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Biomedical subjects

B Wang

Publications and source records attributed to B Wang.

At least 721 records · Page 40Linked to original sources
PubMed1995

Structure-function studies of mEGF: probing the type I beta-turn between residues 25 and 26.

The interaction between epidermal growth factor (EGF) and its receptor molecule is not completely understood and has received much attention recently. Studies combining site-directed mutagenesis and NMR spectroscopy have identified a number of EGF residues that are required for activity and are believed to interact directly with the receptor. Instead of focusing on these residues, this study combines site-directed mutagenesis and NMR spectroscopy to probe the role of the type I beta-bend located between residues 25 and 26 of the N-terminal subdomain of the protein. Ser25 of murine EGF is replaced by Pro in an attempt to stabilize this turn conformation to produce a variant of mEGF with increased activity relative to that for the native protein. Ser25 is also replaced by Ala, which is found at position 25 in human EGF (hEGF), as a more conservative replacement. Receptor binding studies demonstrate that both mutations produce about a 30% reduction in binding affinity, which is shown to result from local changes within the loop or minor perturbations of residues neighboring the loop rather than from long-range perturbations of the beta-sheet of the N-terminal subdomain. The type I beta-turn appears to remain intact in both mutants; however, replacement with Pro seems to introduce more flexibility into this region of the protein. These results demonstrate that perturbation of this beta-turn has little effect on EGF-receptor interactions.

Animals↗
PubMed1995

Regulation of thymocyte development through CD3: functional dissociation between p56lck and CD3 sigma in early thymic selection.

We studied the extent of functional linkage between CD3 sigma and p56lck in pre-TCR-dependent thymocyte development. Differentiation of DN to DP cells was examined by treatment of RAG2/CD3 sigma and RAG1/p56lck double-deficient mice with anti-CD3 epsilon antibodies. The results suggest that CD3 sigma has no specific role in this maturation step, but may be important for amplification of signaling through the pre-TCR. In contrast, p56lck is the main protein tyrosine kinase associated with signaling through the pre-TCR-CD3 complex. In DP thymocytes, the Ca2+ response to anti-CD3 epsilon was totally abolished in CD3 sigma-I-but only reduced in p56lck-I-mice, and in vivo responses to anti-CD3 epsilon differed from one another. Thus, CD3 sigma and p56lck are functionally not tightly associated and their deficiencies cause distinct developmental defects.

Animals↗
PubMed1995

Severe colitis in mice with aberrant thymic selection.

Tg epsilon 26 mice display an arrest very early in T cell development that has a profound effect on the architecture of thymic stromal cells. We have recently demonstrated that transplantation of wild-type bone marrow cells restores the thymic microenvironment of fetal but not adult Tg epsilon 26 mice. Here, we report that T cell-reconstituted adult Tg epsilon 26 mice develop a spontaneous wasting syndrome characterized by extensive inflammation of the colon, resembling human ulcerative colitis. Colitis in these animals was marked by substantial infiltration of the colon by activated thymus-derived CD4+ T cells. Importantly, bone marrow-transplanted Tg epsilon 26 mice previously engrafted with a fetal Tg epsilon 26 thymus did not develop colitis. These results suggest that T cells selected in an aberrant thymic microenvironment contain a population of cells able to induce severe colitis that can be prevented by T cells that have undergone normal thymic development.

Animals↗
PubMed1995

Phage libraries displaying cyclic peptides with different ring sizes: ligand specificities of the RGD-directed integrins.

We have isolated selective ligands to the cell surface receptors of fibronectin (alpha 5 beta 1 integrin), vitronectin (alpha v beta 3 and alpha v beta 5 integrins) and fibrinogen (alpha IIb beta 3 integrin) from phage libraries expressing cyclic peptides. A mixture of libraries was used that express a series of peptides flanked by a cysteine residue on each side (CX5C, CX6C, CX7C) or only on one side (CX9) of the insert. A majority of the integrin-binding sequences derived from the CX9 library contained another cysteine, indicating preferential selection of conformationally constrained cyclic peptides. Each of the four integrins studied primarily selected RGD-containing phage sequences but favored different ring sizes and different flanking residues around the RGD motif. A cyclic peptide ACRGDGWCG was synthesized based on a phage sequence that bound particularly avidly to the alpha 5 beta 1 integrin. This peptide inhibited cell attachment to fibronectin at about 5-fold lower concentrations than the most potent cyclic peptides described earlier. The most interesting structure appeared to contain two disulphide bonds. One such peptide, ACDCRGDCFCG, was synthetized and shown to be at least 20-fold more potent inhibitor of alpha v beta 5- and alpha v beta 3-mediated cell attachment to vitronectin than similar peptides with a single disulphide bond and 200-fold more potent than commonly used linear RGD peptides. These results emphasize the importance of conformational restriction as a means of improving the potency of integrin-binding peptides and point to a new way of designing effective peptides by resticting the peptide conformation with more than one cyclizing bond.

