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Biomedical subjects

D Kreisel

Publications and source records attributed to D Kreisel.

At least 19 recordsLinked to original sources
PubMed2004

Myocardial tissue engineering and regeneration as a therapeutic alternative to transplantation.

Ischemic cardiomyopathy leading to congestive heart failure remains the leading source of morbidity and mortality in Western society and medical management of this condition offers only palliative treatment. While allogeneic heart transplantation can both extend and improve the quality of life for patients with end-stage heart failure, this therapeutic option is limited by donor organ shortage. Even after successful transplantation, chronic cardiac rejection in the form of cardiac allograft vasculopathy can severely limit the lifespan of the transplanted organ. Current experimental efforts focus on cellular cardiomyoplasty, myocardial tissue engineering, and myocardial regeneration as alternative approaches to whole organ transplantation. Such strategies may offer novel forms of therapy to patients with end-stage heart failure within the near future.

Animals↗
PubMed2001

Multiparameter flow cytometric approach for simultaneous evaluation of T lymphocyte-endothelial cell interactions.

Since vascular endothelium is now recognized as an immunologically active tissue, a better understanding of the relationship between endothelial cells and T lymphocytes is critical to the field of solid organ transplantation. Investigations of endothelial cell-T cell interactions have been limited by methodology. We developed a flow cytometric method allowing for concurrent investigation of multiple cell populations within the same culture that can be applied to these complex interactions. Allogeneic CD8+ or CD4+ T cells labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) were added to a murine endothelial cell monolayer, in which endothelial proliferation was not inhibited by irradiation or addition of a cell cycle-blocking agent. At specific time points, the coculture was analyzed by flow cytometry. T-cell proliferation could be detected by gating on the T-cell subset and evaluating the CFSE fluorescence peaks. By directly analyzing cellular division, we minimized erroneous interpretation of the data encountered by previous studies, which utilized (3)H-thymidine incorporation as sole measure of proliferation. Further subgating on cells that divided facilitated the study of CD8+ lymphocyte activation, differentiation, and acquisition of effector function. By gating on the endothelial cell population, phenotypic changes such as upregulation of surface MHC molecules or immune-mediated apoptosis could be detected. In conclusion, we present a flow cytometric approach that could have important applications for clinical immunological monitoring in allogeneic or xenogeneic transplantation, and might provide the requisite information to better tailor immunotherapy to prevent chronic rejection.

Animals↗
PubMed2001

A simple method for culturing mouse vascular endothelium.

Vascular endothelium is an important site for a wide array of immunological processes such as inflammation, atherosclerosis and allograft rejection. Culture methods of mouse vascular endothelium would provide an important in vitro correlate to immunological murine in vivo models. We describe a simple method to culture mouse vascular endothelium from thoracic aorta. Our cultured cells express typical phenotypic (CD105, CD31, CD106), morphological and ultrastructural (intercellular junctions, Weibel-Palade bodies) markers of vascular endothelium. They also possess functional receptors for uptake and processing of acetylated low-density lipoproteins. The mouse vascular endothelium within our system expresses high levels of MHC class I and MHC class II after activation with IFN-gamma. In addition, these cells express the accessory molecules CD80 and CD54, while they lack constitutive expression of CD86 and CD40, providing them the means to function as antigen presenting cells. Alloreactive CD4(+) and CD8(+) T lymphocytes demonstrate evidence of DNA synthesis after co-culture with activated vascular endothelium indicating their commitment to proliferation. In conclusion, we describe a simple culture system to isolate and grow mouse vascular endothelium, which provides a powerful tool to study biological interactions in vitro.

Animals↗
PubMed2001

Emergent lung retransplantation after discovery of two primary malignancies in the donor.

