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Biomedical subjects

B Wang

Publications and source records attributed to B Wang.

At least 757 records · Page 42Linked to original sources
PubMed1994

A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene.

A severe immunodeficiency involving a complete loss of T lymphocytes and natural killer cells was observed in independent lines of transgenic mice containing > 30 copies of the human CD3E gene (pL12). T-cell- natural killer (NK)- mice could also be generated by using a gene fragment pL12 delta 1 (without exons 4A and 5) coding for the CD3-epsilon transmembrane region and its 55-amino acid nonenzymatic cytoplasmic tail. The abnormally small thymus gland in the homozygous transgenic animals, which was approximately 1% the size of a wild-type thymus, contained only a few (2-4%) prethymocytes with a Thy-1+Pgp-1+IL-2R alpha- CD3-4-8- phenotype. In mice with lower copy numbers of the transgene thymocyte development was blocked at the Thy-1+Pgp-1-IL-2R alpha+CD3-4-8- stage, and normal NK activity was detected. Mice generated with high-copy numbers of a transgene pL12 delta 2 (pL12 delta 1 minus exons 6), coding for a truncated protein from which the CD3-epsilon extracellular domain, its transmembrane region, and most of its cytoplasmic region were absent, contained normal numbers of T lymphocytes and NK cells. These transgene effects suggested that recruitment of signal-transduction molecules by the cytoplasmic tail of this protein played an important role in the abrogation of both lineages. Taken together these observations support the notion that T lymphocytes and NK cells stemmed from a common precursor.

Animals↗
PubMed1994

Targeted mutations in the Caenorhabditis elegans POU homeo box gene ceh-18 cause defects in oocyte cell cycle arrest, gonad migration, and epidermal differentiation.

We used targeted gene inactivation to analyze the function of a Caenorhabditis elegans POU gene, ceh-18, and to dissect its functional domains in vivo. In ceh-18 mutants, oocytes exhibit an incompletely penetrant failure to arrest in diakinesis of meiotic prophase I and instead undergo multiple rounds of DNA replication without cytokinesis. ceh-18 is expressed in the gonadal sheath cells that signal the oocyte, but not in the oocyte. This suggests that ceh-18 affects, directly or indirectly, a sheath cell signal that causes oocytes to maintain diakinesis arrest. ceh-18 also participates in directing gonad migration and in specifying the differentiated phenotypes of epidermal cells during postembryonic development. Analysis of targeted deletions that disrupt half of the POU domain selectively by deleting either the POUhd or the POUsp alone, indicates that each CEH-18 POU subdomain is sufficient for partial activity in vivo.

Amino Acid Sequence↗
PubMed1994

Limonene chemoprevention of mammary carcinoma induction following direct in situ transfer of v-Ha-ras.

Monoterpenes, including limonene and its in vivo rat plasma metabolites, have been shown to be inhibitors of protein isoprenylation of small G proteins, including p21 ras. In addition, dietary limonene has been shown to be capable of preventing the development and causing the regression of chemically induced mammary carcinomas, many of which contain activated ras oncogenes. On the basis of these observations, it was hypothesized that a possible mechanism by which limonene exerts its effects on the chemoprevention and regression of mammary tumors involves the inhibition of protein isoprenylation of the small G protein p21. In the first study, we asked whether dietary limonene was able to prevent the development of mammary carcinomas which were induced using direct retroviral gene transfer of v-Ha-ras into the mammary parenchyma in situ. Limonene modified neither the rate of gene transfer nor the stability of gene expression. However, limonene did greatly inhibit the formation of mammary carcinomas induced by the insertion of activated ras. In a follow-up study, we asked whether chemoprevention by limonene was preferentially effective against a subset of chemically induced mammary carcinomas with activated ras. Rats were fed limonene to prevent the development of N-nitroso-N-methylurea-induced mammary tumors, a majority of which contain the activated Ha-ras oncogene. As expected, limonene administration increased the latency period and lowered the frequency of mammary carcinoma development as compared to controls. However, tumor characterization revealed that limonene treatment did not alter the percentage of carcinomas with activated ras. These studies are consistent with the above studies in that limonene is effective in preventing mammary carcinomas with activated ras. Interestingly, carcinomas without activated ras were prevented to the same extent as those with the activated oncogene.

Animals↗
PubMed1994

Measuring H type 1 and H type 2 antigens in human saliva by immunoassay using artificial antigens as standard substances.

A time-resolved fluorometric immunoassay for water-soluble H antigens of ABH blood group substances has been developed. Introducing artificial antigens (trisaccharide-albumin complexes for H type 1 and H type 2) as reference substances, H blood group substances in human saliva were measured. The monoclonal antibody, anti-H 1E3, reacted with both H type 1 and type 2 chains, and the commercially available anti-H reacted with H type 2 chain. Using these two antibodies we found 10-20-fold higher concentration of H type 1 compared with that of H type 2 in human saliva. The H type 2 was not found in the saliva samples from nonsecretors, irrespective of ABO phenotypes. The results suggest that approximately 90% of A and B blood group substances in human saliva are built on type 1 chains.

