Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 1,189 records · Page 66Linked to original sources

PubMed1997

Proton nuclear magnetic resonance studies on huwentoxin-I from the venom of the spider Selenocosmia huwena: 2. Three-dimensional structure in solution.

The three-dimensional structure in aqueous solution of native huwentoxin-I, a neurotoxin from the venom of the spider Selenocosmia huwena, has been determined from two-dimensional H NMR data recorded at 500 and 600 MHz. Structural constraints consisting of interproton distances inferred from NOEs and dihedral angles from spin-spin coupling constants were used as input for distance geometry calculation with the program XPLOR 3.1. The best 10 structures have NOE violations < 0.3 A, dihedral violations < 2 degrees, and pairwise root-mean-square differences of 1.08 (+/- 0.20) A over backbone atoms (N, C alpha, C). The molecule adopts a compact structure consisting of a small triple-stranded antiparallel beta-sheet and five beta-turns. A small hydrophobic patch consisting of Phe 6, Trp 28, and Trp 31 is located on one side of the molecule. All six lysine residues are distributed on the molecular surface. The three disulfide bridges are buried within the molecule. The structure contains an "inhibitor cystine knot motif" which is adopted by several other small proteins, such as omega-conotoxin, agatoxin IVA, and gurmarin.

Amino Acid Sequence↗

PubMed1997

Developing a mammary gland is a stat affair.

The mammary gland is a recent acquisition on the phylogenetic scale of organ evolution and is characterized by an unparalleled regenerative capacity. With each pregnancy an expanded lobulo-alveolar compartment rises on the ductal compartment and differentiates to secrete large amounts of milk during lactation. After weaning of the young the entire alveolar compartment undergoes apoptosis and is remodeled to return to a virgin-like state. Evolution recruited old hands from existing signaling pathways to guide and accomplish the extraordinary task of repeatedly building and destroying this highly specialized tissue. Seventy years ago it was known that the presence of estrogen, progesterone, and prolactin (PRL) was essential for ductal and alveolar development. The recent ability to generate mice from which genes have been deleted by homologous recombination has made it possible to gain molecular insight into the signaling pathways used by these hormones to effect mammary differentiation. In the cast of characters progesterone and PRL are on center stage. After binding to its receptor, PRL activates the JAK-STAT pathway leading to transcription of genes which induce alveolar proliferation and differentiation. In vivo experiments have shown that JAK-Stat signaling is mandatory for adult mammary gland development and lactation. Two Stat molecules, Stat3 and Stat5, appear to have opposite functions and their relative activity may serve to control developmental cycles of mammary tissue. While Stat5 activity has been linked to alveolar proliferation and function, Stat3 activity correlates with the loss of alveolar function, cell death and the initiation of mammary tissue remodeling.

Animals↗

PubMed1997

Crystal structure of RhoA-GDP and its functional implications.

RhoA, a ubiquitous intracellular GTPase, mediates cytoskeletal responses to extracellular signals. A 2.1 A resolution crystal structure of the human RhoA-GDP complex shows unique stereochemistry in the switch I region, which results in a novel mode of Mg2+ binding.

Crystallography, X-Ray↗

PubMed1997

Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects.

Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance abuse. Substance abuse is associated with novelty seeking, a heritable human personality trait which may be influenced by alleles of the dopamine D4 (DRD4) gene exon III VNTR. Consequently Kotler et al analysed the DRD4 VNTR in opiate-dependent subjects from Israel, and found a significant excess of the 7-repeat allele. We have attempted to replicate this finding using a Han Chinese case-control sample of 121 heroin-dependent subjects and 154 normal controls. We found two 7-repeat alleles which occurred exclusively in the patient group, and overall there was an excess of longer alleles, which did not reach significance (chi 2 = 7.04; P = 0.07). When the D4 VNTR was divided into 'long' (5-7 repeats) and 'short' (2-4 repeats), a significant excess of long alleles was observed in the patient group (P = 0.023, one-tailed), with an odds ratio of 2.30 (95% CI 1.07-4.93). We conclude that our findings support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for heroin abuse.

Adolescent↗

PubMed1997

Oxytocin and milk removal are required for post-partum mammary-gland development.

