Comparison of outcomes with low-dose anti-thymocyte globulin, basiliximab or no induction therapy in pediatric kidney transplant recipients: a retrospective study

It is unclear which induction therapy yields the best outcomes in pediatric kidney transplantation. Retrospective data of 88 children receiving a renal allograft between November 1996 and October 2003 were analyzed. Patients received ATGI (n = 12), BI (n = 29), or NAI (n = 47). The mean ATG dose was 5.1 +/- 2.1 mg/kg. At 12 months, graft survival rates were 91.7%, 100%, and 97.9% for ATGI, BI, and NAI groups, respectively. Acute rejection rates at 12 months were 0 (ATGI), 20.6% (BI), and 10.7% (NAI). The mean GFR for ATGI (42.4 +/- 25.9 mL/min) was lower than for BI (78.3 +/- 27.2 mL/min), and NAI (66 +/- 28.3 mL/min) at 12 months (p < 0.05). One ATGI patient developed CMV pneumonia but none developed post-transplant lymphoproliferative disorder. Although there was no renal allograft survival benefit with either ATGI or BI, relative to NAI, the absence of acute rejection and equivalent rates of viral infections in the higher-risk ATGI recipient group suggests that the treatment strategy is promising. A large prospective study is needed to better define the role of ATGI in pediatric kidney transplantation.     

Catecholestrogens induce oxidative stress and malignant transformation in human endometrial glandular cells: protective effect of catechol-O-methyltransferase

Prolonged exposure to unopposed estrogens is a major risk factor for the development of endometrial cancer. Oxidative metabolism of estradiol (E(2)) into the catecholestrogens (CEs), 4-hydroxyestradiol (4-OHE(2)) and 2-hydroxyestradiol (2-OHE(2)), may play an important role in estrogen carcinogenicity. CEs can be oxidized to the corresponding ortho-quinone derivatives with concomitant formation of the reactive oxygen species (ROS). Catechol-O-methyltransferase (COMT) is the major enzyme involved in the detoxification of CEs in extrahepatic tissues. We investigated the potential of E(2), 2-OHE(2) and 4-OHE(2) to induce microsatellite instability (MSI) and neoplastic transformation of immortalized human endometrial glandular (EM) cells. We also investigated the functional significance of COMT gene expression on modulating the effects of E(2) and CEs in EM cells. Our data indicated that E(2) and 4-OHE(2) induce MSI, ROS and neoplastic transformation in EM cells. The capacity of E(2) and its catechol metabolites to induce MSI, ROS and neoplastic transformation in EM cells is ranked as follows: 4-OHE(2) > E(2) > 2-OHE(2). Knockdown of COMT expression in EM cells resulted in increased estrogenic milieu and increased estrogen-induced cell proliferation. More importantly, knockdown of COMT increased the propensity of E(2) or CEs to induce ROS, MSI and neoplastic transformation of EM cells. In contrast, overexpression of COMT in EM cells significantly reduced the cellular estrogenic milieu and protected against E(2)- or CEs-induced, ROS, MSI and neoplastic transformation. The capacity of E(2) or CEs to induce neoplastic transformation of human endometrial glandular cells in vitro may suggest that E(2)-induced endometrial cancer is mediated by its metabolism into CEs. Our study clearly indicates that COMT gene expression plays a critical role in modulating the hormonal and carcinogenic effects of E(2) and CEs and, consequently, modifies the risk for E(2)-induced endometrial cancer. To the best of our knowledge, this is the first study to (i) demonstrate the potential capacity of estrogen and its catechol metabolites to induce neoplastic transformation of immortalized human endometrial glandular cells; and (ii) illustrate the important role of COMT gene expression in protecting against E(2)-induced endometrial cancer.     

Intraductal papilloma of the breast in association with preoncogenic gene of breast cancer

We reported a case of an African American woman who went to the hospital with palpable right breast lump with bloody nipple discharge at University of Texas Medical Branct at Galvestion. The modalities of breast imagings included mammography and ultrasongraphy. The method used for viral identification was Linear Array HPV genotyping test. Intraductal papilloma revealed as high density tubular or rounded lobular masses with partially circumscribed, obscured margins and clustered punctate microcalcifications on mammograms. Ultrasound showed as intraductal masses with dilated ducts. The core biopsy demonstrated duct filled with papillary lesion and post excision revealed intraductal papilloma. HPV DNA types 16, 33, 58 and 71 were detected after use of Linear Array HPV genotyping test.     

