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Biomedical subjects

L Huang

Publications and source records attributed to L Huang.

At least 109 records · Page 6Linked to original sources

Clustering of cardiovascular risk factors with diabetes in Chinese patients: the effects of sex and hyperinsulinaemia.

OBJECTIVE: This study was designed to investigate factors which affect the clustering of cardiovascular risk factors with diabetes in Chinese patients. RESEARCH DESIGN AND METHODS: Six hundred and fifty-four patients with diabetes were assessed comprehensively for diabetes complications and cardiovascular risk factors in a metropolitan hospital in Beijing, China. Insulin resistance and secretion were also evaluated by measurement of glucose and insulin levels before and after a meal tolerance test. Results were analysed according to patient groups stratified by the number of cardiovascular risk factors coexisting with diabetes. RESULTS: Cardiovascular risk factors were common in Chinese diabetic patients. The clustering of three or more of these factors with diabetes occurred more often than by chance alone and was associated with postprandial hyperinsulinaemia. Patients with a high number of risk factors were more prone to macrovascular events but did not have higher albuminuria. Using the commonly adopted lower threshold for diagnosing obesity and central obesity in women, there were more women with multiple risk factors. However, this disappeared if the same criteria were used for men and women. Even in the presence of diabetes, cardiovascular risk factors were inadequately controlled in most patients. CONCLUSIONS: The concurrence of diabetes and other cardiovascular risk factors which constitute the metabolic syndrome is a common phenomenon in urban Chinese diabetic patients. It is associated with hyperinsulinaemia and possibly the female sex. This study emphasises the importance of public health measures to control cardiovascular risk factors in patients with diabetes.

Aged↗

Enhanced protection from renal ischemia-reperfusion [correction of ischemia:reperfusion] injury with A(2A)-adenosine receptor activation and PDE 4 inhibition.

BACKGROUND: We previously demonstrated in rats and mice that agonists of A(2A)-adenosine receptors (A(2A)-ARs) reduce renal injury following ischemia-reperfusion. We now extend these studies and examine the effects of ATL-146e (formerly DWH-146e), an A(2A)-AR agonist, and rolipram, a type IV phosphodiesterase (PDE 4) inhibitor, on murine renal injury following ischemia-reperfusion. METHODS: C57BL/6 mice were treated with rolipram, ATL-146e, or both compounds combined and were subjected to renal ischemia for 32 minutes and reperfusion for 24 to 48 hours. In vitro studies were performed on suspended and adhering human neutrophils. RESULTS: Continuous delivery of rolipram or ATL-146e during reperfusion reduced renal injury in a dose-dependent manner. Maximal protection was observed when ATL-146e was infused for six hours during reperfusion. Elevated plasma creatinine and myeloperoxidase activity produced by ischemia-reperfusion were reduced by rolipram (0.1 ng/kg/min) and ATL-146e (10 ng/kg/min) by up to approximately 60% and 70%, respectively. Co-infusion of both compounds produced a maximum reduction of plasma creatinine of approximately 90% and myeloperoxidase activity. In vitro studies on suspended and adhering human neutrophils demonstrated that selective stimulation of A(2A)-ARs by ATL-146e increased cAMP accumulation, reduced oxidative activity of activated neutrophils, and decreased activated neutrophil adherence. These responses were potentiated by rolipram. CONCLUSIONS: We conclude that the combined infusion of ATL-146e and rolipram leads to enhanced renal tissue protection from ischemia-reperfusion by mechanisms that may include reduced neutrophil adherence/recruitment and release of reactive oxygen species.

3',5'-Cyclic-AMP Phosphodiesterases↗

Differential regulation of hepatic bile salt and organic anion transporters in pregnant and postpartum rats and the role of prolactin.

