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Biomedical subjects

J M Ross

Publications and source records attributed to J M Ross.

At least 37 records · Page 2Linked to original sources
PubMed1998

Identification of distinct metabolic pools of aggrecan and their relationship to type VI collagen in the chondrons of mature bovine articular cartilage explants.

The metabolism and distribution of newly synthesized aggrecan present in the extracellular matrix of intact explant cultures of mature articular cartilage was investigated with respect to type VI collagen-stained chondrons. Using biochemical, autoradiographical and novel confocal immunohistochemical techniques it was shown that aggrecan exists as a number of distinct pools that are located within the extracellular matrix of the tissue. The first was identified as a pool of high specific radioactivity, much of which appeared in the medium one day after incubation with radiolabeled sulfate. Of the radiolabeled aggrecan remaining within the extracellular matrix, three pools were differentiated on the basis of time and location within the extracellular matrix. One pool was resident within the pericellular microenvironment associated with the chondron, one migrated into the territorial matrix adjacent to the chondron and one was sequestered long term in the interterritorial matrix. Analysis of the kinetics of loss of radiolabeled aggrecan macromolecules present in the region of matrix defined by the chondron suggests that this pool rapidly turns over and is a precursor to the pools of aggrecan present in the territorial and interterritorial matrix. There were marked differences in the distribution of newly synthesized aggrecan present in these regions of the extracellular matrix in explant cultures maintained with or without fetal calf serum. In the absence of serum, more of the newly synthesized aggrecan moved into the territorial and interterritorial matrix indicating that the presence of serum in the culture medium influenced the tissue distribution of aggrecan. This work indicates that the pericellular microenvironment of the chondron plays an important role in the retention and maturation of aggrecan prior to the sequestration of aggrecan complexes into the functional load bearing matrices of adult articular cartilage.

Aggrecans↗
PubMed1998

Fibrillin containing elastic microfibrils support platelet adhesion under dynamic shear conditions.

The vascular subendothelium contains macromolecular structures called microfibrils. Type VI collagen is one protein found in microfibrils that supports platelet adhesion and aggregation and we have previously evaluated the roles of platelet receptors and vWf involved in these processes under physiological shear conditions. Here we investigate the ability of fibrillin containing elastic microfibrils to support mural thrombus formation. Our results show that elastic microfibril surfaces support platelet adhesion under low shear conditions at a level similar to collagen VI tetramers. However, the degree of aggregation on the elastic microfibril surface is much higher. Both adhesion and aggregation were shown to be mediated by the GPIIb-IIIa platelet receptor. Elastic microfibrils do not support the formation of mural thrombi under high shear conditions. These results suggest roles for both collagen VI and fibrillin containing elastic microfibrils in modulating the platelet response to blood vessel injury.

Actin Cytoskeleton↗
PubMed1997

Double-label immunofluorescence study of glutamic acid decarboxylase in the fetal and adult ovine pancreas by light and confocal microscopy: evidence for predominant beta-cell coexpression.

Glutamic acid decarboxylase (GAD) is present in the central nervous system and in several nonneuronal tissues including the pancreatic islets. There are two isoforms with molecular weights of 65 kDa (GAD65) and 67 kDa (GAD67). The cellular specificity of the two molecular forms of GAD and their levels within the mammalian islets may be species-dependent, being coexpressed in both beta and in non-beta cells. We have examined the ovine pancreas, from the adult and fetal stages of late gestation, for the expression of GAD65 within the islet cells by double-label immunofluorescence light and confocal microscopy. In the adult tissue, GAD65 was colocalized in a majority of the beta cells (> 95%), with only a few glucagon and somatostatin cells (< 5%) showing immunolocalization. During the fetal stages GAD65 also showed a similar predominant beta-cell coexpression. The enzyme was also detected in a few fetal glucagon (< 5%) but not somatostatin cells. In the degenerating large fetal islets, GAD65 was also observed in the majority of the residual beta cells. These results demonstrate that in the ovine pancreas GAD65 is expressed during fetal development and is predominantly beta-cell-restricted. This pattern of expression is maintained during adult life. However, the physiological role of pancreatic GAD and/or its biosynthetic product, gamma-aminobutyric acid, in islet function in the sheep and in other ruminants remains unclear.

