A possible short-term prediction of potential carcinogenicity of chemical compounds in vivo by means of a promoting activity test (PAT).

Carcinogens of chemically unrelated structure and different organotropism cause a mitotic stimulation of adrenocortical epithelia in vivo. A similar response is observed in liver regenerating rats following partial hepatectomy or intoxication by carbon tetrachloride. It is very probable from these and other results that the short-term effect (48 hours p. applic.) is brought about by the emergence of humoral growth stimulators which are evidenced in restorative regeneration and, therefore, accounts for the promoting activity of carcinogens. Special problems resulting from false positive (indomethacin, sodium nitrite) and false negative (7,12-dimethylbenz(a)anthracene, ethionine) findings as well as such of the role of solvents are discussed. The proof of the "contradictory" test result by long-term treatment in the case of trinitroso-trimethylene-triamine, nitroso-ethyltert-butylamine or nitroso-diallylamine has shown the accuracy of this short-term test.


[Histological changes in the placenta following tokolysis therapy (author's transl)].

In 138 tokolytically treated cases of imminent abortion or premature birth the secundines were examined histologically and compared with 390 cases of pathological gravidities or births without tokolysis therapy. The frequency of occurrence of morphologically manifested circulatory disturbances following tokolysis therapy was equal to that in the untreated cases, the rate of ascendent infections was only slightly increased. In tokolytically treated placentas with the histological pattern of "dissociated disturbed maturation" and "Maturitias retarda" are prevailing. Thus in most cases sufficient supply of the fetus is possible and the critical phase of uteroplacental insufficiency with the danger of abortion or premature birth may be overcome. There were no hints at direct influences of tokolysis on placental morphology.


Quantitative ultrastructural characterisation of rabbit erythroblasts and of 3H uridine incorporation into their nuclear components.

Electron microscopic-autoradiographic and morphometric investigations were carried out in erythroblasts from rabbit bone marrow. 1. to obtain quantitative data for the erythroblast classes. 2. to determine quantitative-morphometrically the incorporation rate of 3H uridine into the cell components of the different erythroblast classes. 3. to evaluate the influence of UV irradiation on the incorporation of 3H uridine. According to ultrastructural criteria erythroblasts are divided into 3 classes: basophilic erythroblasts (BE), polychromatic erythroblasts (PE) and orthochromatic erythroblasts (OE). The areas of the 3 classes of erythroblasts are in a ratio of 1:0.5:0.43. In all classes the portion of the nucleus is between 56 and 58.8%. The portion of mitochondria decreases from 13.3% (BE) to 9.3% (PE), and to 6.3% (OE) respectively. Simultaneously the portion of heterochromatin in the nuclear area rises from 24.2% (BE) to 49.8% (PE), and to 63.2% (OE) whereas the percentage of euchromatin decreased correspondingly. Nucleoli were found only in 78% of the BE and in 3.4% of the PE. For the quantitative determination of the silver grains and silver filaments, respectively, the morphometric procedures have been adapted to the particular conditions. So it was necessary to estimate the areas covered by silver grains of filaments. The silver grains or filaments localised in the nuclear area are in the range from 84.6 to 93.4%. The percentage of silver grains of the total cellular area is 14.4% in BE, 6.8% in PE and 4% in OE. In a similar way the relative values of the nucleolus (total) and the euchromatin and heterochromatin are reduced. UV irradiation of bone marrow in vitro for 10 to 20 min does not cause any significant changes in the incorporation of 3H uridine. This result is in contrast to other published experiments on the influence of UV on the RNA synthesis. It is assumed that the irradiation dose was too low to induce a measurable effect on the RNA synthesis or the point of investigation was too early.


[Adaptation of the rat myocardium to long-time application of small doses of isoproterenol (author's transl)].

After long-time application of small doses of isoproterenol an adaptation occurs which is expressed by increased tolerance against toxic amounts of this substance. This study shows the duration of tolerance increasing effect after isoproterenol application.


Immune prophylaxis of experimental cancer by corynebacterium parvum.

Fractionated administration of C.p. i.v. in mice at risk from sarcomas after injection of 0.2 mg MCA leads to a significant prolongation of the period of latency under certain circumstances. Experimental groups which have received the immune stimulator for 6 weeks immediately after the cancerogenic factor show the best results. After tumour manifestation there is no perceptible preventive effect of C.p.


Ultrastructural relations of macrophages to Schwann cells. An experimental study on regenerating peripheral nerves.

The correlations between macrophages and Schwann cells are studied on transsectional sciatic nerves from rats using the electron microscope. As early as 1 day after operation typical macrophages can be found within the endoneurial space of the proximal stump. On the other hand, 1 and 3 days as well as 4 weeks after operation Schwann cells may show cytoplasmic features comparable to that of macrophages. Our findings suggest that (1) macrophages are not able to transform into Schwann cells and (2) Schwann cells can act as phagocytosing cells exhibiting characteristics of macrophages. But in this functional state they can only be diagnosed as Schwann cells if a basement membrane and/or included axons with mesaxons are present.


Studies on a new acute phase protein. I. Immunocytochemical demonstration of the origin.

Synovial fluid of patients with rheumatoid arthritis or traumatic arthritis contains an antigen which is thermostable to boiling temperature and insoluble in ethanol. The antigen was not found in sera of healthy subjects but it is present in numerous sera of patients with different inflammatory diseases. The partial purification of the antigen and the production of specific antisera are described. Immunofluorescent staining of tissue sections and blood smears indicates, that the antigen is a cytoplasmic protein of polymorphonuclear leucocytes. Monocytes contain the antigen to a lower degree, it was not found in eosinophils and lymphocytes. In addition, the influence of different fixing agents and of other pretreatment on the pattern of the cell fluorescence was studied. We propose to designate the antigen as thermostable granulocyte antigen (TSGA).


Killing of untreated target cells by nonimmunized rat macrophages in vitro. I. Studies on the type of effector cells and their capacity to destroy allogeneic target cells.

Spleen cells derived from unsensitized Wistar rats lysed untreated, allogeneic liver cells of high passages (93rd until 159th subculture) as well as allogeneic tumor cells in mixed cultures. On the other hand, rat liver cells between passages 42 and 56 and allogeneic or xenogeneic fibroblasts were not destroyed by rat spleen cells in vitro. The degree of target cell lysis was dependent on the incubation time and effector-target cell ratio. In the rat spleen, the macrophages were detected as effector cells. Rat peritoneal cells showed the same effects as rat spleen cells. Trypsin treatment caused no loss of cytotoxicity of rat macrophages. Thymocytes and blood lymphocytes of rats were not cytotoxic against allogeneic or xenogeneic target cells. The macrophages apparently destroyed target cells by a nonphagocytic form of cell contact. Unstimulated spleen cells of guinea pigs, Syrian hamsters, CBA mice and rabbits were not capable to destroy target cells in allogeneic and xenogeneic systems.


Killing of untreated target cells by nonimmunized rat macrophages in vitro. II. Ultrastructural studies on the interaction of macrophages and rat liver cells.

The sequence of morphological changes following the interactions between macrophages of nonimmunized rats and allogeneic liver cells in vitro were examined by scanning and transmission electron microscopy. The effector cells could be identified as macrophages because of their morphologic characteristics and their ability of latex beads incorporation. The cytotoxic reactions required close contracts between the reactive cells. Effector membrane processes and microvilli attached the target cell surface. Broad contacts and, more frequent, point contacts were observed. After 4 to 5 hrs of incubation the target cells showed pinocytotic activities in the contact regions. Later on submembraneous cytoplasmatic leaks or defects indicated the increasing damage of the target cells. Finally, liver cell ghosts with degenerated organelles were found as morphologic expression of general target cell destruction whereas effector macrophages did not show any damage during the cytotoxic reaction.


Growth stimulation following serum transfer from carcinogen-treated donors to normal rats: a new aspect of early carcinogen actions.

Especially in their early phase of action carcinogens are strong inhibitors of cell proliferation. This is an apparent contradiction to the promoting activity of oncogens in the process of carcinogenesis. Because of obvious similarities between restorative and neoplastic growth processess on the tissue level we have studied the possibility, whether such similarities do exist also with regard to stimulatory activities in the serum. To overcome the non-specific inhibitory effect of a carcinogen, the serum of 2-acetylaminofluorene (AAF) treated male Sprague-Dawley rats was transferred to normal recipients. The results demonstrate that the proliferation of the same tissues (hepatocytes, adrenocortical cells, thymocytes) as in liver regenerating animals were stimulated by the serum of the carcinogen-treated rats. Whether the observed short-term effect corresponds to the so-called promoting activity of the carcinogen(s) is discussed. Nature and origin of the humoral stimulator(s) are still unknown.


Morphometric investigations on endocrine glands. IV. The rat thyroid during liver regeneration after partial hepatectomy with and without application of carcinogenic substances.

Morphometric studies and counting of mitoses in thyroids during regeneration after partial hepatectomy had the following results: 1. During the first days after surgical operation laparotomy caused only a slight reduction of the thyroid function. 2. Up to the 3rd day and especially on the 10th day after partial hepatectomy there is a higher relative percentage of the epithelium in the thyroid, but the mitoses are diminished. 3. Prefeeding with methylnitrosourea and acetylaminofluorene before the surgical 2/3 removal of the liver was answered with subactive thyroids on the 3rd day.


Pulmonary response to kaolin, mica and talc in mice.

Following intratracheal inoculation the pulmonary fibrogenic response of kaolin, mica and talc was investigated in mice over a period of 210 days. All the three dusts incited acute inflammatory reaction at early periods but with mica dust the acute reaction persisted longer. Subsequently there was gradual increase in the fibroblastic activity in the focal areas and mica produced, in addition, many cholesterol cleft-like structures together with marked fibroblastic activity and lymphocytic infiltration. Towards the termination of experiment at 210 days the fibrosis, in general, remained restricted to grade II with kaolin and mica while talc produced thickened interalveolar septa. The transport of dust from lungs to lymph nodes occurred earlier with mica than with kaolin or talc dust accompanied with little fibrotic reaction. The significance of the findings has been discussed.


Estrogens as disposing factors in experimental liver injury.

The activity of hexobarbital metabolising enzymes of the liver is decreased as a consequence of both acute and chronical carbon tetrachloride damage. Simultaneous administration of estrogens was followed by more severe morphological and functional impairment although estrogens are not burdening the healthy liver. The beta receptor blocking propranolol prevented functional lesion, moderated fatty degeneration and liver cell necrosis in chronic carbon tetrachloride injury. A simultaneous estrogen administration decreased the therapeutic efficacy of beta blockade, however functional and morphological protective effects were not completely abolished. Estrogen medication should be rather avoided in hepatic damage.


