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Biomedical subjects

W Lu

Publications and source records attributed to W Lu.

At least 19 recordsLinked to original sources
PubMed1996

Hematotoxicity among Chinese workers heavily exposed to benzene.

Benzene is a well-established hematotoxin. However, reports of its effects on specific blood cells have been somewhat inconsistent and the relative toxicity of benzene metabolites on peripheral blood cells in humans has not been evaluated. We compared hematologic outcomes in a cross-sectional study of 44 workers heavily exposed to benzene (median: 31 parts permillion [ppm] as an 8-hr time-weighted average [TWA] and 44 age and gender-matched unexposed controls from Shanghai, China. All hematologic parameters (total white blood cells [WBC], absolute lymphocyte count, platelets, red blood cells, and hematocrit) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume (MCV), which was higher among exposed subjects. In a subgroup of workers who were not exposed to more than 31 ppm benzene on any of 5 sampling days (n = 11, median 8 hr TWA = 7.6 ppm, range = 1-20 ppm), only the absolute lymphocyte count was significantly different between exposed workers (mean [sd]1.6 [0.4] x 10(3) mu L) and controls (1.9 [0.4] x l0(3) uL, p = 0.03). Among exposed subjects, a dose response relationship with various measures of current benzene exposure (i.e., personal air monitoring, benzene metabolites in urine) was present only for the total WBC count, the absolute lymphocyte count, and the MCV. Correlations between benzene metabolites and hematologic parameters were generally similar, although hydroquinone was somewhat more strongly associated with a decrease in the absolute lymphocyte count, and catechol was more strongly associated with an increase in MCV. Morphologic review of peripheral blood slides demonstrated an excess of red blood cell abnormalities (i.e., stomatocytes and target cells) only in the most heavily exposed workers, with no differences in granulocyte, lymphocyte, or platelet morphology noted. Although benzene can affect all the major peripheral blood elements, our results support the use of the absolute lymphocyte count as the most sensitive indicator of benzene-induced hematotoxicity.

Adult↗
PubMed1996

BDNF enhances the functional reinnervation of the striatum by grafted fetal dopamine neurons.

Transplantation of fetal dopaminergic neurons to the striatum can ameliorate neurological deficits exhibited by experimental animals and human graft recipients with Parkinson's disease. Recovery, however, is incomplete due to suboptimal survival of grafted cells and limited synaptic integration with the host brain. A number of neurotrophic factors have recently been shown to promote the survival and differentiation of dopamine neurons in vitro. In the present study we examined the effects of one such factor, brain-derived neurotrophic factor (BDNF), on the development of fetal substantia nigra following transplantation to the dopamine-depleted striatum of adult rats. Infusion of BDNF greatly enhanced the reinnervation of the host striatum by the engrafted dopamine neurons, as determined by tyrosine hydroxylase immunostaining, and also increased the effect of the graft on locomotor behavior induced by amphetamine administration. These effects became apparent during the 4-week period of BDNF infusion and persisted for an additional 6 weeks following the termination of BDNF delivery. These findings demonstrate that BDNF exerts a significant effect on the functional reinnervation of the striatum by transplanted fetal dopamine neurons in the rat, and suggest that application of this factor might similarly improve the clinical efficacy of neural transplantation employed in the treatment for Parkinson's disease.

Amphetamine↗
PubMed1996

A ribonuclease-resistant method of in situ hybridization histochemistry in rat brain tissue.

Two major problems limiting neurobiological applications of in situ hybridization are: (1) contamination by ribonuclease (RNase), which is difficult to avoid and therefore makes the method difficult to establish for many laboratories, and (2) lack of reproducibility, which makes the method inadequate for detecting and quantifying changes in mRNA levels. We have developed a modified method of in situ hybridization which addresses these problems. RNase resistance is afforded by the inclusion of RNase inhibitors during steps in which mRNA is vulnerable to RNase digestion, alleviating the need to maintain RNase-free conditions during experiments. These changes result in higher levels of specific hybridization, while maintaining low background. In addition, a high level of reproducibility is obtained, both for sections obtained from the same animal and for corresponding sections obtained from different animals. This method has been characterized for preproenkephalin and glutamate receptor GluR 1-4 mRNAs.

Animals↗
PubMed1996

Genes expressed in Brugia malayi infective third stage larvae.

We have used a tag sequencing approach to survey genes expressed in the third stage infective larvae of the human filarial nematode parasite Brugia malayi. RNA was isolated from late vector-stage L3 larvae after days 9 or 10 of infection in mosquitos, and converted to cDNA by reverse transcriptase. Double-stranded cDNA was produced by either conventional methods (non-SL cDNA library) or by PCR using the nematode spliced leader (SLI) and oligo(dT) primers (SL cDNA library). Two clone libraries (one from SL and one from non-SL cDNAs) were constructed in lambda ZapII. A set of these full-length clones was selected and 596 inserts were sequenced from the 5' end. We have identified 364 B. malayi genes (the majority of which are new) that encode housekeeping proteins, structural proteins, proteins of immediate immunological or drug-discovery interest as well as a large class of novel sequences which may prove to have significant involvement in host invasion. Extensive, genome-wide approaches to the analysis of larval gene expression are now possible for B. malayi. We present several examples of this approach.

