Hepatic changes in male ACI/N rats on low dietary levels of sterigmatocystin. Three groups, each consisting of 36 male ACI/N rats, were fed a diet containing 10, 1, or 0.1 ppm sterigmatocystin for life span. There was no dose--effect relationship on tumor incidence or mean survival time. Toxic and preneoplastic changes of the parenchyma such as hyperplastic foci were observed in the liver of experimental groups with dose--effect relation, but hepatocellular carcinoma was observed only in one rat of 10 ppm group. In addition to these lesions, hemangiosarcomas of the liver were also observed in the highest and middle-dose groups, 3/26 and 1/29, respectively. There was not significant difference in the incidence of other tumors in experimental or control groups.


Antitumor effect of thermodifferential chemotherapy with carboquone on Ehrlich carcinoma. A thermodifferential chemotherapy, consisting of systemic administration of antitumor drug and local hyperthermia combined with general hypothermia, was examined and gave satisfactory antitumor results. In search of basic optimal conditions required, this therapeutic system was tested on Ehrlich tumor implanted in the hind limbs of mice. The results obtained were as follows: (a) From the viewpoint of either the antitumor effect or the adverse effect of the therapy, local hyperthermia at 41 degrees for 60 min combined with general hypothermia at 20 approximately 24 degrees was found to be the best thermodifferential condition. (b) The thermodifferential treatment alone without drug administration displayed little antitumor effect. (c) General hypothermia applied not only enhanced the antitumor effect of the drug in loco but also reduced general toxicity of the drug. In the present therapy, carboquone displayed the best antitumor effect among the drugs tested. This suggests that the potentiation of tumoricidal activity of carboquone under the acidic condition produced by cancer cell metabolism in hyperthermia was deeply involved in the effectiveness of this therapy.


The genetics of hexokinase in a mosquito, Culex pipiens. The genetics of hexokinase (HK) variants in a mosquito, Culex pipiens L., was studied using starch gel electrophoresis. Three isozymic forms of HK, all migrating anodally, were present in all three body regions, but in differing proportions. No obvious differences in specificity for three hexose sugars was detected among the three isozymic bands. However, qualitative differences in staining intensity indicate the following order of substrate affinity: glucose greater than fructose greater than mannose. The inheritance of the HK variants is controlled by a pair of co-dominant alleles at a single genetic locus.


Enzyme polymorphism and cyclic parthenogenesis in Daphnia magna. I. Selection and clonal diversity. Genotype frequencies and fecundities were recorded over a period of two years for three polymorphic enzyme loci (Est, Mdh and Got) in a parthenogenetic natural population of Daphnia magna Straus (Crustacea: Cladocera). There was a large excess of heterozygotes at each locus, and some nonrandom association between loci, although 29 different three-locus genotypes were detected. There were small but significant changes in genotype frequencies that did not follow any clear seasonal cycles or overall trends, and the genotypes often differed significantly in fecundity, although the direction of the difference was not constant. These fitness differences were probably not attributable to the specific loci studied.--Models of balancing selection are of two types: segregation-balanced (e.g., heterosis) and competition-balanced (e.g., frequency dependence). Only the latter type can stabilize diversity in a clonal population. The observed selection was not heterotic, but it is not certain that it was stabilizing either. Clonal competition did not lead to victory by a single, fittest clone; genotypic diversity remained high.


Enzyme polymorphism and cyclic parthenogenesis in Daphnia magna. II. Heterosis following sexual reproduction. Cyclical parthenogenesis exaggerates the force of selection relative to recombination and will therefore enhance interlocus effects. Observations of electrophoretic variation in a natural population of Daphnia magna Straus (Crustacea: Cladocera) are interpreted in this light. Sexual reproduction led to Hardy-Weinberg equilibrium, but heterozygote excesses rapidly developed at each of three observed loci during subsequent parthenogenesis. Homozygote fecundity was often lower than that of heterozygotes; this may have been the cause of some of the observed frequency changes. The superior fitness of the enzyme heterozygotes does not imply that selection was necessarily acting on the enzyme loci thermselves, since apparent heterosis is the expected result of linkage disequilibrium.


Fission models of population variability. Most models in population genetics are models of allele frequency, making implicit or explicit assumptions of equilibrium or constant population size. In recent papers, we have attempted to develop more appropriate models for the analysis of rare variant data in South American Indian tribes; these are branching process models for the total number of replicates of a variant allele. The spatial distribution of a variant may convey information about its history and characteristics, and this paper extends previous models to take this factor into consideration. A model of fission into subdivisions is superimposed on the previous branching process, and variation between subdivisions is considered. The case where fission is nonrandom and the locations of like alleles are initially positively associated, as would happen were a tribal cluster or village to split on familial lines, is also analyzed. The statistics developed are applied to Yanomama Indian data on rare genetic variants. Due to insufficient time depth, no definitive new inferences can be drawn, but the analysis shows that this model provides results consistent with previous conclusions, and demonstrates the general type of question that may be answered by the approach taken here. In particular, striking confirmation of a higher-than-average growth rate, and hence smaller-than-previously-estimated age, is obtained for the Yan2 serum albumen variant.


The genetics of Drosophila subobscura populations. IX. Studies on linkage disequilibrium in four natural populations. Gametic frequencies were obtained in four natural populations of D. sub-obscura by extracting wild chromosomes and subsequently analyzing them for inversions and allozymes. The genes Lap and Pept-1, both located within the same inversions of chromosome O, were found in striking nonrandom associations with them of the same kind and degree in all populations studied. On the contrary, the gene Acph, also located within the previously mentioned inversions, was found in linkage disequilibrium with them only in two populations and of opposite directions. This is also the case for the genes Est-9 and Hk, both located within chromosome E inversions. While the gene Est-9 was in strong linkage disequilibrium with the inversions, of the same kind and degree in all populations studied, Hk was found to be in linkage equilibrium. Allele frequencies for the 29 genes studied do not show geographical variation except for the genes Lap, Pept-1 and Est-9, the ones found in linkage disequilibria with the geographically varying gene arrangements. Although mechanical or historical explanations for these equilibria cannot be ruled out, these data cannot be explained satisfactorily by the "middle gene explanation," which states that loci displaying such linkage disequilibria are the ones located near the break points of inversions, while the ones displaying linkage equilibria with them are located in the middle of them. There is no evidence for consistent linkage disequilibria between pairs of loci, except for the closely linked genes of the complex locus, Est-9. This would imply, if it is not a peculiarity of the Est-9 complex, that the linkage disequilibria are found only between very closely linked loci or that, for less closely linked genes, the associations are too weak to be detected by the usual samples sizes.


Cloning of bacteriophage T5 DNA fragments in plasmid pBR322 and bacteriophage lambda gtWES. Bacteriophage T5 was digested with the restriction endonucleases HindIII and EcoRI and the resulting fragments were inserted into the plasmid pBR322 and the bacteriophage lambda gtWES as vectors. Approx. 15% of the phage genome was recovered in recombinant clones. The recombinants were characterized by restriction analysis, DNA/DNA hybridization employing Southern blots, and ability to complement or recombine with amber mutants of T5. The results obtained allow revisions of the physical map of the T5 genome and partial correlation of the physical map with the genetic map.


Comparison of uteroplacental blood flow in normal and in intrauterine growth-retarded pregnancy. Measurements with Indium-113m and a computer-linked gammacamera. Uteroplacental blood flow was studied with a noninvasive method using indium-113m and a computer-linked gammacamera. The blood flow was determined from the ratio of the maximum and the rise time of the isotope accumulation curve of the placenta. Eight pregnancies with intrauterine growth retardation (IUGR) were compared with 11 normal pregnancies. In the IUGR group the mean placental blood flow was only 1/4 of corresponding mean values of the normal group. The difference was highly significant (p less than 0.01).


Hormone serum levels and hormone receptor contents of endometria in women with normal menstrual cycles and patients bearing endometrial carcinoma. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (HPRL), 17 beta-estradiol (E2) and progesterone (P) were estimated in 46 subjects with normal menstrual cycles in whom hysterectomies were performed. Estrogen (ER) and progesterone receptor (PgR) levels in endometrial samples of these patients were estimated, and histological dating of the cycle day was carried out. Similarly, hormone serum levels and ER as well as PgR were estimated in 17 patients with endometrial carcinoma. No correlation between LH, FSH, HPRL and ER as well as PgR was noted in the normal subjects. Correlation between P and ER was observed in this group. Parallel variations between E2 and PgR were recorded in the normal females. In the carcinoma group no correlations between hormone serum levels and receptor contents were found, but ER and PgR correlated with each other. Receptor levels was highest in the well-differentiated group of endometrial carcinoma. The present experiments provide a rationale for progestagen therapy of carcinoma of the endometrium.


Cerebrovascular accidents among users of oral contraceptives. An analysis of Japanese cases. The authors investigated 5 Japanese cases of cerebrovascular accidents among users of oral contraceptives; 4 previously reported and 1 of their own. It is estimated that 200,000 women in this country use oral contraceptives, but, as of the present, only 5 cases of resultant cerebrovascular accidents have been reported. Of particular interest is the fact that 3 of the women had undergone multiple artificial abortions. The appearance of the side effects was dose independent and the symptoms were aggravated for 2 weeks after the cessation of medication.


Suppression of lactation with lisuride.

Suppression of lactation with lisuride. The influence of lisuride, a new semisynthetic ergot derivative, was investigated in women during the puerperium. Treatment with 600 or 900 micrograms lisuride over 14 days (each test group n = 25) caused an immediate drop of elevated prolactin (PRL) levels in all patients in comparison to values seen in normal, nonpregnant women (less than 30 ng/ml). Such a sharp decline was not seen in two control groups of puerperal patients, nursing as well as nonnursing, placebo-treated women. The clinical efficacy in preventing or suppressing lactation was clear cut and comparable to the known PRL lowering effect of bromocryptine. Severe side effects were not observed during lisuride treatment with these dosages. The postsuckling PRL increase was abolished by a single oral dose of lisuride (100, 200, 300 micrograms), similar to that seen with bromocrytine (2.5 mg). The inhibition was dose dependent. Only doses of 200 and 300 micrograms showed, in comparison to a placebo group, a significant long-lasting (greater than 8 h) suppression of PRL secretion.


