Antiestrogen-induced remissions in stage IV breast cancer.

Tamoxifen (NSC-180973, ICI-46474), an antiestrogen, was administered to 39 women with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Patients were selected as eligible for endocrine ablative treatment and with disease not so aggressive as to jeopardize further treatment in case the experimental drug failed. Objective remission was obtained in 19 patients (49%) with a mean duration of 11+ months and ten patients are still in remission. No progression was seen in seven patients (18%) lasting 13+ months with only one patient in relapse. Thirteen patients (33%) have failed. Objective remission was obtained in two premenopausal women even though menstrual cycles were not suppressed; bilateral oophorectomy in one of these patients induced a second remission after relapse from tamoxifen. Objective remissions were obtained in two women with proven complete hypophysectomy a direct action of antiestrogens at the tumor level. Positive estrogen receptors were suggestive of being a good predictor of response. Menopausal status and dominant site of metastasis did not affect the response to tamoxifen in this small series. Tamoxifen did not alter prolactin secretion, and side effects from the drug were usually mild and transient in nature. We conclude that tamoxifen is an effective antitumor agent in patients with stage IV breast cancer; further studies are necessary to determine whether it will equal the therapeutic effect of oophorectomy, adrenalectomy, and hypophysectomy.


Combination chemotherapy in vitro with cis-dichlorodiammineplatinum(II).

Cis-dichlorodiammineplatinum(II) (DDP) was paired with 11 other chemotherapeutic drugs in a search for possible synergistic pairs. Cell lethality was investigated by the colony-formation technique utilizing a long-term culture of human lymphoma cells. Synergistic effects were noted for pair combinations with all alkylating agents, bleomycin, adriamycin, camptothecin, and cytosine arabinoside. Additive effects were recorded for combinations with prednisolone and VP-16-213, while DDP reduced the capacity of cells to absorb sublethal damage induced by alkylating agents.


5-Fluorouracil (5-FU), methyl-CCNU, and vincristine in the treatment of advanced colorectal cancer: phase II study utilizing weekly 5-FU.

We report a phase II trial of 5-fluorouracil (5-FU), methyl-CCNU, and vincristine (FMV) combination chemotherapy in advanced colorectal carcinoma. Ten of 25 patients (40%) achieved an objective tumor regression after treatment with FMV chemotherapy. The main toxicities of FMV were hematologic and gastrointestinal. 5-FU was administered in a weekly rather than a loading-dose schedule which allowed for sensitive adjustment of drug dosages according to hematologic toxicity; only 16% of the patients (four of 25) had a wbc count less than 2000 cells/mm3. FMV is significantly more active than 5-FU alone in the treatment of advanced colorectal cancer; however this regimen does not significantly improve survival in responding patients.


Inhibition of growth and regression of a transplantable rat chondrosarcoma by three retinoids.

An aromatic analog of retinoic acid, all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid (Ro 10-1670), its ethyl esther (Ro 10-9359), and ethyl amide (Ro 11-1430) have been shown to inhibit the growth of a transplantable rat chondrosarcoma. The inhibition observed occurred over a range of tolerated doses. At the higher tolerated dose levels, significant regressions of already established tumors were observed. All three compounds were active when administered ip for 2 or 4 weeks. The ethyl ester, Ro 10-9359, and the etyl amide, Ro 11-1430, were also active when administered for 4 weeks as dietary admixes. In the latter experiments, both compounds were equally effective at tolerated doses, but Ro 11-1430 was less toxic than Ro 10-9359 at higher doses.


Current overview of EORTC clinical trials with tamoxifen.

Based upon concepts derived from estrogen receptor studies, a phase II exploratory trial was conducted where tamoxifen (NSC-180973) was administered concomitantly with cytotoxic chemotherapy in postmenopausal patients with advanced breast cancer. Chemotherapy was composed of two 28-day cycles given alternatively. Cycle A consisted of adriamycin and vincristine, and cycle B consisted of cyclophosphamide, methotrexate, and 5-fluorouracil. Fifty-five patients were fully evaluable. Complete remissions were obtained in 13 (24%) and partial objective remissions in 27 (49%). The overall remission rate was 73%. Toxic side effects ranged from mild to severe. The most significant were nausea and vomiting (most patients), weakness and pain (two thirds of the patients), and hematologic changes (half of the patients). It is concluded that the present combination of endocrine and cytotoxic therapy represents one of the most effective currently available treatments of advanced breast cancer. In an early clinical trial of tamoxifen in premenopausal patients with advanced breast cancer, two objective remissions, lasting 5 and 9+ months respectively, were obtained in ten patients treated. Tamoxifen is worthy of further assessment in premenopausal patients.


Thermoregulatory cold-defense deficits in rats with preoptic/anterior hypothalamic lesions.

This paper discusses the course of recovery from the thermoregulatory deficits produced in rats by electrolytic lesions in the preoptic/anterior hypothalamic area. Severe damage rendered rats ectothermic, that is unable to maintain their body temperatures at normal levels unless they were incubated at an ambient temperature of 30 degrees C. Less severe damage produced rats that maintained subnormal but stable body temperatures at 23 degrees C, but that did not increase metabolic rate or shiver and whose body temperatures dropped drastically in the cold (5 degrees C). As the animals recovered, nonshivering thermogenesis returned. Eventually the rats became excessively hyperthermic in normal room temperatures, due to very high metabolic rates. They were still unable to shiver or increase metabolic rate further in the cold and were therefore still unable to prevent a large drop in body temperature. Muscle tonus and shivering recovered gradually, and oxygen consumption returned to near normal levels. The data are described in terms of levels of integration of the nervous control of thermoregulation.


Neuromuscular blockade: the effects on two hippocampal RSA (theta) systems and neocortical desynchronization.

Neocortical and hippocampal electroencephalographic (EEG) activity were recorded from rats during: (a) spontaneous activities, (b) paralysis produced by curare or gallamine neuromuscular blockade, and (c) urethane anesthesia. All of the patterns of EEG recorded from normal rats were obtained from paralyzed rats including: (a) atropine resistant neocortical desynchronization and fast (6--12 Hz) hippocampal rhythmical slow activity (RSA) normally associated with overt Type I or voluntary movement, (b) atropine sensitive and urethane resistant slow (4--6 Hz) RSA which can be recorded from immobile animals during conditioning procedures, or during brain or sensory stimulation, and (c) large amplitude irregular neocortical and hippocampal EEG which can be recorded from immobile or sleeping animals. Depth profiles of RSA were taken from the hippocampal formation of urethanized and curarized rats during posterior hypthalamic stimulation. The results confirmed findngs of two RSA amplitude maxima with an approximate 180 degree phase difference, one location in stratum oriens of area CA-1, the other in stratum moleculare of the dentate gyrus, and suggest there are two generators of RSA. Atropine sensitive and atropine resistant types of RSA were found in each generator. The results suggest that RSA may be supported by both cholinergic and noncholinergic input to each generator and that neither RSA type could be only the result of proprioceptive feedback from joints or muscles.


Electrophysiology of neural units in goldfish optic tectum.

Axons of retinal ganglion cells showed responses not previously emphasized: (a) many tonic units discharged oscillations, 2--12 spikes per burst, interburst intervals 20--300 msec; (b) phasic units showed concentric or flanking ON and OFF fields, response frequency depended on balance of retinal excitation and inhibition; (c) directional sensitivity was maximal for retinal stimuli moving in naso-temporal direction; (d) in anterior tectum deep afferent layer (DAL) provides for deep electrical sink, fibers of DAL have small fields, mostly in front of fish; (e) color-opponent units are prevalent in the superficial terminal layers, color is spatially and temporally represented. Tectal cell responses were distinguished by large visual fields, spontaneity, multiple spikes and long latencies to optic nerve stimulation, failure to follow above 60 per sec, plasticity of response. Tectal neurons of three classes included (a) cells of one type in upper layers were inhibited in ongoing activity by visual input, receptive fields exceeded 100 degrees, were often oblong, responses did not habituate; (b) cells of second type were excited by visual stimuli, became unresponsive (habituated) or responsive only to stimuli in different position or direction (newness cells); lability precluded field mapping and dishabituation was produced by change in background, extraneous stimulation, and spontaneous firing; (c) pyriform cells in periventricular layer were abundant, difficult to isolate electrically, discharged spontaneously in bursts at intervals of several seconds and responded to visual input by interruption of firing. Some tectal cells responded to non-visual stimuli as well.


Cerebellar nuclear stimulation in generalized penicillin epilepsy.

Comparison was made of the effectiveness of cerebellar cortical and nuclear stimulation in reducing paroxysmal activity induced in cats by parenteral penicillin administration. Vermal cortical and fastigial nuclear stimulation at high frequencies (100 Hz) were both effective in reducing the number and duration of paroxysmal events while the effects of dentate nucleus stimulation were found to be more variable. It was suggested that effective seizure inhibition appeared to be associated with increased fastigial output and resultant reticular excitation.


Visual performance and synapses in the visual cortex of rabbits.

The density of synaptic connections, the length of the contact zones and the number of synaptic vesicles are quantitatively studied in the left and right hemisphere of a group of rabbits a number of which showed marked ocular dominance. No systematic differences in the parameters studied could be observed in the visual cortex between symmetric animals, indicating that the ocular dominance cannot be explained by hemispheric differences in density of synapses.


Melanin in the rat brain.

Melanin was measured in various parts of the rat brain by a spectrophotofluorometric assay. This method could detect natural, Sepia melanin as well as melanin synthesized from L-DOPA. Contrary to published expectations of other investigators, measurable amounts of melanin were found in the brain of albino as well as pigmented rats. The highest concentrations of melanin occurred in the pons-medulla and midbrain, but all regions within the blood-brain barrier contained greater concentrations than samples from many other tissues in the body. No significant change in the melanin content was found after various endocrine manipulations such as removal of the pituitary, pineal, adrenals, thyroid, testes, or ovaries, exposure to constant illumination or darkness, and daily injection for 5 weeks of alpha-MSH, Pro-Leu-Gly-NH2 (MIF-I) or melatonin. As expected, retinal tissue from black-hooded rats contained extremely high levels of melanin whereas that from albino rats contained no melanin. It is thought that the presence of melanin in the brain of albino and pigmented rats may have a function which is still unknown.


[In vitro thyroid diagnosis in surgery of the thyroid].