We characterized expression and activity of the bile salt transporters Na(+)/taurocholate (TC) cotransporting polypeptide (Ntcp), and bile salt export pump (Bsep), and the expression of organic anion transporting polypeptides 1 and 2 (Oatp1 and 2) and multidrug resistance associated protein-2 (Mrp2) in pregnancy and throughout lactation in rats. The V(max) for Na(+)/TC cotransport in basolateral liver plasma membrane was increased 1.7-fold in 2 days postpartum relative to control and pregnant rats. This correlated well with an increase in Ntcp messenger RNA (mRNA) and a 2-fold increase in Ntcp protein. Ntcp mRNA remained significantly elevated until 14 days postpartum but had begun to decline by 21 days postpartum. The maximal secretory rate (nmol/min/g liver) for TC in the single pass isolated perfused liver was also increased by 10%, 31%, and 24% at 2, 14, and 21 days postpartum and correlated with increased expression of Ntcp and Bsep mRNA and protein. Infusion of ovine prolactin (oPRL) to ovariectomized rats increased expression of both Ntcp and Bsep mRNA and protein. These data indicate a coordinate increased expression of bile salt transporters postpartum and by PRL. Mrp2 mRNA was stable in pregnancy and postpartum, whereas Mrp2 protein expression decreased significantly in pregnancy, but returned to control levels postpartum. Organic anion transporting polypeptide 2 (Oatp2) mRNA was decreased in pregnancy and increased postpartum, but changes in Oatp2 protein were not significant. Oatp1 mRNA and protein were unchanged in pregnancy and postpartum.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth.

To understand the physiological functions of exogenous hepatocyte growth factor (HGF) on normal adult animals, we delivered human HGF gene into mice by a hydrodynamics-based in vivo gene transfection approach using a naked plasmid vector. Systemic administration of naked plasmid containing HGF cDNA driven under cytomegalovirus promoter (pCMV-HGF) by rapid injection via the tail vein produced a remarkable level of human HGF protein in the circulation, beginning to appear at 4 hours and peaking at 12 hours following injection. Tissue distribution studies identified the liver as the organ with the highest level of transgene expression. Through weekly repeated injections of plasmid vector, we achieved sustained, long-term, high levels of exogenous HGF expression in mice for 8 weeks. Increases of more than 31% and 16% in liver and body weights were found, respectively, in the mice that received pCMV-HGF plasmid compared with that given the control vector for 8 weeks. Expression of exogenous HGF in vivo activated mitogen-activated protein kinases and induced proliferating cell nuclear antigen expression in normal adult liver and kidneys. These data suggest that systemic administration of naked plasmid vector is a convenient, safe, and highly efficient approach to introduce and maintain exogenous HGF gene expression in vivo in a controllable fashion. Our results also indicate that long-term expression of human HGF in mice markedly activates growth-related signal transduction events, promotes cell proliferation, and leads to liver and overall body growth in whole adult animals.

Animals↗

Transparent morphology of the thoracoabdominal wall.

The transverse rectus abdominis myocutaneous (TRAM) flap has become the gold standard for autologous breast reconstruction in the last decade. The deep inferior epigastric perforator (DIEP) flap is a refinement of the conventional myocutaneous flap, which is based on anatomic studies of the abdominal wall. These authors have performed a transparent morphologic study of the abdominothoracic wall, in order to visualize the vessel architecture and relationships. The methodology of specimen processing, the anatomic findings, and modifications of surgical incisions are illustrated and discussed.

Abdominal Muscles↗

Is the postretention relapse of maxillary and mandibular incisor alignment related?

Previous studies suggest a poor association between initial and postretention pattern of incisor irregularity. One explanation may be that the incisor movements are limited by the boundaries provided by the incisors in the opposite arch. If so, postretention malalignment of the maxillary and mandibular incisors may be related. To test this hypothesis, long-term postretention study models of 96 patients with acceptable occlusion at the time of appliance removal were examined. The occlusal surfaces of the postretention study models were photocopied, and tooth anatomical contact points were digitized. An algorithm was used to fit the dental arch to the digitized points. The amount of incisor rotation and anatomical contact point displacement of maxillary and mandibular anterior teeth, relative to their respective dental arches, were computer generated. Overbite, the number of occlusal contact points in the anterior segment, and concavity of the lingual surfaces of the maxillary incisors were recorded manually. Statistical analyses demonstrated a significant association (P <.05) between the overall irregularity of the maxillary and mandibular incisors. The association did not differ among subgroups that were stratified according to overbite or number of occlusal contacts. No associations were found for the overall amount of incisor rotation in the 2 arches (P >.05). The amount and direction of displacement of antagonistic pairs of maxillary and mandibular central incisors were also associated (P <.05), but not the amount and direction of rotation (P >.05). The lingual configuration of the maxillary incisors did not affect the pattern of mandibular incisor malalignment.

Adult↗

The nature of after-hours telephone medical practice by GI fellows.

