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Biomedical subjects

B Wang

Publications and source records attributed to B Wang.

At least 667 records · Page 37Linked to original sources
PubMed1996

Effects of UVC irradiation on cultured mouse embryonic limb bud cells.

Effects of UVC irradiation (UVC) at a dose range from 0 to 30 J/m(2) were investigated on the cultured embryonic limb bud cells (LBC), isolated from fore- and hindlimbs of day 11 mouse embryos. Although dose-dependent inhibition was found for both cellular proliferation and chondrogenesis, the chondrogenic proteoglycan (PG) synthesis was more sensitive to UVC than cellular proliferation when compared at ID(50), the inhibitory dose that reduced assessment value by 50% of the control. No significant difference in induction and repair kinetics of UV-induced cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts ((6-4)PPs) were found between LBC and NIH3T3 mouse cell line. The fluorescent light (FL) treatment of LBC pre or post UVC irradiation did not affect repair kinetics of CPDs and (6-4)PPs, cellular proliferation, formation of PG-producing nodule and the PG synthesis.

3T3 Cells↗
PubMed1996

Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways.

Mutants of the Saccharomyces cerevisiae ataxia telangiectasia mutated (ATM) homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1 checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1, have overlapping functions in response to DNA damage and replication blocks that in mutants can be provided by overproduction of RAD53. Both MEC1 and TEL1 were found to control phosphorylation of Rad53p in response to DNA damage. These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family. Because several members of this pathway are conserved among eukaryotes, it is likely that a RAD53-related kinase will function downstream of the human ATM gene product and play an important role in the mammalian response to DNA damage.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1996

Molecular detection of bacterial DNA in venereal-associated arthritis.

OBJECTIVE: To evaluate the utility of polymerase chain reaction (PCR) amplification in detecting DNA from venereal-associated microorganisms in the synovial fluid of patients with inflammatory arthritis. METHODS: Oligonucleotide primers were developed for nested PCR based on Chlamydia, Ureaplasma, and Neisseria DNA sequences. PCR products were detected by gel electrophoresis and dot-blot hybridization. Primers specific for the target bacterial DNA were used to search for bacterial DNA in 61 synovial fluid specimens from patients with inflammatory arthritis, including several clinically associated with venereal infection. RESULTS: Five of the 61 synovial fluid specimens were positive for Neisseria gonorrhoeae DNA. Four of the 5 patients had clinical diagnoses of gonococcal arthritis; the other patient had an unexplained monarthritis. One specimen from a patient with a clinical diagnosis of gonococcal arthritis was negative for N gonorrhoeae. Three of the 61 specimens were positive for Chlamydia DNA. Two were derived from patients with clinical diagnoses of reactive arthritis or Reiter's syndrome, and 1 was from a patient with unexplained monarthritis. One of the 61 specimens was positive from Ureaplasma DNA; this sample was from a patient with a clinical diagnosis of Reiter's syndrome. In an additional patient with Reiter's syndrome, Ureaplasma DNA was also found in prostate biopsy tissue and a urine sample obtained after prostate massage (synovial fluid not available). CONCLUSION: These data support the classification of these 3 venereal-associated arthritides as infectious processes, and suggest that PCR for bacterial DNA is a useful method for detecting infectious agents in synovial fluid.

Adolescent↗
PubMed1996

The role of CD8+ T cells in the initiation of insulin-dependent diabetes mellitus.

While it is generally accepted that T cells are critical for the development of diabetes in the non-obese diabetic (NOD) mouse, the precise functions of the CD4+ and CD8+ subsets remain ill-defined. Transfer experiments have provided evidence that CD4+ cells are the disease initiators, provoking massive mononuclear leukocyte infiltration into the pancreatic islets, while CD8+ cells play an effector role, responsible for the final destruction of islet beta cells. It was surprising, then, to find that NOD mice carrying a null mutation at the beta 2-microglobulin (beta 2-mu) locus, and thereby lacking major histocompatibility complex class I molecules and CD8+ T cells, developed neither insulitis nor diabetes. Here, we argue that the absence of insulitis in these animals results from their lack of CD8+ cells because islet infiltration is also absent when NOD mice are treated with an anti-CD8 monoclonal antibody (mAb) at a young age. Interestingly, the anti-CD8 effect is only observed when the mAb is injected during a discrete age window--2 to 5 weeks after birth. Transfer experiments indicate that the lack of CD8+ cells during this period somehow alters the phenotype of CD4+ cells, preventing them from expressing their insulitis potential. This is not because they are generally immuno-incompetent nor because they are generally more prone to differentiating into cells with Th2 characteristics. Given that neither the beta 2-mu mutation nor anti-CD8 treatment affect insulitis in a T cell receptor transgenic (tg) mouse strain with a CD4+ T cell repertoire highly skewed for an anti-islet cell reactivity, the most straight-forward interpretation of these observations is that CD8+ cells are required for effective priming and expansion of autoreactive CD4+ cells.