After a brief outline of the physiology of the thyroid hormones and the laboratory tests measuring thyroid function, the dosage of normalised T4 (T4N) in patients suffering from various thyroid diseases and subjected to surgical operation is discussed. As the fundamental presupposition of thyroid surgery is that the operation is made in conditions of euthyroidism, the use of a quick and reliable preoperative test giving an exact evaluation of the patient's thyrometabolic conditions is necessary. In conclusion it is stated, on the basis of experience acquired in 90 patients operated for various thyriod diseases, that the last thyrometabolic evaluation can be based on T4N dosage.


Lymphomatoid contact dermatitis: a syndrome produced by epicutaneous hypersensitivity with clinical features and a histopathologic picture similar to that of mycosis fungoides.

Four cases have been studied which were clinically suggestive of mycosis fungoides because of their infiltrated plaque-like lesions, but in which the suspicion of a topical hypersensitivity arose when a positive patch test was obtained with the striker part of a box of matches.


An antigen from Parthenium hysterophorus Linn.

The increasing incidence of contact dermatitis due to the wild growth of the weed Partheium hysterophorus Linn. in many parts of India has prompted chemical analysis coupled with clinical testing to isolate the offending agent. Results are present to show that parthenin, a sesquiterpene lactone, is the major antigen which produces contact dermatitis in sensitive human beings.


The effect of perfume "ageing" on the allergenicity of individual perfume ingredients.

An ingredient of a perfume which is a sensitizer may become hypoallergenic by interacting with other ingredients during the ageing process of the perfume. Thus, a patient with an exquisite allergic sensitivity to cinnamic aldehyde tolerates two perfumes containing cinnamic aldehyde without acquiring a dermatitis. There are several theories of why cinnamic aldehyde can become a non-sensitizer in a perfume mixture. Testing with a mature perfume may be much more significant than testing with individual ingredients.


Quinazoline Yellow SS in cosmetics.

Five cases of allergic contact dermatitis from Quinazoline Yellow SS (D and C Yellow 11) in cosmetics are described, three from a lipstick and two from a rouge stick. Four of them showed marked oedema spreading to the eyelids and down to the neck. Two of them required systemic steroids. All four had strongly positive patch tests to the dye and to the cosmetic used.


Transepidermal water loss in adhesive tape induced dermatitis.

As an index of skin barrier function, transepidermal water loss (TEW) was investigated in subjects reactive to adhesive tapes. Tape reactive subjects showed no difference in TEW in untreated skin when compared to non-reactive subjects. Plastic tape and transparent tape produced varying degrees of dermatitis in reactive subjects; the TEW was increased up to 40-fold of the baseline values correlating with the degree of dermatitis. Paper tape and plastic film without adhesive did not produce dermatitis and increased water loss. Regeneration of skin damage was accompanied by a decrease of TEW values. The general problem of tape reactors and tape irritation is discussed.


Sensitivity to 35 essential oils.

Two hundred consecutive patients and 50 subjects positive to balsams were tested with the 35 essential oils most frequently used in Polish cosmetics. The frequency of sensitivity to the particular oils is noted and the index of sensitization calculated as the amount of oil/kg used annually for the production of Polish cosmetics per one patient positive to this oil. The correlation of positive tests to essential oils with positive tests to four balsams of the standard series is shown.


Contact sensitivity to emulsifiers.

Common emulsifiers were tested in over 1,200 patients with eczema. Triethanolamine stearate tested at 5% in petrolatum caused irritant reactions in 9.5% of the patients. On the other hand, non-ionic emulsifying agents tested at 10-20% produced irritation in only a few cases. Allergic reactions were found in 2.1% of those tested. Lanette, sorbitan sesquioleate, the Spans, polyoxyethylene oxypropylene stearate, polyoxyethylene sorbitol lanolin derivative, and triethanolamine stearate each elicited allergic reactions in 0.3-0.7% of the cases. The Tweens caused an allergy in only two cases, but glycerol monostearate caused no reaction at all. Five out of six patients sensitive to sorbitan sesquioleate reacted positively to the Spans as well. The patients allergic to one or more emulsifiers were also sensitive to several other substances included in our routine test series with the exception of four patients who reacted only to the emulsifying agents.


Standardization of patch tests in Japan.

In order to standardize patch tests in Japan a comparative study of our former method of patch testing with that recommended by the International Contact Dermatitis Research Group (ICDRG) was carried out with the collaboration of dermatologists in the Mid-Japan Dermatological Society. The following differences were observed between the two methods of patch testing: 1. Four out of five ICDRG allergens which were common in Japanese standard allergen series--formaldehyde, potassium dichromate, cobalt chloride and nickel sulfate--showed higher reactivity than those of Japanese allergens. The other allergen, paraphenylenediamine (PPD), showed the same reactivity as Japanese PPD. Cobalt chloride of ICDRG origin showed a particularly higher reactivity than the Japanese one (a=0.05) 2. Higher reactivity was observed at the 48-h reading when aqueous reagents were patch-tested using Torii-Ban, Miniplaster and Leukotest, which are all popular in Japan. This higher reactivity could be attributed to the lint gauze of plasters which are pre-treated with fluorescent whitener. 3. The incidence of reactivity of the ICDRG allergens in Japan was also studied in order to establish a new standard allergen series.


Photoepicutaneous testing: influence of the vehicle, occlusion time and concentration of the test substances on the results.

The effects of various vehicles, the occlusion time and the concentration of the test substances on the phototoxic reactions were studied using the Finn Chamber method in photoepicutaneous testing, with methoxsalen and coal tar as test substances. Petrolatum proved to be a suitable base for methoxsalen and carbowax for coal tar. The optimal concentration of coal tar was 5% and that of methoxalen 0.03-0.05%. The optimal occlusion time for methoxsalen was 1-2 hours and for coal tar 24 hours. It was concluded that in order to obtain the most reliable results, these parameters should be determined separately for every photosensitizing compound to be tested.


[Comparative study of the mutagenic effect of several chemical substances on Syrian hamsters].

The authors carried out experiment on 38 Syrian hamsters, treated with cyneb, tetracycline and chlorpromasine in groups for a period of tree days. They examined the changes in the cariotypes of the animals as well as the changes in the mytotic activity of bone-marrow cells. Data were based on the analysis of 3045 metaphasic plates and 190,000 cells. It was established that the examined substances possessed mutagenic effect on the Syrian hamster in doses applied in vivo. This effect was mostly manifected in the animals treated with cyneb, followed by chlorpromasine and tetracycline. The same chemical substances reduced the mytotic activity of the bone-marrow cells. The data of the experiments in vivo correlated positively with the results of the experiments in vitro of human lymphocytic cultures, treated with the indicated substances.


[Morphologic changes in the testes of white rats chronically subjected to vofatox 50].

The chronic action of the preparation vofatox 50 causes changes in the spermatopoeitic epithelium of white rats, which depend on the doses and duration of intoxication. There is an increased vascular permeability and degenerative changes in the spermatogenic epithelium, a reduction of the mitotic process and also index of spermatogenesis at the initial stages. The later changes are manifested by more formed changes in the spermatopoietic cells, appearance of gigantic multicellular forms, lack of sprematozoa in a large number of canaliclues and fibrosis of blood vessels. The changes in the testis are the result of the general toxic action of the preparation.


[Biochemical changes in the placenta of white rats treated with basfungin].

The author carried out experiments on white rats and discussed the role of the placental insufficiency in the perinatal pathology under the action of fungicide basfugine. After administration of the preparation singly at the critical 13th day of embriogenesis and repeatedly during the course of the gestation the author examined biochemically the activity of the following enzymes: glucose-6-phosphatdehydrogenase, lactatdehydrogenase and thermostable alkaline phosphatase. Basfungine, administered in effective teratogenic doses, inhibited the activity of the indicated enzymes in the placenta, manifesting in this way its functional insufficiency, which was most probably the substantial moment in the pathogenesis of the induced anamaly in the fetal development.


[Formation and development of motor-defense conditioned reflexes in rats of different ages].

The analysis of the reflex conditioned activity of rats at various age groups showed that there were differences in it. There was a considerable strength of the excitatory process in young rats, aged one and a half months. The positive reflexes to sound and light stimuli were formed compatively quickly (on the average after 8,6 and 4,8 combinations of the conditioned stimulus with the unconditioned stimulus) in comparison with the animals of mature age (respectively 16,5 and 8 combinations). In the old rats the author observed a lowering of the strength of the excitatory process and slower formation and stabilization of the positive conditioned reflexes. A gradual formation of the inhibitory function occurs during the process of ontogenetic development and this finds an expression in the unpossibility for the fromation of differentiation in young animals and the presence of such in 10-month old rats. The level of the differentiations in these animals reached 60,1% and 76,9%. The latent period changed with the advancement of age. In adult animals there was some shortenint ofthelatent period in comparison with the young animals although the difference was statistically insignificant. There was an increase of the absolute values of the latent period again after the occurrence of the old age (5,2'' and 4,52''). The indicated peculiarities in the formation and course of the conditioned reflexes probably were connected with various degree in the fluctuations of the strength of the exitiatory and inhibitory processes in the central nervous system during ontogenesis.


[Changes in renal enzyme activity in rats with experimental hypertension].

The study was carried out on rats of the Wistar strain with experiments hypertension by the method of Selye, modified by Kolarova. These authors examined the activity of the enzymes of protein metabolism (GOT, GPT, AP), of glycolysis (ALD, LDH, alpha-HBDH) and of the citric cycle (MDH) in the left and right kidney at various intervals after modeling the process (3th, 15th, 30th and 90th day). The activity of the enzymes of the glycolytic chain and the cycle of Krebs in the left kidney was lowered at all stages of the experiment. Transaminase activity diminished progressively. Such a dynamics revealed the activity of adenosine phosphate as well. The activity of all examined enzymes of the right kidney showed phase changes-after initial elevation on the third day there was a lowering at the later stages of the experiment. The altered activity off the left kidney was connected with the disturbed vascularization with subsequent metabolic changes. The changes in the enzymic activity in the right kidney were assumed as a consequence of the occurred adaptive hyperfunction.


[Organ hematocrit and determining the blood content of tissue homogenates].