OBJECTIVE: Gastroenterology fellows on-call often serve as the initial or only contact for patients calling "after hours" with questions and symptoms. These fellows are rarely trained specifically in how to handle these calls. The aim of this study was to determine whether there are particular topics in telephone medicine that ought to be covered in new fellow training. Therefore, we sought to evaluate the nature of after-hours pages initiated by patients and to document the advice given by fellows. METHODS: The content of 100 patient-initiated telephone calls with GI fellows was recorded prospectively over 7 months. We included pages received between 5 PM and 8 AM daily as well as daytime calls on weekends. Fellows documented the time and length of the call, the issue raised by the patient, the advice given, and the patient's gender and attending gastroenterologist. When a particular patient paged more than once in a 24-h period, the repeat calls were not counted toward the 100-call tally. RESULTS: Twenty-two percent of calls occurred between 11 PM and 7 AM. Eighty-three percent of calls lasted less than 10 min. Sixty-seven percent of patients called because of symptoms. Only 30% of patients calling with symptoms were referred to the emergency room. Although only 1 of 13 patients with procedure-related (i.e., postendoscopy) symptoms required admission to the hospital, 18 of 54 (33%) patients with nonprocedure-related symptoms required admission either immediately or within a month of calling after hours. CONCLUSIONS: Most after-hours calls from patients are related to symptoms. Patients calling with postprocedure symptoms rarely require admission to the hospital. Conversely, a significant number of patients calling with non-procedure-related symptoms require admission within 30 days. Fellowship directors should consider providing training to fellows in the evaluation of symptoms over the telephone.

Fellowships and Scholarships↗

A theoretical study of passive control of duct noise using panels of varying compliance.

It is theoretically demonstrated that, in a duct, a substantial amount of sound energy can be transferred to flexural waves on a finite wall panel when the upstream portion of the panel is made to couple strongly with sound. The flexural wave then loses its energy either through radiating reflection sound waves or by internal friction. The effectiveness of the energy transfer and damping is greatly enhanced if the panel has a gradually decreasing in vacuo wave speed, which, in this study, is achieved by using a tapered membrane under tension. A high noise attenuation rate is possible with the usual viscoelastic materials such as rubber. The transmission loss has a broadband spectrum, and it offers an alternative to conventional duct lining where a smooth air passage is desired and nonacoustical considerations, such as chemical contamination or cost of operation maintenance, are important. Another advantage of the tapered panel is that, at very low frequencies, typically 5% of the first cut-on frequency of the duct, sound reflection occurs over the entire panel length. This supplements the inevitable drop in sound absorption coefficient, and a high transmission loss may still be obtained at very low frequencies.

Journal Article↗

Critical role for alpha/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T cells.

Under conditions of high antigenic load during infection with invasive lymphocytic choriomeningitis virus (LCMV) strains, virus can persist by selective clonal exhaustion of antigen-specific CD8(+) T cells. In this work we studied the down-regulation of the virus-specific CD8(+)-T-cell response during a persistent infection of adult mice, with particular emphasis on the contribution of the interferon response in promoting host defense. Studies were conducted by infecting mice deficient in receptors for type I (alpha/beta interferon [IFN-alpha/beta]), type II (IFN-gamma), and both type I and II IFNs with LCMV isolates that vary in their capacity to induce T-cell exhaustion. The main conclusions of this study are as follows. (i) IFNs play a critical role in LCMV infection by reducing viral loads in the initial stages of infection and thus modifying both the extent of CD8(+)-T-cell exhaustion and the course of infection. The importance of IFNs in this context varies with the biological properties of the LCMV strain. (ii) An inverse correlation exists between antigen persistence and responsiveness of virus-specific CD8(+) T cells. This results in distinct programs of activation or tolerance (functional unresponsiveness and/or physical elimination of antigen-specific cells) during acute and chronic virus infections, respectively. (iii) A successful immune response associated with definitive viral clearance requires an appropriate balance between cellular and humoral components of the immune system. We discuss the role of IFNs in influencing virus-specific T cells that determine the outcome of persistent infections.

Acute Disease↗

Kaposi's sarcoma-associated herpesvirus K-bZIP protein is phosphorylated by cyclin-dependent kinases.

