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Biomedical subjects

H Hu

Publications and source records attributed to H Hu.

At least 199 records · Page 11Linked to original sources
PubMed1997

Arsenic in drinking water and incidence of urinary cancers.

The associations between arsenic ingestion and cancers of the bladder and kidney have been documented in Taiwan. To evaluate further such associations for urinary cancers of various cell types, we conducted an ecologic study encompassing 243 townships using cancer registry data of patients diagnosed between 1980 and 1987. We used the proportions of wells with various specified arsenic levels in each township as indicators of exposure and evaluated the effects of urbanization and smoking by an urbanization index and the number of cigarettes sold per capita. In both genders, we observed associations of high arsenic levels in drinking water with transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined. We also observed such associations in adenocarcinomas of the bladder in males, but not in squamous cell carcinomas of the bladder or renal cell carcinomas or nephroblastomas of the kidney. There was also a positive association between the urbanization index and transitional cell carcinomas of the ureter in males. The number of cigarettes sold per capita was not a good predictor for urinary cancers. The results indicate that the carcinogenicity of arsenic may be cell type specific.

Adolescent↗
PubMed1997

Isolation and characterization of soluble boron complexes in higher plants. The mechanism of phloem mobility of boron.

Boron (B) polyol complexes have been isolated and characterized from the phloem sap of celery (Apium graveolens L.) and the extrafloral nectar of peach (Prunus persica L.). In celery the direct analysis of untreated phloem sap by matrix-assisted laser desorption-Fourier transform mass spectrometry, with verification by high-performance liquid chromagraphy and gas chromatography-mass spectrometry, revealed that B is present in the phloem as the mannitol-B-mannitol complex. Molecular modeling further predicted that this complex is present in the 3,4 3',4' bis-mannitol configuration. In the extrafloral nectar of peach, B was present as a mixture of sorbitol-B-sorbitol, fructose-B-fructose, or sorbitol-B-fructose. To our knowledge, these findings represent the first successful isolation and characterization of soluble B complexes from higher plants and provide a mechanistic explanation for the observed phloem B mobility in these species.

Biological Transport↗
PubMed1997

Direct inhibition of expressed cardiac L-type Ca2+ channels by S-nitrosothiol nitric oxide donors.

NO donors have complex effects on Ca2+ currents in native cardiac cells, with reports of direct stimulation and indirect cGMP-mediated inhibition or stimulation. To investigate the molecular basis of these effects, we tested the effects of one class of NO donors, S-nitrosothiols (RSNOs), on expressed cardiovascular L-type Ca2+ channels (alpha 1C +/- beta 1a +/- alpha 2 or alpha 1C +/- beta 2a +/- alpha 2) in human embryonic kidney (HEK293) cells. The RSNO compounds we used were S-nitroso-N-acetylpenicillamine (SNAP, 5 to 10 nmol/L or 100 to 800 mumol/L), S-nitrosocysteine (SNC, 100 mumol/L or 1 mmol/L), and S-nitrosoglutathione (GSNO, 1 mmol/L). Currents were measured using whole-cell patch recordings with 2 to 10 mmol/L Ba2+ as the charge carrier. SNAP reduced the amplitude of barium currents (IBa) through all the subunit combinations, with and EC50 of 360 mumol/L for alpha 1C + beta 1a channels. SNC or GSNO also inhibited IBa, albeit less potently. The inhibitory effect of SNAP was not affected by methylene blue (10 to 30 mumol/L) or 8-bromo-cGMP (200 to 400 mumol/L). The effects are relatively specific for Ca2+ channels, as expressed cardiac or skeletal muscle Na+ channels, which have a similar overall architecture, were barely affected by SNAP at concentrations as high as 1 mmol/L. We conclude that in the HEK293 expression system, the S-nitrosothiol NO donors inhibit L-type Ca2+ channels by a mechanism independent of cGMP.

Animals↗
PubMed1997

In vivo bone lead measurement in suburban teenagers.

