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Biomedical subjects

D Tice

Publications and source records attributed to D Tice.

10 recordsLinked to original sources

Prolongation of porcine islet xenograft survival in mice after therapy with immunosuppressive peptides.

BACKGROUND: Recently, peptides derived from the heavy chain of HLA-B2702 have been shown to modulate immune responses. In this study, we examined the use of these peptides for immunosuppression in a pig to mouse islet xenograft model. METHODS: Purified porcine islets were transplanted in autoimmune (non-obese diabetic) and non-autoimmune (streptozotocin-injected CBA or C57/Bl6) diabetic mice. Various dosing regimens of HLA-derived peptides with and without antilymphocyte therapy were administered to recipient mice. Graft rejection was determined by daily serum glucose determinations, and, at selected time points, grafts were removed to demonstrate function and provide immunohistochemical examination. RESULTS: HLA-derived peptides were demonstrated to prolong graft survival in both pretransplant and posttransplant treatment regimens. This effect was increased with concomitant antilymphocyte therapy. CONCLUSIONS: Further elucidation of the mechanism of action of these immunomodulatory peptides may help in the development of novel immunosuppressive protocols.

Adjuvants, Immunologic↗

Racial differences in performance of invasive cardiac procedures in a Department of Veterans Affairs Medical Center.

Racial differences have recently been described in hospital practice, most notably with regard to cardiac procedure utilization. To evaluate the possible reasons behind these differences, we analyzed statistics generated from a surgical referral conference at a large, tertiary care Veterans Affairs hospital between the years 1988 and 1996. In this setting, there is no financial incentive for physicians to recommend or perform invasive procedures, as all physicians are salaried employees of the Veterans Administration. Furthermore, all patients presented at conference have already had cardiac catheterization and are felt to be potential candidates for surgery or angioplasty. Cardiac therapeutic procedures (surgery or percutaneous transluminal coronary angioplasty) were recommended for 1075 of 1474 (72.9%) Caucasian patients and 207 of 322 (64.3%) African-American patients (odds ratio 1.497, 95% confidence interval 1.160 to 1.932, p = 0.0022). Of those patients presented with the option of an invasive procedure, 32 of 207 (15.4%) African-American patients and 89 of 1075 (8.3%) Caucasian patients refused any invasive procedure (odds ratio 2.026, 95% confidence interval 1.311 to 3.130, p = 0.0025). We conclude that reluctance by African-American patients to undergo invasive cardiac procedures may help explain observed disparities in race-related cardiac care.

Black or African American↗

Natural killer cell activity in rats infused with Intralipid.

The effect of Intralipid on the natural killer (NK) cell activity of healthy male Fisher 344 adult rats was investigated. They were cannulated via the right jugular vein and continuously infused for five days with: normal saline plus heparin, 5% Intralipid plus heparin, or 10% Intralipid plus heparin. Control groups comprised of cannulated rats receiving no infusion and rats undergoing no operative procedures. Following the five-day infusion, rats were exsanguinated under ether anesthesia and mononuclear cells (MNC) harvested from the peripheral blood. NK activity was measured in a standard four hour 51Cr release assay against YAC-1 target cells. NK cell activity in rats infused with 5% Intralipid did not differ significantly from rats in both control groups or rats infused with saline. Infusion of rats with 10% Intralipid resulted in a significant increase in NK activity compared with all other groups.

Animals↗

Unique subset of thymic epithelial cells defined by the expression of a novel neuroendocrine antigen.

Murine monoclonal antibodies (MoAbs) were produced against a rat medullary thyroid carcinoma to identify neuroendocrine differentiation antigens. One of these antibodies (1D4) identified a novel 62- to 69-kDa antigen expressed by subsets of immune system epithelial and neuroendocrine cells. This antigen is expressed by distinct subsets of thymic epithelial and splenic reticular cells and is shared by discrete subsets of anterior pituitary and thyroid neuroendocrine cells. In the thymus, 1D4 expression identified a unique subset of stellate-shaped Ia+ medullary epithelial cells which did not react with thymosin alpha-1 antisera nor with the MoAb A2B5 specific for a GQ ganglioside expressed by thymic hormone-producing cells. The availability of the 1D4 MoAb should facilitate further characterization of 1D4+ immune system epithelial cells and may advance our understanding of neuroendocrine-immune system interactions.