Time factor in oxygen transfer from mother to fetus. The time factor in the oxygen transfer from mother to fetus was studied by the tcPO2 technique. When a fairly constant fetal circulation made estimation possible, the decrease in fetal tcPO2 synchronous with and due to the uterine contractions in more than 400 events was always delayed 50--60 sec. Since the time lag in the increase in fetal tcPO2 following administration of pure oxygen to the mother was found to be of the same order of magnitude, the placental part of the delay in the oxygen transfer from mother to fetus can be assumed to be 50--60 sec. This determination supports the prevalent hypothesis that type II dips or late decelerations in the fetal heart rate are caused by hypoxia while type I dips or early decelerations are initiated by other factors.


Fate of vasoactive biogenic amines and activity of enzyme phenylethanolamine-N-methyltransferase in rat adrenal gland during the course of pregnancy, parturition and postpartum. Influence of pregnancy, parturition and postparturition upon natural evolution of adrenaline, dopamine and enzyme of adrenaline synthesis, phenylethanolamine-N-methyltransferase in the adrenal gland was studied. Adrenaline content of the adrenal gland showed a progressive decrease from the 14th to the 18th day postcoitum. The mean values for adrenaline remained lower than the value of day 14 throughout the course of pregnancy up to day 21 postcoitum. At parturition (0 to 4 h) adrenaline declined again to its minimum value but was accompanied by an increase in the adrenal adrenaline level 24 h postpartum. The activity of enzyme phenylethanolamine-N-methyltransferase followed a similar pattern of evolution as that of adrenaline during pregnancy and postpartum. Dopamine concentration of the adrenal gland showed nonsignificant increases during days 14--18 postcoitum. At day 20 postcoitum adrenal dopamine was decreased to its minimum value and this decrease persisted up to day 21 postcoitum. At day 22 postcoitum, adrenal dopamine increased sharply to its maximum value but was again back to the level of day 21 at 0 h parturition. At 24 h postpartum, dopamine content decreased maximally again. The results presented here suggest that the content of vasoactive biogenic amines and the enzyme of adrenaline synthesis go through important natural variations during pregnancy, parturition and postpartum from day 14 postcoitum to 24 h postpartum. This phenomenon does not seem to be merely a cyclic effect. All these variations can be attributed to modified endocrine activity of the pregnant animals by correlating natural variations in steroid hormone levels with the observed changes in biogenic amines, since it is well established that most of the hormonal and nonhormonal steroids affect catecholamine regulation. The observed changes in amine levels could have important influence for the termination of pregnancy.


Adaptation of the influenza virus A2-pol 29/69 to the cells of the Chinese hamster lung (CHL) and to the cells BHK-21. In the course of research of the possibilities of adapting the influenza virus serotype A 2-Pol 29/69 to BHK-21 and CHL cells its production was established in the investigated combinations. An indication of virus replication is an increase in infectious and haemagglutination titres within 48 h after infection and gradual increase in haemadsorption. Observation of the influence of trypsin (10 microgram/ml) indicates that trypsin increases the capability of viruses to penetrate the cells. The cytopathic effect was not observed in cells infected with influenza virus.


Effect of mercury nitrate on the histochemical activity of some dehydrogenases in primary cultures of rat kidney tubular cells. Direct effect of sublethal and lethal doses of mercury nitrate on histochemical activity of G6PDH, LDH and SDH was investigated in primary cultures of rat tubular cells. Enzyme activities were studied histochemically after administration of mercury nitrate for periods extending from 5 min. to 24 hrs and also after 2,3,4 and 5 following days. The sublethal doses of mercury nitrate containing 1 microgram and 5 microgram of mercury were found to decrease histochemical activity of the studied dehydrogenases as early as 10 and 15 minutes. Their inhibitory effect was much stronger after 24 h and depended on the dose of mercury compound. The lethal doses of mercury nitrate containing 15 microgram and 20 microgram of mercury depressed the activity of dehydrogenases within 5 min. after administration. The loss of enzyme activities usually preceded the appearance of necrotic signs in the cultured cells. It was also found that the cultured cells of kidney tubules treated with sublethal doses of mercury nitrate were usually able to regain the normal level of the enzymic activity within 2-5 days.


Foot glands in Perna indica and Perna viridis (Pelecypoda: mytilidae) histology and histochemistry. The foot of Perna viridis is found to contain three main types of glands, the white gland, phenol gland and the enzyme gland. But in Perna indica there are only two glands, the phenol gland and the enzyme gland. Besides these, mucous glands are found in both of the species. The shape and size of the cells of these glands vary from species to species. Glycogen and 1 : 2 glycol groups are found in these gland cells. Proteins rich in disulfides and sulfhydryls are present in the phenol glands of both the species and in the white gland of p. viridis but they vary in the intensity of staining. The presence of phenols is confirmed in the phenol gland cells. Phospholipids and lipoproteins are intense in the white and phenol gland cells. They are absent in the enzyme gland. Alkaline and acid phosphatases activity in the enzyme gland cells could be demonstrated. The secretions of these glands help in the formation of the byssus threads. The mucous gland cells are subepithelial localised they secrete acid and neutral mucopolysaccharides together with glycoproteins. Which participate in the attachment of the byssus disc.


[Role of brown adipose tissue in the thermal response to chlorpromazine in rats during cold exposure (author's transl)]. Significance of the intercapsular brown adipose tissue (IBAT) in the thermal response to chlorpromazine (CPZ) during acute and chronic cold exposure was studied in rats. Adult male Wistar-Imamichi rats were exposed to 4 degrees C for 1 (cold-exposed) or 30 days (cold-acclimated). Intraperitoneal injection of 10 mg/kg CPZ caused a more marked and lasted hypothermia in acute cold-exposed rats as compared with that seen in control or in cold-acclimatized rats. Hypothermia induced by CPZ was unaffected by removal of IBAT either in control or acute cold-exposed rats. But in cold-acclimated rats, the removal of IBAT potentiated the hypothermia by CPZ. The relative weight of IBAT in cold-acclimated rats was about 3 times heavier than that in control and acute cold-exposed rats. CPZ had no effect on the relative weight of IBAT in all groups examined. Total lipids in IBAT showed no significant changes following CPZ administration in rats of all groups. In acute cold-exposed rats, serum FFA level progressively decreased after CPZ injection. The noradrenaline concentration in IBAT increased after chronic cold exposure and CPZ suppressed this elevation. The results suggest that the thermogenesis related sympathetic activity in the IBAT plays a mediatory role in thermal response to CPZ during cold acclimation.


[Comparison of the effects of dobutamine with dopamine and isoproterenol on inotropism and chronotropism in the mammalian heart (author's transl)]. The effects of dobutamine on inotropism and chronotropism of the heart were studied in vivo and in vitro and were compared with those of dopamine and isoproterenol. These compounds increased epicardial contractile force and the heart rate of the open-chest, bilaterally vagotomized dog under pentobarbital anesthesia. The dose-ratio for the contraction was [dobutamine: dopamine: isoproterenol = 1:0.8:40] and for the heart rate, [= 1:1:300]. Both drugs augmented the twitch contraction of the isolated dog ventricular papillary muscle with the dose-ratio of [dobutamine: dopamine: isoproterenol = 1:0.7:11]. This mechanical response was associated with an elevation of the plateu voltage and an increase in repolarization of the action potential, but with no alteration of the maximum rate of rise of the action potential, the resting potential and the input membrane resistance. The discharge frequency of the rabbit S-A node pacemaker potential was accelerated chiefly due to an increase in the slope of the diastolic slow depolarization. With concentration of these catecholamines for the equivalent positive inotropic potency on the papillary muscle, this effect of isoproterenol was more potent than the effects of dobutamine and dopamine. These positive inotropic and chronotropic actions of the catecholamines were abolished by a beta-receptor antagonist. Those actions of dopamine were markedly reduced by reserpine pretreatment. In addition, dobutamine had little vascular effect. These results indicatte that dobutamine has a positive inotropic effect and a less positive chronotropic effect and that such is due to the direct action on the ventricular myocardium and the S-A node through beta 1-adrenergic receptors.


[Pharmacological effects of dobutamine and several catecholamines on various smooth muscles (author's transl)]. Pharmacological effects of dobutamine (DOB), a positive inotropic drug, on smooth muscles were compared with those of catecholamines such as norepinephrine (NE), epinephrine (E), isoproterenol (ISO) and dopamine (DA). DOB acted as a partial agonist and simultaneously as an antagonist on alpha-adrenergic receptors in the thoracic artery. Large doses of DOB induced uterine contraction in rabbits, but antagonised the contraction of the vas deferens of guinea pigs, as was induced by electrical stimulation. However, DOB showed a potent activity, similar to that seen with NE or E as an alpha-adrenergic agonist, on the portal vein. Doses of DOB required to produce a relaxation in the trachea of guinea pigs both in vitro and in vivo were 1/250 and 1/600 of ISO, respectively, and were considerably less regarding inhibition of uterine motility in rats. Inhibiting activity of DOB on the transport rate of intestinal contents in mice and gastro-intestinal motility of rabbits was much less than the activity seen with ISO, E and NE. Spasmolytic activity of DOB was also less than that of ISO, NE and E, but was more than that of DA. It is concluded that DOB is a more selective beta 1-agonist than ISO because of its weaker activity on alpha- and beta 2-receptors. The alpha-agonist activity of DOB in the portal vein was however, potent.


[Simulation of K-contracture curve in smooth muscle (author's transl)]. 40 mM K-induced isometric contracture of guinea pig taenia coli in the presence of 30 microM dantrolene showed a rapidly rising peak followed by a plateau and then a low sustained tonic contraction. The plateau was delayed by low Ca so that two phasic contractions, fast and slow, were separated from each other. In K-contracture after 15 sec contact with normal Ca following low Ca condition, the fast phasic contraction but not the slow one regained its tension depressed by preceding low Ca, while the slow phasic contraction recovered from its delay. In the presence of 0.2 microM verapamil, K-contracture consisted of the fast phasic contraction without plateau and of the low tonic contraction. The results suggest that K-contracture in the normal state consists of three components, the fast and slow phasic contractions and the tonic contraction, and that dantrolene inhibits a tonic contraction, whereas verapamil inhibits the slow phasic and the tonic contraction. Thus, the contraction curve of each component was tentatively expressed by exponential function, and for simulation of the observed curves a computer was utilized to synthesize the curves using the components of varying parameters. The simulation was successful when based on the above suggestion.


