Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 253 records · Page 14Linked to original sources

PubMed2001

Human immunodeficiency virus type 1-infected persons with residual disease and virus reservoirs on suppressive highly active antiretroviral therapy can be stratified into relevant virologic and immunologic subgroups.

A significant percentage of human immunodeficiency virus type 1 (HIV-1)-infected persons treated with highly active antiretroviral therapy (HAART) will develop plasma HIV-1-specific virion RNA levels <50 copies/mL. HIV-1-infected persons receiving virally suppressive HAART were studied with a viral outgrowth assay of the patients' peripheral blood mononuclear cells (PBMC), and a quantitative polymerase chain reaction assay was used to analyze HIV-1 2-long terminal repeat (2-LTR) circular DNA in PBMC, which indicates new HIV-1 infections of cells in vivo. Viral outgrowth in vitro correlated inversely with the level of peripheral blood CD4(+) T lymphocytes. Detection and quantitation of 2-LTR circular DNA correlated strongly with viral outgrowth patterns and inversely with CD4(+) T lymphocyte counts. Relevant subgroups of HIV-1-infected subjects on suppressive HAART with residual viral disease and reservoirs can now be stratified.

Anti-HIV Agents↗

PubMed2001

Crystallization and preliminary X-ray analysis of cardiotoxic phospholipase A2 from Ophiophagus hannah (king cobra).

An acidic phospholipase A2 exhibiting cardiotoxicity, myotoxicity and anti-platelet activity was isolated from Ophiophagus hannah (king cobra) from Guangxi, China. It contains an unusual 'pancreatic loop'. The enzyme was purified to homogeneity and crystallized using polyethylene glycol and ethylene glycol as precipitants. The crystal belongs to space group C2, with unit-cell parameters a = 117.92, b = 62.94, c = 57.16 A, beta = 100.93 degrees. Diffraction data were collected to 2.6 A.

Animals↗

PubMed2001

Expressed sequence tags from a NaCl-treated Suaeda salsa cDNA library.

Past efforts to improve plant tolerance to osmotic stress have had limited success owing to the genetic complexity of stress responses. The first step towards cataloging and categorizing genetically complex abotic stress responses is the rapid discovery of genes by the large-scale partial sequencing of randomly selected cDNA clones or expressed sequence tags (ESTs). Suaeda salsa, which can survive seawater-level salinity, is a favorite halophytic model for salt tolerant research. We constructed a NaCl-treated cDNA library of Suaeda salsa and sequenced 1048 randomly selected clones, out of which 1016 clones produced readable sequences (773 showed homology to previously identified genes, 227 matched unknown protein coding regions, 16 anomalous sequences or sequences of bacterial origin were excluded from further analysis). By sequence analysis we identified 492 unique clones: 315 showed homology to previously identified genes, 177 matched unknown protein coding regions (101 of which have been found before in other organisms and 76 are completely novel). All our EST data are available on the Internet. We believe that our dbEST and the associated DNA materials will be a useful source to scientists engaging in stress-tolerance study.

Blotting, Northern↗

PubMed2001

Experimental yellow fever virus infection in the Golden Hamster (Mesocricetus auratus). I. Virologic, biochemical, and immunologic studies.

This report describes the clinical laboratory findings in golden hamsters experimentally infected with yellow fever (YF) virus. An accompanying paper describes the pathologic findings. Following intraperitoneal inoculation of a virulent strain of YF virus, hamsters developed a high-titered viremia (up to 109/mL) lasting 5--6 days and abnormal liver function tests. YF hemagglutination-inhibiting antibodies appeared 4 or 5 days after infection, often while viremia was still present. The mortality rate in YF-infected hamsters was variable, depending on the virus strain and the age of the animals. Clinical and pathologic changes in the infected hamsters were very similar to those described in experimentally infected macaques and in fatal human cases of YF, which indicates that the golden hamster may be an excellent alternative animal model, in place of nonhuman primates, for research on the pathogenesis and treatment of YF and other viscerotropic flavivirus diseases.

Animals↗

PubMed2001

Experimental yellow fever virus infection in the Golden hamster (Mesocricetus auratus). II. Pathology.

