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S C Jordan

Publications and source records attributed to S C Jordan.

At least 19 recordsLinked to original sources
PubMed2006

Effect of induction therapy protocols on transplant outcomes in crossmatch positive renal allograft recipients desensitized with IVIG.

Here we retrospectively examine the efficacy of two antibody induction regimens using Zenapax or Thymoglobulin in patients with positive complement-dependent cytotoxicity crossmatches (CDC-CMXs) desensitized with IVIG (intravenous immunoglobulin). Between January 1999 and March 2005, 97 patients with (+) CDC-CMXs received kidney transplants (43 deceased donors/54 living donors). All patients received at least 2 g/kg IVIG (maximum four doses) until an acceptable CMX was obtained. Patients were divided into two groups: 1. IVIG + Zenapax (n = 58), 2. IVIG + Thymoglobulin (n = 39). A total of 94% of patients in Group 1 and 84% in G2 have at least 2 years of follow up. Patient and graft survival was 96%/84% in Group 1 and 100%/90% in Group 2, p = NS. The number and severity of AR episodes were similar (36% Group 1 vs. 31% Group 2, p = NS) as was the incidence of C4d (+) antibody-mediated rejection (AMR) (Banff Grade II/III) (22% Group 1 vs. 21% Group 2). Mean serum creatinines (SCrs) at 24 months were similar (Group 1: 1.4 +/- 0.7 vs. G2: 1.5 +/- 0.7 mg/dL). Induction therapy with Zenapax or Thymoglobulin results in excellent patient, graft survival and graft function at 2 years. There was no increased risk of viral infections or malignancies with either agent. Neither agent was effective in reducing the incidence of AMR.

Acute Disease↗
PubMed2006

Intravenous gammaglobulin (IVIG): a novel approach to improve transplant rates and outcomes in highly HLA-sensitized patients.

Intravenous immunoglobulin (IVIG) products are derived from pooled human plasma and have been used for the treatment of primary immunodeficiency disorders for more than 24 years. Shortly after their introduction, IVIG products were also found to be effective in the treatment of autoimmune and inflammatory disorders. Over the past 2 decades, the list of diseases where IVIG has a demonstrable beneficial effect has grown rapidly. These include Kawasaki disease, Guillain-Barre syndrome, myasthenia gravis, dermatomyositis and demyelinating polyneuropathy. Recently, we have described a beneficial effect on the reduction of anti-HLA antibodies with subsequent improvement in transplantation of highly HLA-sensitized patients as well as a potent anti-inflammatory effect that is beneficial in the treatment of antibody-mediated rejection (AMR). These advancements have enabled transplantation of patients previously considered untransplantable. These studies and relevant mechanism(s) of action will be discussed here.

Graft Rejection↗
PubMed2005

Successful use of oral ganciclovir for the treatment of intrauterine cytomegalovirus infection in a renal allograft recipient.

Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns and is the leading infectious cause of congenital birth defects. Female renal allograft recipients who develop CMV infection during pregnancy are at risk for both graft dysfunction and fetal morbidity. DNA-based analysis of amniotic fluid (AF) from at-risk pregnancies has been suggested as an adjunct/substitute for traditional culture. We have shown that CMV-polymerase chain reaction of AF is a useful diagnostic test for congenital CMV infection. Using this test we diagnosed CMV infection in the fetus of a 30-year-old renal transplant recipient. As termination was not an option for the family, the patient was extensively counseled and treated with oral ganciclovir. This resulted in clearance of the virus from the AF and the delivery of a healthy newborn girl, free of CMV disease. This is the first reported case to our knowledge of successful use of maternal ganciclovir to treat intrauterine CMV infection in a pregnant renal transplant recipient.

Adult↗
PubMed2003

Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients.

