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T Cox

Publications and source records attributed to T Cox.

At least 73 records · Page 4Linked to original sources
PubMed1993

Linkage mapping of the cystathionine beta-synthase (CBS) gene on human chromosome 21 using a DNA polymorphism in the 3' untranslated region.

We used single-strand conformation polymorphism (SSCP) to detect DNA polymorphisms in the 3' untranslated (3'UT) region of the gene for cystathionine beta-synthase (CBS). A polymorphism due to a T-to-C substitution at nucleotide 549 of the 3'UT region with heterozygosity of 46% has been identified. Genotypes for this polymorphism have been obtained in all of the informative CEPH families, and CBS has been placed in the linkage map of human chromosome 21.

Base Sequence↗
PubMed1993

Evaluation of growth hormone in thalassaemic boys with failed puberty: spontaneous versus provocative test.

Growth hormone (GH) secretion was determined by evaluating ultradian GH profiles for 12 h and GH responses to insulin stimulated hypoglycaemia (ITT) in 28 stunted boys with beta-thalassaemia major aged 15.2-17.4 years, who presented with pubertal failure (FP). Healthy non thalassaemia prepubertal boys (n = 10) aged 7.5-8.8 years, were studied as controls. All patients had normal responses to ITT with peak GH levels > or = 15 mU/l. Basal GH concentrations (mean +/- sem) (1.65 +/- 0.03 mU/l vs 2.58 +/- 0.27 mU/l; P < 0.05) and the stimulated GH responses (peak GH = 15.4 +/- 0.20 mU/l vs 21.08 +/- 0.78 mU/l; P < 0.001) were significantly lower in the patients with failed puberty than in the controls, indicating that the FP patients had diminished GH reserve and secretory capacity. Moreover, all the GH peak parameters including the maximum spontaneous concentrations (MX-GH) and the area under the GH curve (AUC) were significantly lower in the thalassaemic patients than in the controls (MX-GH = 5.2 +/- 0.21 mU/l vs 20.42 +/- 0.14 mU/l; P < 0.001; AUCb = 421.22 +/- 4.31 mU/l vs 712.20 +/- 3.42 mU/l; P < 0.001). These observations suggest that the thalassaemic patients had endogenous neurosecretory GH deficiency (GHND). Priming with sex steroid did not cause any improvement in the spontaneous or stimulated GH secretory patterns in thalassaemic patients. It was noteworthy that in neither the patients nor the control subjects, was there a significant correlation between the maximum stimulated and the MX-GH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Phase I/pharmacokinetic/biochemical study of the nitroimadazole hypoxic cell sensitiser SR2508 (etanidazole) in combination with cyclophosphamide.

SR2508 sensitises certain hypoxic tumor cells in vitro and in vivo to the cytotoxic action of radiation and alkylating agents. The mechanism of sensitisation may derive in part from depletion of glutathione (GSH) and possibly inhibition of GSH-dependent enzymes in target cells. We treated 46 evaluable patients with cyclophosphamide 750-1000 mg m-2 followed by SR2508 at eight dose levels ranging from 2.5 to 15.0 g m-2. Each patient received SR2508 as a single agent initially, followed a week later by the combination of cyclophosphamide and SR2508. Initially, myelosuppression was the major toxicity; potentiation of cyclophosphamide-induced leukopenia by SR2508 required a dose reduction of cyclophosphamide to 750 mg m-2 at SR2508 doses above 7.2 g m-2. At doses above 9.4 g m-2 an acute syndrome of muscle pains and painful paresthesias of the extremities lasting 12-24 h was observed to occur with increasing severity. This side-effect was intolerable in two of three patients treated at 15.0 g m-2. The only other reproducible side-effect was nausea and vomiting which was controllable with antiemetics. Plasma and urine SR2508 concentrations were measured by HPLC in 45 patients. Plasma elimination curves fit a 2-compartment model. The mean terminal half-life at each dose level ranged from 5.1-5.8 h. The mean area under the plasma concentration-time curve was linearly related to dose, and mean total body clearance ranged from 46.6-94.0 ml-1 min-1 m-2; renal clearance accounted for 65.7-79.3%. Pretreatment with cyclophosphamide did not influence the kinetics of SR2508 in individual patients. Examination of the glutathione content of peripheral mononuclear cells and tumour samples showed that depletion to below 50% of control occurred in the majority of patients. GSH transferase inhibition occurred with a similar time-course, but to a lesser extent. These data suggest that the further evaluation of this regimen should be conducted with SR2508 administration preceding that of cyclophosphamide and that its evaluation in cyclophosphamide-sensitive tumours is warranted.

