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J Hall

Publications and source records attributed to J Hall.

At least 181 records · Page 10Linked to original sources
PubMed1997

Co-integration and expression of bacterial and genomic transgenes in the pancreatic and intestinal tissues of transgenic mice.

Previous studies in the mammary gland have reported the 'rescue' of poorly expressed cDNA transgenes by their co-integration with a genomic sequence specifically expressed in the mammary tissue. To determine whether a highly expressed genomic sequence co-integrated with a cDNA sequence can rescue expression in other tissues, the expression of a bacterial gene, celE', encoding endoglucanase E' (EGE'), was investigated in the pancreatic and intestinal epithelia of transgenic mice. To rescue pancreatic expression, the human growth hormone genomic sequence was co-integrated with the bacterial gene, whereas to rescue intestinal expression, the genomic sequence encoding the intestinal fatty acid binding protein was used. In both studies the number of transgenics expressing celE' was significantly increased (60%) by the use of a genomic sequence, but only in the intestinal tissues was the level of celE' expression improved. However, this improvement was modest, representing at maximum only a doubling in the levels of EGE'. Thus permissive integration or rescue may be general, but the overall level of rescue is often insubstantial compared to the endogenous expression of the transgene genomic DNA.

Animals↗
PubMed1997

Prolonged allogeneic and xenogeneic microchimerism in unmatched primates without immunosuppression by intrathymic implantation of CD34+ donor marrow cells.

Engraftment of stem cell-enriched donor marrow implanted in the thymus of a foreign host might facilitate acceptance of donor-specific organ or tissue grafts. To test this hypothesis, allogeneic and xenogeneic CD34+ marrow cells from unrelated adult male baboons and humans were injected intrathymically in eight infant female baboons, both with and without standard cyclosporine-based immunosuppression. In allogeneic experiments, male (donor) cells, of both T- and B-cell lineages, were detected by PCR in the peripheral blood of all six recipients and persisted for at least 15 months in 2/4 recipients studied longtutudinally. Donor-derived skin grafts survived twice as long as third party grafts in unimmunosuppressed recipients. In xenogeneic protocols, human male (donor) cells were demonstrable for 7 and 15 months, respectively, in two baboon recipients with evidence that implanted human CD34+ cells had produced lymphoid progeny. Survival of donor-specific skin xenografts was prolonged in one of two recipients. These experiments demonstrate that the intrathymic injection of CD34+ marrow cells can result in long-lasting lymphohematopoietic microchimerism in unrelated primates even without immunosuppression and can alter donor-specific skin graft survival.

Animals↗
PubMed1997

Cloning and characterization of the Arabidopsis cyclic phosphodiesterase which hydrolyzes ADP-ribose 1'',2''-cyclic phosphate and nucleoside 2',3'-cyclic phosphates.

In eukaryotic cells, pre-tRNAs spliced by a pathway that produces a 3',5'-phosphodiester, 2'-phosphomonoester linkage contain a 2'-phosphate group adjacent to the tRNA anticodon. This 2'-phosphate is transferred to NAD to give adenosine diphosphate (ADP)-ribose 1", 2"-cyclic phosphate (Appr>p), which is subsequently metabolized to ADP-ribose 1"-phosphate (Appr-1"p). The latter reaction is catalyzed by a cyclic phosphodiesterase (CPDase), previously identified in yeast and wheat. In the work presented here, we describe cloning of the Arabidopsis cDNA encoding the 20-kDa CPDase that hydrolyzes Appr>p to Appr-1"p. Properties of the bacterially overexpressed and purified Arabidopsis enzyme are similar to those of wheat CPDase. In addition to their transformation of Appr>p, both enzymes hydrolyze nucleoside 2',3'-cyclic phosphates to nucleoside 2'-phosphates. For the Arabidopsis CPDase, the apparent Km values for Appr>p, A>p, C>p, G>p, and U>p are 1.35, 1.34, 2.38, 16.86, and 17.67 mM, respectively. Southern analysis indicated that CPDase in Arabidopsis is encoded by a single copy gene that is expressed, at different levels, in all Arabidopsis organs that were analyzed. Indirect immunofluorescence, performed with transfected protoplasts, showed that CPDase is localized in the cytoplasm. Based on substrate specificity and products generated, the plant enzyme differs from other known cyclic phosphodiesterases. The Arabidopsis CPDase does not have recognizable structural similarity or motifs in common with proteins deposited in public data bases.

