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Biomedical subjects

B Wang

Publications and source records attributed to B Wang.

At least 649 records · Page 36Linked to original sources
PubMed1997

The evaluation of intra- and extra-cranial circulation in subclavian steal syndrome.

OBJECTIVE: To compare the efficacy of transcranial Doppler ultrasound (TCD) and digital subtraction angiography (DSA) in identifying the clinical and hemodynamic relationship between intra- and extra-cranial circulation and subclavian steal syndrome. METHODS: Sixteen patients were collected. The intra- and extra-cranial arteries were insonated with Doppler ultrasound. DSA and brain CT were performed in all patients. The relationship between the grade of arterial stenosis showing in DSA and the flow direction showing in TCD was studied. RESULTS: TCD showed reversal flow of the vertebrobasilar artery in 13 patients, normal flow in 3, which was influenced obviously by fist-clenching. In the hyperemia test, the flow velocity and the direction changed significantly in all patients. The steal phenomenon of the middle cerebral artery (MCA) was coincident with that of the arterial cerebral artery (ACA) in 2 cases. Stenosis of MCA or ACA was found in 5 cases (31%). Nine patients were treated with arterial bypass or angioplasty. TCD was performed during the follow-up. CONCLUSIONS: Reversal flow of the vertebral artery may occur in rest or only in exercise, depending on the grade of subclavian arterial stenosis. Hyperemia test is the most sensitive index. It is necessary to monitor blood flow in the MCA and basilar artery in hyperemia test. The coexistence of intra- and extra-cranial arterial stenosis is common.

Adult↗
PubMed1997

Comparison of birth weight by gestational age between China and the United States.

OBJECTIVE: To probe into the similarities and differences of birth weight by gestational age between China and the United States by a comparative study. METHODS: For China, we used the records of 24,150 single livebirth neonates. These records were collected between February 1986 and May 1987 from 43 hospitals and health care units in 15 large and middle cities in the South and North of China. For the United States, we used the natal records of National Center for Health Statistics from 1980 to 1987, selecting infants whose parents were coded as white and with higher socioeconomic backgrounds in the birth records. A total of 6,295,102 singleton livebirth neonates were selected. We used a method based on probability plots to define birth weight distributions. RESULTS: The 50th and 95th percentiles of birth weights by gestational age of American newborns with white parents were more than those of Chinese newborns. The 50th percentile values of birth weights of American male and female newborns were 357 g and 277 g (about 10% and 8% respectively of the birth weight of a term newborn) more than those of Chinese male and female newborns respectively at 40 weeks of GA. CONCLUSIONS: American white newborns were heavier than Chinese newborns. The differences were mainly due to race-specific influences, and were related to the differences in socioeconomic and educational background. We suggest that the references of birth weight by gestational age should be formulated separately in China and in the U.S.

Asian People↗
PubMed1997

[Clinical studies of surgical methods for lobar and segmental bile ducts of the right liver].

OBJECTIVE: To Study the operative approach and the method of exposure and cutting open for every lobar and segmental bile ducts and solve the surgical treatment of the complex multiple stones complicated with bile ducts stenosis in the right liver. METHODS: Liver specimens of 30 adults were dissected to explore the lobar and segmental bile ducts and vessels. The exposure and cutting open of right intrahepatic bile ducts were well from the diaphragmatic face of the right hepatic lobe. This method was used in 10 patients with the disease. RESULTS: All the patients were succesfully treated. Follow-up for 3-36 months, showed that 80% patients had excelent results, and 20% good ones. CONCLUSION: The exposure and cutting open of the intrahepatic bile ducts from the diaphragmatic face of the right liver may take stones and solve bile duct stenosis in the every lobes and segment of the right liver.

Adult↗
PubMed1997

[Repair of cornea-sclera defect by autogenous sclera graft from the same eye].