BACKGROUND: Sensitization to human leukocyte antigens (HLA) is a significant barrier to transplantation. Currently, no proven therapy exists to improve access to transplantation for highly sensitized patients. Here, we report a novel approach using intravenous immune globulin to modulate anti-HLA antibody and improve the chances for successful transplantation. PATIENTS AND METHODS: Forty-five highly HLA-sensitized patients presented as candidates for living-donor kidney transplantation (n=28), cadaveric kidney transplantation (n=15), or heart transplantation (n=2). All patients had a positive CDC crossmatch (CMX) with their donors. In living-donor recipients, intravenous immune globulin (IVIG) was added to the CMX evaluation to determine whether blocking antibodies present in IVIG could inhibit cytotoxicity. For those who showed in vitro inhibition with IVIG (n=26), IVIG was administered (usually as a single dose, 2 g/kg) and the CDC CMX was repeated against the prospective donor immediately after IVIG infusion. If negative, the patient underwent transplantation with their living-donor kidney within 24 to 72 hr. A similar but modified protocol was performed for cadaver donor candidates, all of whom were highly sensitized and had had CMX positivity with multiple donors, negating transplantation. Reductions in CMX positivity, posttransplantation serum creatinine level, number and severity of rejection episodes, and patient and graft survival rates were determined. RESULTS: Forty-two patients underwent transplantation. IVIG treatment completely abrogated the donor-specific CMXs in 35 of 42 patients. In the remaining 7 patients, the CDC CMX was inhibited, but flow cytometry CMXs remained positive. A total of 13 (31%) of 42 recipients developed rejection episodes 3 to 49 days after transplantation. Three grafts (7%) were lost to rejection. Mean serum creatinine level at 24 months was 1.4+/-0.4 mg/dL. Patient and graft survival rates were 97.6% and 89.1%, respectively, at 24 months. CONCLUSIONS: The in vitro IVIG CMX technique predicts the ability of IVIG to reduce anti-HLA antibody levels in highly sensitized patients. Subsequent in vivo IVIG treatment of responders eliminates the positive CDC CMX and allows for successful transplantation. Thus a positive CMX result is not necessarily a contraindication for transplantation and allows access to transplantation for patients for whom it was previously contraindicated.

Adolescent↗
PubMed2003

Childhood nephrotic syndrome in relapse is associated with down-regulation of monocyte CD14 expression and lipopolysaccharide-induced tumour necrosis factor-alpha production.

Interleukin-13 (IL-13) is a known modulator of monocyte function, down-regulating monocyte surface markers such as CD14 and proinflammatory cytokines. We have shown previously that lymphocyte IL-13 gene expression was up-regulated during relapses in children with steroid-responsive nephrotic syndrome (SRNS). In this study, we examined the monocyte mRNA expression and lipopolysaccharide (LPS)-stimulated intracellular production of tumour necrosis factor-alpha (TNF-alpha) and IL-8 in children with SRNS during relapse and remission. Additionally, we investigated CD14 mRNA levels, CD14 surface expression and its soluble component (sCD14) in serum. Our results showed that the percentages of TNF-alpha positive monocytes following LPS stimulation were significantly lower in nephrotic children in relapse (64.4 +/- 13.7%) compared to remission (81.6 +/- 9.0%, P < 0.005). This was associated with down-regulation of CD14 mRNA, as well as both membrane and sCD14 in patients with nephrotic relapse (82.9 +/- 10.1% and 1.23 +/- 0.30 micro g/ml, respectively) compared to remission (93.9 +/- 3.2% and 1.77 +/- 0.82 micro g/ml, respectively) (P < 0.003). Although we demonstrated a decrease in LPS-stimulated intracellular production of TNF-alpha in monocytes from patients with nephrotic relapse, we were unable to show a concomitant decrease in mRNA expression during relapses. This could be explained by down-regulation of gene expression at the translational rather than transcriptional level. In conclusion, it is conceivable that up-regulation of T-cell IL-13 production in children with active nephrotic relapse was associated with suppression of monocyte CD14 expression, down-regulating pro-inflammatory cytokine production, and could account for the increased susceptibility to bacterial sepsis seen in nephrotic children in active relapse.

