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Biomedical subjects

J Tan

Publications and source records attributed to J Tan.

At least 109 records · Page 6Linked to original sources

[Effects of high manganese on cerebral development of the offspring of rats].

Pregnant rats were divided into three groups. Two groups are exposed to manganese from drinking water contaminated with manganese in 10 and 2 g/L respectively. Cerebral development of the offspring of rats was studied. The results are as follows. (1) The thickness of frontal and parental cortex of high dose Mn-exposed groups was significantly reduced, but glial fibrillary acid protein (GFAP) and the densities of its products were increased. (2) Cingular cortex was thickened, GFAP and the density of its products of cingular cortex was increased in both Mn-exposed groups compared with the control group. (3) The area, GFAP and the densits of its products of corpus callosium in the high Mn-exposed group were significantly increased compared with those in both low Mn-exposed and control groups.

Animals↗

Cloning and characterization of a 5.9 kb promoter region of the human pyruvate dehydrogenase alpha subunit gene.

A human genomic clone containing a 5.9 kb promoter region of the human pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) was isolated from a human X-chromosome library. The nucleotide sequence showed two Alu repeats at the -2880 and -2200 bp regions. Comparison between the -1400 bp E1alpha promoter and the -1241 bp E1beta promoter revealed a 57% homology, with a high degree of homology at the putative protein binding regions in these two promoters. Computer-aided transcription factor binding consensus sequence analysis revealed the presence of PPAR, HOXD, MyoD and other tissue-specific transcription factor binding sites. Promoter function analysis using the chloramphenicol acetyltransferase reporter gene indicated that the -2.2 kb/-1.7 kb and -5.9 kb/-5.2 kb regions of the E1alpha promoter may possess negative regulatory elements which are likely to function in a tissue-specific manner.

Amino Acid Sequence↗

In vivo magnetic resonance spectroscopy of human fetal neural transplants.

To better define the survival and cellular composition of human fetal neurotransplants in vivo, we performed quantitative 1H MRS to determine the concentration of the neuronal amino acid [N-acetylaspartate] within MRI-visible grafts. In all, 71 grafts in 38 patients [24 Parkinson's disease (PD), 14 Huntington's disease (HD)] were examined, as well as 24 untreated PD and HD patients and 13 age-matched normal controls. MRI appearances of edema were present in three out of 71 grafts, the remainder being consistent with histologically identified viable neural transplant tissue. N-acetylaspartate (NAA), creatine, choline, myoinositol and glutamine plus glutamate (Glx) were identified in all post-transplant putamens, with abnormal metabolites, lactate and/or lipid detectable in only three patients. Of 71 grafts, 19 occupied more than 60% of the MRS-examined volume (VOI) (mean 84.2 +/- 3%; range 61-100%). In those, [NAA] was 8.50 +/- 0.99 mM in eight PD spectra and 6.59 +/- 0.81 mM in 11 HD spectra, and was not significantly different from controls. In contrast, transplanted fetal neurones contain less than 0.4 mM of the neuronal amino acid NAA. This suggests that established fetal neurotransplants in the human putamen of both PD and HD patients are populated by adult neurones, axons and dendrites.

Adult↗

Inhibition of Alzheimer's beta-amyloid induced vasoactivity and proinflammatory response in microglia by a cGMP-dependent mechanism.

beta-amyloid (Abeta) peptides are the major protein components of senile plaques in Alzheimer's disease (AD) brains. Vascular damage and reactive gliosis are found colocalized with amyloid deposits in AD brains, suggesting that the vasculature may be a clinically significant site of AD pathology. Our results show that freshly solubilized Abeta1-40 enhances the vasoconstriction induced by endothelin-1 (ET-1) and increases resistance to relaxation triggered by nitric oxide (NO), suggesting that Abeta may oppose the NO/cGMP pathway. Using specific inhibitors and activators of the NO/cGMP pathway, we show that Abeta vasoactivity is not due to a modulation of nitric oxide synthase (NOS) or soluble guanylyl cyclase (sGC). However, we find that a selective cGMP phosphodiesterase (cGMP-PDE) inhibitor (dipyridamole) is able to interactively block the enhanced vasoconstriction as well as the opposition to relaxation induced by Abeta, suggesting that Abeta could effect the activity of this enzyme. Cyclic GMP levels, but not cAMP concentrations, are reduced after Abeta treatment of rat aortic rings, further substantiating this hypothesis. Moreover, in examination of this pathway in another cell type pertinent to AD, we find that Abeta induces a proinflammatory response in microglia as evidenced by increased leukotriene B4 release. We show that both dipyridamole and compounds which increase cGMP levels prevent Abeta-induced microglial inflammation. Our results suggest that therapeutic intervention aimed at reduction of microglial-mediated inflammation via inhibition of cGMP-PDE or elevation of cGMP may be beneficial in the treatment of AD.

