Die Bedeutung des Natriums für den renal-tubulären Calcium-Transport bei Rana ridibunda

Zusammenfassung In Anlehnung an frühere Experimente zur Na⁺-Abhängigkeit der renal-tubulären Transporte von Glucose, PAH und Urea wurden Versuche über die Bedeutung des Na⁺ für die Ca⁺⁺-Reabsorption an der isolierten künstlich perfundierten Niere von Rana ridibunda durchgeführt.Erniedrigung des Na⁺-Angebotes von 76,5 auf 20,0 mMol/l vermindert sowohl die Menge reabsorbierten Natriums als auch die des reabsorbierten Calciums, letztere allerdings weniger als erstere. Der Quotient reabsorbiertes Na⁺/reabsorbiertes Ca⁺⁺ verschiebt sich zugunsten des Ca⁺⁺.Fehlendes Na⁺-Angebot auf der Lumen- oder der Blutseite der Tubulusepithelien hat keinen sicheren Einfluß auf die Menge reabsorbierten Calciums, dagegen sinkt die Reabsorptionsrate von Ca⁺⁺ auf weniger als 10% des filtrierten, wenn Na⁺ weder auf der Lumen- noch auf der Blutseite angeboten wird.Die Ca⁺⁺-Reabsorptionsrate ist gesteigert bei Angebot von Ca⁺⁺ ausschließlich auf der Lumenseite, vermutlich wegen des unter physiologischen Bedingungen nicht existenten Konzentrationsgradienten, der blutwärts gerichtet ist. Bei Angebot von Ca⁺⁺ nur von der Blutseite erscheint kein Ca⁺⁺ im Harn: die Tubulusepithelien sind für Ca⁺⁺ im Richtungssinne der Sekretion undurchlässig.Durch die Hemmstoffe der Na⁺-Reabsorption Convallatoxin und Furosemid wird auch die Reabsorption von Ca⁺⁺ — sogar relativ stärker als die von Na⁺ — gehemmt. Da in den Versuchen mit Hemmstoffen das Na⁺-Angebot (extracelluläre Konzentration) konstant bleibt, wird geschlossen, daß die Ca⁺⁺-Reabsorption mit dem Na⁺ über dessen Transport gekoppelt ist.Im Prinzip folgt die Verknüpfung der Ca⁺⁺-Reabsorption mit dem Na⁺ den gleichen Gesetzmäßigkeiten wie die Verknüpfung des Na⁺ mit den Transporten von Glucose, PAH und Harnstoff. Damit ist ein weiteres Indiz für die Vermutung gewonnen, daß die Na⁺-Abhängigkeit ein zellphysiologisches Prinzip von weiter Gültigkeit ist.

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Summary With regard to earlier experiments about the influence of Na⁺ on the tubular transport of glucose, PAH and urea, the effect of Na⁺ on the reabsorption of Ca⁺⁺ in the isolated artificially perfused kidney of Rana ridibunda was studied.Lowering of the Na⁺-concentration from 76.5–20.0 mMol/l results in a decrease of the reabsorbed amounts of both Na⁺ and Ca⁺⁺, the decrease being less marked in the latter. The quotient Na⁺ reabsorbed/Ca⁺⁺ reabsorbed changes in favour of the calcium.Lack of Na⁺ on the luminal or the contraluminal side of the tubular wall does not significantly influence the amount of Ca⁺⁺ being reabsorbed. If, however, Na⁺ is missing on both sides the rate of reabsorption of Ca⁺⁺ falls below 10% of the filtered amount.The rate of Ca⁺⁺-reabsorption increases if Ca⁺⁺ is offered on the luminal side only. Presumably this increase is due to a concentration gradient for Ca⁺⁺ which does not exist under physiological conditions. If Ca⁺⁺ is offered on the contraluminal side only, no Ca⁺⁺ appears in the urine. Apparently the tubular epithelium is impermeable for Ca⁺⁺ from the blood to the tubular lumen.The decrease of the reabsorption of Ca⁺⁺ brought about by substances inhibiting the reabsorption of Na⁺ such as Convallatoxin and Furosemid is relatively more marked than the concomitant inhibition of the reabsorption of Na⁺.Since in the experiments with the above mentioned inhibitors the extracellular Na⁺-concentration remains constant, it is concluded that the Ca⁺⁺-reabsorption is coupled with the transport of Na⁺.In principle the Na⁺-dependence of the Ca⁺⁺-reabsorption follows the same pattern as the Na⁺-dependence of the transports of glucose, PAH and urea, thus supporting our contention that the Na⁺-dependence of active transports is a physiological mechanism of general importance.