OBJECTIVE: Bone represents a biologically active long-term storage site for lead, and bone lead data on teenagers are limited. Therefore, this study was designed to identify the distribution of bone lead in a teenage population and to explore the environmental and demographic factors associated with bone lead concentrations in young, nonoccupationally exposed subjects. DESIGN: A cross-sectional study of bone lead levels in high school students. PARTICIPANTS: A total of 168 students at a suburban Boston high school. Subjects (90 boys, 78 girls) ranged in age from 13.5 to 19 years and included 40% nonwhite minorities. Of the 168 subjects, 45 lived in homes constructed before 1960. None of the participants reported a history of lead poisoning. OUTCOME MEASURES: Tibial bone lead concentrations were measured in vivo for 60 minutes using K x-ray fluorescence. Lead exposure information was obtained by self-administered questionnaire. RESULTS: Point estimates of bone lead levels ranged from -7.15 to 14.23 microg lead/g bone mineral (microg/g), (mean, 4.0 microg/g; standard deviation, 4.4 microg/g). The reported measurement uncertainties accompanying each of the point estimates ranged from 2.56 to 9.01 microg/g (mean, 3.9 microg/g; standard deviation, 1.0 microg/g). Bone lead levels were not associated with the demographic factors of age, sex, or race. Additionally, current home conditions (housing age, traffic level) were not predictive of bone lead levels, even though these factors were predictive of in-home lead concentrations. CONCLUSIONS: These results demonstrate that although bone lead levels are measurable in this age group, the common predictors of blood and bone lead concentrations are not explanatory for bone lead levels.

Adolescent↗
PubMed1997

Decrease in birth weight in relation to maternal bone-lead burden.

OBJECTIVES: Birth weight predicts infant survival, growth, and development. Previous research suggests that low levels of fetal lead exposure, as estimated by umbilical cord blood-lead levels at birth, may have an adverse effect on birth weight. This report examines the relationship of lead levels in cord blood and maternal bone to birth weight. METHODS: Umbilical cord and maternal venous blood samples and anthropometric and sociodemographic data were obtained at delivery and 1-month postpartum. Blood-lead levels were analyzed by atomic absorption spectrophotometry. Maternal tibia and patella lead levels were determined at 1-month postpartum with use of a spot-source 109Cd K-X-ray fluorescence instrument. The relationship between birth weight and lead burden was evaluated by multiple regression with control of known determinants of size at birth. RESULTS: Data on all variables of interest were obtained for 272 mother-infant pairs. After adjustment for other determinants of birth weight, tibia lead was the only lead biomarker clearly related to birth weight. The decline in birth weight associated to increments in tibia lead was nonlinear and accelerated at the highest tibia lead quartile. In the upper quartile, neonates were on average, 156 grams lighter than those in the lowest quartile. Other significant birth weight predictors included maternal nutritional status, parity, education, gestational age, and smoking during pregnancy. CONCLUSIONS: Our results indicate that bone-lead burden is inversely related to birth weight. Taken together with other research indicating that lead can mobilize from bone into plasma without detectable changes in whole blood lead, these findings suggest that bone lead might be a better biomarker than blood lead. Because lead remains in bone for years to decades, mobilization of bone lead during pregnancy may pose a significant fetal exposure with health consequences, long after maternal external lead exposure has declined.

Birth Weight↗
PubMed1997

[Separation of soybean agglutinin by hydrophobic-interaction chromatography].

The soybean agglutinin (SBA) was separated with hydrophobic-interaction chromatography (HIC) in this work. HIC of the crude lectin extract of SBA was performed on Phenyl-Sepharose CL-4B column, 10 cm x 2.5 cm i.d., at a flow-rate of 1.0 mL/min. A 20 mL sample of the crude extract was applied to the column previously equilibrated with the buffer, 0.01 mol/L PBS containing ammonium sulfate (60% of saturation concentration). The column was eluted with the starting buffer, then with the buffer containing 30% saturation of ammonium sulfate, and finally with 0.01 mol/L PBS. Fractions were detected by UV absorbance at 280 nm and assayed for hemagglutinating activity. The results show that the purification-fold was as high as 35 and the recovery of activity was 100%.

Chromatography↗
PubMed1997

Localization of upstream silencer elements involved in the expression of cone transducin alpha-subunit (GNAT2).