[The role of lysosomal enzymes in adjuvant-induced uveitis in rabbits (author's transl)]. Acid phosphatase and beta-glucuronidase were used as marker enzymes of lysosome, and their role in adjuvant-induced uveitis was studied. These enzyme activities in the iris-ciliary processes were increased in the inflamed tissues. Changes in these enzyme activities in the tissues paralleled the development of uveitis. While protein concentration in the aqueous humor as a parameter of vascular permeability was significantly correlated with these enzyme activities, there was no correlation in the leucocyte counts in the aqueous humor. Topically applied dexamethasone reduced the increase in the aqueous protein, the leucocyte migration and the swelling of the iris-ciliary processes, while topically applied indomethacin reduced only the leucocyte migration among these inflammatory parameters. Acid phosphatase activities in the inflamed tissues were reduced also by dexamethasone, but not by indomethacin.


[Interaction of d-pseudoephedrine with water soluble extracts of Platycodi Radix on acute toxicity (author's transl)]. Effect of various combinations of Platycodi Radix water soluble extracts (Pla), 1-ephedrine (1-eph), d-pseudoephedrine (d-pseudo) and Ipecacuanhae Radix water soluble extracts (Ipe) on acute toxicity were examined in mice. Oral LD50 of Ipe, d-pseudo and 1-eph was 490 (415--578) mg/kg, 1550 (1360--1767) mg/kg and 1400 (1102--1778) mg/kg, respectively, while that of Pla was over 10 g. LD50 of Pla Ipe, d-pseudo and 1-eph given intraperitoneally was 1400 (1228--1596) mg/kg 235 (210--263) mg/kg, 245 (229--262) mg/kg and 300 (259--348) mg/kg, respectively. The ratio of the predicted LD50 value, which was calculated on the assumption that each component drug would be additively toxic when combined, to the observed LD50 value was used for comparison. The combination of d-pseudo with Pla gave a significantly greater LD50 value than the predicted LD50 value, while the combination of 1-eph with Pla showed a LD50 value which was not significantly different from Finney's additive model. A combination of d-pseudo with 1-eph and Ipe, and of 1-eph with Ipe showed a LD50 value which was not significantly different from that of the additive model.


[Hypotensive effects of diltiazem hydrochloride in the normotensive, spontaneously hypertensive and renal hypertensive rats (author's transl)]. In conscious and anesthetized normotensive rats, intravenous administration of diltiazem (0.1--3 mg/kg) produced a dose-related decrease in blood pressure. Administration of diltiazem (1--50 mg/kg) into the duodenum of anesthetized rats also reduced the blood pressure in a dose related manner. In parallel with the change in blood pressure, the heart rate increased in conscious rats and decreased in anesthetized animals. Such an increase in the heart rate was suppressed by pretreatment with propranolol. Similarly, in conscious spontaneously hypertensive rats (SHR), diltiazem dose-dependently decreased the blood pressure and increased the heart rate after intravenous administration (0.03--1 mg/kg). Oral administration of diltiazem (100 mg/kg) also reduced the blood pressure of SHR. In addition, the progressive increase in blood pressure in young SHR was significantly suppressed by chronic oral administration of diltiazem (30 mg/kg). The blood pressure in conscious renal hypertensive rats was also decreased with diltiazem (50 mg/kg p.o.). On the other hand, it was demonstrated that the pressor responses to norepinephrine and angiotensin II in the anesthetized normotensive rats were non-competitively inhibited by intravenous administration of diltiazem at a dose which had no effect on the blood pressure.


[Comparative studies on the chemical modifications of Ehrlich ascites tumor cell membranes by hydrophobic drugs (cepharanthine, papaverine and cholesterol) (author's transl)]. Comparative studies were done on the actions of hydrophobic drugs (cepharanthine, papaverine and cholesterol) regarding chemical modifications of Ehrlich ascites tumor cell membranes. Changes in membrane potential monitored by using cyanine dye (diS-C3-(5)) were induced by cepharanthine and papaverine, but not by cholesterol. Increase in membrane permeability of K+ ions induced with lysolecithin was strongly inhibited in the order of papaverine, cholesterol and cepharanthine. Oxygen uptake by the cells was also strongly inhibited by papaverine, but the inhibitory effect by cepharanthine was little and cholesterol had no effect. Membrane fluidity was decreased in the order of cholesterol, cepharanthine and papaverine. From these results, it was suggested that papaverine maintained the compartmentation of K+ ion and membrane fluidity by regulating the intracellular mitochondrial metabolism or by inhibiting the membrane bound ATPase nucleotidase activity. The membrane stabilizing effect of cepharanthine and cholesterol probably was due to decrease in the membrane fluidity because of the hydrophobic association to the lipid bilayer of the cell membranes.


[Cathartic activity of spasmogens in mice, rats and guinea pigs (author's transl)]. To examine the effect of spasmogens on propulsive motility in the intestine, cathartic activity of drugs was investigated. Mice, rats and guinea pigs were individually observed in cages with 20 separate small rooms in which a sheet of filter paper covered the botton of case for observation of feces. The effect was evaluated 1 hr after drug administration. Cathartic activity of spasmogens was the most marked in mice followed by rats, but was rarely observed in guinea pigs. Cholinergic drugs and cholinesterase inhibitors had a cathartic effect in mice and rats, but the activity differed. Drugs such as acetylcholine and physostigmine produced a low cathartic activity even at sublethal and lethal doses. Other drugs as bethanechol, pilocarpine and neostigmine had a dose dependent cathartic effect at doses below lethal ones and were found to be clinically useful for intestinal relaxation after laparotomy. Among autacoids which contract the intestine by direct action on smooth muscles, histamine and bradykinin had no cathartic effect in mice and rats. 5-HT and prostaglandin E2 were dose dependent with a marked cathartic effect in both species. 5-HTP produced the same cathartic activity as that seen with 5-HT in mice, but had no cathartic effect in rats. The cathartic effect of BaCl2 was low, but dose dependent in both species. We recommend this method for the study of the effect of various compounds on the propulsive motility of the intestine.


[Effects of benzodiazepine derivatives on gamma-motor system in rats (author's transl)]. Effects of four benzodiazepine derivatives on gamma-activity were examined in the anesthetized rat. Diazepam and 5-(o-chlorophenyl)-1-methyl-7-nitro-1, 3-dihydro-2H-1, 4-benzodiazepin-2-one(ID-690) in a dose of 2.5 mg/kg (i.p.) showed depressant effects on gamma-activity. The depressant effects of 5.0 mg/kg (i.p.) lasted for more than 60 min. Nitrazepam had a slightly weaker effect than the above two drugs and the effect was evident after an administration of 5.0 mg/kg; the effect of 10 mg/kg(i.p.) lasted for more than 90 min. The effect of clonazepam was much weaker than effects of the other three drugs. A dose of 20 mg/kg(i.p.) was required to produce an obvious depressant action, and the effect appeared after a longer latency of about 20 min. ID 690 (5.0 mg/kg, i.p.) depressed the augmented response of the gamma-activity in response to pinna stimulation. The effect of diazepam on the augmented responses was observed with the same dose. In contrast, much higher doses of nitrazepam and clonazepam were required to induce an obvious depressant effect on the augmented gamma-activity. It is suggested that the difference in potency in depressing gamma-activity of these derivatives is one of the factors characterizing their pharmacological properties.


[Effects of oxythiamine and pyrithiamine on rat liver. --Biochemical and morphological changes in the thiamine deficient rat (author's transl)]. We studied biochemical changes in the rat liver in a thiamine (T) deficient state as induced by oxythiamine (OT), pyrithiamine (PT) and thiamine deficient diet (TDD) and simultaneously observed morphological changes under light and electron microscope. Severe loss of weight was observed in the OT treated rats fed on TDD (OTD) and such was frequently accompanied by a complete loss of righting reflex. Biochemical changes commonly found in T deficient groups were decrease in serum total protein, alkaline phosphatase activity and liver lipids, and increase in serum total cholesterol and transaminase activity. Microscopically, most of the liver cells were atrophied and necrosis was observed in the OTD group. Electron microscopically, ultrastructural changes revealed active Kupffer cells, microvilli and Golgi apparatus, and decrease in rough endoplasmic reticulum (rER) associated with increasing detached ribosomes and smooth ER. Abnormal nucleus and mitochondria were found in the OTD group. These results suggest that a T deficiency occurs readily and easily within a short time when a T antagonist, particularly OT, is used together with the TDD, while a much longer time is required to produce a T deficiency with only the TDD.


[Effects of d-pseudoephedrine on tracheo-bronchial muscle and the cardiovascular system (author's transl)]. The action of d-psuedoephedrine on bronchial smooth muscle, respiratory resistance and blood pressure was compared with that of 1-ephedrine. The following results were obtained. 1) Administration of dl-isoproterenol on isolated guinea pig tracheal muscle previously constricted with acetylcholine (ACh) or histamine (his) was the most effective and d-pseudoephedrine had the same effect as 1-ephedrine. The relaxing effect of dl-isoproterenol, 1-ephedrine or d-pseudoephedrine on ACh or His induced tracheal constriction was competitively antagonized by the pretreatment of propranolol. 2) The intravenous or sublingual administration of d-pseudoephedrine on the increased respiratory resistance induced by His produced the same effect as 1-ephedrine. 3) The increase in blood pressure with d-pseudoephedrine was weaker than that of 1-ephedrine. 4) When 1-ephedrine of d-pseudoephedrine was repeatedly injected into the same animal, signs of tachyphylaxis were observed. It was found that d-pseudoephedrine, the main alkaloid of Ephedrine Helba, exhibited the relaxing effect on bronchial smooth muscles as did 1-ephedrine. The respiratory resistance increased by His was inhibited by the sublingual administration of d-pseudoephedrine and 1-ephedrine.


[Effects of diazepam on rage reaction elicited by the lateral hypothalamus (LH) and on single unit activities in the LH and the basal medial amygdaloid nucleus (Abm) in cats (author's transl)]. Effects of diazepam were examined on the whine reaction elicited by LH stimulation and on unit activities in the LH and Abm in cats. The spontaneous firing frequency of Abm neurons was 5 to 30 spikes/sec and in all 6 neurons isolated the firing frequency increased by non-nociceptive and/or clap-stimulation. Diazepam decreased the spontaneous firing frequency of all Abm neurons isolated and the increased firing frequency elicited by non-nociceptive and/or clap-stimulation was also depressed by diazepam. The spontaneous firing frequency of neurons in the LH was 4 to 5 spikes/sec and all 6 neurons isolated firing frequency increased by non-nociceptive stimulation. Only one of 6 neurons, however, was activated by clap-stimulation. Diazepam decreased the spontaneous firing frequency of all LH neurons. Out of 6 neurons responsive to non-nociceptive stimulation, 3 were also depressed by diazepam. The other neurons were not affected by diazepam. These results suggest that depressed action of diazepam on the whine reaction elicited by the LH stimulation may be related to the decrease of firing in the Abm and/or the LH by diazepam.


