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Biomedical subjects

X Bai

Publications and source records attributed to X Bai.

At least 73 records · Page 4Linked to original sources

Effects of the novel GH secretogogue, hexarelin on GH secretion and phosphatidylinositol hydrolysis by human pituitary somatotrophinomas in cell culture.

The effects of the novel GH-releasing hexapeptide, Hexarelin, on cultured human pituitary somatotrophinomas were investigated. Hexarelin (0.01-100 nmol/L) dose-dependently stimulated GH secretion up to 4.6-fold. Maximal effects occurred with 10 nmol/L. These effects were very similar to those observed with GHRP-6. The effects of Hexarelin were reduced by phloretin, an inhibitor of protein kinase C (PKC). The rate of phosphatidylinositol (PI) hydrolysis was markedly increased by Hexarelin in a dose-dependent manner. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs in a PKC-dependent manner, probably via activation of the PI transduction system.

Adenoma↗

TPA enhances growth hormone (GH) secretion effect of GH-releasing hormone (GHRH) by human gsp-positive pituitary somatotrophinomas.

In recent years, one of the most exciting advances in the researches of pituitary adenomas is the discovery that 30%-40% of human pituitary somatotrophinomas carry somatic mutations of the gene for the alpha-subunit of the stimulatory GTP-binding protein, Gs (Gs alpha). These mutations, termed gsp oncogenes, may play an important role in the tumorigenesis of pituitary adenomas. Of 10 somatotrophinomas examined, 3 (30%) were proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction (PCR). GHRH exerted a significant stimulatory effect on GH secretion in 2 of 3 gsp-positive and 4 of 7 gsp-negative tumors. Moreover, phorbol ester, 1, 2-tetradecanoylphorbol-13-acetate (TPA), enhanced stimulation of lated the GH secretion effect exerted by GHRH in gsp-positive somatotrophinomas, whereas this effect was not observed in gsp-negative tumors. This result suggests that the protein kinase C signal system as well as adenylyl cyclase-cAMP-protein kinase A intracellular signal transduction system plays a pivotal role in GH secretory control of GHRH, which may work together via a cross-talk mechanism.

Adenoma↗

Development and validation of a quantitative polymerase chain reaction assay to evaluate minimal residual disease for T-cell acute lymphoblastic leukemia and follicular lymphoma.

The presence of occult disease in cancer patients after therapy is one of the major problems faced by oncologists. For example, although 95% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients have a complete therapeutic response to multiagent chemotherapy, half will relapse, indicating that they must have harbored low levels of residual cancer cells at the end of therapy. Sensitive detection assays promise to help identify those patients that carry this minimal residual disease (MRD) and are at risk of relapse. We have developed and validated a quantitative polymerase chain reaction (PCR) assay targeting tumor-specific chromosomal rearrangements, including del(1) involving the tal-1 locus in pediatric T-ALL and t(14;18) involving the bcl-2 locus in follicular lymphoma. This quantitative PCR assay utilizes a synthetic internal calibration standard (ICS) that contains priming sequences identical to those found flanking the chromosomal rearrangement breakpoints. Using this ICS-PCR method, the limits of detection were 5 tumor cells at ratios of 1 tumor cell in 10(5) normal cells and a linear range up to 100% tumor cells. This ICS-PCR method has also performed well in terms of precision and accuracy as indicated by low coefficients of variation, minimal random, proportional, and constant errors, and good clinical sensitivity and specificity characteristics. This technique will allow for the evaluation of parameters such as the rate of therapeutic response and the levels of MRD as predictors of patient outcome.

Base Sequence↗

The human uniqueness of HIV: innate immunity and the viral Tat protein.

