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Biomedical subjects

J Dickson

Publications and source records attributed to J Dickson.

At least 19 recordsLinked to original sources

Pretreatment plasma TGF beta 1 levels are prognostic for survival but not morbidity following radiation therapy of carcinoma of the cervix.

PURPOSE: To determine whether pretreatment plasma-transforming growth factor beta 1 (TGF beta 1) levels are prognostic for tumor control and late morbidity following radiation therapy in carcinoma of the cervix. METHODS AND MATERIALS: The study was comprised of 79 patients undergoing radiotherapy with curative intent for Stage I-III carcinoma of the cervix. TGF beta 1 levels were analyzed using ELISA. Late morbidity was measured using the Franco-Italian glossary. Data were available for the pretreatment levels of circulating tumor markers that represent disease burden, and for peripheral blood lymphocyte radiosensitivity measured as SF2. RESULTS: Pretreatment TGF beta 1 levels were a significant prognostic factor for survival and local control. There were weak significant correlations of TGF beta 1 levels with disease stage and the levels of circulating tumor markers (CA125, TPA). There was a weak significant correlation between TGF beta 1 levels and normal cell radiosensitivity (lymphocyte SF2). There was no relationship between TGF beta 1 levels and grade of morbidity and pretreatment TGF beta 1 levels were not a significant prognostic factor for the probability of developing late morbidity. CONCLUSION: In carcinoma of the cervix, pretreatment TGF beta 1 levels reflect tumor burden and are a significant prognostic factor for survival. Despite an underlying weak relationship of TGF beta 1 levels with intrinsic normal cell radiosensitivity, pretreatment levels are not prognostic for the probability of developing late complications. This finding does not rule out the possible usefulness of measurements toward the end of treatment once tumor burden has been reduced.

Adenocarcinoma↗

Coupling photochemical reaction detection based on singlet oxygen sensitization to capillary electrochromatography

Despite the impressive separation efficiency afforded by capillary electrochromatography (CEC), the detection of UV-absorbing compounds following separation in capillary dimensions remains limited by the short path length (5-75 microm) through the column. Moreover, analytes that are poor chromophores present an additional challenge with respect to sensitive detection in CEC. This paper illustrates a new photochemical reaction detection scheme for CEC that takes advantage of the catalytic nature of type II photooxidation reactions. The sensitive detection scheme is selective toward molecules capable of photosensitizing the formation of singlet molecular oxygen (1O2). Following separation by CEC, UV-absorbing analytes promote groundstate 3O2 to an excited state (1O2) which reacts rapidly with tert-butyl-3,4,5-trimethylpyrrolecarboxylate, which is added to the running buffer. Detection is based on the loss of pyrrole. The reaction is catalytic in nature since one analyte molecule may absorb light many times, producing large amounts of 1O2. The detection limit for 9-acetylanthracene, following separation by CEC, is approximately 6 x 10(-9) M (S/N = 3). Optimization of the factors effecting the S/N for four model compounds is discussed.

Journal Article↗

UK CropNet: a collection of databases and bioinformatics resources for crop plant genomics.

The UK Crop Plant Bioinformatics Network (UK CropNet) was established in 1996 in order to harness the extensive work in genome mapping in crop plants in the UK. Since this date we have published five databases from our central UK CropNet WWW site (http://synteny.nott.ac.uk/) with a further three to follow shortly. Our resource facilitates the identification and manipulation of agronomically important genes by laying a foundation for comparative analysis among crop plants and model species. In addition, we have developed a number of software tools that facilitate the visualisation and analysis of our data. Many of our tools are made freely available for use with both crop plant data and with data from other species.

Crops, Agricultural↗

Hepatocellular carcinoma after long-term tamoxifen therapy.

We describe a case of hepatocellular carcinoma (HCC) after long term tamoxifen therapy in a 71-year-old woman. The patient was prescribed tamoxifen for 12 years following right mastectomy and axillary node clearance for breast carcinoma in 1985. In 1997, she complained of abdominal pain and fullness. An abdominal ultrasound scan showed lesions in the right lobe of liver which were thought to be metastases. However, a biopsy showed primary HCC. Studies in rats suggest that tamoxifen is involved in hepatic carcinogenesis but studies in humans have failed to show any increased risk. However, these studies followed up patients for less than five years. An increased risk of HCC may not become apparent until after a decade or more of tamoxifen therapy. In addition, HCC in tamoxifen treated patients may be under-reported since there may be reluctance to biopsy liver tumours which are assumed to be secondary carcinoma of the breast.

Aged↗

Effects of concurrent verbalization on a time-critical, dynamic decision-making task.

