Search PubMed⌕ Search

Biomedical subjects

S A Ross

Publications and source records attributed to S A Ross.

At least 91 records · Page 5Linked to original sources

Comparative studies of metabolism of 4-desmethyl, 4-monomethyl and 4,4-dimethyl sterols in Manduca sexta.

To investigate the metabolism and possible deleterious effects of 4-methyl and 4,4-dimethyl steroids in Manduca sexta, the 4,4-dimethyl sterols lanosterol and cycloartenol, the 4-methyl sterol obtusifoliol and the 4,4-dimethyl pentacyclic triterpenoid alpha-amyrin were fed in an artificial agar-based diet at various concentrations. Utilization and metabolism of these four compounds were compared with sitosterol, stigmasterol, brassicasterol, ergosterol and 24-methylenecholesterol, 24-alkyl sterols that are readily dealkylated and converted to cholesterol in Manduca and in most phytophagous insects. None of the 4-methylated compounds significantly inhibited development except at very high dietary concentrations. The delta 24-bonds of lanosterol and cycloartenol were effectively reduced by the Manduca delta 24-sterol reductase enzyme, as is the delta 24-bond of desmosterol which, in most phytophagous insects, is an intermediate in the conversion of sitosterol, stigmasterol and other C28 and C29 phytosterols to cholesterol. On the other hand, the 24-methylene substituent of obtusifoliol was not dealkylated. Each of the 4-desmethyl C28 and C29 sterols was readily converted to cholesterol, and a significant amount of 7-dehydrocholesterol was derived from ergosterol metabolism. The reason for the differences in substrate specificity of these sterols is not clear, but the information may be useful in the development of new, specific, mechanism-based inhibitors of sterol metabolism.

Animals↗

One-year acarbose treatment raises fasting serum acetate in diabetic patients.

alpha-Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1-year, double-blind, placebo-controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 +/- 5 vs 71 +/- 4 mumoll-1) or glycosylated haemoglobin (HbA1C; 7.2 +/- 0.3 vs 7.4 +/- 0.3%). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 +/- 4 vs 2 +/- 3 mumoll-1 (p < 0.02) and reduced HbA1C by -0.59 +/- 0.16 vs -0.13 +/- 0.20% (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non-esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1C, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1-year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side-effects or changes in blood glucose control or serum lipids.

Acarbose↗

Effects of enalapril and nitrendipine on the excretion of epidermal growth factor and albumin in hypertensive NIDDM patients.

OBJECTIVE: To compare the effect of the antihypertensive drugs nitrendipine and enalapril on the excretion of epidermal growth factor (EGF) and albumin in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) subjects. RESEARCH DESIGN AND METHODS: After a 4-week washout period, mildly hypertensive (systolic blood pressure [sBP] > or = 140 mmHg and/or diastolic blood pressure [dBP] > or = 90 mmHg) NIDDM patients with albuminuria (15-200 micrograms/min) were randomized into an 8-month-long therapy with either nitrendipine (n = 11) or enalapril (n = 10). Blood pressure, EGF, and microalbumin excretion were measured at baseline and throughout the treatment period. RESULTS: A significant fall in sBP was noticed in the enalapril group and in dBP in the nitrendipine group. In the enalapril group, EGF excretion progressively increased from 188 to 214 nmol/mmol creatinine after 6 weeks and to 274 after 8 months of therapy (P = 0.03). There was a significant fall in albumin excretion while patients were on enalapril, but in the nitrendipine group, neither albuminuria nor EGF excretion changed significantly. There was no correlation of improved EGF excretion with a decrease in albuminuria or BP. CONCLUSIONS: The angiotensin-converting enzyme inhibitor enalapril has been effective in decreasing albumin and increasing EGF excretion. Measurement of urinary EGF may provide a new valuable index of renal function.

Adult↗

Persistence and pain. Women and healing in the Gospel offer insights to Catholic healthcare providers.

