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S Baird

Publications and source records attributed to S Baird.

At least 55 records · Page 3Linked to original sources
PubMed1990

Membrane topology of epoxide hydrolase.

The amino acid sequences of epoxide hydrolase from rat, rabbit and human have been subjected to hydropathy analysis and a novel model for the membrane topology of this enzyme is presented. The enzyme would appear to be retained in microsomal membranes by a single transmembrane segment located at the N-terminus and the majority (96%) of the protein is exposed at the cytosolic membrane surface. This model is significantly different from a scheme suggested by analysis of the rat enzyme alone which proposed six transmembrane domains (Porter et al. (1988) Arch. Biochem. Biophys. 248, 121-129). Experiments with rat microsomal membranes were conducted to distinguish between the two models and used proteolytic enzymes and non-permeant chemical probes. Epoxide hydrolase of intact and permeabilised membranes was resistant to digestion by a number of proteinases. However, this is likely to be related to a compact fold of the protein rather than membrane association since purified, delipidated enzyme preparations were also resistant to proteolysis. While the use of proteinases did not provide useful membrane topological information, experiments with the fluorescent probe, 3-azido-2,7-naphthalenedisulphonate strongly support the view that the majority of the protein is indeed exposed at the cytosolic surface of the membranes. The analysis illustrates the caution which must be employed in the formulation of topological models based on hydropathy plots alone and the value of considering homologous proteins.

Animals↗
PubMed1990

The role of xenobiotic glucuronidating enzymes in drug resistance of tumour tissues and cells.

Xenobiotic and endobiotic glucuronidation is regulated by many cellular features such as (a) access of substrates to a family of microsomal enzymes, the UDP-glucuronosyltransferases (UDPGTs) and (b) mechanisms of transport and excretion of glucuronides from the cell. We have isolated molecular biological probes identifying human UDPGTs to facilitate the examination of mechanisms regulating the functional expression of UDPGTs during natural development, in genetic diseases and in cancer cells. UDPGTs are encoded by a multigene family. Seven rat and four human UDPGT cDNAs have been cloned and expressed in cell culture to determine their substrate specificity and ability to glucuronidate xenobiotics. Analysis of the amino acid sequences of cloned UDPGTs has provided information about their method of synthesis and topological orientation with the lumen of the endoplasmic reticulum (ER). The location of hepatic UDPGT raises interesting questions about the role of possible transporters essential for functional glucuronidation. Measurement of the UDPGT activities and UDPGT mRNA in carcinoma tissue and in hepatic nodules from rats suggest that increases in the level of a phenol-UDPGT may contribute to drug resistance in cancer. Human UDPGTs stably expressed in cell lines have been used to study the glucuronidation of carcinogens and anticancer drugs. Human phenol UDPGT will catalyse the glucuronidation of carcinogens. The high levels of expression of human phenol UDPGT in tissue culture cells could also lead to an increased resistance to xenobiotic toxicity caused by mitoxantrone, mitomycin C, and adriamycin. This molecular cell biology approach is being used to further assess the glucuronidation and effective toxicity of anticancer drugs.

Animals↗
PubMed1989

Graded neuropsychological impairment and elevated gamma-glutamyl transferase in chronic alcoholic men.

This study hypothesizes that distinct biochemical and metabolic disturbances associated with liver injury may be related to specific cognitive changes in alcoholics. In 132 alcoholic men admitted to an alcohol treatment program, increases in gamma-glutamyl transferase (GGT) values were correlated with impairment in several measures of visuoperceptual and visuoconceptual functioning. The association between plasma levels of GGT and neuropsychological performance was independent of the relative contribution of other laboratory measures of liver injury and of alcohol consumption histories. These observations support the hypothesis that elevated levels of GGT are distinctly associated with neuropsychological deficits and suggest that possible mechanisms beyond severe hepatic dysfunction and alcohol consumption underlie cognitive deficits in alcoholics.

Adult↗
PubMed1988

Use of laboratory tests to monitor heavy drinking by alcoholic men discharged from a treatment program.

Changes in blood test values from the time of discharge from an alcohol treatment program to 3-month follow-up were studied in two consecutive series of alcoholic men. The parallel combination of a percent increase in gamma-glutamyltransferase (GGT) of greater than or equal to 20%, in aspartate aminotransferase (SGOT) of greater than or equal to 40%, and in alanine aminotransferase (SGPT) of greater than or equal to 20% over discharge values was developed as a rule and then cross-validated to identify those alcoholic men who had resumed drinking at follow-up. Serial determination of these three test values in combination can be used to distinguish recovering alcoholics who remain abstinent from those who resume drinking.

