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Biomedical subjects

Y Ge

Publications and source records attributed to Y Ge.

At least 109 records · Page 6Linked to original sources
PubMed1996

Flt3-ligand production by human bone marrow stromal cells.

Bone marrow stromal cells are important sources of cytokines and growth factors which participate in regulation of proliferation and differentiation of hematopoietic stem and progenitor cells. Recently flt3/flk-2-ligand (flt3-L), a new growth factor which uses a membrane tyrosine kinase receptor, was cloned. It is expressed in transmembrane and soluble forms and stimulates/co-stimulates proliferation and colony formation of hematopoietic stem/progenitor cells. It has not been reported whether flt3-L is produced by cells of the hematopoietic bone marrow microenvironment. We demonstrate the expression of flt3-L in bone marrow fibroblasts (BMF) and in stromal cells of adherent layers of long-term bone marrow cultures by RT-PCR, Northern blot, immunocytochemistry and FACS analysis. The latter two methods localized flt3-L intracellularly and on cell membranes. Treatment with interleukin-1 alpha increased the expression of flt3-L in BMF. This demonstrates production and modulation of flt3-L in stromal cells of human bone marrow.

Base Sequence↗
PubMed1995

Truncated WT1 mutants alter the subnuclear localization of the wild-type protein.

WT1 encodes a zinc-finger protein, expressed as distinct isoforms, that is inactivated in a subset of Wilms tumors. Both constitutional and somatic mutations disrupting the DNA-binding domain of WT1 result in a potentially dominant-negative phenotype. In generating inducible cell lines expressing wild-type isoforms of WT1 and WT1 mutants, we observed dramatic differences in the subnuclear localization of the induced proteins. The WT1 isoform that binds with high affinity to a defined DNA target, WT1(-KTS), was diffusely localized throughout the nucleus. In contrast, expression of an alternative splicing variant with reduced DNA binding affinity, WT1 (+KTS), or WT1 mutants with a disrupted zinc-finger domain resulted in a speckled pattern of expression within the nucleus. Although similar in appearance, the localization of WT1 variants to subnuclear clusters was clearly distinct from that of the essential splicing factor SC35, suggesting that WT1 is not directly involved in pre-mRNA splicing. Localization to subnuclear clusters required the N terminus of WT1, and coexpression of a truncated WT1 mutant and wild-type WT1(-KTS) resulted in their physical association, the redistribution of WT1(-KTS) from a diffuse to a speckled pattern, and the inhibition of its transactivational activity. These observations suggest that different WT1 isoforms and WT1 mutants have distinct subnuclear compartments. Dominant-negative WT1 proteins physically associate with wild-type WT1 in vivo and may result in its sequestration within subnuclear structures.

Binding Sites↗
PubMed1994

Cellular distribution of endotoxin after injection of chemically purified lipopolysaccharide differs from that after injection of live bacteria.

Lipopolysaccharide (LPS) chemically extracted from gram-negative bacteria is often used in animal models to study endotoxemia. Laser confocal microscopy and immunofluorescence staining for comparison of injections of live Escherichia coli O111:B4 bacteria with LPS extracted from the same strain showed that cellular localization and time course in rat organs were markedly different after the two injections. Fluorescent staining and image analysis software allowed quantitative comparison of LPS within tissues at different times and doses. Antigenic LPS was detected in all tissues 1 hour after injection of both bacteria and LPS and was present in liver and spleen over the 28-day study period. Whole bacteria were identified in tissue macrophages for the first 48 h after injection; later, bacterial cell walls were replaced by diffuse antigenic material throughout the cytoplasm. Antigenic LPS was localized within hepatocytes only after injection of chemically purified LPS. Cellular localization of LPS in tissues is dependent on the form injected. Animal models that use purified LPS may not be representative of gram-negative bacteremia.

Animals↗
PubMed1994

[Clinical assessment of physical dependence potential of dihydroetorphine hydrochloride (DHE)].

This paper reports the DHE substitution clinical trial in 38 heroin addicts. The CINA (Clinical Institute Narcotic Assessment) scale was used to assess physical dependence potential. The CINA scale contains 10 opioid withdrawal signs (nausea, vomiting, gooseflesh, sweating, restlessness, tremor, larcrimation, nasal congestion, yawning, changes in heart rate and systolic blood pressure) and 3 opiate withdrawal symptoms (abdominal pain, muscle pain and feeling hot or cold). For each subject admitted to the Drug Detoxification and Treatment Center his (her) status on each of the 13 items of CINA were immediately rated. Then, naloxone 0.4 mg was injected iv to precipitate withdrawal symptoms and at 5, 10, 15 min after the naloxone injection, the CINA score of each patient was rated again. The differences among the scores of pre- and post-naloxone injection is a measurement of the degree of withdrawal symptoms. Then, a single dose of DHE was administered sublingually to each patient, all withdrawal symptoms disappeared. These results show that DHE can compete with naloxone for opioid receptors. A good dose-response relationship was found between the 100% suppressive withdrawal sign doses of DHE and the degree of withdrawal sign in heroin addicts. The physical dependence potential of DHE given to heroin addicts sublingually was probably more than that of methadone given to heroin addicts orally by making reference to the report of Dr. Peachy.

