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Biomedical subjects

H Hu

Publications and source records attributed to H Hu.

At least 217 records · Page 12Linked to original sources

Investigation of a naphthalene pitch by high-resolution solid-state dynamic nuclear polarization.

The possibility of applying the dynamic nuclear polarization (DNP) technique to a study of char is explored with a naphthalene-derived pitch. It is shown that a 13C DNP enhancement factor of about 10(2) is obtained when the polarization is directly transferred from the unpaired electrons to the 13C nuclei. An undistorted spectrum with an enhancement factor of 8 is obtained by the DNP cross-polarization magic-angle spinning nuclear magnetic resonance (DNP-CP-MAS NMR) method. With such a high increase in S/N, it is possible to measure the 13C polarization time (Tp) and the spin-lattice relaxation time (T1) of the system in a reasonable experimental time. The resultant values are Tp = 19 s and T1 = 38 s, respectively. Based on the DNP enhancement as a function of the microwave frequency, it is found that the predominant DNP mechanism in the pitch is the solid-state effect.

Carbon Isotopes↗

The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone.

Transplantation studies have been used to show that tangential migration of olfactory bulb interneuron precursors is retarded in NCAM-mutant mice, and that this defect reflects loss of NCAM polysialic acid (PSA). In contrast, radial migration of cells within the bulb did not require PSA. Reciprocal transplantations between wild-type and mutant mice have revealed that the mutation affects the in vivo migration environment in the subventricular zone, and not movement of individual cells. However, in vitro migration of the cells into a PSA-negative collagen matrix environment was also PSA dependent. The surprisingly similar results obtained in the in vivo and in vitro environments is consistent with the observation that migration of subventricular cells occurs as streams of closely apposed cells in which the PSA-positive cells appear to serve as their own migration substrate.

Animals↗

A septum-derived chemorepulsive factor for migrating olfactory interneuron precursors.

During mammalian brain development, immature neurons often migrate considerable distances. A dramatic example is the rostral migration of olfactory interneuron precursors from near the septum to the olfactory bulb via a subventricular pathway. Heterotopic transplantations establish that this migration is unidirectional and that guidance cues operate over a considerable distance. The guidance cues for this translocation have not been identified, and the present studies provide evidence that a diffusible chemorepulsive factor, secreted by caudal septum but not by other tissue regions surrounding the pathway, may be involved. This activity is functionally distinct from that produced by factors that influence vertebrate axon outgrowth, such as netrin-1, netrin-2, and collapsin-1/semaphorin-III. The presence of this activity in the floor plate/ventral spinal cord as well as the septum suggests that it may influence other types of cell migration.

Animals↗

Expression and characterization of a divalent chimeric anti-human CD3 single chain antibody.

Murine anti-CD3 monoclonal antibodies (MoAbs) are used in clinical practice for immunosuppression. However, there are two major drawbacks to this treatment: the associated cytokine release syndrome and human anti-mouse antibody response. To overcome these side-effects, the authors generated a chimeric anti-human CD3 single chain antibody, scUCHT1. It is an IgM variant of UCHT1, a mouse IgG1 MoAb directed against human CD3. scUCHT1 consists of the light and heavy variable chain binding domains of UCHT1 and a human IgM Fc region (CH2 to CH4). scUCHT1 was produced by COS-7 and SP2/0 transfectants, and mainly assembled in a dimeric form. It retained the binding specificity and affinity of the parental MoAb UCHT1. In contrast to UCHT1, scUCHT1 did not induce T-cell proliferation and cytokine release (TNF-alpha and IFN-gamma) in in vitro assays. These results suggest that the engineered chimeric anti-CD3 single chain antibody (scUCHT1) may be useful in clinical immunosuppressive treatment.

Animals↗

The relationship of blood lead and dietary calcium to blood pressure in the normative aging study.