Alzheimer Disease↗

A perspective of gene therapy in the glaucomas.

Gene therapy in the anterior and posterior segment tissues may have the potential to favorably influence aqueous hydrodynamics and retinal ganglion cell biology, thereby preventing, delaying, or minimizing glaucomatous damage to the optic nerve. We demonstrated the feasibility of using a herpes viral vector (ribonucleotide reductase defective HSV-1, hrR3) to deliver the lacZ reporter gene to living cat and rat eyes. Cats received injections into the anterior chamber and rats into the vitreous cavity. In cats, lacZ expression was detectable at 1 to 2 days in the anterior outer portion of the ciliary muscle and the lining of the intertrabecular spaces of the corneoscleral and uveal meshwork. Rat eyes showed lacZ expression in the retinal pigment epithelium and photoreceptor outer segments 2 days after injection.

Animals↗

The effect of leptin on Lep expression is tissue-specific and nutritionally regulated.

Leptin, the product of the Obese (Lep) gene, orchestrates behavioral and metabolic responses to nutrient intake. Here, we demonstrate tissue-specific autoregulation of Lep. Moderate increases in circulating leptin considerably decreased Lep expression in adipose tissue and induced lep expression in skeletal muscle, a tissue that normally does not express this gene. Changes in nutrient availability resulted in rapid alterations in Lep autoregulation. These findings demonstrate negative feedback regulation of Lep in fat, and indicate that leptin secretion can function as a vehicle of 'cross-talk' between adipose tissue and skeletal muscle, leading to tissue-specific modulation of the 'leptin signal'.

Adipose Tissue↗

Long-term effect of hyperbaric oxygenation treatment on chronic distressing tinnitus.

Tinnitus is still a phenomenon with an unknown pathophysiology with few therapeutic measures. During the last two decades, hyperbaric oxygenation therapy (HBO) has been used in the treatment of sudden deafness and chronic distressing tinnitus. In this study, we prescribed HBO to 20 patients who had had severe tinnitus for more than one year and who had already had other forms of tinnitus therapy with unsatisfactory results. Four patients could not cope with the pressure gradient. The effect of HBO was assessed using subjective evaluation and VAS scores before and after HBO. Follow-up continued until one year after treatment. Six patients had a reduction of tinnitus and accompanying symptoms, eight patients did not notice any change and two patients experienced an adverse effect. Any outcome persisted with minor changes until one year after treatment. HBO may contribute to the treatment of severe tinnitus, but the negative effect on tinnitus should be weighed carefully.

Adaptation, Psychological↗

Distribution of two HIV-1-resistant polymorphisms (SDF1-3'A and CCR2-64I) in East Asian and world populations and its implication in AIDS epidemiology.

Chemokine receptor CCR2 and stromal-derived factor (SDF-1) are involved in HIV infection and AIDS symptom onset. Recent cohort studies showed that point mutations in these two genes, CCR2-64I and SDF1-3'A, can delay AIDS onset > or = 16 years after seroconversions. The protective effect of CCR2-64I is dominant, whereas that of SDF1-3'A is recessive. SDF1-3'A homozygotes also showed possible protection against HIV-1 infection. In this study, we surveyed the frequency distributions of the two alleles at both loci in world populations, with emphasis on those in east Asia. The CCR2-64I frequencies do not vary significantly in the different continents, having a range of 0.1-0.2 in most populations. A decreasing cline of the CCR2-64I frequency from north to south was observed in east Asia. In contrast, the distribution of SDF1-3'A in world populations varies substantially, and the highest frequency was observed in Oceanian populations. Moreover, an increasing cline of the SDF1-3'A frequency from north to south was observed in east Asia. The relative hazard values were computed to evaluate the risk of AIDS onset on the basis of two-locus genotypes in the east Asian and world populations.