     

The PAR1 (YAP1/SNQ3) gene of Saccharomyces cerevisiae,ac-jun homologue,is involved in oxygen metabolism

Summary The PAR1/SNQ3 gene of S. cerevisiae, which increases resistance to iron chelators in multi-copy transformants, is identical to the YAP1 gene, a yeast activator protein isolated as a functional homologue of the human c-jun oncogene by binding specifically to the AP-1 consensus box. The observed H₂O₂-sensitivity of par1 mutants has been attributed to an increased sensitivity to reduced oxygen intermediates. Accordingly, par1 mutants did not survive an elevated oxygen pressure and were very sensitive to menadione and methylviologene, two chemicals enhancing the deleterious effects of oxygen. The specific activities of enzymes involved in oxygen detoxification, such as superoxide dismutase, glucose 6-phosphate dehydrogenase and glutathione reductase, were decreased in par1 mutants and increased after PAR1 over-expression. As in the case of oxygen detoxification enzymes, the cellular levels of glutathione were similarly affected. These observations indicate that PAR1/YAP1/SNQ3 is involved in the gene regulation of certain oxygen detoxification enzymes. The finding that H₂O₂ promotes DNA-binding of human c-jun is consistent with a similar function for PAR1/YAP1/SNQ3 and c-jun in cellular metabolism.Dedicated to Professor Dr. R. W. Kaplan on the occasion of his 80th birthday     

Partial rescue of the Dazl knockout mouse by the human DAZL gene

Y-chromosomal DAZ (deleted in azoospermia) and autosomal DAZ-like (DAZL) comprise a gene family involved in gametogenesis. Y-chromosomal and autosomal genes only co-exist in humans and old world monkeys, indicating that DAZ genes are a recent acquisition of the Y chromosome. In most mammals, the ancestral Dazl alone is sufficient to complete gametogenesis. It is not yet understood why humans and old world monkeys have a second set of genes that are apparently necessary for spermatogenesis, since deletions removing the Y-chromosomal DAZ are often associated with azoo- or oligospermia. We used transgenic mice carrying either human DAZL or human DAZ on a mouse Dazl null background to investigate the functions of the human homologues. Both transgenes enabled prophase spermatocytes to be produced, mainly of the leptonema/zygonema stage, but failed to promote differentiation into mid- to late pachytenes. The presence of human DAZL resulted in a larger amount of early germ cells compared with that observed in DAZ. The degree of rescue was independent of copy number, integration site or presence of the DAZ repeat region for the DAZ transgenes. These findings confirm that DAZL and DAZ can only substitute for early functions of the murine homologue resulting in the establishment of the germ cell population and partial progression into meiosis.     

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48 m2/g) were compared with beta-tricalcium phosphate (beta-TCP), hydroxyapatite (HA) ceramics (both ca. 0.5 m2/g surface) and demineralized bone matrix (DBM). Before implantation in the back of SCID mice carriers were freshly loaded with 2x10(5) expanded human MSC or loaded with cells and kept under osteogenic conditions for two weeks in vitro. Culture conditions were kept free of xenogenic supplements. Deposits of osteoid at the margins of ceramic pores occurred independent of osteogenic pre-induction, contained human cells, and appeared in 416 MSC/CDHA composites compared to 216 MSC/beta-TCP composites. ALP activity was significantly higher in samples with MSC versus empty controls (p<0.001). Furthermore, ALP was significantly (p<0.05) higher for all ceramics when compared to the DBM matrix. Compared to previous studies, overall bone formation appeared to be reduced possibly due to the strict human protocol. Ectopic bone formation in the novel biomaterial CDHA varied considerably with the cell pool and was at least equal to beta-TCP blocks.     

Infantile hemangioma is a proliferation of beta 4-negative endothelial cells adjacent to HLA-DR-positive cells with dendritic cell morphology

Although hemangioma is referred as to the most common tumor in infancy, the underlying pathogenetic events and the biologic origin of this benign vascular neoplasm have remained obscure. By using immunohistochemistry on frozen sections of infantile hemangiomas, we show here that proliferating endothelial cells abundantly expressed alpha(v)beta(3) but lacked beta(4) integrins. Instead, regressing and involuting infantile hemangiomas due to treatment with IFN-alpha showed positive staining of beta(4) integrin, which might point to the angiogenic significance of beta(4) integrin in infantile hemangiomas. Moreover, immunofluorescence analysis revealed the existence of HLA-DR(+), mostly CD68(+) and partly DC-SIGN/CD209(+) cells with dendritic cell morphology in the intimate vicinity of hemangiomatous vessels. Such cells were also detected in the dermal microvascular unit in normal skin. The coupled occurrence of vascular structures and perivascular cells that were stained positive with markers of monocyte or macrophage or dendritic cells might suggest that the development of infantile hemangioma is a result of vasculogenesis, that is, the formation of primitive blood vessels from angioblasts, rather than of angiogenesis, that is, the sprouting of capillaries from preexisting vessels.     

Über Funktionsänderungen markhaltiger Kaltblüternerven nach Adrenalektomie und Zufuhr rindenwirksamer Steroide in Abhängigkeit von der Ionenverteilung

Ohne ZusammenfassungBenutzte Symbole und Abkürzungen NNR Nebennierenrinde - DOCA Desoxycorticosteronacetat - K _i intracelluläres Kalium (sinngemäß für Natrium) - K _a extracelluläres Kalium (sinngemäß für Natrium) - Q Ladung - E _m Membranruhepotential - _m Zeitkonstante der Membran - R _m Membranwiderstand - C _m Membrankapazität