Showing papers by "University of Zurich published in 1978"

Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey.

Abstract: Corticofugal projections were examined by means of the autoradiographic tracer method in 21 macaca fascicularis. The labeled material was injected into the main body representation areas of the precentral motor cortex and into various regions of Brodmann's areas 6, 8 and 9 of the frontal lobe. The ipsilateral subthalamic nucleus receives a moderately strong and somato-topically organized projection from Woolsey's precentral motor cortex. This projection is mainly restricted to the lateral moiety. The remaining nucleus is occupied by less intensive projections from premotor and prefrontal areas. It is concluded that the subthalamic nucleus is a convergence site of pallidal and corticomotor and frontal projections. Cortical afferents may exert an influence on the pallido-subthalamic-pallidal inhibitory feedback loop.

Insulin‐Like Growth Factors I and II: Some Biological Actions and Receptor Binding Characteristics of Two Purified Constituents of Nonsuppressible Insulin‐Like Activity of Human Serum

Abstract: The insulin-like growth factors I and II, two purified constituents of nonsuppressible insulinlike activity opf human serum, have nbeen compared with regard to some bniological actions in vitro and some receptor-binding characteristics. 1 In the presence of an excess of insulin-antibodies the insulin-like growth factors I and II (a) stimulate the net gas exchange in rat adipose tissue (fat pad assay) to a similar extent; (b) enhance 3-O-methylglucose transport, glucose oxidation and lipogenesis from glucose in rat adipocytes, with slight but significant differences in potency; (c) inhibit lipolysis in adipose tissue from fastedrefed rats, again with slight potency differences. 2 In adipose toissue and adipocytes the biological activity of insulin-like growth factors I and II is between 1/35 and 1/125 of that of insulin on a molar basis. 3 Insulin-like growth factors I and II are equally potent mitogens (stimulation of DNA-synthesis and cell multiplication in cultured chick embryo fibroblasts). 4 Insulin-like growth factors I and II stimulate 35SO42- incorporation into rat costal cartilage with minor differences in potency. 5 In rat adipocytes, insulin-like growth factors I and II compete with insulin for binding to thje insulin receptor. However, their potencies in ‘displacing’125I-labeled insulin are between 75 (for factor II) and 290 times (for factor I) lower than that of insulin. In addition, the factors I and II bind to binding sites specific for the factors and for which insulin does not compete. Considerable differences between factors I and II exist regarding their specific binding and their potencies in competing for binding of labeled factors I and II. 6 In chick embryo fibroblasts and isolated chick embryo chondrocytes the insulin-like growth factors I and II compete more or less equally for binding to a binding site specific for the factors and which appears to mediate their effects on cell growth and sulfation. 7 Indsulin-like growth factors I and II bind specifically to a partially purified carrier protein of human serum. Pronounced differences in specific binding and their potencies of competition are observed. Thus, the insulin-like growth factors I and II, two structurally closely related polypeptides, display more or less similar activities in various biological systems in vitro. In all of these, their biological potency can be reasonably correlated with their potency of competition either for the insulin receptor (fat cells) or for a specific binding site (fibroblasts and cyhondrocytes). In some of the radioactive ligand systems, where the biological function of binding sites for insulin-like growth factor is still unknown (such bindings sites are found in fat cells and on the serum carrier protein), clear cut differences between factors I and II are apparent.

Nonsuppressible insulin-like activity (NSILA) from human serum: recent accomplishments and their physiologic implications.

