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Biomedical subjects

L Fuller

Publications and source records attributed to L Fuller.

At least 91 records · Page 5Linked to original sources
PubMed1985

T cell lines and clones preferentially recognizing kidney-associated antigens in end-stage renal disease.

The specificity in the mixed lymphocyte kidney culture (MLKC) of T cell lines and clones derived from human end-stage renal disease (ESRD) kidneys was studied using collagenase dispersed kidney cells compared with lymphocytes as stimulating cells. These experiments were performed because of previous studies in which infiltrating lymphocytes freshly isolated from ESRD kidney tissue at nephrectomy (as well as autologous splenic T cells) were seen to directly generate this lymphoproliferative MLKC response when stimulated with autologous renal cortical cells. In the current studies, histopathologic staining of tissues and suspensions of infiltrating kidney lymphocytes showed predominance of OKT4 labeled phenotypes, and the stimulation indices in MLKC in general showed a direct relationship with the percentage of helper cells seen in the infiltrates. When T cell lines and clones derived from lymphocytes infiltrating the ESRD kidneys were tested in MLKC, there was evidence of kidney-associated, as opposed to lymphocyte-associated (MLC) reactivity using (3H) thymidine uptake as a reflection of a lymphoproliferative response. Several cell lines and clones derived from these T lymphocytes exhibited a dual reactivity. They served as responding cells in the MLKC reaction and completely suppressed a non-specific allogeneic MLC when added as third-party cells. Quantitatively, some clones suppressed when third-party x-irradiated cells were only 5% of the responding cell number in coculture. In addition to the dual reactivity, phenotypic analysis of these same cell lines and clones employing monoclonal antibodies revealed that individual cells expressed both OKT4 and OKT8 determinants. However, approximately 90% of the cells in the MLC enhancing line were labeled with OKT4. These results indicate that there is a complexity in the autologous MLKC response in that cells with both helper/inducer and suppressor/cytotoxic function take part in the reaction. Although delayed-type hypersensitivity to kidney-associated antigens is inferred as a result of these in vitro assays, nonspecific suppression of other Ia-dependent reactions can simultaneously occur.

Antibodies, Monoclonal↗
PubMed1985

The acceptability of sweet and savoury sip feeds.

Successful dietary supplementation by sip feeding can be difficult to achieve when the flavour is unpleasant to the patient. The palatability of nine varieties of sip feed were assessed by 20 hospital patients with non-malignant conditions and by 16 control subjects, using a single-blind randomised technique. Sweet flavours were preferred to savoury flavours; chocolate, strawberry and banana were the favourites, chosen in similar numbers by both patients and controls. Sweet flavours were often correctly identified, with the exception of egg nog, but savoury flavours were recognised less frequently. The results have implications for the success of supplementation.

Adult↗
PubMed1983

Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation.

In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (TH):T suppressor/cytotoxic (TS/C) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and TH:TS/C ratios between 0.15 to 2.10, ratios of greater than 0.8 correlated with AMLR responses (13/13), and ratios of less than 0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the TH:TS/C ratios or with the AMLR pre- or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The "naturally occurring" T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated TH and TS/C subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient pairs the Tx cells of the (normal) donor inhibited the recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhibitor found in normal peripheral blood, appears to be a cell that is highly sensitive to the effects of biologic or pharmacologic immunosuppressive agents.

Cell Count↗
PubMed1983

Unusual aspects of Kawasaki syndrome.

Kawasaki syndrome (mucocutaneous lymph node syndrome) occurs predominantly in children. The criteria for diagnosis include unresponsive fever; lesions of the skin and conjunctival mucous membrane; edema, rashes and other abnormalities of the hands and feet, and cervical lymphadenopathy. Unusual features occur in the cardiovascular, gastrointestinal and central nervous systems, as well as elsewhere. The variety of findings may be misleading, and the diagnostic criteria must be kept in mind.

Aspirin↗
PubMed1982

Effects of histocompatibility testing versus immunoreactive predisposition on kidney transplant survival.

