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Biomedical subjects

J Kaye

Publications and source records attributed to J Kaye.

At least 91 records · Page 5Linked to original sources
PubMed1992

Involvement of the same region of the T cell antigen receptor in thymic selection and foreign peptide recognition.

The Ag receptor (TCR) on T lymphocytes has been shown to be specific for foreign antigenic peptides bound to MHC-encoded molecules. During T cell differentiation in the thymus this same TCR mediates the recognition of MHC molecules in the absence of foreign Ag, a process termed positive selection. To analyze the structural relationship between MHC-restricted Ag recognition and positive selection, we characterized two different transgenic lines of mice bearing TCR specific for pigeon cytochrome c and the Ek class II MHC molecule. The two TCR expressed in these animals differed by only one amino acid in the V-J junction of the alpha-chain. In vitro, we find that this TCR difference alters Ag fine specificity. Analysis of transgenic animals demonstrates that this change in the putative third complementarity determining region of the TCR also alters the specificity of positive selection in the thymus. These results suggest that the diversity of a TCR region that can be shown to affect the specificity of foreign Ag recognition may be influenced by selection in the thymus. The findings presented here are discussed in relation to the possible role of self-peptides in positive selection.

Amino Acid Sequence↗
PubMed1992

In vivo and in vitro clonal deletion of double-positive thymocytes.

To study the processes of thymic development, we have established transgenic mice expressing and alpha/beta T cell antigen receptor (TCR) specific for cytochrome c associated with class II major histocompatibility complex (MHC) molecules. The transgenic TCR chains are expressed by most of the thymocytes in these mice, and these cells have been shown to efficiently mature in association with Ek- and Ab-encoded class II MHC molecules. This report describes a characterization of the negative selection of these transgenic thymocytes in vivo that is associated with the expression of As molecules. Negative selection by As molecules appears to result in the deletion of a late stage of CD4/CD8 double-positive thymocytes in that there is a virtual absence of transgenic TCR bearing CD4 single-positive thymocytes. This phenotype is accompanied by the appearance of CD4/CD8 double-negative thymocytes and peripheral T cells that are functionally antigen reactive. The process of negative selection has also been investigated using an in vitro culture system. Upon presentation of cytochrome c by Eb-expressing nonthymic antigen-presenting cells, there occurs an antigen dose-dependent deletion of the majority of CD4/CD8 double-positive thymocytes. In contrast, presentation of Staphylococcal enterotoxin A by Eb in vitro results in minimal deletion of double-positive thymocytes. In addition, we use this in vitro model to examine the effects of cyclosporin A on negative selection. In contrast to its effects on mature T cells, and the findings of others in vivo, cyclosporin A does not inhibit antigen-induced deletion of double-positive thymocytes. Finally, a comparison of the antigen dose responses for thymocyte deletion and for peripheral T cell activation indicates that double-positive thymocyte recognition is more sensitive than mature T cells to antigen recognition.

Animals↗
PubMed1992

Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted.

A mutant of herpes simplex virus type 1 (HSV-1) in which glycoprotein H (gH) coding sequences were deleted and replaced by the Escherichia coli lacZ gene under the control of the human cytomegalovirus IE-1 gene promoter was constructed. The mutant was propagated in Vero cells which contained multiple copies of the HSV-1 gH gene under the control of the HSV-1 gD promoter and which therefore provide gH in trans following HSV-1 infection. Phenotypically gH-negative virions were obtained by a single growth cycle in Vero cells. These virions were noninfectious, as judged by plaque assay and by expression of beta-galactosidase following high-multiplicity infection, but partial recovery of infectivity was achieved by using the fusogenic agent polyethylene glycol. Adsorption of gH-negative virions to cells blocked the adsorption of superinfecting wild-type virus, a result in contrast to that obtained with gD-negative virions (D. C. Johnson and M. W. Ligas, J. Virol. 62:4605-4612, 1988). The simplest conclusion is that gH is required for membrane fusion but not for receptor binding, a conclusion consistent with the conservation of gH in all herpesviruses.

