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Biomedical subjects

S Ball

Publications and source records attributed to S Ball.

At least 19 recordsLinked to original sources
PubMed2001

SHIRPA, a protocol for behavioral assessment: validation for longitudinal study of neurological dysfunction in mice.

Mouse models of neurological abnormalities are only valuable if accurately assessed. The three-stage SHIRPA procedure is used for the standardised assessment of mouse phenotype and has been reported in a high throughput experiment in which different mutants were ascertained at one age point using stage 1 of the protocol. In this study we have validated SHIRPA using a large cohort with one single mutation, 'legs at odd angles that causes neurological dysfunction. The cohort aged from 1 to 16 months during this study and this is the first longitudinal SHIRPA analysis.

Animals↗
PubMed2001

Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease.

Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia that usually presents early in infancy and is inherited in 10% to 20% of cases. Linkage analysis has shown that DBA in many of both dominant and recessive DBA families mapped to chromosome 19q13.2 leading to the cloning of a gene on chromosome 19q13.2 that encodes a ribosomal protein, RPS19. However, subsequently, mutations of the RPS19 gene have only been identified in 25% of all patients with DBA. This study analyzed 14 multiplex DBA families, 9 of which had 19q13.2 haplotypes inconsistent with 19q linkage. A genome-wide search for linked loci suggested the presence of a second DBA locus in a 26.4-centimorgan (cM) interval on human chromosome 8p. Subsequently, 24 additional DBA families were ascertained and all 38 families were analyzed with additional polymorphic markers on chromosome 8p. In total, 18 of 38 families were consistent with linkage to chromosome 8p with a maximal LOD score with heterogeneity of 3.55 at D8S277 assuming 90% penetrance. The results indicate the existence of a second DBA gene in the 26.4-cM telomeric region of human chromosome 8p23.3-p22, most likely within an 8.1-cM interval flanked by D8S518 and D8S1825. Seven families were inconsistent with linkage to 8p or 19q and did not reveal mutations in the RPS19 gene, suggesting further genetic heterogeneity. (Blood. 2001;97:2145-2150)

Chromosomes, Human, Pair 19↗
PubMed2001

Discovery of radio emission from the brown dwarf LP944-20.

Brown dwarfs are not massive enough to sustain thermonuclear fusion of hydrogen at their centres, but are distinguished from gas-giant planets by their ability to burn deuterium. Brown dwarfs older than approximately 10 Myr are expected to possess short-lived magnetic fields and to emit radio and X-rays only very weakly from their coronae. An X-ray flare was recently detected on the brown dwarf LP944-20, whereas previous searches for optical activity (and one X-ray search) yielded negative results. Here we report the discovery of quiescent and flaring radio emission from LP944-20, with luminosities several orders of magnitude larger than predicted by the empirical relation between the X-ray and radio luminosities that has been found for many types of stars. Interpreting the radio data within the context of synchrotron emission, we show that LP944-20 has an unusually weak magnetic field in comparison to active M-dwarf stars, which might explain the previous null optical and X-ray results, as well as the strength of the radio emissions compared to those at X-ray wavelengths.

Journal Article↗
PubMed2001

Mother to son transmission of del(1) (q42.1q42.3).

Familial transmission of cytogenetically visible autosome deletions is rare in humans. We describe here a case of mother to son transmission of an interstitial deletion of the distal long arm of chromosome one, breakpoints q42.1q42.3. This is the smallest described deletion of this region to date.

Abnormalities, Multiple↗
PubMed2001

Why is there so much end-stage renal failure of undetermined cause in UK Indo-Asians?

