Biomedical subjects

S A Ross

Publications and source records attributed to S A Ross.

At least 73 records · Page 4Linked to original sources

PubMed1997

Small weight loss on long-term acarbose therapy with no change in dietary pattern or nutrient intake of individuals with non-insulin-dependent diabetes.

OBJECTIVES: To see if the long-term treatment of non-insulin dependent diabetes (NIDDM) with the alpha-glucosidase inhibitor acarbose affects food intake and body weight. DESIGN: Randomized, double-blind, placebo-controlled, parallel design clinical trial of 12 months duration. SUBJECTS: Subjects with NIDDM in four treatment strata: 77 on diet alone, 83 also treated with metformin, 103 also treated with sulfonylurea and 91 also treated with insulin. MEASUREMENTS: Two 3 day diet records were obtained before randomization to acarbose or placebo therapy, and additional 3 day diet records were obtained at 3, 6, 9 and 12 months after randomization. Body weight was also measured at these times. RESULTS: Of the 354 subjects randomized, 279 (79%) completed at least 9 months of therapy and, of these, 263 (94%) provided at least one diet record during the baseline period and two diet records during the treatment period. After one year, subjects on acarbose had lost 0.46 +/- 0.28 kg, which differed significantly from the 0.33 +/- 0.25 kg weight gain on placebo (P = 0.027). The difference in weight change between acarbose and placebo did not differ significantly in the different treatment strata. Being in the study had significant effects on diet, including a reduction in energy intake from 1760-1700 Kcal/d (P < 0.05), a reduction in simple sugars intake from 18.5-17.4% of energy (P < 0.001), and reductions in the number of different foods consumed (33-30, P < 0.001) and the number of meals eaten per day (4.7-4.3, P < 0.001). However, compared to placebo treatment, acarbose had no effect on energy intake, nutrient intakes, or dietary patterns. CONCLUSIONS: In subjects with NIDDM on weight-maintaining diets, long-term acarbose therapy results in a small weight loss, but has no effect on energy or nutrient intakes. The weight loss induced by acarbose may be due partly to reduced doses of concomitant oral agents and insulin and partly to energy loss due to increased colonic fermentation.

Acarbose↗

PubMed1997

Phytochemical analysis of Geigeria alata and Francoeuria crispa essential oils.

Phytochemical analyses of Geigeria alata (Benth. & Hook.) and Francoeuria crispa (Forssk., Cas.) (Asteraceae) essential oils were performed. G. alata oil showed moderate in vitro cytotoxicity (IC50, micrograms/ml against tumor cells; P388: 2.0, A-549: 2.5 and HT-29: 5.0), and also showed weak anti-HIV activity. S-Carvotanacetone, the major component of F. crispa oil (93.0%), was isolated and its structure was elucidated by 2D-NMR analysis.

Animals↗

PubMed1997

Retinoic acid as a therapy for emphysema?

In concert with its action as a morphogen during embryonal development, retinoic acid appears to be able to regenerate lung alveoli in an experimental model of elastase-induced emphysema in rats, thereby inhibiting manifestation of the disease. The application to humans is now an interesting possibility.

Animals↗

PubMed1997

Insulin stimulates cell surface aminopeptidase activity toward vasopressin in adipocytes.

We previously discovered that insulin stimulates the marked translocation of a novel membrane aminopeptidase, designated vp165 for vesicle protein of 165 kDa, to the cell surface in adipocytes. To examine the hypothesis that this enzyme acts on peptide hormones, we assessed the relative affinity of the enzyme for 22 peptide hormones by measuring the inhibitory effect of each on the hydrolysis of a fluorogenic substrate, and we directly assayed the cleavage of four of these. Angiotensin III, angiotensin IV, and Lys-bradykinin bound to the enzyme with half-saturation constants between 20 and 600 nM and were cleaved by vp165. Vasopressin bound with lower affinity but at saturation was cleaved more rapidly. Subsequently, the effect of insulin on the rates of cleavage of 125I-labeled vasopressin by intact 3T3-L1 and rat adipocytes was determined. With both cell types, vasopressin cleavage was stimulated approximately threefold. These findings indicate that a physiological role for vp165 may be the processing of peptide hormones and that insulin could enhance the cleavage of extracellular substrates by eliciting the translocation of vp165 to the cell surface.

3T3 Cells↗

PubMed1997

Factors influencing the estimation of the albumin excretion rate in subjects with diabetes mellitus.

