The influence of propanediol-1,3 on the development of the legs, wings and lower beak of the chick embryo. In seven series of 31-34 chick embryos each, the influence of the position of the egg during incubation and of the administration of 0.05 ml propanediol-1,3 on the 5th day of incubation on the development and growth of the limbs and beak were studied. Isotonic saline injected embryos served as controls. The embryos were sacrificed at the age of 15 days. Incubation of the egg in a vertical position, with the air chamber pointing upward, proved to result in a slight, through significant reduction in the length of the limbs and beak. Propanediol was highly toxic if injected in the immediate vicinity of the embryo. If injected at some distance from the embryo, either into the air chamber or into the yolk, the agent proved to be teratogenic: measurements showed a considerable retardation of the longitudinal growth of the limbs and beak, the latter being a parrot beak in 60 per cent of the cases, whereas both the tibia and the metatarsals were, moreover, bent posteriorward. Histological studies of the tibia showed an underdevelopment of the periosteal bone collar and, at the angle of the bone, a replacement of the posterior part of this collar by endochondral bone trabeculae. The abnormalities observed are dissimilar to those demonstrated in hereditary congenital chondrodystrophy and in micromelic conditions induced by insulin or sulfonamides.


The fine structure of the epithelium of prostate glands in adult female mastomys erythroleucus Temm. The prostate glands in adult female Mastomys were studied with the light and the electron microscope. In the light microscopy, each prostatic acinus is lined by a single layer of tall cuboidal secretory epithelial cells which are surrounded by a capsule composed of a few layers of elongated and flattened cells. The acinar secretory epithelial cells show no presence of the supranuclear light areas in their cytoplasm and tend to be more readily stained with toluidine blue in the perinuclear and the upper basal cytoplasm than in the rest cytoplasm. In the electron microscopy, sharply localized pittings are occasionally found on the luminal surface and further the secretory granules which are closely situated to the apical cell surface are recognized. In the supranuclear cytoplasm, several well-developed Golgi apparatuses appear individually and early developing secretory granules are also observed. In the perinuclear and the upper basal cytoplasm the rough endoplasmic reticulum is well developed while in the lower basal cytoplasm the smooth endoplasmic reticulum is conspicuously developed and predominates.


[Effect of aflatoxin B1, of some of its metabolites and of culture extracts from "Aspergillus parasiticus" on virulent bacteriophages (author's transl)]. Aflatoxin B1 has different effects on bacteriophages: it inhibits some virulent strains and induces lysogenic bacteria. In this experiments we have used several classes of phages of enterobacteria, streptococci, staphylococci and Bacillus. We have tested different substances: cristallized aflatoxin B1, metabolites of the same mycotoxin and culture extracts from a toxinogenic strain of Aspergillus parasiticus. The inhibitory effects observed are different for each strain, and for a given phage the substances do not show the same action.


[Embryotoxicity and the immunodepressive action of tetracycline and its epi- and anhydro- derivatives]. The toxic effect of tetracycline and its epi- and anhydro-derivatives on growing chick embryos and the spleen cells of immunized mice was studied. High acute toxicity of 4-epianhydrotetracycline with respect to the chick embryos was found. Its LD50 was 4.8 times lower than toxicity of tetracycline hydrochloride. The characteristics of the acute toxicity was confirmed by the data on the embryo survival by the time of hatching. The same survival rate, i. e. 12 per cent was observed with the use of tetracycline and 4-epianhydrotetracycline in doses of 1000 and 100gamma per embryo respectively. Comparative investigation of the effect of tetracycline and anhydrotetracycline on the spleen cells revealed high toxicity of anhydrotetracycline which induced the same decrease in the number of the antibody-producing cells as tetracycline when used in doses 40 to 100 times lower than those of tetracycline. High toxicity of the anhydro-derivatives of tetracycline was also observed with respect to their teratogenic effect. Extremely pronounced anomalies in the embryo development were observed after exposure to 500gamma of 4-epianhydrotetracycline.


[Polysaccharide biological activity dependent on structural characteristics]. Anti-Influenza and interferonogenic activity of polysaccharides from the glucane class produced extracellularly by the yeast-like organism Aureobasidium pollulans was studied on albino mice. The polysaccharides differed from each other by the branching level and content of bonds beta-C1-C3 and alpha-C1-C between the monomers. At the moment of the drugs administration to the albino mice the level of the early interferon was in correlation with the following 2 factors: the level of the polysaccharide branching and the percentage of bonds beta-C1-C3, while the amount of interferon produced in 24 hours correlated only with the percentage of bonds beta-C1-C4. The anti-influenza activity of the polysaccharides depended on the level of interferon production induced by them in the mice. Preparations stimulating production of sufficient amounts of both early and later interferon had the maximum activity.


[The effect of formamide on the achromatic apparatus and the chromosomes of dividing pleurodele eggs: an electron microscope study]. Electron microscope studies of blastulae of Pleurodeles waltlii Michah., treated with formamide (0,5 M for 17 hours), show various abnormalities concerning centrospheres, chromosomes and microtubules as well. At the prophase stage, the centrospheres may display at their outer region an accumulation of dense bodies, which shows a temporary blocking of these centrospheres. At metaphase the poles of pluripolar mitoses appear more or less separated from the material which contains the chromosomes of the equatorial region. Each of these poles contains an unique centriole and therefore it is considered as resulting of the subdivision of a normal anaphasic pole. Astral and spindle microtubules are very reduced in number and more or less shortened. The chromosomes are without any recognizable kinetochcre, they show various degrees of condensation. All these electron microscope observations confirm the light microscope ones, and we may conclude that formamide has a double action on microtubules formation and on the ultrastructure of chromosomes, the latter perhaps by a direct action on DNA protein complexes.


[Murine model for experimental studies on attenuated mutants of a Pasteurella multocida strain with pathogenicity for the calf. 1. Isolation and biological characterization of streptomycin-dependent mutants (Sm-d) and their examination for immunogenicity in comparison with thermally inactivated pathogens]. An experimental study was conducted into the immunisation of mice to a strain of Pasteurella multocida with pathogenicity for calf. Here are the results: (a) Stable Sm-d mutants were isolated. (b) The genetic stability of this mutant type was established by unsubstantiable reversion up to the magnitude of 10(-8) or - in cases in which 20 Sm-id revertants maximum occurred in 10(-8) Sm-d germs--by prolongation of the generation period of these suppressor mutants which can be defined also as minus mutants. (c) Stable attenuation of selected Sm-d mutants has been established in mice by intraperitoneal application of 108 germs. (d) Live germs with restricted reproduction exhibited more immunogenicity to thermally inactivated antigen.


[Results of vaginal cytology studies and examination of the arborization phenomenon of the vaginal mucus for the determination of estrus cycle activity in sheep]. Vaginal smears were taken by means of a metal spatula from the dorsal part of the vaginal vestibule of sexually mature sheep with intach genitals for the purpose of following up changes in the vaginal cell structure. The smears were taken daily over the whole testing period of 35 days. The cells were defferentiated by means of the dyeing method according to Papanicolaou as well as by using Shorr's staining which had been modified according to Pundel. Differentiation was made between occurrences ob basal, parabasal, intermediary, and superficial cells, with the view to figuring out the cycle phases. That vaginal smear method, when used in two or three folloow-up examinations on the basis of random checks, has proved to enable determination of cyclic activity of a complete herd. This is of great importance to heart synchronization or heart induction, since all results so far have shown that all success depended strongly on the given degree of cyclic activity of the sheep concerned.


[Grass tetany in cattle].

[Grass tetany in cattle]. An optimal magnesium supply of dairy cows during pasture period is still a pressing problem in our farms and husbandry. Experiences are described concerning the application of different magnesium concentrated preparations in cases of grass tetany in 1970 to 1975 in the district of Potsdam. In 224 cows with magnesium concentrations values in the serum below 1.8 mg/100 ml a 25% MgSO4-solution, Parevert and Vers. A, a test solution of VEB Tierarzneimittelwerk Leipzig are used as a metaphylactic treatment. Losses by grass tetany could be reduced after application of the named preparations. Also in cases of low dosage a further, at least temporary drop of magnesium values in the serum could be prevented. Metaphylactic measures are recommended for andangered herds.


Artificial induction of lactation in ewes: the involvement of progesterone and prolactin in lactogenesis. An attempt has been made to evaluate the importance of prolactin and 'progesterone withdrawal' for lactogenesis. The experimental model system used was the ovariectomized, non-pregnant ewe induced to lactate artifically by treatment with trigger hormone (either oestrogen, glucocorticoid or oxytocin) alone or in combination with progesterone. It appears from the results that prolactin is important in the lactogenic responses elicited by oestrogen and oxytocin but not as important in the response elicited by glucocorticoid. Moreover, the results suggest that, in the ewe, an appropriate positive hormonal stimulus will overcome the inhibitory influence of progesterone on lactogenesis.


The suppressive effect of halothane on DNA synthesis of immunocytes. Mice, previously immunized with sheep erythrocytes, were anaesthetized with halothane and the splenic lymphoid cells were incubated with 3H-thymidine at 1-h intervals. Abiphasic response was observed; 0.9 and 1.5% halothane reduced 3H-thymidine incorporation into the primed lymphoid cells by 83 and 94% respectively, while 0.4% halothane stimulated it by 5% of control at 3H. Immunosuppression by halothane may be the result of reduced 3H-thymidine uptake of the dividing immunocytes.


[Enzymatic splitting of antibodies bound to immobilized antigen as a means of Fab fragments preparation]. A method of Fab fragments preparation by enzymatic splitting of antibodies bound to specific antigen immobilized on an insoluble support is described. The complex of rat muscle glyceraldehyde-3-phosphate dehydrogenase (GAPD), immobilized on Sepharose 4B, with anti-rat GAPD rabbit antibodies was digested with papain. The antigen was inaccessible to proteolysis under conditions employed. After 4 hrs of incubation with papain the antibody was completely split into non-precipitating fragments. The products of proteolysis not bound to Sepharose, were eluted with 0.1 M givcine buffer pH 2.5, and shown to correspond to Fab fragments.


