Search PubMed⌕ Search

Biomedical subjects

H Huang

Publications and source records attributed to H Huang.

At least 451 records · Page 25Linked to original sources
PubMed1995

Interaction of cis- and trans-diamminedichloroplatinum with metallothionein in vivo.

The properties of platinum (II) complexes to induce the biosynthesis of metallothionein (MT) were investigated in rabbits following injections of K2PtCl4, cis and trans isomers of DDP (diammine-dichloroplatinum). It was demonstrated that cis-DDP has an ability to induce MT specifically in the liver, whereas trans-DDP appears to be unable to stimulate the biosynthesis of MT in either the liver or the kidneys. In contrast, K2PtCl4 is effective to elevate the MT level in both tissues. However, all of these platinum complexes are rather poor stimulators for MT biosynthesis compared to cadmium and zinc compounds. Preinjection with Zn(NO3)2 significantly enhances the amount of Pt associated with the MT fractions compared to that resulting from injections with either cis- or trans-DDP without Zn(NO3)2 pretreatment. Metallothionein containing Pt was purified and identified from the liver and kidneys of rabbits after preinjections with Zn(NO3)2 followed by repeated injections of cis-DDP and trans-DDP, respectively. It was found for the first time that a relatively higher degree of Pt was associated with MT fractions in the case of trans-DDP treatment than that of cis-DDP injection. On this basis, the role of MT was discussed in relation to its involvement in the metabolism of cis-DDP, and the difference of the antitumor activity and toxicity between cis- and trans-DDP.

Animals↗
PubMed1995

DNA-DNA interstrand cross-linking by cis-diamminedichloroplatinum(II): N7(dG)-to-N7(dG) cross-linking at 5'-d(GC) in synthetic oligonucleotides.

The nucleotide sequence specificity of the DNA-DNA interstrand cross-linking reaction of cis-diamminedichloroplatinum(II) (cis-DDP) was studied in synthetic oligonucleotides. Of six self-complementary DNAs tested, only those containing the central sequence 5'-d(GC) formed appreciable interstrand cross-linked product, as assayed by denaturing polyacrylamide gel electrophoresis (DPAGE). The nucleotide connectivity of the interstrand cross-link was defined by sequence random oxidative fragmentation followed by DPAGE, revealing that dG residues on opposite strands at the sequence 5'-d(GC) were connected to one another. The covalent structure of the cross-link was established following hydrolysis of the phosphodiester backbone of a structurally homogeneous sample of a cis-DDP interstrand cross-linked DNA tetradecamer. HPLC analysis of the hydrolysate returned all of the deoxynucleoside residues from the starting DNA except for two deoxyguanosine residues. Also returned was diammine-bis-[N7-(2'- deoxyguanosyl)]platinum(II)2+, identified by a combination of spectroscopic methods, and comparison to a synthetic authentic sample. This study directly establishes that cis-DDP forms interstrand cross-links at the duplex sequence 5'-d(GC), linking deoxyguanosine residues on opposite strands at N7 through a bridging platinum atom. Computer simulation of the interstrand cross-linked product using molecular mechanics energy minimization and molecular dynamics revealed significant structural reorganization at the site of the cross-link including a ca 40 degrees angle between the platinated guaninyl residues, which propagated to adjacent residues by base stacking to yield duplexes bent by some 30 degrees toward the major groove.

Antineoplastic Agents↗
PubMed1995

A study of patient satisfaction and adherence to preventive care practice guidelines.

