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Biomedical subjects

A Wise

Publications and source records attributed to A Wise.

At least 55 records · Page 3Linked to original sources
PubMed1996

Meta-analysis of brain and cranial size in schizophrenia.

Several meta-analyses are presented that address the issue of brain and/or cranial size reductions in schizophrenia. Separate meta-analyses were conducted for brain size (n = 27 studies), intracranial size (n = 18) or extracranial size (n = 8). For each meta-analysis, the weighted composite effect size (d) was tested for statistical significance (the direction of the effect size was negative if patients with schizophrenia had smaller structure size than controls). The influence of several potential modifiers of effect size (age, methods, region, gender) was individually evaluated. The composite effect sizes for studies of brain, intracranial and extracranial measures were d = -0.26, (p < 0.0001), d = -0.18, (p = 0.0012), and d = +0.14, (p = 0.16), respectively. Thus, the review found evidence for a small, but statistically significant reduction in brain and intracranial size in schizophrenia, but no evidence for a reduction in extracranial size. Studies based on axial image slices had significantly larger effects (d = -0.60) than the studies based on sagittal images (d = -0.09) (chi(2) = 14.0, p = 0.0002). In summary, the findings clearly support a small yet highly significant reduction of brain and intracranial size in schizophrenia.

Brain↗
PubMed1996

A constitutively active mutant of the alpha 1B-adrenergic receptor can cause greater agonist-dependent down-regulation of the G-proteins G9 alpha and G11 alpha than the wild-type receptor.

Rat 1 fibroblasts transfected to express either the wild-type hamster alpha 1B-adrenergic receptor or a constitutively active mutant (CAM) form of this receptor resulting from the alteration of amino acid residues 288-294 to encode the equivalent region of the human beta 2-adrenergic receptor were examined. The basal level of inositol phosphate generation in cells expressing the CAM alpha 1B-adrenergic receptor was greater than for the wild-type receptor, The addition of maximally effective concentrations of phenylephrine or noradrenaline resulted in substantially greater levels of inositol phosphate generation by the CAM alpha 1B-adrenergic receptor, although this receptor was expressed at lower steady-state levels than the wild-type receptor. The potency of both phenylephrine and noradrenaline to stimulate inositol phosphate production was approx. 200-fold greater at the CAM alpha 1B-adrenergic receptor than at the wild-type receptor. In contrast, endothelin 1, acting at the endogenously expressed endothelin ETA, receptor, displayed similar potency and maximal effects in the two cell lines. The sustained presence of phenylephrine resulted in down-regulation of the alpha subunits of the phosphoinositidase C-linked, pertussis toxin-insensitive, G-proteins G9 and G11 in cells expressing either the wild-type or the CAM alpha 1B-adrenergic receptor. The degree of down-regulation achieved was substantially greater in cells expressing the CAM alpha 1B-adrenergic receptor at all concentrations of the agonist. However, in this assay phenylephrine displayed only a slightly greater potency at the CAM alpha 1B-adrenergic receptor than at the wild-type receptor. There were no detectable differences in the basal rate of G9 alpha/G11 alpha degradation between cells expressing the wild-type or the CAMalpha 1B-adrenergic receptor. In both cell lines the addition of phenylephrine substantially increased the rate of degradation of these G-proteins, with a greater effect at the CAM alpha 1B-adrenergic receptor. The enhanced capacity of agonist both to stimulate second-messenger production at the CAM alpha 1B-adrenergic receptor and to regulate cellular levels of its associated G-proteins by stimulating their rate of degradation is indicative of an enhanced stoichiometry of coupling of this form of the receptor to G9 and G11.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1996

Antigen receptors on immature, but not mature, B and T cells are coupled to cytosolic phospholipase A2 activation: expression and activation of cytosolic phospholipase A2 correlate with lymphocyte maturation.

The Ag receptors on mature B and T cells are not coupled to the activation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid release. Moreover, phorbol esters such as PMA, which can activate cPLA2 via mitogen-activated protein (MAP) kinase in most cell types, also failed to induce the release of arachidonate from mature cells, suggesting that the cPLA2 pathway may not be functional in mature lymphocytes. Interestingly, Western blot analysis revealed that cPLA2, which had previously been thought to be expressed ubiquitously, is not expressed in mature B or T cells and that cytosolic phospholipase A2 expression could not be up-regulated in lymphocytes following culture with a range of cytokines most likely to be involved in an immune response such as IL-1 alpha, IL-3, or TNF-alpha. In contrast, cPLA2 was shown to be expressed and activated in thymocytes and immature B cells under conditions in which ligation of the Ag receptors led to growth arrest and/or apoptosis. Taken together, these data suggest that cPLA2 does not play a role in Ag receptor-mediated lymphocyte activation, but may be involved in the molecular mechanisms underlying lymphocyte maturation and/or self tolerance by clonal deletion.