Two infants with bilateral renal agenesis who were bridged by chronic peritoneal dialysis to kidney transplantation

Bilateral renal agenesis is associated with severe oligohydramnios and was considered incompatible with postnatal life due to severe pulmonary hypoplasia. The use of renal replacement therapy was limited by significant morbidity and mortality associated with dialysis in very young infants with major pulmonary pathology. In the United States, there is a tremendous controversy about whether or not the use of prenatal amniotic fluid infusions provides a benefit to fetuses with bilateral renal agenesis. One of the critical issues identified is that there are, as yet, no children reported who had achieved long‐term survival. Previous reports all indicated these children died shortly after birth or after unsuccessful peritoneal dialysis. We present two infants with a prenatal diagnosis of bilateral renal agenesis whose mothers elected to undergo prenatal amnioinfusions. One was born at 28 weeks with a birthweight of 1230 g and the other born at 34 weeks with a birthweight of 1940 g. We present the details of both cases, with initial management on chronic peritoneal dialysis, which started shortly after birth, as a bridge to living related kidney transplants.     

Evaluation of Previously Assigned Antibody Concentrations in Pneumococcal Polysaccharide Reference Serum 89SF by the Method of Cross-Standardization

An enzyme-linked immunosorbent assay (ELISA) and the antibody concentrations assigned to different pneumococcal capsular polysaccharide types were used to estimate concentrations of antibody to additional pneumococcal types in reference serum 89SF and to confirm assigned antibody values. This was possible because the slopes of curves of antibody binding to all polysaccharide types evaluated (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) were similar. The point estimates for total anti-pneumococcal antibody and immunoglobulin G (IgG) antibody determined by cross-standardization by an ELISA based on use of methylated human serum albumin (mHSA) to improve the efficiency of polysaccharide binding to the ELISA plate differed by less than 40% from those reported by Quataert et al. (Clin. Diagn. Lab. Immunol. 2:590–597, 1995) for types 1, 4, 6B, 7F, 9V, 14, 18C, and 23F. However, large differences were found between the assigned values and those obtained by our mHSA ELISA for types 3 and 19F. The mHSA ELISA and the direct polysaccharide coat ELISA may not measure antibodies to the same epitopes on polysaccharides of types 3 and 19F. The functional importance of these different antibody specificities is being investigated. We have thus confirmed the assigned IgG antibody values for most types by a different method and have extended antibody assignments to several additional types.     

Base-enhanced catalytic water oxidation by a carboxylate–bipyridine Ru(II) complex

In aqueous solution above pH 2.4 with 4% (vol/vol) CH₃CN, the complex [Ru^II(bda)(isoq)₂] (bda is 2,2′-bipyridine-6,6′-dicarboxylate; isoq is isoquinoline) exists as the open-arm chelate, [Ru^II(CO₂-bpy-CO₂⁻)(isoq)₂(NCCH₃)], as shown by ¹H and ¹³C-NMR, X-ray crystallography, and pH titrations. Rates of water oxidation with the open-arm chelate are remarkably enhanced by added proton acceptor bases, as measured by cyclic voltammetry (CV). In 1.0 M PO₄^3–, the calculated half-time for water oxidation is ∼7 μs. The key to the rate accelerations with added bases is direct involvement of the buffer base in either atom–proton transfer (APT) or concerted electron–proton transfer (EPT) pathways.Metal-complex catalyzed water oxidation continues to evolve with new catalysts and new mechanistic insights (1–9). Studies on single-site Ru catalysts such as [Ru^II(Mebimpy)(bpy)(OH₂)]²⁺ [Mebimpy is 2,6-bis(1-methylbenzimidazol-2-yl)pyridine; bpy is 2,2′-bipyridine; Fig. 1], both in solution and on surfaces, reveal mechanisms in which stepwise oxidative activation of aqua precursors to Ru^V=O is followed by rate-limiting O–O bond formation (10–15). The results of kinetic and mechanistic studies have revealed the importance of concerted atom–proton transfer (APT) in the O–O bond-forming step. In APT, the O–O bond forms in concert with H⁺ transfer to water or to an added base (11, 12, 16–19). APT can promote dramatic rate enhancements. In a recent study on surface-bound [Ru(Mebimpy)(4,4′-((HO)₂OPCH₂)₂bpy)(OH₂)]²⁺ [4,4′-((HO)₂OPCH₂)₂bpy is 4,4′-bis-methlylenephosphonato-2,2′-bipyridine] stabilized by atomic layer deposition, a rate enhancement of ∼10⁶ was observed with 0.012 M added PO₄³⁻ at pH 12 compared with oxidation at pH 1 (20).Open in a separate windowFig. 1.Structures of [Ru^II(Mebimpy)(bpy)(OH₂)]²⁺ (Left) and [Ru^II(CO₂-bpy-CO₂)(isoq)₂] [1] (Right).Sun and coworkers (21, 22) have described the Ru single-site water oxidation catalysts, [Ru^II(bda)(L)₂] (H₂bda is 2,2′-bipyridine-6,6′-dicarboxylic acid, HCO₂-bpy-CO₂H; L is isoquinoline, 4-picoline, or phthalazine). They undergo rapid and sustained water oxidation catalysis with added Ce^IV. A mechanism has been proposed in which initial oxidation to seven coordinate Ru^IV is followed by further oxidation to Ru^V(O) with O–O coupling to give a peroxo-bridged intermediate, Ru^IVO–ORu^IV, which undergoes further oxidation and release of O₂ (21, 22). We report here the results of a rate and mechanistic study on electrochemical water oxidation by complex [1], [Ru^II(CO₂-bpy-CO₂)(isoq)₂] (isoq is isoquinoline) (Fig. 1). Evidence is presented for water oxidation by a chelate open form in acidic solutions. The chelate open form displays dramatic rate enhancements with added buffer bases, and the results of a detailed mechanistic study are reported here.     