PURPOSE: Patient satisfaction ratings are being used to judge physicians' quality of care and to determine physician reimbursement. We therefore studied the association between patient satisfaction and the quality of medical care received by patients in physicians' offices. PATIENTS AND METHODS: Patient satisfaction was measured in a survey of patients cared for by 48 primary care physicians in a health maintenance organization in Southern California. Evidence that patients were offered or received preventive care services was determined by patient survey and medical record abstraction, respectively. The medical records of 3,249 randomly selected elderly patients (65 to 75 years old) were studied. Of these patients, 2,799 completed a patient satisfaction and preventive care services survey (response rate 86.1%), 2,654 completed a patient satisfaction survey (response rate 81.7%), and 2,258 completed a quality-of-life survey (response rate 69.5%). RESULTS: Patients were generally satisfied with their physicians' care (median satisfaction score 4.2; scale 1 to 5, 5 being most satisfied). Patients who received or were offered mammography, clinical breast examination, influenza vaccine, pneumococcal vaccine, tetanus vaccine, exercise counseling, and smoking cessation counseling were more satisfied with their medical care than those patients who did not (P < 0.001 for all tests). After controlling for the physician who was providing the medical care, there was still a statistically significant relationship between these factors and patient satisfaction. CONCLUSIONS: We found a significant association between patient satisfaction and the performance of some but not all preventive care services. However, we cannot be certain whether there is a relationship between patient satisfaction and quality of patient care.

Aged↗
PubMed1995

Trypanosoma cruzi induces endothelin release from endothelial cells.

The potential role of endothelin-1 (ET-1) in the pathogenesis of focal microvascular spasm, previously implicated in the etiology of Chagas' cardiomyopathy, was investigated. There was an increase in ET-1 in the supernatants of Trypanosoma cruzi--infected human umbilical vein endothelial cells (HUVEC). Infection of HUVEC and vascular smooth muscle cells had no effect on the synthesis of transforming growth factor-beta, which induces ET-1 synthesis. Bioassay studies of isolated rat aortic rings revealed that the increases in ET-1 production were associated with augmented contractile responses, which were significantly attenuated by preincubation with the ETA receptor antagonist, BQ-123. When big ET was incubated with the parasite, there was no conversion of the precursor to the active hormone (ET-1), demonstrating that the parasite did not possess the necessary converting enzyme. These observations suggest the potential importance of ET-1 in the etiology of the microvascular spasm associated with Chagas' disease.

Animals↗
PubMed1995

Mapping and sequence analysis of the gene encoding the beta subunit of the epithelial sodium channel in experimental models of hypertension.

OBJECTIVE: To investigate whether mutations in the beta subunit of the epithelial sodium channel (Scnn1b) contribute to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR) and the Dahl salt-sensitive rat. DESIGN: We determined the chromosome location of the rat Scnn1b gene, tested for cosegregation with blood pressure, and sequenced near full-length Scnn1b complementary DNAs (cDNAs) from SHR and Dahl salt-sensitive rats. METHODS: Chromosome mapping was performed by somatic cell hybrid analysis and by linkage analysis in recombinant inbred strains derived from SHR and Brown-Norway rats. Cosegregation analysis was performed by testing for correlations between blood pressure and Scnn1b genotypes in these strains. DNA sequencing was performed on cDNAs prepared from reverse-transcribed messenger RNA derived from rat kidney. RESULTS: The Scnn1b gene was closely linked to the Sa gene on rat chromosome 1. Blood pressure correlated significantly with Scnn1b gene in the recombinant inbred strains. Analysis of near full-length Scnn1b cDNAs from SHR and Dahl rats failed to reveal any coding sequence mutations that could affect the predicted amino acid sequence of the Scnn1b protein. CONCLUSION: The Scnn1b gene maps near the Sa gene in a region of rat chromosome 1 involved in the inherited control of blood pressure. If disordered activity of the epithelial cell sodium channel contributes to the pathogenesis of hypertension in the SHR or Dahl models, it must stem from genetic lesions in sequences that regulate Scnn1b function or in sequences important to the structure or function of the other sodium channel subunits.

Animals↗
PubMed1995

Membrane topology and site-specific mutagenesis of Pseudomonas aeruginosa porin OprD.