Animals↗
PubMed1996

Health research literacy: a new approach to involving rural general practitioners in research and evaluation.

Rural general practitioners (GPs) are currently involved in two concurrent and systematic programs of research/evaluation. These programs are generated, respectively, by initiatives in rural health and in general practice. This paper examines the consequences of this involvement by GPs as implementers and/or targets of components of each of these programs, and concludes that it is appropriate that they be provided in a systematic way with the knowledge and skills base they need to empower them to participate in (both developmentally and at the implementation level) and/or to appraise the research impinging on their lives. Six broad levels of involvement in rural health research are identified for rural doctors in this paper, which proposes an innovative strategy--health research literary--to assist doctors at these various levels of involvement.

Australia↗
PubMed1996

Sequences in the -35 region of Escherichia coli rpoS-dependent genes promote transcription by E sigma S.

sigma S is an alternate sigma factor which functions with RNA polymerase to activate transcription of genes that are involved in a number of stress responses, including stationary-phase survival and osmoprotection. The similarity of the sigma S protein to sigma D (Escherichia coli's major sigma factor) in the regions thought to recognize and bind promoter sequences suggests that sigma S- and sigma D-associated RNA polymerases recognize promoter DNA in a similar manner. However, no promoter recognition sequence for sigma S holoenzyme (E sigma S) has been identified. An apparent conservation of cytosine nucleotides was noted in the -35 region of several sigma S-dependent promoters. Site-directed mutagenesis and reporter gene fusions were used to investigate the importance of the -35 cytosine nucleotides for sigma S-dependent transcription. Substitution of cytosine nucleotides for thymidine at the -35 site of the sigma D-dependent proU promoter effectively abolished transcription by E sigma D but allowed E sigma S to direct transcription from the mutant promoter. Inclusion of the sigma D consensus -10 hexamer strengthened transcription by E sigma S, demonstrating that both E sigma D and E sigma S can recognize the same -10 sequences. Conversely, replacement of -35 site cytosine nucleotides with thymidine in the sigma S-dependent osmY promoter reduced transcription by E sigma S and increased transcription by E sigma D. Our data suggest that DNA sequences in the -35 region function as part of a discriminator mechanism to shift transcription between E sigma D and E sigma S.

Amino Acid Transport Systems↗
PubMed1995

The role of palmitoylation of the guanine nucleotide binding protein G11 alpha in defining interaction with the plasma membrane.

Mutations of Cys-9 to serine, Cys-10 to serine and a combination of both alterations were produced in a cDNA encoding murine G11 alpha to potentially interfere with the ability of the expressed polypeptides to act as substrates for post-translational palmitoylation. Each of these mutants and the wild-type protein were expressed in simian COS-1 cells. Mutation of either cysteine-9 or cysteine-10 decreased the degree of palmitoylation of the protein by some 80% compared with the wild-type, while the double mutant totally failed to incorporate [3H]palmitate. By contrast, in all transfections the endogenously expressed simian G11 alpha incorporated [3H]palmitate to similar levels. Particulate and cytoplasmic fractions from these cells were subjected to SDS/PAGE under conditions which allow resolution of primate and rodent forms of G11 alpha. Immunoblotting of these fractions demonstrated that in all cases the endogenously expressed simian G11 alpha was exclusively associated with the particulate fraction, as was the transfected and expressed wild-type murine G11 alpha. By contrast, each of the mutated forms of murine G11 alpha displayed a distribution in which approx. 70% of the expressed protein was present in the particulate fraction and 30% in the supernatant. To examine the conformation of the particulate expressed forms of murine G11 alpha, these fractions were treated with various concentrations of sodium cholate and immunoblots were subsequently performed on the solubilized and remaining particulate proteins. Whereas essentially all of the endogenous simian G11 alpha was solubilized by treatment with 1% (w/v) sodium cholate and some 50% with 0.32% cholate, expressed wild-type murine G11 alpha was more recalcitrant to solubilization. However, that fraction of wild-type murine G11 alpha which was solubilized behaved identically to the endogenous simian G11 alpha on Superose-12 gel-exclusion chromatography. The particulate fraction of the C9S/C10S double mutant of murine G11 alpha was highly resistant to solubilization by sodium cholate, whereas the particulate fractions of the two single cysteine to serine mutants were intermediate to the wild-type and double mutant in their ability to be solubilized by this detergent. These data demonstrate that the palmitoylation status of the cysteine residues at positions 9 and 10 in murine G11 alpha plays a central role in defining membrane association of this G-protein and indicate that much of the particulate fraction of the expressed palmitoylation-resistant mutants is likely to represent non-functional rather than correctly folded protein.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Degradation of G11 alpha/Gq alpha is accelerated by agonist occupancy of alpha 1A/D, alpha 1B, and alpha 1C adrenergic receptors.