In order to rescue the serious cornea-sclera defect, normal piece of a sclera from the damaged eye was used to serve as a donor material to repair the cornea-sclera defect. Eighteen cases were treated by transplantation of sclera graft with the operation to decompress the intra-ocular tension and to perform an artificial pupil from 1979 to 1994. Because the ocular-store seriously lacks in mostly internal locality, in the 18 cases, laceration of avulsive in 5 cases, severe corneal fistula complicated to other corneal diseases in 8 cases, locolized staphyloma of aornea in 2, laceration of sclera fistula in 1. The resulte were: The repairs were all healed up in an average of 20 days. The tension returned to normal and the vision was improved. The scleral graft was fused with the cornea, and the white area form the graft tended to reduce in size gradually with increase in transparency. There was no sign of iritis and rejection reaction. Follow-up of 3 to 36 months showed that the grafting operation was simple and an easy method, at the same time, once gained effect if would prevent or cure blindness.

Adolescent↗
PubMed1996

Contribution of the CD28 molecule to allergic and irritant-induced skin reactions in CD28 -/- mice.

The CD28 molecule is thought to be essential for the costimulatory signals and is required for mitogenic activation of T cells. The aim of this study was to evaluate the contribution of CD28 in contact hypersensitivity using CD28 gene-targeted (CD28 -/-) mutant mice. Contact hypersensitivity to dinitrofluorobenzene and oxazolone was significantly decreased in CD28 -/- mice compared with that in normal (C57BL/6) mice. Significant increases in IL-2 mRNA were detected in the skin after dinitrofluorobenzene challenge in normal mice, while this response was blunted in CD28 -/- mice. In addition, responses to irritant chemicals (croton oil and phenol) were also impaired in CD28 -/- mice. IL-2, IFN-gamma, and TNF-alpha mRNA levels were lower in CD28 -/- mouse skin treated with phenol. T cells from CD28 -/- mice did not bind to epidermal cells derived from normal mice, while cocultivation of T cells with epidermal cells from normal mice demonstrated a significant binding. These results indicate that the CD28 molecule is required not only for optimal induction of allergic contact dermatitis, but also for the development of irritant-induced skin inflammation. The expression of B7-1 and B7-2 molecules on epidermal cells was induced by an allergen treatment in normal and CD28 -/- mice, whereas only B7-2 was induced after irritant treatment. Lack of CD28 signaling may influence cutaneous inflammation by modulating skin cytokine profiles, possibly due to the decreased contact of T cells with other cell populations expressing ligands for CD28. In addition, the results of this study suggest that allergic contact dermatitis and irritant dermatitis have overlapping pathophysiologic mechanisms, but subtle differences exist.

Animals↗
PubMed1996

Insulin-induced in situ phosphorylation of the insulin receptor located in the plasma membrane versus endosomes.

The binding of insulin to the plasma membrane insulin receptor initiates two dynamic processes: (i) autophosphorylation of the receptor on tyrosine residues, activating the intrinsic tyrosine kinase activity required for insulin signaling, and (ii) endocytosis of the receptor. Recent evidence (Kublaoui et al., J. Biol. Chem. 270, 59-65, 1995) demonstrates that in stimulated adipocytes, the internalized insulin receptor is not only more highly phosphorylated than the receptor remaining on the plasma membrane of the cell, but that IRS-1 binding and phosphorylation also occur in the endosomes. These data suggest that the intracellular insulin receptor mediates insulin action. Utilizing 3T3-L1 adipocytes, we substantiate and extend these findings to document the distribution of receptor between the plasma membrane and the endosomal compartment of insulin-stimulated cells and map the extent and location of the tyrosine phosphorylation sites on the receptor residing in these two cellular locations. We find that following insulin stimulation (i) 90% of the receptor-associated phosphate is located in the endosomal compartment, (ii) the endosomal receptor is most highly phosphorylated in the tyrosine kinase domain, and (iii) significant levels of juxtamembrane domain phosphorylation are detected in the endosomal receptor. These data support the role of the endosomal insulin receptor as the major transducer of insulin action.

3T3 Cells↗
PubMed1996

Proline-rich sequences mediate the interaction of the Arg protein tyrosine kinase with Crk.