Ventilatory responses to hypercapnia during bupivacaine spinal anesthesia

The effect of spinal anesthesia with isobaric 0.5% bupivacaine on ventilatory responsiveness to CO2 rebreathing was studied in ten unpremedicated patients. Minute ventilation (VE) at end-tidal PCO2 = 55 mm Hg increased from 18.7 +/- 6.7 L/min (mean +/- SD) to 22.3 +/- 10.1 L/min after induction of spinal anesthesia (P less than 0.05). Occlusion pressure (P0.1) at PCO2 = 55 mm Hg also increased, from 3.8 +/- 1.5 to 5.0 +/- 1.7 cm H2O (P less than 0.05). Spinal anesthesia was not associated with significant changes in vital capacity, maximal inspiratory pressure, resting end-tidal PCO2, or the slopes or intercepts of the lines relating VE or P0.1 to PCO2. These results show an increased ventilatory responsiveness to CO2 with bupivacaine spinal anesthesia.     

In vitro properties of a newly established medulloblastoma cell line, MCD-1

Medulloblastomas are poorly differentiated brain tumors believed to arise from primitive pleuripotential stem cells, and tend to express mixed neuronal and glial properties. In the present study, we examined immunohistochemical and neurotransmitter phenotypic properties in a newly established medulloblastoma cell line, MCD-1. MCD-1 cells were immortal, not contact-inhibited, but did not grow in soft agar. Immunohistochemical studies showed positive staining for neurofilament protein (NF), neuron-specific enolase (NSE), synaptophysin, MAP 2, τ, NCAM 180, vimentin, and S-100 protein. The cells expressed specific uptake of glutamate, serotonin, and choline, but not GABA or dopamine. A significant increase in process extension was seen in response to agents that enhance intracellular cyclic AMP, especially 3-isobutyl-1-methylxanthine (IBMX). Process formation induced by IBMX was associated with a decrease in cell proliferation as evidenced by a reduction in numbers of cells incorporating 5-bromo-2-deoxyuridine (BrdU). No increase in process extension was observed following exposure to NGF or retinoic acid. MCD-1 cells were shown to produce transforming growth factor beta (TGFβ), and were immunopositive for mutant p53. Transfection assays with the PG13-Luc reporter plasmid, which contains a p53-responsive enhancer element and a luciferase reporter gene, suggested MCD-1 cells are deficient in wild-type p53 and do not activate p53 on treatment with the anticancer agent adriamycin. The MCD-1 cell line is suggested to represent an abnormally differentiated cell type, which has some properties consistent with a multipotent neuronal phenotype while retaining some properties of immature cells of a glial lineage. The MCD-1 cell line can be used to provide a model of a medulloblastoma cell line that is resistant to growth-controlling and anticancer agents.