We have previously reported, and confirm here, that the human innate system of natural antibodies includes two, each of which is reactive, presumably by happenstance, with a specific sequence of HIV Tat protein. Comparison of cohorts of HIV+ and normal (HIV-) sera indicate that, following a period of post-infection latency, the titers of those natural antibodies decline and other Tat reactive antibodies, as evidence of induced immune response, do not arise. That human-typical pattern of innate/adaptive reactivity with HIV Tat protein is shared by chimpanzees, but not by other mammals tested in this study, in which those natural antibodies are not present, and apparently induced Tat-reactive antibodies do arise. Evidence of a temporal relationship between the decline of the Tat reactive natural antibodies and progression of HIV pathogenesis, including demise of CD4+T cells, suggests a role for those antibodies in retardation of that pathoprogression. However, that providential arrest of Tat-related pathogenicity may be limited by the immune system recognition of the natural antibody-reactive sequences of Tat as "self" with consequent induction of tolerance and restriction of production of those antibodies. The limited occurrence of progression to AIDS in chimpanzees may reflect an additional innate characteristic, one of resistance to tolerance-based diminishment of the protective natural antibodies. Although not yet defined, that characteristic may be shared by the occasionally observed HIV+ humans known as LTNP (longterm-non-progressors).

Animals↗

Isolation and characterization of SYN1, a RAD21-like gene essential for meiosis in Arabidopsis.

The proper pairing, recombination, and segregation of chromosomes are central to meiosis and sexual reproduction. The syn1 mutation was previously identified as a synaptic mutant in a T-DNA-tagged population of plants. SYN1 has been isolated and found to exhibit similarity to Schizosaccharomyces pombe RAD21 and RAD21-like proteins, which are required for chromosome condensation and sister chromatid cohesion during mitosis. Plants homozygous for syn1 are male and female sterile and show defects in chromosome condensation and pairing beginning at leptonema of meiosis I. Fragmentation of the chromosomes was observed at metaphase I. Alternative promoters produced two SYN1 transcripts. One transcript was expressed at low levels in most tissues, whereas the other was expressed only in prebolting buds. DNA blot analyses suggest that Arabidopsis contains a small RAD21 gene family. Consistent with the DNA blot data, a second Arabidopsis RAD21-like gene has been identified. These results suggest that different RAD21-like proteins play essential roles in chromosome condensation and pairing during both meiosis and mitosis.

Amino Acid Sequence↗

[Effects of high fluoride intake on the fluoride of femora, teeth and some biochemical indexes in rats].

In order to approach practicable indexes for assessing the effects of the products which are intended to be used to prevent endemic fluorosis, Wistar rats were fed with fluoridated water(50 mg/L) for four weeks. After only one week treated with fluoride, a higher activity of NAG(N-acetyl-beta-D-glucosaminidase) in urine, ChE(cholinesterase) in blood and increased urinary excretion of fluoride (compared with the control, P < 0.01) were observed, and these changes were lasted to the end of the fourth week of the study, but hydroxyproline in serum and urine had not been changed in both groups. After four weeks, the fluoride levels in the femora and teeth of fluoride treated group were ten times higher than that of the control group. According to the results, fluoride in bones and teeth must be taken as key indexes, the activities of NAG in urine and ChE in blood should be taken into consideration for assessing the effects of fluoride protagonist.

Acetylglucosaminidase↗

[Survey of jugular bulb with MRA in sudden sensorineural hearing loss].

To evaluate the correlation between the size and position of the jugular bulb and the sudden sensorineural hearing loss(SSHL), the diameter and height of all jugular bulbs were measured with magnetic resonance angiography and analysed with statistics in 15 cases with SSHL and 35 cases without SSHL(as control). The ipsilateral and the contralateral bulbs of the SSHL were more asymmetrical than that of the control. The mean diameter and height of the ipsilateral bulbs of SSHL were larger than that of the dominant side bulbs of the control. It indicates that the heteroplasia of jugular bulbs which were greatly enlarged and bulgy upward might be related to SSHL.

Adult↗

Inactivation of p16 gene in leukemia.

To determine the frequency of p16 gene inactivation in leukemia cells, and to evaluate their value in the prediction of their clinical outcome. Bone marrow or peripheral blood samples from 48 patients with leukemia were examined by multiplex polymerase chain reaction (MPCR) to detect p16 gene homozygous deletion, and restriction enzyme PCR to detect p16 gene methylation. p16 gene inactivation were detected in 10 of the 48 patients (20.4%). They were five patients with p16 homozygous deletion, and five patients with p16 methylation, respectively. p16 gene inactivation correlates with adverse prognosis features. The patients with p16 inactivation had poor response to chemotherapy, and had significantly shorter survival times than the patients in whom p16 gene was preserved (P<0.001). The inactivation of p16 gene play a key role in the pathogenesis and the progression of some leukemia. The detection of p16 gene is reliable prognostic factor that predict shortened survival times.