Cells of clones of rat 1 fibroblasts transfected to express the molecularly defined alpha 1A/D, alpha 1B, or alpha 1C adrenoreceptors and prelabeled with myo-[3H]inositol were each shown to generate high levels of inositol phosphates when exposed to the alpha 1 adrenoreceptor agonist phenylephrine. Maintained exposure of each of these cells to phenylephrine resulted in a large down-regulation of the receptors and also a marked down-regulation of cellular levels of both of the phosphoinositidase C-linked G-proteins Gq alpha and G11 alpha. To examine the mechanism of phenylephrine-induced down-regulation of Gq alpha and G11 alpha, pulse-chase 35S-amino acid labeling experiments were performed with each of the alpha 1A/D, alpha 1B, and alpha 1C adrenoreceptor-expressing cell lines. The rate of degradation of G11 alpha/Gq alpha, which was adequately modeled by a monoexponential with half-life between 33 and 40 h in each of the cell lines in the absence of agonist, was accelerated substantially (some 4-fold) in the presence of phenylephrine. By contrast, the rate of degradation of the G-protein Gi2 alpha, which would not be anticipated to be activated by members of the alpha 1 adrenoreceptor family, was unaltered by the presence of phenylephrine. Levels of mRNA encoding Gq alpha and G11 alpha were not substantially altered by exposure of the cells to phenylephrine in any of the cell lines studied.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1995

Meta-analyses of studies of ventricular enlargement and cortical sulcal prominence in mood disorders. Comparisons with controls or patients with schizophrenia.

BACKGROUND: The findings of ventricular enlargement and increased sulcal prominence are well documented in schizophrenia, but the consistency of similar findings in mood disorders is less well appreciated. Reliable documentation of the presence of these structural abnormalities in mood disorders would require a reassessment of their significance for both schizophrenia and mood disorders. In this article, we meta-analytically review the literature on ventricular enlargement and cortical sulcal prominence in patients with mood disorders compared with controls and patients with schizophrenia. METHODS: Four meta-analytic reviews were conducted, two comparing patients with mood disorders with normal controls on ventricular enlargement (meta-analysis 1) or sulcal prominence (meta-analysis 2) and two comparing patients with mood disorders with schizophrenic patients on these same measures (meta-analyses 3 and 4). RESULTS: Meta-analyses 1 and 2 revealed statistically significant (P < .001) moderate composite effect sizes (d) for the comparisons of patients with mood disorders with controls on both ventricular enlargement (d = 0.44) and sulcal prominence (d = 0.42). Meta-analysis 3 further revealed that patients with schizophrenia have significantly greater ventricular enlargement than patients with mood disorders (P = .002), but the effect size was small (d = -0.20). There were too few studies comparing these patient groups on sulcal prominence to support a quantitative meta-analysis. CONCLUSIONS: This review documents the presence of ventricular enlargement and increased sulcal prominence in mood disorders. Patients with mood disorders have less ventricular enlargement than patients with schizophrenia, but this effect is small. These results reinforce previous suggestions of the nonspecificity of structural brain changes in schizophrenia and mood disorders.

Adult↗
PubMed1995

Expression of the human beta 2-adrenoceptor in NCB20 cells results in agonist activation of adenylyl cyclase and agonist-mediated selective down-regulation of Gs alpha.

