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Biomedical subjects

X Huang

Publications and source records attributed to X Huang.

At least 127 records · Page 7Linked to original sources
PubMed2001

Dependence of permeability transition pore opening and cytochrome C release from mitochondria on mitochondria energetic status.

The dependence of Ca2+-induced permeability transition pore (PTP) opening and cytochrome c (Cyt. c) release from mitochondria on mitochondria energetic status was investigated. Results of test the PTP opening and Cyt. c release of isolated rat liver mitochondria with different mitochondrial respiratory substrates, electron transport inhibitors and uncoupler by spectrophotometry and western blotting showed that, Cyt. c release from mitochondria by PTP opening. PTP opening and Cyt. c release showed more sensitive and responsive with FADH-linked succinate than with NADH-linked glutamate plus malate as substrate. Partial or full inhibition of electron flow with electron flow inhibitors resulted in partial or full inhibition of PTP opening and Cyt. c release, respectively. Partial recovery of electron flow with electron sponsors resulted in partial recovery of PTP opening and Cyt. c release. PTP opening and Cyt. c release were completely interrupted by uncoupler. These results indicated PTP opening and Cyt. c release are characterized by respiratory substrate selectivity, electron flow dependence and energy coupling reliance. Hence, PTP opening and Cyt. c release tightly depend on mitochondria energetic status. These findings suggested also that it is possible to regulate apoptosis by altering mitochondrial energetic status to alter PTP opening and Cyt. c release.

Animals↗
PubMed2001

Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer's-type neurodegenerative pathways.

Oxidative stress may have an important role in the progression of neurodegenerative disorders such as Alzheimer's disease (AD) and prion diseases. Oxidative damage could result from interactions between highly reactive transition metals such as copper (Cu) and endogenous reducing and/or oxidizing molecules in the brain. One such molecule, homocysteine, a thiol-containing amino acid, has previously been shown to modulate Cu toxicity in HeLa and endothelial cells in vitro. Due to a possible link between hyperhomocysteinemia and AD, we examined whether interaction between homocysteine and Cu could potentiate Cu neurotoxicity. Primary mouse neuronal cultures were treated with homocysteine and either Cu (II), Fe (II or III) or Zn (II). Homocysteine was shown to selectively potentiate toxicity from low micromolar concentrations of Cu. The toxicity of homocysteine/Cu coincubation was dependent on the ability of homocysteine to reduce Cu (II) as reflected by the inhibition of toxicity with the Cu (I)-specific chelator, bathocuproine disulphonate. This was supported by data showing that homocysteine reduced Cu (II) more effectively than cysteine or methionine but did not reduce Fe (III) to Fe (II). Homocysteine also generated high levels of hydrogen peroxide in the presence of Cu (II) and promoted Abeta/Cu-mediated hydrogen peroxide production and neurotoxicity. The potentiation of metal toxicity did not involve excitotoxicity as ionotropic glutamate receptor antagonists had no effect on neurotoxicity. Homocysteine alone also had no effect on neuronal glutathione levels. These studies suggest that increased copper and/or homocysteine levels in the elderly could promote significant oxidant damage to neurons and may represent additional risk factor pathways which conspire to produce AD or related neurodegenerative conditions.

Alzheimer Disease↗
PubMed2001

Chronic potassium depletion induces renal injury, salt sensitivity, and hypertension in young rats.