[Effects of gamma-oryzanol on norepinephrine contents in the brain and stomach of rats (author's transl)]. Norepinephrine (NE) content in the brain slightly but significantly increased when gamma-oryzanol (100 mg/kg, s.c.) was given once daily for 1, 5 or 10 days, while NE in the gastric area was not affected. The turnover rate of brain NE tended to decrease with the administration of gamma-oryzanol. From the results, it is likely that successive doses of gamma-oryzanol increase brain NE by inhibiting degradation or release of NE.


[Analgesic activity of a non-steroidal anti-inflammatory agent, tolmetin sodium in experimental animals (author's transl)]. Effect of tolmetin sodium on the pain-like responses caused by various nociceptive stimuli was examined in experimental animals. Tolmetin sodium showed a potent inhibitory activity on the acetic acid-induced writhing in mice and rats, and its potency, (ED50 = 23.4 and 3.01 mg/kg, p.o.) was about 2.4--10.3 times that of ibuprofen and aspirin. The hypertension induced by intraarterial injection of bradykinin toward the spleen of dogs was inhibited by tolmetin sodium (ED50 = 80 mg/kg, i.v.), but the hypertension by a simultaneous injection of bradykinin and PGE1 was not inhibited by tolmetin sodium and sulpyrine, though pentazocine inhibited both hypertensions. The pain-like response caused by pressing mechanically the inflamed paws or joints of rats induced by kaolin-carrageenin or adjuvant was inhibited by tolmetin sodium (30--100 or 20--40 mg/kg, p.o., respectively), and the potency was approximately equal that of ibuprofen and phenylbutazone. Tolmetin sodium produced a significant inhibition of the pain-like response induced by electrical stimulation of tooth pulp of dogs, but showed no effect when the methods of Haffner and D'Amour-Smith were applied to mice. Anti-writhing action of tolmetin sodium was not antagonized by naloxone. From these results, it was concluded that tolmetin sodium has a potent inhibitory activity on the pain-like responses induced by the chemical nociceptive stimuli and by the mechanical pressure stimulus of the inflamed tissue, especially on the writhing. The analgesic activity probably involves a peripheral mechanism.


Lithium treatment in affective disorders from viewpoint of transcultural psychopharmacology: therapeutic plasma level. The double-blind controlled studies on lithium carbonate therapy conducted in Japan have demonstrated that there are no significant correlations between clinical effectiveness and serum lithium level in manic patients as well as depressed patients and also that Japanese patients seem to require less lithium carbonate than their U.S. counterparts as an effective therapeutic dose, both in terms of mean maximum dose and serum level. Although any international comparison cannot be fully valid without using transculturally standardized assessment, the data of these studies were examined from the viewpoint of transcultural psychopharmacology and compared to the data from studies in U.S.A.


Three cases of unipolar delusional depression responsive to L-dopa. We reported three cases of unipolar delusional depression which took a characteristic two-stage clinical course. Anxiety and agitation with persecutory delusions predominated the picture at first, but they were soon replaced by severe psychomotor retardation or stupor associated with delusions of poverty and guilt. The administration of L-Dopa in the latter stage brought about a rapid improvement both in mood and psychomotor activity. We considered these cases in the light of the recent biochemical studies on affective psychosis.


Dectection of spinal cord lesion using skin electrode recordings of spinal evoked potential. The multi-channel recording of somatosensory spinal evoked potential (SSEP) was carried out on 30 patients with various neurological disorders. In some cases, SSEP changes corresponded well with the lesioned level. In general, the lesions of thoraco-cervical level were difficult to detect, because the appearance rate of SSEP peaks are reduced over the thoraco-cervical spine even in normal controls. In cases with spinal type of MS, SSEP revealed marked changes and subclinical sensory demyelinating lesions were detectable. Chronological SSEP recording in patients with acute transverse myelitis revealed functional improvements corresponding with clinical recovery. Surface and non-invasive SSEP recording is useful for detecting lesions in the spinal cord or peripheral nerves. It also offers valuable information about chronological modification of the lesions, and may reveal subclinical changes in certain neurological disorders.


A case of hypogonadotropic eunuchoidism associated with familiar periodic paralysis--induction of paralytic attacks by testosterone administration. A case report was made of a 24-year-old man suffering from hypogonadotropic eunuchoidism associated with a hypokalemic type of familiar periodic paralysis. The attacks were observed only during the period of continual administration of the oil solution of 115.7 mg of testosterone enanthate and 20.0 mg of testosterone propionate, intramuscularly as a depot. From the findings on this patient, it was concluded that testosterone might possibly play a role in the occurrence of attacks in the case of periodic paralysis.


Wilson's disease; increased aluminum in liver. Interaction of trace metal metabolism was studied in a patient with Wilson's dease. Atomic absorption analysis showed markedly increased urinary excretion of copper and aluminum and an increased aluminum content was found in the biopsied liver by neutron activation analysis. These findings suggest a complicated pathogenetic mechanism involving other metals besides copper in the Wilson's disease.


First autopsy report of a multiple sclerosis case in Hokuriku District of Japan. The first autopsy of a case of multiple sclerosis from the District of Hokuriku was reported. The patient, a 50-year-old house-wife, born in Toyama Prefecture, had noticed a paresthesia of her face, fatigue, numbness and weakness in the right limbs, dimness of vision and gait disturbance at ave 44. Furthermore, in the course of the disease, she had suffered from visual disorder, tetraplegia, hyperreflexia, pyramidal signs and cerebellar syndroms such as dysarthria, nystagmus, intention tremor and ataxia. She also showed symptoms of euphoria and dementia. After a course of six years she died of bronchopneumonia. Remissions and exacerbations were noted four times during her clinical history. Histopathologically, there were many recent and old demyelinating lesions of varying sizes and shapes in all parts of the central nervous system, namely the cerebrum, brainstem, spinal cord and optic nerve. In contrast to the clinical symptoms, the cerebellum itself revealed less plaques than the other areas of the brain. According to the observed distributions of the lesions, our case can be classified as belonging to the optico-cerebro-spinal type in the Ikuta and Zimmerman classification. The demyelinated lesions were characterized by a perivenular distribution of the plaques, lack of tissue necrosis, paucity of inflammatory reaction and marked fibrous gliosis of varying degrees.


Frontal kindling in rabbits and its influence on visual and auditory evoked response. Frontal kindling in rabbits, prolongation of the duration of afterdischarge concomitant and clinical manifestations and the epileptic foci (primary and independent secondary foci) were revealed. Auditory and visual evoked responses were recorded after completion of the kindling phenomenon. 1. Electrical stimulations, 300 microA, 60 Hz. 1 msec in duration, 2 sec train, were applied once a day. Clinical manifestations were divided into five stages: 1) the arrest of behavior or no response, 2) the adversive movement with a tonic and/or clonic convulsion of left paw, 3) the adversive movement following mastication, facial spasms and postictal stupor, 4) falling down abruptly and generalized convulsive seizure, and 5) generalized seizure followed by rotatory movement, vocalization and myoclonus. The appearance of five generalized convulsions was defined as a completion of the kindling phenomenon. 2. The duration of afterdischarge increased stepwisely from 2--3 sec to more than 400 sec. However, there was no constant duration of AD even though the animal showed generalized convulsion after completion of the kindling phenomenon. 3. Visual and auditory evoked responses were recorded after completion of kindling. There was a change in the auditory evoked response but not in the visual. A shortening of the latency of P2 component (73.3 msec in peak latency), N2 component (146.7 msec in peak latency) and amplification of the amplitude of N2 component were noticed. Thus, the intermittent weak electrical stimulation on the frontal cortex in rabbits induced generalized convulsion and produced primary and independent secondary epileptic focus on EEG, and the change of auditory evoked response was recognized in kindled animals.


[The anti-allergic effect of an oral calcium preparation. Controlled double-blind study]. The effect of an orally applied calcium preparation (Frubiase Calcium forte) was investigated and compared with a placebo in 20 adolescent patients submitted to a random double-blind test on the immediate allergic reaction. The prick test with histamine and grass pollen mixed extract showed a highly significant statistical decrease (p less than 0,001) of wheal extension after an oral dose 1 x 6 Frubiase Calcium forte fluid ampoules, when compared to the test before application.


[Vascular nevi and tumors of the skin].

[Vascular nevi and tumors of the skin]. Diagnosis and classification of dysontogenetic and neoplastic lesions of blood- and lymph-vessels depend upon the presence or absence of proliferating vascular elements and of non-involutive connective tissue and muscular wall structures. Angiectatic and angiokeratotic nevi, capillary and cavernous angiomas, glomangiomas and malignant vascular tumors are presented in a survey with special reference to frequent diagnoses.


[The effect of the membrana interossea antebrachii on the turning movement of the hand]. In human cadaveric forearm specimens the membrana interossea antebrachii was examined morphologically and biomechanically. Macroscopical, submacroscopical and microscopical findings reveal new facts about the structure, texture and the microscopical details of the membrana interossea. By measuring the interosseous space and by straingage measurement of elongation of the interosseous membrane during pronation and supination the influence of the membrana interossea antebrachii on pronation and supination of the hand was analyzed biomechanically.


[Therapy of hyperlipoproteinemia. Additive effect of the lipid-lowering agent d-triiodothyronine during dietetic treatment]. Combined treatment of hyperlipidaemia with a 1000-calorie-diet and d-triiodothyronine resulted in a lowering of serum cholesterol, triglycerids and lipoproteins. Concerning cholesterol and beta-lipoproteins there was an addition of reducing effects of simultaneous dietary and drug treatment. Triglycerids are influenced by the combined treatment or by dietary treatment alone to the same extent. The levels of free fatty acids rise during combined treatment while there is no change by diet alone. These observations indicate a most successful lowering of cholesterol and beta-lipoproteins by the combined therapy, but there is an increase of free fatty acids as a metabolic side effect of d-triiodothyronine.


[Neomycin resorption from the normal and inflammatorily altered peritoneum]. The clinical problem of the resorption of Neomycin from the normal and inflammatory altered peritoneal cavity was studied experimentally in the guinea pig. In a total of 197 guinea pigs the pharmacokinetics of Neomycin in serum and perilymph after injection subcutaneously or in normal and inflammatorily altered peritoneal cavity of the guinea pig were determined. No statistically significant difference between the pharmacokinetics of Neomycin in serum and perilymph of the different series could be found. The possible clinical relevance of the results is discussed.