Administration, Sublingual↗
PubMed1993

HLA-DR and -DQB1 genotyping in a Chinese population.

Using molecular biological methods, 58 unrelated Chinese from Shanghai were typed for HLA-DR and DQ. The Shanghai population possesses the principal HLA-DR and DQ characteristics of the oriental populations but with an increase of the DRB1*12 allele. So HLA typing of populations appears to be important not only for anthropological studies but also for transplantations and HLA associations with diseases.

Alleles↗
PubMed1993

Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum.

A novel member of the serine/threonine protein kinase gene family, designated sgk, for serum and glucocorticoid-regulated kinase, was identified in a differential screen for glucocorticoid-inducible transcripts expressed in the Con8.hd6 rat mammary tumor cell line. sgk encodes a protein of 49 kDa which has significant sequence homology (45 to 55% identity) throughout its catalytic domain with rac protein kinase, the protein kinase C family, ribosomal protein S6 kinase, and cyclic AMP-dependent protein kinase. sgk mRNA is expressed in most adult rat tissues, with the highest levels in the thymus, ovary, and lung, as well as in several rodent and human cell lines. sgk mRNA was stimulated by glucocorticoids and by serum within 30 min, and both inductions were independent of de novo protein synthesis. The transcriptional regulation by glucocorticoids is a primary response, since the promoter of sgk contains a glucocorticoid response element consensus sequence 1.0 kb upstream of the start of transcription which is able to stimulate chloramphenicol acetyltransferase reporter gene activity in a dexamethasone-dependent manner. Antibodies that specifically recognize sgk-encoded protein on an immunoblot were generated. This protein was shown to increase in abundance with glucocorticoid treatment in a manner which paralleled the mRNA accumulation. This is the first report of a presumed serine/threonine protein kinase that is highly regulated at the transcriptional level by glucocorticoid hormones and suggests a novel interplay between glucocorticoid receptor signalling and a protein kinase of the second messenger family.

Amino Acid Sequence↗
PubMed1993

Glucocorticoids induce a G1/G0 cell cycle arrest of Con8 rat mammary tumor cells that is synchronously reversed by steroid withdrawal or addition of transforming growth factor-alpha.

Con8 mammary tumor cells are an epithelial cell line derived from the 7,12-dimethylbenz(alpha)anthracene-induced 13762NF rat mammary adenocarcinoma. The synthetic glucocorticoid dexamethasone suppresses the growth of Con8 cells, and after 5 days of treatment with this steroid, Con8 cells undergo less than 0.5 population doublings. This growth arrest is accompanied by a 30-fold elevation in c-jun transcript levels, no change in c-fos expression, and a moderate increase in total AP-1 transcriptional activity. Dexamethasone inhibited DNA synthesis within one cell cycle, and flow cytometry of propidium iodide-stained nuclei demonstrated that dexamethasone growth-suppressed cells had a DNA content indicative of a specific cell cycle block in either G1 or G0. Consistent with a G1/G0 arrest of the cell cycle, dexamethasone did not prevent Con8 cells from entering the S phase after release from synchronization at the G1/S boundary by a double thymidine block. Analysis of [3H]thymidine incorporation and autoradiography of [3H]thymidine-labeled nuclei revealed that after either dexamethasone withdrawal or the addition of transforming growth factor-alpha (TGF alpha), Con8 cells synchronously reinitiate cell cycle progression. Northern blot analysis demonstrated that an induction of transcripts for the G1 marker genes c-myc and cyclin D1 occurs before cells enter the S-phase. After dexamethasone withdrawal, c-myc and cyclin D1 expression transiently peak at 2 and 4 h, respectively. In contrast, c-myc expression peaked at 0.5-1 h, whereas cyclin D1 expression was induced at 2 h and maintained at a high level after the addition of TGF alpha. Our results demonstrate that glucocorticoids induce a specific block of the cell cycle progression of a rat mammary tumor cell, and that after synchronous progression through the cell cycle, the temporal expression pattern for c-myc and cyclin D1 is distinct for dexamethasone release vs. the addition of TGF alpha to glucocorticoid-suppressed cells.

