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Biomedical subjects

P Pfeffer

Publications and source records attributed to P Pfeffer.

At least 19 recordsLinked to original sources

Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma.

Analyses of the human PAX-5 locus and of the 5' region of the mouse Pax-5 gene revealed that transcription from two distinct promoters results in splicing of two alternative 5' exons to the common coding sequences of exons 2-10. Transcription from the upstream promoter initiates downstream of a TATA box and occurs predominantly in B-lymphocytes, whereas the TATA-less downstream promoter is active in all Pax-5-expressing tissues. The human PAX-5 gene is located on chromosome 9 in region p13, which is involved in t(9;14)(pl3;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype and in derived large-cell lymphomas. A previous molecular analysis of a t(9;14) breakpoint from a diffuse large-cell lymphoma (KIS-1) demonstrated that the immunoglobulin heavy-chain (IgH) locus on 14q32 was juxtaposed to chromosome 9p13 sequences of unknown function [Ohno, H., Furukawa, T., Fukuhara, S., Zong, S. Q., Kamesaki, H., Shows, T. B., Le Beau, M. M., McKeithan, T. W., Kawakami, T. & Honjo, T. (1990) Proc. Natl. Acad. Sci. USA 87,628-632]. Here we show that the KIS-1 translocation breakpoint is located 1807 base pairs upstream of exon 1A of PAX-5, thus bringing the potent Emu enhancer of the IgH gene into close proximity of the PAX-5 promoters. These data suggest that deregulation of PAX-5 gene transcription by the t(9;14)(pl3;q32) translocation contributes to the pathogenesis of small lymphocytic lymphomas with plasmacytoid differentiation.

Amino Acid Sequence

[Pancreas transplantation. A 10-year material].

A programme for pancreas transplantation was initiated in Oslo in 1983. Of a total of 100 transplants so far, 14 were performed as pancreas transplantation alone (PTA) in non-uremic diabetics (n = 9), or as pancreas after kidney (PAK), i.e. in diabetic patients with a functioning renal transplant (n = 5). Duct occluded segmental grafts were used until 1988, when the pancreaticoduodenal technique with bladder drainage was introduced. Since 1991, owing to a low graft survival rate in PAK and PTA cases, all pancreas transplantations have been performed simultaneously with a renal transplant, giving a one-year survival of 82%, 83% and 93% for kidney, pancreas and patient respectively. The authors give a brief overview of the experience gained during ten years, with a pancreas transplant rate of ten/year.

Adult

Aortoiliac reconstruction in preparation for renal transplantation.

Aortoiliac angiography has always been an integral part of the pretransplantation work-up of renal transplant candidates in Norway. The present study was undertaken to investigate the value of this routine. Based on the angiograms of approximately 1400 patients evaluated for renal transplantation during the 7-year period 1984-1991, 26 were found to have aortic and/or iliac atherosclerosis requiring pretransplant vascular reconstruction. Fifteen of the 26 patients had aneurysm of the abdominal aorta and 11 had extensive aortoiliac occlusive disease. A prosthetic graft was inserted in 25 patients and endarterectomy of the aortic bifurcation was performed in one. The cause of death was coronary heart disease in four of six patients who died before, and in one patient who died after, transplantation. Sixteen patients received a renal transplant while four patients are still on the waiting list. Fifteen of the recipients are alive, 14 with functioning renal transplants. The low yield of patients below 40 years of age requiring vascular reconstruction calls into question the routine use of angiographic investigation of renal transplant candidates below this age. However, we recommend this routine for the higher age groups because it often provides the surgeon performing the transplantation with valuable information. Aortoiliac reconstruction as preparation for renal transplantation is advocated when atherosclerosis of a degree that may preclude transplantation is found. Because of the high risk of myocardial infarction in these patients, one must be especially aware of coronary atherosclerosis when evaluating patients for this procedure.

Adult

Fibro-muscular renal artery disease treated by extracorporeal vascular reconstruction and renal autotransplantation: short- and long-term results.

