Search PubMed⌕ Search

Biomedical subjects

G K Brown

Publications and source records attributed to G K Brown.

At least 37 records · Page 2Linked to original sources
PubMed2001

Detection of Ehrlichia platys in dogs in Australia.

OBJECTIVE: To describe the detection of Ehrlichia platys in free-roaming dogs in Central Australia. PROCEDURE: Blood samples were collected from four dogs and examined for bacterial 16S ribosomal DNA using Polymerase Chain Reaction (PCR)-based assays. The three positive samples obtained were then sequenced and identification of the PCR product carried out. As a result of all three samples being identical to or closely related to part of the 16S rRNA gene of E. platys, blood samples were subsequently obtained from a further 24 dogs. These samples were screened using a PCR-assay to determine the presence of Ehrlichia DNA using genus-specific primers. The positive samples obtained from the screening process were then subjected to a further PCR-assay using E. platys specific primers. RESULTS: Of 28 dogs sampled, Ehrlichia DNA was detected in the blood of 13 dogs. Sequencing of the amplicons obtained indicated a high homology with the 16S rRNA gene for E. platys. When the E. platys-specific PCR was performed for 10 of those dogs, the 678 bp product obtained from the PCR amplification confirmed the identification as part of the 16S rRNA gene of E. platys in all 10 dogs. CONCLUSION: This study reports for the first time Ehrlichia carriage by dogs in Australia. It also indicates the usefulness of the PCR technique in rapidly and accurately identifying diseases that are otherwise difficult to detect. By using universal primers directed against bacterial 16S ribosomal DNA and sequencing analysis, the detection of potentially pathogenic Ehrlichia organisms that had not previously been found in Australia has been made possible.

Animals↗
PubMed2001

Mean Beck Depression Inventory-II scores by severity of major depressive episode.

The Beck Depression Inventory-II total scores of 35 (14%) outpatients who were diagnosed with a mild DSM-IV Major Depressive Episode (MDE), 144 (55%) outpatients with a moderate MDE, and 81 (31%) outpatients with a severe MDE were compared. The mean BDI-II total scores were, respectively, 18 (SD = 8, 99% CI 12-23), 27 (SD = 10, 99% CI 24-29), and 34 (SD = 10, 99% CI 30-37) (F2.257 = 33.25, p<.001). The mean BDI-II total score of the outpatients with a severe specifier was significantly higher than the mean BDI-II total score of the outpatients with a moderate specifier which was, in turn, significantly higher than the mean BDI-II total score of the outpatients with a mild specifier.

Adult↗
PubMed2000

Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency.

Defects in the pyruvate dehydrogenase (PDH) complex are an important cause of primary lactic acidosis, a frequent manifestation of metabolic disease in children. Clinical symptoms can vary considerably in patients with PDH complex deficiencies, and almost equal numbers of affected males and females have been identified, suggesting an autosomal recessive mode of inheritance of the disease. However, the great majority of PDH complex deficiencies result from mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1). The major factors that contribute to the clinical variation in E1alpha deficiency and its resemblance to a recessive disease are developmental lethality in some males with severe mutations and the pattern of X-inactivation in females. To date, 37 different missense/nonsense and 39 different insertion/deletion mutations have been identified in the E1alpha subunit gene of 130 patients (61 females and 69 males) from 123 unrelated families. Insertion/deletion mutations occur preferentially in exons 10 and 11, while missense/nonsense mutations are found in all exons. In males, the majority of missense/nonsense mutations are found in exons 3, 7, 8 and 11, and three recurrent mutations at codons R72, R263 and R378 account for half of these patients with missense/nonsense mutations (25 of 50). A significantly lower number of females is found with missense/nonsense mutations (25). However, 36 females out of 55 affected patients have insertion/deletion mutations. The total number of female and male patients is thus almost the same, although a difference in the distribution of the type of mutations is evident between both sexes. In many families, the parents of the affected patients were studied for the presence of the PDHA1 mutation. The mutation was never present in the somatic cells of the father; in 63 mothers studied, 16 were carriers (25%). In four families, the origin of the new mutation was determined to be twice paternal and twice maternal.

