Biomedical subjects
Publications and source records attributed to K M Robinson.
The effects of changing the size of stimuli between learning and recognition sessions were examined for word and picture materials. Size changes did not affect correct recognition of items as new or old, for either words or pictures. However, size alteration impaired recognition memory for the size of word stimuli. With pictures, impaired size recognition was noted with changes only from large to small.
The relationship of caregiver health, past marital adjustment, as well as received social support to caregiving burden was studied in 78 wives who served as primary caregivers to husbands with irreversible memory impairment for an average of 4 years and 10 months. In addition, socioeconomic status and attitudes toward asking for help were investigated. This paper is based on the same data set as a previous article that focused on depression. Past marital adjustment was a significant (p less than .001) predictor of subjective burden and accounted for 20% of the total explained variance (22%). Socioeconomic status and attitude toward asking for help were the significant (p less than .001) predictors of objective burden and accounted for 12% of the total variance (17%). Received social support did not predict caregiver adjustment. The finding that past marital adjustment was significantly related to subjective burden suggests that caregivers with unhappy past marriages may need intervention in order to reframe past grievances in their marriages. Findings regarding social status indicate that caregivers with a higher income could purchase services, thus decreasing the amount of disruption in their lives and households.
The growth of the cultured human breast carcinoma cell line NUB 1 as well as that of other cultured malignant cells has been shown to be inhibited by addition of gamma-linolenic acid (GLA) to the culture medium. It has previously been suggested that these findings may be attributed to correction of a GLA deficiency in malignant cells, with supplementation of this fatty acid leading to increased prostaglandin (PG) production and consequent growth inhibition. To test this hypothesis the effect of 50 micrograms/ml concentrations of GLA and its sequential metabolite dihomo-gamma-linolenic acid (DGLA) and cell growth, morphology and prostaglandin (PGE and PGF) production by NUB 1 cells was investigated. GLA increased PGE and PGF production, inhibited cell growth and caused accumulation of lipid containing cytoplasmic granules. While treatment with DGLA increased PG production to a significantly greater extent than GLA administration it had no apparent effect on cell growth of morphology and did not inhibit cell growth. These findings suggest that some action other than the ability to increase PG production may be responsible for the inhibitory effects produced by GLA in malignant cells.
Castanospermine-glucosides (CS-glcs) are new compounds which have been evaluated as glycohydrolase inhibitors in rats. 7-O-alpha-D-Glucopyranosyl-CS (7 alpha-glc-CS) and 8 alpha-glc-CS were potent sucrase inhibitors with IC50s of 40 and 30 nM, respectively. Their sucrase inhibition was poorly reversible. They were much weaker liver lysosomal alpha-glucosidase inhibitors with IC50s of 40,000 nM. 1 alpha-glc-CS and 8 beta-glc-CS were both weaker and less selective sucrase inhibitors. In vivo, 7 alpha-glc-CS and 8 alpha-glc-CS effectively reduced the glycemic response to an oral 2 g/kg sucrose load at doses less than or equal to 1 mg/kg. 8 alpha-glc-CS was effective when administered up to 4 hr before sucrose. The known glucohydrolase inhibitors 1-deoxynojirimycin and N-hydroxyethyl-1-deoxy-nojirimycin were also potent sucrase inhibitors (IC50s = 200 and 400 nM, respectively) but their sucrase inhibition was readily reversible in vitro and their in vivo duration of action was much shorter than for the CS-glcs. Among the glucohydrolase inhibitors tested, the prolonged in vivo duration of action could be predicted by poor reversibility from sucrase. These CS-glcs provide a new generation of sucrase inhibitors which may be useful in the treatment of diabetes mellitus.
This paper presents a summary of the development of a Diploma in Nursing course available through distance teaching. In particular it highlights areas of collaboration both at the institutional and personal levels which extend across national boundaries. It is clear from the analysis that the success of the project depended on this extensive collaboration and that such collaboration represents one of the strengths of distance learning. Finally, it explores some of the potential consequences and conflicts inherent in collaborative projects.
A model for family caregiving was developed that linked social support and caregiving burden. A component of the theoretical model suggests that caregivers with high social skills will be able to mobilize social support in their environments more effectively, resulting in a decrease in their perceived caregiving burden. A pilot intervention study explored whether there was any difference in caregiving burden for subjects receiving social skills training and subjects in a control group. Results at pretest revealed no significant differences between the groups. Results at posttest revealed that a significant decrease in both objective and subjective burden occurred for the treatment group. These results indicate that further investigation about how best to support the caregivers who regularly care for and assist their elderly members is of prime importance.
