discussed with reference to the proposed mechanism of action of bromocriptine and to the use of multiple drug therapy in Parkinsonism.


Hyperactivity induced by tetrahydroisoquinoline derivatives injected into the nucleus accumbens. Several derivatives of tetrahydroisoquinoline were injected bilaterally into the nucleus accumbens of rat 2 h after a nialamide pretreatment and activity recorded in cages fitted with photocells. 1,2,3,4-Tetrahydroisoquinoline, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, 1,2,3,4-tetrahydro-6,7-dihydroxy-1-(3,4-dihydroxybenzyl)-isoquinoline (tetrahydropapaveroline) and 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline caused virtually no change in locomotor activity and 2-methyl-1,2,3,4-tetrahydroisoquinoline and 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline caused only modest hyperactivity responses. However, 3-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline and 3-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline were both shown to markedly increase activity in a dose-dependent manner. Of these two compounds, the 3-methyl-6,7-methylenedioxyderivatives was most active and equalled the effectiveness of dopamine. The responses to dopamine and to 3-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline were both threshold at 3.125 mug and maximum at 50 mug. Both effects developed within 1-2 h and persisted for at least 6 h. The hyperactivity induced by dopamine was antagonised in a dose-dependent manner by haloperidol: propranolol and aceperone were without effect. Similar results were obtained for these blocking agents against the responses to 3-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline and 2-methyl-1,2,3,4-tetrahydroisoquinoline but aceperone and propranolol, in addition to haloperidol, were shown to inhibit the hyperactivity induced by 3-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline.


Mechanism of action of granulopoiesis inhibiting factor (chalone). I. Evidence for a receptor protein on bone marrow cells. Rat bone marrow cells respond to granulopoiesis inhibiting factor by a reduced incorporation of tritiated thymidine. Cells treated with low concentrations of trypsin lose their ability to respond to the factor if protein synthesis is partially inhibited by low doses of cycloheximide. Responsiveness is retained if protein synthesis is permitted after enzyme treatment. The data suggest that a protein receptor on the external surface of the target cells is required for the action of granulopoiesis inhibiting factor on bone marrow cells.


The acid mucopolysaccharides (glycosaminoglycans) in secondary cultures of embryonic rat fibroblasts. In secondary cultures of embryonic rat fibroblasts the protein-free acid mucopolysaccharides were separated by cetylpyridinium chloride fractionation and identified afterwards. The following acid mucopolysaccharides were found: hyaluronic acid, chondroitin, 2 heparan sulphate fractions, chondroitin-4-sulphate, chondroitin-6-sulphate, and dermatan sulphate.


The dynamics of histoenzymatic changes in the kidney in acute poisoning with benzene. The experiments were carried out in mice which were divided into 4 experimental groups and a control group. In the course of the experiment SD, NADH2-tetrazolium reductase; ATP-ase, G-6-P-ase and AP were observed. It was found that acute benzene intoxication causes the disturbances in the enzymatic activities of the cells of the main segment of the nephron. The impairment of tissue respiration and oxygen phosphorylation and of active transport is due to benzene intoxication. Benzene leads to injury of the endoplasmatic reticulum in the cells of the kidney.


