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Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 577 records · Page 32Linked to original sources

Kinetics of BRCA1 regulation in response to UVC radiation.

To investigate changes in BRCA1 following DNA damage, we exposed MCF-7 cells to increasing doses of ultraviolet C. We observed an increase in BRCA1 protein levels above 78 J/m2. This increase was observed as early as 5 min after irradiation. BRCA1 levels were then observed to decrease after 2 h, consistent with the previously published data. By pretreating with cycloheximide prior to irradiation, we observed a decrease in the protein half-life, from 3.5 h to 53 min, suggesting that a decrease in protein half-life may cause the lower levels of BRCA1 after irradiation. We also observed an increase in BRCA1 mRNA within 15 min of irradiation, followed by a decrease after 4 h. These data suggest that newly translated protein may contribute to increases in BRCA1 protein levels. The very rapid changes in BRCA1 support its role as a sensor of DNA damage, as opposed to being a repair gene.

BRCA1 Protein↗

Microdetermination of proteins using m-carboxychlorophosphonazo as detection probe by enhanced resonance light scattering spectroscopy.

Proteins can be determined using a common spectrofluorometer to detect the intensity of resonance light scattering (RLS). Under acidic conditions, the reaction between m-carboxychlorophosphonazo (CPA-mK) and proteins enhances the weak light scattering of CPA-mK drastically. This enhanced intensity is proportional to the concentration of proteins. The linear ranges for human serum albumin are 0.5-35.0 microg/mL, with detection limits of 0.104 microg/mL. The method yields results comparable to those of the calorimetric method using Coomassie Brilliant Blue G-250 (CBB) with relative standard deviations of 0.72-2.10% (n = 10). There is almost no interference by amino acids and most of the metal ions.

Algorithms↗

Association of splicing defects in PTEN leading to exon skipping or partial intron retention in Cowden syndrome.

Cowden syndrome (CS) and Bannayan Zonana syndrome (BZS) are two autosomal dominantly inherited conditions characterized by hamartomas. Mutations in PTEN, a tumor suppressor gene located on chromosome 10q23, have been identified in patients with phenotypic findings of both CS and BZS. These mutations are found throughout the entire gene, with exon 5 being the most common site, and include point mutations, insertions and deletions. To date, 11 point mutations at the splice junctions of the PTEN gene have been reported, however, data on the alterations in the transcripts have been lacking. In this study, we have identified three novel splice site mutations in PTEN, in two families with CS and in one individual with BZS. One mutation affected the splice-acceptor site, which resulted in out-of-frame skipping of an entire exon. By contrast, the other two mutations affected the splice-donor sites, and both showed inclusion of partial intronic sequences in the transcript due to activation of cryptic splice sites. These data demonstrate mRNA alterations as a consequence of splice site mutations in the PTEN gene.

Child↗

Age and menopause-related changes in phalangeal bone density of Japanese women, measured by a digital image processing method.

The bone density (BD), phalangeal index (PLI), and metacarpal index (MCI) of the proximal phalangeal and metacarpal bones of the index finger of the nondominant hand were measured, using a digital image processing (DIP) method, in a total of 345 normal Japanese women. In this study, two different locations were measured and the BD, PLI, and MCI decreased significantly after the age of 50 years (P < 0.01 vs values for women in their third decade). The BD, PLI, and MCI of the proximal phalangeal and metacarpal bones showed a significant decrease in postmenopausal groups compared with the pre-menopause group (P < 0.01), which indicated that not only trabecular bone but also cortical bone had an accelerative bone loss in the postmenopausal women. The BD in proximal phalangeal and metacarpal bones decreased by 0.69% and 0.74% / per year, respectively, and there were no significant differences between these annual decreases. The BD of proximal phalangeal bone had a good correlation with that of the metacarpal bone (r = 0.77; P < 0.01), which suggested that the measurement of proximal phalangeal BD was as useful as the measurement of metacarpal BD in screening for osteoporosis (coefficient of variation; CV, 0.64%). The data suggest that DIP has a potential application in screening for osteoporosis.

Adult↗

Triterpenoid saponins from Ardisia mamillata.

