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Biomedical subjects

S Ball

Publications and source records attributed to S Ball.

At least 73 records · Page 4Linked to original sources
PubMed1997

Starches from A to C. Chlamydomonas reinhardtii as a model microbial system to investigate the biosynthesis of the plant amylopectin crystal.

Wide-angle powder x-ray diffraction analysis was carried out on starch extracted from wild-type and mutant Chlamydomonas reinhardtii cells. Strains containing no defective starch synthases as well as mutants carrying a disrupted granule-bound starch synthase structural gene displayed the A type of diffraction pattern with a high degree of crystallinity. Mutants carrying a defect for the major soluble starch synthase (SSS), SSS II, were characterized by a switch to the B type of diffraction pattern with very low crystallinity. Mutant strains carrying SSS I as the only glucan elongation enzyme regained some of their crystallinity but switched to the C type of diffraction pattern. Differential scanning calorimetry analysis correlated tightly with the x-ray diffraction results. Together with the electron microscopy analyses, these results establish C. reinhardtii as a microbial model system displaying all aspects of cereal starch synthesis and structure. We further show that SSS II is the major enzyme involved in the synthesis of crystalline structures in starch and demonstrate that SSS I alone builds a new type of amylopectin structure.

Amylopectin↗
PubMed1997

Basilar artery response to hyperventilation in panic disorder.

OBJECTIVE: The purpose of this study was to measure the response of basilar artery blood flow to hyperventilation in patients with panic disorder. METHOD: Transcranial Doppler ultrasonography was used to measure basilar artery flow during rest and after hyperventilation in 16 patients with panic disorder and eight normal comparison subjects. The subjects rated their dizziness at each phase. RESULTS: The patients with panic disorder demonstrated greater reduction in flow rates and greater increases in dizziness than the normal comparison subjects. CONCLUSIONS: The greater basilar artery sensitivity to hyperventilation shown by panic disorder patients suggests a possible mechanism for the development of neurological symptoms during panic attacks.

Adult↗
PubMed1997

Cost effectiveness in the treatment of heart failure with ramipril. A Swedish substudy of the AIRE study. Acute Infarction Ramipril Efficacy.

We estimated the cost effectiveness of adding the ACE inhibitor ramipril to conventional treatment in patients with heart failure after acute myocardial infarction. These estimates were based on the Acute Infarction Ramipril Efficacy (AIRE) study and on complementary Swedish healthcare resource use data for a subset of patients. The average follow-up period was 15 months (minimum 6 months, maximum 3.8 years). The perspective of the analysis was that of the county councils (third-party payers), and we focused on the cost of drugs and hospitalisation. The marginal cost effectiveness of the treatment was estimated over 3 treatment periods: 1, 2 and 3.8 years. The cost-effectiveness ratios varied between SEK14,148 and SEK33,033 per life-year gained ($US1 = SEK7.70. Pounds 1 = SEK12.40) for the 3 treatment periods. Adding ramipril to conventional treatment for heart failure after acute myocardial infarction is therefore cost effective, and compares favourably with the cost effectiveness of other common medical therapies in the cardiovascular field.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Control of starch composition and structure through substrate supply in the monocellular alga Chlamydomonas reinhardtii.

In Chlamydomonas, as in higher plants, synthesis of ADP glucose catalyzed by ADP-glucose pyrophosphorylase is rate-limiting for the building of starch in the chloroplast. We have isolated disruptions of the STA1 ADP-glucose pyrophosphorylase structural gene that rendered the enzyme less responsive to the allosteric activator 3-phosphoglycerate. The structure and composition of the residual starch synthesized by all mutants of the STA1 locus is dramatically altered. The residual polysaccharide is shown to be devoid of amylose despite the presence of granule-bound starch synthase, the amylose biosynthetic enzyme. In addition, the fine structure of the mutant amylopectin revealed the presence of an altered chain-length distribution. This distribution mimicks that which is observed during growth and photosynthesis and differs markedly from that observed during storage. We therefore propose that low nucleotide sugar concentrations are either directly or indirectly responsible for the major differences observed in the composition or structure of starch during storage and photosynthesis.

Amylopectin↗
PubMed1996

Prevalence and correlates of anger attacks: a two site study.