Acquired Immunodeficiency Syndrome↗

Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age.

The timing and nature of the arrival and the subsequent expansion of modern humans into eastern Asia remains controversial. Using Y-chromosome biallelic markers, we investigated the ancient human-migration patterns in eastern Asia. Our data indicate that southern populations in eastern Asia are much more polymorphic than northern populations, which have only a subset of the southern haplotypes. This pattern indicates that the first settlement of modern humans in eastern Asia occurred in mainland Southeast Asia during the last Ice Age, coinciding with the absence of human fossils in eastern Asia, 50,000-100,000 years ago. After the initial peopling, a great northward migration extended into northern China and Siberia.

Africa↗

Immunocytochemical detection of ornithine decarboxylase.

Ornithine decarboxylase (ODC), a regulatory enzyme of polyamine biosynthesis, is involved in cell growth and differentiation. Lack of information about the exact cellular and subcellular localization of ODC is one of the main obstacles to precise interpretation of the biological roles of the ODC/polyamine system. Here we describe the development and optimization of an immunocytochemical method to detect ODC in cells and tissues. For this purpose a monoclonal antibody (MP16-2) against a defined epitope of ODC protein was developed. Specificity of the antibody for ODC was substantiated by Western blotting and ELISA analysis using cell and tissue homogenates. In cultured cells, optimal staining results were obtained after fixation with crosslinking fixatives followed by permeabilization with methanol. In rat tissues, ODC immunoreactivity was best preserved in paraffin sections fixed with Bouin's fixative. Antigen retrieval using SDS and citrate buffer substantially increased ODC immunostaining and decreased background staining. Localization studies of ODC in different cell lines showed that strongest staining for ODC was found in the nucleoplasm of mitotic cells, whereas confluent cells showed moderate perinuclear staining. Immunocytochemical studies of various rat tissues showed high cytoplasmic immunostaining of ODC in epithelial cells of kidney, prostate, and adrenal medulla of testosterone-treated rats, in glandular epithelium of small intestine, and in pancreas of neonatal and adult rats. (J Histochem Cytochem 47:1395-1404, 1999)

3T3 Cells↗

Differential uterine expression of estrogen and progesterone receptors correlates with uterine preparation for implantation and decidualization in the mouse.

The present investigation examined the spatiotemporal expression of estrogen receptors (ER-alpha and ER-beta) and progesterone receptor (PR) in the periimplantation mouse uterus (days 1-8). ER-alpha messenger RNA (mRNA) was detected at much higher levels in the periimplantation uterus compared with that of ER-beta mRNA, the levels of which were very low in all uterine cells during this period. Results of in situ hybridization demonstrated expression of ER-alpha mRNA primarily in the luminal and glandular epithelia on days 1 and 2 of pregnancy. On days 3 and 4, the accumulation was localized primarily in stromal cells in addition to its presence in the epithelium. Following implantation on day 5, the accumulation of this mRNA was more condensed in the luminal and glandular epithelia, but declined in the subluminal epithelial stroma at the sites of implanting embryos. On days 6-8, the accumulation of ER-alpha mRNA was primarily localized in the secondary decidual zone (SDZ) with more intense localization in the subepithelial cells at the mesometrial pole. In contrast, signals were very low to undetectable in the primary decidual zone (PDZ), and no signals were detected in implanting embryos. The undifferentiated stroma underneath the myometrium also showed positive signals. The immunolocalization of ER-alpha protein correlated with the mRNA localization. Western blot analysis showed down-regulation of ER-alpha in day 8 decidual cell extracts consistent with the down-regulation of ER-alpha mRNA in decidual cells immediately surrounding the embryo on this day. The expression pattern of PR was also dynamic in the periimplantation uterus. On day 1, the accumulation of PR mRNA was very low to undetectable, whereas only a modest level of accumulation in the epithelium was noted on day 2. On days 3 and 4, the accumulation of this mRNA was detected in both the epithelium and stroma. In contrast, the expression was restricted only to the stroma with increased signals at the sites of implantation on day 5. On days 6-8, PR mRNA accumulation increased dramatically throughout the deciduum. The localization of immunoreactive PR correlated with the mRNA distribution in the periimplantation uterus. Taken together, the results demonstrate that the expression of ER-alpha, ER-beta, and PR is differentially regulated in the periimplantation mouse uterus. This compartmentalized expression of ER and PR provides information regarding the sites of coordinated effects ofestrogen and progesterone in the preparation of the uterus for implantation and decidualization during early pregnancy.