BACKGROUND: Chronic hypokalemia has been associated with renal hypertrophy, interstitial disease, and hypertension in both adult animals and humans. However, the effects of potassium (K(+)) depletion on the rapidly growing infant have not been well studied. The purpose of this study was to determine the effects of severe chronic dietary K(+) depletion on blood pressure (BP) and renal structural changes in young rats. METHODS: Sprague-Dawley rats (50 +/- 5 g) were fed either a control or a potassium-deficient diet (<0.05% K(+)) for 14 to 21 days. At the end of this period, the blood pressure (BP) was measured in all rats, and six rats in each group were sacrificed to determine changes in renal histology and renin-angiotensin system (RAS) activity. The remaining rats in each group were then switched to a high-salt (6% NaCl)--normal-K(+) (0.5%) diet or were continued on their respective control or K(+)-deficient diet for an additional six days. Blood pressure measurements were done every three days until the end of the study. RESULTS: K(+)-depleted animals had significant growth retardation and increased RAS activity, manifested by high plasma renin activity, recruitment of renin-producing cells along the afferent arterioles, and down-regulation of angiotensin II receptors in renal glomeruli and ascending vasa rectae. K(+)-depleted kidneys also showed tubulointerstitial injury with tubular cell proliferation, osteopontin expression, macrophage infiltration, and early fibrosis. At week 2, K(+)-depleted rats had higher systolic BP than control rats. Switching to a high-salt (6% NaCl)--normal-K(+) diet resulted in further elevation of systolic BP in K(+)-depleted rats, which persisted even after the serum K(+) was normalized. CONCLUSION: Dietary potassium deficiency per se increases the BP in young rats and induces salt sensitivity that may involve at least two different pathogenic pathways: increased RAS activity and induction of tubulointerstitial injury.

Animals↗
PubMed2001

Disturbed expression of Fas/FasL on CD4(+) and CD8(+)T cells in Behcet's disease, Vogt-Koyanagi-Harada syndrome, and idiopathic anterior uveitis.

AIMS: To evaluate the expression of Fas/FasL antigen on peripheral blood T lymphocytes in patients with Behcet's disease, Vogt-Koyanagi-Harada (VKH) syndrome, and idiopathic anterior uveitis. METHODS: The expression of Fas and FasL on peripheral blood T lymphocytes was determined using flow cytometry in 26 patients with Behcet's disease (BD), 17 patients with VKH syndrome, 25 patients with idiopathic anterior uveitis, and 43 healthy individuals (controls). RESULTS: A higher proportion of CD4(+) T cells expressing Fas was noted in patients with Behcet's disease (25.70 +/- 7.32%), VKH syndrome (19.60 +/- 11.02%), and idiopathic anterior uveitis (20.81+/- 7.40%) compared with controls (14.02 +/- 6.30%). The expression of Fas on CD8(+) cells from patients with Behcet's disease (9.47 +/- 6.97%) and VKH syndrome (6.84+/- 5.5%) was also higher than that seen in controls (3.47+/- 2.75%). There was no difference in FasL expression on T cells between patients and controls except that a lower expression of FasL on CD8(+) T cells was noted in patients with idiopathic anterior uveitis. CONCLUSION: A disturbed expression of Fas and FasL on T cells is present in patients with Behcet's disease, VKH syndrome, and idiopathic anterior uveitis, which may be involved in the perpetuation and recurrence of uveitis.

Adult↗
PubMed2001

Potential of pyrazolooxadiazinone derivatives as serine protease inhibitors.

As a part of an investigation on molecular hybrids as new serine protease inhibitors, the pyrazolo [4,3-c][1,2,5]oxadiazin-3(5H)-one ring system was selected as a model of potential mechanism-based inhibitors. Due to the inherent reactivity of this system an optimal balance between susceptibility to nucleophilic attack and stability in solvents was sought prior to development as therapeutic agents. Substitutions on N5 and C7 of the supporting pyrazole ring with either aliphatic or aromatic groups (compounds 2 a-m) and the replacement of the carbonyl oxygen on the reactive oxadiazinone ring with sulfur (compounds 3a,i) were explored. Two members (2i and 2k) of this class of inhibitors displayed time-dependent inhibition of HLE suggesting mechanism-based inhibition. The observation that HLE generated a product(s) from compound 2i which displayed an identical UV-Visible spectrum to that observed during non-enzymatic hydrolysis further supports this proposal. FlexX-based docking of these compounds into a model of the human leukocyte elastase (HLE) active site produced a molecular model of the inhibitor-enzyme interaction.

Binding Sites↗
PubMed2001

Clinical correlates of estrogen replacement therapy use and duration of use among medicaid recipients.

