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Biomedical subjects

C Haisch

Publications and source records attributed to C Haisch.

At least 19 recordsLinked to original sources

A gene transfer method for the study of chimerism derived from donor bone marrow in organ transplant recipients.

Transduction of DBMC with the neo gene did not negatively affect the viability of DBMC or the graft-prolonging effect of DBMC infusion and provided a sensitive method to monitor DBMC-derived chimerism at a microchimeric level for at least 6 months by molecular and immunohistochemical techniques. Selection of neo-transduced DBMC with G418 prior to infusion will enable more uniform neo expression and will provide novel opportunities to further investigate chimerism in primates.

Animals

A gene transfer method for the study of chimerism derived from donor bone marrow in organ transplant recipients.

Transduction of DBMC with the neo gene did not negatively affect the viability of DBMC or the graft-prolonging effect of DBMC infusion and provided a sensitive method to monitor DBMC-derived chimerism at a microchimeric level for at least 6 months by molecular and immunohistochemical techniques. Selection of neo-transduced DBMC with G418 prior to infusion will enable more uniform neo expression and will provide novel opportunities to further investigate chimerism in primates.

Animals

Organ preservation without extreme hypothermia using an Oxygen supplemented perfusate.

All methods of organ preservation depend upon hypothermia to depress metabolism during storage. Yet, hypothermia may represent the rate-limiting factor in organ preservation. A new perfusate has been developed which supports organ preservation without extreme hypothermia. The perfusate consists of a complex fluid supplemented with an oxygen carrying perfluorocarbon emulsion, Oxygent (Alliance Pharmaceutical Corp,). The perfusate was used to preserve canine kidney autografts using pulsatile preservation at 32 degrees C and static storage at 25 degrees C. Upon autografting the dogs produced urine within minutes of reperfusion. These results indicate the new perfusate may have significant potential in organ preservation without extreme hypothermia.

Animals

Postmortem organ salvage using an Oxygen supplemented perfusate.

The world-wide shortage of organs for clinical transplantation is caused by the limited existing donor pool of heartbeating cadavers. Attempts to expand into the nonheartbeating cadaver population have been hindered by warm ischemic damage. We evaluated if a new Oxygent (Alliance Pharmaceutical Corp.) supplemented perfusate could be used to salvage canine kidneys postmortem. The kidneys preserved in the Oxygent perfusate could be maintained in situ for time points ranging from one-eight hours postmortem; enough time to declare death and obtain consent for organ donation. In contrast, the control kidneys yielded abnormal histologic findings and impaired flow dynamics. These results suggest that new perfusate may have significant potential to expand the existing organ donor pool.

Adenosine

Reduction in primary nonfunction of pancreas islet transplants with antithymocyte globulin agents, deoxyspergualin, and splenectomy.

These results suggest that DSG and RATG are an especially favored combination in reducing PNF of discordant pig islet xenografts, probably related to the effect of DSG on the macrophage, humoral antibody, or blockade of NK cell activity. More effective immunosuppression such as demonstrated in this study could well be critical in permitting the application on discordant islet xenografts to human clinical diabetes.

Animals

Functional diversity in vascular endothelial cells: role in coxsackievirus tropism.

Six plaque-purified virus isolates were obtained from liver and heart tissues of a DBA/2 mouse infected 7 days earlier with 10(4) PFU of coxsackievirus group B type 3. Each virus isolate was assayed in vitro for infectivity to vascular endothelial cells (VEC) of the liver, lungs, and heart. Both the percentage of VEC infected and the mean progeny PFU produced per infected VEC were determined. Virus isolates from the heart showed greater infectivity and replication in heart VEC than in VEC derived from either the liver or lungs. Similarly, virus isolated from the liver preferentially infected liver VEC. Virus receptor expression varied between VEC populations, as demonstrated by binding studies with a [35S]methionine-radiolabeled heart virus and by enzyme-linked immunoadsorption assay studies with a monoclonal antibody to the coxsackievirus group B type 3 receptor on heart tissue. Finally, the heart and liver virus isolates were injected (10(4) PFU) intraperitoneally into BALB/c mice. After 7 days, the animals were sacrificed, and the hearts, livers, and lungs were evaluated for tissue injury and virus concentrations. Viruses originally isolated from the heart preferentially infected the heart when reinjected into animals and caused severe myocarditis. Viruses originally derived from the liver most consistently reinfected the liver, although significant virus concentrations were also detected in the heart. The liver virus isolates, however, were incapable of causing myocarditis. Thus, selective tropism of viruses for particular organs in vivo corresponds to the ability of these isolates to infect VEC in vitro.

Animals

Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography.

The ability of noninvasive risk stratification using dipyridamole-thallium-201 (Tl-201) imaging and radionuclide ventriculography to predict perioperative and long-term cardiac events (myocardial infarction or cardiac death) was evaluated in 36 uremic diabetic and 29 nondiabetic candidates for renal allograft surgery. Of the 35 patients who underwent renal allograft surgery 8 +/- 7 months after the study, none had transient Tl-201 defects (although 13 had depressed left ventricular ejection fraction) and none developed perioperative cardiac events. During a mean follow-up of 23 +/- 11 months, 6 (9%) patients developed cardiac events. Logistic regression analysis was used to compare the predictive value of clinical data (including age, sex, diabetes, chest pain history, allograft recipient) and radionuclide data. Presence of transient Tl-201 defect and left ventricular ejection fraction were the only significant predictors of future cardiac events (p less than 0.01). No other patient variables, including diabetes or receiving a renal allograft, had either univariate or multivariate predictive value. All 3 patients with transient Tl-201 defects had cardiac events compared with only 3 of 62 (5%) patients without transient Tl-201 defect (p less than 0.0001). Mean left ventricular ejection fraction was lower in patients with cardiac events (44 +/- 13%) compared with patients without cardiac events (57 +/- 9%, p less than 0.005). Overall, 5 of 6 patients with cardiac events had either transient Tl-201 defects or depressed left ventricular ejection fraction. Dipyridamole-Tl-201 imaging and radionuclide ventriculography may be helpful in identifying uremic candidates for renal allograft surgery who are at low risk for perioperative and long-term cardiac events.

Adult

Clinical and experimental aspects of viral myocarditis.

Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated.

Animals