The authors determined the mean normal values of organ homogenates and their significance in evaluating blood amount, contained in the organs. They used radioisotope method with two kers 131 J and 51Cz for determining organ hematocrit. The hematocrit values of the organ blood differed significantly from the venous hematocrit as the values of the spleen were higher, but those of liver, kideny, cerebrum, testis and skeletal muscles-lower. On the basis of these data they proposed to apply respective correction factors, checking the differences between venous and organ hematocrits, when the amount of blood in single organs, determined by hemoglobin content, was estimated. The validity of this correction was illustrated by experimental results.


[Technic for cannulating the great lymph duct in dogs].

The authors described in details the technique for cannulation of the terminal part of the main lymph ductus in dogs. They shared their experience in operating 23 dogs. The authors described the approach to ductus thoracicus, cervical region and most frequent difficulties connected with its finding and preparation. All encountered anatomic variants of the chest ductus were presented. The most critical moment of the operation--introduction of the cannula in the ductus was described in details and the authors proposed some technical methods enhancing quicker and easier cannulation.


Ambivalent effect of protein binding on computed distributions of metal ions complexed by ligands in blood plasma.

Although the absolute concentrations of metal complexes in blood plasma are controlled by protein binding, the percentage distribution of transition metal ions amongst low molecular weight ligands is not. Thus, computer simulations which omit protein equilibria can nevertheless afford reliable information about such metals in the biofluid.


Subcellular localization of O-acetylserine sulfhydrylase in spinach leaves.

A combination of differential centrifugation and isopycnic sucrose density gradient centrifugation of extracts from spinach leaves (Spinacia oleracea L.) shows that about 20% of the O-Acetylserine sulfhydrylase are associated with chloroplasts. No appreciable amounts of O-Acetylserine sulfhydrylase band with mitochondrial and peroxisomal marker enzymes.


Some properties of cholinesterase of the plant nematode Aphelenchoides ritzema-boosi.

Activity and properties of cholinesterase from Aphelenchoides ritzema-boosi, a plant feeding nematode, were investigated by testing the reaction of the enzyme with different substrates and inhibitors. Butyrylthiocholine was a better substrate than propionyl- and acetylthiochine. When compared with mammaliian erythrocyte and plasma cholinesterase, the nematode enzyme was found to be extremely insensitive towards a number of well-known organophosphorus and carbamate inhibitors.


Interaction between the soluble and particulate neuraminidases of chick liver.

The sum of the neuraminidase activities found in the isolated soluble and particulate fractions of chick liver was considerably higher than that observed in the cytoplasmic extract from which these fractions were obtained. Addition of increasing amounts of particulate neuraminidase to a constant amount of the soluble preparation resulted in a progressive loss of enzyme activity.


Light stimulated 'shunt-metabolism' succinate-alpha-ketoglutarate-isocitrate cycle and accumulation of citric acid in Aspergillus niger.

Studies with light of the visible range had shown that light plays significant role in the biosynthesis and accumulation of citric acid in Aspergillus niger. Accumulation of 14C-labelled carbon atoms in alpha-ketoglutaric, isocitric, succinic and glycolic acids in the cultures grown under illumination suggest a probable 'shunt-metabolism' leading to the succinate-alpha-ketoglutarate-isocitrate (SKI) cycle. This shunt metabolism minimizes the accumulation of citric acid in cultures due to depletion of intermediates.


Adriamycin-induced chromosome damage: elevated frequencies of isochromatid aberrations in G2 and S phases.

Analysis of chromosomes from cells treated with adriamycin during G2 and S phases showed a high frequency of isochromatid-type of breaks, in addition to the expected chromatid breaks. These are interpreted as independent breaks on sister chromatids because of preferential effects of the drug in specific chromosome regions. The break points are likely to be different, but morphologically such breaks would be indistinguishable from isochromatid or chromosome breaks.


Actinomycin-resistant antiviral activity associated with preparations containing chicken interferon.

Crude and purified preparations containing chicken interferon show a 2fold antiviral activity. One is inhibited by actinomycin and leads to total inhibition if interferon is added to cells before actinomycin, the other is insensitive to actinomycin and leads to partial inhibition if interferon is added simultaneously with or after actinomycin.


[Phagocytosis of liposomes by mouse peritoneal macrophages (author's transl)].

Uptake of 14C-cholesterol or 3H-cholesterol labelled liposomes, stimulation of 14C-glucose oxidation, as well as ultrastructural and autoradiographical experiments have shown that liposomes are phagocytized by mouse peritoneal macrophages. Further results have shown that degradation of liposomes was not complete 2h after uptake.


Gonadectomy and growth of Taenia crassiceps (Cestoda) cysticerci in mice.

Gonadectomy of SWR of both sexes significantly reduced the number of cysticerci of Taenia crassiceps, 60 days post infection. There was a significant decrease in the total number of larvae and the number of nonbudding individuals, corresponding with increased number of budding larvae. This indicates that the asexual multiplication of cysticerci in populations from gonadectomized mice was inhibited.


The generation of toxic activity from trypanosoma congolense.

Trypanosoma congolense organism, on incubation at 20 degrees C for 91/2h, were found to generate phospholipase like activity which was capable of mediating lysis of both nucleated cells and erythrocytes as well as acute inflammatory response on intradermal inoculation.


The influence of early nutrition and environmental rearing on brain growth and behaviour.

Preweaning malnutrition permanently reduced brain size and cellular content but in spite of changes in the adrenocotical stress response no learning deficit was observed. Differential rearing environments did not influence the effects of malnutrition.


The glycocalyx of the epithelial cells of the colon, observed in normal and ulcerous colitic conditions.

Biopsies of subjects affected by ulcerous colitis were stained with ruthenium Red. Alterations of the cellular coat and glycocalyx of the epithelial cells of the colon were identified.


Modification of visual signals by nigral stimulation.

Responses of the lateral geniculate neurons to light were modified by stimulation of the substantia nigra. Nigral stimulation often caused enhancement of firing in neurons responding primarily to flash, but it usually had the contrary effect on units inhibited by light.


Study of the characteristics of the inotropic effect of insulin in rabbit papillary muscle.

The effect of insulin was examined with emphasis on the alteration in the force-frequency relation. The results show that insulin does not change the time to peak tension nor the time of contraction. The inotropic effect was significant and did not depend upon the frequency of stimulation. However, there was a definite dependence of the magnitude of the inotropic effect on temperature. Previous studies have indicated that the inotropic effect is not a result of increased substrate availability or changes in cAMP phosphodiesterase activity. These results and those reported here are consistant with the hypothesis that insulin's inotropic effect is due to increases in intracellular Ca++.


Reticular potentials evoked by electrical stimulation of individual semicircular canals.

Responses of pontine reticular formation neurons following single shock electrical stimulation of single semicircular canals were recorded with tungsten microelectrodes in 40 curarized guinea-pigs. The field and unitary potentials obtained from 62 reticular sites, exhibited latency values ranging from 0.3 to 2.5 msec. The early latencies (0.3-0.5 msec) have been interpreted as responses mediated by primary vestibular fibres projecting directly to the reticular substance.


Effects of three synthetic peptides analogous to neurophypophyseal hormones on the excitability of giant neurones of Achatina fulica Férussac.

Deamino-dicarba-(D-D)oxytocin and D-D-Arg-vasotocin at 10(-4)Kg/l showed an excitatory effect on the periodically oxcillating neurone (PON) of Achatina fulica Férussac. D-D-Arg-vasopressin had no effect.


Potentiation by taurine of the inotropic effect of ouabain and the content of intracellular Ca++ and taurine in the heart.

Under certain conditions, taurine (3.0mM) potentiated cardiac contractile response to ouabain in the normal medium. The potentiation by taurine was also observed in the low K+ medium, in which the positive inotropic effect of ouabain increased. The potentiation as seen in both media was, at least in part, due to the increase by taurine of Ca++ content in the heart. Taurine in the heart was not directly related to this potentiation.


[Microscopical investigations on the 'vessel sealing' effect of calcium ions (author's transl)].

The effect of locally applied calcium on the vascular permeability is studied under the conditions of an acute inflammatory reaction. Using the Sephadex-inflammation, local elevated calcium concentration neither inhibited oedema formation, nor were reduction of inflammatory signs at all observed on the microscopical level.


Comparison of the ototoxic effect of kanamycin on albino and pigmented rats, studied using an operant method.

A study was made of the effect of daily administration of kanamycin (400 mg kg-1) on the hearing of Wistar albino and Lister hooded (pigmented) rats, which had been conditioned to discriminate an acoustic signal. In all animals except one, the drug caused severe, permanent hearing impairment and there was no difference between albino and pigmented rats in onset or degree. Other work has suggested a mediatory role for melanin pigment in such drug ototoxicity but the significance of this must be questioned in view of the failure to find any differences in functional deficit.


Pseudolymphoma of skin induced by oriental hornet (Vespa orientalis) venom.

Intradermal injection of saline suspension of Vespa orientalis venom sac to 57 black mice caused a local nodule composed of lymphocytes, few histiocytes and plasma cells 10 to 12 days following the injection. This reaction simulates the pseudolymphoma reaction observed in humans following arthropode stings.


[Morphological effects of concanavalin A on amphibian embryonic cells differentiating in vitro (author's transl)].

Concanavalin A exerts an irreversible inhibitory effect on the differentiation of cultured embryonic amphibians cells in vitro. Cytological changes and distrubances of cell attachment, and spreading to the culture support occur in parallel. Polykaryons have been noticed in treated cultures.


Intracisternal A type particles of the extraocular muscle of hereditary muscular dystrophy mouse.

Intracisternal A type virus (IA) particles were observed in the extraocular muscle fiber of hereditary muscular dystroph mouse. The particles appeared approximately 65-75 mmu in diameter, with electron lucent cores.


A transmission and scanning electron microsope study of primary neural induction.

Normal primary neural induction has been further studied by TEM and SEM. A single mesoderm cell is usually in contact with several ectoderm cells. The mesoderm cells are also contacting other mesoderm cells. It is suggested that ectoderm cells are induced in groups and that induction is synchronized by these contacts. At the points of contact between mesoderm and ectoderm cells cytoplasmic changes are present in the induced tissue.


Nephrocompensatory growth following thymectomy.

Thymectomy performed 28 days before unilateral nephrectomy produced significant inhibition in compensatory renal growth (CRG) in 3-6-month-old rats. Sera from thymectomized animals are not deprived of their renotrophic activity, but thymectomy of serum recipients almost abolished the capability of renotrophic serum to produce CRG.


