Identification of urinary dipeptidase as the released form of renal dipeptidase

Beckwith-Wiedemann syndrome (BWS) comprises of a number of childhood abnormalities, often associated with one or more tumors. Thirty-eight patients were investigated to determine clinical and/or biological signs associated with a tumor presence. Our patients exhibited a higher incidence of tumor development (21%) than that previously reported, underlying the care with which such patients should be followed, when particular clinical features are observed: visceromegaly affecting three organs (liver, kidney, spleen), and also family history with sign of BWS such as macroglossia, omphalocele, hemihypertrophy, embryonic tumor), high body weight at birth (> or = +2 standard deviations and diastasis recti.     

Cleavage of rhesus rotavirus VP4 after arginine 247 is essential for rotavirus-like particle-induced fusion from without

We recently described our finding that recombinant baculovirus-produced virus-like particles (VLPs) can induce cell-cell fusion similar to that induced by intact rotavirus in our assay for viral entry into tissue culture cells (J. M. Gilbert and H. B. Greenberg, J. Virol. 71:4555-4563, 1997). The conditions required for syncytium formation are similar to those for viral penetration of the plasma membrane during the course of viral infection. This VLP-mediated fusion activity was dependent on the presence of the outer-layer proteins, viral protein 4 (VP4) and VP7, and on the trypsinization of VP4. Fusion activity occurred only with cells that are permissive for rotavirus infection. Here we begin to dissect the role of VP4 in rotavirus entry by examining the importance of the precise trypsin cleavage of VP4 and the activation of VP4 function related to viral entry. We present evidence that the elimination of the three trypsin-susceptible arginine residues of VP4 by specific site-directed mutagenesis prevents syncytium formation. Two of the three arginine residues in VP4 are dispensable for syncytium formation, and only the arginine residue at site 247 appears to be required for activation of VP4 functions and cell-cell fusion. Using the recombinant VLPs in our syncytium assay will aid in understanding the conformational changes that occur in VP4 involved in rotavirus penetration into host cells.     

Age and ethnicity affect the risk and outcome of focal segmental glomerulosclerosis

In patients with proteinuria, African-American (AA) ethnicity is reported to be a risk factor for focal segmental glomerulosclereosis (FSGS) and its progression to end-stage renal disease (ESRD). We reviewed our single-center experience to determine the probability of FSGS and its progression to ESRD based on ethnicity and age at presentation in children with proteinuria with or without nephrotic syndrome. Proteinuria without systemic disease or acute glomerulonephritis was the presenting feature in 17% (236/1,403) of children in the renal patient database of Texas Children's Hospital, Baylor College of Medicine. Histopathological diagnoses were established in 107 of 236 patients (45%). FSGS was identified in 65 patients, accounting for 28% of all patients with proteinuria and 61% of patients who underwent renal biopsy. FSGS was more prevalent in AA (45%) than in non-AA patients (22%) (P=0.001), and AA patients with FSGS were older at presentation (12.7+/-4.4 years) than non-AA patients (5.6+/-4.6 years) (P<0.001). Among patients who underwent renal biopsy, increasing age at presentation increased the probability of having FSGS in AA but not non-AA patients (P=0.04). Five-year actuarial renal survival of FSGS was worse in AA (8%) than in non-AA patients (31%) (P=0.01). These data suggest an increased risk and worse outcome of FSGS in AA compared with non-AA children.     

Multiple Na,K-ATPase Subunits Colocalize in the Brush Border of Mouse Choroid Plexus Epithelial Cells

(1) Background: The unusual accumulation of Na,K-ATPase complexes in the brush border membrane of choroid plexus epithelial cells have intrigued researchers for decades. However, the full range of the expressed Na,K-ATPase subunits and their relation to the microvillus cytoskeleton remains unknown. (2) Methods: RT-PCR analysis, co-immunoprecipitation, native PAGE, mass spectrometry, and differential centrifugation were combined with high-resolution immunofluorescence histochemistry, proximity ligase assays, and stimulated emission depletion (STED) microscopy on mouse choroid plexus cells or tissues in order to resolve these issues. (3) Results: The choroid plexus epithelium expresses Na,K-ATPase subunits α1, α2, β1, β2, β3, and phospholemman. The α1, α2, β1, and β2, subunits are all localized to the brush border membrane, where they appear to form a complex. The ATPase complexes may stabilize in the brush border membrane via anchoring to microvillar actin indirectly through ankyrin-3 or directly via other co-precipitated proteins. Aquaporin 1 (AQP1) may form part of the proposed multi-protein complexes in contrast to another membrane protein, the Na-K-2Cl cotransporter 1 (NKCC1). NKCC1 expression seems necessary for full brush border membrane accumulation of the Na,K-ATPase in the choroid plexus. (4) Conclusion: A multitude of Na,K-ATPase subunits form molecular complexes in the choroid plexus brush border, which may bind to the cytoskeleton by various alternative actin binding proteins.     

Structural study of titanium oxide films synthesized by ion beam-assisted deposition

The application of titanium dioxide (TiO(2)) films as surgical implant coatings for antibiotic attachment depends crucially on their available surface area and thus their surface morphology and crystallinity. Here, we report our fabrication of high Wenzel ratio TiO(2) films targeted to increase the film surface area using the ion beam-assisted deposition (IBAD) technique at high-deposition temperatures (approximately 610 degrees C). The modulation of the films' surface morphology was accomplished by varying the chemical identity of the concurrent ion beams bombarded on the films during the e-beam evaporation process. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) were employed to investigate the surface morphology of the as-deposited films. X-ray diffractometry (XRD) revealed that these nanocrystalline films primarily consist of anatase phase TiO(2). Wenzel ratio, the ratio of the actual surface area to the projected area, of IBAD films prepared with argon, oxygen, and nitrogen ion beams was measured to be 1.52, 1.31 and 1.49, respectively. The effect of the differences in chemical reactivity and ion size of these three type ion beams are discussed to explain the present results.     

