Hepatitis C infection in patients with chronic hepatitis B: curiosity or co-factor?
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Biomedical subjects
Publications and source records attributed to P Martin.
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The TGF beta family of growth factors has been implicated as playing a significant role in many aspects of embryonic morphogenesis, and also as a mediator of adult tissue repair processes. Unlike the situation in the adult, tissue repair in the embryo does not result in scarring, and it has been suggested that this might be due, in part, to reduced levels of growth factors, particularly TGF beta, at the wound site. We have examined the expression patterns of TGF beta genes following wounding of limb bud lesions in cultured E11.5 mouse embryos. The timetable of wound closure was investigated by standard light and electron microscopy from the time of wounding until the lesion had re-epithelialised 24 hours later. The expression of transcripts for each of the three TGF beta genes was examined at various time points during the healing process using radioactive in situ hybridisation to tissue sections and wholemount non-radioactive in situ hybridisation to embryo pieces. Within 1 to 3 hours of wounding, transcripts encoding TGF beta 1 were rapidly induced within the epithelial cells of the wound margin, particularly those cells at the ventral aspect of the wound. By 3 to 6 hours post-wounding, TGF beta 1 transcripts were detectable in the mesenchyme of the wound bed. No TGF beta 3 induction was observed, and possible TGF beta 2 induction was largely obscured by endogenous expression associated with pre-cartilage mesenchymal condensation. Immunocytochemical analysis of tissue sections of the wound demonstrated a rapid induction of TGF beta 1 protein within 1 hour post-wounding, but also a subsequent rapid clearance of the protein from the wound site such that, by 18 hours post-wounding, TGF beta 1 levels had returned to near background. These data are discussed in terms of the molecular mechanisms underlying embryonic wound healing and the significance of the results to an understanding of scarring following adult tissue repair.
The inner ear of the mouse develops from a roughly spherical epithelial vesicle, the otocyst, which undergoes a series of complex shape changes to produce the functionally important parts of an adult inner ear; in particular, a coiled cochlea--which houses the auditory apparatus, a saccule and utricle containing sensors of gravity and linear acceleration, and three precisely shaped and oriented semicircular canals, with which angular acceleration is detected. This paper follows the development of the shape of the mouse inner ear from simple otocyst until a stage when the vesicle has become a rather squat miniature model of its adult self. We have been able to visualize clearly these complex shape changes by injecting an opaque marker into the lumina of a series of fixed ears. We have further concentrated on the mechanism of formation of the semicircular canals using light-, electron-microscopic, and dye-marking techniques. Classic embryological texts describe the canals developing from outpocketings of the epithelial ear rudiment, whose opposite walls meet, fuse, and "disappear" in the central canal plate region to leave a tube of epithelium encircling their margin. To trace the fate of these "disappearing" epithelial cells we have dye-marked all of the otic epithelial cells at a stage prior to canal formation in mouse embryos which we then grow in roller culture until their canals have formed. From these marking experiments we show that the disappearing cells of the canal plate neither die nor become transformed into mesenchymal cells, but rather, most are retracted back into the canal tube epithelium at either side of the site of fusion. We speculate that this mechanism of epithelial resorption may be a common way of "losing" epithelial cells during embryonic morphogenetic remodellings.
The polymorphism of the D1S80 locus has been analyzed in a population sample of 203 unrelated individuals living in Madrid (central Spain) by PCR and subsequent semi-dry discontinuous polyacrylamide gel electrophoresis (Tris-chloride/Tris-glycine buffer system) followed by silver staining. The electrophoretic system described in this study offers high resolution in the separation of the different D1S80 alleles allowing the detection of microvariability around the allele T22 in the spanish population. Twenty different alleles containing 17-40 repeats of the basic 16 bp unit were distinguished. The alleles T18 and T24 were found to be relatively common in Spain, as in other populations, with frequencies of 0.224 and 0.372, respectively. No evidence of significant deviations from Hardy-Weinberg equilibrium was found in these preliminary population data.
Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) (Hologic QDR 1000) and by 153Gd dual-photon absorptiometry (DPA) (Novo Lab 22a) in 120 postmenopausal women. Though a high correlation existed between the two techniques, the ratio between DXA and DPA values was not constant. Using DXA we observed a higher dependence of BMD on weight than in the DPA measurements. To investigate the different behaviour of DXA and DPA machines with weight, we analysed the effects of increasing thickness of soft tissue equivalents on the BMD of the Hologic spine phantom and on the BMD equivalent of an aluminium standard tube. Increasing tissue-equivalent thickness caused the phantom BMD measured by DPA to decrease significantly but had not effect on the DXA measurements. The different behaviour of DPA and DXA equipment with regard to the phantoms could account for the differences observed in the relations between BMD and weight in the patients. Using multiple regression we studied the influence of weight and body mass index on the relation between BMD measured by the two techniques. The introduction of either of these variables into the regression resulted in an improvement of the prediction of the DXA values from the DPA values. However, the residual standard error of the estimate was still higher than the combined precision errors of the two methods, so that no simple relation allows a conversion of BMDDPA into BMDDXA. Our results confirm that BMD is positively correlated with weight in postmenopausal women; the influence of weight on BMD is blunted when the Novo Lab 22a DPA machine is used for measuring bone mineral.
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In this paper we report our light and electron microscopic studies of the healing of a simple excisional lesion to the E11.5 mouse embryo hindlimb. The wounded living embryo is cultured in a roller bottle and under such conditions the lesion is completely re-covered with epithelium by 24 hr. We discuss how our studies of such a simple wound healing model may offer insight into the mechanisms of tissue repair generally.
Bacterial superantigens have two immunologically important features. They bind MHC class II molecules and stimulate T cells bearing certain V beta TCR phenotypes. Superantigens such as SEA, SEB, and TSST bind to each of the three HLA class II isotypes (DR, DQ, and DP). Allotypic variation seems to play an important role in superantigen binding to class II molecules, but the functional implications of these differences remain largely unknown. In the present investigation, we studied the effects of SEA, SEB, and TSST on allostimulation of HLA-DR-, DQ-, and DP-allospecific T-cell clones. To avoid direct stimulation of T-cell responses by the superantigens, SEA and/or SEB nonresponsive T-cell clones were selected. We show that SEA strongly inhibited DQ- and DP-specific T-cell responses. In contrast, SEB and TSST had only weak inhibitory effects. DR-specific T-cell responses were unaffected or only weakly inhibited by the superantigens tested. The inhibition appeared not to be due to induction of cytotoxicity or suppression of either T cells or EBV-LCLs by SEA. In conclusion, the bacterial superantigen SEA can block alloantigen-specific stimulation of T clones in vitro. These results suggest that SEA binds to certain MHC class II molecules in a way that prevents MHC-TCR interactions.
The effects of carbon loading and endcapping on the solid-phase extraction onto C18 bonded silica gel of a range of beta-blockers from aqueous buffer and from dog plasma has been investigated. The highest extraction efficiencies were obtained for those phases with carbon loadings of between 5 and 16% for phases without endcapping or 10.5-14% for endcapped material. With carbon loadings of 18 and 22% (plus endcapping) poor extractions from the matrix were obtained combined with further losses at the wash steps. Matrix effects were observed with dog plasma which accentuated the effects seen with buffer. These results are best explained by assuming that a cationic interaction of the secondary amino group present in the analytes with residual silanols on the silica surface is primarily responsible for the extraction of these analytes.
Olfactory hallucinations are rarely mentioned as a symptom of depressive disorder. This paper presents a review of the literature including a conceptual clarification and epidemiological aspects with an emphasis on the significance of olfactory hallucinations for psychopathology, in particular with respect to sensory perception and body self-awareness. The close relation to the olfactory reference syndrome is pointed at. Olfactory hallucinations are considered important for the biological interpretation of affective disorders. In this regard disturbed olfactory perception can be understood as an example of disturbed brain function in the state of depression. Olfactory symptoms are shown to be elements connecting primary affective disorders with other neuropsychiatric diseases as well as with neuroanatomical and neurophysiological models. A primary role is accordingly attributed to the temporal lobe epilepsies in which olfactory hallucinations as well as affective disturbances occur. The need for further investigation in this field is pointed out.
Cerebral edema is the leading cause of death in patients with fulminant hepatic failure (FHF). Emergency OLT is often a life-saving therapy for FHF but severe cerebral edema is a contraindication to transplantation. We attempted to identify clinical and biochemical factors associated with the development of severe intracranial hypertension in FHF. Fever, psychomotor agitation, and arterial hypertension were more frequently observed preceding episodes of severe intracranial hypertension, and more than 50% of FHF patients with uncontrolled intracranial hypertension sustained severe brain injury in our series. These observations suggest that vigorous treatment of fever, arterial hypertension, and agitation are important aspects of the intensive care management of FHF patients to maintain their OLT candidacy.