[Growth and functional activiy of the adrenal cortex during fetal development during exposure to hypoxic and hyperoxic conditions]. A study was made of lipid, cholesterol, and ascorbic acid content in the adrenal cortex of rabbit fetuses developing under conditions of normal pregnancy and under the action of hypoxic and hyperoxic exposures during its third trimester. It appeared that in normal pregnancy the adrenal cortex was activated, this being associated with the adaptive motor reactions of the developing fetus. The action of moderate hypoxic exposures led to a greater activation of moderate hypoxic exposures led to a greater activation of the adrenal cortex, this being expressed in a marked fall of lipid, cholesterol and ascorbic acid content. The weight of the total muscle mass and of the fetuses increased as a whole. The adrenal cortex became disactivated under conditions of the hyperoxic exposures; this is expressed in a marked increase in the content of the mentioned formations. The weight of the total mass and of the fetuses decreases.


Interactions of antiestrogens with human breast cancer in long-term tissue culture. A variety of antiestrogens can be shown to antagonize estrogen action in animal model systems. Several of these compounds are useful in the management of metastatic human breast cancer. To further elucidate their mechanism of action, we studied several of these compounds using human breast cancer cell lines maintained in long-term tissue culture as a model system. Antiestrogens including tamoxifen (NSC-180973; ICI-46474), nafoxidine. CI-628, and clomiphene citrate inhibit macromolecular synthesis below control levels in two human breast cell lines. This effect is limited to cell lines which contain estrogen receptors. Simultaneous addition of as little as 1000-fold less estradiol prevents antiestrogen effects. Sequential addition of estrogen for up to 48 hours to cells incubated in antiestrogen reverses inhibition. If cells are continued in antiestrogen alone for more than about 3 days, inhibitory effects become irreversible. The cells detach from the surface of the culture vessel and are no longer viable. Tamoxifen competes with 3H-estradiol for specific receptor sites but with about a 100-fold lower apparent affinity. Direct binding of 3H-tamoxifen and 3H-estradiol to duplicate cytoplasmic extracts reveals equivalent numbers of binding sites but a 20-fold lower affinity for the antiestrogen. There is reasonable agreement between concentrations of tamoxifen which bind to receptor and concentrations which inhibit cells.


Evaluation of an intermittent schedule of dibromodulcitol in breast cancer. Dibromodulcitol was administered orally on Days 1-10 every 3-4 weeks to 29 patients with metastatic breast carcinoma refractory to previous combination chemotherapy. Initial doses between 70 and 280 mg/m2/day were utilized. The dose was escalated as tolerated in subsequent cycles in individual patients. Hematosuppression was dose-limiting. At doses of greater than 200 mg/m2/day leukopenia (greater than 1000 cells/mm3) and thrombocytopenia (greater than 25,000 platelets/mm3) occurred in one of 28 cycles and two of 27 cycles respectively. In contrast, at doses of less than or equal to 200 mg/m2/day leukopenia and thrombocytopenia occurred in four of 18 cycles and five of 18 cycles respectively. Recovery of leukocytes (less than 4000 cells/mm3) and platelets (less than 100,000 platelets/mm3) by Day 29 after the start of therapy was also delayed at higher doses. Responses were observed in three of 29 evaluable patients and subjective improvement of osseous disease in one additional patient. A dose of 180 mg/m2/day X 10 Every 28 days is recommended in previously treated patients to avoid severe hematologic side effects.


Rapid analytic method for adriamycin and metabolites in human plasma by a thin-film fluorescence scanner. A rapid and highly sensitive method is described for the quantitative determination of adriamycin and metabolites in plasma. Adriamycin (Ad) with daunorubicin added as the internal standard was extracted from plasma with chloroform-isopropanol (1:1), separated by thin-layer chromatography (TLC), and quantitated in situ via a fluorescence scanning technique. This method represents one of the very few reliable quantitative TLC methods and is suitable for the routine determination of Ad in plasma in amounts as low as 2 ng/ml. Plasma Ad levels at 24 hours in rabbits and in patients both given a 1-mg/kg dose, previously regarded as difficult to be measured, are now easily measurable using as little as 0.5 ml of plasma. Multiple samples (ten to 15) can be analyzed by this method within a day.


Phase I study of oral mitomycin C.

Phase I study of oral mitomycin C. This study demonstrates that the gastrointestinal absorption of oral mitomycin C is variable and that myelosuppression correlates most closely with the peak serum concentration. The probable maximal-tolerated dose of oral mitomycin C is 45-50 mg/m2.


[Effect of duodenal contents of patients with pancreatitis following its introduction into the duodenum of healthy rats]. The authors examined 18 rats--6 controls and 12 experimental. After duodenostomy by means of a puncure of the duodenal wall duodenal content from healthy persons was administered in the duodenum of control rats. In the experimental group of animals duodenal content form patients with pancreatitis was administered. Duodenum, pancrea, liver and kidneys were examined histomorphologicaly. The obtained results showed that there were no substantial deviations from the norm in the histomorphological picture of the examined organs after administration of duodenal content. In the organs of the experimental group these changes could be characterized as acute necrotic pancreatitis, acute duodenitis, acute finely dotted dystrophy of liver and slightly, manifested acute renal insufficiency. the authors suggested the occurrence of some toxic substances in the duodenal content in patients with acute pancreatitis.


Subunit structure of 27 S thyroid iodoprotein. The dissociation of thyroid 27 S iodoprotein by sodium dodecyl sulfate (SDS) and by succinic anhydride was investigated by means of ultracentrifugation and polyacrylamide gel electrophoresis. The iodoprotein obtained from either a human or hog was dissociated into three kinds of subunits (S-19, S-17 and S-12) by SDS treatment. At increased concentrations of SDS, the S-12 subunit was predominant among the dissociation products. The succinylation of 27 S iodoprotein showed essentially the same dissociation pattern as in the case of SDS treatment. This dissociation products of the protein preparations of different animals were qualitatively the same as those of thyroglobulin of the respective animals, confirming the hypothesis that 27 S iodoprotein was composed of two molecules of thyroglobulin. However, the extent of dissociation of 27 S iodoprotein measured by S-12 formation showed higher resistancy of the protein to the dissociating agents than that of thyroglobulin. The contents of sialic acid and hexose as well as iodoamino acids of 27 S iodoprotein were found to be the same as, or not far from, those of thyroglobulin; The dissociability and chemical composition of 27 S iodoprotein was discussed with reference to the subunit structure of the protein.


A model for evaluation of the peroral insulin therapy: short-term treatment of alloxan diabetic rats with oral water-in-oil-in-water insulin emulsions. Alloxan diabetic rats with fasting blood glucose levels above 300 mg/100 ml were treated with oral administration of water-in-oil-in-water (W/O/W) insulin emulsions at a dose of 50 U/100 g body weight, three times daily for 10 to 14 days. The course of diabetes was followed by determinations of glucose levels in blood and urine. During treatment with oral W/O/W insulin emulsions, daily excretion of urinary glucose decreased by about 30 to 40% (2 to 3 g/day) in all of the five rats studied, and returned to the pre-treatment levels after the treatment being discontinued. During treatment, a significant reduction in fasting blood glucose levels was observed in 4 out of 5 rats, giving the decrease by 18 to 44%. Quantitative estimates suggested that the effectiveness of 50 U/100 g of oral W/O/W insulin emulsions was comparable to that after intramuscular regular insulin at a dose of 0.5 U/100 g. Although oral W/O/W insulin emulsions are still of low efficiency, these results would indicate that diabetes can be controlled by effective oral insulin preparations.


Assortative mating between chromosome forms of the mole rat, Spalax ehrenbergi. Females of two parapatric chromosomal forms (2n = 52 and 2n =58) of the fossorial mole rat, Spalax ehrenbergi, in Israel, were tested for mate selection between two alternative, a homo- and a heterochromosomal, males. Estrous females significantly preferred the male of their own chromosomal form, on the basis of several behavioural criteria. The evolutionary significance of the positive assortative mating found, lies presumably in reinforcing reproductive isolation between the chromosome forms, thereby contributing to finalize speciation.


Olfactory discrimination as an isolating mechanism in speciating mole rats. Olfactory discrimination was tested in two chromosome forms of the speciating fossorial rodent, Spalax ehrenbergi, in Israel. Females of the chromosome forms 2n = 52 and 2n = 58 were tested for male odour discrimination, the source of odour being either case litter or urine. Estrous females of both forms preferred homochromosomal odurs, whereas diestrous females showed no discrimination. These results suggest that olfactory discrimination may serve as a reproductive isolating mechanism in the speciation of mole rats.


Evidence of diurnal fluctuation of sensitivity to noradrenaline in the rat-the role of the thyroid. The capacity for heat production, under the influence of the same amount of noradrenaline, in the rat was significantly higher in the evening (20.00 h) than in the morning (07.00 h). Thyroidectomy produces not only a lower level of heat production, but also a complete disappearance of the differences between the morning and the evening experiments.


Fine structrual relation between pancreatic excretory ductules and intercellular spaces. Horse-radish peroxidase injected into the femoral vein of intact rats, or infused at 30 cm H2o pressure into the main pancreatic duct of intact dogs, entered easily the interstitial spaces surrounding acini and acinar cells. The latter are interconnected at their luminal segments by zonulae occuldentes. These junctions form a barrier to tracer penetrating from the interstituim towards the lumen of terminal ductules. However, the intraductally infused peroxidase entered the interstitial spaces, probably through the pressure injured acinar cells, as did colloidal carbon particles when infused intraductally.


Foetal blood abnormality associated with hypodactyly in the hd strain of rat. The homozygous foetuses of hypodactyl rats (hd strain) present an obvious red blood cell macrocytosis (day 14 of gestation). This blood abnormality could give rise to thrombosis leading to early necrosis of the extremities.


[Role of the determinance factor in formation of systemic connections during ontogenesis]. Behaviour of differentiating neuroblasts was studied in the nervous tissue culture of the newborn rats cortex and medulla oblongata of the rabbit embryo. The phasic-contrast microscopy and study of fixated preparations revealed that distribution of the neuroblasts over the substrate, their mutual orientation, the character  of their branches growth and formation of contacts occur in vitro involving certain stages of morphological forming of the brain systemic organization. The clear trend of the neuroblasts behaviour to formation of certain connections suggests their genetic determinance. The distribution of neuroblasts over the substrate from different brain areas has its own phenotypic features.


[Effect of fat on the evacuatory function of the stomach]. In dogs with a postpyloric fistula, the food with relatively large content of fat passed out of the stomach by equal portions although not exponentially. The size of these portions seem to be determined by the ability of small intestine to digest and absorb the portion of fat which has passed the pyloric sphincter. Besides, the fat in the food increases pH of chyme in the duodenum. Similar findings are reported for healthy subjects and patients with the duodenum ulcer. The inhibitory effect of fat on the stomach and duodenum motility depends on the initial background of contractile activity of the digestive tract. The positive role of fat in self-convalescence from the ulcer disease is suggested.


