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Biomedical subjects

R Stephens

Publications and source records attributed to R Stephens.

At least 73 records · Page 4Linked to original sources

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

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

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

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

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

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

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

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

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

Microplate immunocapture assay for plasminogen activators and their specific inhibitors.

We report a convenient sensitive enzyme activity assay for urokinase and tissue-type plasminogen activators, based on a solid-phase microtitre plate method using readily available polyclonal antibodies. The sensitivities for urokinase (active and proenzyme) and tissue activator were better than 1 ng/ml. The specificity was very high, with no significant contribution of urokinase in tissue activator assays or vice versa. This method is particularly useful for the assay of urokinase proenzyme in samples containing inhibitors. We describe how this assay may also be used to measure specific inhibitors of plasminogen activators, making use of their rapid formation of stable complexes with solid-phase activator. Inhibitors may be assayed in samples containing proenzymes.

Binding, Competitive

Impaired neutrophil function during anesthesia and surgery is due to serum factors.

Neutrophil function was assessed in patients undergoing anesthesia and surgery using a chemiluminescence (CL) assay. With the anesthetic agents enflurane and nitrous oxide, peroperative CL (99.1 mV; 13.8 SEM: postinduction but prior to surgery) was significantly lower than the preoperative value (146.5 mV; 14.1 SEM) with a mean fall of 30% (P less than 0.001). CL measurements taken 24 hr postoperatively were significantly increased (193.9 mV; 16.4 SEM) over the pre- and peroperative values, showing mean increases of 32 and 96%, respectively (P less than 0.001 in both cases). The inhibitory influence on CL appeared to be due to serum factors since peroperative patients' sera inhibited control neutrophils. Significantly depressed levels of the complement component C3 and IgG detected during the peroperative period (P less than 0.05) may explain this phenomenon. Postoperatively, C3 and IgG levels returned to normal. The transient decrease in peroperative neutrophil function may be a contributory factor to the establishment of postoperative sepsis in surgical patients.

Anesthesia, Inhalation

Prune belly syndrome and retroperitoneal germ cell tumor.

The prune belly syndrome is a congenital set of anomalies that includes cryptorchidism. Despite the known risk of testicular tumors in cryptorchid testes, what may be the first case of a germ cell tumor complicating the prune belly syndrome is described herein.

Cryptorchidism

Improved survival duration with combination chemotherapy induction for multiple myeloma: a Southwest Oncology Group Study.

Four hundred forty previously untreated patients with active multiple myeloma were entered into a randomized trial (Southwest Oncology Group [SWOG] study 7927/28) comparing vincristine, melphalan, Cytoxan (Mead Johnson & Company, Evansville, Ind), and prednisone (VMCP) alternating with vincristine, BCNU, Adriamycin (Adria Laboratories, Columbus, Ohio) and prednisone (VBAP) with or without levamisole with vincristine, Cytoxan, and prednisone (VCP) with or without levamisole for induction therapy. The treatment groups were well balanced for all of the known major prognostic factors. Patients receiving VMCP-VBAP responded (greater than or equal to 75% regression) more frequently to induction therapy, both without (54%) and with (44%) levamisole v VCP without (28%) or with (28%) levamisole (P less than .001). In addition, patients receiving VMCP-VBAP (+/- levamisole) had a survival duration determined to be significantly increased by all forms of analysis: 48 and 33 months for VMCP-VBAP without and with levamisole v 29 and 26 months for VCP without and with levamisole (P = .011 overall). Levamisole did not improve response rates or survival duration (P greater than or equal to .1), nor did it prolong remission in the maintenance phase (P = .85). Analysis of SWOG study 7704/05 (updated April 1985) confirmed improved survival for combination therapy v MP, but no benefit for levamisole. The overall findings support the use of VMCP-VBAP as an excellent treatment option for remission induction in patients with active myeloma of all stages and prognostic categories.

Actuarial Analysis