Ultrastructure of perineurial cells during peripheral nerve regeneration. Electron microscopical investigations on the so-called amputation neuroma.

The ultrastructural morphology of perineurial cells was examined after transsection of the sciatic nerve of rats. The material prepared for investigation was taken from the proximal nerve stump and the so-called amputation neuroma at different times after operation. We found that perineurial cells begin to activate in the first week, and in the further course of regeneration they modulate their cytoplasmic structure corresponding to the function of proliferation or synthesis. Besides the reconstitution of a diffusion barrier the perineurial cells may exert a stabilizing function in regenerating nerve tissue comparable to myofibroblasts in granulation tissue, and may be engaged in remodeling of connective tissue fibers. The relations of perineurial cells to other cells of peripheral nerves under the condition of regeneration are discussed.


Effects of calcitonin on epidermal regeneration and collagen synthesis in rabbits with experimental wounds.

The cellular and metabolic effects induced by calcitonin on regenerative epidermal cells, fibroblasts and collagen fibers during wound healing were studied in rabbits. Electron microscopy revealed marked changes at 2 and 5 days post-wounding in epidermal cells and fibroblasts in calcitonin-treated rabbits such as: an increase in keratohyaline granules, tonofilaments, polysomes and a hypertrophy of nuclei in the epidermal cells. Fibroblasts are hypertrophied and surrounded by large areas of mature collagen fibers, namely at 5 and 14 days. Electron microscopic autoradiography revealed an increase in the incorporation of 3H-thymidine mostly in the nuclear chromatin, 3H-uridine in the nucleoli, 3H-leucine in the endoplasmic reticulum, polysomes and newly formed keratin layers, and 3H-proline over fibroblasts and collagen fibers. Most of the cellular and metabolic effects are evident at 2.5 hours and gradually decline by 5 and 24 hours of hormone administration. Scanning electron microscopy showed changes in the keratin pattern and collagen fibers. At 5 days after wounding and calcitonin treatment, a typical scaly pattern of keratin can be noted while in controls it is smooth and homogeneous. At 14 days post-wounding the collagen fibers are hypertrophied, with an extensive network of fibrils in calcitonin-treated rabbits. These findings demonstrate that synthetic salmon calcitonin stimulates protein synthesis, keratinogenesis and collagen formation in epidermal cells and fibroblasts during wound healing.


[Nuclear DNA synthesis rate and labelling index: effects of carcinogenic and non-carcinogenic chemicals on its behaviour in the organism of growing CBA-mice. The thymidine-incorporation-screening-system (TSS) (author's transl)].

During the last few decades there has been an extraordinary accumulation of man-made chemicals in the human environment. There is a growing consensus in oncology that a large proportion of human cancers are environmental in origin by exposure of man to such carcinogenic chemicals. These chemicals in the majority of all cases have not been tested to prove their carcinogenicity. Testing of new chemical compounds is needful prior to their introduction into commerce, foods, agriculture or the working places to prevent human cancer. To test such a large number of possibly carcinogenic chemicals, economical and rapidly practicable bioassays are necessary. In the following we compare some well known bioassays with our autoradiographic thymidine-incorporation-screening-system and other assays based on biochemical quantification of DNA synthesis as parameter for identification of carcinogenic substances. The partial inhibition of the whole DNA synthesis in a proliferating cell population after treatment with toxic and carcinogenic chemicals is an early common response especially in hepatectomized animal, livers caused by the effects of those substances. However, by quantitative evaluation of the nuclear DNA synthesis rate as a basic parameter using autoradiographs of kidney and liver of juvenile growing CBA-mice, it is possible to differentiate carcinogenic from non-carcinogenic chemicals by means of silver grain counting after 3H-TdR incorporation. Contrarily the "whole DNA synthesis" expressed by the percentual 3H-labelling index of kidney and liver did not permit such a differentiation in our experimental arrangement. We could demonstrate that carcinogenic compounds of different chemical classes partially inhibit the nuclear DNA synthesis rate significantly over a time period longer than 24 hours. The tested non-carcinogenic compounds did not show this suppressive effect on the nuclear DNA synthesis rate.


Clotting factors added to fibroblast cultures. Their action on glycosaminoglycans and other parameters.

To monolayer cultures of embryonic rat fibroblasts in the proliferative and stationary phase of growth there were given: thrombin, fibrinogen or fibrin supernatant, respectively. Their effects on cell proliferation, glucose consumption and glycosaminoglycans were recorded and observed to be more pronounced in serum-depleted and confluent cultures. Thrombin in serum-supplemented cultures was nearly ineffective. In serum-free stationary cultures glucose consumption, GAG concentration and, above all, hyaluronic acid were increased. Fibrinogen stimulated the metabolism of stationary fibroblasts (glucose, GAG, particularly hyaluronic acid) more strongly in serum-depleted medium. A number of protease inhibitors were ineffective in abolishing the fibrinogen action pointing to the efficacy of the intact fibrinogen molecule. The supernatant of the fibrinogen-thrombin-reaction, separated after 3 hours, likewise increased glucose consumption, GAG and hyaluronic acid concentration possibly due to effects of the fibrinopeptides A or B. However, contamination of fibrinogen with other active compounds cannot be excluded as yet. Surprisingly, fibrin generated on the fibroblast monolayer did not stimulate the cells. Therefore fixation of the active compounds of the fibrin supernatant (fibrinopeptides) during the process of fibrin polymerization has to be assumed. According to these observations thrombin, fibrinogen and components of the fibrin supernatant contribute to the increase of hyaluronic acid and cell activation in the oedematous phase of inflammation at sites free from fresh-formed fibrin.


On methods of silver grain counting in histoautoradiograms.

Visual silver grain counting in histoautoradiograms is a slow and tedious procedure. In this study different methods of automation of grain counting, possibilities of use as well as their advantages and disadvantages are critically compared. By means of autoradiograms of 3H-phenylalanine-labelled rat liver specimens the possibilities of automated image analyses are demonstrated. The use of these techniques enables rapid counting of silver grain densities over cell nuclei and cytoplasm.


Activators of serum lipoprotein lipase in alloxan diabetic rats.

The amount of free fatty acid (FFA) liberated with intralipid in post-heparin guinea-pig serum, when serum from alloxan diabetic rat is incubated, is higher than that liberated when serum from healthy rats is used. The above effect is probably due to larger quantities of lipoprotein lipase present in the diabetic serum.


Estimation of the methylating capacity in the pineal gland of the rat with special reference to the methylation of N-acetylserotonin and 5-hydroxytryptophol separately.

In the present paper, an extension is presented of an earlier described method, by which the methylating capacity of the pineal gland can be determined. Supplementary to the earlier method, the synthesis of melatonin and 5-methoxytryptophol can now be qualified and quantified separately.


Antifungal properties of leaf extract of Ranunculus sceleratus L.

Studies on various antifungal properties of the leaf extraxt of Ranunculus sceleratus L. showed that it was thermostable up to 100 degrees C, retained activity on autoclaving, and remained active up to 15 days at room temperature. It possessed quick fungicidal action, tolerance against heavy fungal inoculum, activity on broad pH range, broad fungicidal spectrum, non-phytotoxicity and non-systemic activity. The extract was lethal at 1:40 dilution and its volatile vapours were also fungitoxic.


Cadmium-113 FT NMR-spectra of rabbit liver metallothioneins.

Cadmium-113 FT NMR-spectra of rabbit liver metallothionein-I and -II gave 6 and 7 NMR-signals, respectively, at between 610 and 670 ppm downfield from aqueous Cd(CIO4)2 solution (0.1 M).


In vitro studies on lysosomes radiosensitivity in different gaseous atmospheres.

Radiosensitivity of lysosomes was investigated in vitro in different gaseous atmospheres. Results show a higher sensitivity when X-irradiation was performed in nitrous oxide. Possible reasons for this observation are considered.


Chaetogaster limnaei K von Baer 1872 on Lymnaea tomentosa: ingestion of Fasciola hepatica cercariae.

The fresh water mollusc, Lymnaea tomentosa, the intermediate host of the liver fluke is heavily infested under natural conditions with ectocommensal annelid, Chaetogaster limnaei. These annelids which destroy the larval stages of Fasciola hepatica have been observed in the laboratory. The association of C. limnaei with the snail intermediate host is of value in exploiting a control measure against economically important liver fluke disease.


Collagen synthesis of cultured fibroblast from Werner's syndromes of premature aging.

The difference of collagen producibility between 2 groups of skin fibroblasts from patients with Werner's syndrome with skin change and with normal skin, and the difference of collagen accumulation to cell layer between skin fibroblast from Werner's syndrome and controls were studied.


Transient ischemic alteration of synaptosomal neutral amino acid uptake.

The effect of cerebral ischemia and postischemia on the synaptosomal uptake of some neutral amino acids was determined in mongolian gerbils at various periods of time. A transiently increased uptake of 3H isoleucine, 14C cycloleucine and 3H phenylalanine in the synaptosomes was found after 3 min of bilateral common carotid occlusion which returned to normal at 30 min of reestablished cerebral blood circulation.


Changes in free amino acids and peptides in the haemolymph of Glossina austeni during the reproductive cycle.

The animo acids in the deproteinized haemolymph of Glossina austeni females, before and after hydrolysis, have been determined at 12 different times during the 1st 2 pregnancy cycles. Hydrolysis resulted in a large increase in the concentrations of tyrosine, phenylalanine, aspartate and lysine, indicating that these amino acids are present mainly as peptides in the haemolymph. The rate of transfer of the aromatic amino acids to the offspring, based upon the amino acid content of the larval gut, must be exceptionally high and has been estimated to be at least 7.9 microgram/h.


Superoxide dismutase activity decreases during erythrocyte aging.

Superoxide dismutase activity was determined by the adrenalin method in bovine erythrocytes separated according to age. Progressive loss of the enzyme activity was found, down to ca 65% of that of the youngest cells.


Effect of experimental chronic renal failure upon the production of urea, as measured by the liver arginase activity in rats.

A significant diminution in liver arginase activity of chronic renal failure uremic rats is described, thus implying that the experimental finding of an increased urea production is not due to a depressed arginase activity.


Vasomotor escape from adrenaline, noradrenaline or acetylcholine in the dog hind limb.

The noradrenaline, adrenaline and acetylcholine-induced vasoregulatory escape was demonstrated in the vascular bed of intact of skinned and denervated dog's hind limb. Escape effect disappeared or decreased markedly under elevation tissue pressure in the examined hind limb. These data indicate that tissue pressure factor may take part in the mechanism of the escape phenomenon.