In vitro culture of larval amphibian erythroblasts.

A larval erythroblast culture method is described. By this method, it is possible to cultivate for several weeks a homogeneous population of cells (5-10(5) cells/ml medium on average after 4 or 5 days of culture), which are relatively synchronous with regard to their state of differentiation.


Alternative complement pathway: activity levels in allogeneic pregnancy.

Classical and alternative complement pathway activities have been evaluated in sera of women in progressive stages of gestation and in pregnant mice belonging to outbred or inbred matings, as compared to suitable controls. While classical C pathway was found to be unmodified, the alternative one attained in pregnancy significantly higher activity levels. Results are discussed in the light of mother-conceptus relationships.


Mast cells in the pinna of Balb/c 'nude' (nu/nu) and heterozygotes (ny/+)mice.

The relative number of mast cells in the ear lobes' skin (pinna) of nude (athymic) nu/nu and normal (thymic) nu/+ heterozygotes of Balb/c mice was similar. The results obtained contradict some suggestions about the general influence of the thymus on the number of mast cells in the skin and suggest the existence of some local factor(s) in regulation of skin mast cell numbers.


Lack of platelet factor-3 activation after incubation of platelet-rich plasma with kaolin in the rat.

Stypven times, measured in rat platelet-rich plasma (P.R.P.) after incubation with kaolin, did not shorten as incubation proceeded, thus reflecting the lack of development of platelet factor-3 (PF3) availability in this test system. Repeated freezing and thawing of P.R.P. or aggregation with collegan did result in PF-3 availability. Aggregation and PF-3 availability were inhibited by the compound VK774. These findings add another aspect to the list of species differences in platelet function.


Serum and bile modifications in the guinea-pig following chronic treatment with PGE1 and PGE2.

PGE1 increases cholesterolemia without lipemia modifications. In bile there are not modifications in cholesterol levels and total lipids appear diminished. PGE2 raise the lipemia and have no effect in cholesterolemia, moreover bile cholesterol and total lipids exhibit no changes. Both PGE1 and PGE2 decreased the bile volume.


Ovarian LDH activity in gonadotropin-treated immature rats.

Lactate dehydrogenase (LDH) activity was studied in the ovaries of immature rats treated with pregnant mare serum gonadotropin (PMS). LDH activity increased sharply at 36 h after PMS injection in the ovarian tissue as well as in the blood. It was suggested that the increase of LDH activity in the ovary may be related to its increasing ability to secrete estrogen.


The micro-focal x-ray unit and its application to bio-medical research.

The micro-focal X-ray unit is a modified Cosslett and Nixon X-ray microscope of greater operational stability and flexibility. Its combination with a closed circuit television system provides a quick method of obtaining a point source of X-rays to examine the detailed structure of organs and biological specimens.


Directional non-uniformity of pulsatile intramyocardial pressure.

A method using piezoelectric ceramics was newly devised which permitted measurements of intramyocardial pressure. In open-chest dogs, a directional non-uniformity of the intramyocardial pressure was observed, which may be attributable to the variation in the myocardial fibre orientation.


A heated stage and tissue culture chamber for electrophysiology.

A simple, inexpensive heating circuit is described for use with a warmed microscope stage, small tissue bath, and heated tissue culture chamber. A major consideration in the design of the apparatus is a compatability with electrophysiological studies. Thus, proper shielding and low profile for microelectrode positioning are featured.


Lung carcinomas induced by oral administration of N-bis(2-hydroxypropyl)nitrosamine in rats.

The oral administration of N-bis(2-hydroxypropyl)nitrosamine (DHPN) in drinking water induced lung tumors in high incidence in rats at 25 weeks. Histologically, they were adenoma, adenocarcinoma, squamous cell carcinoma, and combined squamous cell and adenocarcinoma. Metastases of adenocarcinoma were observed in regional lymph nodes. The development of tumors in other sites was seen in the liver, thyroid, kidney, ureter, urinary bladder, and pancreas. The incidence of lung tumor was distinctly higher than that of other sites. These results indicate that the target organ of DHPN was the lung and that oral administration of this chemical carcinogen was responsible for the development of lung carcinomas in rats.


Mouse strain differences in macrophage activation and anti-tumor activity induced by Propionibacterium acnes (anaerobic coryneforms).

Effect of Propionibacterium acnes on macrophage activation and antitumor activity was examined in ddN and SL mice. (1) Carbon clearance was enhanced to the same extent by P. acnes  treatment in both strains. (2) Number of peritoneal macrophages increased to the same extent by P. acnes treatment in both strains. (3) Adhesiveness of peritoneal macrophages, as demonstrated by inhibition or migration or an increase in spreading cells, was enhanced more efficiently in ddN than in SL mice P. acnes treatment. (4) Mice of both strains died in a similar patterns, when they were not pretreated in any way. The treatment with P. acnes conferred antitumor activity of a higher degree in ddN than in SL mice. (5) Peritoneal macrophages of ddN mice treated with P. acnes exhibited an antitumor activity in in vivo neutralization test. These results suggest that strain difference in augmentation of antitumor activity by P. acnes is ascribed to distinct sensitivity of macrophage functions to a stimulative effect of P. acnes in the mouse strains.


Comparative studies on the antitumor effect on intravenous administration of carbazilquinone and mitomycin-C.

Comparison between Carbazilquinone and Mitomycin-C, both of which contain aziridinyl, carbamoyloxy, and quinonyl groups, was made for their therapeutic effect upon intravenous administration. Although both agents exhibited a significant effect on plasmacytoma X5563 in C3H/He mice to a similar extent, Mitomycin-C was not as effective on lympholeukemia L-1210 and on the lung metastasis of Ehrlich carcinoma in (C57BL/6 X DBA/2)F1 (BDF1) mice as was Carbazilquinone. Possible interpretations regarding this discrepancy are discussed.


Biochemical study of pyloric metaplasia in the mucosa regenerating over iodoacetamide-induced fundic ulcers in rat stomach.

The molecular species and content of pepsinogen in regenerated mucosa over fundic ulcers induced in a rat stomach by iodoacetamide were found to be the same as those in normal pyloric mucosa, but different from those in normal fundic mucosa.


Damage and repair of rat liver DNA by simultaneous oral administration of amines and nitrite.

The effect of simultaneous oral administration of dimethylamine or aminopyrine and sodium nitrite on the damage and repair of rat liver DNA was studied by the use of centrifugation in alkaline sucrose gradient. Fragmentation of the intact DNA was observed significantly shortly after combined treatment with aminopyrine and nitrite when no liver necrosis occurred yet and the damaged DNA at the lower dosage level of aminopyrine with nitrite was found to be repaired in contrast to the increased activity of serum aminotransferase. The lowest effective dose on DNA damage at 2 hr after administration was about 40 mg/kg of aminopyrine and 80 mg/kg of sodium nitrite. This effect was equal to that caused by single oral administration of 2 to 10 mg/kg of dimethylnitrosamine, while dimethylamine at 160 or 320 mg/kg together with 80 mg/kg of sodium nitrite produced no pronounced DNA damage. The significant damage of rat liver DNA by aminopyrine and nitrite correlates well with the easier nitrosation of aminopyrine and the occurrence of high incidence of malignant liver tumors in rats fed aminopyrine together with nitrite already reported by Lijinsky.


Effect of 4-hydroxypyrazolo[3,4-d]pyrimidine (allopurinol) administration of growth of Ehrlich tumor cells.

Effect of the administration of 4-hydroxypyrazolo([3,4-d]pyrimidine (allopurinol) on the growth of Ehrlich ascites tumor cells was investigated in an in vivo system. Oral administration of allopurinol (0.1% in diet) suppressed the growth of both ascites and solid types of the tumor after the implantation of Ehrlich tumor cells in mice. The inhibitory action depended on the dose but was lost repidly when the administration was interrupted. Possible mechanisms involved in the inhibitory effect of allopurinol on tumor growth were briefly discussed.


Growth of mammary tumors in a high and a low mammary tumor strains of mice established from the same basal stock of Swiss albino.

The growth of spontaneous mammary tumors and of tumors transplanted into the animals with different hormonal conditions was compared between SHN and SLN strains of female mice established from the same basal stock of Swiss albino as a high and a low mammary tumor strains, respectively. There were little differences between strains in the growth of spontaneous mammary tumors of multiparous mice which appeared first. The growth of transplanted mammary tumors was not affected by the hormonal conditions of the hosts in either strains. However, the tumors became palpable one week after transplantation in SHN, which was 2 weeks earlier than in SLN. These findings indicate that the selection of animals for mammary tumorigenesis is effective on the time and frequency of malignant transformation of mammary cells and on the ""take'' of transplanted tumor cells, but not on the growth potentiality of already established tumors. They further suggest autonomy in the growth of mammary tumors in both strains of mice.


[Altitude adaptation. V. (conclusion). Morbidity and mortality. Literature].

The ability to adapt to extreme conditions is a continously working principle of man's evolution, in a permanent orientation to an optimal equilibrium between man and environment. A paradigm of biological adaptation is the condition of hypoxia at high altitudes, as one of the few environment constellations to which a pure biological and thus genetically based answer could be possible. The majority of adaptations are influenced by technological actions, which partially modify the environment in compensating unfavourable constellations (heating, clothing, housing, etc.). It is discussed, how far the adaptation to high altitudes produces transitory or permanent alterations with reference to constitution, perseverance, cold-sensitivity, diseases, duration of life, fertility, course of pregnancy, adaptations at the organ- and tissue-level, blood-composition, fluid-equilibrium of the body etc., which guarantee the survival of the individual and its successful reproduction with regard to the continuance of a mendel population. The elucidation of the question on genetic determination of features characteristic for high altitude inhabitants is difficult because we know next to nothing about the genetic determination of physiologic parameters. Studies on ethnic marker-genes (Ethiopia, South-America) give no reference to population differences. Remarkable is a striking prevalence of the blood-group O for all populations of high altitudes, but one must consider the effects of isolation in terms of the increase in the homozygote recessive alleles. We can propose, that in the primary settlement at high altitudes a "hard selection" was working, a kind of biological assortation-process from the beginning, which eliminated those individuals, who proved to be (for genetic reasons?) not adaptable. A good example for this are observations of cattle, from which 50% do not develop pulmonary hypertension when exposed to altitude, that means they already have a higher initial fitness. The non-adaptable animals have to be returned to the lowlands. In the F1-generation only 2% of the animals remaining at high altitude, develop "brisket disease". Possibly that means a sort of "out-mendeling" of "pulmonary-hypertension-genes", which may manifest themselves in the condition of hypoxia. Also the good adaptation of llamas is partially due to the fact that the camelids per se possess an outstanding O2 affinity and morphologically different red blood cells, which predispose this species to inhabit high altitudes. Parallel to considerations like these it could be imaginable, that e.g. the indianids of mongoloids in general, are genetically composed as fit to inhabit lowlands as well as highlands, in contrast to caucasoids and negroids. The largest mountain areas of the world (the Andes: 12 X 10(6)), the Himalayas 12 X 10(6)) are inhabited by populations of mongoloid ancestry, for about 10,000 years, a period, which ought to be long enough to make possible genetic specialisation, although it is not yet possible to prove it...


