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Biomedical subjects

D J Thomas

Publications and source records attributed to D J Thomas.

At least 109 records · Page 6Linked to original sources
PubMed1994

The graduation of secondary structure elements.

A method of graduating (i.e., least-squares fitting) a smooth polynomial curve through long elements of protein secondary structure is described. It uses the Chebyshev polynomials of a discrete (integer) variable with several restraints to prevent artifactual curvatures. A new recursion formula is given which allows the evaluation of the polynomials on rational-number points as well as on the integer points. High-order splines suitable for interpolation between integer points are also discussed. The new method finds applications in graphics and in structural analysis.

Computer Graphics↗
PubMed1994

Increased mdr1 gene transcript levels in high-grade carcinoma of the bladder determined by quantitative PCR-based assay.

Overexpression of the multidrug resistance (mdr1) gene has been implicated in resistance to a number of the chemotherapeutic agents currently used in the treatment of bladder cancer (doxorubicin, vincristine and epirubicin). We report the development and validation of a quantitative assay for the determination of mdr1 gene transcript levels based on reverse transcription and the polymerase chain reaction (PCR), sensitive to less than 2-fold variations in transcript levels. Using these techniques, mdr1 mRNA levels were investigated in 32 primary untreated transitional cell carcinomas of the bladder. mdr1 mRNA was detected in all samples, with levels varying between individual tumours over a 63-fold range. These variations were not associated with the proliferative status of the tumour. mdr1 mRNA levels were significantly higher in poorly differentiated high-grade (G3) tumours than in well- and moderately differentiated low-grade (G1 and G2) tumours (P = 0.0057). The results suggest that this relationship may extend to mdr1 mRNA levels being an indicator of poor prognosis, as anticipated on the basis of the observed relationship to tumour stage and grade. No evidence was found to implicate mdr1 mRNA levels as a predictor of tumour recurrence or progression. Given that mdr1 mRNA levels are increased in a proportion of high-grade bladder tumours that are routinely subjected to chemotherapy, we discuss the possibility that mdr1 mRNA levels may be clinically significant as determinants of chemotherapeutic response and outcome in bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Women and heart disease: living with lifestyle changes--a pilot study.

Although deductively derived motivational models have identified cognitive mediators that encourage a person to initiate cardiovascular health behaviors, these models do not explain the low compliance level regarding health behavior change. Understanding the meaning of health change for the person in the context of her life could help nurses develop programs aimed at facilitation of life-long health behaviors that foster cardiovascular health. The author, using hermeneutic phenomenology, describe and interpret women's efforts to make lifestyle changes to reduce their coronary risk factors. Many participants related that they tried to follow orders but were not given specific information how to comply. Implications for nursing are in community education.

Adaptation, Psychological↗
PubMed1994

P53 expression, ploidy and progression in pT1 transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate a potential role for overexpression of the p53 protein in the identification of pT1 bladder tumours destined to progress. PATIENTS AND METHODS: The protein expression of the tumour suppressor gene p53, nuclear ploidy and tumour grade were studied in 25 patients with pT1 bladder tumours. Follow-up data was available for 21 tumours over a 10 year period. p53 expression was determined by immuno-histochemistry on paraffin embedded sections and flow cytometry was performed on cell suspensions derived from the same blocks. RESULTS: Ten of 21 (48%) tumours progressed to muscle invasive disease. Nuclear staining for the protein was seen in 16 (64%) tumours and of these nine (56%) progressed. All tumours with abnormal DNA content and all high grade tumours demonstrated overexpression of p53. Significantly more patients with high levels of p53 expression (> 10% nuclear staining) progressed compared with tumours with less than 10% of nuclei staining (P = 0.007). However, grade was the most specific predictor of progression (100%), with all grade 3 tumours progressing and grade was also the most significant prognostic indicator in terms of survival (P = 0.025). CONCLUSION: Tumour grade is likely to remain as the most useful aid to management decisions in pT1 bladder tumours.

Aged↗
PubMed1993

Magnetic resonance imaging of spinal cord in multiple sclerosis by fluid-attenuated inversion recovery.

