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PubMed2001

Positive selection of an MHC class-I restricted TCR in the absence of classical MHC class I molecules.

The H-2Ld alloreactive 2C T cell receptor (TCR) is commonly considered as being positively selected on the H-2Kb molecule. Surprisingly, 2C TCR+ CD8+ single-positive T cells emerge in massive numbers in fetal thymic organ culture originating from 2C transgenic, H-2KbD(b-/-) (2C+KbD(b-/-)) but not in fetal thymic organ culture from beta2-microglobulin(-/-) 2C transgenic animals. Mature CD8+ T cells are observed in newborn but not in adult 2C+KbD(b-/-) mice. These CD8+ T cells express the alpha4beta7 integrin, which allows them to populate the intestine, a pattern of migration visualized by intrathymic injection of FITC and subsequent accrual of FITC-labeled lymphocytes in the gut. We conclude that the 2C TCR is reactive not only with H-2Ld and H-2Kb, but also with nonclassical MHC class I products to enable positive selection of 2C+ T cells in the fetal and newborn thymus and to support their maintenance in the intestine.

Animals↗
PubMed1982

Molecular cloning of a cDNA sequence encoding a trophectoderm-specific marker during mouse blastocyst formation.

A cDNA clone has been isolated from a trophoblastoma cDNA library. The mRNA complementary to this sequence directs the in vitro synthesis of proteins. The two-dimensional electrophoretic pattern of migration of these proteins is superposable to that of the trophoblastoma intermediate filament proteins recognized by monoclonal antibody (mAb) TROMA-1. This mAb had previously been shown to label trophectoderm cells but not inner cell mass cells. With a sensitive binding assay (ultrasensitive enzymatic radioimmunoassay), these in vitro synthesized proteins were recognized by mAb TROMA-1. The proteins are immunoprecipitated by an antiserum directed against trophoblastoma intermediate filament proteins and by a serum directed against a major cytoskeletal protein found in murine extraembryonic endodermal cell lines (Endo-A) [Oshima R. G. (1981) J. Biol. Chem. 256, 8124-8133]. The cDNA sequence detects specific mRNA(s) migrating with 18S ribosomal RNA in trophoblastoma but not in embryonal carcinoma cells.

Animals↗
PubMed2003

Connexin 32 mutation in a Turkish family with X-linked Charcot-Marie-Tooth disease.

In the present work, we describe a large Turkish family (N=39) with Charcot-Marie-Tooth disease, which is the most commonly inherited peripheral neuropathy. The subjects were from four generations, including six hemizygote patients and nine heterozygote carrier females. Symptoms appeared in late childhood in males (mean age=13.5) but later in carrier females (mean age=33.5). The peripheral nerve conduction was more severely affected in males than females. Genomic DNA was isolated from peripheral white blood cells. Using SSCP technique (single strand conformation polymorphism analysis), abnormal patterns of migration were observed in 15 subjects: 6 of them were hemizygote males and 9 were heterozygote carrier females. We identified a mutation of the Cx32 gene, consisting of a guanine to adenine transition at position 271 (271G-A). The results suggested relations between degenerative processes and position of Cx32 mutations.

Adolescent↗
PubMed2006

3D non-linear analysis of the acetabular construct following impaction grafting.

The study investigates the short-term behaviour of the acetabular construct following revision hip arthroplasty, carried out using the Slooff-Ling impaction grafting technique; using 3D finite element analyses. An elasto-plastic material model is used to describe the constitutive behaviour of morsellised cortico-cancellous bone (MCB) graft, since it has been shown that MCB undergoes significant plastic deformation under normal physiological loads. Based on previous experimental studies carried out by the authors and others, MCB is modelled using non-linear elasticity and Drucker Prager Cap (DPC) plasticity. Loading associated with walking, sitting down, and standing up is applied to the acetabular cup through a femoral head using smooth sliding surfaces. The analyses yield distinctive patterns of migration and rotation due to different activities. These are found to be similar to those observed in the clinical setting.

Acetabulum↗
PubMed2004

SIMCOAL 2.0: a program to simulate genomic diversity over large recombining regions in a subdivided population with a complex history.