Adult↗
PubMed1993

Interference with glycated hemoglobin by hemoglobin F may be greater than is generally assumed.

An automated electrophoretic method to measure glycated hemoglobin (Hb A1) was compared with manual affinity methods. Good correlation between methods was found. The electrophoretic method showed good run-to-run precision, good linearity, was free from interference by the labile aldimine fraction, and required less time and considerably less consumable expense than the affinity methods. However, as previously reported, Hb F comigrating with Hb A1 caused spurious increases in glycated Hb levels as compared with the affinity methods. This effect was linearly dependent on the Hb F concentration. Using the discrepancy between concentrations of Hb A1 by electrophoresis and glycated hemoglobin by affinity methods, 330 patients were screened in two hospitals for Hb F. A 12% frequency of elevated Hb F (defined as a level that is more than 2%) was found in patients from a community-tertiary care hospital, which is significantly greater than the 1.5% frequency commonly thought to occur in the adult population at large, whereas patients from a Veterans Administration Hospital showed an elevated frequency of 2.2%. Based on this and other studies, it is concluded that the frequency of elevated Hb F in adults may very substantially among different medical centers. The authors recommend against using this method and suggest that laboratories that persist in using it should periodically assess the frequency in patients with Hb F levels greater than 2% of total hemoglobin, replacing the method if an unacceptably high frequency is found.

Artifacts↗
PubMed1993

MRI in neurofibromatosis 1. The nature and evolution of increased intensity T2 weighted lesions and their relationship to intellectual impairment.

Thirty eight patients with neurofibromatosis 1 (NF1) had neurological examinations, intellectual assessments and MRI scans. Increased intensity lesions on T2 weighted images were found in 13 patients. These abnormalities were more common in patients aged under 18 years. The lesions occurred predominantly in the basal ganglia, brainstem and cerebellum, and were multiple in 11 patients. They did not produce symptoms or neurological deficit in any patient and did not enhance with gadolinium-meglumine-triamine-pentaacetic acid contrast medium (Gd-DTPA). In 2 patients, however, the abnormalities exerted mass effect distorting the brain and in 3 patients they occurred in conjunction with known gliomas. The lesions remained unchanged over a three year follow up period. The nature of the lesions is uncertain but the fact that they may produce mass effect and occur in association with gliomas suggests that they have malignant potential. There was no correlation between the presence of these abnormalities and intellectual impairment.

Adolescent↗
PubMed1993

Occupational health: control and monitoring of psychosocial and organisational hazards at work.

This paper considers the conceptualizations which underpin the traditional approach to occupational health and offers a critique; much of which points up the importance of psychosocial and organizational issues. It then explores the possible development of a new 3 factor model of concern - organisational health - based on health, work and organisation. It takes as its thesis the need to address the problems posed by psychosocial and organisational hazards at work and the argument that these can be managed effectively within the framework of practice that has proved successful for the more tangible workplace hazards.

Conflict of Interest↗
PubMed1992

Linkage mapping of the carbonyl reductase (CBR) gene on human chromosome 21 using a DNA polymorphism in the 3' untranslated region.

A DNA polymorphism has been found in the 3' untranslated region of the carbonyl reductase gene (CBR). Genotypes of the members of the CEPH pedigrees have been obtained and used in linkage analysis to map the CBR gene in the linkage map of human chromosome 21. The gene maps between the interferon-alpha receptor (IFNAR) and the D21S55 loci.

Alcohol Oxidoreductases↗
PubMed1992

Cloning and linkage mapping of three polymorphic tetranucleotide (TAAA)n repeats on human chromosome 21.