The K8 locus in Kaposi's sarcoma-associated herpesvirus (KSHV) is syntenic with the Epstein-Barr virus (EBV) BZLF (Z) locus and expresses three alternatively spliced transcripts. The fully spliced transcript encodes K-bZIP, the KSHV homologue of the EBV immediate-early transcriptional transactivator Z. Here we show that despite the presence of alternatively spliced transcripts, the protein from the fully spliced RNA, K-bZIP, is the principal product detectable in KSHV-infected B cells. The protein is detected only in lytically infected cells and is localized to the nucleus. We further characterized K-bZIP by determining its phosphorylation status. Phosphoamino acid analysis revealed phosphorylation on serine and threonine. Analysis of the sites of K-bZIP phosphorylation by tandem mass spectrometry revealed that K-bZIP was phosphorylated on Thr 111 and Ser 167. These phosphorylation sites are contained within cyclin-dependent kinase (CDK) recognition sites with the consensus sequence (S/T)PXR, suggesting that K-bZIP could be phosphorylated by CDKs. We tested this hypothesis using an in vitro kinase reaction performed in whole-cell extracts that resemble in vivo conditions more closely than standard in vitro kinase reactions. We found that the three CDK-cyclin complexes we tested phosphorylated K-bZIP but not the control ORF 73 protein, which contains four (S/T)PXR sites. Ectopic expression of K-bZIP cannot reactivate KSHV from latency, and single and double mutants of K-bZIP in which alanines replaced the phosphorylated serine and/or threonine also failed to induce lytic replication. These studies indicate that K-bZIP is a substrate for CDKs and should inform further functional analyses of the protein.

Amino Acid Sequence↗

Insights into regulation and function of the major stress-induced hsp70 molecular chaperone in vivo: analysis of mice with targeted gene disruption of the hsp70.1 or hsp70.3 gene.

The murine hsp70 gene family includes the evolutionarily conserved hsp70.1 and hsp70.3 genes, which are the major proteins induced by heat and other stress stimuli. hsp70.1 and hsp70.3 encode identical proteins which protect cells and facilitate their recovery from stress-induced damage. While the hsp70 gene family has been widely studied and the roles of the proteins it encodes as molecular chaperones in a range of human pathologies are appreciated, little is known about the developmental regulation of hsp70.1 and hsp70.3 expression and the in vivo biological function of their products. To directly study the physiological role of these proteins in vivo, we have generated mice deficient in heat shock protein 70 (hsp70) by replacing the hsp70.1 or hsp70.3 gene with an in-frame beta-galactosidase sequence. We report here that the expression of hsp70.1 and hsp70.3 is developmentally regulated at the transcriptional level, and an overlapping expression pattern for both genes is observed during embryo development and in the tissues of adult mice. hsp70.1-/- or hsp70.3-/- mice are viable and fertile, with no obvious morphological abnormalities. In late embryonic stage and adult mice, both genes are expressed constitutively in tissues exposed directly to the environment (the epidermis and cornea) and in certain internal organs (the epithelium of the tongue, esophagus, and forestomach, and the kidney, bladder, and hippocampus). Exposure of mice to thermal stress results in the rapid induction and expression of hsp70, especially in organs not constitutively expressing hsp70 (the liver, pancreas, heart, lung, adrenal cortex, and intestine). Despite functional compensation in the single-gene-deficient mice by the intact homologous gene (i.e., hsp70.3 in hsp70.1-/- mice and vice versa), a marked reduction in hsp70 protein expression was observed in tissues under both normal and heat stress conditions. At the cellular level, inactivation of hsp70.1 or hsp70.3 resulted in deficient maintenance of acquired thermotolerance and increased sensitivity to heat stress-induced apoptosis. The additive or synergistic effects exhibited by coexpression of both hsp70 genes, and the evolutionary significance of the presence of both hsp70 genes, is hence underlined.

Alleles↗

Non-invasive quantitative assessment of oxidative metabolism in quadriceps muscles by near infrared spectroscopy.

BACKGROUND: Near infrared spectroscopy can be used in non-invasive monitoring of changes in skeletal muscle oxygenation in exercising subjects. OBJECTIVE: To evaluate whether this method can be used to assess metabolic capacity of muscles. Two distinctive variables abstracted from a curve of changes in muscle oxygenation were assessed. METHODS: Exercise on a cycle ergometer was performed by 18 elite male athletes and eight healthy young men. A measuring probe was placed on the skin of the quadriceps muscle to measure reflected light at two wavelengths (760 and 850 nm), so that the relative index of muscle oxygenation could be calculated. Exercise intensity was increased from 50 W in 50 W increments until the subject was exhausted. During exercise, changes in muscle oxygenation and blood lactate concentration were recorded. The following two variables for assessment of muscle oxygenation were then abstracted and analysed by plotting curves of changes in muscle oxygenation: the rate of recovery of muscle oxygen saturation (R(R)) and the relative value of the effective decrease in muscle oxygenation (D(eff)). RESULTS: Data analysis showed a correlation between muscle oxygenation and blood lactate concentration at the various exercise intensities and verified the feasibility of the experiment. Data for the athletes were compared with those for the controls using the Aspin-Welch test of significance; t = 2.3 and 2.86 for R(R) and D(eff) respectively. There were significant differences (p = 0.05) between the athletes and the control group with respect to these two variables. CONCLUSION: R(R) and D(eff) may be distinctive variables that can be used to characterise muscle oxidative metabolism during human body movement.