Animals↗

Uterine decidual response occurs in estrogen receptor-alpha-deficient mice.

Embryo-uterine interactions leading to the attachment reaction is followed by stromal cell proliferation and differentiation into decidual cells (decidualization) at the sites of blastocyst apposition. In rodents, decidualization is also induced by application of an artificial stimulus (intraluminal oil infusion) in a pseudopregnant uterus, or to one that has been appropriately prepared by exogenous progesterone (P4) and estrogen. The process of decidualization is under the control of these steroids in the presence of blastocysts or deciduogenic stimuli. Although it is well known that estrogen is required for the induction of progesterone receptors in the uterus, the functional importance of estrogen in the process of decidualization is poorly understood. To better understand the role of estrogenic actions in decidualization, we used wild-type and estrogen receptor-alpha knock-out (ERKO) mice for induction of decidualization employing a defined steroid hormonal treatment schedule. Our results demonstrate that P4 alone induces decidualization in ovariectomized wild-type or ERKO mice in response to intraluminal oil infusion in the absence of estrogen. A combined treatment of either estradiol-17beta (E2) or its catecholmetabolite 4-hydroxyestradiol-17beta(4-OH-E2) with P4 does not potentiate the decidual response produced by P4 treatment alone in either ovariectomized wild-type or ERKO mice. The induction of decidual response was associated with up-regulation of decidual cell marker genes, such as progesterone receptor, metallothionein-1, and cyclooxygenase-2. The results suggest that the stromal cell sensitivity to decidualization is critically dependent on P4-regulated events, and estrogenic induction of progesterone receptor via classical nuclear ER-alpha is not critical for this process.

Animals↗

Expression of the GLT-1 subtype of Na+-dependent glutamate transporter: pharmacological characterization and lack of regulation by protein kinase C.

Several subtypes of Na+-dependent glutamate transporters have been pharmacologically differentiated in brain tissues. Five distinct cDNA clones that express Na+-dependent glutamate transport activity have been isolated. One goal of the current study was to compare the pharmacological properties of the rat GLT-1 subtype of transporter to those identified previously using rat brain tissues. To accomplish this goal, GLT-1 was stably transfected into two different cell lines that express low levels of endogenous transport activity (MCB and L-M (TK-)). Several clones stably transfected with GLT-1 were isolated. In each cell line, Na+-dependent glutamate transport activity was saturable with similar Km values (19 and 37 microM). The pharmacological properties of GLT-1-mediated transport in these cell lines paralleled those observed for the predominant pharmacology observed in cortical crude synaptosomes. These data are consistent with other lines of evidence that suggest that GLT-1 may be sufficient to explain most of the Na+-dependent glutamate transport activity in cortical synaptosomes. Although recent studies using HeLa cells have suggested that GLT-1 can be rapidly up-regulated by activation of protein kinase C (PKC), modulation of PKC or phosphatase activity had no effect on GLT-1-mediated activity in these transfected cell lines. To determine if GLT-1 regulation by PKC is cell-specific, HeLa cells, which endogenously express the EAAC1 subtype of transporter, were stably transfected with GLT-1. Although EAAC1-mediated activity was increased by activation of PKC, we found no evidence for regulation of GLT-1. Despite the present findings, GLT-1 activity may be regulated by PKC under certain conditions.

ATP-Binding Cassette Transporters↗

Strategic uses of information technology in health care: a state-of-the-art survey.

The general perception that the use of information technology (IT) in health care is ten to fifteen years behind IT in other industrial sectors such as banking, manufacturing, and airline is rapidly changing. Health care providers, faced with an unprecedented era of competition and managed care, are now exploring the opportunities for using IT to improve the quality while simultaneously reducing the cost of health care. A revolution is taking place in the health care industry, with IT playing an increasingly important role in its delivery. In recent years, for example, the industry spent approximately $12 billion to $14 billion a year on IT. Further exponential growth is expected as the health care industry implements electronic medical records, upgrades hospital information systems, sets up intranets for sharing information among key stakeholders, and uses public networks, such as the Internet, for distributing health-related information and for providing remote diagnostics. Along with these drastic changes and the new approach to health care, the field of health/medical informatics and telematics has also experienced significant growth in the last few years. This article identifies and surveys the critical information technologies that are being adopted to provide strategic benefits to the various health care constituencies including hospitals and health maintenance organizations (HMOs).