PURPOSE: To localize cis-acting elements involved in the expression of the cone-specific G-protein, cone transducin alpha-subunit (GNAT2). METHODS: In this study, the authors used a genomic clone, HGLG3, to sequence 3139 base pairs of the upstream region of the GNAT2 gene and to localize cis-acting elements involved in the expression of GNAT2. Upstream elements were localized functionally by transfection of chloramphenicol acetyltransferase gene constructs containing nested deletions of this upstream region into WERI-Rb1 cells. Cell specificity of the localized elements was determined by transfection of the HeLa cells. Trans-acting factor-binding sites to functional cis-acting elements were determined by DNasel footprinting. Cell specificity of protein interaction with footprinted regions was tested by electrophoretic mobility shifts with nuclear extracts from WERI-Rb1 and HeLa cells. RESULTS: Transfection of WERI-Rb1 and HeLa cells revealed the presence of a strong, noncell-specific silencer region between -1130 and -23, a weak, cell-specific promoter between -151 and -10, and a stronger, noncell-specific element between +143 and +167. DNaseI footprinting showed three major footprints (S1, S2, and S3) between -807 and -176, indicating the binding sites for putative negative trans-acting factors. Individual footprinted sequences had similar electrophoretic mobility shifts when they were incubated with nuclear extracts from either WERI-Rb1 or HeLa cells, suggesting that these cells express the same negative factors. CONCLUSIONS: The expression of the GNAT2 gene is controlled by a strong silencer region, a weak upstream cell-specific promoter, and a strong downstream element. The silencer region interacts with similar proteins from retina- and nonretina-derived cell lines.

Base Sequence↗
PubMed1997

Cytokine messenger RNA expression by donor-specific cytotoxic T-cell clones after allogeneic heart transplantation.

BACKGROUND: After heart transplantation, expression of various cytokines can be detected in endomyocardial biopsy specimens both in the presence and in the absence of rejection. In this study we have analyzed the contribution of donor-specific CD8+ cytotoxic T cells to intragraft cytokine expression. METHODS: T cells were propagated from endomyocardial biopsy specimens in medium containing interleukin-2 and interleukin-4. From the T-cell lines obtained, T-cell clones were generated by limiting dilution. A number of 15 CD8+ donor-specific cytotoxic T-cell clones were generated from a single T-cell line and were analyzed for their cytokine messenger RNA expression. The cytokine profile of the clones was studied on the mRNA level by reverse transcriptase polymerase chain reaction. RESULTS: Almost all clones expressed mRNA for interleukin-1 beta, interleukin-4, and interleukin-10, and 75% of the clones expressed mRNA for interleukin-1 alpha, interleukin-9, and tumor necrosis factor-beta. In about half of the clones expression of interleukin-2, interleukin-6, interleukin-8, and interferon-gamma was detected. Tumor necrosis factor-alpha was only detected in one of the clones. The cytokine profiles exhibited a considerable heterogeneity. The 15 clones had previously been analyzed for their T-cell receptor V beta-gene family expression and T-cell receptor V-D-J region sequence. Homology in the V-D-J regions of the clones indicated that the 15 clones were derived from a limited number of progenitor cells. Interestingly, clones derived from one progenitor expressed a different mRNA cytokine profile. CONCLUSIONS: This study shows that donor-specific cytotoxic T cells can contribute to the spectrum of locally produced cytokines. The cytokine expression of these cytotoxic T cells seems not to be limited to a distinct profile.

CD8-Positive T-Lymphocytes↗
PubMed1996

Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A.

A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta I, beta II, gamma, delta, epsilon and eta PKC isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzenesulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R-enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b, was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.

Animals↗
PubMed1996

Determinants of bone and blood lead levels among community-exposed middle-aged to elderly men. The normative aging study.

Levels of lead in bone serve as a dosimeter for cumulative exposure to lead; moreover, lead in bone may serve as an internal source of circulating lead many years after environmental exposure has ceased. The authors measured lead in blood and used a K-x-ray fluorescence instrument to measure lead in the tibia (cortical) and patella (trabecular) bones in a cross-sectional survey of 719 middle-aged to elderly male participants in the Normative Aging Study who were without unusual occupational exposures to lead and who were healthy when enrolled in 1962-1965. Blood lead levels ranged from < 1 to 27.9 micrograms/dl, with a geometric mean of 5.7 micrograms/dl. Tibia and patella lead level ranges (geometric means) were < 1-51 (20.8) micrograms/g and 3-77 (29.8) micrograms/g, respectively. In backwards elimination multivariate regression models that considered age, race, education, retirement status, measures of both current and cumulative smoking, and alcohol consumption, the factors that remained significantly related to higher levels of both tibia and patella lead were higher age and measures of cumulative smoking, and lower levels of education. In the final model predicting blood lead that began with these same covariates and also included tibia and patella lead, the factor that accounted for the dominant portion of the variance in blood lead was patella lead. After adjustment for measurement error, a rise in patella lead from the median of the lowest to the median of the highest quintiles (13-56 micrograms/g) corresponded to a rise in blood lead of 4.3 micrograms/dl. The authors conclude that bone lead levels are substantial and comprise the major source of circulating lead in these men.