DNA Methylation↗

Cytokine and chemokine mRNA expressing cells in muscle tissues of experimental autoimmune myasthenia gravis.

In-situ hybridization with labeled oligonucleotide probes was applied to explore cytokine and chemokine mRNA expression in sections of striated muscle, the target organ in experimental autoimmune myasthenia gravis (EAMG), induced in Lewis rats by immunization with acetylcholine receptor (AChR) and complete Freund's adjuvant (CFA). A transient burst of TNF-alpha, IL-1beta and IL-6 mRNA expressing cells was detected during the early phase of EAMG. This cytokine pattern was related to muscular infiltration of macrophages. Levels of IL-4, IL-10, IFN-gamma, cytolysin and TGF-beta mRNA expressing cells were low and observed mainly during the early phase of EAMG. C-C chemokine RANTES, MCP, MIP-1alpha and MIP-2 mRNA expressing cells were not detected over the course of EAMG. The low and transient expression of cytokines in EAMG muscle tissues suggests that the immune effector responses are unlikely operated by infiltrating cells in muscle. Muscular infiltrations in EAMG are unlikely due to local accumulation of C-C chemokines.

Animals↗

Superantigen-activated T cells redirected by a bispecific antibody inhibit vesicular stomatitis virus replication in vitro and in vivo.

A bispecific Ab (BsAb) that binds the TCR on T cells and the G protein of the vesicular stomatitis virus (VSV) can redirect staphylococcal enterotoxin B (SEB)-activated T cells to kill VSV-infected cells and to inhibit VSV replication in vitro. Inhibition of virus replication in our system is dependent upon the specificity of the Ab for the viral protein. IFN-gamma does not play a very important role in this phenomenon, which is mainly mediated by the release of Pfp from CD8+ T cells. We have used a Stat1 knockout mouse model in which VSV infection is lethal. Infusion of staphylococcal enterotoxin-activated B T cells and bispecific Ab significantly slowed virus progression and prolonged the survival of VSV-infected Stat1 knockout mice in vivo.

Animals↗

Hormone secretion by cell culture of human GH-PRL secreting pituitary adenomas: effects of bromocriptine.

Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is unclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.

Adenoma↗

Genetic co-inactivation of macrophage- and T-tropic HIV-1 chemokine coreceptors CCR-5 and CXCR-4 by intrakines.

CC-chemokine receptor (CCR)-5 is the principal coreceptor for the entry of macrophage (M)-tropic HIV-1 viruses into a cell, while CXC-chemokine receptor (CXCR)-4 is the principal coreceptor for T cell line (T)-tropic HIV-1. In this study, we utilized a novel intracellular chemokine (intrakine) strategy to co-inactivate genetically both CCR-5 and CXCR-4 in human lymphocytes. The principle of co-inactivation of CCR-5 and CXCR-4 was illustrated by targeting the CC-intrakine and CXC-intrakine to the lumen of the endoplasmic reticulum (ER) for intracellular blockade of the transport of newly synthesized chemokine coreceptors to the cell surface. The lymphocytes with the phenotypic knock-out of CCR-5 and CXCR-4 were found broadly to resist the infection of M-tropic, T-tropic and dual-tropic HIV-1 viruses. Moreover, the transduced lymphocytes retained normal cell features, including the responsiveness to mitogen and recall antigen stimulation. Thus, this study to our knowledge, is the first to demonstrate that genetic co-inactivation of the M- and T-tropic HIV-1 principal coreceptors in lymphocytes or other cells could be a viable strategy for the long-term control of HIV-1 infection.

Cell Line↗

[Mechanism of coronary vasodilation in myocardial regional hypoxia].