A 50-year-old woman underwent single lung transplantation for advanced chronic obstructive pulmonary disease. Shortly after the procedure, it was discovered that the donor suffered from both a renal cell carcinoma and a spindle-cell sarcoma of the ascending aorta, which had metastasized to the spleen. The patient was emergently listed for a retransplantation and underwent bilateral lung transplantation after a new donor became available 4 days after the initial transplantation procedure. After 24 months, the patient is without evidence of malignancy. This case illustrates the role of immediate retransplantation for patients who have inadvertently received thoracic organs from donors harboring occult malignancies.

Adult↗
PubMed2000

Immune monitoring in xenotransplantation: the multiparameter flow cytometric mixed lymphocyte culture assay.

Xenotransplantation requires monitoring of complex cellular interactions in vitro. A tool to monitor cell proliferation in detail would be instrumental in understanding these cellular interactions in heterogeneous xenogeneic lymphocyte cultures and in patients after xenotransplantation. To accomplish this, we used a fluorescent cell proliferation marker, 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), in combination with flow cytometry. CFSE, a green fluorescent molecule, binds covalently to intracellular macromolecules. Each cell division reduces the fluorescent intensity per cell by half and shows a characteristic multipeak pattern in flow cytometric analysis. For this study, human lymphocytes were labeled with CFSE and cultured in the presence of irradiated porcine lymphocytes. Cell proliferation was detected in CFSE-labeled lymphocytes in both a single and a multiparameter flow cytometry setting. Concurrently, tritiated ((3)H) thymidine incorporation, a common method to measure gross cell proliferation, was assessed. The kinetics of CFSE-labeled cell proliferation correlated with (3)H-thymidine incorporation in that both methods showed a lag phase for days 1-3 and a log phase for days 4-7. Multiparameter flow cytometric monitoring of mixed lymphocyte cultures allowed phenotyping and assessment of viability of proliferating populations in heterogeneous xenogeneic stimulated human lymphocyte cultures and complemented the classical (3)H-thymidine incorporation assay. The use of this technique will allow a wide array of immunologic parameters to be measured in a heterogeneous xenogeneic mixed lymphocyte culture. The information gained from these assays is essential to understanding the biological significance of xenogeneic cellular interaction and for monitoring the immune status of the xenotransplanted patient.

Cell Division↗
PubMed2000

Replacement of graft-resident donor-type antigen presenting cells alters the tempo and pathogenesis of murine cardiac allograft rejection.

BACKGROUND: Graft-resident antigen presenting cells (APCs) are potent stimulators of the alloresponse. To test whether replacement of graft-resident donor-type APCs with those of recipient-type alters allorecognition and the pathogenesis of both acute and chronic rejection, we created chimeric hearts for transplantation into naive recipients. METHODS: To replace donor-type APCs with those of recipient-type, chimeric animals were created by bone marrow transplantation (BMT) in fully allogeneic mouse and rat strain combinations. The degree of APC replacement in chimeric organs was assessed phenotypically and functionally. Chimeric hearts were transplanted heterotopically into untreated recipients. RESULTS: Flow cytometric and immunohistochemical analysis did not detect residual bone marrow recipient-type APCs in mouse BMT chimeras. Although semi-quantitative reverse transcription polymerase chain reaction detected 0.001-0.01% residual cells, APCs isolated from chimeric organs were functionally unable to stimulate donor-type cells. When transplanted into naive recipients, chimeric mouse hearts had significantly prolonged survival but were nevertheless rejected acutely. Similar results were obtained in the ACI --> LEW rat strain combination. However, in the PVG --> DA rat model, the majority of chimeric hearts survived >100 days and all long-surviving hearts developed cardiac allograft vasculopathy. CONCLUSIONS: BMT leads to near complete replacement of organ-resident APCs. The virtual absence of donor-type APCs in chimeric hearts delays or prevents acute rejection in a strain-dependent manner. In contrast, this type of graft modification does not prevent cardiac allograft vasculopathy. This suggests that, although the CD4+ direct pathway may play a role in acute rejection, it is not essential for the development of chronic rejection in rodent cardiac allografts.

Acute Disease↗
PubMed2000

Hand-assisted laparoscopic vertical banded gastroplasty: early results.