Animals↗
PubMed1992

The UL16 gene of human cytomegalovirus encodes a glycoprotein that is dispensable for growth in vitro.

The UL16 gene of human cytomegalovirus (HCMV) encodes a predicted translation product with features characteristic of glycoproteins (signal and anchor sequences and eight potential N-linked glycosylation sites). Antisera were raised against the UL16 gene product expressed in Escherichia coli as a beta-galactosidase fusion protein. The antisera detected a 50-kDa glycoprotein in HCMV-infected cells that was absent from purified virions. The UL16 glycoprotein was synthesized at early times after infection and accumulated to the highest levels at late times after infection. A recombinant HCMV in which UL16 coding sequences were interrupted by a lacZ expression cassette was constructed by insertional mutagenesis. Analysis of the phenotype of the recombinant virus indicated that the UL16 gene product is nonessential for virus infectivity and growth in tissue culture.

Antibodies, Viral↗
PubMed1992

Osteopathy: the 'orthodox' alternative.

Janice Kaye believes that osteopathy can significantly reduce employee absenteeism. Here she explains its unique system of treatment and argues for its use in OH departments.

Absenteeism↗
PubMed1991

Comparison of rapid immunofluorescence assay to cell culture isolation for the detection of influenza A and B viruses in nasopharyngeal secretions from infants and children.

In the hospital setting it is often critical to isolate patients appropriately in order to prevent nosocomial infection. This is especially true with respiratory infection in infants and young children. At the present time a rapid immunofluorescence assay (IFA) for respiratory syncytial and parainfluenza viruses is routinely carried out in our laboratory. During January and February of 1990 we used monoclonal antibodies specific for influenza A and B viruses (Baxter-Bartels, Bellevue, WA) in this rapid IFA. 152 samples of NPS were tested by cell culture isolation (CCI) and IFA for the presence of influenza antigens. Twenty-seven samples were positive by both methods, and 114 were negative by both. Three samples were positive by IFA and negative by CCI, while eight samples were positive by CCI and negative by IFA. Five of these eight samples were not positive until 10 to 14 days after inoculation into cell culture, suggesting that the virus inoculum was small. Using CCI as the 'gold' standard, IFA was 90% sensitive and 93% specific. Because of its turn-around time (2-4 h) and acceptable sensitivity and specificity, IFA for influenza viruses will be a routine test in our diagnostic laboratory during the influenza season.

Animals↗
PubMed1991

HLA-A2, or a closely linked gene, confers susceptibility to early-onset sporadic Alzheimer's disease in men.

There is a weak association between Alzheimer's disease (AD) and the histocompatibility antigen HLA-A2, suggesting that A2 has either a minor role in AD or a major role in a subtype of it. To test these alternatives, we studied 54 consecutively ascertained AD patients diagnosed by NINCDS-ADRDA criteria. Patients had a higher frequency of A2 than control subjects, primarily due to the elevated frequency of this antigen in men with early onset of dementia (less than or equal to 60 years): 92% of early-onset men had A2 as compared with 44% of controls. This finding suggests that A2, or a closely linked gene, confers susceptibility to early-onset AD in men. Furthermore, A2 appears to be primarily associated with sporadic AD, rather than with the familial subtype.

Age Factors↗
PubMed1991

Structure and specificity of the T cell antigen receptor.

The antigen receptor on T lymphocytes is a multi-chain complex of which two chains determine its specificity for antigen. Although these receptor chains possess genetic and structural similarities with membrane-bound immunoglobulin, the B cell antigen receptor, they endow T cells with a distinct specificity. Unlike B cells, T cells recognize foreign antigenic properties only in the form of proteolytic fragments bound to molecules encoded by the major histocompatibility complex. In addition, one stage of the development of T cells in the thymus is dependent upon an antigen receptor-mediated event. Utilizing the response to a well defined antigen as a model system, we discuss the relationship between receptor structure and the specificity of these recognition events.

Amino Acid Sequence↗
PubMed1990

A T cell receptor V alpha region selectively expressed in CD4+ cells.

