PREVALENCE OF MITRAL VALVE PROLAPSE IN HONG KONG CHINESE A CLINICAL AND AUTOPSY STUDY

The prevalence of mitral valve pro.lapse in Chinese was determined by screening 156 heal- thy subjects and by patholobic examination of 86 adult autopsies. Mitral valve prolapse was found in 7.7% in the clinical study and 5.8% in the autopsy study. A slight female preponderance was noted.     

Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy in human lung cells

Hexavalent chromium [Cr(VI)] compounds are established human lung carcinogens. The carcinogenicity of Cr(VI) is related to its solubility, with the most potent carcinogens being the insoluble particulate Cr(VI) compounds. However, it remains unknown why particulate Cr(VI) is more carcinogenic than soluble Cr(VI). One possible explanation is that particulates may provide more chronic exposures to chromate over time. We found that aneuploid cells increased in a concentration- and time-dependent manner after chronic exposure to lead chromate. Specifically, a 24-hour lead chromate exposure induced no aneugenic effect, whereas a 120-hour exposure to 0.5 and 1 microg/cm2 lead chromate induced 55% and 60% aneuploid metaphases, respectively. We also found that many of these aneuploid cells were able to continue to grow and form colonies. Centrosome defects are known to induce aneuploidy; therefore, we investigated the effects of chronic lead chromate exposure on centrosomes. We found that centrosome amplification in interphase and mitotic cells increased in a concentration- and time-dependent manner with 0.5 and 1 microg/cm2 lead chromate for 120 hours, inducing aberrant centrosomes in 18% and 21% of interphase cells and 32% and 69% of mitotic cells, respectively; however, lead oxide did not induce centrosome amplification in interphase or mitotic cells. There was also an increase in aberrant mitosis after chronic exposure to lead chromate with the emergence of disorganized anaphase and mitotic catastrophe. These data suggest that one possible mechanism for lead chromate-induced carcinogenesis is through centrosome dysfunction, leading to the induction of aneuploidy.     

Pulse sequence optimization for MR imaging using a paramagnetic hepatobiliary contrast agent

Paramagnetic agents enhance contrast between tissues in magnetic resonance (MR) imaging by altering tissue relaxation times. The effect of these changes on MR image intensity depends in part on the choice of operator-controlled pulse sequence parameters. With the newly described paramagnetic hepatobiliary contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine), Fe(EHPG)-, an in vivo experimental analysis of pulse sequence optimization was performed on the rat. We compared the enhancement of the liver divided by background noise, EL/N, of standard inversion-recovery (IR) and spin-echo (SE) T1-weighted pulse sequences and several pulse sequences theoretically predicted to have improved EL/N. Optimization of the echo time (TE = TEmin) gave a substantial (greater than 60%) increase in EL/N over the standard IR and SE pulse sequences. Images obtained with optimized repetition rate and inversion time gave only a slight additional improvement. Within the uncertainties of our relaxation measurements, the measured changes in EL/N with pulse sequence optimization corresponded well with theoretical predictions. With the experimental and theoretical data, the importance of using a short echo time to obtain maximal T1 contrast in contrast-enhanced MR imaging and the relative merits of optimized SE versus IR pulse sequences for contrast-enhanced MR imaging are discussed.     

Cysteine scanning and modification reveal major differences between BK channels and Kv channels in the inner pore region

BK channels are regulated by two distinct physiological signals, transmembrane potential and intracellular Ca(2+), each acting through independent modular sensor domains. However, despite a presumably central role in the coupling of sensor activation to channel gating, the pore-lining S6 transmembrane segment has not been systematically studied. Here, cysteine substitution and modification studies of the BK S6 point to substantial differences between BK and Kv channels in the structure and function of the S6-lined inner pore. Gating shifts caused by introduction of cysteines define a pattern and direction of free energy changes in BK S6 distinct from Shaker. Modification of BK S6 residues identifies pore-facing residues that occur at different linear positions along aligned BK and Kv S6 segments. Periodicity analysis suggests that one factor contributing to these differences may be a disruption of the BK S6 α-helix from the unique diglycine motif at the position of the Kv hinge glycine. State-dependent MTS accessibility reveals that, even in closed states, modification can occur. Furthermore, the inner pore of BK channels is much larger than that of K(+) channels with solved crystal structures. The results suggest caution in the use of Kv channel structures as templates for BK homology models, at least in the pore-gate domain.     

Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa

Mouse spermatozoa express a pH-dependent K(+) current (KSper) thought to be composed of subunits encoded by the Slo3 gene. However, the equivalence of KSper and Slo3-dependent current remains uncertain, because heterologous expression of Slo3 results in currents that are less effectively activated by alkalization than are native KSper currents. Here, we show that genetic deletion of Slo3 abolishes all pH-dependent K(+) current at physiological membrane potentials in corpus epididymal sperm. A residual pH-dependent outward current (I(Kres)) is observed in Slo3(-/-) sperm at potentials of >0 mV. Differential inhibition of KSper/Slo3 and I(Kres) by clofilium reveals that the amplitude of I(Kres) is similar in both wild-type (wt) and Slo3(-/-) sperm. The properties of I(Kres) suggest that it likely represents outward monovalent cation flux through CatSper channels. Thus, KSper/Slo3 may account for essentially all mouse sperm K(+) current and is the sole pH-dependent K(+) conductance in these sperm. With physiological ionic gradients, alkalization depolarizes Slo3(-/-) spermatozoa, presumably from CatSper activation, in contrast to Slo3/KSper-mediated hyperpolarization in wt sperm. Slo3(-/-) male mice are infertile, but Slo3(-/-) sperm exhibit some fertility within in vitro fertilization assays. Slo3(-/-) sperm exhibit a higher incidence of morphological abnormalities accentuated by hypotonic challenge and also exhibit deficits in motility in the absence of bicarbonate, revealing a role of KSper under unstimulated conditions. Together, these results show that KSper/Slo3 is the primary spermatozoan K(+) current, that KSper may play a critical role in acquisition of normal morphology and sperm motility when faced with hyperosmotic challenges, and that Slo3 is critical for fertility.     

P2X_2和P2X_3受体在小鼠咽粘膜味蕾内的分布

应用免疫组织化学双标记技术研究ATP受体的P2X2和P2X3受体亚型在小鼠咽部粘膜味蕾和邻近组织内的分布,探究ATP在咽部味觉及一般感觉信号传导中的作用。在咽部各水平粘膜味蕾内均可观察到许多P2X2受体阳性味细胞和基细胞,未见P2X2受体阳性的神经纤维。许多降钙素基因相关肽(CGRP)阳性神经纤维围绕在味蕾周围,并发出分支与P2X2受体阳性味细胞和基细胞形成密切接触。P2X3受体多在咽部粘膜上皮味蕾内的神经终末表达,P2X3受体阳性纤维在粘膜基底部形成纤维束并与粘膜下P2X3受体阳性纤维相连,其分支在味蕾基底部形成神经丛,由神经丛发出神经终末到达顶部的味孔和味蕾各部,未见味蕾细胞表达P2X3受体。在无味蕾的粘膜上皮内,也观察到少量P2X3受体阳性神经终末。CGRP阳性纤维缠绕在味蕾周围,并发出分支与味蕾内的P2X3受体阳性纤维形成密切接触。上述结果表明ATP可能是咽粘膜内味觉信号感受与传导的神经递质。