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Biomedical subjects

J A Goss

Publications and source records attributed to J A Goss.

70 records · Page 4Linked to original sources
PubMed1993

Prevention by thymectomy of tolerance induced by intrathymic injection of donor splenocytes.

BACKGROUND: We have recently demonstrated indefinite donor-specific cardiac allograft survival after the intrathymic injection of donor splenocytes and simultaneous injection of antilymphocyte serum (ALS) in a fully major histocompatibility complex-mismatched rat combination. In this study we performed thymectomy to determine the length of time required for donor alloantigen to be present in the recipient thymus to induce tolerance. METHODS: Male Buffalo (BUF; RT1b) rats at 4 to 8 weeks of age underwent intrathymic injection of 25 x 10(6) Lewis (LEW; RT1(1)) splenocytes and simultaneously received an intraperitoneal injection of 1 ml ALS. To determine the kinetics of tolerance induction, the BUF recipients underwent thymectomy on days 1, 3, or 7 after the initial intrathymic injection of alloantigen and intraperitoneal ALS. Twenty-one days after intrathymic alloantigen injection and ALS, all rats underwent transplantation with a heterotopic LEW cardiac allograft. RESULTS: Thymectomy performed 1 (mean survival time, 6.8 days) and 3 (mean survival time, 8.0 days) days after donor alloantigen injection and ALS did not affect the normal rejection of LEW cardiac allografts. In contrast, thymectomy 7 days after intrathymic alloantigen injection and ALS resulted in indefinite survival of cardiac allografts in 75% of recipients (mean survival time > 77.0 days). In addition, allospecific cytotoxic T lymphocyte activity and interleukin-2 production were markedly decreased in those recipients undergoing thymectomy after 7 days compared with untreated control rats and recipients undergoing thymectomy 1 and 3 days after alloantigen injection. CONCLUSIONS: The presence of the thymus for at least 7 days after intrathymic alloantigen injection and intraperitoneal ALS allows the development of indefinite donor-specific cardiac allograft tolerance.

Animals↗
PubMed1992

Kupffer cell autoregulation of IL-1 production by PGE2 during hepatic regeneration.

The mammalian liver possesses the ability to regenerate to its original size after a 70% partial hepatectomy (PHx). The capacity of rat Kupffer cells (KC) isolated at specific intervals following PHx to produce interleukin-1 (IL-1) and prostaglandin E2 (PGE2) in response to endotoxin (LPS) was evaluated in standard RPMI-1640 (1200 microM L-arginine) and arginine-depleted RPMI-1640 (10 microM L-arginine) media. Regenerating liver KC 48-120 hr following PHx responded to LPS with a significantly greater (p less than 0.05) production of IL-1 in standard RPMI-1640. When 10 microM L-arginine RPMI-1640 was used to simulate the high arginase activity low L-arginine levels of the hepatic microenvironment, regenerating liver KC production of IL-1 was further increased (p less than 0.05). During the same time period, regenerating liver KC also produced significantly (p less than 0.01) more PGE2 than sham KC in both high and low arginine media. When the cyclooxygenase inhibitor indomethacin (10 microM) was added to low arginine cultures, the PGE2 production was inhibited, and IL-1 production was upregulated (p less than 0.05). We conclude that during hepatic regeneration KC IL-1 production is elevated but controlled in an autoregulatory fashion by KC PGE2 production.

Animals↗
PubMed1992

Intrathymic injection of donor alloantigens induces donor-specific vascularized allograft tolerance without immunosuppression.