Two saponins were isolated from the roots of Ardisia mamillata HANCE. Their structures were established on the basis of MALDI-TOFMS, 1H, 13C NMR and 2D NMR (COSY, HOHAHA, HETCOR, HMBC and ROESY) spectra, and on chemical evidence, to be ardisimamilloside A, 3-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 4)-[beta-D-glucopyranosyl-(1 --> 2)]-alpha-L-arabinopyranosyl]-3beta, 16alpha,28alpha-trihydroxy-13beta,28-epoxy-oleanan+ ++-30-al; and ardisimamilloside B, 3-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 4)-[beta-D-glucopyranosyl-( 1 --> 2)]-alpha-L-arabinopyranosyl]-beta3-hydroxy-13beta,28- epoxy-oleanan-16-oxo-30-al.

Carbohydrate Conformation↗

Light-induced disappearance of nitrite in the presence of iron (III).

Understanding of rapid disappearance of nitrite in natural waters and its impact on nitrogen natural cycling has remained limited. We found that NO2- disappeared rapidly in pH 3.2 aqueous Fe(III) solutions both in sunlight and in 356 nm light. Quantum yields of the NO2- loss at 356 nm were 0.049-0.14 for initial levels of 10-80 microns NO2- and 200 microns Fe(III). The NO2- loss (at 356 nm) followed apparent first-order kinetics. The rate constants were 1.3 x 10(-3) (40 microns NO2-) and 4.1 x 10(-4) s-1 (80 microns NO2-) for 100 microns Fe(III), and 2.3 x 10(-3) (40 microns NO2-) and 7.5 x 10(-4) s-1 (80 microns NO2(-1)) for 200 microns Fe(III) (t1/2 = 8.7, 27.9, 5.1, and 15.3 min, respectively). The rate constants were directly proportional to [Fe(III)]0 and inversely proportional to [NO2-]0. Agreement between the rate constants obtained experimentally and those calculated mechanistically supports the hypothesis that NO2- was oxidized to NO2 by .OH radicals from photolysis of FeOH2+ complexes, and at high [NO2-]0 (e.g., 80 microns) relative to [Fe(III)]0, hydrolysis of NO2 or N2O4 to form NO3- and NO2- could be significant. This study showed that light and Fe(III)-induced oxidation of NO2- (rate = approximately 10(-1)-10(-2) microns s-1) was more rapid than its direct photolysis (rate = approximately 10(-4) microns s-1), and the photolysis could be a significant source of .OH radicals only in cases where the Fe(III) level is much lower than the NO2- level ([Fe(III)]/[NO2-] < 1/80). This study suggests that the light and Fe(III)-induced oxidation of NO2- would be one potential important pathway responsible for the rapid transformation of NO2- in acidic surface waters, especially those affected by acid-mine drainage or volcanic activities. This study also may be of interest for modeling certain acidic atmospheric water environments.

Hydrogen-Ion Concentration↗

Quality-of-life evaluation using Short Form 36: comparison in hemodialysis and peritoneal dialysis patients.

Short Form 36 (SF-36) is a well-documented health-related quality-of-life (HRQOL) instrument consisting of 36 questions compressed into eight scales and two primary dimensions: the physical and mental component scores. This tool was used to evaluate QOL among peritoneal dialysis (PD) and hemodialysis (HD) patients. The results of 16,755 HD and 1,260 PD patients (728 continuous ambulatory PD [CAPD] and 532 continuous cycling PD [CCPD]) completing an SF-36 during 1996 were analyzed. Three analyses of variance were performed, consisting of (1) no adjustment, (2) case mix (age, sex, race, and diabetes), and (3) case mix plus laboratory parameters. PD patients were younger (P < 0.001), a larger fraction were white (P < 0.001), fewer had diabetes (P < 0.001), and had lower serum albumin concentrations (P < 0.001) and higher creatinine, hemoglobin, and white blood cell count values (P < 0.001) than HD patients. Diabetes was present in a larger fraction of CCPD than CAPD patients (P < 0.001). HD and PD patients scored similarly for scales reflecting physical processes. PD patients scored higher for mental processes, but only after statistical adjustment for the laboratory measures. Scores on scales reflecting physical processes were worse, and those reflecting mental processes were better among CCPD than CAPD patients. HD and CAPD scores were similar. CCPD patients perceived themselves as more physically impaired but better adjusted than HD or CAPD patients. These descriptive data show that perception of QOL among PD and HD patients is similar before adjustment, but PD patients score higher for mental processes with adjustment. CCPD patients score worse for physical function and better for mental function than either CAPD or HD patients. We cannot, however, exclude the influence of therapy selection.

