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Biomedical subjects

W Hu

Publications and source records attributed to W Hu.

302 records · Page 17Linked to original sources
PubMed1987

Modulation of Friend virus infectivity in vivo by administration of purified preparations of human lactoferrin and recombinant murine interleukin-3 to mice.

Purified iron-saturated human milk lactoferrin (LF) and purified recombinant murine interleukin-3 (IL-3) were assessed in vivo for their effects on replication of spleen focus forming viruses (SFFV) in spleens of DBA/2 mice injected with the polycythemia-inducing strain of the Friend virus complex. LF and IL-3, inoculated 2 hr prior to the administration of the polycythemia-inducing strain of the Friend virus complex, respectively decreased and increased the replication of SFFV in mice as assessed by the spleen focus forming unit assay in primary and secondary DBA/2 mice. Since virus infectivity is associated with the DNA synthetic phase of the cell cycle and it has been shown elsewhere that LF decreases and IL-3 increases the percent of hematopoietic progenitor cells in S-phase in vivo, the results suggest that the opposing actions of LF and IL-3 on replication of SFFV may reflect the actions of these molecules on cycling of the target cells for SFFV.

Animals↗
PubMed1986

Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases.

Several recombinant cowpox viruses were constructed and used to identify a viral gene that controls the production of hemorrhage in lesions caused by the Brighton Red strain of cowpox virus (CPV-BR). This gene is located in the KpnD fragment of CPV-BR DNA, between 31 and 32 kilobases from the end of the genome. This position corresponds well with that predicted from analyses of the DNA structures of spontaneously generated deletion mutants. The gene responsible for hemorrhage encodes a 38-kDa protein that is one of the most abundant early gene products. The 11-base-pair sequence GAAAATATATT present 84 base pairs upstream of its coding region is also present upstream of three other early genes of vaccinia virus; therefore, this sequence may be involved in the regulation of transcription. There is extensive similarity between the predicted amino acid sequence of the 38-kDa protein and the amino acid sequences of several plasma proteins that are inhibitors of various serine proteases involved in blood coagulation pathways. This suggests that the viral protein may possess a similar biological activity, which may enable it to effect hemorrhage by inhibiting one or more of the serine proteases involved in the host's normal processes of blood coagulation and wound containment.

Amino Acid Sequence↗
PubMed1984

Spontaneous deletions and duplications of sequences in the genome of cowpox virus.

Examination of the genomes of 10 white-pock variants of cowpox virus strain Brighton red (CPV-BR) revealed that 9 of them had lost 32 to 38 kilobase pairs (kbp) from their right-hand ends and that the deleted sequences had been replaced by inverted copies of regions from 21 to 50 kbp long from the left-hand end of the genome. These variants thus possess inverted terminal repeats (ITRs) from 21 to 50 kbp long; all are longer than the ITRs of CPV-BR (10 kbp). The 10th variant is a simple deletion mutant that has lost the sequences between 32 and 12 kbp from the right-hand end of the genome. The limits of the inner ends of the observed deletions (between 32 and 38 kbp from the right-hand end of the CPV-BR genome) appear to be defined by the location of the nearest essential gene on the one hand and the location of the gene that encodes "pock redness" on the other. The genomes of the deletion/duplication white-pock variants appear to have been generated either by single crossover recombinational events between two CPV-BR genomes aligned in opposite directions or by the nonreciprocal transfer of genetic information. The sites where such recombination/transfer occurred were sequenced in four variants. In all of them, the sequences adjacent to such sites show no sequence homology or any other unusual structural feature. The analogous sites at the internal ends of the two ITRs of CPV-BR also were sequenced and also show no unusual features. It is likely that the ITRs of CPV-BR and of its white-pock variants, and probably those of other orthopox-virus genomes, arise as a result of nonhomologous recombination or by random nonreciprocal transfer of genetic information.

Base Sequence↗
PubMedDate not supplied

Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology.

Both oxidative damage and inflammation have been implicated in age-related neurodegenerative diseases including Alzheimer's Disease (AD). The yellow curry spice, curcumin, has both antioxidant and anti-inflammatory activities which confer significant protection against neurotoxic and genotoxic agents. We used 22 month Sprague-Dawley (SD) rats to compare the effects of the conventional NSAID, ibuprofen, and curcumin for their ability to protect against amyloid beta-protein (Abeta)-induced damage. Lipoprotein carrier-mediated, intracerebroventricular infusion of Abeta peptides induced oxidative damage, synaptophysin loss, a microglial response and widespread Abeta deposits. Dietary curcumin (2000 ppm), but not ibuprofen, suppressed oxidative damage (isoprostane levels) and synaptophysin loss. Both ibuprofen and curcumin reduced microgliosis in cortical layers, but curcumin increased microglial labeling within and adjacent to Abeta-ir deposits. In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented Abeta-infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced Abeta deposits. Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention.

Amyloid beta-Peptides↗
PubMedDate not supplied

Proteomics in cancer research.