Attitude to contraception among 16-20-year olds

In October 1989 a representative sample consisting of 359 women (response rate = 77.9%) and 400 men (response rate = 76.3%) aged 16-20 years old was interviewed by the professional interviewer staff of the Institute for Social Research. The purpose of the investigation was to illustrate whether AIDS and "Safe sex"-campaigns have influenced young people. This paper consider the attitudes to contraception among teenagers. Generally, the reports are in accordance with an increasing popularity of the condom. Almost all answered that it was all right for a girl to bring a condom. The majority (313 (89.4%) among women and 311 (78.7%) among men) reported both partners to be responsible in relation to contraception. Still, it is commonly the female who brings up the question. Communication about contraception between the female and the male partner is of importance in order to impede sexually transmitted diseases and reduce the number of legally induced abortions among teenagers. The widespread attitude towards contraception as being a joint concern forms an appropriate basis to attain equality between the sexes in relation to communication about contraception.     

Evolution of the cranial computed tomography scan in child abuse

Computed tomography (CT) scans obtained at the time of clinical presentation have occasionally been reported to be normal in children with history and findings of significant abusive head injury. We have retrospectively observed abnormalities in "normal" scans of some similar children. We have also seen abnormalities develop on serial scanning. To determine how frequently these situations occur, we reviewed charts of 34 children with a final diagnosis of child abuse who also had cranial CT scans performed. Their CT scans were retrospectively reviewed by a pediatric radiologist. Eleven (11/34) CT scans had initially been interpreted as normal. Four (4/11) of these had been reinterpreted during the hospitalization as abnormal, affecting medical (1) and legal (3) outcome. Repeat scanning in three of the remaining seven resulted in surgical drainage of a subdural effusion (1) and affected legal outcome (2). Four of the seven initial scans felt normal throughout the hospitalizations were judged abnormal on retrospective review. This evaluation was confirmed in the two rescanned. Initial CT interpretation most often failed to appreciate changes in parenchymal density and small amounts of falcine or cortical subdural blood. Subsequent scans also showed evolving effusions and infarcts. Changes were noted in 1 1/2 to 5 days. The CT scan frequently shows subtle changes in the immediate posttrauma period. If the child does not recover promptly, subsequent scans frequently result in significant changes in clinical and legal management.     

Comparative study of the pharmacokinetics of amitriptyline oxide and trimipramine after single administration in healthy male probands and patients with renal failure

The pharmacokinetics of the antidepressants amitriptyline oxide and trimipramine and their major metabolites amitriptyline, nor-triptyline and desmethyltrimipramine, were studied in twelve healthy male subjects (aged from 22 to 62 years) and twelve patients (aged from 25 to 73 years) with severe renal impairment (glomerular filtration rate < 10 ml/min). Oral single doses of 60 mg amitriptyline oxide and 50 mg trimipramine, separated by a washout period, were administered to all study participants. Blood and urine samples were collected up to 120 hours after administration. For trimipramine and desmethyltrimipramine, a new HPLC method was developed. The "Fischer Somatic and Undesired Effects Check List" was used for the assessment of adverse events. The mean plasma half-life and AUC of amitriptyline oxide and its metabolites were significantly higher in patients than in healthy adults. For trimipramine the AUC was significantly higher in patients. The plasma half-life of trimipramine was longer in patients, but statistically not significant. The maximum plasma concentrations for both drugs and metabolites were at an average distinctly higher in patients. Clearance rate of amitroptylinoxide and trimipramine also differed between the two groups. Correlating with these results a high incidence and a longer persistence (in most cases > 12 hours) and more pronounced adverse effects were noted in the patient group, whereas in volunteers adverse events were only observed up to approximately eight hours.     

Heat conduction by liquid helium II in capillary tubes. IV. Mutual friction under pressure

We report measurements of supercritical heat conduction in liquid helium II at pressures above the vapor pressure. The measurements were made in glass capillary tubes of diameter 50.5 and 366.8 m in the temperature range from 1.2 to 2.1 K. As in our previous results at the vapor pressure, a clear distinction can be made between two regimes in which the average separation of vortex lines is either comparable with or larger than the size of the flow channel. In the wider tube, at high relative velocities v between the superfluid and normal component, where the vortex spacing is small, a modified form of Gorter-Mellink mutual friction F _sn is observed which varies as F_sn=A_snv(v–v₀)². The coefficient A increases with pressure, and its variation with T/T(p) is in fairly good agreement with Schwarz ' microscopic theory of superfluid turbulence. However, the absolute magnitude of A is in general larger than in Schwarz ' theory and also larger than most other experimental values. In the narrower tube the measurements are all in the regime where the vortex spacing is comparable with the tube size, and they do not agree with the predictions of the Gorter-Mellink law. At present, the data cannot be analyzed quantitatively in the terms of the vortex line density, because B, the vortex line scattering coefficient, is not known at high pressures.Preparation of this paper was supported by a U.S. National Science Foundation grant DMR 7901073 and by a UK Science Research Council Senior Fellowship (DFB).SRC Senior Fellow.