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Biomedical subjects

L Chess

Publications and source records attributed to L Chess.

At least 37 records · Page 2Linked to original sources
PubMed1986

A human monoclonal macroglobulin with specificity for alpha(2----8)-linked poly-N-acetyl neuraminic acid, the capsular polysaccharide of group B meningococci and Escherichia coli K1, which crossreacts with polynucleotides and with denatured DNA.

We have described an IgM antibody from a patient with macroglobulinemia specifically reacting with poly-alpha(2----8)N-acetyl neuraminic acid (NeuNAc) the capsular polysaccharide of two important human pathogens, group B meningococcus and E. coli K1. This antibody has a narrowly defined specificity in its interactions with polysaccharides, being unable to bind poly-alpha(2----9)NeuNAc or alternating poly-alpha(2----8)alpha(2----9)NeuNAc. However, it shows interesting crossreactivity with seemingly unrelated polynucleotides and denatured DNA, supporting the hypothesis that charged groups with a given spacing may determine the specificity of antigen-antibody interactions on otherwise dissimilar molecular structures. Despite the crossreactivity with denatured DNA and polynucleotides, the antibody does not appear to have adverse effects in the patient. The antibody protects newborn rats against E. coli K1 infection, as well as the standard horse antiserum H46, and one would expect it to prove useful in humans as an adjunct to antibiotic therapy in infections with group B meningococcus and E. coli K1. We have attempted to clone the antibody-producing cells from peripheral blood, and have shown that the relevant cells are present and can be cultured.

Aged↗
PubMed1986

Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1.

Tumor necrosis factor/cachectin (TNF) has been implicated as a mediator of the host response in sepsis and neoplasia. Recent work has shown that TNF can modulate endothelial cell hemostatic properties, suggesting that endothelium is a target tissue for TNF. This led us to examine whether endothelial cells have specific binding sites for TNF and augment the biological response to TNF by elaborating the inflammatory mediator, IL-1. Incubation of 125I-recombinant human TNF with confluent, cultured human umbilical vein endothelial cells resulted in time-dependent, reversible, and saturable binding. Binding was half-maximal at a TNF concentration of 105 +/- 40 pM, and at saturation 1,500 molecules were bound per cell. Heat-treated TNF, which is biologically inactive, did not bind to endothelium. In addition to surface binding, TNF induced the elaboration of IL-1 activity by endothelial cells in a time-dependent manner. Generation of IL-1 activity required protein synthesis and was half-maximal at a TNF concentration of 50 +/- 20 pM. IL-1 activity from TNF-treated endothelium could be adsorbed by an immobilized antibody to IL-1. Heat-treated TNF was ineffective in eliciting endothelial cell IL-1. These data indicate that TNF can bind specifically to endothelium and initiate a cascade of inflammatory and coagulant events on the vessel surface potentially central to the host response to neoplasia and sepsis.

Cells, Cultured↗
PubMed1986

The T4 glycoprotein is a cell-surface receptor for the AIDS virus.

Taken together, our studies suggest a mechanism of AIDS virus infection that initially involves the specific association of the AIDS virus with T4 molecules on the cell surface. This association does not require additional T-cell-specific molecules and can be demonstrated on both B lymphocytes and epithelial cell lines. The T4-AIDS virus complex is likely to be internalized in endosomes via receptor-mediated endocytosis. The virus can then fuse with the vacuolar membrane, releasing the viral nucleocapsid into the cytoplasm to undergo uncoating. Viral replication does not appear to require the environment of a T lymphocyte because active infection is also observed in human T4+ B lymphocytes and epithelial cell lines. Moreover, the T4 gene is expressed in the brain as well as in lymphocytes, providing an explanation for the dual neurotropic and lymphotropic character of the virus. In this manner, a T-lymphocyte surface protein thought to be important in mediating effector cell-target cell interactions has been exploited by a human lymphotropic virus to target the AIDS virus specifically to populations of T4+ cells.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Self-regulation of procoagulant events on the endothelial cell surface.

