The azoospermic factor on the Y chromosome

Azoospermia is the most frequent cause of male infertility. After excluding the obvious urological reasons and the effect of Klinefelter's syndrome, azoospermia may be caused by an abnormality in the crucial gene(s) expressed during male germ cell differentiation. Recently, two candidate genes for azoospermia have been cloned from the azoospermic factor (AZF) locus on the Y chromosome long arm (Yq). One is YRRM (Y chromosome RNA recognition motif) gene, and the other is DAZ (deletion in azoospermia) gene. Both genes encode RNA binding protein and their expression is restricted to the testis. Therefore they are good candidates for AZF, although their function remains unclear. Here, the genes on the Y chromosome possibly involved in spermatogenesis and the role of the Y chromosome in evolution are discussed.     

Possible Involvement of Protein Kinase C in the Modulation of Inotropic and Chronotropic Effects Induced by Ouabain in Rat Right Atrial Muscles

Modulations of the inotropic and chronotropic effects of ouabain and protein kinase C (PKC) stimulation with phorbol esters in rat right atria were examined. Cumulative administration of ouabain (3–30 μm ) caused a positive inotropic effect in a concentration-dependent manner, but did not produce a chronotropic effect. A single administration of ouabain (30 μm ) also had similar effects: +744 ± 84% (n = 23, P < 0.01) in the contractile force and ?0.7 ± 1.3% (n = 23, P > 0.05) in the sinus rate. Addition of phorbol esters reinforced the ouabain-evoked positive inotropic effect: 26.5 ± 8.9% (n = 6, P < 0.05) with 100 μm 4-β-phorbol-12,13-dibutyrate (PDB), and 6.4 ± 3.3% (n = 6, P > 0.05) with 100 μm 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Simultaneously, the mixture of ouabain and phorbol ester raised the resting tension. Phorbol esters alone caused a positive inotropic effect (by about 21–27%). Non-PKC activating phorbol ester, 4-α-phorbol-12,13-didecanoate (PDD, 100 μm ), did not have any effect. Pretreatment with the PKC inhibitor (staurosporine 100 μm ) significantly decreased the ouabain-induced positive inotropic effect and caused a negative chronotropic effect, but H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride) (5 μm ) had no effect. These results suggest that PKC stimulation may be involved in the ouabain-evoked responses in the right atria of rat as seen by increased cellular Ca²⁺ concentration (and Ca²⁺-sensitivity); thus the positive inotropic effect may not be due only to modulation of Na⁺/K⁺ pump activity.     

Gas chromatographic-mass spectrometric metabolic profiling of patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome

The metabolic profiles of three patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré syndrome were studied by simultaneous analysis, after urease treatment of urinary organic acids, carbohydrates, polyols and amino acids using gas chromatography/mass spectrometry (GC/MS). All three patients persistently showed lactic aciduria, phosphaturia, glucosuria and generalized amino aciduria. This abnormal urinary metabolic profile was observed before the onset of any clinical symptoms, indicating that chemical diagnosis may be done presymptomatically. In one patient, the concentration of lactate increased in parallel with the severity of the clinical condition, whereas the urinary levels of 3-hydroxybutyrate, amino acids and glucose fluctuated and showed only a general tendency to increase with the clinical course. The above results suggest that simultaneous GC/MS analyses, without fractionation, of urinary metabolites facilitate not only the early chemical diagnosis either before or after the first onset, but also follow-up studies, providing an important index for the evaluation of the severity and clinical course in patients with this disorder.     

Radionuclide assessment of left ventricular performance on exercise after external conduit operation

Only limited information is available concerning left ventricular (LV) response to exercise after an external conduit operation for cyanotic congenital heart disease. Sixteen patients who had undergone external conduit repair (EC group) were studied with multi-gated cardiac pool imaging using a supine bicycle ergometer on 20 occasions. Six patients with a history of Kawasaki disease without coronary artery stenosis served as controls (control group). Myocardial imaging and cardiac catheterization were also performed in the EC group. There was no significant difference in left ventricular ejection fraction (LVEF) at rest between the groups. However, on exercise, LVEF of the EC group was significantly lower than that of the control group. Nine patients in the EC group showed a perfusion defect (PD) on 12 occasions. LVEF on exercise of the patients with PD was significantly lower than that of the patients without PD. Furthermore, only the patients with PD showed a LVEF decrease of 5% or more in response to exercise. In the EC group, a significant inverse relationship was demonstrated between right ventricular systolic pressure (RVP) and LVEF response to exercise. However, two out of four patients who underwent external conduit replacement improved their LVEF response to exercise with successful reduction of RVP. These findings indicate that an impaired left ventricular response to exercise was common in patients after external conduit operations. Myocardial damage and right ventricular outflow tract obstruction could be the causes of this left ventricular dysfunction.