[Influence of change in feeding regime and food deprivation on circadian rhythm of adrenal cortical activity in rats (author's transl)]. The effects of food deprivation on circadian periodicity of plasma corticosterone levels were studied in adult male rats kept under regular light-dark alternation (light: 7 AM - 7 PM). Blood samples were obtained by tail vein sampling method. Plasma levels of corticosterone determined by this method were comparable to those obtained by decapitation both in the morning and evening. Twenty-four hour patterns of plasma corticosterone levels determined at 4 hour intervals using these two different methods were also essentially similar, indicating that the tail vein sampling method is reliable and useful for the study on adrenocortical rhythm. A restriction of feeding time between 10 AM and 6 PM for 2 weeks resulted in a phase shift of the circadian rhythm of plasma corticosterone levels. A peak appeared at 8 AM and the value was significantly higher than that at 6 PM. These findings confirmed the facts reported by Johnson and Levine, and Krieger. Overt circadian periodicity of plasma corticosterone levels persisted in rats fasted for three days. However, after the 5th day of food deprivation, the circadian rhythm was abolished and a flat 24 hour pattern of higher levels was observed. These results indicated that the feeding pattern plays an important role in establishing of circadian rhythm of adrenocortical activity.


[Effects of ferulic acid on FSH, LH and prolactin levels in serum and pituitary tissue of male rats (author's transl)]. The existence of substances in corn germ, which induce a positive response in pigeon crop test, has been previously reported by Okamoto and Takahashi in 1974. Following this first experiment, one of these substances was identified as ferulic acid by purification. In the present experiment FSH, LH and prolactin levels in the serum and the pituitary tissue of castrated male rats and EP (estradiol benzoate and progesterone) treated male rats were determined by radioimmunoassay at 5 to 180 min. after intravenous injection with 1 mg of ferulic acid. It was noted that FSH release only was promoted significantly at 5 min. after the injection, whereas LH and prolactin releases were inhibited at 5 to 10 min. after the injection. A rebound effect was noted in LH and prolactin releases after the injection.


[Inhibitory effect of 2-(2-fluoro-4-biphenylyl)propionic acid (Flurbiprofen) on prostaglandin synthesis]. Inhibitory effects of 2-(2-fluoro-4-biphenylyl) propionic acid (Flurbiprofen, FP-70) on prostaglandin (PG) synthesis and PG activity were investigated both in vivo and in vitro. FP-70 at 0.64 micronM showed 50% inhibitory effect on PG synthesis from arachidonic acid in cell-free homogenate of guinea pig lung. PGE2 and PGF2alpha in the sample of lung homogenate incubated with arachidonic acid were separated by thin-layer chromatography in solvent AI system. FP-70 inhibited strongly both synthesis of PGE2 and PGF2alpha at 3 micron, but inhibited more extensively the synthesis of PGE2 than that of PGF2alpha at 0.3 micronM. FP-70 at 1 mg/kg, p.o. inhibited mostly arachidonic acid potentiation of carrageenin-induced edema in the rat paw, but did not inhibit PGE2 potentiation of carrageenin-induced edema. FP-70 also did not inhibit the contraction of rat stomach strip induced by PGE2. From the above and previously5) reported results, FP-70 proved to inhibit PG synthesis but not PG activity. It is suggested that the potent anti-inflammatory action of FP-70 is the result of inhibition of PG synthesis.


[Effects of l-methyl-5-(O-fluorophenyl)-7-chloro-1,3-dihydro-2H-1,4-benzodiazepin-2-One (ID-540) on operant behavior in rats]. Effects of ID-540, a new benzodiazepine derivative, on operant behavior were studied and compared with those of diazepam in rats for the purpose of determining the characteristics on behavioral pharmacology. Four schedules used were as follows: Fixed interval (FI-60sec) of food reinforcement and differential food reinforcement of low rate (DRL20sec) for positively reinforced behavior, Sidman-type avoidance response for negatively reinforced behavior and conflict behavior induced by simultaneously rewarding with food and punishing with electric shock. In the experiments on FI-60sec schedule, the responses at the early stage (0 approximately 30 min after administration of the drug) were increased by both ID-540 and diazepam at lower doses (0.5 approximately 4 mg/kg p.o.), but inhibited at higher doses (8 approximately 32 mg/kg p.o.). The effect of ID-540 lasted longer than that of diazepam. In the experiments on DRL20sec schedule, neither drug accelerated the responses, but decreased the lever-press response and total number of reinforcements at higher doses (4 mg/kg or more) showing the disturbance of discrimination on time. In Sidman-type avoidance responses, ID-540 did not show any inhibitory effect, thus a neuroleptic-like effect of ID-540 was not demonstrated. In experiments on FI-60sec and Sidman-type avoidance schedules, the effect of ID-540 was not changed by a consecutive administration for 10 days. Conflict behavior is considered to resemble the anxiety states in humans, and in related experiments, ID-540 increased the lever-press response which delivered a food-pellet and an electric shock simultaneously at a dose of 0.0625 mg/kg (i.p.). Change in other behavior was not observed at this dose level. Maximum effect of ID-540 was observed at a dose of 0.5 mg/kg (i.p.). Maximum effect of diazepam on conflict behavior was seen at a dose of 4 mg/kg (i.p.). The potency of ID-540 on conflict behavior was estimated to be about 8 times that of diazepam.


[Activity of neurons of the hypothalamic suprachiasmatic nuclei and circadian rhythms: the role of the suprachiasmatic nuclei in rhythmic activities of neurons in the lateral hypothalamic area and ventromedian nuclei and the control of the pineal gland]. Unit activity of lateral hypothalamic area (LHA) and ventromedian nuclei (VMN) was recorded in urethane anesthetized male rats. A 5 to 10 sec, a 3 to 5 min and a circadian rhythmicity were observed. In about 15% of all neurons, spontaneous activity of LHA and VMN showed reciprocal relationships. Subthreshold stimuli applied at a slow rate in the septum and the suprachiasmatic nuclei (SCN) suppressed the rhythms without changing firing rates. On the other hand stimulation of the optic nerve at a rate of 5 to 10/sec increased firing rates in one third of neurons of SCN. Iontophoretically applied acetycholine increased 80% of tested neurons of SCN, whereas norepinephrine, dopamine and 5HT inhibited 64%, 60% and 75% of SCN neurons, respectively. These inhibitions were much stronger in neurons, the activity of which was increased by optic nerve stimulation. Stimulation of the SCN inhibited the tonic activity in cervical sympathetic nerves. These data suggest that SCN plays a significant role in controlling the rhythmic activity of LHA, VMN and the pineal gland. Dopamine and 5HT may be involved in regulation of the firings of SCN neurons.


[Role of the adrenergic system in lateral hypothalamic self stimulation behavior: effects induced by intraventricular injection of epinephrine, norepinephrine, isoproterenol and dopamine]. A bipolar electrode was stereotaxically implanted in or near the medial forebrain bundle at the level of the posterior lateral hypothalamus of male albino Wistar-Imamichi rats. The relationship between the adrenergic system and the lateral hypothalamic self-stimulation (SS) behavior was investigated by intraventricular injection (by the use of the modelled hypodermic needle) of catecholamines. l-Epinephrine(Ep), l-norepinephrine (NE) facilitated the SS behavior dose-dependently. On the other hand, l-isoproterenol and dopamine revealed no detectable effects. Phentolamine inhibited the SS behavior, but propranolol had no marked effects. Facilitation by NE for the SS behavior was not induced when the current was cut off at the time of the injection of NE. These results suggest the following: a) the adrenergic or the noradrenergic system in the brain may play a more important role in the positive reinforcement of the lateral hypothalamic SS behavior than does the dopaminergic system. b) The action of Ep or NE may be facilitated through alpha-receptors rather than through beta-receptors. c) Facilitation by NE for the lateral hypothalamic SS behavior may not be due to the non-specific facilitation of lever pressing, but rather may be related to intracranial stimulation.


[Changes in the substantia nigal self-stimulation behavior caused by intraventricular injection of norepinephrine, dopamine and GABA]. A bipolar electrode was stereotaxically implanted in the substantia nigra of male albino Wistar-Imamichi rats. Effects of l-norepinephrine (NE), dopamine (DA) and gamma-aminobutyric acid (GABA), injected into the lateral ventricle, on the substantia nigral self-stimulation (SS) behavior, and the effect of alpha- and beta-adrenergic receptor antagonists on the facilitation induced by NE were investigated. NE but not DA facilitated the SS behavior and GABA showed no constant effects on the behavior. Facilitation by NE of SS behavior was inhibited by phentolamine, but not by propranolol. These results suggest that the noradrenergic system in the brain may play a more significant role in the positive reinforcement of the substantia nigral SS behavior than does the dopaminergic or GABA-ergic system, and that the action of NE may be facilitated through alpha-receptors rather than through beta-receptors.


[Clinical and pathological considerations of Plummer's disease (author's transl)]. Four cases of Plummer's disease were experienced and its clinical and pathological characteristics were considered. Clinically, three cases were thyrotoxic or slightly toxic, but one was non-toxic. Thyroid scintigrams showed hot nodules which revealed autonomic production of thyroid hormone, and the depleted uptake of 131I in the thyroid glands around the nodules was recovered to normal after the surgical extripation of the nodules. Histologic findings of the extripated nodules were follicular adenoma or adenomatous goitor. On electron-microscopy, epithelial cells of the thyroid follicules in the nodules from all cases contained numerous secretory granules significantly increased in number, while development of the general cytoplasmic organelles varied from case to case. Capillaries in the nodules were fenestrated. Thus, the nodules were electron-microscopically revealed active secretion of thyroid hormone. The electron-microscopical examinations may be useful in the study of Plummer's disease.


