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Biomedical subjects

R Stephens

Publications and source records attributed to R Stephens.

At least 19 recordsLinked to original sources
PubMed1992

Phospholipid composition of cultured human endothelial cells.

Detailed analyses of the phospholipid compositions of cultured human endothelial cells are reported here. No significant differences were found between the phospholipid compositions of cells from human artery, saphenous and umbilical vein. However, due to the small sample sizes, relatively large standard deviations for some of the phospholipid classes were observed. A representative composition of endothelial cells is: phosphatidylcholine 36.6%, choline plasmalogen 3.7%, phosphatidylethanolamine 10.2%, ethanolamine plasmalogen 7.6%, sphingomyelin 10.8%, phosphatidylserine 7.1%, lysophosphatidylcholine 7.5%, phosphatidylinositol 3.1%, lysophosphatidylethanolamine 3.6%, phosphatidylinositol 4,5-bisphosphate 1.8%, phosphatidic acid 1.9%, phosphatidylinositol 4-phosphate 1.5%, and cardiolipin 1.9%. The cells possess high choline plasmalogen and lysophosphatidylethanolamine contents. The other phospholipids are within the normal biological ranges expected. Phospholipids were separated by high-performance liquid chromatography and quantified by lipid phosphorus assay.

Cell Extracts↗
PubMed1991

In situ hybridization with single-stranded RNA probes to demonstrate infrequently elevated gli mRNA and no increased ras mRNA levels in meningiomas and astrocytomas.

Using computer-assisted digital image-analysis, the level of ras and gli messenger RNA (mRNA) in neoplasms of meningeal and glial origin was determined in an attempt to correlate these parameters with histological tumor severity. We used single-stranded, asymmetric, radiolabelled RNA probes to detect the amount of ras and gli mRNA present in formalin-fixed, paraffin-embedded tumor material. Such archival material can provide an immediate, larger sample base than with fresh samples. The extent of ras mRNA expression in 25 brain tumors was not significantly different than normal cerebellum. However, five of 74 astrocytomas of relatively high malignant potential demonstrated gli mRNA levels above normal cerebellum.

Analysis of Variance↗
PubMed1991

Reversal of multidrug resistance in HL-60 cells by verapamil and liposome-encapsulated doxorubicin.

The means of circumventing multidrug resistance was investigated in HL-60 and HL-60R (a drug resistance variant) cell lines. The HL-60R cell line was developed from the parent line by serial exposure to increasing concentrations of doxorubicin over a 4-month period. This drug resistant cell line expressed P-glycoprotein in its cell surface and is 80-fold more resistant than the parent cell line. Multidrug resistance, as evaluated by a cell cytotoxicity assay using doxorubicin, can be overcome by use of verapamil. Multidrug resistance can also be circumvented when doxorubicin is encapsulated in liposomes. The combination of verapamil and doxorubicin-encapsulated liposomes does enhance circumvention of multidrug resistance beyond the effect of each agent alone, implying a synergistic effect. The lipid composition of the liposomes does affect the rate of drug uptake but not the overall cytotoxic effect of doxorubicin. The synergistic reversal of multidrug resistance by doxorubicin-encapsulated liposomes and verapamil suggests a multifactorial basis for drug resistance in this cell line.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Improved radioimmunotherapy of colorectal cancer xenografts using antibody mixtures against carcinoembryonic antigen and colon-specific antigen-p.

Radioimmunotherapy of GW-39 human colonic tumor xenografts grown in the hamster cheek pouch with 131I-labeled NP-4 anti-(carcinoembryonic antigen) (CEA) and 131I-labeled Mu-9 anti-(color-specific antigen-p) (CSAp) murine monoclonal antibodies, administered in combination, was more effective than using either antibody alone for tumor masses less than 0.5 cm3 in size. The antibody mixture had no therapeutic advantage for larger tumors. Therapeutic efficacy was determined by measuring the change in tumor size over time, quantifying the absolute number of tumors responding to radioantibody therapy, and determining the percentage growth inhibition of each treatment at various times after radioantibody administration. Several mechanisms are discussed to explain the improved tumoricidal effect of the antibody mixture noted in this model system, such as (a) the possibility that an antibody mixture could target a greater number of tumor cells, (b) the potential for antibody mixtures to provide better tumor distribution and (c) the possibility that antibodies administered in combination can increase the magnitude of tumor uptake of individual radioantibodies, thereby resulting in a greater radiation dose delivered to the tumor.

Animals↗
PubMed1991

Incidence of numerical chromosome anomalies in human pregnancy estimation from induced and spontaneous abortion data.

Induced abortion data provided an estimate of 4.7% numerical chromosome anomalies for women with a clinically recognized pregnancy at the end of the 7th week after the last menstrual period (LMP). This frequency requires that 51.9% of spontaneous abortions occurring after the 7th week should be chromosomally abnormal if the frequency of numerical chromosome anomalies at term (live and stillbirths combined) is 0.53%. Cytogenetic data from surveys of spontaneous abortion suggested a lower incidence of 39.7%. However, this figure is likely to be an underestimate because chromosome anomalies are almost certainly over-represented among the many early abortuses which lack embryonic tissue and hence are not karyotyped. The frequency of numerical chromosome anomalies at conception, arising from meiotic errors, was estimated from sperm karyotype data combined with information on the relative frequencies of maternal and paternal errors in the aetiology of trisomies. This provided a minimum estimate of 20%.

Abortion, Induced↗
PubMed1991

Effects of self-monitored exercise on selected blood chemistry parameters of end-stage renal disease patients.

The effects of exercise on patients with end-stage renal disease (ESRD) is relatively unexplored. Of the complications associated with kidney failure, anemia and abnormal blood lipids profiles are among those that exercise may alter. Thus, the purpose of this study was to determine the effects of a self-monitored exercise program on the blood chemistry status in ESRD patients. The program consisted of aerobic activity maintained for a minimum of 15 min at least three times per week at an intensity of 10.8 +/- 2.13 on the Borg rating of perceived exertion scale (this scale correlates with heart rate and is used in cases where heart rate is not a reliable predictor of exercise intensity such as hemodialysis patients). Monthly blood samples were taken to assess the patients status regarding anemia and blood lipids. Results indicate no significant differences (P greater than 0.05) were seen from the beginning of the program until the end of the eighth month as seen below: [table; see text] Values are X +/- SEM. These data indicate that a self-monitored exercise program of moderate intensity may not be beneficial in helping regulate the anemia and altered blood lipid status of ESRD patients. Thus, since no physiological benefits are apparent with a self-monitored exercise program of low intensity, it is important to realize the potential risk involved with patients undertaking an unsupervised exercise program. These data illustrate that ESRD patients need supervised exercise programs in order to elicit a physiological training response.

Adult↗
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↗