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Biomedical subjects

Q Gu

Publications and source records attributed to Q Gu.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effects of radiation on wound healing.

The pathological changes of radiation on wound healing in rats were observed by macroscopic, microscopic, and electronmicroscopic examination and detection of collagen types. We found that the wound healing process was obviously delayed by irradiation. First, the early phase inflammatory response was severely inhibited. In particular, the number of infiltrating macrophages and neutrophils was decreased, blood vessels were injured, and hemorrhage was evident. Second, the formation and maturation of granulation tissue were slowed down, fibroblasts were injured, and transcription of types and collagen mRNAs and synthesis and secretion of collagen were reduced. Finally, the reepithelialization process was delayed and the healing time was prolonged.

Animals↗
PubMed1997

Developmental expression and regulation of alpha 1 adrenergic receptors in cultured cortical neurons.

The expression and distribution of alpha 1 receptors in cultured neurons derived from rat visual cortex were studied with confocal microscopy using the fluorescently labeled alpha 1 adrenergic receptor selective antagonist BODIPY FL prazosin. The receptors were found to be clustered on neuronal somata and on proximal dendrites. We found that expression of the alpha 1 receptor is regulated both by neuronal excitability and by the usage of the receptor itself. The specificity of receptor regulation to the blockade of a particular receptor class was also studied. We approached this by comparing the effects of treatment with the alpha 1 adrenoreceptor antagonist prazosin and M1 muscarinic receptor antagonist pirenzepine on the expression of alpha 1 and M1 receptors in cultured cortical neurons. The results showed that blockade of muscarinic receptors with pirenzepine up-regulated muscarinic receptor expression selectively without changing alpha 1 receptor expression. Conversely blockade of alpha 1 receptors up-regulated alpha 1 expression but not muscarinic receptor expression. This implies that the expression levels of M1 and alpha 1 receptors are both regulated through specific signal transduction pathways. The interactions between neuronal activity and receptor activation (or blockade) on receptor expression were studied as well. In these experiments we compared the effects of high K+, tetrodotoxin (TTX), prazosin, and noradrenaline on the expression of alpha 1 and M1 receptors in cultured neurons. The results show that high K+ exposure increased both alpha 1 and M1 receptor expression regardless of the presence of receptor agonists or antagonists. On the other hand, TTX exposure reduced both alpha 1 and M1 receptor expression regardless of the presence of the receptor agonists or antagonists. This implies that regulation of receptor number is predominantly regulated by neuronal activity rather than by receptor occupancy.

Animals↗
PubMed1997

Serotonin facilitates synaptic plasticity in kitten visual cortex: an in vitro study.

We have addressed the role of serotonin-2C (5-HT2C) receptors in the development and maintenance of synaptic plasticity in the kitten visual cortex. In visual cortical slices, taken from 40- to 80-day-old kittens, bath application of serotonin markedly facilitated the induction of both long-term depression (LTD) and long-term potentiation (LTP). Field potential responses to white matter stimulation were recorded from layer IV after a regime of low frequency stimulation (LFS; 1 Hz, 15 min), which reliably induced LTP or LTD in younger kittens (less than 30 days of age). At 40-80 days, this protocol almost never induced LTD or LTP in layer IV. However, in 50% of the visual cortical slices studied in 40-80-day-old kittens, LTD or LTP was induced, if serotonin (1 or 10 microM) was co-applied with LFS. No such serotonin facilitation of long-term plasticity was ever detected in > 120-day-old animals, indicating that serotonin facilitates synaptic plasticity within a defined period of visual cortical development. Serotonergic 5-HT2C receptors are likely to contribute to the synaptic plasticity observed in layer IV, since mesulergine, an antagonist of the 5-HT2C receptor, completely blocked synaptic modifications induced by the combination of low frequency stimulation and serotonin application.

Aging↗
PubMed1997

A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor.

Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent survival factors for sympathetic, sensory and central nervous system neurons. GDNF mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-alpha) and the transmembrane protein tyrosine kinase Ret. In contrast, the mechanism by which the NTN signal is transmitted is not well understood. Here we describe the identification and tissue distribution of a GPI-linked protein (designated NTNR-alpha) that is structurally related to GDNFR-alpha. We further demonstrate that NTNR-alpha binds NTN (K[d] approximately 10 pM) but not GDNF with high affinity; that GDNFR-alpha binds to GDNF but not NTN with high affinity; and that cellular responses to NTN require the presence of NTNR-alpha. Finally, we show that NTN, in the presence of NTNR-alpha, induces tyrosine-phosphorylation of Ret, and that NTN, NTNR-alpha and Ret form a physical complex on the cell surface. These findings identify Ret and NTNR-alpha as signalling and ligand-binding components, respectively, of a receptor for NTN and define a novel family of receptors for neurotrophic and differentiation factors composed of a shared transmembrane protein tyrosine kinase and a ligand-specific GPI-linked protein.

Amino Acid Sequence↗
PubMed1997

The Ca2+/calmodulin binding domain of the Ca2+-ATPase linked to the Na+,K+-ATPase alters transport stoichiometry.

Using Xenopus oocytes as an expression system, we have investigated ion-transport and ouabain-binding properties of a chimeric ATPase (alpha1-CBD; Ishii and Takeyasu (1995) EMBO J. 14, 58-67) formed by the alpha1-subunit of chicken Na+,K(+)-ATPase (alpha1) and the calmodulin binding domain (CBD) of the rat plasma membrane Ca2(+)-ATPase. alpha1-CBD can be expressed and transported to the oocyte plasma membrane without the beta-subunit, and shows ouabain binding. In contrast to ouabain binding, this chimera requires the beta-subunit for its cation (Na+ and K+) transport activity. alpha1-CBD exhibits an altered stoichiometry of Na(+)-K+ exchange. A detailed analysis of 22Na+ efflux, 86Rb+ uptake, pump current and ouabain binding suggests that the chimeric molecule can operate in an electrically silent 2Na(+)-2K+ exchange mode and, with much lower probability, in its normal 3Na(+)-2K+ exchange mode.

Animals↗
PubMed1997

Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding proteins and protein kinase C-alpha.

We previously reported the cloning of a cDNA encoding human phosphatidylcholine-specific phospholipase D1 (PLD1), an ADP-ribosylation factor (ARF)-activated phosphatidylcholine-specific phospholipase D (Hammond, S. M., Tsung, S., Autschuller, Y., Rudge, S. A., Rose, K., Engebrecht, J., Morris, A. J., and Frohman, M. A. (1995) J. Biol. Chem. 270, 29640-29643). We have now identified an evolutionarily conserved shorter splice variant of PLD1 lacking 38 amino acids (residues 585-624) that arises from regulated splicing of an alternate exon. Both forms of PLD1 (PLD1a and 1b) have been expressed in Sf9 cells using baculovirus vectors and purified to homogeneity by detergent extraction and immunoaffinity chromatography. PLD1a and 1b have very similar properties. PLD1a and 1b activity is Mg2+dependent but insensitive to changes in free Ca2+ concentration. Phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate activate PLD1a and 1b but a range of other acidic phospholipids are ineffective. PLD1a and 1b are highly responsive to activation by GTP-gammaS-liganded ADP-ribosylation factor-1 (ARF-1) and can also be activated to a lesser extent by three purified RHO family monomeric GTP-binding proteins, RHO A, RAC-1, and CDC42. Activation of PLD1a and 1b by the RHO family monomeric GTP-binding proteins is GTP-dependent and synergistic with ARF-1. Purified protein kinase C-alpha activates PLD1a and 1b in a manner that is stimulated by phorbol esters and does not require ATP. Activation of PLD1a and 1b by protein kinase C-alpha is synergistic with ARF and with the RHO family monomeric GTP-binding proteins, suggesting that these three classes of regulators interact with different sites on the enzyme.