Age Factors↗
PubMed1996

Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET.

Transcranial magnetic stimulation with a focal coil was used to map the cortical representation of a hand muscle in four healthy subjects. In each subject, the three-dimensional locations of the magnetic stimulation positions and about 400 positions on the surface of the head were digitized. The amplitude-weighted center of gravity of each subject's map was found, and a line perpendicular to the local head surface was projected inward. The digitized heads were registered with the subjects' MRIs using the scalp contours. The coordinate transformations yielded by this process were used to map the stimulation positions and the perpendicular line into the MRIs. Brain areas imaged with positron emission tomography (PET) and 15O-labeled water, activated by movement of the same muscle, were registered with the MRIs using the brain contours. In all cases, the magnetic stimulation lines encountered the surface of the brain at the anterior lip of the central sulcus and ran along the precentral gyrus a few millimeters anterior to the central sulcus, coming within 5-22 mm of all the PET activation maxima. This technique demonstrates the accuracy of transcranial magnetic stimulation for locating the primary motor area.

Adult↗
PubMed1996

Triterpenoid saponins from Bupleurum smithii var. parvifolium.

Four triterpenoidal saponins, prosaikogenin A and saikosaponins b1, n and o, were isolated from the roots of the title plant for the first time. Saikosaponin O is a new compound, which was identified as 3 beta,16 beta,23,28-tetrahydroxyolean-11,12(18)-diene-3-O-beta-D-glucopy ran osyl-(1-->2)-beta-D-glucopyranosyl-(1--> 6)-[beta-D-glucopyranosyl-(1-->2)]-beta-D-glucopyranoside.

Carbohydrate Conformation↗
PubMed1996

Studies on the thermokinetic characterisation of actin polymerization and the effect of cisplatin.

The microcalorimetic measurement for studying the thermokinetic of actin polymerization in vitro was employed for the first time. The thermodynamic parameters of actin polymerization at 310.15 K are reported as delta Hm = 49.26 kJ/mol, delta Gm = 25.62 kJ/mol and delta Sm = 241.54 J/K.mol. The thermogram shows that polymerization of actin is a complicate process in which multistep reactions occur corresponding to exothermic and endothermic effects. Cisplatin, at lower concentration, affects the polymerization of G-actin resulting in a decrease of delta Hm; and, at higher concentration, induce the crosslinking and depolymerization of F-actin in the equilibrium system of G/F. The experimental results show that as the concentration of cisplatin increases, the sign of delta Hm changes from positive to negative, i.e. the magnitude and sign of delta Hm of actin polymerization depends on the concentration of cisplatin.

Actins↗
PubMed1996

Comparison of the cellular composition of benign prostatic hyperplasia in Chinese and Caucasian-American men.

OBJECTIVES: To compare the cellular composition of benign prostatic hyperplasia (BPH) in Chinese and Caucasian-American men. METHODS: Surgical specimens of the prostate were obtained from 9 Chinese and 8 Caucasian-American men undergoing cystoprostatectomy for invasive transitional cell carcinoma. The mean ages of the Chinese and Caucasian-American men were 66.8 years and 66.4 years, respectively (P = 0.94). The mean prostate weight of the Chinese and Caucasian-American men was 53.4 g and 32.1 g, respectively (P = 0.01). Double immunoenzymatic staining with antibodies against actin and prostatic acid phosphatase and computer-assisted color image analysis were performed on whole-mount tissue sections. The percent area density of smooth muscle (SM), connective tissue (CT), epithelium (E), and epithelial lumen (L) were obtained by analyzing 30 fields from each specimen. RESULTS: The mean percent area density of SM, CT, E, and L in the prostate of Chinese men was 32%, 9.1%, 10.8%, and 48.5%, respectively. The mean percent area density of SM, CT, E, and L in the prostate of Caucasian-American men was 52.5%, 27.9%, 12.8%, and 7%, respectively. Overall, the prostates of Chinese men contained significantly more glandular lumen and significantly less SM and CT. CONCLUSIONS: The present study demonstrates that the cellular composition of BPH in the prostates of Caucasian-American and Chinese men is different. These cellular differences may account for previously observed differences in the incidence of clinical BPH.