Abstract: It is now known that nonsuppressible insulin-like activity extracted from human serum (NSILA-S) consists of at least two chemically and biologically closely related polypeptides with a molecular weight of 7500. Their primary and tertiary structures strikingly resemble that of human proinsulin and suggest a common phylogenetic ancestor. Beyond their acute insulin-like actions on insulin target tissues the two polypeptides exert pronounced effects on growth of cultured cells and on sulfation, RNA and protein synthesis of cartillage. For these reasons they have been termed insulin—like growth factors (IGF I and II). In adipose tissue, their biologic potency is ∼60 times lower than that of insulin and corresponds to their weak affinity for the insulin receptor rather than to their high affinity for a specific IGF-receptor whose functional role is still unclear. By contrast, their biologic potency in heart and skeletal muscle is close to that of insulin ( 1 2 – 1 5 ) although their affinity for the insulin receptor is ∼100 times lower than that of insulin. Therefore, the insulin-like actions of IGFs on muscle appear to be mediated by the IGF-receptor. In fibroblasts and chondrocytes, binding of IGFs to specific high affinity IGF-receptors correlates closely with their effects on growth indices and sulfation. The latter effects occur at ∼50 times lower concentrations than with insulin. In native blood, IGFs are tightly associated with a specific carrier protein and the free forms are barely detectable. Binding to the carrier blocks their action on insulin target tissues, which explains the absence of acute insulin-like effects of endogenous IGF in vivo. In contrast, tissues concerned with growth may possess mechanisms to “extract” IGFs from the carrier complex. IGFs are under the control of growth hormone: total IGF levels are increased in acromegalics and decreased in hypopituitary and Laron dwarfs. This characteristic and their distinct biologic properties coin IGFs as members of the somatomedin family. The close relationship is further underlined by the pronounced cross-reactivity with somatomedins in radioreceptor and radioimmunoassays. Low serum IGF values are also found in patients with liver cirrhosis. Among other evidence, this points to the liver as one site of production of IGFs. Total IGF levels were not found to be elevated in 15 patients with hypoglycemia caused by extrahepatic tumors. Antibodies that allow to discriminate between the two species of IGF have recently been raised in rabbits. From the results of the radioimmunoassays, it becomes apparent that normal human serum contains 4–6 times more IGF II than IGF I. In acromegalic patients, only IGF I is elevated, whereas IGF II lies within the normal range. In hypopituitary and in Laron dwarfs, but also in patients with liver cirrhosis, IGF I is more drastically reduced than IGF II. Thus, IGF I may be the more important growth factor, and the two seem to be regulated differently. Besides carrier-bound IGFs, another large molecular weight peptide with nonsuppressible insulin-like activity is present in human serum. It is not interconvertible to small molecular weight IGF and it is not active on sulfation of cartilage. Therefore, it represents an entity different from IGFs. Thus, bioassays carried out in whole serum detect different insulin-like activities: Since carrier-bound IGF is inactive on adipose tissue the fat pad assay measures large molecular weight NSILA rather than IGF, whereas the sulfation assay reflects the serum level of carrier-bound IGFs and other somatomedins.

Analysis of the adolescent growth spurt using smoothing spline functions.

Abstract: Height growth velocity curves between 4.5 and 17.75 years were estimated, using smoothing spline functions, for 112 boys and 110 girls from the Zurich Longitudinal Study (1955--1976). Parameters characterizing the growth process, such as peak height velocity and age at peak height velocity, were calculated directly from the estimated curves. The variability of parameters describing the adolescent growth spurt is large, both between and within sexes. Peak height, defined as increase of height velocity during the growth spurt, and age at peak height velocity both characterize the sex difference in growth in a highly significant manner. Peak height of at least 4 cm/year is found in 70% of the boys, but in only 11% of the girls. The age at peak height velocity averages 12.2 years in girls and 13.9 years in boys and has a wide range of 5.7 years and 3.8 years respectively. The sex difference in adult height of 12.6 cm is composed of the following 4 factors: +1.6 cm caused by more prepubertal growth in boys, +6.4 cm by the boys' delay in spurt, +6.0 cm by the more extensive spurt in boys and -1.4 cm by more post-spurt growth in girls. Correlations between parameters indicate that the adult height depends neither on the duration of growth, nor on the duration and height of the peak. Minimal pre-spurt height velocity and peak height velocity, but not peak height, are age- and height-dependent. Partial correlations given adult height reveal two compensating mechanisms between growth in the prepubertal and in the pubertal period. Small prepubertal height and low height velocity with respect to adult height are followed by a late adolescent spurt and vice versa. Small height at the onset of the spurt with respect to adult height is followed by a longer lasting, but not higher spurt and vice versa.

QB DNA-containing hybrid plasmids giving rise to QB phage formation in the bacterial host.

Abstract: Hybrid plasmids consisting of PCRI and a complete DNA copy of the RNA genome of coliphage QB, inserted in either orientation, elicit the formation of phage QB when introduced into Escherichia coli

Comparison of cloned rabbit and mouse beta-globin genes showing strong evolutionary divergence of two homologous pairs of introns.

Abstract: Cloned β-globin genes of both mouse and rabbit each contain a large and a small intervening sequence (intron) of about equal length at precisely the same positions relative to the coding sequence The homologous introns show some sequence similarity, particularly at the junctions with the coding sequence They most probably arose from a common ancestral sequence and diverged substantially during evolution