The oxytocin (OT)-neurophysin preprohormone is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. OT is cleaved from its precursor, transported from the magnocellular neurons to the posterior pituitary and secreted during labour and upon the suckling stimulus of pups. OT induces the contraction of myoepithelial cells surrounding the mammary alveoli, which leads to the ejection of milk. Mice deficient in OT are unable to nurse their young. Administration of OT enabled OT-deficient dams to nurse. We now show that OT and milk removal are also required for post-partum alveolar proliferation and mammary-gland function. Alveolar density and mammary epithelial-cell differentiation at parturition was similar in wild-type and OT-deficient dams. However, within 12 h after parturition approx. 2% of the alveolar cells in wild-type dams incorporated DNA and proliferated, but virtually no proliferation was detected in OT-deficient dams. Continuous suckling of pups led to the expansion of lobulo-alveolar units in wild-type but not in OT-deficient dams. Despite suckling and the presence of systemic lactogenic hormones, mammary tissue in OT-deficient dams partially involuted. Our studies demonstrate that post-partum alveolar proliferation requires not only systemic lactogenic hormones, such as prolactin, but also the presence of OT in conjunction with continued milk removal.

Animals↗

PubMed1997

Characterization of protein kinase C in photoreceptor outer segments.

Protein kinase C (PKC) has been implicated in regulating several proteins involved in phototransduction. This contribution characterizes the biochemical and immunological properties of PKC isozyme(s) in the photoreceptor outer segment. Activity measurements revealed that at least 85% of the PKC in this specialized compartment belongs to the subfamily of Ca2+-regulated (conventional) PKCs. Of the known Ca2+-dependent PKCs, only PKC alpha was immunodetected by western blot analysis of rod outer segment proteins. However, the ratio of immunoreactivity to enzyme activity for rod outer segment PKC was no more than 40% of that for brain PKC, using antibodies against conventional PKCs. Therefore, at least half the Ca2+/lipid-stimulated activity in rod outer segment preparations cannot be accounted for by the known isozymes, suggesting the presence of a previously uncharacterized isozyme. Despite extensive tests using a variety of antibodies against different domains of PKC alpha, PKC alpha could not be detected in rod outer segments by immunofluorescence of retinal sections. In summary, our data reveal that most of the PKC in photoreceptor outer segments is of the conventional type and that most, if not all, of this conventional PKC activity comes from a novel isozyme(s).

Animals↗

PubMed1997

Peroxynitrite-induced apoptosis in human intestinal epithelial cells is attenuated by mesalamine.

BACKGROUND & AIMS: Peroxynitrite (PN), a potent oxidant, has been implicated in the pathogenesis of gut inflammation and epithelial cell apoptosis. The aim of this study was to investigate mesalamine, a standard therapy for inflammatory bowel disease, to see if it attenuates PN-induced cytotoxicity in human intestinal epithelial cells and if mesalamine directly interacts with PN or its precursor, nitric oxide. METHODS: T84 and HT29 cells were divided in several protocols: mesalamine was administered 2 hours before, simultaneously, or 30 minutes after PN. T84 cells, grown in filter chamber inserts, were used to determine if basolateral or apical administration of PN initiated apoptosis and epithelial barrier function. The effects of mesalamine on PN decomposition and NO half-life were determined. RESULTS: Mesalamine resulted in a dose-dependent decrease in PN-induced apoptosis, whether mesalamine was administered before (>10 micromol/L; IC50, 16 micromol/L), simultaneously (25-200 micromol/L; IC50, 24 micromol/L), or 30 minutes (200 micromol/L) after PN exposure. Mesalamine protected the epithelial barrier function of T84 cells against PN. Mesalamine rapidly degraded PN, whereas the half-life of NO was not affected. CONCLUSIONS: The beneficial effects of mesalamine in the treatment of inflammatory bowel disease may involve an attenuation of PN-induced cell injury and apoptosis through direct and indirect mechanisms without affecting NO levels.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

Status of the eradication of indigenous wild poliomyelitis in the People's Republic of China.