[Effects of 4-hydroxypentenal on the noncancerous and the cancerous ectocervix uteri hominis (author's transl)]. 4-hydroxy-2,3-transpentenal (HPE) represents the 5-C-homologue of a series of hitherto unknown alpha,beta-unsaturated aldehydes. The marked inhibition of DNA-biosynthesis by these chemical compounds, particularly by HPE, suggests blocking of mitosis by HPE due to direct action on the S-phase. It is known that DNA-biosynthesis as well as energy metabolism are generally more disturbed by HPE in animal tumor cells (Ehrlich ascites and solid tumors, NK/Ly sarcoma 37, sarcoma 180, plasmocytoma G, murine Harding-Passey melanoma) than in normal cells (liver, kidney, jejunum, spleen, thymus); for details see BICKIS et al. 1969; RINDLER et al. 1970; KAPFER et al. 1972). After systemic administration of HPE the concentration of the cytotoxic agent in the blood caysed a bituceabke but merely selective inhibition of the metabolism in experimental animal tumors; however, it was not sufficient to produce therapeutic results. The low stability of HPE in the blood and in the peritoneal cavity is to be attributed to its affinity to SH-groups. Therefore the biological tests had to be confined to the local administration of HPE. In this histological study of the action of HPE the substance was administered directly to the human portio vaginalis uteri (ecto- and endocervix) in cases of carcinomatous alterations, in cases of non-carcinomatous affections as well as in normal portions. In this test 42 women were treated with HPE. 3 patients were observed clinically only, the other 39 cases were investigated also histologically. The histological studies were performed on the extirpated uterus (36 cases), the resected portio (1 case) and only on a conus (2 cases). In 17 of these patients examined histologically the portio was clinically free of pathological symptoms. They suffered from such more or less commonplace gynecological disorders as displacement of the uterus, incontinentia urinae relativa, uterus myomatosus, endometriosis and cystical adnexal tumors. 7 patients suffered from ectopies, 8 from Ca coli uteri, 7 were affected by invasive cancer of the cervix. 8 of the patients were older than 50 years, the others were aged between 25 and 50 years. Mode of HPE administration: 1. Application of a small HPE-soaked linen patch fixed on a Sta Seal impression of the vagina (Sta Seal=dental silicon impression paste). 2. Application by means of a small linen patch in a portio cap. The inner surface of a portio cap corresponding to the vaginal uterus in shape and size was coated with a circular linen patch. The unneeded segment was cut off. After moistening with the aldehyde (HPE) it was fit tightly to the inner surface of the cap and, in situ, to the portio surface as well. In several cases the portio  did not fill the cap completely and did not contact the tissue in the region of the os uteri. Consequently, there the aldehyde effect was lower than in the lateral regions of the portio. Therefor 3...


The influence of age on the wound healing of experimental myocardial infarction in rats. In 6-weeks-old, 5-months-old and 21-months-old rats myocardial infarction was induced by coronary artery ligature. After performing the ligature the animals were administered 3H-thymidine, 3H-proline or 35S-sulphate at different times. The following parameters were determined: number of DNA- and tropocollagen-synthesizing connective tissue cells at the infarction border and at the infarction site; mean silver grain density above the nuclei or cells; duration of a cycle; number of mitoses, and incorporation of radioactive sulphate at the infarction site. In addition, the labelling and mitotic indices as well as the percentage of the standard deviation from the mean values were estimated. The following results were obtained: 1. The rate of granulation tissue formation in the necrotic zone is determined by the mitotic activity of the cells. With advancing age the cell cycles are being prolonged which results in retardation of wound healing. 2. The disturbed DNA-replication in old age is not associated with a time shift in the occurrence of the mitotic and labelling peaks. 3. With advancing age the number of fibroblasts synthesizing collagen precursors decreases. There exists no age-dependence of the 3H-proline incorporation rate, of the intracellular  transport, of the synthesis of collagen precursor and of the release of labelled tropocollagen. In all age-groups under study these processes last approximately 4 hours. 4. Collagen fibre formation is accompanied by an increased synthesis of acid mucopolysaccharides. In infarction callosities the content of acid mucopolysaccharides mostly is constant. 5. The proliferating endothelial cells have a pronounced metabolic activity and a markedly short generation time.


Affinity chromatographic preparation of arterial heavy meromyosin subfragment-1. Heavy meromyosin subfragment-1 (HMM S-1) was prepared by papain digestion of arterial myosin or actomyosin and was purified by agarose-ATP affinity chromatography. Proteolysis of crude arterial myosin suspensions was preceded by solubilization. HMM-S-1 thus obtained consisted mainly of a 90,000 dalton polypeptide and fully retained the K+- and Ca2+-ATPase of the parent myosin. Its affinity to agarose-ATP was comparable to that of skeletal muscle HMM S-1.