Adolescent↗
PubMed2001

Cyclosporine microemulsion- and mycophenolate mofetil-related lymphoid aggregates are not associated with acute rejection.

BACKGROUND: Microemulsion cyclosporine, mycophenolate mofetil, and prednisone have become a common immunosuppressive protocol in renal transplantation. We identified lymphocytic infiltrates in transplant fine-needle aspirates and core biopsies from patients on this regimen without acute rejection clinically or by standardized morphological criteria and investigated this inflammatory response. METHODS: Twenty-eight aspirates from 21 patients were included and assessed in the standard fashion. Nine core biopsies showing interstitial lymphocytic infiltration were evaluated with antibodies against CD3, CD4, CD8, CD20, CD30, CD56, KP1, and epithelial membrane antigen (EMA). Aspirates and biopsies were assessed for tubular cell major histocompatibility complex (MHC) class II antigen and for gamma-interferon (gamma-IFN), interleukin-4 (IL-4), and IL-10 mRNAs by reverse transcription-polymerase chain reaction. RESULTS: Fifteen aspirates showed immune activation solely due to mature lymphocytes and monocytes; 13 had no immune activation. All aspirates were negative for MHC class II antigens. Of 6 activated aspirates assessed for gamma-IFN mRNA, 5 were negative. All 21 patients had similar clinical characteristics and recovered renal function without rejection treatment. The core biopsies had lymphocytes in 5-30% of the interstitium. The cells were 70-85% CD3+, with 50-85% CD4+, 3-10% KP1+, and rare cells CD56+. No T-cell activation was present (EMA- and CD30-). Seven biopsies were assessed and were negative for gamma-IFN mRNA; only one biopsy had weakly positive MHC class II staining. Two activated aspirates were negative for IL-4 and IL-10 mRNA, while three biopsies each contained IL-4 and IL-10 mRNAs. CONCLUSIONS: Inactive interstitial lymphoid infiltrates are frequent in patients on this drug regimen and should not be interpreted as acute rejection, particularly in aspirate samples. These lymphocytes may play a role in long-term allograft acceptance.

Antigens, CD↗
PubMed2001

Prolongation of allograft survival with viral IL-10 transfection in a highly histoincompatible model of rat heart allograft rejection.

BACKGROUND: The ability to express genes with potential immunoregulatory capacity could reduce the immunogenicity of allografts and result in long-term graft survival. In this study, we examine the feasibility of transferring viral interleukin-10 (vIL-10) gene into rat hearts using adenovirus by intracoronary administration. The subsequent effects of delivered vIL-10 alone or with subtherapeutic doses of cyclosporine A (CsA) on parameters of allograft rejection (AR) were also examined. METHODS: Recombinant adenovirus vectors containing vIL-10 (Ad-vIL-10) or beta-galactosidase (Ad-beta-gal) were derived from adenovirus type 5. vIL-10 expression in supernatants of transfected COS7 cell cultures and in transfected heart allografts were examined by enzyme immunoassay (EIA) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Rat heart transplants (LEWS->ACI) were performed in five groups [group 1: no treatment, group 2: Ad-beta-gal, group 3: AdvIL-10, group 4: CsA (10 mg/kg), and group 5: Ad-vIL10+CsA (10 mg/kg)]. Allograft survival was determined by palpating heartbeats. Allograft tissues were also submitted for histological study. RESULTS: vIL-10 expression was shown in both transfected COS7 cells and heart isografts. Animals transfected with vIL-10 showed prolongation of graft survival (19.6 vs. 12 days, P<0.001) when compared to beta-gal transfected controls. Animals treated with a single low dose injection of CsA showed no significant prolongation of graft survival compared to controls (11.7 vs. 10.5 days). Animals treated with both vIL-10 and CsA demonstrated a synergistic prolongation of allograft survival compared with controls and with animals treated with CsA or vIL-10 treatment alone (36.7 days vs. 11.7, P<0.001 or 36.7 vs.19.6, P<0.001, respectively). Histological study showed that allografts from untreated controls exhibited extensive AR with loss of graft architecture by day 7 posttransplant while those from the vIL-10 group showed less AR. The best pathological scores were seen in vIL-10 + CsA-treated animals. CONCLUSIONS: 1) Delivering Ad-vIL-10 into donor hearts by intracoronary perfusion results in overexpression of vIL-10 and significantly prolongs cardiac allograft survival in a highly histoincompatible rat model. 2) Subtherapeutic doses of CsA do not prolong allograft survival, but act synergistically with vIL-10 to significantly prolong graft survival beyond that achieved with either agent alone.

