Search PubMed⌕ Search

Biomedical subjects

A D Kirk

Publications and source records attributed to A D Kirk.

At least 55 records · Page 3Linked to original sources
PubMed1999

Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154.

Clinical islet cell transplantation has resulted in insulin independence in a limited number of cases. Rejection, recurrence of autoimmunity, and impairment of normal islet function by conventional immunosuppressive drugs, e.g., steroids, tacrolimus, and cyclosporin A, may all contribute to islet allograft loss. Furthermore, intraportal infusion of allogeneic islets results in the activation of intrahepatic macrophages and endothelial cells, followed by production of proinflammatory mediators that can contribute to islet primary nonfunction. We reasoned that the beneficial effects of anti-CD154 treatment on autoimmunity, alloreactivity, and proinflammatory events mediated by macrophages and endothelial cells made it an ideal agent for the prevention of islet allograft failure. In this study, a nonhuman primate model (Papio hamadryas) was used to assess the effect of humanized anti-CD154 (hu5c8) on allogeneic islet engraftment and function. Nonimmunosuppressed and tacrolimus-treated recipients were insulin independent posttransplant, but rejected their islet allografts in 8 days. Engraftment and insulin independence were achieved in seven of seven baboon recipients of anti-CD154 induction therapy administered on days -1, 3, and 10 relative to the islet transplant. Three of three baboons treated with 20 mg/kg anti-CD154 induction therapy experienced delayed rejection episodes, first detected by elevations in postprandial blood glucose levels, on postoperative day (POD) 31 for one and on POD 58 for the other two. Re-treatment with three doses of anti-CD154 resulted in reversal of rejection in all three animals and in a return to normoglycemia and insulin independence in two of three baboons. It was possible to reverse multiple episodes of rejection with this approach. A loss of functional islet mass, as detected by reduced first-phase insulin release in response to intravenous glucose tolerance testing, was observed after each episode of rejection. One of two baboons treated with 10 mg/kg induction therapy became insulin independent post-transplant but rejected the islet graft on POD 10; the other animal experienced a reversible rejection episode on POD 58 and remained insulin independent and normoglycemic until POD 264. Two additional baboon recipients of allogeneic islets and donor bone marrow (infused on PODs 5 and 11) were treated with induction therapy (PODs -1, 3, 10), followed by initiation of monthly maintenance therapy (for a period of 6 months) on POD 28. Rejection-free graft survival and insulin independence was maintained for 114 and 238 days, with preservation of functional islet mass observed in the absence of rejection. Prevention and reversal of rejection, in the absence of the deleterious effects associated with the use of conventional immunosuppressive drugs, make anti-CD154 a unique agent for further study in islet cell transplantation.

Animals↗
PubMed1999

Transplantation tolerance: a look at the nonhuman primate literature in the light of modern tolerance theories.

Ever since the beginning of clinical transplantation, investigators have searched for a way to transplant tissues from one person to another without chronic immunosuppression. That goal, known as allograft tolerance, has remained clinically elusive. In the past decade, however, many of the fundamental principles of tolerance have been redefined, and biological agents capable of exploiting them in vivo have been developed. Accordingly, experimental methods for tolerance induction have rapidly evolved in concert with a growing understanding of physiological tolerance to self and the development of novel immunoreactive reagents. In general, old world monkeys have become the pre-clinical testing ground for methods that have shown reasonable promise for clinical application, particularly antibodies or other biological agents with limited cross-species reactivity. As such, a survey of the nonhuman primate experience in transplantation is representative of all reasonably successful experimental attempts to develop clinically applicable tolerance regimens. This article summarizes many of the concepts currently unfolding in the tolerance literature. It also reviews the techniques for tolerance induction that have been and are currently being investigated in nonhuman primates. The validity of these models is summarized, and the older literature is reinterpreted in light of recent changes in our understanding of tolerance.

ABO Blood-Group System↗
PubMed1998

Infant pediatric liver transplantation results equal those for older pediatric patients.