OBJECTIVE: To evaluate alternative methods of calculating the albumin excretion rate (AER) in the absence of complete and accurate patient documentation, since microalbuminuria in patients with diabetes mellitus is associated with serious complications and since patients often make errors in recording the volume and timing of urine collection, making AER calculations inaccurate. DESIGN: Prospective study. SETTING: Recruitment sites, including all native reserves, across southern Alberta. PARTICIPANTS: Population-based group of 1286 subjects with diabetes mellitus participating in the Southern Alberta Study of Diabetic Retinopathy. INTERVENTIONS: Timed AERs were measured in the subjects; urinary albumin concentration was measured by radioimmunoassay. OUTCOME MEASURES: A formula for the prediction of AER was based on the clinical data from the subjects. Several factors were considered in developing the formula: insulin-using status, weight, sex and urine and serum creatinine concentrations. RESULTS: A mathematical model for estimation of the AER was developed; incorporation of insulin use, sex and weight provides a more accurate estimate of AER. According to this model, women typically appear to have a lower AER than men and heavier people appear to have a higher AER than people with lower body weight. CONCLUSIONS: The use of mathematical formulae to calculate the AER provides an accurate estimate of the AER, particularly when data related to the volume and timing of urine collection are missing. These formulae will be valuable in large epidemiologic screening programs.

Alberta↗

PubMed1996

Cytosine-specific chemical probing of DNA using bromide and monoperoxysulfate.

Bromination of cytosine and formation of a piperidine-labile site are observed when two simple salts, KBr and KHSO5, are allowed to react with single-stranded oligodeoxynucleotides. Selectivity for C compared with T, G or A is typically a factor of 4 or more; selectivity for Cs in a single-stranded region such as a C-bulge is nearly a factor of 10 compared with duplex Cs. Low reactivity and little base selectivity are observed using duplex DNA, although increased concentrations of reagents lead to complete degradation of the DNA. The results suggest that these conditions for in situ generation of Br2 constitute a useful tool for examination of the exposure of a non-duplex cytosine base in folded DNA structures.

Bromides↗

PubMed1996

Characterization of the insulin-regulated membrane aminopeptidase in 3T3-L1 adipocytes.

A novel membrane aminopeptidase has been identified as a major protein in vesicles from rat adipocytes containing the glucose transporter isotype Glut4. In this study we have characterized this aminopeptidase, referred to as vp165, in 3T3-L1 adipocytes. The subcellular distributions of vp165 and Glut4 were determined by immunoisolation of vesicles with antibodies against both proteins, by immunofluorescence, and by subcellular fractionation and immunoblotting. Relative amounts of vp165 at the cell surface in basal and insulin-treated cells were assayed by cell surface biotinylation. These experiments showed that vp165 and Glut4 were entirely colocalized and that vp165 increased markedly at the cell surface in response to insulin, in a way similar to Glut4. When intact cells were assayed with a novel, membrane-impermeant fluorogenic substrate for vp165, we found that insulin stimulated aminopeptidase activity at the cell surface. This observation provides direct evidence for the functional consequence of vp165 translocation.

3T3 Cells↗

PubMed1996

Quantitative clinical measure of spasticity in children with cerebral palsy.

OBJECTIVE: This investigation developed an objective measure to quantify the degree of spasticity. DESIGN: Specifications included a single variable that integrated key elements characterizing spasticity: velocity, range of motion, and resistance to passive motion. A dynamometer at a children's hospital quantified the passive resistance of the hamstrings to knee extension for a range of motion at 4 different speeds for the prospective descriptive investigation. PATIENTS: A convenience sample of six children with able bodies and 17 children with spastic diplegic cerebral palsy volunteered. DATA PROCESSING: Torque-angle data were processed to calculate the work done by the machine on the children for each speed and then determine the slope of the work-velocity curves. This slope was considered to be the measure of spasticity and it was hypothesized that children with cerebral palsy would have a greater slope than children with able bodies. An independent test determined whether a significant difference existed between groups (p < .05). RESULTS: Torque-angle data for children with able bodies indicated little change in passive resistance as a function of speed. Similar data for children with cerebral palsy indicated larger resistive torques with increasing speed. Slope from the work-velocity data was close to zero for children with able bodies [.003 J/(degrees/sec)], while the corresponding slope for children with cerebral palsy was approximately 10 times greater [.031 J/(degrees/sec)] and significantly different (p < .05). CONCLUSION: The slope of the work-velocity data integrates three major components characterizing spasticity, it is a single number that can easily be evaluated and interpreted in a clinical setting, and it utilizes a machine that is available at many centers.

