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Biomedical subjects

H A Gritsch

Publications and source records attributed to H A Gritsch.

At least 55 records · Page 3Linked to original sources
PubMed1995

Combined simultaneous kidney/bone marrow transplantation.

On the basis of observations in patients with long-term (28-30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8) unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8 years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 +/- 11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2 mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/- 1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P = NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P < .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.

Adolescent↗
PubMed1995

The superiority of tacrolimus in renal transplant recipients -- the Pittsburgh experience.

Tacrolimus is a superior immunosuppressive agent in patients undergoing renal transplantation. In adults, the 1- and 3-year actuarial patient survivals were 95% and 92%, and the 1- and 3-year actuarial graft survivals were 89% and 80%. For first cadaver kidneys, the 1- and 3-year actuarial graft survivals were 91% and 82%, with a projected half-life of 11.9 years. Sixty-nine percent of successfully transplanted patients were weaned off steroids. In pediatric patients, the 1- and 4-year actuarial patient survivals were 100% and 96%, and the 1- and 4-year actuarial graft survivals were 99% and 85%. Seventy-three percent of successfully transplanted children were weaned off steroids. Tacrolimus was also useful as a rescue agent, with an initial success rate of 74%. Tacrolimus has been used successfully in kidney/ pancreas transplantation, with 100% patient, 95% kidney, and 79% pancreas graft survival. Tacrolimus should be considered the immunosuppressive agent of choice in renal transplantation.

Adolescent↗
PubMed1994

Specific tolerance across a discordant xenogeneic transplantation barrier.

Successful induction of tolerance across disparate (discordant) species barriers could overcome the organ shortage that presently limits clinical transplantation. We demonstrate here that xenogeneic swine thymic transplants can induce tolerance to swine antigens in mice, while positively selecting functional host CD4+ T cells. Immunologically normal C57BL/10 mice were thymectomized and depleted of T and natural killer cells; then they received transplants of fetal pig thymus and liver fragments. Mature mouse CD4+ T cells developed in the pig thymus grafts and migrated to the periphery. Swine grafts grew markedly and no anti-pig IgG response was produced. Mixed lymphocyte reactions confirmed that the new T cells were functional and were tolerant to pig antigens.

Animals↗
PubMed1994

The importance of nonimmune factors in reconstitution by discordant xenogeneic hematopoietic cells.

Bone marrow transplantation has been shown to induce donor-specific tolerance in rodent models. This approach could potentially be applied to xenotransplantation across discordant species barriers. To evaluate host factors resisting hematopoietic cell engraftment, we have developed two model systems utilizing the combination of swine into severe combined immunodeficient (SCID) mice. SCID mice lack functional B and T lymphocytes, and can therefore be used to evaluate nonimmune factors resisting marrow engraftment, and for adoptive transfer studies to test the role of immune cells and antibodies. First we transplanted swine bone marrow cells into SCID mice conditioned with whole-body irradiation (4 Gy). For nine weeks following the intravenous administration of 10(8) swine bone marrow cells, up to 3.8% of peripheral blood leukocytes were of swine origin, as determined by flow cytometry (FCM). These cells were all of the myeloid lineage. Swine IgG was also detectable in the serum for up to 14 weeks. The bone marrow of the reconstituted mice contained low percentages of swine myeloid cells, and swine myeloid progenitors could be detected for up to 20 weeks after bone marrow transplantation. In a second model, we grafted thymus and liver tissue from 45-69-day-old swine fetuses under the kidney capsule of 4 Gy-irradiated SCID mice. A suspension containing 10(8) swine fetal liver cells (FLC) was also administered i.p. Long-term repopulation with swine T cells was observed, with up to 1.5% swine T cells detected in the WBC, peritoneum, and spleen for at least 5.5 months postgrafting. These T cells expressed either CD4 or CD8, whereas up to 17.6% of cells in the thymic grafts expressed both CD4 and CD8. The i.p. FLC suspension was required for optimal long-term graft maintenance. Our studies show that (1) low level myeloid and B lymphocyte reconstitution can be achieved by transferring adult swine BMC to irradiated SCID recipients; (2) swine myeloid progenitors were detectable long-term in BMC of these mice, suggesting that stem cell engraftment was achieved; and (3) T cell reconstitution of SCID mice by swine progenitors requires cotransplantation of a swine stromal environment, as is provided by fetal swine thymus/liver grafts. We conclude that nonimmune factors such as those provided by species-specific stromal environments are important for reconstitution of some lineages by discordant hematopoietic stem cells.

Animals↗
PubMed1994

Renal transplantation at the University of Pittsburgh: the impact of FK506.

