PubMed Health⌕ Search

Biomedical subjects

S Munn

Publications and source records attributed to S Munn.

At least 19 recordsLinked to original sources
PubMed2006

Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine.

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.

Adult↗
PubMed2001

Co-stimulatory blockade and tolerance induction in transplantation.

Recipients of organ and tissue transplants require lifelong immunosuppression to prevent rejection. Better understanding of the processes culminating in allograft rejection has led to novel approaches to modulating the immune response. Co-stimulatory signals between antigen-presenting and -responding cells are essential for a normal alloimmune response, and blockade of these pathways during initial graft-host interaction may be used to ameliorate or prevent a destructive response from proceeding. A large number of experimental studies now support this concept, and early clinical trials have been initiated. Despite some early difficulties and many unanswered questions, co-stimulatory blockade has major potential as a future immune-modulating mechanism for use in clinical transplantation.

Animals↗
PubMed2000

The kinetics of CD154 (CD40L) expression in peripheral blood mononuclear cells of healthy subjects in liver allograft recipients and X-linked hyper-IgM syndrome.

UNLABELLED: The costimulatory pathways play a key role in T cell activation during allograft rejection (AR). Inhibition of the T cell costimulatory molecule CD154 (CD40 ligand) has been effective in producing long-term allograft survival in rodents and non-human primates. The role of the CD40-CD154 pathway in human orthotopic liver transplantation (OLT) has not been examined. AIM: To describe the patterns of CD154, CD69 and CD152 (CTLA4) expression in OLT recipients and to determine their temporal relationship to AR. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 15 OLT allograft recipients just prior to and for seven consecutive days postoperatively. Gene and protein expression of CD154, CD69 and CD154 were examined by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FC), respectively. RESULTS: FC failed to demonstrate an up-regulation of CD154 and CD152 protein expression during the first postoperative week. Intracellular FC did not increase the sensitivity. There was an increased level of CD3+ CD8+ T cells expressing CD69 at the time of rejection compared to that on day 0. RT-PCR demonstrated a sporadic expression of CD154 and CD69 mRNA, with no correlation to episodes of acute cellular rejection. In vitro stimulation of PBMCs revealed an impaired up-regulation of CD154 in patients receiving conventional immunosuppression compared to healthy controls. The assays were validated using positive and negative controls, including a family with X-linked hyper-IgM syndrome. CONCLUSION: We found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Immunosuppression resulted in impaired responses to ex vivo stimulation. Lymphocyte costimulatory pathways play a critical role in mediating acute allograft rejection. However, we found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Furthermore, stimulation in vitro resulted in less up-regulation of CD154 than for healthy controls.

Abatacept↗
PubMed2000

Differential validity of the Defense Mechanism Manual for the TAT between Asian Americans and Whites. Thematic Apperception Test.

Thematic Apperception Test (Murray, 1943) responses of 69 Asian American (hereafter, Asian) and 83 White students were coded for defenses according to the Defense Mechanism Manual (Cramer, 1991b) and studied for differential validity in predicting paper-and-pencil measures of relevant constructs. Three tests for differential validity were used: (a) differences between validity coefficients, (b) interactions between predictor and ethnicity in criterion prediction, and (c) differences between groups in mean prediction errors using a common regression equation. Modest differential validity was found. It was surprising that the DMM scales were slightly stronger predictors of their criteria among Asians than among Whites and when a common predictor was used, desirable criteria were overpredicted for Asians, whereas undesirable ones were overpredicted for Whites. The results were not affected by acculturation level or English vocabulary among the Asians.

Acculturation↗
PubMed1998

Langerhans cell histiocytosis of the skin.

Cutaneous involvement in Langerhans cell histiocytosis (LCH) occurs in 50% of cases and may be the presenting feature. It is, therefore, important to recognize the wide spectrum of clinical disease that this disorder may adopt in the skin. Cutaneous involvement is not necessarily a benign feature and many patients progress to multi-system disease. There are a number of treatments available for cutaneous LCH. The rationale is to start with the simplest treatment and progress to systemic or interventional therapy as needed.

Adult↗
PubMed1996

Effects of glucose ingestion versus infusion on pulsatile insulin secretion. The incretin effect is achieved by amplification of insulin secretory burst mass.