High‐Resolution Proton‐Magnetic‐Resonance Studies of Chromatin Core Particles

Abstract: The binding of histones in chromatin core particles and in core particles depleted of histones H2A and H2B has been studied by high-resolution proton nuclear magnetic resonance (NMR) at 270 MHZ. At low ionic strengths it is shown that histones H3 and H4 are bound in the core particle. Further, whereas the apolar regions of H2A and H2B are also bound to the core particle, the basic N-terminal and C-terminal regions are more mobile and give rise to sharp resonances in the NMR spectrum of the core particle. Between 0.3 and 0.6 M NaCl there is further release of basic regions of histones H3 and H4 from the complex. The dissociation of the core particle between 0.6 and 2.0 M NaCl is accompanied by the release of the structured apolar regions of the histones as evidenced by the appearance of a complex aromatic spectrum and perturbed upfield ring-current-shifted methyl resonances. Arginine residues are implicated in the binding between histones and DNA and 69% of these residues are found in the apolar regions of the histones. The interactions between histones and DNA in the core particle thus involves H3 and H4 and the apolar regions of H2A and H2B. It is suggested that these basic regions of H2A and H2B have binding sites outside the core particle.

Is sex determination in germ line and soma controlled by separate genetic mechanisms

Abstract: IN sexually dimorphic animals, the determination of sex is a major branch point in development. Although mutations producing sex reversal shed some light on the processes by which this determination is reached, many questions remain unanswered. Autosomal mutations such as polled in the goat1, sex reversed (Sxr)2 in the mouse and transformer (tra)3,7 in Drosophila cause chromosomal females to become phenotypic males, although they are sterile and their gonads agametic. The nature of this sterility suggests that the sex of germ cells in Drosophila, and perhaps in other species, might be determined by different sets of genes from those which operate in somatic tissue. Here we test this hypothesis by constructing mosaics in Drosophila where germ cells of one genotype are surrounded by soma of another. We find that the transformer mutation affects only the somatic sexual differentiation, and that it has no effect on the differentiation of germ cells. Thus we conclude that the agametic nature of transformed flies is due to the absence of functional male germ cells and at least with respect to tra, germ line and soma have separate sex-determining genes.

On social differentiation in groups of captive female hamadryas baboons

Abstract: The social differentiation in small groups of captive female hamadryas baboons was examined. Two positions could be distinguished: The highest ranking female, denoted as central individual, monopolized nearly all the presenting, mounting and grooming interactions. The lower ranking females, denoted as peripheral individuals, competed for access to the central female. All dyads of a group were arranged in a rank order according to the amount of sociopositive interaction which they reached within the group. This order of prevalence of dyads was positively correlated with the sum of dominance ranks of the dyad and the mutual attraction as estimated by choice tests. A multiple rank correlation demonstrated that the influence of the sum of ranks and of mutual attraction were nearly independent. If an individual's relationship to the central female had a higher rank of prevalence than that of its rival, it intervened more often and more successfully when the rival tried to interact with the central female. Interventions served to defend rather than to establish relationships. The results are compared with other studies that discuss basic principles governing structuring processes in nonhuman primate groups.

fs(1)K10 , a germline-dependent female sterile mutation causing abnormal chorion morphology in Drosophila melanogaster

Abstract: Females homozygous for a newly isolated mutation induced by ethyl methane sulphonate,fs(1)K10, lay abnormally shaped eggs in which the dorsal appendages of the chorion are enlarged and fused ventrally. The eggs are usually not fertilized and development is never normal beyond the blastoderm stage. The mutant was mapped to the tip of the X-chromosome with a meiotic position of 1–0.5 and a cytological location between 2B17 and 3A3. Using germ line mosaics constructed by transplantation of pole cells, it was shown that the abnormal morphology and the sterility are obtained only when the germ line is homozygous for the mutant.

Aberrant subclavian artery (arteria lusoria): sex differences in the prevalence of various forms of the malformation. Evaluation of 1378 observations.

Abstract: 43 original and 1335 previously published observations of aberrant subclavian artery (A. lusoria) were analyzed. The sex distribution varied for different types of the malformation: females predominated over males in instances of right aberrant subclavian artery and if pre-stenotic A. lusoria was combined with coarctation of the aorta. Male predominance was found in cases of combination of post-stenotic A. lusoria with coarctation and of aberrant left subclavian artery. An equal sex distribution was observed for A. lusoria combined with interruption of the aortic arch. Clinical, pathological and embryological aspects of the condition are discussed.

A syndrome of severe midface retraction, multiple skull anomalies, clubfeet, and cardiac and renal malformations in sibs.

Abstract: A brother and sister presented with an uncommon malformation syndrome consisting of severe midface hypoplasia, congenital heart defect, hydronephrosis, clubfeet, hypertrichosis, hypoplasia of dermal ridges, and radiographic skeletal anomalies in the skull, hands and feet. The boy died shortly after birth; the girl lived for 16 months and exhibited severe failure to thrive, epilepsy, diminished growth, and profound motor and intellectual retardation. Additional observations include postaxial hexadactyly in the girl, and mesomelic brachymelia and peculiar, narrow fingernails in the boy. The occurrence of the syndrome in two sibs of different sex suggests autosomal-recessive inheritance.