Adult↗
PubMed1996

The relationship of bone and blood lead to hypertension. The Normative Aging Study.

OBJECTIVE: To test the hypothesis that long-term lead accumulation, as reflected by levels of lead in bone (as opposed to blood which reflects recent lead exposure), is associated with an increased odds of developing hypertension. DESIGN: Case-control study of participants in the Veterans Administration (now Department of Veterans Affairs) Normative Aging Study, a 30-year longitudinal study of men. PARTICIPANTS: Of 1171 active subjects who were seen between August 1991 and December 1994, 590 (50%) participated in this investigation and had data on all variables of interest. MAIN OUTCOME MEASURES: Hypertension was defined as taking daily medication for the treatment of hypertension or systolic blood pressure higher than 160 mm Hg or diastolic blood pressure of 96 mm Hg or higher during the time of examination. Levels of lead in the tibia (representing cortical bone) and the patella (representing trabecular bone) were measured in vivo with a K x-ray fluorescence (KXRF) instrument. Levels of lead in blood were measured by graphite furnace atomic absorption spectroscopy. RESULTS: Blood lead levels were low, ranging from less than 0.05 to 1.35 micromol/L (<1 to 28 microgram/dL), with a mean (SD) of 0.30 (0.20) micromol/L (6.3[4.1] microgram/dL). Bone lead levels were similar to those described in other general populations. In comparison to nonhypertensives, mean levels of lead in blood and both tibia and patella bone lead levels were significantly higher in hypertensive subjects. In a logistic regression model of hypertensive status that began with age, race, body mass index, family history of hypertension, history of ethanol ingestion, pack-years of smoking, dietary sodium intake, dietary calcium intake, blood lead, tibia lead, and patella lead, the variables that remained after backward elimination were body mass index, family history of hypertension, and level of lead in the tibia. An increase from the midpoint of the lowest quintile to the midpoint of the highest quintile of tibia lead from 3 to 37 micrograms per gram of bone mineral was associated with an increased odds ratio of hypertension of 1.5. CONCLUSION: Our findings suggest that long-term lead accumulation, as reflected by levels of lead in bone, may be an independent risk factor for developing hypertension in men in the general population.

Age Factors↗
PubMed1996

A longitudinal study of low-level lead exposure and impairment of renal function. The Normative Aging Study.

OBJECTIVE: To determine whether low-level lead exposure is associated with impaired renal function. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Subjects were 459 men randomly selected from the participants of the Normative Aging Study who were originally recruited from healthy veterans in the greater Boston area in 1961 and were periodically examined at the Department of Veterans Affairs Outpatient Clinic every 3 to 5 years. We reconstructed blood lead concentrations for the period between 1979 and 1994 using samples of either archived red blood cells or fresh whole blood. MAIN OUTCOME MEASURES: Serum creatinine concentration. RESULTS: After adjustment for age, body mass index, smoking, alcohol consumption, educational level, and hypertension, blood lead concentration was positively and significantly associated with concurrent concentration of serum creatinine (P=.005). A 10-fold increase in blood lead level predicted an increase of 7 micromol/L (0.08 micrograms/dL) in serum creatinine concentration, which is roughly equivalent to the increase predicted by 20 years of aging. The association was also significant among subjects whose blood lead concentrations had never exceeded 0.48 micromol/L (10 micrograms/L) throughout the study period. The age-related increase in serum creatinine level was earlier and faster in the group with the highest-quartile levels of long-term lead exposure than in the group with the lowest-quartile levels. CONCLUSIONS: Low-level exposure to lead may impair renal function in middle-aged and older men. Longitudinal data suggest an acceleration of age-related impairment of renal function in association with long-term low-level lead exposure.

Age Factors↗
PubMed1996

Exploring the interaction between D-xylose isomerase and D-xylose by free energy calculation.

