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Biomedical subjects

W Tu

Publications and source records attributed to W Tu.

At least 19 recordsLinked to original sources

The psychosocial impact of serological diagnosis of asymptomatic herpes simplex virus type 2 infection.

OBJECTIVES: To evaluate the impact of a positive herpes simplex virus type 2 (HSV-2) serological test on psychosocial functioning among people with no known history of genital herpes. METHODS: Individuals (age 14-30 years) without a history of genital herpes were recruited from an urban university setting and sexually transmitted diseases (STD), primary care, and adolescent clinics. Participants completed a questionnaire addressing psychological functioning, psychosocial adjustment, and perceived quality of sex and were offered free HSV-2 antibody testing. 33 HSV-2 positive people and 60 HSV-2 negative people demographically matched from the same source of recruitment were re-evaluated at a 3 month follow up visit. HSV-2 positive participants also completed a genital herpes quality of life (GHQOL) measure. RESULTS: Of the 33 who were HSV-2 seropositive, four did not recall their diagnosis. In comparing those who were HSV-2 positive with those who were negative, repeated measures analysis of variance indicated there were no significant differences over time on any of the measures. None the less, many HSV-2 positive individuals indicated that the diagnosis had a notable impact on their quality of life. Also, among the HSV-2 positive people, lower GHQOL at the 3 month follow up was predicted by higher interpersonal sensitivity (r = -0.44, p<0.05), lower social support (r = 0.40, p<0.05), and quality of sex (r = 0.62, p<0.01) at baseline. CONCLUSIONS: A diagnosis of asymptomatic HSV-2 infection does not appear to cause significant lasting psychological difficulties. Those for whom the diagnosis had the greatest impact were interpersonally vulnerable before the diagnosis. These results suggest that assessment of interpersonal distress may be important to include as part of pretest and post-test counselling.

Adaptation, Psychological↗

Gender differences in sexual behaviours in response to genitourinary symptoms.

OBJECTIVE: To understand gender differences in sexual behaviours in response to genitourinary symptoms. METHODS: 473 (239 female and 234 male) subjects were enrolled at an STD clinic regardless of symptoms or infection status. Subjects completed a 30 day calendar recall interview of genitourinary symptoms, coital activity, sexual partners, and condom use. RESULTS: Of the total of 473 participants, 261 (55%) reported symptoms (61% women and 39% men). STI prevalence was 73% and 75% for symptomatic women and men, respectively. For black women the probability of coitus was decreased in the presence of vaginal discharge (OR 0.64, 95% CI 0.47 to 0.89). No change in coital activity was seen in non-black women in the presence of vaginal discharge. Having vaginal discharge did increase the likelihood of condom use by their partners (OR 2.48, 95% CI 1.05 to 5.88), if coitus occurred. Urethral discharge was not associated with coitus or condom use in men. However, in men, dysuria was associated with increased likelihood of condom use (OR 4.25, 95% CI 1.57 to 11.56) if coitus occurred. CONCLUSION: Black women altered both coital activity and condom use behaviours in response to vaginal discharge. In contrast, non-black women did not modify coital activity. Men increased condom use when having dysuria but did not alter coital activity. Changes in sexual behaviours may alter the risk of STI transmission independent of interactions with the healthcare system. STI education and prevention programmes need to better understand these gender and racial differences in developing effective strategies to reduce STI transmission.

Adolescent↗

The combination of X-ray-mediated radiosurgery and gene-mediated immunoprophylaxis for advanced intracerebral gliosarcomas in rats.

Rats with advanced, imminently lethal, approximately 4 mm diameter, left-sided intracerebral 9L gliosarcoma (9LGS), a well characterized malignant tumor with some similarities to human high-grade astrocytomas, were used as a therapy model 14 days post-implantation of 10(4) cells. Such tumor-bearing rats die within two weeks (median, 6 days) thereafter if untreated. However, if these tumors are exposed on day 14 to 12-25 Gy of an electron-equilibrated 6 MV photon beam (radiosurgery), survival is extended about 5-6 fold to a median of 34 days, but long-term survival (> 1 year) is increased only to approximately 18%. Multiple subcutaneous inoculations of radiation-disabled 9LGS cells post-radiosurgery (immunoprophylaxis) extended lifespan and long-term (> 1 year) survival minimally (median, 37 days; 25%, respectively). In sharp contrast, radiosurgery followed by multiple subcutaneous inoculations of radiation-disabled 9LGS cells that had been transfected with granulocyte macrophage colony stimulating factor (GMCSF), a cytokine with demonstrated immune-enhancing properties (i.e. gene-mediated immunoprophylaxis, GMIMPR) increased long-term survival to approximately 67%. To our knowledge, these results are the first to show that the combination of photon radiosurgery and GMIMPR is effective for an advanced, imminently lethal brain tumor in a mammal. These data raise the possibility that GMIMPR following radiation therapy might prove effective for the treatment of some human malignant gliomas.