Amino Acid Sequence↗
PubMed2000

Suicide prevention in late life: directions for science and practice.

Suicide among the elderly is a critical public health problem, yet there remains limited information on risk factors to target due to the few number of controlled studies that could help isolate and focus on the most potent risk factors. We suggest that because there are no proven, effective interventions showing reduced suicidal behaviors in older adults, the best current approach is to improve detection and treatment of later-life depression. This effort may be especially effective in primary care settings, where the majority of our nation's elderly seek and receive their mental health care. We review approaches to assessment and treatment of later life depression that seem most relevant for later life suicide prevention. Testing and determining whether these treatment approaches are effective is an immediate goal on the path to advancing the science and practice of late-life suicide prevention.

Aged↗
PubMed2000

Glucose transporters: structure, function and consequences of deficiency.

There are two mechanisms for glucose transport across cell membranes. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. In all other cells, glucose transport is mediated by one or more of the members of the closely related GLUT family of glucose transporters. The pattern of expression of the GLUT transporters in different tissues is related to the different roles of glucose metabolism in different tissues. Primary defects in glucose transport all appear to be extremely rare and not all possible deficiencies have been identified. Deficiency of the secondary active sodium/glucose transporters result in glucose/galactose malabsorption or congenital renal glycosuria. GLUT1 deficiency produces a seizure disorder with low glucose concentration in cerebrospinal fluid and GLUT2 deficiency is the basis of the Fanconi-Bickel syndrome, which resembles type I glycogen storage disease.

Animals↗
PubMed2000

Risk factors for suicide in psychiatric outpatients: a 20-year prospective study.

To determine the risk factors for suicide, 6,891 psychiatric outpatients were evaluated in a prospective study. Subsequent deaths for the sample were identified through the National Death Index. Forty-nine (1%) suicides were determined from death certificates obtained from state vital statistics offices. Specific psychological variables that could be modified by clinical intervention were measured using standardized scales. Univariate survival analyses revealed that the severity of depression, hopelessness, and suicide ideation were significant risk factors for eventual suicide. A multivariate survival analysis indicated that several modifiable variables were significant and unique risk factors for suicide, including suicide ideation, major depressive disorder, bipolar disorder, and unemployment status.

Adult↗
PubMed1999

Dichloroacetate stabilizes the mutant E1alpha subunit in pyruvate dehydrogenase deficiency.

OBJECTIVE: To determine whether dichloroacetate (DCA) treatment can increase pyruvate dehydrogenase (PDH) activity in PDH-deficient cell lines harboring pathogenic mutations in the PDH E1alpha gene. BACKGROUND: PDH deficiency is a nuclear-encoded mitochondrial disorder and a major recognized cause of neonatal encephalomyopathies associated with primary lactic acidosis. Over the last decade, DCA has been used therapeutically, but it has not been clear which patients might benefit. Recent studies suggest that chronic DCA treatment may act by increasing the stability of mutant E1alpha polypeptide. The relative effects of DCA treatment on PDH-deficient cell lines with E1alpha mutations primarily affecting polypeptide stability or catalytic activity were determined and the mechanism of enhancement of residual PDH activity explored. METHODS: The effect of chronic 5-day DCA treatment on PDH activity was assessed in PDH-deficient cell lines containing the R378H, R141Q, K387(FS), and R302C E1alpha mutations. PDH subunit turnover and steady-state E1alpha levels before and after DCA treatment were measured in the R378H mutant line. RESULTS: Chronic DCA treatment resulted in 25% (p = 0.0434), 31% (p = 0.0014) increases in PDH activity in the K387(FS) and R378H cell lines, both of which are associated with decreased mutant polypeptide stability. In the R378H mutant cell line, chronic DCA treatment increased steady-state E1alpha levels and slowed the rate of E1alpha turnover twofold. In contrast, PDH activity did not change in the chronically DCA-treated R302C mutant line, in which the mutant polypeptide has normal stability and reduced catalytic activity. CONCLUSIONS: Chronic DCA treatment can increase PDH activity in PDH-deficient cell lines harboring mutations that affect E1alpha stability, suggesting a biochemical criterion by which DCA-responsive patients might be selected.