Adenosine Diphosphate Ribose↗
PubMed1997

Design of a cost-effectiveness study within a randomized trial: the LIPID Trial for Secondary Prevention of IHD. Long-term Intervention with Pravastatin in Ischemic Heart disease.

The Long-term Intervention with Pravastatin in Ischemic Heart Disease (LIPID) trial is a double-blind, randomized, placebo-controlled trial evaluating the long-term effect of pravastatin on coronary mortality in patients with a previous myocardial infarction or unstable angina-ischemic heart disease (IHD). It is planned to run for at least five years with 9014 patients from 85 centers in Australia and New Zealand. The trial will monitor cause-specific mortality and major clinical events associated with each treatment. Running in parallel with the main study is a prospective economic analysis, the objectives of which are (1) to estimate the effectiveness of pravastatin compared with placebo in terms of survival, quality of life (QOL), and quality-adjusted life-years (QALY); (2) to estimate the resource usage associated with pravastatin compared with placebo-in particular, to study whether it alters resource usage through prevention of disease progression; and (3) to use this information for a cost-utility analysis with cost per quality-adjusted life-year as the unit of analysis. A novel aspect of the design is the use of a preliminary cost-effectiveness analysis, based on "best-guess" values, and a sensitivity analysis over plausible ranges to guide the choice of subsample size. Some data, such a mortality, days spent in hospital, major clinical events, and drug use, are being collected within the main LIPID trial. However, additional subsamples for the cost-effectiveness study will include information on quality of life, time off work, and resources used, such as time in hospital, procedures, and medications taken. The methods and sample sizes for these substudies have been a crucial issue in validity and feasibility.

Absenteeism↗
PubMed1997

In vitro fertilization for male infertility: when and how?

The first observation that in vitro fertilization (IVF) was useful for treating oligozoospermia and oligoasthenozoospermia was reported by Fishel and Edwards in 1982. This was followed by a series of cases indicating the value of IVF in such cases. Conventional IVF has been modified and refined to achieve increased rates of conception in cases of male factor infertility. Methods such as high insemination concentration IVF for the treatment of teratozoospermia and microscopic IVF for the treatment of oligozoospermia have had some impact on fertilization and pregnancy rates; however, reports of success are varied. The recent advent of micromanipulation and, in particular, intracytoplasmic sperm injection (ICSI) has overshadowed the use of these modified IVF procedures. Because of the high fertilization and pregnancy rates achieved with ICSI, other micromanipulation techniques (subzonal insemination and partial zona dissection) have been abandoned; there have also been suggestions that other more conventional techniques, i.e. IVF, should also be abandoned and that ICSI become the sole technique for the treatment of infertility. The rapid increase in the number of centres using ICSI has led to extreme pressure for individual units to achieve high fertilization and pregnancy rates and there is a temptation to assign all patients to ICSI treatment. It is important that, in this highly competitive environment, new techniques are not applied haphazardly and reduced to the mere injection of gametes and achievement of pregnancy regardless of the cause of infertility. In his 1986 IVF--Historical Perspective, Fishel quoted Auguste Comte: 'to understand science it is necessary to know its history'. IVF has much recent history in animal and also human work. Although ICSI is the most significant therapeutic advance in male infertility treatment, its application to human IVF is only 4 years old, with a paucity of animal studies on which to rely. For this reason IVF still plays a very important role in the treatment of male factor infertility and should only be ruled out when it has failed previously or the number of available sperm is limited.

Decision Making, Computer-Assisted↗
PubMed1997

The sequence-specific cleavage of RNA by artificial chemical ribonucleases.