Amino Acid Sequence↗
PubMed1995

Immunization by direct DNA inoculation induces rejection of tumor cell challenge.

Direct DNA inoculation is the basis for a new technology that has been successfully used for in vivo induction of both humoral and cellular immune responses. However, the immunological parameters of this new approach remain to be evaluated in detail. We report here that direct DNA inoculation can induce protection from malignant tumor cell challenge through the generation of specific immune responses directed against antigens displayed on the tumor cells. The protected mice remain tumor-free for more than 1 year post-challenge. Memory responses upon tumor rechallenge were observed for both humoral and cellular immunity. Inoculated animals were able to reject otherwise lethal tumors several months following the original DNA inoculation protocol. These in vivo protective responses suggest that further analysis of this technology for vaccine development or immune therapeutic strategies is warranted.

Animals↗
PubMed1995

Over-expression of CD3 epsilon transgenes blocks T lymphocyte development.

We have reported previously that mice carrying > 30 copies of the human CD3 epsilon transgene completely lose their T lymphocytes and NK cells (36). Here we demonstrate by immunohistology that in the most severely immunodeficient mouse, tg epsilon 26, the thymus is very small, has sizeable vacuoles and does not contain recognizable T lymphocytes except for a small percentage of Thy-1+ cells and B cells. Cell surface phenotyping and TCR alpha and -beta rearrangement studies confirm that the arrest in T lymphocyte development precedes the arrest in rag-1null, rag-2null and TCR beta nuli mice. Since the T cell progenitors in which the arrest occurred were absent in the transgenic mice, indirect approaches were taken to examine the causes of the block in T cell development. Analyses of 12 independently established mutant mouse lines, generated with five different transgenic constructs, revealed that the severity of the abrogation in T cell development was dependent on the number of copies of transgenes. Since the number of transgene copies generally correlated with the levels of expression of the transgenic CD3 epsilon proteins, we concluded that over-expression of the CD3 epsilon protein was the likely cause of the block in T lymphocyte development. The T cell immunodeficiency was caused by either the human or the murine CD3 epsilon protein. Since transgene coded mRNAs were found in significantly higher quantities than endogenous CD3 epsilon mRNAs in fetal thymi on days 13 and 14 of gestation, over-expression took place very early in development, probably prematurely. Over-expression of the CD3 epsilon transgene in thymocyte precursors may therefore affect T lymphocyte development in the absence of TCR and possibly in the absence of the other CD3 proteins. More importantly, over-expression of the CD3 epsilon protein in thymocytes of mice with a low copy number of transgenes had a significant effect on late thymic development. Over-expression of the CD3 epsilon protein in immature thymocytes mimicked the effects caused by exposure of CD4- CD8- thymocytes to anti-CD3 epsilon treatment: apoptosis and lack of TCR beta expression. We therefore speculate that in the homozygous tg epsilon 26 animals the arrest in T cell development was caused by excessive signal transduction events rather than by a toxic effect of the transgenic protein.

Amino Acid Sequence↗
PubMed1995

The long-term effects of internal mammary chain irradiation and its role in the vascular supply of the pedicled transverse rectus abdominis musculocutaneous flap breast reconstruction.