Animals↗

Variation in indirect cell-mediated lympholysis.

The ability of an allograft recipient to respond to donor mononuclear cells in an indirect cell-mediated lympholysis (ICML) assay is an in vitro correlate of allograft rejection, but the value of this correlation depends upon the assay's reliability. We had observed inconsistency in the cytotoxic response of normal human mononuclear cells (MNC) to the same allogeneic stimulator MNC when cytotoxicity was measured repeatedly on different occasions by micro-ICML. We, therefore, investigated the extent and reasons for this inconsistency. Method variation, determined by duplicate ICML of 18 stimulator: responder MNC, was not statistically significant. Variation in cytotoxicity over time was greater but still not statistically significant. The contribution to method variation of 51Cr release from 3 different sets of target cells, cultured and labeled in duplicate, was minimal (6.33%). We then asked if in vitro generation of effector MNC under laboratory conditions was a major cause of ICML variation. We tested this using a stable transplant's in vivo sensitized effector cells against donor MNC in a direct CML (DCML) and obtained consistent results. Finally, to gain an understanding of some of the factors which might influence the generation of in vitro cytotoxicity, we measured the frequencies of cell surface antigens (DR, TAC, transferrin, Leu 2 and 3) concomitantly with ICML on day 6 of culture. Statistical analysis of the results led us to conclude that the micro-ICML is reproducible. The magnitude of lysis depends upon activated target cells (TAC- and transferrin-positive) and an increase in the proportion of helper/inducer to cytotoxic/suppressor T-lymphocytes during effector cell generation.

Antigens, Surface↗

Immune rosettes of T and B lymphocytes in infertile women with endometriosis.

We examined the cell-mediated immune response in women with pelvic endometriosis by quantitating their T and B lymphocytes. The study was conducted on heparinized peripheral blood and peritoneal fluid. The results were compared with those in a control group of women without evidence of endometriosis. Each patient underwent laparoscopy as part of her infertility evaluation. The ability of T cells to form rosettes with sheep erythrocytes was used to estimate the percentage of total and active T cells. B lymphocytes were quantitated by erythrocyte antibody complement binding capacity. In addition, T and B lymphocytes were assayed with the Immunobead technique using specific monoclonal antibodies. The helper T cell (T4) and suppressor T cell (T8) subsets of lymphocytes were evaluated with specific monoclonal antibodies coupled to microbeads. The results demonstrated an increased number of T and B cells in peritoneal fluid and peripheral blood from patients with endometriosis as compared with controls. Furthermore, the ratio T4:T8 was significantly increased in patients with endometriosis. These results suggest a cell-mediated immune response in the presence of endometriosis.

Autoimmune Diseases↗

Quantitative evaluation of cardiac parasympathetic activity in normal and diabetic man.

Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inversely related to the RR variation (r = 0.89, P less than 0.01). Heart rate was increased (P less than 0.0001) and RR variation decreased (P less than 0.05) during beta-adrenergic stimulation with isoproterenol and during parasympathetic blockade with atropine (both P less than 0.0001). Hence, the cardiac effects of beta-adrenergic stimulation may mimic the effects of diminished parasympathetic function. To evaluate parasympathetic control of RR variation, independently of possible effects of increased sympathetic activities, studies were performed during beta-adrenergic blockade with propranolol. RR variation during propranolol was less both in 14 diabetic subjects without clinical symptoms of autonomic neuropathy (P less than 0.005) and in 8 diabetics with clinical symptoms of autonomic neuropathy (P less than 0.001) when compared with 22 age-comparable normal subjects. The measurement of RR variation was very reproducible with a day-to-day coefficient of variation of 9.7 +/- 2.8% (x +/- SEM) in diabetic subjects with stable hyperglycemia. It is concluded that supine RR variation during a deep respiratory rate and during beta-adrenergic blockade is a sensitive, quantitative, and reproducible method to evaluate parasympathetic nervous activity in normal and diabetic subjects. Furthermore, cardiac parasympathetic activity may be diminished in diabetic subjects before clinical symptoms of autonomic neuropathy are evident.