Adenoviridae↗
PubMed2001

Antithrombin III inhibits lymphocyte proliferation, immunoglobulin production and mRNA expression of lymphocyte growth factors (IL-2, gamma-IFN and IL-4) in vitro.

BACKGROUND: Antithrombin III (AT-III) is a physiological inhibitor of thrombin and other serine proteases, and has antiinflammatory properties. Thrombin is known to enhance T lymphocyte activation in vitro and serine proteases can act as costimulators for lymphocyte proliferation and cytokine production. We have previously shown that AT-III significantly inhibited allograft rejection in a highly histoincompatible model of rat lung transplantation and in vitro cell proliferation in ConA-stimulated rat spleen cells. In this study, we examined the involvement of cytokine gene expression in the above inhibitory effect of AT-III. We also examined the effect of AT-III on several in vitro immune reactions in human peripheral blood mononuclear cells (PBMCs). METHODS: mRNA expression of cytokines/cytokine receptor important in lymphocyte activation was examined. Rat spleen cells were stimulated with Con-A with/without AT-III and submitted for reverse transcriptase-polymerase chain reaction (RT-PCR). To assess the effect of AT-III on human PBMCs, we examined the effects of AT-III on cell proliferation of human PBMCs stimulated in mixed lymphocyte reaction (MLR) (allogeneic stimulation), with OKT3 (T cell receptor activation) and with PHA (mitogenic stimulation). The effect of AT-III on PWM-stimulated immunoglobulin (Ig) production by human PBMCs was also examined. All experiments for cell proliferation were performed in 10% serum and in serum-free (SF) media to determine whether AT-III exerted its effects through its interaction with thrombin in serum. RESULTS: mRNA expression of IL-2, gamma-IFN and IL-4 in ConA-stimulated rat spleen cells was nearly completely inhibited by AT-III at 15 IU/ml. mRNA levels for IL-6, IL-2R and TGF-beta1 were not significantly affected by AT-III. AT-III showed a dose-dependent inhibition of cell proliferation in human PBMCs. At 15 IU/ml, cell proliferation was inhibited by approximately 86%, approximately 81% and approximately 56% in the MLR-, OKT3- and PHA-stimulated PBMCs, respectively in both serum and SF media. AT-III inhibited PWM-stimulated Ig production in a dose-dependent manner. IgG, IgM and IgA production was reduced by approximately 60%, 80% and 70%, respectively in cultures incubated with 15 IU/ml AT-III. CONCLUSIONS: (1) Inhibition of IL-2, gamma-IFN and IL-4 mRNA expression might be responsible for inhibition of cell proliferation by AT-III in ConA-stimulated rat spleen cells, (2) AT-III inhibits cell proliferation in the MLR-, OKT3- and PHA-stimulated human PBMCs, and Ig production in PWM-stimulated human PBMCs, (3) The immune regulatory effects of AT-III are independent of its interaction with thrombin since similar levels of suppression were seen in SF media, and (4) These results suggest that AT-III has potent inhibitory effects on lymphocyte activation and cytokine production and may have potential applications as an immunomodulatory agent.

