Another cause of tracheal tube failure.
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Biomedical subjects
Publications and source records attributed to J McLean.
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We have examined the spatiotemporal structure of simple receptive fields in the cat's striate cortex by cross-correlating their spike trains with an ensemble of stimuli consisting of stationary bright and dark spots whose position was randomized on each 50 msec frame. Receptive fields were found to be either separable or inseparable in space-time and responses to moving stimuli were predicted from the spatiotemporal structure of the cell under study. Most simple cells with separable spatiotemporal receptive fields were not direction selective. All simple cells with inseparable spatiotemporal receptive fields were found to prefer movement in one direction. The optimal speed and direction were estimable from the slope of individual subregions observed in the space-time plane. The results are consistent with a linear model for direction selectivity.
Three hundred and fifty six homosexually active men were recruited in 1988 for a study by interview of sexual behaviour. Thirty two per cent had homosexual passive anal sex in the previous month and 60% in the year before interview. Anal sex and unprotected anal sex were more common with regular than non-regular partners. Heterosexual sex was reported by 4% of men in the last month and 10% for the last year. Sixteen per cent of heterosexually active men reported anal sex with a female partner. Fewer men described themselves as bisexual than would be expected from the sample's recent sexual histories. More attention is needed to the definition and measurement of "bisexuality" to understand its role in HIV transmission.
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A subpopulation of the CD3+ peripheral T lymphocytes express the TCR-gamma/delta complex. Three distinct TCR-gamma forms that differ in size and in the ability to form a disulfide bridge with the TCR-delta subunit have been described. In this study we analyze the structural difference between the non-disulfide-linked 55-kD and 40-kD TCR-gamma chains. The 40-kD TCR-gamma form contains a smaller polypeptide backbone and carries less carbohydrate compared with the 55-kD TCR-gamma form. A cDNA clone corresponding to the 40-kD TCR-gamma subunit lacks one copy of the second exon of the constant region that is present in the other TCR-gamma subunit. This exon copy encodes part of the connector region that is located between the constant domain and the membrane spanning region. We show that the number of potential N-linked glycan attachment sites are the same for the two TCR-gamma forms. Since these attachment sites are located in the connector region we conclude that the connector region influences the amount of N-linked carbohydrates added to the core TCR-gamma polypeptide, probably by affecting the conformation of the protein. In contrast to the TCR-beta constant region usage, the TCR-gamma constant regions are unequally expressed. Virtually exclusive usage of disulfide-linked complexes were found in some individuals, while both the disulfide-linked and the 40-kD, non-disulfide-linked TCR-gamma forms were detected in other subjects. The ability to distinguish these TCR-gamma/delta forms now makes it possible to study the mechanisms that govern their selection and to determine if they correspond to functionally distinct isotypes.
The human T cell receptor delta (TCR delta) gene encodes one component of the TCR gamma delta-CD3 complex found on subsets of peripheral blood and thymic T cells. Human TCR delta diversity was estimated by characterizing rearrangements in TCR gamma delta cell lines and determining the structures of complementary DNA clones representing functional and nonfunctional transcripts in these cell lines. One V delta segment and one J delta segment were identified in all functional transcripts, although a distinct J delta segment was identified in a truncated transcript. Further, one D delta element was identified, and evidence for the use of an additional D delta element was obtained. Thus human TCR delta genes appear to use a limited number of germline elements. However, the apparent use of two D delta elements in tandem coupled with imprecise joining and extensive incorporation of N nucleotides generates unprecedented variability in the junctional region.
N-pro-opiomelanocortin (N-POMC) is secreted from the same precursor as ACTH and beta-endorphin. Elevated plasma ACTH and beta-endorphin/beta-lipotrophin concentrations have been reported in depression, however there have been no previous studies of N-POMC. Twenty-five patients with major depression and 18 control subjects were studied at five timepoints to examine diurnal rhythm and the effect of a dexamethasone suppression test. N-POMC was measured using a newly developed two-site recognition immunoradiometric assay (IRMA). This demonstrated advantages of sensitivity, specificity and simplicity compared with existing radioimmunoassays. N-POMC exhibited a pattern of diurnal rhythm and suppression in response to dexamethasone as described for other POMC derived peptides. Depressed subjects had higher levels of N-POMC at 0900 h post-dexamethasone than did control subjects. In conclusion, the results of this study are consistent with a hypothesis of cosecretion of POMC-derived peptides. N-POMC has a similar pattern of abnormal concentrations to ACTH and beta-endorphin/beta-lipotrophin in depression. This constitutes probable evidence of POMC-derived peptide resistance to glucocorticoid feedback in this condition.
