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Biomedical subjects

N S Kenyon

Publications and source records attributed to N S Kenyon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of ketamine sedation on glucose clearance, insulin secretion and counterregulatory hormone production in baboons (Papio hamadryas).

Since the effects of ketamine sedation seem to differ between subspecies of baboons, we assessed the endocrine response to an intravenous glucose tolerance test (IVGTT) in 12 hamadryas baboons. The first phase insulin secretion, basal insulin, and glucose levels, as well as the glucose clearance, were significantly lower in sedated baboons as compared to fully awake animals. Glucagon and cortisol were significantly higher, while growth hormone was lower during ketamine sedation. Papio hamadryas appears to be a promising pre-clinical model for the study of endocrine replacement therapy in insulin-dependent diabetes. However, the data obtained must be interpreted with the knowledge that the anesthetic employed to allow for testing of the animals does have an effect on the parameters described in this report.

Anesthetics, Dissociative↗
PubMed1997

Long-term function (6 years) of islet allografts in type 1 diabetes.

Eight type 1 diabetic patients, ages 29-41 years, with mean diabetes duration of 23 years (range 18-29 years) received islet transplants from 1 to 5 donors. Seven patients had stable kidney allografts 1-11 years before the islet transplant, and one patient had a simultaneous islet-kidney allograft. Patients' blood glucose control was poor as reflected by the mean +/- SD HbA1c of 9.1 +/- 1.7% before transplant. Of the first three patients, two (1 and 3) achieved insulin independence for 36 and 38 days, respectively. Two recipients rejected their islet grafts within 1 month (2 and 8) and therefore were excluded from analysis. The HbA1c and insulin requirement of the six remaining patients who had persistent islet function for more than 60 days was significantly reduced from 9.3 +/- 1.9 to 6.4 +/- 1.0% (P = 0.002) and from 0.75 +/- 0.15 to 0.35 +/- 0.12 U x kg(-1) x day(-1) (P < 0.001), respectively. The two patients with the longest graft survival (4 and 6) achieved a normalization or near-normalization of their HbA1c levels during 6 years in the absence of severe episodes of hypoglycemia. As demonstrated by a decline in C-peptide response during Sustacal challenge tests over a 6-year period, there was a diminution of islet allograft function over time, despite persistence of normal or near normal HbA1c. We concluded that transplantation of allogeneic islets with an islet mass comparable with whole or segmental pancreas transplants in type 1 diabetic patients can result in long-term islet allograft function; further, we concluded that, in conjunction with small dosages of exogenous insulin, a functioning islet allograft can result in near-normalization of blood glucose levels and significant improvement in HbA1c. The occurrence of severe hypoglycemic episodes observed for patients in the Diabetes Control and Complications Trial was not observed in recipients with functioning islet transplants, despite the continuous need for exogenous insulin therapy to sustain normal HbA1c over the 6-year follow-up. The significant improvement in metabolic control observed for the patients described in this study, and the potential to significantly decrease or halt the progression of diabetic complications, support the continued application of islet allotransplantation as a treatment modality for type 1 diabetic patients.

Adult↗
PubMed1994

Expression of proliferation-associated antigens (PCNA, p120, p145) during the reentry of G0 cells into the cell cycle.

Flow cytometric bivariate analysis was used to evaluate the expression of PCNA, p120, and p145 during the G0 reentry of CHO-K1 cells into the cell cycle. CHO-K1 cells were placed in a G0-like state using serum depletion and stimulated to reenter the cell cycle by replating into fresh, serum-containing medium. At discrete intervals after stimulation, replicate samples were stained for either PCNA, p120, or 145; stained for DNA (Coulter DNA-Prep); evaluated on the EPICS Profile I; and analyzed on the EPICS ELITE workstation. PCNA stained less than 10% of the G0 cells; in contrast, however, 30-35% of the G0 cells were positive for p120 and p145. Eight hours after stimulating G0 cells to reenter the cell cycle (during G0/G1), p120 reached 88% positivity, while p145 and PCNA were 63% and 30% positive, respectively. Cells in S phase (12 and 16 h following G0 stimulation) were greater than 90% positive for all three antigens. PCNA had the greatest change throughout the G0 reentry process, both in percentage positive and quantitatively (mean channel fluorescence). This report indicates that all three proliferation-associated antigens studied are differentially expressed during the reentry of G0 cells into the cell cycle. Furthermore, these antigens may be useful in the early detection of G0 recruitment.

Animals↗
PubMed1994

Enhanced assessment of DNA/proliferative index by depletion of tumor infiltrating leukocytes prior to monoclonal antibody gated analysis of tumor cell DNA.