An analysis of conditions allowing corynebacterium parvum to cause either augmentation or inhibition of natural killer cell activity against tumor cells in mice.

Abstract: We have analyzed the impact of in vivo administration of Corynebacterium parvum on the mouse immune system against murine tumors, using the natural cytotoxic ability against tumors of normal mouse lymphoid cells as a baseline. A striking difference was found depending on the route of administration. Intravenous inoculation of bacteria would result in a significant decrease or sometimes complete abolition of natural cytotoxicity toward tumor cells of the spleen cells of treated mice. On the other hand, the intraperitoneal route of administration resulted in a dramatic increase in cytolytic ability of the peritoneal exudate cells. Both routes of treatment had the most significant impacts on the local cell population (IV = spleen, IP = peritoneal exudate cells) with only minor effects on other cell populations. Analysis of the spleen cell population from IV-treated mice did also demonstrate a significant reduction in the T lymphocyte function, but in contrast to the natural cytotoxicity this could be corrected for by the removal of suppressor cells of an adherent nature. The lytic cells induced in the peritoneal exudate by the Corynebacterium parvum bacteria were all found to be natural killer, NK, cells with no significant activity found amongst macrophages using short-term cytolytic assays.

The kinetics of the bimolecular sel-reaction of t-butyl radicals in solution. I. Termination rates

Abstract: Termination rate constants 2Kt for the self-reaction of t-butyl radicals in twelve different solvents are determined as a function of temperature by kinetic electron spin resonance. In the entire range measured, 7. 107 < 2Kt < 2 · 1010 dm3 mol−1 s−1, they are well described by the von Smoluchowski equation for diffusion controlled reactions, using a spin statistical factor, a temperature and solvent independent, isotropic reaction diameter, and diffusion coefficients for t-butyl estimated following empirical or semiempirical prescriptions. Methods for the prediction of diffusion coefficients are critically discussed, and rules for the estimation of termination rate constants of steric unhindered alkyl radicals are suggested.

Structures of Addition Products of Acetylenedicarboxylic Acid Esters with Various Dinucleophiles. An application of C, H‐spin‐coupling constants

Abstract: Heterocyclic compounds obtained by addition of acetylenedicarboxylic acid esters to thioureas, cyclic amidines and o-difunctionalized aromatic systems have been studied by 13 C-NMR. In particular, C,H-spin-coupling constants over two and three bonds were used to differentiate between the various constitutional isomers and to establish the configuration of trisubstituted exocyclic C,C-double bonds. The configurational significance and diagnostic value of vicinal cis and trans C,H-spin coupling is again demonstrated in the present series.

Conflicting visual-vestibular stimulation and vestibular nucleus activity in alert monkeys.

Abstract: In alert Rhesus monkeys (Macaca mulatta) neuronal activity of vestibular nuclei was recorded during pure vestibular and conflicting visual-vestibular stimulation. Pure vestibular stimulation consisted of rotating the monkey about the vertical axis in complete darkness. During conflicting visual-vestibular stimulation the monkeys were rotated in the light within a vertically striped cylinder mechanically coupled to the turntable. The conflict is that although the monkey is accelerated, there is no relative movement between visual surrounding and the animal. In the conflict situation thresholds of neuronal modulation and of nystagmus were raised compared with those during pure vestibular stimulation. Nystagmus slow-phase velocity could always be dissociated from the neuronal activity, the nystagmus often being totally suppressed whereas the neuronal activity was only attenuated. This suggests a further information processing between vestibular and oculomotor nuclei in the generation of nystagmus.

Serum IgE in atopic dermatitis: relationship to severity of cutaneous involvement and course of disease as well as coexistence of atopic respiratory diseases.

Abstract: Serum IgE concentrations were determined according to the radioimmunosorbent technique (RIST, Phadebas) on 116 adult patients with atopic dermatitis of varying severity and activity. Geometric mean IgE levels of patients with atopic dermatitis were significantly higher compared with the mean level of ninety-three non-atopic adult subjects without parasitic infestation. Severity of the atopic dermatitis was highly correlated to the levels of serum IgE. Severe chronic cases with ever-recurrent exacerbations show the most extreme values. In the moderate forms of atopic dermatitis, coexistent bronchial asthma causes a greater increase in the IgE values. Among the mild or abortive forms higher IgE levels were found in cases with allergic rhinitis than in the cases with 'pure' atopic dermatitis. Other findings in connection with IgE in atopic dermatitis are summarized. The pathogenetic significance of IgE in the cutaneous changes is briefly discussed.