Interleukin 1 (IL-1) is a potent mediator of inflammatory and immunologic phenomena. In addition, IL-1 may be intimately involved in the regulation of hemostasis, since interaction of IL-1 with endothelial cells has been reported to induce tissue factor activity. We demonstrate that perturbation of the endothelial cell induces augmented IL-1 release. Human umbilical vein endothelial cells perturbed by treatment with lipopolysaccharide produced enhanced amounts of IL-1 activity. IL-1 activity from lipopolysaccharide-treated endothelial cell supernatants could be absorbed by an antibody to IL-1 coupled to Sepharose. Elaboration of IL-1 activity was dependent on the dose of lipopolysaccharide and occurred in a time-dependent manner. Addition of cycloheximide blocked generation of IL-1 activity. A physiological vessel wall perturbant, the coagulation enzyme thrombin, induced comparable amounts of IL-1 activity in endothelial cell cultures. This effect was specific for the enzyme, since active site-blocked thrombin and prothrombin had no effect on IL-1. In addition, IL-1-containing supernatants from thrombin-stimulated endothelial cells induced tissue factor procoagulant activity in fresh endothelial cell cultures. Thus, in contrast to the multiple, known inhibitory mechanisms that block thrombin procoagulant activity, these data suggest a circle of interaction in which thrombin induces endothelial cell elaboration of IL-1, a mediator of endothelial cell procoagulant activity. Endothelial cell production of IL-1 in response to perturbation allows these cells to play an integral role in the regulation of the inflammatory and coagulation systems.

Animals↗
PubMed1985

Perturbation of the T4 molecule transmits a negative signal to T cells.

We investigated the functional role of the T4 molecule in the activation of T cells by OKT3. T4+ cells were induced to proliferate by OKT3 and erythrocyte rosette-negative accessory cells in the presence or absence of OKT4C, OKT4, and OKT1. OKT4C (IgG1), and not OKT4 (IgG2) or OKT1 (IgG1) inhibited proliferation when OKT4C was added during the first 24 h of cell culture. The inhibition of OKT3 activation by OKT4C did not require Ia+ accessory cells, since T4+ cells could be activated by OKT3 in the presence of Ia- U937 cells, and this activation was markedly inhibited by OKT4C. Furthermore, T4+ cells could be induced to proliferate by OKT3 covalently linked to Sepharose beads, in the absence of any accessory cells. Under these conditions, OKT4C, but not OKT4 or OKT1 significantly inhibited proliferation. These data demonstrate that at least one mechanism by which anti-T4 antibodies inhibit T cell activation is independent of any putative role of T4 molecules in the recognition of Ia on target cells. The data are compatible with the idea that perturbation of the T4 molecules can transmit a negative signal to T4+ cells.

Antibodies, Monoclonal↗
PubMed1985

The distribution of accelerations of the human fetal heart rate at 38 to 40 weeks' gestational age.

In order to further understand the use of antepartum fetal heart rate monitoring we measured the distribution, in time, of two, three, or five fetal heart rate accelerations of greater than or equal to 15 bpm for greater than or equal to 15 seconds and of greater than or equal to 10 bpm for greater than or equal to 6 seconds in 12 healthy pregnant women at 38 to 40 weeks' gestation. The length of time necessary to measure 50% or 95% of intervals containing five accelerations would be substantially reduced by changing to a definition of two or three accelerations. However, an observation interval of at least 80 minutes is required to include the longest time interval of two, three, or five accelerations. These data may suggest new strategies for decreasing time and expense of fetal heart rate testing.

Female↗
PubMed1985

Neuropathy and anti-myelin-associated glycoprotein IgM M proteins: T cell regulation of M protein secretion in vitro.

In patients with plasma cell dyscrasia, individual clones of antibody-producing cells proliferate abnormally and secrete monoclonal antibodies or M proteins in excess. The cause of the monoclonal proliferation of lymphocytes and M protein secretion is unknown and it is not known whether the M protein-secreting B cells are autonomous or capable of responding to regulatory T cells. We carried out experiments using lymphocytes from a patient with neuropathy and plasma cell dyscrasia whose IgM M protein bound to the myelin-associated glycoprotein (MAG) to determine whether secretion of the M protein in vitro was responsive to T cell help or suppression. M protein secretion was measured by an enzyme-linked immunosorbent assay system for measuring anti-MAG IgM, and the number of M protein-secreting lymphocytes was enumerated by a reverse hemolytic plaque assay specific for the M protein idiotype. The patient's B cells were maximally stimulated by pokeweed mitogen-activated autologous OKT4+ T-helper cells and the helper effect was inhibited by OKT8+ suppressor/cytotoxic T cells. Low levels of M protein secretion in the absence of T cells were also observed and there was partial stimulation of M protein secretion by T cells in the absence of pokeweed mitogen.