Adenocarcinoma↗
PubMed1992

Sequence, higher order repeat structure, and long-range organization of alpha satellite DNA specific to human chromosome 8.

We have characterized alphoid repeat clones derived from a chromosome 8 library. These clones are specific for human chromosome 8, as demonstrated by use of a somatic cell hybrid mapping panel and by in situ hybridization. Hybridization of the clones to HindIII digests of human genomic DNA reveals a complex pattern of fragments ranging in size from 1.3 to greater than 20 kb. One clone, which corresponds in size to the most prevalent genomic HindIII fragment, appears to represent a major higher order repeat in the chromosome 8 centromere. The DNA sequence of this clone reveals a dimeric organization of alphoid monomers. Restriction analysis of two other clones indicates that they are derivatives of this same repeat unit. The chromosome 8 alphoid clones hybridize to EcoRI fragments of genomic DNA ranging up to 1000 kb in length and reveal a high degree of polymorphism between chromosomes. Distribution of higher order repeat units across the centromere was examined by two-dimensional gel electrophoresis. Repeat units of the same size class tended to cluster together in restricted regions of centromeric DNA.

Base Sequence↗
PubMed1992

Digital subtraction angiography in the preoperative diagnosis of congenital heart disease.

From December of 1986 through February of 1990, digital subtraction angiography was performed on 156 patients, and specific diagnoses of congenital heart disease were made on the basis of information gathered by this imaging technique, supplemented by the physical examination. No other imaging techniques were used, for this was a prospective study designed to determine the accuracy of digital subtraction angiography alone in the diagnosis of congenital heart disease. When 80 of these 156 patients underwent subsequent operation, 75 were shown to have been diagnosed correctly, for an accuracy rate of 93.75%. Two patients died, for a mortality rate of 2.5%. The diagnostic value of digital subtraction angiography is discussed, as well as the compensative management of its artifacts.

Journal Article↗
PubMed1991

A hybrid cell mapping panel for regional localization of probes to human chromosome 8.

We have characterized a panel of somatic cell hybrids that carry fragments of human chromosome 8 and used this panel for the regional localization of anonymous clones derived from a chromosome 8 library. The hybrid panel includes 11 cell lines, which were characterized by Southern blot hybridization with chromosome 8-specific probes of known map location and by fluorescent in situ hybridization with a probe derived from a chromosome 8 library. The chromosome fragments in the hybrid cell lines divide the chromosome into 10 intervals. Using this mapping panel, we have mapped 56 newly derived anonymous clones to regions of chromosome 8. We have also obtained physical map locations for 7 loci from the genetic map of chromosome 8, thus aligning the genetic and physical maps of the chromosome.

Animals↗
PubMed1989

Immunoglobulins and complement in splenectomised and autotransplanted subjects.

Serum immunoglobulins and complement factors were investigated retrospectively in 35 splenectomised (n = 28) and autoreplanted (n = 7) patients following trauma. The main deficiency of the immune system following splenectomy was a reduction in the concentrations of serum IgM, C3, and Factor B with normal IgG, IgA and C4 values. These changes were not correlated with the time elapsed after splenectomy. However, patients who had splenic tissue autoreplantation had normal values of immunoglobulins and complement factors compared with healthy controls. Splenic replantation may be able to stop a fall in immunoglobulin and complement factor values after splenectomy.

Adolescent↗
PubMedDate not supplied

III. New developments: 2. Virtual MR endoscopy in the central nervous system.

Recent advances in three-dimensional (3D) data acquisition and postprocessing technologies have been playing a important role in widening the potential applications of 3D display. The authors described new applications of a virtual endoscopic algorithm for 3D display of high resolution MR images: (a) intracranial intravascular virtual MR endoscopy using the 3D fast imaging with steady state precession (FISP) sequence, and (b) virtual MR endoscopy of the cerebrospinal fluid (CSF) spaces using the constructive interference in steady state (CISS) three-dimensional Fourier transform (3DFT) sequence. The virtual endoscopic images were displayed with use of a commercially available perspective volume-rendering algorithm. Our initial experience showed that virtual MR endoscopy can be performed to observe the intracranial arteries and CSF spaces from the viewpoints within themselves. Although the clinical use of the intracranial virtual MR endoscopy has not been established yet, the images obtained are very attractive and further investigations in this field will be expected.

Central Nervous System↗
PubMedDate not supplied

Cavernous transformation of the portal vein secondary to tumor thrombosis of hepatocellular carcinoma: spiral CT visualization of the collateral vessels.