[Effect of S-propyl-mercapto-cysteine on lipid metabolism (author's transl)]. When intra tissue reduction of thiamine propyldisulfide (TPD) occurs the following changes take place : TPD+cysteine leads to thiamine+propyl-mercapto-cysteine (PMC). We have reports that PMC has an effect of blood cholesterol lowering or not. In the present paper experiments were conducted to determine whether the effect of TPD on blood cholesterol lowering lies in PMC or not. The following results were obtained. 1) It was shown that when PMC was added to liver homogenate, no change was seen in the biosynthesis of cholesterol where TPD inhibited the biosynthesis. 2) When administered to normal animals while PMC showed no change in the total blood cholesterol value, TPD produced a decrease. While no change in total liver cholesterol value was induced by both, total liver, fatty acid showed a decrease by both. The biosynthesis of liver cholesterol from acetate-1-14C showed a decrease by both PMC and TPD, while the uptake from mevalonic acid-2-14C showed no change by both. The uptake of total liver fatty acid from acetate-1-14C while showing no change by PMC, showed an increase by TPD. 3) In cholesterol fed animals, the increase of blood cholesterol and total liver cholesterol was inhibited by TPD but PMC showed no effect. The biosynthesis of liver cholesterol from acetate-1-14C, showed an inhibitory effect on the lowering of biosynthesis in cholesterol fed animals by both TPD and PMC. And it was shown that the effect of TPD was larger. The total fatty acid value and the lowering of the uptake of total liver fatty acid from acetate-1-14C was inhibited to a similar extent by both TPD and PMC. From the above results, it may be said that even when PMC, a degenerative product of TPD is administered, either no effect is seen on the cholesterol metabolism or even when there is an effect, it would be negligible. Therefore, it may be surmized that the total structure of TPD exerts its effect on cholesterol and while the effect on fatty acid metabolism shows the same degree as TPD no characteristic features are seen.


[Studies on screening for cholesterol-lowering agents using phenyl- and chromane substituted compounds (author's transl)]. Sixteen phenyl compounds and twenty chromane compounds substituted by geranoyl, farnesoyl, phytonoyl, retinoyl and linolenoyl synthesized by Eisai Co., Ltd were used. Male mice were fed a cholesterol or a normal basal diet which 0.3% compound was added for 10 or 31 days. Effect of these compounds on the cholesterol level of serum and liver were examined and compared to that of CPIB. As a results of this series of experiments hypocholesteremic agents were screened as follows: 3 phenyl compounds (N76009, N76011, N76012), and 6 chromane compounds (N-76-H-23, N-76-H-25, N-76-H-27, N-76-H-35, N-76-H-37, N-76-H-38). Among these compounds, N-76-H-38, (formula: see text) was found to be the most favorable cholesterol-lowering agent.


[Chemico-analytical studies on the water content of the human tissues. 1. Investigation of the method of oven-drying at 105 degrees C (author's transl)]. By heating at 105 degrees C in a constant temperature electric oven, a 35 ml crucible becomes completely dry in an hour and 2 grams of human tissue in 48 hours. Within 5 minutes after taken out from an oven and allowed to stand in a room, a dried crucible and tissue become wet with moisture in the air and their water content reaches equilibrium and saturation. Thereafter the weight of the crucible remains constant for 5 days, that of the tissue for 30 minutes. A major portion of increased weight of a crucible containing tissue by moisture depends on the moisture of a crucible, whereas the moisture of tissue is extremely small being under 1.0%. Consequently it is sufficient to cool samples taken out from an oven in a room and to weigh within 30 minutes. There is no necessity for cooling them in a desiccator.


[Experimental and clinical studies of transvenous electrophrenic respiration (author's transl)]. The transvenous electrophrenic respiration (EPR) is one of the effective and relatively simple method for artificial respiration. Twenty seven mongrel dogs were subjected to the experiment which were subdevided into 4 groups. Stimulation is 44 times in group 1, 22 times in group 2 and 3. Ventilation is carried out by Harverd Respirator in group 4. The normal arterial pressure, the normal minute ventilatory volume and the normal arterial blood gases were unchanged for a 5 hour period of experiment in group 2. However, the frequent stimulation such as 44 times/min. in group 1 yielded the hypotension, the decreased ventilatory volume and brought the congestion of the portal venous area and rendered the subjects to death. The systemic pressure remained in slightly lowered levels in group 2, 3 and 4 at the end of a 24 hour of experiment. The ventilatory volume decreased one third of initial values in group 2 and 3 at the end of a 24 hour of experiment. The pulmonary arterial pressure decreased in group 3 significantly, whereas it increased in positive pressure respiration in group 4. Intermittent clinical application of EPR was performed in three patients. The arterial pressure, minute ventilatory volume, arterial gases and central venous pressure were maintained normal. The following conclusions were obtained: 1) EPR is more physiologic than positive pressure respiration in ventilatory and circulatory aspects. 2) Undesiable conditions of stimulation cause complications such as neural fatigue, portal hypertension, etc. 3) Intermittent clinical application of EPR has been quite successful in supporting the ventilation of the patients.


Genetic characterization of methotrexate-resistant chinese hamster ovary cells. In a previous report, we described the selection and partial characterization of three methotrexate (Mtx)-resistant Chinese hamster ovary cells (CHO) (1). Class I cells contained an apparent structural alteration in dihydrofolate reductase. Class II cells had an alteration affecting the permeability of the drug. Class III cells, selected from Class I cells, had an increased activity of the altered enzyme. In the work described here, it has been shown that the spontaneous mutation rate to Class I resistance is in the order of 2 X 10-9 mutations per locus per generation and that in single-step mutagenized selections the number of resistant colonies of Class I and II are about equal. Class I and Class III resistance is expressed codominantly in somatic cell hybrids, whereas the Class II resistant marker is a recessive trait.


Cytoplasmic inheritance in mammalian tissue culture cells. A series of intraspecific, interspecific and interorder somatic cell cybrids and hybrids have been prepared by fusions in which one of the parents contained the cytoplasmically inherited marker for chloramphenicol (CAP) resistance. A clear relationship has been established between the expression of the CAP-resistant (CAP-R) determinants in the fusion products and the genetic homology of the parents. With increased genetic divergence, the acceptability of the CAP-R mitochondria decreased. Intraspecific cybrids and hybrids of the same strain were stable for the CAP-R marker, while those between strains were stable only in CAP. Intergeneric mouse-hamster cybrids occurred at a high frequency but were unstable in CAP, while CAP suppressed hybrid formation 100-fold. Interorder cybrids (CAP-R human X CAP-S mouse) occurred either at a moderate frequency and were stable at a low frequency and were unstable in CAP. Interorder hybrids could only be formed by challenging HAT-selected hybrids with CAP or by direct selection in ouabain and CAP. Reciprocal interorder crosses between CAP-R mouse and CAP-S human cells were unsuccessful. Interspecific cybrids contain only the chromosomes of the CAP-S parent. Interspecific hybrids selected directly in CAP segregated the chromosomes of the CAP-S parent, while hybrids selected in HAT and then CAP segregated those of the CAP-R parent. The mitochondrial DNA(mtDNA) of all mouse-human cybrids and most HAT and then CAP-selected hybrids contain only the mtDNA of the CAP-S mouse parent. However, preliminary evidence suggests that one of these hybrids contains both mouse and human mtDNA sequences.


Time sequence and morphological evaluations of cells fused by polyethylene glycol 6000(1). Mouse L cells (clone 1D) were fused with polyethylene glycol (PEG). The fusion sequence was determined by using sequential light microscopy of the same group of cells, scanning electron microscopy (SEM),transmission electron microscopy, and freeze-etching. The cells were found to fuse only 1 min after PEG had been washed off at small localized areas. Larger fusion images were found after 3 min. Intramembrane particles were observed to have a tendency to aggregate after PEG treatment, but a direct correlation of this activity with the fusion process could not be made. No pathological changes were noted at longer times after PEG removal, except for the extensive widening of the rough-surfaced endoplasmic reticulum (RER) in some cells. It is proposed that fusion does not occur if apposing cells have many microvilli at the area of apparent contact.


Congenital dislocation of the hip in the newborn. A correlation of clinical, roentgenogrhic and anatomical findings. This study correlates roentgenography, arthrography, morbid anatomy and histology in four newborn infants with congenital dislocation of the hip. Three died shortly after birth. In two of these, manipulative reduction was impossible. Both demonstrated secondary adaptive changes at autopsy, indicating that the dislocation had been present for some time in utero. The first had a paralytic dislocation (meningomyelocele), and the second showed no pathologic findings other than the dislocated hip. The third infant had a dislocation that was reduced at birth. The child died of pneumonia on the 15th day. At autopsy, no secondary adaptive changes were found in the hip. The fourth infant, who had undergone open reduction because of a dislocation irreducible at birth, was retrospectively found to have an intrauterine dislocation when the maternal roentgenogram was reviewed. Significant secondary adaptive changes were noted at the time of operation.


Intra-oral temperatures in man with special reference to involvement of the central incisors and premaxillary alveolar process in lepromatous leprosy. The predilection of lepromatous leprosy for body sites substantially below core temperature is well known, and within the oral cavity the premaxillary alveolar process and upper central incisor teeth are especially affected. In this study, intra-oral temperatures were recorded by means of a series of thermistor probes applied to the teeth and labial surfaces of the gums of normal subjects. The temperature distribution established showed a close correlation with the known pattern of involvement of teeth and supporting structures derived from clinical, pathological and archeological data. Relatively low temperature of the premaxillary alveolar process was demonstrated, a factor which may be of prime importance for the localization of disease in this region, as it is for other tissues in the lepromatous patient.


Androgenic status of lepromatous leprosy patients with gynecomastia. The androgenic status of 24 lepromatous leprosy male patients, 12 with and 12 without gynecomastia, was studied in comparison with that of 12 normal healthy males. Plasma testosterone levels were significantly diminished in the gynecomastia group as compared to levels in either of the control groups. The patients without gynecomastia showed values not significantly lower than those of normal males. Histopathologic examination of the leprous testes showed a variable admixture of inflammatory, degenerative anf fibrotic changes which were more severe and more frequent in the patients with gynecomastia than in those without it. Parenchymatous liver function tests showed greater derangement in the gynecomastia group as compared to the controls Histopathology of the liver showed lepromatous infiltration in patients with and without gynecomastia though the changes in liver were minimal in patients who showed total testicular degeneration in the biopsies.


A mare mule--dam or foster mother?

A mare mule--dam or foster mother? A female, horse-like foal was apparently born to a mare mule from mating to a Shetland stallion. The presence of three pregnant Shetland mares in the same pasture, however, raised some questions about parentage, even though all three mares apparently gave birth to single foals within 6 weeks after the birth of the propositus. The transferrin system indicated that the foal was not born to the mare mule but was the offspring of one of the Shetland mares. Apparently one Shetland mare gave birth to twins 3 to 6 weeks apart, and the mare mule came into lactation spontaneously and adopted the first twin. The offspring was determined to be a horse by appearance, karyotype, blood type, and voice.