[Detection of major genes for quantitative morphologic characteristics on family material, sib pairs and parent-child pairs, using as an example head length in man].

The detection of major genes affecting quantitative morphological characters from data of families, sib-pairs and parent-child pairs (with the example of head length in man). The major genes of human head length are defined utilizing three different combinatorical methods of maximum likelihood estimation. To prove the discriminatory power of methods, it is necessary in further research to work with empirical or simulated sets of multivariate data of which the genetical structure is known.


[The so-called pressure zone of the cerebellum].

Systematic studies on the so-called cone of basal parts of the cerebellum employing a scale of either qualitative and quantitative intensity revealed the following: A cone extension of basal cerebellum parts is to be observed in 80.9% of random post-morten examination cases with insignificant differences in sex. Cerebellum cone frequency amounts to 12.8% in babies, up to 66.7% in infants from 1 to 14 years of age, and to 91.8% in persons above 15 years of age. Cones are not found in foetusses. Cones are almost exclusively formed with the participation of those cerebellum parts adjacent to the tonsils, so that the termin "tonsil cone" is incorrect. Cerebellum cones can be distinguished by various degrees in size. The 1st degree corresponds to a cone height of 5 mm, 2nd degree between 5 and 10 mm, and 3rd degree to 10 mm and above. Statistical analysis shows that the cone height follows normal distribution, the mean value of height being 4.8 mm. No correlation has been found between the cone height and clinically detected state of cerebral pressure as well as between space requiring processes during the post-mortem examination. Hence the term "pressure cone" is wrong. There is a positive correlation between cone formation and other so-called morphological symptoms of cerebral pressure. But it is doubtful, whether these symptoms may be regarded as a result of pressure on the brain. The occurrence of a cerebellum basal sphere cone is considered a normal filling up process of any internal space in the skull during brain acceleration. It is only in exceptional cases of cone sizes 10 mm and more, that cone formation is significant for the diagnosis of a possible increase in cerebral volume. Considering the obviously minimal significance of basal cerebellum cone in diagnosing an increase in cerebral volume, the following is a suggestion to prove a condition of cerebral pressure by means of complementary space determination of the skull.


[Development of the skeleton in the sheep and the goat. IV. Osteogenesis of the cranium].

1. The osteogenesis of the cranium was studied on a precisely dated embryological and postnatal material from merino-sheep and goats (crossbreed). 2. The order and duration of the appearance of ossification centers were determined (see Fig. 6). 3. It was noticed that, in small ruminants, the beginning of cranial ossification indifferent to other parts of the skeleton is not staged in time. Sexual dimorphism was only manifested by larger proportions of the male fetuses. An exception was noted only in os interparietale, which in male fetuses appeared 4 to 5 days later in male fetuses. 4. The cranial bones of small ruminants, showed a high degree of ossification at birth.


The behaviour of acetylcholinesterase activity in neurons of the bulbous part of the reticular formation in albino rats after bilateral vagotomy.

The influence of a bilateral vagotomy on the acetylcholinesterase activity (AChE) in the neurons of the bulbous part of the reticular formation of albino rats was investigated. An increase in the reaction to acetylcholinesterase (AChE) was ascertained in the large as well as the small neurons 8 h after the transection of the vagus nerves, which indicates their decreased activity. It may be assumed that a bilateral vagotomy causes a decrease in the activity of cholinergic mechanisms within the periphery of the reticular formation neurons.


Monoamine oxidase activity in blood platelets in alcoholism.

A newly developed assay for monoamine oxidase (MAO) activity in blood platelets was applied in 50 alcoholic patients. The assay is the direct measurement of serotonin oxidation by MAO employing a double microcolumn technique on Sephadex G-10 and Amberlite CG-50 for separating 5-HIAA formed, which is measured fluorimetrically. Rebound of MAO activity levels after withdrawal of alcohol was observed to be more pronounced in the patients with delirium tremens than those who exhibited no outstanding abstinent symptomatology. MAO activity levels measured in the 1st week of alcohol withdrawal were 3.49 +/- 1.15 (Mean +/- S.D) nmol/mg protein/hour in the alcoholic patients with delirium tremens, a value significantly lower than that in the subjects without (p less than 0.01) and that in the male normal subjects (p less than 0.001). Four weeks after withdrawal of alcohol, the reduced MAO activity levels in the alcoholic population were restored to normal levels. These data demonstrate that physical dependency for alcohol occurred evidently in the alcoholic patients examined. Delirium tremens and other psychotic symptoms in alcoholism may be manifested as impaired serotonin metabolism in the brain, which may be due to MAO inhibition caused by excessive alcohol intake.


Reduction of blood platelet serotonin levels in manic and depressed patients.

Blood platelet serotonin levels were measured in unmedicated 12 manic and 74 depressive patients with 118 normal control subjects employed. Blood platelets were separated by multiple centrifugation in the medium of Na2-EDTA solution, and the loss of serotonin during collecting procedures was about 11%. The mean value of blood platelet serotonin levels in depressed patients was 594 +/- 288 ng/mg platelet protein (+/- S.D.), which was significantly lower than that for normal controls, 780 +/- 253 ng/mg protein (p less than 0.001). Age does not account for the reduction of serotonin levels both in depressed and in normal population. Unipolar and involutional depressed patients exhibited to have the most pronounced reduced levels of serotonin of various subtypes of depression, while bipolar depressed patients, neurotic and chronic characterological depressed patients as well as patients with first-episode depression had the values which were comparable with those in normal controls. Manic patients did not show enhancement but did reduction of serotonin levels, the mean being 580 +/- 152 ng/mg protein, which made a contrast with their clinical manifestations of exhilaration and hyperactivity. Changes in blood platelet serotonin levels were determined before, during and after administration of L-5-HTP with a maintenance dose of 300 mg daily in nine depressed patients. Serotonin levels in all subjects were lifted to normal levels during the L-5-HTP treatment, while clinical symptoms were not improved with the treatment. Reduction of blood platelet serotonin levels in depressed patients may be due to their psychobiological distinction, which involves abnormal biogenic amine metabolism in the brain.


A biofeedback study of postural sway.

An experiment was performed to control postural sway under auditory and visual feedback signals using a new apparatus. The subjects of 52 healthy high school girls were divided into 13 small groups. Each small group had four subjects who were assigned to one of the following four groups; 1) visual feedback group, 2) auditory feedback group, 3) auditory and visual feedback group, and 4) control group. Comparisons were made as to the duration of the green lamp being on, which indicated sway stayed around the initial central gravity. The results showed that auditory and visual feedback groups had a significant increase in the duration as compared to other three groups. With regard to the changes in the areas of postural sway, the largest increase was seen in the auditory and visual group. While the three feedback groups showed downward curves, the control group showed an upward one. Thus it is suggested that postural sway can be voluntarily controlled by a combination of an auditory feedback procedure and a visual feedback procedure, but not by either of them independently.


Hypokalemic myopathy due to chronic alcoholism.

A patient with hypokalemic myopathy occurring in the context of chronic alcoholism was reported. A 56-year-old male patient, heavy drinker for 20 years, complained of marked weakness and acutely developing pains in his limbs. The principal clinical findings were weakness and tenderness of the proximal limbs and girdle muscle. He was unable to lift his head or any extremities from the bed. Deep tendon reflexes were diminished, but not absent. There was no sensory disturbance except for muscle tenderness. These clinical manifestations disappeared gradually by abstinence from drinking, and potassium administration therapy, and the patient recovered completely on the 26th day after onset. On the day after admission (8th day), serum potassium value was 2.2 mEq/L, and serum CPK activity was 4270 IU. The ECG pattern was consistent with a diagnosis of low potassium content in serum, and the EMG pattern was consistent with a diagnosis of myopathy. These electrophysiological findings had a tendency to recover from this pattern to normal range correspondingly with clinical improvement. The repeated muscle biopsies showed that vacuolation, hyaline degeneration and significant phagocyte infiltration were observed in the muscle on the 9th day after the onset of muscle weakness, and that these pathological findings disappeared almost completely three weeks later. The frequently repeated examinations of potassium content and CPK activity in sera showed that there was a close correlation between these biochemical abnormalities and clinical improvement. The pathogenesis of alcoholic myopathy and significance of CPK abnormality in chronic alcoholism were discussed.


Effects of electrical stimulation of the substantia nigra on responses of the lateral geniculate body neurons to light.

Effects of electrical stimulation of the substantia nigra on responses of the lateral geniculate neurons to light were studied. Responses of the neurons to flash were enhanced or inhibited by conditioning stimulation of the substantia nigra. Enhancement of firing by nigral stimulation more often occurred in neurons excited primarily by flash, but inhibition was more commonly observed in those which showed a primary neuronal silence after light.


Effects of psychotropic drugs upon the hypothalamic rage response in cats.

Effects of Chlorpromazine (CPZ), Haloperidol (HLP), Pentobarbital (PTB), and Diazepam (DZP) upon thresholds of the hypothalamically elicited rage response, i.e., directed attack and treat responses, were studied in chronic cats. All these drugs elevated the directed attack thresholds. CPZ and HLP elevated also the threat response thresholds and produced ataxia, but DZP did not show these effects. From these results, it is suggested that CPA and HLP suppressed the amygdalo-ventromedial hypothalamic nuclear and cerebellar functions and DZP suppressed the afferent pathway of the direct attack. PTB showed intermediate effects between the above two groups.