The numerical quadrature thermodynamic integration method is used to investigate enzyme-substrate interaction of D-xylose isomerase. A screening function for the coulombic interaction is introduced into the simulation to correct the effect of finite cut-off radius for the non-bonded interaction. The binding free energy difference for D-xylose with D-xylose isomerase and its N184D mutant has been calculated, and the result 3.9 +/- 1.2 kJ/mol agrees well with experimental data of 4.38 kJ/mol. In addition, the structure and dynamics of enzyme-substrate complex were simulated for mutant and wild-type enzyme, respectively. Analysis of the structures and intramolecular interactions of the complexes were found to be valuable for understanding the reaction mechanism of the enzyme D-xylose isomerase.

Aldose-Ketose Isomerases↗
PubMed1996

Detection of aneuploidy in human spermatozoa using fluorescence in situ hybridization (FISH).

Fluorescence in situ hybridization (FISH) with chromosome specific alpha-satellite DNA probes was used to estimate the rates of aneuploidy of chromosomes 1, 17, 18, X and Y in human ejaculated sperm. Sperm samples were collected from six donors, and biotinylated DNA probes, D1Z5, D17Z1, D18Z1, DXZ1 and DYZ3 were hybridized to interphase sperm which had been pretreated with dithiothreitol to expand their nuclei. A minimum of 3,000 sperm per donor were analyzed. The hybridization efficiency was 99.68% for all the five probes. The frequencies of aneuploidy for chromosomes 1, 17 and 18 were 0.65%, 0.66%, and 0.61%, respectively. For XX- and YY-sperm the frequencies were 0.28% and 0.27%, respectively. To estimate the diploidy and disomy rates, a mixture of D17Z1 and D18Z1 were used as probes, and the frequency of diploid sperm was calculated to be 0.27%. After subtraction of the diploidy rate, the disomy rates for chromosomes 1, 17, and 18 were estimated to be 0.38%, 0.39% and 0.33%, respectively. The proportion of X- and Y-bearing sperm were 49.90% and 49.66%, consistent with an expected 1:1 ratio.

Aneuploidy↗
PubMed1996

Factors accounting for different responses of pulmonary and cerebral vessels to hypoxia.

The roles of sympathicus, sensory neuropeptides (SNP), cyclooxygenase metabolites (COX-M), lipoxygenase metabolites (LOX-M), endothelium derived relaxing factor (EDRF), reactive oxygen (ROS) and potassium channels (PC) in the hypoxic pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilation (HCVD) were investigated in intact rats, rabbits and dogs. The results showed that during hypoxia, the excitation of sympathicus caused a constriction of both pulmonary and cerebral vessels, while SNP, EDRF and the opening of voltage sensitive PC caused the dilation of both of them; LOX-M mediated HPV and HCVD, COX-M might serve as their modulators; the blockade of ATP sensitive PC induced by hypoxia mediated HPV, but had no effect on HCVD; the reduction of O2-. in the lung might potentiate HPV, however, O2-. remained unchanged in brain during hypoxia. It is suggested that the alterations of LOX-M, ROS and the ATP sensitive PC are the factors accounting for the difference in the response of pulmonary and cerebral vessels to hypoxia.

Animals↗
PubMed1996

Mechanically activated currents in chick heart cells.

As predicted from stretch-induced changes of rate and rhythm in the heart, acutely isolated embryonic chick heart cells exhibit whole-cell mechanosensitive currents. These currents were evoked by pressing on cells with a fire polished micropipette and measured through a perforated patch using a second pipette. The currents were carried by Na+ and K+ but not Cl-, and were independent of external Ca2+. The currents had linear I/V curves reversing at -16 mV and were completely blocked by Gd3+ >/= 30 microM and Grammostola spatulata venom at a dilution of 1:1000. Approximately 20% of cells showed time dependent inactivation. In contrast to direct mechanical stimulation, hypotonic volume stress produced an increase in conductance for anions rather than cations-the two stimuli are not equivalent. The cells had two types of stretch-activated ion channels (SACs): a 21 pS nonspecific cation-selective reversing at -2 mV and a 90 pS K+ selective reversing at -70 mV in normal saline. The activity of SACs was strongly correlated with the presence of whole-cell currents. Both the whole-cell currents and SACs were blocked by Gd3+ and by Grammostola spatulata spider venom. Mechanical stimulation of spontaneously active cells increased the beating rate and this effect was blocked by Gd3+. We conclude that physiologically active mechanosensitive currents arise from stretch activated ion channels.

Action Potentials↗