Scripture can enlighten us on the difficult times Catholic healthcare providers face today. Two stories from Mark's Gospel offer helpful insights to persons engaged in the institutional context of healing. These stories are of the woman with the "flow of blood" (Mk 5:25-34) and of the Syro-Phoenician woman (Mk 7:24-30). The women were determined to receive the healing they needed. They went for it, and got it, despite considerable obstacles. I suggest five insights we might draw from these two narratives of healing. These women were persistent. Sometimes it takes a great deal of persistence to find God in all the ordinariness, the numbing everydayness we encounter in our daily work. Like these women, the healing you seek for those you care for takes place in a hostile world. Catholic healthcare institutions themselves face some hostility from other institutions. The stories remind us that we must feel our own pain and that of others. The capacity to hurt and to feel the hurt of others helps us persevere in the face of this hostile world. Both women did what others could--and should--have done for them. Each of these women found in herself a place of strength she could draw on. This place of strength is the presence of God. I hope that Catholic healthcare providers are aware of God's presence in them and in those to whom they minister. I hope they work against the "quick-fix" mentality of much of modern healthcare and modern consumerism. Catholic healthcare recognizes the sacramentality of life on earth, struggling always to find the God who is revealed where we least expect her.

Catholicism↗

Clinical experience with acarbose: results of a Canadian multicentre study.

Current therapeutic options for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) focus on regimens that primarily lower fasting blood glucose concentrations. In several short-term studies, the alpha-glucosidase inhibitor, acarbose, has been reported to significantly lower post-prandial plasma glucose levels as well as HbA1c. The primary objective of this present study was to assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic control. Over a 1-y period, acarbose or placebo was administered to 4 groups of patients: those managed by diet only, diet and sulfonylurea, diet and biguanide, and diet and insulin. In all treatment groups, the addition of acarbose resulted in significant reductions in postprandial blood glucose levels. Additionally, HbA1C was significantly lower after 12 months of acarbose therapy, compared with placebo, in all groups except the diet and insulin group. The addition of acarbose consequently expands the armamentarium available to clinicians for the optimization of glycemic control in patients with NIDDM.

Acarbose↗

The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial.

OBJECTIVE: To evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving glycemic control in patients with non-insulin-dependent diabetes mellitus. DESIGN: A 1-year, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Seven university-affiliated, community-based, tertiary care diabetes clinics. PATIENTS: 354 patients with non-insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316). MEASUREMENTS: At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured. RESULTS: Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4 mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels. CONCLUSIONS: Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication.

Acarbose↗

Retinoic acid enhances adhesiveness, laminin and integrin beta 1 synthesis, and retinoic acid receptor expression in F9 teratocarcinoma cells.

The teratocarcinoma-derived F9 cells respond to retinoic acid (RA) and RA plus dibutyrylcyclic adenosine monophosphate (dcAMP) by differentiating into endoderm cells, which elaborate a laminin and type IV collagen-rich matrix. We found that the induction of differentiation is accompanied by a small but consistent increase in cell adhesiveness to a variety of substrates, including laminin. Therefore we investigated biochemical mechanisms involved in this phenomenon. Endoglycosidase treatment showed that laminin contains complex and hybrid oligosaccharide structures. RA enhanced general biosynthesis of laminin without a specific increase in galactose incorporation: this sugar was mainly in polylactosamine structures in the A chain of laminin and as terminal galactose alpha 1,3 galactose in the B chain. Laminin receptor analysis showed that RA decreased laminin binding protein-37 (LBP-37) but increased the amount of beta 1 integrin, suggesting the involvement of beta 1 integrin in the attachment process. Northern blot analysis showed increased expression of retinoid receptors within hours of RA exposure. These studies demonstrate that RA increases cell to substrate interactions by increasing the biosynthesis of laminin and beta 1 integrin. These effects are most likely subsequent to the RA-induced biosynthesis of the retinoid receptors.

Cell Adhesion↗

Determinants of diet glycemic index calculated retrospectively from diet records of 342 individuals with non-insulin-dependent diabetes mellitus.

