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H Xu

Publications and source records attributed to H Xu.

At least 649 records · Page 36Linked to original sources
PubMed1994

Characteristics of women with a family history of ovarian cancer. I. Galactose consumption and metabolism.

BACKGROUND: Galactose metabolism may be a risk factor for ovarian cancer based upon evidence that galactose causes ovarian failure and that ovarian cancer arises from premature ovarian failure. This study examines galactose-1-phosphate uridyl transferase (GALT) activity in women with a family history of ovarian cancer (FOC) to determine if low GALT activity occurs in women who are at risk for but in whom ovarian cancer has not yet developed. METHODS: The authors studied 106 premenopausal women (FOC patients) with one primary or two second-degree relatives with ovarian cancer compared with 116 age matched control subjects without a family history of ovarian cancer (FOC controls). All women completed questionnaires and had blood drawn to measure GALT activity and genotype. RESULTS: Mean erythrocyte GALT activity, in micromoles of hexose conversion per hour per gram of hemoglobin was 21.5 in FOC patients, significantly lower than the mean of 23.1 observed in FOC control subjects, (P = 0.001). FOC patients more frequently displayed the Duarte variant of galactosemia as detected by electrophoresis. In a subset of 87 patients and 113 control subjects for whom DNA was available, the allelelic frequency of the Duarte variant based upon molecular genetic detection of the N314D mutation that is associated with the Duarte variant was 15.5% among FOC cases compared with 7.5% among control subjects (P < 0.02). Galactose consumption did not differ between FOC patients and control subjects. CONCLUSION: Galactose metabolism differs between women with and without a family history of ovarian cancer, suggesting that it may be a genetic risk factor for ovarian cancer, possibly mediated through oocyte toxicity from galactose.

Adult↗
PubMed1994

Leukocytosis and resistance to septic shock in intercellular adhesion molecule 1-deficient mice.

Intercellular adhesion molecule 1 (ICAM-1) is one of three immunoglobulin superfamily members that bind to the integrins lymphocyte function associated 1 (LFA-1) and Mac-1 on leukocytes. We have generated mice that are genetically and functionally deficient in ICAM-1. These mice have elevated numbers of circulating neutrophils and lymphocytes, as well as diminished allogeneic T cell responses and delayed type hypersensitivity. Mutant mice are resistant to lethal effects of high doses of endotoxin (lipopolysaccharide [LPS]), and this correlates with a significant decrease in neutrophil infiltration in the liver. Production of inflammatory cytokines such as tumor necrosis factor alpha or interleukin 1 is normal in ICAM-1-deficient mice, and thus protection appears to be related to a diminution in critical leukocyte-endothelial interactions. After sensitization with D-galactosamine (D-Gal), ICAM-1-deficient mice are resistant to the lethal effect of low doses of exotoxin (Staphylococcus aureus enterotoxin B [SEB]), which has been shown to mediate its toxic effects via the activation of specific T cells. In this model, ICAM-1-mediated protection against SEB lethality correlates with a decrease in the systemic release of inflammatory cytokines, as well as with prevention of extensive hepatocyte necrosis and hemorrhage. ICAM-1-deficient mice sensitized with D-Gal, however, are not protected from lethality when challenged with low doses of endotoxin (LPS). These studies show that the different contribution of ICAM-1 in the activation of either T cells or macrophages is decisive for the fatal outcome of the shock in these two models. This work suggests that anti-ICAM-1 therapy may be beneficial in both gram-positive and -negative septic shock, either by reducing T cell activation or by diminishing neutrophil infiltration.

Animals↗
PubMed1994

Defective muscle basement membrane and lack of M-laminin in the dystrophic dy/dy mouse.

M-laminin is a major member of the laminin family of basement membrane proteins. It is prominently expressed in striated muscle and peripheral nerve. M-laminin is deficient in patients with the autosomal recessive Fukuyama congenital muscular dystrophy but is normal in patients with the sex-linked Duchenne and Becker muscular dystrophies. We have examined M-laminin expression in mice with autosomal recessive muscular dystrophy caused by the mutation dy. The heavy chain of M-laminin was undetectable in skeletal muscle, heart muscle, and peripheral nerve by immunofluorescence and immunoblotting in homozygous dystrophic dy/dy mice but was normal in heterozygous and wild-type nondystrophic mice. Immunofluorescence confirmed the presence of other major basement membrane proteins in the dystrophic mice. Very low levels of M-laminin heavy chain mRNA were detected by Northern blotting of muscle and heart tissue from dy/dy mice, suggesting that M-laminin heavy-chain mRNA may be produced at very low levels or is unstable. Information about the chromosomal localization of the M heavy-chain in human and mouse suggests that a mutation in the M-chain gene causes the muscular dystrophy in dy/dy mice. The dy mouse may provide a model for autosomal muscular dystrophies in humans and facilitate studies of functions of M-laminin.