We report the cloning, sequencing, and mapping of three short sequence repeat polymorphisms due to tetranucleotide (TAAA)n repeats from human chromosome 21. These DNA markers (D21S221, D21S225, D21S226) have been cloned from the chromosome 21-specific plasmid library of J. C. Fuscoe, C. C. Collins, D. Pinkel, and J. W. Gray (1989, Genomics 5: 100-109) and were shown to be polymorphic by polymerase chain reaction amplification and polyacrylamide gel electrophoresis. Genotypes were determined in informative CEPH pedigrees and used in linkage analysis relative to other mapped markers on human chromosome 21. One of these markers, D21S221, is closely linked to the amyloid precursor protein gene (APP), which has been implicated in the etiology of familial Alzheimer disease in some families.

Base Sequence↗
PubMed1992

Linkage mapping of the AML1 gene on human chromosome 21 using a DNA polymorphism in the 3' untranslated region.

We have detected a polymorphism in the 3' untranslated region of the AML1 gene, which is located at the breakpoint on chromosome 21 in the t(8;21)(q22;q22.3) translocation often associated with patients with acute myeloid leukemia. Informative CEPH families were genotyped for this polymorphism and used to localize the gene on the linkage map of human chromosome 21. The AML1 gene is located between the markers D21S216 and D21S211, in chromosomal band 21q22.3.

Base Sequence↗
PubMed1992

The evaluation of patients with a suspected pituitary microadenoma: computer tomography compared to magnetic resonance imaging.

OBJECTIVES: To perform a prospective study to compare the ability of magnetic resonance imaging (MRI) and computer assisted tomography (CT) to predict the position of a tumour within the pituitary fossa and to assess the clarity of the image generated by the two modalities in patients with suspected pituitary microadenomas. DESIGN: Nineteen patients were investigated with CT and MRI scans and underwent trans-sphenoidal exploration of the pituitary fossa. Both scans were assessed blind and independently by three neuroradiologists, A, B, and C; A and B examined the CT scans and B and C the MRI scans. The predicted site was then compared to the size and position of the tumour at surgery. PATIENTS: Twenty-five patients were recruited and had both CT and MRI scans, 19 subsequently underwent trans-sphenoidal exploration of the pituitary fossa and formed the study population. RESULTS: The joint opinions of A and B of the CT scans were correct in 10/19, and those of B and C of the MRI scans were correct in 17/19 cases, P = 0.008. Observer agreement was used to assess the clarity of the image. A and B agreed about the site of the tumour on the CT scan in 14 of 19 cases (Kappa statistic 0.556); B and C agreed on the MRI scans in 19/19 cases (Kappa statistic 1), P = 0.025. After the exclusion of five cases found to be macroadenomas at surgery, the joint opinions of A and B of the CT scans were correct in 8/14, and those of B and C of the MRI scans were correct in 12/14 cases, P = 0.133. A and B agreed about the site of the tumour on the CT scan in 12/14 cases (Kappa statistic 0.653), B and C agreed on the MRI scans in 14/14 cases (Kappa statistic 1, no significant difference). CONCLUSIONS: In the assessment of suspected pituitary microadenomas MRI is the imaging technique of choice in view both of its greater diagnostic accuracy and the avoidance of radiation exposure.

Adenoma↗
PubMed1992

The role of cytokines in the pathogenesis of hepatic granulomatous disease in Schistosoma mansoni infected mice.

Cytokines are important in the cell-mediated response to Schistosoma mansoni eggs. We have found that Th2 cytokine responses (e.g. IL-4 and IL-5) are augmented after egg laying begins while Th1 responses (IL-2 and IFN-gamma) are down regulated in S. mansoni infected mice. Treatment of mice with anti-IL-5 monoclonal antibodies (Mab) suppressed the eosinophil response almost completely but did not affect granuloma size and slightly increased hepatic fibrosis. Anti-IL-4 treatment abolished IgE responses in infected mice and decreased hepatic fibrosis slightly. Anti-IFN-gamma treatment had no effect on hepatic pathology. Anti-IL-2 treatment decreased granuloma size significantly and decreased hepatic fibrosis markedly. Anti-IL-2 treatment dramatically decreased IL-5 secretion by splenic cells in vitro and decreased peripheral blood and tissue eosinophilia. In contrast IL-4 secretion was unaffected and serum IgE was normal or increased. IL-2 and IFN-gamma secretion by splenic cells of treated mice were slightly but not significantly increased suggesting that anti-IL-2 treatment is affecting Th2 rather than Th1 responses.

