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While studying the T cell receptor (TCR) repertoire of normal individuals, we found that more tha... more While studying the T cell receptor (TCR) repertoire of normal individuals, we found that more than 20 % of adults have low levels of circulating VB3.1 + T cells in both CD4 and CD8 populations. A similar frequency was found in fetal cord blood samples, suggesting that in most cases, the Vfl3.1 l ~ phenotype is inherited. In support of this conclusion, children expressing low levels were only found in families where one of the parents expressed this phenotype. In two large families, genetic studies showed that low expression was a recessive trait and dependent on inheritance of particular TCR VB gene complexes. Family members with the low phenotype, however, expressed VB3.1 genes with normal sequences and expressed normal levels of receptor per cell. Results from these families suggest that up to 50 % of normal individuals may carry a VB3.1 allele that is defective in its ability to rearrange effectively. In another large family, low expression in one individual was shown not to be d...
A method for detecting the presence of a pathogen in a whole blood sample, the method comprising:... more A method for detecting the presence of a pathogen in a whole blood sample, the method comprising: (a) providing a whole blood sample of a subject; (b) mixing the whole blood sample with an erythrocyte lysis agent to produce destroyed red blood cells; (c) after step (b), centrifuge the sample to form a supernatant and a pellet, discarding part or all of the supernatant, and resuspend the pellet to form an extract, optionally washing the pellet before resuspend the pellet and repeat optionally step (c); (d) lysis the extract cells to form a lysate; (e) placing the lysate of step (d) in a container and amplifying a nucleic acid in the lysate to form an amplified lysate solution comprising the target nucleic acid, wherein the target nucleic acid is characteristic of the pathogen to be detected; (f) after step (e) mixing the amplified lysed solution with 1x106 to 1x1013 magnetic particles per milliliter of the amplified lysed solution to form a liquid sample, wherein the magnetic particl...
Vascular Endothelium, 1998
Cholesterol ester transfer protein (CETP) mediates the transfer of neutral lipids between HDL and... more Cholesterol ester transfer protein (CETP) mediates the transfer of neutral lipids between HDL and the lower density lipoproteins VLDL and LDL. Elevated serum HDL, which is a negative risk factor for atherosclerosis is associated with lower levels of CETP activity. CETP-deficient humans have been identified and described as generally free of atherosclerosis and prone to longevity. The objective of this sutdy is to determine whether anti-CETP autoantibodies could be induced in experimental animals by vaccination as a novel approach to the reduction of CETP activity and thereby alter the cell helper epitope of tetanus toxoid, a B cell epitope derived from the C-terminus of CETP, and an N-terminal cysteine was synthesized and used to immunize transgenic mice expressing human CETP (CETP mice) and New Zealand white rabbits after primary vaccination and two booster injections. The anti CETP autoantibodies were directed against the neutral lipid binding site since they competed with monoclonal antibody TP2, known to inhibit CETP activity, for binding to recombinant human CETP. In a small study using a hyper-cholesteremia rabbit model, the vaccinated group has significantly reduced aortic atherosclerotic lesions compared to non-vaccinated controls (p<.01).
World Journal of Surgery, 2007
Over the last 50 years, several attempts have been made to harness the power and economy of vacci... more Over the last 50 years, several attempts have been made to harness the power and economy of vaccines in the fight against cardiovascular disease. Vaccines directed to lipoproteins, cholesterol itself, and molecules involved in cholesterol metabolism have all demonstrated success in modifying progression of disease in animal models of atherosclerosis. One vaccine that elicits antibodies to cholesteryl ester transfer protein has also progressed into the realm of human clinical testing. This review summarizes the published scientific work describing the various approaches that have been tried, their strengths and weaknesses, and where this field may go in the future.
