Biomedical subjects
W E Braun
Publications and source records attributed to W E Braun.
HLA molecules in autoimmune diseases.
The association of certain autoimmune diseases with HLA molecules is being refined through the use of sequence-specific oligonucleotide probes and amino acid sequencing, together with continuing elucidation of the functional features of HLA molecules derived from the milestone description by Bjorkman of the HLA molecular structure. The association of insulin-dependent diabetes mellitus and HLA began with weak associations of Class I antigens (B8 and B15) and progressed to Class II antigens (DR3 and DR4), then to subtypes of DR4 (Dw4, 10, and 14), and now to DQ molecules including the absence of aspartic acid at position 57 of the DQ beta chain and the presence of arginine at position 52 of the DQ alpha chain. In rheumatoid arthritis (RA) the HLA antigen association remains with certain Class II molecules of the DR series (DR4 and DR1) that share amino acid sequences with a restricted number of other DR antigens seen in RA, as well as a segment of the gp 110 protein of the Epstein-Barr virus. Although ankylosing spondylitis has a strong association with the Class I antigen B27, that association is not explained by any of the B27 subtypes defined by monoclonal antibodies, by the eight variable amino acids in B27 subtypes, or by the two unique amino acids on B27. The remarkable antibody cross-reactivity among lymphocytes bearing B27, a synthetic peptide sequence (63-84) of B27, and the 188-193 sequence of K. pneumoniae nitrogenase has provided strong support for molecular mimicry being an important mechanism in the association of HLA molecules with disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Transplantation. Presidential address.
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Donor-specific antibodies. Clinical relevance of antibodies detected in lymphocyte crossmatches.
Positive donor crossmatches due to lymphocytotoxic antibodies generally have an adverse effect on allograft survival, but with numerous variations. Different laboratory techniques used to characterize lymphocytotoxic antibody, new antibody systems, such as those incited by endothelial/monocyte and epithelial antigens, the variable tempos and histopathologic changes of early rejections caused by these antibodies, and the specific features imposed by each organ, all combine to make the once simple crossmatch test a complex, clinical and laboratory crossroads, that directs the initial and perhaps ultimate course of the allograft. An integrated assessment of these factors is provided in this article.
Outcome of renal transplantation in patients with a functioning graft for 20 years or more.
In the present study long-term morbidity, quality of life and over-all rehabilitation were assessed in 14 patients with a functioning renal allograft for 20 years or longer. Followup ranged from 20 to 27 years (mean 22.5 years). All patients enjoyed excellent and stable renal function, and the mean serum creatinine level at 20 years was 1.3 mg. per dl. Complications related to long-term immunosuppressive therapy comprised infection in 8 patients (57%), malignancy in 7 (50%), cardiovascular disease in 6 (43%), cataracts in 3 (21%) and avascular necrosis of the hip in 2 (14%). Over-all quality of life was excellent in 13 patients who were able to return to work, participate in pre-illness levels of activity and enjoy sexual activity. While successful renal transplantation allows patients with end stage renal failure to resume relatively normal lives, these patients remain prone to complications resulting from long-term immunosuppressive therapy.
Long-term complications of renal transplantation.
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Ineffectiveness of dipyridamole SPECT thallium imaging as a screening technique for coronary artery disease in patients with end-stage renal failure.
The efficacy of dipyridamole single photon emission computed tomography (SPECT) thallium as a screening test for coronary artery disease (CAD), was studied in 45 patients with end-stage renal failure undergoing evaluation for renal transplantation. Coronary arteriography, dipyridamole SPECT thallium imaging and clinical follow-up were performed in all patients. Nineteen patients (42%) had an obstruction of 50% or more in at least one coronary artery. Fourteen patients had a positive thallium scan, but 7 of these were false-positives (sensitivity 37%, specificity 73%). The sensitivity was considerably lower than that quoted for non-ESRF patients in the literature, and significantly lower than a control group of 19 patients without ESRF having comparable severity and distribution of CAD. Five of the 6 patients who died of cardiac causes over a mean follow-up period of 25 months had normal thallium imaging, but all had significant coronary artery disease at cardiac catheterization. Dipyridamole SPECT thallium imaging has not proved a useful screening test for angiographically significant CAD, and does not predict cardiac prognosis in this population.
Laboratory and clinical management of the highly sensitized organ transplant recipient.
Just a short time ago high levels of preformed lymphocytotoxic antibodies in potential renal transplant recipients constituted an almost insurmountable obstacle to finding a suitable donor. Breakthroughs in the areas of serology (e.g., removal of IgM antibodies and the use of CLL cells for serum screening), strategy (use of a calculated cumulative probability of transplantability to determine the necessary donor pool size), and therapy (the use of Staph A immunosorbent columns to remove IgG from the patient's serum and the advent of recombinant erythropoietin) are rapidly evolving to the point where there is promise of substantially improving the chances of transplanting highly sensitized patients.
Nephrotic range proteinuria with "minimal change glomerulopathy" in human renal allografts: report of four cases.