The peripheral TCR V beta repertoire is strongly influenced by the processes of negative selection (deletion) and positive selection in the thymus. In order to investigate whether such selection events influence the V alpha repertoire, we have produced an anti-V alpha 11 mAb. This antibody was made by immunization with a chimeric TCR:Ig protein containing V alpha 11 in place of the VH of an IgG2a, lambda Ig. This scheme optimizes the specificity of immunization and facilitates the screening procedure. The antibody recognizes a panel of V alpha 11-expressing T cell clones. Analysis of mouse strains indicates that the antibody recognizes V alpha 11 only in mice of the C57 background. The expression of the epitope on peripheral T cells is strongly biased to the CD4+ subset, suggesting positive selection of V alpha 11 on class II MHC molecules. In some strain comparisons, the percentage of V alpha 11-expressing T cells in the CD4+ subset was elevated in I-E+ relative to I-E- strains. These data suggest that V alpha 11 can differentially influence the selection of T cells into the CD4+/CD8+ subsets.

Animals↗
PubMed1989

Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor.

T lymphocytes are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC). There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus. As a result of this positive selection, thymocytes that express antigen receptors with a threshold affinity for self MHC-encoded glycoproteins preferentially emigrate from the thymus and seed peripheral lymphoid organs. The specificity for both foreign antigen and MHC molecules is imparted by the alpha and beta chains of the T-cell antigen receptor (TCR). Two other T-cell surface proteins, CD4 and CD8, which bind non-polymorphic regions of class II and class I MHC molecules respectively, are also involved in these recognition events and play an integral role in thymic selection. In order to elucidate the developmental pathways of class II MHC-restricted T cells in relation to these essential accessory molecules, we have produced TCR-transgenic mice expressing a receptor specific for a fragment of pigeon cytochrome c and the Ek (class II MHC) molecule. The transgenic TCR is expressed on virtually all T cells in mice expressing Ek. The thymuses of these mice contain an abnormally high percentage of mature CD4+CD8- cells. In addition, the peripheral T-cell population is almost exclusively CD4+, demonstrating that the MHC specificity of the TCR determines the phenotype of T cells during selection in the thymus.

Animals↗
PubMed1989

Expression of a hybrid immunoglobulin-T cell receptor protein in transgenic mice.

We have constructed a hybrid immunoglobulin (VDJH)-T cell receptor (C alpha) gene using the VDJH exon from a digoxin-specific antibody. This gene was used to make a line of transgenic mice. The hybrid VDJH-C alpha protein is expressed on a subset of T cells in these mice, and we have shown that it forms part of a functional TCR complex by the criteria of coprecipitation and comodulation of CD3 and TCR beta chain components and T cell activation with anti-idiotypic antibodies or digoxin. Furthermore, in cells expressing the hybrid protein, there is allelic exclusion of endogenous TCR alpha genes. We discuss the implications for the comparative structure of T cell receptors and immunoglobulins.

Alleles↗
PubMed1989

Anthropometry for children's spectacle frames.

Facial measurements of 154 Caucasian children aged 5-14 were taken, to provide statistical information for spectacle frame manufacturers. The main differences compared with adult measurements were in the following dimensions: temple width, head width, bridge height, projection, splay angle and front to bend. The range of the 'distance between rims' measurement of adults, was similar to that of children. A number of differences between this group and a small group of Afro-Caribbean children was encountered.

Adolescent↗
PubMed1989

Radiological loosening after cemented hip replacement for juvenile chronic arthritis.

We reviewed the results of 14 total hip replacements in patients with juvenile chronic arthritis. The mean age at operation was 16 years (range 12 to 22 years); follow-up was from four to 11 years (mean 8.5 years). Postoperatively pain relief was sustained in all but one hip, while movement generally remained significantly restricted. No hip has as yet required a revision operation, although eight hips (57%) show radiological changes suggestive of impending failure. All patients had severe polyarticular involvement with associated restriction of locomotor activity. Potential causes contributing to loosening such as continuing diaphyseal bone growth and increased immunocompetence in adolescence are discussed.

Adolescent↗
PubMed1988

Analysis of specificity for antigen, Mls, and allogenic MHC by transfer of T-cell receptor alpha- and beta-chain genes.