Adult↗

Importance of topical hypothermia to ensure uniform myocardial cooling during coronary artery bypass.

Recent reports have suggested that the delivery of cardioplegia to regional myocardium is impaired in patients with severe coronary artery disease. This study was designed to determine whether or not topical hypothermia is a necessary adjunct to systemic hypothermia and potassium cardioplegia to provide adequate cooling in regional myocardium supplied by stenotic or occluded coronary arteries. Twenty-two patients ranging in age from 47 to 68 years were included in the study. Patients were placed on bypass and cooled to 28 degrees C. Temperature was measured over the right and left coronary artery distributions. The aorta was then cross-clamped and 1,000 cc of potassium blood cardioplegia, 5.7 degrees to 11 degrees C (mean 8.7 degrees), was infused into the aortic root at a mean pressure of 99 mmHg. Temperature was measured and 6 L of cold electrolyte (Plasma-lyte) solution, 2.3 degrees to 5.1 degrees C (mean 3.5) was poured over the heart into the pericardial well. The temperature measurements were then repeated. Myocardial temperature in regional myocardium supplied by normal coronary arteries after the injection of cardioplegia was less than 15 degrees C. However myocardium distal to a severe stenosis or complete occlusion was significantly warmer (p less than 0.001). Topical hypothermia reduced myocardial temperature to less than 15 degrees C in regional myocardium supplied by severely diseased vessels (p less than 0.001). These data demonstrate that the combination of systemic hypothermia and potassium cardioplegia alone does not provide adequate myocardial cooling in patients with severe coronary artery disease and emphasize the need for intraoperative myocardial temperature monitoring to ensure optimal protection during the ischemic period.

Aged↗

Predictive value of in vitro colony and cluster formation in acute nonlymphocytic leukemia.

Granulocytic-monocytic colony-forming activity of marrow cells was evaluated at presentation in 20 patients with acute nonlymphocytic leukemia (ANLL). A double-layer agar culture was employed to determine colony- and cluster-forming activity. All patients underwent induction chemotherapy with cytosine arabinoside and daunorubicin. Five patients died during induction. Eight of the 11 patients entering complete remission had absent or decreased colony and cluster growth of marrow cells. Four patients who failed to obtain a complete remission produced increased or only cluster growth in culture. Our data support the conclusions of others that decreased colony and cluster formation in vitro is associated with a more favorable response to induction chemotherapy for ANLL.

Acute Disease↗

Quantitative evaluation of sympathetic and parasympathetic control of iris function.

The use of quantitative measurements of pupil size as an index of autonomic nervous system (ANS) activity in normal and diabetic subjects is described. The dual innervation of the iris by the parasympathetic (PNS) and sympathetic (SNS) nervous system was demonstrated by measurement of steady-state pupil size before and after changes in ANS activity by pharmacologic agents. In the presence of total PNS blockade, dark-adapted pupil size was a reliable index of SNS activity to the iris. Latency time (time from light stimulation to initial pupil response) appeared to be a good index of PNS activity. However, increased SNS activity may also prolong the latency time. Thus, consideration of SNS activity is necessary when evaluating the latency time. In 25 diabetic subjects, there was evidence of impaired SNS activity (smaller dark-adapted pupil size during total PNS blockade) and PNS activity (prolonged latency time). In a subgroup of diabetic subjects without clinical manifestations of autonomic neuropathy and normal subjects, both dark-adapted pupil size during PNS blockade (SNS index) and latency time (PNS index) were abnormal. The coefficient of variation for these two indices was less than 5% in glycemic stable diabetic subjects. Thus, these two indices are reliable and sensitive measures of the SNS and PNS activity to the iris in normal and diabetic subjects.

Adult↗