Based on work spanning 50 years, several groups have recently achieved the specific cleavage of RNA by attaching RNA-cleaving chemical moieties to antisense oligonucleotides. Such artificial chemical ribonucleases have potential as a possible next generation of antisense compounds and also as probes for structural and functional investigations of RNA. Different chemical moieties, such as polyamines, imidazoles, and metal complexes, have been used as the catalytic part of the artificial nucleases. To be of practical use as therapeutics, however, the conjugates must fulfil a number of strict requirements, such as ease of preparation, chemical stability, selectivity, nontoxicity, and, for metal complexes, inertness to loss of cation from the ligand. In addition, high cleavage efficiency is essential to overcome short lifetimes of cellular mRNA targets, and the reaction should not depend on additional cofactors. Based on these criteria, we believe that metal complexes, in particular macrocyclic lanthanide complexes, have the best chance of success for said purpose.

Base Sequence↗
PubMed1997

Large scale identification of genes involved in cell surface biosynthesis and architecture in Saccharomyces cerevisiae.

The sequenced yeast genome offers a unique resource for the analysis of eukaryotic cell function and enables genome-wide screens for genes involved in cellular processes. We have identified genes involved in cell surface assembly by screening transposon-mutagenized cells for altered sensitivity to calcofluor white, followed by supplementary screens to further characterize mutant phenotypes. The mutated genes were directly retrieved from genomic DNA and then matched uniquely to a gene in the yeast genome database. Eighty-two genes with apparent perturbation of the cell surface were identified, with mutations in 65 of them displaying at least one further cell surface phenotype in addition to their modified sensitivity to calcofluor. Fifty of these genes were previously known, 17 encoded proteins whose function could be anticipated through sequence homology or previously recognized phenotypes and 15 genes had no previously known phenotype.

Cell Membrane↗
PubMed1997

Comparison of second trimester biometry in singleton and twin pregnancies conceived with assisted reproductive techniques.

The objective of this study was to investigate the size of singleton vs twin pregnancies at the time of a second trimester dating scan. The analysis included 86 infants from 63 pregnancies achieved with assisted reproductive techniques, comprising 40 singletons and 46 twins. Measurements of second trimester biparietal diameter (n = 85) and femur length (n = 74) were plotted against the precisely known gestational age. A common regression line was calculated for each parameter and the residuals for singletons and twins were compared. Gestational age and weight at birth were also analysed for each group. There was no significant difference between singletons and twins in biparietal diameter or femur length in second trimester. In contrast, twins had a lower mean birthweight, gestational age at birth, and weight-for-gestational age centile compared with singletons. Singleton babies from these pregnancies had an average birthweight centile of 49.8% (i.e. close to the median for spontaneously conceived pregnancies in our population). We concluded that the same pregnancy dating charts can be used for singletons and twins. At corresponding gestational age, twins are smaller than singletons at birth because of slower growth in the third trimester.

Anthropometry↗
PubMed1997

Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation.

The functionality of the p53-mediated pathway, activated in response to DNA damage, has been assessed in primary fibroblast cell cultures and Epstein-Barr virus-transformed lymphoblastoid cell lines derived from Nijmegen breakage syndrome (NBS) patients. This autosomal recessive disease is characterized by microcephaly, growth and mental retardation, chromosomal instability, radiosensitivity, and high cancer incidence. The recent mapping of the NBS gene to chromosome 8q21 demonstrates that NBS is genetically distinct from ataxia telangiectasia (AT). Changes in p53 protein levels were significantly reduced and delayed in all the NBS fibroblast cell cultures and lymphoblastoid cell lines examined compared to normal cultures over a 4-h period postirradiation (5 Gy). The transcriptional activation of p21(WAF1/CIP1) mRNA was also lower in 12 NBS fibroblast cultures examined. In agreement with an abrogated p53 function, NBS cells exposed to ionizing radiation show an abnormal cell cycle arrest at G1-S and a prolonged accumulation of cells in the G2 phase. In contrast, exposure to the alkylating agent methyl methanesulfonate results in similar increases of p53 and p21(WAF1/CIP1) mRNA in both cell types. The ATM gene transcript was found to be expressed at similar levels in NBS and normal cells, whereas it was strongly reduced in the AT homozygote cells examined. These results suggest that the ATM gene product cannot substitute for that of the NBS gene in the signaling of cellular damage produced by ionizing radiation and that both are involved in the activation of p53. The suboptimal p53-mediated response could contribute to the high cancer risk and radiosensitivity seen in NBS patients.