Female↗

Toxicological evaluation of New Zealand deer velvet powder. Part I: acute and subchronic oral toxicity studies in rats.

Potential toxic effects of acute and subchronic dosage regimens of deer velvet powder have been assessed in rats following OECD guidelines. In the acute study, rats of both sexes were exposed to a single dose of 2 g/kg body weight. There was no mortality or other signs of toxicity during 14 days' observation. Furthermore, no significant alteration either in relative organ weights or their histology was discernible at terminal autopsy. In the 90-day subchronic study, deer velvet was administered in 1 g/kg daily doses by gavage to rats. A control group of rats received water only. There was no effect on body weight, food consumption, clinical signs, haematology and most parameters of blood chemistry including carbohydrate metabolism, liver and kidney function. No significant differences were seen between the mean organ weights of the adrenal, kidney and brain in rats treated with deer velvet and control rats. However, there was a significant difference (P<0.05) in the group mean relative liver weight (3.52 +/- 0.30 vs 3.81 +/- 0.26 g/100 g body weight) of deer velvet-treated and control male rats. The gross necropsy and pathological examination of rats treated with deer velvet did not reveal any abnormalities in tissue morphology. Based on these results, it may be concluded that rats had no deer velvet treatment-related toxicological and histopathological abnormalities at the doses administered, despite the observed minor changes in liver weight.

Administration, Oral↗

A reverse nuclear factor-kappaB element in the rat type II nitric oxide synthase promoter mediates the induction by interleukin-1beta and interferon-gamma in rat aortic smooth muscle cells.

The rat type II nitric oxide synthase (iNOS) promoter contains two nuclear factor-kappaB (NF-kappaB)-binding sites, one upstream (-965 to -956 bp) and one downstream (-107 to -98 bp), which are important for iNOS induction. We have identified a third NF-kappaB site located at -901 to -892 bp whose sequence is identical to that of the upstream site but with the opposite orientation ("the reverse NF-kappaB site"). We hypothesized that the reverse NF-kappaB site, like the other two sites, is important for iNOS induction. With the use of a rat iNOS promoter fragment of -906 to -887 bp as probe, electrophoretic mobility shift assays were performed on nuclear proteins extracted from rat aortic smooth muscle cells (RASMCs) treated with interleukin-1beta (IL-1beta, 100 U/ml) +/- interferon-gamma (IFN-gamma, 250 U/ml) for 30 min. IL-1beta, but not IFN-gamma, induced a DNA-protein complex that was supershifted by either anti-NF-kappaB p50 or anti-NF-kappaB p65 antibody. The functionality of the reverse NF-kappaB site was evaluated by mutation experiments and transfection assays. The wild-type and mutated -1.4 kb rat iNOS promoter-luciferase constructs were transfected into RASMCs. Compared with the wild type, reverse-NF-kappaB site (-901 to -892 bp) deletion, substitution of T for C at -894 bp, and substitution TTT for CCC at -896 to -894 bp decreased the IL-1beta-induced promoter activity by 67% (p < 0.001), 45% (p < 0.001), and 56% (p < 0.001), respectively. These deletion/substitutions also decreased the IL-1beta- and IFN-gamma-induced promoter activity by 74% (p < 0.001), 53%(p < 0. 001), and 63% (p < 0.001), respectively. In conclusion, a p50 and p65 NF-kappaB heterodimer binds to a reverse-NF-kappaB site on the rat iNOS promoter and contributes to iNOS induction by IL-1beta and IFN-gamma in RASMCs.

Animals↗

Phospholipid composition and levels are not altered in fibroblasts bearing presenilin-1 mutations.

