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Biomedical subjects

R A Anderson

Publications and source records attributed to R A Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium.

AIMS: To determine if the stress of corticosteroid treatment increases chromium (Cr) losses and if corticosteroid-induced diabetes (steroid diabetes) can be reversed by supplemental chromium. METHODS: The effects of corticosteroid treatment on chromium losses of 13 patients 2 days prior to steroid administration and the first 3 days following treatment were determined. Since steroid-induced diabetes was associated with increased chromium losses and insufficient dietary chromium is associated with glucose intolerance and diabetes, we treated three patients with steroid-induced diabetes with 600 microg per day of chromium as chromium picolinate. RESULTS: Urinary chromium losses following corticosteroid treatment increased from 155+/-28 ng/d before corticosteroid treatment to 244+/-33 ng/d in the first 3 days following treatment. Chromium supplementation of patients with steroid-induced diabetes resulted in decreases in fasting blood glucose values from greater than 13.9 mmol/l (250 mg/dl) to less than 8.3 mmol/l (150 mg/dl). Hypoglycaemic drugs were also reduced 50% in all patients when given supplemental chromium. CONCLUSIONS: These data demonstrate that corticosteroid treatment increases chromium losses and that steroid-induced diabetes can be reversed by chromium supplementation. Follow-up, double-blind studies are needed to confirm these observations.

Adrenal Cortex Hormones↗
PubMed1999

Preliminary experience of the use of a gonadotrophin-releasing hormone antagonist in ovulation induction/in-vitro fertilization prior to cancer treatment.

Therapeutic regimens for the treatment of malignant disease may compromise future fertility. One approach to circumvent this is the cryopreservation of embryos created before treatment for the malignancy. Conventional regimens using gonadotrophin-releasing hormone (GnRH) agonists are time consuming, requiring pituitary down-regulation before gonadotrophin administration, thus the duration of treatment is approximately 20-30 days. GnRH antagonists, however, do not cause an initial stimulation of gonadotrophin secretion and can thus be administered during the later stages of follicular maturation to prevent premature luteinization and ovulation. The duration of ovulation induction/in-vitro fertilization (IVF) treatment is thus reduced. In this study, case histories are reported of six women with newly diagnosed malignancies who requested ovulation induction/IVF prior to chemotherapy or surgery in which we have used the GnRH antagonist Cetrorelix. Gonadotrophin administration was started in the early follicular phase, and Cetrorelix (0.25 mg s.c. daily) was added from day 6 of treatment. Subsequent to human chorionic gonadotrophin (HCG) administration oocytes were recovered and successful fertilization and embryo cryopreservation was achieved in all cases. The median duration of treatment was 12 days (range 8-13, including induction of luteolysis in two patients). These results illustrate the potential use and advantages of a GnRH antagonist in ovulation induction/IVF when the need for immediate initiation of treatment and its duration are critical factors.

Adult↗
PubMed1999

RN participation in organizational decision making and improvements in resident outcomes.

In the study on which this article is based, nursing homes with the most improvements in resident outcomes had greater registered nurse (RN) participation in decision making than did homes with the least improvements. The results suggest that nursing homes that want to improve quality can use RN participation to make improvements without significantly increasing costs. Complexity theory served as a framework for the study.

Decision Making, Organizational↗
PubMed1999

Avoidable costs of comprehensive case management.

Comprehensive case management has become an industry standard and its pervasiveness raises questions about the ubiquitous need for this service. Analyzed from the perspective of transaction cost analysis and access, we argue that in some cases comprehensive case management is an avoidable cost incurred because of system problems that limit access to otherwise eligible clients. Implications are discussed.

Attitude of Health Personnel↗
PubMed1999

Acyl-coenzyme A:cholesteryl acyltransferase 2.

In addition to acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1), an enzyme in the endoplasmic reticulum of cells found ubiquitously throughout the body, data recently obtained in at least three mammalian species, including nonhuman primates, mice and humans, demonstrate the presence of an additional ACAT (EC 2.1.3.26), termed ACAT2, which is localized to the endoplasmic reticulum of liver and intestine. Data suggest that ACAT2 may be the enzyme responsible for cholesteryl ester secretion into apolipoprotein B-containing lipoproteins. We have hypothesized that oversecretion of cholesteryl esters produced by the action of hepatic ACAT2 could account for the increased atherogenicity associated with cholesteryl ester-enriched LDL in nonhuman primates. In such cases, ACAT2 is an appealing target for therapy to reduce coronary heart disease.