Animals↗
PubMed2001

Association of parvovirus B19 infection with idiopathic collapsing glomerulopathy.

BACKGROUND: Collapsing glomerulopathy (CG), a disorder with severe glomerular and tubular involvement, occurs either as an idiopathic lesion or in some patients with human immunodeficiency virus (HIV) infection known as HIV-associated nephropathy (HIVAN). We previously reported a renal transplant recipient with de novo CG and red cell aplasia in association with persistent parvovirus B19 (PVB19) infection. This prompted us to look for an association between PVB19 infection and CG. METHODS: DNA from archived biopsies of patients with CG was analyzed for PVB19 by polymerase chain reaction (PCR). Results were compared with HIVAN, idiopathic focal segmental glomerulosclerosis (FSGS), and controls. In situ hybridization (ISH) was done to localize PVB19 in renal biopsies. Peripheral blood specimens of patients with CG, HIV infection, healthy controls, and randomly selected hospitalized patients (sick controls) were also analyzed for PVB19. RESULTS: PVB19 DNA was detected in renal biopsies of 18 out of 23 (78.3%) patients with CG, 3 out of 19 (15.8%) with HIVAN, 6 out of 27 (22.2%) with FSGS, and 7 out of 27 (25.9%) controls (P < 0.01, CG vs. HIVAN, FSGS, and controls). PVB19 was detected in peripheral blood of 7 out of 8 (87.5%) CG patients, 3 out of 22 (13.6%) with HIV infection, 4 out of 133 (3%) healthy controls, and 2 out of 50 (4%) sick controls (P < 0.001, CG vs. HIV infected, healthy, and sick controls). PVB19 was identified in glomerular parietal and visceral epithelial and tubular cells by ISH. CONCLUSIONS: The significantly higher prevalence of PVB19 DNA in renal biopsies and peripheral blood of CG patients suggests a specific association between PVB19 infection and CG. In susceptible individuals, renal epithelial cell infection with PVB19 may induce CG.

Biopsy↗
PubMed2000

Hydrophobic extracts of a Chinese herb (CMX-13) exhibit potent immunosuppressive properties and prevent acute rejection in a highly histoincompatible model of rat lung transplantation.

BACKGROUND: The potential of higher plants as sources for new immunosuppressive medications is well recognized. In our experiments we investigated the immunosuppressive effect of a highly refined and potent extract of a Chinese herbal preparation, CMX-13, on inhibiting acute allograft rejection (AR) in a highly histoincompatible rat lung transplant model, BN-->LEW, and on lymphocyte activation and cytokine gene expression in vitro. METHODS: Left lung transplants: the control group (group 1) received only dimethylsulfoxide (DMSO) which is the solvent for CMX-13. Group 2 received intramuscular cyclosporin A (CsA, 25 mg/kg) on day 2 posttransplant. Group 3 and 4 received i.p. CMX-13 (0.5 mg/day, low dose and 5 mg/day, high dose, respectively) on day 1, 2, and 3 posttransplant. All animals were killed on day 6 posttransplant. Several pathological categories of inflammation were examined. In vitro experiments: rat spleen cells were incubated with Con A or irradiated stimulator cells with/without serial dilutions of CMX-13 or CsA. Cell proliferation was measured by 3H-thymidine incorporation. mRNA expression of interleukin-2 and interferon-gamma was examined by reverse transcriptase-polymerase chain reaction. RESULTS: The severity of AR in animals receiving high dose CMX-13 was significantly reduced (stage II, P<0.05) compared with controls (stage IV). Significant differences were also seen when more specific parameters of inflammation were examined (necrosis, 0 vs. 1.7+/-1.0, P<0.05; interalveolar hemorrhage, 0 vs. 3.0+/-0.9, P<0.05). The responses seen in the animals treated with high dose CMX-13 were similar to those in the CsA group. CMX-13 inhibited T cell proliferative responses induced by Con A and alloantigen stimulation in a dose-dependent manner that were similar to CsA. Interleukin-2, and interferon-gamma mRNA expression in Con A-stimulated spleen cells was not inhibited by CMX-13 although CsA showed significant inhibition. CONCLUSIONS: 1) CMX-13 significantly reduces the stage of AR and parameters of inflammation in a highly histoincompatible rat lung transplant model. 2) CMX-13 has equal potency to CsA in the inhibition of Con A and alloantigen stimulated rat spleen cell proliferation. 3) CMX-13 showed no inhibitory effects on IL-2 and gamma-IFN mRNA expression, suggesting that its mechanism of action is different from CsA. 4) CMX-13 or derivatives may have potential utility as an immunosuppressive agent(s) in modulation of AR and management of other inflammatory and immunological disorders.

