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Biomedical subjects

H Hu

Publications and source records attributed to H Hu.

At least 145 records · Page 8Linked to original sources

[Effect of knockout AT1a receptor gene on transplasmamembrane calcium influx in aortic smooth muscle cells].

OBJECTIVE: To investigate the mechanism of angiotensin II receptor subtype (AT1a) mutant on angiotensin II (Ang II) mediated transplasmamembrane calcium influx in aortic smooth muscle cells (SMCs) from AT1a knockout and wild type mice. METHOD: Aortic SMCs were isolated and cultured. Intracellular free calcium concentration [Ca2+]i was measured using Fura-2/AM fluorescentic technique. RESULTS: Ang II caused a marked increase in [Ca2+]i in both cell types [AT1a group: (204 +/- 22) nmol/L vs (108 +/- 9) nmol/L]; CONTROL: [(194 +/- 19) nmol/L vs (110 +/- 7) nmol/L]. Administration of both calcium channel blocker, nifedipine and GTP-gamma s significantly inhibited Ang II effect, in contrast, application of pertussin toxin (PTX) activated the Ang II mediated calcium influx. The response of AT1a knockout cells was more sensitive to nifedipine and were enhanced by PTX. CONCLUSION: Calcium influx induced by Ang II can be regulated by PTX insensitive and non-Gi protein in AT1a knockout cells.

Animals↗

[Effects of relative imbalance between endothlin-1 and nitric oxide on pathogenesis of the ascaris-induced asthma in dogs].

OBJECTIVE: To investigate the effects of relative imbalance between endothlin-1 (ET-1) and nitric oxide (NO) on pathogenesis of the ascaris-induced asthma in dogs. METHODS: Allergy induced asthma in dogs was established by inhaling ascaris antigen via an ultrasonic neblizer. At first, effects of ET-1 on respiratory system resistance (Rrs) and compliance (Crs) were studied in asthmatic dogs. Then, the roles of ET-1 and NO in regulating airway hyperresponsiveness (BHR) of asthma were investigated. Finally, effects of ET-1 on airway smooth muscle proliferating were observed. RESULTS: After intravenous injection of ET-1, there was a significant maximal increase in Rrs with (14.33 +/- 0.53) mm Hg.L-1.s-1 in normal dogs and (30.75 +/- 3.38) mm Hg.L-1.s-1 (P < 0.05) in asthmatic dogs. Also, there was a significant maximal decrease in Crs with (24.9 +/- 1.2) L/mm Hg in normal dogs and (14.8 +/- 0.9) L/mm Hg (P < 0.05) in asthmatic dogs. The dose-dependent bronchoconstriction in dogs was induced by three different doses of ET-1 (0.25, 0.5, 1.0 microgram/kg). ET-1 dose-response curve was significantly shifted upward by L-NMMA (P < 0.05). This effect was inhibited by L-arg (P < 0.05). Histological studies showed that ET-1 can stimulate airway smooth muscle proliferating and thickening after one week of ET-1 (4.0 micrograms/kg) i.v. administration. CONCLUSIONS: ET-1 might be involved in BHR that may be associated with immediate asthma response (IAR) in asthmatic dogs. ET-1 may be important for airway remodeling. The relative imbalance between ET-1 and NO may contribute to pathogenesis of asthma.

Animals↗

[A clinical trial of 14 and 15 membered macrolides in treating six cases of diffuse panbronchiolitis].

OBJECTIVE: To observe the therapeutic effect of macrolides in treating diffuse panbronchiolitis (DPB). METHODS: 14- and 15-ring macrolides were used in the treatment of six confirmed cases of DPB for 3 approximately 24 months. The improvement in symptoms, X-ray findings, lung function and results of blood gas analysis was recorded. RESULTS: Symptoms such as cough, sputum expectoration and exertional dyspnea alleviated significantly during the first 2 weeks. PaO(2) level, FEV(1)%, and vital capacity (VC) increased remarkably. Diffuse small nodular lesions on chest X-ray or CT decreased in size within a few months. CONCLUSION: Macrolides have significant therapeutic effect on DPB and the patients have good tolerance to them. However, the mechanism of its action, the selection of the best macrolide, the most suitable dosage and the appropriate period of treatment still need further investigation.