BACKGROUND: Minimally invasive hand-port-assisted laparoscopic vertical banded gastroplasty has the potential to reduce postoperative complications after bariatric surgery. METHODS: We analyzed the postoperative course of 46 hand-port-assisted laparoscopic vertical banded gastroplasties (LVBG) completed between January 1998 and April 1999. RESULTS: The operating time for the LVBG was shorter (140.8 +/- 6.0 vs 180.2 +/- 6.3 min; p < 0.05). Individuals were able to ambulate sooner (1.36 +/- 0.09 vs 2.44 +/- 0.16 days; p < 0.05), and start oral intake earlier (2.7 +/- 0.27 vs 3.7 +/- 0.17 days; p < 0.05) than the open vertical banded gastroplasty (VBG) controls. Three staple line leaks were detected in this group. Two leaks resolved without clinical sequelae, but one patient developed intraabdominal sepsis. This complication extended the average hospital stay to 6.8 +/- 2.00 days, as compared to 7.71 +/- 0.18 days for historical controls. By discounting this patient from the analysis, we arrive at a more representative length of hospitalization of 4.82 +/- 0.34 days (p < 0.05). CONCLUSIONS: LVBG offers a good alternative to the standard open VBG. Although this procedure has a relatively short learning curve, it should be done at centers with an interest in bariatric surgery.

Adult↗
PubMed2000

Calcium ionophore activation of chronic myelogenous leukemia progenitor cells into dendritic cells is mediated by calcineurin phosphatase.

We have previously demonstrated that Ph+ myeloid progenitor cells of patients with chronic myeloid leukemia (CML) can acquire characteristics of mature dendritic cells (DC) following calcium mobilization with calcium ionophore (A23187, CI). In this study we characterize the intracellular signaling pathway by which CI induces the acquisition of DC features in these leukemic cells. CI-induced activation of CML cells is attenuated by the calcineurin phosphatase inhibitor cyclosporin A (CsA) as well as the calmodulin (CaM) antagonist W-7. These cause ablation of both the CI-induced immunophenotypic expression of DC markers and immunostimulatory properties in mixed leukocyte responses (MLR). Minimal blocking effect was observed when Ca(2+)/CaM kinase II (281-301) inhibitor was added to the cultures. These findings suggest a Ca(2+)-dependent mechanism for the CI-induced activation of CML cells into antigen-presenting cells (APC), which is primarily mediated through the CaM/calcineurin pathway.

Calcimycin↗
PubMed2000

Donor antigen-presenting cells are important in the development of obliterative airway disease.

OBJECTIVE: Obliterative airway disease, which resembles obliterative bronchiolitis histologically, develops in murine heterotopic tracheal allografts. Chimeric tracheas were used to examine whether donor-type antigen-presenting cells are important in the development of obliterative airway disease. To separate the contributions of CD4(+) and CD8(+) direct pathways, we transplanted tracheas from knockout mice lacking major histocompatibility complex (MHC) class I or II antigens. METHODS: Chimeric tracheas were created via bone marrow transplantation in fully MHC-mismatched combinations. Tracheas from naive B6, autologously reconstituted B6, chimeric B6 bearing recipient-type C3H antigen-presenting cells, MHC class I knockout B6 (B6(I-)), MHC class II knockout B6 (B6(II-)), or C3H mice were transplanted into C3H recipients. The tracheas were harvested at days 14 and 28. RESULTS: At day 28, isografts showed no occlusion, normal respiratory epithelium, and minimal infiltrates. Naive or autologously reconstituted B6, B6(I-), and B6(II-) tracheas showed minimal occlusion at day 14 but contained intraepithelial infiltrates. By day 28, the naive or autologously reconstituted B6 tracheas had occlusion of 69.5% +/- 11.6% (mean +/- standard error of the mean), and in comparison, B6(I-) and B6(II-) tracheas had occlusions of 53.0% +/- 16.3% and 52.2% +/- 15.9%, respectively (P =. 20,.19). In chimeric B6 tracheas, minimal occlusion was seen at day 14 and remained 33.6% +/- 16.2% (P =.039) at day 28. Subtle epithelial changes and minimal infiltrates were seen. CONCLUSIONS: Obliterative airway disease appears to involve donor-type antigen-presenting cells and develops in the absence of either MHC class I or II antigens. These findings suggest that either CD8(+) or CD4(+) direct allorecognition is important in the development of obliterative airway disease.