Effect of maternal parity on aneuploidy in early mouse embryos. An attempt to evaluate the incidence of chromosomal aneuploidy in mouse blastocysts recovered from females of various ages and parity levels revealed an insignificant regression coefficient for aneuploidy on age of the female and its square, and an insignificant correlation coefficient for aneuploidy with the number of previous offspring born to the dam. However, significant regression coefficients were obtained for aneuploidy on parity of the dam and its square. These results indicate that not only does aneuploidy increase with parity level, but the rate of increase accelerates as parity level increases. Possible explanations for the increase in aneuploidy and its detrimental effect on reproductive efficiency were discussed.


Stochastic selection in both haplophase and diplophase. A population genetic model incorporating the evolutionary forces of zygotic selection, gametic selection and non-Mendelian segregation has been analyzed for the case in which all selection coefficients and the segregation parameter are assumed to be random variables that are uncorrelated from generation to generation. The diffusion approximation of the model is developed, and the subsequent analysis shows that one of four limiting outcomes of the stochastic process may obtain--an allele may be fixed or lost almost surely and irrespective of the initial gene frequency, the gene frequency may converge to a unique stationary distribution, or an allele may be fixed or lost with probabilities depending on the initial gene frequency. These outcomes correspond rather closely with the possible outcomes of the deterministic model--fixation or loss of an allele, convergence to a stable equilibrium, or the existence of an unstable equilibrium.


Predator prey interactions with time delays. A general (Volterra-Lotka type) integrodifferential system which describes a predator-prey interaction subject to delay effects is considered. A rather complete picture is drawn of certain qualitative aspects of the solutions as they are functions of the parameters in the system. Namely, it is argued that such systems have, roughly speaking, the following features. If the carrying capacity of the prey is smaller than a critical value then the predator goes extinct while the prey tends to this carrying capacity; and if the carrying capacity is greater than, but close to this critical value then there is a (globally) asymptotically stable positive equilibrium. However, unlike the classical, non-delay Volterra-Lotka model, if the carrying capacity of the prey is too large then this equilibrium becomes unstable. In this event there are critical values of the birth and death rates of the prey and predator respectively (which hitherto have been fixed) at which "stable" periodic solutions bifurcate from the equilibrium and hence at which the system is stabilized. These features are illustrated by means of a numerically solved example.


Animal experiments on thiamine avitaminosis and cerebral function. Before industrial production of thiamine becam possible, among many beriberi patients some showed symptoms of encephalopathy, the cerebral form of the disease. In this animal experiment, thiamine-deficient rats showed failure or blocking of the operant behavior in the maze box, pole climbing box and shuttle box, indicating orientation disturbance and defective memory. This Wernicke's syndrome-like sign dramatically disappeared by treatment with thiamine. Potentiated narcosis with thiopental or alcohol induced in thiamine-deficient rats and mice was readily reversible by thiamine administration. These phenomena are associated with thiamine content of the brain and are found long before histopathological changes in the brain of deficient animals. It is easily surmised that thiamine deficiency in the brain may block the brain metabolism and subsequently cause changes in any chemical substances in the brain, refracting on biophysical phenomenon, such as EEG. However, in the present study, generally speaking, no meaningful results concerning these points were obtained.


[Genetic difference in extinction of a conditioned behavior in mice (author's transl)]. The conditioned avoidance behavior from electric shock were examined in thirty male mice of inbred JCL: ICR and DDF with a newly-designed apparatus which had a wide square open field implanted shock-electrodes in floor and a fixed arc running path way where electric shock current could be delivered or not. Data were recorded on running traces and times from the start point to the goal and analysed statistically. 1. In acquisition training, both the JCL: ICR and the DDF acquired to run the way correctly and any difference between them could not be observed. While in extinction, the JCL: ICR were more rapid than the DDF. 2. After the 2nd acquisition training, all mice were trained to run of the field where electric shocks were delivered including the way. The DDF ran into the goal correctly along the way, while the JCL: ICR did not, but ran straight into the goal. The straight-trace of the JCL: ICR could not be changed by the following acquisition. 3. After a eight weeks' pause of acquisition, all mice were tested on retention without shock delivery. The both the JCL: ICR and the DDF ran correctly along the way, and showed a full score by a few trials of aquisition-training. 4. No change in behavior between the strains was found when high voltage shock were delivered during running the way. But in evaluation trials after the delivery only the JCL: ICR showed some changes in running trace and time. 5. Arguments on the difference in the process of extinctions between the strains were proved that may be associated with the genetic difference of a inhibitory mechanism.


[A trial measurement of individual noise exposure by time-zone in a day (author's transl)]. Noise has been measured usually for a particular source or place and not for each individual exposed. It has been thought to be of great significance if individual noise exposure is recorded in various kinds of noise environment and auditory effects of noise on each individual can be discussed. The present study, having each of examinees carry 10-Channel Noise Exposure Meter with him, intended to know about dose or equivalent sound level (Leq) of individual nois exposure for a whole day and for each of eight time-zones in a day. The examinees were 12 male married workers in a factory manufacturing electronic machines in Kawasaki City, Kanagawa Prefecture, Japan. They were divided into two groups; those who were working in a noisy workshop (Group N, 8 workers) and those who were working in a less noisy workshop (Group N-N 4 workers). Time-zones were categorized as follows: (a) time from rising to leaving home for the place of work, (b) commuting time in the forenoon, (c) working time in the forenoon, (d) noon recess time, (e) working time in the afternoon, (f) commuting time in the afternoon, (g) time from returning home to going to bed, and (h) sleeping time. Leq (c) and Leq (b) were highest and Leq (h) was lowest for Group N among the eight Leq values in the day, while Leq (b) and Leq (f) were highest for Group N-N. Statistically significant differences of Leq for each time-zone between the two groups were found in Leq (c), Leq (d) and Leq (e), whose energy average sound levels for Group N and Group N-N were 84.2 and 59.4 dB, 72.7 and 61.4 dB, and 85.5 and 61.4 dBrespectively. Energy average equivalent sound levels of Leq (24) were 81.0 dB for Group N and 66.7 dB for Group N-N. Leq (24) for Group N were primarily determined by the noise exposure in the working time (c and e), while those for Group N-N by that in the commuting time (b and f). Practical disadvantages in the course of individual application of 10-Channel Noise Exposure Meter were also pointed out. It was shown that it is possible individually to measure the noise exposure dose for each time-zone in a day or daily noise exposure pattern, and the noise exposure dose over 24-hour. It may be recommended that many typical noise exposure patterns and 24-hour noise exposure doses for each of the groups classified by sex, age, kind of job, kind of commuting methods, kind of residential area of residential area and so forth should be surveyed further, which will be useful for estimating the auditory effects of noise on a population. Also, the relationships between Leq and such effects as annoyance or interference with daily activities should be examined to ease the measurement of noise.


Analysis of combined effects of benzene with radiation on chromosomes in cultured human leukocytes. Three experiments were carried out on 53-hr cultured human leukocytes on chromosome mutagenicity of benzene with particular reference to combined effects with gamma-radiation and inhibitory effect on rejoining of radiation-induced chromosome breaks. The results and their analyses were summarized as follows: 1) Benzene can induce mainly chromatid-type deletions, especially gaps, suggesting that the cells in their late S-G2 stage have a higher susceptibility to chromosome breakage by benzene. 2) The aberration tield of dicentrics and rings induced by 100 rads irradiation can significantly be enhanced by the treatment of benzene equal to or in excess of 0.2 mM. 3) Quantitative analyses using newly defined "Synergetic effect factor" revealed that combined cytogenetic effect of benzene with radiation could be synergetic exclusively in dicentrics and rings, being almost additive in the other types of aberration. 4) The experiment with dosage fractionation method showed that the more strongly benzene could inhibit the rejoining of radiation-induced chromosome breaks, the higher concentration it was treated at. Related iwth these results, possible inducps, and the repair and its inhibition of radiation-induced DNA-strand(s) breaks. Further studies for related effects by benzene are needed on protein synthesis, activities of repair enzymes and fine structure of chromosomes.


[An epidemiologic study on vibration hazards among workers at the state forests in Kyushu (author's transl)]. There are only very few reports of epidemiologic analysis on vibration hazards among the workers at the state forests of Japan since 1970. It was necessary to perform investigations on the state of vibration hazards anew, through some labor hygienic policies on the prevention of the hazards, such as regulation of the time of using vibrating tools, had been executed to some extent since 1970. From the data of physical check-ups of 861 chain saw users of 24 District Forestry Offices in Kumamoto, Miyazaki and Kagoshima Prefectures in the south of Kyushu, the transition of vibration hazards was studied by using the incidence and prevalence of Raynaud's phenomenon and paresthesia of the fingers as indices. From the yearly transition of the hazards, a tendency was observed of increasing patients with vibration syndrome during the period from 1962 to 1970 when countermeasures on vibration hazards were not sufficient. However, since 1970 the occurrence of Raynaud's Phenomenon has shown a tendency to decrease among the workers with short history of using chain saw and the occurrence of paresthesia of the fingers as indices. From the yearly transition of the hazards, a tendency was observed of increasing patients with vibration syndrome during the period from 1962 to 1970 when countermeasures on vibration hazards were not sufficient. However, since 1970 the occurrence of Raynaud's Phenomenon has shown a tendency to decrease among the workers with short history of using chain saw and the occurrence of paresthesia of the fingers to increase among those with long history. The results are suggestive of making clear the pathophysiology of vibration hazards.