Although anger attacks have been described in depressed outpatients, they have not been well studied in other disorders. In Study 1, we examined the prevalence of anger attacks in 50 outpatients with panic disorder. In Study 2, we replicated the initial findings at an independent site and examined the specificity of anger attacks by comparing their occurrence in patients with panic disorder, patients with other non-panic anxiety disorders and patients with a depressive disorder. At both sites, we also explored the relationship between anger attacks and demographic and clinical characteristics, such as gender, presence and severity of depression, and social anxiety measures. In both sites, the prevalence of anger attacks in patients with panic disorder was approximately one-third. However, anger attacks were not unique to panic disorder, with similar rates emerging for patients with other anxiety disorders. Furthermore, patients with depressive diagnoses had twice the prevalence of anger attacks than did anxiety patients. At both sites, those with anger attacks were significantly more depressed and were likely to have either current or past history of major depression. Anger attacks were not associated with social anxiety measures, but were related to cluster B, cluster C and self-defeating personality disorder traits. Our findings support the notion that anger attacks are best conceptualized as an associated feature of depression.

Adolescent↗
PubMed1996

Novel mutations and polymorphisms in the Fanconi anemia group C gene.

Fanconi anemia (FA) is an autosomal recessive disorder associated with hypersensitivity to DNA cross-linking agents and bone marrow failure. At least four complementation groups have been defined, and the FA group C gene (FAC) has been cloned. We have screened 76 unrelated FA patients of diverse ethnic and geographic origins and from unknown complementation groups for mutations in the FAC gene either by chemical cleavage mismatch analysis or by single-strand conformational polymorphism (SSCP). Five mutations were detected in four patients (5.3%), including two novel mutations (W22X and L496R). Nine polymorphisms were detected, seven of which have not been described previously (663A-->G, L190F, IVS6 + 30C-->T, I312V, V449M, Q465R, and 1974G-->A). Six of the nine polymorphisms occurred in patients or controls from the Tswana or Sotho chiefdoms of South Africa and were not found in 50 unrelated European controls. Restriction site assays were established for all 8 pathogenic mutations identified in the FAC gene to date and used to screen a total of 94 unrelated FA patients. This identified only one other group C patient, who was homozygons for the mutation IVS4 + 4A-->T. This study indicates that the proportion of FA patients from complementation group C is generally likely to be less than 10%. Guidelines for the selection of FA patients for FAC mutation screening are proposed.

Cell Cycle Proteins↗
PubMed1996

An early antigen-presenting cell defect in HIV-1-infected patients correlates with CD4 dependency in human T-cell clones.

We have used a defined panel of nine HIV peptide-specific T-cell clones (TLC) generated from a healthy volunteer to evaluate the antigen-presenting cell (APC) function of human immunodeficiency virus-1 (HIV- 1)-infected patients. Peripheral blood mononuclear cells (PBMC) from HLA-matched seropositive and uninfected volunteers were compared for their capacity to present peptide to TLC specific for the V3 loop of HIV- 1 envelope glycoprotein gp120, influenza haemagglutinin or the mycobacterial 19,000 MW antigen APC from uninfected volunteers (HIV- APC) invariably presented peptides to all TLC with comparable efficiency. In contrast using APC from HIV- 1-infected subjects (HIV+ APC) three patterns of responsiveness were observed. The first group of TLC was not stimulated by HIV+ APC even early in infection. The second responded to all APC comparably. The third and intermediate group, responded to APC from some clinically asymptomatic, but not acquired immune deficiency syndrome (AIDS), patients. The two additional TLC, derived from other donors and with specificity for non-HIV peptides, showed similar variation in response to HIV+ APC. The different patterns of response to HIV APC did not correlate with the fine specificity or cytokine phenotypes of the TLC. Neither was the defect due to decreased levels of expression of APC molecules involved in delivering the first or second signal required for T-cell activation APC mixing experiments showed no evidence of APC-derived inhibitory factor. Furthermore, the defect was independent of T cells or their products and was equally expressed in monocytes and dendritic cells. Instead, responsiveness was inversely related to the degree of CD4 dependency suggesting that the underlying mechanism was a CD4 APC-associated gp120 interaction. The early appearance of this defect in HIV- 1 infection co-incident with the loss of recall responses is consistent with a role for APC dysfunction in pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Decreasing catheter-related infection and hospital costs by continuous quality improvement.