Acute Disease↗
PubMed2000

Nephrocalcinosis and renal cysts associated with apparent mineralocorticoid excess syndrome.

Apparent mineralocorticoid excess (AME) syndrome is a rare inherited disorder caused by 11beta-hydroxysteroid dehydrogenase (11-HSD 2) isozyme deficiency in the kidney. This enzyme is responsible for oxidizing cortisol to its inactive metabolite cortisone. An elevated tetrahydrocortisol (THF) and allotetrahydrocortisol (aTHF) to tetrahydrocortisone (THE) ratio in the urine is pathognomonic of AME syndrome. Clinical features include hypertension, hypokalemia, alkalosis, reduced plasma renin activity (PRA), low aldosterone levels, and occasionally nephrocalcinosis. Here we describe a 13-year-old boy who presented with severe hypertension, hypokalemia, low PRA and aldosterone levels, and elevated THF plus aTHF/THE ratio in the urine consistent with a diagnosis of AME syndrome. On ultrasound examination, he had severe nephrocalcinosis, and bilateral renal cysts. Renal cysts have not been previously reported in AME syndrome. The development of nephrocalcinosis and renal cysts may be associated with chronic long-standing hypokalemia. An early diagnosis and treatment of AME syndrome could help to prevent these sequelae, and to preserve renal function.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

The role of cytokines and cytokine gene polymorphism in T-cell activation and allograft rejection.

INTRODUCTION: Cytokines are largely responsible for the regulation of immunoregulatory events and therefore play an important role in transplantation immunology. Recent advances in genetics have made it possible to study the role of cytokine gene polymorphisms in allograft rejection. METHODS: This review describes studies that have analysed genetic variants in relation to renal disease and transplantation. RESULTS AND CONCLUSION: Polymorphism of cytokine gene promoters can significantly influence the level of cytokine production, which in turn affects the amount of immunosuppression needed. It is possible that in future, genotyping of transplant recipients with respect to their cytokine gene polymorphisms may help determine their risk of allograft rejection, and thus, provide a guide to individualised immunosuppression in the post-transplant period.

Animals↗
PubMed1999

Immunological characterization of anti-endothelial cell antibodies induced by cytomegalovirus infection.