Animals↗
PubMed1994

Compartmental distribution of tumor-specific monoclonal antibodies in human melanoma xenografts.

Monoclonal antibodies (MAb) are attractive for tumor therapy because of their exquisite specificity. Although a majority of tumor cells in small (< or = 20 mg) solid tumors can be labeled following systemic administration of antitumor cell MAbs, little quantitative information is available as to the distribution of these MAbs within the several compartments that comprise solid tumors. Our goal was to provide such data in a well-characterized melanoma xenograft system. In accord with earlier work, i.v.-injected, melanoma-specific MAbs 436 and IND1, directed, respectively, against the 125 kD and HMW-melanoma-associated antigens, accumulated in M21 and SK-MEL-2 tumor xenografts in amounts of approximately 20% of injected dose/g. However, only 20-24% of the MAbs present in tumor xenografts was bound to tumor cells; the great majority (76-80%) was in the tumor extracellular fluid (ECF) and collagenous residue fractions. These results could not be accounted for by MAb degradation or release of MAbs from tumor cells during xenograft dissociation. Rather, they reflected in large part interactions of MAbs with antigens which tumors had shed into the ECF. Thus, 48 h after i.v. injection of 20 micrograms of melanoma-specific, biotin-tagged MAb, 46-66% of that present in the tumor ECF was complexed with melanoma-associated antigens. Overall, 61-73% of the MAbs recovered from tumor xenografts were bound to tumor antigens (either to tumor cells themselves or to tumor-shed antigens). In contrast, only approximately 4% of a melanoma-nonspecific MAb (B72.3) accumulated per g tumor after i.v. injection and nearly all of this was free in the ECF. Consistent with these data, fluorescence microscopy revealed that i.v.-injected, fluorescein-tagged MAbs achieved highest concentrations in tumor stroma, particularly at the tumor-host interface. Flow cytometry of dissociated solid tumors revealed that both the fraction of MAb-labeled tumor cells and the amount of MAb/tumor cell could be increased by increasing the administered i.v. dose of melanoma-specific MAb. Nonetheless, even at the highest i.v. injected dose (300 micrograms), 15-37% of tumor cells lacked detectable MAb labeling. Taken together, the data indicate that delivery of tumor cell-specific MAbs to solid tumors cannot be equated with their delivery to tumor cells. This distinction is important for immunotherapeutic approaches that require MAb contact with tumor cells.

Animals↗
PubMed1994

Adult hypolactasia, milk consumption, and age-specific fertility.

Beta-galactosidase (lactase) allows the digestion of lactose as its component sugars, galactose and glucose. Considerable variation exists worldwide in the prevalence of adults who lose the ability to digest lactose after infancy (hypolactasia) as well as in the amount of milk products they consume. Clearly, those populations in which hypolactasia is infrequent and milk consumption high will have greater dietary exposure to galactose. Because there is clinical and experimental evidence that galactose may be toxic to ovarian germ cells, the authors sought to determine whether age-specific fertility rates in various countries correlate with the prevalence of adult hypolactasia and per capita milk consumption by analysis of published data on these variables. The authors found significant correlations among these variables such that fertility at older ages is lower and the decline in fertility with aging is steeper in populations with high per capita consumption of milk and greater ability to digest its lactose component. These demographic data add to existing evidence that dietary galactose may deleteriously affect ovarian function.

Adolescent↗
PubMed1994

Viral transduction of trkA into cultured nodose and spinal motor neurons conveys NGF responsiveness.

The trkA gene encodes the tyrosine kinase receptor that transduces the NGF signal. We have used a defective herpes simplex virus-1 (HSV-1) vector containing a full-length rat trkA sequence (pHSVtrkA) to express NGF receptors in primary cultures of neonatal nodose neurons and embryonic spinal motor neurons which are normally unresponsive to NGF. Transduction of rat neonatal nodose ganglion neurons and spinal motor neurons with pHSVtrkA resulted in expression of functional NGF receptors. Stimulation of these receptors by NGF resulted in the survival and the morphologic and biochemical differentiation of these neurons. These observations indicate that nodose and spinal motor neurons can express the downstream signal transduction apparatus necessary to mediate the survival and differentiating effects mediated by ligand binding to trkA and that transduction with pHSVtrkA can effectively convert NGF nonresponsive neurons into responsive ones.

Animals↗
PubMed1994

Dihydrocodeinone-hydrazone, dihydrocodeinone-oxime, naloxone-3-OMe-oxime, and clocinnamox fail to irreversibly inhibit opioid kappa receptor binding.

