Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

Metallothionein and Fas (CD95) are expressed in squamous cell carcinoma of the tongue

Metallothionein (MT) is a chelator present in myoepithelial cells, whilst the Fas-receptor (APO-1, CD95) has been described primarily in human T Jurkat cells. 20 cases of carcinoma of the tongue were investigated immunocytochemically with regard to MT, Fas and Bcl-2. In normal oral squamous epithelium, MT is located in the basal/parabasal dividing cells only. In well-differentiated nests of carcinomas, MT is observed almost entirely in peripherally located cells. In situ end-labelling indicates apoptosis in the centre of these nests, but not in the peripheral areas. Less-differentiated areas show more general MT-positivity, but little apoptosis. All 24 tumours are Fas-positive, but normal epithelia are mainly negative (P < 0.0001). Bcl-2 protein was sparse in the tumours compared with MT and Fas (P < 0.0001). We thus suggest that MT, possibly due to its chelating properties, may contribute to delaying cells entering apoptosis, both in normal epithelium near the base and in less-differentiated regions of carcinoma. Moreover, Fas may be present in cells of human malignancies, as well as those of established malignant cell lines.     

Pattern and process of growth of the abnormal human fetus

Identifying patterns of fetal growth alteration benefits both the clinician and the researcher. Twenty-four measurements in three variable sets (anthropometric measures, organ weights, and long-bone measures from radiographs) were taken on fetuses both with and without pathological conditions that are suspected to result in growth alteration. In addition, radiographs of each case were examined for the presence or absence of ossification centers. Based on least-squares regressions of the normal group, we calculated standardized residuals for the affected group to identify patterns of growth alteration. A large sample of fetuses between 15 and 42 weeks of gestational age with a variety of pathological conditions is described and evaluated for growth alterations. Symmetric and asymmetric growth alteration was detected in a small part of the sample and was predominantly isolated to fetuses in the late third trimester. Although patterns of growth alteration have been suggested as a means for noninvasive diagnoses of syndromes (such as trisomy 21), no consistent patterns are discernible in the current group. The sample provides a unique opportunity to evaluate fetal growth in terms of the interaction between genetic and environmental influences.     

Replica time integrators

This paper is concerned with the classical problem of wave propagation in discrete models of nonuniform spatial resolution. We develop a new class of Replica Time Integrators (RTIs) that permit the two‐way transmission of thermal phonons across mesh interfaces. This two‐way transmissibility is accomplished by representing the state of the coarse regions by means of replica ensembles, consisting of collections of identical copies of the coarse regions. In dimension d, RTIs afford an O(n^d) speed‐up factor in sequential mode, and O(n^{d + 1}) in parallel, over regions that are coarsened n‐fold. In this work, we restrict ourselves to the solution of the 3d continuous wave equation, for both linear and non‐linear materials. By a combination of phase‐error analysis and numerical testing, we show that RTIs are convergent and result in exact two‐way transmissibility at the Courant–Friedrichs–Lewy limit for any angle of incidence. In this limit, RTIs allow step waves and high‐frequency harmonics to cross mesh interfaces in both directions without internal reflections or appreciable loss or addition of energy. The possible connections of RTIs with discrete‐to‐continuum approaches and, in particular, with the transition between molecular dynamics and continuum thermodynamics are also pointed to by way of future outlook. Copyright © 2011 John Wiley & Sons, Ltd.     

Tricubic interpolation in three dimensions

The purpose of this paper is to give a local tricubic interpolation scheme in three dimensions that is both C¹ and isotropic. The algorithm is based on a specific 64 × 64 matrix that gives the relationship between the derivatives at the corners of the elements and the coefficients of the tricubic interpolant for this element. In contrast with global interpolation where the interpolated function usually depends on the whole data set, our tricubic local interpolation only uses data in a neighbourhood of an element. We show that the resulting interpolated function and its three first derivatives are continuous if one uses cubic interpolants. The implementation of the interpolator can be downloaded as a static and dynamic library for most platforms. The major difference between this work and current local interpolation schemes is that we do not separate the problem into three one‐dimensional problems. This allows for a much easier and accurate computation of higher derivatives of the extrapolated field. Applications to the computation of Lagrangian coherent structures in ocean data are briefly discussed. Copyright © 2005 John Wiley & Sons, Ltd.     

Targeting acetylcholinesterase molecules to the neuromuscular synapse

The functional integrity of the neuromuscular synapse requires that sufficient numbers of acetylcholinesterase (AChE) molecules be localized on the specialized extracellular matrix between the nerve terminal and the post-synaptic membrane. Multiple interrelated levels of regulation are necessary to accomplish this complex task including the spatial and temporal restriction of AChE mRNA expression within the muscle fiber, local translation and assembly of AChE polypeptides, and focused accumulation of AChE molecules on the extracellular matrix. This is accomplished in part through the organization of other extracellular matrix molecules into a complex which further associates with acetylcholine receptors and their accompanying molecules. Finally, the mature neuromuscular junction contains molecules which can act as receptors for the attachment of AChE which in turn may allow for the turnover of this enzyme at the synapse. This brief review will focus mainly on contributions from our laboratory towards understanding the mechanisms involved in organizing AChE molecules at the neuromuscular synapse.     

Role of medical capsule and transverse metatarsal ligament in hallux valgus deformity

The role of the medial capsule and transverse metatarsal ligament in hallux valgus deformity including stability of the first metatarsophalangeal and adjacent joints was investigated in vitro. The three-dimensional positions of the proximal phalanx, first metatarsal, and second metatarsal before and after sectioning the medial capsule and metatarsal ligament were measured using a magnetic tracking system. Valgus deformity of the hallux increased with medial capsule sectioning an average of 22.3 degrees +/- 6 degrees. Valgus deformity of the hallux increased with medial capsule and metatarsal ligament sectioning an average of 27.4 degrees +/- 9.1 degrees. Valgus deformity of the hallux did not change significantly after sectioning the metatarsal ligament only. No significant changes were found in varus and eversion of the first metatarsal, in valgus of the second metatarsal, in the distance between first and second metatarsal heads after sectioning the medial capsule, or in the metatarsal ligament. This study shows the importance of the medial capsule in hallux valgus deformity. The transverse ligament did not contribute substantially to cause the deformity.     

Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex

Huntingtin is the protein product of the gene for Huntington's disease (HD) and carries a polyglutamine repeat that is expanded in HD (>36 units). Huntingtin-associated protein (HAP1) is a neuronal protein and binds to huntingtin in association with the polyglutamine repeat. Like huntingtin, HAP1 has been found to be a cytoplasmic protein associated with membranous organelles, suggesting the existence of a protein complex including HAP1, huntingtin, and other proteins. Using the yeast two-hybrid system, we found that HAP1 also binds to dynactin P150(Glued) (P150), an accessory protein for cytoplasmic dynein that participates in microtubule-dependent retrograde transport of membranous organelles. An in vitro binding assay showed that both huntingtin and P150 selectively bound to a glutathione transferase (GST)-HAP1 fusion protein. An immunoprecipitation assay demonstrated that P150 and huntingtin coprecipitated with HAP1 from rat brain cytosol. Western blot analysis revealed that HAP1 was enriched in rat brain microtubules and comigrated with P150 and huntingtin in sucrose gradients. Immunofluorescence showed that transfected HAP1 colocalized with P150 and huntingtin in human embryonic kidney (HEK) 293 cells. We propose that HAP1, P150, and huntingtin are present in a protein complex that may participate in dynein-dynactin-associated intracellular transport.