[Occupational chronic arsenical poisoning. On the cutaneous manifestations (author's transl)]. A physical examination with detailed dermatological examination was made on 28 Japanese male workers, 22 to 63 years old, who had been exposed to arsenic for one to 24 years, in processes manufacturing lead arsenate, calcium arsenate and so on to be used as insecticides. Many corn-like punctate keratoses were seen on the palms and soles of 7 workers. The histopathological features in 6 specimens of punctate keratoses of palms and other regions of 4 workers were hyperkeratosis, acanthosis and elongation of rete ridge, but no malignant changes, although there were mild disorderly arrangements in part of stratum malpighii. Multiple lesions of sharply demarcated dullred patch with scale were found on the trunk and extremities of 3 workers. These lesions histopathologically showed the typical feature of Bowen's disease. Characteristic bronze pigmentation on the trunk and extremities was seen in 6 workers, and 5 of these 6 workers showed tiny normal or depigmented skin (raindrops) throughout the involved areas. These corn-like punctate keratoses mainly on the palms and soles, multiple Bowen's disease and diffuse bronze pigmentation with raindrop areas of hypopigmentation on the trunk and extremities were manifest almost in the same individuals, and it was concluded that they were characteristic cutaneous symptoms of chronic arsenical poisoning. There was no correlation between the intensity of cutaneous manifestations and the term of exposure to arsenic. Cutaneous manifestations due to arsenic were generally recognized as follows: diffuse pigmentation appears at first in one to two years after exposure to arsenic, then punctate hyperkeratotic lesions appear mainly on the palms and soles, and Bowen's lesions occur after several years or more. The use of arsenic has been abandoned in this factory since January, 1971. Diffuse bronze pigmentation now seems to be considerably lightened, as long time has passed after exposure to arsenic. However, since punctate hyperkeratotic lesions on the palms, soles and others may, though rarely, undergo malignant transformations, new lesions of Bowen's  disease may further occur and these lesions may develop to invasive squamous cell carcinoma, physical examinations of the workers exposed to arsenic should be continued and careful observation of them is necessary for the future.


[Work load due to stamping task as a simple repetitive hand work (author's transl)]. An experimental study was carried out on stamping task using no conveyers with short work cycle which was taken as featuring simple repetitive hand work. Each phase of this work was allowed to each subject. Seventeen healthy adults, 8 males and 9 females, were engaged in the 120 minutes, stamping task. They were tested by their function of concentration maintenance (TAF), by flicker frequency and 30 items of subjective symptoms as advocated by the Japan Association of Industrial Health. Quantities of work for each 10 minutes were calculated. The results obtained were as follows: 1) Number of stamped cards by male subjects was more than that by female subjects. 2) Pace of work performance in the female subjects was being kept more in balance with their capacity in comparison with the male subjects. 3) The results of TAF and FF tests showed that the body load in the male subjects were greater than in the female subjects.


[Health effect of long-term diet mercury contaminated tuna. Part II. Accumulation and retention of mercury and selenium in organs and clinical symptoms (author's transl)]. Health effects of long-term tuna diet in cats were examined. The cats were fed daily with three kinds of tuna, containing different concentrations of mercury and selenium. The following results were obtained. 1) A high correlation was noted between the amount of fish intake and the mercury level in hair and blood samples of cats. 2) Mercury levels in organs were elevated corresponding with the amount of tuna consumption, but the distribution of mercury in organs of cats exposed to mercury in tuna flake differed from that in tuna fresh meat. In the liver, the ratio of methyl mercury to the total mercury was very low with an average of 11.5% of the ratio. 3) With regard to selenium, there was no correlation between intake of selenium and selenium levels in the cerebrum, celebellum, and kidneys, exept in the liver (r=0.766). 4) None of the cats had definite methyl mercury poisoning, but some slight disturbances were noted in several cats.


Toxicity of propoxur to rats by subacute inhalation. Male and female rats were exposed to propoxur (2-isopropoxyphenyl-N-methyl-carbamate) aerosol, concentrations averaging 5.7, 18.7 and 31.7 mg/m3 air, for 6 hours daily on five days in a week over a period of 12 weeks. The effects were depressions of plasma by 20 to 30%, and of erythrocyte and brain cholinesterase activities which were caused by the highest air concentration of 31.7 mg/m3. On the basis of the physical, biochemical, phamacokinetic and metabolic behaviors of propoxur, a maximum allowable concentration of 2.5 mg/m3 air is suggested.


Studies on muscular strength-myogram (MSMG). Part 1. A new device of apparatus for measuring muscular strength-myogram. 1. A new apparatus, consisting of a strain gauge and a carrier amplifier, was devised for measuring back muscular and shoulder arms strength by the author. This apparatus was applied for analysing myogenic disorder related to muscular fatigue or pain. 2. Muscular strength with load and its myogram were recorded simultaneously, and their changes during the exertion were analysed. 3. Muscular strength-myograms of sternocleidomastoid muscle, upper trapezius muscle, deltoid muscle, rhomboid muscle and lumbodorsal muscle were observed from the back muscular strength-myogram, and those of teres minor muscle and major pectoral muscle from the shoulder arm strength-myogram. 4. It seemed paradoxically that the amplitude of action myogram increased in proportion to the grade of lowering of muscular strength caused by muscular fatigue or pain.


Aging and activity of 5-aminolevulinate hydrolyase in the blood of humans and rats. Activity of 5-aminolevulinate hydrolyase (delta-aminolevulinic acid dehydrase, ALAD, EC 4.2.1.24) in the blood was determined in relation to age in humans and rats, and the following findings were obtained: (1) In the group which consisted of 47 women (mean age 46, ranged 24 to 62 years) living in a rural district, where the atmospheric lead concentration was 0.5 micron/m3, a significant negative correlation between ALAD activity and age was observed statistically (r = -0.54). However, in the group which consisted of 53 women of similar age group living in an urban district, where the atmospheric lead concentration was 1.9 microng/m3, showed a lower level of the ALAD activity than that of the former group and no correlation was found r = -0.01) between ALAD activity and age. (2) The ALAD activity of intact rats showed a decrease with age. The decrease proceeds rapidly within 8 weeks of age and becomes stable after reaching 25 weeks of age or 300 g of body weight. The value of the activity after 25 weeks of age was about one tenth of that at 5 weeks of age or 100 to 130 g of body weight. (3) Fifteen intact rats weighing 240 to 705 g were divided into three groups according to their body weight and were injected with lead acetate solution equivalent to 1 mg Pb/kg intraperitoneally in order to examine the sensitivity to lead in rats that have variation of ALAD activity by age or by body weight. The ALAD activity of these rats fell to the same level in all groups independently of the activity or the body weight before injection.


Changes of the vibratory sensation threshold in workers using vibrating tools. Vibratory sensation thresholds of ten fingertips of each person were measured by each of the three frequencies in groups using three kinds of vibrating tools and the control groups. The subject groups were using leg-drill (n=37), chipping-hammer (n=25) and chain-saw (n=19). The control groups were engaged in desk work or outdoor work in a bureau of forest management (n=24), a local forest office (n=30) and a gas company (n=22) (Table 1). The tested frequencies were 63 Hz, 125 Hz and 250 Hz. The room temperature was kept at 20 degrees C. 1) The threshold values were found in such order as V greater than IV greater than III greater than I and II-finger in the subject groups, whereas I and V greater than II, III and IV-finger in the control groups. No significant difference between left and right hands was found in any group, both the subject and the control. 2) The threshold values were significantly higher in the chipping-hammer group and the chain-saw group than in the control (p less than 0.05 at 63 Hz, p less than 0.01 at 125 Hz and 250 Hz). They were higher in the leg-drill group than in the control but it was statistically not significant. 3) Regression analysis was performed about age and experience-years of the subject groups which were thought to have an effect upon the threshold change. But the effect of both factors to the threshold values were small in all subject groups. 4) The patterns of threshold values made up by each of the three frequencies were different among the three subject groups. The chipping-hammer group had the higher vibratory sensation threshold shift in the order of 250 Hz, 125 Hz and 63 Hz, the leg-drill group had almost equal threshold shift among the three frequencies, and the chain-saw group had the intermediate tendency between the other two groups. 5) Frequencies of 125 Hz and 250 Hz were more advantageous than that of 63 Hz in order to discriminate between the subject group and the control. Both 125 Hz and 250 Hz vibratory sensation threshold should be measured to find early disorders of vibration disease if possible, because the relation between thresholds of 125 Hz and 250 Hz was not so linear. 6) The observed significant differences of threshold values among the control groups were thought to be caused by different climatic circumstances.


Cold water immersion test in patients with vibration disease. Peripheral vascular disorder is one of the most important symptoms in diagnosing vibration disease. Several kinds of tests have been introduced to evaluate the peripheral vascular function. Among those tests, cold water immersion test has been mostly applied. In Japan, the generally used method is to measure the skin temperature of one finger of the hand immersed up to the wrist joint in water at 5 degreesC for 10 minutes. However, because the suffering during the test is so severe and some unfavorable warning symptoms have been observed during group examinations, a safer and milder method is more desirable. In order to examine the applicability of the test by using water at 10 degreesC in comparison with that at 5 degreesC, and to know the degree of suffering during the tests, a comparative study was performed. Sixteen students and 29 patients with vibration disease joined in this study. The results suggest that water at 10 degreesC can be effective stimulus, if the immediate rewarming response is used for evaluation. The self-rating scores revealed that the suffering was milder in case of water of 10 degreesC than at 5 degreesC for both the students and the patients. And the patients seemed to suffer more from chest discomfort than the students.


[Factor analysis of Cornell Medical Index and Medical Data Index (author's transl)]. Structures of Cornell Medical Index and Medical Data Index were examined by factor analysis. Both of the translated questionnaires were self-administered by six hundred male employees. Questions of low response rate less than 5 and 6% were excluded, and 117 and 70 questions were analysed finally by the method of varimax rotation for CMI and MDI respectively. Ten factors were extracted. Cummulated contribution ratio of them amounted to 72.0 and 84.1% for CMI and MDI respectively. The first two factors were common for the both questionaires and had pronounced contribution ratio amounting to 36.7 and 29.3% for CMI and MDI respectively. The first factors was composed of questions related to autonomic inbalance, gastrointesinal symptom and fatigue, so it was named a tendency of many physical complaints. This factor was considered to be characteristic and representative one in such general health questionnaires, which was closely related to response set of the respondent. The second factor of the questionnaires was named mental instability. The two major factors would correspond to the first and the second component of the Subjective Fatigue Complaint Test (1970) by Japan Association of Industrial Health. Not also CMI but MDI were found to have a poor scalability except for the two major factors.


[Effects of signal-shock contingency probability on gastric lesions in rats as a function of shock region (author's transl]. Effects of signal-shock contingency probability on stress pathology were studied with 2 regions of electric shock and with (a) only sound signal presentations (NS), (b) unrelated presentations of the signal and tail shock (TS) or foot shock (FS) (NPS), (c) signal presentations all of which were paired with the TS or FS (100 PS), or (d) signal presentations, 50% of which were paired with a TS or FS (50 PS). Rats in NPS and 50 PS groups with TS showed more stress-induced pathology than animals in the 100 PS groups with TS. However, the 100 PS group with FS resulted in greater gastric lesions than NPS, 50 PS, or NS group. The interaction between shock region and signal-shock contingency probability plays an important role.