Lipid alterations have been reported in brain regions affected by Alzheimer disease (AD). The mechanisms causing these changes are poorly understood because it is difficult to study dynamic, biochemical processes in post-mortem brain. Fibroblasts derived from AD patients offer an alternative model to study disease-related alterations in lipid metabolism. Therefore, we measured the phospholipid levels and composition of fibroblasts from individuals bearing two different presenilin-1 mutations and compared these values to appropriate control fibroblasts. There were no differences between groups in phospholipid composition or in individual phospholipid levels, including the plasmalogens. Cholesterol levels and the cholesterol/phospholipid ratio were not different between presenilin-1 mutation bearing and control fibroblasts. Although these presenilin-1 mutation bearing fibroblasts have a number of biochemical changes related to AD, the absence of a change in phospholipid levels suggests that under these conditions, these cells are not useful in studying the mechanisms underlying the alterations in brain phospholipid levels associated with AD. However, these results do not preclude the possible use of other fibroblasts bearing AD-related mutations, e.g., APP mutations, to examine AD-related changes in brain lipid metabolism, or of these fibroblasts under different conditions.

Alzheimer Disease↗

Detection of integrins in cataract lens epithelial cells.

PURPOSE: To detect the expression of integrin subunits in lens epithelial cells (LECs) of human cataracts. SETTING: Research Laboratory, International Intraocular Implant Training Centre, Tianjin Medical University, China. METHODS: The circular sections of the anterior capsules with attached LECs were obtained during cataract surgery from 100 patients. The LECs were stained with an avidin-biotin-complex immunohistochemical technique using 5 monoclonal antibodies specific for alpha subunits 2, 3, 5 and beta subunits 1, 2. RESULTS: All integrin subunits studied were found to varying degrees in specimens. The positive percentages were 70%, 65%, 75%, 70%, and 80%, respectively. CONCLUSION: Integrin subunits were present in LECs of human cataracts. These molecules may serve in the adhesion of LECs to the lens capsule and play a role in cell-posterior capsule interaction after cataract surgery.

Antibodies, Monoclonal↗

Homology modeling of the insect chitinase catalytic domain--oligosaccharide complex and the role of a putative active site tryptophan in catalysis.

Knowledge-based protein modeling and substrate docking experiments as well as structural and sequence comparisons were performed to identify potential active-site residues in chitinase, a molting enzyme from the tobacco hornworm, Munduca sexta. We report here the identification of an active-site amino acid residue, W145. Several mutated forms of the gene encoding this protein were generated by site-directed mutagenesis, expressed in a baculovirus-insect cell-line system, and the corresponding mutant proteins were purified and characterized for their catalytic and substrate-binding properties. W145, which is present in the presumptive catalytic site, was selected for mutation to phenylalanine (F) and glycine (G), and the resulting mutant enzymes were characterized to evaluate the mechanistic role of this residue. The wild-type and W145F mutant proteins exhibited similar hydrolytic activities towards a tri-GlcNAc oligosaccharide substrate, but the former was approximately twofold more active towards a polymeric chitin-modified substrate. The W145G mutant protein was inactive towards both substrates, although it still retained its ability to bind chitin. Therefore, W145 is required for optimal catalytic activity but is not essential for binding to chitin. Measurement of kinetic constants of the wild-type and mutant proteins suggests that W145 increases the affinity of the enzyme for the polymeric substrate and also extends the alkaline pH range in which the enzyme is active.

Amino Acid Sequence↗

Perioperative alterations in plasma endothelin-1 and echocardiographic correlates of right heart function.

OBJECTIVE: To determine whether greater changes in plasma endothelin-1 (ET-1) concentrations and right ventricular systolic pressure occur after major thoracic surgery than after major abdominal operations. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Patients undergoing elective thoracotomies (n = 12) or laparotomies (n = 10). INTERVENTIONS: ET-1 was measured from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). Transthoracic echocardiography was performed before surgery and on postoperative day 2 to evaluate right-sided heart function. MEASUREMENTS AND MAIN RESULTS: After abdominal and thoracic surgery, systemic and estimated pulmonary vascular pressures were normal in both groups and unaffected by surgery. Plasma ET-1 concentrations decreased from baseline values during the first postoperative week with no differences between the groups. CONCLUSIONS: In patients without organic heart disease, plasma ET-1 levels do not increase in response to major abdominal or thoracic surgery. Whether or not plasma ET-1 concentrations are elevated in patients developing clinically significant postoperative pulmonary hypertension requires further study.

