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Biomedical subjects

R Stephens

Publications and source records attributed to R Stephens.

At least 109 records · Page 6Linked to original sources
PubMed1991

Factors affecting adherence of end-stage renal disease patients to an exercise programme.

Recently it has been shown that regular exercise is both physiologically and psychologically beneficial to patients with end-stage renal disease (ESRD). However, ESRD patients traditionally have a high non-adherence level to their self-care and medical regimens. To date, their adherence to exercise programmes has not been studied. Background information about employment, medical history, previous exercise habits and locus of control was obtained from 40 volunteer ESRD patients who started exercise at home. Twenty-eight participants maintained the exercise programme, consisting of aerobic activity lasting an average of 25 min, four times per week, for 12 weeks. The adherent patients were found to have encouraging support groups (75 versus 25%), to be between 41 and 60 years of age (64 versus 33%), to have been on dialysis for between 2 and 5 years, and to have loci of control (feeling of control over life events) classed as 'internal' (68 versus 25%). Factors such as sex, race, employment status and depression were found to have little influence on adherence. The major finding of this study was that patients adherent to exercise could be distinguished by unique psychological and psychosocial factors, and that adherence in this population was higher (70 compared with 50%) than some estimates for the general population.

Adult↗
PubMed1990

Murine monoclonal antibodies to colon-specific antigen p.

A previous report described the production of monoclonal antibodies Mu-1, -2, -3, and -4 against colon-specific antigen p. We now report the tissue distribution of the reactive epitopes. Each of the monoclonal antibodies was reactive with epitopes shared by the entire length of the intestine, with Mu-2 and Mu-3 determinants being present in the stomach as well. Mu-1 and Mu-4 appeared to have a more restricted distribution than did Mu-2 and Mu-3, which were present in several nongastrointestinal tissues. Unfortunately, these MAbs were not ideal for in vivo use against colorectal carcinoma. Mu-1 was not present in neoplastic colon tissue, Mu-2 and Mu-4 were reactive with granulocytes, and Mu-3 was reactive with kidney tubules and connective tissue. An additional fusion was performed from which Mu-9 was selected for further study. Among normal adult tissues this monoclonal antibody gave reactivity restricted to the intestines. The stomach and all nonintestinal tissues were negative by immunoperoxidase. Among colon tumors 60% were positive for the Mu-9 epitope. The data suggest Mu-9 may be a good candidate for in vivo targeting of diagnostic and therapeutic agents to colon cancer.

Adenocarcinoma, Mucinous↗
PubMed1990

Enucleation of tumor versus partial nephrectomy as conservative treatment of renal cell carcinoma.

In patients with renal insufficiency, solitary kidney, or bilateral renal malignancies, conservative surgery for renal cell carcinoma has been suggested. The authors treated 17 such patients with either enucleation of tumor or partial nephrectomy. Overall survival from disease in this series was 58.8%. Seventy percent of patients undergoing enucleation and 42.9% undergoing partial nephrectomy survived with a mean follow-up period of 5 years. Survival or local recurrence rate after enucleative surgery is an effective treatment of renal carcinoma in selected patients, and despite concerns about tumor invasion of the pseudocapsule, the clinical data do not indicate any difference in survival. There was no significant difference between enucleation of tumor and partial nephrectomy regarding morbidity, mortality, or recurrence rate.

Adult↗
PubMed1990

Application of automated image analysis to demonstrate the correlation between ras p21 expression and severity of gliomas.

We found a direct correlation between increasing ras p21 protein immunopositivity and severity of human glioma using computer-assisted, digital-image processing to quantify the amount of p21 immunoreactive to the monoclonal antibody RAP-5. We determined that there was a significant difference in reactivity between glioblastoma multiformes and more-differentiated astrocytomas (experiment-wise error less than 0.05). This result confirmed the conclusions made on the same tumors using standard light microscopy and visual examination. Immunohistochemistry quantized by automated image analysis may be a useful adjunct to current histopathological strategies since it decreases assay subjectivity and variation.

Antibodies, Monoclonal↗
PubMed1990

Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion.

