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Biomedical subjects

G Turner

Publications and source records attributed to G Turner.

At least 145 records · Page 8Linked to original sources
PubMed1995

Linkage analysis of a large pedigree with hereditary sideroblastic anaemia.

A large pedigree showing a history of pyridoxine responsive X linked sideroblastic anaemia was screened with several polymorphic DNA markers from the X chromosome. Linkage analysis between each marker and disease status was performed, giving a maximum two point lod score of 3.64 at zero recombination with the microsatellite marker PGK1P1 at Xq11.2-12. Close linkage to PGK at Xq13.3, one of the candidate regions for X linked sideroblastic anaemia, was excluded. Linkage to DNA markers distal to PGK and at Xp21 was also excluded. Multipoint linkage analysis was performed with markers located between Xq11.2-21. The maximum map specific lod score obtained was 3.56 at PGK1P1 (Xq11.2-12). Linkage remained significant over the interval 20 cM proximal to PGK1P1 and 5 cM distal to PGK1P1, with definite exclusion around the PGK locus. The most likely location of the gene involved in sideroblastic anaemia in this pedigree is therefore within the pericentromeric region of the X chromosome. This region includes the erythroid 5-aminolaevulinate synthetase gene of the haem synthesis pathway, which is a candidate gene for X linked sideroblastic anaemia located at Xp11.21.

Alleles↗
PubMed1995

Parathyroid hormone (PTH)/PTH-related protein receptor messenger ribonucleic acid expression and PTH response in a rat model of secondary hyperparathyroidism associated with vitamin D deficiency.

The aim of the present work was to characterize at the molecular level the mechanism of PTH resistance in a rat model of secondary hyperparathyroidism resulting from vitamin D deprivation. PTH/PTH-related protein (PTHrp) receptor messenger RNA (mRNA) expression, assayed by ribonuclease protection analysis, was studied in the kidney, femoral epi/metaphysis, and diaphysis. In addition, in the kidney, PTH/PTHrp receptor mRNA expression was correlated to receptor function by measuring adenyl cyclase activity in crude renal membranes after stimulation by PTH (10(-10) - 10(-6) M), forskolin (0.1 and 0.2 mM), NaF (5 and 10 mM), and isoproterenol (1 and 10 microM). Four groups of rats were studied to investigate the effects of calcium, PTH, and/or vitamin D status. The first group received a control diet (D+D+). The second group received a diet deficient in vitamin D until death (D-D-). In the two other groups that also received a vitamin D-deficient diet, the hypocalcemia and the hyperparathyroidism were later corrected, by either vitamin D supplementation (D-D+) or lactose and high calcium diet (D-Ca+), 1 week before death. The results revealed a 2-fold decrease in the PTH-induced adenyl cyclase activity of the renal membranes in the D-D- rats compared to those in the three other groups. There was no significant difference in the four groups in adenyl cyclase activity stimulated by forskolin, NaF, and isoproterenol. The decrease in PTH-induced adenyl cyclase activity was associated with an approximately 2-fold increase in PTH/PTHrp receptor mRNA expression in the kidneys of the D-D- rats compared to controls. Normalization of PTH/PTHrp receptor mRNA expression was observed after vitamin D supplementation (D-D+ rats), but not after correction of the hypocalcemia and secondary hyperparathyroidism by oral lactose and calcium supplementation. In the epi/metaphysis, an approximately 2-fold increase in PTH/PTHrp receptor mRNA was also observed in the D-D- rats compared to the controls; this increase was partially corrected upon normalization of the calcemia and PTH levels with either vitamin D (D-D+ group) or lactose/calcium (D-Ca+ group). In the diaphysis, no change in the expression of PTH/PTHrp receptor mRNA was observed in any group.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1995

Predictors of recidivism to a juvenile assessment center.

We report the results of a study of the predictors of recidivism to a Juvenile Assessment Center in Hillsborough County, Florida, involving over 2,000 youths processed at the center during its first 8 months of operation. Consistent with previous research, younger aged youths, youths with abuse or neglect histories, with previous arrests for property, violence, or drug offenses, with potential vocational, leisure-recreation, and family problems, or who were arrested on property felony charges were likely to recidivate. The program activity and policy implications of these results are discussed.

Adolescent↗
PubMed1994

Genetic linkage mapping for a susceptibility locus to bipolar illness: chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and Xpter.