Amino Acid Sequence↗
PubMed1996

Absence of clinical, virological, and immunological signs of progression in HIV-1-infected patients receiving active anti-interferon-alpha immunization: a 30-month follow-up report.

Twenty-seven HIV-1-infected patients, 16 at early stage of disease and without concomitant antiretroviral therapy and 11 at more advanced stage of disease receiving antiretroviral therapy, have been followed since their enrollment, November 1992 and July 1993, respectively, in phase I/II studies to evaluate safety and immunogenicity of an anti-interferon-alpha (IFN-alpha) vaccine, aimed at modulating the impaired cytokine network in AIDS patients by counteracting IFN-alpha overproduction. We compared clinical, virological, and immunological markers of disease progression, including circulating IFN-alpha levels in a 24- to 30-month follow-up period with those of 62 patients fulfilling the same enrollment criteria and comparable for sex, risk factor, and age, regularly followed at our center. Anti-IFN-alpha immunization consisted of four-six intramuscular injections 1 month apart of a water-in-oil emulsion of 500 micrograms formalin-inactivated recombinant IFN-alpha-2b (iIFN-alpha) followed by intramuscular injections of 250 micrograms iIFN-alpha adsorbed onto calcium phosphate every 3 months. Neither clinical deterioration nor a CD4+ cell count decrease from pretreatment values was observed in IFN-alpha-immunized patients in the follow-up period, whereas clinical and immunological disease progressions were observed among open-comparison patients. Furthermore, statistical analysis showed a strong association between occurrence of clinical manifestations and high circulating IFN-alpha titers, while nonprogression of IFN-alpha-immunized patients was associated with decreased levels of circulating IFN-alpha.

Adolescent↗
PubMed1996

[Clinical and experimental study of RA mixture in treatment of rheumatoid arthritis].

The RA mixture is composed of Tripterygium Wilfordii (TW) and other Chinese medicinal herbs with effect of expelling Wind, activiting blood circulation, invigorating the Kidney and Qi. The authors treated rheumatoid arthritis (RA) patients with RA mixture and compared it with D-penicillamine as control. The two group's therapeutical effect is similar (P > 0.05), but the side effect occuring ratio in treatment group was obviously lower than that of control group (P < 0.01). After treatment with RA mixture, the patient's human lymphocytic antigen-degenerative reaction (HLA-DR+) cell, CD4/CD8 ratio reduced and auto-mixed lymphocytic reaction (AMLR) level enhanced (P < 0.05). The results of animal experiment showed that swelling of RA model mouse's joint could be reduced by both RA mixture and TW. Comparing with TW, RA mixture had stronger effect in controlling the inflammation of synovial cell and fibroid degeneration of fibrocytes. At the same time, RA mixture had stronger effect in protecting the immune organ from atrophy and protecting functions of cellular immunity. All above suggest that RA mixture reduce the syndroms of RA by improving distribution of T lymphocyte subsets and the functions of cellular immunity. The other Chinese medicinal herbs in the RA mixture could enhance TW's therapeutical effect and reduce it's side effect.

Adult↗
PubMed1996

[Canonical correlation of body composition and pulmonary function in children aged eight to twelve].

Canonical correlation of body composition and pulmonary ventilation function in school boys and girls aged 8 to 12 and normally developed was analyzed. Skinfolds of triceps and subscapular angle were measured, and body composition was estimated as body fat percentage (BF%), body fat (BF) and lean body mass (LBM). Ventilation function was measured. Results indicated that correlation between body composition and ventilation function mainly attributed to a positive correlation between LBM and vital capacity (VC) and a negative correlation between BF% and a ratio of expiratory reserve volume (ERV) to VC. It suggests effects of body composition on ventilation function mainly attributed to LBM and BF%.

Body Composition↗
PubMed1995

Subsets of midbrain dopaminergic neurons in monkeys are distinguished by different levels of mRNA for the dopamine transporter: comparison with the mRNA for the D2 receptor, tyrosine hydroxylase and calbindin immunoreactivity.