[Functional hemispheric asymmetries in perception of digit and line orientation orientation (author's transl)]. In Exp. I, right-handed Ss made the "same" or "diffeeent" judgement to paired digits serially presented to the right and left visual field, and exhibited erroneous judgements in the left visual field lead condition. These results suggest the left hemisphere superiority. In Exp. II, the Ss were requested to make the "same" or "different" judgment and to press a key as fast as possible to the paired line orientation. The right visual field lead condition product more errors than the left visual field lead condition. This suggests the right hemisphere superiority. But no difference appeared between both conditions in the reaction time. The opposite hemispheric superiority, found in perceiving verbal and non-verbal materials in the 2 experiments, would be attributed to the basic difference in "perceptual" process.


[Spectral analytical study on the developmental properties of EEG in children: Generalized and localized components of EEG spectra in the normal and the mentally retarded children (author's transl)]. The purpose of the present study was to elucidate the developmental properties of EEG in the normal and the mentally retarded children through regional differences and regional regional interrelationships. The localized components appearing at 1 or 2 regions tended to show low coherences in relation to the occipital region. The generalized component, observed over all regions, indicated lower coherences in the theta component than in the alpha one. It may be inferred that the theta component shown in the developing children may be differenciated from the component around 10 Hz.


[An experimental approach to eye-movements: comparison of response patterns between normal subjects and schizophrenic patients (author's transl)]. This experiment attempted to analyse eye movements (opthalmograph) when Ss freely observed 7 types of stimuli projected on the screen. 2 kinds of Ss, a normal control group (5 males, 5 females) and a schizophrenic experimental group (6 males), participated and their response patterns were compared. The results indicated that the schizophrenic group was inferior to the normal Ss in the number of fixations, the mean duration of single fixation, the scan path patterns of the eye mark, the frequency changes of the eye movements within a presentation time, and the dispersion of fixations. These results seemed to show that the schizophrenic group was not able to process much information, and had poor contact with the outer world.


Delayed hypersensitivity tests with Mycobacterium leprae purified protein derivative. Skin tests were conducted on 3 lepromatous, 3 dimorphous and 6 tuberculoid leprosy patients and 3 others not suffering from leprosy with lepromin, purified protein derivative from M. leprae of armadillo origin and tuberculin. Results show that a delayed hypersensitivity reaction could be produced with PPD in 72 hours on all Mitsuda positive cases, with one anomalous exception, without cross reaction to tuberculin. The results were promising from the point of view of substituting lepromin with PPD in usual tests.


Microtubules and actin filaments in teleost visual cone elongation and contraction. Teleost retinal cones contract in light and elongate in darkness. This paper describes the disposition of microtubules and cytoplasmic filaments in cone cells of 2 species of fish (Haemulon sciurus and Lutjanus griseus). In Haemulon, the neck-like "myoid" region of the cone changes in length from 5 mu to 75 mu. Maximal observed rates of elongation and contraction are comparable to that of chromosome movement in mitosis (2-3 mu/min). Microtubules presumably participate in cone elongation, since numerous longitudinal microtubules are present in the myoid region, and colchicine blocks dark-induced elongation. Myoid shortening, on the other hand, appears to be an active contractile process. Disruption of microtubules in dark-adapted cones does not produce myoid shortening in the absence of light, and light-induced myoid shortening is blocked by cytochalasin-B. Cone cells possess longitudinally-oriented thin filaments which bind myosin subfragment-1 to form arrowhead complexes typical of muscle actin. Myoid thin filaments are clearly observed in negatively stained preparations of isolated cones which have been disrupted with detergent after attachment to grids. These myoid filaments are not, however, generally preserved by conventional fixation, though bundles of thin filaments are preserved in other regions of the cell. Thus, actin filaments are poorly retained by fixation in precisely the region of the cone cell where contraction occurs. Cone cells also possess longitudinally-oriented thick filaments 130-160 A in diameter. That these thick filaments may be myosin is suggested by the presence of side-arms with approximately 150 A periodicity. The linear organization of the contractile apparatus of the retinal cone cell makes this cell a promising model for morphological characterization of the disposition of actin and myosin filaments during contraction in a nonmuscle cell.


The surface events of fertilization: the movements of the spermatozoon through the sea urchin egg surface and the roles of the surface layers. The sea urchin egg surface at fertilization has been examined with the scanning electron microscope to reveal the movements of the spermatozoon from the exterior, through the surface layers, and into the egg cytoplasm. The layers that the spermatozoon encounter have been studied to determine their physical and chemical natures and their role in early development. By studying the outside of whole eggs and the inner face of surfaces isolated shortly after fertilization, it has been possible to compile data on the movements of the spermatozoon through the egg surface. The spermatozoon initially contacts the egg with the elongated acrosomal process. The vitelline sheet, the outermost layer of the egg, separates slightly next to the attached spermatozoon. As membrane fusion between the gametes occurs, the plasma membrane from the egg engulfs the spermhead, the cortical granules start to discharge their contents, and a spreading surface deformation, concommitant with a distortion of the fibrous cortex, is initiated. A cluster of elongate microville surround the perpendicularly fusing spermatozoon. These microvilli interidigitate as the spermatozoon is forced to lie upon the egg surface between the plasma membrane and the matrix of cortical fibers. The spermatozoon then rotates additionally to enter the egg cytoplasm with the posterior end first; it has rotated 180 degrees through the cell surface. Finally, it detaches into the egg cytoplasm, leaving a scar in the cortex through which it penetrated. The egg cortex, previously unobserved by electron microscopy, is revealed to be composed of 50-200 nm fibers. At fertilization they are uniformly organized but during later development this order is lost. The cortex is from 0.2-0.5 micronm thick and is a contractile structure. The role of the outer surface in releasing the cell from the metabolic constraints of the unfertilized egg is shown, and the apparent differences in the mobilities of the membranes derived from the sperm and from the egg are demonstrated. The relation of these layers to the movements of the spermatozoon, to the activation of the egg, to the block to polyspermy, and to each other are discussed.


Regional brain variations of tryptophan, monoamines, monoamine oxidase activity, plasma free and total tryptophan during the estrous cycle of the rat. Normal 4-day cyclic rats were sacrificed at 10 a.m. and 3 p.m. on proestrus or estrus and at 10 a.m. on metestrus. Noradrenaline (NA), dopamine (DA) and tryptophan (T) concentrations varied only slightly. Serotonin (5-HT) concentrations showed characteristic changing patterns in many hypothalamic, limbic and midbrain structures with a decrease during proestrus and an increase during estrus being observed. Monoamine oxidase (MAO) activity changes were often parallel to the 5-HT changes, but were not as great. The marked changes in 5-HT early in proestrus are a further indication of its inhibitory effect on gonadotropin release mechanisms before the 'critical period'.


Persistent estrus in rats after anterolateral hypothalamic microinjections of 6-hydroxydopamine. Bilateral injections of 30 mug of 6-hydroxydopamine (6-OHDA, as base) into the anterolateral hypothalamic area induced constant vaginal cornification (CVC), polyfollicular ovaries and uterine hypertrophy in cyclic adult female rats. There were no important changes in the vaginal patterns or ovarian and uterine morphology in animals given injections in the same area with the solvent only and in animals given injections with 6-OHDA in the anterior amygdaloid area. It is suggested that the persistent estrus after anterolateral hypothalamic injections of 6-OHDA results from lesions of central catecholaminergic pathways, which are probably involved in gonadotropin secretion.


[Study of the hypothalamus of neonatally castrated rats by the karyometric method]. The sensitivity of different hypothalamic regions to the effect of androgens has been studied during the period of the brain sex differentiation. The castration of animals during the first week of life was shown to result in the marked increase of size of the neuron nuclei in the preoptic, suprachiasmatic, arcuate and ventromedial nuclei of the hypothalamus; the size of neuron nuclei in the dorsomedial nucleus suffered no changes. The dynamics of size of the cell nuclei was followed in different hypothalamic regions with respect to the time of castration.


[Effect of incomplete starvation on development of compensatory testicular hypertrophy during postnatal ontogenesis of rats]. The incomplete starvation of rats during the first month of life resulted in the inhibition of development of the spermatogenic epithelium cells in 80% of seminiferous tubules, preserved the increased permeability of hematotesticular barrier with respect to rivanol and the ability of rats to react by the increase of testis volume in response to unilateral castration. The data obtained confirm our hypothesis according to which there is a definite correlation between the degree of spermatogenesis completion, the function of hematotesticular barrier and the ability of animals for compensatory hypertrophy of testis.


[Absorption of testosterone-7alpha-3H by reproductive tract tissues of male-embryo rats in vitro]. The dynamics of testosterone-7alpha-3H consumption by the reproductive tract rudiments (tubules, urogenital sinus and genital tubercle) and the muscles has been studied in the in vitro experiments immediately after the isolation of embryos (16-21 days of development), as well as after the preliminary two days cultivation in the diffusion chambers (13-20 days of development). In the first series of experiments, the selective, specific consumption of the labelled androgen was observed at all stages under study, whereas in the second series of experiments the specific and selective consumption in the organs-targets was noted from the 15th day of development (in the genital tubercle and urogenital sinus). No selective consumption in the tubules was noted.


Effects of imipramine, chlorimipramine, and fluoxetine on cataplexy in dogs. Four narcoleptic dogs with cataplexy were given trials with the serotonin uptake blockers imipramine and chlorimipramine (known to be effective in treating cataplexy in humans). An even more selective serotonin uptake blocker, fluoxetine, was also tested. Injections of placebo, test compound, and placebo were given respectively on 3 successive days. Anticataplectic effects were measured approximately 30 min, 3 hr, and 6 hr postinjection by recording elapsed time and number of cataplectic episodes during the dogs' attempts to eat ten pieces of a desired food presented in a standard fashion. Imipramine (1 mg/kg) and fluoxetine (1.5 and 3.0 mg/kg)significantly improved performance, while chlorimipramine (0.5-5 mg/kg) had no clear effect. Data were not totally consistent with the notion that serotonin uptake blockers improve cataplexy in dogs, since chlorimipramine was not effective in these animals.