Subadult and adult hamsters were inoculated intraperitoneally with 10(6) TCID(50) of yellow fever (YF) virus (Jimenez strain). Four animals from each group were subjected daily to histologic examination for 9 days. The liver showed spotty necrosis on day 3 after infection, which was followed by steatosis and focally confluent necrosis. In surviving hamsters, hepatocyte regeneration began on day 8, which was accompanied by decreasing steatosis. The spleen initially exhibited lymphoid hyperplasia, which was followed by lymphoid depletion and increased phagocytosis by splenic macrophages. Focal pancreatic acinar necrosis and spotty adrenal cortical necrosis were seen transiently between days 5 and 7. Viral antigen was detected immunohistochemically in the liver and the spleen. TUNEL analysis showed a dynamic change of hepatocyte necrapoptosis, with activity corresponding to the severity of disease. The histopathologic changes were more severe in younger (subadult) animals. The YF-hamster model appears to be an accurate and inexpensive experimental system for studying the pathophysiology and treatment of YF.

Adrenal Glands↗

PubMed2001

Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV.

Human Reg and Reg-related genes constitute a multi-gene family belonging to the calcium (C-type) dependent lectin superfamily. Regenerating gene family members are expressed in the proximal gastrointestinal (GI) tract and ectopically at other sites in the setting of tissue injury. By high-throughput sequence analysis of a large inflammatory bowel disease library, two cDNAs have been isolated which encode a novel member of this multigene family. Based on primary sequence homology, tissue expression profiles, and shared exon-intron junction genomic organization, we assign this gene to the regenerating gene family. Specific protein structural differences suggest that the current three regenerating gene subtypes should be expanded to four. We demonstrate that Reg IV has a highly restricted tissue expression pattern, with prominent expression in the gastrointestinal tract. Reg IV mRNA expression is significantly up-regulated by mucosal injury from active Crohn's disease or ulcerative colitis.

Amino Acid Sequence↗

PubMed2001

[Analgesic effect of neurolytic celiac plexus block guided by ultrasonography in advanced malignancies].

OBJECTIVE: To investigate the analgesic effect of celiac plexus block with anhydrous alcohol in patients suffering form advanced abdominal malignancies. METHODS: Ultrasonographically demonstrated and guided, 20 to 50 ml of anhydrous alcohol is injected into the celiac plexus and superior mesenteric plexus by fine needle of 22G. The injecting angle between the needle and the aorta is 20 to 30 degree. The injecting fields mainly located around the celiac plexus and the dorsal part of tumor are also injected. Sometimes if the tumor is rather large, an appropriate amount of alcohol was injected inside too. RESULTS: Twenty-eight cases of advanced abdominal malignancies were treated, among whom 96.4% achieved analgesic effect of different degree, 53.6% (15 cases) achieved the period of pain relief over three days, and 42.8% (12 cases) achieved partial relief. The analgesic effect is correlated with the amount of alcohol injected, i.e. no complete relief was observed in the four patients who received less than 12 ml, while two out of six could get transient complete relief in those who received 15 to 28 ml. In the group of 30 to 50 ml, 72.2% (13 cases) could get complete pain relief. Nine cases with big tumor received injection in side the tumor, with six tumors resulting in shrinkage or necrosis, significant pain relief also achieved in these cases. Complications occurred in nine cases (32.1%), with four cases of postural hypotension, two cases of vomiting, two cases of hiccup and one case of diarrhea. CONCLUSION: Neurolytic celiac plexus block guided by ultrasonography is a safe and effective modality in the management of intractable pain resulted from advanced abdominal malignancies.

Abdominal Neoplasms↗

PubMed2001

Ecological degradation in protected areas: the case of Wolong Nature Reserve for giant pandas.

It is generally perceived that biodiversity is better protected from human activities after an area is designated as a protected area. However, we found that this common perception was not true in Wolong Nature Reserve (southwestern China), which was established in 1975 as a "flagship" protected area for the world-renowned endangered giant pandas. Analyses of remote sensing data from pre- and post-establishment periods indicate that the reserve has become more fragmented and less suitable for giant panda habitation. The rate of loss of high-quality habitat after the reserve's establishment was much higher than before the reserve was created, and the fragmentation of high-quality habitat became far more severe. After the creation of the reserve, rates of habitat loss and fragmentation inside the reserve unexpectedly increased to levels that were similar to or higher than those outside the reserve, in contrast to the situation before the reserve was created.