METHODS: From July 1984 to July 1995, 99 pediatric patients underwent 127 orthotopic liver transplants (OLT) at the University of Wisconsin Children's Hospital. The patients were divided into four groups according to age at time of transplant: group I, 0 to 6 months (n = 20); group II, 6 to 12 months (n = 18); group III, 1 to 2 years (n = 10); and group IV, 2 to 18 years (n = 51). A retrospective analysis was performed to compare these four groups with regard to preoperative indications and demographics, intraoperative technique, complications, and survival. All patients were followed up for 2 to 13 years. RESULTS: Biliary atresia was the most common indication for OLT in all four groups. The average waiting period varied from 19+/-18 days for group I to 44+/-64 days for group IV. Reduced-size liver transplant (I, 41%; II, 52%; III, 28%; IV, 21%), split-liver transplant (I, 0%; II, 7.4%; III, 17%; IV, 2.9%), or whole-liver transplant techniques were used. Although postoperative Intensive Care Unit stay was longer for the 0- to 6-month-old patients (I, 20+/-64; II, 7.6+/-9; III, 13+/-17; IV, 6.8+/-14 days), the total hospital stay (I, 43+/-63; II, 33+/-34; III, 32+/-20; IV, 29+/-31 days) was similar for all patients. The incidence of hepatic artery thrombosis (I, 19%; II, 19%; III, 27%; IV, 16%), biliary tract complications (I, 4.8%; II, 15%; III, 20%; IV, 14%), and retransplantation (I, 9.5%; II, 41%; III, 33%; IV, 14%) were not significantly different between the four groups. Portal vein thrombosis (I, 9.5%; II, 11%; III, 6.6; IV, 0%) and primary nonfunction (I, 9.5%; II, 7.4%; III, 0%; IV, 3.1%) occurred more frequently in the 0- to 6-month and 6- to 12-month groups, however, the 1-, 5-, and 10-year survival rate for patients (I, 85%, 79%, 79%; II, 89%, 74%, 74%; III, 80%, 80%, 80%; IV, 84%, 75%, 75%, respectively) and primary liver allografts (I, 69%, 69%, 69%; II, 72%, 72%, 63%; III, 70%, 70%, 70%; IV, 71%, 57%, 57%, respectively) were not significantly different (P = .98 and P = .83). CONCLUSION: These results demonstrate that OLT can be effectively performed on infants of all ages and that OLT should not be delayed because of age.

Adolescent↗
PubMed1997

Posttransplant diastolic hypertension: associations with intragraft transforming growth factor-beta, endothelin, and renin transcription.

BACKGROUND: Diastolic hypertension after renal transplantation leads to significant chronic morbidity and mortality. Recently, calcineurin phosphatase inhibition by cyclosporine or tacrolimus has been postulated to lead to diastolic hypertension through the induction of transforming growth factor-beta (TGF-beta) and resultant endothelin-mediated renal arteriolar vasospasm. METHODS: To investigate this hypothesis in humans, the allografts of 40 stable renal allograft recipients were biopsied 2 to 3 years after transplantation. Both cyclosporine and tacrolimus patients were included. Biopsies were divided and processed for histology and RNA extraction. RNA was then converted to cDNA and evaluated by semiquantitative polymerase chain reaction (actin-standardized, high-performance liquid chromatography-quantitated) for TGF-beta, endothelin, and renin transcription. Inflammatory cytokine gene transcription was also evaluated. Blood pressure was measured during the clinic check-in before biopsy. Variables were evaluated by Spearman rank correlation coefficient (rs) analysis. RESULTS: Diastolic hypertension was prevalent in the study population, with 40% of individuals having diastolic pressure >90 mmHg. TGF-beta and endothelin transcription were detected in 88% of biopsies studied, and renin transcription was detected in 91%. Intragraft transcription of TGF-beta (rs=0.61, P=0.0003) and endothelin (rs=0.43, P=0.0188) was strongly correlated with increasing transcription intragraft renin. In turn, renin transcription was strongly correlated with increasing diastolic blood pressure (rs=0.55, P=0.0015). Histological correlation of fibrosis score did not predict the degree of hypertension, nor did it correlate with TGF-beta transcription. Inflammatory cytokine transcription was not related to renin transcription or diastolic hypertension but was correlated with histological evidence of immune graft injury. CONCLUSIONS: These data support the hypothesis that posttransplant diastolic hypertension is a result of TGF-beta-induced, endothelin-mediated arteriolar vasoconstriction and subsequent activation of the renin-angiotensin pathway. These effects are independent of immune-mediated graft injury.

