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C M Zmijewski

Publications and source records attributed to C M Zmijewski.

At least 19 recordsLinked to original sources
PubMed1999

Hyperacute rejection of a pulmonary allograft. Immediate clinical and pathologic findings.

The clinical and pathologic findings seen in hyperacute rejection are well documented in renal and cardiac allografts. We describe the second case of hyperacute rejection in a pulmonary allograft and detail the immediate clinicopathologic findings. The patient underwent a single lung transplant for severe COPD with postoperative course complicated by acute rejection and graft failure. Eleven days later, the patient underwent a second transplant with intra-operative course complicated by rapid pulmonary edema and copious production of frothy, pink fluid from the bronchial orifice of the allograft followed by death within four hours of anastomoses. Intraoperative biopsy and autopsy demonstrated platelet/fibrin thrombi, marked interstitial neutrophilia, alveolar edema, and antibody deposition on the endothelial surface and vasculature walls. Prior to the first transplant, the patient's serum had 0% panel reactive antibody and was crossmatch compatible with the first allograft. The patient's serum prior to the second transplant contained cross-reacting antibodies to the donor's B and T lymphocytes. The immediate clinical findings in this case are similar to the findings in a previously reported case. This report is the first documentation of the immediate pathologic features of hyperacute rejection in a lung allograft which are similar to those seen with other organ allografts.

Fatal Outcome↗
PubMed1997

Juvenile rheumatoid arthritis-like polyarthritis in chromosome 22q11.2 deletion syndrome (DiGeorge anomalad/velocardiofacial syndrome/conotruncal anomaly face syndrome).

OBJECTIVE: To investigate the association of polyarthritis and chromosome 22q11.2 deletions. METHODS: Eighty patients with chromosome 22q11.2 deletion syndrome followed up at The Children's Hospital of Philadelphia were examined for evidence of arthropathy or arthritis. Patients with chromosome 22q11.2 deletion syndrome and polyarthritis underwent laboratory evaluations of immunologic function to determine the relationship of their immunodeficiency to the polyarthritis. RESULTS: The prevalence of polyarthritis in patients with chromosome 22q11.2 deletion syndrome was markedly increased over the prevalence of polyarticular juvenile rheumatoid arthritis (JRA) in the general population. All 3 patients with polyarthritis had evidence of impaired T cell function. Two of the patients with polyarthritis also had IgA deficiency. CONCLUSION: The chromosome 22q11.2 deletion syndrome represents a primary T cell disorder which can be associated with a JRA-like polyarthritis. All 3 patients with polyarthritis had evidence of more extensive immunoregulatory derangements than those typically seen in patients with chromosome 22q11.2 deletion, and these derangements may have predisposed to the development of polyarthritis.

Arthritis↗
PubMed1996

Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy.

Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule.

Alleles↗
PubMed1995

Genetic polymorphism of the human tumor necrosis factor region in insulin-dependent diabetes mellitus. Linkage disequilibrium of TNFab microsatellite alleles with HLA haplotypes.

The TNF region within the MHC includes a number of immunologically important genes. Microsatellites TNFa and TNFb adjacent to TNF exhibit extensive polymorphism. Employing a PCR-based technique, we identified TNFab haplotypes and defined their distribution in 97 controls and 48 diabetics of Caucasoid origin in a search for other genes within the MHC potentially associated with IDDM. Twenty-five different TNFab haplotypes were identified. A significant difference (p < 0.0005) in frequency between patients and controls was found for TNFa1b5 (relative risk 53). However, no other TNFab microsatellites demonstrated significantly different frequencies. Among diabetics TNFa1b5 was found to be in linkage disequilibrium with HLA-DR3-B18, a haplotype known to be associated with IDDM. Thus the increased frequency of TNFa1b5 among diabetics could reflect a linkage disequilibrium with a gene within the TNF region or with other genes, including the HLAs, which characterize this haplotype. In both controls and diabetics TNFa2b3 and TNFa7b4 were in linkage disequilibrium with DR3-B8 and DR7, respectively. Among diabetics, TNFa2b1 and TNFa6b5 were in linkage disequilibrium with DR4-B62 and DR4-B44, respectively. It is intriguing that TNFab haplotypes, represented by a short piece of about 200 nucleotides in the untranslated region upstream of TNF beta gene, maintain strong linkage disequilibria with different HLA haplotypes extending over 1 million base pairs. The identification of TNFab microsatellites exhibiting a high polymorphic index in a region lacking known polymorphic markers may provide potentially important information regarding the association of HLA haplotypes with autoimmune diseases, as they are in close proximity to other genes of immunologic importance.

Alleles↗
PubMed1994

ABO antibodies.

Explore the source record for details and available documents.

ABO Blood-Group System↗
PubMed1994

Familial autoimmune myasthenia gravis.