[Psychotic depression. 1. Classification, etio-pathophysiology, epidemiology, sympatomatology, diagnosis]. The term "depression" is used to describe a normal mood, a medical symptom, and a collection of psychiatric symptoms. As a normal mood, depression is a common human reaction to a significant loss; as a medical term, it is also used to describe the sadness seen in patients who have other severe medical and psychiatric disorders. Most often, however, "depression" refers to a group of psychiatric syndromes or illnesses with well defined symptoms only one of which is sadness. Depression syndromes are probably universal. There are accounts of depressive illness throughout history from almost every human society. The universality of depressive illness is also reflected in the frequency of depression as a theme of the world's great literature. Studies of the biochemical correlates of psychotic depression have focused on two major hypotheses. The first proposes that affective disorders result from functional changes in the central noradrenergic systems. The second postulates that the primary abnormality is in central serotonergic pathways. These two hypotheses are supported by the pharmacological effects of antidepressant drugs.


[Diagnosis of prostatic carcinoma].

[Diagnosis of prostatic carcinoma]. Carcinoma of the prostate can be easily detected by rectal examination which is a part of the routine check-up for the early recognition of cancer in males after 45 years. Approximately 14,000 to 16,000 new cases with prostatic carcinoma are found in West-Germany annually. In former times patients with advanced carcinoma were treated with little success. Today the aim is the early detection of the disease in a curable stage. Exact clinical staging and morphological grading is fundamental for optimal therapy.


[Neuropharmacologic and neurotoxic studies on the Renshaw mechanism]. Recurrent axon collaterals of alpha-motoneurons formed with Renshaw cells cholinergic synapses. The effects of ethanol, pyritinol-HCl and type A botulinum toxin on this central nervous cholinergic synapse were studied. Ethanol caused a marked increase in Renshaw cell activity. The excitatory influence effects above all the Renshaw cell synapses directly. Pyritinol-HCl decreased the activity of Renshaw cells. The increase of Renshaw cell activity, caused by ethanol, changed into a decrease after pyritinol-HCl application so that pyritinol-HCl has a protective effect on this cholinergic system. The injection of the neurotoxin botulinum type A into the muscle or even into the ventral root was without effect on the Renshaw cell activity during the test period. Only the direct application of botulinum toxin type A into the spinal cord led to a decrease of the early and the late response of Renshaw cells. The results are discussed and the clinical relevance is considered. The cholinergic Renshaw cell synapse is not only considered as a special synapse but also as a model for cholinergic transmission which is assumed in several parts of the central nervous system.


[Vaginal metastases as the ist signs of primary occult hypernephroid kidney neoplasms]. Based on the literature and own observations it is pointed out that in cases of vaginal tumors as a rule a consequent search for tumors of the kidneys is necessary, because vaginal tumors may be metastases of primarily not identified hypernephroid carcinomas. The frequency of such metastases is reported to be about 2%. A search for kidney tumors is necessary, if histological findings of the vaginal tumor are clearly suspect for hypernephroid carcinoma, or if it cannot be clearly identified as a primary vaginal tumor or--as a metastasis--gives no certainty to be a metastasis of a primary tumor of other localization. Because of the relative statistical frequency of vaginal metastases from carcinomas of the kidneys a consiliary gynecological check up is necessary if the diagnosis of the tumor was primarily a urologic one to ensure that there are no vaginal metastases. Further diagnostic and therapeutic procedures are discussed.


[Hormonal contraception and lipid metabolism. Prospective and retrospective studies of lipid metabolic parameters during the use of contraceptives]. Remarkable changes of several parameters of lipid metabolism were observed in a retrospective study of women, who had used different oral contraceptives for a longer time, in comparison with women without any hormonal contraception. In contrast, under the conditions of a prospective double-blind study no statistically significant alterations of the same parameters were seen under the use of two oral contraceptives different in dosage. Nevertheless, oral contraceptives should not be prescribed to patients with hyperlipidaemia.


[The special case: rare gynecologic emergency of uterine perforation in placenta percreta]. The term placenta percreta signifies a penetration of placenta villus growing through the myometrial wall to the serosal side. The incidence has been reported to vary between 1:1000 to 1:70 000. Thus uteral rupture as a result of placenta percreta is a rare event. Signs of severe shock as leading signs predominate. Immediate laparotomy with hysterectomy is the therapy of choice. The final diagnosis is based on histology.


[The special case: squamous epithelial carcinoma of the cervix after cryotherapy in a 23 year old patient]. A case report is given of a 23 year old woman with an invasive squamous cancer of the uterine cervix 10 months after cryotherapy of an "ectopic area". The development in this case is reason for stressing the indispensable points in cryo-, thermo- and laser-therapy of the cervix: 1. proper pretherapeutic evaluation and documentation by means of cytology, colposcopy, and histology; 2. adequate extent of therapy; 3. exact follow-up after treatment.


[Prevention of thrombosis during therapy of gynecologic neoplasms]. Blood coagulation, but especially diagnosis, prophylaxis and therapy of thromboembolic complications are of special importance in gynaecology. Besides connatal factors acquired factors are to be considered. Carcinomas enhance hypercoagulation, especially if x-ray treatment is performed. There exists a great number of diagnostic and therapeutic possibilities, though adequate prophylaxis is much more efficient than extensive diagnosis. Among the many possibilities of prophylaxis of thromboembolic complications the subcutaneous application of heparin in subclinical doses is especially efficient. Application is simple, paractically painless, additionally healing is enhanced by heparin.


[The protective effect of piracetam during delivery]. It was evaluated by continuous cardiotocogram-, tcpO2-and EEG-registration sub partu to what extend these parameters are influenced by application of Piracetam (10 g i.v./h) to the mother. A group of 26 primigravida between 18 and 23 years of age with normal course of delivery at term was analyzed. Piracetam was applicated to 17 patients in the beginning of cervix dilatation, whereas the other patients got Laevulose as a placebo infusion. The results permit the conclusion that Piracetam provides a stabilization of cerebral functions with a certain resistence against transient hypoxia during the expulsion period. The EEG-registration demonstrates after application of Piracetam an activation of alpha-waves with simultaneous reduction of delta-waves, the CTG shows a reduced quantity of decelerations during the expulsion period. The data obtained by computerization correlate with the Apgar-Index (fetal outcome) after application of Piracetam, which was better than 9 in all cases.


[Surgical treatment of axillary hyperhidrosis]. Surgical treatment of hyperhidrosis axillaris is described using a housed razor blade to remove subcutaneous sweat glands.


[Can we defend a 10 per cent rate of cesarean sections? Experiences with 2000 cesarean sections (ending)]. During a period of 13 years 2000 Caesarean sections were performed in a total of 20 584 deliveries. That means a frequency of 9,7%. Maternal mortality was zero. Maternal morbidity was 72% if one includes all minor complications. Counting only the major postoperative complications the morbidity in our Caesarean sections was not higher than 1%. Perinatal mortality was 2,2%. If one excludes all premature children and not viable malformations, a perinatal mortality of 0,65% results. Conditions for good results in mother and child after Caesarean section are: prospective management of delivery, consequent prenatal care, optimal supervision in the delivery room, favourable peri-operative circumstances, elective prophylaxis with antibiotics and elective prophylaxis against thromboembolism.


[Selective proximal vagotomy without drainage in uncomplicated duodenal ulcer. Technic and frequency of recurrence]. 899 cases of slective promimal vagotomy were operated between 1974-1978 in the Surgical University Hospital Erlangen. The underlying disease was in all cases a chronical duodenal ulcer. The primary operative mortality was 0,6%. Intraopeatively measurements to control the sufficiency of the vagotomy Burge and Grassi proved to be necessary. We could verify by endoscopy a recurrence rate of 5,8-16,5% in the 1.-4. postoperative year. Only 58% of the recurrences could be found by x-ray investigations. 75-82% of the patients had a clinically perfect and good result. In patients with a proven recurrent ulcer there was nevertheless a good clinical result in 64%. Clinical results and complaints of the patients are therefore not sufficient as follow-up after selective proximal vagotomy and early detection of a recurrent ulcer. We believe, that one endoscopy per year is necessary.


[Ophthalmomimics. Polygraphic EMG study on oculo-facial simultaneous movements and functions of the autochthonous ear muscles]. Ophthalmomimic is the interaction between the extraocular eye muscles and the mimic muscles. Beside their original phylogenetic assisting function in looking and hearing, the ophthalmomimic muscles now serve in psychological communication: The play with the white of the eye ball can be interpreted as devotion ("to turn a blind eye to"); attention ("to be all eyes"); caution ("to have small eyes and to prick up one's ears"). Further on are examined function and innervation of the involuntary M. retro-auricularis (M. transversus auriculae) of the external ear, so far neglected. Practical diagnostic use could be shown, among others, in early ocular forms of myasthenic syndromes and by the help of the oculoauricular phenomenon for the differentiation between nuclear and peripheral-distal pareses of the abducens nerve.


Hydrazonopropionic acids, a class of hypoglycemic substances. 1. Hypoglycemic effect of 2-(phenylethylhydrazono)- and 2-(2-cyclohexyl-ethylhydrazono)-propionic acid. The two hydrazone-compounds 2-(phenylethylhydrazono)-propionic acid (PEHP) and 2-(2-cyclohexyl-ethylhydrazono)-propionic acid (CHEHP) significantly lowered the blood glucose level in several laboratory animals fasted 48 hours (guinea pigs, mice, hamsters and rats). In the guinea pig, PEHP produced a three times stronger hypoglycemic effect than phenelzine, its corresponding hydrazine. Conversely both hydrazono compounds decreased the monoamine oxidase activity much less, than phenelzine. CHEHP (145 mumol/kg) inhibited this enzyme by less than 14%. After oral administration both hydrazones (200 mumol/kg) also produced a distinct hypoglycemic effect. The blood glucose lowering properties of the two hydrazones were most manifest in fasted guinea pigs, diabetic mice and rats with streptozotozin diabetes.


Total cortisol and L/S-ratio in amniotic fluid in late pregnancies complicated by diabetes mellitus. 68 samples of amniotic fluid from 47 women with varying severity of diabetes mellitus and 48 samples from 43 normal women were obtained in the 31st to 40th week of pregnancy before onset of labour. The concentration of total cortisol and the L/S-ratio in amniotic flud were determined and related to gestational age. There was a continous rise of total cortisol with advancing gestational age in the diabetic pregnancies similar to that found in normal pregnancy. Diabetic pregnancies were associated with slightly lower amniotic fluid cortisol levels without significant difference to values found in normal pregnancy. The severity of the disease did not affect the cortisol levels in amniotic fluid. There was no correlation between total cortisol levels and L/S-ratios in amniotic fluid. Determination of total cortisol in amniotic fluid can thus not replace measurements of L/S-ratios to predict fetal lung maturation.