A large nationwide outbreak occurred in 1989-1990 in China, in which nearly 10,000 poliomyelitis cases were reported. After two rounds of oral poliovirus vaccine (OPV) supplemental activity in nearly every province in the 1992-1993 winter season, no wild poliovirus was detected in 1993 in 22 provinces in the middle of China that contained 86% of the population. During the first national immunization days (NIDs) conducted in December 1993 and January 1994, 83 million children 0-47 months of age were immunized. In 1994, wild poliovirus was identified in only 6 of 2397 children with stool specimens tested. After a second NID in December 1994 and January 1995, no wild poliovirus was detected in 1995 despite a very high level of virus surveillance. In summary, double-round mass supplemental OPV immunizations in children 0-3 years old in two consecutive winters eliminated wild poliovirus from 23% of the world's population (1.2 billion people).

Child, Preschool↗

PubMed1997

Leaf nutrition and photosynthetic performance of sugar maple (Acer saccharum) in stands with contrasting health conditions.

Leaf nutrition and photosynthetic performance of sugar maple (Acer saccharum Marsh.) were compared between two sugar maple stands in northwestern Vermont with contrasting health conditions as indicated by annual basal area growth, degree of crown dieback, and foliar appearance. Observations made during the diurnal cycle of both stands showed no apparent leaf water stress. In both stands, leaves had similar concentrations of major non-structural carbohydrates (starch and sucrose). Over two consecutive growing seasons (1991 and 1992), we consistently observed lower leaf Ca and Mg concentrations in the declining stand than in the healthy stand. Compared with the healthy stand, lower leaf chlorophyll concentrations and apparent leaf chlorosis were observed in the declining stand, and some trees had very low foliar Ca and Mg concentrations (0.31 +/- 0.03% and 0.09 +/- 0.01%, respectively). Trees in the declining stand had lower light-saturated net photosynthetic rates on a dry mass basis at both ambient CO(2) (P(n,amb)) and saturating CO(2) (P(n,sat)) than trees in the healthy stand. There were significant linear correlations between P(n,amb) and leaf mass per unit area (LMA) and between P(n,sat) per unit leaf area and LMA. There were also linear correlations between both P(n,amb) and P(n,sat) and leaf N when expressed on an area basis in both stands, indicating that variation in LMA may have been largely responsible for the observed photosynthesis-nitrogen relationship. The values of P(n,amb) and P(n,sat) were not significantly correlated with leaf N on a mass basis but were weakly correlated with leaf Ca and Mg on a mass basis. We conclude that low leaf Ca or Mg concentrations may limit leaf CO(2) assimilation and tree carbohydrate status in the declining stand.

Journal Article↗

PubMed1997

Root carbohydrate reserves, mineral nutrient concentrations and biomass in a healthy and a declining sugar maple (Acer saccharum) stand.

Soil and root characteristics were contrasted between a "declining" and a "healthy" sugar maple (Acer saccharum Marsh.) stand in Vermont, USA. The declining stand had lower basal area increment and more crown dieback than the healthy stand. Soil pH and base cation content were lower and soil water content was higher at the site of the declining stand than at the site of the healthy stand, whereas soil temperature did not differ significantly between the sites. In live fine roots, concentrations of K and Ca were marginally (P < 0.07) lower in the declining than in the healthy stand, whereas concentrations of N, P, Mg, and Al were not significantly different (P = 0.13 to 0.87) between stands. Starch and soluble sugar concentrations of fine and coarse roots did not differ significantly between stands, indicating that crown dieback did not affect carbohydrate supply to the roots in the declining stand. Throughout the growing season, the standing live and dead root biomass were significantly higher in the declining stand than in the healthy stand, indicating that more carbon was allocated to roots and that root turnover was higher in the declining stand than in the healthy stand.

Journal Article↗

PubMed1997

Cerebral glucose utilization is reduced in second test session.

Cerebral glucose utilization was higher during the first positron emission tomography (PET) session than during the second session, as assayed using the PET [18F]fluorodeoxyglucose method in male human volunteers. This difference was due largely to data from subjects with low-trait anxiety, since subjects with high anxiety showed similar metabolism in both PET sessions. High-anxiety subjects showed greater right/ left ratios of cerebral metabolism than low-anxiety subjects, particularly during the second PET session. These findings suggest that the level of anxiety may be an important variable to consider in PET studies using multiple sessions.