Semen electrolytes in normal and infertile subjects. II. Zinc.

Zinc levels in seminal plasma of normal subjects are compared with those of oligospermic, asthenospermic and azoospermic. A linear direct relationship seems to exist between zinc in seminal plasma and motility of spermatozoans. The possible implications of this are discussed.


Determination of infarct size in rats with 86rubidium.

A quick method is presented which allows the determination of infarct sizes within hearts of experimental animals like rats. The method is based on the drop of 86Rb uptake in infarcted hearts, and has been compared with infarct sizes determined morphometrically. The standard deviation of this method is low (6.5%) because an internal standard in used (noninfarcted myocard - usually right ventricle tissue - has been used).


Motor nerve terminal defect following tenotomy.

Post-tetanic potentiation and the underlying post-tetanic repetition in cat soleus muscle require normal motor nerve terminals. These indices of nerve terminal viability are depressed 10 days and absent 15 days after tenotomy of the soleus muscle.


Interaction of vinblastine analogues with tubulin.

Studies of the interaction between vinblastine-like alkaloids and their receptor, i.e. tubulin, are reported. They shed some light on the structure-activity relationships in this medicinally important series: the configurations at C14' and C16' as well as the presence of the methoxycarbonyl group on C16' seem to play an essential role in the determination of biological activity.


Metabolism of hydrazines and hydrazides by the intestinal microflora.

Intestinal microorganisms are able to effect the metabolic reductive fission of hydrazines but not hydrazides during incubation in vitro.


Separation and quantitative determination of imipramine and desipramine from rat biological samples by high pressure liquid chromatography.

Imipramine and its metabolite, desipramine, have been determined in several rat biological samples by high pressure liquid chromatography. The method allows one to detect 15 ng in column of both drugs with a lower sensitivity limit of 20 microgram1-(1).


Effect of the administration of (d-Ala) 2methionine-enkephalin on the serotonin metabolism in rat brain.

The effect of cerebroventricular injection of [D-Alanine] methionine-enkephalin (DALA), a synthetic analog of met-enkephalin, on the serotonergic system of rat brain has been studied. This opioid peptide caused an increase in 5HT turnover which was particularly evident in the limbic forebrain. This effect was completely antagonized by naloxone pretreatment.


Antiparkinsonian drug doses and neuroleptic receptors.

The clinical potency of 3 drugs, apomorphine, N-propylnorapomorphine, and bromocryptine, have been found to be closely correlated to their potencies in competing for 3H-haloperidol and 3H-spiroperidol both of which label the dopamine receptor. This correlation indicates that the direct binding assay may be used to predict clinical potencies of anti-parkinsonian drugs, and indicates that agonists as well as antagonists compete potently for 3H-neuroleptic binding.


Enhancement of p-aminohippurate accumulation in renal cortical slices after repeated administrations of various organic anionic drugs to rats of different ages.

After repeated administrations of various organic anionic drugs to rats of different ages, an enhancement of paminohippurate accumulation was observed in renal cortical slices from adult but not from newborn and infant rats. The effect can be interpreted as specific substrate-induced stimulation of the organic anion transport.


Radioimmunological determination of prostaglandin D2 synthesis in human thrombocytes.

A specific radioimmunoassay for prostaglandin D2 was developed. Using the radioimmunoassay, prostaglandin D2 synthesis by human thrombocytes was measured. While the cyclooxygenase inhibitor indomethacin inhibits formation of prostaglandin D2, increased formation of prostaglandin D2 was observed in the presence of the thromboxane synthetase inhibitor imidazole.


Wound healing properties of naphthaquinone pigments from Alkanna tinctoria.

From the roots of Alkanna tinctoria Tausch, the alkannin esters of the following acids were isolated and identified: beta,beta-dimethylacrylic acid, beta-acetoxy-isovaleric acid, isovaleric acid, and angelic acid. These esteric pigments showed excellent wound healing properties in a clinical study on 72 patients with ulcus cruris.


Cerebral edema in the rat with galactosamine induced severe hepatitis.

With D-galactosamine hydrochloride severe hepatitis was induced in rats and the water content of cerebrum, cerebellum and brain stem determined. The animals showed a parallel increase in cerebral water content and occurrence of cerebral symptoms.


Effect of pretreatment with prednisolone on the phagocytic activity of mouse peritoneal macrophages in vitro.

The phagocytic activity on in vitro cultured mouse peritoneal macrophages derived from animals treated with 6-alpha-methyl-prednisolone was examined. The statistical evaluation of results showed an increase of phagocytic activity of macrophages derived from treated animals in comparison with controls.


Inhibition of rat hepatic dimethylnitrosamine demethylase by cyclic and acyclic nitrosamines and secondary amines.

Inhibition of hepatic dimethylnitrosamine (DMN) metabolism by a variety of cyclic and acyclic nitrosamines was demonstrated. Nitrosoproline, a noncarcinogenic nitrosamine, behaved differently from the carcinogenic nitrosamines as an inhibitor for DMN-demethylase. Secondary amines corresponding to the nitrosamines inhibited DMN-demethylase in a manner similar to the nitrosamines.


Attraction of primordial germ cells by notochord in seven somites chick embryo.

Chemical studies in chick embryo have indicated the existence of proteoglycan in notochordal sheath. Primordial germ cells were observed with scanning electron microscope on the notochord dorsal face, surrounded with perichordal material. We postulate the identification of such a material with proteoglycan which could attract primordial germ cells to the notochord.


Determination of proliferative compartments in human tumors.

Extracorporeal normothermic perfusion with radioactive thymidine allows a cytological, hostological and structural analysis of proliferative compartments of human kidney carcinomas in whole-tumor autoradiograms.


Isolation of a growth-stimulating agent from human skin fibroblast cultures.

Cell-free supernatants were harvested from cultures of human skin fibroblasts, were applied on to DEAE-cellulose columns, and the first fraction eluted with phosphate-buffered saline contained the growth-stimulating agent. The eluted fraction was then passed through a series of amicon membranes. After passing through PM-10, the filtrate stimulated growth of bovine vascular endothelial, canine myocardial, and human mammary carcinoma cells.


Inhibition of Ehrlich ascites carcinoma (EAC) growth by carbonyl iron.

Treatment of Ehrlich ascites carcinoma (EAC) cells with carbonyl iron (20 mg/ml) produces a significant decrease in growth rate of tumor inoculum both in Swiss and in C57BL/6 mice. Possible interaction of the carbonyl iron or Fe+++ions with cell surface is suggested.


Exogenous melatonin and melanophore development in Xenopus.

Xenopus larvae raised from stage 21 in melatonin solution and upon a dark background had fewer head melanophores at stage 48 than control animals not exposed to melatonin. Rearing larvae in melatonin solution seems to mimic rearing larvae on a light background.


The lack of an effect of cholinergic agonists on anterior pituitary prolactin production in vitro.

The addition of dopamine to anterior pituitary incubations resulted in a marked decrease (88% for 3H prolactin and 69% for RIA prolactin) in prolactin release. Incubation with the cholinergic agonists carbacol, arecoline and nicotine resulted in no significant change in prolactin secretion.


Daily change in pineal N-acetyltransferase activity in a diurnal mammal, the ground squirrel.

Pineal N-acetyltransferase (NAT) activity in the ground squirrel, a diurnal mammal, was found to have a daily fluctuation with peak activity during the dark time. This same daily change is found in nocturnal mammals and diurnal birds. NAT may play an important role in keeping track of light and dark cycles.


[Quantitative study of the modifications observed in somatotropic cells of thymectomized rats. Opotherapic substitution with a thymic extract].

Removal of thymus is followed by a degranulation of somatotropic cells, by an increase of the surface of the granular endoplasmic reticulum, and of the plasma level of growth hormone. An opotherapic substitution was realized with a thymic extract.


Effects of thyroid state on brain stem responses to iontophoretic noradrenaline.

Responses to iontophoretic NA were increased in hyperthyroid rats and decreased in hypothyroid animals. No effect was observed on acetylcholine and glycine responses tested in the same way.


Experiments on the mechanism of the inhibition of mitochondrial Ca2+ transport by La3+ and ruthenium red.

The effects of La3+ and ruthenium red on the energy-linked uptake of Ca2+ mediated by a synthetic neutral Ca2+ ionophore have been investigated in rat liver mitochondria. The results indicate that unspecific surface charge effects do not play a major role in the mechanism of inhibition of mitochondrial Ca2+ transport by La3+ and ruthenium red.


The isolation and structure of 13,18-dehydroglaucarubinone, a new antineoplastic quassinoid from Simarouba amara.

An investigation of the Guyana plant Simarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2'-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2'-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid 2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388.


(+/-)9,10-Dihydroxy-delta6a(10a)-tetrahydrocannabinol and (+/-)8,9-dihydroxy-delta6a(10a)-tetrahydrocannabinol: 2 new cannabinoids from Cannabis sativa L.

The structures of 2 new polyhydroxylated cannabinoids, (+/-)9,10-dihydroxy-delta6a(10a)-tetrahydrocannabinol and (+/-)8,9-dihydroxy-delta6a(10a)-tetrahydrocannabinol, obtained from a hexane extract of an Indian Cannabis variant were determined by spectral means and correlation with cannabinol.


Effect of seasonal variations and cold acclimation on serum transaminase activity of common Indian frog Rana tigrina.

A definite seasonal change is observed in 2 transaminases, SGOT and SGPT of R. tigrina. Cold acclimation significantly depresses transaminase activity of serum.


Changes in mouse liver superoxide dismutase activity and lipid peroxidation during embryonic and postpartum development.

In inbred mice possessing 'high' and 'low' tissue superoxide dismutase (SOD) activity, it was observed that the difference in the SOD activities of the liver homogenates during development attains the maximum characteristic of the strain by about the 150th day. Subsequently, the SOD activity change displays a tendency in contrast with the age and the basic state. In the course of the development, a difference was also observed between the 2 mouse strains in the lipid peroxidation variation.


[Hybridization between Mus musculus L. and Mus spretus Lataste under laboratory conditions (author's transl)].

2 species of mice Mus musculus brevirostris and Mus spretus are sympatric in Southern France and reproductively isolated. However, under laboratory conditions, they breed and give fully viable F 1 hybrids. This indicates that premating isolating mechanisms probably occur in nature and have yet to be investigated. Moreover, it now enables us to introduce new genetical markers in laboratory strains.


Lactate dehydrogenase polymorphism in Mus musculus L. and Mus spretus Lataste.