Cell Line↗
PubMed1999

Suicide ideation at its worst point: a predictor of eventual suicide in psychiatric outpatients.

Scales for measuring current suicide ideation (SSI-C), suicide ideation at its worst point in the patient's life (SSI-W), and hopelessness (BHS) were administered to 3,701 outpatients seeking psychiatric treatment. Thirty patients from this sample eventually committed suicide, within a mean of 4 years from the initial assessment. Based on cut-off scores derived from receiver operating characteristic (ROC) analyses, the SSI-W had an odds ratio of 13.84 for predicting suicide, whereas the SSI-C and the BHS had odds ratios of 5.42 and 6.43, respectively. The assessment of suicide ideation at its worst point identifies a subgroup of patients at relatively high risk for eventual suicide. Robust interventions and periodic monitoring for suicide ideation and hopelessness are recommended to reduce long-term suicide risk.

Adult↗
PubMed1998

Arginine 302 mutations in the pyruvate dehydrogenase E1alpha subunit gene: identification of further patients and in vitro demonstration of pathogenicity.

Three further patients with mutations in the codon for arginine 302 of the E1alpha subunit of the pyruvate dehydrogenase complex have been identified. Mutations in this codon have now been found in nine patients with pyruvate dehydrogenase deficiency in seven unrelated families, in sharp contrast to the great majority of other PDH E1alpha mutations which have been described in single individuals only. Because of the relatively high frequency of this mutation and because very few PDH E1alpha mutations have been demonstrated to be causative, we have established a system for analysing the consequences of defined mutations using transfection of normal and mutant PDH E1alpha cDNA into transformed human fibroblasts which have no endogenous E1alpha mRNA or protein. Using this test system, we have demonstrated that the R302C mutation results in the production of PDH E1alpha protein which is devoid of enzymic activity.

Arginine↗
PubMed1998

SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome.

Leigh Syndrome (LS) is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions that is commonly associated with systemic cytochrome c oxidase (COX) deficiency. COX deficiency is an autosomal recessive trait and most patients belong to a single genetic complementation group. DNA sequence analysis of the genes encoding the structural subunits of the COX complex has failed to identify a pathogenic mutation. Using microcell-mediated chromosome transfer, we mapped the gene defect in this disorder to chromosome 9q34 by complementation of the respiratory chain deficiency in patient fibroblasts. Analysis of a candidate gene (SURF1) of unknown function revealed several mutations, all of which predict a truncated protein. These data suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease.

Amino Acid Sequence↗
PubMed1998

Inadequate response to therapy as a predictor of suicide.

The role of response to cognitive therapy as a predictor of suicide was investigated by comparing 17 outpatients with mood disorders who committed suicide with 17 matched patients who did not commit suicide. The suiciders attended significantly fewer sessions of cognitive therapy and dropped out of therapy more frequently: 88% of the suiciders, compared to 53% of the controls, were rated by their therapists as requiring more treatment at termination. They also had higher levels of hopelessness at the termination of therapy. The results suggest that premature termination of therapy and inadequate response to treatment have unfavorable prognostic significance for eventual suicide.

Adult↗
PubMed1997

Localization of human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB1) within a YAC contig in Xp11.21.

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a potent regulator of glycolysis. Previous studies assigned the gene for human liver PFK-2/FBPase-2 (HGMW-approved symbol PFKFB1) to the X chromosome; however, precise localization remained ambiguous, with the gene variously placed between Xcen-q13, Xq27-q28, and Xp11.22-p11.21. We have localized the gene within a YAC contig clustered around ALAS2 (human erythroid delta-aminolevulinate synthase) in Xp11.21 and have identified eight YACs positive for the gene. Four of these overlapping YACs were mapped using rare-cutter restriction enzymes to provide in-depth characterization of an 820-kb region encompassing the PFK-2/ FBPase-2 and ALAS2 genes. PFK-2/FBPase-2 was found to lie close (within approx. 250 kb) and telomeric to ALAS2. Three putative CpG islands were also detected in the region.