Adenosine Diphosphate Ribose↗
PubMed1997

Blockade of serotonin-2C receptors by mesulergine reduces ocular dominance plasticity in kitten visual cortex.

We have investigated the role of serotonin-2C (5-HT2C) receptors in modulation of ocular dominance plasticity in kitten visual cortex. A small quantity of the 5-HT2C receptor blocker, mesulergine, was infused into the visual cortex of one hemisphere of 5- to 7-week-old kittens using osmotic minipumps, while the control hemisphere received vehicle solution. At the same time, one eyelid of the experimental animals was sutured shut. The ocular dominance distributions in the visual cortex (area 17) were assessed using extracellular recording methods after 1 week of combined mesulergine infusion and monocular deprivation. We found that the majority of the neurons remained binocularly responsive in the mesulergine-treated hemisphere, while most of the neurons recorded were either unresponsive or only weakly responsive to the deprived eye in the control hemisphere. Local infusion of mesulergine into the kitten visual cortex thus reduced the shift of ocular dominance that normally occurs in animals of these ages following monocular deprivation. The blocking effect seems to be distance-dependent and therefore dose-dependent: the farther away the recording sites were from the injection site, the fewer binocularly responsive cells were found. These results are relevant to previous findings indicating transient overexpression of 5-HT2C receptor in visual cortex of kittens at these ages. The data suggest that the 5-HT2C receptor system may be involved in the formation and modification of ocular dominance columns in the developing visual cortex.

Animals↗
PubMed1997

HLA and longevity or aging among Shanghai Chinese.

Twenty-two centenarians and one hundred and seventy-nine nonagenarians (mean age 93 +/- 1.04 years) in the Shanghai Region of China were phenotyped for alleles of A (13 types), B (21 types) and C (6 types) loci of the human leukocyte antigen (HLA). The frequencies of HLA antigens were compared with 211 healthy adults whose ages ranged from 20 to 50 years. It was observed that A9 was highly associated with longevity (frequency in the longevity group is 38%, the control group 24%, P = 0.002). A30 showed marked inverse correlation (frequency in the longevity group is 8%, the control group 17%, P = 0.008). Cw3, Cw6 and Cw7 were also inversely correlated (P = 0.02, 0.04 and 0.02, respectively). Thus, it is likely that A9 may contribute to longevity while A30, Cw3, Cw6 and Cw7 may be associated with aging. The average superoxide dismutase (SOD) contents of erythrocytes in 48 cases with the HLA-A9 (without A30) antigen in the longevity group and in 13 cases with the HLA-A30 (without A9) antigen in the control group were 555 +/- 96 and 593 +/- 58 micrograms/gHb, respectively (t = 1.375, P > 0.05).

Adult↗
PubMed1997

The aging retarding effect of 'Long-Life CiLi'.

