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M D Cooper

Publications and source records attributed to M D Cooper.

At least 109 records · Page 6Linked to original sources
PubMed1994

Fluoxetine effects on cerebral glucose metabolism.

In a counterbalanced, double-blind, placebo-controlled trial, 40 mg of fluoxetine was administered to four healthy adult volunteers (three men, one woman; age range 20-39 years), 90 min before injection of 6-7.5 mCi of [18F]-2-deoxyglucose to measure cerebral metabolic rate of glucose (CMRglu). Subjects were engaged in a visual monitoring task shortly before and during scanning with a PETT-VI tomograph. Global CMRglu did not differ when placebo (8.93 +/- 0.96 mg 100 g-1 min-1) was compared to fluoxetine (8.22 +/- 0.86 mg 100 g-1 min-1; paired t-test = 0.82, df = 3, p < 0.48). However, statistical parametric mapping of differences in CMRglu between placebo and fluoxetine conditions revealed regional effects of fluoxetine shown by decreased metabolism in the amygdaloid complex, hippocampal formation and ventral striatum, and by increased metabolism centered in the right superior parietal lobe (Brodmann area 7). Parametric mapping for use in PET studies of glucose metabolism represents a significant new tool for studying drug effects in humans.

Adult↗
PubMed1994

A novel subpopulation of primed T cells in the human fetus.

Virgin and memory T cells reciprocally express high levels of the RA or the RO isoforms of CD45, respectively. In an examination of T cell expression of these two CD45 isoforms during human development, the RO+RA- "memory" T cells were infrequent in the newborn blood and spleen, but comprised approximately half of the T cells in adult tissues. These anticipated findings probably reflect the immunologic naivete of the newborn. Surprisingly, however, RO+RA- T cells were relatively abundant in fetal spleen and in cord blood samples from premature births, comprising approximately 25% and 10% of the T cells in these tissues, respectively. This early peripheral wave of RO+RA- T cells was composed of polyclonal T cells in both the CD4 and CD8 subpopulations. The fetal RO+ cells of CD4+ phenotype frequently expressed the CD25-alpha chain subunits that characterize high affinity IL-2 receptors, and were able to proliferate in response to exogenous IL-2. In further contrast with their RO+ memory T cell counterparts in adults, the fetal T cells were unresponsive to mitogenic anti-CD2 and anti-CD3 antibodies. We conclude that the data suggest an embryonic population of autoreactive T cell clones with anergic characteristics.

Adolescent↗
PubMed1994

T cell migration during development: homing is not related to TCR V beta 1 repertoire selection.

T cell precursors enter the chick thymus in three waves during embryonic life. Each wave of thymocyte precursors colonizing the thymus gave rise to a similar TCR V beta repertoire in thymus, spleen and intestine both in terms of V beta 1 and J beta usage as well as in the length of V beta-D beta-J beta junctions. Seventeen V beta 1s were utilized, and a new J beta segment was found. In the progeny of the third wave, more nucleotides were deleted at the 5' end of the J beta segment, but the overall size of the CDR3 was conserved by a concomitant increase of N nucleotide addition at the V beta-D beta-J beta junctions during rearrangement. This CDR3 modification was observed in the spleen but not in the intestine, implying that progeny of the third wave migrate preferentially to the spleen, a possibility that was confirmed by adoptive cell transfers into congenic chickens. Very low frequencies of non-productive rearrangements in the intestine suggested that negative selection may occur in this organ. The present analysis indicates that V beta 1+ T cells in spleen and intestine are primarily of thymic origin, this colonization of both organs occurs in waves and is not characterized by preselection of the TCR V beta 1 repertoire.

Amino Acid Sequence↗
PubMed1994

Switch recombination in normal IgA1+ B lymphocytes.

Most B lymphocytes in normal individuals express two classes of cell-surface immunoglobulins, IgM and IgD. The specificity of the two antigen receptors is identical since they are produced by transcription and differential splicing of the same variable region gene segment to the heavy-chain constant region gene segments for both mu and delta heavy chains. B lymphocytes expressing other immunoglobulin isotypes, IgG, IgA, or IgE, are rare and not well characterized. Particularly controversial is the molecular mechanism of their isotype switch. Here we use high-gradient magnetic cell sorting and fluorescence-activated cell sorting to purify surface IgA1-bearing B lymphocytes from human blood for cellular and molecular analysis. These cells express no immunoglobulin class other than IgA1 and are a relatively uniform population with regard to expression of other cell-surface molecules. They are resting cells in terms of cell cycle and activation marker analysis. The molecular basis for class switching in the IgA1+ cells is not differential transcription or splicing. Rather, switch recombination involving deletion of DNA has occurred on both immunoglobulin heavy-chain gene loci, including the allelically excluded one, and appears to have been directed to IgA1 under normal physiological conditions.