UNLABELLED: We present an extension of the program SIMCOAL, which allows for simulation of the genomic diversity of samples drawn from a set of populations with arbitrary patterns of migrations and complex demographic histories, including bottlenecks and various modes of demographic expansion. The main additions to the previous version include the possibility of arbitrary and heterogeneous recombination rates between adjacent loci and multiple coalescent events per generation, allowing for the simulation of very large samples and recombining genomic regions, together with the simulation of single nucleotide polymorphism data with frequency ascertainment bias. AVAILABILITY: http://cmpg.unibe.ch/software/simcoal2/.

Algorithms↗
PubMed2006

Cochlear implanted pupils in Scottish schools: 4-year school attainment data (2000-2004).

The Achievements of Deaf Pupils in Scotland (ADPS) project has been tracking the educational attainment of deaf pupils in Scotland's schools since 2000. At the time of writing, the database contains records for 1,752 deaf pupils (2000-2005). Here 4-year aggregate educational attainment data are reported for a subset of 152 school-aged deaf pupils with cochlear implants notified to the ADPS database between June 2000 and June 2004. The data describe primary and secondary school results in reading, writing, and math for this subgroup, as well as placement and communication characteristics. The educational attainment of the group of deaf pupils with cochlear implants is clearly marked when the deaf pupil population is disaggregated for hearing loss, achieving comparatively higher average attainment in both 5-14 Curriculum National Tests (Mathematics in particular) and Standard Grades. Therefore the gap in performance relative to the national population data is reduced for those deaf pupils, although it still widens at higher levels of achievement for the National Tests. Although most pupils with cochlear implants are placed in the mainstream, there is no pattern of migration toward mainstream schools. Some deaf pupils with cochlear implants moved out of mainstream to other types of placement, and this has implications for health-economic cost-utility assessments of cochlear implantation that favor mainstream education by drawing upon the relative cost of different placement types. These findings suggest that the ADPS program of research can contribute school outcome data as valuable real-life outcome measures in wider assessments of the benefit of cochlear implants to deaf children and deaf young people.

Adolescent↗
PubMed1989

DNA polymorphism in a subdivided population: the expected number of segregating sites in the two-subpopulation model.

Using the two subpopulation model, the expected numbers of segregating sites in a number of DNA sequences randomly sampled from a subdivided population were examined for several types of population subdivisions. It is shown that, in the case where the pattern of migration is symmetrical such as the finite island model, the expected number of segregating sites is independent of the migration rate when two or three DNA sequences are randomly sampled from the same subpopulation, but depends on the migration rate when more than three DNA sequences are sampled. It is also shown that the population subdivision can increase the amount of DNA polymorphism even in a subpopulation in some cases.

DNA↗
PubMed1993

Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria.

Taking advantage of the 'illegitimate' transcription of the phenylalanine hydroxylase (PAH) gene, we have been able to analyse the PAH cDNA sequence of hyperphenylalaninemic children in circulating lymphocytes. Using this approach, we have also identified 3 novel mutations in cDNA from liver and lymphocytes of two patients. One mutation, detected by the abnormal pattern of migration of an amplified fragment, is a C to T transition in the splice acceptor site of intron 10, which resulted in the skipping of exon 11 with the premature termination of RNA translation downstream from exon 12 (-3 IVS10). The other two mutations are missense mutations in exons 10 and 11 (respectively, L333F and E390G). The present study supports the view that circulating lymphocytes give easy access to PAH gene transcripts whose nucleotide sequence is identical to that reported in liver and therefore represent a useful tool for molecular genetic studies in phenylketonuria.

Amino Acid Sequence↗
PubMed1990

Geographical patterns of cancer mortality in Argentina.

Mortality rates in 1980, for the major cancer sites, are presented for Argentina as a whole, and for the 22 provinces, the capital city, and the southern territories. In comparison with other countries, national mortality rates are high for oesophageal cancer and cancer of the larynx, and moderately elevated for cancers of the lung, colon, breast, and bladder in males. The rates of tobacco-related cancers (lung, bladder and larynx) were much higher in males than females, and in males showed similar geographical patterns. In females, breast cancer rates by province showed a positive correlation with those for cancer of the colon, and a negative correlation with cervical cancer. There were marked geographical variations, quite different in the two sexes, in the mortality from oesophageal cancer. It is suggested that, although some of these variations within Argentina may be related to ethnic differences and patterns of migration from neighbouring countries, for the majority the explanations must lie in different exposures to environmental of lifestyle factors, such as diet.

Argentina↗
PubMed1996

Effect of Pravastatin in the Treatment of Patients with Type III Hyperlipoproteinemia.