Adolescent↗

PubMed1996

The volatile oil composition of fresh and air-dried buds of Cannabis sativa.

The composition of the steam-distilled volatile oil of fresh and air-dried, indoor-grown marijuana was studied by GC/FID and GC/MS. In all, 68 components were detected of which 57 were fully identified. Drying of the plant material had no effect on the qualitative composition of the oil and did not affect the ability of individuals familiar with marijuana smell to recognize the odor.

Cannabis↗

PubMed1996

Neuron-specific enolase as an aid to outcome prediction in head injury.

A statistically significant elevation was observed in serum and CSF neuron-specific enolase (NSE) levels in patients with major head injury, relative to control individuals. No correlation was noted between serum NSE and either APACHE II, Injury Severity Score (ISS), Glasgow Outcome Score (GOS) or Glasgow Coma Scale (GCS). A significant correlation was noted between CSF NSE levels and GCS, but not between CSF NSE and APACHE II, ISS or GOS. Of the patients with major head injury, 100% had NSE CSF levels above the normal level, while 47% had elevated serum NSE levels. In nine patients with major head injury, changes in CSF levels reflected changes in serum NSE levels. In all nine patients, serum NSE decreased to reach normal values, regardless of the outcome as predicted by the GOS. Therefore, while NSE would appear to be a marker of neuronal cell damage, other markers are also essential.

Adult↗

PubMed1996

A new metabolite of retinol: all-trans-4-oxo-retinol as a receptor activator and differentiation agent.

All-trans-4-oxo-retinol, a metabolite of retinol synthesized in mouse embryonal carcinoma F9 cells, is active in inducing differentiation of these cells. It also functions as a ligand of retinoic acid receptors and a transcriptional activator of reporter genes. These findings may dispel the notion that retinoic acids are the only transactivators of retinoid receptor-dependent pathways. However, there are weaknesses that need to be addressed in order to confirm the relevance of this retinol-mediated signaling pathway.

Animals↗

PubMed1996

Retinoic acid response elements as positive and negative regulators of the expression of the homeobox b-1 gene.

Retinoic acid-dependent homeobox Hoxb-1 gene expression offers an unanticipated example of both a positive and a negative transcriptional activity of RA, as exerted at different times during embryogenesis. A paradigm for the transduction of positive and negative signaling is the discovery that retinoic acid response elements (RAREs), positioned in the 3' enhancer and 5' promoter of the Hoxb-1 gene, may function respectively as positive and negative regulators, thereby permitting a diffused (early positive) as well as segmentally specified and limited (late negative) expression of the gene. This molecular action of retinoic acid may provide a mechanism for our understanding of normal embryogenesis and of the interference with this process by ectopic retinoic acid, thereby leading to teratogenesis.

Abnormalities, Drug-Induced↗

PubMed1996

Beta-carotene increases lung cancer incidence in cigarette smokers.

Clinical trials were designed to validate the protective effect of beta-carotene in populations of cigarette smokers at high risk for lung cancer development. Strikingly, an increase in lung cancer resulted following beta-carotene supplementation in two separate studies in Finland and the United States. These trials were conducted without any evidence that beta-carotene prevents lung cancer in animal models.

Aged↗

PubMed1996

Homobotcinolide: a biologically active natural homolog of botcinolide from Botrytis cinerea.

A novel natural product exhibiting biological activity was isolated from a strain of Botrytis cinerea that had infected raspberry fruit (Rubus ideaus). Liquid fermentation and bioassay-directed fractionation of the organism yielded a compound with molecular formula C22H38O8 that is trivially named homobotcinolide. It significantly inhibited etiolated wheat coleoptile growth. Greenhouse-grown bean, corn, and tobacco plants were also affected by exogenous application of homobotcinolide, severe chlorosis and necrosis being exhibited in corn. The compound is a polyhydroxylated nonalactone esterified with 4-hydroxy-2-decenoic acid.

Biological Assay↗

PubMed1996

A role for the disulfide bond spacer region of the Chlamydomonas reinhardtii coupling factor 1 gamma-subunit in redox regulation of ATP synthase.