Animals↗

PubMed2001

Gene structure and expression of the targeting subunit, RGL, of the muscle-specific glycogen-associated type 1 protein phosphatase, PP1G.

The type I phosphatase associated with glycogen, PP1G, plays an important role in glycogen metabolism. PP1G is targeted to glycogen by the R(GL) subunit, which regulates the function of the enzyme. We report the cloning and characterization of the gene as well as the pattern of expression of the R(GL) subunit from mouse. The gene covers more than 37 kb, is composed of four exons and three introns, and codes for a 1089 residue polypeptide with a calculated molecular weight of 121,000. The amino acid sequence has 60% identity with the human and rabbit R(GL). The 5' flanking region of the gene contains a TATA box, c-Myc sites, and a potential cAMP-responsive element. Muscle specific motifs, such as MyoD and MEF-2, were also found. The A-T rich 3'-UTR contained several polyadenylation signals, two associated with poly(A) down-stream consensus motifs. ARE elements, which regulate mRNA stability, were dispersed throughout the 3'-UTR. Northern analysis of poly(A) mRNA from various murine tissues indicates a major transcript of 7.5 kb in skeletal muscle and heart. Western analysis demonstrates that R(GL) protein is present in skeletal and cardiac muscle from mouse, rat, and rabbit but not in L6 myoblasts, L6 myotubes, 3T3 L1 fibroblasts, 3T3 L1 or rat primary adipocytes, confirming that expression of the gene is specific to striated muscle. Analysis of skeletal muscle from rats made diabetic by streptozotocin treatment reveals that the level of R(GL) protein is the same as in control animals, indicating that expression is not regulated by insulin.

3' Untranslated Regions↗

PubMed2001

Chip-based quantitative capillary electrophoresis/mass spectrometry determination of drugs in human plasma.

A chip-based capillary electrophoresis/mass spectrometry (CE/MS) system is described for the on-chip separation and coupled electrospray detection of selected small drug molecule compounds. These studies include the quantitative determination of carnitine and acetylcarnitine in analytical standard solutions as well as imipramine and desipramine in fortified human plasma samples. A clinical human plasma sample was also analyzed following the normal administration of desipramine to a volunteer, and the parent drug was determined using the described chipbased CE/MS technique. In each instance, stable isotope-incorporated internal standards were used. The chip-based CE system was microfabricated from glass and coupled to a micro ion spray device constructed in-house. The atmospheric pressure ionization system employed in this work was a PE Sciex API III tandem triple quadrupole system operated in the selected ion monitoring (SIM) mode. The results from the work reported here demonstrate the feasibility for carrying out rapid (30 s) chipbased quantitative CE/MS determinations of samples containing small-molecule compounds. Using SIM CE/ MS techniques, the described API III quadrupole system provided acceptable ion current electropherograms from subpicomole levels of the targeted compounds loaded onto the chip. The corresponding electropherograms for the standard solution of carnitines at the 1-500 microg/mL level were obtained via SIM CE/MS techniques (R2 > 0.99). In addition, analyses of fortified samples of imipramine desipramine were measured relative to their corresponding d3 internal standards to obtain calibration curves ranging from 5 to 500 microg/mL in human plasma (R2 > 0.99). The intra-assay precision ranged from 4.1 to 7.3% RSD. The intra-assay accuracy ranged from 94.0 to 104%. These results demonstrate the feasibility for on-chip CE separation and electrospray mass spectrometric determination in applications for bioanalytical measurements for these important compounds in synthetic mixtures and human plasma extracts.

Acetylcarnitine↗

PubMed2001

Application of gel microdroplet and flow cytometry techniques to selective enrichment of non-growing bacterial cells.