Magnetic resonance imaging examination of the upper spinal cord was done in sixteen adult patients with clinically definite multiple sclerosis (MS) by T2 weighted fluid attenuated inversion recovery (FLAIR) scanning in which the signal from cerebrospinal fluid was suppressed. These scans were compared with matched images obtained with conventional T1 and T2 weighted pulse sequences (including contrast enhancement). 6 lesions (five patients) were seen with the conventional scans and 37 lesions (fourteen patients) were seen with the FLAIR scans. The FLAIR sequence considerably improves the ability of MRI to demonstrate spinal involvement in MS.

Adult↗
PubMed1993

Identification of 5'-flanking regions affecting the expression of the human decay accelerating factor gene and their role in tissue-specific expression.

Decay accelerating factor (DAF) is a complement regulatory protein that protects host tissue from complement-mediated damage by preventing the assembly and/or promoting the dissociation of C3 and C5 convertases. To identify and analyze the DNA sequence elements responsible for controlling DAF expression, the 5'-flanking region of the human DAF gene was cloned. Sequencing of 880 nucleotides upstream from the ATG codon revealed the absence of classic TATA or CAAT boxes. RNase protection and primer extension assays revealed a series of transcription start sites in a 10 nucleotide region located 86 nucleotides upstream from the ATG (the first of these start sites is numbered +1). Using HeLa, K562, EBV, and Molt 4 cells, DAF mRNA and protein were analyzed by Northern and Western blot. The DAF mRNA and protein levels roughly correlated, suggesting transcriptional control of gene expression. K562 and HeLa expressed high levels, EBV expressed intermediate levels, and Molt 4 expressed essentially no detectible DAF mRNA or protein. Regions of DAF 5'-flanking DNA were subcloned into plasmids containing the chloramphenicol acetyltransferase reporter gene and tested in transient transfection assays. The construct extending from -206 to +84 (-206/+84) had transcriptional activity in the DAF-positive HeLa, K562, and EBV lines, but no activity in the DAF-negative Molt 4 line. In the three DAF-positive lines, major enhancer activity was demonstrated between -206 and -77, and between -77 and -54 (containing cAMP responsive element and AP-1 binding site). Additional deletion of the region between -54 and -34 (containing an Sp1 binding site) reduces chloramphenicol acetyltransferase activity further but the low numerical values preclude statistical significance. The identification of transcription start sites and enhancer regions in the DAF gene will be important for studies of the mechanisms whereby cytokines and other factors may modulate DAF expression.

Antigens, CD↗
PubMed1993

Osteotoxicity of cadmium and lead in HOS TE 85 and ROS 17/2.8 cells: relation to metallothionein induction and mitochondrial binding.

Epidemiological, experimental and clinical data indicate that cadmium and lead are osteotoxins in man and other species. The relative sensitivities of a clonal human osteosarcoma cell line (HOS TE 85) and a clonal rat osteosarcoma cell line (ROS 17.28) to the cytotoxic effects of cadmium and lead were tested in serum-free media without added growth factors. The rat osteosarcoma cells were more sensitive to cadmium with cytotoxicity and inhibition of proliferation at 0.25 versus 0.75 and 1.0 mumol l-1 cadmium, respectively, for human osteosarcoma cell lines. The lower sensitivity to cadmium of human osteosarcoma cells is attributed, at least partly, to induction of metallothionein synthesis by cadmium and zinc in this cell line; in the rat osteosarcoma cell line, they do not induce metallothionein synthesis. Human osteosarcoma cells were more sensitive than rat osteosarcoma cells to lead with inhibition (IC50) of proliferation at 4 mumol l-1 lead and cytotoxicity at 20 versus 6 and over 20 mumol l-1 lead, respectively, for these variables in rat osteosarcoma cells. Both cell lines attained the highest lead concentration in the 15,000 x g (mitochondrial) fraction. The lead in the mitochondrial, microsomal, nuclear and cytosolic fractions of the human cell line did not decrease during 24 h post-washout. Binding of lead was much less stable in the less sensitive rat cells, with 50-100% loss of mitochondrial, microsomal and nuclear lead during 24 h post-washout.