Over a 16-year period (1973-1989), 63 renal autotransplants were performed in 59 patients for fibro-muscular dysplasia (FMD) with renal artery stenoses (42 kidneys) or aneurysms (21 kidneys). About two-thirds of the autotransplants were performed before percutaneous transluminal angioplasty (PTA) was established for clinical use. However, vascular disease at a site or type not suitable for PTA was present in 57 (90%) of the kidneys. Hypertension was the leading symptom in 56 patients, including four in whom renal autotransplantation was performed as an emergency for acute renal artery occlusion or malignant hypertension. Blood pressure returned to normal or improved in 51 (91%) and remained unchanged in five patients (9%) following autotransplantation. Three patients with renal artery aneurysm in whom haematuria and loin pain were the indications for treatment, became asymptomatic following surgical intervention. Bilateral renal autotransplantation was performed synchronously in one and sequentially in three patients. There were no operative deaths, but two kidneys were lost postoperatively in two 2-year-old children owing to renal vascular thrombosis. In the follow-up period (mean 4.3 years), one additional kidney was lost at 3 months owing to progressive FMD. Blood pressure and renal function remained stable in all other patients. Based on the excellent results achieved in this series, it is concluded that extracorporeal vascular repair and renal autotransplantation is a safe procedure for the patient as well as the kidney affected by FMD. The procedure is advocated as an alternative to in situ reconstruction in patients with renal artery disease not accessible to PTA, such as aneurysms and complex branch renal artery stenoses.

Adolescent

Influence of renal angiography in living potential kidney donors.

The angiograms of 258 potential kidney donors were retrospectively reviewed to assess the influence of angiography for deciding whether or not to accept the potential donor for nephrectomy and which kidney to use for transplantation. Twenty-five potential donors were rejected. In only 8 of these was angiography necessary to reveal the pathology. Angiography was found to be important in deciding which kidney to donate. In 81 donors the right kidney was used for donation and in 50 this decision was based on findings at angiography.

Adult

Identification of D-sorbitol 3-phosphate in the normal and diabetic mammalian lens.

The 31P NMR spectra of mammalian lenses show, in addition to previously identified compounds such as ATP, Pi, glycerophosphorylcholine, and alpha-glycerophosphate, an unusual phosphorylated metabolite resonating at 6.5 ppm. The concentration of this compound increases manyfold in the lenses of diabetic rats concomitant with activation of the aldose reductase pathway. We have purified this material and have identified it as D-sorbitol 3-phosphate. It appears likely that this unusual metabolite of sorbitol may reflect or be part of the metabolic aberration of diabetes in the lens.

Animals

Human heart transplantation. Rejection risk factors.

The present analysis of risk factors in human cardiac transplantation is based on a review of 682 endomyocardial biopsies from 52 grafts in 51 recipients. Acute rejection was diagnosed in 149 biopsies (21.8%). The cumulative 1-year graft survival was 91.5 4%. Four out of seven patients died of irreversible rejection. An univariate analysis using the linearized rate of total rejection showed significantly higher frequency of acute rejection when donor and recipient differed for two HLA-DR antigens compared to zero or one HLA antigen disparity (p less than 0.01), as well as in patients treated with low dose steroids, Cyclosporine (CyA) and Azathioprine (p less than 0.01), compared to treatment with CyA high dose steroids. Other risk factors were graft ischemia extending 60 minutes (p less than 0.05) and patient age exceeding 40 years (p less than 0.05). A multivariate analysis using the competing risk hazard model for irreversible (= lethal) rejection was performed. The presence of two HLA-DR mismatches between donor and recipient was found to be an independent risk factor (relative risk = 8.9), and immunosuppression with CyA and high dose steroids without Azathioprine another (relative risk = 15.3). Potential risk factors such as donor and recipient sex, donor age, prior surgery and time on extracorporeal circulation were not of significant prognostic value neither in regard to rejection nor irreversible rejection.

Azathioprine