Adult↗

PubMed1997

Catechol-O-methyltransferase Val158Met polymorphism: frequency analysis in Han Chinese subjects and allelic association of the low activity allele with bipolar affective disorder.

Catechol-O-methyltransferase catalyses the O-methylation of biologically active or toxic catechols and is a major component of the metabolism of drugs and neurotransmitters such as L-dopa, noradrenaline, adrenaline, and dopamine. Human catechol-O-methyltransferase activity is an autosomal partially dominant trait and is strongly associated with a valine to methionine substitution at codon 158 of the protein. About 25% of Caucasians have low activity, 50% intermediate activity and 25% high activity as determined by either phenotypic or genotypic measurement. In black populations, the low activity allele (Met158; COMTL) is less frequent with about 7% being homozygous. Using a PCR based genotyping assay, we report that the Met158 allele is also less frequent in normal Han Chinese subjects with about 3% of the population being homozygous. Because of its role in catecholamine metabolism and several lines of evidence pointing to a locus for psychosis near the COMT gene on chromosome 22q11, we have analysed the COMT Val158Met polymorphism as a candidate susceptibility factor for bipolar affective disorder. We report an association between bipolar affective disorder and the Met158 allele (p = 0.004) and genotype (p = 0.01) in 93 affected Chinese subjects and 98 controls. We hypothesize that either the low activity allele of catechol-O-methyltransferase is a risk factor for bipolar affective disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism.

Bipolar Disorder↗

PubMed1997

Role of the Fas/Fas ligand pathway in apoptotic cell death induced by the human T cell lymphotropic virus type I Tax transactivator.

Two distinct human diseases have been described in association with human T cell lymphotropic virus type I (HTLV-I) infection: adult T cell leukaemia and tropical spastic paraparesis/HTLV-I-associated myelopathy. Although comprehensive understanding of specific mechanisms underlying pathogenesis of either disease has not yet been achieved, the viral regulatory protein Tax is believed to play a significant role. Previous studies demonstrated the potential of Tax to transform host cells. Here, it is shown that the Tax transactivator has in addition the potential to induce T cell death by apoptosis. Using an inducible system (Jurkat cell line JPX-9), significant apoptotic cell death upon Tax expression was observed. In an attempt to detect the cellular genes mediating this effect, it was found that induction of Tax was associated with marked upregulation of the Fas ligand (FasL) gene. Tax-induced apoptosis was inhibited when the Fas/FasL pathway was interrupted by YVAD-cmk, the inhibitor of ICE-like proteases. Transient expression experiments provided additional support for the putative role of endogenous FasL in Tax-induced apoptosis. Upon cotransfection with Tax-expressing plasmid, the transcriptional activity of the FasL promoter was found to be significantly upregulated in Jurkat cells and several other cell lines, as measured by reporter gene expression. Furthermore, cotransfection using different Tax mutants demonstrated that both CREB and NF-kappaB activation domains of Tax protein were required for the transactivation to take effect.

Adult↗

PubMed1997

The development of nao li shen and its clinical application.

The traditional Chinese medicine Nao Li Shen (containing ginseng, gastrodia tuber, chuanxiong rhizome and red sage root) is used in craniocerebral injury, cervical spondylosis and cerebrovascular diseases. The preparation, as an orally administered liquid, was tested in Mongolian gerbils and shown to increase tolerance to ischaemia and anoxia. Clinical use of the preparation resulted in improvement in 96% of 202 patients, as judged by right cerebral blood flow, TCD and CT examination. We conclude that Nao Li Shen has a positive curative effect upon craniocerebral injury and sequelae of cerebrovascular diseases.

Adult↗

PubMed1997

Cloning and characterization of the Streptomyces peucetius dnmZUV genes encoding three enzymes required for biosynthesis of the daunorubicin precursor thymidine diphospho-L-daunosamine.