BACKGROUND: We have previously shown that the levels of anti-endothelial cell antibodies (AECA) determined by an enzyme immunoassay are elevated during cytomegalovirus (CMV) infection in cardiac and renal transplant recipients. In a separate study, high levels of AECA are associated with higher frequency of humoral allograft rejection (AR), chronic AR and lower 2 year allograft survival in cardiac transplant recipients. These results suggests that high levels of AECA produced during CMV infection may have a pathogenic role or be a risk factor for humoral AR, chronic AR and decreased allograft survival. Here we examined the reactivity of AECA against endothelial cells and other tissues to further characterize AECA induced by CMV infection. METHODS: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis was performed. RESULTS: The number and intensity of bands reactive with human umbilical vein ECs (HUVECs) increased during and after CMV infection. AECA(+) plasma reacted with multiple antigens expressed not only on endothelial cells but also on human fibroblasts, keratinocytes, platelets (PLs), peripheral blood mononuclear cells (PBMCs), Raji cells and THP-1 cells. Each individual's AECA(+) plasma showed different patterns of reactivity against these cells, whereas each plasma showed similar patterns of reactivity against ECs, PLs or peripheral blood mononuclear cells obtained from different individuals. AECA(+) plasma also showed a similar pattern of reactivity against HUVECs pretreated with/without interferon-gamma/tumor necrosis factor-alpha. The reactivity of preabsorbed sera with PLs significantly decreased against most reactive antigens expressed on PLs and other cell types. CONCLUSIONS: (1) Antibodies induced by CMV infection are not specific to endothelial cells and appear to react with multiple cell types, (2) AECA (+) plasma react with multiple antigens expressed on various cell types that are primarily constitutively expressed on these cells and are not individual specific, (3) CMV-induced antibodies in AECA (+) plasma are primarily autoantibodies. These results suggest that the elevated AECA levels seen in CMV-infected transplant recipients may represent a polyclonal activation of humoral immune responses induced by CMV, which is of uncertain pathogenic significance.

Autoantibodies↗
PubMed1999

Prolongation of skin allograft survival is associated with reduced Th1 cytokine responses in the WKY-->F344 rat model.

BACKGROUND: We have reported previously that F344 rats develop a spontaneous tolerance to WKY lung allografts and show long-term retention of donor-specific skin grafts placed 35 days after lung transplantation. In this study, we investigated the immunologic mechanisms that may be responsible for the prolonged skin graft survival in animals tolerized with lung allografts. METHODS: In the rejection group, WKY skin grafts were placed on normal F344 rats, whereas, in the tolerance group, the skin grafts were placed on F344 rats that had received a WKY lung transplant 35 days before skin grafting. Th1 (interleukin [IL]-2 and interferon-gamma [IFN-gamma]) and Th2 (IL-4 and IL-10) cytokine as well as transforming growth factor-beta1 mRNA expression in skin grafts and in draining lymph nodes were determined by reverse transcription-polymerase chain reaction. Macrophage and lymphocyte infiltration in skin grafts and the number of Langerhans cells in epidermal sheets of the grafts were examined by immunohistochemistry. RESULTS: IL-2 and IFN-gamma mRNA expression was significantly decreased in both the skin grafts and the draining lymph nodes of the tolerance group, compared to the rejection group, whereas IL-10 and transforming growth factor-beta1 mRNA expression was similar in both groups and IL-4 mRNA was rarely detected. Decreased and delayed CD8+, macrophage, and natural killer cell infiltration in the skin grafts from the tolerance group was also detected. Similar reduction in the number of Langerhans cells in the epidermis of the grafts from both groups was seen on day 1 after skin grafting, and thereafter the number remained stable in both groups. CONCLUSIONS: Reduced expression of Th1 cytokines and decreased infiltration of CD8+ cells, macrophages, and natural killer cells in the skin grafts may be responsible for prolongation of skin graft survival in the tolerance group.

Animals↗
PubMed1999

Antithrombin III treatment improves parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection.

