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Biomedical subjects

S Ball

Publications and source records attributed to S Ball.

At least 55 records · Page 3Linked to original sources

Biochemical characterization of the chlamydomonas reinhardtii alpha-1,4 glucanotransferase supports a direct function in amylopectin biosynthesis

Plant alpha-1,4 glucanotransferases (disproportionating enzymes, or D-enzymes) transfer glucan chains among oligosaccharides with the concomitant release of glucose (Glc). Analysis of Chlamydomonas reinhardtii sta11-1 mutants revealed a correlation between a D-enzyme deficiency and specific alterations in amylopectin structure and starch biosynthesis, thereby suggesting previously unknown biosynthetic functions. This study characterized the biochemical activities of the alpha-1,4 glucanotransferase that is deficient in sta11-1 mutants. The enzyme exhibited the glucan transfer and Glc production activities that define D-enzymes. D-enzyme also transferred glucans among the outer chains of amylopectin (using the polysaccharide chains as both donor and acceptor) and from malto-oligosaccharides into the outer chains of either amylopectin or glycogen. In contrast to transfer among oligosaccharides, which occurs readily with maltotriose, transfer into polysaccharide required longer donor molecules. All three enzymatic activities, evolution of Glc from oligosaccharides, glucan transfer from oligosaccharides into polysaccharides, and transfer among polysaccharide outer chains, were evident in a single 62-kD band. Absence of all three activities co-segregated with the sta11-1 mutation, which is known to cause abnormal accumulation of oligosaccharides at the expense of starch. To explain these data we propose that D-enzymes function directly in building the amylopectin structure.

Journal Article↗

Genetic and biochemical evidence for the involvement of alpha-1,4 glucanotransferases in amylopectin synthesis

We describe a novel mutation in the Chlamydomonas reinhardtii STA11 gene, which results in significantly reduced granular starch deposition and major modifications in amylopectin structure and granule shape. This defect simultaneously leads to the accumulation of linear malto-oligosaccharides. The sta11-1 mutation causes the absence of an alpha-1,4 glucanotransferase known as disproportionating enzyme (D-enzyme). D-enzyme activity was found to be correlated with the amount of wild-type allele doses in gene dosage experiments. All other enzymes involved in starch biosynthesis, including ADP-glucose pyrophosphorylase, debranching enzymes, soluble and granule-bound starch synthases, branching enzymes, phosphorylases, alpha-glucosidases (maltases), and amylases, were unaffected by the mutation. These data indicate that the D-enzyme is required for normal starch granule biogenesis in the monocellular alga C. reinhardtii.

Journal Article↗

Rates of personality disorders in substance abusers: a comparison between DSM-III-R and DSM-IV.

The publication of the DSM-IV represents the first revision in 7 years to the DSM-III-R diagnostic criteria. The purpose of the current study is to evaluate the impact of changes to the Axis II criteria on diagnostic rates in a substance abusing population. We interviewed 370 patients entering treatment using a modified version of the SCID-II, which allowed for the diagnosis of both DSM-III-R and DSM-IV Axis II diagnoses. Prevalence rates for each Axis II disorder are given, as well as kappa statistics showing diagnostic agreement between the two systems. The results of this study indicate good rates of diagnostic agreement between the two systems with a few notable exceptions. Poor rates of diagnostic agreement were obtained for the histrionic and dependent diagnostic categories. No single diagnostic change appears to be responsible for the prevalence rate differences between the two systems.

Adult↗

The use of tailed octamer primers for cycle sequencing.

Studies have been carried out on the use of octamer oligonucleotides tailed with different base analogues as primers in cycle sequencing reactions. 5-Nitroindole tails improved the performance as primers of a number of octamers. A tail length of three or four 5-nitroindole residues significantly increased the sequencing signal intensity for almost all primers. The use of incomplete libraries of tailed octamer primers for primer walking is discussed.

Base Sequence↗

Amylose is synthesized in vitro by extension of and cleavage from amylopectin.