With an increase in breast-sparing surgery and adjuvant radiotherapy, there has been a concomitant increase in the complexity of breast reconstruction. The effects of radiotherapy on the internal mammary artery were evaluated with respect to flap viability for conventional transverse rectus abdominis musculocutaneous breast reconstruction using the irradiated rectus muscle. Twenty-eight women who received postoperative irradiation for breast cancer were studied. All women had unilateral irradiation, and evaluation of the internal mammary arteries was performed at least 1 year after the completion of radiotherapy to allow for fibrosis and long-term vascular changes. Examination of the internal mammary artery (upper and lower chains) was performed using color Doppler sonography to assess vessel diameter, peak systolic velocity, and blood flow. The nonirradiated side was compared to the radiated internal mammary artery as an internal control. Based on the details of prior radiotherapy, the 28 women were designated into two groups. Group I included 14 women with radiation portals that specifically treated the internal mammary chain; the average dose to the internal mammary chain was 47.44 Gy. Group II comprised 14 patients that received tangential portals that did not directly target the internal mammary chain region; the average radiation dose was 48.21 Gy to the chest wall. No statistical difference was observed in group I between the irradiated and nonirradiated side for vessel diameter (p = .8631) or peak systolic velocity (p = .2646). However, an increase in blood flow on the irradiated side was significant (p = .0321).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Functional design features and initial performance characteristics of a magnetic-implant guidance system for stereotactic neurosurgery.

A helmet with a roughly cubic array of six super-conducting coils is used to apply force on a small permanent magnet pellet in brain or in brain phantom material. This apparatus, called the Magnetic Stereotaxis System, will be used to deliver drugs and other therapies directly into deep brain tissues, under control of a computer and fluoroscopic imaging system. This paper considers only the force application aspects of the instrument. The primary design features of the helmet and power supply controls are presented, along with field plot data and single-axis motion results. The field plot data show that agreement with the finite-element iron-free field calculations is sufficiently high (> 1%) for the instrument. These preliminary motion data indicate accuracy better than 2 mm for the impulsive pellet motion, even though the visual position observations had significantly greater error than the completed imaging system will have. The companion paper will take up analysis of the control aspects of the motion, and our recent solutions to difficulties found in the experimental work described here.

Brain↗
PubMed1995

Characteristics of an improved magnetic-implant guidance system.

The previous companion paper described the motivation, design, and early experiments of a Magnetic Stereotaxis System. The part of the system considered in these papers is a helmet with a roughly cubic array of six superconducting coils used to apply force on small permanent magnet pellets in brain and in brain phantom material. This apparatus will be used to deliver drugs and other therapies directly into deep brain tissues, under control of a computer and fluoroscopic imaging system. Here, we analyze the general stability problems of controlling the currents in the coils for impulsive stepwise motion of the pellet, subject to quench avoidance in the superconducting coils, and in the face of Earnshaw's theorem governing stability in static magnetic fields. We also describe solutions that have been found to the primary difficulties limiting controlled pellet motion in the studies presented in the companion paper.

Brain↗
PubMed1995

Human immunodeficiency virus type 1 preintegration complexes containing discontinuous plus strands are competent to integrate in vitro.

Despite intensive study, the mechanism by which many retroviruses complete reverse transcription has remained unclear. Most retroviruses and all lentiviruses fail to synthesize a full-length second strand of the viral cDNA (plus strand) efficiently in infected cells. For human immunodeficiency virus type 1, we find in synchronous infection experiments that full-length plus strands are rare (< 1% of products) at times when integration is likely taking place. Subviral nucleoprotein complexes containing such discontinuous cDNA can be extracted from infected cells and used to generate integration products in vitro. Analysis of such integration products using two-dimensional gel electrophoresis revealed that the discontinuous viral DNA was efficiently integrated into an added target DNA. These data support a model in which the discontinuities in the plus strand need not be sealed until after integration, potentially by the enzymes that are already thought to repair DNA gaps at the junctions between host and viral DNA.

Cell Line↗
PubMed1995

Effects of prenatal exposure to low-dose beta radiation from tritiated water on the neurobehavior of mice.

Pregnant adult C57BL/6J mice, randomly assigned to 1 of 4 groups, 3 of them were irradiated with beta-rays from tritiated water (HTO) by a single intraperitoneal injection on the 12.5th day of gestation. Their offspring received cumulative doses of 0, 5, 10 or 30 cGy in utero. Male pups were trained and examined using a set of behavioral tests that included avoidance acquisition and avoidance maintenance, open field test, hole-board dipping, a water maze, and a food labyrinth. Results were found for most parameters in the 10 and 30 cGy groups that differed significantly from results for the controls, indicating that the behavioral teratogenic effect of prenatal exposure to chronic beta-ray radiation from HTO may be greater than the same dose of acute X- or gamma-irradiation and that 10 cGy may be the lowest detectable dose level at which behavioral changes is detactable under the conditions used in this experiment.

