Experimental evaluation of a new device for percutaneous transrenal ureteral occlusion

PURPOSE: To develop a device for percutaneous transrenal ureteral occlusion. MATERIALS AND METHODS: The device was a double-body Gianturco-R?sch biliary stent constrained at the junction of the two stents to create an hourglass shape. One stent was coated with silicone. One device was percutaneously placed in each of nine pigs through a 9-F Teflon sheath. Urographic and hematologic follow-up was performed for up to 12 weeks. RESULTS: Seven pigs showed immediate, complete ureteral occlusion, and two pigs exhibited persistent incomplete high-grade obstruction. All animals exhibited varying degrees of hydronephrosis and hydroureter. No device migration was noted. Minor complications were encountered during device placement in three pigs. Mucosal folds and villus-like projections that arose from the lamina propria protruded into the lumen of the ureter at the cranial end of the covered stent and around the wire of the caudal stent. Varying degrees of mural inflammation and edema were noted. CONCLUSION: Transrenal ureteral occlusion with the described device appears to be a viable method for treating urinary fistulas.     

Systematic screening of the LDL-PLA2 gene for polymorphic variants and case-control analysis in schizophrenia

Systematic scans of the genome using microsatellite markers have identified chromosome 6p21.1 as a putative locus for schizophrenia in multiply affected families. There is also evidence from a series of studies for a role of abnormal phospholipid metabolism in schizophrenia. In light of these findings, and the role of platelet activating factor in neurotransmission and neurodevelopment, we have examined the LDL-PLA2 (plasma PAF acetylhydrolase, PAF-AH) gene, a serine dependent phospholipase that has been mapped by hybrid mapping to chromosome 6p21.1, as a positional candidate gene for schizophrenia. The gene was systematically screened using SSCP/HD analysis for polymorphisms associated with the disease. Four polymorphic variants were found within the gene and studied in a group of 200 schizophrenic patients and 100 controls. The variant in exon 7 (Iso195Thr) was found to be weakly associated with schizophrenia (p = 0.04) and the variant in exon 11 (Val379Ala) almost reached significance (p = 0.057). After correcting for multiple testing no significant associations were detected. Haplotype analysis combining pairs of polymorphisms also provided no evidence for association of this gene with schizophrenia in our sample of patients.     

Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome?

In human pregnancy, placental cytotrophoblasts that invade the uterus downregulate the expression of adhesion receptors that are characteristic of their epithelial origin, and upregulate the expression of adhesion receptors that are expressed by vascular cells. We suggest that this transformation could be critical to endovascular invasion, the process whereby cytotrophoblasts invade the uterine spiral arterioles and line their walls (Zhou et al. J. Clin. Invest. 1997. 99: 2139-2151.). To better understand the in vivo significance of these findings, we tested the hypothesis that in preeclampsia, an important disease of pregnancy in which endovascular invasion is abrogated, cytotrophoblasts fail to adopt a vascular adhesion phenotype. In experiments described here we stained placental bed biopsy specimens from age-matched control pregnancies and from those complicated by preeclampsia with antibodies that recognize adhesion molecules that are normally modulated during this transformation. In preeclampsia, differentiating/invading cytotrophoblasts fail to express properly many of these molecules, including integrin, cadherin, and Ig superfamily members. These results suggest that preeclampsia is associated with failure of cytotrophoblasts to mimic a vascular adhesion phenotype. The functional consequences of this abnormality are unknown, but are likely to affect negatively cytotrophoblast endovascular invasion and uterine arteriole remodeling, thereby compromising blood flow to the maternal-fetal interface.     

Gastrointestinal involvement in Henoch-Sch?nlein syndrome: CT findings

OBJECTIVE: The purpose of this study was to describe the CT features of gastrointestinal involvement in seven patients with Henoch-Sch?nlein syndrome. CONCLUSION: Although the incidence of Henoch-Sch?nlein syndrome is low, it should be considered when CT scans show multifocal areas of bowel-wall thickening, mesenteric edema, vascular engorgement, and nonspecific lymphadenopathy. It should be considered especially in young patients with acute gastrointestinal symptoms.     

Heterologous expression of rat epitope-tagged histamine H2 receptors in insect Sf9 cells

1. Rat histamine H2 receptors were epitope-tagged with six histidine residues at the C-terminus to allow immunological detection of the receptor. Recombinant baculoviruses containing the epitope-tagged H2 receptor were prepared and were used to infect insect Sf9 cells. 2. The His-tagged H2 receptors expressed in insect Sf9 cells showed typical H2 receptor characteristics as determined with [125I]-aminopotentidine (APT) binding studies. 3. In Sf9 cells expressing the His-tagged H2 receptor histamine was able to stimulate cyclic AMP production 9 fold (EC50=2.1+/-0.1 microM) by use of the endogenous signalling pathway. The classical antagonists cimetidine, ranitidine and tiotidine inhibited histamine induced cyclic AMP production with Ki values of 0.60+/-0.43 microM, 0.25+/-0.15 microM and 28+/-7 nM, respectively (mean+/-s.e.mean, n=3). 4. The expression of the His-tagged H2 receptors in infected Sf9 cells reached functional levels of 6.6+/-0.6 pmol mg(-1) protein (mean+/-s.e.mean, n=3) after 3 days of infection. This represents about 2 x 10(6) copies of receptor/cell. Preincubation of the cells with 0.03 mM cholesterol-beta-cyclodextrin complex resulted in an increase of [125I]-APT binding up to 169+/-5% (mean+/-s.e.mean, n=3). 5. The addition of 0.03 mM cholesterol-beta-cyclodextrin complex did not affect histamine-induced cyclic AMP production. The EC50 value of histamine was 3.1+/-1.7 microM in the absence of cholesterol-beta-cyclodextrin complex and 11.1+/-5.5 microM in the presence of cholesterol-beta-cyclodextrin complex (mean+/-s.e.mean, n=3). Also, the amount of cyclic AMP produced in the presence of 100 microM histamine was identical, 85+/-18 pmol/10(6) cells in the absence and 81+/-11 pmol/10(6) cells in the presence of 0.03 mM cholesterol-beta-cyclodextrin complex (mean+/-s.e.mean, n=3). 6. Immunofluorescence studies with an antibody against the His-tag revealed that the majority of the His-tagged H2 receptors was localized inside the insect Sf9 cells, although plasma membrane labelling could be identified as well. 7. These experiments demonstrate the successful expression of His-tagged histamine H2 receptors in insect Sf9 cells. The H2 receptors couple functionally to the insect cell adenylate cyclase. However, our studies with cholesterol complementation and with immunofluorescent detection of the His-tag reveal that only a limited amount of H2 receptor protein is functional. These functional receptors are targeted to the plasma membrane.     