First variation at the Ldh-A locus and a new allele at the Ldh-B locus are reported in a M. musculus population dimorphic at the Ldh-A locus and in a M. spretus population trimorphic at the Ldh-B locus.


Environmental temperature and the growth of Taenia crassiceps cysticerci in mice.

Mice kept a low (5 +/- 1 degrees C) and high (35 +/- 1 degrees C) temperature harboured significantly less Taenia crassiceps cysticerci than controls kept at 21 +/- 1 degrees C. This effect was more pronounced in heat-stressed than in cold-stressed animals and more in males than in females.


Demonstration of the presence of M-creatine kinase in mammalian myogenic cell lines.

Unequivocal identification of M-CK in cell extracts from fused cells of myogenic cell lines is difficult due to almost identical behaviour of the M-CK and a contaminating enzyme activity in electrophoresis. If CK dimers present in cell extracts were subjected to dissociation and reassociation in the presence of exogenous B-CK subunits, the formation of easily identifiable MB-CK was demonstrated, indicating the presence of M-CK in the myogenic rat cell lines.


Evidence for the metabolism of phospholipids and triacylglycerols in human Ascaris lumbricoides.

Human Ascaris lumbricoides has the necessary mechanism for the biosynthesis and degradation of phospholipids and triacylglycerols, as in most other species. Piperazine decreases the level of triacylglycerols of this parasite by stimulating the activity of lipase and partially inhibiting the activity of phosphatidate phosphatase.


Kinetics of interferon action.

A kinetic analysis of the action of interferon with different preparations in chick embryo fibroblast cell culture gives additional evidence for interaction of interferon with the cell surface, compatible with the idea that interferon is not taken up by the cells. With certain assumptions the binding constant is in the range of 10(13) [l/Mol].


Norepinephrine as principal catecholamine in a specific neurone of an invertebrate (Boophilus microplus: Acarina).

Norepinephrine has been identified as the principal catecholamine in individual neurons of the synganglion of an arthropod, the cattle tick Boophilus microplus. This suggests that norepinephrine may have a hitherto unsuspected major physiological role in at least one group of invertebrates.


Seasonal changes in the electrical parameters of the small intestine, colon and bladder mucosa of land tortoises (testudo hermanni hermanni Gmelin).

During hibernation of tortoises, a marked decrease in the short-circuit current together with an increase in the electrical resistance are observed across the small intestine, colon and bladder mucosa and D-aldosterone (which is decreased in the plasma) has no effect on these parameters.


The sequential uptake of (14C) deoxyglucose in brain after embolic stroke.

An i.v. bolus of (14C) deoxyglucose was injected into 4 groups of rats which simultaneously were embolized through the internal carotid artery. 15 and 30 min post embolization there was a massive decrease in (14C) deoxyglucose uptake in both deep and cortical structures. At 4 h a small zone of increased (14C) deoxyglucose uptake persisted around each embolized microsphere.


Autonomic response of the fish to pyrogen.

Lipopolysaccharide (LPS) applied to the anterior brainstem of the carp caused lightening of body colour. This indicates that an increase in set point temperature is responsible for increased cutaneous autonomic activity following LPS-administration.


Origin and course of an afferent component of the facial nerve within the central nervous system.

The mesencephalic nucleus of trigeminal gives rise to an afferent component of the facial nerve. This nucleus contains large unipolar afferent cell bodies which give rise to an axon which courses caudally through the brainstem and exists via the facial nerve to terminate distal to the stylomastoid foramen.


Coffee and cola beverage consumption as heart disease risk factors in men.

The relationship of coffee drinking and cola beverage consumption to recognized heart disease risk factors was studied in 365 adult men. Cola beverage consumption was not positively related to any risk factor. Heavy coffee drinking seemed to reflect a life style characterized by infrequent eating, which was significantly correlated to all the heart disease risk factors studied.


Evidence for cross bridge slippage in a stretched muscle fibre.

Bundles of glycerol-extracted psoas fibres which were contracted by immersion in a saline containing 15 mM MgATP and 12 micron free Ca++ were subjected to up to 3 stretches (rise time 0.8 msec) each of amplitude 1% Li at intervals of 10 msec. The elastic tension responses to these stretches were all of comparable size and the peak tensions reached during the stretches were in each case followed by a rapid tension decline almost to the tension values before the stretches. This indicates that stretch-induced detachment and reattachment of cross bridges to the actin filament occurred within 10 msec (slippage).


Circadian rhythmicity in phosphorylase activity and glycogen content in the heart muscle of the scorpion, Heteromentrus fulvipes, C.L. Koch.

Maximal activity levels of phosphorylase A and AB at 20.00 h alternate with minimal levels at 08.00 h of the day, while the glycogen content exhibited a reverse trend in the heart of the scorpion, Heterometrus fulvipes.


Changes in the concentration of vasoactive intestinal peptide in intestinal lymph in response to vagal stimulation in the calf.

Stimulation of both vagi caused a significant rise in arterial plasma vasoactive intestinal peptide (VIP) concentration in 3--5-week-old calves with cut splanchnic nerves. This was associated with a pronounced rise in the VIP concentration of intestinal lymph showing that vagal stimulation causes release of VIP from splanchnic viscera.


Effect of methyl ester of aristolic acid from Aristolochia indica Linn. on fertility of female mice.

Methyl ester of aristolic acid, a pure compound isolated from the roots of Aristolochia indica (Linn.), was found to exert 100% abortifacient activity at a single oral dose of 60 mg/kg b. wt when administered on 6th or 7th day of pregnancy; 20 and 25% abortifacient effect were observed at the same dose on day 10 and 12, respectively.


Effects of inflammatory mediators on the glomerular localization of intravenously administered ferritins.

Effects of inflammatory mediators such as serotonin, histamine, and bradykinin upon glomerular localization of i.v. administered ferritins have been investigated. These mediators appear to enhance accumulation of the i.v. injected ferritins in the glomerular capillary walls of rats.


Learned aversion and rearing movement in rats given LiCl, PbCl2 or NaCl.

The effects of an i.p. injection of 0.15 M LiCl resembled closely the effects of another toxic substance, 0.005 M PbCl2, on conditioned aversion to saccharin and rearing movements in male rats. The findings suggest that nonspecific aversive after-effects of a LiCl injection can account fully for prompt effects of LiCl on rearing behavior.


Experimental production of local osteomalacia.

The newly deposited bone which was laid down on necrotic bone in the experimentally produced osteochondral chips in the knee joint of 16 sheep and rabbits remained unmineralized and undermineralized in which respect it resembled osteomalatic bone. Local factors which interfere with the mineralisation of a new covering bone should be considered in the pathogenesis of osteomalacia, in healing of aseptic bone necrosis and fractures, and incorporation and fate of bone transplants.


Cytogenetic effects of delta-9-tetrahydrocannabinol (delta9-THC) on hamster bone marrow.

Single s.c. injections of 10 or 1000 mg/kg of delta9-THC did not induce discernable chromosomal damage but caused significant mitotic inhibition in the bone marrow of Syrian hamsters.


Alkaline phosphatase activity in normal and denervated skeletal muscle.

Changes in the specific activity of alkaline phosphatase in the normal and denervated skeltal muscle have been studied both histochemically as well as biochemically for a maximum period of 8 weeks of its postnatal development. In the normal muscle, a heterogenous population of fibres with respect to the enzyme distribution is observed. Relatively higher levels of enzyme in the denervated muscle and also the proliferation of extrafibillar connective tissue in the diseased muscle show its specific association with the lytic processes.


Effect of amputation and limb regeneration on the pars distalis of the newt, Notophthalmus viridescens.

A study of the pituitary of the newt, Notophthalmus viridescens, during limb regeneration indicated no observable changes in histology or ultrastructure of any of the cells of the pars distalis when compared with the pars distalis of unamputated control newts.


A mechanism of formation of desmosome-like structures between synovial intimal cells.

Desmosomes or desmosome-like structures do not occur between normal synovial cells but such structures do develop between the synovial cells in cases of traumatic arthritis, rheumatoid arthritis and villonodular synovitis. Morphological evidence is presented suggesting that such structures develop as a result of the interaction of fibrin trapped between synovial cells and the plasmamembrane of these cells.


Subcellular localization of noradrenaline and ATP in C1300 mouse neuroblastoma.

A density and velocity gradient centrifugation study of C1300 mouse neuroblastoma showed that ATP is nearly absent from noradrenaline-containing granules and is mainly localized in mitochondria, suggesting that in this tissue ATP is not involved in the storage of noradrenaline.


Effects of exogenous thyroxine on the surface morphology of the developing chick anterior corneal epithelium.

The production of microvilli on the developing chick anterior corneal epithelium is drastically accelerated by the administration of exogenous thyroxine and the effects are seen as early as 2 days after injection. Thiouracil administration slightly retards the production of microvilli though its effects are not so pronounced.


Tissue distribution and nucleic acid binding of chlorambucil-3H in tumor-bearing rats.

In tumour and normal rat tissues prolonged alkylation of DNA and RNA by chlorambucil-3H occurs over periods of 24 h. It is suggested that this may indicate the slow release of an alkylating moiety from an intracellular drug-macromolecule complex.


Effect of vitamin E on post irradiation death in mice.

The 30-day survival after exposure to 800 Rad 60Co gamma radiation has been compared for female mice maintained on vitamin E deficient, vitamin E supplemented or regular lab rations before and/or after irradiation. Pre- or post-irradiation dietary supplementation had no effect on survival; however, injection of alpha-tocopherol immediately after irradiation significantly reduced radiation lethality.


In vitro cytostatic effect of adenine-arabinoside (Ara-A) and cytosine-arabinoside (Ara-C).

Adenine-arabinoside, a new antiviral drug with questionable bone marrow toxicity, inhibits colony formation by myeloid precursor cells in vitro. Compared to cytosine-arabinoside this cytotoxicity is roughly one third.


Iron malabsorption and hypochromic anemia in a case of Turner's syndrome.

Refractory hypochromic anemia was investigated in an adult with Turner's syndrome. Reduced iron absorption, serum iron, and iron incorporation were found in association with increased iron binding capacity and plasma iron turnover. 14 of 57 additional XO subjects were found anemic.


Influence of a mixture of chemical protectors on the lymphoid regeneration of bone marrow and thymus in irradiated mice.

In mouse, the administration of chemical protectors before an irradiation induces a more rapid bone marrow regeneration and an increased lymphoid rebound. In the thymus, the late atrophy is reduced. Separately administrated, the protectors decrease greatly the thymocytes number but have no effect on the marrow population.