OBJECTIVE: To determine the efficacy and safety of pravastatin in the treatment of subjects with Type III hyperlipoproteinemia. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: Four lipid research clinics in the United States. PATIENTS: Twenty subjects between 18 and 70 years old with three diagnostic features of Type III hyperlipoproteinemia: very-low-density lipoprotein cholesterol (VLDL-C)/total plasma triglyceride ratio in excess of 0.30; beta-migrating VLDL pattern on agarose-gel electrophoresis; and the homozygous apolipoprotein E phenotype E(2)/E(2). After 4 weeks of dietary control, the subjects were eligible if their mean plasma total cholesterol level was at least 250 mg/dl and mean plasma trigylceraide level was at least 220 mg/dL. INTERVENTIONS: Subjects were randomly assigned to pravastatin 40 mg hs or placebo hs at the start of the first 6-week double-blind treatment period. After completing this phase, subjects entered a 4-week placebo/drug washout phase before crossing over to the opposite treatment for the second 6-week double-blind treatment period. MEASUREMENTS: Plasma VLDL-C and low density lipoprotein cholesterol (LDL-C) after ultracentrifugation and total triglyceride, cholesterol and high-density lipoprotein cholesterol (HDL-C) after 6 weeks of treatment; adverse clinical events and abnormal laboratory results. RESULTS: After 6 weeks of pravastatin theraphy, plasma levels of VLDL-C and LDL-C decreased 49% and 39%, respectively (p less-than-or-equal 0.01 vs. placebo). Total cholesterol and triglyceride concentrations decreased 36% and 22%, respectively (p less-than-or-equal 0.001 vs. placebo). Levels of HDL-C increased 8% (p less-than-or-equal 0.01 vs. placebo). Pravastatin was tolerated well. One marked laboratory abnormality, an asymptomatic elevation of creatine phosphokinase, resolved upon completing pravastatin treatment. CONCLUSIONS: Pravastatin lowers plasma VLDL-C, LDL-C, total cholesterol, and triglyceride and raises HDL-C in subjects with Type III hyperlipoproteinemia. The safety profile is excellent. Pravastatin reductase inhibitor therapy affords a useful approach to the management of Type III or remnant removal disease.

Journal Article↗
PubMed2002

Ethanol induces morphological and dynamic changes on in vivo and in vitro neural crest cells.

BACKGROUND: Fetal alcohol syndrome (FAS) is an embryopathology related to maternal alcohol drinking. The information concerning the factors involved in the prenatal mechanisms of ethanol action at the cellular and molecular levels is scarce. Because several abnormal changes in FAS involve regions colonized by cell lineages derived from neural crest cells (NCCs), it is reasonable to propose that epigenetic alteration of this cell population can represent an important component of the etiopathogeny. The aim of this work was to evaluate the direct effect of ethanol on a chick embryo model, as well as on in vitro NCC morphology and dynamic behavior. METHODS: After ethanol treatment, in ovo or cultured chick embryos were used to determine the anatomical development of and to quantify the migratory parameters and apoptosis of NCCs. Scanning electron microscopy was performed on ethanol-perfused (and control) cultures of cephalic and trunk NCCs; the actin cytoskeleton was evaluated, and morphometric and dynamic parameters were determined after time-lapse videorecording. Recovery capacity after ethanol treatment was also determined. RESULTS: Chick embryos submitted to conditions sufficient to induce FAS in mammals displayed developmental disruptions frequently accompanied by cephalic/facial anomalies. In vitro studies also indicated that cephalic and trunk NCCs exposed to ethanol exhibited significant and permanent changes regarding cell shape, surface morphology, apoptotic cell death, cytoskeleton, and distance and velocity traveled, as well as an abnormal pattern of migration. CONCLUSIONS: Taking into account that even a limited period of abnormal behavior may imply serious consequences in the final cues of an embryonic cell population, our results indicate that the biological effects of ethanol on early development-even during a short time-could induce permanent ontogenetic perturbations of NCCs, with potentially dramatic effects on embryonic morphogenesis. These results support an important participation of NCCs in the etiopathogeny of FAS.

Animals↗
PubMed1981

Comparison of T antigen-associated host phosphoproteins from SV40-infected and -transformed cells of different species.