Aging↗
PubMed1997

The significance of subendothelial von Willebrand factor.

von Willebrand factor (vWf) serves to bridge between receptors on the platelet cytoplasmic membrane and the extracellular matrix. In addition to circulating in plasma, vWf is deposited into the extracellular matrix of the subendothelium where it is associated with type VI collagen microfibrils, but not with the elastin-associated microfibrils which are present in the deepest portion of the subendothelium at the zone of the internal elastic lamina. The reaction of platelets to type VI collagen in flow systems is qualitatively different from the shear rate dependent adhesion and aggregation response which is observed with fibrillar type I collagen, exhibiting a response only at low shear rates. The adhesion response to type VI collagen is dependent upon vWf, GP Ib and the GP IIb-IIIa complex. Platelets exposed to purified fibrillin-containing elastin-associated microfibrils adhere and aggregate at low shear rates; this response appears to involve GP IIb-IIIa but not GP Ib. The data are consistent with the hypothesis that type VI collagen is a physiologically relevant binding site for vWf in subendothelium.

Animals↗
PubMed1996

General practice training in Uganda. Part 1: Setting, personnel, and facilities.

Making lasting changes to health care in developing countries is a challenge to industrialized nations. This two-part article outlines how a general practice training project was established in Uganda to prepare postgraduate students to work in rural hospitals. Part 1 covers the setting, those involved, and the facilities available to launch such a project.

Canada↗
PubMed1996

General practice training in Uganda. Part 2: Training program and clinical practice.

Enabling a developing country to become self-sufficient in health care is a major feat. This two-part article outlines how a general practice training project was established in Uganda to prepare postgraduate students to work in rural hospitals. The first part looked at the setting, personnel, and facilities. Part 2 outlines the curricula and clinical practice.

Canada↗
PubMed1995

Platelet adhesion and aggregation on human type VI collagen surfaces under physiological flow conditions.

Type VI collagen is a subendothelial constituent that binds von Willebrand factor (vWF) and platelets. The interaction of platelets with type VI collagen and the roles of platelet glycoprotein (GP) receptors and vWF were studied under flow conditions using epi-fluorescent videomicroscopy coupled with digital image processing. We found that surface coverage was less than 6% on collagen VI at a relatively high-wall shear rate (1,000 s-1) and was approximately 60% at a low-wall shear rate (100 s-1). The molecular mechanisms involved in low-shear platelet binding were studied using monoclonal antibodies to platelet GPIb and GPIIb-IIIa, and polymeric aurin tricarboxylic acid. Anti-GPIIb-IIIa was the most effective in eliminating adhesion (surface coverage, 0.8%), followed by anti-GPIb (4.3%), and ATA (12.6%). Experiments with von Willebrand disease blood indicate that vWF is involved in platelet adhesion to collagen VI at 100 s-1. In the absence of vWF, there may be direct binding of platelet GPIIb-IIIa complexes to collagen VI. Adhesion and aggregation on collagen VI are different in shear rate dependence from collagen I. Our results suggest a possible role for collagen VI and vWF in platelet adhesion and aggregation in vascular regions with low shear rates.

Animals↗
PubMed1995

The decision to enter a randomized trial of tamoxifen for the prevention of breast cancer in healthy women: an analysis of the tradeoffs.

OBJECTIVE: Interest in breast cancer prevention has led to the Breast Cancer Prevention Trial (BCPT), a controversial randomized trial of tamoxifen for women at risk for breast cancer. The goal of our study was to determine whether the potential benefits of enrolling in the randomized trial of prophylactic tamoxifen outweigh the potential risks. METHODS: We used a decision analytic model based on the available data on tamoxifen treatment benefits in women with breast cancer and extrapolated to its use in healthy women. RESULTS: For a 50-year-old woman with a breast cancer risk twice that of the average woman her age, the BCPT offers an increase in life expectancy of about 9 days, a gain that is modest compared with other health interventions. For women ages 35 to 60 who meet the minimum risk of breast cancer for trial eligibility, the trial increases life expectancy by about 8 or 9 days. Assumptions about the effect of tamoxifen on the incidence of endometrial and liver cancer and on quality of life associated with tamoxifen did not alter our findings. CONCLUSIONS: Advocates and opponents of the BCPT should temper their concerns to reflect the modest absolute benefits and harms associated with the trial. Although women at increased risk for breast cancer should be aware of the likely overall benefit associated with entry into the trial, for most women, entry into the BCPT is unlikely to alter substantially their length of life, in either a beneficial or harmful manner.

Adult↗
PubMed1995

Ploidy and Tn-antigen expression in the detection of transitional cell neoplasia in non-tumour-bearing patients.

