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Biomedical subjects

U Wolf

Publications and source records attributed to U Wolf.

At least 73 records · Page 4Linked to original sources

X-linked genes of the H-Y antigen system in the wood lemming (Myopus schisticolor).

H-Y antigen was investigated in 18 specimens representing six different sex chromosome constitutions of the wood lemming (Myopus schisticolor). The control range of H-Y antigen was defined by the sex difference between normal XX females (H-Y negative per definitionem) and normal XY males (H-Y positive, full titer). H-Y antigen titers of the X*Y and X*0 females were in the male control range, while in the X*X and X0 females the titers were intermediary. Data were obtained with two different H-Y antigen assays: the Raji cell cytotoxicity test and the peroxidase-antiperoxidase (PAP) method. Fibroblasts, gonadal cells, and spleen cells were checked. Presence of full titers of H-Y antigen in the absence of testis differentiation is readily explained by the assumption of a deficiency of the gonad-specific receptor of H-Y antigen. Since sex reversal is inherited as an X-linked trait, genes for this receptor are most likely X-linked. The implications of our findings are discussed in connection with earlier findings concerning H-Y antigen in XY gonadal dysgenesis in man and the X0 situation in man and mouse.

Animals↗

Stress-induced reduction of gastric acid in the rat is not associated with increased tissue somatostatin.

In zero, mildly and severely stressed rats, gastric acid secretion, aortal and portal venous gastrin, venous glucagon and somatostatin in gastric, duodenal mucosa and in pancreas were examined. Serum gastrin and gastric acid secretion are reduced markedly by both kinds of stress, whereas plasma glucagon rises steadily with stress. As somatostatin in the tissues of stressed rats is not different from unstressed controls, gastrin and gastric acid reduction may not be attributed to an endocrine or paracrine action of somatostatin.

Animals↗

Genetic heterogeneity of XY gonadal dysgenesis (Swyer syndrome): H-Y antigen-negative XY gonadal dysgenesis associated with inflammatory bowel disease.

A 16 1/2-year-old girl was studied because of ileitis, lack of pubertal development, and primary amenorrhea. She had a 46,XY chromosome constitution in lymphocytes in fibroblasts without structural defects of X or Y. She was H-Y antigen negative. This observation supports the concept of causal heterogeneity of XY gonadal dysgenesis (Swyer syndrome). Two groups have been established: (1) H-Y antigen-positive forms, which are more common, possibly due to gonad-specific receptor defects (total failure or reduced receptor affinity), (2) H-Y antigen-negative forms possibly due to mutation in the H-Y generating system, either of the structural gene (presumably autosomal) or of a controlling gene (on the sex chromosomes). The H-Y antigen status may be of value in determining which patients are at risk for gonadoblastoma or dysgerminoma.

Adolescent↗

Sex-reversed XY females with campomelic dysplasia are H-Y negative.

Three families with infants affected with campomelic dysplasia, a genetically determined mesenchymal disease frequently associated with sex reversal were studied. Two XY females with ovarian gonadal differentiation and typical clinical features of campomelic dysplasia could be tested for H-Y antigen and were found to be H-Y negative.

Bone and Bones↗

Genetic aspects of H-Y antigen.

While it remains to be clarified what detection of H-Y antigen by current methods means, the existence of a factor governing testicular differentiation of the indifferent gonadal anlage seems to be well established. There are various kinds of evidence that H-Y antigen as a biologically meaningful factor has a complex genetical basis. There is the contribution of the Y chromosome which, independent of the number of other chromosomes, especially of X chromosomes, leads to a male phenotype. The X chromosome must be involved also because structural aberrations of its distal short arm influence the expression of the H-Y structural gene. Due to examples of autosomal inheritance of various forms of sex reversal, an autosomal gene is assumed to be involved as well. Arguments are presented favoring the assumption that the structural H-Y gene is autosomal, while genes on the X and Y chromosomes have a controlling function. This genetic control mechanism for H-Y antigen seems to have evolved secondary to placentation in mammals. In non-mammalian vertebrates, H-Y antigen is controlled by other factors, e.g. steroid hormones. While the functional role of H-Y antigen in directing differentiation of the heterogametic gonad appears to have been preserved during evolution, the mechanism of its control has changed. This latter mechanism is only poorly understood.