Estrogen replacement therapy (ERT) is used not only for the short-term control of menopausal symptoms but long-term for disease prevention. This study examined the influence of selected clinical conditions on the use of ERT and the duration of ERT use among women enrolled in a state Medicaid program. We identified 60,531 women, aged >/=45 years, who were enrolled in Maryland Medicaid continuously for at least 2 of 3 years. ERT use was determined through prescription claims submitted for reimbursement. The presence or risk of selected clinical conditions (e.g., osteoporosis, heart disease, estrogen-sensitive cancers) was determined by screening Medicaid claims files for related diagnoses, procedures, or prescription claims. Multiple logistic regression was used to model ERT use, and proportional hazards regression was used to model duration of use. Fourteen percent of these women filled an ERT prescription, with use varying by age, race, and place of residence. Oral dosage forms were the most popular (80.8%), followed by vaginal cream or ring (22.2%), and transdermal patch (7.3%). In adjusted models, osteoporosis, heart disease, hypertension, hyperlipidemia, diabetes, ovarian cancer, and thromboembolic disease were positively associated and dementia and breast cancer were negatively associated with ERT use. None of these medical conditions predicted the duration of estrogen therapy. Use of ERT was very low among these women despite coverage of prescription medications, and the presence of clinical indications had no influence on the length of therapy among these women despite known benefits for long-term preventive therapy.

Aged↗
PubMed2001

A buckwheat protein product suppresses 1,2-dimethylhydrazine-induced colon carcinogenesis in rats by reducing cell proliferation.

This study was conducted to examine the effect of consumption of buckwheat protein product (BWP) on 1,2-dimethylhydrazine (DMH)-induced colon tumor in rats. Male growing Sprague-Dawley rats were fed diets containing either casein or BWP (net protein level, 200 g/kg; n = 20/group) for 124 d. The rats were gavaged weekly with DMH (20 mg/kg body) for the first 8 wk. Food intake and growth were unaffected by dietary manipulation. Dietary BWP caused a 47% reduction in the incidence of colonic adenocarcinoma (P < 0.05), but did not affect the incidence of colonic adenomas. BWP intake tended to reduce the number of colon adenocarcinomas (P = 0.16). Consumption of BWP significantly reduced cell proliferation and expression of c-myc and c-fos proteins in colonic epithelium. The results suggest that dietary BWP has a protective effect against DMH-induced colon carcinogenesis in rats by reducing cell proliferation.

1,2-Dimethylhydrazine↗
PubMed2001

Cholecystokinin-regulated exocytosis in rat pancreatic acinar cells is inhibited by a C-terminus truncated mutant of SNAP-23.

INTRODUCTION: Exocytosis is thought to result from the fusion of vesicle and plasma membranes caused by the formation of a trans-complex between proteins of the vesicle-associated membrane protein (VAMP) family on the vesicle with members of the syntaxin and synaptosomal-associated protein of 25 kd (SNAP-25) families on the plasma membrane. In the pancreatic acinar cell, synaptosomal-associated protein of 23 kd (SNAP-23) is the major SNAP-25 isoform expressed in pancreatic acinar cells, but its role in acinar cell exocytosis has not been determined. AIMS: To examine the role of SNAP-23 in regulated exocytosis in acinar cells, we subcloned into adenoviral vectors SNAP-23, SNAP-25, and dominant negative mutants in which the C-terminal domains corresponding to the botulinum neurotoxin A cleavage sites are deleted. METHODOLOGY AND RESULTS: High-efficiency infection of rat pancreatic acini in culture with these adenoviruses by subcellular fractionation showed that the overexpressed SNAP-23, SNAP-25, and their truncated mutant proteins were uniformly targeted to the zymogen granules and plasma membrane. To maximally stimulate apical exocytosis from these infected acini, we used the cholecystokinin-phenylethyl ester analog (CCK-OPE), which does not show inhibition of secretion from maximal levels at high doses. CCK-OPE-stimulated amylase release from adenovirus-cytomegalovirus (AdCMV)-SNAP-23 or AdCMV-SNAP-25-infected acini to the same extent as from acini infected with the empty vector. In contrast, CCK-OPE-evoked enzyme secretion from AdCMV-SNAP-23deltaC8- and AdCMV-SNAP-25(1-197)-infected acini were inhibited by 60% and 40%, respectively. The identical targeting of the mutant SNAP-23 and SNAP-25 proteins to the same membrane compartments as SNAP-23 suggests that the inhibition of secretion was a result of their competition against endogenous SNAP-23. This is supported by the fact that this inhibition by the mutant proteins was partially reversed or rescued when the AdCMV-SNAP-25AC8- or AdCMV-SNAP-25(1-197)-infected acini were co-infected with wild-type SNAP-23 or SNAP-25. CONCLUSION: From these results, we conclude that SNAP-23 plays a role in CCK-evoked regulated exocytosis in the acinar cells.