Amino Acid Sequence↗
PubMed1999

N- and C-terminal external domains of human herpesvirus-6 glycoprotein H affect a fusion-associated conformation mediated by glycoprotein L binding the N terminus.

Human herpesvirus-6 (HHV-6), like other betaherpesviruses, shows cell fusion with wild-type strains, and this cellular spread is mediated by the glycoprotein gH/gL complex. Anti-fusion monoclonal antibodies (MAbs) specific for HHV-6 glycoprotein gH inhibit infection and prevent cellular spread by syncytia formation. Reactivity of these MAbs with gH deletion mutants suggests a conserved C-terminal fusion-associated domain. A conserved motif here has an N-glycosylation site and characteristics of a beta turn. Motif deletion abrogated MAb recognition while co-expression with glycoprotein gL restored this conformational epitope, indicating the importance of folding and not glycosylation at this site. Our previous studies showed gL binding to gH at an N-terminal domain specific for betaherpesviruses. To further examine the function of this N-terminal domain, a betaherpesvirus-specific motif was deleted. This mutant gH still bound gL, and was recognized by the anti-fusion MAbs; however, recognition was now primarily in the immature form and reduced during processing to the mature form. A model is discussed whereby gL binding gH at the N-terminal domain acts to draw together the C-terminal extracellular domain and this interaction affects a functional conformation during glycoprotein maturation.

Animals↗
PubMed1999

Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement.

OBJECTIVE: To study the effect of total body irradiation (14.4 Gray) in childhood and adolescence on ovarian and uterine characteristics, and to investigate the response to physiological sex steroid serum concentrations. DESIGN: All long term post-pubertal female survivors of total body irradiation who had been treated in paediatric centres in Scotland were identified. Their ovarian and uterine characteristics were studied. SETTING: Recruitment was from follow up oncology clinics. SAMPLE: Nine women were identified, eight of whom were assessed and five progressed to detailed investigation. A control population of 12 women treated for acute leukaemia, but not treated with total body irradiation, and five healthy women with no history of childhood malignancy were recruited as controls. METHODS: Ovarian function was determined by measurement of serum gonadotrophins and sex steroids. Uterine response to physiological sex steroid replacement was investigated in women with ovarian failure, and to endogenous sex steroid production in women with ovarian function by ultrasound scan. The physiological sex steroid replacement was achieved with transdermal oestradiol patches and self administered vaginal progesterone pessaries. MAIN OUTCOME MEASURES: Determination of ovarian function and uterine response to physiological sex steroid serum concentrations. RESULTS: Six of eight women treated with total body irradiation had ovarian failure; preservation of function was seen in two girls treated pre-pubertally who had biochemical evidence of incipient ovarian failure. Four women with ovarian failure had reduced uterine volume, undetectable blood supply and absent endometrium at baseline assessment; after three months of physiological sex steroid replacement treatment uterine blood supply and endometrial response were not significantly different from controls; uterine volume improved but remained significantly smaller than controls and correlated with age at total body irradiation. CONCLUSIONS: Ovarian failure after total body irradiation is common and risk relates to age at treatment. Physiological sex steroid replacement improved uterine measures and these women may benefit from assisted reproductive technology.

Adolescent↗
PubMed1999

Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men.

The effects of chromium picolinate (CrPic) supplementation and resistance training (RT) on skeletal muscle size, strength, and power and whole body composition were examined in 18 men (age range 56-69 yr). The men were randomly assigned (double-blind) to groups (n = 9) that consumed either 17.8 micromol Cr/day (924 microg Cr/day) as CrPic or a low-Cr placebo for 12 wk while participating twice weekly in a high-intensity RT program. CrPic increased urinary Cr excretion approximately 50-fold (P < 0.001). RT-induced increases in muscle strength (P < 0.001) were not enhanced by CrPic. Arm-pull muscle power increased with RT at 20% (P = 0.016) but not at 40, 60, or 80% of the one repetition maximum, independent of CrPic. Knee-extension muscle power increased with RT at 20, 40, and 60% (P < 0.001) but not at 80% of one repetition maximum, and the placebo group gained more muscle power than did the CrPic group (RT by supplemental interaction, P < 0.05). Fat-free mass (P < 0.001), whole body muscle mass (P < 0.001), and vastus lateralis type II fiber area (P < 0.05) increased with RT in these body-weight-stable men, independent of CrPic. In conclusion, high-dose CrPic supplementation did not enhance muscle size, strength, or power development or lean body mass accretion in older men during a RT program, which had significant, independent effects on these measurements.