Adult↗

Increased contractility and altered Ca(2+) transients of mouse heart myocytes conditionally expressing PKCbeta.

Activation of protein kinase C (PKC) in heart muscle signals hypertrophy and may also directly affect contractile function. We tested this idea using a transgenic (TG) mouse model in which conditionally expressed PKCbeta was turned on at 10 wk of age and remained on for either 6 or 10 mo. Compared with controls, TG cardiac myocytes demonstrated an increase in the peak amplitude of the Ca(2+) transient, an increase in the extent and rate of shortening, and an increase in the rate of relengthening at both 6 and 10 mo of age. Phospholamban phosphorylation and Ca(2+)-uptake rates of sarcoplasmic reticulum vesicles were the same in TG and control heart preparations. At 10 mo, TG skinned fiber bundles demonstrated the same sensitivity to Ca(2+) as controls, but maximum tension was depressed and there was increased myofilament protein phosphorylation. Our results differ from studies in which PKCbeta was constitutively overexpressed in the heart and in studies that reported a depression of myocyte contraction with no change in the Ca(2+) transient.

Aging↗

NMDA antagonists in the superior colliculus prevent developmental plasticity but not visual transmission or map compression.

Partial ablation of the superior colliculus (SC) at birth in hamsters compresses the retinocollicular map, increasing the amount of visual field represented at each SC location. Receptive field sizes of single SC neurons are maintained, however, preserving receptive field properties in the prelesion condition. The mechanism that allows single SC neurons to restrict the number of convergent retinal inputs and thus compensate for induced brain damage is unknown. In this study, we examined the role of N-methyl-D-aspartate (NMDA) receptors in controlling retinocollicular convergence. We found that chronic 2-amino-5-phosphonovaleric acid (APV) blockade of NMDA receptors from birth in normal hamsters resulted in enlarged single-unit receptive fields in SC neurons from normal maps and further enlargement in lesioned animals with compressed maps. The effect was linearly related to lesion size. These results suggest that NMDA receptors are necessary to control afferent/target convergence in the normal SC and to compensate for excess retinal afferents in lesioned animals. Despite the alteration in receptive field size in the APV-treated animals, a complete visual map was present in both normal and lesioned hamsters. Visual responsiveness in the treated SC was normal; thus the loss of compensatory plasticity was not due to reduced visual responsiveness. Our results argue that NMDA receptors are essential for map refinement, construction of receptive fields, and compensation for damage but not overall map compression. The results are consistent with a role for the NMDA receptor as a coincidence detector with a threshold, providing visual neurons with the ability to calculate the amount of visual space represented by competing retinal inputs through the absolute amount of coincidence in their firing patterns. This mechanism of population matching is likely to be of general importance during nervous system development.

2-Amino-5-phosphonovalerate↗

Engineered collagen-PEO nanofibers and fabrics.

Type I collagen-PEO fibers and non-woven fiber networks were produced by the electrospinning of a weak acid solution of purified collagen at ambient temperature and pressure. As determined by high-resolution SEM and TEM. fiber morphology was influenced by solution viscosity, conductivity, and flow rate. Uniform fibers with a diameter range of 100-150 nm were produced from a 2-wt% solution of collagen-PEO at a flow rate of 100 microl min(-1). Ultimate tensile strength and elastic modulus of the resulting non-woven fabrics was dependent upon the chosen weight ratio of the collagen-PEO blend. 1H NMR dipolar magnetization transfer analysis suggested that the superior mechanical properties, observed for collagen-PEO blends of weight ratio 1:1, were due to the maximization of intermolecular interactions between the PEO and collagen components. The process outlined herein provides a convenient, non-toxic, non-denaturing approach for the generation collagen-containing nanofibers and non-woven fabrics that have potential application in wound healing, tissue engineering, and as hemostatic agents.

Collagen↗