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Biomedical subjects

M H Brown

Publications and source records attributed to M H Brown.

At least 109 records · Page 6Linked to original sources
PubMed1986

Hypothalamic circuits and circadian rhythms: effects of knife cuts vary with their placement within the suprachiasmatic area.

The suprachiasmatic nucleus (SCN) of the hypothalamus and its efferent projections are necessary for the generation of circadian rhythms. To further investigate the role of SCN connections in the generation of behavioral rhythms, intact and blinded-castrated male rats housed in constant conditions were given horizontal knife cuts aimed dorsal to the SCN, or sham surgery. Rhythms of locomotor activity and drinking behavior were monitored using a microcomputer. Cuts that spared the SCN failed to abolish rhythms. Effects of cuts that damaged the SCN ranged from changes in period length of the rhythms to abolition of drinking rhythms. These and previous results indicate that connections between the SCN and the paraventricular nucleus of the hypothalamus are not necessary for the expression of behavioral rhythms.

Animals↗
PubMed1986

Molecular cloning of the human T-lymphocyte surface CD2 (T11) antigen.

CD2 (T11, sheep erythrocyte receptor) is a surface antigen of the human T-lymphocyte lineage. cDNA clones encoding CD2 have been isolated by using the purified, denatured CD2 to raise a rat antiserum. Positive clones were recognized in a phage lambda gt11 expression library prepared from the human leukemia T-cell line J6. The DNA sequence contained an open reading frame encoding 360 amino acids. The N-terminal 24 amino acids were characteristic of a signal peptide and were followed by a region that matched all 25 residues of the CD2 N terminus previously determined by amino acid sequencing. The predicted amino acid sequence is consistent with that of a transmembrane glycoprotein containing three potential N-glycosylation sites on the N-terminal side of a 26-amino acid hydrophobic segment. There is a large cytoplasmic domain of 125 amino acids that is rich in proline and in basic residues. RNA blot-hybridization analysis demonstrated hybridization only in those T cells that were positive for surface CD2 antigen. There are limited regions of sequence similarity to members of the immunoglobulin supergene family.

Amino Acid Sequence↗
PubMed1986

Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1.

The monoclonal antibody UCHL1 identified an antigen present on most thymocytes, a subpopulation of resting T cells within both the CD4 and CD8 subsets, and on mature activated T cells. The UCHL1 determinant is also present on cells of the myeloid lineage, but not normal B cells or NK cells. Functionally, UCHL1 identifies a subpopulation of T cells which proliferates maximally to soluble antigen and provides maximum help for PWM-stimulated immunoglobulin synthesis. In contrast, the UCHL1- cells do not induce immunoglobulin synthesis and do not proliferate in the presence of soluble antigen, although both the UCHL1- and the UCHL1+ fractions of T cells proliferate well in the presence of PHA. By standard immunoprecipitation techniques and SDS page, the antigen recognized by UCHL1 was found to have a molecular weight of 180,000-185,000. Preclearing experiments using antibodies identifying the leucocyte common antigen, LCA, and the lymphocyte function-associated antigen, LFA-1, which have similar molecular weights to UCHL1, showed that the UCHL1 determinant is not biochemically related to these antigens.

Animals↗
PubMed1986

Regulation of antibody production by an antigen-specific EBV-transformed B-lymphoblastoid cell line: effect of high-dose antigen and antigen-pulsed T cells.

A B-cell line (C1B2) secreting monoclonal IgG antibody to influenza virus haemagglutinin (HA3) was obtained by Epstein-Barr virus (EBV) transformation of human tonsillar B cells activated in vitro to influenza A/X31. Antibody secretion by C1B2 was completely inhibited by purified HA3 at concentrations above 100 ng/ml. By contrast, high doses of HA3 had no effect on EBV-transformed B-cell lines making antibody of unrelated specificity. Inhibition of specific antibody secretion by HA3 continued for at least 3 days after the removal of soluble antigen, but this could be partially reversed by treatment with pronase, suggesting that inhibition was due to 'effector cell' blockade by binding of antigen to surface Ig receptors. T cells pulsed with high doses of antigen also suppressed antibody secretion by C1B2, but this effect was probably due to a tolerogenic signal delivered to the B cell by HA3 complexed to the T-cell membrane rather than suppression by antigen-induced Ts, or carryover of free antigen. These experiments demonstrate two independent mechanisms of high-dose tolerance in vitro, and show that monoclonal B-lymphoblastoid lines of known specificity can be used to study regulation of specific antibody production at the level of the B cell.