BACKGROUND: Previous studies have demonstrated a positive relationship between elevated blood lead (BPb) and blood pressure (BP), but few have additionally examined the role of dietary calcium. METHODS: The cross-sectional relationship between BPb and BP and the possible protective influence of increased dietary calcium on that relationship was examined among 798 male participants in the Normative Aging Study (NAS), a cohort of older men with relatively low BPb levels. RESULTS: The age range of these subjects was 43-93 years (mean = 66.1, SD = 7.4 years) and blood lead concentrations ranged form 0.5 to 35 mcg/dl (median = 5.6 mcg/dl). For the cohort overall, neither ln blood lead nor dietary calcium were significantly correlated with BP. In multivariate linear regression analyses that adjusted for age, body mass index, dietary calcium intake (adjusted for total calorie intake), alcohol intake, sitting heart rate, kilocalories/week expended in exercise, haematocrit, and smoking status, a unit increase in ln BPb predicted an increase on 1.2 mmHg diastolic blood pressure (DBP) (95% CI : 0.11, 2.2; P = 0.03). Adjusted calcium intake of 800 mg/day predicted a decrease of 3.2 mmHg systolic blood pressure (SBP) (95% CI : -5.6, -0.24, P = 0.03). There was no evidence of an interaction between dietary calcium intake and blood lead on BP. When the analyses were restricted to those men <=74 years old, a unit increase in ln BPb predicted an increase of 1.6 mmHg DBP (n = 681; 95% CI : 0.42, 2.7; P = 0.007). However, when men on antihypertensive medication (AHM) were excluded from the analyses, ln BPb was not significantly associated with increased DBP nor was adjusted calcium significantly associated with SBP. CONCLUSIONS: The study did support the hypothesis that increased BPb was associated with increased DBP in a cohort of older men with low blood lead, but there was no evidence of interaction between BPb and dietary calcium on BP. However, the relationship between increased BPb and DBP did not hold when those on anti-hypertensive medications were excluded.

Adult↗

CD28 co-stimulatory regimes differ in their dependence on phosphatidylinositol 3-kinase: common co-signals induced by CD80 and CD86.

CD80 (B7-1) and CD86 (B7-2) ligation of CD28 provide co-stimulatory signals required for optimal lymphokine production in response to TCR zeta-CD3 ligation. CD28 binds to several intracellular proteins including phosphatidylinositol 3-kinase (Pl3-kinase), the tyrosine kinase ITK and the growth factor receptor-bound protein/Son of Sevenless (GRB-2/SOS) complex. Previously, we showed that TCR zeta-CD3 and CD28 co-stimulation required Pl3-kinase binding to the pYMNM motif of the cytoplasmic domain of the co-receptor. In this study, we have investigated whether CD28-associated Pl3-kinase is required for CD80 and CD86 co-stimulation, as well as in co-signaling that involves different primary signals (i.e. TCR zeta-CD3 versus phorbol ester/lonomycin). In the presence of anti-CD3, ligation of CD28 by both CD80 and CD86 was found to induce Pl3-kinase recruitment and IL-2 production. Furthermore, mutations at Y-191 and M-194 within the pYMNM motif blocked the ability of both ligands to induce IL-2. CD80 and CD86 therefore share a common signaling pathway leading to IL-2 production. By contrast, CD28 mediated co-stimulation involving receptor ligation plus phorbol ester/lonomycin induced IL-2 independent of Pl3-kinase binding to CD28. These data indicate that TCR zeta-CD3-dependent CD80 and CD86 co-signaling requires Pl3-kinase binding to the CD28pYMNM motif, while phorbol ester and lonomycin can bypass this requirement in CD28 co-stimulation.

Animals↗

The effect of helical pitch and beam collimation on the lesion contrast and slice profile in helical CT imaging.

A model is presented in this paper to describe how the contrast of a reconstructed object and slice sensitivity profile are affected by (1) the table speed or helical pitch, (2) the x-ray collimations, (3) the size of the object, (4) the alignment between the reconstructed slice and the object, (5) the distance of the object from the axis of rotation, and (6) the helical CT reconstruction algorithm employed. This contrast model is validated by both computer simulations and experiments. With this model, the contrast of a reconstructed object, slice sensitivity profile, and the longitudinal MTF can be accurately predicted. The optimal scan strategy and the point of diminishing returns can be determined prior to scanning. Several conclusions can be drawn from this model. First, overlapping reconstruction significantly improves overall scan contrast sensitivity of helical CT. Second, with a given x-ray collimation, low pitch helical scans provide better longitudinal resolutions. Third, with a given volume coverage rate (i.e., a given table speed), narrow collimation high pitch helical scans provide better longitudinal resolutions than wide collimation low pitch ones and therefore are recommended for high-contrast thin-slice applications. A lesion conspicuity model is also established.