Flow cytometry has become an important tool for the analysis of breast tumors, and assessment of S phase fraction and DNA ploidy are potential indicators of tumor aggression. Due to masking or dilution of infrequent tumor cell events, the presence of normal cell types, such as inflammatory cells and fibroblasts, can interfere with accurate DNA analysis of solid tumor samples. MDA-MB-175-VII human breast carcinoma cells, WI-38 human lung fibroblast cells, and peripheral blood leukocytes were mixed, in varying proportions, in order to represent human breast tumor samples. The cells were subsequently treated with CD45 conjugated magnetic microspheres to deplete tumor infiltrating leukocytes, thus enriching for tumor cells. The tumor cell mixtures were then stained with a pan-cytokeratin specific monoclonal antibody or with a monoclonal antibody that reacts with breast epithelial membrane antigen (EMA). When used in combination with monoclonal antibody gating, utilization of this bead-based technology resulted in enhanced precision of DNA analysis.

Antibodies, Monoclonal↗
PubMed1992

Expression of proliferation associated antigens in the cell cycle of synchronized mammalian cells.

Flow cytometric bivariate analysis was used to investigate the expression of PCNA, p120 and p145 during the cell cycle of a mammalian cell line (CHO-K1). Initially, aliquots of cells in exponential and plateau (G0) phase were analyzed for proliferation associated antigen expression. Expression of PCNA and p145 during G0 was markedly depressed (less than 12% positive) while 54% of the G0 cells stained positive for p120. The fluorescent intensity (mean channel fluorescence) of these G0 positive p120 cells, however, was only slightly above the mean channel fluorescence (MCF) of cells stained with a negative isotype control. In asynchronous cultures, all three antigens were expressed in greater than 70% of the cells, with PCNA staining being greater than 95%. Cells were then synchronized using mitotic selection (mitotic index of 97%) and antigen levels were measured as cells progressed synchronously through the cell cycle. From DNA analysis histograms, it appeared that the degree of synchrony was approximately 90% throughout the remainder of the cell cycle. The bivariate DNA/PCNA, DNA/p120, and DNA/p145 histograms for mitotic cells indicated that both p120 and p145 expression were elevated (percent positive and MCF) while PCNA levels were near controls (MCF). In early G1, all three markers were depressed (less than 12% positive); however PCNA levels rose precipitously in mid-G1 (greater than 50% positive). In late G1 to early S, p145 levels increased concomitantly with increases in p120. All three antigens were elevated throughout S phase and began to decline as cells moved from G2/M to G1 of the next cell cycle with p145 expression decreasing first. This report indicates that all three proliferation associated antigens studied are differentially expressed in the cell cycle and therefore may be useful in detecting and assessing the proliferation state.

Animals↗
PubMed1990

Ultraviolet light immunomodulation of canine islets for prolongation of allograft survival.

Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200-300 J/m2 (n = 3, P less than 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53-112% (P less than 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35-74% (P less than 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200-600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2, n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and greater than 100.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Experience with islet immunoalteration in dogs: in vitro and in vivo studies.

In an attempt to prolong canine islet allograft survival, in the presence of minimal or no recipient immunosupression, two methods of islet immunoalteration were utilized prior to transplantation. With or without administration of subimmunosuppressive doses of cyclosporin A (CSA) to recipients, treatment of islets with anti-class II monoclonal antibody (moab) and complement (C) resulted in prolongation of allograft survival when treatment was combined with a culture period of 7 days. Transplantation of ultraviolet light (UV) irradiated, 24 hour cultured islets into recipients of subimmunosuppressive doses of CSA also resulted in modest prolongation of allograft survival.

Animals↗
PubMed1989

Primary response to lysozyme (HEL) and HEL-LPS in neonatal A/J mice: presence of characteristic adult pattern of regulatory idiotype and fine specificity restriction.

The adult primary murine plaque-forming cell (PFC) response to hen egg-white lysozyme (HEL) is characterized by a predominant idiotype (IdXE) (congruent to 50% of population) and a predominant specificity (congruent to 50% of population) for a determinant dependent on the 3 amino-terminal residues of HEL (TIP-dependent PFC). IdXE and TIP specificity, however, are not congruent: approximately 1/3 of each population do not overlap (1). To determine whether these characteristics result from a prolonged selection process during development, we compared the neonatal A/J response profile to HEL-CFA with the adult A/J response and found that the adult pattern was present for mice immunized as early as 5 days of age. At 5 days, A/J splenic PFC were 80% TIP dependent, 71% IdXE positive compared to the adult levels of 56% (+/- 14) TIP dependent, 43% (+/- 19) IdXE positive. To attempt to address the B cells directly and avoid the need for antigen-specific T-dependent processes, we studied the PFC response to HEL-LPS conjugates in adult and 12-day-old A/J mice. At the earliest age studied (12 days), the indirect splenic PFC had similar idiotypy and specificity as the adult, and the response was similar to that induced by HEL-CFA. Although the absolute IgM PFC level was equal in adult and neonate, only 11% of the adult PFC response was IgM while a large proportion of the 12-day-old HEL-LPS response was IgM. This IgM PFC response was also characterized by the same idiotypy and specificity as the IgG PFC response. These results suggest that the characteristic adult mosaic of specificity and idiotypy in the anti-HEL response may exist prior to antigenic stimulation since it occurs as early as 5 days after immunization and in the IgM PFC responses. Although IdXE predominance may merely reflect the germ line repertoire, T cells may also be involved in an idiotype-based selection, the mechanism of which has not been determined.

Age Factors↗