The midbrain dopamine system can be divided into two groups of cells based on chemical characteristics and connectivity. The dorsal tier neurons, which include the dorsal pars compacta and the ventral tegmental area, are calbindin-positive, and project to the shell of the nucleus accumbens. The ventral tier neurons are calbindin-negative and project to the sensorimotor striatum. This study examined the distribution of the mRNAs for the dopamine transporter molecule (DAT) and the D2 receptor in the midbrain of monkeys by using in situ hybridization. The distribution patterns were compared to that of tyrosine hydroxylase and calbindin immunohistochemistry. The results show that high levels of hybridization for DAT and the D2 receptor mRNA are found in the ventral tier, calbindin-negative neurons and relatively low levels are found in the dorsal, calbindin-positive tier. Within the dorsal tier, the dorsal substantia nigra pars compacta has the least amount of both messages. These results show that in monkeys, the ventral tegmental area and the dorsal pars compacta form a dorsal continuum of dopamine neurons which express lower levels of mRNA for DAT and D2 receptor than the ventral tier. DAT has been shown to be involved in the selective neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Different levels of DAT mRNA and calbindin may explain the differential effects of MPTP neurotoxicity.

Animals↗
PubMed1995

Determination of amino acids by on-line capillary electrophoresis-electrospray ionization mass spectrometry.

On-line capillary electrophoresis-electrospray ionization mass spectrometry (CE-ESMS) has been used for the separation and detection of amino acid mixtures. Four natural amino acids, histidine, tryptophan, phenylalanine, aspartic acid, and a tripeptide, glutathione, were separated and determined. Protonated molecules were detected in the CE-ESMS mode with detection limits of about one pmol. Optimum CE-ESMS operating conditions for amino acid analysis were determined employing acetic acid solutions as CE electrolytes. The examined parameters included capillary diameter (50-100 microns internal diameter), applied separation voltage (20-30 kV), and concentration of electrolyte (10-60% acetic acid). Stable working conditions were maintained when the CE currents were less than 18 microA. The use of electrolyte solutions such as those described here instead of true buffer solutions may have advantages for CE-ESMS systems which employ a "sheathless" interface.

Amino Acids↗
PubMed1995

Water molecules participate in proteinase-inhibitor interactions: crystal structures of Leu18, Ala18, and Gly18 variants of turkey ovomucoid inhibitor third domain complexed with Streptomyces griseus proteinase B.

Crystal structures of the complexes of Streptomyces griseus proteinase B (SGPB) with three P1 variants of turkey ovomucoid inhibitor third domain (OMTKY3), Leu18, Ala18, and Gly18, have been determined and refined to high resolution. Comparisons among these structures and of each with native, uncomplexed SGPB reveal that each complex features a unique solvent structure in the S1 binding pocket. The number and relative positions of water molecules bound in the S1 binding pocket vary according to the size of the side chain of the P1 residue. Water molecules in the S1 binding pocket of SGPB are redistributed in response to the complex formation, probably to optimize hydrogen bonds between the enzyme and the inhibitor. There are extensive water-mediated hydrogen bonds in the interfaces of the complexes. In all complexes, Asn 36 of OMTKY3 participates in forming hydrogen bonds, via water molecules, with residues lining the S1 binding pocket of SGPB. For a homologous series of aliphatic straight side chains, Gly18, Ala18, Abu18, Ape18, and Ahp18 variants, the binding free energy is a linear function of the hydrophobic surface area buried in the interface of the corresponding complexes. The resulting constant of proportionality is 34.1 cal mol-1 A-2. These structures confirm that the binding of OMTKY3 to the preformed S1 pocket in SGPB involves no substantial structural disturbances that commonly occur in the site-directed mutagenesis studies of interior residues in other proteins, thus providing one of the most reliable assessments of the contribution of the hydrophobic effect to protein-complex stability.

Alanine↗
PubMed1995

Distribution of preproenkephalin messenger RNA in the basal ganglia and limbic-associated regions of the monkey telencephalon.

We studied the distribution of preproenkephalin messenger RNA in the monkey forebrain, using a free-floating method for in situ hybridization histochemistry. Autoradiographs reveal a high level of specific hybridization to preproenkephalin messenger RNA in the monkey striatum and forebrain regions. In the monkey striatum, the distribution of preproenkephalin messenger RNA is heterogeneous. There is variation in the general labeling pattern between regions of the striatum. For example, a particularly densely labeled area of preproenkephalin messenger RNA is observed in the ventral part of the caudal putamen. In addition, at the macroscopic level, there are patches of specific hybridization intermingled with areas containing less specific labeling. This forms a mosaic-like pattern. At the microscopic level, densely labeled individual cells are found among those with little or no specific labeling. Adjacent sections, processed for in situ hybridization and immunohistochemistry, show some correlation between the perikarya containing preproenkephalin messenger RNA and enkephalin-positive fibers in the striatum. Specific hybridization to preproenkephalin messenger RNA is evident throughout the cortical mantle, primarily concentrated in layers 2 and 3. Particularly high levels of preproenkephalin messenger RNA are found in specific limbic-associated cortices, including the piriform allocortex, the agranular area of the orbitofrontal cortex, the agranular insular cortex and the caudal field of the entorhinal cortex. Specific labeling is also present in the granular cell layer of the dentate gyrus and in the amygdaloid complex. This study reveals heterogeneous distribution of dense preproenkephalin messenger RNA in the basal ganglia and high levels of preproenkephalin messenger RNA in specific limbic-associated regions of the monkey telencephalon.