Modification of lymphocyte response to phytomitogens by polycations and polyanions.

The stimulating effect on mitogen-induced lymphocyte response by polycationic compounds such as polylysine, DEAE dextran protamine and methylated albumin, is studied at different serum-protein concentrations and mitogen concentrations. It is suggested that the polar interaction between polycationic compounds and glycoproteins are of major importance for reactivity of lymphocytes to mitogens.


Possible influence of prolactin on intestinal hypertrophy in pregnant and lactating rats.

The increase in intestinal weights during lactation, and to a lesser extent during pregnancy, is inhibited by bromocriptin. This suggests that increased prolactin secretion might be responsible for gut hypertrophy during lactation.


Evidence for in vitro release of neurophysin by the rat pineal gland.

Cultured pineal ependymal cells from rat fetuses release into their incubation media immunoreactive neurophysin. The presence of neurophysin was assessed by radioimmunoassay. The culture medium was found to contain 440 pg neurophysin per mg protein.


CNS stimulation effect on the sexual maturation of the female rat.

In the immature rat, CNS stimulants administration to pregnant mare serum gonadotropin (PMSG) primed rats resulted in significant (p less than 0.01) ovarian and uterine hypertrophy when compared to animals treated with PMSG only. Meanwhile precocious puberty was produced by pentylenetetrazol treatment alone. The results of this experiment may indicate that administration of CNS stimulants has a specific action on the release of endogenous gonadotropin.


A quick and modified Winkler-method for measuring O2-consumption of aquatic animals.

A modified procedure for measuring O2-consumption, based on Winkler-method, is described. Instead of KI and HCl (or H2SO4) triphenylmethane-dye leukoberbelinblue I and citric acid are used.


[Effect of clonazepam on neuronal activity in the sensomotor cortex of rat brain].

In tests on flaxedyl immobilized rats the effect of clonazepam on the action produced by gamma-aminobutyric acid, acetylcholine and L-glutamate, delivered microionophoretically to neurons of the sensomotor brain cortex, was investigated. Clonazepam was found to potentiate the inhibiting action of gamma-aminobutyric acid and reduce the exciting effect of acetylcholine and L-glutamate on the spontaneous neuronal activity. The ability of clonazepam, like other tranquilizers of the benzodiazepine series, to augment the sensitivity of the receptive neurons formations to gamma-aminobutyric acid and also influence the ionic permeability of the post-synaptic membrane is suggested.


[Effect of proteolysis inhibitors on serum proteinase activity and its antitryptic activity in postischemic toxemia].

Parenteral administration to animals of the antikallikrein serum containing 200gamma/ml of antibodies to the pancreatic kallikrein (10 ml/kg), ingitryl (1.5 Un/kg) and of tracilol (10 000 Un/kg) exerts in post-ischemic toxemia an inhibiting effect on the protamine-splitting blood serum activity and does not affect the benzoylarginine-paranitroanilide rate of splitting. Changes of the blood serum ability to bind trypsin and manifestation of the protamine-splitting activity during the first 9 hours of observation are of an undulating nature and the changes of these characteristics are reciprocal.


[Effect of estradiol and tocopherol on peroxidation of erythrocyte membrane lipids following ultraviolet irradiation].

The effect of the antioxidants estradiol and tocopherol on the lipid photoperoxidation in the erythrocyte membranes of rats under UV-irradiation was investigated. Both agents are shown to inhibit the release of potassium ions and hemoglobin provoked by UV-rays, estradiol activity being higher as compared to that of tocopherol. High activity of estradiol is due to the fact that this antioxidant does not lose its antiradical properties when its molecules are exposed to UV-irradiation.


[Clinical study of the diuretic preparation moduretic].

In 75 patients with circulatory insufficiency of various degree the diuretic effect of moduretic was studied. In 25 of them besides the potassium and sodium metabolism and in 33 others, with a background of chronic ischemic disease of the heart and hypertensive disease, the state of the hemocoagulation system was investigated in the moduretic medication. In 24 patients with hypertensive disease of the I--IIA stage subject to study was the effect of moduretic on the arterial pressure, with this drug administered by mouth in doses of 3 to 1/2 tablet a day. The drug proved to have a marked duretic effect in patients with different degree of circulatory insufficiency. It increases sodium excretion with urine and retains potassium in the organism, without causing hyperkaliemia. In patients with circulatory insufficiency of the I degree the drug can provoke thrombogenesis and in cases of the IIA, IIB and III degree may be considered a drug of choice. Moduretic brings down the systolic and diastolic pressure in patients with hypertensive disease of the I and II stages.


[Effect of dexamethasone on water-salt metabolism and renal function in healthy humans].

Dexamethazone at a single dose of 2 mg caused in the next 24 hours retention in the organism of a healthy man of a liquid and salts against the background of an abrupt fall of excretion by the kidneys of 17-oxycorticosteroids. Most distinctly this effect manifested itself after an aqueous test (20 ml/kg). A functional test with dexamethazone may be used clinically in assessing the condition of the hormonal link of the water-electrolyte metabolism regulation and renal function.


[Pharmacologic characteristics of triftazin syrup].

The neurotropic activity, toxicity and pharmacokinetics of triftazine in the form of syrup and powder were subjected to a comparative study on albino mice, rats and dogs. Investigations demonstrated that as follows from the tests under study these drugs display an egual depressing activity. Triftazine from the syrup was found to quicker enter the blood and was detected later in it (after 24 hours). The toxicity of peroral triftazine administered to mice and rats is the same for both dosage forms, it being somewhat higher for intraperitoneal triftazine syrup.


[Clearance and transformation of inosine in the body].

In 5 patients with myocardial infarction the ways of the inosine transformation and its clearance rate following injection of this drug in an amount of 200 to 400 mg were studied. After inosine introduction into the organism it is shown to immediately break down to hypoxanthine which makes determination of its half-time body retention period practically impossible. The half-time body retention period for hypoxanthine was about 3 min. The beneficial influence of inosine on the myocardium is apparently due to stimulation of some glycolysis reactions and pentosophosphate shunt at the expense of riboso-1-phosphate.


The aortic sinus vortex.

This paper describes an analytic and a numerical method for the aortic sinus problem. Both methods are based on the dynamics of point vortices, and both exploit a particular conformal mapping from a model aortic sinus to the upper half plane. The analytic description is based on an isolated point vortex in equilibrium with a free stream. This inviscid model is used to study the stability of the aortic sinus vortex and to elucidate the mechanism of aortic valve closure, but it cannot be used to study the formation of the sinus vortex and it gives a somewhat incorrect picture of the flow pattern. These difficulties are overcome by the introduction of a numerical method for the aortic sinus problem with fluid viscosity. We use Chorin's vortex method combined with conformal mapping. The conformal mapping approach gives an explicit formula for the vortex velocities and it resolves the singularities associated with the corners of the domain. This method is then used to study the formation of the sinus vortex and to confirm the predictions of the point vortex model with respect to the role of the vortex in valve closure.


Indirect estimation of physiological distribution functions.

Multicompartment models, such as sums of exponential decays and sums of effects of different ventilation-perfusion ratios, are cast in the form of integrals. Difficulties in obtaining the density function in such an integral from measured values of the integral are attributed to amplification of error in the inversion solution and to the limited number of measurement points. The present approach to control the effect of the error is regularization with the use of a non-negativity constraint on the density function. The answers are sums of the influence or kernel functions of the integral wherever the sum is positive, and zero elsewhere. Such non-negative answers not only ensure that true density functions are obtained but also permit the answer to fall abruptly to zero. For example, a delta function can be much more closely approximated with the non-negativity constraint than without. A rule is developed to choose the value of smoothing parameter so as to minimize an approximate upper bound on the integral of the squared error of the answer. This typically tends to result in some oversmoothing. Functions tested without error and with 2% relative error are as follows: one of the kernel functions (best results); rectangular boxes and delta functions (fair results); and wide boxes (poor results).


Experimental autoimmune myasthenia gravis: the rabbit as an animal model.

Rabbits immunized with acetylcholine (ACh) receptor purified from Torpedo electroplax were studied after they were paralyzed and exhibiting respiratory distress. Intercostal muscles from the immunized rabbits had reduced amplitude of miniature end-plate potentials (MEPPs) as well as reduced junctional ACh sensitivity. However, a large percentage of the cells studied (40%), which exhibited no MEPPs, had junctional ACh sensitivity that was 45% of normal. It is suggested that, unlike myasthenic patients, such paralyzed and dying rabbits may have, in addition to postsynaptic damage, neurons that are damaged or separated from the muscle. Serums from six paralyzed rabbits inhibited binding of [3H]ACh and [125I]alpha-bungarotoxin to Torpedo ACh-receptor to varying degrees: 18.8--95.5% and 42.5--86.1%, respectively. Immune serums also inhibited the carbamylcholine-induced 22Na efflux from Torpedo microsacs, but neither they nor the immunoglobulins inhibited neuromuscular transmission when applied to intercostal muscles from a control rabbit. The data suggest that homology between receptor and antibody is important for inhibition of ACh binding to its receptor and its function. The role of complement in pathogenesis is also discussed, and so is the relationship of the ACh-receptor to its ionic channel.


Atherosclerosis and aging.

Atherosclerosis reflects interactions among several independent, age-related alterations of both structure and metabolism. While intrinsic aging appears to play a role, particularly in relation to the biology of arterial wall cells, atherosclerosis can best be considered an age-related disease that can be profoundly influenced by both environmental and genetic factors, rather than simply the inevitable consequence of intrinsic aging. Since intrinsic aging processes are as yet poorly understood and genetic manipulation is still only a theoretical possibility, efforts should be directed at understanding and reversing the environmental risk factors that act over time and accelerate atherosclerosis throughout the life span.


Senile dementia.

The Alzheimer type of senile dementia (SDAT) accounts for more than 50% of such cases, and is a very common disorder as well as being very costly in emotional, economic, and medical terms. It carries a markedly shortened life expectancy. Gray-to-white-matter ratios change and the brain shrinks slightly in the course of normal aging, but SDAT brains may not be significantly more atrophic than are normal controls. Cortical neurons are diminished in number in normal aging, but counts from frontal and midtemporal regions of SDAT specimens are not different from age-matched controls. There is loss of dendrites and of dendritic spines in both normal and abnormal aged specimens. Neurofibrillary tangles are made up of paired helical filaments that appear to be chemically and immunologically related to normal neurofibers. Neuritic plaques are made up of an amyloid core surrounded by abnormal axonal endings. Both plaques and tangles are to be correlated with the presence of senile dementia. There is some evidence for an infectious etiology of SDAT. Choline acetyltransferase is markedly reduced in cortical tissue of these patients, but the muscarinic receptors of acetylcholine are normal.


