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Biomedical subjects

D Pearson

Publications and source records attributed to D Pearson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Differential regulation of biglycan and decorin by retinoic acid in bovine chondrocytes.

The small, leucine-rich proteoglycans, decorin and biglycan, are prominent components of many extracellular matrices and are differentially regulated in various tissues. We have examined the effects of retinoic acid (RA) on the expression of biglycan and decorin at the protein and mRNA levels in cultured bovine articular chondrocytes. Biglycan protein expression is rapidly turned off after 1-2 days of treatment with RA. In contrast, decorin protein expression is increased 12-18-fold following 3 days of RA treatment. The level of biglycan mRNA was also rapidly reduced upon RA treatment, mirroring the protein expression. The reduction was apparent by 6 h, and, by 4 days, the levels were nearly undetectable. In contrast, decorin mRNA was induced upon treatment with RA. The increase in decorin message levels was first apparent by 24 h, reaching maximum by 2 days, and remained constant through 4 days. The repression of biglycan mRNA displayed equal sensitivity to RA concentrations from 10(-5) to 10(-9) M. Decorin mRNA was induced in a dose-dependent fashion by RA. Retinoic acid at a concentration of 10(-5) M, the highest dose examined, resulted in maximal induction of the message, and control levels were obtained with 10(-8) M. The protein synthesis inhibitor cycloheximide inhibited the induction of decorin mRNA, indicating that the induction by RA was a secondary event. In contrast, the repression of biglycan by RA was not significantly altered by cycloheximide, showing that the repression was a direct effect. Actinomycin D inhibited the induction of decorin mRNA, indicating that transcription was required for the induction. Nuclear run-on assays confirmed that RA was regulating biglycan mRNA expression at the transcription level. A 24-h RA treatment decreased the level of transcription of the biglycan gene 5-fold. In contrast, no increase in transcription from the decorin gene could be detected by nuclear run-on assays. Therefore, the elevation in decorin mRNA levels observed after RA treatment was the result of a post-transcriptional event, most likely the consequence of stabilization of the message. This study demonstrates that the genes for these two similar proteoglycans are under very different forms of regulation by RA in chondrocytes. The pattern of differential expression of biglycan and decorin could serve as an additional marker for indicating changes of the cartilage phenotype.

Amino Acid Sequence↗
PubMed1992

The extraction and use of facial features in low bit-rate visual communication.

A review is given of experimental investigations by the author and his collaborators into methods of extracting binary features from images of the face and hands. The aim of the research has been to enable deaf people to communicate by sign language over the telephone network. Other applications include model-based image coding and facial-recognition systems. The paper deals with the theoretical postulates underlying the successful experimental extraction of facial features. The basic philosophy has been to treat the face as an illuminated three-dimensional object and to identify features from characteristics of their Gaussian maps. It can be shown that in general a composite image operator linked to a directional-illumination estimator is required to accomplish this, although the latter can often be omitted in practice.

Face↗
PubMed1992

Comparison of two oestrogen receptor assays in the prediction of the clinical course of patients with advanced breast cancer.

We have examined two new oestrogen receptor (ER) assays--an enzyme immunoassay (EIA) and an immunocytochemical assay (ICA) in a large series of primary breast tumours to compare their potential as predictors of (1) response to endocrine therapy and (2) survival in patients developing advanced breast cancer. Response to endocrine therapy was categorised at 6 months (UICC criteria). ER-ICA appears the better predictor of response to endocrine therapy than ER-EIA. Combining ICA and EIA results did not improve the prediction of response. With both assays patients with ER positive tumours survived longer from the time of diagnosis of advanced disease than those with ER negative tumours. The predictive power of these assay for progression of disease appears slightly better for the ER-ICA.

Aged↗
PubMed1992

Peritoneal dialysis training in a patient with multiple congenital anomalies.

We report an adult patient with multiple congenital anomalies including absent right arm, short stature, and scoliosis who has been trained and successfully performs continuous cycling peritoneal dialysis independently. Motivated patients with end stage renal disease and various anomalies should be considered for peritoneal dialysis training.

Abnormalities, Multiple↗
PubMed1991

Constitutive expression of the urokinase plasminogen activator gene in murine RAW264 macrophages involves distal and 5' non-coding sequences that are conserved between mouse and pig.