Sexual and parasexual approaches to the genetic analysis of the laboratory mouse, Mus musculus.

The mouse genetic map has been characterized largely through breeding studies based on the principles of Mendelian genetics. More recently, specific genetic information has been obtained from somatic cell studies using the techniques of in situ hybridization and somatic cell hybridization. The genetic analysis possible through these sexual and parasexual approaches is described, and specific linkage information from recent somatic cell studies is reviewed.


Somatic hybridization in higher plants.

Somatic hybridization in higher plants has come into focus since methods have been established for protoplast fusion and uptake of foreign DNA and organelles by protoplasts. Polyethylene glycol (PEG) was an effective agent for inducing fusion. Treatment of protoplasts with PEG resulted in 5 to 30% heterospecific fusion products. Protoplasts of different species, genera and even families were compatible when fused. A number of protoplast combinations (soybean + corn, soybean + pea, soybean + tobacco, carrot + barley, etc.) provided fusion products which underwent cell division and callus formation. Fusion products initially were heterokaryocytes. In dividing heterokaryocytes, random distribution of mitotic nuclei was observed to be accompanied by multiple wall formation and to result in chimeral callus. Juxtaposition of mitotic nuclei suggested nuclear fusion and hybrid formation. Fusion of heterospecific interphase nuclei was demonstrated in soybean + pea and carrot + barley heterokaryons. Provided parental protoplasts carry suitable markers, the fusion products can be recognized. For the isolation and cloning of hybrid cells, fusion experiments must be supplemented with a selective system. Complementation of two non-allelic genes that prevent or inhibit growth under special culture conditions appears as the principle on which to base the selection of somatic hybrids. As protoplasts of some species have been induced to regenerate entire plants, the development of hybrid plants from protoplast fusion products is feasible and has already been demonstrated for tobacco.


The stimuli to accommodation in the optometric examination.

The study of the stimuli to accommodation has been a topic of particular interest to vision scientists for the past 40 years. Currently, as revealed by a review of the literature, there are 11 different stimuli to accommodation. While it is difficult enough to hold 10 stimuli constant to measure the effect of a single stimulus, stimulus control becomes an even bigger problem when we consider stimulus interactions. With 11 different stimuli there are 2,047 possible stimulus combinations. In the present paper, the authors discuss at length the relationship between stimulus control problems and clinical optometric routine.


Prevalence of undiagnosed eye/vision disorders in a VA hospital.

A study population of one hundred and one subjects, chosen according to recommended epidemiologic procedures to assure an accurate representation of the total Birmingham veteran population, were given complete optometric examinations. The primary criterion for inclusion in the study was a need for coming to the hospital on the interview day for any health problem other than visual or ocular. The results of the statistical analysis showed agreement between the Birmingham veteran population and the general population with regard to vision and ocular disorders. Presbyopia was found to be the most prevalent vision disorder, and fifty-four per cent of the study population needed either prescription lenses for the first time or a significant change in their present spectacles for maximum visual acuity. When this figure is projected nationally, fifty-four percent of the fourteen million outpatients treated last year in VA medical care facilities would represent 7,616,000 veterans in need of vision care services annually. In fact, since the sample average age was 46, and the average age for veterans nationally is 55, the figure for those with uncorrected vision defects may be even higher.


An interdisciplinary team approach--a case report.

A case study is presented as a means of demonstrating the advantage of an interdisciplinary approach. The paper familiarizes the reader with the contributions to be made by a team composed of an optometrist, speech pathologist/audiologist, psychologist, and educational diagnostician. Based on the authors' experiences, it would appear that the total team approach is a most beneficial way of assisting the child with a learning disability.


A defense against professional liability? Precision measurement of the corneal topography.

New techniques must be developed if optometry is to be adequately armed against malpractice liability--especially in terms of contact lenses. An instrument capable of both measuring and recording corneal topography is essential to development of the optometrist's first line of defense: Proper instrumentational record-keeping.


Adverse response to prism therapy in strabismus.

The recent literature on prism therapy in strabismus is reviewed. A case is reported in which an esotrope, treated by means of prism neutralization to effect sensory orthotropia, responded with a marked increase in the angle of squint. Guidelines are suggested to minimize risk of such adverse effect when prism therapy is attempted.


Changes in corneal curvature and refractive error upon refitting with flatter hydrophilic contact lenses.

Eight subjects who wore hydroxy-ethylmethacrylate (HEMA) contact lenses showed a steepening in corneal curvature and an increase of minus in their post-wear refraction after three months of wear. After one year or more of wear, with the previously noted changes still present, these patients were fitted with a flatter series lenses which they wore for three months. Significant results are noted in corneal curvature and post-wear refractive error.


A classification for congenital limb malformations.

The classification for congenital limb malformations adopted by the American Society for Surgery of the Hand, the International Federation of Societies for Surgery of the Hand, and the International Society of Prosthetics and Orthotics is presented. This method groups similar patterns of deficiencies according to the parts that have been primarily affected by certain embryological failures, whether the insult involves a total part (skeletal and soft tissue) or only the dermomyofascial structures. The main categories of this classification are (I) failure of formation of parts. (II) failure of differentiation (separation) of parts, (III) duplication, (IV) overgrowth, (V) undergrowth, (VI) congenital constriction band syndrome, and (VII) generalized skeletal abnormalities. The rationale and method of use of the classification are discussed. This method has been tested and used in a variety of centers and has been found to be properly conceived and practical.


Random determination of a developmental process: reversal of normal visceral asymmetry in the mouse.

Situs inversus viscerum in the mouse has been shown to be inherited as an autosomal recessive trait (gene symbol iv) with reduced penetrance. It is hypothesized that the normal allele at the iv locus exhibits complete dominance and controls normal visceral asymmetry. Absence of this control allows the situs of visceral asymmetry to be determined in a random fashion. This hypothesis also appears to apply to the inheritance of situs inversus in man and to the experimental production of situs inversus.


Biochemical genetic variation in populations of golden trout, Salmo aguabonita: evidence of the threatened Little Kern River golden trout, S.a. whitei.

Eight wild populations of the High Sierra golden trout, Salmo aguabonita, and one domestic stock of rainbow trout, Salmo gairdneri, were examined for biochemical-genetic variation in eight protein systems. Variation within the eight systems was determined by at least 10 loci in both golden and rainbow trout and all the alleles identified in rainbow trout were observed as electro-phoretically identical phenotypes in golden trout. Variation was observed at an average of 51 percent of the loci in the golden trout samples and for five of the 10 loci in the rainbow trout. Average heterozygosity ranged from 12.6 to 13.9 percent for seven of the golden trout populations with one showing a low value of 5.4 percent. A comparable estimate of 12.1 percent was found for the rainbow stock. On the basis of genetic variation and allele frequencies at three loci, the eight golden trout populations were divided into two distinct groups. Three populations sampled from the Little Kern River basin tended to be genetically distinct from two additional Little Kern River basin populations and from three geographically distinct populations sampled from the eastern Kern River area. The former three populations were hypothesized to be of a recent rainbow-golden hybrid origin. Trout in the other two Little Kern River basin populations, sampled in head-waters of a stream tributary to the Little Kern River, were considered to be the threatened Little Kern golden trout, S. a. whitei Evermann, due to their high degree of genetic similarity to the geographically distinct subspecies S. a. aguabonita sampled from the eastern Kern River area. The finding of substantial genetic variation in the wild golden trout populations indicates that this threatened species is not at present genetically impoverished and thus does not appear to be in immediate danger of extinction through lack of adaptive capability.


Aspartate aminotransferase activity and glutamic dehydrogenase in the cerebellar cortex in several species of animals. A histochemical study.

The histochemical study of the consumption of glutamic acid by way of the aspartate aminotransferase and the glutamic dehydrogenase in the cerebellar cortex of several species of animals have demonstrated that in that nerve centre exists some structures in which the mentioned consumption is specially or exclusively realized by means of one way and not for other different one. Is observed, as well, that in the rats, chicken and lizard, the baskets that surround the Purkinje cells are constituted by basket cells axons and by recurrent collaterals of Purkinje axons and that those structures have an intense aspartate aminotransferase activity, but not glutamic dehydrogenase. The aspartate aminotransferase activity was not observed on the other side, in the perikarya of the Purkinje cells of the related animals. However, there exists intense glutamic dehydrogenase activity. On the other hand, in the toad was not observed baskets with aspartate aminotransferase activity but this enzyme was presented on the other side in the perikarya of the Purkinje cells. All these observations have suggested the possibility that this special utilization of the glutamic acid is in some way concerned with the transmission phenomenons of the nerve impulse.


[Electronmicroscopical and morphometrical study of rat hippocampal synapses].

The neuronal structure and synaptology of the hippocampus of the rat are studied using neurohistological, electron microscopical and morphometrical methods. After Golgi-impregnations the neurons of the hippocampus were classified by reason of special morphological features (pericaryon, dendritic, ramification, course and termination of the axons). The neurons of the hippocampus show from the region CA4 towards the region CA1 an increasing "pyramidalization" which is explained respecting the neuronal structure and synaptic architectonics as the result of a specific presynaptic representation of afferents at the neurons. The high degree of differentiation of the CA1-pyramids speaks for the progressive developmental tendency in the phylogenesis of these pyramids compared to the neocortical neurons. The ultrastructural investigations of the hippocampus show that each individual layer of the regions CA1, CA3 and CA4 has a characteristic synaptic architectonics. In all hippocampal layers the axo-spino-dendritic contacts are the most frequent type of synapses with the structural characteristics of the excitatory synapses; the synaptic contact appears as "Bouton en passage" respectively as "Bouton terminal". The axosomatic synapses of the stratum pyramidale (CA1 to CA3) predominantly are developed as symmetrical contacts with inhibitory function. As the terminals of the basket cells they represent the morphological correlate for the recurrent inhibitation of the pyramids by the inhibitory effecting basket cells. In the supra- and infrapyramidal layers of the regions CA3 and CA4 special contacts are developed for the connection withe the mossy fiber terminals--at the pericarya and the main dendrites as so-called somatic and dendritic protrusions and as micro-dendrites. As has been established for the neocortex, the dendritic spines are the decisive receptive postsynaptic structural characteristic of the hippocampus as well. Pre- and postsynaptic elements show a broad scope of variation in forming their structures. This also applies to the intrahippocampal systems with their highly complex structure which is the morphological expression of an extremely high degree of differentiation. The morphometrical investigations of the ultrastructure of synapses enclose the calculation of the number of synapses per mm3 of the volume of layers, the average individual volume of synapses, the presynaptic portion of volume of the relative volume of cortex of the hippocampal layers as well as the average number and size of the synaptic vesicles. The average number of synapses per mm3 brain tissue runs in CA1 to 5,9 X 10(9), in CA3 to 7,9 X 10(9) andin CA4 to 8,7 X 10(9) synapses per mm3. The average individual volume of synapses amounts to 0,2-0,3 mm3 whereas the average portion of volume of the presynaptic structures per relative cortical volume comes to 14% in CA1, 16-19% in CA3 and 15% in CA4.