The T cell receptor (TCR) delta protein is expressed as part of a heterodimer with TCR gamma, in association with the CD3 polypeptides on a subset of functional peripheral blood T lymphocytes, thymocytes, and certain leukemic T cell lines. A monoclonal antibody directed against TCR delta was produced that binds specifically to the surface of several TCR gamma delta cell lines and immunoprecipitates the TCR gamma delta as a heterodimer from Triton X-100 detergent lysates and also immunoprecipitates the TCR delta subunit alone after chain separation. A candidate human TCR delta complementary DNA clone (IDP2 O-240/38), reported in a companion paper, was isolated by the subtractive library approach from a TCR gamma delta cell line. This complementary DNA clone was used to direct the synthesis of a polypeptide that is specifically recognized by the monoclonal antibody to TCR delta. This complementary DNA clone thus corresponds to the gene that encodes the TCR delta subunit.
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The human T cell receptor (TCR) gamma polypeptide occurs in structurally distinct forms on certain peripheral blood T lymphocytes. Complementary DNA clones representing the transcripts of functionally rearranged TCR gamma genes in these cells have been analyzed. The expression of a disulfide-linked and a nondisulfide-linked form of TCR gamma correlates with the use of the C gamma 1 and C gamma 2 constant-region gene segments, respectively. Variability in TCR gamma polypeptide size and disulfide linkage is determined by the number of copies and the sequence of a repeated segment of the constant region. Thus C gamma 1 and C gamma 2 are used to generate structurally distinct, yet functional, T3-associated receptor complexes on peripheral blood lymphocytes. Tryptic peptide mapping suggests that the T3-associated TCR gamma and delta peptides in the nondisulfide-linked form are distinct.
A monoclonal antibody (mAb) with framework reactivity against the T cell receptor (TCR) alpha beta complex is characterized. The mAb, beta Framework 1 (beta F1) is capable of immunoprecipitating the TCR alpha beta complex from 125I-labeled human T cell tumors, immunocompetent T cell clones, and peripheral blood lymphocytes (PBL). beta F1 recognizes the separated TCR beta subunit in Western blotting. Because it does not bind to the surface of viable T cells but does react with the plasma membrane form of the TCR after treatment with membrane solubilizing agents, the beta F1 mAb reacts with a "hidden" determinant on the TCR beta subunit. After solubilization with 70% ethanol, the TCR alpha beta complex is shown to exist on greater than 92% of T3+ human PBL, whereas 2 to 8% of T3+ PBL do not react with the mAb. The beta F1 mAb demonstrates the existence of differently glycosylated surface 125I-labeled TCR alpha-chains (alpha, alpha', alpha") in association with a common TCR beta-chain on the HPB-MLT T cell leukemia. Reactivity of the beta F1 mAb on thymus tissue sections is similar to that of anti-Leu-4 (anti-T3). The beta F1 mAb should prove useful as a research tool for both the immunochemical characterization and isolation of virtually any alpha beta T cell receptor, whether from individual T cell clones or polyclonal populations of T lymphocytes. Recognition of T cell receptors in histologic tissue sections suggests that the beta F1 mAb may be useful in the clinical diagnosis of T cell lineage neoplasms. In failing to recognize all T3+ lymphocytes, it allows the identification of novel populations of T3+ lymphocytes that may express non-alpha, non-beta T cell receptors.
The HLA-DRw6 haplotype of the class II major histocompatibility complex (MHC) antigens exhibits unusual complexity and cannot be uniquely typed serologically. The DR beta chains expressed by consanguineous homozygous DRw6 typing cells WT46 and WT52 were biochemically analyzed using three monoclonal antibodies (mAb) that recognize denatured DR beta chains. The results of isoelectric focusing and N-terminal sequencing demonstrate that each DRw6 B-cell line expresses two DR beta chains. Evidence of an exchange of mAb epitopes involving the two DR beta chains of one of these cell lines was obtained and may be explained by a recombinational mechanism involving reciprocal exchange of genetic segments of the DR beta chains, one of which may encode the putative DRw6 chain and the other the chain carrying the MT2 allotypic determinant. Since a recombinational hot spot has been shown to occur uniquely in the mouse MHC within the E beta gene, the occurrence of a recombination within the human homolog, DR(MT2) beta, could reflect some specific feature of this MHC region. Comparison of the DR beta chains of the WT46 and WT52 cell lines with those of a third DRw6 cell line, LB, suggests that two alleles of MT2 occur.