The induction of donor-specific tolerance could prevent the side effects of immunosuppression while improving allograft survival. Male adult Buffalo (RT1b) rats underwent an intrathymic (IT), portal venous (PV), intrasplenic (IS), or subcutaneous (SQ) injection of 25 x 10(6) major histocompatibility complex (MHC) mismatched Lewis (RT1(1)), UV-B-irradiated Lewis (RT1(1)), ACI (RT1a), or syngeneic Buffalo (RT1b) splenocytes. At the completion of the donor alloantigen injection, 1 mL rabbit anti-rat lymphocyte serum (ALS) was administered intraperitoneally to the Buffalo recipients, and 21 days later a heterotopic Lewis or ACI heart was transplanted. Intrathymic injection of donor alloantigen induced a donor-specific tolerance that allowed the cardiac allograft to survive indefinitely (mean survival time [MST] > 140.7 days) in 84% of the recipients without further immunosuppression, whereas groups receiving antigen injections at other sites (PV, IS, and SQ) plus ALS rejected cardiac allografts in normal fashion (MST approximately 8.0 days). Buffalo recipient rats with long-term surviving Lewis cardiac allografts after Lewis IT injection and ALS subsequently rejected a heterotopic third-party ACI cardiac allograft in normal fashion (MST approximately 7 days), whereas a second Lewis cardiac allograft was not rejected (MST > 116 days). Microchimerism is unlikely because Lewis allograft survival was also prolonged (MST > 38.7 days) in rats receiving UV-B-irradiated splenocytes IT, which cannot proliferate. Survival of Lewis renal allografts was also prolonged, but not indefinitely, in Buffalo recipients possessing a long-term surviving Lewis cardiac allograft (MST approximately 17.6 days versus 7 days for control). This model emphasizes the potential role of exposure of immature thymocytes to foreign donor alloantigens during maturation in the thymic environment for the development of unresponsiveness to an MHC-mismatched donor-specific vascularized allograft.

Animals↗
PubMed1992

Prostaglandin E2 production during hepatic regeneration downregulates Kupffer cell IL-6 production.

The liver possesses the remarkable ability to regenerate to its original size after a 70% partial hepatectomy. There has been little effort to characterize the Kupffer cells' role in this unique mammalian reparative physiologic phenomenon. The capacity of rat Kupffer cells (KC) isolated at specific intervals after partial hepatectomy to produce interleukin-6 (IL-6) and prostaglandin E2 (PGE2) in response to endotoxin was evaluated in standard RPMI-1640 (1200 microM L-arginine) and arginine-depleted RPMI-1640 (10 microM L-arginine) media. Regenerating liver KC 48 to 120 hours after partial hepatectomy responded to endotoxin stimulation with a significantly greater (p less than 0.05) production of IL-6 in standard RPMI-1640. Because Kupffer cells function in an environment where high arginase activity results in negligible L-arginine levels, the 10 microM L-arginine RPMI-1640 was used to simulate the true hepatic microenvironment. Production of IL-6 by regenerating liver KC was further increased (p less than 0.05) by placing these same KC in 10 microM L-arginine RPMI-1640 tissue culture media. During the same period, regenerating liver KC produced significantly (p less than 0.01) more PGE2 than sham-operated KC in both standard and low-arginine media. When the cyclo-oxygenase inhibitor indomethacin (1 x 10(-5) M) was added to cultures, the PGE2 production was inhibited, and IL-6 production was upregulated (p less than 0.05) in arginine-depleted cultures. The authors conclude that during hepatic regeneration KC IL-6 production is elevated but controlled in an autoregulatory fashion by KC PGE2 production.

Animals↗
PubMed1992

Beneficial effect of syngeneic pancreatic islet transplantation on liver atrophy and hepatocellular function after portacaval shunt.

BACKGROUND: Hepatic insufficiency, which continues to be a source of morbidity after portacaval shunt (PCS), can be prevented by syngeneic pancreatic islet transplantation into the portal vein before PCS. This study investigated the ability of syngeneic pancreatic islet transplantation after PCS to prevent hepatic atrophy and rescue hepatocellular function. METHODS: Approximately 1200 to 1400 syngeneic rat pancreatic islets were transplanted through a heparinized catheter into the left lobes of the liver 3, 7, and 21 days after end-to-side PCS. Normal rats received no treatment, and PCS control rats received PCS only, without islet transplantation. Hepatocellular function (caffeine clearance) and hepatic blood flow (indocyanine green clearance) were analyzed at 42 and 49 days after PCS. On day 51 after PCS, the left and right lobes of the liver were divided, weighed, and sectioned for histologic studies. RESULTS: Caffeine clearance in the animals at 3 days (p less than 0.05) and at 7 days (p less than 0.05) after end-to-side PCS was significantly improved versus control PCS animals, indicating that hepatocellular function could be rescued after creation of a PCS. Indocyanine green clearance of all groups with PCS was significantly (p less than 0.001) decreased versus normal animals, showing that hepatic blood flow was uniformly decreased by PCS in all groups. The weight of the transplanted left lobes was significantly greater than the untransplanted right lobes of the groups at 3 days (p less than 0.01) and at 7 days (p less than 0.05) after end-to-side PCS compared with control animals, indicating that liver atrophy was prevented in the islet-transplanted lobes but not in those lobes without a transplant. CONCLUSIONS: Islet transplantation early after PCS can prevent liver atrophy and significantly improve hepatocellular function.