Mutant allele frequencies among domestic cats in some eastern areas of Canada: regional homogeneity of factors in Canadian Atlantic Provinces and the French colony of Saint Pierre.

Surveys to determine mutant allele frequencies in domestic cats of the Canadian Atlantic Provinces (Halifax, Nova Scotia; Fredericton, New Brunswick; Charlottetown, Prince Edward Island; St. John's Newfoundland) and the French colony of Saint Pierre, Saint Pierre et Miquelon, reveal a general regional homogeneity for most factors. Despite diverse historical patterns of settlement, a strong common component of origin is indicated. This is tentatively identified as late 18th and early 19th century British. One mutant, polydactyly, which is of New England origin appears to have been distributed largely by loyalist refugees from New England at the time of the American Rebellion. No elements of a specific Acadian (French) character have yet been identified. Siamese cats have been "introduced" to the region in recent years and are now so abundant that they will undoubtedly cause a significant change in some mutant allele frequencies over the next few decades. Interregional exchanges of cats no doubt are contributing to homogenizing the populations of the area, but the practice of sterilization of pets offsets this to some degree.


Retinotectal system of the tortoise, Testudo horsfieldi, Gray (morpho-functional study in the norm and after enucleation).

The optic nerve and mesencephalic optic centre (tectum opticum, TO) of the tortoise, Testudo horsfieldi, Gray, in the norm and after the enucleation have been studies using Golgi's method, electron microscopy and the electrophysiological technique. The optic nerve comprises about 400,000 fibres represented by two classes of axons: myelinated (10%) and unmyelinated (90%). The diameters of the former vary within 0.3-3 mum, of the latter within 0.3-1.1 mum. The neurogramms of the optic nerve contain two components corresponding to the two rates of conduction through different groups of fibres (1.3 musec and 0.5 musec). The stratified synaptic organization of the TO has been investigated. The optic terminals are shown to join in complex synaptic formations at certain levels of the upper layers of the TO (Strata I, II and III). The process of degeneration in the optic system of Testudo is drastically stretched in time. It was demonstrated by the electrophysiological control that the TO potentials induced in response to the nerve stimulation were not registered any longer only 6-6.5 months after the enucleation. Certain groups of retinal fibres of the optic nerve and their terminals in the TO are shown to degenerate differently and asynchronously. Earlier unknown types of destructive changes of the terminals (vesicular, neurofilamentous, glycogen and others) are described. It is suggested that the different types of degeneration of the optic fibres and their terminals are the result of possible biochemical heterogeneity of the retinal ganglious cells. The comparison of the terms and types of degeneration of different groups of nervous fibres in the optic nerve and their terminals in the TO has revealed some correlations suggesting that the myelinated optic fibres produce nervous terminals degenerating by the "dark" type, whereas the unmyelinated optic axons may be subdivided into several groups, each producing nervous terminals subjected to a definite type of destruction ("clear", "vesicular", "neurofilamentous" etc.). The localization of certain groups of therminals at certain levels of the cortical plate of the TO confirms the electrophysiological data on the stratified organization of the retino-tectal projections in the TO of lower vertebrates. It has been shown by the comparison of the results obtained with those reported for Emys orbicularis, L. that the two species have marked differences in the morpho-functional characteristics of the retino-tectal system, neuronic composition of the TO, the character of destructive changes of the terminals after the enucleation and the component composition of polysynaptic complexes and glomerules. Probably these differences may come from the peculiarities of the perception and transformation of visual information in the species.


A simple and sensitive fluorometric assay method for taurine using high-voltage paper electrophoresis.

A simple and sensitive fluorometric assay method for taurine (2-aminoethanesulfonic acid) has been developed. For the separation of taurine, high voltage paper electrophoresis subsequent to column chromatographic procedures was employed. Fluorescent product of taurine was yielded by spraying fluorescamine (4-phenylspiro [furan-2(3H), 1'-phthalan]-3, 3'-dione) and borate buffer on the paper, and the fluorescence was assayed spectro-fluorometrically after eluting with 50% ethanol. The linear relationship between the concentration of taurine and fluorescence developed was achieved over the concentration ranges of 0.5-10 nmoles, and the recoveries obtained were 90-100%. The specificity of this method for taurine was satisfactory and structural analogues involved in the metabolic pathway of taurine did not interfere with the assay. Examples for tissue levels of taurine in various organs of the rat as determined by this new method are also presented.


Effect of strontium on the epiphyseal cartilage plate of rat tibiae-histological and radiographic studies.

Following dietary administration of strontium carbonate, histological and radiographic changes in the epiphyseal cartilage plate of the rat tibiae were examined in the present study. The weight gain of the rat fed a strontium diet was less than that of the control rats. Longitudinal growth of tibiae and endochondral ossification were inhibited by strontium administration. The widths of both proximal and distal cartilage plates increased enormously as has also been shown by other investigators. Sizes of chondroblasts in columns of proximal cartilage plate in rats fed a strontium diet were smaller than those of the control rats and were not different between upper and lower parts. It is suggested that strontium inhibits bone growth through the inhibitory action on the maturation process of chondroblasts and the succeeding endochondral ossification.


Linkage of the cadmium resistance locus to loci on mouse chromosome 12.

The autosomal recessive gene cdm that confers resistance to cadmium-induced testicular necrosis in certain inbred strains of mice has been mapped on Chromosome 12 near varitint-waddler (Va). A 3-point cross involving Va, cdm, and amylase-1 (Amy-1) indicated the following gene order and approximate distances: Va-8-cdm-17-Amy-1. The cdm locus is the first polymorphic locus to be placed on Chromosome 12.


A method to predict the probabilities to homozygous recessives and of heterozygotes.

Where the occurrence of homozygous recessives and heterozygotes is known in the pedigrees of prospective sires and dams, a method and appropriate tables are given to predict the minimum probability 1) that progeny will be homozygous recessive, or 2) that progeny of dominant phenotype are heterozygous.


Effects of palytoxin on isolated intestinal and vascular smooth muscles.

Palytoxin (PTX), the most potent marine toxin isolated from the Zoanthid, Palythoa tuberculosa, was studied to determine the effect on isolated smooth muscles. In guinea pig taenia coli PTX at above 3 X 10(-10) g/ml caused a contraction which slowly subsided under isotonic recording. Under isometric recording PTX at above 1 X 10(-10) g/ml caused a contraction which depended on the spontaneous activity. The PTX-induced contraction was not affected by atropine, tripelenmamine or tetrodotoxin but was inhibited by 5 mM Mg, norephinrphrine, isoprenaline or papaverine. PTX at above 1 X 10(-9) g/ml induced an increase in spike frequency and a slight depolarization accompanied with a contraction when measured using a sucrose gap method. In some cases the spike generation was almost abolished after a long exposure to higher dose of PTX and the developed tension gradually decreased. Under isometric recording PTX caused a sustained contraction in rabbit aorta, dog mesenteric and coronary arteries at above 1 X 10(-10) and 1 X 10(-11) g/ml, respectively, in a dose-dependent manner. The coronary artery was most sensitive among the preparation used. PTX-induced contraction in aorta was irreversible, was not influenced by phentolamine but diminished with 5 mM Mg and disappeared in a D-600 or Ca-free medium. PTX is thus an extremely potent and direct stimulant which acts on smooth muscles.


Cumulative effects of penfluridol, a long-acting neuroleptic drug, as assayed by its behavioral actions.

Penfluridol, a long-acting neuroleptic drug, was repeatedly given to rats well trained on the discriminated avoidance schedule (intertrial interval, 25 sec; warning duration, 5 sec), and accumulation of the effects were investigated by observing the behavioral changes. When penfluridol was orally given in a dose of 2-8 mg/kg once daily for 10 consecutive days, the suppression of avoidance response was progressively enhanced until the 3rd-4th day. But from the 4th day, the maximum level of suppression was maintained during the later medication. On its withdrawal, the avoidance response was gradually restored, returning to the initial level in 3-4 days. When 8 mg/kg was given at 1-2 weeks after the withdrawal, the same suppression was observed as after the single administration of the same dose. The progressive enhancement of suppression in the early half of the medication period evidently indicated the cumulative effect. The degree of suppression during the plateau showed a linear correlation with the dosage, and was estimated to be about 3,5 times as high as in the corresponding single administration.


Horse, ass, and mule chromosomes.

Karyotypes of the horse with 64 chromosomes, the ass with 62 chromosomes, and the mule with 63 chromosomes are presented. The chromosome complements of each species and their mule hybrid are analyzed and compared.


Studies on cyclic nucleotides in the adrenal gland. V. Adenylate cyclase in the adrenal medulla.

Effects of various chemical agents eliciting the catecholamine-release on the adenylate cyclase-cyclic AMP generating system have been studied in the secretory process of the bovine adrenal medulla slices. Cyclic AMP levels were not affected at the interval of the maximal increase of the catecholamine-release by acetylcholine, but increased gradually some time after the end of the release/or at the beginning of the restoration of catecholamine in the medulla tissue. This delayed increase in the medullary cyclic AMP is not attributed to a direct involvement in 'stimulus-secretion coupling process' of the medullary secretion, but rather may be caused by release of intracellular catecholamine.


The genetics of Artemia salina. VII. Reproductive isolation.

Fifteen of 20 gonochoristic Artemia populations are crossfertile with diploid San Francisco shrimps, producing fertile F1 and viable F2 progeny. Partial sex linkage of white eye was observed and frequency of crossing over between the white and sex loci did not exceed the range of values observed in San Francisco shrimps. Possible mechanisms for wide dispersal of this diploid genotype are discussed. Five populations are reproductively isolated from San Francisco shrimps: Mono Lake, Hidalgo, Lake Urmia, San Bartolomeo, and Tunisia. The last two are inter-fertile.