OBJECTIVES: a) To reduce the rate of catheter-related infection, using improved skin preparation and catheters impregnated with silver sulfadiazine and chlorhexidine; b) to decrease the number of unnecessary guidewire exchanges of existing catheters by substituting suspected catheter-related sepsis for fever alone as an indication to change an indwelling catheter; and c) to decrease the hospital costs associated with guidewire exchanges and new catheter insertions. DESIGN: Sequential, prospective, descriptive studies using a continuous quality management approach. SETTING: A 20-bed trauma intensive care unit at a university teaching hospital. PATIENTS: Patients (n = 147) admitted from July 1 to December 31, 1992 (phase 1); 34 patients admitted in June and September 1993 (phase 2); and 156 patients admitted between January 1 and June 30, 1994 (phase 3). INTERVENTIONS: Phase 1: Proportions of catheter-related infections and catheter-related bacteremia were compared with our prior reported results. Indications for guidewire exchange were analyzed, and the rate of catheter-related infection for each indication was derived. Phase 2: The rate of catheter-related infection was determined for a trial group of triple-lumen catheters impregnated with silver sulfadiazine and chlorhexidine. Phase 3: Four components were altered. Impregnated triple-lumen catheters were used instead of unprotected catheters. Chlorhexidine skin cleanser was substituted for povidone-iodine solution during initial aseptic preparation during catheter insertion and subsequent guidewire exchange. Suspected catheter-related sepsis was substituted for fever as an indication for guidewire exchange. The "safe" period (the time before considering changing a catheter because catheter-related sepsis was suspected) was extended from 2 to 4 days. MEASUREMENTS AND MAIN RESULTS: The overall rate of catheter-related infection in phase 1 was 15% (15% for triple-lumen catheters and 16% for introducers). Catheters changed for site inflammation had a 46% rate of catheter-related infection, significantly higher than for all other indications, including fever (p < .03). The rate of catheter-related infection was significantly (p = .0002) higher for catheters in place for > 10 days compared with lesser durations. Fever was the indication for 42% of all guidewire exchanges. In phase 2, the catheter-related infection rate was 2% (one positive of 48 catheters), significantly (p = .0231) lower than the phase 1 rate. In phase 3, the overall rate of catheter-related infection was 8.6%, significantly (p = .0067) lower than the 15% rate in phase 1. The proportion of protected triple-lumen catheter catheter-related infections decreased significantly (p = .0024) from 15% to 6%. The rate of catheter-related infection for introducers was the same in both phases (p = .33). The days of catheterization for all catheters increased from 4.5 +/- 2.6 to 5.4 +/- 3.6 (p < .0001). The days for triple-lumen catheters increased from 4.7 +/- 2.7 to 7.0 +/- 3.9 (p < .0001). For introducers, there was no difference in the days of catheterization. The proportion of catheters changed for suspected catheter-related sepsis decreased significantly (p < .0001) to 23% from the 42% changed for fever in phase 1. The proportion of catheter-related infections for catheters changed for fever was 18% in phase 1. The proportion of catheter-related infections for catheters changed for suspected catheter-related sepsis was 13% in phase 3 (p = .43). The total number of catheters used per patient in phase 3 was 1.9 +/- 1.4, significantly lower than the 2.6 +/- 2.7 catheters used in phase 1 (p = .0018). The number of triple-lumen catheters decreased from 1.8 +/- 1.2 to 1.0 +/- 1.2 in phase 3 (p = .0001). CONCLUSIONS: Catheters impregnated with silver sulfadiazine and chlorhexidine had a smaller proportion of catheter-related infection compared with unprotected catheters. Fever alone as an indication for guidewire exchange resu

Anti-Infective Agents↗
PubMed1996

Campath-1G in vivo confers a low incidence of graft-versus-host disease associated with a high incidence of mixed chimaerism after bone marrow transplantation for severe aplastic anaemia using HLA-identical sibling donors.

We have evaluated the effect of in vivo Campath-1G on engraftment and GVHD in 23 patients with severe aplastic anaemia transplanted from HLA-identical sibling donors. In 14 patients Campath 1g was given pre-transplant for up to 9 days in an attempt to overcome graft rejection (group 1). In nine patients Campath-1G was given pre-transplant, but also continued post-transplant until day +5 to reduce GVHD (group 2). There were three patients with late graft failure in group I following initial neutrophil engraftment, and four cases of grade II+ GVHD. In group II, two patients had early graft failure (no take), and there were no cases of acute GVHD out of seven evaluable patients. One patient in group I developed chronic GVHD of the liver, and two patients (one in each group) had transient localised chronic GVHD. PCR of short tandem repeats was used to evaluate chimaeric status in 13 patients. Of 11 patients with initial neutrophil engraftment, only one had 100% donor haemopoiesis at all times. The remaining patients had either transient mixed chimaerism or persistence of recipient (< 20%) cells. We conclude that in vivo Campath-1G is associated with a high incidence of mixed chimaerism which tips the balance away from GVHD but towards graft rejection.