Antigens, CD↗
PubMed1994

Identification of T-cell receptor alpha-chain genes in the chicken.

T-cell receptor (TCR) alpha-chain (TCR alpha) and beta-chain (TCR beta) genes are well characterized in mammals, while only TCR beta genes have been identified in other vertebrates. To identify avian TCR alpha genes, we used monoclonal anti-CD3 antibodies to isolate chicken TCR alpha for peptide sequence analysis. Degenerate oligonucleotide probes were then used to isolate a candidate TCR alpha cDNA clone that hybridized with a 1.7-kb mRNA species present only in alpha beta T cells and in tissues populated by these cells. Southern blot analysis revealed gene rearrangement in thymocytes and alpha beta T-cell lines. The TCR alpha cDNA candidate encoded an open reading frame of 275 amino acids, the predicted variable (V)-, joining (J)-, and constant (C)-region amino acid sequences of which shared approximately 40%, 60%, and 25% homology with corresponding mammalian sequences. A single C alpha gene and approximately 25 V alpha genes were identified by using region-specific probes. The V alpha cDNA probe isolated from a V beta 1+ cell line reacted with transcripts from one of five V beta 2+ cell lines, suggesting shared use of V alpha genes by V beta 1+ and V beta 2+ T cells and the existence of other V alpha gene families. A genomic V alpha sequence was flanked by classical recombination signal sequences but, unlike previously defined V genes, the leader and V alpha region were encoded by a single exon. The data indicate evolutionary conservation of the basic TCR alpha gene structure in birds and mammals.

Amino Acid Sequence↗
PubMed1994

Characterization of avian natural killer cells and their intracellular CD3 protein complex.

Natural killer (NK) cell activity appears to be conserved throughout vertebrate development but NK cells have only been well characterized in mammals. Candidate NK cells have been identified in the chicken as cytoplasmic CD3+ and surface T cell receptor (TCR)/CD3- (TCRO) lymphocytes that often express CD8. The fact that the TCRO cells are abundant in the embryonic spleen before T cells enter this organ allowed us to cultivate the embryonic TCRO cells using growth factors derived from activated adult lymphocytes. These TCRO cells were cytotoxic for an NK target cell line. They expressed cell surface CD8, a putative interleukin-2 receptor, CD45 and a receptor for IgG, but did not express CD4, major histocompatibility complex class II or immunoglobulin. Biochemical analysis of the cytoplasmic CD3 antigen revealed two of the three CD3 gamma, delta and epsilon homologues, and RNA transcripts for the third. The CD3 monoclonal antibody also precipitated a 32-kDa dimer that may represent a heterodimer of different CD3 constituents. TCR alpha and beta gene transcripts were not detected in the TCRO cells. These results indicate that the avian TCRO cell is the mammalian NK cell homologue. The shared evolutionary features of T cells and NK cells in birds and mammals support the idea that they derive from a common progenitor.

Animals↗
PubMed1994

The murine BP-3 gene encodes a relative of the CD38/NAD glycohydrolase family.

The murine BP-3 antigen is a variably glycosylated glycosyl-phosphatidylinositol (GPI)-linked molecule that is selectively expressed by early B and T lineage cells and a discrete subpopulation of reticular cells in the peripheral lymphoid organs. It is also expressed on the brush border of intestinal epithelial cells, the lumenal surface of renal collecting tubules and mature myeloid cells. To further explore the nature of the BP-3 antigen, we purified the protein, obtained peptide sequences and used these to isolate cDNA clones. Two BP-3 cDNA clones were found to share the same open reading frame, but to utilize different polyadenylation sites. Expression of a full-length cDNA clone confirmed that it encodes the BP-3 antigen. Northern blot analysis with this cDNA probe revealed BP-3 transcripts of 1.3 and 2.3 kb in various tissues and cell lines representing myeloid, B and T cell lineages, while a probe containing the most 3' untranslated region of the longer cDNA clone hybridized only with the 2.3 kb RNA species. Analysis of the BP-3 cDNA sequence indicates that it represents a previously undescribed gene that shares significant homology with genes encoding nicotinamide adenine dinucleotide (NAD) glycohydrolase of Aplysia californica and the CD38 antigens in mouse and human. However, cells expressing the recombinant BP-3 protein did not exhibit NADase activity, suggesting that it may be a distant relative of NAD hydrolase with different function.