Autoantibodies↗
PubMed1985

The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes.

The T cell surface glycoproteins T4 and T8 are thought to mediate efficient cell-cell interactions in the immune system and in this way may be responsible for the appropriate targeting of subpopulations of T cells. We have used gene transfer combined with subtractive hybridization to isolate both cDNA and functional genomic clones encoding the T8 protein. The sequence of the cDNA reveals that T8 is a transmembrane protein with an N-terminal domain which shares significant homology to immunoglobulin variable region light chains. This immunoglobulin-like structure is likely to be important in the function of T8 during differentiation and in the course of the immune response.

Amino Acid Sequence↗
PubMed1985

The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family.

The surface glycoproteins T4 and T8 define different functional subsets of T lymphocytes and may act as recognition molecules mediating appropriate interactions between the T cell and its target. Previously we employed gene transfer and subtractive hybridization to isolate a T8 cDNA; now we have isolated and sequenced a cDNA clone encoding the T4 molecule. The deduced protein sequence reveals that T4 is an integral membrane protein that shares significant amino acid and structural homologies with members of the immunoglobulin supergene family. The overall structure of T4 consists of an N-terminal variable (V)-like domain, a joining (J)-like region, a third extracellular domain, a membrane-spanning region homologous to class II MHC beta-chains, and a highly charged cytoplasmic domain. Comparison of the protein sequences deduced from the T4 and T8 cDNAs reveals structural similarities consistent with their postulated role as recognition molecules, as well as differences suggesting that the two proteins recognize different structures on the target cell.

Amino Acid Sequence↗
PubMed1979

Participation of monocyte-macrophages and lymphocytes in the production of a factor that stimulates collagenase and prostaglandin release by rheumatoid synovial cells.

Cultured mononuclear cells from human peripheral blood produce a soluble factor (MCF) that stimulates collagenase and prostaglandin E2 (PGE2) release by cultured rheumatoid synovial cells up to several hundred fold. These target rheumatoid synovial cells lack conventional macrophage markers. To determine which mononuclear cells are the source of MCF, purified populations of monocyte-macrophages, thymus-derived (T) lymphocytes, and bone marrow-derived (B) lymphocytes were prepared. The monocyte-macrophages alone produced levels of MCF that were proportional to cell density but unaffected by phytohemagglutinin or pokeweed mitogen. No detectable collagenase activity was produced by the cultured monocyte-macrophages or lymphocytes. Purified T lymphocytes produced levels of MCF approximately or equal to 1--3% those of purified monocyte-macrophages in the presence or absence of the above lectins. Purified T lymphocytes modulated the production of MCF by the monocyte-macrophages, however, in a manner dependent upon relative cell densities and the presence of lectins. For example, at optimal ratios of T lymphocytes: monocyte-macrophages, MCF production was markedly stimulated by pokeweed mitogen. Thus, interactions of T lymphocytes and monocyte-macrophages could be important in determining levels of MCF, which regulate collagenase and PGE2 production by target synovial cells in inflammatory arthritis.

Arthritis, Rheumatoid↗
PubMed1979

The induction of TNP-altered, self-reactive human cytotoxic T cells by soluble factors: the role of Ia antigens.

This report demonstrates that human peripheral blood T lymphocytes, triggered by allogeneic cells or soluble antigens, elaborate helper factor(s) that promotes the in vitro differentiation of TNP altered-self reactive human CTL. Helper factor(s) alone is not sufficient for the generation of these killer cells, but requires the presence of TNP-derivatized autologous stimulators during sensitization. Additional experiments were performed with antisera to a human Ia-like antigen, p23, 30. These studies indicate that human Ia-like antigens play an important role in both the induction of helper factor(s) and in the functional activity of preformed helper factor(s) molecules.

Cytotoxicity, Immunologic↗
PubMed1978

Normal erythropoietic helper T cells in congenital hypoplastic (Diamond-Blackfan) anemia.