We describe a family with parental consanguinity and five of 10 siblings affected by late-onset autoimmune myasthenia gravis. We propose a genetic mechanism as a predisposing factor in this family. Our analysis excludes the major histocompatibility complex, the beta subunit of the acetylcholine receptor, and the T-cell receptor alpha and beta subunits as candidate genes for the disorder in this family.

Aged↗
PubMed1992

Positive crossmatches against mandatorily shared kidneys.

From October 1987 through February 1990 approximately 8.5% (29/341) of all donor kidneys shipped under the UNOS Mandatory Sharing Policy were denied to 27 intended recipients due to a positive final crossmatch [XM(+)]. The intended recipients included 18.5% hispanics and 7.4% blacks compared to 2.4% and 1.6%, respectively, for XM(-) recipients (1-3). Further, more were highly sensitized with 81% having a current PRA greater than 10% and 56% with a peak PRA greater than 80% compared to 65% and 14%, respectively, for XM(-) recipients. More importantly, 19/27 (70%) of the recipient candidates may have had irrelevant positive XMs. The XM(+) patients were classified into five categories defined by: I) autoantibodies; II) transfusions in the 2 weeks prior to the availability of the donor; III) the XM technique; IV) highly sensitized regraft candidates with current and peak PRAs greater than 85% and V) antibody to unreported MHC antigens. Of these, 70% may have been denied a transplant due to IgM autoantibodies or the use of XM techniques lacking extensive evaluation. The authors propose that all XM(+) mandatorily-shared kidneys be examined for IgM autoantibody and that kidneys not be denied to potential recipients due to IgM autoantibody. In addition, to minimize exclusions based on positive B-cell XMs, it is proposed that mandatorily-shared kidneys be shared on the basis of the DR subtypes, insofar as is currently practical.

Histocompatibility Testing↗
PubMed1992

Renal transplantation at the University of Pennsylvania Medical Center: an update of results in the cyclosporine era.

This chapter presents a summary of living-related, living-unrelated, and cadaver renal transplantation performed at the University of Pennsylvania Medical Center between January 1984 and October 1992. Over the past 9 years, 895 patients (557 males, 338 females, mean age 42 yrs) received 942 renal transplants; 599 patients received kidneys from cadaver donors (n = 627) and 296 patients received kidneys (n = 315) from living donors of all types. During this period, 151 patients were retransplanted, sometimes more than once (159 total retransplants, 124 secondary grafts, and 35 third or more transplants). An analysis of patient ant graft survival rates (calculated by actuarial methods) for different categories of transplant recipients was performed. Black recipients, as a racial subcategory, had the poorest graft outcome, especially when followed over the long term. Graft survival rates for Black recipients who were retransplanted with cadaver grafts were even worse and were noted to be similar to the diabetic population that received cadaver retransplants (66% vs 62% at 1 yr and 32% vs 25% at 5 yrs). Diabetic recipients of living-donor transplants had excellent graft survival results, similar to nondiabetic, living-donor recipients (patient survival rates 98% and 92% vs 97% and 92% at 1 and 5 yrs; graft survival rates 92% and 82% vs 92% and 82% at 1 and 5 yrs). HLA-identical recipients of first cadaver grafts demonstrated the best outcome in the entire cadaver series (graft survival rates 91% and 83% at 1 and 5 yrs, respectively). HLA-identical recipients of second or more cadaver grafts had poorer results than expected (50% graft survival at 1 yr) despite a 100% patient survival rate. HLA-identical recipients of living-related grafts had the best graft survival rates (96% at 1 yr and 94% at 5 yrs) and superior graft survival rates for retransplanted grafts as well (100% at 1 and 5 yrs). We conclude that in the last decade, patient and graft survival rates for cadaveric and living-donor renal transplants have improved dramatically relative to the results obtained in the pre-CsA era. Long-term graft survival in Black recipients remains lower than in other races, suggesting the need to analyze other factors to explain poorer graft survival in this recipient population. Results in diabetic recipients continue to be excellent at our center, encouraging the continuation of our aggressive approach to try to transplant diabetics as early as possible, particularly when a living donor is available.

Academic Medical Centers↗
PubMed1992

Demonstration of passenger leukocytes in a case of Epstein-Barr virus posttransplant lymphoproliferative disorder using restriction fragment length polymorphism analysis.

