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Biomedical subjects

P Chi

Publications and source records attributed to P Chi.

9 recordsLinked to original sources

Synapsin dispersion and reclustering during synaptic activity.

Presynaptic modulation of synaptic transmission provides an important basis for control of synaptic function. The synapsins, a family of highly conserved proteins associated with synaptic vesicles, have long been implicated in the regulation of neurotransmitter release. However, direct physiological measurements of the molecular mechanisms have been lacking. Here we show that in living hippocampal terminals, green fluorescent protein (GFP)-labeled synapsin Ia dissociates from synaptic vesicles, disperses into axons during action potential (AP) firing, and reclusters to synapses after the cessation of synaptic activity. Using various mutated forms of synapsin Ia that prevent phosphorylation at specific sites, we performed simultaneous FM 4-64 measurements of vesicle pool mobilization along with synapsin dispersion kinetics. These studies indicate that the rate of synapsin dispersion is controlled by phosphorylation, which in turn controls the kinetics of vesicle pool turnover. Thus synapsin acts as a phosphorylation-state-dependent regulator of synaptic vesicle mobilization, and hence, neurotransmitter release.

Action Potentials↗

Glucocorticoid-mediated destabilization of cyclin D3 mRNA involves RNA-protein interactions in the 3'-untranslated region of the mRNA.

Glucocorticoids regulate the expression of the G(1) progression factor, cyclin D3. Cyclin D3 messenger RNA (CcnD3 mRNA) stability decreases rapidly when murine T lymphoma cells are treated with the synthetic glucocorticoid dexamethasone. Basal stability of CcnD3 mRNA is regulated by sequences within the 3'-untranslated region (3'-UTR). RNA-protein interactions occurring within the CcnD3 3'-UTR have been analyzed by RNA electrophoretic mobility shift assay. Three sites of RNA-protein interaction have been mapped using this approach. These elements include three pyrimidine-rich domains of 25, 26, and 37 nucleotides. When the cyclin D3 3'-UTR was stably overexpressed, the endogenous CcnD3 mRNA was no longer regulated by dexamethasone. Likewise, overexpression of a 215-nucleotide transgene that contains the 26- and 37-nucleotide elements blocks glucocorticoid inhibition of CcnD3 mRNA expression. These observations suggest that the 215-nucleotide 3'-UTR element may act as a molecular decoy, competing for proteins that bind to the endogenous transcript and thereby attenuating glucocorticoid responsiveness. UV-cross-linking experiments showed that two proteins of approximate molecular weight 37,000 and 52,000 bind to this 3'-UTR element.

3' Untranslated Regions↗

Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication.

Human cytomegalovirus is a herpesvirus that induces numerous cellular processes upon infection. Among these are activation of cyclin-dependent kinase 2, which regulates cell cycle progression in G1 and S phase. We report here that inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2 activity by roscovitine inhibits HCMV DNA synthesis, production of infectious progeny, and late antigen expression in infected cells in a dose-dependent manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant negative mutant, whereas expression of wild-type Cdk2 has no effect on viral replication. These data indicate that activation of cellular Cdk2 is necessary for HCMV replication.

Antigens, Viral↗

Receptor and betagamma binding sites in the alpha subunit of the retinal G protein transducin.

Transmembrane receptors for hormones, neurotransmitters, light, and odorants mediate their cellular effects by activating heterotrimeric guanine nucleotide-binding proteins (G proteins). Crystal structures have revealed contact surfaces between G protein subunits, but not the surfaces or molecular mechanism through which Galphabetagamma responds to activation by transmembrane receptors. Such a surface was identified from the results of testing 100 mutant alpha subunits of the retinal G protein transducin for their ability to interact with rhodopsin. Sites at which alanine substitutions impaired this interaction mapped to two distinct Galpha surfaces: a betagamma-binding surface and a putative receptor-interacting surface. On the basis of these results a mechanism for receptor-catalyzed exchange of guanosine diphosphate for guanosine triphosphate is proposed.

Aluminum Compounds↗

Epidemiologic paradox in multiple births among Asians in Illinois. Correlation between risk factors and outcomes.

OBJECTIVE: To determine if the plural birth rate, maternal risk factors and neonatal outcomes among Asian American populations residing in Illinois are homogeneous or heterogeneous with regard to maternal risk factors and neonatal outcomes and to attempt to establish correlations between maternal risk factors and neonatal outcomes. STUDY DESIGN: A total of 1,145,962 computerized birth certificate files were analyzed for 11 Asian subgroups giving birth in Illinois in the years 1989-1994. RESULTS: The multiple birth rates varied between 6 per 1,000 (Vietnamese) to 15 per 1,000 (Cambodian) (heterogeneity among all groups, P < .005). The percent of neonates born at gestational ages 22-33 weeks varied between 0 (Cambodian) to 28 (Thai). Japanese women showed the highest rate of neonates with birth weight less than 2,500 g after adjustment for race: 15.38 per 1,000. Women from Cambodia and Laos had the highest sum of maternal risk factors; those from the Philippines and Thailand had the least. The lowest collective adverse neonatal outcomes were in infants born to women from Cambodia and Laos. CONCLUSION: The 11 subgroups of Asians living in Illinois demonstrate heterogeneity with respect to multiple birth rate, selected maternal risk factors and adverse neonatal outcomes. After considering all maternal risk factors and neonatal outcomes, the two groups (Cambodians and Laotians) with the poorest maternal risk factors had the lowest rate of poor neonatal outcomes. This is the first time that this epidemiologic paradox has been observed in twins of Asian ancestry.

