A morphometric study of spermatogenesis in the testes of mice of a senescence accelerated strain

The morphometric parameters of spermatogenic cells in a mouse strain prone to accelerated senescence (SAM-P), a novel murine model of spontaneously promoted aging, were compared with those of a SAM resistant strain (SAM-R) after birth until 40 weeks (mean life span of SAM-P). A mixture of gonocytes and spermatogonia were present in the testis in 1-week-old mice, and no gonocytes were observed in 2-week-old mice. At 6 weeks of age, the absolute number of spermatogonia in SAM-P was 27% greater than that in SAM-R, whereas the cell number in 40-week-old SAM-P was 17% less than in SAM-R. Primary spermatocytes were first observed in 3-week-old animals, and the cell numbers in SAM-P at 3, 5 and 6 weeks were 78%, 31% and 25%, respectively, greater than in SAM-R, whereas the cell number in SAM-P at 40 weeks was 30% less than SAM-R. Round spermatids were first observed in all SAM-P at 4 weeks old, but 20% of SAM-r had no spermatids and the rest had only a few. At 5 and 6 weeks old, the absolute numbers of round spermatids in SAM-P was about 34% and 41%, respectively, greater than in SAM-R, whereas the cell number in 40-week-old SAM-P was about 34% less than SAM-R. These results indicate that testicular maturation begins at an earlier age in SAM-P than SAM-R. Furthermore, at the age of 40 weeks signs of testicular deterioration are evident in SAM-P mice only     

Change in taste preference related to aging of taste cells in rat

Following the suppression of renewal of rat taste cells by vinblastine sulphate, the preference for sucrose decreased markedly while the aversion to quinine did not change. The results suggest that the sensitivity of taste cells to sucrose decreases with their aging, but the sensitivity to quinine increases.     

Plasma adenosine concentrations are elevated in Dahl salt-sensitive rats

We measured plasma levels of adenosine in Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) to examine the potential role of adenosine in cardiovascular regulation in this type of hypertension. Plasma adenosine concentrations were significantly higher in DS than in DR. The NaCl content in the diet did not affect plasma adenosine concentration in either DS or DR. Significant positive correlation was found between adenosine concentrations and systolic blood pressure when the data for DS and DR were analyzed together. These results suggest that adenosine may play an important role in the pathophysiology of hypertension in DS.     

TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function

Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.     

Haploinsufficiency of NSD1 causes Sotos syndrome

We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.     

Role of adenosine A1 and A2 receptors in the regulation of aldosterone production in rat adrenal glands

To investigate the roles of adenosine A1 and A2 receptors in the regulation of aldosterone production, we examined the effects of adenosine and adenosine agonists (N6-cyclohexyl adenosine; selective adenosine A1 receptor agonist and 5'-N-ethylcarboxamine adenosine; selective adenosine A2 receptor agonist) on aldosterone and cyclic AMP production in rat adrenal capsular cells. Neither adenosine nor 5'-N-ethylcarboxamine adenosine caused significant effects on basal aldosterone or cyclic AMP production. Also, adenosine (10(-3) M) showed no consistent effects on aldosterone and cyclic AMP production induced by ACTH. On the other hand, N6-cyclohexyl adenosine exhibited a significant inhibition of basal aldosterone and cyclic AMP production at doses of 10(-4) M and 10(-3) M; furthermore, 10(-3) M N6-cyclohexyl adenosine inhibited aldosterone and cyclic AMP production stimulated by ACTH. These results suggest that adenosine A1 receptors are coupled to and inhibit adenylate cyclase and may be involved in the inhibition of aldosterone production.     

Dissociation of digoxin-like immunoreactivity and Na+,K+-ATPase inhibitory activity in rat plasma

We measured endogenous digitalis-like factor (EDF) in rat plasma during acute saline infusion by two different procedures. Na+,K+-ATPase inhibitory activity in the rat plasma significantly increased during saline loading (7.8 +/- 2.2 vs 2.5 +/- 0.9%, with and without acute saline loading, respectively, p less than 0.05). On the other hand, the plasma digoxin-like immunoreactivity significantly decreased during acute saline loading (16.9 +/- 1.6 vs 32.0 +/- 2.8 pg digoxin equivalents/ml, with and without acute saline loading, respectively, p less than 0.01). These results indicate that the major substances detected by digoxin-like immunoreactivity and direct Na+,K+-ATPase inhibitory activity are completely different, at least in rat plasma.     

Cyclic AMP in neuroblastoma, ganglioneuroma and sympathetic ganglia.

Tissue content of cyclic AMP was as much as 10 times greater in ganglioneuroma than in neuroblastoma. This high cyclic AMP in ganglioneuroma was not significantly different from that of sympathetic ganglia.