Adult↗
PubMed1997

CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates.

Selective inhibition of T cell costimulation using the B7-specific fusion protein CTLA4-Ig has been shown to induce long-term allograft survival in rodents. Antibodies preventing the interaction between CD40 and its T cell-based ligand CD154 (CD40L) have been shown in rodents to act synergistically with CTLA4-Ig. It has thus been hypothesized that these agents might be capable of inducing long-term acceptance of allografted tissues in primates. To test this hypothesis in a relevant preclinical model, CTLA4-Ig and the CD40L-specific monoclonal antibody 5C8 were tested in rhesus monkeys. Both agents effectively inhibited rhesus mixed lymphocyte reactions, but the combination was 100 times more effective than either drug alone. Renal allografts were transplanted into nephectomized rhesus monkeys shown to be disparate at major histocompatibility complex class I and class II loci. Control animals rejected in 5-8 days. Brief induction doses of CTLA4-Ig or 5C8 alone significantly prolonged rejection-free survival (20-98 days). Two of four animals treated with both agents experienced extended (>150 days) rejection-free allograft survival. Two animals treated with 5C8 alone and one animal treated with both 5C8 and CTLA4-Ig experienced late, biopsy-proven rejection, but a repeat course of their induction regimen successfully restored normal graft function. Neither drug affected peripheral T cell or B cell counts. There were no clinically evident side effects or rejections during treatment. We conclude that CTLA4-Ig and 5C8 can both prevent and reverse acute allograft rejection, significantly prolonging the survival of major histocompatibility complex-mismatched renal allografts in primates without the need for chronic immunosuppression.

Abatacept↗
PubMed1997

A survivor of breast cancer with immunity to MUC-1 mucin, and lactational mastitis.

The human mucin, MUC-1, is a transmembrane glycoprotein that is produced by both normal an malignant epithelium. The MUC-1 produced by malignant epithelium is underglycosylated, which leads to the expression by tumors of novel T and B cell epitopes on the mucin polypeptide core. Similar underglycosylation occurs in the lactating breast. In this report, we describe a long-term survivor of breast cancer whose tumor strongly expressed the T- and B-cell-stimulatory epitopes. Five years after presenting with the tumor, the patient had her first pregnancy, at which time she developed fulminant lymphocytic mastitis. We demonstrate that the lactating breast produced mucin expressing the same "tumor-specific" epitopes as the original cancer. The patient had circulating anti-mucin antibodies of both the IgM and IgG isotypes (these are not found in normal controls), and mucin-specific cytotoxic T lymphocytes in the peripheral blood. Limiting-dilution analysis for mucin-specific cytotoxic T lymphocytes in three different experiments yielded frequencies of 1 in 3086, 1 in 673, and 1 in 583, compared to approximately 1 in 10(6) in normal controls. The patient remains clinically free of carcinoma after 5 additional years of follow-up. We propose that the original tumor primed the patient's immune response against the mucin epitopes, and that the re-expression of these epitopes on the lactating breast evoked a secondary immune response. It is tempting to speculate that the vigor of her anti-mucin immunity may have helped protect this patient against recurrent tumor.

Adult↗
PubMed1996

Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys: HLA-DR3 as a risk factor for the development of posttransplant hepatitis.

BACKGROUND: Exposure to hepatitis C virus (HCV) and subsequent infection after renal transplantation lead to significant clinical hepatitis in approximately 50% of graft recipients. METHODS: One hundred thirty-two consecutive renal allotransplant patients, who underwent transplantation of kidneys from HCV-positive cadaveric donors, were studied to investigate the relationship between donor and recipient HLA type and the risk of developing clinical hepatitis. Specific attention was directed toward the DR3 and DR4 alleles, as these had previously been associated with worse prognoses in autoimmune and viral hepatitis. RESULTS: Overall, 42% of patients receiving kidneys from donors seropositive for HCV developed clinical hepatitis. This was unrelated to preoperative recipient HCV serum reactivity (P=0.65). Patients receiving kidneys from seropositive donors with HCV RNA as detected by PCR were more likely to develop hepatitis than those receiving kidneys from PCR-negative donors (56% vs. 11%; P=0.005). The presence of the DR3 allele was associated with a significant risk of clinical hepatitis (P=0.025); 80% of DR3-positive recipients (n=34) progressed to hepatitis compared with 42% of DR3-negative patients. No other recipient HLA type was significantly related to prognosis. All patients receiving a donated kidney that expressed the B41 allele developed hepatitis, compared with 55% of recipients of non-B41 grafts (P=0.039). No association between the development of clinical hepatitis and HLA compatibility was found. CONCLUSIONS: These results suggest that both HLA type and viral presence as assayed by polymerase chain reaction, influence the risk of disease progression after transplantation of HCV-positive kidneys. Application of these associations may decrease the relative risk of a recipient contracting HCV hepatitis after cadaveric renal transplantation.