The limiting toxicity of low dose continuous infusion 5-fluorouracil (200-300 mg/m2/day) is often palmar-plantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42%-82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at a dose of 200 mg/m2/day until toxicity or progressive disease forced discontinuation. The first signs of the syndrome developed at a median of 2 months following infusion initiation and, unless treatment was interrupted, became progressively worse. The incidence of moderate to severe PPE was 71% in the 14 previously untreated patients (exact 95% confidence intervals of 42-92%). Seventy-eight percent of the responders in the no prior treatment group developed PPE. The incidence of moderate to severe PPE was only 27% in the 11 previously treated patients (exact 95% confidence intervals of 6-61%). The higher incidence of PPE in the previously untreated patients probably resulted from a longer total infusion time (median = 7.3 months) than the previously treated (median = 4.5 months). The longer infusion time in turn was a result of the higher response rates (64 vs 18%) in the previously untreated versus treated groups. Five previously untreated patients who developed PPE received 50 or 150 mg of pyridoxine/day when moderate PPE changes were noted. Reversal of PPE without interruption of the 5-FU was seen in 4/5 patients. Four of these patients who received pyridoxine had responded to 5-FU treatment. No adverse affect of pyridoxine on clinical response was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Colonic Neoplasms↗
PubMed1990

Effects of the Schirmer test on the fibrinolytic system in the tear fluid.

Human tear fluid was collected with blunted glass capillaries before and after performing the Schirmer test (ST). The test caused an increase in the tear fluid (TF) plasmin concentration (from 0.40 +/- 0.29 microgram ml-1 (mean +/- S.E.M.) to 1.14 +/- 0.26 microgram ml-1; Mann-Whitney test P less than 0.001) and a decrease in plasminogen activator activity (from 2.04 +/- 0.24 IU ml-1 to 1.04 +/- 0.17 IU ml-1; Mann-Whitney test P less than 0.002). In the filter paper used for ST, that segment that had been in contact with the conjunctiva (5 mm) usually contained higher amounts of plasmin than the following 5 mm of the paper overhanging the lidmargin. The present results indicate that the TF collection may affect the plasminogen activator-plasmin system in TF, depending on the collection method used.

Fibrinolysin↗
PubMed1990

Release of thyrotropin and prolactin by a thyrotropin-releasing hormone (TRH) precursor, TRH-Gly: conversion to TRH is sufficient for in vivo effects.

The mechanism by which TRH-Gly (pGlu-His-Pro-Gly), a biosynthetic precursor of thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NH2), stimulates pituitary thyrotropin (TSH) and prolactin release has been studied in urethane-anesthetized 2-month-old (250 g) male Sprague-Dawley rats and in vitro with GH3 cells, a rat anterior pituitary tumor cell line. We used specific radioimmunoassays to measure TRH-Gly and TRH levels in rat cortex, hypothalamus, medulla, eyes and whole blood as a function of the intracisternal (IC) dose of TRH and TRH-Gly administered 40 min prior to sacrifice. IC injection of 1.0 mg of TRH-Gly led to a significant (p less than 0.005) increase in the TRH levels in hypothalamus, medulla and blood. The relative potency of IC and intracardiac (IK) TRH and TRH-Gly release of rat TSH was compared by radioimmunoassay and further refined using estimates based on in vivo kinetics of TRH-Gly alpha-amidation. The binding of TRH-Gly to the plasma membrane receptors for TRH on GH3 cells was also investigated. In regard to TSH release, TRH-Gly given IC had only 0.042% of the potency of TRH given IC and was consistent with its rate of IC alpha-amidation. IK TRH-Gly had 0.16% of the potency of IK TRH of TSH release and was also consistent with its rate of intravascular conversion to TRH. The mean peak TSH response occurred at 20 min after IC TRH-Gly or IC TRH injection but the post-peak decline was slower for IC TRH-Gly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Individual differences in spatial and identity information processing in iconic memory.

The literature on iconic memory has provided conflicting evidence on the rate of loss of spatial location and identity information from iconic storage in non-retarded individuals. Some studies which have used the partial report technique indicate that information on spatial location is lost more rapidly than information on identity, while others indicate no difference in the rate of loss for the two types of information. The present investigation was a replication and extension of previous studies to help resolve the discrepancies in findings and to provide a more refined definition of what is meant by information on spatial location and identity. Correlations indicate that there may be two distinct subgroups among the borderline to mild mentally retarded population in terms of their iconic processing abilities.

Adult↗
PubMed1990

Surgical management of gastric cancer.