Characterization of the dnmZ, dnmU, and dnmV genes from the daunorubicin-producer Streptomyces peucetius by DNA sequence analysis indicated that these genes encode a protein of unknown function plus a putative thymidine diphospho-4-keto-6-deoxyglucose-3(5)-epimerase and thymidine diphospho-4-ketodeoxyhexulose reductase, respectively. Inactivation of each of the three genes by gene disruption and replacement in the wild-type strain demonstrated that all of them are required for daunosamine biosynthesis.

Amino Acid Sequence↗

PubMed1997

Substrate-dependent expression of Na+ transport and shunt conductance in A6 epithelia.

A6 epithelia grown in tissue culture vary enormously in their baseline rates of Na+ transport due to differences in growth media, serum, and other unknown factors. To evaluate the effect(s) of substrates on expression of Na+ transport, we determined short-circuit currents, open-circuit voltages, and electrical resistances of mature confluent A6 epithelia grown on a variety of commercially available permeable supports. Because the cells, growth conditions, and all other factors were the same, differences in transport could be attributed alone to the substrate on which the cells were grown. Tissues were grown on both large- and small-diameter inserts of the same type with differing ratios of edge length to area so that the contribution of the edge and tight junction conductances to the combined shunt conductance of the inserts could be evaluated. Shunt and cellular conductances and the cellular Thévenin electromotive force were determined after aldosterone stimulation and amiloride inhibition of Na+ transport. Marked and extreme differences were observed not only for expression of Na+ transport (controls, 0.09-3.94 microA/cm2; aldosterone, 1.53-28.2 microA/cm2) due to changes of apical membrane conductance but also for the development of junctional conductances (3,250 to < infinity omega.cm2) and edge conductances (13,175 to < infinity omega.cm) among substrates.

Amiloride↗

PubMed1997

Steroid hormone-dependent expression of blocker-sensitive ENaCs in apical membranes of A6 epithelia.

Weak channel blocker-induced noise analysis was used to determine the way in which the steroids aldosterone and corticosterone stimulated apical membrane Na+ entry into the cells of tissue-cultured A6 epithelia. Among groups of tissues grown on a variety of substrates, in a variety of growth media, and with cells at passages 73-112, the steroids stimulated both amiloride-sensitive and amiloride-insensitive Na+ transport as measured by short-circuit currents in chambers perfused with either growth medium or a Ringer solution. From baseline rates of blocker-sensitive short-circuit current between 2 and 7 microA/cm2, transport was stimulated about threefold in all groups of experiments. Single channel currents averaged near 0.3 pA (growth medium) and 0.5 pA (Ringer) and were decreased 6-20% from controls by steroid due to the expected decreases of fractional transcellular resistance. Irrespective of baseline transport rates, the steroids in all groups of tissues stimulated transport by increase of the density of blocker-sensitive epithelial Na+ channels (ENaCs). Channel open probability was the same in control and stimulated tissues, averaging approximately 0.3 in all groups of tissues. Accordingly, steroid-mediated increases of open channel density responsible for stimulation of Na+ transport are due to increases of the apical membrane pool of functional channels and not their open probability.

Aldosterone↗

PubMed1997

Regulated stimulation of epithelial cell DNA synthesis by fibroblast-derived mediators.

Interactions of interstitial fibroblasts with nearby epithelial cells are thought to play a role in lung growth and development. The present studies support this premise. Medium conditioned by second-passage lung fibroblasts (FCM) stimulated both DNA synthesis and accumulation in low-density (2 x 10(4)/cm2) cultures of type II alveolar epithelial cells. FCM effects did not require serum; they were time- and dose dependent, with half-maximal FCM activity at 1:8 dilution. A maximal response to FCM required 30 h of exposure. FCM activity was reduced in medium from fibroblasts treated with dexamethasone, suggesting physiological regulation. Type II cells subjected to cyclic mechanical stress demonstrated an increased response to FCM compared with static cultures. FCM activity did not appear to be accounted for by hepatocyte growth factor, keratinocyte growth factor, acidic fibroblast growth factor, or fibronectin. These results suggest that early passage lung fibroblasts release, by regulated pathways, one or more factors that stimulate DNA synthesis by type II cells. Sensitivity to FCM appears to be elevated in type II cell cultures subjected to cyclic mechanical stress.

Animals↗