Viro-immunopathogenesis of HIV disease: implications for therapy.
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Biomedical subjects
Publications and source records attributed to W Lu.
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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.
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.
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.
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.
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The neonatal calf diarrhea virus-Cody (NCDV-Cody) strain was found to contain a mixture of rotaviruses with G6 and G8 VP7 genes. Challenge exposure of calves with the mixed virus inoculum indicated that both viruses were maintained by passage in vivo. This is the first P1:G8 rotavirus to be characterized in cattle in the United States.
As a drug for lymphosarcoma, pingyangmycin (A5) is not widely used because of its toxicities, short half-life and low affinity to lymph. For the purpose of delivering A5 to the lymph system to strengthen and sustain its effects and to lower its toxicities, its gelatin microspheres-in-oil emulsion (S/O) was studied in vitro and in vivo. By ultrasonication, gelatin microspheres with diameters of 1.67 +/- 0.69 microns were homogeneously dispersed in oil to form the S/O, which was a pseudoplastic flow and stable under 0 degrees C for at least 1 month. With the content of 14.03 +/- 0.15 mg.ml-1, A5 released from the emulsion in a zero order rate with t0.5 of 12.0 h. In vivo experiments showed that the S/O emulsion exhibited potent lymphotropicity, prolonged plasma concentration and a probably lower pulmonary toxicity.
Radial keratotomy without T-cutting was performed on 245 eyes of 124 patients with 6-8 months of post-operative follow-up. The results showed that post-operatively astigmatism was increased in 74 eyes (30.2%) with the increased range from +0.50 to +3.50DC, decreased in 27 eyes (11.0%) and not changed in 144 eyes (58.8%). The main causes of astigmatic change included microperforations, irregular incisions, incisions across the central optical zone and various depths of incisions, etc.
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Fluorescence assay was applied to the determination of magnolol in rabbit blood, and the best way to administer the bark of official magnolia per rectal was established by orthogonal test. Then the two routes of administration were compared by AUC of magnolol and per rectal was found better than P.O. In addition, the modified isolated rectum-bag method was applied successfully to the research on rectal administration of bark of official magnolia.
Delayed fluid resuscitation of burn shock may lead to many harmful effects. We investigated the injury of heart of burned rats having no fluid resuscitation, immediate and delayed fluid replacement. We used electron spin resonance (ESR) to determine the presence of oxygen free radicals (OFR). We also found significant increase in malondialdehyde (MDA) in delayed resuscitation group. The activity of lactate dehydrogenase isoenzyme (LDH) and creatine phosphokinase isoenzyme (CPK-MB) were increased in the latter group. Immediate fluid replacement can not protect the heart perfectly. Some new measure should be added to the fluid replacement in burn shock.
The observation on the indexes of cortisol, estradiol, estriol and testosterone showed that incretory function of malignant tumor patients had different extent of pathologic changes, after radiotherapy and chemotherapy, making the change strengthened. Acupuncture can regularize this disorder of incretory function of patients treated with radiotherapy and chemotherapy to some extent.
One hundred twenty cases of malignant pleural effusion were treated by intrapleural administration of large doses of DDP (500-1,000 mg) followed by iv infusion of sodium thiosulfate for 3 days. Each patient received 1-4 cycles of treatment. Of 120 cases, 89 had their effusion completely disappeared and in 6 of them, it was accompanied by complete regression of tumors in the lung. Partial response was observed in 19 cases with an overall response rate of 90.0%. The median remission period was 6.4 month. Severe (grade III and IV) gastrointestinal, renal toxicity and myelosuppression occurred in 46,8 and 12 cases, respectively, Two patients died of severe intoxication.
A TLC-densitometric method was applied to determine aesculin in rabbit blood. The best way for ash bark rectal administration was found by orthogonal design [L4(2(3))]. The two routes of administration (per rectal, P.O.) were compared by bioavailabilities and the result indicated that per rectal was better than P.O. Modified isolated rectum-bag method was applied successfully to finding the best way for rectal administration of ash bark.
Echicetin, a protein isolated from Echis carinatus snake venom, inhibited platelet aggregation and secretion induced by low concentrations of thrombin ( < 0.2 U/ml), by binding to platelet glycoprotein Ib (GPIb). The inhibition was not observed when the platelets were stimulated with higher concentrations of thrombin ( > 0.2 U/ml). Echicetin competed with thrombin for binding to the high affinity site on GPIb. Thrombin also inhibited 50% of the binding of 125I-echicetin to the platelets.