ADP-ribosyl Cyclase↗
PubMed1994

T cell development in the chicken.

This review summarizes our current view of gamma delta and alpha beta T cell development in the chicken. In it we emphasize the functional interplay between the gamma delta and alpha beta T cell subpopulations.

Animals↗
PubMed1994

Examination of the glycocalyx of four species of Staphylococcus by transmission electron microscopy and image analysis.

The coagulase-negative staphylococci have become important pathogens in human infections involving foreign bodies. The bacterial glycocalyx is a major mediator of attachment of these organisms to medical devices, but the glycocalyx is sometimes difficult to demonstrate. A combination of the techniques of transmission electron microscopy (TEM) and image analysis enabled investigators to reveal the glycocalyx which was previously indiscernible. Eight strains of coagulase-negative staphylococci, including Staphylococcus epidermidis, S. hominis, S. lugdunensis, and S. schleiferi subspecies schleiferi, were grown, treated with anti-staphylococcal serum to stabilize the glycocalyx, and examined by TEM. Image analysis of negatives was then used to enhance the visual images which showed far more glycocalyx than previously seen by TEM alone.

Bacterial Capsules↗
PubMed1994

Designing women.

Explore the source record for details and available documents.

Creativity↗
PubMed1994

Clonal hematopoiesis and acquired thalassemia in common variable immunodeficiency.

BACKGROUND: Common variable immunodeficiency (CVID) is defined by hypogammaglobulinemia and increased susceptibility to infections. The gene defect responsible for CVID remains unknown. METHODS: During the course of their CVID disease, a female and three male patients developed microcytic anemia. The investigation of this anemia forms the basis for this report. RESULTS: Reticulocyte globin chain synthesis studies revealed the abnormal alpha/beta ratios that are pathognomonic of thalassemia. Through transcriptional analysis of the glucose-6-phosphate-dehydrogenase (G6PD) locus of the active X-chromosome in blood cells, we determined that the female patient has clonal reticulocytes, platelets, granulocytes, and B and T lymphocytes. CONCLUSIONS: The simultaneous presence of globin synthesis abnormalities and panhypogammaglobulinemia suggests that a common insult at the stem cell level could contribute to the development of CVID and acquired thalassemia.

Adolescent↗
PubMed1993

Characterization of an IgM Fc-binding receptor on human T cells.

The existence of an IgM receptor on human T cells has been suggested by T cell rosetting with IgM-coated erythrocytes. In this study we used immunofluorocytometry to demonstrate that 1) after short-term culture, a majority of the T cells can bind IgM at easily detectable levels, 2) human and mouse IgM preparations bind to human T cells but other Ig isotypes do not, 3) the IgM binding is saturable and inhibitable only by Ig of IgM isotype and 4) the Fc portion of IgM is involved in the binding to a protease-sensitive cell surface protein. Biochemical analysis of the T cell receptor for IgM reveals a cell surface protein of 60 kDa in comparison with the 58 kDa Fc mu receptors (Fc mu R) on B-lineage cells. Although Fc mu R expression is up-regulated after B cell activation, the reverse is true after T cell activation. In addition, the T cell Fc mu R is relatively resistant to phospholipase C treatment. These results indicate that T- and B-lineage cells express Fc mu R with different biologic characteristics.

Animals↗
PubMed1993

Expression of surrogate light chain receptors is restricted to a late stage in pre-B cell differentiation.

Surrogate light chain (psi LC) genes are transcriptionally active in progenitor B (pro-B) cells before immunoglobulin genes are rearranged. Current hypothetical models suggest that the psi LC proteins may couple with surrogate or conventional heavy chain proteins to form cell surface receptors that signal the progressive differentiation of pro-B, precursor B (pre-B), and immature B cells. Monoclonal antibodies were produced and used to examine the synthesis, expression, intermolecular interaction, and function of psi LC during B cell differentiation. The results indicate that, while psi LC production spans several developmental stages, cell surface expression is confined to a relatively late stage in normal pre-B cell differentiation, during which receptor cross-linkage does not impede cell growth or B cell differentiation.