Pseudomonas aeruginosa OprD is a 420-amino-acid protein that facilitates the uptake of basic amino acids, imipenem and gluconate across the outer membrane. OprD was the first specific porin that could be aligned with members of the non-specific porin super-family. Utilizing multiple alignments in conjugation with structure predictions and amphipathicity calculations, an OprD-topology model was proposed. Sixteen beta-strands were predicted, connected by short loops at the periplasmic side. The eight external loops were of variable length but tended to be much longer than the periplasmic ones. Polymerase chain reaction (PCR)-based site-specific mutagenesis was performed to delete separately short stretches (4-8 amino acid residues) from each of the predicted external loops. The mutants with deletions in the predicted external loops L1, L2, L5, L6, L7 and L8 were tolerated in both Escherichia coli and P. aeruginosa. The expressed mutant proteins maintained substantial resistance to trypsin treatment in the context of isolated outer membranes. Proteins with deletions in loops L1, L5, L6, L7 and L8 reconstituted similar imipenem supersusceptibility in a P. aeruginosa OprD:: omega background. The L2-deletion mutant only partially reconstituted super-susceptibility, suggesting that loop L2 is involved in imipenem binding. These data were generally consistent with the topology model.

Amino Acid Sequence↗
PubMed1995

Identification and activation of autocrine renin-angiotensin system in adult ventricular myocytes.

To date, the demonstration that the molecular components of the renin-angiotensin system (RAS) are present in adult ventricular myocytes is lacking. In addition, whether the RAS is upregulated under conditions of overload and myocyte hypertrophy in vivo remains to be determined. By employing an in vivo model of ischemic cardiomyopathy in rats, we document that adult myocytes express genes for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) receptors. Moreover, renin, ACE, and ANG II receptor mRNAs increased in stressed myocytes undergoing cellular hypertrophy. At the protein level, the percentage of myocytes containing renin, ANG I, and ANG II was significantly increased in the overloaded heart. The number of binding sites for ANG II per myocyte also markedly increased under this setting. These results provide direct evidence of the existence of a myocyte RAS, which may be activated in pathological states of the heart to support myocyte growth and contractile function.

Angiotensinogen↗
PubMed1995

Mapping of quantitative trait loci for blood pressure and cardiac mass in the rat by genome scanning of recombinant inbred strains.

In the HXB and BXH recombinant inbred strains derived from the spontaneously hypertensive rat and the normotensive Brown Norway rat, we determined the strain distribution patterns of 500 genetic markers to scan the rodent genome for quantitative trait loci regulating cardiac mass and blood pressure. The markers spanned approximately 1,139 cM of the genome and were tested for correlations with left ventricular mass adjusted for body weight, and with systolic, diastolic, and mean arterial pressures. The marker for the dopamine 1A receptor (Drd1a) on chromosome 17 showed the strongest correlation with left ventricular heart weight (P = .00038, r = -0.59) and the relationship to heart weight was independent of blood pressure. The markers showing the strongest correlations with systolic, diastolic, and mean arterial pressure were D19Mit7 on chromosome 19 (P = .0012, r = .55), D2N35 on chromosome 2 (P = .0008, r = .56), and Il6 on chromosome 4 (P = .0018, r = .53), respectively. These studies demonstrate that the HXB and BXH strains can be effectively used for genome scanning studies of complex traits and have revealed several chromosome regions that may be involved in the genetic control of blood pressure and cardiac mass in the rat.

Animals↗
PubMed1995

Air pollution and unscheduled hospital outpatient and emergency room visits.

We conducted a time-series analysis of daily hospital visits and air pollution data to assess acute effects of air pollution on daily unscheduled outpatient visits to internal medicine, pediatric, and emergency departments in the No. 3 Affiliated Hospital of Beijing Medical University in Beijing, China. Sulfur dioxide was marginally significantly associated with total outpatient visits (beta = 41.5, SE = 24.2) and significantly associated with internal medicine (beta = 14.6, SE = 6.7), pediatric (beta = 12.7, SE = 3.7), and emergency room visits (beta = 6.8, SE = 2.7). Total suspended particulates (TSP) was a significant predictor for total outpatient (beta = 21.1, SE = 7.7) and pediatric visits (beta = 3.4, SE = 1.3) and a marginally significant predictor of internal medicine visits (beta = 4.2, SE = 2.2). In a season-specific analysis, SO2 was a significant predictor for total hospital outpatient visits in summer, although the mean daily SO2 concentration was only 17 micrograms/m3 (maximum = 51 micrograms/m3). In winter, SO2 was significantly associated with internal medicine, pediatric, and emergency room visits, and TSP was associated with total outpatient visits. This study suggests an exposure-response relationship between TSP and SO2 and hospital outpatient visits, both at high air pollution levels and at levels well below air quality standards recommended by the World Health Organization.