Animals↗

Gastric secretion, mucosal erosions and porto-systemic gastrin gradients as influenced by different degrees of stress in the rat.

Gastric fistula rats (n = 79) were either left as unstressed (fistula closed) controls or gastric secretion, microcirculation (MBF), mucosal stress ulcers were studied in secretory rats subjected to zero (= freely movements allowed), mild, severe restraint stress for 8 h. In all rats gastrin in portal vein and aorta was measured in addition after discontinuation of either protocol. Acid secretion and MBF are progressively reduced by increasing stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Serum gastrin (controls - aorta 53+/- SEM 5, portal vein 73 +/- 9 pg/ml) rises sharply in portal and systemic blood with institution of acid diversion via the outside (zero stress - 136 +/- 21, 398 +/- 98 pg/ml), but declines with increasing stress (severe stress - 82 +/- 16, 101 +/- 27 pg/ml) despite otherwise identical experimental conditions. It is concluded that (1) acid secretion rate and MBF are lowered by stress, but stress ulcers are associated with either increased acidity (mild stress) or peptic activity (severe stress) of gastric juice in the absence of elevated gastrin, (2) enhanced sodium fluxes via gastric lumen and lower acid suggest disruption if mucosal barrier by severe stress, and (3) restraint stress ulcers may be the expression of a combination of disturbances, mainly of metabolic and endocrine nature.

Animals↗

Cell reorganization in vitro of heterosexual gonadal cocultures.

Male and female gonadal cells of newborn rats were cocultured in varying proportions. As low a proportion as 20% of male cells essentially yielded tubular structures. At lower quotas of testicular cells, however, only follicular structures occurred. Mixed structures were not observed except one experiment (20% male cells). When ovarian cells were cocultivated with male nongonadal cells, no conversion occurred. It is assumed that H-Y antigen secreted by male gonadal cells is bound by the ovarian receptor sites and induces conversion into tubular structures. H-Y antigen integrated into the cell membrane of nongonadal male cells does not seem to be able to exert this morphogenetic effect.

Animals↗

XY gonadal dysgenesis: aberrant testicular differentiation in the presence of H-Y antigen.

Six patients with pure nonmosaic 46,XY gonadal dysgenesis (XY GD) and histocompatibility H-Y antigen titers in the normal male range (H-Y+) are presented. Clinical characteristics included a female phenotype, masculine skeletal characteristics, signs of virilization, and primary amenorrhea. All individuals had unambiguous female external genitalia, a hypoplastic uterus, bilateral tubes, and streak gonads. Histomorphologic evaluation of the gonads revealed various abortive testicular and ovarian elements capable of steroid production. Gonadal tumors were found in 4 patients (gonadoblastoma, dysgerminoma, granulosa cell tumor, myxofibroma). Plasma and urinary androgens and basal and stimulated gonadotropin levels were elevated prior to gonadectomy. Data show that the presence of the H-Y antigen per se does not guarantee normal testicular organogenesis. It is hypothesized that defective H-Y antigen binding to its gonadal receptors triggers aberrant testicular differentiation in 46,XY H-Y+ GD.

Adult↗

A gene controlling H-Y antigen on the X chromosome. Tentative assignment by deletion mapping to Xp223.