To examine the erythropoietic function of T and null cells in congenital hypoplastic (Diamond-Blackfan) anemia, we fractionated the peripheral blood of three normal subjects and three affected patients into subclasses of null, T and B cells. Mixtures of these cells were co-cultured in plasma clots in the presence of erythropoietin. Erythroid colonies grew in cultures of normal null cells if either normal or patient T cells were co-cultured with them. Null cells of patients with hypoplastic anemia did not produce erythroid colonies under any culture conditions. We conclude that in this disorder, T cells function normally as helper cells in erythropoiesis and do not suppress colony formation, whereas the erythroid progenitor cells in the peripheral blood null-cell fractions are deficient in either number of function.

Adolescent↗
PubMed1978

Human erythroid burst-forming unit: T-cell requirement for proliferation in vitro.

Human mononuclear leukocytes were fractionated into populations of null, T and B cells by immunoabsorbent column chromatography followed by E-rosette formation and purification of T cells by differential centrifugation and osmotic lysis. The unfractionated and fractionated cell populations were first separately cultured for 14 days in plasma clots in the presence of two international units erythropoietin. Typical erythroid burst-forming unit (BFU-E)-derived colonies grew in the unfractionated cell cultures but not from T- or B-cell cultures. BFU-E colonies grew in null cell cultures but most of the colonies were small and variably hemoglobinized with less than three subcolonies. When intact T cells were added to null cells and cocultured, many typical large BFU-E colonies with more than 10 well homogenized subcolonies appeared. Increasing numbers of large BFU-E colonies in null cell cultures were induced by stepwise addition of T cells but not by the addition of B cells. A conditioned medium in which T cells had been induced to divide by tetanus toxoid substituted for intact T cells in this T-cell-dependent BFU-E colony formation observed in null cells. These findings demonstrate that the BFU-E, a committeded erythroid stem cell, resides in the null cell fraction of peripheral blood, but its proliferative capacity and differentiation in vitro requires a soluble product of T cells. Such experiments now permit a new approach to the assessment of various disorders of erythropoiesis. Erythroid hypoplasia in a particular case may be due to dysfunction of the committed precursor cell or to a failure of a helper effect induced by T cells.

B-Lymphocytes↗
PubMed1978

Antibody-dependent cellular cytotoxicity by allosensitized human T cells.

Peripheral human T cells, isolated by sheep erythrocyte-rosette formation and density centrifugation, were highly cytotoxic to both Ab-coated autologous lymphocytes and antibody (Ab)-coated chicken erythrocytes when stimulated in mixed lymphocyte culture, but were not lytic when freshly purified, or when unstimulated in 6-day culture. Allosensitized T cells were shown to effect this activity by a specific effector-target cell interaction dependent on Ab, as indicated by: (a) induction of killing by Ab to target cells not lysed in the absence of Ab. (b) inhibition of Ab-dependent killing by aggregated Ig. The mechanism by which allosensitized T cells effect antibody-dependent cellular cytotoxicity is discussed.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Isolation and characterization of naturally occurring subclasses of human peripheral blood T cells with regulatory functions.

By utilizing naturally occurring autoimmune antibodies from patients with juvenile rheumatoid arthritis, we have isolated and functionally characterized two unique subpopulations of T cells. JRA+ T cells, i.e., those identified by sera from these patients, react poorly in response to allogeneic cells, respond to Con A but not PHA, and do not help in the synthesis and secretion of Ig by B cells. In contrast, JRA- T cells, i.e., those not identified by sera from these patients, respond very well to allogeneic cells, proliferate well in response to PHA but not Con A, and more interestingly, can greatly enhance the secretion of Ig by B cells.

Antigens↗
PubMed1978

Replication of herpes simplex virus and cytomegalovirus in human leukocytes.

Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear leukocyte cultures of one of five donors, and to a limited degree in untreated B lymphocytes of three of five donors; HSV replication was not detected in unstimulated T lymphocytes (five donors). There was no evidence of enhanced uptake of 3H-thymidine in the untreated donor cells that replicated HSV. CMV replication was not detected during 9 to 10 days of infection in untreated or mitogen-treated mononuclear leukocytes and lymphocyte subpopulations from the same adult donors or in neonatal cord blood leukocytes. The ability of the cells to support HSV or CMV replication did not correlate with the presence of specific antiviral antibodies in the donor serum. HSV replication in B, T, and myeloid cell lines to high titers over 5 days of infection, whereas CMV failed to replicate in any of the hemic cell lines. A persistent HSV infection has been established in a T cell line (CEM) with high titers of infectious virus being produced concurrently with growth of the cells over the first 11 weeks of infection.

Antibodies, Viral↗