Adolescent↗
PubMed1995

Sequence characterization of ENU-induced mutants of glucose phosphate isomerase in mouse.

Four of five mutations producing GPI1 null lethal phenotypes in the homozygous state, which were previously identified from the offspring of male mice, spermatogonially treated with N-ethyl N-nitrosourea (ENU), have been characterized at the nucleotide level by reverse transcription of RNA from heterozygotes for mutant and wild-type alleles and cycle sequencing with cDNA-derived primers. In three of the mutations studied, a single nucleotide substitution, altering the predicted amino acid on translation, was observed in the mutant allele. In Gpi1-sam1H amino acid residue 277, TCA Ser (wild type), is altered to CCA Pro, and in Gpi1-sbm3H and Gpi1-sbm4H amino acid residue 510 Asp GAC (wild type) is altered to GGC Gly. These ENU-induced mutations occur at A-T base pairs in agreement with the current view of the mechanism of action for this mutagen. These changes also occur at residues implicated as being important in the catalytic functioning of the enzyme, from crystallographic studies, and may explain the loss of enzyme function. The fourth identified mutation, Gpi1-sbm2H, is a deletion of amino acid residues Arg134 to Leu162 inclusive, which may arise from incorrect splicing of mRNA; a fifth mutation has remained undetermined.

Animals↗
PubMed1995

Sequence characterization of alleles Gpi1-Sa and Gpi1-Sb at the glucose phosphate isomerase structural locus.

The sequences of alleles Gpi1-sa and Gpi1-sb at the glucose phosphate isomerase structural locus have been determined from cDNA of the mouse inbred strains 101/H Gpi1-sa and C3H/HeH Gpi1-sb by RT PCR and direct sequencing of the amplified products. Four individual nucleotide differences were observed between the two alleles. The difference at amino acid residue 94, (Gpi1-sa GAT Asp, Gpi1-sb AAT Asn) may account for the differing electrophoretic migration, isoelectric point, and thermostability of the two alleles. Two of the other observed differences in the coding region (amino acid residue 12 Leu, Gpi1-sa CTC, Gpi1-sb CTG and amino acid residue 17 Arg, Gpi1-sa CGC, Gpi1-sb CGT) are silent and do not affect the predicted amino acid residues on translation. The fourth observed difference is located within the 3' noncoding sequences of the cDNA. The change at amino acid residue 94 is associated with the presence of a Hinf1 restriction site in Gpi1-sb, which is absent in Gpi1-sa, and may be a useful method for determining this marker.

Alleles↗
PubMed1995

The associations between immigrant status and risk-behavior patterns in Latino adolescents.

PURPOSE: The purpose of this study was to identify differences in patterns of risk-taking behavior among Latino adolescents with respect to immigrant status and in comparison to their native non-Hispanic white counterparts. METHODS: In fall of 1988 and spring of 1989 a confidential Teen Health Risk Survey was administered to 1,789 students at two high schools in northern California, both of which have a school health center on-site, and which had large numbers of Latino students enrolled. We divided the Latino adolescent population into two groups: Latinos who were born in the United States (native-born Latinos) and Latinos who had immigrated to the United States (Latino immigrants). Eight different risk-taking behaviors were identified for this study: alcohol, cigarette, marijuana, illicit drug use, self-violence, drunk driving, unintended pregnancy, and violence. RESULTS: We found that in general, Latino students engaged in a greater number of risk-taking behaviors than native non-Hispanic whites. The mean number of risk behaviors was highest for Latino immigrants (1.78), followed by native-born Latinos (1.71), and native non-Hispanic whites (.99). A t-test revealed that non-Hispanic whites were statistically different from both Latino populations in either level of risk-taking behavior (p < 0.05). CONCLUSIONS: This sample of immigrant Latino students appeared to be vulnerable to engaging in risk-taking behaviors and did not exhibit the anticipated cultural protective factors associated with recent immigrants. The extent and variety of risk-taking behaviors clearly call for the development of culturally sensitive and accessible health education and health care services within a broader array of social, educational and support services.