Amylose synthesis was obtained in vitro from purified Chlamydomonas reinhardtii starch granules. Labeling experiments clearly indicate that initially the major granule-bound starch synthase extends glucans available on amylopectin. Amylose synthesis occurs thereafter at rates approaching or exceeding those of net polysaccharide synthesis. Although these results suggested that amylose originates from cleavage of a pre-existing external amylopectin chain, such transfer of chains from amylopectin to amylose was directly evidenced from pulse-chase experiments. The structure of the in vitro synthesized amylose could not be distinguished from in vivo synthesized amylose by a variety of methods. Moreover high molecular mass branched amylose synthesis preceded that of the low molecular mass, suggesting that chain termination occurs consequently to glucan cleavage. Short pulses of synthesis followed by incubation in buffer with or without ADP-Glc prove that transfer requires the presence of the glucosyl-nucleotide. Taken together, these observations make a compelling case for amylopectin acting as the in vivo primer for amylose synthesis. They further prove that extension is followed by cleavage. A model is presented that can explain the major features of amylose synthesis in plants. The consequences of intensive amylose synthesis on the crystal organization of amylopectin are reported through wide angle x-ray analysis of the in vitro synthesized polysaccharides.

Amylopectin↗

Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I-iomazenil SPET study.

BACKGROUND: The role of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in schizophrenia has previously been investigated using postmortem material. Recently, using single photon emission tomography (SPET) with the selective benzodiazepine antagonist 123I-Iomazenil as the radioligand, we have demonstrated an in vivo relationship between reduced GABAA/benzodiazepine receptor binding and the severity of positive symptomatology in schizophrenia. The present study aimed to build on this using the same in vivo scanning techniques, and relating findings to cognitive functioning. METHODS: Ten nonpsychiatric control subjects and 15 schizophrenic patients, matched for age and handedness, were scanned. A battery of neuropsychologic tests was also administered. RESULTS: Correlational analysis revealed a pattern of increased correlations between GABAA/benzodiazepine receptor binding and task performance, in the schizophrenic group compared to the control group. CONCLUSIONS: Findings are preliminary but suggest a relationship between reduced GABAA/benzodiazepine receptor binding and poorer cognitive functioning, involving memory and visual attention processes, in the schizophrenic group but not in the control group. A role for GABA in the pathophysiology of schizophrenia is suggested. Limitations of the present study and suggestions for future research are discussed.

Adult↗

Starch granules: structure and biosynthesis.

The emphasis of this review is on starch structure and its biosynthesis. Improvements in understanding have been brought about during the last decade through the development of new physicochemical and biological techniques, leading to real scientific progress. All this literature needs to be kept inside the general literature about biopolymers, despite some confusing results or discrepancies arising from the biological variability of starch. However, a coherent picture of starch over all the different structural levels can be presented, in order to obtain some generalizations about its structure. In this review we will focus first on our present understanding of the structures of amylose and amylopectin and their organization within the granule, and we will then give insights on the biosynthetic mechanisms explaining the biogenesis of starch in plants.

Carbohydrate Conformation↗

Identification of microdeletions spanning the Diamond-Blackfan anemia locus on 19q13 and evidence for genetic heterogeneity.

Diamond-Blackfan anemia (DBA) is a rare pure red-cell hypoplasia of unknown etiology and pathogenesis. A major DBA locus has previously been localized to chromosome 19q13.2. Samples from additional families have been collected to identify key recombinations, microdeletions, and the possibility of heterogeneity for the disorder. In total, 29 multiplex DBA families and 50 families that comprise sporadic DBA cases have been analyzed with polymorphic 19q13 markers, including a newly identified short-tandem repeat in the critical gene region. The results from DNA analysis of 29 multiplex families revealed that 26 of these were consistent with a DBA gene on 19q localized to within a 4.1-cM interval restricted by loci D19S200 and D19S178; however, in three multiplex families, the DBA candidate region on 19q13 was excluded from the segregation of marker alleles. Our results suggest genetic heterogeneity for DBA, and we show that a gene region on chromosome 19q segregates with the disease in the majority of familial cases. Among the 50 families comprising sporadic DBA cases, we identified two novel and overlapping microdeletions on chromosome 19q13. In combination, the three known microdeletions associated with DBA restrict the critical gene region to approximately 1 Mb. The results indicate that a proportion of sporadic DBA cases are caused by deletions in the 19q13 region.

Chromosome Mapping↗

Personality disorders in substance abusers: relation to substance use.

