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P Robson

Publications and source records attributed to P Robson.

At least 19 recordsLinked to original sources
PubMed1995

Modulated expression of glycoprotein oligosaccharides identifies phenotypic differentiation in squamous carcinomas of the human cervix.

This study has examined changes in expression of complex oligosaccharides during the development of invasive squamous carcinoma of the human cervix to determine whether particular oligosaccharide structures that might influence the phenotypic behavior of individual human cervical cancers were expressed during neoplasia. An extensive panel of lectins capable of identifying all the core and antennary oligosaccharide structures commonly encountered in human epithelia was chosen to probe a range of 11 benign and 26 malignant cervical tissues, all of the latter being clinically stage I. Lectin histochemistry was performed both before and after tissue desialylation using the enzyme neuraminidase to identify masking of oligosaccharide determinants by sialic acid. Nonneoplastic cervical epithelial cells were found to express only type I antennary structures (Gal beta 1-->3GalNAc-) usually modified by sialic acid linked 2-->6 to terminal Gal- or GalNAc residues. Type II oligosaccharide structures (Gal beta 1-->4GlcNAc-) were not identified in these normal tissues. No other terminal antennary modifications were detected on nonneoplastic cervical squamous epithelia. Conversely, neosynthesis of type II oligosaccharides was detected by Erythrina cristagalli (ECG) binding in 50% of the squamous carcinomas. Five terminal antennary modifications were commonly identified in the carcinomas that were not identified in normal cervical epithelia and comprised the oligosaccharides bound by lectins RCA, SBA, BS-1, LTA, and UEA-1. Synthesis of these oligosaccharides resulted in expression of structures similar to those recognized as ligands for extracellular matrix-binding proteins. We suggest that expression of such novel oligosaccharide structures may be an important promotor of local invasion and further dissemination of human cervical carcinomas through enhanced binding of malignant cells to stromal matrix proteins. This study has demonstrated that identification of expressed oligosaccharide structures is an objective method of identifying individual tumor cell phenotypes and may form the basis of a useful functional classification of human cervical squamous carcinomas.

Carcinoma, Squamous Cell↗
PubMed1995

Decreased elastin synthesis in normal development and in long-term aortic organ and cell cultures is related to rapid and selective destabilization of mRNA for elastin.

We have previously shown that aortic organ cultures from 1- to 3-day-old chickens initially mimic the high levels of elastin production seen in vivo. However, more prolonged incubation of these tissues results in decreased synthesis of elastin. In the present study, we demonstrate that decreased production of elastin in these aortic organ cultures is selective for elastin compared with collagen and is correlated with decreased steady state levels of mRNA for elastin. These decreases in steady state levels of elastin mRNA are due at least in part to a rapid and selective destabilization of mRNA for elastin, the half-life of which falls from approximately 25 hours in fresh aortic tissues to approximately 15 hours after incubation for only 8 hours. Destabilization of elastin mRNA can be prevented by incubation in the presence of blockers of DNA transcription (5,6-dichlorobenzimidazole riboside and actinomycin D) and mRNA translation (cycloheximide). Furthermore, the half-life of aortic elastin mRNA decreases from approximately 25 hours in the 1-day-old chicken to approximately 7 hours in the 8-week-old chicken, demonstrating that destabilization of mRNA is an important contributing factor in the decline in production of aortic elastin taking place during normal postnatal growth.

Age Factors↗
PubMed1993

Characterization of lamprin, an unusual matrix protein from lamprey cartilage. Implications for evolution, structure, and assembly of elastin and other fibrillar proteins.

Lamprin, an insoluble non-collagen, non-elastin protein, is the major connective tissue component of the fibrillar extracellular matrix of lamprey annular cartilage. Here we demonstrate that the soluble monomer of lamprin is a family of highly hydrophobic, self-aggregating proteins with molecular masses of 12 and 10 kDa. Two mRNAs for soluble lamprin were identified (0.9 and 2 kilobases), differing principally in the length of their 3'-untranslated tails. Variants of soluble lamprin appear to arise both as the products of multiple genes and by alternate splicing. Although not generally homologous to any other protein, soluble lamprins contain a tandemly repeated peptide sequence (GGLGY) which is present in both silkmoth chorion proteins and spider dragline silk. Strong homologies to this repeat sequence are also present in several mammalian and avian elastins. Monoclonal antibodies to VGVAPG, a repeated sequence in human elastin, also cross-react with lamprin. We suggest that these proteins share a structural motif which promotes self-aggregation and fibril formation in proteins through interdigitation of hydrophobic side chains in beta-sheet/beta-turn structures, a motif that has been preserved in recognizable form over several hundred million years of evolution.

Amino Acid Sequence↗
PubMed1992

The calcium channel antagonist nifedipine causes confusion when used to treat opiate withdrawal in morphine-dependent patients.

Several animal studies have suggested that calcium channel antagonists may be clinically effective in the treatment of opiate withdrawal. In this study we aimed to examine whether the alpha 2-adrenoceptor agonist clonidine and the calcium channel antagonist nifedipine were equally effective in attenuating the naltrexone-precipitated opiate withdrawal syndrome. We planned to study 16 morphine-dependent in-patients in a double-blind trial. However, the study had to be abandoned after only four patients were entered into it because the first two patients treated with nifedipine became severely confused following naltrexone. The mechanism underlying the development of delirium in these two patients is uncertain, but might possibly relate to a large unopposed release of noradrenaline within the central nervous system. These findings suggest that the calcium channel antagonist nifedipine is not effective in the clinical treatment of opiate withdrawal. Whether other calcium channel antagonists also cause confusion when used in this clinical condition is uncertain at present, but in any future studies investigating their efficacy considerable care is required in their use.