Aged↗
PubMed1999

The insulin-like growth factor system in the GT1-7 GnRH neuronal cell line.

Evidence suggests that insulin-like growth factors (IGFs; IGF-I and IGF-II) are involved in the regulation of reproductive function including the development of the gonadotropin-releasing hormone (GnRH) neuronal system and the modulation of GnRH secretory activities. To further characterize the regulatory role of the IGF system on GnRH neuronal function, we have examined the gene expression of IGF-I, IGF-II, IGF-I receptor (IGF-IR), and IGF-binding proteins (IGFBPs) in a GnRH neuronal cell line (GT1-7 cells). The relative effects of IGFs and insulin on GnRH secretion by these cells was also investigated. RT-PCR analysis demonstrated IGF-I, IGF-II and IGF-IR mRNAs in GT1-7 cells. The mRNAs for IGFBP-2, -3, -4, -5 and -6 but not IGFBP-1 were also detected. Immunoreactive protein bands for IGFBP-2, -4 and -5 but not for other IGFBPs were demonstrated by Western blot with IGFBP-5 appearing to be the most abundant IGFBP secreted by GT1-7 cells. IGFBP-5 production by GT1-7 cells was stimulated by both IGF-I and IGF-II in a dose-dependent manner with approximately equal potency, whereas insulin caused no significant effect. GnRH secretion by GT1-7 cells treated with IGF-I or IGF-II but not insulin showed an increase (80-100%) at 2 h of treatment followed by a decrease (46%) at 6 h that continued up to 24 h. We conclude that the expression of IGFs, IGF-IR and IGFBPs and their interactions in the regulation of GnRH secretion by GT1-7 cells as demonstrated by our study provide a basis for an autocrine regulatory role for the IGF system in GnRH neuronal secretory activities.

Animals↗
PubMed1999

7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men.

The synthetic steroid 7alpha-methyl-19-nortestosterone (MENT) is a potent androgen that is resistant to 5alpha-reductase. It thus has decreased activity at the prostate and may have advantages over testosterone-based regimens in long term treatment or as part of a male contraceptive. Administration to eugonadal men results in suppression of gonadotropins, but its ability to support androgen-dependent behavior has not been investigated. For sustained release administration, MENT acetate was used, because its diffusion characteristics were more suitable for use in implants. However, upon release the acetate is rapidly hydrolyzed, and MENT is the biologically active moiety in circulation. We studied the effects of MENT on sexual interest and activity, spontaneous erection, and mood states in comparison with testosterone enanthate (TE) in 20 Caucasian and Chinese hypogonadal men recruited in Edinburgh and Hong Kong (n = 10 in each center). Outcomes were measured using a combination of daily diaries, semistructured interviews, and questionnaires. Nocturnal penile tumescence (NPT) was also recorded in the Edinburgh group. After withdrawal of androgen replacement treatment (wash-out phase) for a minimum of 6 weeks, subjects were randomized to two groups in a cross-over design. Drug treatment regimens were of 6-week duration and consisted of two implants, each containing 115 mg MENT acetate, inserted s.c. into the upper arm and removed after 6 weeks and two injections of TE (200 mg, i.m.) 3 weeks apart. MENT treatment resulted in stable plasma MENT concentrations of 1.4 +/- 0.1 nmol/L after 3 weeks and 1.3 +/- 0.1 nmol/L after 6 weeks (mean +/- SEM; all men). Nadir testosterone concentrations were 3.6 +/- 0.6 nmol/L at the end of the wash-out phase and 9.4 +/- 0.6 nmol/L 3 weeks after each injection. There were no differences in hormone concentrations between centers. There were no adverse toxicological effects. There were only minor differences between the two treatments. Both MENT and TE treatment resulted in significant increases in sexual interest and activity, spontaneous erection (both by self-report and NPT measurement), and increases in positive moods, with decreases in negative moods in the Edinburgh group. In the Hong Kong group, both treatments increased waking erection, with a trend toward increased sexual interest and activity. Mood states appeared to be less affected during the wash-out phase than in Edinburgh men and showed no significant response to either treatment. These results demonstrate that MENT has similar effects on sexual activity and mood states as testosterone in hypogonadal men. As NPT is a physiological androgen-dependant outcome, these data provide further evidence for the androgenicity of MENT. The lack of detected effect of either androgen in Hong Kong men other than on waking erection illustrates the importance of the cultural context of symptomatology and its measurement. The appropriate dose of MENT remains to be determined, but these results support its development as a potential androgen replacement therapy.