Previous studies have documented high but variable rates of DSM personality disorders (axis II) in clinical samples of substance abusers. Distinguishing between personality disorder symptoms that are independent versus substance-related (SR) is a particular challenge for diagnosing comorbid axis II disorders in substance abusers. DSM-IV guidelines currently recommend excluding axis II symptoms that are accounted for by an axis I disorder, including a substance use disorder. In this study, axis II diagnoses were made on a heterogenous clinical sample of 370 patients entering treatment for substance use disorders. Axis II diagnoses were made according to DSM-III-R criteria using the Structured Clinical Interview for DSM-III-R (SCID-II), which was modified to determine, on an item-by-item basis, whether symptoms were attributed to subjects' substance use disorders or independent of these disorders. The majority (57.0%) of substance use disorder patients met criteria for at least one comorbid axis II disorder, with cluster B (45.7%) being particularly prominent, especially antisocial personality disorder (ASP) (27.0%) and borderline personality disorder (BPD) (18.4%). Notably, inclusion of SR symptoms led to a substantial number of newly diagnosed cases, especially for ASP (19.2%) and BPD (11.4%). Including SR symptoms improved the reliability of ASP and did not change the reliability of BPD diagnoses. Generally, patients with SR and independent personality disorders had a similar clinical profile.

Adult↗

A reappraisal of the role of Gram's stains of tracheal aspirates in guiding antibiotic selection in the surgical intensive care unit.

BACKGROUND: Tracheal aspirate Gram's stains are used to guide antibiotic selection in empiric pneumonia treatment in the surgical intensive care unit (SICU). We questioned whether Gram's stains predict the organism cultured. METHODS: A retrospective review of prospectively collected data. RESULTS: Gram's stains correlated with the cultured organism in 284 of 543 (52%) SICU cultures and in 226 of 403 (56%) trauma intensive care unit (TICU) cultures. Gram-negative rod (GNR) stains yielded GNR organisms in 182 of 205 (89%) SICU cultures and in 160 of 176 (91%) TICU cultures. Gram-positive coccus (GPC) stains yielded GPC organisms in 75 of 228 (33%) SICU cultures and in 52 of 149 (35%) TICU cultures. Noncorrelates in the GPC group were predominantly GNRs (185 of 250 (74%)). CONCLUSION: When the clinical decision has been made that empiric antibiotic coverage is necessary, GNR coverage should be instituted regardless of Gram's stain result. The decision to institute GPC coverage needs to be supported by clinical data other than the Gram's stain.

Adolescent↗

Empiric therapy of sepsis in the surgical intensive care unit with broad-spectrum antibiotics for 72 hours does not lead to the emergence of resistant bacteria.

BACKGROUND: It is our practice to treat suspected sepsis with imipenem/cilastatin and gentamicin (IMP/GENT) for 72 hours while awaiting culture results. We wanted to determine if this practice engenders antimicrobial resistance. METHODS: Review of prospectively collected data regarding use of IMP/GENT and microbial sensitivity to imipenem/cilastatin during the first and last 7 months of a 19-month study period (October 1, 1995, to April 30, 1997). RESULTS: The susceptibility of appropriate organisms to imipenem/cilastatin was 76% in the early period and 80% in the late period (p = 0.42). Pseudomonas aeruginosa was more susceptible in the late period (88 vs. 62%; p = 0.007). Resistance to gentamicin (30% early vs. 21% late; p = 0.02) and representative cephalosporins (cefoxitin, 52% early vs. 61% late; p = 0.35; ceftazidime, 26% early vs. 23% late; p = 0.76) did not develop during the study period. The incidence of fungemia was the same in both periods (4 of 467 admissions vs. 3 of 599 admissions; p = 0.48). CONCLUSION: This protocol did not lead to the emergence of resistant bacteria.

Adolescent↗

Cicatricial pemphigoid rarely involves the scalp.

We present a case of cicatricial pemphigoid with significant scarring alopecia as a major manifestation and review our series of cicatricial pemphigoid patients in Oxford (UK). Only four of 54 patients had scarring alopecia of the scalp. While rare, this manifestation poses a difficult management problem; patients find this cosmetically distressing and there are no successful treatments available to date.

Alopecia Areata↗

Association of a redefined proximal mouse chromosome 11 imprinting region and U2afbp-rs/U2af1-rs1 expression.