Adult↗
PubMed1988

MOHS for head and neck mucosal cancer: report on 111 patients.

Microscopically Oriented Histologic Surgery (MOHS) has been applied to primary epidermoid cancers of the mucosal tissues of the head and neck since 1979. In that time we have treated 170 patients and maintained excellent records, losing no patients to follow-up. One hundred three patients have been followed for 2 years. Of this group, only nine patients have developed local recurrences; three were salvaged, six were not. This presentation reviews the concept of MOHS and its application to head and neck mucosal lesions. The results are analyzed, and conclusions are drawn regarding what we have learned about the biologic behavior of head and neck tumors and the role of MOHS in treating these neoplasms.

Carcinoma, Squamous Cell↗
PubMed1987

Microscopically oriented histologic surgery for head and neck mucosal cancer.

Frozen section directed surgery, called MOHS, has been successfully utilized in the resection of primary epidermoid tumors of the head and neck. For the 93 cases reviewed in this study, 70% had microscopically identified tumor 1 cm away from clinically evident disease. Tumor spread was along planes of least resistance, most commonly in the submucosa. Microscopically directed excisions were able to trace and remove these tumor extensions. Local control in 93 patients with 2-year follow-up was 91% and, with salvage of recurrences, was 95%. The authors' observations suggest three important concepts. First, epidermoid cancer of the head and neck grows as a continuous neoplasm. Second, this work casts serious doubt on the concept of "field cancerization" or multiple primaries as a cause of local recurrence. Third, conventional frozen section analysis of surgical margins is highly unlikely to discover microscopic extensions because many tumor extensions are thin, finger-like projections which require examination of the entire surgical margin to detect.

Carcinoma, Squamous Cell↗
PubMed1986

Structure of a Bacillus subtilis endo-beta-1,4-glucanase gene.

The nucleotide sequence of the portion of a Bacillus subtilis (strain PAP115) 3 kb Pst I fragment which contains an endo-beta-1, 4-glucanase gene has been determined. This gene encodes a protein of 499 amino acid residues (Mr = 55,234) with a typical B. subtilis signal peptide. Escherichia coli which has been transformed with this gene produces an extracellular endoglucanase with an amino-terminus corresponding to the thirtieth encoded amino acid residue. The gene is preceded by a cryptic reading frame with a rho-independent terminator structure, and itself has such a structure in the immediate 3'-flanking region. We have also identified, in the 5'-flanking region, nucleotide sequences which resemble promoter elements recognized by Bacillus RNA polymerase E sigma 43. Comparison of the encoded amino acid sequence to other known beta-glucanases reveals a small region of similarity to the encoded protein of the Clostridium thermocellum celB gene. These similar regions may contain substrate-binding and/or catalytic sites.

Amino Acid Sequence↗
PubMed1986

Lack of correlation between the accumulation of plus-strand leader RNA and the inhibition of protein and RNA synthesis in vesicular stomatitis virus infected mouse L cells.

The inhibition of protein synthesis in mouse L cells infected by vesicular stomatitis virus (VSV) requires expression of two regions (one large and one small) of the viral genome, as determined by target size analysis. The inhibition of host RNA synthesis was also shown to be dependent on expression of two regions of the VSV genome, most likely the same ones. In some cases, such as in cells infected by mutants T1026R1, or tsG41 at 40 degrees, or moderately uv irradiated VSV, only one of the two regions was expressed, yet cellular protein and RNA synthesis was decreased. This suggests that the product of each region of the viral genome can act independently. In these instances the severity of the inhibition was dependent on both the length of the infection period and the multiplicity of infection. The identity of neither gene product is known, but it has been suggested that small product is plus-strand leader RNA. As shown herein, however, there was no correlation between the extent of host macromolecular synthesis inhibition and the quantity of leader RNA in infected cells.

Animals↗
PubMed1985

Glucanase gene diversity in prokaryotic and eukaryotic organisms.

A number of bacteria and eukaryotes produce extracellular enzymes that degrade various types of polysaccharides including the glucans starch, cellulose and hemicellulose (xylan). The similarities in the modes of expression and specificity of enzyme classes, such as amylase, cellulose and xylanase, suggest common genetic origins for particular activities. Our determination of the extent of similarity between these glucanases suggests that such data may be of very limited use in describing the early evolution of these proteins. The great diversity of these proteins does allow identification of their most highly conserved (and presumably functionally important) regions.

Amino Acid Sequence↗
PubMed1983

Analysis of B-cell antigens in normal reactive lymphoid tissue using four B-cell monoclonal antibodies.