Age-associated pathological changes in male rats.

The selection of rats for aging research and the interpretation of experimental results require knowledge of spontaneous age-associated lesions in specific stocks and strains. We have compared selected age-associated pathological changes, as determined by postmortem examination of 113 outbred Crl:CD(SD)BR male retired breeder rats 12--39 months old, with those reported by others in a group of 122 virgin male 12- to 33-month-old F344 rats, an inbred strain from the same commercial source as the outbred rats. Numerous degenerative, inflammatory, and neoplastic lesions occurred in both groups. The wide prevalence and severity of many of the lesions suggest that they could be the source of significant variability in the results of specific aging studies, by their direct and indirect effect(s) on target organs. The prevalence of spontaneous lesions should be defined for each stock or strain intended for use in aging research by postmortem examination of representative groups of animals at various ages. Antemortem diagnostic screening of old rats may also be useful in culling animals bearing lesions that could add to the variability of experimental results, or in selecting for specific lesions that are of research interest themselves.


Homologous insemination.

Between July 1, 1969, and October 31, 1977, 619 patients were evaluated for infertility. Homologous insemination (AIH) was employed in 53 patients, many of whom had other contributory causes of infertility. There have been 14 single pregnancies in 11 women, including 4 spontaneous abortions, 1 ectopic pregnancy, 8 term deliveries, and 1 pregnancy in progress. Twenty women are currently under treatment. Another 16 women had unsuccessful AIH prior to beginning donor insemination. Seven subsequently conceived with donor semen. Specific indications for AIH and the recommended technique are discussed in detail as well as the occurrence and management of concomitant infertility factors in this study group. It is concluded that AIH does have a role in the management of certain infertile couples.


Clinical experience with the copper 7 intrauterine device.

This paper reports further observations on our previous study of 203 Copper 7 intrauterine insertions performed in 199 women. There have now been accumulated 3799 woman-months of use. At least a 2-year period of observation has been attained from first insertion until these data were analyzed. The Copper 7 intrauterine device (IUD) continues to be an acceptable contraceptive method with regard to effectiveness, continuation, and lack of serious complications. Those patients who elected to have their copper 7 IUDs removed for planned pregnancy were also analyzed with regard to fertility capacity. Possible complications with the need to change the copper 7 IUD and risk of prolonged use were not verified. There was a decrease in contraceptive effectiveness after 12 more months' use.


Preliminary report on the use of the combined multiload contraceptive intrauterine device (ML Cu-250).

The multiload contraceptive intrauterine device (IUD) (ML Cu-250) is made of polyethylene and contains copper wire which is wrapped around the stem, providing 250 sq mm of exposed copper surface area. The IUD was inserted in 294 women comprising 1884 women-months of use. Four pregnancies and three expulsions occurred. In 13 instances the ML Cu-250 IUD was removed for medical reasons (side effects). The net cumulative pregnancy rate for a 12-month period after insertion was 3.9% and the expulsion rate was 1.6%; the medical removal rate was 8.2%. No perforations or tubal pregnancies occurred. Our results with the ML Cu-250 was compared with our previous experience with other IUDs. It seems that the comparatively low pregnancy, expulsion, and medical removal rates render the ML Cu-250 a good device for clinical use.


Microscopic vasoepididymostomy: specific microanastomosis to the epididymal tubule.

A new microscopic technique for vasoepididymostomy is described. Conventional approaches to epididymal obstruction rely on the formation of a fistulous tract after the walls of the vas deferens are grossly sutured to the outer tunic of the epididymis; such methods have a low success rate. With a direct and accurate end-to-end anastomosis of the inner lumen of the vas deferens specifically to the epididymal tubule there is a greater likelihood of normal patency. Furthermore, such an anastomosis can be performed at the lowest possible level of the epididymis, allowing a greater opportunity for sperm maturation.


Infertility in men with retrograde ejaculation: the action of urine on sperm motility, and a simple method for achieving antegrade ejaculation.

The profound effect of urine on sperm motility is demonstrated. Two patients with retrograde ejaculation and infertility who achieved antegrade passage of semen by ejaculation on a full bladder are described. The use of this method of management in patients with infertility due to retrograde ejaculation is discussed.


A possible mechanism for the detrimental effect of varicocele on testicular function in man.

Seminiferous epithelium histology, Leydig cell density, and in vitro testosterone synthesis were quantitated in bilateral testicular biopsies from men with varying degrees of unilateral or bilateral varicoceles. Results were correlated with plasma levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and testosterone (T), as well as with semen quality. In patients with bilateral varicoceles, spermatogenesis, Leydig cell density, plasma T levels, and in vitro T synthesis were significantly lower than in patients with unilateral varicoceles. Varicoceles appeared to affect maximally the latest stages of spermatogenesis. A negative correlation between FSH and LH levels and spermatogenesis was observed; however, a dissociation between the two gonadotropins occurred when spermatogenesis declined. Plasma T levels were within the normal range in all patients. The T:LH ratio was significantly correlated with spermatogenesis and sperm motility. Leydig cell density was abnormally low in oligospermic patients, and it was significantly correlated with in vitro T synthesis, spermatogenesis, sperm motility, and semen volume. Sperm count and motility were significantly correlated in this group of patients, suggesting a common pathophysiology for the effect of varicocele on spermatogenesis and sperm motility. This common pathophysiology appears to be disturbed Leydig cell function resulting in decreased testicular androgen production, in turn causing inadequate spermatogenesis and epididymal function.


The effect of temperature on the velocity of human spermatozoa as measured by time-lapse photography.

A method of time-lapse photography for the assessment of sperm velocity is presented. The intersampling variation was not significant, nor was the effect of dilution. Sperm velocity increased with temperature within the range 25 degrees C to 40 degrees C. The possible clinical use of the technique is discussed.


[Comparative characteristics of hypothalamo-cortical and reticulo-cortical evoked potentials].

In anesthetized and immobilized cats, single shock stimulation of the postero-lateral hypothalamus (Hp) and mesencephalic RF elicited positive-negative evoked potentials in gyrus sigm. anterior (GSA) with a latency of 0.8--2.5 msec and 1.0--3.0 msec for hypothalamo-cortical (HC) and reticulo-cortical (RC) EPs respectively. In gyr. suprasylv. ant. (GSSA) HC and RC EPS with initial negative wave were recorded with a latency of 1.0--3.5 and 0.5--4.0 msec resp. The HC and RC EPs followed frequency of stimulation up to 40/sec and were capable of obvious postetanic potentiation. Paired stimuli revealed that the main positive wave of HC and RC EPs appeared in GSA at an interval of 5--10 msec. In GSSA the surface negative potential appeared at an interval of 10 msec. Full recovery occurred at an interval of 150--200 msec. A biphasic change of excitability of cortical neurons occurred in response to conditioning stimuli. Comparative study of recovery cycles of HC EP to paired stimuli of Hp or mesencephalic RF in one case and of conditioning stimulation of the RF and testing stimulation of Hp in other, suggest predominance of "convergent" cortical neurons with polysensory input from Hp and RF. The characteristics of functional organization of hypothalamo-cortical system of integration are discussed.


[Effect of thyroxine on the hypothalamic concentration of biogenic amines in rats of different ages].

Male rats of 2.0--2.5 and 8--12 months old received intraperitoneally thyroxin T4 (2 mcg/100 g daily during 8 days) or placebo. T4 significantly increased the noradrenaline concentration in the young rats' hypothalamus. No difference was revealed in concentrations of dophamine, 5--OIAA, or serotonin in either group. The data obtained are discussed from the standpoint of a possible mechanism of changing thresholds for the homeostatic inhibition in the hypothalamo-hypophyseal-thyroid system with ageing.


[Elaboration of a conditioned alimentary reflex and protein turnover in hippocampal neurons and neuroglia].

A single session of the food conditioning in rats entailed an increase of labelled phenylalanine incorporation into the proteins of the nuclei and, particularly, of the cytoplasm of CA3 hippocampal neurons. In the trained animals, as compared with active control group, a session repeated in 3 days returned the turnover of neuronal proteins to the control level, while the same session in 6 days of decreased the protein turnover below the control level. No changes occurred in the course of the experiment in the perineuronal neuroglial cells. Predominant involvement of neuronal protein metabolism is outlined in the metabolic reconstruction within the whole neuron-neuroglia unit in the course of conditioning.


[Reactions of neurons of the acoustic area of the cerebellar vermis in cats to binaural presentation of tone signals].

In anesthetized and immobilized cats, interaural time differences at dichotic stimulation with pure tone were characteristic for maximal activity of each neuron of the cerebellar vermis lobuli VI and VII. The responses of neurons to interaural time differences were the best both at more than 10 dB above the threshold intensity and up to 2.0--2.5 kHz frequency. The maximal change of activity in specific range of time delays when fo above 4 kHz occurred irrespective of the spectrum of tone signal. Two types of neurons were revealed: responding 1) at time delays different from 0, and 2) when time delay was 0. This suggests that each of these types of neurons may play a different part in organization of elements of the localizing behaviour.


[Analysis of the regulatory influence of effector cells on 3H-catecholamine synthesis in an adrenergic neuron].

In isolated organs of the white rats activation of noradrenaline-H3 and dophamine-H3 synthesis during action of the alpha-adrenoblocking agent phentolamine (1.10(-6) M) and inhibition of the amines synthesis under influence of the alpha-adrenoreceptor activator mezaton (1.10(-5) M) were due to a release from cells-effectors of respective humoral factors and to the latters' effect upon the processes of amine formation in the adrenergic neuron. Formation of the humoral factors altering the rate of catecholamines-H3 synthesis is associated with activation of the protein synthesis in cells-effectors and occurs during change of the functional state (excitation or blockade) of the post-synaptic adrenoreceptors. The processes occurring at the time in the adrenergic neuron, are not correlated with protein formation. The possibility of existence of a common mechanism for feed-back transsynaptic regulation of synthesis and neuronal uptake of noradrenaline via adrenoreceptors of cells-effectors by means of changing the intensity of thyrosin and noradrenaline transport into the neuron is discussed.


[Noradrenaline uptake by the isolated hearts of rats adapted and dysadapted to hypoxia].