Adenoviridae↗
PubMed2001

Bacterial population in Russian space station "Mir".

We had the opportunity to investigate the bacterial population in air samples, condensation water, and inner wall swabs from the Russian space station Mir. From the first and second air samples during the mission, 29 and 7 bacterial colonies were collected, respectively. The values were equivalent to 16.8 and 4.0 cfu/100 liter air, respectively. Condensation water was collected from three different sites. The total viable bacterial counts were 2.1 x 10(6), 5.2 x 10(2), and 3.0 x 10(1) cfu/ml. The phylogenetic position of each isolate was determined by total 16S rDNA sequencing. Bacteria from air samples were mainly Gram-positive (35/36 colonies), and staphylococci occupied dominant specifically (23/36 colonies). On the other hand, Gram-negative bacteria were mainly isolated from condensation water samples. Most strains were thought to be opportunistic pathogens or environmental bacteria (such as those that inhabit soil, water, or air) found on earth. However, 6 of 23 isolates were suspected to be new species according to phylogenetic analysis and quantitative DNA-DNA hybridization data. The isolation of the other levels 3 and 2 bacteria, using specific selective media, was unsuccessful because all samples were heavily contaminated with fungi. To overcome this situation, PCR methods were applied to survey most levels 3 and 2 pathogenic bacteria in the condensation water samples. Up to 380 different primers for bacterial pathogens were used in this study. Only Mycobacterium avium 16S DNA sequences, however, could be amplified from the three water samples. The average bacteria count was estimated to be about 10(4) organisms/ml water.

Air Microbiology↗
PubMed2001

Channeling of substrates and intermediates in enzyme-catalyzed reactions.

The three-dimensional structures of tryptophan synthase, carbamoyl phosphate synthetase, glutamine phosphoribosylpyrophosphate amidotransferase, and asparagine synthetase have revealed the relative locations of multiple active sites within these proteins. In all of these polyfunctional enzymes, a product formed from the catalytic reaction at one active site is a substrate for an enzymatic reaction at a distal active site. Reaction intermediates are translocated from one active site to the next through the participation of an intermolecular tunnel. The tunnel in tryptophan synthase is approximately 25 A in length, whereas the tunnel in carbamoyl phosphate synthetase is nearly 100 A long. Kinetic studies have demonstrated that the individual reactions are coordinated through allosteric coupling of one active site with another. The participation of these molecular tunnels is thought to protect reactive intermediates from coming in contact with the external medium.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2001

Ca(2+) influx and cAMP elevation overcame botulinum toxin A but not tetanus toxin inhibition of insulin exocytosis.

Previous reports showed that cleavage of vesicle-associated membrane protein-2 (VAMP-2) and synaptosomal-associated protein of 25 kDa (SNAP-25) by clostridial neurotoxins in permeabilized insulin-secreting beta-cells inhibited Ca(2+)-evoked insulin secretion. In these reports, the soluble N-ethylmaleimide-sensitive factor attachment protein target receptor proteins might have formed complexes, which preclude full accessibility of the putative sites for neurotoxin cleavage. In this work, VAMP-2 and SNAP-25 were effectively cleaved before they formed toxin-insensitive complexes by transient transfection of insulinoma HIT or INS-1 cells with tetanus toxin (TeTx) or botulinum neurotoxin A (BoNT/A), as shown by immunoblotting and immunofluorescence microscopy. This resulted in an inhibition of Ca(2+) (glucose or KCl)-evoked insulin release proportionate to the transfection efficiency (40-50%) and an accumulation of insulin granules. With the use of patch-clamp capacitance measurements, Ca(2+)-evoked exocytosis by membrane depolarization to -10 mV was abolished by TeTx (6% of control) but only moderately inhibited by BoNT/A (30% of control). Depolarization to 0 mV to maximize Ca(2+) influx partially overcame BoNT/A (50% of control) but not TeTx inhibition. Of note, cAMP activation potentiated Ca(2+)-evoked secretion by 129% in control cells but only 55% in BoNT/A-transfected cells and had negligible effects in TeTx-transfected cells. These results indicate that, whereas VAMP-2 is absolutely necessary for insulin exocytosis, the effects of SNAP-25 depletion on exocytosis, perhaps on insulin granule pool priming or mobilization steps, could be partially reversed by higher levels of Ca(2+) or cAMP potentiation.