Adult↗
PubMed1999

The casein kinase Ialpha isoform is both physically positioned and functionally competent to regulate multiple events of mRNA metabolism.

Casein kinase I is a highly conserved family of serine/threonine protein kinases present in every organism tested from yeast to humans. To date, little is known about the function of the higher eukaryotic isoforms in this family. The CKI isoforms in Saccharomyces cerevisiae, however, have been genetically linked to the regulation of DNA repair, cell cycle progression and cytokinesis. It has also been established that the nuclear localization of two of these isoforms is essential for their function. The work presented here demonstrates that the higher eukaryotic CKIalpha isoform is also present within nuclei of certain established cell lines and associated with discrete nuclear structures. The nature of its nuclear localization was characterized. In this regard, CKIalpha was shown to colocalize with factors involved in pre-mRNA splicing at nuclear speckles and that its association with these structures exhibited several biochemical properties in common with known splicing factors. The kinase was also shown to be associated with a complex that contained certain splicing factors. Finally, in vitro, CKIalpha was shown to be capable of phosphorylating particular splicing factors within a region rich in serine/arginine dipeptide repeat motifs suggesting that it has both the opportunity and the capacity to regulate one or more steps of mRNA metabolism.

Animals↗
PubMed1999

Long-term complications and post-treatment follow-up of patients with Wilms' tumor.

An increasing number of children with Wilms' tumor can expect to be cured, reflecting the undisputed progress made in the treatment of children with this renal cancer. However, it does underscore the need to screen survivors for late effects of cancer therapy. Some of the late effects, such as those following radiation therapy, should be expected after a considerable latent period. Others, such as those occurring after the administration of certain chemotherapeutics agents, are commonly immediate, usually transient, but occasionally permanent. Although children seem to tolerate acute toxicities of therapy better than do adults, the growing child may be more vulnerable to the delayed adverse sequelae of cancer therapy, such as effects on growth, fertility, and neuropsychological function. This article reviews many of the late effects seen in survivors of Wilms' tumor and the way in which these effects relate to the different therapeutical modalities used (surgery, chemotherapy, and radiation).

Antineoplastic Agents↗
PubMed1998

Identification of a form of acyl-CoA:cholesterol acyltransferase specific to liver and intestine in nonhuman primates.

The present study demonstrates that two different forms of the intracellular cholesterol esterification enzyme acyl-CoA:cholesterol acyltransferase (ACAT) are present in the nonhuman primate hepatocyte; one is similar to that originally cloned from human genomic DNA, here termed ACAT1, while a second gene product, termed ACAT2, is reported here. The primate ACAT2 gene product was cloned from an African green monkey liver cDNA library. Sequence analysis of an isolated, full-length clone of ACAT2 cDNA identified an open reading frame encoding a 526-amino acid protein with essentially no sequence similarity to the ACAT1 cDNA over the N-terminal 101 amino acids but with 57% identity predicted over the remaining 425 amino acids. Transfection of the cloned ACAT2 cDNA into two different mammalian cell types resulted in the production of abundant ACAT activity which was sensitive to ACAT inhibitors. Northern blot analysis showed that the ACAT2 mRNA was expressed primarily in liver and intestine in monkeys. In contrast, ACAT1 mRNA was expressed in almost all tissues examined. Topologic predictions from the amino acid sequence of ACAT2 indicates that it has seven trans-membrane domains in a configuration that places the putative active site of the enzyme in the lumen of the endoplasmic reticulum. This orientation of ACAT2 in the endoplasmic reticulum membrane, in addition to its expression only in liver and intestine, suggests that this enzyme may have as a primary function, the secretion of cholesteryl esters into apoB-containing lipoproteins.

Amino Acid Sequence↗
PubMed1998

Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation.