From January 1979 to August 1981, 76 primary renal transplants were performed at the University of Miami-Jackson Memorial Hospital. Fifty-five of these were from living, related (LR) donors and 21 were from cadaver (CAD) donors. Histocompatibility typing for HLA-A, -B, and -DR antigens and of mixed lymphocyte culture (MLC) were performed. In LR patients the ability to generate donor-specific and nonspecific suppressor cells in vitro was tested preoperatively. Serial posttransplant immunologic monitoring was used in all patients by determining total T-cell numbers (E rosette-forming cells) as well as helper and suppressor T-cell subsets by use of monoclonal antibodies. Overall patient and graft survival was 90% and 87%, respectively. In this study MLC reactivity did not correlate with DR typing in CAD recipients, most of whom had marked reaction despite one or two DR antigen matches. Graft survival was also independent of MLC reactivity in both LR and CAD patients. The ability of LR recipients to generate donor-specific suppressor cells in vitro before transplantation did correlate significantly with absence of rejection episodes. Immunologic monitoring with T-cell subsets had prognostic significance for the detection of patients with excessive immunosuppression and high risk for development of infection (P less than 0.001). Thus, the responder status of many transplant recipients seemed as important as the current assessment of histocompatibility in influencing graft survival.

Antibodies↗
PubMed1981

Responses of canine lymphocytes to allogeneic and autologous Islets of Langerhans in mixed cell cultures.

Because successful allotransplantation of islets of Langerhans isolated by collagenase digestion has been difficult in many animal species, we asked whether isolated islet preparations might have tissue specific determinants conferring amplified immunogenicity in vitro. Lymphocyte proliferative responses ([(3)H]thymidine uptake) were studied in beagle dogs in mixed culture combinations of lymphocyte vs. lymphocyte (MLC) and lymphocyte vs. islet (MLIC). In five MLC responder and five nonresponder pairs, peripheral blood lymphocytes of dogs A and B were used as responding cells, and dog B x-irradiated lymphocytes (Bx), x-irradiated (or nonirradiated) islets (BI), or hepatic cells (BH) were used as stimulating cells in primary and secondary reactions. For the secondary reactions, A + Bx, A + BI, or B + BI were incubated for 9 d (A'B, A'BI, B'BI, respectively) before addition of new stimulating cells. The results showed that islets were autostimulatory, eliciting a tissue-specific lymphoproliferative response in a primary MLIC. Thus, B + BI reactivity was evident at 3,5, and 7 d in primary culture, whereas collagenase-digested liver cells, or lymphocytes obtained from collagenase-digested lymph nodes did not stimulate autologous lymphocytes. A separate reactivity was observed in the allogeneic A + BI combination in MLC responder pairs, and the peak response of A + BI at 9 d was markedly greater than that of B + BI, suggesting the presence of major histocompatibility complex lymphocyte-defined locus determinants in the islet preparations, in addition to islet-specific determinants. A secondary reaction was observed if lymphocytes were primed with islets and challenged with islets (A'BI + BI or B'BI + BI), but not if they were challenged with lymphocytes (A'BI + Bx, B'BI + Bx) or hepatic cells (A'BI + BH, B'BI + AH). Furthermore, priming of lymphocytes with autologous islets (B'BI) led to exclusion of any reactivity against allogeneic lymphocytes, i.e., B'BI suppressed A + Bx, and B'BI also markedly suppressed phytohemagglutinin-stimulated lymphoproliferative responses. Experiments were performed that excluded the possibility that the insulin levels present in the MLIC, the presence of passenger lymphocytes in the islets, or the maintenance of islets in tissue culture for 1-7 d affected the observations. These results provide evidence for the existence of alloantigens as well as tissue-specific antigens on collagenase-isolated islets of Langerhans.

Animals↗
PubMed1981

Kidney transplantation by use of splenectomy and transfusions, cadaver haplotype matching, suppressor cell assays, and T-cell monitoring.