The presentation and surgical management of gastric cancer is changing as a result of advances in endoscopy and preoperative imaging techniques. One surgeon's experience with 44 cases operated on between 1982 and 1988 is reviewed. Endoscopy was performed in 93% of cases. A sub-total gastrectomy was performed in 23 cases, a total gastrectomy in 13, and a proximal gastrectomy in eight. Of the cancers, 13 involved local or distant structures (d+), 18 had lymph node involvement (+) and 13 were node free (-). Of the first 22 patients, only four had a node (-) lesion compared to nine of the second 22 patients (p = ns). There were two postoperative deaths (4.5%) and eight postoperative complications (20%). Mean hospital stay for (d+) patients (36.2 +/- 22.8 days) was significantly longer than that of the node (-) group (18.3 +/- 5.7 days) (p less than 0.02). Over half the (d+) group died within six months and survival was significantly worse than in the node (-) group for the following three years. No patient in the node (-) group has developed recurrent carcinoma after a mean follow up of 21 months (6 months - 4 years). Early results suggest that subtotal gastrectomy is curative in node (-) patients. Extensive gastrectomies may not be justified in patients with advanced gastric cancer if symptoms do not warrant it, as hospital stay is likely to be prolonged and long term survival is poor.

Aged↗
PubMed1989

Smoking and occupational allergy in workers in a platinum refinery.

OBJECTIVE: To test the hypothesis that smoking increases the risk of sensitisation by occupational allergens. DESIGN: Historical prospective cohort study. SETTING: Platinum refinery. SUBJECTS: 91 Workers (86 men) who started work between 1 January 1973 and 31 December 1974 and whose smoking habit and atopic state (on skin prick testing with common allergens) had been noted at joining. MAIN OUTCOME MEASURES: Results of skin prick tests with platinum salts carried out routinely every three to six months and records of any respiratory symptoms noted by the refinery's occupational health service. Follow up was until 1980 or until leaving refinery work, whichever was earlier. RESULTS: 57 Workers smoked and 29 were atopic; 22 developed a positive result on skin testing with platinum salts and 49 developed symptoms, including all 22 whose skin test result was positive. Smoking was the only significant predictor of a positive result on skin testing with platinum salts and its effect was greater than that of atopy; the estimated relative risks (95% confidence interval) when both were included in the regression model were: smokers versus non-smokers 5.05 (1.68 to 15.2) and atopic versus non-atopic 2.29 (0.88 to 5.99). Number of cigarettes smoked per day was the only significant predictor of respiratory symptoms. CONCLUSION: Smokers are at increased risk of sensitisation by platinum salts.

Adolescent↗
PubMed1989

Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin.

Immobilized vitronectin was found to bind both purified plasminogen activator inhibitor type 1 (PAI-1) and the PAI-1 in conditioned culture medium of human sarcoma cells. Similarly, immobilized PAI-1 bound both purified vitronectin and vitronectin from normal human serum. These interactions were demonstrated using both enzyme immunoassay and radioiodinated proteins. Solid-phase vitronectin bound PAI-1 with Kd 1.9 x 10(-7) M, and the reverse interaction gave a Kd 5.5 x 10(-8) M. Evidence was also found for a second type of binding with a Kd below 10(-10) M. The molar ratios of the two proteins in the complex at the saturation levels were approximately one molecule of soluble PAI-1 bound per three molecules of immobilized vitronectin and approximately one molecule of soluble vitronectin being bound per one molecule of immobilized PAI-1. Binding of PAI-1 to vitronectin did not lead to an irreversible loss of the ability of PAI-1 to inhibit urokinase (u-PA) and tissue-type plasminogen activator (t-PA). Active u-PA released vitronectin-bound 125I-labeled PAI-1 radioactivity, suggesting that u-PA interacts with the complex. The Mr 50,000 urokinase cleavage product of PAI-1 also bound to vitronectin, but this bound fragment did not inhibit u-PA. Binding of PAI-1 to vitronectin did not interfere with the ability of vitronectin to promote the adhesion and spreading of cells. These results suggest that the interaction between vitronectin and PAI-1 may serve to confine pericellular u-PA activity to focal contact sites where cells use proteolysis in regional detachment.

Glycoproteins↗
PubMed1989

Down-regulation of proteolytic activity in 12-O-tetradecanoyl-phorbol-13-acetate-induced K562 leukemia cell cultures: depletion of active urokinase by excess type 1 plasminogen activator inhibitor.