Controlled trials have shown that a diet with a low glycemic index improves blood glucose and lipid control in patients with diabetes. To study the distribution and determinants of diet glycemic index, we obtained two 3-d diet records from 342 free-living subjects with non-insulin-dependent diabetes. Mean +/- SD 24-h intakes were as follows: energy, 7170 +/- 1890 kJ; fat, 33.6 +/- 6.5% of energy; protein, 20.1 +/- 3.2% of energy; available carbohydrate, 45.3 +/- 7.2% of energy; and dietary fiber, 17.2 +/- 6.4 g. Diet glycemic index values (85.4 +/- 4.55, range, 70-97.8) were normally distributed. Diet glycemic index was inversely associated with intake of simple sugars, whether expressed in grams (r = -0.426), percent of energy (r = -0.446), or percent of carbohydrate (r = -0.453, P < 0.001). By step-wise-multiple-linear regression, grams carbohydrate and percent protein were also independently related to diet glycemic index. Differences in diet glycemic index between men and women, and between subjects on different types of diabetes therapy were explained by differences in intake of simple sugars.

Blood Glucose↗

The presence of tumour necrosis factor in CSF and plasma after severe head injury.

In a cohort of victims of traumatic brain injury, 18 out of 50 patients had a plasma tumour necrosis factor (TNF) concentration above 2 pg/ml within 24 h of injury (mean 12.19, SD 45.96 pg/ml). Twenty-six had CSF samples available of which 17 demonstrated TNF concentrations above 1 pg/ml (mean 3.98, SD 3.61 pg/ml). We conclude that traumatized brain parenchyma is a significant source of TNF activity and implicate the cytokine in cellular metabolic derangements following head injury.

Adolescent↗

A novel sialidase which releases 2,7-anhydro-alpha-N-acetylneuraminic acid from sialoglycoconjugates.

The leech (Macrobdella decora) was found to contain two sialic acid-cleaving enzymes: an ordinary sialidase and a novel sialic acid-cleaving enzyme. This novel enzyme released 2,7-anhydro-alpha-N-acetylneuraminic acid (Neu2,7-anhydro5Ac) instead of alpha-N-acetylneuraminic acid (Neu5Ac) from 4-methylumbelliferyl-Neu5Ac, glycoproteins, and gangliosides. We have partially purified this novel sialidase from M. decora. We have also isolated Neu2,7-anhydro5Ac released from 4-methylumelliferyl-Neu5Ac and whale nasal keratan sulfate in pure form. The novel sialidase produced Neu2,7-anhydro5Ac only from sialoglycoconjugates, but not from free Neu5Ac. The structure of Neu2,7-anhydro5Ac produced by the novel sialidase was established by chemical analysis, mass spectrometry, and NMR spectroscopy. NMR analysis showed that instead of the original 2C5 conformation, the pyranose ring of Neu2,7-anhydro5Ac was in the 5C2 conformation, which makes the formation of the 2,7-anhydro bridge possible.

Animals↗

Phosphorylation of the polymeric immunoglobulin receptor required for its efficient transcytosis.

The endosomal compartment of polarized epithelial cells is a major crossroads for membrane traffic. Proteins entering this compartment from the cell surface are sorted for transport to one of several destinations: recycling to the original cell surface, targeting to lysosomes for degradation, or transcytosis to the opposite surface. The polymeric immunoglobulin receptor (pIgR), which is normally transcytosed from the basolateral to the apical surface, was used as a model to dissect the signals that mediate this sorting event. When exogenous receptor was expressed in Madin-Darby Canine Kidney (MDCK) cells, it was shown that phosphorylation of pIgR at the serine residue at position 664 is required for efficient transcytosis. Replacement of this serine with alanine generated a receptor that is transcytosed only slowly, and appears to be recycled. Conversely, substitution with aspartic acid (which mimics the negative charge of the phosphate group) results in rapid transcytosis. It was concluded that phosphorylation is the signal that directs the pIgR from the endosome into the transcytotic pathway.

Alanine↗

Recreational sun exposure in Puerto Rico: trends and cancer risk awareness.