Animals↗
PubMed1993

Cyclic adenosine monophosphate response in primary and subcultured bladder epithelial cells: inhibition by 12-O-tetradecanoylphorbol-13-acetate.

Primary and first-passage dog urothelial cells (DUC and DUC-P1, respectively) exhibited an active catalytic subunit for the cyclic adenosine monophosphate (cAMP) second messenger system. Dramatic increases in cAMP levels were observed following the addition of forskolin, which elicited a time- and dose-response--dependent increase in cAMP levels. Increases in intracellular cAMP levels preceded media increases in cyclic nucleotide levels and were observed at the earliest time examined (5 minutes). The lowest effective concentration of forskolin was between 1 and 10 mumol/L. cAMP level increases as large as 20- to 100-fold were observed in cells and media. Preincubation of primary and subcultured cells with 0.1 mumol/L 12-O-tetradecanoylphorbol-13-acetate (TPA) for 60 minutes reduced the magnitude of the forskolin-induced increase in cAMP levels. To determine the mechanism by which TPA elicits its effect in primary cultures, the following test agents were used: 1.0 mumol/L staurosporine and 25 mumol/L sphingosine, protein kinase C inhibitors; 35 mumol/L cycloheximide, a protein synthesis inhibitor; 3.0 mumol/L indomethacin, an inhibitor of prostaglandin synthesis; and 0.5 mmol/L RO-20-1724, a cyclic nucleotide phosphodiesterase inhibitor. Staurosporine and sphingosine were the only agents that prevented the effect of TPA. The specificity of the TPA effect was evaluated with the following test agents: 0.2 nmol/L epidermal growth factor (EGF), 0.1 mumol/L 4 alpha-TPA (a stereoisomer of TPA), or 1.0 mumol/L A23187. In contrast to TPA, none of these agents reduced forskolin-mediated increases in cAMP. Results indicate forskolin cAMP responsiveness and regulation of this response by TPA in both primary and subcultured cells.(ABSTRACT TRUNCATED AT 250 WORDS)

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed1993

Toward more reliable printed stereo.

The printing and displaying of pictures as stereo pairs has been widespread for a long time, and yet it is still a common experience that published stereo pairs can be difficult to fuse, can cause eye-strain, can give a false or confusing sense of depth, and are sometimes even front-to-back inverted. This short note is intended to describe simply how to minimize or eliminate these common problems. The method is to match the focus and the convergence cues at the viewer's eyes, and to calculate the geometry reliably and accurately to better than the crude approximation now almost universally in use. Experience has shown that stereo so printed is acceptable to many people who normally cannot use the technique, and that a more secure sense of positioning and depth can be achieved.

Computer Graphics↗
PubMed1993

Bromodeoxyuridine labelling of transitional cell carcinoma of the bladder--an index of recurrence?

Nineteen patients with newly diagnosed transitional cell carcinoma of the bladder consented to receive an intravenous bolus of bromodeoxyuridine (BrdUrd) 3 to 6 h prior to transurethral resection of bladder tumour. Routine paraffin embedded sections were stained with anti-BrdUrd monoclonal antibody in order to determine the S phase fraction of the bladder tumours and to correlate this with tumour grade, category and the development of recurrence during follow-up. BrdUrd labelling of nuclei was reliably detected in 100% of the tumours. The mean labelling index of Ta tumours (n = 8) was 3.14%; in T1 tumours (n = 7) it was 8.6% and in T2-3 tumours (n = 4) it was 16.4%. A similar correlation was found in association with tumour grade. The patients were followed up for a mean of 23 months (range 18-30). Seven of the 15 superficial tumours recurred during the period of follow-up. These tumours had a mean labelling index (at diagnosis) of 8.4%, whereas the tumours that did not recur had a mean labelling index of 3.4%. The in vivo determination of BrdUrd uptake in transitional cell carcinoma of the bladder may be useful in predicting which superficial tumours are likely to recur following resection and so rationalise both the time to follow-up and intravesical chemoprophylaxis.