Reports on a survey of 1990 and 1991 graduates entering the speech and language therapy profession in the UK and on the experiences of six new therapists in one "good practice" area, Ayrshire and Arran Health Board. Results show that new therapists were given a great deal of help and support from professional managers, and valued it highly. They chose posts which offered a mixed client load and good induction packages. Pre-service training reflected work carried out in service, but all client groups had not been accessed during training. Issues relating to throughput and case-load management required most support. They made successful personal adaptations to the work environment, and managers found them effective overall. Calculates the costs of supporting new therapists. Highlights the need to maintain professional support and discusses the potential difficulties involved in doing so in relation to NHS reforms.
After differential screening of a cDNA library constructed from quail neuroretina cells (QNR) infected with the v-myc-containing avian retrovirus MC29, we have isolated a cDNA clone, Pax-QNR, homologous to the murine Pax-6, which is mutated in the autosomal dominant mutation small eye of mice and in the disorder aniridia in humans. Here we report the characterization of the Pax-QNR proteins expressed in the avian neuroretina. From bacterially expressed Pax-QNR peptides, we obtained rabbit antisera directed against different domains of the protein: paired domain (serum 11), domain between the paired domain and homeodomain (serum 12), homeodomain (serum 13), and carboxyl-terminal part (serum 14). Sera 12, 13, and 14 were able to specifically recognize five proteins (48, 46, 43, 33, and 32 kDa) in the neuroretina. In contrast to proteins of 48, 46, and 43 kDa, proteins of 33 and 32 kDa were not recognized by the paired antiserum (serum 11). Paired-less and paired-containing proteins exhibited the same half-life (6 h) and were phosphorylated mostly on serine residues. Immunoprecipitations performed with subcellular fractions of neuroretinas showed that the paired-containing proteins were located in the nucleus, whereas the 33- and 32-kDa proteins were found essentially in the cytoplasmic compartment. However, immunofluorescence experiments performed after transient transfections showed that p46 and p33/32 were also located in vivo into the nucleus. Thus, the Pax-QNR/Pax-6 gene can produce proteins with two DNA-binding domains as well as proteins containing only the DNA-binding homeodomain.
In this study of hepatitis C virus (HCV) infection prevalence in France, the prevalence of antibodies to HCV (as tested by second generation ELISA, with RIBA-2 confirmation in ELISA 2 positive samples) was found to be low (0.3%) in the healthy general population. HCV infection prevalence increased in the general population in association with African or Asian origin and risk factors such as bisexuality, previous history of transfusion, and intravenous drug abuse. The prevalence of anti-HCV infection was also higher in specific patient groups infected with HIV or a history of transfusion or haemodialysis.
A prospective, randomized, double-blind study to determine the postoperative efficacy of steroids in tonsillectomy was performed in 49 children. A single dose of intravenous dexamethasone or placebo was administered after each child was anesthetized. Postoperatively each child was examined for objective signs of trismus (measured by interincisor distance), temperature elevation, and weight loss, as well as for subjective signs of mouth odor, oral intake, pain, level of activity, and analgesic usage. There were no statistical differences noted in any of the variables compared in the two groups and the complication rates were also similar.
PURPOSE: To evaluate high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in patients with lymphoid malignancy who had received prior radiation therapy. PATIENTS AND METHODS: Fifty-seven patients with non-Hodgkin's lymphoma (NHL; n = 23), Hodgkin's disease (HD, n = 32), or acute lymphoblastic leukemia (ALL; n = 2) with a history of previous radiation therapy were treated with cyclophosphamide (Cy; 7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2) (CBV) followed by ABMT. RESULTS: The projected 2-year probabilities of survival, event-free survival (EFS), and relapse were .31, .24, and .76, respectively. For patients with intermediate- and high-grade lymphoma and HD the probabilities were .27, .10, and .14 for EFS and .57, .90, and .77 for relapse. The probability of nonrelapse mortality in the first 100 days post-ABMT was 33%. Idiopathic pneumonia syndrome (IPS) was observed in no patients who received carmustine 300 mg/m2 and 23% of patients who received carmustine 600 mg/m2 (P = .05). Eight-three percent of patients who received mediastinal radiation therapy less than 3 months before transplant developed IPS, compared with 13% who received radiation therapy more than 3 months before transplant (P = .001). CONCLUSION: ABMT following high-dose CBV resulted in long-term disease-free survival in 25% of patients with lymphoid malignancies who had previously received dose-limiting radiation therapy. Fatal IPS and a high relapse rate were major factors limiting successful outcome following ABMT. The morbidity and mortality rates associated with the administration of carmustine 600 mg/m2 were prohibitively high, especially in patients who received mediastinal radiation immediately before ABMT, and were not associated with a decrease in post-ABMT relapse.