There is a high incidence of end-stage renal failure (ESRF) of undetermined cause in the Indo-Asian population of the UK. We studied patients presenting from the district of Brent and Harrow, which has a large Indo-Asian community, and whose renal services are largely provided by our centre. The diagnosis and ethnicity of patients starting renal replacement therapy and/or undergoing renal biopsy were collated. The incidences of ESRF, rates of renal biopsy and underlying diagnoses were calculated for Indo-Asians and Caucasians. Requirement for renal replacement therapy in Indo-Asians presenting to our centre from Brent and Harrow was 221/10(6)/year; no underlying diagnosis was identified in 77/10(6)/year. Renal biopsy rate in these patients was 456/10(6)/year, and the diagnostic categories significantly over-represented compared to Caucasians were: hypertension and ischaemia, focal segmental glomerulosclerosis (FSGS), idiopathic interstitial nephritis (IIN), diabetic nephropathy, minor glomerular abnormality, lupus nephritis and non-specific advanced chronic renal disease (p<0.001). The first three of these had a combined incidence of 135/10(6)/year in Indo-Asians and 31/10(6)/year in Caucasians. ESRF of undetermined cause is common in UK Indo-Asians, as is requirement for renal biopsy. Hypertension with ischaemia, FSGS and IIN are over-represented in the Indo-Asian population, and should be targeted for early diagnosis and treatment in this group.

Adult↗
PubMed2001

Starchless mutants of Chlamydomonas reinhardtii lack the small subunit of a heterotetrameric ADP-glucose pyrophosphorylase.

ADP-glucose synthesis through ADP-glucose pyrophosphorylase defines the major rate-controlling step of storage polysaccharide synthesis in both bacteria and plants. We have isolated mutant strains defective in the STA6 locus of the monocellular green alga Chlamydomonas reinhardtii that fail to accumulate starch and lack ADP-glucose pyrophosphorylase activity. We show that this locus encodes a 514-amino-acid polypeptide corresponding to a mature 50-kDa protein with homology to vascular plant ADP-glucose pyrophosphorylase small-subunit sequences. This gene segregates independently from the previously characterized STA1 locus that encodes the large 53-kDa subunit of the same heterotetramer enzyme. Because STA1 locus mutants have retained an AGPase but exhibit lower sensitivity to 3-phosphoglyceric acid activation, we suggest that the small and large subunits of the enzyme define, respectively, the catalytic and regulatory subunits of AGPase in unicellular green algae. We provide preliminary evidence that both the small-subunit mRNA abundance and enzyme activity, and therefore also starch metabolism, may be controlled by the circadian clock.

Amino Acid Sequence↗
PubMed2001

Predictors of bone mass by peripheral quantitative computed tomography in early adolescent girls.

This cross-sectional study used peripheral quantitative computed tomography (pQCT) to evaluate the influences of age, body size, puberty, calcium intake, and physical activity on bone acquisition in healthy early adolescent girls. The pQCT technique provides analyses of volumetric bone mineral density (vBMD) (mg/cm(3)) for total as well as cortical and trabecular bone compartments and bone strength expressed as polar strength strain index (mm(2)). Bone mass of the nondominant distal and midshaft tibia by pQCT and lumbar spine and hip by dual X-ray absorptiometry (DXA) were measured in 84 girls ages 11-14 yr. Pubertal stage, menarche status, anthropometrics, and 3-d food intake and physical activity records were collected. Total and cortical bone mineral content and vBMD measurements by pQCT were significantly related to lumbar spine and femoral neck BMD measurements by DXA. We did not note any significant determinants or predictors for trabecular bone mass. Body weight was the most important predictor and determinant of total and cortical bone density and strength in healthy adolescent girls. Menarche, calcium intake, height, body mass index, and weight-bearing physical activity level age were also identified as minor but significant predictors and determinants of bone density and strength. Bone measurements by the pQCT technique provide information on bone acquisition, architecture, and strength during rapid periods of growth and development. Broader cross-sectional studies using the pQCT technique to evaluate the influence of age, gender, ethnicity, puberty, body size, and lifestyle factors on bone acquisition and strength are needed.

Adolescent↗
PubMed2001

Early screening for dyslexia--a collaborative pilot project.