Arg is a ubiquitously expressed member of the Abelson family of nonreceptor protein-tyrosine kinases. Defining the Arg sequences that mediate its interaction with other proteins is essential to elucidating its role in cellular signaling. In this report we demonstrate that Arg associates with c-Crk, an adaptor protein composed of an SH2 domain and two SH3 domains, and examine the molecular mechanism of the interaction. In vitro experiments revealed that three proline-rich sequences with distinct specificities for SH3 domains are located in the Arg C-terminal domain, just C-terminal to the kinase domain, and that two of these sequences bind to the Crk N-terminal SH3 domain. These two sequences conform to the PxLPxK/R motif that has been observed in other proteins that bind the Crk N-terminal SH3 domain. The interaction of Arg with c-Crk in living cells was confirmed by the detection of coimmunoprecipitation in coinfected Sf9 cells. In addition, increased phosphorylation of c-Crk was observed in cotransfected COS cells, indicating that Crk is an Arg substrate. The site of c-Crk phosphorylation by Arg was identified as tyrosine 221, a residue whose modification has been shown to result in an intramolecular SH2 interaction and a folded conformation. These experiments extend the known Arg protein interacting motifs to include SH3 binding sites and suggest that Arg may function as an effector as well as a regulator of Crk activity.

Animals↗
PubMed1996

Differential inhibition of HIV-1 preintegration complexes and purified integrase protein by small molecules.

To replicate, HIV-1 must integrate a cDNA copy of the viral RNA genome into a chromosome of the host. The integration system is a promising target for antiretroviral agents, but to date no clinically useful integration inhibitors have been identified. Previous screens for integrase inhibitors have assayed inhibition of reactions containing HIV-1 integrase purified from an Escherichia coli expression system. Here we compare action of inhibitors in vitro on purified integrase and on subviral preintegration complexes (PICs) isolated from lymphoid cells infected with HIV-1. We find that many inhibitors active against purified integrase are inactive against PICs. Using PIC assays as a primary screen, we have identified three new anthraquinone inhibitors active against PICs and also against purified integrase. We propose that PIC assays are the closest in vitro match to integration in vivo and, as such, are particularly appropriate for identifying promising integration inhibitors.

Anthraquinones↗
PubMed1996

Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair: in vivo evolution of vpr quasispecies in blood and plasma.

Earlier studies on HIV-1 strains from HIV-1-infected long-term nonprogressors (LTNP) have reported that nef deletions and/or attenuations may be crucial in the survival of these patients. Other reports have suggested that the nef gene may not be the only gene involved, but attenuations in other accessory genes (vif, vpr, vpu), which play an important role in the viral life cycle, may be similarly important in chronic HIV-1 infection in LTNPs. Here we show the molecular and phylogenetic analyses of the vpr gene in HIV-1 strains derived from both blood and plasma of an HIV-1 infected long-surviving mother-child pair which has survived for > 13 years with HIV infection: both have maintained stable CD4+ T-cell counts. Analyses of blood-and plasma-derived HIV-1 vpr clones indicated the presence of defects (insertions and deletions) and length polymorphisms. Interestingly, all the vpr defects in PBMCs and plasma were clustered at the C-terminus of the Vpr protein, between amino acid residues 83 and 89, which has been implicated in the G2 cell cycle arrest as a step to early HIV-1 infection. In contrast, the vpr sequence analysis of HIV-1 strains derived from 30 different patients, who either died of AIDS-related illnesses or have AIDS, showed neither C-terminal defects nor length polymorphism in the vpr gene. Also, secondary structure predictions suggest that the naturally occurring mutations at the C-terminal region (aa 83-89) have the potential to affect the secondary structure of the Vpr protein. Also, in some cases, the out-of-frame mutations and the length polymorphisms affect the tat gene reading frame. Together, these mutations may have potential significance in conferring chronic HIV-1 infection in this long-surviving nonprogressing mother-child pair.

Adolescent↗
PubMed1996

Subcellular localization of the Arg protein tyrosine kinase.