The majority of peripheral T lymphocytes bear cell-surface antigen receptors comprised of a disulphide-linked alpha beta dimer. In an immune response, this receptor endows T cells with specificities for foreign antigenic protein fragments bound to cell surface glycoproteins encoded in the major histocompatibility complex (MHC). At a high frequency (greater than 1%), the same population of T lymphocytes responds to allogeneic MHC glycoproteins, or to differences at other genetic loci termed Mls, in conjunction with MHC. The alpha beta-antigen receptor has been implicated in alloreactivity and Mls reactivity. In fact, many monoclonal T-cell lines recognize a foreign protein fragment bound to self-MHC molecules and, in addition, recognize allogeneic MHC glycoproteins, an Mls-encoded determinant, or both. For at least one T-cell clone, a monoclonal antibody directed against the alpha beta antigen receptor has been shown to block activation induced by either antigen-bound self-MHC or by allogeneic MHC. However, it remains to be demonstrated directly that a single alpha beta receptor can mediate antigen specificity, alloreactivity and Mls reactivity, a prerequisite to understanding the structural basis of these high-frequency cross-reactivities. To address this issue we have performed transfers of receptor chain genes from a multiple-reactive T-cell clone into an unrelated host T lymphocyte. We now demonstrate definitively that the genes encoding a single alpha beta-receptor chain pair can transfer the recognition of self-MHC molecules complexed with fragments of antigen, allogeneic MHC molecules, and an Mls-encoded determinant (presumably in conjunction with MHC). In this case the transfer of antigen specificity and alloreactivity requires a specific alpha beta-receptor chain combination, whereas Mls reactivity can be transferred with the beta-chain gene alone into a recipient expressing a randomly selected alpha-chain.

Animals↗
PubMed1988

NIH conference. Alzheimer disease: clinical and biological heterogeneity.

The clinical and biological features of Alzheimer disease are not uniform in their expression; heterogeneity is evident in the disease's clinical, anatomic, and physiologic characteristics. The presence of considerable intersubject and intrasubject heterogeneity suggests that subtypes of the disease exist. We define subtypes of Alzheimer disease in regard to the behavioral features (for example, predominant right or left hemisphere, or symmetrical impairment), inheritance (familial or sporadic), dosage of chromosome 21 (presence of the Down syndrome), time course of progression, age of onset (presenile or senile), and presence or absence of motor deficit (myoclonus or signs of an extrapyramidal syndrome). Studies of regional cerebral glucose metabolism with positron emission tomography and [18-fluorine] fluorodeoxyglucose show focal alterations in glucose use, with cerebral metabolic asymmetries in patients with Alzheimer disease that are related to the nature of the cognitive deficit. Serial roentgenographic computed tomographic studies show heterogeneous rates of lateral ventricle enlargement in the disease that are related to rates of cognitive decline. Similar anatomic and physiologic abnormalities are also found in persons 45 years of age or older who have the Down syndrome. Furthermore, patients with Alzheimer disease who have extrapyramidal dysfunction or myoclonus are a distinct subgroup, with specific abnormalities of central monoamine markers of dopamine metabolism, serotonin metabolism, and the hydroxylation cofactor, biopterin. The concept of subtypes in Alzheimer disease serves as a model with which the interactions of genetic influences with environmental factors can be examined.

Alzheimer Disease↗
PubMed1988

Ipratropium bromide in the treatment of the 'rhinorrhoea syndrome'.

Conventional treatments for non-allergic perennial rhinitis have proven somewhat unsuccessful in the control of rhinorrhoea when it is the predominant symptom. Hence, a double-blind cross-over trial of Ipratropium, a parasympatholytic, and placebo were carried out over a 12-week period. There was a significant reduction in rhinorrhoea during active treatment, with the most noticeable effect being in the moderate-to-severe rhinorrhoea group. No significant effect was noted on nasal obstruction or sneezing and no serious side-effects were seen. A carry-on effect was noted when active treatment was used initially. However, the group given active treatment following placebo had a better result overall. A strong placebo effect was also noted in both groups, in keeping with a trial of this order.

Adolescent↗