Adult↗

[Synthetic assessment of health impact of cerebrovascular diseases on potential health days of life lost].

OBJECTIVE: To assess synthetically the impact on population health caused by cerebrovascular diseases. METHODS: Incidence, duration of disease, disabilities and deaths of cerebrovascular diseases were analyzed with potential health days of life lost (PHDLL) as an indicator in urban areas of Changsha, Hunan Province. RESULTS: The PHDLL caused by cerebrovascular disease totaled 2 624.94 days per thousand of population, 33.01% of them attributed to deaths and 53.44% to chronic disability. CONCLUSION: Hemorrhagic cerebrovascular disease mainly lead to death and ischemic one caused chronic disability.

Adolescent↗

[79 cases: a clinical analysis of hoarseness in children].

OBJECTIVE: To research the clinical characters of the hoarseness in children. METHOD: 79 cases are analysed retrospectively. RESULT AND CONCLUSION: Age for this disease is usually 3 years old. People with irritable character are more easy to get it. Vocal nodule is the main cause to chronic hoarseness in children. Conservative treatment is important.

Adolescent↗

Blockade of bepridil on IA and IK in acutely isolated hippocampal CA1 neurons.

The effects of bepridil, an antianginal agent with antiarrhythmic action, on voltage-dependent K+ currents in the CA1 pyramidal neurons acutely isolated from rat hippocampus were studied by means of whole-cell patch clamp techniques. Current recordings were made in the presence of TTX to block Na+ current. Depolarizing test pulses activated two components of outward K+ currents: a rapidly activating and inactivating component, IA; and a delayed component, IK. Results showed that bepridil reduced the amplitude of IA and IK, and exerted its inhibitory action in time- and dose-dependent manner. Half-blocking concentrations (IC50) of bepridil on IA and IK were 17.8 microM and 1.7 microM, respectively. 10 microM bepridil suppressed IA and IK by 46.7% and 77.1% at +30 mV of depolarization, respectively. When IK was activated nearly uncontaminated with IA by holding at -50 mV, 10 microM bepridil inhibited IK by 71.6% at +30 mV of depolarization; 10 microM bepridil positively shifted the voltage-dependent of activation curves of IA and IK 12.1 mV and 28.7 mV, respectively. These results suggested that blockade on K+ currents by bepridil is preferential for IK, and contributes to the protection brain against ischemic damage.

Animals↗

The localization of the brain-specific inorganic phosphate transporter suggests a specific presynaptic role in glutamatergic transmission.

Molecular cloning has recently identified a vertebrate brain-specific Na+-dependent inorganic phosphate transporter (BNPI). BNPI has strong sequence similarity to EAT-4, a Caenorhabditis elegans protein implicated in glutamatergic transmission. To characterize the physiological role of BNPI, we have generated an antibody to the protein. Immunocytochemistry of rat brain sections shows a light microscopic pattern that is suggestive of reactivity in nerve terminals. Excitatory projections are labeled prominently, and ultrastructural analysis confirms that BNPI localizes almost exclusively to terminals forming asymmetric excitatory-type synapses. Although BNPI depends on a Na+ gradient and presumably functions at the plasma membrane, both electron microscopy and biochemical fractionation show that BNPI associates preferentially with the membranes of small synaptic vesicles. The results provide anatomic evidence of a specific presynaptic role for BNPI in glutamatergic neurotransmission, consistent with the phenotype of eat-4 mutants. Because an enzyme known as the phosphate-activated glutaminase produces glutamate for release as a neurotransmitter, BNPI may augment excitatory transmission by increasing cytoplasmic phosphate concentrations within the nerve terminal and hence increasing glutamate synthesis. Expression of BNPI on synaptic vesicles suggests a mechanism for neural activity to regulate the function of BNPI.

Animals↗

Solution properties of single-walled carbon nanotubes

Naked metallic and semiconducting single-walled carbon nanotubes (SWNTs) were dissolved in organic solutions by derivatization with thionychloride and octadecylamine. Both ionic (charge transfer) and covalent solution-phase chemistry with concomitant modulation of the SWNT band structure were demonstrated. Solution-phase near-infrared spectroscopy was used to study the effects of chemical modifications on the band gaps of the SWNTs. Reaction of soluble SWNTs with dichlorocarbene led to functionalization of the nanotube walls.