Effects of hypo- and hyper-thyroidism on in vivo lipogenesis in fed and fasted rats. Thyroidectomized rats (T) daily injected with either 0, 0.1, 1.8 or 25 microgram of L-thyroxine/100 g body wt. were compared with intact controls (C). The appearance of radioactivity in fatty acids 30 min after the i.p. injection of (3-14C)pyruvate was reduced in adipose tissue and enhanced in liver of T+25, being no differences between the other groups and C. (14C)-Fatty acids are reduced with 3 h of fasting only in the adipose tissue of T+1.8 and C, while 24 h produces a reduction in liver in the T+1.8, T+25 and C, and in adipose tissue in the T+1.8 and C animals. The highest percentage of radioactivity was observed in the liver glyceride glycerol fraction, being greater in T+25 than in the other groups. Fasting produces an increment in the (14C)-glyceride glycerol fraction. Being significant only in thehypothyroid animals in both liver and adipose tissue. The most sensitive parameter to fasting was the formation of (14C)-non-saponifiable lipid in both the C and T+1.8 animals, while it does not change in T+0 or T+0.1, but is enhanced within 24 h in the adipose tissue of T+25. It is proposed that most of the observed changes are due to the other endocrine disfunction s which appear in hypo- and hyperthyroidism, as the in vivo results do not comply with in vitro effects of thyroxine onlipogenesis of others.


Low muscle and liver glycogen contents in dogs treated with thyroid hormones. Muscle biopsies for glycogen determinations were taken from dogs before (controls) and after prolonged treatment with thyroid hormones (T4 or T3). The glycogen content in quadriceps femoris was measured before exercise, immediately after its cessation, and during 24h of post-exercise recovery. The effect of thyroxine treatment on the liver glycogen content both at rest and following physical effort was also studied. A marked decrease in the muscle glycogen content determined at rest was found both in T4 and T3-treated dogs in comparison with controls. Physical exercise diminished the muscle glycogen store to similar values in control and thyroid hormone-treated dogs, but the rate of the muscle glycogen utilization during exercise was lower in the latter. The rate of the post-exercise muscle glycogen synthesis was considerably inhibited in thyroid hormone-treated dogs, but 1 hr glucose infusion, applied immediately after cessation of exercise, accelerated the rate of glycogen re-synthesis, so it was close to that in controls without infusion. Thyroxine treatment also affected the liver glycogen store. Both at rest and after physical exercise significantly lower liver glycogen contents were found in T4-treated dogs than in controls.


Mosaic character of spermatogenesis in carriers of the sex reversed factor in the mouse. The "sex reversed" factor leads to development of XX male mice. It is inherited on one of the autosomes and transmitted through XY-Sxr carrier males. In the latter, spermatogenesis is studied under the aspect of gene dosis effects produced by the presence of the Sxr factor in addition to the Y chromosome. A mosaic pattern of normal and defective spermatogenesis is described. The defective areas are characterized by failure in late pachytene and metaphase I, and by appearance of spermatids with very large nuclei which degenerate in cap phase. The defects correspond to those observed in X0-Sxr spermatogenesis. Our interpretation is that in the normal areas only the Y chromosome, and in the defective areas the Sxr factor is expressed.


Study of FSH-TSH functional overlap by cockerel testicle test. Comparison of the neonatal effects of FSH and TSH in the cockerel testicle test revealed that the latter caused a greater increase of testicular weight, tubular diameter and testicular interstital tissue. This finding suggests the possibility of FSH-TSH functional overlap during the perinatal critical period of receptor maturation.


Evidence for Na-retaining humoral agents and vasoconstrictor humoral agents in hypertension-prone Dahl 'S' rats. Prevention of NaCl-induced hypertension in Dahl 'S' rats with thiazide. Dahl 'S' rats become hypertensive when fed a high NaCl diet but remain normotensive on a low NaCl diet. Dahl 'R' rats are normotensive on either diet. For a given perfusion pressure, isolated 'S' kidneys excrete 50% less Na than 'R' kidneys. Therefore, we searched for a Na-retaining hormone in 'S' rats. Kidneys were isolated without ischemia from normal rats and were continuously perfused at 125 mm Hg with blood from Dahl 'S' and 'R' rats, all on low NaCl diets. Kidneys and adrenals had been extirpated from the perfusing rats. During 15 min of perfusion, the isolated 'normal' kidneys excreted a mean of 164 micronEq of Na/min/100 g during 26 perfusion experiments with blood from 'R' rats. The 'normal' kidneys excreted a mean of 84 micronEq Na during 24 perfusions with blood from 'S' rats. Thus, the normal kidneys excreted half as much Na when perfused with 'S' blood compared with 'R' blood (p less than 0.02). Seemingly, a Na-retaining humoral agent is present in the blood of 'S' rats on a low Na diet in the absence of renal and adrenal tissue. Moreover, in these normal kidneys, perfusion with 'S' blood induced a 16% higher renal vascular resistance than perfusion with 'R' blood (p less than 0.01), indicating vasoconstricting agents in 'S' blood. However, the Na-retaining humoral effect in 'S' blood could lead to Na retention by 'S' kidneys in vivo, which could partially account for the susceptibility of 'S' rats to NaCl hypertension. Hypertension in Dahl 'S' rats can be almost completely prevented by concomitant treatment with thiazide diuretics which act mainly on the kidney to facilitate Na excretion. This result is in agreement with the hypothesis that a shift in the pressure natriuresis curve, reducing Na excretion for a given arterial pressure, is partially responsible for the great sensitivity to NaCl hypertension in the 'S' rat. The Na-retaining hormone may contribute to this shift.


Pure trisomy 17p in 60% cells.

Pure trisomy 17p in 60% cells. A patient with pure trisomy of the short arm of chromosome 17 in 60% of the examined cells is reported. She presented a variant chromosome 1 with partial pericentric inversion and increased centromeric heterochromatin in one chromosome 17. The cytogenetic findings are discussed. The clinical findings are compared to those found in other reported cases of partial trisomy 17 and a delineation of a pure trisomy 17p attempted.


Interstitial deletion 13q syndromes: a report on two unrelated patients. A partial monosomy 13 by interstitial deletion was found in the complement of two patients with mental retardation and mild dysmorphic features. Neither of the patients had a retinoblastoma, even though the second patient had a 13q14 deletion. The karyotype-phenotype correlation in the two patients suggests the need to reconsider the clinical profile of these rare chromosomal syndromes in a large series of subjects.


An uncommon phenotypical variant in the Shereshevsky-Turner syndrome. Three young girls of short stature and with somatic anomalies typical for the Shereshevsky-Turner syndrome are described. Signs of sexual maturation and menarche appeared on time. Later on, menstrual periods came to resemble juvenile bleedings. Karyotypes determined in lymphocyte culture were 45,X/46,XX/47,XXX; 45,X/46,XXp-; and 46,XXp-, respectively. A possibility of spontaneous sexual maturation in patients with the Shereshevsky-Turner syndrome is discussed.


Mutagenic effects of isonicotinic acid hydracide in Fanconi's anemia. Isonicotinic acid hydracide (INH) increases substantially the chromosomal instability in Fanconi's anemia (FA) cells. The same concentrations of INH do not significantly break chromosomes in heterozygous or normal cells. INH does not induce alkylation or cross-links in the DNA, like other mutagens known to increase breakage in FA cells. Possible mechanisms of the effect of INH are discussed. One consequence of this experiment is the possibility of an exact and doubtless prenatal diagnosis of a homozygous FA fetus.


Calculating genetic risk figures using a programmable pocket calculator. In autosomal irregular dominant as well as in sex-linked recessive inheritance, heterozygosity probabilities for up to six or eight pedigree members with unknown genotype can easily be calculated using a programmable pocket calculator. The application of the underlying combinatorial programs is explained by means of two relevant examples. Genetic counsellors without a computer at hand are provided with a simple and accurate method for calculating genetic risk figures taking into account pedigree data, incidence and/or mutation rate, reproductive fitness, as well as penetrance or results of heterozygosity tests of the disease in question.


On the nature of sickle-cell disease in the Arabian Peninsula. The sickle-cell gene contributes substantially to the presentation of anaemia in certain areas of the Arabian Peninsula. However, the clinical presentation of the homozygous state of Hb S is less severe than that observed in other ethnic groups, such as American negroes. In the present paper, biosynthesis studies performed on reticulocytes from heterozygotes and homozygotes for the Hb S give further indications of the mild nature of sickle-cell disease in Arabia. Comparison of two affected families, from Saudi Arabia and Jordan, showed that clinical manifestation of the disease is mirrored by the biochemical and haematological findings in affected individuals. The results are discussed in terms of the effect of co-existing thalassaemia and/or iron deficiency with Hb S. It is suggested that both genetic and acquired conditions play a role in the clinical features of the disease. The mechanisms responsible for regulation of alpha-chain synthesis by iron (haem) deficiency are discussed.


Frequency of sister chromatid exchanges in cigarette smokers. The effect of cigarette smoking on the frequency of sister chromatid exchanges (SCE'S) was investigated in a group of adult men. It was observed that there was a significant increase in the mean SCE frequency per cell in smokers. Both the duration of smoking and the number of cigarettes smoked per day appeared to influence SCE frequency.


Partial deficiency of red cell 6-phosphogluconate dehydrogenase: a family study. A family with partial deficiency of erythrocytic 6PGD is described. Biochemical and electrophoretic analysis suggest that the partial deficiency is due to a silent PGD0 allele. Chromosomal analysis and assay of closely linked markers do not reveal a grossly detectable deletion.


Omphalocele and partial trisomy 1q syndrome. A male infant with partial trisomy 1q syndrome (46,XY,der(21),t(1;21)(q25;q22)pat) is described. Clinical findings include small for gestational age, hypoglycemia, ocular hypertelorism, microphthalmia, coloboma of the iris, low-set ears, beak nose, micrognathia, micropenis, cryptorchidism, presacral dimple, flexion contractures of the fingers, bifid thumb, Simian crease, and overriding toes. In addition, he had a large omphalocele not previously seen in trisomy 1q. Postmortem findings include underdeveloped cerebellum, a thymus with moderate depletion of thymocytes, a large PDA, ASD, small adrenal, and fatty change of the liver. The grandfather, father, and a male sibling have translocation t(1;21)(q25;q22). A family history of repeated spontaneous abortions is present.