Adolescent↗

Myocardial protection in the hypertrophied right ventricle.

Hypertrophied right ventricle presents a sensitive state that may not be adequately protected by modern cardioplegic methods. Cardiac metabolism, performance, and ultrastructure were measured in response to 1 hour of cardioplegic arrest in 15 pigs with right ventricular hypertrophy using intermittent hypothermic crystalloid, blood, and Flusol DA 20%-based cardioplegia. Reperfusion time was 1 hour. One hour after a 60-minute cross-clamp period, there were no differences in light microscopy. Total energy stores increased in 4 of 5 animals given blood cardioplegia compared with 1 of 5 for each of the other groups. Cardiac performance data also showed better results for animals treated with blood cardioplegia. After 30 minutes of reperfusion, animals receiving blood cardioplegia recovered 131% +/- 42% of preoperative systolic performance compared with 106% +/- 49% for Fluosol-treated animals and only 82% +/- 27% recovery for the crystalloid-treated group. After 60 minutes of reperfusion, the blood group showed 119% +/- 20% recovery compared with 89% +/- 23% and 85 +/- 50% recovery for Fluosol- and crystalloid-treated hearts, respectively. In conclusion, blood cardioplegia provided better protection than did crystalloid or Fluosol DA 20% cardioplegia when animals with right ventricular hypertrophy underwent 1 hour of cardioplegic arrest. It may have repaired damaged myocardium, leaving better hearts after cross-clamping than before.

Adenine Nucleotides↗

Cystic echinococcosis in the Xinjiang/Uygur Autonomous Region, People's Republic of China. II. Comparison of three levels of a local preventive and control program.

A project to compare different levels of a hydatid disease control program was instigated and evaluated in 16 randomly selected villages in the Xinjiang/Uygur Autonomous Region, PRC (China). Factors tested included the effect of: 1) the role of a village hydatid disease control officer, 2) the use of praziquantel-medicated "bait" tablets for treatment of Echinococcus granulosus tapeworms in dogs, and 3) the use of educational materials for children and adults. Evaluation of contrasting treatment levels was done by determining infection rates of E. granulosus in about 25 dogs examined from each of the 16 villages before and after the trial period, and by use of pre- and post-treatment questionnaires distributed to 40 randomly selected households in each village. Optimum results were obtained in those villages which received medicated tablets and support visits from a control officer on a monthly basis (so-called "moderate intervention level").

Adolescent↗

Cystic echinococcosis in the Xinjiang/Uygur Autonomous Region, People's Republic of China. I. Demographic and epidemiologic data.

Demographic and epidemiologic data on those factors potentially related to the prevalence and transmission of hydatid disease caused by Echinococcus granulosus were collected in 1987 from each household in 85 villages in the two communities of Yuanhucun and Ershilidian within Hutubi County in the Xinjiang/Uygur Autonomous Region, PRC, with additional questionnaire data collected from approximately 40 households randomly selected from each of 16 villages within those communities. Yuanhucun and Ershilidian represent a combined area of 522.7 square km, and have 4,853 households with 25,684 inhabitants. Of those households, 69.9% are of the Han ethnic group, 22.1% Hui, 5.3% Uygur, and 2.7% Kazak. The total number of animals censused included 4,169 dogs, 41,369 sheep, 3,673 goats, 2,639 cattle, 5,400 pigs, 1,472 horses, and 59 donkeys. Levels of infection of the causative organism of cystic hydatid disease in various hosts were: dogs harboring Echinococcus granulosus tapeworms - 63 (16.2%) positive of 390 examined in 16 villages; domestic animals with hydatid cysts - 1,593 (88.6%) sheep of 1,797 examined, 69 (56.1%) of 123 goats, and 47 (94.0%) of 50 cattle; and 15 surgeries in inhabitants from 85 villages during the last 16 months prior to completion of the survey (annual case rate of 43.8/100,000). Questionnaire data collected from inhabitants in 16 villages showed that about 82% of the families owned at least one dog and 78% owned sheep. Of those families with sheep, most (84%) killed sheep for meat at least periodically, 76% had seen hydatid cysts in liver or lungs of butchered animals, and 77% routinely gave raw offal to their dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