Alleles↗
PubMed1996

Simultaneous pancreas--kidney transplantation: recent experience at the University of Wisconsin.

After a decade of rapid development, simultaneous pancreas--kidney (SPK) transplantation has become routine at the University of Wisconsin (UW). Since developing the concept of direct drainage of pancreas allograft exocrine secretions into the urinary bladder at UW in 1982, we performed 381 SPK transplantations in this technique. Patient and graft survival following SPK transplantation has increased significantly from our early experience to the recent time. The one- and five-year patient survival rates for the entire series of 381 SPK transplantations were 96% and 88% respectively. The actuarial one- and five-year kidney allograft survival rates in these patients were 87% and 78%. The pancreas allograft survival rates were similar at 86% and 74%. Several changes are responsible for our current high level of success. UW preservation solution, improved surgical technique, advances in immunosuppression, and expeditious diagnosis and treatment of complications.

Adult↗
PubMed1995

Rapid, comprehensive analysis of human cytokine mRNA and its application to the study of acute renal allograft rejection.

Cytokine mRNA analysis was performed on human renal allograft needle core biopsies by a PCR-based assay. The assay was specifically developed to be capable of simultaneous analysis of multiple interleukin transcripts (IL-1-IL-12), as well as those of other relevant cytokines, by one person in less than 1 day from cultured cells or directly from tissue samples. It was initially used on preparations containing known amounts of plasmid DNA encoding individual cytokine cDNA sequences, confirming that the sensitivity of this technique was both well defined and comparable for all target sequences tested. Analysis of human PBLs prior to stimulation, after polyclonal stimulation with PHA and after simultaneous treatment with PHA and MP or CyA, was also performed to show a proportional relationship between mRNA levels measured by PCR and protein release measured by ELISA (R2 = 0.86). This correlation was not adversely altered by pharmacologic immunosuppression by MP or CyA. Thus, this method of PCR primer design and usage was appropriate for the clinical study of cytokine mRNA levels during allograft rejection. Direct study of cytokine mRNA in allograft biopsy tissue showed that IL-2 was specifically and significantly (p = 0.006) elevated during ACR when compared to other causes of graft dysfunction. Transcripts from the IFN-gamma and IL-6 genes were also increased in ACR (p = 0.001 and 0.017, respectively), whereas increased IL-8 mRNA was correlated with irreversible loss of graft function (p = 0.02). TNF-alpha, IL-1 beta, and IL-10 gene transcripts were also detected during ACR, but were not quantitatively increased compared to other forms of graft injury (p > 0.2). We conclude that acute cellular rejection is associated with intragraft mRNA from the IL-2 gene. Other transcripts, including those from the IFN-gamma, IL-6, and IL-8 genes, are detected in increased amounts during this process. Messenger RNA from the TNF-alpha, IL-1 beta and IL-10 genes is also detected during ACR, but the presence of these transcripts is not exclusive to this process.

Base Sequence↗
PubMed1995

Simultaneous pancreas-kidney transplantation at the University of Wisconsin.

After a decade of rapid development, SPK transplantation has become routine at our center. There are several developments responsible for the current high level of success: UW preservation solution, improved surgical technique, advances in immunosuppression, and expeditious diagnosis and treatment of complications. The critical modifications in surgical technique have included the avoidance of systemic heparinization, complete mobilization of the iliac vein for a tension-free anastomosis between an unmodified donor portal vein and the recipient iliac vein, oversewing of the revised duodenal staple lines and meticulous hemostasis. The most important recent improvement in immunosuppression is the use of mycophenolate mofetil, which has dramatically reduced rejection. Finally, PDC leaks, the principal and potentially most devastating complication of SPK transplantation, are rapidly diagnosed and treated expeditiously.