Previous work from our lab identified two subtypes of the opioid kappa receptor. Whereas the kappa1 receptor can be labeled by [3H]U69,593 (5 alpha,7 alpha,8 beta-(-)- N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl]-phenyl- benzeneacetamide), the kappa2 receptor can be labeled by [125I]OXY (6 beta-125iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan). Other data demonstrate that [125I]IOXY, like [3H]bremazocine, labels two populations of kappa2 receptors in guinea pig brain: kappa2a and kappa2b binding sites. In the present study, we tested the hypothesis that certain dihydrocodeinone and oxicodone derivatives, which have been shown to irreversibly block low affinity [3H]naloxone binding sites, would also bind irreversibly to opioid kappa receptor subtypes. We also tested the novel irreversible mu receptor antagonist, clocinnamox (14 beta-(p-chlorocinnamoylamino)-7,8-dihydro-N-cyclopropylmethylno rmorphinone mesylate). Wash-resistant inhibition (WRI) assays were conducted to detect apparent irreversible inhibition. The proportion of WRI attributable to inhibition of receptor binding, termed receptor inhibition (RI), was calculated by the equation: RI = WRI (wash-resistant inhibition) - SI (supernatant inhibition or inhibition attributable to residual drug.) Dihydrocodeinone-hydrazone, dihydrocodeinone-oxime and naloxone-3-OMe-oxime failed to produce any wash-resistant inhibition of kappa receptor binding. In contrast, preincubating guinea pig membranes with 1 microM clocinnamox produced a substantial degree of wash-resistant inhibition (greater than 90%) at kappa1 and kappa2 binding sites. However, as indicated by supernatant inhibition values of 70% to 90%, there was a large amount of residual clocinnamox which remained despite the use of an extensive washing procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Zn2+ inhibits the anion transport activity of band 3 by binding to its cytoplasmic tail.

Zn2+ can induce a conformational change of Band 3 with concomitant inhibition of its anion transport activity of human erythrocyte membrane vesicles only from the cytoplasmic side. The Zn2+ inhibition exhibits a dose-dependent manner with an apparent half maximal concentration of 50 microM ZnCl2 and can be reversed by 0.5 mM EDTA, but not by 1 mM dithiothreitol. The Zn2+ effect is specific and no similar inhibitory action could be observed by other divalent cations (Cu2+, Mn2+, Mg2+ or Sr2+).

Anion Exchange Protein 1, Erythrocyte↗
PubMed1994

The entire nucleotide sequence and genomic organization of potato aucuba mosaic potexvirus.

The entire nucleotide sequence (7057 nucleotides) of cDNA clones of potato aucuba mosaic virus (PAMV) was determined. The genome contains five major putative open reading frames (ORFs), designated from the 5' terminus as encoding putative proteins with M(r) of 187,379 (187 K), 26,326 (26 K), 12,101 (12 K), 8,183 (8 K) and 27,114 (27 K). The genomic organization of PAMV is essentially the same as that of several other potexviruses. The sizes and composition of the proteins encoded by the ORFs are generally similar to those found in other potexviruses. The genome and the capsid protein gene of PAMV, are the largest among the potexviruses sequenced to date.

Amino Acid Sequence↗
PubMed1994

Transfection of the mouse ICAM-1 gene into murine neuroblastoma enhances susceptibility to lysis, reduces in vivo tumorigenicity and decreases ICAM-2-dependent killing.

We determined the expression of intercellular adhesion molecules (ICAM) on neuro-2a cells in order to evaluate whether they were involved in cytolysis of murine neuroblastoma. Fluorescence-activated cell sorting analysis revealed that the control neomycin-resistance-gene-transduced line (neuro-2a/LN) had poor expression of ICAM-1 (mean channel fluorescence, MCF = 3.7). An ICAM-1-positive transfectant of neuro-2a (neuro-2a/ICAM-1+) (MCF = 64.3) was generated to evaluate directly the role of this adhesion molecule in cytolysis. Neuro-2a/ICAM-1+ was more sensitive to LAK killing (69.7% at an effector-to-target ratio of 100:1) compared to neuro-2a/LN (48.6%) (P < 0.001). Blocking of neuro-2a/LN and neuro-2a/ICAM-1+ lysis with anti-ICAM-1 monoclonal antibodies (mAbs) did not account for all the LFA-1-dependent killing. These data indicate that even in neuro-2a/ICAM-1+ cells, other LFA-1 ligands participated in the effector-target interaction. Therefore, we examined these cell lines for ICAM-2 expression. Both neuro-2a/LN and neuro-2a/ICAM-1+ lines expressed ICAM-2 (MCF = 16.4 and 16.5). ICAM-2 accounted for the majority of the LFA-1-dependent killing in the ICAM-1-negative target, neuro-2a/LN, while ICAM-1 played a primary role in the cytolysis of the ICAM-1+ transfectant. Inhibition of lysis in the presence of anti-ICAM-1 and ICAM-2 mAbs was comparable to that seen with the addition of anti-LFA-1 mAb, indicating that other LFA-1 ligands were not involved in this system. ICAM-1 expression was associated with decreased in vivo tumorigenicity, mice inoculated with neuro-2a/ICAM-1+ cells had a significantly longer survival compared to those receiving neuro-2a/LN cells (median survival time 35.5 versus 24.5 days) (P < 0.001). It is important to note that ICAM-1 transfection of murine neuroblastoma did not alter its metastatic potential. We conclude that transfection of mouse neuroblastoma with ICAM-1 increases its sensitivity to in vitro lysis and reduces its in vivo tumorigenicity. In ICAM-1-negative murine neuroblastoma cells, ICAM-2 plays a primary role in cell-mediated lysis.