A comparison of withdrawal in rats implanted with different types of morphine pellets. Time course and duration and physical dependence was investigated in rats implanted subcutaneously with 3 different types of morphine (M) pellets. Each was formulated according to the method of Gibson and Tingstand [8], but differed in surface area and hardness. Animals were maintained for 19 days after implantation and physical dependence was assessed every other day. Severity of naloxone (Nx)-induced withdrawal was quantified by the use of a composite symptom score and weight loss. Withdrawal severity was greatest following implantation of a pellet (Type C) of large surface area and low hardness rating, and least following implantation of a pellet (Type A) of small surface area and high hardness rating. Abstinence severity which resulted from implantation of a pellet (Type B) of moderate surface area and low hardness rating was intermediate. When 2 pellets were implanted the difference between Type C and B was amplified. It was concluded that formulation per se was not sufficient for specifying M pellet characteristics.


Blockade of apomorphine's discriminative stimulus properties: relation to neuroleptic activity in neuropharmacological and biochemical assays. Using a food-reinforced two-lever operant conditioning procedure, rats were trained to discriminate 0.16 mg/kg apomorphine from saline. Eight neuroleptics of the phenothiazine, butyrophenone or diphenylbutylamine type were investigated for thsir ability to antagonize the discriminative stimulus properties of apomorphine. The same drugs were also assayed for in vivo antagonism of apomorphine-induced stereotyped behavior as well as for in vitro inhibition of stereospecific 3-H-haloperidol binding in rat striatal tissue preparations. The data are consistent with the hypothesis that apomorphine exerts its discriminative stimulus properties by a mechanism similar to that underlying its stereotypogenic action. The loci involved in these two phenomena are likely to be distinct.


Diminished reaction to a novel stimulus during amphetamine withdrawal in rats. This experiment determined whether reaction to a novel stimulus was diminished in a dose-dependent fashion following 8 consecutive days of d-amphetamine administration. Thirty-two male rats were injected with saline, 0.5, 2.5, or 5.0 mg/kg of d-amphetamine (each N = 8). On the ninth day, all animals received saline injections and were tested (a) in the presence of a novel stimulus, or (b) in the absence of a novel stimulus. Reaction to the novel stimulus varied inversely with the dose of d-amphetamine which had been received during the drug administration period. This reduction in reaction to the novel stimulus did not seem to depend on (a) the level of amphetamine-induced sterotypy at the end of the drug administration period (b) general reduction of activity, or (c) interference by drug-conditioned responses.


[Synthesis of nucleic acids and proteins in the appendix of chickens infected with Eimeria tenella]. A comparative study was carried out of the synthesis of DNA, RNA and protein in blind appendages of the intestine of healthy and infected with E. tenella chickens. It was established that the inclusion of P32 into DNA and C14 - orotic acid into RNA increases in 2-10 days after the infection. An intensive inclusion of C14-lysine into protein of blind appendages was observed in 2-6 days after the infection of chickens. Under the effect of the parasite an activation of metabolism of DNA, RNA and protein takes place in blind appendages of the host's intestine.


Incidence and significance of precipitating antibodies in occupational and non-occupational extrinsic non-atopic (type III) asthma (bronchial asthma with precipitins). Precipitating antibodies against different organic enviromental dusts were studied in 37 patients with suggestive symptoms of nonatopic bronchial asthma, comparatively with a group of 4 patients with atopic asthma and with a group of asymptomatic subjects, exposed to the same organic dusts as the majority of patients. Precipitins were found present in over 75% of the sera from patients with infectious type non-atopic asthma and were associated with positive semidelayed type skin tests as well as with positive bronchial provocation tests a few hours after antigen inhalation. No precipitins were found in the sera from patients with atopic asthma. Precipitating antibodies were also found but in lower percentages (30%) and at lower titers, in clinically asymptomatic subjects who were occupationally exposed to the respective antigens. It was demonstrated that the presence of precipitins in the sera of patients with bronchial asthma is a valuable diagnostic element which confirms the clinical and anamnestic data. The pathogenic role of precipitins is not yet clear. It might be related to the amount of these precipitins in the serum.


Some aspects of the kinetics of emiocytosis in prolactin cells. Some aspects of the kinetics of emiocytosis of secretory granules were investigated in pituitary prolactin cells of lactating female rats. Most of the emiocytotic events were directed towards those areas of the cells which were covered with a basal lamina. Diameters of the secretory granules within the emiocytotic pockets and of the openings of the pockets to the exterior were measured. An inverse relationship between the size of the granule and the diameter of the foramen was noted. A mechanism is proposed relative to the processes involved in the release of secretory granules from prolactin cells.


Platelet storage in the spleen in idiopathic thrombocytopenic purpura and congestive splenomegaly. The kinetics of 51Cr-tagged platelets was studied in 10 patients with idiopathic thrombocytopenic purpura and in 8 patients with congestive splenomegaly. The surgically removed spleens were examined for their platelet content and for their microscopic structure. In idiopathic thrombocytopenic purpura the life-span of platelets was reduced, the number of platelets washed out from the spleen averaged 4.36 X 10(10)/100 g splenic tissue (intrasplenic platelet reserve). The index platelets per g splenic tissue/platelets per ml whole blood reflecting the tendency of platelets to concentrate in the spleen was 8.06. Microscopically, extensive phagocytosis of platelets by macrophages and a preserved lienal architecture were seen. In the group of congestive splenomegaly the life-span of platelets was not significantly shortened and the intrasplenic platelet reserve agreed with the figure found in idiopathic thrombocytopenic purpura. The spleen was characterized by fibroid degeneration and endothelial hypertrophy causing partial obstruction of the sinusoids. It is concluded that while the intrasplenic platelet reserve is nearly the same in idiopathic thrombocytopenic purpura and congestive splenomegaly, in idiopathic thrombocytopenic purpura hypersequestration while in congestive splenomegaly platelet storage predominates.


[Headache].

[Headache]. Headache is an alarm sympton, whether there is an organic disease (lesional headache) or a perturbation of one of the various functions of the head (functional headache). Lesional headaches follow a sinusitis or an arthrosis, or accompany a "temporal arteritis of Horton". Funstional headaches include several varieties. 1. Trigemellar neuralgia. 2.Vascular algi originating from the basal arteries, the large cerebral venous sinuses or the branches of the external carotid. Among these are: a) headaches due to a dilatation of the internal wall, causing "Horton headache", migraine-like psychosomatic migraine and hormonal migraines (premenstrual, menstrual, menopausal or linked to the use of contraceptive pills); b) headaches caused by an angiospasm of the arteriole, which is the case in exposure to the cold, in traumatic headaches (malfunction of temporomandibular articulation, dry alveolitis), in psychosomatic angiospastic algias and in ethmoidal artery algias preciously described by the author in 1949 (Godin's disease).3. Headaches due to psychic hypertension. 4. Postconcussional psychogenic headaches. 5. Neurotic headaches. The author gives a detailed description of the subjective symptoms in each case, including localisation, from, intensity, duration course and associated phenomenons. This facilitates greatly the differential diagnosis and the choice of complementary examinations. Necessary biological investigations should be performed (e.g. hormonal balance). One should however avoid to increase the number of complementary examination which would only delay treatement and would expose patients to somatisation. Furthermore, in each case drug treatment, periarterial infiltration technics of the temporal, internal frontal, facial, mastoid and occipital arteries are described. The necessity of questioning the patient at lenght and to listen to him to enable him to verbalise conscious conflicts is emphasized. A serious medicopsychlogical examination and a relaxation treatment to reduce anxiety and muscular tension are advised in some cases.


The maltase activity of bovine serum as an aid to the study of the amylase i locus. A method has been described for the detection of maltase activity in starch gels. This method has been used to resolve the difficulties encountered when analysing animals with weak AmIB activity for Ami genotype. It was found that, with the herd of the Hannah Research Institute, the heterozygote excess observed could be explained largely on the basis of these weak AmIB bands.


[Vitamin E activity of stored forages and incidence of myopathy in calves]. Two experiments to study nutritional muscular dystrophy (N.M.D.) in calves were conducted in northern Ontario, where the disease is prevalent. In the first experiment, ninety Shorthorn cows were used. They were divided into three groups and fed the following forages during the winter of 1972-1973. Group I - Silage. Group II. - Heated-air-dried hay. Group III. - Field-dried hay. Chemical analysis of the forage during storage showed that the silage had a higher tocopherol content than the other two forages. This higher content had a direct effect on plasma tocopherol concentrations in the cows, since tocopherol levels were found to be higher in the group fed silage than in the other two groups. The highest mortality rate-eight dead calves-was in the group fed heated-air-dried hay; one calf died in each of the other two groups. Hence, it is evident that the severity of N.M.D. symptoms in calves is directly linked with the quantity of selenium or vitamin E ingested. The substances act synergistically to protect against the disease. In a second experiment, a herd of forty-seven Shorthorn cows, some of which had calves with N.N.D. and some of which had healthy offspring, were studied to measure the activity of serum creatine phosphokinase. The dams were found to have the same C.P.K., whether or not their calves suffered from N.M.D.


[Abortive infection of mice inoculated intraperitoneally with Chlamydia ovis]. A mouse adaptated strain of Chlamydia ovis, when inoculated in the peritoneal cavity, caused the death of both pregnant and non pregnant mice. In addition, mice inoculated late in pregnancy (12 to 16 days after breeding) aborted 4 to 6 days after inoculation. Chlamydia was recovered from foetuses and from the organs of the mice (Liver, Spleen, Lungs). The severity of the disease was related to the inoculum concentration, so it was possible to induce late abortions with a rapid recovery of the females, like in the natural infection of the ewes. In the same conditions, the original Chlamydia strain maintained by passage on yolk sac, induced only an inapparent disease transmissible to the young mice.


[Study of hydrolysis of aminoalcohol ethers, phenol and choline under the action of horse blood serum cholinesterase]. Hydrolysis of ethers of saturated and unsaturated alcohols and ethers, e.g. phenol and choline, under the action of horse blood serum cholinesterase, was studied. The reactivity towards enzymatic hydrolysis is decreased due to a greater length of the chain in the alcohol residue of the benzoic acid aminoethers; at nCH2 = 4 the compound is a poor substrate. An increase in nydrophobicity of the acyl residue of the ether molecule also leads to a decrease in the Vmax and Km values. In case of cholinesterase substrates, an increase in the molecule hydrophobicity results in an increase of its non-productive absorption on the active surface of the enzyme, which decreases its hydrolysis. Aminobutynol benzoates are hydrolyzed by cholinesterase more rapidly as compared to the ethers of corresponding aminobutanols and their homologs.