Simian virus 40 (SV40)-infected and -transformed cell contain, in addition to the virus-coded tumour antigens, one or more 48K to 56K host tumour antigens. At least part of this class of host proteins exists as a fast-sedimenting complex with the SV40 large T antigen. The host proteins associated with the large T antigen in SV40-transformed monkey, mouse and human cells and SV40-infected monkey cells were compared by two-dimensional gel electrophoresis and V8 partial proteolysis peptide mapping. Although these proteins differed slightly in apparent mol. wt. and peptide pattern, they migrated identically in isoelectric focusing gels. These results suggest that the cellular proteins associated with large T antigen in different hosts are very closely related to each other. Despite their similarities, the 55K proteins from different host cells form complexes of different stabilities with large T antigen, as judged by spontaneous dissociation of the complexes during storage, and the fractions of the 55K cellular protein and large T antigen found free and in the complexed form in each different host cell.

Animals↗
PubMed2001

Nanostructured copper filaments in electrochemical deposition.

In this Letter we report a novel self-organized copper electrodeposition in an ultrathin layer of CuSO4 electrolyte. The macroscopic fingering branches of the deposit consist of long copper filaments covered with periodic corrugated nanostructures. The mechanism of the nanostructure formation is explored and the origin of the significant descent of the branching rate in electrodeposition is discussed. We suggest that this growth phenomenon provides deeper insights into the role of diffusion and migration on pattern formation in electrodeposition.

Journal Article↗
PubMed1989

Loss of forestomach motility in sheep experiencing ruminal lactic acidosis is not dependent on duodenal acidification by lactic acid.

Reticuloruminal motility, duodenal myoelectrical activity, and the pH and lactic acid concentrations of ruminal and duodenal contents were monitored in rumen fistulated sheep that were intraruminally loaded with finely ground wheat (50 g/kg). Following ruminal loading, reticuloruminal motility was enhanced. However, within 6 hours of loading, forestomach motility was impaired and within 9 hours ruminal stasis occurred. During loss of forestomach motility, lactic acid concentrations in ruminal contents increased and may, in part, have contributed to the decrease in pH of ruminal fluids. The levels of lactic acid within duodenal contents also rose, however, the pH of duodenal contents remained unchanged. During the loss of reticuloruminal motility, premature regular spiking activity (RSA) and/or abnormal patterns of migrating myoelectric complexes (MMC) were not observed on the duodenum. These findings indicate that loss of forestomach motility in ruminal lactic acidosis may not be a consequence of acidification of the proximal duodenum by lactic acid produced in the forestomach.

Acidosis, Lactic↗
PubMed1998

Molecular epidemiology of hepatitis C in Australia.

The aim of this study was to determine the distribution of hepatitis C virus (HCV) genotypes in Australian patients with hepatitis C and to identify factors associated with particular genotypes. Serum isolates of HCV-RNA were genotyped using a commercial oligonucleotide hybridization (line probe) assay. Relationships between demographic factors, mode of HCV transmission and HCV genotype were assessed by logistic regression analysis. Among 463 patients with hepatitis C, 425 tested positive for HCV-RNA and a single HCV genotype was identified in 420 cases. The patients' places of birth were Australia or New Zealand (62%), Asia (13%), Europe (12%), Mediterranean (6%), Middle East (6%) and other countries (< 1%). The most common genotypes were type 1 (52%) or type 3 (32%); type 2 (9.3%), type 4 (5.5%) and type 6 (1.7%) were less common. Patients with genotype 1b were older (48 +/- 13 years, P< 0.001) and patients with genotype 3 were younger than the remaining patients (37 +/- 11 years vs 42 +/- 12 years, P< 0.001). Among type 1 isolates, 1b was more common for patients born outside Australia compared with those born in Australia (50% vs 13%, P< 0.001) whereas non-1b subtypes were more common among Australian-born patients. Likewise, 21 of 23 (91%) patients with type 4 were from Egypt and six of seven (86%) with type 6 were from Vietnam. The relative importance of parenteral risk factors for HCV also varied according to geographic origin. Thus, a definite risk factor for HCV acquisition was identified in > 95% of Australian-born patients, but in only 33% of Asian or Mediterranean-born patients. Logistic regression analysis indicated that region of birth and risk factor (intravenous drug use or not) would allow 98% of type 4 cases and 76% of type 1b cases to be identified correctly. In summary, region of birth, patterns of migration over time and risk factors for transmission of HCV interact to determine the distribution of HCV genotypes in a multi-racial community like Australia.

Adult↗