'Long-Life CiLi' ('CiLi') oral liquid, is composed of superoxide dismutase (SOD), polysacchairide, vitamin C, vitamin E and trace elements which were all extracted from a natural plant fruit Cili (Rosa roxburghii Tratt) in Guizhou, China. A set of indices were evaluated after administration of 'CiLi' 10 ml Bid, for two months in 50-75 years old healthy people, the mean value of NK cell activity (22.4 +/- 10.8-->27.5 +/- 12.9%, P < 0.05), SOD (453.0 +/- 24.2-->468.6 +/- 21.3 micrograms/gHb, P < 0.001), Catalase (15.5 +/- 1.7-->17.4 +/- 3.0 U/mgHb, P < 0.001) and GSH content (2.3 +/- 0.3-->2.6 +/- 0.5 mg/gHb, P < 0.001) in erythrocytes and 'delta CO, CI, SV, SI, LVET, LVETI and AC' values increased significantly, while the serum LPO level (4.20 +/- 0.78-->3.78 +/- 0.50 nmol/ml, P < 0.001), total microcirculation weighed value (1.87 +/- 1.0-->0.92 +/- 0.5, P < 0.001), delta PVR (-241.7 +/- 733.2-->187.9 +/- 938.2, P < 0.05) and the light reaction time (Simple RT, red light: 383 +/- 128-->332 +/- 68.9 ms, P < 0.05; selective RT: red light 709 +/- 287-->566 +/- 119 ms, P < 0.05; green light 639 +/- 162-->536 +/- 80 ms, P < 0.01) decreased significantly. There were no significant differences in the control group. The mean life span of fruit flies were significantly elongated for low, medium and high concentrations 'CiLi' treatment groups than in the control group (Female: 57.6 +/- 11.3-->62.1 +/- 12.8; 69.6 +/- 14.7; 62.6 +/- 12 days; P < 0.05 approximately 0.001. Male: 56.3 +/- 9.6-->64.9 +/- 12.4; 64.5 +/- 14.5; 64.8 +/- 14.1 days, P < 0.001). It is suggested that 'CiLi' has an aging retarding and geroprotection effect.

Aged↗
PubMed1997

Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury.

Traumatic brain injury (TBI) is associated with primary and secondary injury. A thorough understanding of secondary injury will help to develop effective treatments and improve patient outcome. In this study, the GM model of controlled cortical impact injury (CCII) of Lighthall (1988) was used with modification to induce lateral TBI in rats. Forebrain mitochondria isolated from ipsilateral (IH) and contralateral (CH) hemispheres to impact showed a distinct difference. With glutamate + malate as substrates, mitochondria from the IH showed a significant decrease in State 3 respiratory rates, respiratory control indices (RCI), and P/O ratios. This decrease occurred as early as 1 h and persisted for at least 14 days following TBI. The State 3 respiratory rates, RCI, and P/O ratios could be restored to sham values by the addition of EGTA to the assay mixture. A significant amount of Ca2+ was found to be adsorbed to the mitochondria of both the IH and the CH with higher values seen in the IH. The rate of energy-linked Ca2+ transport in the IH was significantly decreased at 6 and 12 h. These data indicate that CCII-induced TBI perturbs cellular Ca2+ homeostasis and results in excessive Ca2+ adsorption to the mitochondrial membrane, which subsequently inhibits the respiratory chain-linked electron transfer and energy transduction.

Animals↗
PubMed1997

Dietary selenium increases selenoprotein W levels in rat tissues.

Two experiments were conducted to evaluate the influence of dietary selenium (Se) on tissue levels of selenoprotein W (Se-W) in rats. Se dependent glutathione peroxidase (GPX) activity and Se levels were also determined for comparative measurements. In the first experiment, rats were fed a basal diet deficient in Se or supplemented with either 0.1 or 4.0 mg Se (as selenite) per kg diet for 6 wk. Se-W levels were significantly higher in muscle, spleen and testes of rats fed 0.1 mg Se per kg diet compared to those fed the deficient diet (controls), and those fed 4.0 mg Se per kg diet had significantly higher levels in muscle, brain and spleen (P < 0. 05) than those fed 0.1 mg Se per kg diet. No further increases, however, occurred in the tests. There was a significant increase (P < 0.05) of mRNA encoding Se-W in muscle with each increase of dietary Se. In the second experiment rats were fed the basal diet or this diet plus 0.01, 0.03, 0.06, 0.1, 1.0, 2.0 or 4.0 mg Se per kg diet. The levels of Se-W in muscle did not increase (P < 0.05) until 0.06 mg Se per kg diet were fed to rats. A very marked increase (P < 0.05) occurred when 1.0 mg Se per kg diet was fed with no further increases with higher levels. There was a linear increase of Se-W in brain (r = 0.89) and spleen (r = 0.98) with the Se concentration in the diet up to 0.1 mg Se per kg where a plateau was reached. The testes showed a different pattern in that a very marked increase (P < 0.01) occurred when only 0.01 mg Se per kg diet was fed where an inflection was reached. Except for muscle, GPX activities reached a plateau in all tissues when diets containing 0.06 to 0.1 mg supplemental Se per kg were fed. The Se concentration in these tissues increased at a linear rate with the Se concentration in the diets up to 0.1 mg Se per kg where it continued to rise at a different rate. The results indicate that in rats, the regulation of Se-W by Se is different for various tissues and differs from that for GPX.