ABO Blood-Group System↗
PubMed1994

Responses of neurons in the ventrolateral orbital cortex to noxious cutaneous stimulation in a rat model of peripheral mononeuropathy.

The responses of ventrolateral orbital cortex neurons to noxious cold pressor were compared in rats with loose ligatures tied around their sciatic nerve with those in rats in which the sciatic nerve was exposed but not ligated. In ligated rats more cells responded to cold pressor and their average afterdischarges were longer. There were no differences in the background firing rate or the magnitude of response to the cold pressor between the two groups.

Animals↗
PubMed1994

BR140, a novel zinc-finger protein with homology to the TAF250 subunit of TFIID.

The Br140 protein was initially identified due to its co-purification with an integrin. We have cloned and sequenced the cDNA corresponding to the Br140 protein. Analysis of the amino acid sequence indicates that Br140 has features characteristic of gene regulatory proteins, including zinc fingers. Furthermore, Br140 has a homology to a family of transcriptional co-activators, one of which is a characterized component of the general transcriptional machinery. Immunologic studies indicate that Br140 has a broad tissue distribution and is abundant in testes and spermatogonia. Br140 is primarily a nuclear protein. These results suggest that Br140 may be a part of the general transcriptional machinery.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Cortical magnetic and electric fields associated with voluntary finger movements.

Multichannel recordings of both movement-related magnetic fields (MRMFs) and movement-related cortical potentials (MRCPs) were simultaneously recorded in association with voluntary unilateral self-paced index finger abduction movement in two normal volunteers. 1) Slow magnetic field (readiness field; RF) can be detected several hundred msec before the movement onset, and its field distribution indicates the existence of the largest generator source over the contralateral primary motor area. Taken together with the vertex-maximal Bereitschaftspotential which corresponds to the earlier part of the RF, the complexity of this magnetic field suggested by relatively low correlation value in single dipole model indicates the co-activation of other underlying generators besides this largest dipole. 2) The utilization of MRMF with MRCP facilitates the separation of two distinct electrophysiological events in proximity to the movement onset, which are difficult to be determined by the technique of MRCP only. Those are the motor field (MF) and the movement evoked field I (MEFI) in MRMF, and the parietal peak motor potential (ppMP) and the frontal peak motor potential (fpMP) in MRCP, which occur approximately 20 and 100 msec after EMG onset, respectively. These two subcomponents may imply the culmination of motor cortex and sensory feedback activation, respectively. Combined study of MRMF and MRCP will provide better definition of cortical events related to voluntary movement than the study of either modality alone.

Adult↗
PubMed1994

Head surface digitization and registration: a method for mapping positions on the head onto magnetic resonance images.

We have developed a method for mapping positions on the head, such as anatomical landmarks, electrode locations, and stimulation sites, onto magnetic resonance (MR) images of the head. This method is based on the registration of two representations of the head surface: a series of contours obtained from MR images and a set of points measured from the head. The three-dimensional coordinates of each head point were acquired with the use of a magnetic digitizer, whose source was removed from the equipment and mounted on top of the subject's head. This arrangement seemed less uncomfortable for the subject than head immobilization and allowed the acquisition of many points without compromising the precision of the measurements. The digitized head surface was registered to MR image head contours using a surface registration algorithm. The registration provided the rotation and translation parameters needed for mapping head positions onto MR images. The precision of this mapping method has been estimated to be in the range of 3 to 8 mm. This method has been used to map dipole sources in electroencephalography and magneto-encephalography and to impose maps of scalp sites used in transcranial magnetic stimulation onto MR and PET images of the brain.

Adult↗
PubMed1994

Immunotherapeutic strategies targeting rheumatoid synovial T-cell receptors by DNA inoculation.

Immunotherapy against autoreactive T-cell receptors (TCRs) has been reported to have promise in several animal models of autoimmune diseases. Facilitated DNA inoculation has many potential advantages as a modality for development of specific immune responses. Specifically, this technology is able to deliver exogenous antigens for processing via both the endogenous pathway, with subsequent presentation by class-I major histocompatibility (MHC) antigens, and the exogenous pathway, with subsequent presentation by class-II MHC antigens. This allows for induction of both arms of the cellular immune system. These cellular immune responses may be particularly important in targeting and controlling pathogenic cell populations. The application of this technology to the treatment of human autoimmune diseases depends on the availability of readily manipulated systems for the evaluation of specific interventions. Here we report the full length cloning and expression of TCRs from rheumatoid arthritis synovial tissue. These were developed by recombinant polymerase chain reaction, cloning and retroviral transduction into a TCR-alpha/beta-negative murine T-cell hybridoma. Reconstitution of CD3 expression was confirmed by flow cytometry. Similar constructs have been developed for TCR-based immunotherapy by facilitated inoculation of DNA intramuscularly. Preliminary analysis of immune responses in mice indicates that these constructs elicit anti-TCR responses. These studies indicate the ability to reconstitute expression of potentially autoreactive human TCRs in a model system wherein specific immune responses elicited against these TCRs by various immunogens can be evaluated.