We are conducting a genome search for a predisposing locus to bipolar (manic-depressive) illness by genotyping 21 moderate-sized pedigrees. We report linkage data derived from screening marker loci on chromosomes 2, 3, 4, 7, 9, 10p, 11p, 22, and the pseudoautosomal region at Xpter. To analyze for linkage, two-point marker to illness lod scores were calculated under a dominant model with either 85% or 50% maximum penetrance and a recessive model with 85% maximum penetrance, and two affection status models. Under the dominant high penetrance model the cumulative lod scores in the pedigree series were less than -2 at theta = 0.01 in 134 of 142 loci examined, indicating that if the disease is genetically homogeneous linkage could be excluded in these marker regions. Similar results were obtained using the other genetic models. Heterogeneity analysis was conducted when indicated, but no evidence for linkage was found. In the course of mapping we found a positive total lod score greater than +3 at the D7S78 locus at theta = 0.01 under a dominant, 50% penetrance model. The lod scores for additional markers within the D7S78 region failed to support the initial finding, implying that this was a spurious positive. Analysis with affected pedigree member method for COL1A2 and D7S78 showed no significance for linkage but for PLANH1, at the weighting functions f(p) = 1 and f(p) = 1/sqrt(p) borderline P values of 0.036 and 0.047 were obtained. We also detected new polymorphisms at the mineralocorticoid receptor (MLR) and calmodulin II (CALMII) genes. These genes were genetically mapped and under affection status model 2 and a dominant, high penetrance mode of transmission the lod scores of < -2 at theta = 0.01 were found.

Bipolar Disorder↗
PubMed1994

Counselling risk figures for fragile X carrier females of varying band sizes for use in predicting the likelihood of retardation in their offspring.

We have derived risk figures for fra(X) syndrome carrier mothers based on their DNA status. Clinical and molecular information was analysed in 200 carrier mothers and their offspring. Individuals were classified as affected by a requirement for special education. Risk figures were calculated using the genotype of the intellectually normal offspring in order to reduce ascertainment bias. Analysis was made on women with differing mutation size to predict the proportion of affected offspring. Using this method the following risk figures were derived: 1. For carrier women with an increase (delta) of 0.06-0.14 Kb, the risk for having an affected son was 29% (1 in 3.5) and 25% for daughters (1 in 4). This predicts an overall 73% chance of a normal child. 2. For delta size 0.15-0.24 Kb, the risk of having an affected son was 46% (1 in 2.2) and 32% for daughters (1 in 3.1), predicting a 61% chance of a normal child. 3. For delta size > 0.24 Kb, normal transmitting male offspring were not seen, i.e., the risk for males was 50% (1 in 2) and for females 32% (1 in 3.1) which predicts a 59% chance of a normal child.

Adult↗
PubMed1994

Pericentromeric genes for non-specific X-linked mental retardation (MRX).

Extensive linkage analyses in three families with non-specific X-linked mental retardation (MRX) have localized the gene in each family to the pericentromeric region of the chromosome. The MRX17 gene is localized with a peak lod of 2.41 (theta = 0.0) with the trinucleotide repeat polymorphism at the androgen receptor (AR) gene locus. This gene lies in the interval between the markers DXS255 and DXS990, as defined by recombinants. The MRX18 gene maps to the interval between the markers DXS538 and DXS1126, with a peak lod score of 2.01 (theta = 0.0) at the PFC gene locus. In the third family (Family E) with insufficient informative meioses for assignment of an MRX acronym, the maximum lod score is 1.8 at a recombination fraction of zero for several marker loci between DXS207 and DXS426. Exclusions from the regions of marker loci spanning Xq support the localization of the MRX gene in Family E to the pericentromeric region. Localizations of these and other MRX genes have determined that MRX2 and MRX19 map to distal Xp, MRX3, and MRX6 map to distal Xq, whilst the majority cluster in the pericentromeric region. In addition, we confirm that there are at least two distinct MRX genes near the centromere as delineated by the non-overlapping regional localizations of MRX17 and MRX18. Determination of these non-overlapping localizations is currently the only means of classifying non-syndromal forms of mental retardation and determining the minimum number of MRX loci.

Adolescent↗
PubMed1994

X-linked mental retardation with heterozygous expression and macrocephaly: pericentromeric gene localization.

A family is described with X-linked mental retardation (XLMR) with affected males in 2 generations. The manifestations are macrocephaly and heterozygous expression. Linkage analysis gives a 2-point lod score of 3.31 (theta = 0.0) at the AR, DXS991, and MAOB marker loci. The gene is localized by recombination events between DXS1068 (Xp) and DXS1125 (Xq). This condition in this family may be similar to that described by Atkin et al., 1985 (Am J Med Genet 21:697-705).

Adult↗
PubMed1994

Analysis of the regulation of the Aspergillus nidulans acuD gene, encoding isocitrate lyase, by construction of a hybrid promoter.

In order to confirm functionally that a 208 bp fragment of the 5'-flanking sequence of the acuD gene of Aspergillus nidulans is the region responsible for acetate inducibility and catabolite repression, a hybrid promoter was constructed by insertion of this fragment into the promoter of the (highly expressed) oliC gene of A. nidulans. Analysis of expression of the lacZ reporter gene fused to the oliC/acuD promoter showed induction by acetate at much higher levels than wild-type acuD expression. Acetate inducibility of the hybrid promoter was dependent on the facB gene, demonstrating that a facB-dependent upstream activating sequence (UAS) for acetate must be located in the 208 bp acuD fragment. In parallel, partial relief of the transcriptional repression of acetate inducibility by sucrose and glucose was observed in a creA- background, showing that the 208 bp acuD fragment also responds to the creA gene. In addition, the results show that combination of a regulatory element from a low-expression promoter (acuD) with a high-expression constitutive promoter (oliC) leads to amplification of the level of regulated expression.