Demonstration of Y/autosomal translocations using distamycin A. The condensation of the brightly fluorescing Y-heterochromatin is prevented by cultivating leukocytes in a medium containing distamycin A. This technique provides a reliable method for the identification of those Y/autosomal translocations in which Y heterochromatin is involved. A case of a familiar Y/22 translocation and the distamycin A technique are described.


A new translocation in Burkitt's tumor cells. A t(8;22)(q24;q11) translocation was found in blood, bone marrow, and ascites cells from a European Burkitt's lymphoma. Cell surface markers were identified as monoclonal IgG. The relationship between these two unusual findings is questionable in this cytologically typical Burkitt's lymphoma.


Partial trisomy 7q and probable partial monosomy of 5p in the son of a mother with a reciprocal translocation between 5p and 7q. An underweight male newborn revealed a complex pattern of abnormal findings including severe neurologic dysfunction, a catlike cry, defective ossification of the calvarian bones, hypertelorism, downward slanting palpebral fissures, epicanthal folds, a short and flat nose with a flattened bridge, broad thumbs, clenched fingers 3--5 on the right hand, simian creases, a congenital heart defect, internal hydrocephalus, and bilateral hydronephrosis. He died on day 26 of his life. Chromosome examination disclosed a maternally inherited reciprocal translocation between 5p and 7q, resulting most probably in monosomy of 5p15 and trisomy of 7q32 leads to qter (46,XY,der(5), t(5;7)(p15;q32)mat).


Heritable fragile sites on human chromosomes. III. Detection of fra(X)(q27) in males with X-linked mental retardation and in their female relatives. The fragile site at Xq27 which is associated with X-linked retardation with macroorchidism has been studied in 21 retarded males. These males were from 12 families, and studies of nine of the familes were possible. Detection of carrier females is difficult, especially with increasing age. The fragile site was demonstrated in only five of 13 obligate carrier females. It is concluded that using present methods, cytogenetic detection of carriers is fairly reliable in females aged less than 20--25 years but unreliable in older females.


Heritable fragile sites on human chromosomes. IV. Silver staining. The chromosomal gaps associated with fragile sites at 2q11, 10q23, 11q13, 16q22, 20p11 and Xq27 do not stain with silver nitrate as do NOR regions of the acrocentric chromosomes.


Genetic studies of complement C4 in man. A C4 variant found in about 5% of the population is described. The fast-moving part of this variant is governed by an allele (Fx) codominant to F. The Fx allele is in very strong linkage disequilibrium with HLA-B17 as the linkage disequilibrium parameter accounted for nearly 100% of the haplotype frequency of B17,Fx. The strong association is also evidenced by the study of 11 families segregating for the Fx allele. There was no instance of recombination between C4 and HLA in 36 informative meioses.


Characterization of some erythrocyte G6PD variants by isoelectric focusing. The existence of a microheterogeneity of glucose-6-phosphate dehydrogenase (G6PD) in human erythrocyte lysates has been previously demonstrated using isoelectric focusing (Der Kaloustian et al., 1974; Turner et al., 1975). The application of this method, modified in some aspects, to the identification of various G6PD variants led to interesting conclusions. The results reported here have been obtained from a study of four distinct molecular types: Gd(-) Mediterranean, Gd(-) Kabyle, the African Gd(+) A, and a new almost undescribed G6PD variant with severe enzyme deficiency named Gd(-) Muret.


H-Y antigen in Swyer syndrome and the genetics of XY gonadal dysgenesis. The H-Y antigen is a plasma membrane antigen involved in the organogenesis of the mammalian testis. Its expression on human cells is determined by a Y-linked gene. Phenotypic females affected by 46,XY gonadal dysgenesis (Swyer's syndrome) can be either H-Y-positive or H-Y-negative. In this paper we report H-Y antigen and endocrine studies in a sibship with three affected sisters. Immunological studies were performed on two of the patients, and a clearly positive expression was detected in both cases. Endocrine studies consisted in the investigation of the hypothalamic-pituitary-gonadal axis, which revealed that gonadal hormone insufficiency is the only endocrine abnormality associated with the syndrome. A new genetic interpretation and calssification of XY gonadal dysgenesis is proposed.


H-Y antigen-positive male pseudohermaphroditism with 45,X/46,XYq-mosaicism. A 42-year-old male had short stature, microphallus, hypospadias, a bifid scrotum, abdominal undifferentiated testes, a uterus, bilateral fallopian tubes, and 45,X/46,XYq-mosaicism in his blood, skin, and germinal tissue and tissue surrounding the tests as determined by means of G-, Q-, and C-banding. An H-Y antigen assay on skin fibroblasts was positive, indicating that the locus for this antigen is not located in the brightly fluorescent region of the Y chromosome.


X-linked dominant chondrodysplasia punctata. Review of literature and report of a case. X-linked dominant chondrodysplasia punctata is a syndrome consisting of skeletal, ocular, and cutaneous anomalies with asymmetric involvement of the body. The skin lesions, the hallmark of this condition, are distributed in a linear or blotchy pattern and include congenital ichthyosiform erythroderma, systematized atrophoderma mainly involving the hair follicles, and circumscribed alopecia. The remaining scalp hair is in part normal and in part irregularly twisted and coarse. The eyebrows and lashes are sparse. The nails may be flattened and split into layers. Thirty-five cases of this new syndrome are reviewed, and an additional observation is reported. The ratio of females to males is 36:0. The concept of X-linked dominant chondrodysplasia punctata has been suggested, and it has been postulated that there is a connection between the mosaic phenotype and the limitation to the female sex. Both facts would be explained by an X-linked gene giving rise to a pattern of lyonization in females, and lethal in hemizygous males. The classification of chondrodysplasia punctata thus includes three forms: the rhizomelic type, the Conradi-Hünermann type, and the X-linked dominant type. Two of these, the rhizomelic type and the X-linked dominant type, are well-defined entities. Whether the Conradi-Hünermann type, after separation of the X-linked form, is still heterogeneous, remains to be determined.


Improved screening test for abnormal hemoglobins from dried blood samples. A method is described wherein blood samples taken from adults or newborns and dried on filter paper can be used for hemoglobin analysis within 2 years after sampling. The samples are eluted in 8 M urea in the presence of 5% 2-mercaptoethanol and 2% of the neutral detergent Nonidet P-40. Then the individual alpha, beta, gamma, and epsilon chains are separated by means of electrofocusing in 8 M urea-PAA gels. Up to 96 samples can be applied to a gel using multiple syringes. Several hundred samples can be analyzed daily by one person. This method may be especially useful for preventive programs against sickle cell anemia as well as for human mutation monitoring systems.


Microcinematographic demonstration of synchronous and asynchronous myoepithelial contractions in mouse submandibular gland rudiments in organotypic culture. Time-lapse phase-contrast cinematography revealed contractile activity within mouse submandibular salivary gland rudiments in organotypic culture. Three types of contraction were distinguishable. In type I (voiding contractions), all portions of the gland contracted synchronously, and the active state ranged from 30 min to 2 hr. In type II (priming contractions), all portions of the gland contracted synchronously, but the active state was shorter, ranging from 4 to 10 min. In type III (churning contractions), isolated foci in lobules or secretory units throughout the gland contracted asynchronously and had very short active states of about 1 min. By electron microscopy, myoepithelial cells could first be demonstrated in submandibular glands developing either in vitro or in vivo, at 21 days postconception. Contractions in the cultured rudiments began as early as 18 days postconception. Since neither smooth nor striated muscle could be identified in these glands by electron microscopy, the contractions are believed to result from myoepithelial activity that apparently may begin before ultrastructural evidence of myoepithelial differentiation is clearly present. Although, for over a century, myoepithelium has been presumed to have a contractile function and indirect evidence has lent ample support to this presumption, the present study represents the first direct cinematographic demonstration and characterization of myoepithelial contractions, under conditions in vitro.


Adult rat lung in organ culture: maintenance of histotypic structure and ability to synthesize phospholipid. The maintenance of adult rat lung explants in organ culture was assessed both morphologically and biochemically. A comparison of several culture media indicated that Ham's F12K plus 1.0 microM dexamethasone, which maintained the explants for 14 days, was superior. The ability of the explants to synthesize dipalmitoylphosphatidylcholine increased with the length of cultivation to values greater than the noncultivated controls. The DNA content remained constant for 7 days, and a relatively normal structural relationship between type I and type II pneumocytes was maintained. Explants cultivated in Ham's F12K without dexamethasone did not maintain a histotypic morphology; the type II pneumocytes appeared to proliferate and the ability to synthesize phosphatidylcholine decreased.


Human vaginal epithelial multilayer tissue culture. Fragments of normal human adult vagina, when explanted onto glass slides gave rise to outgrowing sheets of pure epithelium, which had microscopic morphological features in common with normal vaginal epithelium. Infrequent fibroblast contamination was observed. Proliferating epithelial cells formed multilayers of stratified squamous epithelium and demonstrated a progressive decrease in proliferative activity after 14 days. Continuous lines of epithelial cells were not obtained. Even in the absence of estrogens, transmission electron microscopy revealed evidence of keratinization of the superficial cells of the multilayer. Scanning electron microscopy of the surface of mature epithelial cells in culture revealed ultrastructural features that closely resembled those present on the surface of exfoliated cells obtained by scraping the vagina in vivo. This in vitro tissue culture model of human vaginal epithelium may provide a simple method of studying factors that influence vaginal epithelium growth, maturation and function.


Long-term culture of human aortas. Development of atherosclerotic-like plaques in serum-supplemented medium. Segments of human thoracic aorta were maintained in long-term explant culture for 18 weeks in serum-supplemented medium. The aortas were grossly normal in appearance, and random samples fixed for light microscopy prior to culture revealed a normal morphology. The intima contained no more than five layers of smooth muscle cells. After 7 days in culture, the intima was noticeably thicker than the uncultured segments. The increased thickness was due to proliferating smooth muscle cells and production of extracellular material. After several months in culture, extracellular material consisting of collagen and flocculent material was present in areas resembling atherosclerotic fibrous plaques. A peripheral growth, which formed around the explant, was composed of fibroblastlike cells and added to the overall thickness of the intima. However, aortic segment maintained for up to 2 months in serum-free culture medium showed no cellular proliferation. This study demonstrates that changes resembling early stages of atherosclerosis occur in human aortas maintained in explant culture using routine culture procedures.