With the human genome sequence now determined, the field of molecular medicine is moving beyond genomics to proteomics. In the field of cancer research, the key question is: how can oncologists best use techniques of proteomics in basic research and clinical application? In the postgenomic era, proteomics promises the discovery of biomarkers and tumor markers for early detection and diagnosis, novel protein-based drug targets for anticancer therapy, and new endpoints for the assessment of therapeutic efficacy and toxicity. This review paper will explore key themes in proteomics and their application in clinical cancer research.

Forecasting↗
PubMedDate not supplied

Targeted therapy for epithelial ovarian cancer: current status and future prospects.

Despite advances in surgery and chemotherapy, less than 20% of patients with stage III or IV ovarian cancer survive long-term. In the past, cytotoxic regimens have been developed empirically, combining active agents at maximally tolerated doses, often without a clear rationale for their interaction. Advances in understanding the biology of ovarian cancer have identified multiple molecular targets that differ in normal and malignant cells. Targets include cell cycle regulators, growth factor receptors, signal transduction pathways, molecules that confer drug resistance, and angiogenic mechanisms. A number of targeted agents have entered clinical trials. Small molecular weight inhibitors, monoclonal antibodies, and antisense and gene therapy are all being evaluated alone and in combination with cytotoxic drugs. In contrast to earlier studies, the impact of each agent on the designated target can be assessed and agents can be matched to the genotype and phenotype of malignant and normal cells. In the long run, this should facilitate individualization of more effective, less toxic therapy for women with ovarian cancer.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Clinical application of oxaliplatin in epithelial ovarian cancer.

Platinum remains the most active drug class in ovarian cancer treatment; however, new single-agent and combination therapies are needed to improve the clinical outcome of ovarian cancer therapies. Oxaliplatin, a third-generation platinum derivative, has shown effective antitumor activity and a favorable toxicity profile in epithelial ovarian cancer. Preclinical evidence of the synergistic cytotoxic effect of oxaliplatin in combination with several other chemotherapeutic agents and clinical evidence of the absence of any dose-limiting hematologic toxicity associated with this agent have made oxaliplatin an attractive compound for combination agent therapy. This article reviews the current status of the clinical application of oxaliplatin alone and in a combination regimen in epithelial ovarian cancer treatment.

Antineoplastic Agents↗
PubMedDate not supplied

Catalytically assisted electrochemical oxidation of dye Acid Red B.

This study focused on the degradation of dye Acid Red B in a catalytic electrolysis system with a semiconductor suspended in the electric field. The study showed that the addition of titanium dioxide substantially enhances the degradation of dye and that a semiconductor catalyst can improve electrolysis efficiency. This catalytic system has great potential to be applied commercially with the development of the catalyst. Analytical measurements show that some acidic compounds are produced in the treatment process and that biodegradability of the solution increases after electrolysis because of the breakdown of molecules. The UV-visible spectrum also indicates that the conjugated bonds of dye Acid Red B must be destroyed and that the molecules are broken into small ones. Furthermore, the results from the IR spectrum indicate that the nitrogen-nitrogen double bond of dye Acid Red B must be oxidized to nitrate. Electrochemical measurements show an apparent dye oxidation peak from 0.65 to 0.85 V (versus the saturated calomel electrode) in dye solution (10 g/L), confirming that dye is oxidized in this catalytic system.

Catalysis↗
PubMedDate not supplied

Ultrastructural localization of insulin-like growth factor-2 (IGF-2) to the secretory granules of insulin cells: a study in normal and diabetic (GK) rats.

By using biochemical and light-microscopical techniques, insulin-like growth factor-2 (IGF-2) has recently been found in adult pancreas, co-localized immunohistochemically with insulin in the islet B-cells. The purpose of this study was to trace IGF-2 immunoreactivity (IR) at the ultrastructural level in normal and diabetic Goto-Kakizaki (GK) rats. Using a pre-embedding technique and immuno-gold-silver staining, IGF-2 antibody binding was localized exclusively to the halo of a subset of secretory beta-granules in normal rats. Insulin IR occurred more frequently in the granules. GK rats had, in addition to normal-looking islets, some islets with irregular shape and an increased amount of fibrous tissue, so-called "starfish-shaped" islets. In these, beta-granules were usually found, but most of the B-cells were also occupied by large, usually electron-translucent vesicles, some resembling crinophagic bodies, i.e., the sign of intracellular degradation of secretory granules. In starfish-shaped islets, IGF-2 IR was localized to the halo of beta-granules, as in GK islets with normal appearance. Occasionally, IGF-2 IR was also found in the cytoplasm and even in adjacent fibroblasts. Insulin IR was restricted to beta-granules. Because the lysosomes have IGF-2 receptors, the presence of IGF-2 peptide in secretory granules could explain why some granules are guided to lysosomes for degradation.

Animals↗
PubMedDate not supplied

Anomalies of the TGF-beta postreceptor signaling pathway in ovarian cancer cell lines.