Arg and c-Abl are ubiquitously expressed proteins which represent the mammalian members of the Abelson family of nonreceptor protein tyrosine kinases (PTKs). In contrast to most nonreceptor PTKs, c-Abl is located in the nucleus and cytoplasm. In this study the subcellular localization of Arg was examined to gain insight into its possible functions. Using indirect immunofluorescence, Arg was detected in the cytoplasm but not the nucleus of both transiently transfected COS cells and stable NIH3T3 transfectants. Arg is expressed as IA and IB isoforms which bear alternative amino termini, with the IB isoform containing a potential myristic acid acceptor sequence. Modification of ArgIB by myristic acid was confirmed by the detection of [3H]myristic acid labeling and the observation that labeling was abolished by mutating Gly-2. These results indicate that the subcellular localization of Arg is distinct from that of c-Abl and thus suggest that the two proteins have different functions in intracellular signaling. In addition, Arg, like c-Abl, is expressed as myristoylated and nonmyristoylated isoforms, suggesting that it may have dual cytoplasmic subcellular localizations, and possibly participate in diverse signaling pathways.

3T3 Cells↗
PubMed1996

Transcriptional regulation of the human NAD(P)H:quinone oxidoreductase (NQO1) gene by monofunctional inducers.

The upstream region of the human NAD(P)H:quinone oxidoreductase (NQO1) gene contains a functional antioxidant responsive element (ARE) and an overlapping 12-O-tetradecanoyl-phorbol-13-acetate responsive element (TRE), with the sequence TGACTCAGCA. We show that the ARE (TGACNNNGCA) is required for induction by redox cycling phenolics (p-benzoquinone, catechol and hydroquinone), which are monofunctional inducers and induce NQO1 without the requirement for activation by cytochrome P-450. The TRE (TGACTCA) is involved only in basal expression. A plasmid containing overlapping ARE-TRE (TGACTCAGCA) sequences (-587 to -379) from the NAD(P)H:quinone oxidoreductase gene was transiently transfected into Hep G2 cells. In the absence of inducers, basal expression was 4-fold higher than in F9 cells (which lack AP-1 activity). Using subcloned oligonucleotides containing the ARE-TRE sequence (-473 to -440), the ARE sequence alone (TCA changed to GAC) and the TRE sequence alone (GC changed to TA), the basal level of expression was in the order: TRE > TRE-ARE > ARE in Hep G2 cells. Using F9 cells, basal expression was detected using the combination ARE-TRE sequence or the ARE, but not the TRE alone, p-Benzoquinone, catechol and hydroquinone, but not resorcinol, induced gene expression in both Hep G2 and F9 cells via the ARE-TRE and ARE sequences, but the TRE sequence did not contribute to this induction. We therefore conclude that induction of human NAD(P)H:quinone oxidoreductase by monofunctional inducers is via the ARE and not the TRE, and that the induction is mediated by proteins other than Fos and Jun.

Amino Acid Sequence↗
PubMed1996

The immunosuppressant 15-deoxyspergualin [correction of 1,5-deoxyspergualin] reveals commonality between preT and preB cell differentiation.

15 [correction of 1,5] deoxyspergualin (DSG) is a potent immunosuppressant whose mechanism of action is still somewhat of a mystery. We have studied the generation of lymphocytes in mice treated with this drug. The differentiation of T cells in the thymus was blocked at an important early control point: the CD4-8- --> CD4+8+ transition, known to depend on the expression of a preTCR complex that includes the variable TCR-beta, but not TCR-alpha, chain. In clear contrast, a later control point, the CD4+8+ --> CD4+8- or CD4-8+ transition, dependent on the display of a conventional alpha:beta TCR complex, appeared unaffected, as did activation of mature T cells both in vitro and in vivo. Interestingly, preB cell differentiation in the bone marrow was blocked at a precisely equivalent point: the A-C --> C' transition, controlled by expression of a pre-receptor complex containing the Ig heavy, but not light, chain. Mature B cells seemed unperturbed. These findings have theoretical implications, suggesting common signaling pathways in early lymphocytes that are distinct from those employed by more mature cells, and are also of practical interest, to be considered in the design of DSG treatment protocols.