Tissue distribution and characteristics of xanthine oxidase and allopurinol oxidizing enzyme.

Tissue distribution and levels of allopurinol oxidizing enzyme and xanthine oxidase with hypoxanthine as a substrate were compared with supernatant fractions from various tissues of mice and from liver of mice, rats, guinea pigs and rabbits. The allopurinol oxidizing enzyme activities in liver were quite different among the species and the sex difference of the enzyme activity only in mouse liver. In mice, the highest activity of allopurinol oxidizing enzyme was found in the liver with a trace value in lung, but the enzyme activity was not detected in brain, small intestine and kidney, while the highest activity of xanthine oxidase was detected in small intestine, lung, liver and kidney in that sequence. The allopurinol oxidizing enzyme activity in mouse liver supernatant fraction did not change after storage at -20 degrees C or dialysis against 0.1 M Tris-HCl containing 1.15% KCl, but the activity markedly decreased after dialysis against 0.1 M Tris-HCl. On the contrary, the xanthine oxidase was activated 2 to 3 times the usual activity after storage at -20 degrees C or dialysis of the enzyme preparation. These results indicated that allopurinol was hydroxylated to oxipurinol mainly by the enzyme which is not identical to xanthine oxidase in vivo. A possible role of aldehyde oxidase involved in the allopurinol oxidation in liver supernatant fraction was dicussed.


Rat strain differences in the acquisition of conditioned avoidance responses and in the effects of diazepam.

Adult male albino rats of three strains--Wistar, Sprague-Dawley and Holtzman--were trained to press a lever to avoid electric shocks under Sidman-type (R-S interval-20 sec; S-S interval=5 sec) and discriminated avoidance (ITI-15 sec; warning duration=5 sec) schedules, and the acquisition processes of avoidance responses, and the properties of behavioral baselines were investigated. Under both schedules, Wistar strain rats, though showing poorer results than the other two in the beginning, rapidly progressed with the repetitive training, and finally displayed excellent and stable performances. Srague-Dawley strain rats were poorer in performances, with delayed acquisition and prolonged warm-up effect in the within-session performance. The results of Holtzman strain rats ranked between the two. After the establishment of stable behavioral baselines under both schedules, 0.5, 1.0 and 2.0 mg/kg of diazepam were given subcutaneously, and it was found that in Wistar and Holtzman strain rats, the avoidance responses were inhibited together with increase of delivered shocks in parallel to the doses. In Sprague-Dawley strain rats, however, the avoidance responses were conversely improved with 0.5 and 1.0 mg/kg, while such tended to be inhibited with 2.0 mg/kg, with marked concomitant ataxia. As definite strain differences in avoidance response were demonstrated herein, selection of the most appropriate strain should be made when designing behavioral experiments.


Irreversible inhibitory effect of atropine on contractile responses to drugs in isolated rabbit ileum.

Effect of atropine sulfate (atropine) on the contractile responses to acetylcholine chloride (ACh), potassium chloride (K) and barium chloride (Ba) was investigated in isolated rabbit ileum. Tension of the strips suspended in the bath medium (Locke solution, 30 degrees C) was isotonically recorded. The K(ED50)- and Ba(ED50)-induced contractions were not affected by atropine at 3.0 X 10(-4) mM, which reversibly abolished the ACh(ED100)-contraction. After washout of 6.0 X 10(-4) mM atropine, the phasic, but not the tonic, component of ACh(ED50)-, K(ED50)- and Ba(ED50)- contractions was to some extent inhibited irreversibly. On the contrary, such irreversible inhibition of the phasic component was not produced by atropine methylbromide even in the high concentration of 3.0 X 10(-3) mM. The irreversible inhibitions by atropine of 6.0 X 10(-4) mM on the phasic component of ACh- and K-contractions were protected by pretreatment with a high concentration of ACh or K. Further, these irreversible inhibitions by atropine were potentiated by the absence of Ca and were abolished by the increase of Ca content in bath media. These results suggest that the irreversible inhibition of the contractile responses to drugs by atropine in high concentration may be due to the interference with the mobilization of Ca in the deep layer of the membrane, rather than by a blockade of muscarinic receptor sites.


Mitigation of caffeine-induced fetopathy in mice by pretreatment with beta-adrenergic blocking agents.

In a previous experiment, fetopathic effects of caffeine were significantly reduced by pretreatment with propranolol at dosage levels of 2.5 to 10 mg/kg. The present experiments were undertaeken to investigate the relation between time intervals of propranolol pretreatment and its effect on reducing fetopathy. Furthermore, the effect of timolol, another beta-adrenergic blocking agent, on reducing fetopathy was compared with that of propranolol. Propranolol (5 mg/kg) administered 15, 30 or 60 minutes before caffeine treatment significantly reduced the caffeine-induced fetopathy. The optimal effect was found when propranolol was given 30 minutes before caffine. The reduction in fetopathy by timolol pretreatment was comparable to that of propranolol. The results lend support to the hypothesis that the fetopathic effect of caffeine is linked with released catecholamines in material or fetal issues of mice.


[Differential diagnosis of myocardial dystrophy of different etiology developing after physical overexertion].

A total of 46 sportsmen with dystrophy of the myocardium due to chronic physical overexertion were subjected to an electrocardiographic examination in conjunction with functional tests (orthostatic, physical load tests, potassium chloride and inderal tests). The derangement of the repolarization phase on the ECG arising in myocardial dystrophy on account of physical overexertion was found to have a diverse genesis and can be caused by the development of neurodystrophy, disorders in the electrolytes metabolism (substantial losses of potassium) and by myodystrophic cardiosclerosis. The available data made it possible to educe criteria for differential diagnosis of myocardial dystrophy of diverse genesis arising due to physical overexertion.


[Physical work capacity in rheumatic heart defects in children].

Physical performance of children with rheumatic heart diseases depends upon the activity of rheumatism (rheumatism carditis) and specificity distinguishing the given disease. Spiroergometric examinations under a load of 1 w/kg is a highly informative method of evaluating the physical performance capacity of children with rheumatic heart diseases. By using this method it is possible to obtain quantitative and qualitative functional characteristics of their cardiopulmonary system, to disclose latent cardiac insufficiency. The data obtained help improve the rehabilitation of rheumatic patients.


[Arteriosclerosis in men doing physical and mental work].

In males engaged in doing physical and mental work a morphometric study with due consideration given to their condition of nurishment (in a group of practically healthy only), smoking habits and heteditary-familial history with respect to cardio-vascular diseases, was undertaken. Use was made of the autopsy materials obtaned in studying the epidemiology of atherosclerosis in some cities of the USSR. In persons doing brain work, well nourished, with long-standing smoking habits and adverse hereditary-familial history the intensity of atherosclerosis in the aorta and coronary arteries was more pronounced that in individuals doing manual work and exposed to the same risk factors. This gives reason to believe that the occupational factors does influence the development of atherosclerosis (above all in the coronary arteries) to a greater degree than the other ones, mentioned above.


[Age-specific characteristics of functional disorders of the cardiovascular system and respiration in experimental atherosclerosis].

Results of investigations into age-specific peculiarities inherent in the contractile function of the cardiac ventricular myocardium, hemodynamics of the lesser circulation, oxygen supply of the organism in young (6--12 months old) and old (3 1/2--4 1/2 year old) rabbits in normalcy and with experimental atherosclerosis are reported. The contractility of the left ventricle myocardium in old animals was down as compared to the normal in young ones. Induction of atherosclerosis impairs this important function of the myocardium to a still greater degree. In old animals hemodynamics of the lesser circulation is characterized by a rising systolic pressure in the right ventricle and of the tension-time index (TTI) as contrasted against the young one in normalcy and with atherosclerosis. Against this background an additional action on the organism is attended by more pronounced pathological manifestations, i.e. in reactions of the cardiovascular system (including the lesser circulation). The initial manifestations of hypoxia recorded in older animals, as compared to the younger ones in normality, become more intensive in cases of induced atherosclerosis. There is reduced consumption of oxygen, oxygen saturation of arterial and, especially, mixed venous blood, as well as oxygen tension in the arterial blood. The recorded changes are of significance in clarifying the caused and conditions conducive to the development of atherosclerosis and to the intensification of its manifestations in an old organism.


[Vascular plasmorrhagia in experimental hypertension].

The permeability of the vascular wall to the penetration into it of fibrinogen and serum protein in experimental hypertension of rats (ischemic renal and corticosteroid hypertension) was studied. Use was made of the indirect variant of Coons' method involving application of antisera to the mouse fibrinogen and to serum protein of rats. The development of the study models of experimental hypertension in rats was accompanied by an elevated vascular permeability and insudation of the plasma into the vasal wall. The disruption of the vascular permeability was more pronounced in arterioled of different organs of rats with DOCA-saline hypertension.


[Comparative analysis of blood coagulation and various indicators of microcirculation in patients with coronary arteriosclerosis and hypertension in the age aspect].

In patients with hypertensive disease and coronary atherosclerosis the blood-clotting potential increases on account of a rise in the level of procoagulants and inhibition of fibrinolysis. Age-specific differences in the characteristics of the coagulation and fibrinolytic system of the blood are levelled out parallel with the development of atherosclerosis and progressive evolution of hypertensive disease. In patients of advanced age a tendency toward a compensatory increased activity of erythrocytic anticoagulation  factors is noted, finding its expression in a drop of the procoagulants level, and increase of anticoagulants and in a rising fibrinolytic activity. Changes in the state of the conjunctival microcirculation and the retinal hemodynamics correlate with the intensity of the pathological process and shifts in the blood coagulation system.


[Characteristics of pathogenesis of hypoxia in arterial hypertension in old age].

In 135 patients of advanced and senile age with essential hypertension hemodynamics and gas composition of the blood were investigated by the methods of the dye dilution after Stewart-Hamilton, Sechenov-van Slyke and micro-Astrup. The patients of this age category were found to suffer predominantly from the hemodynamic type of essential hypertension characterized by an increased cardiac ejection. Hypoxia develops chiefly after the hypoxic and tissular types. An increased cardiac ejection in patients of advanced and senile age with essential hypertension is considered to be a possible compensatory reaction to manifestations of hypoxia.