The T-cell receptor (TCR) gamma gene product occurs in association with T3 (CD3) polypeptides on the surface of human T lymphocytes. TCR gamma lymphocytes express arrays of T3 polypeptides distinct from those typically observed on TCR alpha beta lymphocytes. This report demonstrates that identical T3 gamma, delta, and epsilon polypeptides are synthesized by TCR gamma lymphocytes and TCR alpha beta lymphocytes. However, the processing of T3 delta oligosaccharides is distinct in the two cell types. This observation may suggest distinct quaternary structures of these receptor complexes. Despite these structural differences, the T3 molecule on TCR gamma lymphocytes is functional. It is associated with and comodulates with TCR gamma and it serves as a substrate for protein kinase C-mediated phosphorylation. Anti-T3 monoclonal antibodies induce a rapid increase in cytoplasmic free calcium, indicating that the receptor complex is involved in signal transduction and triggering of TCR gamma lymphocytes.
The amino acid sequence of human apolipoprotein D, a component of high density lipoprotein, has been obtained from the cloned cDNA sequence. The 169-amino acid protein has no marked similarity to other apolipoprotein sequences, but has a high degree of homology to plasma retinol-binding protein and other members of the alpha 2u-globulin protein superfamily. Apolipoprotein D mRNA has been detected in human liver, intestine, pancreas, kidney, placenta, adrenal, spleen, and fetal brain tissue. Tissue culture cells transfected with the cloned cDNA secrete material that reacts with anti-apoD antibodies.
The human lecithin-cholesterol acyltransferase (LCAT) gene has been sequenced to completion. The gene is divided into six exons spanning approximately 4,200 bp. Exon five codes for amino acids homologous to the interfacial active site of several lipases, and also codes for an amphipathic alpha-helix resembling the carboxy terminus of apolipoprotein E. Blot hybridization data suggest that there is only one LCAT gene in humans. The 1550 base LCAT mRNA can be detected in liver and HepG2 (hepatocyte) cells, but not in small intestine, spleen, pancreas, placenta or adrenal tissue.
cDNA and genomic cloning has been used to determine the mRNA and amino acid sequence of human plasma lecithin-cholesterol acyltransferase (LCATase; EC 2.3.1.43). The mature protein was found to contain 416 amino acid residues with a hydrophobic leader sequence of 24 amino acids. An unusual feature of the message is that the poly(A) signal AATAAA overlaps the COOH-terminal glutamic acid and stop codons, and the 3' untranslated region is only 23 bases. The protein itself is distinguished by a number of extended sequences of hydrophobic amino acids, one of which contains a hexapeptide identical with the interfacial binding segment of the active site of pancreatic lipase and is similar to the same site of lingual lipase. The cloned cDNA allows the expression of active LCATase by transfected tissue culture cells.
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Intranasal flunisolide is an effective treatment for allergic rhinitis. Flunisolide has high bioavailability when administered to normal subjects (50% of an intranasal dose reaches the systemic circulation) with minimal systemic effects. Bioavailability in patients with active rhinitis averages 62.4 +/- 15.7%. The oral dose bioequivalent to 100 micrograms intranasally is 500 micrograms. To define the comparative trial and systemic effects of intranasal flunisolide in patients with active allergic rhinitis, a multicenter, randomized, double-blind, placebo-controlled study was conducted during the 1983 ragweed hayfever season. Ninety-nine patients with ragweed hayfever for greater than or equal to 2 years and positive prick skin tests to ragweed were randomly allocated to one of three treatment groups: 0 = oral flunisolide 500 micrograms b.i.d. and intranasal placebo b.i.d.; N = intranasal flunisolide 50 micrograms per nostril b.i.d. and oral placebo b.i.d.; P = intranasal and oral placebo b.i.d. Treatment continued for 4 weeks. Patients kept daily symptom scores. Patients were evaluated by a blinded observer every 2 weeks and were globally evaluated at the study's end. Data were analyzed for each center and pooled. There were no significant differences in symptom severity of sneezing, nasal congestion, and throat itch in the 0 (oral flunisolide) and P (placebo) groups. N (nasal flunisolide) was significantly more effective than O or P (P less than or equal to 0.005) for each symptom for at least one 2-week period. Global evaluation demonstrated control of overall hayfever severity for N (nasal flunisolide) but not for O (oral flunisolide). We conclude that the therapeutic efficacy of flunisolide is achieved by topical and not by systemic action.