Animals↗
PubMed1996

Identification of ArgBP1, an Arg protein tyrosine kinase binding protein that is the human homologue of a CNS-specific Xenopus gene.

Arg and c-Abl represent the mammalian members of the Abelson family of nonreceptor protein-tyrosine kinases. To gain insight into the biological role of Arg we used the two-hybrid approach to identify interacting proteins. Using a C-terminal segment of Arg we identified a novel protein, ArgBP1 (Arg binding protein 1). ArgBP1 contains a C-terminal SH3 domain, several PEST sequences, a serine rich domain and an SH3 binding site. ArgBP1 is ubiquitously expressed as two transcripts of approximately 2.2 kb and approximately 8 kb with highest levels in brain, heart and testis. The association of ArgBP1 with Arg in living cells was confirmed by coimmunoprecipitation in cotransfected COS cells. Analysis of the mechanism of association indicated that the ArgBP1 SH3 domain binds to a C-terminal Arg SH3-binding site, and that an N-terminal ArgBP1 proline-rich sequence binds to the Arg SH3 domain. Immunostaining indicated that the subcellular localization of ArgBP1 is cytoplasmic. The similarity of the ArgBP1 expression pattern and subcellular localization to those of Arg and the potential for a highly specific and potentially strong association mediated by two pairs of SH3 domain/proline-rich motif interactions, suggest that ArgBP1 is likely to be a regulator and/or effector of Arg function.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Multiple structural elements define the specificity of recombinant human inhibitor-1 as a protein phosphatase-1 inhibitor.

The cDNA encoding human brain protein phosphatase inhibitor-1 (I-1) was expressed in Escherichia coli. Following PKA phosphorylation at a threonine, recombinant human I-1 was indistinguishable from rabbit skeletal muscle I-1 as a potent and specific inhibitor of the type-1 protein serine/threonine phosphatase (PP1). N-Terminal phosphopeptides of I-1 that retained the selectivity of intact human I-1 highlighted a functional domain that mediates PP1 inhibition. Substituting alanine in place of threonine-36 eliminated I-1 phosphorylation by PKA and its phosphatase inhibitor activity. An acidic residue was substituted in place of the phosphoacceptor to produce I-1(T35D), a constitutive phosphate inhibitor. I-1(T35D) was an equally effective inhibitor of PP1 and the type-2 phosphatase, PP2A. However, CNbr digestion of I-1(T35D) yielded an N-terminal peptide that showed 100-fold increased specificity as a PP1 inhibitor. This provided new insight into a unique conformation of the phosphorylated I-1 that accounts for selective inhibition of PP1 activity. Truncation of an active I-1 phosphopeptide identified an N-terminal sequence that was reduced in addition to threonine-35 phosphorylation to inhibit PP1 activity. Biosensor studies demonstrated that PP1 bound to both Phosphorylated and dephosphorylated I-1 and suggested that distinct elements of I-1 structure accounted for PP1 binding and inhibition. Our data point to multiple interactions between the I-1 functional domain. and the PP1 catalytic subunit that define this phosphoprotein as a physiological regulator of the type-1 protein phosphatase.

Amino Acid Sequence↗
PubMed1996

Checkpoints in the progression of autoimmune disease: lessons from diabetes models.

In the last few years, data from experiments employing transgenic models of autoimmune disease have strengthened a particular concept of autoimmunity: disease results not so much from cracks in tolerance induction systems, leading to the generation of anti-self repertoire, as from the breakdown of secondary systems that keep these cells in check. T cells with anti-self specificities are readily found in disease-free individuals but ignore target tissues. This is also the case in some transgenic models, in spite of overwhelming numbers of autoreactive cells. In other instances, local infiltration and inflammation result, but they are well tolerated for long periods of time and do not terminally destroy target tissue. We review the possible molecular and cellular mechanisms that underlie these situations, with a particular emphasis on the destruction of pancreatic beta cells in transgenic models of insulin-dependent disease.

Animals↗