Canada↗

Update on topical acne treatments.

Topical acne treatment can positively benefit patients with acne. This review summarizes clinical and prescribing information on currently available topical agents. The efficacy of the medications included in this report is supported by properly designed randomized clinical trials.

Acne Vulgaris↗

Hepatic radioembolization with Yttrium-90 glass microspheres for treatment of primary liver cancer.

OBJECTIVE: To study the clinical results of hepatic radioembolization with Yttrium-90 (90Y) glass microspheres in the treatment of primary liver cancer. METHODS: Seventeen patients with liver cancer were treated with glass microspheres from August 1996 to May 1998. Hepatic radioembolization with 90Y and lipiodol-ultrafluid was used. Percutaneous port-catheter system (PCS) implantations via femoral artery were performed in 12 patients. RESULTS: In the 17 patients, their mean ratio of absorbed doses between tumor and normal liver was 2.4:1. CT showed a significant reduction in tumor size in 11 of the 17 patients. Average survival was 19.5 months. The indwelling catheters of all the 12 patients were patent and no catheter tip locations were found. CONCLUSIONS: 90Y glass microsphere is one of the best radioisotopes. Not only good responses to the therapy of 90Y glass microspheres can be achieved in patients with metastatic liver cancer, but also in those with primary liver cancer, specially the localized or hypervascular mass. The patients with massive arterioportal shunt should not be limited to this form of radiation therapy. The percutaneous PCS implantation via the femoral artery is a new passageway for the treatment of primary liver cancer with 90Y glass microspheres and other interventional therapy.

Adult↗

[Effect of T lymphocyte in the acute rejection of liver xenograft].

OBJECTIVES: To study whether T cell take part in the acute rejection of liver corcondant xenograft. METHODS: The orthotopic liver transplantation model introduced by Hariharas was established. In grafts, CD4, CD8 and Fas-L were examined by immunohistochemistry at day 1, 3, 5, 7 post-transplantant respectively, and apoptosis in grafts was observed by histology and TUNEL (Terminal Deoxynucleotidyl Transferse-mediated dUTP nick-end Labelling,). RESULTS: In xenogenic grafts, T cell infilitration occurred at day 3, peaked at day 5, including CD4, CD8 subsets. The expression of Fas-L was found at day 4, peaked at day 5-6. The more severe the acute rejection is, the more the quantities of the expression of Fas-L is, the more the quantities of apoptosis is in grafts. CONCLUSIONS: T lymphocytes participate in the acute rejection of liver xenograft.

Animals↗

[HLA-amino acid residue matching standard and immunogenic response].

OBJECTIVE: To provide a standard for HLA-amino acid residue matching (Res M) for Chinese population and to evaluate its immunogenic response and sensitization to allograft. METHODS: Based on the setting up of DNA typing technique and the analysis of the distribution of HLA antigen frequencies, a new matching policy of Res M of 17 residues (10 amino acid residues for class I and 7 DR supertypic groups for class II) was presented and prospectively applied to 163 first-cadaver kidney transplants. Comparing with the 6-antigen matching program, the immunogenic response and sensitization of Res M to allograft were assayed using the mixed lymphocyte culture (MLC), cytokine in culture liquid, immune competent cells in the peripheral blood and specific anti-HLA IgG antibodies with PRA-STAT technique. RESULTS: The rate of Res-matched transplants increased significantly from 1.2% by Ag M to 39.9%. Immunogenic response and sensitization to allograft of recipients with Res-matched, containing index of stimulation (SI) of MLC, gamma-IFN representing Th1 cell, IL-10 representing Th2 cell, CD4+, CD8+, CD28+ T cell and the ratio of CD4/CD8, as well as the level of sHLA-IgG representing sensitization to allograft, were similar to those of Ag-matched transplants. Those parameters showed no difference between Res-matched and Ag-matched recipients, but showed significant difference in Res-mismatched or Ag-mismatched transplants. CONCLUSION: The New Res M can increase the rate of Res-matched transplants by a big margin, minimize the sensitization and immunogenic response to allograft, and be suitable to the clinical application to organ transplantation in Chinese Han population.

Amino Acids↗