In the present studies, we used a recently validated canine model to determine 1) if glucose ingestion stimulates insulin secretion by amplifying the pulsatile component of insulin release, and if so, 2) whether this effect is achieved preferentially through burst mass or frequency modulation, and 3) if the mechanism of incretin effect of insulin secretion is mediated via the pulsatile mode of secretion. We report that 30 g of glucose ingestion stimulates an approximately 550% increase in the overall rate of insulin secretion (1.8 +/- 0.2 to 11.6 +/- 1.5 pmol.kg-1.min-1), which is achieved via an approximately 400% increase in the mass of insulin secreted per burst (202 +/- 38 to 1,003 +/- 147 pmol/pulse, P < 0.001) and a approximately 40% increase in burst frequency (8.7 +/- 0.5 to 12.3 +/- 0.6 pulse/h, P < 0.001). Of the insulin secreted after glucose ingestion, 68% (+/-4) was released in discrete secretory bursts. Further analyses showed that the incretin effect of ingested (GPO) versus infused glucose (GIV) is achieved through regulation of pulsatile insulin secretion. Glucose ingestion led to an approximately 70% greater rate of insulin secretion than intravenous glucose delivery (10.0 +/- 1.6 vs. 5.9 +/- 0.9 pmol.kg-1.min-1, P < 0.005, GPO vs. GIV). This incretin effect was achieved by the specific mechanism of an approximately 70% greater pulse mass (930 +/- 196 vs. 558 +/- 97 pmol/pulse, P < 0.02, GPO vs. GIV) but with a comparable pulse frequency (13.1 +/- 0.9 vs. 12.0 +/- 0.5 pulses/h, P = 0.14, n = 9 dogs, GPO vs. GIV). We conclude that in vivo glucose regulates overall insulin secretion almost exclusively by amplification of the pulsatile mode of insulin secretion, and that the incretin effect is achieved by preferential enhancement of insulin secretory burst mass.

Animals↗
PubMed1996

Strict anatomical coexistence of vitiligo and psoriasis vulgaris--a Koebner phenomenon?

We describe a patient who developed typical psoriatic plaques covering completely or partly the vitiliginous areas of her skin. Her psoriasis was strictly limited to the vitiliginous patches with no involvement of the normal skin. Strict anatomical coexistence of both diseases is extremely rare and suggests a causal mechanism, possibly due to a Koebner phenomenon, but genetic and environmental factors may also be involved.

Aged↗
PubMed1995

The response of women to gender stereotyping during a health interview.

Gender-stereotypical responses and critical health information were examined in this posttest-only experiment. Thirty-eight university women students and staff were randomly assigned to a gender-stereotyped or a nonstereotyped health interview. Gender-biased cues were embedded in three of the five questions in the gender-stereotyped interview. Women in the gender-stereotyped interview responded with significantly more gender-stereotypical responses. However, no subjects felt affected by the gender-biased cues. Findings suggest that women affirm gender-biased questions asked in health interviews.

Adolescent↗
PubMed1995

Infectious complications following pancreatic transplantation: incidence, microbiological and clinical characteristics, and outcome.

The infectious complications following pancreatic transplantation in 34 consecutive recipients were analyzed during a mean follow-up of 39 months. Twenty-seven recipients (79%) developed a mean of 2.1 serious infectious complications. Three of the six deaths (overall mortality, 18%) were infection related. Thirty-three percent of severe infectious episodes were caused by bacteria (72% by gram-positive cocci) and 26% by fungi (87% by Candida species); severe cytomegalovirus (CMV) infection accounted for 33% of infectious complications. CMV disease and organ involvement occurred most frequently in the donor-seropositive/recipient-seronegative group (36%), followed by the donor-seronegative/recipient-seropositive group (25%). In four patients (12%) Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disease (PTLD) developed, directly resulting in two deaths. PTLD developed in two of the three EBV-seronegative and two of the 31 EBV-seropositive recipients. Infections due to herpes simplex and zoster viruses and Pneumocystis carinii (2, 3, and 1, respectively) developed in 6 patients. The use of OKT3 for rejection therapy was associated with symptomatic CMV disease and EBV-related PTLD. In summary, severe infectious complications are the main cause of morbidity and death among patients who undergo pancreas transplantation. Aggressive antimicrobial prophylactic regimens are required to decrease the effects of such complications.

Adolescent↗
PubMed1995

Pulsatile insulin secretion accounts for 70% of total insulin secretion during fasting.