OBJECTIVE: To determine if coronary vasodilation is dependent upon adrenergic activation during myocardial regional. METHODS: Studies were conducted in 10 Mongrel dogs of either sexes, in which LAD was perfused with normoxic (CAO2 = 18.4-20.4 ml/100 ml) or regional hypoxic (CAO2 = 7.8-8.1 ml/100 ml) blood with coronary perfusion system by self-control methods. RESULTS: No significant differences were observed in hemodynamic values with regional hypoxia compared with normoxia before adrenergic receptor blocker was given, but coronary blood flow increased by 225%. There were significant differences in dp/dt max, dp/dt min after adrenergic blocker was given. Whether there was regional hypoxia or not, coronary blood flow still increased by 190%. CONCLUSION: Coronary vasodilation is independent upon adrenergic activation during myocardial regional hypoxia.

Adrenergic beta-Antagonists↗

[Enzymatic synthesis of cephradine].

Cephradine was synthesized by gamma-alumina-immobilized form of the penicillin G acylase of Bacillus megaterium with D-phenyglycine methylester hydrochloride (CH DGME.HCl) as acyl donor and 7-aminodeacetoxycephalosporanic acid (7-ADCA) as acyl acceptor. 0.1 g of 7-ADCA was dissolved by adding 2.5 ml of distilled water and about 0.25 ml of 2 mol/L NaOH in a 25 ml flask. To the solution, after 0.25 g of CHDGME.HCl was added, 0.1 mol/L phosphate-0.05 mol/L citric acid buffer, pH 7.5 was added to result in a volume of 5 ml with pH 7.5 Then 1 g(220 IU) of immobilized enzyme was added. The flask was shaken on a rotary shaker at 110 r/min and 25 degrees C for 5 h. The conversion rate of 7-ADCA was 81%. In an expanded experiment in 500 ml of reactive volume, 11.8 g of cephradine was obtained from 10 g of 7-ADCA. The conversion rate of 7-ADCA was 80% with about 87% yield of cephradine. Enzymatic synthesis was inhibited in varying degrees by phenylacetic acid, phenoxyacetic acid and cephalosporin G.

Bacillus megaterium↗

Adenylyl cyclase 6 is selectively regulated by protein kinase A phosphorylation in a region involved in Galphas stimulation.

Receptors activate adenylyl cyclases through the Galphas subunit. Previous studies from our laboratory have shown in certain cell types that express adenylyl cyclase 6 (AC6), heterologous desensitization included reduction of the capability of adenylyl cyclases to be stimulated by Galphas. Here we further analyze protein kinase A (PKA) effects on adenylyl cyclases. PKA treatment of recombinant AC6 in insect cell membranes results in a selective loss of stimulation by high (>10 nM) concentrations of Galphas. Similar treatment of AC1 or AC2 did not affect Galphas stimulation. Conversion of Ser-674 in AC6 to an Ala blocks PKA phosphorylation and PKA-mediated loss of Galphas stimulation. A peptide encoding the region 660-682 of AC6 blocks stimulation of AC6 and AC2 by high concentrations of Galphas. Substitution of Ser-674 to Asp in the peptide renders the peptide ineffective, indicating that the region 660-682 of AC6 is involved in regulation of signal transfer from Galphas. This region contains a conserved motif present in most adenylyl cyclases; however, the PKA phosphorylation site is unique to members of the AC6 family. These observations suggest a mechanism of how isoform selective regulatory diversity can be obtained within conserved regions involved in signal communication.

Adenylyl Cyclases↗

Phenotypic knockout of HIV type 1 chemokine coreceptor CCR-5 by intrakines as potential therapeutic approach for HIV-1 infection.

A genetic defect in a CC-chemokine receptor (CCR)-5, the principal coreceptor for the macrophage-tropic HIV type 1 (HIV-1), recently was found to naturally protect CCR-5-defective, but healthy, individuals from HIV-1 infection. In this study, we mimic the natural resistance of the CCR-5-defective individuals by designing a strategy to phenotypically knock out CCR-5. The inactivation of the CCR-5 coreceptor is accomplished by targeting a modified CC-chemokine to the endoplasmic reticulum to block the surface expression of newly synthesized CCR-5. The lymphocytes transduced to express the intracellular chemokine, termed "intrakine," were found to be viable and resistant to macrophage-tropic HIV-1 infection. Thus, this gene-based intrakine strategy targeted at the conserved cellular receptor for the prevention of HIV-1 entry should have significant advantages over currently described approaches for HIV-1 therapy.

Acquired Immunodeficiency Syndrome↗