Animals↗
PubMed1998

Changing presentation and management of neutropenic enterocolitis.

OBJECTIVE: To characterize the current clinical presentation and management of neutropenic enterocolitis. DESIGN: Retrospective review of records of oncology unit patients requiring general surgical consultation for abdominal complaints in a 1-year period. SETTING: Oncology unit of a tertiary care, university teaching hospital. PATIENTS AND INTERVENTIONS: Fourteen patients diagnosed as having neutropenic enterocolitis were managed conservatively with operation reserved for failure of conservative therapy. MAIN OUTCOME MEASURES: Clinical data from patients at the time of presentation and during treatment for neutropenic enterocolitis. RESULTS: All 14 patients diagnosed as having neutropenic enterocolitis were receiving chemotherapy for solid tumors or leukemias. Seven patients were undergoing stem cell or autologous bone marrow transplantation. Presenting symptoms and physical examination findings were nonspecific. All patients except one had neutropenia at the time of diagnosis. Computed tomographic scans of the abdomen were the most useful confirmatory study for the diagnosis of neutropenic enterocolitis. All patients except one had resolution of neutropenic enterocolitis with conservative therapy. One patient whose course of conservative management failed had protracted neutropenia and required operation for resection of bowel with full-thickness necrosis. CONCLUSIONS: Neutropenic enterocolitis has evolved from a complication of patients with leukemia to a disease of patients receiving high-dose chemotherapy for many malignancies, solid as well as hematologic. Diagnosis of neutropenic enterocolitis continues to be a challenge, as patients typically present with nonspecific gastrointestinal tract symptoms. Neutropenia and computed tomographic scan findings are useful adjuncts in diagnosing neutropenic enterocolitis. Timely conservative treatment frequently allows resolution of neutropenic enterocolitis without operation.

Adult↗
PubMed1995

Surgical antibiotic prophylaxis and Clostridium difficile toxin positivity.

OBJECTIVE: To examine a possible relationship between prophylactic antibiotic therapy (PAT) and the development of Clostridium difficile toxin (CDT) positivity. DESIGN: Retrospective case-control study. SETTING: Tertiary care medical center in New York, NY. PATIENTS: A total of 357 patients, admitted from November 1992 to April 1994, with positive. CDT assays. Of these, 23 patients (6%) received only PAT for elective surgical procedures. Thirty-nine patients were matched as controls for age, sex, and surgical procedure. MAIN OUTCOME MEASURES: Both CDT positivity and inappropriate use of PAT. RESULTS: Appropriate PAT was used in 26 (42%) of 62 patients (17% cases, 56% controls). The Mantel-Haenszel estimator for the summary odds ratio for the development of CDT positivity from inappropriate use of PAT was 5.1 (95% confidence interval, 1.10 to 23.64). Main duration between the operation and the final antibiotic dose was significantly longer in the CDT-positive group compared with the control group (3.1 vs 1.7 days, P < .05). The length of hospital stay was significantly longer in the CDT-positive group compared with the control group (16.5 vs 10.2 days, P < .05). CONCLUSIONS: The prolonged use of PAT in elective surgical cases increases the risk of developing CDT positivity. The appropriate use of PAT could significantly reduce health costs by eliminating unnecessary doses of antibiotics, by decreasing the rate of CDT positivity, and by shortening the hospital stay. Restrictive policies may need to be implemented to prevent further antibiotic misuse.

Adult↗