Animals↗
PubMed1991

Ion channels in boar sperm plasma membranes: characterization of a cation selective channel.

Plasma membranes isolated from cauda epididymal and ejaculated boar sperm were inserted into planar lipid bilayers and examined for the presence of ion channels. Channel fusion was frequently observed; the most prominent was a nonselective cation channel which conducted K, Na, Cs, Ca, and Ba. Channel opening did not show a strict dependence on voltage but was partially blocked by verapamil, nitrendipine, and ruthenium red. A channel with these characteristics was observed when plasma membranes were isolated by high-pressure nitrogen cavitation (650 psi, 78% sperm head plasma membranes) or at very low nitrogen pressures (50 psi, 90% sperm head plasma membranes), suggesting that this channel may be present in the plasma membrane overlying the sperm head.

Animals↗
PubMed1991

Detection of hereditary haemochromatosis in an HLA-identical pedigree showing discordance between HLA class I genes and the disease locus.

Hereditary haemochromatosis is a recessive disease in which primary hepatocellular carcinoma, complicating cirrhosis, is responsible for about one-third of deaths in affected homozygotes. We describe a unique HLA haplo-identical pedigree showing parent-to-offspring transmission of hereditary haemochromatosis in whom HLA typing studies, including class I and class II allogenotype analysis, were of no benefit in identifying affected homozygotes. However, affected siblings in the pre-cirrhotic stage of haemochromatosis, with apparent discordance between the haemochromatosis allele and class I loci on chromosome 6, were detected by undertaking a family study, using analysis of serum parameters of iron status in combination with magnetic resonance imaging (MRI). This pedigree emphasises the critical importance of genetic and non-invasive methods for the identification of asymptomatic homozygotes before cirrhosis develops.

Alleles↗
PubMed1991

Risk factors for immediate prosthetic postmastectomy reconstruction.

The charts of 44 women who underwent 47 immediate postmastectomy prosthetic breast reconstructions (IPMPBR) with subpectoral prostheses (long-term implant, long-term expandable implant or tissue expanders followed by long-term prosthetic placement) were retrospectively reviewed. Follow-up was from 3 to 49 months (median 18 months). Patient ages ranged from 31 to 77 years (median 42) but 82 per cent were under 60 years old. Indications for mastectomy were infiltrating cancer in 30 patients, intraductal cancer in 11, lobular carcinoma in situ in two and prophylaxis in one. There were 11 patients with pathologic Stage I, 15 with Stage II, three with Stage III and one with Stage IV breast cancer. Adjuvant chemotherapy (CTX) was given to 17 women, adjuvant hormonal treatment to nine, and radiation therapy (RT) to five. One patient had prosthesis extrusion and removal. Two patients had late periprosthetic infections (PPI) with consequent prosthesis removal. CTX did not have a significant association with PPI (two of 14 with CTX vs 0 of 29 without, P = 0.1). However, fill port migrations, prosthesis deflations, and greater than 1 complication were significantly associated with these infections (two of three vs 0 of 38, P = 0.004; two of two vs 0 of 45, P = 0.001; two of four vs 0 of 43, P = 0.006). Skin flap cellulitis and postoperative seroma were also associated with PPI (P less than 0.003 and less than 0.006, respectively). These factors were all also significantly associated with involuntary prosthesis loss (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cognition and mood in relation to the performance of squash tasks.