Journal Article↗

Electrocardiographic conduction disturbances in association with low-level lead exposure (the Normative Aging Study).

Recent research indicates that cumulative exposure to lead may be more toxic than previously thought. This study was undertaken to examine the relation of low-level lead exposure to electrocardiographic (ECG) conduction disturbances among 775 men who participated in the Normative Aging Study (average age 68 years; range 48 to 93). We used K-x-ray fluorescence to measure lead levels in the tibia and patella, and graphite furnace atomic absorption spectroscopy to measure blood lead levels. The mean (SD) values for blood lead, tibia lead, and patella lead were 5.8 (3.4) microg/dl, 22.2 (13.4) microg/g, and 30.8 (19.2) microg/g, respectively. Bone lead levels were found to be positively associated with heart rate-corrected QT and QRS intervals, especially in younger men. Specifically, in men <65 years of age, a 10 microg/g increase in tibia lead was associated with an increase in the QT interval of 5.03 ms (95% confidence interval [CI], 0.83 to 9.22) and with an increase in the QRS interval of 4.83 ms (95% CI, 1.83 to 7.83) in multivariate regression models. In addition, an elevated bone lead level was found to be positively associated with an increased risk of intraventricular block in men <65 years of age and with an increased risk of atrioventricular (AV) block in men > or = 65 years of age. After adjustment for age and for serum high-density lipoprotein (HDL) level, a 10 microg/g increase in tibia lead was associated with an odds ratio (OR) of 2.23 (95% CI, 1.28 to 3.90) for intraventricular block in men <65 years of age and with an OR of 1.22 (95% CI, 1.02 to 1.47) for AV block in men > or = 65 years of age. Blood lead level was not associated with any of the ECG outcomes examined. The results suggest that cumulative exposure to lead, even at low levels, may depress cardiac conduction.

Aged↗

Relation of nutrition to bone lead and blood lead levels in middle-aged to elderly men. The Normative Aging Study.

The relations of nutritional factors to lead accumulation in the body were examined cross-sectionally among 747 men aged 49-93 years (mean 67 years) in the Normative Aging Study in 1991-1995. Means (standard deviations) for blood lead, tibia lead, and patella lead were 6.2 (4.1) microg/dl, 21.9 (13.3) microg/g, and 32.0 (19.5) microg/g, respectively. In multiple regression models adjusting for age, education level, smoking, and alcohol consumption, men in the lowest quintile of total dietary intake levels of vitamin D (including vitamin supplements) (<179 i.u./day) had mean tibia and patella lead levels 5.6 microg/g and 6.0 microg/g higher than men with intake in the highest quintile (> or =589 i.u./day). Higher calcium intake was associated with lower bone lead levels, but this relation became insignificant when adjustment was made for vitamin D. The authors also observed inverse associations of blood lead levels with total dietary intake of vitamin C and iron. When analyses were controlled for patella lead, age, smoking, and alcohol consumption, men in the lowest vitamin C intake quintile (<109 mg/day) had a mean blood lead level 1.7 microg/dl higher than men in the highest quintile (> or =339 mg/day), while men in the lowest iron intake quintile (<10.9 mg/day) had a mean blood lead level 1.1 microg/dl higher than men in the highest quintile (> or =23.5 mg/day). This study suggests that low dietary intake of vitamin D may increase lead accumulation in bones, while lower dietary intake of vitamin C and iron may increase lead levels in the blood.

Aged↗

Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1alpha (SDF-1alpha) and SDF-1beta are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage.