Adolescent↗
PubMed1995

The human SB1.8 gene (DXS423E) encodes a putative chromosome segregation protein conserved in lower eukaryotes and prokaryotes.

We report that the human gene SB1.8 (DXS423E) encodes a protein of 1233 amino acids that is highly homologous (30% identity) to the essential yeast protein SMC1 which is required for the segregation of chromosomes at mitosis. Both SB1.8 and SMC1 contain an N-terminal NTP binding site, a central coiled-coil region and a C-terminal helix-loop-helix domain, and have structural features in common with the force generating proteins myosin and kinesin. SB1.8 also exhibits regions of homology and overall structural similarity to the prokaryote (Mycoplasma hyorhinis) protein 115p. Thus SB1.8 and SMC1 are members of a highly conserved and ubiquitous family of proteins that appear to have a fundamental role in cell division. In addition we show that SB1.8 (DXS423E) maps to a cosmid contig that lies centromeric to the OATL2 locus at chromosome Xp11.2.

Amino Acid Sequence↗
PubMed1995

Haemopoietic growth factor production by normal and aplastic anaemia stroma in long-term bone marrow culture.

Defective marrow stroma, or microenvironment, have been proposed as one of several mechanisms to account for bone marrow failure in aplastic anaemia (AA). This could involve defects in positive- or negative-acting haemopoietic regulator expression by AA stroma, or alteration of normal stroma-stem cell interactions. We have used a sensitive bioassay to investigate production of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-3, IL-6 and stem cell growth factor (SCF), by normal and AA stroma in long-term bone marrow culture (LTBMC). LTBMC were grown to confluence, irradiated and harvested to yield a single cell suspension. These cells were cocultured with normal target bone marrow mononuclear cells (BMMC), or CD34+ cells, in clonogenic assays, in the absence of exogenous cytokines. Cytokines responsible for the colony-stimulating activity (CSA) and burst-promoting activity (BPA) produced by stromal cells were identified by neutralizing antibodies to specific cytokines. All normal stroma populations produced G-CSF and GM-CSF, 93% produced IL-3, 80% produced IL-6, and 70% produced SCF. Similarly, all AA stroma produced G-CSF and GM-CSF, and 71% produced SCF. In contrast, only 71% of AA stroma produced IL-3 and 36% produced IL-6. Target cell stimulation was not dependent on direct stroma-target cell contact, suggesting production of soluble cytokines. However, although both IL-6 and G-CSF were detected in LTBMC supernatants by enzyme-linked immunoassay (ELISA), IL-3 and GM-CSF were undetectable, perhaps indicating low-level local production of these factors.

Adolescent↗
PubMed1995

Studies of hemidesmosomes in human amnion: the use of a detergent extraction protocol for compositional and ultrastructural analysis and preparation of a hemidesmosome-enriched fraction from tissue.

A method is described for the sequential detergent and high ionic strength extraction of human amnion with the progressive enrichment of the intermediate filament (IF) cytoskeleton and its associated structures including hemidesmosomes (HD). TEM of the extracted epithelium in situ reveals IF bundles beneath the apical cell surface, around the nucleus and at the lateral edges of the cells where association with desmosomes occurs. IF bundles are also very prominent within basal cell processes where they loop through the cytoplasm adjacent to the HDs. A novel connecting filament network is observed running between the IFs and the hemidesmosomal dense plaque. The adjacent IF network contains both cytokeratin and vimentin, the latter revealed much more fully as a result of the extraction protocol. The hemidesmosomal plasma membrane contains integrin subunits alpha 6 and beta 4 and these are quantitatively retained as the basal cell surface during extraction, while nonjunctional plasma membrane is solubilised. Integrin beta 1 is found at the basolateral cell surface but, like actin, is extracted quantitatively and is not present in HDs. The extracted epithelial cells may be recovered by scraping and the IF network depolymerised to produce a particulate fraction containing short residual IFs, associated thin filaments and plaque material. This fraction contains immunoreactive cytokeratin and vimentin. Integrin alpha 6 beta 4 has been used as a biochemical criterion of the presence of HD material in the fraction. Both subunits are highly enriched. The fraction also contains the hemidesmosomal components HD1, BP230 and BP180. This method is likely to be useful in further characterisation of the HD.

Actins↗