We attempted to modulate several determinants of the host immunologic profile to improve kidney transplant survival: (1) genotype matching of the cadaver donor with the recipient, (2) assessment in recipients of living related donors (LRD) for predisposition to generate suppressor cells in mixed lymphocyte culture (MLC), (3) pretransplant splenectomy and transfusions, and (4) posttransplant immunologic monitoring. Between January, 1979, and July, 1980, 48 primary renal transplants were performed and followed up between 6 and 24 months. Pretransplant splenectomy was performed, and transfusions were administered in 38 of 48 and 48 of 48 patients, respectively. Donors and recipients of 10 of 11 cadaveric transplants were genotyped and selected for one HLA haplotype identity. All 10 proved to also be one DR antigen matches. There were no cadaveric kidney losses, but one surgical antibody to T cell subtest were used to modulate rejection therapy. The LRD group (n = 37) included 13 HLA-identical, seven haploidentical low MLC reactors, and 17 haploidentical high MLC reactors. Three deaths occurred (diabetes and myocardial infarction, stroke, and pancreatitis). A three-component coculture assay was used in the LRD group before transplantation to determine the capacity to generate specific and nonspecific MLC suppressor cells. Suppressor cells were seen in 17 patients given standard immunosuppression postoperatively without rejection episodes. However, in 20 patients incapable of generating suppressor cells, seven biopsy-proved rejection episodes occurred. There were no kidney losses, with 44 of 48 surviving recipients demonstrating normal renal function.

Adolescent↗
PubMed1980

The development of obesity in genetically diabetic-obese (db/db) mice pair-fed with lean siblings. The importance of thermoregulatory thermogenesis.

The importance of reduced thermoregulatory thermogenesis as a mechanism for the high metabolic efficiency of the diabetic-obese (db/db) mouse has been investigated. Young db/db mutants were pair-fed to the ad libitum food intake of lean siblings for two weeks at two different environmental temperatures, 23 and 33 degrees C. At 23 degrees C, a temperature at which there is a substantial demand for thermoregulatory thermogenesis, the diabetic-obese animals deposited 51% more total energy and 75% more fat than the lean mice. At 33 degrees C (thermoneutrality) where there is no requirement for thermoregulatory heat, the mutants deposited 25% more fat than lean animals, but there was no significant difference in the total energy gain of the two groups. Pair-feeding resulted in a reduced protein deposition at both temperatures in the diabetic-obese animals compared to the lean. It is concluded that the high metabolic efficiency of the diabetic-obese mutant, like that of the obese (ob/ob) mouse, is caused by a low energy expenditure on thermoregulatory thermogenesis.

Animals↗
PubMed1980

In vitro generation of human mixed lymphocyte culture suppressor cells. I. Cellular characterization and specificity.

The mixed leukocyte culture (MLC) of peripheral blood lymphocytes (PBLs) from two prospective kidney transplant recipients and their respective donors, produced a primed cell population that functioned as suppressors. The primed cells suppressed the primary and secondary MLC when added as third components, without demonstrable cytotoxic cells. Suppressor cells were derived from the MLCs of related pairs that were genotyped to be: (1) serologically defined (SD) identical and lymphocyte-defined (LD) nonidentical, and (2) HLA (total MHC) identical. Primed cells derived from MLC of unrelated HLA nonidentical subjects also showed similar effects. Two general patterns of inhibition were observed: a marked specific suppression of the autologous responding cells and, to a lesser degree, nonspecific suppression. The T cell fraction derived from the primed suppressor population was suppressive, the cells with B cell characteristics were not suppressive. The suppressive effect of cells generated in MLC was serially monitored after kidney transplantation. The suppressive activity of the primed cells was absent in the early postoperative period (4 weeks), perhaps because of high dose immunosuppression, but later in the course suppression was evident again (2 to 5 months). Manipulation of this T suppressor cell population may prove to be of value in enhancing graft acceptance.

B-Lymphocytes↗
PubMed1978

Purification of the extracellular opacity factor of a strain of group A Streptococcus M type 2.

The extracellular Opacity Factor elaborated by a strain of group A streptococcus M type 2 was purified by ammonium sulphate precipitation, DEAE-cellulose and hydroxylapatite column chromatography and Sephadex G-200 gel filtration. Gel filtration experiments indicated that the Opacity Factor is consituted of high molecular weight proteins or protein aggregates which appear to dissociate into subunits of 66000 minimum molecular weight as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The purified preparations had no group A carbohydrate of T protein antigens. Passive haemagglutination and indirect immunofluorescence tests indicated that Opacity Factor is distinct from the M type 2 protein antigen.

Antibody Formation↗