Mice with maternal and paternal disomy for chromosome 11 (Chr 11) show growth retarded and overgrowth phenotypes, respectively, which can be attributed to genomic imprinting. Previous studies have defined the region of Chr 11 responsible (the Chr 11 imprinting region) as lying proximal to the T30H translocation breakpoint at the borders of G-bands 11B1.2 and 11B1.3. Evidence is presented here with two new translocations, T57H and T41Ad, which sequentially reduce the size of the imprinting region and locate it proximal to the T41Ad breakpoint in G-band 11A3.2. It therefore lies close to the centromere. The imprinted gene, U2af1-rs1, is known to be located within the original region and has been regarded as a candidate for the imprinting effects. Meiotic and mitotic chromosome FISH analysis, together with U2af1-rs1 expression studies are now described which show that the gene lies within the newly defined imprinting region and that its expression levels relate to the presence/absence and number of functional paternal alleles. U2af1-rs1 therefore remains a candidate gene for the Chr 11 imprinting effects. However, another recently reported imprinted gene, Meg1/Grb10, that lies within the region is also a good candidate, as it encodes a growth factor receptor. Meg1/Grb10 maps about 15 cM from U2af1-rs1 and is separated by conserved regions showing homology with two different human chromosomes. For these reasons, and because the two human homologues of U2af1-rs1 and Meg1/Grb10 also lie on different chromosomes, it would seem likely that the two genes identify two distinct imprinting domains within the small proximal region of mouse Chr 11.

Animals↗

Disruption of the Kamin blocking effect in schizophrenia and in normal subjects following amphetamine.

The Kamin blocking effect (KBE) is an established animal learning paradigm measuring selective processing, in which reduced blocking reflects allocation of greater processing resources to non-relevant information. Two KBE tasks are described below. Results from studies using the first (between-subjects) task indicate that KBE is abolished in acute schizophrenics with positive psychotic symptoms. It is also abolished in the relatives of schizophrenic subjects, although interpretation of this finding is hampered by poor performance of subjects in the control condition. The second (within-subjects) task indicated abolition of KBE in schizophrenic patients with positive psychotic symptoms. Administration of acute amphetamine to normal human subjects did not significantly disrupt performance on the first task. Whilst for the second task, although blocking was limited to placebo subjects, overall pre-exposure effects are not sufficiently strong to indicate specific drug effects.

Amphetamine↗

The diagnosis and racial origin of 394 patients undergoing renal biopsy: an association between Indian race and interstitial nephritis.

BACKGROUND: There is a high incidence of renal disease in the ethnically Indian population in the United Kingdom, the pathological basis for which is only partly understood. This study attempted to define associations between renal biopsy diagnosis and race. The aim was thereby to identify types of renal disease which may contribute to the observed predisposition to renal failure in the Indian population served by our centre. METHOD: A single-centre-based retrospective analysis of the final diagnosis and corresponding ethnicity in 394 consecutive patients undergoing native renal biopsy for the investigation of abnormal renal function or urinary sediment. RESULTS: A highly significant association between a diagnosis of interstitial nephritis and Indian race was observed. There were 30 cases of interstitial nephritis, of whom 17 were Indian. In 15 of the Indian patients no aetiology could be established. The clinical features, outcomes, and the effect of steroid therapy in the Indian patients with idiopathic interstitial nephritis are described. CONCLUSION: Idiopathic interstitial nephritis is associated with Indian racial origin. This pathology may significantly contribute to the high incidence of end-stage renal failure in Indian patients resident in the United Kingdom.

Adult↗

Dissociative symptoms in panic disorder.

The present study examined the prevalence and correlates of dissociative symptoms in patients with panic disorder and patients with other nonpanic anxiety disorders. A total of 56 patients with anxiety disorders (13 with panic disorder alone, 16 with comorbid panic and other anxiety, and 27 with other anxiety disorders) were assessed with structured clinical interviews and a battery of questionnaires. Although 69% of patients with panic disorder experienced depersonalization or derealization during their panic attacks, panic disorder patients were no more likely to experience dissociative experiences as assessed by the Dissociative Experience Scale than patients with other anxiety disorders. In the entire sample, the prevalence of dissociative experiences was very low and well within nonpathological ranges. The correlates of dissociative symptoms were severity of depression, social anxiety, and personality disorders. The implications of these findings for conceptualizing the nature of dissociative symptoms within an anxiety population are discussed.

Adult↗