Simultaneous pancreas-kidney transplantation in a human immunodeficiency virus-positive recipient: a case report.

BACKGROUND: After the development of highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV), there has been increased interest in organ transplantation for this selected population. There is a lack of reports about pancreas transplant in HIV+ recipients. CASE REPORT: We report the case of a 43-year-old HIV+ man who presented with type 1 diabetes for 25 years and end-stage-renal disease. He underwent dialysis therapy for the prior 3 years. His CD4 count was 830 cells/mL and a negative viral load was achieved after 3 months of antiretroviral therapy. His nutritional status was favorable; no opportunistic infections had occurred. A simultaneous pancreas-kidney transplantation (SPKT) was performed from a 19-year-old deceased trauma victim. Pancreas implantation was enteric-portal drainage. No induction immunosuppression was used, but rather tacrolimus, sodium mycophenolate, and steroids. In the postoperative period, there was a delayed kidney graft function requiring hemodialysis for 14 days. On postoperative day 11, a kidney biopsy specimen showed mild rejection, which was successfully treated with steroids. The patient was discharged after 22 days; he was normoglycemic and insulin-independent with a serum creatinine value of 1.9 mg/dL. Currently, his outcome has been uneventful, without a readmission or opportunistic infections. After 5 months postoperation, the viral load is negative and the CD4 count is 460 cells/mL. The current serum creatinine level is 1.1 mg/dL; no insulin has been required. COMMENT: HIV has been considered to be an absolute contraindication to organ transplantation, because of the infection risk due to severe immunosuppression, to interactions between antiretroviral and immunosuppressive drugs, and to reluctance to offer an organ to a terminal patient. However, transplants in HIV+ patients have shown good results, when a patient has an acceptable CD4 level, a low viral load, and minimal antiretroviral therapy.

Specific binding of MAR/SAR DNA-elements by mutant p53.

Inactivation of the tumor suppressor p53 by single missense point mutations characterizes a large number of human tumors. At least some mutant p53 proteins not only have lost the tumor suppressor function, but at the same time reveal a variety of dominant oncogenic properties. The molecular basis of this 'gain of function' is still unknown. In this report we describe a new biochemical activity of mutant p53, the specific high-affinity interaction with MAR/SAR DNA-elements (nuclear matrix/scaffold attachment regions). This DNA-binding activity can be distinguished from the previously reported DNA-binding activities of p53 by its specificity for mutant p53, the high binding affinity, and the domains of the mutant p53 molecule involved in MAR/SAR DNA-binding. The MAR/SAR-binding region of mutant p53 maps to a bipartite domain consisting of the mutated core region and the C-terminal 60 amino acids, carrying the unspecific DNA-binding domain and the oligomerization motif. MAR/SAR elements are considered as important regulatory elements in a variety of nuclear processes. We propose a model according to which the specific interaction of mutant p53 with MAR/SAR elements might interfere with these processes, thereby exerting pleiotropic oncogenic effects.

Specific and complex interactions of murine p53 with DNA.

Biologically active mutant p53 from Balb/c mouse tumor cells (Meth A) was analysed for its specific interaction with DNA. Restricted phage lambda DNA, representing DNA of high complexity with regard to sequence and secondary structure, was used to probe for such an activity in a target-bound DNA-binding assay, using doubly immunopurified p53. A single lambda DNA fragment was specifically retained with very high affinity (KD = 10(-10) M). Specific DNA binding was shown to be an intrinsic property of p53, as it could be blocked with p53-specific monoclonal antibodies PAb122 and PAb421. The characteristics of the DNA binding of p53 to this lambda DNA fragment, as well as the structural properties of this fragment, suggested the possibility that p53 might be able to interact with nuclear matrix attachment region (MAR) DNA. Indeed, established genomic MAR elements were specifically bound by Meth A p53, whereas no binding was observed to an AT-rich control DNA. The interaction of p53 with MAR elements in vitro is compatible with the idea that p53 in vivo is involved in the regulation of replication and/or expression of cellular DNA. Complex DNA interactions were not restricted to mutant p53 from Meth A cells. Mutant p53 of a different conformational phenotype (PAb246+ 'wild-type' as opposed to PAb246- 'mutant' for p53 from Meth A cells) from minimally transformed T3T3 cells, as well as genotypic wild-type p53 expressed by a recombinant baculovirus in insect cells, exhibited similar DNA-binding properties.

Hypoxemia during hemodialysis using acetate versus bicarbonate dialysate.

To evaluate the extent and cause(s) of dialysis-related hypoxemia, we studied 10 patients, 7 days apart using acetate (AC) and bicarbonate dialysate (HCO3). We measured arterial blood gases, WBC, minute ventilation (VE) and inspired and expired gas concentrations and calculated the respiratory quotient (R) and the alveolar-arterial oxygen difference (A-a)DO2 before and during hemodialysis. 8 patients developed hypoxemia. Arterial PO2 (PaO2) dropped similarly at 30 min from 93 +/- 5 to 78 +/- 6 (p less than 0.05) and 89 +/- 4 to 79 +/- 5 mm Hg (p less than 0.05) with AC and HCO3, respectively. R and VE decreased during AC (p less than 0.05). (A-a)DO2 increased at 30 min and correlated with the drop in PaO2 during both AC (r = 0.68, p less than 0.025) and HCO3 (r = 0.76, p less than 0.025). The fall in PaO2 also correlated with the fall in WBC count for both AC and HCO3 (r = 0.63, p less than 0.005). The increase in arterial pH during HCO3 (up to 7.45 +/- 0.01) was significantly greater than that during AC (up to 7.42 +/- 0.01) (p less than 0.025), and coincided with a relative decrease in VE. We conclude that (1) HCO3 does not prevent hypoxemia, and (2) hypoventilation V/Q abnormalities and increase in arterial pH, contribute variably to dialysis related hypoxemia depending on the type of dialysate and the time during dialysis.

Hypercalcemia in active pulmonary tuberculosis.

We ascertained the incidence of hypercalcemia in 79 consecutive patients with active pulmonary tuberculosis and a control group of 79 patients with chronic obstructive pulmonary disease. Twenty-two patients developed hypercalcemia (serum calcium greater than 10.5 mg/dl) within 4 to 16 weeks after initiation of chemotherapy for tuberculosis. The duration of hypercalcemia ranged from 1 to 7 months, and remission occurred spontaneously in all patients. The mean daily vitamin D supplement was greater in hypercalcemic patients than in the normocalcemic group. There was a positive correlation between daily vitamin D supplement and degree and duration of hypercalcemia. Mean serum calcium in patients with tuberculosis was higher than in patients with chronic obstructive pulmonary disease supplemented with the same dose of vitamin D. Hypercalcemia appears to be related to the activity of pulmonary tuberculosis and the intake of vitamin D; the exact mechanism, however, remains unknown.