Biomedical subjects

Peter I Lobo

Publications and source records attributed to Peter I Lobo.

4 recordsLinked to original sources

PubMed2006

Correction of renal hypertension after kidney transplantation from a donor with Gitelman syndrome.

The relationship between the kidney and blood pressure control is complex. Monogenetic forms of hypertension have recently been identified that implicate specific mutations responsible for blood pressure control. The thiazide sensitive Na-Cl cotransporter (NCC) has been implicated in the control of blood pressure, however a direct link between the kidney NCC and blood pressure regulation is lacking. Here, we report a case of chimerism in which a kidney from a patient with Gitelman syndrome was transplanted into a non-Gitelman hypertensive recipient. After transplantation, postural hypotension resulted, necessitating discontinuation of all antihypertensive medications used for treatment of calcineurin-induced hypertension. This is the first reported case of acquired Gitelman syndrome after transplantation. Transplantation of a Gitelman "kidney" into a hypertensive recipient provides additional support for the role of the kidney NCC in blood pressure regulation. Furthermore, this case suggests the potential use of thiazide diuretics in the treatment of calcineurin-induced hypertension.

Antihypertensive Agents↗

PubMed2004

Prospective study of the immune effects of normalizing the hemoglobin concentration in hemodialysis patients who receive recombinant human erythropoietin.

Partial correction of anemia by erythropoietin improves hemodialysis (HD)-associated immunosuppression. It is not known whether hemoglobin normalization improves immune status further. The authors prospectively compared the immune function of HD patients with congestive heart failure or ischemic heart disease on erythropoietin therapy randomized to normal versus anemic blood hemoglobin concentration. HD patients were randomized into a normal hemoglobin group (n = 17, target hemoglobin of 14 +/- 1 g/dl) or an anemic hemoglobin group (n = 18, target hemoglobin 10 +/- 1 g/dl). Delayed-type hypersensitivity, CD4 and CD8 counts, anti-tetanus toxoid antibody levels, erythrocyte complement receptor 1 expression, and lymphocyte proliferative responsiveness were measured. The observation period was 1 yr, and the trial was open label. Target hemoglobin was achieved and maintained in both groups. Significantly improved cutaneous reactivity was seen in the normal hemoglobin group (P = 0.003). The prevalence of anergy decreased in the normal hemoglobin group (from 60 to 20%) but increased in the anemic hemoglobin group (from 57 to 86%). The anemic hemoglobin group had higher CD8 counts compared with baseline (P = 0.0001) and compared with the normal hemoglobin group (P = 0.038). Both groups had significant increases in tetanus toxoid antibody levels after vaccination but without significant differences between groups. The anemic hemoglobin group had a progressive increase in erythrocyte complement receptor 1 levels compared with baseline (P = 0.002) and relative to the normal hemoglobin group (P = 0.023). There was no consistent pattern of altered proliferative responsiveness of lymphocytes. The data suggest that certain aspects of immune function, particularly delayed-type hypersensitivity, may be improved in HD patients by normalization of hemoglobin through the administration of increased doses of erythropoietin.

Aged↗

PubMed2003

Rapid apoptosis induced by Shiga toxin in HeLa cells.

Apoptosis was induced rapidly in HeLa cells after exposure to bacterial Shiga toxin (Stx1 and Stx2; 10 ng/ml). Approximately 60% of HeLa cells became apoptotic within 4 h as detected by DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and electron microscopy. Stx1-induced apoptosis required enzymatic activity of the Stx1A subunit, and apoptosis was not induced by the Stx2B subunit alone or by the anti-globotriaosylceramide antibody. This activity was also inhibited by brefeldin A, indicating the need for toxin processing through the Golgi apparatus. The intracellular pathway leading to apoptosis was further defined. Exposure of HeLa cells to Stx1 activated caspases 3, 6, 8, and 9, as measured both by an enzymatic assay with synthetic substrates and by detection of proteolytically activated forms of these caspases by Western immunoblotting. Preincubation of HeLa cells with substrate inhibitors of caspases 3, 6, and 8 protected the cells against Stx1-dependent apoptosis. These results led to a more detailed examination of the mitochondrial pathway of apoptosis. Apoptosis induced by Stx1 was accompanied by damage to mitochondrial membranes, measured as a reduced mitochondrial membrane potential, and increased release of cytochrome c from mitochondria at 3 to 4 h. Bid, an endogenous protein known to permeabilize mitochondrial membranes, was activated in a Stx1-dependent manner. Caspase-8 is known to activate Bid, and a specific inhibitor of caspase-8 prevented the mitochondrial damage. Although these data suggested that caspase-8-mediated cleavage of Bid with release of cytochrome c from mitochondria and activation of caspase-9 were responsible for the apoptosis, preincubation of HeLa cells with a specific inhibitor of caspase-9 did not protect against apoptosis. These results were explained by the discovery of a simultaneous Stx1-dependent increase in endogenous XIAP, a direct inhibitor of caspase-9. We conclude that the primary pathway of Stx1-induced apoptosis and DNA fragmentation in HeLa cells is unique and includes caspases 8, 6, and 3 but is independent of events in the mitochondrial pathway.

Apoptosis↗

PubMed2002

Improved specificity and sensitivity when using pronase-digested lymphocytes to perform flow-cytometric crossmatch prior to renal transplantation.

Several laboratories have resorted to flow-cytometric crossmatch (FCXM) in an effort to prevent hyperacute and accelerated renal allograft rejections. The currently employed FCXM has problems with both false-positive and -negative reactions, largely as a result of irrelevant IgG binding to Fc IgG receptors. In 1980, we circumvented this problem by digesting Fc IgG receptors with pronase, and demonstrated that, with immunofluorescence microscopy (IF), detection of IgG anti-HLA antibodies was highly sensitive and specific. In 1995, we introduced the pronase technique to FCXM and showed that this enzyme did not decrease HLA expression. We present herein a prospective study at our institution to determine whether FCXM using pronase-digested (PD) lymphocytes is as sensitive and more specific than FCXM with undigested (UD) lymphocytes when compared with the highly sensitive and specific IF assay. In analyzing the 186 donor-specific pre-renal-transplant crossmatches, we found that PD FCXM was as sensitive and specific as IF and was able to detect weak IgG anti-HLA antibodies that bound to B cells. Fourteen of these patients would have been denied transplants if one were to have relied on UD FCXM. The data clearly indicate that PD FCXM can reliably be used to detect weak IgG anti-HLA antibodies before renal transplantation.

Antibodies↗