Castanospermine is a potent inhibitor of rat intestinal glycohydrolases in vitro and prevents the hyperglycemic response to an oral sucrose challenge in vivo. Among the glycohydrolases tested, castanospermine was most effective against sucrase with an IC50 of 1.1 x 10(-7) M. In vivo, a significant effect was seen at doses less than 1 mg/kg in both normal and streptozotocin-treated rats. Castanospermine has a prolonged duration of activity in vivo with significant activity when administered 4 hours before sucrose.
Castanospermine is a potent inhibitor of rat hepatic lysosomal alpha-glucosidase in vitro. The alkaloid showed time-dependent inhibition with an IC50 of 5 X 10(-6) M without preincubation and 1 X 10(-7) M with 1 hr of preincubation. Inhibition appeared competitive without preincubation but noncompetitive after preincubation. The time-dependent inactivation of the enzyme followed pseudo-first-order kinetics with an inactivation constant of 1.2 X 10(3) M-1 sec-1. The apparent irreversibility of enzyme inhibition by castanospermine is postulated to be by tight-binding inhibition.
MDL 25,637 is a novel compound designed as a transition-state inhibitor of alpha-glucohydrolases. This compound inhibits rat intestinal sucrase, maltase, isomaltase, glucoamylase and trehalase activities at micromolar concentrations. It is a much weaker inhibitor of alpha-amylase and lactase. Inhibition of sucrase was competitive with sucrose. In mice, MDL 25,637 inhibited the rise in serum glucose after a sucrose or starch load but not after a glucose load. MDL 25,637 also reduced the glycemic response to sucrose in rats. The drug was most effective when administered 0 to 30 min before the sucrose load and was as effective in streptozotocin-treated rats as in normals. The inhibition by MDL 25,637 of intestinal glucohydrolases is an effective means of reducing the hyperglycemic response to an oral sucrose or starch load and, as such, warrants further investigation as a potential drug for the treatment of diabetes mellitus.
Prostaglandin production by two continuous human esophageal carcinoma cell lines HCU 18 and HCU 39 derived from poorly and moderately differentiated source tumors, respectively, was investigated. Behavior of both lines in vitro and upon sc inoculation into athymic randombred BALB/c nude mice was also assessed. Approximately half the xenografts induced by HCU 18 cells were invasive, whereas those initiated by HCU 39 cells were all well encapsulated. Although metastases were not detected in mice given injections of HCU 39 cells, metastatic tumors developed in 2 mice inoculated with HCU 18 cells. In addition, HCU 18 cells produced significantly more prostaglandin E (PGE) and prostaglandin F (PGF) than HCU 39 cells. These findings suggest a relationship between PGE and PGF production by human esophageal carcinoma cells and their invasive and metastatic potential in athymic mice.
The effects of gamma-linolenic acid (GLA) on growth of cells of the continuous murine sarcoma line M52B were investigated in vitro. Prostaglandin (PG) production by these cells after GLA treatment was also measured. GLA inhibited the growth of M52B cells and became overtly toxic at high doses or after long periods of exposure to lower doses. The inhibitory effects of GLA were accompanied by an increase in PGE production by M52B cells. However, the rise in PGE was not statistically significant. Accordingly the extent to which PGE may contribute to the inhibition observed with GLA remains unclear. In order to establish whether these in vitro effects could be reproduced in vivo, athymic nude mice bearing murine sarcoma allografts were fed either standard laboratory diets or diets supplemented with 35% evening primrose oil, which contains 10% GLA. As there was no significant difference in tumour volumes between the two groups at the end of the treatment period, the oil-enriched diet was concluded to be without effect on tumour growth in this in vivo model.