The gamma-subunit of chloroplast coupling factor 1 contains a disulfide bond which is involved in the redox regulation of the enzyme. In all the sequence plant gamma-subunits this disulfide bond is separated by a five amino acid spacer region. To investigate the regulatory significance of this region genetic transformation experiments were performed with Chlamydomonas reinhardtii. C. reinhardtii strain atpC1 (nitl-305, cw 15, mt-), which does not accumulate the CF1 gamma-subunit polypeptide, was independently transformed with two constructs, each bearing mutations within the disulfide bond spacer region between Cys198 and Cys204 of the gamma-subunit. Successful complementation was confirmed by phenotypic selection, Northern blot analysis, and reverse transcription polymerase chain reaction. Whereas wild-type thylakoid membrane particles catalyze in vitro, PMS-dependent photophosphorylation that is stimulated 2-fold by the addition of DTT, similar particles from each of the mutant strains exhibit rates of ATP synthesis that are independent of DTT. Consistent with these results, wild-type CF1 ATPase activity is stimulated by DTT which is in contrast to the ATPase activities of both the mutant strains which are independent of DTT addition. These results suggest a role of the gamma-subunit disulfide bond spacer region in the redox regulation of chloroplast ATP synthase.

Amino Acid Sequence↗

PubMed1996

A Clinical Informatics Network (CLINT) to support the practice of evidence-based health care.

CLINT, which stands for Clinical Informatics NeTwork, is one of the clinical informatics initiatives in development at McMaster University's Health Information Research Unit. CLINT is a microcomputer-based system of over 60 workstations providing 24 hour availability of a set of clinical information resources to clinicians throughout our teaching hospital. CLINT encompasses three domains: (1) a user adaptable clinician-computer interface, (2) unique evidence-based health care content, and (3) automated data collection and viewing tools. An objective of the CLINT project is to determine CLINT's impact on the practice of health care. Early analysis of our data has revealed that over the past year, there has been widespread use of CLINT by clinicians from all clinical domains. Our next task is to evaluate CLINT's usefulness.

Clinical Medicine↗

PubMed1995

Retinoic acid and methotrexate specifically increase PHA-E-lectin binding to a 67-kDa glycoprotein in LA-N-1 human neuroblastoma cells.

Retinoic acid (RA) decreased growth and increased morphologic differentiation of human neuroblastoma LA-N-1 cells. These phenomena correlated with a specific enhancement of PHA-E lectin binding to a glycoprotein of MW 67 kDa (gp67). Gp67 was found susceptible to N-glycanase and displayed BSA binding by affinity chromatography analysis. The chemotherapeutic agent methotrexate (MTX) also reduced growth and induced differentiation of LA-N-1 cells. In addition, the cells responded to MTX as well as to doxorubicin by a marked increase in PHA-E binding to gp67. We conclude that reduced growth and induction of morphological differentiation of LA-N-1 cells correlates with increased binding of PHA-E to gp67.

Amidohydrolases↗

PubMed1995

Role of the Chlamydomonas reinhardtii coupling factor 1 gamma-subunit cysteine bridge in the regulation of ATP synthase.

The gamma-subunit of coupling factor 1 (CF1) contains a cysteine bridge that is thought to be involved in the redox control of enzymatic activity. In order to test the regulatory significance of this disulfide bond, genetic transformation experiments with Chlamydomonas reinhardtii were performed. C. reinhardtii strain atpC1 (nit1-305, cw 15, mt-), which is null for the gamma-subunit, was transformed and complemented with gamma-subunit constructs containing amino acid substitutions localized to the cysteine bridge between Cys198 and Cys204. Successful complementation was confirmed by phenotypic selection, Northern blot analysis, reverse transcription polymerase chain reaction, and cDNA sequencing. CF1 ATPase activities of the soluble enzymes were measured in the presence and absence of dithiothreitol (DTT). Mutant CF1 enzymes showed no effect of DTT although increased activity was observed for the wild-type enzyme. In vitro, phenazine methosulfate-dependent photophosphorylation assays revealed that wild-type CF1 exhibits a 2-fold stimulation in the presence of 25 mM DTT, whereas each of the mutant enzymes has activities that are DTT-independent. Growth measurements indicated that despite the absence of a regulatory disulfide/dithiol, the mutant strains grew with the same kinetics as wild type. This study provides evidence to illustrate the involvement of the gamma-subunit in the redox regulation of ATP synthesis in vivo. This work is also the first demonstration in C. reinhardtii of stable nuclear transformation using mutated genes to complement a known defect.

Animals↗