Antibodies, Monoclonal↗
PubMed1985

T cell-replacing factor in specific antibody responses to influenza virus by human blood B cells.

In man, B cell maturation factors obtained from T cells or T cell lines have been shown to induce antibody formation in mitogen or anti-immunoglobulin activated B cells, and in some continuous B cell lines, but the relationships between these factors and B cell differentiation factors in antigen-specific antibody responses is unclear. We have now shown that supernatants from phytohemagglutinin-activated tonsil cells, or from the Gibbon Ape T cell line MLA-144, can substitute for T cells in the specific antibody response by human blood B cells to influenza virus. Thus, T cell-depleted non-rosette-forming (E-) cells prepared from peripheral blood mononuclear cells made antibody when cultured with antigen and factor together, whereas control cultures of E- cells with either antigen or factor alone did not. Moreover, E- cells cultured with factor and influenza virus strain A/X31 made antibody to A/X31, but not the non-cross-reacting strain, B/HK (and vice versa) showing that the response was antigen specific. The activity in these supernatants, therefore, fulfilled the functional definition of T cell-replacing factor (TRF). The possibility that interleukin 2 (IL 2) present in the TRF-containing supernatants was expanding residual T cells in the E- preparations to provide normal T cell help was excluded in three different ways. First, E- cells depleted of T (Leu4+) cells to undetectable levels made normal amounts of antibody when cultured with antigen and TRF. Secondly, a limiting dilution technique was employed to show that help in cultures of E- cells and TRF was not mediated by antigen-specific T helper cells. Thirdly, TRF-containing supernatants depleted of IL2 retained activity, whereas purified IL2 was inactive. Preliminary purification of TRF by gel filtration on Ultrogel AcA54 columns showed that all the activity eluted in a single peak between 35 000 and 43 000 molecular weight. This distinguishes human TRF from IL 2 and from other B cell maturation factors with a molecular weight range of 15 000-20 000 which act on continuous B cell lines. In addition to TRF, supernatants from phytohemagglutinin-activated tonsils also contained a factor which could induce polyspecific IgM production, but only in cultures containing significant numbers of T cells. This additional activity may have been due to IL 2, and provides an explanation for the apparent T cell-dependent effects sometimes observed in experiments designed to test B cell differentiation factors on T cell-depleted normal B cells.

Antibodies, Viral↗
PubMed1985

Antigen-specific suppression of anti-influenza antibody production in man. Possible role of a membrane-antigen complex.

E rosette-forming (E+) cells from human secondary lymphoid tissue were incubated with high dose influenza A virus (Mem-Bel) in an attempt to generate suppressor T cells. Suppression was assayed by transferring the antigen-pulsed E+ cells into effector cultures consisting of E+ and E- cells stimulated with immunogenic amounts of either the inducing virus Mem-Bel) or the non-cross-reacting influenza B virus (B/HK). The transfer resulted in marked inhibition of IgG, IgA and IgM antibody production to Mem-Bel but not to the control antigen, B/HK virus. The suppressive effect was specific at the level of induction as well as expression since E+ cells exposed to high dose Mem-Bel could provide help to an effector culture containing E- cells and optimal dose of B/HK virus. However, metabolically active cells did not appear to be required for suppression. Thus, it could be elicited (a) after only 15 min incubation of E+ cells with high-dose virus and (b) by E+ cells exposed to irradiation, incubated in the presence of metabolic inhibitors, or disrupted by repeated freeze thawing. In contrast, treatment of E+ cells with pronase reversed the suppressive effect. Interestingly, virus heated to 70 degree C failed to induced suppression, while retailing the ability to elicit a normal helper response. Suppression induced by exposure to standard amounts of high-dose antigen was mediated by T cells of both helper/inducer (Leu-3a+) and suppressor/cytotoxic subsets (Leu-2a+), but not by B cells. Two groups of observations pointed to the B cell as the target of suppression. First, suppression could still be transferred to effector cultures in which helper T cells had been replaced by T cell-replacing factor or suppressor T cells removed by irradiation. Second, significant inhibition of antibody production was obtained when the transfer of antigen-pulsed E+ cells was delayed for up to 120 h after initiation of the effector culture. Taken together the results suggest that suppression in this system is due to the formation of an antigen bridge between specific receptor sites on the T cell membrane and the target. Although not dependent on triggering of metabolically active suppressor T cells the phenomenon highlights the need for care in interpreting the mechanism of suppression by high-dose antigen and could, in addition, represent a biologically important control mechanism capable of rapid inhibition of effector T cells and B cells in sites of high antigen concentration.