An ongoing collaborative project, currently being piloted in 12 Wiltshire primary schools, is described. The aim is to provide a means of identifying potentially dyslexic children by the end of Key Stage 1 (Year 2) with a view to early intervention. The causal links identified by research between phonological skills and literacy development are taken as the theoretical basis of an initial screening procedure, and an intervention package is implemented for identified children. Those demonstrating persistent difficulties one year later are further assessed over a school term using an assessment package designed to identify those children showing a dyslexic profile. Further intervention is then planned and implemented.

Child, Preschool↗
PubMed2000

Two imprinted gene mutations: three phenotypes.

Genetic modifications of imprinted genes have been generated in the mouse to investigate the regulation of their expression. They show classical imprinted gene inheritances. Here we describe two imprinted gene mutations deriving from mutagenesis experiments. One is expressed only when transmitted through males. It causes a prenatal growth retardation which resembles that of the Igf2 knockout and maps close to the locus on chromosome 7. Differences from the knockout, which include an abnormal head phenotype, homozygous lethality, and an inability to rescue a TME: (Igf2r-deficient) lethality, suggest that Igf2 itself may not be directly affected. The second mutation maps close to the GNAS: cluster of imprinted genes on distal chromosome 2. It gives two distinct phenotypes according to parental origin, a gross neonatal oedema with microcardia and a postnatal growth retardation. The oedema phenotype is effectively lethal and resembles that of mice with paternal partial disomy for distal chromosome 2, as well as that of mice having a maternally derived GNAS: exon 2 knockout. However, the second growth retardation phenotype differs from that of the maternal partial disomy and the paternal knockout. A hypothesis to explain the phenotypes associated with the three genotypes based on the NESP:/NESPAS: sense/antisense and GNASXL: transcripts in the GNAS: cluster is offered.

Aneuploidy↗
PubMed2000

Cloned pigs produced by nuclear transfer from adult somatic cells.

Since the first report of live mammals produced by nuclear transfer from a cultured differentiated cell population in 1995 (ref. 1), successful development has been obtained in sheep, cattle, mice and goats using a variety of somatic cell types as nuclear donors. The methodology used for embryo reconstruction in each of these species is essentially similar: diploid donor nuclei have been transplanted into enucleated MII oocytes that are activated on, or after transfer. In sheep and goat pre-activated oocytes have also proved successful as cytoplast recipients. The reconstructed embryos are then cultured and selected embryos transferred to surrogate recipients for development to term. In pigs, nuclear transfer has been significantly less successful; a single piglet was reported after transfer of a blastomere nucleus from a four-cell embryo to an enucleated oocyte; however, no live offspring were obtained in studies using somatic cells such as diploid or mitotic fetal fibroblasts as nuclear donors. The development of embryos reconstructed by nuclear transfer is dependent upon a range of factors. Here we investigate some of these factors and report the successful production of cloned piglets from a cultured adult somatic cell population using a new nuclear transfer procedure.

Animals↗
PubMed2000

The debranching enzyme complex missing in glycogen accumulating mutants of Chlamydomonas reinhardtii displays an isoamylase-type specificity.

To investigate the functions of debranching enzymes in starch biosynthesis, we have partially purified and characterized these activities from wild type and mutant sta7 Chlamydomonas reinhardtii. Mutants of the STA7 locus substitute synthesis of insoluble granular starch by that of small amounts of glycogen-like material. The mutants were previously shown to lack an 88 kDa debranching enzyme. Two distinct debranching activities were detected in wild-type strains. The 88 kDa debranching enzyme subunit missing in glycogen-producing mutants (CIS1) is shown to be part of a multimeric enzyme complex. A monomeric 95 kDa debranching enzyme (CLD1) cleaved alpha-1,6 linkages separated by as few as three glucose residues while the multimeric complex was unable to do so. Both enzymes were able to debranch amylopectin while the alpha-1,6 linkages of glycogen were completely debranched by the multimeric complex only. Therefore CLD1 and the multimeric debranching enzyme display respectively the limit-dextrinase (pullulanase) and isoamylase-type specificities. Various mutations in the STA7 locus caused the loss of both CIS1 and of the multimeric isoamylase complex. In contrast to rice and maize mutants that accumulate phytoglycogen owing to mutation of an isoamylase-type DBE, isoamylase depletion in Chlamydomonas did not result in any qualitative or quantitative difference in pullulanase activity.