Academic Medical Centers↗
PubMed1994

The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts.

The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, cannot be inhibited with currently available immunosuppressants. In two clinically relevant xenotransplantation models, this study evaluated the effect of C inhibition using recombinant soluble complement receptor type 1 (sCR1) on HAR. In an ex vivo model in which porcine cardiac Xgs were perfused with human blood, cardiac function ceased within 34 min when the perfusate blood was untreated (n = 3). When the perfusate blood was treated with sCR1 (300 micrograms/ml), cardiac Xg function was maintained for up to 4 hr (n = 3). Immunohistologic examination of these Xgs demonstrated deposition of C3b/iC3b and C3d in Xgs perfused with untreated human blood but only C3d deposition in those Xgs perfused with sCR1-treated human blood. These findings are consistent with the cofactor activity of sCR1 for factor I-mediated degradation of deposited C3b/iC3b to C3d. Treatment with sCR1 also prevented the histopathologic changes of HAR observed when untreated blood was used as the perfusate. In an in vivo pig-to-primate heterotopic cardiac xenotransplantation model, in which porcine Xgs transplanted into untreated cynomolgus monkey recipients underwent HAR in 1 hr or less (n = 3), a single intravenous bolus of sCR1 (15 mg/kg) administered to the recipient immediately before Xg reperfusion markedly inhibited total and alternative pathway serum C activity and prolonged Xg survival to between 48 and 90 hr (n = 5). These studies confirm the important role of C activation in HAR of porcine cardiac Xgs by primates and indicate that sCR1 may be a useful agent for xenotransplantation.

Animals↗
PubMed1993

Characterization of T cells expressing the gamma/delta antigen receptor in human renal allografts.

To investigate the role of gamma/delta+ T cells in allograft rejection, we have studied the TCR phenotype and function of lymphocytes infiltrating rejecting, rejected, and nonrejecting human renal allografts. Two-color immunohistologic staining showed that 19% of rejecting biopsies and 40% of rejected nephrectomies had significant infiltration (> 10% of the total T-cell population) with gamma/delta+ T cells. No biopsies from nonrejecting kidneys showed > 10% gamma/delta+ T cells. Flow-cytometry analysis of T-cell populations expanded from rejecting and rejected allografts demonstrated that 33% of biopsy- and 40% of nephrectomy-derived populations had significant percentages (> 10%) of gamma/delta+ T cells. Six cell lines with increased numbers of gamma/delta+ T cells were tested for cytolytic activity against the NK target cell line K562 and compared with cytotoxic activity of exclusively alpha/beta T-cell populations. Lysis was noted by all gamma/delta+, but no gamma/delta-, populations. To confirm that the cytotoxicity of these gamma/delta+ T-cell populations was not MHC directed, one nephrectomy-derived population with 69% gamma/delta+ T cells by cytometry and > 50% by immunohistology was studied extensively. High levels of killing were seen against the NK targets K562 and Daudi as well as other malignant, benign, and third-party renal cell lines, but relevant alloantigen-expressing targets were not killed. Sterile cell sorting was used to isolate the gamma/delta+ T cells. The gamma/delta+ cells displayed enhanced killing of K562 while the gamma/delta- cells showed no cytolytic activity. Cytotoxicity mediated by gamma/delta+ T cells was also demonstrated against donor-derived, untransformed renal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotoxicity, Immunologic↗
PubMed1993

Variables affecting the T cell receptor V beta repertoire heterogeneity of T cells infiltrating human renal allografts.