Animals↗

Downregulation of free ubiquitin: a novel mechanism of p53 stabilization and neuronal cell death.

Neuronal death through activation of the p53 stress response pathway has been implicated in the pathogenesis of neurodegenerative disorders. The mechanisms regulating p53 accumulation and function in neurons are poorly understood. Recent evidence has demonstrated that Mdm2 is a major inhibitor of p53 that binds to and targets p53 for ubiquitin-mediated degradation. Here we demonstrate increased expression and co-localization of p53 and Mdm2 in the nuclei of degenerating neurons following treatment with either the excitotoxin, kainic acid, or the topoisomerase I inhibitor, camptothecin. Co-immunoprecipitation studies showed that p53-Mdm2 complexes were present in neuronal lysates. Dual immunofluorescence microscopy demonstrated that these complexes accumulated in neurons with a striking decrease in free ubiquitin levels. Exogenous ubiquitin restored p53 degradation to extracts from injured neurons confirming that Mdm2 function was intact. Finally, antisense-mediated downregulation of ubiquitin in cultured hippocampal neurons resulted in p53 and Mdm2 accumulation as well as apoptotic death. These results point to a novel mechanism to stabilize p53 and promote neuronal cell death in the central nervous system.

Animals↗

FK506, but not cyclosporin A, prevents mitochondrial dysfunction during hypoxia in rat hepatocytes.

Hepatic ischemia/reperfusion injury occurs in the clinical situations including liver transplantation. FK506 and cyclosporin A (CsA) are reported to be hepatotrophic agents in addition to being a powerful immunosuppressive agent. Studies were performed to determine whether the drugs influence a mitochondrial dysfunction under the hypoxic conditions in primary culture model of rat hepatocytes. The Anaeropack system was used for cell culture to create a hypoxia. Cells were treated with FK506 or CsA under the normoxic and hypoxic conditions. Hypoxia markedly decreased intracellular adenosine 5'-triphosphate (ATP) contents and the ketone body ratio (KBR, acetoacetate/beta-hydroxybutyrate) in culture medium as compared with normoxia. FK506 prevented the decreases of ATP contents and the KBR. In contrast, CsA had no effect on either ATP contents or the KBR. FK506, but not CsA, increased the KBR under the normoxic conditions. Under the hypoxic conditions, heat shock protein 70 (Hsp70) was detected after reoxygenation. FK506 enhanced the induction of Hsp70, but CsA again had no effect on Hsp70 induction. These results indicate that FK506 protects the hypoxia injury in part by preventing the mitochondrial dysfunction in concert with the enhancement of heat shock response in hepatocytes.

Adenine Nucleotides↗

Decreased yield, phenotypic expression and function of immature monocyte-derived dendritic cells in cord blood.

Dendritic cells are critical for the induction of both primary immune responses and immunological tolerance, as well as for the regulation of T-helper 1 (Th1) and 2 (Th2) immune responses. As neonates are notably deficient in Th1 response and cord blood transplantation is noted to result in less graft-versus-host disease (GvHD), we compared the phenotypic and functional characteristics of monocyte-derived dendritic cells (DCs) that favour Th1 development from cord blood and adult peripheral blood to understand the underlying mechanisms of these observations. Our results showed that: (1) after culture for 7 d with interleukin (IL)-4 and granulocyte--macrophage colony-stimulating factor (GM-CSF), cord blood monocytes generated less CD1a(+) cells than adult peripheral blood monocytes, and the CD1a+ cell percentage decreased thereafter; (2) compared with adult blood DCs, cord blood DCs had reduced intensity of expression of CD1a and MHC class II molecules, but the expression levels of CD11c and CD86 were similar; (3) the endocytotic ability of cord blood DCs was reduced compared with adult blood DCs, and this function was related to reduced mannose receptor (MR)-positive cells; (4) furthermore, the ability of cord blood DCs to stimulate CD3(+) T cells in an allogeneic mixed lymphocyte reaction was significantly lower than that of adult blood DCs. These results suggested that the dysfunction of cord blood monocytes in differentiating into professional DCs will affect the activation of naive T cells, especially Th1 development, and may be related to the susceptibility to different infections in the neonates, as well as the lower incidence of GvHD in cord blood transplantation.