Animals↗
PubMed2001

Effects of impulse noise stimulation on electrocorticogram and heart rate.

It is now recognized that high-level impulse noises penetrate the uterus of pregnant sheep, elevate thresholds of fetal auditory-evoked potential and produce damage to fetal inner ear hair cells. However, little is known about functional effects of airborne impulse noise on the late-term fetus. In the present study, the effects of a series of 20 impulses on the behavioral state of 6 fetal sheep were tested. Noise impulses produced 169.3 peak sound pressure level (pSPL) in air. Peak levels recorded near the fetal head averaged 161.1 dB. Impulses delivered to the fetus during periods of NREM sleep resulted in a decrease in average fetal heart rate (FHR) from 185 +/- 22 beats/min (bpm) before stimulation to 174 +/- 23 bpm 2-5 s after stimulation (p < 0.05). During REM sleep, an FHR acceleration occurred (before stimulation: 177 +/- 24 bpm, after stimulation: 189 +/- 31 bpm; p < 0.05). Impulse exposure during NREM sleep resulted in reductions in delta-, theta- and alpha-band powers. As a consequence, total power decreased from 100 to 72 +/- 16% (p < 0.05). During REM sleep, stimulation provoked a short decrease in total band power from 100 to 73 +/- 20% and a similar decrease in the theta- and beta-band powers. The results indicated that impulse noise evoked short-term alterations in FHR and cortical activity. These changes were mediated by auditory brain stem activation that led to cortical desynchronization during both NREM and REM sleep in late-term fetal sheep.

Acoustic Stimulation↗
PubMed2001

TGF-beta is a critical mediator of acute lung injury.

We have shown that the integrin alphavbeta6 activates latent TGF-beta in the lungs and skin. We show here that mice lacking this integrin are completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury (ALI). Pharmacologic inhibition of TGF-beta also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-beta directly increased alveolar epithelial permeability in vitro by a mechanism that involved depletion of intracellular glutathione. These data suggest that integrin-mediated local activation of TGF-beta is critical to the development of pulmonary edema in ALI and that blocking TGF-beta or its activation could be effective treatments for this currently untreatable disorder.

Animals↗
PubMed2001

Pigment epithelium-derived factor (PEDF) in neuroblastoma: a multifunctional mediator of Schwann cell antitumor activity.

Neuroblastoma is notable for its cellular heterogeneity and unpredictable outcome. Tumors are a variable mixture of primitive malignant neuroblasts, more differentiated ganglionic cells, Schwann and endothelial cells. Although often fatal, neuroblastomas can spontaneously regress, possibly due to favorable autocrine and paracrine interactions among these cells. Here, pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis and inducer of neural differentiation, is shown to be produced by ganglionic cells and Schwann cells, but not by more primitive tumor cells. Although undifferentiated neuroblastoma tumor cell secretions were angiogenic primarily due to vascular endothelial growth factor, secretions of Schwann cells were anti-angiogenic due to PEDF. In addition, PEDF was the major factor responsible for Schwann cell's ability to induce tumor cell differentiation in vitro and recombinant PEDF had the same effect in vitro and in vivo. Both the growth and the survival of Schwann cells were enhanced by PEDF. Thus PEDF may serve as a multifunctional antitumor agent in neuroblastomas, inhibiting angiogenesis while promoting the numbers of Schwann cells and differentiated tumor cells that in turn produce PEDF, suggesting that its clinical administration could stimulate a multifaceted antitumor feedback loop with the potential to limit and possibly regress tumor growth.

Angiogenesis Inhibitors↗
PubMed2001

The direct medical costs of alpha(1)-antitrypsin deficiency.