The authors investigated the effects of concurrent verbalization on students' performance on a time-critical, dynamic decision-making task. After training on Fire Chief (a computer microworld that simulates fighting a forest fire; M. M. Omodei & A. J. Wearing, 1993a), 60 research participants were allocated randomly to 1 of 3 experimental conditions: silence, associative verbalization, or procedural verbalization. Participants who verbalized the bases of their decisions (procedural verbalization) performed significantly worse on average than participants in the silence condition. There was a small but non-significant decrement in the performance of participants who verbalized thoughts other than the bases of their decisions while performing the task (associative verbalization). Their average level was between the levels of participants in the silence and procedural-verbalization conditions.

Adolescent↗

Biosocial determinants of hysterectomy in New Zealand.

OBJECTIVES: This study examined the prevalence and biosocial correlates of hysterectomy. METHODS: Data were from a 1995 national survey of women aged 20 to 59 years. We applied piecewise nonparametric exponential hazards models to a subsample aged 25 to 59 to estimate the effects of biosocial correlates on hysterectomy likelihood. RESULTS: Risks of hysterectomy for 1991 through 1995 were lower than those before 1981. University-educated and professional women were less likely to undergo hysterectomy. Higher parity and intrauterine device side effects increased the risk. CONCLUSIONS: This study confirms international results, especially those on education and occupation, but also points to ethnicity's mediating role. Education and occupation covary independently with hysterectomy. Analysis of time variance and periodicity showed declines in likelihood from 1981.

Adult↗

Ophthalmomyiasis and nasal myiasis in New Zealand: a case series.

We report three cases of ophthalmomyiasis in New Zealand, due to the larvae of Oestrus ovis. All three patients reported eye injury caused by a fly. The larvae were removed from the conjunctival sac without difficulty under local anaesthesia. Presenting ocular symptoms of foreign body sensation, irritation, redness and photophobia all resolved swiftly. Topical antibiotic and steroid eye drops were administered. All three patients also developed nasal symptoms such as sneezing, nasal discharge and epistaxis. Otolaryngology follow-up demonstrated nasal myiasis in two patients which was treated with nasal decongestants. In addition, all three patients were treated with ivermectin (Mectizan).

Adolescent↗

Reducing cardiac dose in post-operative irradiation of breast cancer patients: the relative importance of patient positioning and CT scan planning.

Left-sided post-operative radiotherapy fields for the treatment of breast cancer inevitably encompass the heart within the treatment volume, resulting in late mortality which may negate the cause-specific survival advantage of the therapy. The effect of positioning was studied in 11 patients with left-sided tumours and five with right-sided tumours receiving routine post-operative radiotherapy to the breast or chest wall as part of primary therapy for breast cancer. Using the same arrangement of glancing fields for each patient treatment position, the optimum patient positioning resulted in a reduction in cardiac dose compared to our standard patient treatment position. On the left side the reduction in mean cardiac dose was 60% (p < 0.001) and the reduction in maximum dose was 32% (p < 0.001); on the right it was 17% and 31%, respectively. The volume of cardiac tissue irradiated was also reduced for all patients. Using this optimum treatment position, cardiac dose was investigated in a further 10 patients with left-sided tumours and our standard glancing field set-up was compared with 3-dimensional planning. A further reduction of 12% in the mean cardiac dose was achieved. 5 of 10 patients had a further small reduction of 4.6% in the maximum dose and one patient had a further reduction in maximum dose of 58%. In conclusion, sophisticated radiotherapy planning can reduce cardiac doses, but optimum patient positioning is of greater importance. The general application of such relatively simple measures could have a significant positive effect on overall survival from breast cancer.

Breast Neoplasms↗

Evaluation of a low-threshold clinic for opiate-dependent drug users.

This study reports on the development and outcome of a Low Threshold Clinic (LTC) for opiate-dependent drug users. The service originated as a nursing initiative within an inner city Drug Dependency Centre (DDC) and its rationale and treatment approach are explored in relation to the literature and local circumstances. Client baseline and outcome data were systematically gathered to assess service uptake and service efficacy in terms of client outcome. Data are presented for the first two years of operation during which a total of 59 clients entered the LTC. The sociodemographic characteristics and patterns of drug use among this group suggest the service was successful in targeting clients who previously failed to enter traditional treatment programmes despite initial referral to the DDC. Outcome data indicate a tendency for clients to inject less frequently, engage in less criminal activity and, by 12 months, to reduce their dose of prescribed methadone whilst attending the LTC. Tentative conclusions are drawn concerning the value of this service for 'hard-to-reach' drug users and those who may be at a precontemplation stage of change. Recommendations are made for a more comprehensive evaluative study that involves comparison with other treatment approaches.