Transforming growth factor-beta (TGF-beta) can cause cell cycle arrest, terminal differentiation, or apoptosis in most normal epithelial cells, whereas most malignant cell lines are resistant to TGF-beta. Mechanisms of resistance to TGF-beta caused by modulation of cell cycle regulators and/or inactivation of components of the TGF-beta signaling transduction pathway such as C-myc and Smad4 have been demonstrated in human pancreatic cancer and squamous cell carcinoma cell lines. But, this has not been shown in ovarian cancer. To investigate the potential association between loss of sensitivity to TGF-beta and expression status of transforming growth factor receptor II (T beta RII), Smad4, CDC25A and C-myc in fourteen cell lines derived from ovarian cancer, the expression levels of these genes were examined by semi-quantitative RT-PCR. Normal ovarian surface tissues were used as controls. Expression of T beta RII was detectable in all of fourteen cell lines. Expression of Smad4 was decreased in ten cell lines and nine cell lines overexpressed CDC25A, compared to normal controls. CDC25A gene was overexpressed in 88% (8/9) of tumorigenic cell lines as determined by xenografts in nude mice, and only in 20% (1/5) of non-tumorigenic cell lines (P < 0.05). C-myc was not overexpressed in any of these cell lines. The loss of sensitivity to TGF-beta of cell lines derived from ovarian cancers may be related to (1) a decreased expression of Smad4, which mediates TGF-beta induced growth inhibition; and/or (2) an overexpression of CDC25A. This overexpression correlates with increased tumorigenicity of ovarian cancer cell lines. The loss of sensitivity to TGF-beta is not associated with a lack of T beta RII.

Animals↗
PubMedDate not supplied

Intracranial hemorrhage after stenting and angioplasty of extracranial carotid stenosis.

BACKGROUND AND PURPOSE: The transluminal angioplasty and stenting procedure has been recently advocated as a potential alternative to surgical endarterectomy for the treatment of severe extracranial carotid stenosis. This study assesses the incidence and significance of intracranial hemorrhage occurring after this procedure. METHODS: We retrospectively reviewed 104 carotid arteries (96 internal, two external, and six common) in 90 patients (63 male; mean age, 69.4 years; range, 48-88 years) who underwent primary stenting and angioplasty by use of Wallstents (103/104) at three centers between January 1996 and January 1999. Seventy-five (83%) patients were referred by neurosurgery departments. Seventy-one (68%) arteries were symptomatic; the mean stenosis percentage was 85% (range, 40-99%). RESULTS: Four intraparenchymal hemorrhages occurred, representing 4.4% of patients and 3.8% of vessels, after angioplasty and stent placement. The mean preoperative stenosis percentage was 95% (range, 90-99%). One hemorrhage occurred immediately after stent placement, whereas the three other hemorrhages occurred in a delayed fashion (mean, 2.8 days). The mean hematoma size was 4.8 cm (range, 2-8 cm). Three patients had associated subarachnoid or intraventricular bleeding; the fourth had associated subdural hemorrhage. Three hemorrhages were fatal; the fourth experienced two seizures only. No acute neurologic symptoms were present prior to hemorrhages, and there was no postprocedural hypertension in these patients. All had been receiving antiplatelet agents as well as intraprocedural IV heparin. CONCLUSION: Intracranial hemorrhage can occur after carotid angioplasty and stenting. We speculate that this represents cerebral hyperperfusion injury. The 3.8% incidence of cerebral hemorrhage observed is approximately sixfold greater than that reported post endarterectomy (0.6%) (95% CI, 0.2-8.7%). This is not statistically significant in this small study group. This trend may reflect patient selection, different anticoagulation protocols, and/or study population size. Additional data are needed to determine the safety and efficiency of carotid stenting as a treatment for carotid stenosis.

Aged↗
PubMedDate not supplied

Coronary vascular response to platelet-activating factor in the perfused rat heart.

The coronary vascular responses to platelet-activating factor (PAF) were studied in isolated perfused rat hearts. Constant flow rates were maintained and the changes in perfusion pressure were recorded following bolus injections of PAF. The effect of PAF on the perfusion pressure was variable and depended on certain conditions. Firstly, when the starting baseline pressure was 65-75 mm Hg, bolus injections of PAF resulted in an initial decrease followed by an increase in perfusion pressure. However, the decrease in perfusion pressure was less pronounced when the starting baseline pressure was 40 mm Hg. Secondly, the response varied with the amount of PAF that was injected. Injections of 10 fmol-1 pmol of PAF prepared in a solution containing bovine serum albumin resulted in decreases in perfusion pressure that were not followed by increases. A biphasic response, consisting of an initial decrease followed by an increase in perfusion pressure, was observed following injections of 10 and 100 pmol of PAF. Only increases in perfusion pressure were recorded following injections of 1000 pmol of PAF. Thirdly, the response to injection of PAF was dependent on whether it was prepared in a solution containing serum albumin. This study demonstrates that it is possible to observe vasodilation, vasoconstriction and biphasic responses to PAF in the isolated rat heart model.

Animals↗