Four patients who received renal allografts developed nephrotic range proteinuria 2 to 16 months after renal transplantation. Twenty-four-hour urine protein excretion at the time of renal allograft biopsy ranged from 5.9 to 17.0 g/24 hours. The serum creatinine at the time of renal allograft biopsy ranged from 2.0 to 3.9 mg/dl (180 to 350 mumol/L). Biopsies of the allografts demonstrated minimal glomerular abnormalities by light microscopy, immunomicroscopy, and electron microscopy. Two biopsies exhibited severe interstitial fibrosis. These four cases illustrate the unusual finding of "minimal change glomerulopathy" in renal allograft recipients exhibiting nephrotic range proteinuria. All four patients progressed to dialysis 4, 36, 46, and 53 months after transplantation. Transplant nephrectomy was performed in three patients. One showed acute cortical necrosis. Two showed glomerular, vascular, and tubular-interstitial features of chronic rejection.
Two major serologic events in a successful cardiac transplant recipient--circumvention of hyperacute rejection despite a positive donor T lymphocyte crossmatch and late appearance of probable antiidiotypic antibody.
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The HLA histocompatibility system in autoimmune states.
The HLA system of antigens identified serologically and, in some cases, by cellular techniques has shown important associations with numerous autoimmune diseases. As DNA technology becomes more widely used, there is great expectation that restriction fragment length polymorphisms (RFLP) and oligonucleotide probing of the HLA genes will soon provide for clinical use even more definitive relationships with these diseases and possibly insights into their pathogenetic mechanisms.
HLA-DR2 and narcolepsy.
Tissue typing was performed on 14 narcoleptics as defined by both strict sleep laboratory and clinical criteria. Six of these patients were blacks from North America, a race underrepresented in previous studies. All patients were HLA-DR2-antigen positive and had the same HLA-DR2 subtype. Clinical severity of disease was not correlated with HLA-DR2 heterozygosity or (putative) homozygosity. This study confirms that the extremely high association between HLA-DR2 and narcolepsy holds across comparisons of the three races studied to date when both clinical and sleep laboratory data are used. The presence or absence of HLA-DR2 in patients presenting with hypersomnolence may help support or exclude, respectively, a diagnosis of idiopathic narcolepsy.
Management of the sensitized patient awaiting a cadaver allograft.
One of the most difficult problems in renal transplantation, and one that is steadily worsening, is finding acceptable kidneys for the highly sensitized transplant candidate whose antibody level may translate into years of waiting for a cadaver kidney. The causes of such sensitization are well known to be prior allografts, pregnancies, and transfusions. The longer a transplant center has been in existence, the larger is its pool of such highly sensitized patients. Patients who have rejected a previous transplant are a major contributor to this pool, especially when that transplant was poorly matched. Even though rejection losses have been cut from about 50 to 25% since 1973, the dramatic increase in the number of transplants and the sharply lower mortality rate together have led to twice as many patients being returned to waiting lists. As a preventive measure, better human lymphocyte antigen (HLA) matching would help to reduce rejection rates further and, for those that do reject, would lessen their sensitization levels and their waiting time for a second kidney. Measures to diminish the consequences of sensitization have included determining a patient's antibody specificities in order to create a profile of safe donor antigens. Making sensitized patients priority patients and sharing kidneys for them are important measures as well, but the proper definition of a highly sensitized patient requires more than a simple panel reactive antibody (PRA) value. The calculation of the combined probability (pc) of transplantation, based on HLA and ABO gene frequencies, more accurately reflects the true transplantability of a potential recipient.(ABSTRACT TRUNCATED AT 250 WORDS)
Perforation of the colon in renal homograft recipients. A report of 11 cases and a review of the literature.
Colon perforation in renal transplant recipients is a potentially lethal condition that is amenable to appropriate medical and surgical treatment. The 11 cases seen at the Cleveland Clinic (incidence 1.1% of all renal transplant patients) and previous reports in the literature have been reviewed. The pathogenesis is related to a high incidence of diverticular disease in patients with polycystic kidneys and/or chronic renal failure, the effects of long-term immunosuppression, and the transplant procedure itself. The high mortality of this condition (61% overall) is related to the effects of immunosuppression on the response to sepsis and the surgical procedure used. Mortality has fallen from 88% (1970-1974) to 53% (1975-1979), and there are indications that it is continuing to fall. All four cases operated on here since 1980 have survived, giving a total operative mortality of 2/6, and all have maintained excellent allograft function. A high clinical index of suspicion, prompt exteriorization of the perforated colon, reduction of immunosuppression to minimal levels, and effective antibiotic coverage have all contributed to the declining mortality.
A monoclonal antibody detecting a possible public specificity of the HLA-C locus.
An IgM monoclonal antibody (CC-Cl 11) was produced by fusing myeloma cell line SP2/08 with lymphocytes of a Balb/c mouse previously immunized with peripheral blood lymphocytes of an A2, Bw44, B27, Cw1, Cw7, DR5 donor. Reactivity of CC-Cl 11 on a lymphocyte panel of 172 unrelated donors and lysostripping and absorption experiments have shown that CC-Cl 11 recognizes an antigenic determinant common to HLA-Cw1 and Cw3 positive lymphocytes.
HLA-DR antigens in alopecia areata. Preliminary report.
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FLow cytometry quantitation of peripheral blood T-cell subsets as a monitor of renal allograft rejection.
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Renal transplantation. An analysis of logistical and medical factors affecting cadaver organ availability.
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