Aged↗
PubMed1996

The role of CD4 molecules in the induction phase of contact hypersensitivity cytokine profiles in the skin and lymph nodes.

We have previously demonstrated that CD4 gene-targeted mutant mice (CD4- mice) demonstrate hyporesposiveness in contact hypersensitivity (CHS) suggesting that CD4 molecules are required for optimal induction of CHS. In the present study, we wished to examine the mechanisms of this hyporesponsiveness, in particular, we examined whether cytokines were altered in the skin and lymph nodes of CD4- mice following exposure to the contact allergen dinitrofluorobenzene (DNFB). Cytokine mRNA in the ear skin and draining lymph nodes (DLN) were examined by reverse transcription-polymerase chain reaction (RT-PCR) at various times after sensitization. Skin cytokine patterns revealed that in normal mice, interleukin (IL)-2, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha mRNA levels increased at 12 hr sensitization, whereas these cytokines were below the level of detection in CD4- mice. In the DLN of normal mice following the hapten application, sequential upregulation of cytokine mRNA including IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-10, IFN-gamma and TNF-alpha was found. No change was seen for IL-1 alpha, IL-1 beta, IL-10 and TNF-alpha and IL-2, IL-4 and IFN-gamma mRNA levels were below the level of detection in DLN from CD4- mice following the hapten application. However, IL-1 beta, IL-2 and TNF-alpha mRNA levels of lymph node cells from CD4- mice could be upregulated by phorbol myristate acetate in vitro. Flow cytometry study has revealed that the number of Langerhans' cells (LC) in DLN of CD4- mice was similar to that of normal mice, thus, inferring that the alterations of cytokine milieu in the ear skin did not have a significant effect on LC migration to DLN. These results suggest that CD4 molecules are crucial for the induction of certain cytokines in the skin and in inducing sequential cytokine signals in DLN required for optimal development of CHS, but that these changes in cytokines do not effect LC migration.

Animals↗
PubMed1996

Effect of a novel topical immunomodulator, S-28463, on keratinocyte cytokine gene expression and production.

A new immunomodulating agent, imiquimod, has been reported to have antiviral and antitumor activities in animal models. S-28463 (4-amino-2-ethoxymethyl-alpha, alpha-dimethyl-1H-imidazo[4, 5-c]quinoline-1-ethanol), an analog of imiquimod, has more potent antiviral activity in animals than imiquimod. It has also been shown to be more potent at inducing cytokines in human blood in vitro. However, its precise role as an immunomodulator in the skin has not been determined. We investigated the effect of S-28463 on human keratinocyte (KC) production of interferon-alpha (IFN-alpha) and other proinflammatory cytokines, including interleukin (IL)-1alpha, IL-8, and tumor necrosis factor-alpha (TNF-alpha). Human KC were incubated with S-28463 at two concentrations (1 microgram/ml and 10 micrograms/ml) for 6 h. Cytokine gene expression was analyzed by reverse-transcriptase PCR. In human KC, S-28463 stimulated significant increases in IFN-alpha mRNA at both concentrations. IL-1alpha mRNA increased 1.4-fold at 10 micrograms/ml. IL-8 mRNA was upregulated 2.5-fold at 10 micrograms/ml. Twenty-four hours after treatment, IL-1 alpha, IL-8, and TNF-alpha protein were increased, but IFN-alpha was below the level of detection. These results suggest that in the skin, S-28463-induced-IL-1 alpha, IL-8, and TNF-alpha production may be involved in the immunomodulating action of S-28463.

Adjuvants, Immunologic↗
PubMed1996

Interaction between yeast Cdc6 protein and B-type cyclin/Cdc28 kinases.