The human chronic myeloid leukemia cell line K562 acquires several megakaryoblastoid features when cultured in the presence of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We observed strongly increased secretion of several proteins into the culture media of K562 cells within a few hours of TPA treatment. Two of the major secreted polypeptides were identified by immunoprecipitation from media of metabolically labeled cultures as the tissue inhibitor of metalloproteinases (TIMP) and the type 1 plasminogen activator inhibitor (PAI-1). Maximal amounts of PAI-1 mRNA and secretion of PAI-1 polypeptides were observed after 24 hr of TPA treatment and PAI-1 persisted at elevated levels for several days. The induction of PAI-1 mRNA was dependent on de novo protein synthesis. Uninduced and induced cells secreted urokinase plasminogen activator in its single-chain proenzyme form (pro-u-PA), which was cleaved extracellularly to the active two-chain form as shown by pulse-chase labeling experiments. Upon TPA induction, the secretion of u-PA polypeptides increased severalfold, and there was a transient accumulation of pro-u-PA in the culture medium. However, this did not lead to increased u-PA activity in the cultures, since active u-PA was removed by complex formation with the large excess of coinduced PAI-1. Induction of u-PA mRNA was biphasic: The first peak of about tenfold increase in steady-state u-PA mRNA at 3 hr was followed by a steep decline to the baseline level at 12 hr, and a second, slower accumulation of u-PA mRNA occurred over the next few days. The biphasic accumulation of u-PA mRNA was also reflected in u-PA protein synthesis. We conclude that concerted changes in favor of a nonproteolytic extracellular environment occur in TPA-induced K562 cultures undergoing megakaryoblastoid differentiation. These changes include excessive secretion of TIMP and inhibition of the induced u-PA by the simultaneous accumulation of PAI-1.

Cell Line↗
PubMed1989

Medullary sites for TRH analogue stimulation of gastric contractility in the rat.

Medullary sites at which the stable thyrotropin-releasing hormone (TRH) analogue, RX 77368 (p-Glu-His-[3,3'-dimethyl]-Pro-NH2), stimulates gastric contractility were investigated in rats under urethan anesthesia. The peptide analogue was microinjected in 50-100 nl of volume unilaterally into various brain stem nuclei using glass micropipettes (50 microns). Gastric contractility was recorded continuously with acutely implanted strain-gauge force transducers and traces analyzed by computer. RX 77368 (2.6-77 pmol) microinjected into the dorsal vagal complex (DVC) dose dependently stimulated gastric contractility. Peptide action (77 pmol) had a rapid onset with a peak response at 15 min, continued for 45 min after the microinjection, and was blocked by vagotomy. TRH microinjected into the DVC had a shorter duration of action. RX 77368 (0.7-77 pmol) microinjected into the nucleus ambiguus also dose dependently stimulated gastric contractions. In contrast, microinjection of RX 77368 (77 pmol) into the hypoglossal nucleus had no effect. These findings demonstrate that the DVC and nucleus ambiguus are sites of action for TRH-induced stimulation of gastric contractility in the rat. The effect is dose dependent, long lasting, site specific, and vagally mediated. These results are consistent with a possible physiological role for medullary TRH in the vagal regulation of gastric contractility.

Animals↗
PubMed1988

Production of an active urokinase by leukemia cells: a novel distinction from cell lines of solid tumors.

A new screening test is described which enabled rapid determination of the proportion of single-chain and two-chain urokinase produced in the culture supernatants of 18 human cell lines. A clear distinction was found between two groups of cell lines: cells derived from ten solid tumors produced almost exclusively single-chain proenzyme, while the majority of the enzyme found in cultures of eight leukemia cell lines was in the active, two-chain form.

Enzyme Activation↗
PubMed1988

IOL prediction: an evaluation of preoperatively determined intraocular lens power accuracy.

A retrospective survey of 612 eyes that had undergone cataract extraction and IOL implantation was undertaken to evaluate the accuracy of ultrasound biometry combined with keratometry using the SRK regression formula, for the preoperative prediction of intraocular lens powers. A mean error of +0.35 dioptre sphere (DS) (SD +/- 0.98) was found for the series overall, with a significant (P less than 0.005) difference between the distribution of postoperative refractive errors using the S.R.K. formula for IOL prediction and the use of a standard lens of 19.5 DS. The consistency of results was tested for those patients with greater or less than normal axial length. Linear regression analysis showed no correlation between axial length and postoperative refractive error and therefore does not support the adjustment of predicted IOL powers by a factor based on axial length. Statistically significant differences were found between surgeons' results, supporting the practice of A-constant modification for individual surgeons.

Cornea↗
PubMed1988

Rapid appearance of plasmin in tear fluid after ocular allergen exposure.

Specific allergens were applied topically to the conjunctivae of 18 allergic patients. In cases with positive allergic reaction, proteolytic activity, identified as plasmin using zymographic analysis and a monoclonal anticatalytic antibody to plasmin, was found to appear within 3-5 min in the tear fluid, reaching concentrations of 2.2-28.6 micrograms/ml. No plasmin was detected, either in the tear fluid of 30 unchallenged non-atopic control persons, or atopic patients provoked with a test material that had given no reaction in a skin prick test. These findings suggest that generation of plasmin is a consequence of the conjunctival allergic reaction.

Administration, Topical↗