Predicting birth weight by fetal upper-arm volume with use of three-dimensional ultrasonography

Previously, we demonstrated elevated cortisol production/release in response to the administration of the serotonin precursor, L-5-hydroxytryptophan (L-5-HTP) in untreated patients with obstructive sleep apnea (OSA). We hypothesized that if this elevated cortisol response to L-5-HTP was related to OSA, this finding would not be present in OSA patients treated with nasal continuous positive airway pressure (nCPAP). Eleven OSA patients treated for at least 1 month with nCPAP were studied. On two different days, we measured blood cortisol level every 15 min for 4 h following the ingestion of L-5-HTP, 0.4 mg/kg, or placebo, both given with carbidopa, a peripheral tryptophan decarboxylase inhibitor, used to prevent peripheral L-5-HTP metabolism before brain absorption. For a given subject, the cortisol response was calculated as the difference between the area under the curve of the L-5-HTP and placebo responses. In the nCPAP-treated OSA patients, this net cortisol response, 577 +/- 240 min.micrograms/dL, was less than the value found in the previously studied untreated OSA group, 1,198 +/- 227 min.micrograms/dL (p < 0.05) and not different from the previously studied nonapneic control group, 469 +/- 154 min.micrograms/dL. From these results, we speculate that nCPAP treatment reverses the elevated cortisol response to serotonergic stimulation seen in untreated OSA patients.     

Acute lymphoblastic leukemia

Advances in the molecular and immunologic characterization of leukemic cells have greatly aided the diagnosis and risk assignment of ALL, as well as the monitoring of bone marrow samples for minimal residual disease. Currently, 75% of childhood cases have biologically and therapeutically relevant genetic abnormalities. Although gene discoveries in ALL have not been directly translated into effective therapy, there is every reason to believe that this disease will eventually yield to molecular intervention. In the meantime, efforts are being made to enhance the efficacy of existing regimens while reducing their toxic side effects. We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. The challenge now is to identify specific treatments for genetically defined subtypes of ALL.     

A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23

Prenylated Rab GTPases occur in the cytosol in their GDP-bound conformations bound to a cytosolic protein termed GDP-dissociation inhibitor (GDI). Rab-GDI complexes represent a pool of active, recycling Rab proteins that can deliver Rabs to specific and distinct membrane-bound compartments. Rab delivery to cellular membranes involves release of GDI, and the membrane-associated Rab protein then exchanges its bound GDP for GTP. We report here the identification of a novel, membrane-associated protein factor that can release prenylated Rab proteins from GDI. This GDI-displacement factor (GDF) is not a guanine nucleotide exchange factor because it did not influence the intrinsic rates of nucleotide exchange by Rabs 5, 7 or 9. Rather, GDF caused the release of each of these endosomal Rabs from GDI, permitting them to exchange nucleotide at their intrinsic rates. GDF displayed the greatest catalytic rate enhancement on Rab9-GDI complexes. However, catalytic rate enhancement paralleled the potency of GDI in blocking nucleotide exchange: GDI was shown to be most potent in blocking nucleotide exchange by Rab9. The failure of GDF to act on Rab1-GDI complexes suggests that it may be specific for endosomal Rab proteins. This novel, membrane-associated activity may be part of the machinery used to localize Rabs to their correct intracellular compartments.     

Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure

INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of nutritional status, although it is recognized that hypoalbuminaemia may be caused by many factors. We have further examined the relationship between serum albumin and nutrition. METHODS: Nutritional status was assessed by biochemistry, anthropometry, mid-arm muscle circumference, muscle strength (hand grip and back), and lean body mass (from anthropometry, creatinine kinetics and bioimpedance) in a group of 76 stable CAPD patients. Correlations between biochemical and nutritional parameters were sought and data were compared between patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2 months apart) and separately according to subjective global assessment score (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition). RESULTS: In patients with a low SGA score, actual body weight, body mass index, mid-arm muscle circumference, lean body mass, subscapular skinfold thickness, hand grip strength (males and females) and iliac and triceps skinfold thicknesses and back strength (females only) were all significantly less than in patients with a normal SGA score. In contrast, none of these variables differed in either gender when patients were compared according to serum albumin. Serum albumin was correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = -0.39) in females, but not with any index of body composition in either gender. CONCLUSION: Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.