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S P Rainer

Publications and source records attributed to S P Rainer.

11 recordsLinked to original sources
PubMed2002

A two-phase pathogenesis of graft-versus-host disease in mice.

Activation of donor T cells is required for the development of graft-versus-host disease (GVHD), a major complication of bone marrow transplantation. We investigated a murine model of GVHD across major and minor histocompatibility barriers. BALB/c recipients were lethally irradiated and transplanted with 10(7) bone marrow and 5 x 10(6) spleen cells from C57BL/6 donors. There were two separate phases of clinical disease. The first phase was most severe on day 7 after transplant. Weight and condition improved until day 12 and then a second phase of clinical GVHD commenced, which persisted until euthanasia. IL-2 mRNA expression, as a measure of T cell activation, was determined by quantitative PCR. The two phases of clinical GVHD were preceded by two separate peaks of IL-2 mRNA in the spleen. Host MHC class II(+) cells became undetectable by flow cytometry 7 days after transplantation, whereas donor MHC class II(+) cells increased during the first 9 days after transplantation. Removal of donor MHC class II(+) cells from the graft had no effect on the first phase. Possible roles for host and donor antigen-presenting cells (APC) in the two phases of the disease are discussed.

Animals↗
PubMed1996

VCAM-1 expression and network of VCAM-1 positive vascular dendritic cells in advanced atherosclerotic lesions of carotid arteries and aortas.

This study was undertaken to determine whether vascular dendritic cells (VDCs) display VCAM-1 in atherosclerotic lesions. Specimens of carotid artery and aorta were obtained at operation. All the plaques contained VCAM-1+ cells, but VCAM-1 immunoreactivity was irregularly distributed being mainly associated with the zones of neovascularisation in the base of the atherosclerotic plaques. Vascular dendritic cells were identified with DAKO-CD1 a. Alternative parallel sections were stained with either anti-CD1 a or anti-VCAM-1. By comparison of consecutive parallel sections the CD1a+ vascular dendritic cells were located separate from other intimal cells. In some areas networks formed by VCAM-1+ vascular dendritic cells were observed suggesting that cellular networks may mediate a local immune response in atherosclerotic lesions. We speculate that VCAM-1 is involved in the formation of cell-to-cell contacts of vascular dendritic cells in atherogenesis.

Adult↗
PubMed1995

Selective inhibition of nitric oxide production during cardiac allograft rejection causes a small increase in graft survival.

Nitric oxide production is increased in allograft rejection and may have both beneficial and deleterious effects on graft function and survival. In animal models, conventional immunosuppressive agents have been shown to decrease nitric oxide production. The aim of our study was to determine what effect augmentation and selective inhibition of nitric oxide production may have on graft survival by using the model of heterotopic cardiac transplantation in the rat. L-Arginine, the naturally occurring substrate for nitric oxide production, was administered subcutaneously at 200 mg/kg/day. L-NG-monomethyl-L-arginine (L-NMMA) is a selective inhibitor of nitric oxide synthase and was administered at 500 mg/kg/day to allograft recipients from the day of operation. Endogenous nitric oxide production was quantified by analysis of urinary nitrate excretion, and time to rejection was determined by graft palpation. L-Arginine did not significantly alter urinary nitrate excretion by iso- or allografts, suggesting that nitric oxide production is not a substrate-limited process in this model. Graft survival in this group was unchanged. L-NMMA produced a small increase in graft survival from 5.1 +/- 0.1 to 6.3 +/- 0.3 days compared with control allografts (P = 0.001) and abolished the rise in urinary nitrate excretion seen with control allografts. Lower doses of L-NMMA produced dose-related decrements in urinary nitrate excretion, but did not alter graft survival. We found that allograft rejection can proceed to graft loss despite complete inhibition of the increase in nitric oxide production that occurs during untreated rejection. The small increase in graft survival suggests that nitric oxide plays a minor role as a cytotoxic effector molecule in this model of acute rejection.

Animals↗
PubMed1994

Urinary nitrate excretion is a noninvasive indicator of acute cardiac allograft rejection and nitric oxide production in the rat.