The existence of a strict correlation between presence of testicular tissue and presence of H-Y antigen in mammals and man leads to the conclusion that H-Y antigen is an essential differentiation factor in testicular morphogenesis. Presence of low titers of this differentiation antigen even in fertile females indicates that its morphogenetic effect depends on a threshold. Here, studies on H-Y antigen in female individuals with various deletions of the X-chromosome are reported. It turns out that deletion of Xp results in the synthesis of reduced amounts of H-Y antigen, while deletion of Xq does not. In a fertile female with only Xp223 deleted due to an X/Y translocation, including the distal Yq, presence of a reduced H-Y titer allows for the tentative assignment of a controlling gene repressing the H-Y structural gene. From the cases studied, it follows that the H-Y structural gene is autosomal and under the control of X- and Y-linked genes. The conception emerges that interaction between X- and Y-linked genes or their products results in variation of the H-Y antigen titer. The fate of the indifferent gonadal anlage to differentiate into the male or the female direction will depend on the titer of H-Y antigen reached by the action or interaction of the controlling genes involved.

Adolescent↗

Turner syndrome patients are H-Y positive.

H-Y antigen was examined in six patients exhibiting the characteristic features of Turner syndrome. Five of the patients were of the karyotype 45,X, and one was a mosaic 45,X/46, Xi(Xq). H-Y antigen was detected in all of them, however, compared to male controls, their antigen titer was reduced. Within the intermediate range between female and male controls, considerable interindividual variation was detected among the patients which could be due to least in part to biological variation. The findings permit the inference that the H-Y structural gene is not Y-linked, and support the assumptions of an X-linked gene escaping inactivation and of it controlling the expression of the H-Y structural gene. It is probable that the structural gene itself is autosomal. The results also suggest that male gonadal differentiation is dependent on a threshold level of H-Y antigen concentration.

Cytotoxicity Tests, Immunologic↗

Phenotypic conversion of human erythrocytes by H-Y antigen.

Human male erythrocytes absorb H-Y antiserum while those of human females do not. Studies on the mode of attachment of H-Y antigen to the erythrocyte membrane reveal: (1) After several washes H-Y antigen can only be removed from male erythrocytes and not from other male cells such as granulocytes. (2) Female erythrocytes absorb exogenous H-Y antigen and thus become H-Y positive. (3) Complement mediated lysis of erythrocytes by H-Y antiserum is not sex specific but is dependent on the ABO blood group type of the red blood cells. It is concluded that H-Y antigen is unspecifically attached to red blood cells and is therefore not an integral part of the erythrocyte membrane.

ABO Blood-Group System↗

Inhibition of testicular organization in vitro by newborn rat ovarian cell supernatants.

Cell reorganization experiments performed with newborn rat gonadal single cell suspensions resulted in organ-like reorganization after 18 h of rotation culture. When, however, testicular cells were incubated in supernatants of newborn rat ovarian cells, testicular organization was suppressed and the architecture of the reorganized gonad was rather feminine. Supernatants of adult rat ovarian cells did not inhibit testicular organization. The possible mechanisms responsible for the failure of the function of H-Y antigen by the presence of ovarian cell supernatants of newborn rats are discussed.

Animals↗

Mammalian cross-reactive H-Y antigen induces sex reversal in vitro in the avian testis.

Testes of either newborn rats or newly hatched chickens, dissociated into single cell suspensions, reorganize in vitro into their histotypic structures. In birds, the heterogametic female sex is H-Y antigen positive, and not the male as in mammals. Cocultivation of rat and chicken testicular cells results in the reorganization of an ovotestis. A similar result is obtained after cultivation of chicken testicular cells in the supernatant medium of cultured human male Burkitt lymphoma Daudi cells. Rat testicular Sertoli cells as well as Daudi cells are a source of H-Y antigen. The simultaneous application of H-Y antigen and anti-H-Y antiserum prevents ovotestis formation. It is concluded that H-Y antigen which is known to be testis-organizing in mammals, is the ovary-organizing factor in birds.

Animals↗

Familial XX true hermaphroditism and the H-Y antigen.

Two 46,XX sibs, one of female, one of male gender, and both with ambiguous external genitalia and ovotestis, were H-Y positive. The mother was H-Y negative. It is assumed that the underlying mutation was transmitted by the father, resulting in an autosomal dominant mode of inheritance. The common origin and the nature of the mutation leading to XX sex reversal are discussed.

Adolescent↗