Donor-specific, alloreactive T cell lines may be grown from cells infiltrating human renal allografts. These T cell lines utilize restricted T cell receptor (TCR) beta-chain variable (V beta) gene repertoires, although long-term culture appears to be necessary for restriction to be observed. This study was undertaken to determine the effects of potential selective pressures on the TCR repertoires of allograft-infiltrating cells. TCR V beta repertoires of 30 allograft-derived T cell populations, cultured for defined, short time periods, were examined using polymerase chain reaction. When first derived, V beta repertoires of graft-infiltrating T cells were as heterogeneous as those of peripheral blood lymphocytes (PBL). There was no relationship between the length of time an allograft was in situ or the extent of HLA mismatch and repertoire heterogeneity. Repertoire restriction was positively correlated with the length of time cells were cultured in vitro. Long-term, alloreactive mixed lymphocyte reactions (MLR), established from normal, unsensitized PBL, also demonstrated V beta repertoire restriction during expansion in vitro. Restricted alloreactive populations emerged much more slowly from the MLR than from the allograft-derived cultures, however, implying that graft infiltrates contain previously activated populations of T cells. This observation, taken together with the fact that long-term, graft-derived cell lines maintain donor specificity, suggests that functional subsets must be allowed to emerge from heterogeneous infiltrates before TCR repertoire may be correlated with alloreactivity and/or graft rejection.

Biopsy↗
PubMed1993

Characterization of human anti-porcine "natural antibodies" recovered from ex vivo perfused hearts--predominance of IgM and IgG2.

Hyperacute rejection is a major obstacle to successful transplantation of vascularized xenogeneic organs and is believed to be mediated at least in part by performed xenoreactive "natural antibodies" (NAb). In this study, human NAb that could be involved in hyperacute rejection of pig heart xenografts were identified and characterized using an ex vivo model in which pig hearts were perfused with whole blood from individual human or pig donors. This ex vivo perfusion model allows for the continuous monitoring of physiologic parameters of cardiac function as well as sequential sampling of tissue and blood. Pig hearts perfused with allogeneic pig blood maintained normal function for at least 4 hr, whereas those perfused with xenogeneic AB+ human blood never achieved normal function and rejected completely after 30 min. In three separate experiments involving different human blood donors and pig hearts, sequential samples of perfused blood revealed a progressive depletion of anti-porcine NAb. Samples of all three rejected cardiac xenografts were homogenized, and the specifically bound human anti-porcine antibodies were eluted with citric acid. The eluted antibodies were enriched approximately 50-120-fold for anti-porcine reactivity compared with serum from the corresponding donor. Eluates contained NAb of predominantly IgM and IgG2 isotypes. Immunofluorescence histology confirmed the deposition of IgM and IgG2 but not other IgG subclasses in the rejected pig hearts. Since IgG2 utilized predominantly in response to bacterial polysaccharide antigens, our findings are consistent with the possibility that some NAb arise via crossreactivity with microbial antigens and are predominantly directed against carbohydrate rather than protein antigens.

Animals↗
PubMed1993

Ex vivo characterization of human anti-porcine hyperacute cardiac rejection.

Hyperacute rejection (HAR) currently precludes the use of discordant organs for human transplantation. In order to comprehensively evaluate HAR in a clinically applicable species combination, we have developed an ex vivo perfusion model utilizing a neonatal extracorporeal membrane oxygenator circuit; this model allows for functional and sequential biopsy studies of working piglet hearts sustained by human, single donor AB+ type blood. A detailed description of the methods employed is included. Hearts perfused by allogeneic pig blood sustained normal function throughout the study period, while those perfused with human blood lost organized ventricular contraction in 25-34 min with markedly attenuated function. Compared with biopsies from piglet hearts perfused with allogeneic blood and biopsies taken prior to human blood perfusion (t = 0), biopsies of hearts perfused with human blood at t = 15 and 30 min demonstrated significant inflammatory changes involving vessels (endothelial and myointimal swelling and reaction) as well as myocardium (injury and necrosis). By immunohistology, significant vascular deposition of IgM, IgG, fibrinogen, C3, and C1q was seen, along with infiltrates of human leukocytes consisting predominantly of neutrophils, macrophages, and T cells, with occasional B cells and NK cells. Sequential studies of circulating blood demonstrated the progressive consumption of human leukocytes and human anti-porcine antibodies, but no decrease in complement activity as measured by CH50. These findings indicate that the rapid loss of function seen in human anti-porcine cardiac HAR is associated with deposition of IgM and IgG xenoreactive antibody and early complement components and that extensive infiltration by inflammatory cells occurs within 15-30 min. This model provides a useful system for the study of human anti-porcine HAR.

Acute Disease↗