The purpose of the present study was to determine the contributions of discrete insulin secretory bursts vs. basal insulin release to total insulin secretion in vivo. Quantification of the partitioning of pulsatile and basal insulin secretion is complicated by physiological delivery of these pulses into the portal vein and the absence of validated methods of measuring the rates of pulsatile and basal insulin secretion in vivo. We therefore 1) developed a canine model with chronically implanted portal vein catheters, 2) validated an established deconvolution technique as well as a novel direct catheterization technique (Clustcath) for measurement of pulsatile and nonpulsatile insulin secretion rates in this model, and 3) applied these methods to study insulin secretion in the overnight-fasted dog in vivo to determine the contribution of pulsatile vs. basal insulin secretion to total rates of endogenous insulin secretion. Rates of total, pulsatile, and nonpulsatile endogenous insulin secretion measured by Cluscath closely parallel those measured by deconvolution analysis (54 +/- 15 vs. 51 +/- 11, 38 +/- 12 vs. 36 +/- 11, and 16 +/- 4 vs. 14 +/- 4 pmol/min, respectively). Clustcath and deconvolution indicated that the majority of insulin was secreted as pulses (70 +/- 6 and 66 +/- 7%, respectively). These data infer that any process that selectively decreases the pulsatile component of insulin secretion (e.g., diabetes mellitus) will likely have a major impact on total insulin secretion.

Animals↗
PubMed1995

Impact of sampling technique on appraisal of pulsatile insulin secretion by deconvolution and cluster analysis.

Little is known about the optimal experimental conditions for assessing pulsatile insulin secretion in vivo. To address this, we employed a recently validated canine model (n = 12) to determine the consequences of 1) sampling from the systemic circulation (SC) vs. the portal vein (PV), 2) sampling intensity and duration, and 3) deconvolution vs. cluster analysis on assessing pulsatile insulin secretion. PV vs. SC sampling resulted in a approximately 40% higher pulse frequency by deconvolution (9.0 +/- 0.5 vs. 6.6 +/- 0.9 pulses/h, P < 0.02) and cluster analysis (7.5 +/- 0.3 vs. 5.6 +/- 0.6 pulses/h, P < 0.01) due to a higher signal-to-noise ratio (19 +/- 4.8 PV vs. 12 +/- 1.8 SC). PV sampling also disclosed a higher calculated contribution of the pulsatile vs. nonpulsatile mode of delivery to total insulin secretion (57 +/- 4 vs. 28 +/- 5%, P < 0.001). Analysis of the relevance of sampling intensity revealed that 1-min data yielded a markedly higher estimate of pulse frequency with PV sampling than 2-min data (9.0 +/- 0.5 vs. 5.4 +/- 0.5, P < 0.02, deconvolution; 7.5 +/- 0.3 vs. 4.3 +/- 0.6 pulses/h, P < 0.001, cluster). Optimal sampling duration was shown to be 40 min or more. We conclude that the resolving power of the analytical tool, the anatomic site of blood withdrawal, the frequency of blood sampling, and the duration of the total observation interval all significantly influence estimated insulin secretory pulse frequency and the fraction of insulin secreted in pulses. With the assumption that PV 1-min insulin data constitute the "gold standard," our in vivo inferences of 7.5-9.0 insulin pulses/h closely recapitulate in vitro islet secretory activity.

Animals↗
PubMed1994

Coordinate pulsatile insulin secretion by chronic intraportally transplanted islets in the isolated perfused rat liver.

In the present studies we sought to address the following questions: do chronically transplanted intrahepatic islets (IHI-Tx) secrete insulin in a coordinate pulsatile manner, and, if so, is reestablishment of this coordinate pulsatility a function of time after transplantation? We studied isolated perfused livers at 10 mM glucose from 27 rats rendered diabetic with streptozotocin and then transplanted with approximately 2 x 10(3) islets, 2 (n = 5), 7 (n = 5), 30 (n = 5), and 200 (n = 12) d after transplantation. 12 out of 12 of the 200-d IHI-Tx secreted insulin in coordinate pulses (frequency 3.9 +/- 0.3 pulses/h, amplitude 15.2 +/- 2.4 nmol/min). In contrast, one out of five 2-d, zero out of five 7-d, and one out of five 30-d IHI-Tx showed pulsatile insulin secretion. Insulin secretion was markedly greater (76 +/- 13 vs 13 +/- 3 nmol/min, P < 0.0001) in the 200-d versus early IHI-Tx. Pentobarbital 25 micrograms/ml had no effect on total (13.9 +/- 3.9 vs 15.9 +/- 3.9 nmol/min), nonpulsatile (12.9 +/- 3.5 vs 14.1 +/- 3.3 nmol/min), or pulsatile (pulse amplitude 17.6 +/- 4.5 vs 20.0 +/- 4.2 nmol/min, pulse frequency 4.1 +/- 0.3 vs 4.0 +/- 0.7 pulses/h) insulin secretion. Using synaptophysin, islet innervation was documented in 12 out of 12 200-d IHI-Tx but in none of the early IHI-Tx. We conclude that established (approximately 200 d) IHI-Tx secrete insulin in a coordinate pulsatile manner and that establishment of coordinate pulsatile insulin secretion by IHI-Tx is accompanied by increased total insulin secretion and is associated with islet reinnervation.

Animals↗