Persons who sunbathe or engage in other activities at the beach are exposed to large amounts of UV radiation. Four hundred seven adults who visited the beaches of Puerto Rico were surveyed to determine their knowledge about the risks of sun exposure and to evaluate sunscreen use. The group consisted of 195 year-round Puerto Rican residents and 212 tourists. Ninety-five percent believed that the sun can cause skin cancer, although only half of the subset who lived all year in Puerto Rico believed that they personally received enough exposure to be at risk. The majority of the group (83%) understood the meaning of the sun protection factor numbers, although 35% used either nothing or a nonscreening oil. Half of Puerto Rican residents rarely or never used sunscreen protection while sunbathing. When sunscreen was used, the most important factor sought was given as sun protection factor (64%), followed by a perceived ability to aid in tanning (26%).

Adult↗

Immediate heparinisation and surgery in the management of saddle embolism.

Twenty-six patients (age range 40-88 years) with saddle embolism, representing 11% of cases of peripheral embolism, were treated during an 8-year period. A proven intra-cardiac source, including atrial fibrillation and post-infarction mural thrombosis, was observed in 22 cases (85%). The ambiguities in the clinical presentation of saddle embolism were sometimes responsible for delayed recognition. On confirmation of the diagnosis an IV heparin regime was immediately commenced followed by surgery. Our practice of initiating treatment of saddle embolism with immediate systemic heparin infusion resembles that of Blaisdell et al. In contrast, we also advocate a policy of early surgical intervention. Bilateral trans-femoral explorations were undertaken in 21 cases and direct aorto-iliac procedures in five cases. Recurrent embolism occurred in 27% of cases despite postoperative anticoagulant therapy. An overall limb salvage rate of 88.5% was recorded. The postoperative mortality of 30% was accounted for by primary cardiac disease and multiple organ failure. The influence of multiple and recurrent embolism and cardiac instability on the eventual outcome is signifcant. A policy of early systemic heparin therapy and surgery in the management of saddle embolism, enhances limb survival and prevents renal failure.

Adult↗

Spirochetal forms in the dermal lesions of morphea and lichen sclerosus et atrophicus.

Morphea and lichen sclerosus et atrophicus are cutaneous diseases that are manifest by an early edematous stage, followed later by sclerosis and atrophy. They share features with acrodermatitis chronica atrophicans and erythema chronicum migrans, diseases that have been linked to infection by the spirochete Borrelia burgdorferi. A modified silver stain was used to identify the presence of spirochetes in skin biopsy specimens of patients with morphea and lichen sclerosus et atrophicus. Spirochetal forms were identified in the lesional skin of 10 of 25 patients with morphea and in 10 of 21 cases of lichen sclerosus et atrophicus. These spiral forms of bacteria had a significant tendency to occur in early and fully developed lesions of morphea and in early lesions of lichen sclerosus et atrophicus, whereas they tended to be absent in lesions demonstrating late pathological changes.

Atrophy↗

Immunologic studies of patients with diabetes mellitus who have received long term insulin therapy: lymphocyte reactivity to insulin is correlated with impaired immunoglobulin secretion in vitro.

To investigate the influence of chronic antigen stimulation on immune response, 31 diabetics who had been treated from 4 to 39 years with various types of insulin were studied. Of the 31 patients, 22 had an elevated lymphocyte blastogenic response to insulin (beef/pork regular or protamine containing types). There were approximately equal numbers of patients with insulin dependent and noninsulin dependent diabetes whose lymphocytes reacted to the insulin. Of 24 patients who were also studied for the ability of their lymphocytes to secrete immunoglobulin secondary to pokeweed mitogen, 14 were significantly depressed compared to normal controls. Depressed responses tended to occur in both IgG and IgM secretion. Average immunoglobulin secretion of the diabetics' lymphocytes was 1843 and 2667 ng/ml, whereas for the normal subjects, the lymphocyte secretion was 3175 and 6013 ng/ml of IgG and IgM, respectively. (The normal secretion was based on the testing of 64 normal individuals.) Interestingly, 13 of 14 patients with impaired immunoglobulin secretion had a positive lymphocyte proliferative response to insulin (P less than 0.01). This statistically significant correlation between lymphocyte proliferative response to insulin and impaired polyclonal immunoglobulin secretion suggests the possibility that chronic antigen stimulation by insulin alters the normal immune response.

Antibody Formation↗