Biophysical Phenomena↗

Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface.

The envelope protein, gp120, of human immunodeficiency virus type 1 (HIV-1) is heavily glycosylated and sialylated. The heavy sialylation greatly affects the physical properties of the protein, as it resolves into a wide acidic pH range despite the basic pI value predicted for its polypeptide backbone (B. S. Stein and E. G. Engleman, J. Biol. Chem. 265:2640-2649, 1990). However, the functional significance of the heavy sialylation remains elusive. Here, we show that desialylation of HIV-1 with neuraminidase greatly augments the initial virus-cell interaction, leading to remarkably enhanced viral replication and cytopathogenicity. This enhancement appeared to be a direct result of the removal of negatively charged sialic acids but not of the exposure of galactose residues or complement activation. Complementing these results, studies with inhibitors of mannosidase I and mannosidase II showed that the processing of HIV-1 oligosaccharides into the complex type to acquire the terminal sialic acid residues impeded the full replication capacity of the virus and that its prevention also enhanced virus replication and cytopathogenicity. Enhancement of infection by desialylation was found widely, with HIV-1 laboratory strains of different cell tropisms and primary isolates as well as HIV-2 and simian immunodeficiency virus. Thus, the sialylation catalyzed by host cell pathways appeared to reduce the infectivity of human and nonhuman primate lentiviruses. Our results further suggested that desialylation would help increase the titers of HIV-based vectors.

1-Deoxynojirimycin↗

Differential enhancement of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase by tert-butylhydroquinone in rat lung epithelial L2 cells.

Sublethal quinone-mediated oxidative stress stimulates increases in the activities and mRNA levels of gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase (GCS) in rat lung epithelial L2 cells [Kugelman, A. et al. 1994. Am. J. Respir. Cell Mol. Biol. 11:586-592; Shi, M. M. et al. 1994. J. Biol. Chem. 269:26512-26517]. The present study demonstrated that the quinone-induced increases in these two enzymes were differentially regulated. L2 cells were exposed to various concentrations of tertiary-butylhydroquinone (TBHQ) for different periods of times. TBHQ increased the activities and the mRNAs for GGT and the catalytic subunit of GCS; however, the time- and concentration-dependencies differed. With 50 microM TBHQ, GCS activity increased significantly by 6 h whereas the activity of GGT was not increased until later. Under the same conditions, the highest GCS-mRNA level observed was at 6 h whereas the mRNA level of GGT increased after 6 h, reached a higher level at 12 h, and then returned to the control level by 24 h. Differences were also observed in the concentration-dependence of mRNA increases between the GGT and GCS. Actinomycin D (an inhibitor of RNA synthesis) abolished the increase of GCS-mRNA but not the increase in GGT-mRNA, suggesting a difference in regulation by TBHQ between these two genes. Nuclear run-on experiments confirmed that the increase of GCS-mRNA, but not GGT-mRNA was due to increased transcription. The increase in GGT-mRNA probably results from a decreased degradation rate. The differences between these two enzymes demonstrate how cells can use multiple mechanisms for regulating gene expression in response to oxidative stress.

Animals↗

Increased gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase activities enhance resistance of rat lung epithelial L2 cells to quinone toxicity.

Tert-butylhydroquinone (TBHQ) is a monofunctional Phase II enzyme inducer, which produces reactive oxygen species. Incubation with a sublethal concentration of TBHQ increased the activities of both gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase (GCS), although the mechanisms are different (Liu and colleagues, accompanying manuscript). In this study, we found that TBHQ increased intracellular glutathione (GSH) content in rat lung epithelial L2 cells. L2 cells pretreated with a nontoxic concentration of TBHQ (50 microM) acquired resistance to a subsequent challenge with a normally lethal concentration of TBHQ (200 microM). Pretreatment with L-buthionine S,R-sulfoximine (BSO), an inhibitor of GCS, prevented the TBHQ-induced increase in GSH and markedly diminished resistance to 200 microM TBHQ. Similarly, pretreatment with acivicin, an inhibitor of GGT, also prevented the TBHQ-induced increase in GSH and markedly diminished resistance to 200 microM TBHQ. Nevertheless, blockage of GGT by acivicin could be bypassed using 2-oxothiazolidine-4-carboxylate (procysteine) to provide the cell with a source of cysteine. This allowed an increase in GSH and restored resistance in the TBHQ-pretreated cells. The results suggest that elevation of GCS and GGT activities participated in acquired resistance to quinone toxicity.