BACKGROUND: Antithrombin III (AT-III) is an antithrombotic agent with known anti-inflammatory properties that is also known to attenuate acute inflammation, prevent ischemia-reperfusion injury, and disseminated intravascular coagulation (DIC) associated with sepsis and endotoxemia. Here, we examined the ability of AT-III to modify parameters of acute inflammation in a highly histoincompatible model of rat lung allograft rejection (AR). METHODS: After left single lung transplantations (BN-->Lew), recipient animals were treated i.v. with 50 U/kg of human AT-III (low dose group), 500 U/kg of human AT-III (high dose group), or normal saline (control group) on days 2 and 4 posttransplant. All animals were sacrificed on day 6, and several pathological categories of acute inflammation related to AR were scored (0-4). The effect of AT-III on concanavalin A (Con A)-stimulated rat spleen cell proliferation was also examined. RESULTS: The stage of AR, and the degrees of edema, hemorrhage, and necrosis were significantly reduced in the high dose group compared with the control group. AT-III significantly inhibited rat spleen cell proliferation in response to Con A, in a dose-dependent manner. Maximal inhibition was seen at 15 U/ml in culture. Identical inhibition of Con-A-stimulated cultures occurred in both serum free and serum-containing media, indicating that AT-III inhibition of Con-A-stimulated rat spleen cell proliferation is independent of its actions on thrombin. CONCLUSIONS: 1) AT-III treatment significantly improves parameters of acute inflammation seen in a highly histoincompatible model of rat lung AR. 2) AT-III inhibits in vitro T cell proliferation to the potent mitogen Con A, suggesting that protease inhibition may inhibit T cell activation in vitro. 3). The beneficial effects of AT-III on parameters of lung AR relate to the anti-coagulant, anti-inflammatory, and possibly immunoregulatory actions of AT-III.

Acute Disease↗
PubMed1999

The clinical significance of antibodies to human vascular endothelial cells after cardiac transplantation.

BACKGROUND: Vascular endothelial cells are primary targets for injury during both cellular and humoral allograft rejection (AR). In cardiac transplantation, the role of humoral immunity in mediating AR has not been extensively characterized. METHODS: Antibodies against human vascular endothelial cells (AECA) were measured using a cellular ELISA developed from human umbilical vein endothelial cells in 80 consecutive patients after cardiac transplantation. The aim was to determine the incidence of AECA formation after transplantation and their association with different types of AR, graft survival, and development of cardiac allograft vasculopathy (CAV). At least eight serum samples obtained from each patient were examined for AECA and an endomyocardial biopsy was performed at regular intervals during the first year after transplantation. RESULTS: Of the 80 patients examined, 31 were AECA (+) and 49 patients were AECA (-). There were no significant differences between the AECA (+) and (-) groups when examined for age, sex, and pretransplantation ischemia time. A significant correlation was found between the presence of AECA and humoral AR (P<0.015). AECA positivity did not correlate with the presence of cellular AR or the number of rejection episodes. In addition, allograft survival at 2 years after transplantation was significantly better in the AECA (-) group compared with that in the AECA (+) group (89.8% vs. 71.0%, P<0.0004). The persistence of AECA positivity during the first year after transplantation was also associated with a significantly greater incidence of CAV when compared with the patients who were AECA (-) (25.8% vs. 14.3%, P<0.004). CONCLUSIONS: AECA may be important in the mediation of humoral AR, may decrease allograft survival, and may identify a high-risk group for CAV.

Adolescent↗
PubMed1999

Improvement in lupus nephritis following treatment with a Chinese herbal preparation.

OBJECTIVE: To study the effect of a Chinese herbal decoction (CM), which contained 21 different herbs, on clinical remission in a patient with lupus nephritis and chronic nephrotic syndrome. DESIGN: Case report describing the clinical and laboratory markers of lupus activity in the patient before and after treatment with CM. We also studied the in vitro effect of CM and its hydrophobic extract on spontaneous IgG production by peripheral blood mononuclear cells (PBMCs) from 12 patients with systemic lupus erythematosus (SLE) compared with 9 healthy control subjects. RESULTS: Spontaneous PBMC IgG production was significantly higher in patients with SLE (mean +/- SD, 20.4+/-10.6 x 10(-5) g/L) compared with controls (4.7+/-1.9 x 10(-5) g/L) (P<.001). Addition of CM and its hydrophobic extract to PBMCs from patients with SLE resulted in significant suppression of spontaneous IgG production. CONCLUSIONS: The CM may contain some active pharmacological compound with immunosuppressive properties useful in the treatment of SLE. Further controlled studies are important to evaluate the efficacy of this medicine, potential toxic effects, and the possible immunosuppressive mechanisms of the active component(s).

Adolescent↗