Disrupted training of rats for hypoxia during 3 weeks at the normal atmospheric pressure increases their resistance to the profound testing hypoxia. Stability of the noradrenaline (NA) level in conditions of isolated heart perfusion, a decrease in the NA neuronal uptake, and an increasing inhibitory effect of the exogenous NA on the synthesis of dioxyphenylalanine indicate an ample functional reserve in the adrenergic structures of these animals. A longer training (5 weeks) diminishing the resistance of rats to the testing hypoxic influence and entails phenomena of heart deadaptation at the level of its adrenergic structures.


[Organization of the electrical activity of different groups of muscles in rats during locomotion].

The EMG was recorded from the knee synergical group of muscle in the phase of leg move during locomotion in rats. The correlation analysis of the EMG epochs and the pauses in muscular activity respective to the moments of onset and termination of the leg move phase divided it into three independent elements: rise of the leg, maintaining of the leg over support, and stepping on the support. This suggests possible existence of three independent intraspinal subprograms which in different ways organize the work of a single group of muscles during each element of seemingly such a simple movement as the leg move during stepping.


[Strength characteristics and work capacity of the skeletal muscles of dogs at different age periods].

The gastrocnemius and the tibialis anterior muscles revealed an increase in the optimal work and optimal load with ageing reaching maximal values at the grown-up period. Development of these parameters differs in rabbits and dogs. The formers develop maximal values of these parameters for m. gastrocnemius at the period of realization of the standing pose while in dogs these values go on increasing till the grown-up state. This difference is due dissimilarity of the natural ecological courses of development of the motor functions in these animals.


[Changes in the adrenal cortex during adaptation to different regimes of motor activity].

The hypertrophy of the adrenal glands was higher in the rats adapted to long-lasting exercises of moderate and mild intensities. Ultrastructural analysis showed that there were more mitochondria and vesicular cristae as well as the elements of cytoplasmatic reticulum and lipid droplets in the cells of adrenal cortex of the adapted rats. The data obtained suggest two types of adaptational changes in the adrenal cortex: 1) pronounced hypertrophy with low spontaneous functional activity and increased content of cytochrome a--a3; 2) less pronounced hypertrophy with higher content of corticosterone and lower content of cytochrome a--a3 in adrenals.


[Role of CO2 fixation in increasing the body's resistance to acute hypoxia].

In rats, the phenomenon of considerable increase in resistance to acute hypoxia observed after 2-hour stay under conditions of gradually increasing concentration of CO2, decreasing concentration of O2, ANd external cooling at 2--3 degrees seems to be based mainly on changes in concentration of CO2 (ACCORDINGLY, PCO2 and other forms of CO2 in the blood). The high resistance to acute hypoxia develops as well after subcutaneous or i.v. administration of 1.0 ml of water solution (169.2 mg/200 g) NaHCO2, (NH4)2SO4, MgSO4, MnSO4, and ZnSO4 (in proportion: 35 : 5 : 2 : 0.15 : 0.15, resp.) or after 1-hour effect of increased hypercapnia and hypoxia without cooling.


[Comparative characteristics of mechanisms regulating tubocurarine and cold tremor].

Tubocurarine tremor and shivering show identical topography in different muscle groups and identical frequency patterns of the EMG. Electrical stimulation of the medial preoptic area inhibits tubocurarine tremor and shivering. Reflexes from peripheral thermoreceptors are less important in regulating the tubocurarine tremor as compared with the shivering regulation. The data obtained show that tubocurarine tremor is a centrally induced analog of shivering.


[A simple method for the simultaneous analysis of r-T3 and 33'-T2 by mass fragmentography using GC-MS. (Part II. Mass fragmentographic identification of 33'-T2 and r-T3 in biological fluids) (author's transl)].

In view of the previous report of the possibility of 33'-T2 and r-T3 measurements, the identification of these iodinated compounds was performed by mass fragmentography. The peaks at m/e 218, 624 (33'-T2) and m/e 218, 750 (r-T3) were applied to establish the precise qualitative evaluation of unknown peaks. The base peak at m/e 218 (thyroid analogues) was applied to avail itself of simultaneous multiple ion analyses by GC-MS. The following results were obtained. 1) Mass fragmentography makes possible the simultaneous measurements of 33'-T2, r-T3 and other thyroid analogues with 1 ml of serum and urine samples obtained from rats or human beings. 2) This method is very convenient for extracting the compounds from biological fluids, and the procedure can be carried out easily in a short time. The specificity of this method surpasses and cannot be compared to any other existing quantitative methods.


[The effect of enzymes on progesterone-receptor binding and chromatin binding of the complex in the estrogen-primed rabbit uterus (author's transl)].

The present study was designed to determine the characteristics of the progesterone receptor and chromatin binding site ("acceptor") of the progesterone-receptor complex in the rabbit uterus. The uterus was obtained from an estrogen-primed immature female rabbit. The binding of progesterone to the uterine receptor was examined in vitro. The progesterone-receptor binding was reduced only by proteases, and phosphorus moiety may not be related for progesterone-receptor binding. The effects of enzymes on the acceptor of the chromatin were investigated. The progesterone-receptor complex was bound to the dehistonized chromatin. The dehistonized chromatins, which were pretreated with enzymes at 4 degrees C or 37 degrees C for 30 minutes, were incubated with 3H-progesterone prelabeled uterine cytosol at 4 degrees C for 30 minutes, and the radioactivity in the chromatin pellet was counted. Proteases effectively decreased the receptor binding capacity to the dehistonized chromatin in the following order: pronase greater than trypsin greater than papain greater alpha-chymotrypsin. DNAse moderately and phospholipase A slightly decreased its binding capacity. The results may indicate that the acceptor site of the progesterone receptor is nonhistone protein over DNA of chromatin and may contain phosphorus moiety.


[A study on the pathophysiology and diagnosis of adrenocortical insufficiency using angiotensin II blocker (author's transl)].

Angiotensin II analogue (AIIA), 1-sarcosine, 8-isoleucine angiotensin II (Sar1, Ile8-AII), was given in a graded dose to patients with adrenal hypofunction of various etiologies, and the blood pressure response to AIIA was observed to investigate the role of the renin-angiotensin system for the maintenance of blood pressure in the state of adrenal insufficiency. An agonistic pressor response to AIIA was observed in the control subjects without adrenal hypofunction. In contrast with this, patients with Addison's disease showed a blood pressure fall to AIIA. When the test was repeated on the same patients after hydrocortisone replacement, these patients showed a neutral or pressor response. Three patients with adrenalectomy and hydrocortisone replacement showed a pressor response to AIIA in a supine position. When these patients were tilted, fall in blood pressure to AIIA was observed in two of them who had been on a regular diet, whereas one patient who had been on a high sodium diet showed no fall in blood pressure with this procedure. We concluded that the renin-angiotensin system plays an important role in the maintenance of normal or subnormal blood pressure in Addison's disease and in the postural change of adrenalectomized patients on hydrocortisone and regular salt intake. The response of blood pressure to AIIA may be a clue for the diagnosis of Addison's disease and the evaluation of the adequacy of replacement therapy with regard to these patients.


[The effect of hydrocortisone and calcium ion on the catecholamine release from the adrenal medullary slice (author's transl)].

A large dose of hydrocortisone has a protective effect in hemorrhagic and endotoxin shock. In recent years there has been considerable discussion suggesting that the release of catecholamines may be the first step in the chain of events in shock. On the other hand, a large dose of hydrocortisone may inhibit the release of catecholamines, and this effect of hydrocortisone may be attributed to the inhibition of a calcium ion influx across the cell membrane. The present experiments were performed in order to determine whether acetylcholine-and histamine-induced catecholamine release is effected by hydrocortisone and calcium ion in bovine adrenal medullary slices or not. The results were as follows: 1. Acetylcholine or histamine increased catecholamine release from the adrenal medullary slices. 2. The stimulatory effect of acetylcholine or histamine was inhibited by the addition of hydrocortisone. 3. The inhibitory effect of hydrocortisone was proportionally reversed by the increasing amount of added calcium ion in the media. From the above results, it is suggested that hydrocortisone inhibits catecholamine release from the adrenal medullary slices and that the effect of hydrocortisone is due to a blocking of the transfer of calcium ion into the cells.


[A statistical survey of autopsy cases of malignant goiter (author's transl)].

A total of 747 cases of malignant neoplasms of the thyroid reported in the "Annual of the Pathological Autopsy Cases in Japan" during the past 5 years (1969 approximately 1973) were reviewed and statistically analysed. Histological diagnosis in this series were papillary carcinoma in 323 cases (51.8%), follicular carcinoma in 143 cases (22.9%) and anaplastic carcinoma in 102 cases (16.3%). The average age of patients at autopsy was 58 years for papillary carcinoma cases, 62.4 years for follicular carcinoma cases and 61.7 years for anaplastic carcinoma cases. The incidence of metastatsis to lymph nodes and to organs was 47.3% and 51.5%, respectively in cases of follicular carcinoma and 73.3% and 98.0%, respectively in cases of anaplastic carcinoma. Autopsy revealed an otherwise unnoticed thyroid cancer in 457 cases, which accounted for 61.2% of the entire autopsy cases of malignancy of this organ. A so-called multiple cancer, i.e. the concurrence of carcinomas in the thyroid gland and other organs, was seen in 239 cases (32.3%).


[Mycosis fungoides--the practionner confronted with the nosological, diagnostic and prognostic problems of epidermotrophic lymphomas (author's transl)].

The authors have studied 39 cases of mycosis fungoides in the last 3 years. The confrontation between clinical and histological data remains the best means of diagnosis and prognosis. The classical classification into three clinical forms must be maintained; laboratory investigations do not yet supply practical information for prognosis and therapy. At present, the prognosis cannot be established otherwise than on clinical grounds; a pragmatic staging method is needed.


[Woringer and Kolopp's disease (author's transl)].

Woringer and Kolopp's disease is a rare skin disease. Erythemato-squamous, slightly infiltrated lesions with round-shaped islets of normal skin are the clinical hall-marks of the disease. The histological picture is highly specific: a dense epidermal infiltrate disrupts the stratum spinosum, contrasting with a spared dermis. Three different aspects of the disease have been reported: a localized benign type as in Woringer and Kolopp's patient; a disseminated lethal type without visceral involvement and without preexisting lesions, and a disseminated lethal type in which lesions appear on erythematous patches clinically and histologically similar to "parapsoriasis en plaques". It is the opinion of the authors that the third type is not Woringer and Kolopp's disease but an extremely epidermotropic variant of mycosis fungoides. The two other types seem to be variants of the same disease. Several hypotheses about the nature of that disorder are discussed. Most authors think that Woringer and Kolopp's disease is a cutaneous lymphoma because of clinical, histological and ultrastructural similarities with mycosis fungoides. We are presenting evidence favoring the hypothesis of a Merkel cell proliferative disease.