We describe an application of gel microdroplet (GMD) and flow cytometry techniques to selective enrichment of non-growing Leuconostoc mesenteroides cells, which are well culturable on other media, from a mixture with Bacillus subtilis cells in nutrient broth. After encapsulating cells of the mixed population within GMDs and a brief incubation in nutrient broth, the inability of L. mesenteroides cells to form microcolonies within GMDs allowed their discrimination from B. subtilis cells. After staining the GMD mixture with 6-carboxyfluorescein diacetate, which showed no influence on cell viability, the GMDs containing single cells of L. mesenteroides were selectively collected using flow cytometry sorting based on differences in fluorescence intensity. The cells of L. mesenteroides retained viability during the process.

Bacillus subtilis↗

PubMed2001

Synthesis and Structure of [DB24C8)Na][Cd(SCN)3. Formation of a novel linear Cd...Cd...Cd chain with a mer-CdN3S3 coordination confirmation and new coiled [(DB24C8)Na]+ cation.

We report herein a novel coordination solid, [(DB24C8)Na][Cd(SCN)3] (6) (DB24C8 denotes dibenzo-24-crown-8), which exhibits a new type of [Cd(SCN)3-]infinity chain with two unusual stereochemical characteristics: (1) a mer-CdN3S3 coordination and (2) a linear Cd chain with a Cd...Cd...Cd angle of 180 degrees. In addition, the [(DB24C8)Na]+ monocation adopts a new structural type-a coiled structure-for the combination of crown ether DB24C8 and alkali metal Na+. The title compound crystallizes in a monoclinic unit cell of C2/c space group symmetry with lattice parameters a = 16.110(8) A, b = 20.380(5) A, c = 11.01(1) A, beta = 119.87(3) degrees, and Z = 4. The arrangement of the [Cd(SCN)3-](infinity) chains in the crystal lattice in the title compound is approximately hexagonal, creating triangular channels which are filled with [(DB24C8)Na]+ monocations. It was previously reasoned by us that the coiled [(DB24C8)Na]+ monocation, which lacks inversion or mirror symmetries, should enhance the tendency for the formation of the noncentrosymmetric space group of the title crystal, making it a potential second-order nonlinear optical crystal. Interestingly, however, the title compound crystallizes in a centrosymmetric space group (C2/c) and gives rise to no second harmonic generation (SHG). Previously known [Cd(SCN)3-](infinity) chains adopt fac-CdN3S3 coordination and a zigzag Cd chain configuration with a Cd...Cd...Cd angle of 165 degrees. The zigzag chains can align in either parallel or antiparallel fashion, resulting in efficient or no SHG effects, respectively. The linear Cd.Cd.Cd chain configuration observed in the title compound, on the other hand, makes it indistinguishable between parallel and antiparallel alignments. It is concluded that, to ensure the formation of noncentrosymmetric space groups, it is necessary to employ optically pure chiral cations as spacers and/or controllers. Furthermore, to enhance the nonlinear optical responses, [Cd(SCN)3-]infinity chains with fac-CdN3S3 coordination and parallel alignments of the zigzag Cd chains should be used.

Journal Article↗

PubMed2001

[Alteration of subcellular distribution of protein kinase C isoforms in swelling-activated multi-drug-resistant gastric cancer cells and its significance].