During purification of recombinant Cdc6 expressed in yeast, we found that Cdc6 interacts with the critical cell cycle, cyclin-dependent protein kinase Cdc28. Cdc6 and Cdc28 can be coimmunoprecipitated from extracts, Cdc6 is retained on the Cdc28-binding matrix p13-agarose, and Cdc28 is retained on an affinity column charged with bacterially produced Cdc6. Cdc6, which is a phosphoprotein in vivo, contains five Cdc28 consensus sites and is a substrate of the Cdc28 kinase in vitro. Cdc6 also inhibits Cdc28 histone H1 kinase activity. Strikingly, Cdc6 interacts preferentially with B-type cyclin/Cdc28 complexes and not Cln/Cdc28 in log-phase cells. However, Cdc6 does not associate with Cdc28 when cells are blocked at the restrictive temperature in a cdc34 mutant, a point in the cell cycle when the B-type cyclin/Cdc28 inhibitor p40Sic1 accumulates and purified p40Sic1 inhibits the Cdc6/Cdc28 interaction. Deletion of the Cdc28 interaction domain from Cdc6 yields a protein that cannot support growth. However, when overproduced, the mutant protein can support growth. Furthermore, whereas overproduction of wild-type Cdc6 leads to growth inhibition and bud hyperpolarization, overproduction of the mutant protein supports growth at normal rates with normal morphology. Thus, the interaction may have a role in the essential function of Cdc6 in initiation and in restraining mitosis until replication is complete.

CDC28 Protein Kinase, S cerevisiae↗
PubMed1996

Natural killer cell development is blocked in the context of aberrant T lymphocyte ontogeny.

Over-expression of human or mouse CD3-epsilon transgenes profoundly disturbs T lymphocyte and natural killer (NK) cell development. One of these transgenic strains, termed tgepsilon26, displays a very early block in T lymphocyte and NK cell development. We showed previously that the absence of early thymocyte progenitors results in an abnormal thymic microenvironment. Due to this thymic defect, T cell development could not be restored by bone marrow (BM) transplantation in adult tgepsilon26 mice but could in fetal tgepsilon26 mice. Here we examine the effect of this abnormal thymic environment on NK cell development. We demonstrate that NK cell maturation in tgepsilon26 mice was reconstituted by BM derived from completely T cell-deficient mice, i.e. RAG-2(-/-) and TCRbeta x delta-/-, but not from wild-type mice. Moreover, tgepsilon26 mice transplanted with BM from partially T cell-deficient mice, i.e. TCRalpha-/-, TCRbeta-/- and TCRdelta-/- mice, did not reconstitute their NK cell compartment. We conclude from these studies that the thymic environment is not required for NK cell development, but that aberrantly educated alphabeta or gammadelta T lymphocytes can influence NK cell ontogeny. Furthermore, high serum levels of tumor necrosis factor (TNF) were detected in the vast majority of tgepsilon26 mice transplanted with BM cells derived from partially T cell-deficient mice, but never from tgepsilon26 mice transplanted with BM cells derived from completely T cell-deficient mice. The high levels of TNF may play an important role in the observed inhibition of NK cell development, since in vivo treatment with an anti-TNF antibody restored NK cell development.

Animals↗
PubMed1996

Effects of beta radiation from organically bound tritium on cultured mouse embryonic mid brain cells.

Effects of beta radiation from four kinds of organically bound tritium compounds were investigated on cultured mouse embryonic mid brain cells, isolated from 11-d-old mouse embryos. The MBC showed a critical time when they were more radiosensitive. Although dose-dependent inhibition was found for both cellular proliferation and differentiation, the differentiation was more sensitive to radiation than proliferation when compared at ID50, the inhibitory dose that reduced assessment value by 50% of the control. Dose-dependent decrease of DNA and protein contents were also observed. The relative biological effectiveness values, ranging from 4.6 to 8.7, of beta ray from organically bound tritium compounds were obtained when compared with x irradiation at their ID50s on the inhibition of cell proliferation and differentiation, and on the decrease of DNA and protein contents of the cultures. The mixed exposure to x ray and one kind of organically bound tritium compound or to any two kinds of organically bound tritium compound resulted in a more efficiently inhibitory effect on differentiation than the exposure to x ray or to any one kind of organically bound tritium compound alone, especially when methyl-3H-thymidine was used. Doses as low as 0.05 Gy (5 cGy) from a mixed exposure resulted in detectable inhibitory effects.

Animals↗
PubMed1996

Hyporesponsiveness in contact hypersensitivity and irritant contact dermatitis in CD4 gene targeted mouse.