BACKGROUND: For individuals with emphysema because of severe alpha(1)-antitrypsin deficiency, specific therapy called IV augmentation therapy has been available since 1989. Such therapy consists of IV infusion of pooled human plasma alpha(1)-antiprotease. METHODS: To assess the direct medical costs of having alpha(1)-antitrypsin deficiency, the current study surveyed members of the Alpha One Foundation Registry for Individuals With alpha(1)-Antitrypsin Deficiency regarding their annual expenditures for treatment of this disease. Data regarding demographic features, alpha(1)-antitrypsin status, and health-resource utilization were collected from a self-administered questionnaire. Respondents were asked to provide total health-care expenditures, but costs by specific items of care (eg, drugs, physician visits, etc) were not available. RESULTS: Mean annual cost estimates were higher for PI*ZZ-phenotype individuals ($30,948, n = 292) than for non-PI*ZZ-phenotype individuals ($20,673, n = 53; p = 0.049). Among PI*ZZ-phenotype individuals, self-reported costs of health-care services were further analyzed for those 288 individuals whose alpha(1)-antiprotease use status was reported. For the 185 current alpha(1)-antiprotease users, the mean annual cost was $40,123 (median, $36,000). CONCLUSIONS: Annual health-care expenditures by individuals with alpha(1)-antitrypsin deficiency are very high, whether or not they are currently receiving augmentation therapy. Augmentation therapy adds substantial costs, especially for heavier individuals who are receiving weekly infusions.

Direct Service Costs↗
PubMed2001

Artificial carbon dioxide source to attract lesser cornstalk borer (Lepidoptera: Pyralidae) larvae.

Different combinations of urea, urease (in jack bean meal, Canavalia DC.), and water were tested as carbon dioxide sources to attract larvae of lesser cornstalk borer, Elasmopalus lignosellus (Zeller), by using olfactory bioassays with an olfactometer and infrared gas analysis. A combination of urea, jack bean meal, and water was necessary to release a high level of carbon dioxide to attract the larvae. Different proportions of the three ingredients had different carbon dioxide release rates and exhibited different levels of attraction to the larvae. When carbon dioxide concentration was too high, attractiveness declined. Combinations with different amounts of water remained attractive for a period of up to 3 d, depending on the moisture of the samples. When Zonolite was used to simulate the soil conditions in the olfactometer, significantly more larvae located the area near the artificial carbon dioxide sources compared with the control. When combined with the artificial carbon dioxide sources, three insecticides (Lorsban, Temik, and Force) did not obviously affect the release rates of carbon dioxide, and more larvae were attracted to samples with the carbon dioxide source than to the samples without carbon dioxide.

Aldicarb↗
PubMed2001

Concordance for type 1 diabetes in identical twins is affected by insulin genotype.

OBJECTIVE: Monozygotic twins are usually discordant (only one twin affected) for type 1 diabetes. Discordance for disease between such twins implies a role for nongenetically determined factors but could also be influenced by a decreased load of diabetes susceptibility genes. The aim of this study was to determine whether two susceptibility genes were less prevalent in discordant twins compared with concordant twins. RESEARCH DESIGN AND METHODS: We studied 77 monozygotic twin pairs (INS), 40 concordant and 37 discordant, for type 1 diabetes at polymorphism of the insulin gene region on chromosome 11 p and HLA-DQBI. RESULTS: The disease-associated INS genotype (Hph I) was identified in 87.5% of the concordant twins but only in 59.5% (P = 0.005) of the discordant twins. Neither DQB1*0201 nor DQB1*0302 was seen in 2 of 40 (5%) concordant twins compared with 8 of 37 (22%) discordant twins (P = 0.04). No statistical differences were seen between concordant and discordant twins at individual alleles of DQB1. Combining insulin and DQ data, 5% of concordant twins compared with 32.4% of discordant twins had neither DQB1*0201/DQB1*0302 nor the high-risk Hph I INS "++" genotype (P = 0.002). CONCLUSIONS: We conclude that the possession of the high-risk Hph I insulin genotype increases the likelihood of identical twins being concordant for type 1 diabetes and that the "load" of both major histocompatibility complex (MHC) and non-MHC susceptibility genes has an impact on the disease penetrance of type 1 diabetes.

Adolescent↗