Adult↗

Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.

The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R gene of the patient of family 1 had the wild-type sequence. Consequently, the coding region of the aquaporin-2 gene including the exon-intron junctions was sequenced. A novel G to T transversion at codon 202, predictive of an exchange of tryptophan 202 by cysteine, was identified. As the mutation occurs at G-1 of the 5' splice donor site of intron 3, aberrant splicing is also likely. The mutation involves one of the supposed water pore-forming loops. Therefore, both aberrant splicing and amino acid substitution are likely to result in a functionally defective protein. Sequencing of the complete V2R gene of the male patient of family 2 revealed a novel single-base deletion at codon 310 (delta C1001), shifting the reading frame to give an altered amino acid sequence beginning at codon 311. The mutation is unique in predicting a C-terminally extended protein (termination after codon 434 in the mutant receptor instead of codon 371 in the wild-type). The deduced mutant protein is likely to be nonfunctional since the amino acid sequence of the seventh transmembrane domain and the C-terminus is altered.

Amino Acid Sequence↗

Vasopressin V2 receptor mutants that cause X-linked nephrogenic diabetes insipidus: analysis of expression, processing, and function.

We investigated the biochemical and functional properties of five vasopressin V2 receptor mutants (L44F, L44P, W164S, S167L, and S167T) that were recently described in families with a history of X-linked nephrogenic diabetes insipidus. COS.M6 cells transfected with cDNA encoding these mutants acquired < 4% specific [3H]arginine vasopressin (AVP) binding sites on the cell surface in comparison with cells transfected with cDNA coding for the wild-type receptor. Membrane preparations from COS.M6 cells or human embryonic kidney 293 cells expressing these mutants did not respond with an increase in adenylyl cyclase activity in response to AVP, which is in contrast to membranes from cells expressing the wild-type. By analyzing fusion proteins of the V2 receptor and Escherichia coli alkaline phosphatase attached to the carboxyl terminus of the receptor moiety, we found that the mutants L44P, W164S, S167L, and S167T lacked complex glycosylation and were expressed at low levels. The data suggest that the mutants L44P, W164S, S167T, and S167L are misfolded and therefore retained within the endoplasmic reticulum and degraded. In contrast, the fusion proteins carrying the mutant L44F and the in vitro mutant S167A were expressed in their mature form at wild-type levels; however, only the mutant S167A was functionally active. Site-directed mutagenesis of S167 revealed that elimination of the endogenous hydroxyl group (S167A) yielded a protein with properties identical to those of the wild-type receptor, whereas both the introduction of a methyl group (S167T) and the replacement of the hydroxyl group by an isopropyl group (S167L) profoundly disturbed receptor processing. The data show that minute changes at codon 167 nearly abolish expression of a mature protein, thus defining structural requirements of this codon.

Alkaline Phosphatase↗

Second messenger systems in Tourette's syndrome.

Abnormalities within second messenger systems have been hypothesized as the underlying pathophysiologic mechanism in a variety of neuropsychiatric disorders. In the Gilles de la Tourette syndrome (TS) prior studies have shown that the concentration of adenosine 3',5'-monophosphate (cAMP) is reduced in cortical and putamen brain regions. In this study, postmortem cortical tissues from 4 adults (mean age 59.5 years) with the lifetime diagnosis of TS and 5 controls (mean age 63.8 years) were analyzed for functional activities within the cAMP and phosphoinositide systems. In addition, plasma cAMP was quantified in children with TS (n = 33) and controls (n = 17). In frontal (A4, A6) and occipital (A17) cortical tissues there were no significant differences for adenylyl cyclase activity whether assayed under basal conditions or after stimulation with GTP gamma S (a non-hydrolyzable GTP analog), forskolin (a selective enzyme stimulator), or (-)-isoproterenol (a beta-adrenergic agonist). D2 receptor activation (quinpirole) and assessment of the inhibitory guanine nucleotide protein also showed no significant alterations in TS samples. Activity of cAMP phosphodiesterase was increased insignificantly in A4 and A17 TS brain regions. Plasma concentrations of cAMP in plasma were similar in children with TS (135.4 +/- 8.3 pmol/ml) and controls (132.6 +/- 7.9 pmol/ml). Postmortem membrane receptor binding for markers within the phosphoinositide (PI) system showed that TS samples had increased [3H]phorbol ester binding to protein kinase C sites in area A17, but normal binding in A4. In contrast, [3H] inositol 1,4,5-triphosphate binding to IP3 receptors showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