Amino Acid Sequence↗
PubMed1994

DNA inoculation as a novel vaccination method against human retroviruses with rheumatic disease associations.

There are a number of rheumatologic manifestations of human retroviral infections associated with human immunodeficiency virus type I (HIV-I) and the human T-cell leukemia virus type I (HTLV-I) including arthritis, Sjøgren's syndrome-like symptoms as well as other varied autoimmune phenomena. Infection with HTLV-1 may be directly involved in the etiology and/or pathogenesis of an arthritic condition similar to rheumatoid arthritis. We have been characterizing a new vaccination strategy against human retroviral infections, designated DNA inoculation. This procedure involves the intramuscular injection of DNA plasmids which express specific human retroviral antigens. This technique results in the development of humoral and cellular immune responses against these proteins. Specifically, this method has been successfully used to develop immune responses against HIV-I and HTLV-I. The availability of rat and rabbit infection models for HTLV-I, coupled with the successful development of immune responses in these animals after DNA inoculation with an HTLV-I envelope expressing plasmid, will allow the efficacy of this vaccination technique to be evaluated with protection against in vivo viral challenge as an endpoint.

Animals↗
PubMed1994

Facilitated DNA inoculation induces anti-HIV-1 immunity in vivo.

Vaccine design against HIV-1 is complicated both by the latent aspects of lentiviral infection and the diversity of the virus. The type of vaccine approach used is therefore likely to be critically important. In general, vaccination strategies have relied on the use of live attenuated material or inactivated/subunit preparations as specific immunogens. Each of these methodologies has advantages and disadvantages in terms of the elicitation of broad cellular and humoral immune responses. Although most success has been achieved with live attenuated vaccines, there is a conceptual safety concern associated with the use of these vaccines for the prevention of human infections. In contrast, subunit or killed vaccine preparations enjoy advantages in preparation and conceptual safety; however, their ability to elicit broad immunity is more limited. In theory, inoculation of a plasmid DNA that supports in vivo expression of proteins, and therefore presentation of the processed protein antigen to the immune system, could be used to combine the features of a subunit vaccine and a live attenuated vaccine. We have designed a strategy for intramuscular DNA inoculation to elicit humoral and cellular immune responses against expressed HIV antigens. Uptake and expression are significantly enhanced if DNA is administered in conjunction with the facilitating agent bupivacaine-HCl. Using this technique we have demonstrated functional cellular and humoral immune responses against the majority of HIV-1 encoded antigens in both rodents and non-human primates.

AIDS Vaccines↗
PubMed1994

Localization of endothelin receptors in the human prostate.

The objective of the present study was to localize endothelin receptors in the human prostate using quantitative autoradiography. Slide-mounted tissue sections 20 microns. in thickness were obtained from the transition zones of seven patients undergoing radical prostatectomies for low volume prostate cancer. Sarafotoxin (S6C) and BQ123 have been used to distinguish endothelin receptor subtypes (ETA and ETB). The prostatic tissue sections were incubated in four different stock solutions containing the following: 0.1 nM. 125I-endothelin-1 (125I-ET-1) (total ET-1 binding); 0.1 nM. 125I-ET-1 and 100 nM. S6C (total ETA binding); 0.1 nM. 125I-ET-1 and 1 microM. BQ123 (total ETB binding); and 0.1 nM. 125I-ET-1 and 1 microM. ET-1 (nonspecific ET-1 binding). Nonspecific binding accounted for only 12 and 15% of total 125I-ET-1 binding in the stroma and glandular epithelium. Autoradiograms were quantitatively analyzed using a computerized image analysis system. Specific radioactive densities (nCi/mg.) were determined for the stromal and glandular epithelial elements of the prostate. The specific radioactive densities of ETA and ETB binding sites in the stroma were 7.57 +/- 0.65 and 2.98 +/- 0.81. The specific radioactive densities of ETA and ETB binding sites in the glandular epithelium were 1.59 +/- 0.15 and 7.87 +/- 1.35. The present study demonstrates that the predominant endothelin receptors in the stroma and glandular epithelium are the ETA and ETB subtypes, respectively.

Autoradiography↗
PubMed1994

Relationship between prostatic epithelial volume and serum prostate-specific antigen levels.