The 5' flanking regions of the mouse and pig urokinase plasminogen activator (uPA) genes were sequenced and sequence homology interrupted by repeat elements was found to extend to -4.6kb in pig and -6.6kb in mouse. A transient transfection procedure was devised for the murine macrophage cell line RAW264. Pig uPA promoter-CAT constructs were more active than mouse constructs in this assay. This contrast may involve sequence differences within 100 bp of the transcription start site. The selective deletion of distal regions of the promoter (greater than 2.6 kb upstream), and of a conserved element, 5'-AGGAGGAAATGAGG-TCA-3' around -2 kb greatly reduced the activity of reporter constructs in RAW264 cells. Electrophoretic mobility shift assays using the latter sequence identified a single nuclear protein complex. This element has been referred to as PEA3/AP1-like, but the complex did not comigrate with either AP1 or known proteins that bind polypurines (including the macrophage-specific factor PU-1) and was not competed by AP1 or polypurine oligonucleotides. uPA promoters contain multiple AP1 and AP2-like DNA sequences, which were recognised by nuclear proteins expressed constitutively in RAW264 cells. They also contain multiple binding sites for NF kappa B but activated NF kappa B was not expressed in RAW264 cells. The conserved, transcribed 5' non-coding sequences were also required for maximal gene expression. Hence, the uPA promoter contains multiple weak cis-acting elements distributed over 7.0 kb 5' to the translation start site.

Animals↗
PubMed1991

Prospective assessment of the role of five tumour markers in breast cancer.

Retrospective analysis previously identified significant elevation of five tumour markers, carcinoembryonic antigen (CEA), ferritin, orosomucoid. C-reactive protein and erythrocyte sedimentation rate (ESR), in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response. In this study we have prospectively tested these findings. None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups. They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer. There was a significant elevation of all five markers in patients with systemic breast cancer (P less than 0.0001: analysis of variance) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response. Prospective confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer.

Adult↗
PubMed1991

Nuclear and flow cytometric characteristics associated with overexpression of the c-erbB-2 oncoprotein in breast carcinoma.

The overexpression of the c-erbB-2 oncoprotein is now thought by most authors to be associated with adverse prognosis in breast carcinoma. In this study, we investigate the relationship between overexpression of the c-erbB-2 oncoprotein and nuclear size by morphometry in a series of 150 human breast carcinomas, comprising 65 cases of ductal carcinoma in situ (DCIS) and 85 cases of invasive adenocarcinoma. The mean nuclear size for c-erbB-2 positive cases of DCIS was 54.8 micron 2 and invasive carcinoma was 52.1 micron 2 respectively, in contrast with 41.6 micron 2 and 42.5 micron 2 for c-erbB-2 negative cases of DCIS and invasive carcinoma respectively. Flow cytometric examination of DNA in a subset of 91 of these tumours showed no association between tumour cell aneuploidy and c-erbB-2 overexpression. S-phase fraction could be calculated on 20 cases of DCIS and 48 invasive carcinomas. There was a strong association between c-erbB-2 overexpression, S-phase fraction (p less than 0.001) and proliferative index (p less than 0.001) in 20 cases of DCIS. A weak association of S-phase fraction and c-erbB-2 overexpression was seen in 48 invasive carcinomas (p = 0.047). This study confirms the subjective impression that there is a relationship between large tumour cell nuclear size and an overexpression of the c-erbB-2 oncoprotein, and also shows an association with increased tumour cell proliferation.

Adenocarcinoma↗
PubMed1991

Mechanisms of cAMP-mediated gene induction: examination of renal epithelial cell mutants affected in the catalytic subunit of the cAMP-dependent protein kinase.

The precise mechanistic role of the cAMP-dependent protein kinase (cAMP-PK) in cAMP-mediated gene induction remains unclear. Renal epithelial cell mutants were compared to the LLC-PK1 parental cell line for induction of the cAMP-responsive urokinase-type plasminogen activator (uPA) gene, as quantitated by the technique of mRNA solution hybridization. The FIB4 and FIB6 mutants, which possess less than 10% parental cAMP-PK catalytic (C) subunit activity, showed markedly diminished uPA mRNA induction in response to agents elevating intracellular cAMP such as the cAMP analogue 8-bromo-cAMP and the adenylate cyclase-stimulating hormones vasopressin and calcitonin. In contrast, the mutant cells responded to a similar or greater extent than the parental cells in terms of uPA mRNA induction following treatment with the Ca2+/phospholipid-dependent protein kinase activator phorbol 12-myristate 13-acetate (PMA). Elevation of intracellular cAMP was found to induce a translocation of the cAMP-PK C subunit from the perinuclear Golgi region to the nucleus in both parental and mutant cell lines, as shown by immunocytochemical techniques. Results argue for the role of the cAMP-PK C subunit activity and possibly nuclear translocation of the C subunit in cAMP-mediated uPA induction, which is mechanistically distinct from the PMA-stimulated response.

Animals↗
PubMed1991

Objective measurement of therapeutic response in breast cancer using tumour markers.