Cytokine induction of calcium-independent nitric oxide synthase is associated with production of large amounts of nitric oxide (NO). NO is a free radical that is rapidly degraded to nitrite and nitrate. Measurement of plasma and urinary nitrate is an indirect marker of NO production and previous studies have demonstrated that plasma nitrate rises with allograft rejection. The purpose of this study was to examine the temporal relationship between the rise in urinary nitrate excretion and the onset of graft rejection, and to determine the effect of conventional immunosuppression on nitrate excretion. The heterotropic model of cardiac transplantation in the rat was used, with Brown-Norway to Lewis allografts and Lewis to Lewis isograft controls. Twenty-four-hour urine specimens were collected before and after transplantation. Urinary nitrate excretion was measured by gas chromatography/mass spectrometry. Each group was treated with (1) no immunosuppression, (2) dexamethasone (3 mg/kg), or (3) CsA (10 mg/kg) on days 0, 1, and 2. Time to rejection for untreated allografts was 5.1 +/- 0.1 days, extending to 8.4 +/- 0.5 and 9.6 +/- 0.4 days with dexamethasone and CsA treatment, respectively. There was a significant rise in nitrate excretion on days 4, 7, and 9 for control, dexamethasone-treated, and CsA-treated allografts, respectively, preceding evidence of rejection. Untreated allograft rejection was associated with a peak in nitrate excretion 8 times that of basal excretion by isografts. Treatment of the allografts with dexamethasone and CsA significantly attenuated peak nitrate excretion compared with untreated allografts with a only a 2- to 3-fold rise preceding rejection. Results indicate that allograft rejection is associated with a dramatic increase in peak urinary nitrate excretion that is attenuated by standard immunosuppressive therapy. An increase in nitrate excretion precedes evidence of graft rejection, and may serve as a noninvasive marker of graft rejection.

Animals↗
PubMed1992

The pathobiology of subclinical pyelonephritis--an experimental evaluation.

Clinical studies have demonstrated a poor correlation between localization tests, which are designed to determine the site of urinary tract infection, and symptoms of upper urinary tract infection. One explanation is that microorganisms may be present in the kidney but not initiate an inflammatory response with associated symptoms. An animal model has been developed to obtain quantitative information on the comparative pathobiology of lesion-inducing and non-lesion-inducing infections. In this model, non-manipulated kidneys had acquired a persistent microbial flora within 48 hours of the lower urinary tract becoming infected. This bacterial invasion was not associated with gross or histologic changes within the renal parenchyma, but minor foci of inflammatory cells were seen beneath the epithelium lining the calyces. Ureteric urines from such kidneys contained many leukocytes and high numbers of bacteria. These results showed that the kidneys were infected, rather than colonized, and the term "subclinical" infection was appropriate. Antimicrobial agents were variably successful at eradicating the infection. These experimental observations support the concept of subclinical pyelonephritis and may explain the absence of symptoms in the clinically equivalent situation in humans.

Animals↗
PubMed1989

Cardiac transplantation in New Zealand: an initial report.

During the first 18 months of its establishment, the cardiac transplant unit at Green Lane Hospital has undertaken 10 transplant operations. Fifty potential recipients have been referred and 15 were accepted for transplantation. Of the ten who have had surgery, 2 are making good progress at school, 1 is active at home and 5 have returned to work. Two patients have died.

Adult↗
PubMed1978

Goodpasture's syndrome: an analysis of 29 cases.

The pathologic features of 29 cases of Goodpasture's syndrome occurring during a 13-yr period in Auckland have been reviewed and correlated with clinical findings. There were 20 males and nine females in the series; two of the males and three of the females were Maoris. Age at the time of onset of symptoms ranged from 17 to 75 yr, with about 76% of the patients being from 17 to 27 yr of age. Sixteen (55%) of the patients died from less than a week up to about two years following the onset of symptoms, and the remaining 13 are live from 30 weeks to 14 yr after initial presentation. Underlying renal disease varied from mild focal glomerulitis to end-stage glomerulonephritis by light microscopy, but characteristic glomerular changes were seen in all specimens examined by electron and immunofluorescent microscopy. The lungs of 13 of the patients examined at autopsy showed typical abnormalities. The syndrome pursues a notably variable clinical course, affects a considerable proportion of females, occurs over a wide age range, and appears to be disporportionately common among Maoris.

Adolescent↗
PubMedDate not supplied

Cytomegalovirus myocarditis in a heart transplant recipient: sensitive monitoring of viral DNA by the polymerase chain reaction.

A 54-year-old female heart transplant recipient had an acute episode of graft rejection that was treated with high-dose immunosuppression therapy. During this therapy a second febrile illness developed, which was accompanied by hypotension, anemia, and rash. Findings for subsequent myocardial biopsy specimens were negative for cytomegalovirus by culture but were strongly positive for cytomegalovirus deoxyribonucleic acid by the polymerase chain reaction. Histologic observation of viral inclusions in the myocardial fibers supported the diagnosis of cytomegalovirus myocarditis. The polymerase chain reaction therefore can provide a rapid and highly sensitive method for heart transplant patients with suspected cytomegalovirus myocarditis.

Cytomegalovirus↗