Phosphoinositide kinases play central roles in signal transduction by phosphorylating the inositol ring at specific positions. The structure of one such enzyme, type IIbeta phosphatidylinositol phosphate kinase, reveals a protein kinase ATP-binding core and demonstrates that all phosphoinositide kinases belong to one superfamily. The enzyme is a disc-shaped homodimer with a 33 x 48 A basic flat face that suggests an electrostatic mechanism for plasma membrane targeting. Conserved basic residues form a putative phosphatidylinositol phosphate specificity site. The substrate-binding site is open on one side, consistent with dual specificity for phosphatidylinositol 3- and 5-phosphates. A modeled complex with membrane-bound substrate and ATP shows how a phosphoinositide kinase can phosphorylate its substrate in situ at the membrane interface.

Bacterial Proteins↗
PubMed1998

The malaria parasite, Plasmodium falciparum, increases the frequency of multiple feeding of its mosquito vector, Anopheles gambiae.

It has often been suggested that vector-borne parasites alter their vector's feeding behaviour to increase their transmission, but these claims are often based on laboratory studies and lack rigorous testing in a natural situation. We show in this field study that the malaria parasite, Plasmodium falciparum, alters the blood-feeding behaviour of its mosquito vector, Anopheles gambiae s.l., in two ways. First, mosquitoes infected with sporozoited, the parasite stage that is transmitted from the mosquito to a human, took up larger blood meals than uninfected mosquitoes. Whereas 72% of the uninfected mosquitoes had obtained a full blood meal, 82% of the infected ones had engorged fully. Second, mosquitoes harbouring sporozoites were more likely to bite several people per night. Twenty-two per cent of the infected mosquitoes, but only 10% of the uninfected mosquitoes, contained blood from at least two people. We conclude that the observed changes in blood-feeding behaviour allow the parasite to spread more rapidly among human hosts, and thus confirm that the parasite manipulates the mosquito to increase its own transmission.

Animals↗
PubMed1998

Resource allocation and resident outcomes in nursing homes: comparisons between the best and worst.

The purpose of this study was to identify patterns of resource allocation that relate to resident outcomes in nursing homes. Data on structure, staffing levels, salaries, cost, case mix, and resident outcomes were obtained from state-level, administrative databases on 494 nursing homes. We identified two sets of comparison groups and showed that the group of homes with the greatest percentage of improvement in resident outcomes had higher levels of registered nurse (RN) staffing and higher costs. However, comparison groups based on best-worst average outcomes did not differ in resource allocation patterns. Additional analysis demonstrated that when controlling for RN staffing, resident outcomes in high- and low-cost homes did not differ. The results suggest that, although RN staffing is more expensive, it is key to improving resident outcomes.

Aged↗
PubMed1998

Dietary chromium decreases insulin resistance in rats fed a high-fat, mineral-imbalanced diet.

The effects of chromium (Cr) supplementation on diet-induced insulin resistance produced by feeding a high-fat, low-Cr diet were studied in rats to ascertain the role of Cr in insulin resistance. Wistar male rats were maintained for 16 weeks after weaning on a basal diet containing 40% lard, 30% sucrose, and 25% casein by weight and adequate vitamins and minerals without added Cr (-Cr). Fasting levels of insulin, glucose, and triglycerides and the responses during an intravenous glucose tolerance test (IVGTT) were compared as indices of insulin resistance and the effectiveness of dietary Cr. IVGTTs and blood sampling for data analyses were performed over a 40-minute period after IV glucose injection (1.25 g/kg body weight) in overnight-fasted animals under pentobarbital anesthesia (40 mg/kg body weight). All animals were normoglycemic (-Cr, 109 +/- 3 mg/dL; +Cr, 119 +/- 5), with fasting insulin levels elevated in the -Cr group (65 +/- 10 microU/mL) versus the +Cr group (31 +/- 4 microU/mL). Increases in plasma triglycerides in the -Cr group were not significant. Following glucose injection, the rate of glucose clearance was lower in the -Cr group (1.74 +/- 0.22 v2.39 +/- 0.11%/min), and 40-minute glucose areas in the -Cr group tended to be higher than in the +Cr group. The insulin response to glucose injection was 20% higher in the -Cr group. Forty-minute plasma triglyceride areas were lower in +Cr rats (875 +/- 62 v 1,143 +/- 97 mg/dL.min in -Cr rats). These data demonstrate that the insulin resistance induced by feeding a high-fat, nutrient-stressed diet is improved by Cr.

Animals↗