BACKGROUND: We investigated the constituting collateral vessels in cavernous transformation of the portal vein (CTPV) caused by tumor thrombosis of hepatocellular carcinoma (HCC) by using contrast-enhanced spiral computed tomographic (CT) examination. METHODS: Fifty-four histopathologically proven HCC patients with tumor thrombosis-induced CTPV were retrospectively included and assigned to cirrhosis negative (n = 31) and positive (n = 23) groups. Another 15 cirrhotic patients with portal hypertension but no HCC and CTPV were used for comparison. Standardized dual-phase contrast-enhanced spiral CT was performed for all patients. CT appearances of the collateral vessels of CTPV were observed, and their visualization rates were analyzed. RESULTS: Biliary (cystic and paracholedochal veins) and gastric (left and right gastric veins) branches of the portal vein were the most frequently visualized collateral vessels of CTPV. There was a marked difference in CT visualization rates for biliary branches between patients with and without CTPV (83-94% vs. 0). No difference existed in visualization rates for gastric branches across the three groups (77-87% for left gastric, 58-61% for right gastric vein). CONCLUSIONS: Biliary and gastric branches of the portal vein are the major collateral vessels of CTPV. The intergroup differences in CT visualization rates may provide clues to the roles that they might play in the hemodynamic adaptation process of CTPV.

Adult↗
PubMedDate not supplied

Automatic segmentation of the colon for virtual colonoscopy.

Virtual colonoscopy is a minimally invasive technique that enables early detection of colorectal polyps and cancer. Normally, a patient's bowel is prepared with colonic lavage and gas insufflation prior to computed tomography scanning. An important step for 3D analysis of the image volume is segmentation of the colon. The high-contrast gas/tissue interface that exists in the colon lumen makes segmentation of the majority of the colon relatively easy; however, two factors inhibit automatic segmentation of the entire colon. First, the colon is not the only gas-filled organ in the data volume: lungs, small bowel, and stomach also meet this criterion. User-defined seed points placed in the colon lumen have previously been required to spatially isolate the colon. Second, portions of the colon lumen may be obstructed by peristalsis, large masses, and/or residual feces. These complicating factors require increased user interaction during the segmentation process to isolate additional colonic segments. To automate the segmentation of the colon, we have developed a method to locate seed points and segment the gas-filled lumen sections without user supervision. We have also developed an automated approach to improve lumen segmentation by digitally removing residual contrast-enhanced fluid. Experimental results with 20 patient volumes show that our method is accurate and reliable.

Algorithms↗
PubMedDate not supplied

Necessity of carnitine supplementation in semistarved rats fed a high-fat diet.

We investigated the effects of carnitine supplementation on lipid metabolism in semistarved rats. The semistarved rats were fed a high-fat diet and half the normal energy intake for 2 wk. Carnitine was supplied daily at a dose of 250 mg/kg of body weight. The results showed that the concentration of plasma free carnitine increased significantly in semistarved and carnitine-supplemented rats compared with normal and semistarved rats. The activities of muscle carnitine palmitoyltransferase I and preheparin plasma lipoprotein lipase also were significantly increased in semistarved and carnitine-supplemented rats. The plasma triacylglycerol secretion rate was restored to normal by carnitine supplementation in semistarved rats. Urinary excretion of ketone bodies was reduced significantly after carnitine supplementation. We concluded that supplementation of carnitine can significantly increase the concentration of plasma free carnitine and improve lipid metabolism in semistarved rats fed a high-fat diet.

Animals↗
PubMedDate not supplied

Anti-Tumor CC49-zeta CD4 T cells possess both cytolytic and helper functions.

The authors report that the nature of the T-cell-receptor--derived signal in normal CD4+ T cells can induce interleukin-2 (IL-2) secretion or perforin-mediated cytolytic activity. Normal human T cells were genetically modified to express the tumor antigen specific chimeric immune receptor, CC49-zeta. The CC49-zeta chimeric immune receptor is comprised of the intracellular signaling domains of the TCR CD3zeta protein fused to the single chain scFv of the humanized CC49 antibody, which binds the pan-adenocarcinoma tumor antigen TAG-72. Patient-specific T cells genetically modified to express the CC49-zeta receptor have been used in patients with colon cancer. The authors report that both CD4 and CD8 T cells expressing the CC49-zeta receptor mediated the major histocompatibility complex-unrestricted lysis of TAG-72--expressing tumor cells with comparable efficiency. However, although the CC49-zeta receptor mediated target cell lysis, it did not support the production of IL-2, even in the presence of CD28 stimulation. Robust IL-2 secretion and T-cell proliferation were observed when the same CD4 CC49-zeta T cells were stimulated through the CD28 receptor and endogenous T-cell receptor. These results indicate that CD4 T lymphocytes possess the capacity to act as both cytolytic and helper T cells and that this difference in effector function is controlled by the nature of the T-Cell receptor--derived signals.

Antigens, Neoplasm↗