Lymph nodes from 13 cases of reactive hyperplasia were examined with four different monoclonal antibodies to B cells. B-1 recognizes an antigen of 30,000 daltons on B cells. CB-2 was prepared with normal spleen and binds to a glycolipid. BA-1 labels surface immunoglobulin-positive cells, but not T lymphocytes or monocytes. B-532 recognizes an antigenic determinant of 45,000 daltons. Using the immunoperoxidase method on frozen sections of reactive lymph nodes, the staining patterns of these four unique antibodies showed dramatic differences. B-1 labeled 80%-90% of the germinal center cells and 10%-50% of the mantle region. Few interfollicular cells were positive. CB-2 stained predominantly in the mantle area (50%-90% positive cells), with moderate staining in the germinal center as well and less than 1% positive cells in the diffuse cortex. BA-1 exhibited predominant labeling in the mantle (50%-90%), with little staining in the germinal center. A large number of cells in the interfollicular, subcapsular, and medullary regions expressed the BA-1 antigen. The B-5 antibody demonstrated intense staining in the follicle (50%-95%). This staining often appeared to be polarized within the germinal center. The mantle zone demonstrated staining of 30%-50% of the cells. The different staining patterns of the B-cell antibodies, as demonstrated by the in situ distribution of positive cells within the lymph node, may reflect stages of development or activation of the B-cell population.

Antibodies, Monoclonal↗
PubMed1983

Characterization of a monoclonal antibody that reacts with an activation antigen on human B cells: reactions on mitogen-stimulated blood lymphocytes and cells of normal lymph nodes.

We describe a monoclonal antibody that reacts with human B-lymphoid cells. We have characterized the reactions of this antibody on normal blood lymphocytes, with and without pokeweed mitogen stimulation, bone marrow lymphocytes, and on frozen sections of normal lymph nodes. The antibody, B532, appears to recognize an activation antigen on human B cells. This activation antigen can apparently be induced both by infection with Epstein-Barr virus and by stimulation with antigens and mitogens, but it is lost on plasma cells. In normal lymph nodes, the antigen is confined to germinal center cells and some of the cells of the "mantle" that surrounds germinal centers. The antigen is not present on T cells.

Animals↗
PubMed1983

Monoclonal antibodies to murine leukemia virus gp 70 recognize the same T lymphoma cell surface molecules as anti-immunoglobulin.

Chicken antisera to mouse immunoglobulin (anti-Ig) detect molecules on T lymphocytes of mice consisting of "heavy chains" similar in size to IgM mu chains and "light chains" similar in size to lambda or kappa chains. Because these T cell-derived proteins react with anti-Ig and are composed of Ig-like heavy and light chains, these molecules have been viewed as candidates for "IgT," the putative T lymphocyte receptor for antigen. We have demonstrated, by immunoprecipitation and two-dimensional gel analysis, that the lymphoma surface molecule precipitated by chicken anti-Ig is identical to the viral 70,000 dalton glycoprotein (gp 70) expressed by that lymphoma and is unassociated with any "light chain" or equivalent. For each of the three lymphomas analyzed, the gp 70 two-dimensional gel pattern was individually distinctive, and, in each case, the molecules precipitated by anti-Ig exhibited the same pattern as the gp 70. The viral gp 70 does have cross-reacting determinants with mouse IgM as seen by the chicken antiserum. We have substantiated these results by demonstrating that monoclonal antibodies to viral gp 70 precipitate the same molecules as chicken anti-Ig. These findings demonstrate that these T lymphoma cell surface molecules do not represent the T cell immunoglobulin receptor for antigen unless gp 70 itself is an antigen receptor.

Animals↗
PubMed1980

Induction of lymphoma in athymic mice: a model for study of the human disease.

A murine lymphoma, designated L1, was produced in immunologically deficient nude mice after chronic antigenic stimulation by infection with the pinworms Aspiculuris tetraptera and Syphacia obvelata. In vivo, L1 involves primarily the spleen and lymph nodes, with infiltration of liver, kidney, and bone marrow also observed. It is characterized by large clusters of B cells and null cells, and by rare T cells. The lymphoma cells express murine leukemia virus antigens (gp70 and p30) on the surface. L1 can be passaged successfully both in vivo and in vitro. The lymphoblasts that proliferate in vitro are null, but injecton back into the mouse produces a similar pattern of B cells, null cells, and occasional T cells as seen in the mouse-to-mouse transfers. Infectious viruses have been isolated from L1 cells and from tissue culture supernates and have been identified as a B-tropic murine leukemia virus and a xenotropic virus. The possibilities of this model for studying the etiology of human lymphoma are discussed.

Animals↗