Animals↗
PubMed1991

Renal transplantation for systemic lupus erythematosus and recurrent lupus nephritis. A single-center experience and a review of the literature.

Prior to 1975 patients with systemic lupus erythematosus were generally not considered candidates for renal transplantation because of concern that immune complex deposition would rapidly destroy the allograft. However, recent evidence suggests that good patient and graft survival rates can be achieved comparable to other renal diseases. Between September 23, 1963 and July 31, 1990, 1070 renal transplants were performed at Washington University Medical Center (WUMC). During this period, 14 patients with SLE (12 female and 2 male) received 16 renal transplants (7 living-related donor [LRD], 1 living-unrelated donor [LURD], and 8 cadaver [CAD]). The mean age at the time of the first transplant was 32.5 +/- 10.3 years. The duration of disease prior to transplant was 88.0 +/- 45.9 months and the duration of hemodialysis prior to transplant was 36.0 +/- 33.7 months. Of these patients, 7/14 (50%) had negative and 3/14 (21%) positive SLE serology pre- and post-transplant, 3/14 (21%) had negative serology pretransplant that became positive posttransplant, and 1/14 (2%) was positive pretransplant and became seronegative posttransplant. Patient survival was 92.8% (13/14), and of the 16 kidneys transplanted 62.5% (10/16) are still functioning with a mean follow-up period of 43.7 +/- 45 months. The current mean serum creatinine was 1.4 +/- 0.26 mg/dl. One noncompliant patient developed recurrent lupus nephritis bringing the total number of cases reported in the literature to seven. The present study demonstrates that patients with SLE can be transplanted with excellent patient and graft survival and function and a low rate of recurrent lupus nephritis. From a review of the literature, there appears to be an association between positive SLE serology pre- and posttransplant and recurrent lupus nephritis.

Adult↗
PubMed1981

Characterization of the subunit structure of pyruvate carboxylase from Pseudomonas citronellolis.

Pyruvate carboxylase from Pseudomonas citronellolis is composed of non-identical subunits which include a larger biotin-containing polypeptide (alpha) of Mr = 65,000, and a smaller biotin-free polypeptide (beta) of Mr = 54,000. We have investigated these two polypeptides by analyzing their amino acid composition, cyanogen bromide peptide maps, and immunochemistry. The results showed that the subunits of the enzyme have quite different properties. Antibodies prepared against the polypeptides were used as probes of the catalytic functions of the subunits. Immunotitration studies indicated that only anti-alpha inhibited enzyme activity. The antibiotin fraction of this antibody population was removed by passage through biotin-Sepharose (anti-alpha'). Titration curves using anti-alpha' showed identical inhibition when total pyruvate carboxylase activity, ATP/Pi exchange activity, and pyruvate/oxalacetate exchange activity were measured, suggesting that both active sites are located on the alpha polypeptide. The arrangement of the subunits in the quaternary structure was investigated by means of the surface probe carbonic anhydrase linked to toluene isocyanate, and by partial digestion experiments with trypsin, chymotrypsin, and pronase. The results indicated that the alpha polypeptides are on the outside of the molecule and the beta polypeptides are the internal subunits.

Amino Acid Sequence↗
PubMedDate not supplied

Control of monocyte recruitment by chemotactic factor(s) in lesion-prone areas of swine aorta.

Aortic areas predisposed to early atherosclerosis in swine demarcated by Evans blue uptake (blue areas) show preferential intimal penetration by blood monocytes before and during lesion formation. These cells are thought to be the major source of foam cells in these early lesions. To examine mechanisms controlling monocyte migration into these areas, extracts of aortic tissue from both blue and white areas of hypercholesterolemic (H) and normal (N) swine were tested for chemotactic activity against monocytes from N and H swine and neutrophils from H swine. The data indicate that extracts of blue areas from H swine contained at least one, and possibly two, factors chemotactic only for monocytes from H swine, but not N swine. These factors were not present in similar extracts from white areas of H swine, or either blue or white area extracts from N swine. Gel filtration chromatography of crude blue area extracts separated two chemotactically active fractions of molecular weights 68,000 and 5000 that were not present in white area extracts and that elicited a positive chemotactic effect only for H swine monocytes. These findings provide a mechanism explaining our previous findings of preferential monocyte adhesion and intimal penetration in lesion-prone areas, and indicate that control of monocyte recruitment into the artery involves not only alteration of the arterial wall, but also functional changes in the circulating monocyte.

Animals↗