2-Alkoxy-2-propenylidene methanaminiums inhibited gluconeogenesis and stimulated glycolysis by hepatocytes isolated from 48-h-fasted rats and fasted-refed rats, respectively. The order of effectiveness of these compounds was the same as the hypoglycemic response of intact rats found in other studies, i.e., butoxy greater than propoxy greater than ethoxy derivative. Lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios were elevated whereas cellular ATP concentration was decreased by these compounds. The butoxy derivative inhibited the oxidation of [U-14C]glucose to 14CO2 but increased glucose utilization and lactate accumulation by isolated rat diaphragms. The butoxy derivative also inhibited site I reversed electron transfer and the oxidation of NAD+-linked substrates but not succinate by isolated rat liver mitochondria. Methanaminium-induced hypoglycemia in intact rats was accompanied by an increase in blood lactate concentration as well as blood beta-hydroxybutyrate to acetoacetate ratio. The hypoglycemia caused by these compounds is proposed to be due to inhibition of glucose synthesis in the liver along with increased glucose utilization in peripheral tissues, both for want of ATP as a consequence of inhibition of site I electron transfer.
A number of fatty acids have been shown to inhibit the growth of malignant cells in vitro. In particular, gamma-linolenic acid (GLA) has been proposed to act as a precursor for the production of prostanoids especially prostaglandin E1 (PGE1). To test this hypothesis, the effects of GLA on cultured human breast carcinoma cells were compared with those of dihomo-gamma-linolenic acid (DGLA) the metabolite of GLA and the immediate precursor of PGE1. The influence of ethanol (which has been shown to enhance conversion of DGLA to PGE1) on the actions of each of the fatty acids was also investigated. In contrast to the inhibitory effects observed with all concentrations of GLA cell growth was promoted by the presence of 50 micrograms DGLA. Ethanol reduced the action of both GLA and DGLA possibly due to some physicochemical reaction between the alcohol and the fatty acids. The fact that the actions of GLA were not mimicked by DGLA which is the next step towards PG production casts doubt upon the role of PGE1 as mediator of the effects which have been observed with GLA in malignant cells.
Recently, addition of gamma linolenic acid (GLA) which is a precursor of prostaglandin E1 (PGE1) to cell cultures, has been shown to inhibit growth of various carcinoma cells (1,2,3,4). These findings are consistent with Horrobin's proposal that some of the metabolic abnormalities of malignant cells may be due to deficiencies of certain prostanoids. To determine whether the observed effects of GLA are in fact mediated by increasing levels of its metabolites, this study investigated the influence of various inhibitors and stimulants of prostaglandin (PG) synthesis on the effects of GLA on carcinoma cells in vitro. Most of the agents used (aspirin, imidazole, lithium carbonate and ascorbic acid) produced results consistent with the idea that elevation of levels of thromboxane A2 (TxA2) and/or PGE1 may be important as regards the actions of GLA. In sharp contrast was the result obtained with indomethacin. This drug, which could be expected to block conversion of GLA to PGE1 and therefore protect cells against the effects of GLA, actually exaggerated the effects of this fatty acid, thereby causing cell death and desquamation.
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N-[3-(dimethylamino)-2-propoxy-2-propenylidene]- N-methylmethanaminium as the iodide or camsylate salt (MDL-310) is a newly reported chemical which has been shown to produce hypoglycemia in vivo. The studies reported here describe in vivo and in vitro effects of MDL-310 on carbohydrate metabolism. In nonfasted mice, MDL-310 decreased liver glycogen and then produced hypoglycemia, concomitant with a near total depletion of liver glycogen stores. In fasted rats, nonhypoglycemic doses of MDL-310 increased glucose production and utilization as determined by tracer studies with [6-3H]glucose. Hypoglycemic doses decreased glucose production and increased blood lactate, which suggests an inhibition of gluconeogenesis. In isolated rat hepatocytes MDL-310, at concentrations of greater than or equal to 5 X 10(-6) M, inhibited gluconeogenesis from lactate (10 mM) plus pyruvate (2 mM). We conclude that the primary action of MDL-310 is to increase glucose utilization and that decreased production due to the inhibition of gluconeogenesis is involved in the hypoglycemic action. A single metabolic action of MDL-310 to increase glycolytic metabolism of glucose is proposed which could explain both the increase in glucose utilization and decrease in glucose production.
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The nude mouse human tumour xenograft system was used as an in vivo model to investigate the possible effect of gamma-linolenic acid (GLA) both on established tumour xenografts and as a prophylactic agent prior to tumour induction. Eighty-nine nude mice bearing a range of different human tumours were studied and two solvents (each of which presented certain practical problems) were used to deliver GLA parenterally to the animals. GLA treatment was found to have no significant effect on the growth of any of the tumour xenografts investigated.