1. In an unselected adult renal transplant population, FK506 as the primary immunosuppressive agent yielded one- and 2-year actuarial patient survival rates of 95% and 93% and one- and 2-year actuarial graft survival rates of 89% and 83%, respectively. Forty-nine percent of successfully transplanted patients were weaned off steroids. 2. In pediatric renal transplant patients, FK506 has been associated with 100% one- and 3-year actuarial patient survival rates and 98% and 85% one- and 3-year actuarial graft survival rates, respectively. Sixty-two percent of successfully transplanted patients were taken off prednisone, with dramatic improvements in height. 3. FK506 has been used successfully in rescuing 70-74% of adult or pediatric renal transplant patients with an acute rejection that failed conventional therapy. 4. Kidney/bone marrow transplantation under FK506 therapy has been successfully performed without graft-versus-host disease and with routine augmentation of chimerism. 5. The side effects of FK506 included nephrotoxicity, neurotoxicity, and diabetogenicity; they were comparable to those seen with CsA. 6. FK506 is an important new addition to the immunosuppressive armamentarium in renal transplant patients.

Actuarial Analysis↗
PubMed1991

Sensitized B lymphocytes contribute to acute allograft rejection.

The contribution of sensitized B lymphocytes to second-set allograft rejection has been relatively ignored despite their regular appearance in rejecting allografts. This study presents evidence that adoptively transferred sensitized B lymphocytes accelerate the rate of acute allograft rejection in a sublethally irradiated rat cardiac allograft model. Donors of reconstituting B lymphocytes were sensitized with three consecutive ACI skin grafts. Transplantation of a heart from an ACI strain donor into a Lewis strain recipient (complete RT1 mismatch) results in rejection in 6.8 +/- 0.3 days. When the allograft donor and recipient are irradiated with 650 cGy prior to transplantation, rejection occurs at 31.5 +/- 3.0 days. Irradiated recipients reconstituted with 10(6) syngeneic sensitized splenic B cells reject their grafts in 20.1 +/- 2.0 days, while reconstitution with 10(6) unsensitized syngeneic B cells has no effect on the rate of rejection (P = 0.0007). These data strongly suggest that sensitized B lymphocytes have a marked accelerating effect on the tempo of allograft rejection.

Animals↗
PubMed1989

Invasive giant condylomata acuminata: a case report.

We report on a patient with invasive giant condylomata acuminata (Buschke-Loewenstein tumor). This tumor is an exophytic human papilloma viral lesion with downward growth without histological malignancy. The aggressive progression of this lesion requires early surgical excision with clear margins. Delay in recognition of this tumor can otherwise lead to a fatal clinical course.

Adult↗
PubMed1981

Evidence for intragranular processing of pro-opiocortin in the mouse pituitary intermediate lobe.

Mouse pituitary neurointermediate lobes were pulse-incubated in [3H] arginine or [3H] lysine for 10 min and then chase-incubated for periods 0 to 4h. The labeled peptides from the lobes were analysed by immunoprecipitation with specific antisera, and thereafter, by acid-urea polyacrylamide gel electrophoresis. Using this paradigm, the synthesis of a prohormone common to adrenocorticotropin (ACTH) and endorphin was detected in 10 min pulse labeled lobes. Following a chase period, processing of the prohormone to several forms of ACTH (mol. wt. 25000, 23000, and 13000), beta-lipotropin and beta-endorphin was observed. To determine the intracellular site of processing of the prohormone, subcellular fractionation studies of labeled lobes were carried out. Analysis of the fractions from the pulse-labeled lobes revealed that the newly synthesized labeled prohormone was primarily localized in a granule-enriched fraction. In lobes that were pulsed and then chase-incubated for 1 h, there was a decrease in the amount of prohormone and an appearance of processed products in the granule-enriched fraction. In another paradigm, where the secretory granule-fraction was isolated from pulse-labeled lobes and then incubated in vitro for 6 h at pH 5.5, processing of the endogenous labeled prohormone within the isolated granule fraction was observed. These data suggest, that in the mouse neurointermediate lobe, the ACTH/endorphin prohormone (pro-opiocortin) is rapidly packaged into secretory granules after synthesis and processed intragranularly.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Pro-opiocortin processing in the pituitary: a model for neuropeptide biosynthesis.

The biosynthesis of alpha-MSH, beta-endorphin and ACTH in the pituitary is reviewed. These neuropeptides are synthesized from a common pro-protein, pro-opiomelanocortin. The pro-protein is cleaved intragranularly, at pairs of basic residues in the molecule to yield the respective peptide products. An unique, thiol protease (pro-opiocortin converting enzyme) and a carboxypeptidase B-like enzyme, both localized within pituitary secretory granules and having a pH optimum of 5-6, appear to be involved in the proteolytic processing of pro-opiomelanocortin.

Adrenocorticotropic Hormone↗