Animals↗

Occupational and Lifestyle Determinants of Blood Lead Levels among Men in Madras, India.

The objective of this epidemiologic study was to assess the relationship of blood lead levels to occupational exposure to the combustion products of leaded gasoline and to several lifestyle factors (smoking, alcohol consumption, and diet) among men from four occupational groups in Madras, India. Blood lead was measured using graphite-furnace atomic-absorption spectrophotometry. The mean (SD) blood lead levels in 129 blood samples collected from traffic police, bus drivers, and auto-shop workers were 11.2 (8.8), 12 (11.1), and 17.5 (8.4) µg/dL, respectively; the corresponding value for urban controls (office workers) was 4.1 (2.1) µg/dL. In a final multivariate regression model, a non-vegetarian diet and job category remained the strongest predictors of blood lead level (p < 0.05), while smoking, alcohol consumption, and duration of employment were not significantly correlated with blood lead levels. The authors conclude that continued use of leaded gasoline probably plays a dominant role in determining blood lead levels in Madras.

Journal Article↗

Dietary and environmental determinants of blood and bone lead levels in lactating postpartum women living in Mexico City.

Despite the recent declines in environmental lead exposure in the United States and Mexico, the potential for delayed toxicity from bone lead stores remains a significant public health concern. Some evidence indicates that mobilization of lead from bone may be markedly enhanced during the increased bone turnover of pregnancy and lactation, resulting in lead exposure to the fetus and the breast-fed infant. We conducted a cross-sectional investigation of the interrelationships between environmental, dietary, and lifestyle histories, blood lead levels, and bone lead levels among 98 recently postpartum women living in Mexico City. Lead levels in the patella (representing trabecular bone) and tibia (representing cortical bone) were measured by K X-ray fluorescence (KXRF). Multivariate linear regression models showed that significant predictors of higher blood lead included a history of preparing or storing food in lead-glazed ceramic ware, lower milk consumption, and higher levels of lead in patella bone. A 34 micrograms/g increase in patella lead (from the medians of the lowest to the highest quartiles) was associated with an increase in blood lead of 2.4 micrograms/dl. Given the measurement error associated with KXRF and the extrapolation of lead burden from a single bone site, this contribution probably represents an underestimate of the influence of trabecular bone on blood lead. Significant predictors of bone lead in multivariate models included years living in Mexico City, lower consumption of high calcium content foods, and nonuse of calcium supplements for the patella and years living in Mexico City, older age, and lower calcium intake for tibia bone. Low consumption of milk and cheese, as compared to the highest consumption category (every day), was associated with an increase in tibia bone lead of 9.7 micrograms Pb/g bone mineral. The findings of this cross-sectional study suggest that patella bone is a significant contributor to blood lead during lactation and that consumption of high calcium content foods may protect against the accumulation of lead in bone.

Adolescent↗

[Role of sensory neuropeptides in the responses of pulmonary and cerebral blood vessels to acute hypoxia in rats].