Administration, Oral↗
PubMed1997

Race-ethnicity and determinants of carotid atherosclerosis in a multiethnic population. The Northern Manhattan Stroke Study.

BACKGROUND AND PURPOSE: Risk factors for carotid atherosclerosis have been studied in white populations but infrequently in multiethnic cohorts. The aim of this study was to determine the importance of race-ethnicity and other factors associated with carotid atherosclerosis in a mixed population of Hispanics, blacks, and whites. METHODS: As part of the Northern Manhattan Stroke Study, 526 stroke-free community residents (aged > or = 40 years; 41% men, 59% women; 46% Hispanic, 31% black, 23% white) were recruited through random-digit dialing and had vascular risk factor evaluations. Maximum internal carotid artery plaque thickness (MICPT) was measured with B-mode ultrasound. The frequency distribution of MICPT was examined in the three race-ethnic groups, and multivariate regression was performed to identify factors that were independently associated with MICPT. RESULTS: Mean MICPT in the entire sample was 1.5 +/- 1.4 mm, increased directly with age, and was greater in whites and blacks than Hispanics. Other independent determinants of MICPT included smoking, glucose, LDL cholesterol, and hypertension. After we controlled for these covariates, Hispanic (versus non-Hispanic) race-ethnicity was still an independent determinant of less carotid plaque. There was a significant interaction between race-ethnicity and LDL cholesterol, with a greater effect of increasing LDL cholesterol among Hispanics. CONCLUSIONS: Atherosclerotic risk factors were predictive of MICPT in this mixed-ethnic cohort. Hispanics had significantly less carotid plaque after adjustment for other known risk factors, but they also had a greater impact of increasing LDL cholesterol.

Adult↗
PubMed1997

Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke Study experience.

BACKGROUND/OBJECTIVE: Few studies have attempted to validate the "lacunar hypothesis." The accuracy of identifying lacunar and other nonlacunar mechanisms of infarction will be increasingly important in evaluating potential stroke treatments. The aim of this study was to determine the value of lacunar syndromes in predicting radiologic lacunes and the value of clinicoradiologic lacunes in predicting "lacunar infarction" as final stroke mechanism. METHODS: From 1990 to 1994, 591 patients with cerebral infarction, who were from northern Manhattan and over the age of 39, were prospectively examined. Data were collected on the admitting clinical syndrome (lacunar or nonlacunar) and brain imaging findings. Lacunar syndromes were categorized as pure motor hemiparesis (PMH), pure sensory syndrome (PSS), sensorimotor syndrome (SMS), ataxic-hemiparesis (A-H), and other lacunar syndromes. Brain imaging findings were classified as radiologic lacune or nonlacune. Positive predictive values, sensitivities, and specificities of lacunar syndromes for identifying radiologic lacunes were calculated. The final mechanism of infarction was determined after review of all the diagnostic tests and compared among the lacunar groups. RESULTS: Lacunar syndromes occurred in 225 cases. PMH was the most common lacunar syndrome, accounting for 45%, SMS 20%, A-H 18%, and PSS 7%. Lacunar syndromes had an overall positive predictive value (PPV) of 87% for detecting radiologic lacune: PSS 100%, A-H 95%, SMS 87%, and PMH 79%. Among the 195 patients who presented with a lacunar syndrome and had this condition confirmed radiologically, 147 were classified as having a final diagnosis of lacunar mechanism of infarction (PPV = 75%). Atherosclerosis accounted for 17 (9%), cardioembolism 10 (5%), cryptogenic 17 (9%), and other unusual causes 4 (2%). CONCLUSION: While lacunar syndromes, especially PSS and A-H, are highly predictive of lacune, in about one in four patients presenting with lacunar syndromes confirmed radiologically the condition is associated with nonlacunar mechanisms of infarction. Noninvasive neurovascular and cardiac evaluations are still warranted even among patients with lacunes.