Adult↗
PubMed1991

Comparison of behavior therapy and cognitive behavior therapy in the treatment of generalized anxiety disorder.

In a controlled clinical trial, 57 Ss meeting DSM-III-R criteria for generalized anxiety disorder, and fulfilling an additional severity criterion, were randomly allocated to cognitive behavior therapy (CBT), behavior therapy (BT), or a waiting-list control group. Individual treatment lasted 4-12 sessions; independent assessments were made before treatment, after treatment, and 6 months later, and additional follow-up data were collected after an interval of approximately 18 months. Results show a clear advantage for CBT over BT. A consistent pattern of change favoring CBT was evident in measures of anxiety, depression, and cognition. Ss were lost from the BT group, but there was no attrition from the CBT group. Treatment integrity was double-checked in England and in Holland, and special efforts were made to reduce error variance. Possible explanations for the superiority of CBT are discussed.

Analysis of Variance↗
PubMed1989

Development of a new self-report questionnaire to measure self esteem.

In constructing a new self-report questionnaire for measuring self esteem, the aim has been to satisfy psychometric requirements without sacrificing the intuitive meaning of the concept. Self esteem is seen as a composite, and examination of its components may have more analytic or predictive value than 'global' scores. Preliminary reliability and validity data are encouraging.

Adolescent↗
PubMed1989

Psychological profile of social drinkers.

In a cross-sectional study, the psychological profile of light social drinkers was compared with that of heavy social drinkers and alcohol-dependent patients who showed no evidence of clinical depression. The selection of psychological tests was based on the hypothesis that alcohol abuse and depression may sometimes be different expressions of the same disorder, and that the relationship between the two disorders may in part be explicable in terms of shared psychological vulnerability factors. The tests chosen were those thought most likely to predict vulnerability to depression. Dependent patients demonstrated significantly greater distortion of cognitive style than heavy social drinkers, who in turn rated significantly higher than light drinkers. Heavy social drinkers occupied a middle ground with regard to psychological profile between light drinkers and 'alcoholics', sharing some attributes with each. Possible implication for interventions by general practitioners are discussed.

Adult↗
PubMed1988

Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,1-c][1,4]benzoxazines, imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles.

4H-Imidazo[2,1-c][1,4]benzoxazine-2-carboxylic acid (3) was found to possess potent activity in the IgE-induced rat passive cutaneous anaphylaxis model which may be predictive of clinical antiallergic activity. Compared to disodium cromoglycate (DSCG, 1), 3 was less active following iv administration but unlike DSCG showed very significant oral activity. To explore the structural requirements for this activity, a range of tricyclic compounds was prepared and their activities were measured. Individual 2-carboxylic acids derived from imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles showed iv activities up to 10(3) times as potent as DSCG and many of them showed significant oral activity. From these, imidazo[1,2-a]quinoxaline-2-carboxylic acid 114 has been chosen for further development.

Animals↗
PubMed1983

Studies on the metabolism of the new anti-hypertensive agent, indoramin, in man.

The absorption, metabolism and excretion of the new antihypertensive agent indoramin (Baratol) have been studied in male volunteers following oral administration of the drug labelled either with 14C or with tritium. Absorption of the drug proceeded at moderate rate, peak plasma radioactivity levels being seen by 3 h after dosing. Metabolism was extensive as shown by very little unchanged compound appearing in urine. Two major urinary metabolites accounting for some 35-40% of the renally excreted material were identified as acid labile conjugates of indoramin itself and indole 6-hydroxylated indoramin. The pattern of biotransformation appeared to be similar to that in the patas monkey, the species used in the long term safety evaluation of the drug. Excretion of the drug and metabolites occurred primarily via the faeces which accounted for 49.7 +/- 4.9% of the dose. A further 31.7 +/- 2.4% was recovered in the urine. Renal elimination of total radioactivity occurred in an apparently monoexponential manner with a half-life of 11.9 +/- 1.2 h.

Adult↗
PubMed1982

The use of meptazinol as a premedication for surgical patients.

The acceptability of a mixture of meptazinol and hyoscine as a surgical premedication was compared with that of an Omnopon-hyoscine combination in a randomized, double-blind trial involving 101 surgical patients. Blood pressure and respiratory rate were significantly reduced to a similar extent by both premedicant combinations, and this may be interpreted as evidence of a satisfactory alleviation of anxiety by both test mixtures. The two mixtures produced a similar degree of sedation, and both were associated with a useful inhibition of salivary secretion. Side-effects were reported in 25% patients in the meptazinol group, and in 28% of those receiving Omnopon, although a number of these effects may be attributable to hyoscine. There was no difference in the pattern of post-operative analgesic requirements between the two groups, and no unfavourable interaction was noted with any of the anaesthetic agents used.

Adolescent↗
PubMed1981

The hazards of rehabilitation.

Falls are the most common accident occurring to patients in hospital, especially those undergoing rehabilitation. The types, causes, and consequences of such falls are discussed in relation to the patients' age and underlying condition with reference to 386 accidents occurring over a 5-month period in a hospital with 50% geriatric beds. Measures that may reduce the hazard to the patient and minimise the risk of accidents in hospital are suggested.

Accident Prevention↗
PubMed1980

The study of stroke.

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Cerebrovascular Disorders↗