Antibodies, Viral↗
PubMed1985

Hypothalamic circuits involved in the regulation of seasonal and circadian rhythms in male golden hamsters.

Hypothalamic knife cuts were employed to investigate the pathways which mediate the gonadal regression induced by short-day photoperiods in male golden hamsters (Mesocricetus auratus). Bilateral horizontal cuts placed between the suprachiasmatic nucleus and the paraventricular nucleus (PVN), as well as cuts placed through the PVN, prevented testicular regression in animals kept on a photoperiod that provided only 6 hr of light/day. Identical effects were obtained when the cuts were placed just dorsal to the PVN. Unilateral damage or sham surgery failed to block gonadal regression. The entrainment of circadian rhythms of locomotor activity to the light-dark cycle was not affected by cuts that abolished the effects of photoperiod on testicular regression. The results are discussed in the context of current models of neural control of the pineal gland and melatonin production.

Animals↗
PubMed1984

Cloning of the structural gene (hly) for the haemolysin of Vibrio cholerae El Tor strain 017.

We have cloned the DNA encoding the haemolysin of Vibrio cholerae El Tor strain 017 into the plasmid vector pBR322. The resultant plasmid, pPM431, has a 6.2-kb PstI DNA insert which leads to the production of the haemolysin in Escherichia coli K-12. Deletion analysis and transposon mutagenesis have allowed us to localize several regions affecting haemolysin production. A number of these mutants have been analysed in E. coli K-12 minicells. Three proteins have been identified: A, 80 kDal; B, 71 kDal; and C, 22 kDal. A is the haemolysin which appears to be cell-associated in E. coli K-12, and B and C are required for its efficient production. We suggest that the genes for proteins A, B and C be designated hlyA, hlyB and hlyC, respectively.

Cloning, Molecular↗
PubMed1983

Artifacts introduced by spectacle lenses in the measurement of strabismic deviations.

The peripheral prismatic effects of corrective spectacle lenses introduce an artifact when strabismic deviations are measured. Plus lenses decrease and minus lenses increase the measured deviation. This effect begins to become clinically significant with corrective lenses with powers of more than +/- 5 diopters. We developed a simplified model that predicts the magnitude of this effect. The model agreed with actual ray tracing analysis through commonly used spectacle lenses and also agreed closely with clinical data. The clinical use of this model is facilitated by remembering the artifacts produced by +20, +10, -10, and -20 diopter spectacle lenses and interpolating for intermediate values. Correcting for these artifacts should enhance the predictability of strabismus surgery in patients with significant ametropia.

Eyeglasses↗
PubMed1982

Procedure for a simplified collarless metal-ceramic restoration using gold powder.

This technique describes a simple and practical approach to the fabrication of collarless metal-ceramic restorations. Instead of making a duplicate die from the master die, this technique conserves time by blocking out the undercut using impression modeling compound on the master die. The use of gold powder does not require special equipment and produces a precise porcelain abutted margin on the shoulder. Excluding the labial gold collar from the shoulder enhances the esthetic appearance of the restoration. This approach is effective with gold-based and silver-palladium alloys as materials for the metal-ceramic framework. The marginal fit of 10 collarless meta-ceramic crowns cemented on silver plated dies were evaluated by measuring sectioned specimens with a scanning electron microscope. The average gap at the porcelain butt margin was observed to be 30 to 50 mu (Fig. 10).

Crowns↗
PubMed1981

Simplified technique for the removal of a fixed partial denture.

A simplified method of removing a fixed partial denture has been described. The principle of the Class I or II lever systems is used to deliver force along the path of withdrawal. Carefully applied, this technique may permit removal of a restoration with minimal trauma to the prosthesis and supporting teeth. Where reasonable pressure fails to dislodge the restoration, it should be sacrificed rather than risk permanent damage to the abutment.

Dental Abutments↗