Animals↗
PubMed1994

Dietary lipids modify the fatty acid composition of cartilage, isolated chondrocytes and matrix vesicles.

The effects of dietary lipids on the fatty acid composition of hyaline cartilage, epiphyseal chondrocytes (EC) and matrix vesicles (MV) were evaluated in chicks. A basal semipurified diet was fed to chicks containing one of the following lipid sources at 70 g/kg: soybean oil, butter+corn oil, margarine+corn oil or menhaden oil+corn oil (MEC). Articular and epiphyseal growth cartilage were isolated from the proximal tibiotarsus; EC and MV were subsequently released by trypsin (EC 3.4.21.4) and collagenase (EC 3.4.24.3) digestion followed by ultracentrifugation. The fatty acid composition of polar lipids in chick epiphyseal cartilage at three and six weeks, as well as articular cartilage, EC and MV at eight weeks of age revealed the presence of high levels of saturated and monounsaturated fatty acids (up to 85.5%) but low levels of n-6 polyunsaturated fatty acids (PUFA) (2.6-10.2%). Mead acid (20:3n-9, > 3%) was also present in cartilage, EC and MV lipids, and was unaffected by the dietary lipid treatments. Total n-3 PUFA concentrations were the highest in cartilage, EC and MV of chicks consuming MEC. Feeding MEC lowered the levels of 20:4n-6 in cartilage, but increased 20:5n-3 levels. The data are consistent with those reported previously which showed that cartilage tissues are low in n-6 PUFA and that they contain 20:3n-9. We furthermore demonstrated that the PUFA composition of cartilage can be modified by dietary lipids.

Age Factors↗
PubMed1994

Prohormone processing in permeabilized cells: endoproteolytic cleavage of prosomatostatin in the trans-Golgi network.

Many peptide hormones are synthesized as larger precursors which undergo endoproteolytic cleavage at paired basic residues to generate a bioactive molecule. Morphological evidence has implicated either the trans-Golgi network (TGN) or immature secretory granules as the site of prohormone cleavage. To identify the site where prohormone cleavage is initiated, we have used retrovirally infected rat anterior pituitary GH3 cells which express high levels of prosomatostatin, proSRIF, (Stoller TJ, Shields D (1988) J Cell Biol 107, 2087-2095). By incubating these cells at 20 degrees C, a temperature that prevents exit from the Golgi apparatus, proSRIF accumulated quantitatively in the TGN and no proteolytic processing was evident. Following the 20 degrees C block, the cells were permeabilized and proSRIF processing determined. Cleavage of proSRIF to the mature hormone was approximately 35-50% efficient, required incubation at 37 degrees C and ATP hydrolysis, but was independent of GTP or cytosol. The in vitro ATP-dependent proSRIF processing was inhibited by inclusion of chloroquine, a weak base, CCCP, a protonophore, or by pre-incubating the permeabilized cells with low concentrations of N-ethylmaleimide or bafilomycin, both inhibitors of vacuolar-type ATP-dependent proton pumps. These data suggest that ATP is required for generation of an acidic pH in the lumen of the TGN which is necessary for the activity of prohormone processing enzymes. By exploiting a permeabilized cell system, we have demonstrated that proSRIF cleavage is initiated in the TGN, in a reaction which is facilitated by a Golgi-associated vacuolar type ATPase.

Adenosine Triphosphate↗
PubMed1994

Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene.

The classic murine muscular dystrophy strain, dy, was first described almost 40 years ago. We have identified the molecular basis of an allele of dy, called dy2J, by detecting a mutation in the laminin alpha 2 chain gene--the first identified mutation in laminin-2. The G to A mutation in a splice site consensus sequence causes abnormal splicing and expression of multiple mRNAs. One mRNA is translated into an alpha 2 polypeptide with a deletion in domain VI. The truncated protein apparently lacks important qualities of the wild type protein and is unable to provide sufficient muscle stability.

Amino Acid Sequence↗