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Biomedical subjects

R D Watson

Publications and source records attributed to R D Watson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Immune-mediated subepithelial blistering diseases of the mucous membranes. Improving the detection of circulating autoantibodies by the use of concentrated serum samples.

BACKGROUND AND DESIGN: Comparison of detection of circulating autoantibodies before and after concentration of serum samples from patients with suspected immune-mediated subepithelial blistering diseases of the mucous membranes. We determine whether the use of concentrated serum samples from patients with suspected immune-mediated subepithelial blistering diseases of the mucous membranes improves diagnostic sensitivity for circulating antibodies. We studied 13 patients from a university-based referral practice who had no skin lesions and a scarring subepithelial blistering disease of the mucous membranes. Three of these patients had detectable circulating autoantibodies and 10 had negative indirect immunofluorescence study results using standard techniques. The main outcome measures after concentration of serum samples were detection of circulating autoantibodies on salt-split skin by indirect immunofluorescence, immunoblotting, and immunoprecipitation. RESULTS: Of the 10 patients in whom circulating autoantibodies had not been detectable with standard techniques, circulating IgG antibodies were detected in 5 (50%) and circulating IgA antibodies in 3 (30%). Of the 3 patients in whom circulating autoantibodies had been detectable with standard techniques, 1 (33%) had circulating IgA antibodies that immunoblotted the 97-kd linear IgA bullous disease antigen only when concentrated serum samples were used. CONCLUSIONS: The use of concentrated serum samples can improve our ability to detect the presence and antigenic specificity of circulating autoantibodies in patients with suspected but unclassifiable immune-mediated subepithelial blistering diseases of the mucous membranes.

Autoantibodies↗
PubMed1995

Stimulation of ecdysteroidogenesis by small prothoracicotropic hormone: role of calcium.

Insect prothoracic glands are regulated by neuropeptide prothoracicotropic hormones (PTTH). In Manduca sexta PTTH exists as two size variants, big PTTH (approximately 25.5 kDa) and small PTTH (approximately 7 kDa). Previous studies indicate that both size variants employ cAMP as a second messenger and that stimulation of ecdysteroid secretion by big PTTH is Ca(2+)-dependent. In the present study, experiments were performed to assess the role of Ca2+ in small PTTH-stimulated ecdysteroid secretion by prothoracic glands from fifth instar larvae. Basal ecdysteroid secretion was not affected by Ca2+ channel blockers (verapamil or lanthanum) or by omission of Ca2+ from the incubation medium. Treatment of glands with a Ca2+ ionophore (A23187 or ionomycin) produced a concentration-dependent stimulation of ecdysteroid secretion. Stimulation of ecdysteroid secretion by small PTTH was suppressed (1) by Ca2+ channel blockers and (2) in Ca(2+)-free medium. A cAMP analog (Sp-cAMPS) stimulated ecdysteroid secretion in the presence of a Ca2+ channel blocker (verapamil) and in Ca(2+)-free incubation medium, and ionophore-induced ecdysteroid secretion appeared to be suppressed by a cAMP antagonist (Rp-cAMPS). The combined results indicate that basal ecdysteroid secretion is not dependent on external Ca2+, and suggest that small PTTH-stimulated ecdysteroid secretion is mediated by an influx of Ca2+ that precedes cAMP formation.

Animals↗
PubMed1995

Molecular cloning of a cDNA encoding putative molt-inhibiting hormone from the blue crab, Callinectes sapidus.

A cDNA library was constructed using poly(A+) RNA isolated from eyestalk neural ganglia of the blue crab, Callinectes sapidus. The library was screened using a probe generated by PCR based on the published amino acid sequence of molt-inhibiting hormone from the shore crab, Carcinus maenas. DNA sequence analysis of one positive clone revealed a 339 bp open reading frame encoding a 78-residue putative molt-inhibiting hormone and a 35-residue signal peptide. The deduced amino acid sequence of C. sapidus molt-inhibiting hormone is 79% homologous with that of C. maenas. Northern blot analysis, using a fragment of the cloned molt-inhibiting hormone cDNA as probe, revealed specific hybridization to a single band (approximately 1.4 kb) in RNA extracted from eyestalk but not control tissues.

Amino Acid Sequence↗
PubMed1995

Left ventricular diastolic function in hypertensive patients with unstable angina and single coronary artery disease.