Diabetologia, 1994
Lymphoid cell infiltration into pancreatic islets (insulitis) is a well-recognized feature of Typ... more Lymphoid cell infiltration into pancreatic islets (insulitis) is a well-recognized feature of Type i (insulindependent) diabetes mellitus both in humans [1] and in rodents with spontaneous diabetes [2, 3]. The nonobese diabetic (NOD) mouse spontaneously develops an insulin-dependent diabetes. NOD mice exhibit massive infiltrates of lymphoid cells and macrophages into pancreatic islets (insulitis) prior to complete betacell destruction, and insulitis appears as early as 5 weeks of age. Makino and co-workers [4] have shown
The Journal of Parasitology, 1976
... All tubes were carefully filed and broken at the cell-fluid interface, placed in migration ch... more ... All tubes were carefully filed and broken at the cell-fluid interface, placed in migration chambers (Berton), and affixed to the bottom ... that the expression of macrophage in-hibition and disappearance, in addition to the cell-mediated mechanisms previously reported (Coleman et ...
Journal of Immunological Methods, 1993
A soluble, recombinant form of the human T cell receptor (TCR)/3-chain containing the V/33.1 sequ... more A soluble, recombinant form of the human T cell receptor (TCR)/3-chain containing the V/33.1 sequence has been constructed, expressed in Chinese hamster ovary cells, amplified by dihydrofolate reductase selection, and purified in quantities appropriate for the generation of monoclonal antibodies (mAb). The V/33 sequence was chosen because of its reported elevated usage in the synovial T cells of rheumatoid arthritis patients but the approach described should be applicable to other known human V/3 gene sequences. By this method, two mAb were prepared which reacted with up to 10% of normal, live peripheral blood T cells but with reactivity varying greatly among individual donors. Both mAb specifically bound to a murine T cell line transfected with a human TCR V/33.1 and immunoprecipitated a protein of the expected molecular weight for the TCR /3-chain. Both antibodies were mitogenic for T cells and analysis of peripheral blood lymphocyte cultures stimulated with the mAb suggested that both were specific for the V/33.1 subfamily and not D/3 or J/3. Clones expressing V/33, which were derived from mAb-stimulated peripheral blood lymphocytes of a single individual, preferentially (8/13), but not exclusively, utilized the J/32.7 gene segment. The V/33.1 usage showed no preference for the CD8 + or CD4 + subpopulations of normal peripheral blood T cells.
While studying the T cell receptor (TCR) repertoire of normal individuals, we found that more tha... more While studying the T cell receptor (TCR) repertoire of normal individuals, we found that more than 20 % of adults have low levels of circulating VB3.1 + T cells in both CD4 and CD8 populations. A similar frequency was found in fetal cord blood samples, suggesting that in most cases, the Vfl3.1 l ~ phenotype is inherited. In support of this conclusion, children expressing low levels were only found in families where one of the parents expressed this phenotype. In two large families, genetic studies showed that low expression was a recessive trait and dependent on inheritance of particular TCR VB gene complexes. Family members with the low phenotype, however, expressed VB3.1 genes with normal sequences and expressed normal levels of receptor per cell. Results from these families suggest that up to 50 % of normal individuals may carry a VB3.1 allele that is defective in its ability to rearrange effectively. In another large family, low expression in one individual was shown not to be d...
A method for detecting the presence of a pathogen in a whole blood sample, the method comprising:... more A method for detecting the presence of a pathogen in a whole blood sample, the method comprising: (a) providing a whole blood sample of a subject; (b) mixing the whole blood sample with an erythrocyte lysis agent to produce destroyed red blood cells; (c) after step (b), centrifuge the sample to form a supernatant and a pellet, discarding part or all of the supernatant, and resuspend the pellet to form an extract, optionally washing the pellet before resuspend the pellet and repeat optionally step (c); (d) lysis the extract cells to form a lysate; (e) placing the lysate of step (d) in a container and amplifying a nucleic acid in the lysate to form an amplified lysate solution comprising the target nucleic acid, wherein the target nucleic acid is characteristic of the pathogen to be detected; (f) after step (e) mixing the amplified lysed solution with 1x106 to 1x1013 magnetic particles per milliliter of the amplified lysed solution to form a liquid sample, wherein the magnetic particl...