Acetates↗
PubMed1994

Genetic susceptibility to colorectal cancer in patients under 45 years of age.

A study was conducted to assess the genetic contribution to the development of colorectal cancer in young probands. Of 83 patients aged 45 years or under diagnosed with colorectal cancer in one health region over a 2-year period, 65 or their surviving next of kin were available for interview, from whom were obtained 60 detailed and five limited family histories. Five families fulfilled the Amsterdam criteria and a further eight satisfied less strict criteria for hereditary non-polyposis colorectal cancer, a total of 20 per cent of the cohort. Eleven of these families came from the subgroup of 13 probands who had one or more first-degree relatives with colorectal cancer. Overall the relative risk of colorectal cancer in close relatives was 5.2 (P < 0.0001). This risk was highest for female relatives at 9.7 (P < 0.0001) and relatives of female probands at 6.7 (P < 0.0001). This study highlights the importance of taking a family history in this group of patients. Screening by colonoscopy for all close relatives of young patients with colorectal cancer is recommended.

Adult↗
PubMed1994

Analysis of the regulation of penicillin biosynthesis in Aspergillus nidulans by targeted disruption of the acvA gene.

To analyse the regulation of the biosynthesis of the secondary metabolite penicillin in Aspergillus nidulans, a strain with an inactivated acvA gene produced by targeted disruption was used. acvA encodes delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), which catalyses the first step in the penicillin biosynthetic pathway. To study the effect of the inactivated acvA gene on the expression of acvA and the second gene, ipnA, which encodes isopenicillin N synthase (IPNS), A. nidulans strain XEPD, with the acvA disruption, was crossed with strain AXB4A carrying acvA-uidA and ipnA-lacZ fusion genes. Ascospores with the predicted non-penicillin producing phenotype and a hybridization pattern indicating the presence of the disrupted acvA gene, and the fusion genes integrated in single copy at the chromosomal argB locus were identified. Both fusion genes were expressed at the same level as in the non-disrupted strain. Western blot analysis (immunoblotting) revealed that similar amounts of IPNS enzyme were present in both strains from 24 to 68 h of a fermentation run. In the acvA disrupted strain, IPNS and acyl-CoA: 6-aminopenicillanic acid acyltransferase (ACT) specific activities were detected, excluding a sequential induction mechanism of regulation of the penicillin biosynthesis gene ipnA and the third gene aat.

Acyltransferases↗
PubMed1994

Regulation of the expression of the isocitrate lyase gene (acuD) of Aspergillus nidulans.

Analysis of the promoter region of the acetate-induced isocitrate lyase gene (acuD) of Aspergillus nidulans is described. Transcription start sites were detected at positions -163, -170 and approximately -281 upstream of the ATG. Transcription analysis showed that the acuD gene is transcribed during growth on acetate but not on hexoses or glycerol. Expression of the acuD gene was studied under inducing and repressing conditions in cre+, creA, creB and creC mutant strains, showing that the creA(d)-1 mutation led to slight derepression of isocitrate lyase. Regulation of expression of the acuD gene was also studied using an in-frame fusion with the lacZ gene of Escherichia coli. Several deletions were made in order to identify the regions responsible for acetate induction and repression. A deletion of the -412 to -200 bp upstream region resulted in loss of all promoter activity and a smaller deletion within this region abolished most of the acetate inducibility.

Acetates↗
PubMed1994

Glucose-induced inactivation of isocitrate lyase in Aspergillus nidulans.

The existence of a second mechanism of catabolite control of isocitrate lyase of Aspergillus nidulans, in addition to the carbon catabolite repression phenomenon recently reported was analysed. Isocitrate lyase was rapidly and specifically inactivated by glucose. The inactivation was irreversible at all stages in the presence of cycloheximide, showing that reactivation depends on de novo protein synthesis. In addition, analysis of glucose-induced inactivation of isocitrate lyase in a creAd-30 strain showed that the creA gene is not involved in this process.

Aspergillus nidulans↗
PubMed1994

Understanding monochronic and polychronic individuals in the workplace.

Patterning of time is a frequently ignored aspect of human behavior. Individuals handle time durations differently. Responses to time durations were first outlined in the classic work of Hall (in 1959) and include urgency, activity, variety, and whether multiple or isolated tasks are attempted in the same time duration. When patients or other staff vary from the nurse in the way in which time or time perception is handled, difficulty can occur. Understanding the way individuals handle time can assist in dealing with patients and colleagues and is of particular significance in interacting with people from other cultures and races.

Humans↗