Aged↗

Sparfloxacin for the treatment of acute bacterial maxillary sinusitis documented by sinus puncture.

PURPOSE: To evaluate the efficacy and safety of sparfloxacin in the treatment of patients with acute bacterial maxillary sinusitis, the microbiologic etiology of which was determined by maxillary sinus puncture. PATIENTS AND METHODS: Two hundred fifty-three patients enrolled in the open, noncomparative trial received sparfloxacin as a 400-mg loading dose followed by 200 mg once daily doses for a total of 10 days. One hundred ninety-eight patients were clinically evaluable and 82 were also bacteriologically evaluable. All treated patients were included in the safety analysis. Overall success was determined based on clinical success (resolution or reduction of signs and symptoms and sinus x-rays) and bacteriologic success (eradication and presumed eradication of baseline pathogens obtained by maxillary sinus puncture and aspiration). RESULTS: Overall success in the bacteriologically evaluable population at test-of-cure was 91.5% [75/82; 95% confidence interval (85.4%, 97.5%)]. For all pathogens, the eradication rate was 93.2% (109/117 baseline pathogens); individual pathogen eradication rates were 88.9% (16/18) for S. pneumoniae (including those strains exhibiting decreased susceptibility to penicillin); and 100% for H. influenzae (17/17), S. aureus (14/14), and M. catarrhalis (11/11). The majority of adverse events were of mild or moderate severity; the most frequently related adverse events were photosensitivity reaction, headache, nausea, and diarrhea. CONCLUSION: Sparfloxacin had an overall success rate of 91.5% for patients in this study and was generally well tolerated in the treatment of acute bacterial maxillary sinusitis.

Acute Disease↗

Triterpene glycosides from Cimicifuga racemosa.

Eight new triterpene glycosides named cimiracemosides A-H, respectively, and eight known triterpene glycosides were isolated from the rhizome extracts of black cohosh (Cimicifuga racemosa). The new compounds were determined by spectral data to be 21-hydroxycimigenol-3-O-alpha-L-arabinopyranoside (1), 21-hydroxycimigenol-3-O-beta-D-xylopyranoside (2), cimigenol-3-O-alpha-L-arabinopyranoside (3), 12beta-acetoxycimigenol-3-O-alpha-L-arabinopyranoside (4), 24-acetylisodahurinol-3-O-beta-D-xylopyranoside (5), 20(S),22(R), 23(S),24(R)-16beta:23;22:25-diepoxy-12beta-acetoxy-3be ta,23, 24-trihydroxy-9,19-cycloanost-7-ene-3-O-beta-D-xylopyranoside (6), 20(S),22(R),23(S),24(R)-16beta:23;22:25-diepoxy-12beta -acetoxy-3beta, 23,24-trihydroxy-9,19-cycloanost-7-en-3-O-alpha-L-arabinopyrano side (7), and 20(S),22(R),23(S), 24(R)-16beta:23;22:25-diepoxy-12beta-acetoxy-3beta,23, 24-trihydroxy-9,19-cycloanostane-3-O-beta-D-xylopyranoside (8).

Glycosides↗

Bioactive compounds from Psorothamnus junceus.

During a search for bioactive compounds from Psorothamnus junceus, four heterocyclic compounds, psorothamnone A (1), psorothamnone B (2), dalrubone (3), and emorydone (4) were isolated from the ethanol extract of the stem bark. Psorothamnones A (1) and B (2) demonstrated inhibitory activity against protein kinase C (PKC), a key enzyme involved in the signal transduction of cell proliferation and differentiation. Dalrubone (3) and emorydone (4) showed cytotoxicity against several human tumor cell lines.

Drug Screening Assays, Antitumor↗