In 65 patients with systemic breast cancer, a biochemical response index using three tumour markers in combination, carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3) and erythrocyte sedimentation rate (ESR), allowed objective biochemical assessment of response to endocrine therapy. Changes in these three markers at 2, 4 and 6 months showed a highly significant correlation with UICC assessed response at 6 months. At 4 months, changes in these three markers resulted in a selectivity of 93%, with a sensitivity of 92% and a specificity of 82%. Survival of groups of patients assessed biochemically or by UICC criteria for non-progression or progression showed no significant difference. The advantage of the biochemical assessment are that it is objective and reproducible. The assessment gives similar information to the UICC assessment but can be carried out earlier. Changes in the three markers appears to reflect the dynamics of change in tumour mass in response to systemic therapy in contrast to the UICC criteria which reflect structural change.

Adolescent↗
PubMed1991

Metabolic control in diabetic subjects following myocardial infarction: difficulties in improving blood glucose levels by intravenous insulin infusion.

Optimal metabolic control during the first twelve hours after myocardial infarction may be associated with improved survival in diabetic subjects. A comparison of an intravenous insulin infusion regimen aimed at improving blood glucose levels (n = 35), with 'routine control' (n = 34) in the post infarction period has been carried out in diabetic subjects admitted to four Coronary Care Units over a two year period. However, glycaemic control was similar in both groups (intravenous infusion regimen, mean +/- SD capillary blood glucose 10.3 +/- 2.1 mmol/l, 'routine control' glucose 10.7 +/- 3.6 mmol/l). There were no differences in the rates of arrhythmias (31% v 32%), heart failure (46% v 47%) or mortality (17% v 18%). Mortality in diabetic subjects was lower than that quoted in previous studies but was higher than in non-diabetic subjects admitted to the Coronary Care Unit during the same period. Attempts to improve glycaemic control by means of intravenous insulin infusion were unsuccessful.

Aged↗
PubMed1990

Macromolecular interaction on a cAMP responsive region in the urokinase-type plasminogen activator gene: a role of protein phosphorylation.

We have studied the regulation of urokinase-type plasminogen activator gene expression by cAMP in LLC-PK1 cells. We found a cAMP responsive region 3.4 kb upstream of the transcription initiation site, which comprised three protein-binding domains designated A, B, and C. Domains A and B both contain a sequence, TGACG, homologous to a consensus cAMP response element (CRE; TGACGTCA). Effective cAMP-mediated induction was achieved when these two domains were linked with domain C, which by itself did not confer cAMP responsiveness to a heterologous promoter nor contained CRE-like sequence, suggesting a functional cooperation among these domains. Results of competition studies using gel retardation and DNase I footprinting assays suggest that there is a protein-protein interaction between a CRE binding protein and a domain C binding protein. In gel retardation assays, binding of a nuclear protein to domains A and B was strongly augmented by addition of the catalytic subunit of cAMP-dependent protein kinase, whereas the protein binding to domain C was slightly inhibited, suggesting that protein phosphorylation is involved in the regulation of protein-DNA interaction.

Base Sequence↗
PubMed1990

Driving the NHS.

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Automobiles↗
PubMed1990

The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988.

The United Kingdom Children's Cancer Study Group (UKCCSG) malignant germ cell tumour (MGCT) studies were undertaken to establish standard protocols of investigation, staging, and treatment. The efficacy of new drug combinations and the value of serial measurements of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG) were evaluated. Following the initial surgery, staging of the tumour was performed using a variety of investigative approaches. In stage 1 testicular tumours, orchidectomy was performed. In more advanced tumours, and in stage 1 tumours that failed to show the expected decline in AFP or recurred, chemotherapy was used after appropriate surgery. Seventy-three boys, under 14 years of age, with testicular MGCTs have been entered into the UKCCSG studies since 1979. Serum AFP was measured preoperatively, or within 2 weeks of operation, in 70 boys. It was unequivocally elevated in 69. Monitoring by serial AFP measurement proved valuable in assessing response and in early detection of recurrence. HCG was measured in 46 boys, and was raised in three. Sixty-seven (91%) of the tumours were yolk sac (Teilum) tumours, four were immature teratoma, and two were mixed MGCTs. The only non-AFP producing tumour was an immature polydermal teratoma in a 1-year-old boy. Serum HCG was raised in three boys with yolk sac tumours, one with a mixed teratoma, and one 14-year-old boy who had a mixed MGCT. The results of treatment were assessed on April 1, 1989 (median time from diagnosis, 3 years 4 months). Seventy-one boys were alive, 48 of whom had been cured by orchidectomy alone. The remaining 25 patients received chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