Cytotoxicity of glucose analogues in V79 multicell spheroids. 2-Deoxy-D-glucose (2DG) and 5-thio-D-glucose (5TG) are glucose antimetabolites that are known to be selectively toxic to hypoxic cells grown as single cells or as monolayer cultures. These analogues were toxic to Chinese hamster V79 cells grown as multicell spheroids even under aerobic conditions. When spheroids, 500- to 600-microns diameter, were exposed to 7.5 mM of these chemicals for 3 days, the number of clonogenic cells per spheroid dropped to 50% for 5-thio-D-glucose and 20% for 2-deoxy-D-glucose, relative to control values. Survivals were reduced to less than 1% when the experiment was repeated in glucose-free medium. Scanning electron photomicrographs of spheroids treated with 7.5 mM of either analogue showed extensive damage to the outer cells. The cell killing observed was much more than could be predicted on the basis of the hypoxic fraction known to be present in these spheroids. The crowded tumor-like environment may make the cells vulnerable to the cytotoxic action of glucose analogues and other glycolytic inhibitors.


LSH and FSH autonomous secretion in long-term pituitary tissue culture. Pituitary tissue from 2- to 6-day-old male rats was cultivated for up to 136 days in medium containing fetal bovine serum, but without added steroid or hypothalamic extracts. After 40 to 70 days of sustained release of LH and FSH at a very low level, there was an increase in the quantity of both, and a plateau of depressed secretion. LH was identified by immunoreactivity in two radioimmunological systems and in gel chromatography. Little, if any, alpha-subunits were liberated in these cultures. It is concluded that basal production of LH and FSH is a constitutive activity of the gonadotropic cell.


A growth history comparison of the human diploid cells WI-38 and IMR-90: proliferative capacity and cell sizing analysis. Results of growth history studies on IMR-90 and WI-38 showed that the two cell strains were equivalent in population doublings achieved per life span. However, IMR-90 exhibited higher cell yields in phase II than did WI-38. In addition, entry of IMR-90 cells into phase III occurred more abruptly than in WI-38 cultures. Cell sizing analysis showed that phase II and phase III IMR-90 cell populations contained greater numbers of cells in the small volume categories. At senescence, both cell lines contained similar numbers of cells in all size categories. These data suggest that IMR-90 may not be equivalent in all respects to current stocks of WI-38.


Characteristics of a clone of endothelial cells derived from a line of normal adult rat lung cells. A strain of endothelial cells derived from a single cell cloned from a line of normal adult rat lung parenchyma has been maintained in tissue culture for more than 3 years. These cells have been identified as endothelial cells based on the combination of their growth characteristics, cell morphology as observed with both light and electron microscopy, and their physiological properties. They have continued to produce granules, which stain specifically for glycosaminoglycans with Alcian blue, for over 2 1/2 years. During the same period of time, glycosaminoglycans were identified biochemically in both cells and medium. They have maintained the ability to degrade bradykinin over this period as well.


Effect of fetal bovine serum on 3-methylcholanthrene-induced transformation of hamster cells in vitro. Eighteen lots of fetal bovine serum were tested for their ability to support clonal growth and 3-methylcholanthrene-induced morphological transformation of hamster embryo cells in vitro. Most of them supported cloning efficiencies of over 11%. However, cloning efficiency alone was an inadequate criterion for selecting serum for transformation studies, since no transformation was observed with some lots, even though their cloning efficiencies were over 16%. This shows the importance of pretesting serum for its ability to support morphological transformation before it is used in mammalian cell carcinogenesis tests.


The I, i, and HI blood group antigens in extracts of human erythrocytes. Extracts of stromata of human adult and newborn (cord) erythrocytes were prepared with n-butanol. The aqueous phase and butanol phase extracts were examined for the presence of blood group I, i, HI and H substances in inhibition of agglutination experiments. The recovery of HI activity in both the aqueous and butanol phase extracts of adult red cells but only in the aqueous phase of cord cells is reported heare for the first time. The i specificity was present in the aqueous phase but not in the butanol phase of cord erythrocytes, also not previously reported. Although the recovery of I but not i substance in aqueous phase extracts of adult cells had been shown by other workers, examination of the butanol phase extracts for I and i substances had not been documented. In the present study, Ii substances were not demonstrable in any of the butanol phase extracts of adult and cord erythrocytes.


The examination of antigens in highly purified immune complexes. A combination of gel filtration and affinity chromatography was used for preparation of immune complexes (IC) from sera of individuals with systemic lupus erythematosus (SLE) and others with no apparent disease. Overlaying of gels with patient or normal sera, counterstaining with 125I-protein A and autoradiography showed besides immunoglobulins, the presence of 6 unidentified antigens with molecular weights below 42,000 dalton. They were not exclusively associated with SLE IC.


A multivariate analysis of excessive alcohol use involving labeling and self-constructs. Previous studies have focused on predicting whether or not a person is likely to become a problem drinker, but have not employed concepts explaining the process whereby excessive alcohol use emerges. It is proposed that labeling concepts, in combination with a multidimensional conceptualization of the general self-concept, provide the components of a model capable of explaining this process. Automatic Interaction Detector permitted an assessment of the contingent relationships among the labeling and self variables. The findings indicated that the influence of the alcoholic labels of others on self-views and drinking behaviors hinged on self-esteem and self-complexity.


The other side: counselor roles.

The other side: counselor roles. The problem of treating a narcotic-dependent person is probably one of the most difficult confronting those attempting to provide rehabilitation services. Often emphasis has been placed on those persons receiving the services provided rather than those who provide them. In this paper the drug counselor is focused upon, for after all it is he or she who plays the many roles necessary to accomplish this task at hand. The roles include psychotherapist, crisis intervention agent, medical counselor, and client advocate for the addict in treatment. Behaviors, expectations, and responsibilities involved in these counselor roles influence the development of a "healing partnership" involving both the counselor and the client.


Methadone matinenance patients' self-perceived factors responsible for successful rehabilitation. Forty methadone maintenance patients most frequently attributed their past and future successful drug-free rehabilitation to the following factors: A supportive relationship, particularly with a drug-free individual, a satisfying job, and personal coping skills. Conversely, the absence or withdrawal of these events was associated with subsequent reinvolvement with excessive drug use. The importance of incorporating patients' phenomenological experiences and self-appraisals of success into clinical interventions is discussed.


The fetishism of drugs.

The fetishism of drugs. In recent years the general argument has been advanced that the effects of psychoactive drug use on human beings depend as much on the context of use as on the inherent characteristics of the drug itself. Two variations on this general theme have been the "Weil thesis" and the "Lindesmith thesis." The former asserts that drug-induced alterations of consciousness are influenced significantly by the immediate set and setting. The latter argues that the manner in which drug use is socially controlled largely determines use patterns and the long-term effects of use. The theoretical moorings of both these theories are explored, and the evidence relevant to each is assessed. In each case the results are mixed: Although neither tells the whole story in its respective domain, both are necessary for a total understanding of the effects of psychoactive drug use.


Group discussion and drug abuse prevention. The present study examined the usefulness of applying a group discussion technique known as the choice shift procedure to drug abuse prevention. Choice shift discussions produced both immediate and long-term antiabusive changes in college womens' drug attitudes. A second intervention, public commitment, exerted a variable influence on immediate attitude change. These results suggest that the group choice shift procedure could prove to be a useful component of drug abuse prevention programs.


Self-concept and drug involvement among urban junior high school youths. Relationships between self-concept and drug involvement were examined through a survey given to 1,100 urban junior high school youths from mixed socioeconomic and ethnic backgrounds. The students were presented with 14 descriptions of "types" of youth, which they rated in terms of similarity to themselves. Factor analyses produced three "self-image" factors each for both males and females. "Gang" and "drug culture" self-images were positively associated with self-reported drug use (r's for .35 to .46), while an "educational" self-image was negatively associated with drug involvement (r's from -.20 to -.30). Implications for further research and for drug abuse prevention planning are discussed.


Frequency of psychiatric symptoms among 150 opium addicts in Shiraz, Iran. The psychiatric evaluation of 150 opium addicts in Shiraz, Iran, revealed that (1) the addicts had more psychiatric symptoms than the matched control group, and (2) the most frequent symptom among the addicts was depression. Our findings differ from most Western studies, where anxiety and evidence of antisocial behavior were reported as the most common findings.


The relationship between alcoholic patients' milieu perception and measures of their drinking during a brief follow-up period. Patient perceptions of alcoholism treatment programs were assessed by the Ward Atmosphere Scale and the Community Oriented Program Environment Scale. Patient perceptions were related to drinking during a brief follow-up period. The Personal Problem Orientation, Anger and Aggression, and Program Clarity subscales were found to correlate more frequently with patient drinking. Patient perception of the treatment environment, as well as the actual treatment milieu, may be important aspects of the alcoholism treatment process.


Sexual differentiation among marijuana users: reality or inaccuracy. This study, based on data (N = 134) obtained by self-administered questionnaires, examines the extent marijuana users can be sexually differentiated regarding usage patterns, acquisition, distribution, effects on social relationships, and other activities. Generally, no significant sexual variations were observed except that males were more likely to personally purchase, to have sold marijuana, to bring it along when visiting friends, to hesitate having friends be their only source, and to be confirmed about other users knowing of their use. It is suggested that sexual differentiation may reflect lesser involvement and that it may reduce as higher level users are examined.


Mood components of heroin addicted men: psychosocial correlates. A principal components analysis was performed on 200 male heroin addicts' self-ratings on the Profile of Mood States which was given before admission to a methadone maintenance program. Four components were identified as underlying the men's affect-Confused-depression, Vigor-friendliness, Anger-hostility, and possibly Fatigue-inertia; these mood dimensions corresponded to factors described for other clinical populations. A stepwise multiple regression was then performed to discover which of the addicts' background characteristics were related to the mood components. Confused-depression was positively correlated with being White, using marijuana, and seeking treatment without prior screening by a social agency; Vigor-friendliness was positively related to having been referred from a social agency and having started using opiates at a later age;  Anger-hostility was positively correlated with using other drugs, such as Valium, not being religiously active, and smoking marijuana; and Fatigue-inertia was only positively associated with having been referred from a social agency.


Patient autonomy in alcohol rehabilitation. II: Program evaluation. The alcoholism inpatient services at the U.S. Army Hospital Nürnberg are described and assessed with attention to current issues. The results compare favorably with contemporary findings, and include an almost zero dropout rate that relates to giving the patient more "say so" in treatment selection by providing a variety of treatments in a smorgasbord fashion. Abstinent and nonabstinent patients following treatment are contrasted on psychometric and demographic variables.