Animals↗
PubMed1995

[The clinical observation of tetracycline stained teeth covered by composite resin veneer induced of secondary gingivitis]

Using gingival index,sulcus bleeding index and plaque index of 765 tetracycline stained teeth covered by composite resin veneer after 1/2-3 years were observed.It was found that the incidence of gingivitis was over 60%.The reexamination after three months later showed that the three indexes were significantly improved by grinding teeth proper and teaching standard brushing method.

Journal Article↗
PubMed1995

[The changes and clinical significance of interleukin 1 beta in pleural effusion].

An enzyme linked immunosorbent assay was set up by using anti-recombinant human interleukin 1 beta monoclonal antibodies. The interleukin 1 beta, anti-interleukin 1 beta autoantibody and interleukin 1 beta containing immune complex were detected in pleural effusion of 28 patients with bacterial infection cases pleurisy and 13 with lung cancer. The results showed that free interleukin 1 beta could be detectable in the early stage of pleurisy, and then transformed to the immune complex. The interleukin 1 beta containing immune complex were detectable in the pleeural effusions of all the 28 patients with pleurisy, but only two patients with lung cancer. The results suggested that this cytokine behaves differently in these two different kinds of diseases.

Antibodies, Monoclonal↗
PubMed1995

A new method for early diagnosis of carcinoma in bile duct-sonography of common bile duct before and after injection of ceosunin.

42 cases of dilatation (7-15 mm) of extrahepatic bile duct after ceosunin injection (cholagogic method) were observed ultrasonographically. Among the 18 cases of testified obstructive lesions of the bile duct, 13 (72%) showed widening of the bile duct with an increase of calibre from 9.8 mm to 11.7 mm, 3 (16%) had no obvious change, and 2 (12%) shrank. Among the 24 cases of non-obstruction 22 (92%) shrank with a decrease calibre from 9.6 mm to 6.3 mm, and 2 (8%) showed no obvious change. After receiving cholagogue, 9 cases of periampullary carcinoma in the obstructive group were confronted with widening of the bile duct calibre. After longitudinal and transverse rotation scanning method was used, 8 of the 9 cases had their tumor mass visualized. Combined cholagogic and rotation scanning methods raised the lesion manifestation rate of lower bile duct from 41% to 88%. A dilated bile duct unable to show shrinkage of calibre after cholagogue injection is believed to be a criterion for judging the presence of a suspicious case of bile duct obstruction. This criterion has a sensitivity of 89%, specificity of 92%, and accuracy of 90%.

Adenocarcinoma↗
PubMed1995

Preliminary study on controlled hypotension induced by nimodipine in craniocerebral surgery.

Nimodipine, produced in China, was applied to lower the blood pressure (BP) in 20 cases in craniocerebral operation. 0.02% solution of Nimodipine was dripped intravenously (by 0.02% of density), at a preliminary speed of 600-800 micrograms/min, and 4-12 mg of total dose. Mean arterial pressure (MAP) decreased and maintained at 7.3-8.0 kPa, and lasted 30-60 minutes. The scopes of decreasing pressure were 33.0%-37.7% of MAP, 31.6%-35.6% of systolic pressure (SP), and 36.1%-41.9% of diastolic pressure (DP). The results of lowering pressure which reduced the intraoperative bleeding were significant. After withdrawal of drug supply for 15-30 minutes, the BP raised up to the normal level. No "rebounding BP rise" occurred.

Adolescent↗
PubMed1995

[The study on the mechanism of EGF inducing the in vitro meiotic maturation resumption of mouse oocytes].

The effect and mechanism of EGF and progesterone on the meiotic maturation resumption were studied. The results showed that progesterone regulated the action of EGF. The inhibitor of 3 beta-HSD, the key enzyme of progesterone synthesis, Epostane could not only prevent the effect of EGF, but inhibit the progesterone production promoted by EGF in cultured ovary granulosa cells as well. On the other hand, heparin could lessen the function of EGF and progesterone, which implies that calcium participated the effect of EGF and progesterone. Fura-2 was used to indicate the changes of intracellular calcium level in single cumulus cell. It is found that a calcium wave appeared in cumulus cell when EGF or progesterone acted. But Ca2+ level returned to normal immediately after progesterone was added, and Ca2+ in the cumulus cell still remained higher level after EGF acted. This results indicated that calcium in cumulus cell adjusted the action of EGF and progesterone.

Animals↗