Aged↗
PubMed1993

Glutathione-S-transferase pi expression in transitional cell carcinoma of the bladder.

Glutathione-S-transferase pi (GST pi) is a multifunctional protein that acts as an enzyme, involved in the detoxification of drugs and carcinogens. It has been implicated both in drug resistance and malignant transformation of epithelium. Using an indirect immunohistochemical technique, we have evaluated cytoplasmic and nuclear staining in normal urothelium, 23 superficial bladder tumours and 26 invasive tumours. All 26 invasive tumours had been treated with platinum-based chemotherapy. Cytoplasmic staining was seen in normal urothelium and all bladder tumours. Nuclear staining was seen in 1 superficial tumour and in 13 invasive tumours. There was no association between nuclear staining and response to chemotherapy. Nuclear staining was seen in 1 area of dysplasia and in 2 of 3 areas of carcinoma in situ. GST pi expression is not a predictor of response to chemotherapy. Increased intra-nuclear expression of GST pi may be associated with progression of transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell↗
PubMed1993

p53 expression and clinical outcome in prostate cancer.

Abnormally high levels of expression of p53 protein are found in many human cancers. In most cases increased expression is associated with point mutations in one allele of the p53 gene and loss of the other allele. Accumulation of the protein product can be detected by immunohistochemistry. p53 protein expression in 68 men with prostate cancer, followed up for at least 8 years or until death, was assessed by immunohistochemistry. The aim of the study was to determine the association between p53 protein expression, cell cycling and clinical outcome. Nine (13%) of 68 tumours stained positively for p53; all 9 tumours were category T3 or T4. p53 positive tumours had a significantly greater Gleason score than p53 negative tumours. Eight of the 9 p53 positive tumours had > 10% cells in G2 + mitosis, compared with 61% of p53 negative tumours. All 17 patients with p53 positive tumours available for follow-up progressed clinically, compared with 28 of 38 patients (74%) with p53 negative tumours. The median time to progression was 12 months in p53 positive tumours and 24 months in p53 negative tumours. Median survival in p53 positive tumours was 40 months, compared with 76 months in p53 negative tumours. This study demonstrates that overexpression of p53 in a small population of prostate cancers is associated with a poor prognosis in terms of progression and survival.

Aged↗
PubMed1993

Antemortem measurements of neurotransmission: possible implications for pharmacotherapy of Alzheimer's disease and depression.

Aspartic acid, 5-hydroxyindoleacetic acid, glutamic acid, homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol was determined in samples of ventricular fluid from 82 subjects. Laminar distribution of the total number (Bmax value) of serotonin 1A receptors was determined on seven neurosurgical samples of neocortex. Apart from an association in a small subgroup of subjects between homovanillate concentration and corticosteroid medication, no complicating influences of treatment preceding operation were found. The content of the serotonin metabolite alone was significantly reduced in intractable depressive illness (bipolar and major depressive disorders) compared with neurological conditions subdivided into Alzheimer's disease, other dementias and other conditions. There was no other significant difference between these groups for the compounds measured. The total number of serotonin 1A receptors was highest in the superficial layers, being considerably higher than in the rat, irrespective of cortical layer. This part of the study indicated that these receptors are important for regulating activity of human corticocortical glutamatergic neurons. The results are discussed in relation to treating depression with serotonergic agents and targeting corticocortical glutamatergic neurons as well as acetylcholine in Alzheimer's disease.

Adult↗
PubMed1993

Risking infection: an issue of control for liver transplant recipients.

Liver transplantation is a technologic advancement that prolongs and improves the quality of life for people with liver disease. Loss of control over one's body and life is a feeling that begins with the diagnosis of liver disease. This study used a hermeneutic phenomenologic approach to investigate a liver transplant recipient's experience. A dimension of control was revealed within the description of the transplant experience. In an effort to maintain some control, the recipients adjusted the times of their immunosuppressive medications and continued to expose themselves to situations that could increase their risk of infection. Understanding the individual's experience and the implications for nursing are described.

Adult↗