Experience with etomidate: a hypnotic for induction of anaesthesia.

The authors report on their experience with combined etomidate anaesthesia in 500 varied surgical procedures including thoracic and neurosurgery. Specific indications for the new short-term hypnotic etomidate are dealt with, including anaesthesia in poor-risk patients, conditions of shock, spastic bronchitis, and bronchial asthma. When used for the induction of neuroleptic analgesia, etomidate offers certain benefits. Since it induces few side-effects, it is suggested that this preparation is the drug of choice for ambulatory anesthesia, Casesarean section, etc.


Effect of Vaporub and petrolatum on frequency and amplitude of breathing in children with acute bronchitis.

Transthoracic impedance pneumographs from sixty children suffering from acute bronchitis were studied to investigate the effect of Vaporub on the amplitude and frequency of breathing. The experimental technique consisted of an observation period of 70 minutes after a 3-minute treatment with Vaporub or petrolatum as a control. Before the treatment, after an adaptation period of 20 minutes, the pneumogram was recorded for 10 minutes, after the treatment pneumograms were recorded for 70 minutes. The pneumograph data demonstrated an early increase in amplitude up to 33.0%, with subsequent return to slightly above control for the remaining test period. Such an increase was not observed in the Petrolatum-treated group. Breathing frequency demonstrated a progressive decrease to 19.4% of the pre-treatment value at the end of the test period, while the Petrolatum controls were between + 3.6 to - 4.2% difference. It is concluded that Vaporub treatment results in a change in breathing patterns. This, together with the clinical observation of the children suggests a condition of 'easier breathing'.


Effect of Vaporub and petrolatum on skin and rectal temperature in children with acute bronchitis.

Fifty-six children, suffering from acute bronchitis were studied. Skin temperature and rectal temperature were simultaneously recorded over a period of 90 minutes after 3-minute rub therapy on chest and back with either Vaporub or its base Petrolatum. A statistically significant increase in skin temperature as compared to the pre-treatment was observed; with Vaporub, however, the increase was 1.1 degrees C on average at the highest point of a large plateau reaching from 30 to 90 minutes after the treatment. Rubbing Petrolatum alone showed 0.2 degrees C on average on the top of the temperature plateau. Rectal temperature did not show significant changes with either therapy. On comparing temperature data of the same type in healthy children, the time course of the temperature elevation (which also was observed in healthy children after Vaporub treatment), was different from that of bronchitic children. In the bronchitic children the temperature rise was still 0.9 degrees C 60 minutes after treatment. In the healthy children after 60 minutes, the temperature elevation was only 0.4 degrees C above the pre-treatment value.


Effect of Vaporub on the restlessness of children with acute bronchitis.

In this study pneumographs of children with acute bronchitis treated with Vicks Vaporub or Petrolatum were used. Movement artifacts were used as a measure of the so-called "restlessness" of the children. The experimental schedule consisted of a 10-minute phase of recording before a 3-minute treatment with Vaporub or Petrolatum, followed by a 70-minute observation period, during which time pneumograms were also recorded. Thirty-four Vaporub-treated children showed an increase in periods without movement artifacts of up to 213.8%, the Petrolatum controls, twenty-six children, up to 62.4% as compared to the corresponding pre-treatment values. It is concluded that Vaporub is effective in decreasing restlessness in children suffering from acute bronchitis. This effect is quite marked and cannot be due solely to psychological effects of the rub therapy, or to effects of petrolatum without aromatics.


Trasidrex (a fixed combination of slow Trasicor 16o mg and Navidrex 0.25mg) in the treatment of hypertension: a multicentre clinical trial in general practice.

Sixty-two patients with hypertension who were treated with a free combination of Slow Trasicor or Trasicor and Navidrex K were transferred to a fixed combination tablet, Trasidrex (slow oxprenolol 160 mg + cyclopenthiazide 0.25 mg). Blood pressure control was marginally improved and there was no  increase in side-effects.


Effect of thyroidectomy on intracellular amount and distribution of exchangeable Ca2+ in isolated rat liver cells.

The effect of thyroidectomy and replacement therapy on intracellular calcium was studied in isolated rat liver cells. The cells were first loaded with 45Ca and the efflux of isotope followed for 4 h. The cells maintained their viability during this period as judged from staining with trypan blue and rate of respiration. Two different time constants could be resolved by the peeling method. The experiments showed that thyroidectomy markedly reduced the pool of calcium with the slowest turnover while the other pool remained unchanged. Administration of triiodothyronine (T3) to the thyroidectomized animals 48 h before the experiment normalized the rate of respiration but did not restore the slow turnover pool of calcium.


Biosynthesis of labelled anti-müllerian hormone by fetal testes: evidence for the glycoprotein nature of the hormone and for its disulfide-bonded structure.

Tritiated fucose incorporated into proteins released by fetal calf tests into incubation medium proved to be a marker for anti-müllerian hormone (AMH) once non-specific glycoproteins had been eliminated by partial purification. When partially purified incubation medium from fetal calf teste s was fractionated by gel filtration, sucrose density gradient sedimentation or preparative electrofocusing, a single radioactive protein peak co-purified with anti-müllerian activity. Partially purified medium from bull testes--which are devoid of anti-müllerian activity--has a much lower fucose content than that derived from fetal testes. Antisera directed against 'fetal'--but not 'bull'--partially purified incubation medium, and capable of blocking anti-müllerian activity, precipitated the radioactive protein peak. The molecular weight of labelled AMH was 215,000 when determined by gel filtration and 124,000 when determined by density gradient sedimentation. By SDS-PAGE the molecular weight of labelled AMH was 123,000 and dissociation into a 72,000 subunit was demonstrated under conditions which reduce disulfide bonds.


Characteristics of calcitonin degradation in vitro produced by incubation with procine thyroid tissue.

The possibility of calcitonin (CT) degradation by thyroid tissue in vitro was investigated. Tissue slices or a thyroid supernatant solution was incubated with 131I-labeled porcine CT for 30--60 min at 37 degrees C. Calcitonin degradation and deiodination were determined by chromatoelectrophoresis and/or quso adsorption. Degradation of ]131I]CT occurred rapidly in the presence of 50--200 mg porcine thyroid tissues; however, little or no hormone deiodination was observed. Porcine liver, kidney and lung slices also degraded [131I]CT. The data indicate that a nonspecific proteolytic enzyme, capable of rapid CT degradation, is liberated from thyroid tissue slices in vitro. This substance, which is found in the cytosol fraction of thyroid tissue, is heat labile, has a molecular weight between 25,000 and 100,000, displays an acidic pH maximum for CT degradation and is inhibited by sulfhydryl enzyme inhibitors. The liberation of this substance from thyroid slices may explain the relative unresponsiveness of CT secretion observed in previous in vitro studies.


Alleviation of forgetting in preweanling rats.

Three experiments tested the learning and retention of neonatal rats (7, 9, and 12 days of age) with a nondirectional active avoidance task, using a vibrotactile conditioned stimulus. The hypothesis was that the substantial deficit of these animals in 24-hr retention is due, at least in part, to a deficiency in memory retrieval. In Experiment I, a reactivation treatment was found to alleviate the forgetting over the 24-hr period for 12-day olds although having somewhat lesser effect for animals 9 days of age. The reactivation treatment seemed ineffective for rats 7 days of age. Experiments II and III confirmed the reliability of the reactivation effects with 9- and 12-day olds, while adding further control conditions and providing new information concerning the ontogenesis of latent inhibition.


Behavioral persistence following switchovers between environmental enrichment and impoverishment in mice.

Weanling mice were reared in environmental enrichment and/or impoverishment conditions for 2 months. In the 1st experiment, mice were switched from 1 environment into the other after 1 month, and maintained in the opposite environment for 2 or 4 weeks. Switched and nonswitched groups were compared to establish whether the effects of the initial environmental exposure would persist through later opposite environmental experiences. The performance of switched groups tended to differ from that of all nonswitched groups: little behavioral persistence was found. In the 2nd experiment, mice were switched every 7, 14, or 28 days over a 2-month period. These procedures yielded several types of behavioral outcomes; however, no behavioral persistence was evidenced. The data indicate that early life experiences in a particular level of environmental complexity need not permanently modify behavior.


Vocalization in the cat and kitten.

Vocal responses of kittens and mature cats were recorded in a variety of standard behavioral situations. Sonographic analysis of these responses showed similarities of responses obtained repeatedly from different cats within each recording situation. Marked differences in response patterns were noted in different recording situations. The kitten and cat vocal repertoires thus include a variety of specific responses to particular motivational or behavioral circumstances.


Self-recognition and stimulus preference in autistic children.

A common notion regarding autistic children is that they do not show self-recognition. In this study, 7 autistic children were compared to a group of normal infants at the age of self-recognition. Using a videotape "mirror image" and an objective self-recognition criterion, we observed that 6 of the 7 autistic children exhibited self-recognition. In a 2-choice preference situation, autistic children tended to prefer the more predictable mirror image to a previously taped film of self.


Sensory regulation of maternal behavior in rats: effects of pup age.

Maternal behavior (retrieving, crouching, and licking) was induced in Sprague-Dawley virgin female rats by constant exposure to pups aged 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, or 15-16 days. The incidence of spontaneous components of maternal behavior, notably retrieving, was greater towards pups 1-8 days of age than towards older pups, whereas the occurrence of cannibalism did not differ as a function of pup age. With pups 1-2 through 13-14 days, the latency to onset of full maternal behavior was shortest with 1-2-day-old pups (2-day median) and longest with 13-14-day-old pups (7-day median). Females exposed to pups aged 3-4 through 11-12 days did not differ significantly in their latencies, the medians of which ranged from 4.0 to 5.5 days. Only 1 female out of 8 exposed to pups aged 15-16 days became fully maternal, but 5 more displayed components of maternal responsiveness. The optimal nature of neonates and the general attractiveness of a wider range of pup ages as stimuli for the elicitation of maternal behavior in rats, as well as comparisons to mice and hamsters, were discussed.


Comparative studies of the ultrasonic calls of infant murid rodents.

The ultrasonic calls of 10 species of murid rodents including 3 strains of house mice are described and the significance of interspecific similarities and differences is discussed. The calls of newborn murid rodents may be characterized by their gradual onset and cessation, their comparative lack of amplitude and frequency modulation, and, often, by the presence of only 1 frequency component. These common acoustic characteristics may be important in eliciting and/or maintaining various aspects of maternal behavior, both in and out of the nest.