Adult↗
PubMed1997

[The effects of IFN-gamma on the antitumor abilities of immunocytes and chemotherapeutic agents].

We studied the effects of IFN-gamma in immunotherapy and chemoimmunotherapy. The effects of IFN-gamma on TIL and LAK cytotoxicities on K562 tumor cell line and MKN45 gastric cancer tumor were observed. The antitumor effects of 5 chemotherapeutic agents with or without IFN-gamma on SGC7901 gastric cancer cell line were evaluated. The results showed that: (1) IFN-gamma obviously enhanced the cytotoxicities of TIL and LAK on 2 cell line: (2) IFN-gamma also increased the antitumor abilities of 5 agents on SGC7901 cell line. The study suggested that IFN-gamma is useful in immunotherapy and chemoimmunotherapy as an important immunomodulating agent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Taurine influx in cultured rat cardiomyocytes and changes after CVB3 infection.

Monolayer culture of spontaneously contracting rat heart cells was obtained from newborn SD rats and seeded into culture plates. 100TCID50 of coxsackie virus B3(CVB3) (Nancy strain) was added as the infected group. The dynamics of taurine transport across membrane of normal heart cells and changes after infection were examined by using radioactive isotope tracing techniques. The results demonstrated that: (1) two uptake systems of taurine with different affinities and capacities were present in the plasma membrane of cultured rat cardiomyocytes, the Km of high and low affinity were 9.5 x 10(-5) mol/L and 1.3 x 10(-2) mol/L, respectively; (2) taurine transport across membrane was sodium-dependent with a positive linear relationship between amount of taurine influx and extracellular concentration of sodium; in addition, it was also regulated by osmolarity; (3) beta-alanine, a carboxylic analog of taurine, could inhibit the uptake of taurine in dose-dependently; (4) taurine influx was decreased in cultured rat cardiomyocytes after infected with CVB3. (5) the Inhibition ratio of taurine transport was enhanced as the infected time prolonged. This experiment provides a basis for further investigation of kinetic test of taurine transport and more study should be carried out to learn the effect of taurine in viral myocarditis.

Animals↗
PubMed1997

Estrogen: nontranscriptional signaling pathway.

The long-term, genomic actions of estrogen and other steroid hormones are now relatively well understood. In this process, steroids bind to a cytoplasmic/nuclear receptor and the hormone receptor complex that, in turn, binds to DNA and triggers RNA-dependent protein synthesis. This process produces a response over time periods of several minutes to hours to days. Estrogen also exerts a variety of short-term effects (observed in milliseconds to minutes) on target organs that are not compatible with the classical genomic mechanism. These short-term, nontranscriptional actions are thought to be neuromodulatory in nature and critical for cell-cell communication. This chapter discusses current evidence for nontranscriptional effects of estrogen, with major emphasis on electrophysiological results demonstrating rapid, estrogen-induced changes in neuronal excitability. The mechanisms for nontranscriptional estrogen effects are also considered. These mechanisms include nonspecific influences on the lipid bilayer, specific binding to novel membrane receptors, direct modulation of neurotransmitter-ion channel complexes, and direct activation of second messenger systems. Particular attention will be focused on studies from our laboratory investigating mechanisms of estrogenic potentiation of kainate-induced currents in hippocampal neurons. Finally, the physiological relevance of short-term estrogenic actions will be addressed.

Animals↗