CD26 is a leukocyte-activation antigen that is expressed on T lymphocytes and macrophages and possesses dipeptidyl peptidase IV (DPPIV) activity, whose natural substrates have not been identified yet. CXC chemokines, stromal cell-derived factor 1alpha (SDF-1alpha) and 1beta (SDF-1beta), sharing the receptor CXCR-4, are highly efficacious chemoattractants for resting lymphocytes and CD34(+) progenitor cells, and they efficiently block the CXCR-4-mediated entry into cells of T cell line tropic strains of HIV type 1 (HIV-1). Here we show that both the chemotactic and antiviral activities of these chemokines are abrogated by DPPIV-mediated specific removal of the N-terminal dipeptide, not only when the chemokines are produced in transformed mouse L cell line to express human CD26 but also when they were exposed to a human T cell line (H9) physiologically expressing CD26. Mutagenesis of SDF-1alpha confirmed the critical requirement of the N-terminal dipeptide for its chemotactic and antiviral activities. These data suggest that CD26-mediated cleavage of SDF-1alpha and SDF-1beta likely occurs in human bodies and promotes HIV-1 replication and disease progression. They may also explain why memory function of CD4(+) cells is preferentially lost in HIV-1 infection. Furthermore, CD26 would modulate various other biological processes in which SDF-1alpha and SDF-1beta are involved.

Animals↗

Large quantity production with extreme convenience of human SDF-1alpha and SDF-1beta by a Sendai virus vector.

We describe a robust expression of human stromal cell-derived factor-1alpha (SDF-1alpha) and SDF-1beta, the members of CXC-chemokine family, with a novel vector system based upon Sendai virus, a non-segmented negative strand RNA virus. Recombinant SDF-1alpha and SDF-1beta were detected as a major protein species in culture supernatants, reached as high as 10 microg/ ml. This remarkable enrichment of the products allowed us to use even the crude supernatants as the source for biological and antiviral assays without further concentration nor purification and will thus greatly facilitate to screen their genetically engineered derivatives.

Anti-HIV Agents↗

Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation.

We report that chlamydiae, which are obligate intracellular bacterial pathogens, possess a novel antiapoptotic mechanism. Chlamydia-infected host cells are profoundly resistant to apoptosis induced by a wide spectrum of proapoptotic stimuli including the kinase inhibitor staurosporine, the DNA-damaging agent etoposide, and several immunological apoptosis-inducing molecules such as tumor necrosis factor-alpha, Fas antibody, and granzyme B/perforin. The antiapoptotic activity was dependent on chlamydial but not host protein synthesis. These observations suggest that chlamydia may encode factors that interrupt many different host cell apoptotic pathways. We found that activation of the downstream caspase 3 and cleavage of poly (ADP-ribose) polymerase were inhibited in chlamydia-infected cells. Mitochondrial cytochrome c release into the cytosol induced by proapoptotic factors was also prevented by chlamydial infection. These observations suggest that chlamydial proteins may interrupt diverse apoptotic pathways by blocking mitochondrial cytochrome c release, a central step proposed to convert the upstream private pathways into an effector apoptotic pathway for amplification of downstream caspases. Thus, we have identified a chlamydial antiapoptosis mechanism(s) that will help define chlamydial pathogenesis and may also provide information about the central mechanisms regulating host cell apoptosis.

Animals↗

Using ecological data to estimate a regression model for individual data: the association between arsenic in drinking water and incidence of skin cancer.

In ecologic studies, participants are studied by groups, and the exposure status of each group is usually represented by a single indicator, mostly the mean exposure. In this paper, we propose using multiple variables derived from dummy variables at the individual level to describe the exposure. An analysis of the association between arsenic in drinking water and skin cancer was used as an example. Well water arsenic levels and skin cancer incidence from 1980 to 1987 were assessed for 243 townships in Taiwan. We first analyzed the data using the mean arsenic concentration in each township as the only exposure variable. The second analysis used multiple variables to describe arsenic exposure; each variable denoted the percentage of wells with arsenic levels within a specific range in each township. Although the first approach did not identify associations between arsenic levels and skin cancer, the multiple-variable approach identifies a positive association at the highest arsenic exposure category (>0.64 mg/L) in both men and women. Therefore, using multiple variables to describe an exposure in ecologic studies may facilitate a better description of the exposure status and thereby lead to more accurate risk assessment, especially when the dose-response relationship is not linear.

Arsenic↗

Reference deconvolution, phase correction, and line listing of NMR spectra by the 1D filter diagonalization method.