OBJECTIVE: To study the effects of sensory neuropeptides on pulmonary circulation and cerebral blood flow during acute hypoxia in SD rats. METHODS: The changes in hypoxic pulmonary vasoconstriction (HPV) and hypoxic cerebral vasodilatation (HCVD) were observed in mature SD rats pretreated with capsaicin (50 mg/kg) when they were newborn. The hypoxic changes of plasma substance P in the pulmonary circulation and the peptidergic nerve fibers in the lungs were determined with radioimmunoassay and immunohistochemical staining respectively. The effects of exogenous SP on HPV and HCVD were studied as well. RESULTS: The mean pulmonary artery pressure (2.46 +/- 0.07kPa), pulmonary vascular resistance (3665.09 +/- 164.08kPa.s/L) and the percentage change of pulmonary vascular resistance (delta PVR%) during hypoxia (98.67% +/- 4.07%) in group capsaicin (Caps) were higher than those in group Veh (vehicle control) (2.22 +/- 0.04 kPa, 2945.14 +/- 119.23kPa.s/L and 41.21% +/- 2.08% respectively) (t = 2.89, 3.49 and 12.18, P < 0.01) and those in group NC (normal control) (2.22 +/- 0.03 kPa, 2908.19 +/- 130.85 kPa.s/L and 39.13% +/- 1.48%) (t = 3.09, 3.59 and 13.48, P < 0.01). The wave amplitude in rheoencephalogram (H) in group Caps (11.27 +/- 1.02 m omega) was less than those in group Veh (14.96 +/- 1.08 m omega) (t = 2.49, P < 0.05) and group NC (15.86 +/- 1.33 m omega) (t = 2.69, P < 0.05) during normoxia. It increased significantly in groups Veh (41.36% +/- 6.74%) (t = 9.44, P < 0.01) and NC (48.79 +/- 6.10%) (t = 11.21, P < 0.01) during acute hypoxia, however it dropped in group Caps (-23.55 +/- 2.38%). The plasma SP-like immunoreactivity level in the outflow blood of pulmonary circulation increased in hypoxic rats (SPop-SPip = 139.04 +/- 27.97 pmol/L) while it decreased in group Caps (SPop-SPip = -45.84 +/- 6.52 pmol/L) (t = 5.41, P < 0.01). The SP- and CGRP-immunoreactive fibers in lungs appeared to be sparser and thinner during hypoxic inspiration for 3-5 min. SP decreased delta PVR% from 47.42% +/- 4.70% to 20.58% +/- 2.66% (t = 6.84, P < 0.01) while it increased delta H% from 12.51% +/- 4.31% to 37.66% +/- 5.17% (t = 3.93, P < 0.01) during hypoxia. CONCLUSIONS: Sensory neuropeptides might contribute to the modulation of the basic tone of pulmonary and cerebral vessels. They could be released during acute hypoxia modulating HPV and mediating HCVD.

Animals↗

Secretory expression of a single-chain insulin precursor in yeast and its conversion into human insulin.

A synthetic single-chain porcine insulin precursor (PIP) gene and an alpha-mating factor leader sequence (alpha MFL) gene obtained by the PCR method are inserted between the promoter and 3'-terminating sequence of the alcohol dehydrogenase gene ADH1 in plasmid pVT102-U to form plasmid pVT102-U/alpha MFL-PIP. The single-chain insulin precursor is expressed and secreted to the culture medium by Saccharomyces cerevisiae transformed by pVT102-U/alpha MFL-PIP. The precursor is purified and converted into human insulin by tryptic transpeptidation. The purified human insulin is fully active and can be crystallized. The overall yield of human insulin is 25 mg per liter of culture medium.

Base Sequence↗

[Reflex changes in efferent sympathetic nerve activities of visceral organs during PEEP loading in anesthetized dogs].

OBJECTIVE: To study the effects of PEEP 0.98 kPa (1 kPa = 10.2 cmH2O) on the sympathetic nerve activities of visceral organs in anesthetized dogs with intact neuraxis or with vagotomy. METHODS: Renal (RNA), cardiac (CNA), hepatic (HNA) and adrenal gland (AdNA) sympathetic nerve activities were recorded. Mean blood pressure (MBP), central venous pressure (CVP), left atrial pressure (LAP) and airway pressure (AWP) were also measured. RESULTS: AdNA significantly decreased, but RNA, CNA and HNA had a tendency toward decrease during PEEP loading in the intact dogs. However, vagotomy reversed the changes in all nerve activities in the intact dogs. CVP, LAP and AWP significantly increased, while MBP significantly decreased during PEEP loading. CONCLUSION: The results indicated that PEEP loading caused sympathoinhibition in the adrenal gland, kidney, heart and liver, which were mediated by activation of cardiopulmonary baroreceptor.

Animals↗

[Percutaneous cervical discectomy: a report of twenty-five cases].

Twenty-five patients with herniations of the cervical intervertebral disks were treated with percutaneous cervical discectomy. The surgical instruments and technique were improved based on those for percutaneous lumbar discectomy. All the patients well recovered with an average follow-up period of 15.6 months (from 4 to 23 months) and no major complications was encountered. The method is safe, easy and effective. The anatomy, principles and maneuvers related to the operation are discussed in detail.

Adult↗