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.     

Effects of Bepridil Versus E‐4031 on Transmural Ventricular Repolarization and Inducibility of Ventricular Tachyarrhythmias in the Dog

Background: Bepridil (a multiple channel blocker) may markedly prolong the QT interval and induce polymorphic ventricular tachyarrhythmias (VTA). We compared the transmural ventricular repolarization characteristics and inducibility of polymorphic VTA after administration of bepridil versus the pure I_Kr blocker, E‐4031, each administered to five open‐chest dogs. Methods: We used plunge needle electrode to record transmural left ventricular (LV) repolarization and activation‐recovery interval (ARI) to estimate local repolarization. The correlation between paced cycle length and ARI was separately examined in the LV endocardium, mid‐myocardium (Mid), and epicardium. Attempts to induce VTA were made during bradycardia and sympathetic stimulation. Results: Bepridil and E‐4031 prolonged QT interval and ARI in all LV layers, though the magnitude of prolongation was greatest in Mid, increasing the transmural ARI dispersion, particularly during bradycardia. Compared with E‐4031, bepridil caused mild, reverse use‐dependent changes in ventricular repolarization, and less ARI dispersion than E‐4031 during slow ventricular pacing. Both drugs increased ARI_max and cycle length at 50% of ARI_max, though the changes were smaller after bepridil than after E‐4031 administration. Bradycardia after the administration of each drug induced no VTA; however, sympathetic stimulation induced sustained polymorphic VTA in two of five dogs treated with E‐4031 versus no dog treated with bepridil. Conclusions: Unlike the pure I_kr blocker, E‐4031, bepridil exhibited weak properties of reverse use‐dependency and protected against sympathetic stimulation‐induced VTA. It may be an effective supplemental treatment for recipients of implantable cardioverter defibrillator. (PACE 2010; 950–959)     

Suppression of Storms of Ventricular Tachycardia by Epicardial Ablation of Isolated Delayed Potential in Noncompaction Cardiomyopathy

A 65‐year‐old recipient of an implantable cardioverter defibrillator suffering from ventricular noncompaction developed storms of ventricular tachycardia (VT). Epicardial voltage mapping revealed the presence of a large low‐voltage area in the left ventricular apical and inferoposterior wall, and isolated delayed potential was recorded over 1.5 cm in the posterior border between low and normal myocardial voltage. Pacemapping at the delayed potential recording site produced two different QRS depending on pacing output strength, and these two QRS morphologies were similar to clinically documented VTs. During one of the VTs, a mid‐diastolic potential was recorded from the site with the delayed potential, and rapid pacing produced concealed entrainment. After epicardial radiofrequency ablation of the isolated delayed potential, VTs were noninducible and the VT storm was suppressed.     

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.