5-Aminolevulinate Synthetase↗
PubMed1997

Psychometric characteristics of the Scale for Suicide Ideation with psychiatric outpatients.

The psychometric properties of the Scale for Suicide Ideation--Current (SSI-C; Beck, Kovacs & Weissman, 1979, Journal of Consulting and Clinical Psychology, 47, 343-352) and the Scale for Suicide Ideation--Worst (SSI-W; Beck, Brown, Steer, Dahlsgaard & Grisham, 1997, in press) were explored. These 19-item clinician-administered scales measure current suicide ideation (SSI-C) as well as suicide ideation at its worst point in the patient's life (SSI-W). For a sample of 4063 outpatients, both scales were positively correlated with a diagnosis of a principal mood disorder, a diagnosis of a personality disorder, and measures of depression and hopelessness. The relationship between the SSI-W and a history of suicide attempts was stronger (r = 0.50, P < 0.001) than the relationship between the SSI-C and previous suicide attempts (r = 0.31, P < 0.001). For 444 current and 1764 past suicide ideators, the SSI-C and the SSI-W had high internal consistencies (coefficient alpha s = 0.84 and 0.89, respectively). The SSI-C and the SSI-W were moderatedly correlated with each other (r = 0.51, P < 0.001). Iterated maximum-likelihood principal-factor analyses identified comparable Preparation and Motivation dimensions underlying both scales.

Adolescent↗
PubMed1997

Transfection screening for primary defects in the pyruvate dehydrogenase E1alpha subunit gene.

In a significant number of patients with biochemical evidence of a defect in the E1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex, it has not proved possible to identify a mutation in the gene coding regions. To assess the need for more extensive genetic analysis in these patients and to establish a test system in which to study the biochemical consequences of mutations in the E1alpha subunit gene (which is responsible for the great majority of defined cases of pyruvate dehydrogenase deficiency), we have developed a method to screen for E1alpha gene defects based on complementation of the enzyme deficiency in transformed fibroblast cell lines following transfection and expression of the normal cDNA. Using this system, cell lines from patients with a variety of different defined mutations in the E1alpha gene show restoration of enzyme activity. A number of patients have been identified in whom deficient enzyme activity is not restored by expression of the normal cDNA indicating that an alternative explanation for the enzyme defect must be sought.

Cell Line, Transformed↗
PubMed1996

Molecular cloning and tissue-specific expression of mouse kidney 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

A 1932 bp cDNA clone encoding a novel isozyme of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (PFK-2/ FBPase-2) was isolated from a mouse kidney cDNA library. The sequence encodes 519 amino acids and, based on homology to rat heart genomic sequence, appears to be the product of alternative splicing from PFK-2/FBPase-2 gene B with an extended version of exon 15. Northern blot analysis indicated that this clone corresponds to an 8 kb mRNA expressed in multiple tissues, with the strongest signal in kidney, and detects several additional transcripts which may be alternatively spliced from gene B.

Alternative Splicing↗
PubMed1996

Deficiency of respiratory chain complex I is a common cause of Leigh disease.

We reviewed the clinical features and etiologies of Leigh disease in 66 patients from 60 pedigrees. Biochemical or molecular defects were identified in 50% of all pedigrees, and in 74% of the 19 pedigrees with pathologically proved Leigh disease. Isolated deficiency of respiratory chain complex I was found in 7 patients, though the complex was only assayed in 25 patients, making this the second most common biochemical abnormality after complex IV deficiency. Mutations at residue 8993 of mitochondrial DNA were found in only 2 patients. No correlation was found between the clinical features and etiologies. No defects were identified in the 8 patients with normal lactate concentrations in the cerebrospinal fluid.

Blotting, Southern↗