Adult↗

Sexual behavior among adolescent women at high risk for sexually transmitted infections.

BACKGROUND: The temporal pattern of partners and sexual encounters may be key factors in the acquisition and transmission of sexually transmitted diseases (STDs). Behavior among adolescent women is of particular interest because they frequently have the highest prevalence and incidence of infection. GOAL: To examine coital diary data collected during a 7-month longitudinal study of young women at high risk of STDs and to describe their sexual behaviors, with particular attention to issues of partner sequence and overlap. STUDY DESIGN: A 7-month longitudinal study of young women infected with or having a sexual contact infected with Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis attending the STD clinic or one of four neighborhood adolescent health clinics. Data were collected at enrollment and at 1, 3, 5, and 7-month follow-up visits. Coital diaries were kept between visits. RESULTS: The average frequency of coital events was 0.94 per week. The median number of sexual partners during the follow-up period was one, and overlapping of partnerships was an uncommon occurrence. The number of days between the last coital event of a current relationship and the first encounter of a new relationship differed for those choosing a new partner (mean, 20.6 days) and those who returned to a previous partner (mean, 7.9 days; P < 0.001). CONCLUSION: Although at high risk for STDs, high-risk behavior was not common among the study population. Partner choice and the behavior of these partners may be more important elements than personal high-risk behavior in accounting for the high prevalence of sexually transmitted infections among inner-city adolescent women.

Adolescent↗

Changes of CD14 and CD1a expression in response to IL-4 and granulocyte-macrophage colony-stimulating factor are different in cord blood and adult blood monocytes.

Neonates are relatively immature in their immune response; thus, to further clarify the differences of monocyte function and differentiation between neonates and adults, we investigated their CD14(+)CD4(+) and CD14(+)CD16(+) monocyte subpopulations, production of IL-1beta and tumor necrosis factor-alpha induced by lipopolysaccharide, and their CD14 and CD1a phenotypic changes in response to IL-4 and granulocyte-macrophage colony-stimulating factor. Our results showed that 1) the expression of CD14 in cord blood monocytes was significantly lower than that in adult peripheral blood monocytes; 2) both the percentages of CD14(+)CD4(+) cells and CD14(+)CD16(+) cells among CD14(+) monocytes were also significantly lower in cord blood; 3) after stimulation by lipopolysaccharide for 72 h, production of both IL-1beta and tumor necrosis factor-alpha was lower in cord blood than that in adult peripheral blood; and 4) in response to IL-4 or GM-CSF, the phenotype development of CD14 and CD1a in cord blood and adult peripheral blood was different. Down-regulation of CD14 expression in response to IL-4 and GM-CSF was slower in cord blood monocytes than that in adult peripheral blood monocytes. After 9 d of culture in the presence of IL-4 and GM-CSF, the percentage of CD1a(+) monocytes was significantly more increased in cord blood than that in adult peripheral blood. The reduced expression of CD14 and other mature phenotype markers such as CD16 and CD4 as well as the reduced IL-1beta and tumor necrosis factor-alpha production may contribute to the impaired immune response of neonates. Slower down-regulation of CD14 by IL-4 and GM-CSF suggests that differential properties of cord blood monocytes in response to cellular stress signals take a longer time than those of adult peripheral blood monocytes.

Adult↗

[Effects of quinacrine on gut-origin bacteria/endotoxin translocation in rats with gut ischemia/reperfusion injury].

