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Biomedical subjects

K Gleason

Publications and source records attributed to K Gleason.

10 recordsLinked to original sources
PubMed2001

Sequential magnetic resonance monitoring of pulmonary flow with endovascular stents placed across the pulmonary valve in growing Swine.

BACKGROUND: Patients with endovascular stent implantation for the treatment of right ventricular outflow tract obstruction are often left with incomplete relief of the obstruction and significant pulmonary regurgitation. A noninvasive and reproducible method for monitoring such patients is desirable. MRI in the presence of a stent, however, has to overcome the problem of potential metallic artifacts. METHODS AND RESULTS: Under x-ray fluoroscopic guidance, endovascular nitinol stents were placed across the pulmonary valve in 6 young pigs to induce pulmonary regurgitation. Five additional pigs served as controls. Initial MRI was performed after 2 days (13.5+/-1.8 kg) and follow-up after 3 months (32+/-2.9 kg). Pulmonary flow volumes and regurgitant fraction were quantified by velocity-encoded cine (VEC) MRI through (VEC-TS) and distal to (VEC-DS) the stent. VEC-TS was compared with VEC-DS and volumetric measurements of left and right ventricular stroke volumes provided by cine MRI ("gold standard"). Antegrade and retrograde pulmonary flow volumes by VEC-TS were slightly but significantly less than those with VEC-DS and cine MRI. Excellent correlations (r>0.97) for phasic pulmonary flow volumes as measured by VEC-TS and VEC-DS were shown. Pulmonary regurgitant fraction increased from 32.8+/-15% to 49.6+/-17% (P<0.05) over the course of 3 months with VEC-TS. CONCLUSIONS: MRI demonstrates the progression of pulmonary regurgitation in growing swine. VEC MRI has the ability to quantify pulmonary blood flow inside the lumen of nitinol stents. MRI appears to be ideally suited for monitoring patients with endovascular nitinol stents in the pulmonary artery or pulmonary valve position.

Alloys↗
PubMed1985

Familial IgA nephropathy. Evidence of an inherited mechanism of disease.

The evaluation of familial glomerulonephritis in patients with IgA nephropathy who were from central and eastern Kentucky resulted in the discovery of potentially related pedigrees containing 14 patients. An additional 17 members of the pedigrees had clinical glomerulonephritis, and 6 had "chronic nephritis" noted on their death certificates. Six patients with IgA nephropathy had a common ancestor. In addition, both parents of six patients with the disease came from families with other cases of IgA nephropathy. No single HLA haplotype or antigen was found in all the patients with IgA nephropathy. Our data on these pedigrees strongly support an inherited mechanism in the pathogenesis of IgA nephropathy in some patients.

Female↗
PubMed1984

T-cell helper circuits.

T helper cells specific for trinitrophenylated PC-binding myeloma and hybridoma antibodies are induced by priming with PC antigen, idiotype or anti-idiotypic antibody. These T helper cells are specific for a shared idiotope present on T15 and M167. Priming with the isolated heavy chains of T15 or M167, or the light chain of anti-T15 hybridoma antibody is equally effective in generating T helper cells. Evidently, the idiotope that is recognized by T cells is not dependent upon the conformation of the 7s Ig molecule. Collectively, these and other findings indicate the existence of a TH1-TH2-B cellular circuit which is based on the recognition of idiotopic determinants on T cell receptors. The implications of these findings in terms of network theory are explored.

Animals↗
PubMed1983

Idiotype-specific T-helper cells.

In the present study we investigated the induction and fine specificity of T-helper cells that recognize idiotypes. The data presented show that both low-dose priming with anti-T15 antiserum and priming with PC-Hy are effective in stimulating T15-specific T help. Phosphorylcholine-hemocyanin priming can generate these T cells in either PC-responding or nonresponding strains of mice. Furthermore, the PC-primed T-helper cells can also recognize another anti-PC myeloma, M167, that is idiotypically different from T15. The fine specificity of the anti-PC-idiotype recognizing T-helper cells was examined by studying the effect of in vitro inhibitors on the T-cell help. Both PC and PC-BSA as well as T15 and M167 had an inhibitory effect on the T help. Free T15 and M167 heavy chains also blocked the helper activity for T15; T15 and M167 light chains had no effect, however. Viewed collectively, these results show that PC-Hy priming induces T-helper cells that recognize idiotypic determinants common to both T15 and M167, and that the proteins' H chain is the major structural component of the determinant. Finally, the generation of these idiotype-recognizing T cells was found to occur by way of a T-T interaction loop, based on the finding that T-helper cells are induced by PC-Hy priming in animals that lack PC-responding B cells.

Animals↗
PubMed1982

Regulatory idiotypes. T helper cells recognize a shared VH idiotope on phosphorylcholine-specific antibodies.