Vascular Endothelium, 1998
Cholesterol ester transfer protein (CETP) mediates the transfer of neutral lipids between HDL and... more Cholesterol ester transfer protein (CETP) mediates the transfer of neutral lipids between HDL and the lower density lipoproteins VLDL and LDL. Elevated serum HDL, which is a negative risk factor for atherosclerosis is associated with lower levels of CETP activity. CETP-deficient humans have been identified and described as generally free of atherosclerosis and prone to longevity. The objective of this sutdy is to determine whether anti-CETP autoantibodies could be induced in experimental animals by vaccination as a novel approach to the reduction of CETP activity and thereby alter the cell helper epitope of tetanus toxoid, a B cell epitope derived from the C-terminus of CETP, and an N-terminal cysteine was synthesized and used to immunize transgenic mice expressing human CETP (CETP mice) and New Zealand white rabbits after primary vaccination and two booster injections. The anti CETP autoantibodies were directed against the neutral lipid binding site since they competed with monoclonal antibody TP2, known to inhibit CETP activity, for binding to recombinant human CETP. In a small study using a hyper-cholesteremia rabbit model, the vaccinated group has significantly reduced aortic atherosclerotic lesions compared to non-vaccinated controls (p<.01).
World Journal of Surgery, 2007
Over the last 50 years, several attempts have been made to harness the power and economy of vacci... more Over the last 50 years, several attempts have been made to harness the power and economy of vaccines in the fight against cardiovascular disease. Vaccines directed to lipoproteins, cholesterol itself, and molecules involved in cholesterol metabolism have all demonstrated success in modifying progression of disease in animal models of atherosclerosis. One vaccine that elicits antibodies to cholesteryl ester transfer protein has also progressed into the realm of human clinical testing. This review summarizes the published scientific work describing the various approaches that have been tried, their strengths and weaknesses, and where this field may go in the future.
Diabetologia, 1994
Lymphoid cell infiltration into pancreatic islets (insulitis) is a well-recognized feature of Typ... more Lymphoid cell infiltration into pancreatic islets (insulitis) is a well-recognized feature of Type i (insulindependent) diabetes mellitus both in humans [1] and in rodents with spontaneous diabetes [2, 3]. The nonobese diabetic (NOD) mouse spontaneously develops an insulin-dependent diabetes. NOD mice exhibit massive infiltrates of lymphoid cells and macrophages into pancreatic islets (insulitis) prior to complete betacell destruction, and insulitis appears as early as 5 weeks of age. Makino and co-workers [4] have shown
The Journal of Parasitology, 1976
... All tubes were carefully filed and broken at the cell-fluid interface, placed in migration ch... more ... All tubes were carefully filed and broken at the cell-fluid interface, placed in migration chambers (Berton), and affixed to the bottom ... that the expression of macrophage in-hibition and disappearance, in addition to the cell-mediated mechanisms previously reported (Coleman et ...
Journal of Immunological Methods, 1993
A soluble, recombinant form of the human T cell receptor (TCR)/3-chain containing the V/33.1 sequ... more A soluble, recombinant form of the human T cell receptor (TCR)/3-chain containing the V/33.1 sequence has been constructed, expressed in Chinese hamster ovary cells, amplified by dihydrofolate reductase selection, and purified in quantities appropriate for the generation of monoclonal antibodies (mAb). The V/33 sequence was chosen because of its reported elevated usage in the synovial T cells of rheumatoid arthritis patients but the approach described should be applicable to other known human V/3 gene sequences. By this method, two mAb were prepared which reacted with up to 10% of normal, live peripheral blood T cells but with reactivity varying greatly among individual donors. Both mAb specifically bound to a murine T cell line transfected with a human TCR V/33.1 and immunoprecipitated a protein of the expected molecular weight for the TCR /3-chain. Both antibodies were mitogenic for T cells and analysis of peripheral blood lymphocyte cultures stimulated with the mAb suggested that both were specific for the V/33.1 subfamily and not D/3 or J/3. Clones expressing V/33, which were derived from mAb-stimulated peripheral blood lymphocytes of a single individual, preferentially (8/13), but not exclusively, utilized the J/32.7 gene segment. The V/33.1 usage showed no preference for the CD8 + or CD4 + subpopulations of normal peripheral blood T cells.