OBJECTIVE: To study the alteration of expression and subcellular distribution of classical protein kinase (cPKC) isoforms in gastric cancer cells SGC7901 and their multidrug-resistant cell line SGC7901/VCR under condition of swelling activation and to study the significance of such alterations. METHODS: Immuno-fluorescence technique and Western Blotting were used to determine the expression and subcellular distribution of cPKC isoforms in gastric cancer cells SGC7901 and its multidrug-resistant cell line SGC7901/VCR under normal condition and during continuous hypotonic perfusion. The co-expression of p-glycoprotein (Pgp) and protein kinase C alpha (PKC alpha) was visualized by immunofluorescence double labeling and laser confocus microscopy. RESULTS: Under the normal condition, the four isoenzymes of cPKC were expressed in both the cell membrane and the nuclei of the gastric cancer cells SGC7901 and their multidrug-resistant cell line SGC7901/VCR; PKC alpha was strongly positively expressed in the multidrug-resistant cells and positively expressed in the drug-sensitive cells; PKC beta I and PKC beta II were positively expressed in both drug-resistant and drug-sensitive cells, and PKC gamma was strongly positively expressed in both cells. In drug-resistant cell line, cell-swelling and translocation of PKC alpha and PKC gamma were observed ten minutes after continuous hypotonic perfusion. Thirty minutes after the perfusion, almost all the PKCalpha was translocated into the cell membrane of SGC7901/VCR, part of the PKC gamma was translocated into the nucleus, and the cell volume increased to two to three times as much as before. Sixty minutes later, the subcellular distribution of PKCalpha and PKC gamma and the cell volume returned to normal. In drug-sensitive cells, 10 approximately 20 minutes after the continuous hypotonic perfusion nearly all the PKCalpha was translocated into the cell membrane, part of PKC gamma was translocated into the cell membrane, and the cell volume increased to two to three times as much as before. Forty minutes later, PKCalpha and PKCgamma had basically returned to normal. The subcellular distribution of PKCbeta I and PKC beta II remained unchanged in both SGC7901 and SGC7901/VCR. Co-expression of Pgy and PKCalpha was observed in both drug-sensitive and drug-resistant cells, especially in the former. CONCLUSION: Only PKCalpha and PKC gamma isoforms play an important role in the regulation of signal transduction of Pgy and cell volume under continuous perfusion and are related to the expression of PKC alpha and Pgy. PKC beta I and PKC beta II may have nothing to do with such processes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Use of genotypic resistance testing to guide hiv therapy: clinical impact and cost-effectiveness.

BACKGROUND: Genotypic sequencing for drug-resistant strains of HIV can guide the choice of antiretroviral therapy. OBJECTIVE: To assess the cost-effectiveness of genotypic resistance testing for patients acquiring drug resistance through failed treatment (secondary resistance) and those infected with resistant virus (primary resistance). DESIGN: Cost-effectiveness analysis with an HIV simulation model incorporating CD4 cell count and HIV RNA level as predictors of disease progression. DATA SOURCES: Published randomized trials and data from the Multicenter AIDS Cohort Study, the national AIDS Cost and Services Utilization Survey, the Red Book, and an institutional cost-accounting system. TARGET POPULATION: HIV-infected patients in the United States with baseline CD4 counts of 0.250 x 10(9) cells/L. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Genotypic resistance testing and clinical judgment, compared with clinical judgment alone, in two contexts: after initial treatment failure (secondary resistance testing) and before initiation of antiretroviral therapy (primary resistance testing). OUTCOME MEASURES: Life expectancy, quality-adjusted life expectancy, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: Secondary resistance testing increased life expectancy by 3 months, at a cost of $17 900 per QALY gained. The cost-effectiveness of primary resistance testing was $22 300 per QALY gained with a 20% prevalence of primary resistance but increased to $69 000 per QALY gained with 4% prevalence. RESULTS OF SENSITIVITY ANALYSIS: The cost-effectiveness ratio for secondary resistance testing remained under $25 000 per QALY gained, even when effectiveness and cost of testing and antiretroviral therapy, quality-of-life weights, and discount rate were varied. CONCLUSIONS: Genotypic antiretroviral resistance testing following antiretroviral failure is cost-effective. Primary resistance testing also seems to be reasonably cost-effective and will become more so as the prevalence of primary resistance increases.

Anti-HIV Agents↗

PubMed2001

The cost effectiveness of combination antiretroviral therapy for HIV disease.

BACKGROUND: Combination antiretroviral therapy with a combination of three or more drugs has become the standard of care for patients with human immunodeficiency virus (HIV) infection in the United States. We estimated the clinical benefits and cost effectiveness of three-drug antiretroviral regimens. METHODS: We developed a mathematical simulation model of HIV disease, using the CD4 cell count and HIV RNA level as predictors of the progression of disease. Outcome measures included life expectancy, life expectancy adjusted for the quality of life, lifetime direct medical costs, and cost effectiveness in dollars per quality-adjusted year of life gained. Clinical data were derived from major clinical trials, including the AIDS Clinical Trials Group 320 Study. Data on costs were based on the national AIDS Cost and Services Utilization Survey, with drug costs obtained from the Red Book. RESULTS: For patients similar to those in the AIDS Clinical Trials Group 320 Study (mean CD4 cell count, 87 per cubic millimeter), life expectancy adjusted for the quality of life increased from 1.53 to 2.91 years, and per-person lifetime costs increased from $45,460 to $77,300 with three-drug therapy as compared with no therapy. The incremental cost per quality-adjusted year of life gained, as compared with no therapy, was $23,000. On the basis of additional data from other major studies, the cost-effectiveness ratio for three-drug therapy ranged from $13,000 to $23,000 per quality-adjusted year of life gained. The initial CD4 cell count and drug costs were the most important determinants of costs, clinical benefits, and cost effectiveness. CONCLUSIONS: Treatment of HIV infection with a combination of three antiretroviral drugs is a cost-effective use of resources.