Journal Article↗
PubMed2000

Familial cryptic (20;21) translocation identified by in situ hybridization technologies.

We report on a familial cryptic (20;21) translocation [(t20;21)] that was initially suspected with the observation of a single chromosome 21 specific signal in an interphase nuclei by in situ hybridization (FISH) study performed on a 34-week gestation amniotic fluid specimen. The genetic amniocentesis was prompted by the presence of fetal anomalies detected by ultrasound. In addition, there was a family history of a maternal uncle with mental retardation and multiple malformations and an apparently normal karyotype. No obvious aberration could be detected in the G-banded karyotype prepared from the amniotic fluid specimen. A FISH study using a chromosome 21 specific long arm probe and chromosome 20 whole chromosome paint, however, showed an unbalanced rearrangement in the fetus [46,XY, der(21)t(20;21)(q13.2;q22.13 or 22.2) mat]. The mother and maternal grandmother were demonstrated to be balanced translocation carriers. These results were confirmed by multicolor karyotyping. This familial aberration was discovered by chance in the interphase FISH analysis. Our experience with this case, however, serves to emphasize the importance of the reevaluation of patients with mental retardation and congenital malformations of unknown cause and prudent use of multicolor karyotyping in the detection of cryptic cytogenetic rearrangements.

Abnormalities, Multiple↗
PubMed2000

Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group.

BACKGROUND: We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. METHODS: Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. FINDINGS: Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p<O.001). For all five trials the ACE inhibitor group had lower rates of death than the placebo group (1,467/6,391 [23.0%] vs 1,710/6,372 [26.8%]; 0.80 [0.74-0.87]) and lower rates of reinfarction (571 [8.9%] vs 703 [11.0%]; 0.79 [0.70-0.89]), readmission for heart failure (876 [13.7%] vs 1202 [18.9%]; 0.67 [0.61-0.74]), and the composite of these events (2161 [33.8%] vs 2610 [41.0%]; 0.72 [0.67-0.78]; all p<0.0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.

Aged↗
PubMed2000

Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group.

CONTEXT: Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. OBJECTIVE: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure. DESIGN: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year. SETTING: Three hundred thirteen sites in 14 countries. PARTICIPANTS: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy. INTERVENTIONS: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001). MAIN OUTCOME MEASURES: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients. RESULTS: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively). CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.

Adrenergic beta-Antagonists↗
PubMed2000

Gram positive infection in trauma patients: new strategies to decrease emerging Gram-positive resistance and vancomycin toxicity.

Bacterial resistance to antibiotics has become a serious problem in medicine. Particularly worrisome is the increasing incidence of multi-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Not surprisingly, in view of the high incidence of life-threatening infections and heavy antibiotic use, resistance has become very frequent and problematic in intensive care units. The standard approach for the treatment of MRSA is vancomycin or teicoplanin. Long-term therapeutic and unrestricted prophylactic use of vancomycin has given rise to VRE which in turn may lead to the emergence of vancomycin-resistant S. aureus (VRSA) through plasmid mediated transmission. In order to reduce the incidence of VRE and to avoid the emergence of VRSA, vancomycin use should be restricted and alternative antibiotic strategies should be developed. Using those antibiotics to which MRSA are still generally sensitive, perhaps in combination with new ones, such as, quinupristin/dalfopristin, should be entertained. We performed a retrospective review of the Gram-positive infections in our Level 1 Trauma Center Intensive Care Unit, and an analysis of the resistance patterns of the NMSA infections showed that additional resistance rarely develops within less than 5 days. We then designed a new strategy for the treatment of MRSA infections. This strategy consists of the sequential use of a range of antibiotics with activity against MRSA in short 5-7 day pulses until the full clinical course is completed. Studies validating the benefit of this approach are currently in preparation.

Anti-Bacterial Agents↗