Lymphocytic populations of the posttransplant lymphoproliferative disorder in a completely matched renal allograft and a recipient's regional lymph node were examined, using restriction fragment length polymorphism analysis with probe YNH24 to the variable number tandem repeat D2S44. The donor's DNA was found in lymphocytes extracted from both the grafted kidney and the recipient's lymph node 26 days after engraftment. In both these organs, the results of in situ hybridization with a terminally biotin-labeled oligonucleotide probe to the Not I tandem repeat region of the Epstein-Barr virus (EBV) genome, as well as those of Southern blot hybridization to the EBV nuclear antigen region of the EBV genome, were positive. These findings confirmed the presence of the donor's lymphocytes ("passenger leukocytes") in the host nodal tissue in human renal transplantation and implicated EBV as playing a role in the development of posttransplant lymphoproliferative disorder. It is speculated that the EBV proliferative stimulus contributed to the recipient and the donor lymphocyte expansions. Alternatively, the proliferation of both lymphocyte populations could result from a mutual stimulation by minor histocompatibility or other antigens.

Cell Division↗
PubMed1991

Renal transplantation despite a positive antiglobulin crossmatch with and without prophylactic OKT3.

The antiglobulin crossmatch (AGXM) is a sensitive technique employed by many transplant centers to enhance detection of preformed antibody to donor antigens that may cause hyperacute rejection. However, positive AGXM may detect irrelevant or very low titers of anti-HLA antibody precluding transplantation in suitable recipients. To investigate the significance of a positive AGXM, cadaveric renal transplantation was carried out despite a weakly positive AGXM (defined as cell killing above background but not greater than 20%) in 48 recipients. In an initial group (n = 10), maintained on triple therapy (cyclosporine, azathioprine, and prednisone), accelerated acute rejection occurred in 4 recipients and 3 grafts were lost. A subsequent group (n = 38) was treated with a prophylactic course of OKT3 then triple therapy. There were no episodes of accelerated acute rejection (P less than 0.01) although clinical hyperacute rejection claimed one graft and the incidence of delayed graft function was high (75%). The prophylactic OKT3 group had a reduced incidence of acute rejection (0.5 versus 1.0) per recipient and the onset of first episodes was delayed (mean onset: 13 versus 35 days after transplantation). One year actuarial primary graft survival was 88% in the prophylactic OKT3 group as compared with only 50% in the initial group. The outcome in the positive AGXM group was similar to a concurrent group (n = 32) with a negative AGXM and immediate graft function. On the other hand, the subset of positive AGXM regraft recipients treated with prophylactic OKT3 fared poorly, with a 36% (4/11) incidence of primary nonfunction. In summary, a positive AGXM, as defined in this report, is not a contraindication to primary renal transplantation--in fact, the use of the AGXM will identify recipients that would benefit from prophylactic OKT3.

Adult↗
PubMed1989

Delineation of false-positive HIV antibody response in patients with renal failure and history of multiple transfusions.

Four patients with a history of multiple blood transfusions who awaited renal transplantation were tested for human immunodeficiency virus (HIV) infection and found to be positive on enzyme immunoassay (EIA) and negative on Western blot. None of these patients had any clinical evidence of HIV infection. Absorption of these patients' sera with B-lymphoblastoid cell lines (B-LCL) positive for the serologic specificities DR3, DR4 (Dw4, Dw10, Dw14), and DR5 resulted in EIAs that were negative for HIV. Treatment of the B-LCL with an anti-DR monoclonal antibody (L243) interfered with the absorption of the serum sample by B-LCL. This indicates that the initial false-positive EIA results may be due to HLA antibodies. Furthermore, it was shown that these HLA antibodies are not limited in specificity to the HLA type of the host cell used in the preparation of the EIA reagents, but can consist of other DR specificities.

Antibodies, Monoclonal↗
PubMed1989

Equine class II MHC antigens: identification of two sets of epitopes using anti-human monoclonal antibodies.

Six mouse and 13 rat monoclonal antibodies (mAb) recognizing HLA-DR, DQ and DP antigens were used for the detection of cell surface class II MHC antigens of equine lymphocytes. The monoclonal antibodies were tested against peripheral blood lymphocytes (PBL) from a panel of thoroughbred horses, using two-color fluorescence flow cytometry. Seven of these mAbs reacted with both surface immunoglobulin positive (sIg+) and surface immunoglobulin negative (sIg-) lymphocytes. sIg+ cells stained consistently brighter than sIg- cells. The fluorescence pattern did not vary from donor to donor for each of the mAbs tested, except for SFR1-MI.2, which reacted with a variable intensity with cells from 47 of 53 horses tested. Immunoprecipitation with mAb SFR1-MI.2 and analysis by two-dimensional electrophoresis demonstrated the presence of light and heavy chains equivalent to HLA class II alpha and beta chains. Antibody N297 (DQ specific), previously shown to react with an epitope expressed on human B cells but not on mitogen-induced T cells, reacted only with sIg+ cells in 42 of 53 horses tested. The lack of staining of horses sIg- cells with N297 may be due to a low or lack of expression of this determinant on these cells or to a weak cross-reactivity of this antibody with equine antigens.

Animals↗