OBJECTIVE: To explore the influence of quinacrine, which is an inhibitor of phospholipase A2, on gut-origin bacteria/endotoxin translocation in rats with gut ischemia/reperfusion injury. METHODS: Forty-two Wistar rats were randomly divided into normal control (C, n = 6), gut ischemia/reperfusion injury control (IC, n = 12), quinacrine use at 3 hours after the injury(3 h, n = 12), and quinacrine use at 12 hours after the injury (12 h, n = 12) groups. The contents of blood endotoxin and TNF alpha in venae cavae and portal vein were measured in all groups. At the same time, tissue samples from mesenteric lymph nodes, liver, lungs and kidneys were harvested for bacterial culture. RESULTS: Plasma contents of endotoxin and TNF alpha were lowered in both quinacrine treatment groups (P < 0.01). The incidence of bacterial/endotoxin translocation was decreased by quinacrine use in mesenteric lymph nodes, lungs, liver and kidneys after the injury (P < 0.05 approximately 0.01). CONCLUSION: Early application of quinacrine in Wistar rats inflicted by gut ischemia reperfusion injury could obviously lower bacterial/endotoxin translocation and ameliorate the release of pro-inflammatory mediators and cytokines, thus attenuating injury to remote organs.

Animals↗

Preparation and Catalytic Properties of Amphiphilic Copolymer-Stabilized Platinum Metals Colloids.

Several metal colloids stabilized by an amphiphilic copolymer, poly(1-vinylpyrrolidone-co-acrylic acid) (abbreviated as PVPAA), were prepared by refluxing alcohol-water mixed solutions of the corresponding metal precursors. They had small particle sizes and narrow size distributions. Their catalytic activity was tested by hydrogenation of cyclooctene, 1-dodecene, and ortho-chloronitrobenzene (o-CNB). With the introduction of nickel(II) ions to a PVPAA-stabilized platinum catalytic system, selective hydrogenation of o-CNB to ortho-chloroaniline (o-CAN) with 97.1% selectivity and 100% conversion was obtained. Copyright 2000 Academic Press.

Journal Article↗

Insulin-like growth factor 1 promotes cord blood T cell maturation and inhibits its spontaneous and phytohemagglutinin-induced apoptosis through different mechanisms.

Functional immaturity of neonatal T cells is related to their immature phenotype, with the majority of neonatal T cells of naive (CD45RA+) T cells. The progression of T cells from naive cells to effector cells is dependent on the survival of Ag-specific T cells and their resistance to apoptosis. In this study, we showed for the first time that insulin-like growth factor 1 (IGF-1) converted cord blood CD45RA+ T cells to CD45RO+ T cells and inhibited cord blood T cell apoptosis. We found cord blood T cells stimulated with PHA would result in gradual loss of CD45RA and gain of CD45RO expression. IGF-1 further increased the loss of CD45RA and enhanced CD45RO expression in PHA-stimulated cord blood T cells. In addition, IGF-1 prevented cord blood T cells from spontaneous apoptosis through a mechanism other than Fas/FasL. In PHA-activated cord blood T cells, IGF-1 prevented both naive (CD45RA+) and memory/mature (CD45RO+) T cells from apoptosis. Moreover, cord blood T cells cultured with IGF-1 and PHA had a higher resistance to anti-Fas-induced apoptosis as compared with PHA-activated cord blood T cells. IGF-1 also significantly inhibited PHA-induced Fas expression on cord blood T cells. These results demonstrate that IGF-1 promotes the maturation and maintains the survival of cord blood T cells. Its antiapoptotic effect in PHA-activated cord blood T cells may be mediated through the down-regulation of Fas expression.

Antibodies, Monoclonal↗

The combination of boron neutron-capture therapy and immunoprophylaxis for advanced intracerebral gliosarcomas in rats.

Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About 7000 new cases are diagnosed yearly in the USA and GBM is almost invariably fatal within a few years after it is diagnosed. Despite current neurosurgical and radiotherapeutic tumor cytoreduction methods, in most cases occult foci of tumor cells infiltrate surrounding brain tissues and cause recurrent disease. Therefore the combination of neurosurgical and radiotherapeutic debulking methods with therapies to inhibit occult GBM cells should improve prognosis. In this study we have combined boron neutron-capture therapy (BNCT), a novel binary radiotherapeutic treatment modality that selectively irradiates tumor tissue and largely spares normal brain tissue, with immunoprophylaxis, a form of active immunization initiated soon after BNCT treatment, to treat advanced, clinically relevantly-sized brain tumors in rats. Using a malignant rat glioma model of high immunogenicity, the 9L gliosarcoma, we have shown that about half of the rats that would have died after receiving BNCT debulking alone, survived after receiving BNCT plus immunoprophylaxis. Further, most of the surviving rats display immunological-based resistance to recurrent 9LGS growth six months or more after treatment. To our knowledge this study represents the first time BNCT and immunoprophylaxis have been combined to treat advanced brain tumors in rats.

Animals↗