The purpose of this investigation was to determine the role of cognition and mood in the performance of squash tasks, with particular reference to attention and self-reported arousal and stress. Volunteer male subjects (n = 40), divided into three ability groups, 'skilled', 'average' and 'novice', were required to perform two squash tasks with different degrees of difficulty. Order of presentation of the tasks was controlled. Results indicated that subjects completing the easier squash task first performed better on the subsequent difficult task than those subjects who completed the more difficult task first. No differences in scores across tasks were found for subjects completing the tasks in reverse order. Performance was related to level of skill. Furthermore, significant differences in attentional style were revealed when average subjects were compared with skilled and novice players. Skilled players were also found to exhibit significantly different personality characteristics from novice players. Specifically, skilled players exhibited higher levels of extraversion and appeared less neurotic. For the average and novice groups, reports of high levels of stress accompanied those of high levels of arousal and these remained constant throughout the experiment. By contrast, for the skilled group low levels of stress accompanied high levels of arousal. The results are discussed in terms of the effects of these cognitive and mood factors on performance and a suggested direction for future research is offered.

Adolescent↗
PubMed1990

Multi-institutional drug-use evaluation of intraocular irrigating solutions.

A collaborative drug-use evaluation (DUE) of intraocular irrigating solutions (IOISs) at ophthalmic specialty hospitals nationwide is reported. Qualifying criteria for the use of an expensive fortified IOIS product were (1) the duration of surgery is more than 60 minutes, (2) the surgery is performed without a viscoelastic agent, (3) the patient's age is less than 50 years, (4) the patient has diabetes, and (5) the patient has evidence of compromised corneal endothelium. Surgical cases involving the use of IOISs were identified at each institution, and those cases involving fortified IOIS were reviewed for conformance with the criteria established. Of 23 institutions, 10 were able to perform the DUE. The review was concurrent at one institution and retrospective at the other nine. A case had to meet only one criterion to be considered in conformance. The cumulative mean rate of conformance with at least one criterion was 74%; the median conformance rate was 91%. The criteria that most frequently justified the use of fortified IOIS were surgical duration and nonuse of a viscoelastic material. Conformance with the DUE criteria varied with the institution, but valuable knowledge about the use of intraocular irrigating solutions was obtained by all.

Adult↗
PubMed1989

Lymphokine-activated killer function following autologous bone marrow transplantation for refractory hematological malignancies.

Disease recurrence remains the major factor which limits the success of autologous bone marrow transplantation (ABMT) for refractory hematological malignancies. The administration of interleukin 2 (IL2) with or without ex vivo generated lymphokine-activated killer (LAK) cells represents a potential approach to eradicating residual disease after ABMT. However, since LAK precursor activity is radiosensitive, high dose chemoradiotherapy may abrogate LAK function and preclude clinical responsiveness to IL2 after ABMT. Furthermore, since lymphocyte subsets which mediate LAK activity may recover at different rates after ABMT, LAK cells may be phenotypically and/or functionally altered after ABMT. To determine whether IL2 responsive LAK precursor cells are present in the circulation after ABMT, peripheral blood mononuclear cells (PBMC) from 21 patients with acute leukemia or lymphoma were tested for IL2-inducible LAK activity 17-83 days after ABMT. Cells were cultured with IL2 (1000-2000 units/ml) for 4 or 5 days and then tested for cytolytic activity and/or cell phenotype. LAK activity against the Daudi cell line was detected in every PBMC sample from every patient at every time point tested. The Raji cell line and a fresh allogeneic ovarian carcinoma were also lysed by LAK cells generated after ABMT. In the subgroup of patients transplanted for non-Hodgkin's lymphoma, LAK precursor activity appeared comparable to that of healthy controls. Culture with IL2 resulted in increased mean IL2 receptor expression in lymphocytes from patients after ABMT (3.1-9.9%) and from healthy controls (3.1-12.0%). After culture with IL2, the percentage of cells bearing the natural killer cell-associated Leu-19 determinant was significantly higher in patient PBMC than in normal control PBMC (28.3 versus 8.7%). Positive and negative cell selection by fluorescence sorting after culture with IL2 revealed that most of the LAK activity after ABMT was mediated by the Leu-19+ cells. Although CD5+ T-cells were devoid of LAK activity, a subset LAK effectors was CD8+. Thus, LAK activity is rapidly reconstituted after ABMT and is mediated by cells phenotypically similar to those in normal controls. These results support the feasibility of IL2 +/- LAK as consolidative immunotherapy after ABMT.

Antigens, CD↗