To determine the risks when the primary methotrexate (MTX) treatment of cervical pregnancy has an unsatisfactory outcome, we conducted a Medline search on relevant literature published from January 1983 to June 1997. The search yielded 28 publications of 48 cases of cervical pregnancy. These and four new cases from our institutions were used in our study. A cervical pregnancy that presented with a serum beta-human chorionic gonadotrophin concentration of > or = 10,000 mIU/ml [odds ratio (OR) 10.82, 95% confidence interval (CI) 2.59, 45.14], gestational age at > or = 9 weeks (OR 6.44, 95% CI 1.46, 28.52), embryonic cardiac activity (OR 14.29, 95% CI 2.95, 76.92), and crown-rump length of >10 mm (OR 13.33, 95% CI 1.46, 120.48) was considered to be associated with a higher unsatisfactory rate of primary MTX treatment. A concomitant feticide was found to enhance the therapeutic effect of MTX treatment if embryonic cardiac activity was evident (OR 0.13, 95% CI 0.02, 0.68). Administration of a high dose of MTX did not seem to be more effective than a lower one. Our findings supported some previous observations and, more importantly, provided useful clinical information in selecting appropriate candidates for MTX treatment in cases of cervical pregnancy.
Episodic ataxia type 2 (EA2) is an inherited autosomal dominant disorder related to cerebellar dysfunction and is associated with mutations in the pore-forming alpha(1A)-subunits of human P/Q-type Ca(2+) channels (Cav2.1 channels). The majority of EA2 mutations result in significant loss-of-function phenotypes. Whether EA2 mutants may display dominant-negative effects in human, however, remains controversial. To address this issue, five EA2 mutants in the long isoform of human alpha(1A)-subunits were expressed in Xenopus oocytes to explore their potential dominant-negative effects. Upon coexpressing the cRNA of alpha(1A)-WT with each alpha(1A)-mutant in molar ratios ranging from 1:1 to 1:10, the amplitude of Ba(2+) currents through wild-type (WT)-Cav2.1 channels decreased significantly as the relative molar ratio of alpha(1A)-mutants increased, suggesting the presence of an alpha(1A)-mutant-specific suppression effect. When we coexpressed alpha(1A)-WT with proteins not known to interact with Cav2.1 channels, we observed no significant suppression effects. Furthermore, increasing the amount of auxiliary subunits resulted in partial reversal of the suppression effects in nonsense but not missense EA2 mutants. On the other hand, when we repeated the same coinjection experiments of alpha(1A)-WT and mutant using a splice variant of alpha(1A)-subunit that contained a considerably shorter COOH terminus (i.e., the short isoform), no significant dominant-negative effects were noted until we enhanced the relative molar ratio to 1:10. Altogether, these results indicate that for human WT-Cav2.1 channels comprising the long-alpha(1A)-subunit isoform, both missense and nonsense EA2 mutants indeed display prominent dominant-negative effects.
The present study describes the psychological impact of human papillomavirus (HPV)-related conditions or preventive interventions on Taiwanese women. Women with an HPV-related diagnosis or intervention within the past 3 months were invited to participate in a cross-sectional survey before the receipt of HPV-related diagnostic results. Participants completed a 29-item HPV impact profile (HIP), which was a questionnaire designed to represent the full spectrum of potential HPV-related impacts. The HIP assesses worries and concerns; emotional impact; sexual impact; self-image; partner issues and transmission; interactions with doctors; and control/life impact. The final sample size was 249 women from three hospitals. The mean HIP score (0-100) was normal Pap: 28.2; abnormal Pap: 44.3; CIN: 47.5; genital warts: 62.5; abnormal Pap with high-risk HPV positive: 48.8. This study indicates that significant psychological impact is found in women diagnosed with abnormal Pap, CIN, high-risk HPV test positive and genital wart compared to women with a normal Pap. Women with genital warts had the highest psychological impact scores. This is the first quantitative data that can lay the ground work for future studies that enable the comparison of the effectiveness of different interventions in alleviating the psychological burden of HPV-associated infection and preventive interventions in Taiwan.
Two isoforms of rat ether-a-go-go (Eag) K channels, rEag1 and rEag2, are widely expressed in many regions of the brain. The neurophysiological roles of these channels, however, are unclear. We addressed this issue by studying their subcellular localizations in hippocampal neurons. Immunofluorescence studies using markers for different compartments of neurons demonstrated a differential expression pattern of rEag1 and rEag2 K channels in the somatodendritic region. Furthermore, rEag1 K channels were in close proximity to synaptophysin and densin-180, but not GAD65. Our data suggest that both rEag1 and rEag2 K channels may play a pivotal role in the regulation of the excitability of dendrites and somas, and that rEag1 K channels may modulate the postsynaptic signaling of glutamatergic synapses.
Thy-1, a glycosylphosphatidylinositol-linked integral membrane protein of the immunoglobulin superfamily, is a component of both large dense-core and small clear vesicles in PC12 cells. A majority of this protein, formerly recognized only on the plasma membrane of neurons, is localized to regulated secretory vesicles. Thy-1 is also present in synaptic vesicles in rat central nervous system. Experiments on permeabilized PC12 cells demonstrate that antibodies against Thy-1 inhibit the regulated release of neurotransmitter; this inhibition appears to be independent of any effect on the Ca2+ channel. These findings suggest Thy-1 is an integral component of many types of regulated secretory vesicles, and plays an important role in the regulated vesicular release of neurotransmitter at the synapse.
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