Animals↗
PubMed1993

Histidine residue in the zinc-binding motif of aminopeptidase A is critical for enzymatic activity.

The murine BP-1 antigen (also called 6C3) is a homodimeric, phosphorylated cell surface glycoprotein that is expressed on immature B-lineage cells, bone marrow stromal cell lines, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. The amino acid sequence deduced from a BP-1 cDNA predicted a type II integral membrane protein with a zinc-binding motif (His-Glu-Xaa-Xaa-His) found in zinc-dependent metallopeptidases, and functional analysis suggested that BP-1 is aminopeptidase A [APA; L-alpha-aspartyl(L-alpha-glutamyl)-peptide hydrolase, EC 3.4.11.7]. Here we constructed an expression vector in which the BP-1 cDNA was placed downstream from the SR alpha promoter and used this construct to transfect COS-7 and Ltk- cells. Both transfectants expressed the BP-1 antigen on the cell surface and APA activity. The enzymatic activity of recombinant APA was increased by Ca2+ and inhibited by Zn2+, consistent with previous reports with purified APA. Point mutation of one of the histidine residues in the zinc-binding motif to phenylalanine completely abolished APA enzymatic activity, suggesting the structure of the zinc-binding motif of APA is critical for catalytic activity. Both wild-type and mutant BP-1 were glycosylated, transported to the cell surface, and possessed molecular weights similar to native BP-1 molecules on the murine 18.81 pre-B-cell line. The successful expression of both wild-type and mutant APA should allow more precise analysis of the diverse physiological roles of this ectoenzyme.

Amino Acid Sequence↗
PubMed1993

Thymic origin of embryonic intestinal gamma/delta T cells.

Current evidence suggests both thymic and extrathymic origins for T cells. Studies in mice favor an in situ origin for a prominent population of intestinal intraepithelial lymphocytes that express gamma/delta T cell receptor (TCR). This developmental issue is explored in an avian model in which the gamma/delta lymphocytes constitute a major T cell subpopulation that is accessible for study during the earliest stages of lymphocyte development. In the chick embryo, cells bearing the gamma/delta TCR appear first in the thymus where they reach peak levels on days 14-15 of embryogenesis, just 2 d before gamma/delta T cells appear in the intestine. Using two congenic chick strains, one of which expresses the ov antigen, we studied the origin and kinetics of intestinal colonization by gamma/delta T cells. The embryonic gamma/delta+ thymocytes homed to the intestine where they survived for months, whereas an embryonic gamma/delta- thymocyte population enriched in thymocyte precursors failed to give rise to intestinal gamma/delta+ T cells. Embryonic hemopoietic tissues, bone marrow, and spleen, were also ineffective sources for intestinal gamma/delta+ T cells. Intestinal colonization by gamma/delta+ thymocytes occurred in two discrete waves in embryos and newly hatched birds. The data indicate that intestinal gamma/delta T cells in the chicken are primarily thymic migrants that are relatively long-lived.

Age Factors↗
PubMed1993

Intestinal T lymphocytes in the chicken express an integrin-like antigen.

We report the characterization of a molecule recognized on chicken T cells by the murine A19 monoclonal antibody that was generated by immunization with intestinal intraepithelial lymphocytes. Immunofluorescence analysis indicated that both alpha beta and gamma delta T cell subpopulations in the intestine express the A19 antigen, but natural killer cells and B cells do not. The A19-marked T cells were preferentially localized in the intestinal epithelium and less frequently in the underlying lamina propria. T cells appearing in the intestine during embryonic life were A19 negative but acquired the antigen within the first few days after hatching. Although rarely found on cells in non-intestinal tissues at any age, very late expression of the A19 antigen could be induced by concanavalin A stimulation of splenic and circulating T cells. Transforming growth factor beta 1 enhanced this induction of A19 expression. The A19 molecules expressed by intestinal T cells and activated splenic T cells were biochemically identical, consisting of a multi-molecular complex of proteins with approximate M(r) of 205, 145 and 75 kDa under nonreducing conditions and 120, 90 and 28 kDa under reducing conditions. The characteristics of this multimolecular complex and its differential expression suggest that the A19 antigen is a member of the integrin family which may function in the retention of intestinal lymphocytes.

Animals↗