Animals↗
PubMed1995

Three-dimensional simulation of epicardial potentials using a microcomputer-based heart-torso model.

Previous cardiac simulation studies have focused on simulating the activation isochrones and subsequently the body surface potentials. Epicardial potentials, which are important for clinical applications as well as for electrocardiography inverse problem studies, however, have usually been neglected. This paper presents a procedure of simulating epicardial potentials using a microcomputer-based heart-torso model with real geometry. The heart model developed earlier which was composed of more than 60,000 cell units was used in this study. To simulate the epicardial potentials, an epicardial surface model which enclosed the whole heart was constructed. The heart model, together with the epicardial surface model, are mounted in an inhomogeneous human torso model. Electric dipoles, which are proportional to the spatial gradient of the action potential, are generated in all cell units. These dipoles give rise to a potential distribution on the epicardial surface, which is calculated by means of the boundary element method. The simulated epicardial potential maps during a normal heart beat and in patients with left bundle branch block (LBBB) are in close agreement with those reported in the literature.

Action Potentials↗
PubMed1995

Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year.

Forty-four asymptomatic patients infected with human immunodeficiency virus type 1 (HIV-1), who had 200-799 CD4 cells/microL, received oral prednisolone (0.5 mg/kg for 6 months; 0.3 mg/kg thereafter). After 1 year of treatment, no major side effect or AIDS events had occurred. The percentage of DR+ and CD25+ phenotypes in CD4 T cells decreased significantly as did levels of serum IgG, IgA, and beta 2-microglobulin. Serum p24 antigen and HIV RNA levels remained stable. CD4 cell counts increased significantly at all time points (median increase at 1 year, 119 cells/microL). Peripheral blood mononuclear cell apoptosis after overnight stimulation with anti-CD3 monoclonal antibodies was strongly inhibited at all times. In asymptomatic seropositive patients, immunotherapy for 1 year with glucocorticoids was safe and led to sustained increases in CD4 cell counts and to improvement or stabilization of other biologic markers of disease activity.

Adult↗
PubMed1995

Glucocorticoids rescue CD4+ T lymphocytes from activation-induced apoptosis triggered by HIV-1: implications for pathogenesis and therapy.

OBJECTIVE: During HIV-1 infection, CD4+ T lymphocytes migrate to immune-reactive lymphoid organs where they are infected by the virus and/or killed by apoptosis on immunoregulatory stimuli--a potential mechanism underlying fatal CD4+ T-cell depletion observed in AIDS. This study seeks to determine the effects of glucocorticoids (GCC) on the activation-induced T-cell apoptosis triggered by HIV-1. METHODS: CD4+ and CD8+ T cells were purified from HIV-negative donor peripheral blood mononuclear cells (PBMC) by positive selection and exposed to HIV-1 (primary isolates). HIV-1-exposed CD4+ and CD8+ T cells as well as PBMC derived from HIV-1-infected patients were cultured with medium alone or anti-CD3 monoclonal antibodies (MAb)/mitogens in the presence or absence of hydrocortisone or prednisolone. Viral infection kinetics were assessed by polymerase chain reaction and viral replication was measured by p24 enzyme-linked immunosorbent assay. Cell survival, apoptosis, T-cell proliferation, blast cell transformation, and interleukin (IL)-2 receptor (CD25) expression were monitored in parallel for each cell population. RESULTS: Fractionated CD4+ T cells acutely infected by HIV-1 underwent apoptotic death on anti-CD3 MAb/mitogen stimulation. This activation-induced apoptotic cell killing was antagonized by pharmacological doses of prednisolone or hydrocortisone added up to 6 h after stimulation. GCC were also found to be capable of inhibiting the accelerated apoptosis in PBMC (including both CD4+ and CD8+ T-cell fractions) from HIV-1-infected patients. This anti-apoptotic action of GCC overbalanced their downregulatory effect on T-cell proliferation, resulting in an overall improvement of CD4+ T-cell survival in patient PBMC. These effects of GCC were abrogated by the anti-GCC RU 486 and were not associated with significant suppression of CD25 expression and IL-2-dependent T-cell blast transformation; moreover, GCC had no impact on viral infection and replication. CONCLUSION: GCC exert a receptor-mediated anti-apoptotic activity in mature T cells through both activation-induced and HIV-1-triggered pathways and could be potent inhibitors of T-cell apoptosis in HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