The present study was performed to investigate left ventricular diastolic (LVD) function in hypertensive patients with unstable angina. Three groups of 17 patients each were studied. Group 1 consisted of hypertensives with unstable angina (HTU); group 2, normotensives with unstable angina (NTU); and group 3, untreated, uncomplicated hypertensives (HT). The LVD function was assessed echocardiographically by transmitral valve Doppler flow to measure the ratio between the early diastolic filling (E) and the atrial contraction phase (A). An E/A ratio of < 1 was suggestive of LVD dysfunction. Left ventricular mass (LVM), from an M-mode echocardiogram using the Penn-Cube formula, was corrected to body surface area (LVM/S) using a standard nomogram. Data are represented as median values and analyzed by Mann-Whitney test. P was significant at < .05. The HTU group had an E/A ratio of 0.8, and the NTU and HT groups had ratios of 1.17 and 1.1, respectively. There was significant diastolic dysfunction in the HTU group compared with the NTU and HT groups (P = .037 and .049, respectively). Although the LVM/S was significantly higher in the HTU group when compared with the HT group (110.6 and 96.9, respectively, P = .017), there was no significant difference between the HTU and NTU groups (123.1), P = .67. Hypertensive patients with unstable angina have significant LVD dysfunction that seems to be independent of LVM and ischemia. This may be attributable to increased stiffness of the left ventricle or structural left ventricular abnormalities.

Adult↗
PubMed1995

Symptomatic cardiomyopathy as a presentation in Whipple's disease.

A patient presenting with congestive cardiac failure and anaemia underwent investigation which led to the diagnosis of Whipple's disease, associated with dilated cardiomyopathy. Conventional antibiotic therapy for Whipple's disease resulted in resolution of the traditional features of Whipple's disease and a marked improvement in the patient's heart failure.

Aged↗
PubMed1995

ET-1 and PDGF BB induce MEK mRNA and protein expression in mesangial cells.

To evaluate a possible mechanism for the chronic regulation of MAPK/ERK kinase-1 (MEK-1) and p42 mitogen-activated protein kinase (MAPK) we studied the long-term effects of the G-protein-coupled receptor agonist endothelin-1 (ET-1) and the protein tyrosine kinase-coupled receptor agonist platelet-derived growth factor BB (PDGF BB) on MEK-1 and p42 MAPK in glomerular mesangial cells (GMCs). ET-1 and PDGF BB led to a time-dependent increase in MEK-1 mRNA expression without altering p42 MAPK mRNA levels. The effect of ET-1 and PDGF BB on MEK-1 mRNA expression was maximal after 24 h (3.3-fold) or 6 h (2.9-fold). Furthermore, the effect of ET-1 and PDGF BB on MEK-1 mRNA expression was additive (4.2-fold after 6 h) and was inhibited by actinomycin D (5 micrograms/ml). Cycloheximide (10 micrograms/ml) inhibited MEK-1 mRNA induction but stimulated p42 MAPK mRNA expression in both the absence and the presence of ET-1 and/or PDGF BB. The ET-1 and PDGF BB-induced increase in MEK-1 mRNA was accompanied by sustained enhancement of both p45 MEK protein expression after 12 h and by elevation of p42 MAPK activity for up to 24 h. We conclude that, in GMCs, MEK-1 acts like a delayed-early gene, whereas p42 MAPK resembles an immediate-early gene. MEK-1 mRNA and protein levels, as well as p42 MAPK activity, can be chronically regulated by both a seven-transmembrane domain receptor-coupled peptide such as ET-1 and by an agonist binding to a receptor with intrinsic protein tyrosine kinase activity, such as PDGF BB.

Animals↗
PubMed1994

Protein synthesis and ecdysteroidogenesis in prothoracic glands of the tobacco hornworm (Manduca sexta): stimulation by big prothoracicotropic hormone.

The 28-kDa size variant of prothoracicotropic hormone (big PTTH) stimulates ecdysteroidogenesis by prothoracic glands of Manduca sexta. In the present studies, big PTTH stimulated in vitro incorporation of [35S]methionine into proteins of prothoracic glands from Day 7 last instar larvae. In 2-hr incubations, big PTTH elicited an approximately 2-fold increase in total protein-specific activity. The effect appeared to be tissue specific, as big PTTH had no effect on incorporation of label into proteins of control tissue (fat body). Electrophoretic separation of tissue homogenates, followed by autoradiography and densitometric analysis, revealed increased incorporation of radiolabel into numerous glandular proteins. The result suggested that the effect of big PTTH was a general stimulation of protein synthesis, not specific stimulation of a subset of glandular proteins. Big PTTH-stimulated ecdysteroidogenesis was inhibited by cycloheximide, indicating that the increase in protein synthesis is a requisite for enhanced hormone production. Analysis of gland incubation media revealed numerous radiolabeled proteins. The effect of big PTTH on incorporation of [35S]methionine into media proteins was considerably more variable than the effect of big PTTH on tissue incorporation. The result is consistent with the hypothesis that prothoracic glands may release proteins in addition to ecdysteroids.