Air Pollution↗
PubMed1995

Expression of human insulin-like growth factor-binding protein-3 in transgenic mice.

Transgenic mice which expressed human IGF-binding protein-3 (hIGFBP-3) were generated by pronuclear injection of an hIGFBP-3 cDNA driven by the mouse metallothionein 1 promoter. Two of the seven founder mice had measurable levels of hIGFBP-3 in the circulation. The serum levels of hIGFBP-3 increased as the mice were bred to homozygosity and were further induced by supplementing the drinking water with 25 mM ZnCl2. While the birth weight, litter size and body weight of transgenic mice were not significantly different from non-transgenic litter mates or wild-type mice derived from the same genetic background, the transgenic mice demonstrated selective organomegaly. The spleen, liver and heart of mice derived from both founders were significantly heavier compared with organs from non-transgenic mice (P < 0.05, P < 0.005 and P < 0.01 respectively). The weights of the brain and kidney were similar in transgenic and non-transgenic mice. Expression of the transgene was detected in the kidney, small intestine and colon by Northern blot analysis. Western ligand blotting of serum from transgenic mice did not demonstrate any change in the abundance of the IGFBPs detected by this method. When serum from transgenic mice was incubated with 125I-labeled IGF-I and analyzed by Sephacryl S-200 chromatography under neutral conditions a significantly (P < 0.05) increased amount of the radioactivity was found in the 140 kDa ternary complex compared with serum from wild-type mice. Immunoreactive hIGFBP-3 was detected in the 140 kDa ternary complex but the majority of immunoreactive hIGFBP-3 present in transgenic mouse serum eluted in later fractions indicating that it was not associated with the acid-labile subunit. These data demonstrate that modest constitutive expression of hIGFBP-3 has a selective effect on organ growth and development. The establishment of these IGFBP-3 transgenic mouse strains may provide useful models to investigate further the physiological role of IGFBP-3.

Animals↗
PubMed1995

Plasma angiotensin in binephrectomised mice.

Plasma renin-angiotensin parameters were measured before and 24h after binephrectomy (BNx) in male Swiss (Ren-1, Ren-2) and BALB/c (Ren-1) female mice (representing the extremes of differences in tissue renin expression), together with in vivo inhibition of residual renin. Plasma Ang II increased from 18.9 +/- 7.3 to 48.1 +/- 16.9 pg/ml after BNx in conscious Swiss mice (+/- sd, p < 0.001, n = 11&12), renin activity (PRA) increased 2.76 times, angiotensinogen (aogen) increased 4.57 times and renin concentration (PRC) fell by 65%. In BALB/c, Ang II+Ang III decreased slightly (56.6 +/- 11 to 37.7 +/- 14.7, p < 0.05, n = 5&6), PRA was unchanged, aogen increased 12 times and PRC fell by 93%. Plasma ACE decreased by 26% and 28% respectively. Aogen did not increase further when post BNx plasma renin was inhibited with antirenin in vivo during 20h. Thus plasma angiotensin is maintained or considerably increased following BNx in mice and the change is consistent with first-order kinetics with respect to renin and aogen in the circulation. Whether the strain carries one or two renin genes, high renal and extrarenal renin production combined with a low plasma aogen phenotype yields resting angiotensin levels similar to other mammals. A kinetic regulation of aogen levels is proposed in mice wherein Ang II production is limited by low substrate concentration thereby ensuring normotension in the face of abundant extrarenal renin secretion.

Angiotensin II↗