We describe a new way to attack the problem of identifying and quantifying the number of NMR transitions in a given NMR spectrum. The goal is to reduce the spectrum to a tabular line list of peak positions, widths, amplitudes, and phases, and to have this line list be of high fidelity. In this context "high fidelity" means that each true NMR transition is represented by a single entry, with no spurious entries and no missed peaks. A high fidelity line list allows the measurement of chemical shifts and coupling constants with good accuracy and precision and is the ultimate in data compression. There are two parts to the problem. The first is to overcome common imperfections: the non-Lorentzian lineshapes that can arise whenever the magnetic field inhomogeneity is less than perfect, and nonzero time delays that cause frequency-dependent phase errors. The second is to fit the spectral features to a model of Lorentzian lines. We use the recently developed filter diagonalization method (FDM) to accomplish the reference deconvolution, the phase correction, and the fitting, and show good progress toward the goal of obtaining a high fidelity line list.

Fourier Analysis↗

Facilitation of HIV-1 isolation from patients by neuraminidase.

We previously reported that infectivities of human and other non-human lentiviruses including human immunodeficiency virus type 1 (HIV-1) are activated by desialylation of the virion surface [H. Hu et al., J Virol 70: 7,462-7,470 (1996)]. The present study was designed to determine whether neuraminidase (NA) is useful for isolation of HIV-1 from patients. Peripheral blood mononuclear cells (PBMC) or CD4+ cells isolated from the PBMC of infected individuals were cocultured with PBMC or CD4+ cells from uninfected healthy donors, and the efficiency and frequency of virus isolation in the presence of NA were compared with those by a routine conventional procedure. In a total of 41 isolation trials from 28 individuals, the presence of NA markedly increased the frequency of isolation. Furthermore, both the day when virus was first detected and the day when the virus titer was the highest in the cultures were significantly earlier in the presence of NA than in the absence of NA. The deduced amino acid sequences of the V2 and V3 regions of gp120 were identical or very similar between the isolates obtained in the presence or absence of NA, suggesting that both isolation procedures selected a similar population. NA was thus found to facilitate HIV-1 isolation and its use is recommended particularly when isolation is negative by the conventional procedures.

Acquired Immunodeficiency Syndrome↗

Dissociation of ligand-induced internalization of CXCR-4 from its co-receptor activity for HIV-1 Env-mediated membrane fusion.

The C-terminal cytoplasmic tail of chemokine receptors is important for their internalization upon ligand binding. We generated several deletion mutants of the C-terminal cytoplasmic tail of CXCR-4, a co-receptor for T cell line tropic strains of human immunodeficiency virus type 1 (HIV-1), to know whether or not co-receptor internalization is associated with HIV-1 entry. Our data showed that the removal of C-terminal 15 amino acid residues of the cytoplasmic tail from CXCR-4 completely abolished its internalization, but did not affect the co-receptor activity at all. Co-receptor activity was fully retained even when all 45 amino acid residues in the C-terminal cytoplasmic tail had been deleted. These data indicated that no cytoplasmic tail nor internalization of CXCR-4 is required for its co-receptor activity for HIV-1 entry.

Animals↗

Stabilization of a C7 equatorial gamma turn in DMSO-d6 by a ditryptophan crosslink.

Covalent crosslinks can control local peptide conformation. In tripeptide sequences of the general formula Cys-Xxx-Cys, cysteine disulfides have been previously shown to enforce a C7 equatorial gamma-turn conformation (also referred to as an inverse gamma-turn). Much less is known about the effects of dityrosine and ditryptophan crosslinks on local peptide structure. In a series of tripeptides, ditryptophan crosslinks were formed using the two-step process of acid-promoted Mannich dimerization followed by oxidative aromatization. In these peptides, with the general formula Trp-Xxx-Trp (Xxx not equal to Gly), ditryptophan crosslinks were found to stabilize a C7 equatorial gamma-turn conformation in DMSO-d6. Rigorous support for a C7 equatorial conformation in the crosslinked sequence Trp-Pro-Trp came from a variety of 1H NMR experiments and molecular modelling. Interproton distances were derived from NOE buildups that were determined through a series of double pulsed field gradient spin echo (DPFGSE) experiments. In addition, the small temperature dependence of the i+2 NH chemical shifts (delta delta/delta T < 2 ppm/degree C) provided further support for the intramolecular hydrogen bond which defines a gamma-turn.

Cross-Linking Reagents↗