Animals↗
PubMed1993

Ultrastructure of prothoracic glands during larval-pupal development of the tobacco hornworm, Manduca sexta: a reappraisal.

The structure of Manduca sexta prothoracic glands was investigated using a protocol that preserves membranes. During the last larval stadium, prothoracic gland cells increase in diameter, volume, protein content, and perhaps number, enhancing their capacity to produce ecdysteroids. The glands' strand-of-cells morphology, their in situ location, the presence of gap junctions between cells, and junctional foot-like structures within cells support previous findings that prothoracicotropic hormone stimulates ecdysteroidogenesis via Ca(2+)-induced Ca2+ release. A different method of tissue fixation from that previously used to investigate the ultrastructure of Manduca sexta prothoracic glands has revealed a significantly different ultrastructure. These new findings begin to define roles for endoplasmic reticulum and mitochondria in ecdysteroid synthesis and support the hypothesis that the glands secrete the steroid hormone via exocytosis. The structural dynamics of the glands are discussed in the context of the glands' function during Manduca sexta larval-pupal development.

Animals↗
PubMed1993

Stimulation of ecdysteroidogenesis by small prothoracicotropic hormone: role of cyclic AMP.

Prothoracicotropic hormones (PTTHs) stimulate synthesis and secretion of ecdysteroids by insect prothoracic glands. In Manduca sexta, PTTH exists as two size variants, small and big PTTH. Experiments were performed to assess the possible role of cyclic AMP in small PTTH signal transduction. cAMP analogs, or agents that increase intracellular cAMP, stimulated ecdysteroidogenesis. Small PTTH enhanced glandular cAMP levels; the rise in cAMP preceded an increase in ecdysteroid secretion. Prothoracic glands accumulated less cAMP when treated with small PTTH than when treated with big PTTH. A phosphodiesterase inhibitor (1-methyl-3-isobutylxanthine) (MIX) increased the amount of cAMP in glands treated with small but not big PTTH, suggesting that glandular phosphodiesterase activity may be elevated in the presence of small PTTH. PTTH-stimulated ecdysteroid secretion was suppressed by a cAMP antagonist (Rp-cAMPS). The effects of small and big PTTH on ecdysteroidogenesis were non-additive. The combined results suggest that cAMP is employed as a second messenger by both prothoracicotropins, and that there may be subtle differences in their respective mechanisms of action.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Patients with suspected myocardial infarction: effect of mode of referral on admission time to a coronary care unit.

The aim of this prospective study was to determine the delay between the onset of symptoms and arrival in the coronary care unit of patients with suspected acute myocardial infarction, and the relative contribution to the total delay of patient delay, method of referral (self referral or general practitioner referral) and delay in the hospital before reaching the coronary care unit. All patients admitted with chest pain to the coronary care unit at Dudley Road Hospital, Birmingham, over the six month period April-September 1989 were included in the study. Ninety five patients were referred by their general practitioner and 107 patients attended the accident and emergency department directly or arrived by ambulance without contacting their general practitioner. The proportion of self referred and general practitioner referred patients with acute myocardial infarction, angina and non-cardiac chest pain were not significantly different. The total delay was significantly longer for patients who had been referred by their general practitioner (median 5.3 hours) than for self referrals (3.2 hours, P less than 0.001), with a significantly higher proportion of self referrals arriving at the coronary care unit within six hours of the onset of symptoms (77% versus 54%, P less than 0.01). Among general practitioner referrals, initial patient delay accounted for a median of 2.5 hours and the general practitioner's response time for a median of 1.1 hours. The delay in hospital was similar for both groups of patients. In inner city areas, self referral may result in considerably less delay than general practitioner referral allowing a greater proportion of patients to receive effective thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Care Units↗
PubMed1991

Computer graphics representation of a statistical model used with computer-aided diagnosis.

A description of computer graphics of a multidimensional model that is used with computer-aided diagnosis or prognosis is presented. The model is discussed and computer graphics of the model are developed. The computer graphics are suitable as visual supplements for presenting the computer-aided diagnostic model to individuals who may be inexperienced in multivariate statistics.

Animals↗