Priming of BALB/c mice with phosphorylcholine-hemocyanin (PC-Hy) induces T helper cells that are detected in splenic fragment cultures responding to immunization with trinitrophenylated PC-binding myeloma proteins, TEPC 15 (TNP-T15) and MOPC 167 (TNP-M167). Trinitrophenylation did not alter the binding site, idiotype, or isotype of the antibodies as demonstrated by binding studies. To assay idiotype-recognizing helper cells, Ly-2.2-depleted T cells from PC-Hy-primed donor mice were transferred to syngeneic athymic mice. Splenic anti-trinitrophenol fragment cultures were prepared from the nude recipients, and the response to TNP-T15 and TNP-M167 was measured by enzyme-linked immunosorbent assay. The number of responding fragments is dependent on the number of transferred primed T cells. The homing efficiency of 51Cr-labeled helper cells into the spleen of nude recipients was determined. The frequencies of T helper cells taken from PC-Hy-primed donors required for a B cell response to TNP-T15 or TNP-M167 were indistinguishable. The fine specificity of the anti-PC idiotype-recognizing T helper cells was studied by adding hapten (PC) or unconjugated myeloma proteins to fragment cultures as inhibitors at the time of immunization. PC and PC-bovine serum albumin, as well as T15 and M167, inhibited the helper function in vitro. Furthermore, free heavy chains of T15 and M167 partially inhibited T help, but free light chains of both idiotypes had no effect. These findings collectively show that T helper cells, induced by priming with antigen, recognize a shared idiotypic determination on T15 and M167 that is part of the PC binding site. The heavy chains of T15 and M167 appears to be the major structural component of this determinant. Evidently, T helper cells can recognize a shared determinant that is present on idiotypically different myeloma proteins. This determinant appears to be conserved throughout evolutionary and somatic mutations. The role of this shared, binding site-related idiotypic determinant as a regulatory idiotype in T-B cell interaction is discussed.

Animals↗
PubMed1981

Balb/c T cells have the potential to recognize the TEPC 15 prototype antibody and its somatic variants.

Immunization of BALB/c mice with phosphorylcholine-Limulus polyphemus hemocyanin (PC-Hy) induces a population of T cells that recognize the predominant PC-binding antibody, TEPC15 (T15). The splenic fragment culture system was used to examine the specificity of these T cells for a series of PC-binding myeloma and hybridoma antibodies representing the prototype variable region of the heavy chain (VH)T 15 sequence as well as somatic variants of the T15 germ line-encoded sequence. Included in this group of PC-binding proteins were both T15-positive and T15-negative antibodies, as defined by anti-idiotypic antibody. T cell help was identified by the ability to promote TNP-specific B cell responses to trinitrophenylated PC-binding proteins. It was found that T cells generated by immunization with PC-Hy recognize both antibodies with the T15 prototype sequence and the putative somatic variants of this sequence. A population of these T cells appear to recognize common determinants shared by these proteins because immunization with T15 itself also induces the recognition of the somatic variants. This suggests that idiotopes encoded in the T15 germ line gene expressed by the T15 prototype idiotype and the somatic variants can function as targets for T cell recognition and are thus regulatory idiotopes.

Amino Acid Sequence↗
PubMed1981

Generation of idiotype-specific T cell help through network perturbation.

Different manipulations of BALB/c mice were used to generate idiotype-specific help: neonatally induced suppression of the T 15 idiotype and low-dose priming with anti-T15 antibody. The splenic foci culture system was used to study T15-idiotype-recognizing helper T cells under limiting-cell-dose conditions. These treatments induced T15 idiotype-specific help for B cells responding to TNP-T15. Normal or hemocyanin-primed BALB/c mice did not supply T15 idiotype-specific help. The helper cells were sensitive to anti-Thy-1.2 and complement treatment and can distinguish T15 from an idiotype-different, PC-binding myeloma protein, M167, and the TNP binding myeloma protein, M460. These data show that idiotype-specific T helper cells can be induced by at least two different manipulations of the idiotype network. These manipulations presumably do not act directly on the T15-recognizing T cells, but must involve complementary idiotypic circuits that stimulate anti-T15 specific T cells. Furthermore, this study demonstrates that the splenic-fragment culture technique provides a general method to investigate, at the single cell level, idiotypic T-B cell interactions induced by perturbations of the immune network.

Animals↗
PubMed1980

Maturation of B-cell clones.

The maturation of B-cells was investigated in adoptive transfers and splenic foci. Anti-idiotypic antigens were used to identify clones responding to PC and dextran. A distinct temporal hierarchy of responsiveness could be observed in which the anti-TNP response appears first, followed by anti-dextran and anti-PC. Tolerance induction and anti-idiotype suppression were used as markers for maturing B-cells responding in splenic foci. A differential susceptibility to these manipulations establishes two types of progenitor cells. A scheme for the maturational steps of B-cells is proposed.

Animals↗
PubMedDate not supplied

Clinical comparison of St. Jude and porcine mitral valve prostheses.

One hundred and six consecutive patients who had mitral valve replacement with either a St. Jude or porcine heterograft prosthesis were prospectively studied. The 2 groups are similar with respect to 67 clinical and operative factors and allow comparison of valve performance as an independent variable. Total follow-up is 3,312 patient-months (mean 36 months, range 2-57 months, 94% complete). There are no statistical differences in symptomatic improvement or mortality by life table analysis. Valve-related complications expressed as percent per patient-year are: reoperation: 1.8 St. Jude and 3.8 porcine; endocarditis: 1.2 and 1.9; regurgitant murmur: 2.3 and 1.9; hemolysis: 1.8 and 0.0; late thromboembolism: 1.8 and 1.0; hemorrhage: 2.9 and 2.9; and valve failure: 0.0 and 1.0. There were no significant differences found. Actuarial survival at 3 years was 78% in St. Jude and 81% in porcine patients. Forty-six percent of patients with St. Jude valves and 55% of patients with porcine valves were alive and free of all complications at latest follow-up. The clinical performance of St. Jude and porcine mitral valves are similar over this period of intermediate follow-up.

Adult↗