AIDS-Related Opportunistic Infections↗

PubMed2001

The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E.

Cyclin E is required for S phase entry. The subsequent ubiquitin-dependent degradation of cyclin E contributes to an orderly progression of the S phase. It has been shown that phosphorylation of threonine 380 (Thr380) in cyclin E provides a signal for its ubiquitin-dependent proteolysis. We report that SKP2, an F-box protein and a substrate-targeting component of the SCF(SKP2) ubiquitin E3 ligase complex, mediates cyclin E degradation. In vitro, SKP2 specifically interacted with the cyclin E peptide containing the phosphorylated-Thr380 but not with a cognate nonphosphorylated peptide. In vivo, expression of SKP2 induced cyclin E polyubiquitination and degradation. Conversion of Thr380 into nonphosphorylatable amino acids caused significant resistance of cyclin E to SKP2. The presence of the CDK inhibitor p27(Kip1) also prevented the SKP2-dependent degradation of cyclin E. Our findings suggest that SKP2 regulates cyclin E stability, thus contributing to the control of S phase progression.

Amino Acid Sequence↗

PubMed2001

Masked oxo sulfinimines (N-sulfinyl imines) in the asymmetric synthesis of proline and pipecolic acid derivatives.

[structure: see text]. On addition of Et2AlCN/i-PrOH, masked oxo sulfinimines give alpha-amino nitriles that afford oxo alpha-amino acids on hydrolysis. These amino acids cyclize and are reduced to cis proline and cis pipecolic acids derivatives in high ee and good yield. This new procedure avoids many of the limitations related to the preparation of oxo amino acids from proteinogenic amino acids.

Hydrolysis↗

PubMed2001

Sunlight and iron(III)-induced photochemical production of dissolved gaseous mercury in freshwater.

Mechanistic understanding of sunlight-induced natural processes for production of dissolved gaseous mercury (DGM) in freshwaters has remained limited, and few direct field tests of the mechanistic hypotheses are available. We exposed ferric iron salt-spiked fresh surface lake water (Whitefish Bay, Lake Superior, MI) in Teflon bottles and pond water (Oak Ridge, TN) in quartz bottles to sunlight in the field to infer if sunlight and Fe(III)-induced photochemical production of DGM could mechanistically contribute partly to natural photochemical production of DGM in freshwaters. We found that exposure of freshwater spiked with fresh Fe(III) (approximately 5 or 10 microM) to sunlight led to repeatable, significantly larger increases in DGM production (e.g., 380% in 1 h, 420% in 2 h, and 470% in 4 h for Whitefish Bay water) than exposure without the spike (e.g., 200% in 6 h). DGM increased with increasing exposure time and then often appeared to approach a steady state in the tests. Higher Fe(III) spike levels resulted in the same, or even less, DGM production. Storage of the water with or without Fe(III) spike in the dark after sunlight exposure led to significant, apparently first-order, decreases in DGM. These phenomena were hypothetically attributed to sunlight-induced photochemical production of highly reducing organic free radicals through photolysis of Fe(III)-organic acid coordination compounds and subsequent reduction of Hg(II) to Hg(0) by the organic free radicals; the reduction was also accompanied by dark oxidation of Hg(0) by photochemically originated oxidants (e.g., .OH). This study suggests that sunlight and Fe(III)-induced photochemical reduction of Hg(II) could be one of the mechanisms responsible for natural photochemical production of DGM in freshwaters and that Fe species may be influential in mediating Hg chemodynamics and its subsequent toxicity in aquatic ecosystems.

Fresh Water↗