Murine neuroblastoma x embryonic Chinese hamster brain NCB20 cells were transfected with a construct containing the human beta 2-adrenoceptor under the control of a beta-actin promoter. Two clones were selected for detailed analysis: D1, which expressed some 12.7 pmol/mg of membrane protein, and L9, which expressed 1.2 pmol/mg of membrane protein of the receptor. Incubation with the beta-adrenoceptor agonist isoprenaline resulted in stimulation of adenylyl cyclase activity in both of the clones, whereas no such activation was observed in wild-type NCB20 cells. The EC50 for isoprenaline stimulation of adenylyl cyclase activity in membranes of clone D1 (0.8 nM) was significantly lower, however, than in membranes of clone L9 (10.4 nM). Although the maximal adenylyl cyclase stimulation by isoprenaline was similar in both clones, D1 had a higher basal activity. Immunoblotting studies with specific antipeptide antisera directed against various G protein alpha subunits showed that treatment of the cells with isoprenaline resulted in a 35% reduction in the membrane-associated levels of Gs alpha in membranes of clone L9 cells and a 50% reduction in Gs alpha levels in membranes prepared from clone D1. Isoprenaline treatment had no effect on the levels of Gs alpha in wild-type NCB20 cells, and such treatment had no effect on the levels of other G protein alpha subunits such as Gq/G11 and Gi2 in any of the cell lines investigated. Time course analysis revealed that half-maximal loss of Gs alpha in clone D1 was achieved within 1-2 h of addition of agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1995

Two different Escherichia coli proP promoters respond to osmotic and growth phase signals.

proP of Escherichia coli encodes an active transport system for proline and glycine betaine which is activated by both hyperosmolarity and amino acid-limited growth. proP DNA sequences far upstream from the translational start site are strongly homologous to the promoter of proU, an operon that specifies another osmoregulated glycine betaine transport system. Mutation and deletion analysis of proP and primer extension experiments established that this promoter, P1, was responsible for proP's strong expression in minimal medium and its response to osmotic signals. When cells were grown in complex medium, expression from a proP-lacZ fusion was induced three- to fourfold as growth slowed and cells entered stationary phase. Stationary-phase induction was dependent on rpoS, which encodes a stationary-phase sigma factor. Deletion of 158 bp of the untranslated leader sequence between P1 and the proP structural gene abolished rpoS-dependent stationary-phase regulation. Transcription initiation detected by primer extension within this region was absent in an rpoS mutant. proP is therefore a member of the growing class of sigma S-dependent genes which respond to both stationary-phase and hyperosmolarity signals.

Bacterial Proteins↗
PubMed1995

Phytate and zinc bioavailability.

This review discusses evidence from human studies on the effects of dietary phytate on zinc bioavailability. In vitro and animal experiments have implicated calcium as a potentiating factor because it reacts with phytate, and zinc binds to the precipitate. Magnesium also reacts similarly to calcium, but most studies have not considered this factor. Protein provides amino acids, some of which are able to desorb zinc from the precipitate and improve bioavailability. Some predictive ratios, derived from animal studies, have been directly applied to human studies. The studies reviewed included those on: zinc status of groups, apparent absorption of zinc in normal subjects and ileostomists, true absorption using a stable isotope, plasma tolerance, and the accumulation in the body of a radioisotope. It was concluded that detrimental effects of phytate could be demonstrated on zinc bioavailability, but that the studies had not been designed specifically to demonstrate whether the interactions found in animal studies also apply to humans. It is suggested that more targeted research is required before predictive ratios are used for humans.

Animals↗
PubMed1995

A guide to strategic planning.

Strategic planning is a new concept in general practice. Underneath all the jargon, however, it is simply a label for the planning and evaluation processes that most organisations have used in the past. The aim of this paper is to demystify strategic planning as it applies to newly formed Divisions of General Practice.

Family Practice↗
PubMed1994

Isolation of a putative receptor from Zea mays microsomal membranes that interacts with the G-protein, GP alpha 1.

The C-terminal region of a heterotrimeric G-protein alpha-subunit is known to be one of the principal determinants governing its interaction with its cognate receptor. Use of an oligopeptide corresponding to the fifteen C-terminal residues of the Arabidopsis G alpha-subunit (GP alpha 1), as an affinity ligand, led to the resolution of a tightly binding 37 kDa membrane polypeptide from detergent solubilised Zea microsomal fraction membranes. An identical polypeptide bound tightly to an affinity matrix containing recombinant GP alpha 1 protein as ligand: binding and release of this 37 kDa protein was dependent on the activation state of GP alpha 1 which was regulated by inclusion or omission of the G-protein activator AlF-4. Finally, the isolated 37 kDa protein was labelled with the lectin concanavalin A, indicating it to be glycosylated. These data are consistent with the identity of the 37 kDa membrane polypeptide as a receptor that interacts with the Zea homologue of GP alpha 1.

Amino Acid Sequence↗
PubMed1994

Further debate.

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Australia↗