Ataxia Telangiectasia↗
PubMed1997

Analysis of a 103 kbp cluster homology region from the left end of Saccharomyces cerevisiae chromosome I.

The DNA sequence and preliminary functional analysis of a 103-kbp section of the left arm of yeast chromosome I is presented. This region, from the left telomere to the LTE1 gene, can be divided into two distinct portions. One portion, the telomeric 29 kbp, has a very low gene density (only five potential genes and 21 kbp of noncoding sequence), does not encode any "functionally important" genes, and is rich in sequences repeated several times within the yeast genome. The other portion, with 37 genes and only 14.5 kbp of noncoding sequence, is gene rich and codes for at least 16 "functionally important" genes. The entire gene-rich portion is apparently duplicated on chromosome XV as an extensive region of partial gene synteney called a cluster homology region. A function can be assigned with varying degrees of precision to 23 of the 42 potential genes in this region; however, the precise function is know for only eight genes. Nineteen genes encode products presently novel to yeast, although five of these have homologs elsewhere in the yeast genome.

Base Sequence↗
PubMed1997

Diagnosing ADHD (predominantly inattentive and combined type subtypes): discriminant validity of the behavior assessment system for children and the achenbach parent and teacher rating scales.

Compared the effectiveness of discriminating attention deficit/hyperactivity disorder (ADHD) subtypes using the Parent Rating Scale (PRS) and Teacher Rating Scale (TRS) of the Behavior Assessment System for Children (BASC) and the Parent Report Form and Teacher Report Form (TRF) of the Achenbach Child Behavior Checklist (CBCL). To determine the extent to which these scales measured similar behaviors, Pearson Product-Moment Correlations were computed for the parent scales (PRS and CBCL) and for the teacher scales (TRS and TRF). Results indicated that correlations were significant for a number of scales. Discriminant analysis does not suggest a strong advantage of either measure in differentiating children with ADHD from those who do not meet criteria for ADHD, except for the BASC TRS which has better predictive ability for children who do not meet ADHD criteria. For subtypes of ADHD, and specifically the ADHD: Predominantly Inattentive subtype, however, results would favor the use of the BASC PRS and TRS.

Aggression↗
PubMed1997

Neuropsychological profiles of children diagnosed as specific language impaired with and without hyperlexia.

This study compared the neuropsychological profiles of 46 children with Specific Language Impairment (SLI) and 16 children with SLI and Hyperlexia (SLI + H). The results indicated that the essential feature of Hyperlexia is Specific Language Impairment and not reading disability. Thus, Hyperlexia would be best conceptualized as a subgroup of Developmental Language Disorder rather than as a subgroup of Developmental Dyslexia. Further, the SLI + H group exhibited significantly better developed visual/spatial memory which, along with average visual perceptual skills, appears to be the major contributing factor to their elevated word recognition and spelling ability. Finally, it should be noted that both groups of children exhibited decreasing performance on tasks of immediate auditory/verbal memory as the language/semantic demands of the memory task increased. This finding appears to be the result of a limited capacity for immediate verbal processing and not the result of a deficit in verbal learning and recall.

Journal Article↗
PubMed1997

The use of biomarkers to study pathogenesis and mechanisms of cancer: oesophagus and skin cancer as models.

Recent advances in molecular biology have made it possible to use genetic alterations associated with cancer as biomarkers to study the pathogenesis and mechanisms of cancer. However, the lessons that can be drawn from the analysis of alterations in a particular cancer gene are extremely dependent upon the biological context in which they arise. In this article, we discuss the biological significance of alterations in the p53 tumour suppressor gene in cancers of the oesophagus and of the skin. In both tissues, different forms of cancer occur at high frequency (squamous-cell carcinoma and adenocarcinoma in the oesophagus; squamous-cell carcinoma, basal-cell carcinoma and melanoma in the skin). We show that specific patterns of p53 alteration occur in these various cancers and that analysis of these alterations is useful to make inferences about the etiopathogenesis of cancers of the oesophagus and of the skin.

Adenocarcinoma↗