OBJECTIVES: The present study was designed to determine the relationship between serum prostate-specific antigen (PSA) levels and prostatic epithelial volumes. METHODS: Forty-two men between the ages of 50 and 79 years of age with either an abnormal digital rectal examination (DRE) or a serum PSA level > 4 ng/dL underwent transrectal ultrasonography (TRUS) and ultrasound-guided random systematic biopsy of the prostate. The volumes of the peripheral zone (PZ) and transition zone (TZ) were calculated, assuming that the total prostate and TZ are ellipsoidal structures. Six random systematic biopsies were directed into the PZ and four random systematic biopsies were directed into the TZ under ultrasound guidance. Among the 42 patients undergoing prostatic biopsy, adenocarcinoma of the prostate was identified in 21 (50%). Tissue sections obtained from the biopsy specimens of the subjects without histologic evidence of prostate cancer were stained with Mallory trichrome stain, and the percentage area density of epithelium in the biopsy cores was determined using computer-assisted color image analysis. The relationships between serum PSA and total, PZ, and TZ epithelial volumes, and serum PSA and total, PZ, and TZ prostatic volumes were determined using regression analysis. RESULTS: The difference between the mean percentage epithelial density of the PZ (17.79 +/- 1.40%) and TZ (10.32 +/- 0.82%) was statistically significant (p < 0.0001). The mean volumes of epithelium in the PZ and TZ were 4.25 +/- 0.47 cc and 3.39 +/- 0.45 cc, respectively. The p and r2 values for the relationship between serum PSA and total prostatic volume were 0.016 and 0.260, respectively. Statistically significant correlations were also observed between serum PSA levels and TZ epithelial volumes (p = 0.0009; r2 = 0.449) and serum PSA levels and TZ volumes (p = 0.007; r2 = 0.329). Statistically significant correlations were not observed between serum PSA levels and the following parameters: PZ volume, PZ epithelial volume, and total prostatic epithelial volume. CONCLUSIONS: Although the PZ contains a significantly greater area density and absolute volume of epithelium than the TZ, the serum PSA level is most strongly correlated only with the volume of epithelium in the TZ.

Age Factors↗
PubMed1994

Vitamin E uptake into the brain and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity.

The brain uptake index for vitamin E has not been reported previously. This study examined the possible involvement of altered brain vitamin E uptake as an explanation of alterations in vitamin E levels in the brain following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. The brain uptake index of vitamin E was evaluated in control mice and at 1 and 24 h after toxin treatment. Control mice had a brain uptake index of 6.1 +/- 1.2. The toxin induced more than a twofold increase in the vitamin E brain uptake index to 15.2 +/- 6.8 at 1 h after treatment, which returned to control values at 24 h. The dramatic increase in the brain uptake index of vitamin E may explain the increases in vitamin E levels found in some brain regions following MPTP administration.

Animals↗
PubMed1994

Empirical studies of protein secondary structure by vibrational circular dichroism and related techniques. Alpha-lactalbumin and lysozyme as examples.

Vibrational circular dichroism (VCD) has been shown to be sensitive to secondary structure in proteins and peptides and has been used as the basis for quantitative secondary-structure-prediction algorithms. However, the accuracy of these algorithms is not matched by the apparent qualitative sensitivity of the VCD spectra. This report provides examples of the use of VCD to follow structural change spectrally and to clarify the qualitative nature of the structural changes underlying the spectral variation. The VCD spectra and the complementary UV electronic CD (ECD) and FTIR spectra of alpha-lactalbumin (LA) have been studied as a function of pH, denaturation, Ca2+ ion and solvent conditions for several species. Spectral data for lysozyme were compared with those of LA because of their very similar crystal structures. In fact, these proteins in D2O-based pH 7 solution have quite different spectra using these optical techniques. Even for the LA proteins, the human differs from the bovine and goat species. Furthermore, under low pH conditions, where the LAs are in a reversibly denatured, molten globule form, the spectra are more similar, species variation is minimal and the spectral differences from lysozyme are in fact smaller. Our data are consistent with native, pH 7, alpha-lactalbumin having a less well organized structure than lysozyme, possibly in a dynamic sense. Conversely, in the low-pH, molten globule form of LA, tertiary structure is lost which could relax constraints that might distort the helical segments in the native form. The differences between the interpretation of our results and those from X-ray and NMR data may be due to motional sampling of various geometries in LA which all contribute to the spectral signatures seen in optical spectra but whose contributions are washed out in NMR or frozen out in the crystal structure. Part of this flexibility may relate to the rather large 3(10)-helical content in the LA protein structure. Fluctionality may have specific functional effects, perhaps allowing LA to bind better to beta-galactosyl transferase and form the biologically active lactose synthetase complex.

Amino Acid Sequence↗