To determine the role of CD4 molecules in the generation and regulation of contact hypersensitivity (CHS), we treated mice lacking the CD4 gene as a result of targeted disruption with dinitrofluorobenzene to induce CHS. The mutant mice lacking CD4 (CD4(-) mice) showed marked hyporesponsiveness in CHS compared with normal syngeneic C57BL/6 mice (38.3 +/-9.0% of normal at 24 h after the challenge assessed by net ear swelling; p < 0.025). CD4(-) mice had a larger CD4-8- double negative T-cell receptor alpha beta+ cell population in the lymph nodes than did normal mice, and the increase of this cell population was observed in CD4(-) mice after sensitization. Draining lymph node cells from sensitized normal mice restored the responsiveness in CD4(-) mice, but those from sensitized CD4(-) mice were less effective in restoring the CHS response in normal mice. Langerhans cell numbers were normal, and function, as assessed by the ability to present soluble hapten, was not impaired in CD4(-) mice. Skin cytokine profiles demonstrated an increase in interferon-gamma, interleukin-2, and interleukin-4 mRNA levels after challenge in normal mice, whereas this response was blunted in CD4(-) mice. CD4(-) mice also showed hyporesponsiveness in inflammatory reaction to irritant chemicals. These results suggest that the CD4 molecule is required for optimal induction of CHS as well as irritant contact dermatitis and may influence the development of CHS by modulating the cytokine profiles in the skin.

Animals↗
PubMed1996

Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans' cells.

Langerhans' cells (LC) represent the major antigen-presenting cells within the epidermis. Following exposure of the skin to antigen, LC take up antigen, migrate into draining lymph nodes (DLN) and present processed antigen to T lymphocytes, thereby initiating an immune response. The molecular mechanisms responsible for LC migration remain unclear. Cytokines, in particular tumour necrosis factor-alpha (TNF-alpha) have been suggested to influence LC migration. There are two distinct membrane receptors for TNF-alpha, TNF receptor I (TNF-R1, p55) and TNF receptor II (TNF-R2, p75), thought to be responsible for distinct TNF-alpha activities. It is believed that most of TNF biological activities are mediated via TNF-R1. In order to examine the role of TNF-R1 signalling in LC migration, we utilized TNF-R1 gene-targeted mutant mice. Following application of the hapten fluorescein isothiocyanate (FITC), FITC-bearing cells in DLN were examined by flow cytometry. A normal number of FITC+/Ia+ cells (LC) were found in DLN from TNF-R1-deficiency mice, suggesting that TNF-R1-dependent signalling is not crucial for LC migration. To investigate the possibility of signalling through TNF-R2, blocking studies using a neutralizing anti-TNF-alpha antibody were performed. The results revealed that anti-TNF-alpha antibody significantly inhibited LC accumulation in DLN in TNF-R1-deficient mice, thus suggesting that TNF-R2 signalling is involved in LC migration from skin to DLN and that murine LC express TNF-R2.

Animals↗
PubMed1996

In vivo protective anti-HIV immune responses in non-human primates through DNA immunization.

An effective immune response involves the specific recognition of and elimination of an infectious organism at multiple levels. In this context DNA immunization can present functional antigenic proteins to the host for recognition by all arms of the immune system, yet provides the opportunity to delete any genes of the infectious organism which code for antigens or pieces of antigens that may have deleterious effects. Our group has developed the use of nucleic acid immunization as a possible method of vaccination against Human immunodeficiency virus type 1 (HIV-1) [1,2,3,10,11,12]. Sera from non-human primates immunized with DNA vectors that express the envelope proteins from HIV-1 contain antibodies specific to the HIV-1 envelope. These sera also neutralize HIV-1 infection in vitro and inhibit cell to cell infection in tissue culture. Analysis of cellular responses is equally encouraging. T cell proliferation as well as cytotoxic T cell lysis of relevant env expressing target cells were observed. In addition, evidence that DNA vaccines are capable of inducing a protective response against live virus was demonstrated using a chimeric SIV/HIV (SHIV) challenge in vaccinated cynomologous macaques. We found that nucleic acid vaccination induced protection from challenge in one out of four immunized cynomolgus macaques and viral load was lower in the vaccinated group of animals versus the control group of animals. These data encouraged us to analyze this vaccination technique in chimpanzees, the most closely related animal species to man. We observed the induction of both cellular and humoral immune responses with a DNA vaccine in chimpanzees. These studies demonstrate the utility of this technology to induce relevant immune responses in primates which may ultimately lead to effective vaccines.

AIDS Vaccines↗