OBJECTIVE: To study the effectiveness of combining DNA ploidy and the blood-group related membrane antigen Tn as bladder tumour markers which have been individually associated with high tumour grade and poor prognosis. In particular to (i) determine whether use of these two markers would improve tumour detection compared with either alone, particularly of high grade disease and (ii) determine whether intermediate rates of marker expression would occur in bladder cancer patients with no current tumour compared with those with a tumour and a control group with benign prostatic hypertrophy. PATIENTS AND METHODS: A total of 102 patients undergoing cystoscopic monitoring for either benign prostatic hyperplasia (BPH) or for transitional cell carcinoma (TCC) at the Repatriation Hospital and Flinders Medical Centre were included in the study. The patients comprised three study groups, those with BPH (n = 37), with TCC but no tumour present (n = 38) and those with TCC and a tumour present at cystoscopy (n = 27). Exfoliated cells obtained from bladder washings at cystoscopy were double-labelled using a monoclonal antibody to the Tn antigen and a DNA stain, propidium iodide and examined by flow cytometry. RESULTS: Rates of marker expression in 27 patients with tumours were 30% for Tn antigen, 30% for aneuploidy and 48% for either marker. Marker expression was strongly associated with tumour grade, with no expression at grade 1, 38% (3/8) tumours at grade 2 and 90% (9/10) at grade 3. In patients with a history of bladder tumours but no current tumour, rates were intermediate (30%) compared with patients with current transitional cell carcinoma (42%) and control patients (19%). CONCLUSION: The use of Tn antigen combined with DNA flow cytometry can increase tumour detection, particularly of high grade, aggressive disease. Gradation of expression of these markers across patient groups at increasing risk of a tumour, with intermediate expression in patients with no current tumour, suggests that marker expression may be detecting a preneoplastic stage of the disease, which is not possible with cytology. Given two parallel disease processes for superficial papillary and for high grade disease with invasive potential, the expression of high grade tumour markers in cells from cystoscopically normal bladders may represent a pre-clinical stage of aggressive disease. The identification of patients at risk of invasive disease using combinations of tumour markers may offer advantages in clinical management, particularly when no tumour is present and therefore no histopathological assessment is made.

Aged↗
PubMed1993

Mitogen-activated Ca++ channels in human B lymphocytes.

Two complementary experimental methods have been used to examine mitogen-induced transmembrane conductances in human B cells using the Daudi cell line as a model for human B cell activation. Spectrofluorometry was used to investigate mitogen-induced changes in [Ca++]i and transmembrane potential. Activation of human B cells with anti-mu antibodies resulted in a biphasic rise in [Ca++]i, the second phase being mediated by the influx of extracellular Ca++. Ca++ influx was inhibited by high [K+]e, suggesting that this influx was transmembrane potential sensitive. Membrane currents of Daudi cells were investigated using voltage clamp techniques. Before mitogenic stimulation, the cells were electrically quiet. Within several minutes of the addition of anti-mu antibodies to the bath solution, inward currents were observed at negative voltages. Whole-cell currents changed instantly with voltage steps and were transmembrane potential sensitive in that at potentials more positive than -40 mV no currents were detectable. A similar conductance was also activated by the introduction of IP3 into the intracellular solution, suggesting that IP3 generation after surface IgM crosslinking is involved in the activation of this conductance. Both anti-mu and IP3 induced currents were blocked by 1 mM La , which is known to block Ca++ channels. These results strongly support the presence of membrane Ca++ channels in human B cells that function in the early stages of activation. Changes in transmembrane potential appear to be important in regulating Ca++ influx. These mechanisms work in concert to regulate the level of [Ca++]i during the early phases of human B cell activation.

B-Lymphocytes↗
PubMed1993

The framing effect of relative and absolute risk.

OBJECTIVE: To test whether a patient's perception of benefit is influenced by whether the benefit is presented in relative or absolute terms. DESIGN: Questionnaire-based study. SETTING: A general medicine outpatient clinic at a rural tertiary care center associated with a medical school. PATIENTS: 470 of 511 consecutive patients who agreed to answer a questionnaire while waiting for their clinic visit. Mean age was 49.1 years, 62.1% were female, and 51.9% had at least one year of education beyond high school. MAIN OUTCOME MEASURES: Patient response to the choice of two equally efficacious medications for the management of a hypothetical serious disease. The benefit of one medication was stated in relative terms, the other in absolute terms. Patients could choose either medication alone, indicate indifference to the choice of medication, or choose not to answer. MAIN RESULTS: 56.8% of the patients chose the medication whose benefit was in relative terms. 14.7% chose the medication whose benefit was in absolute terms. Only 15.5% were indifferent to the choice of medication. The patients preferred the medication whose benefit was in relative terms across a wide range of ages and educational levels. Further questioning suggested that the patients thought benefit was greater when expressed in relative terms because they ignored the underlying risk of disease and assumed it was one. CONCLUSIONS: The "framing" of benefit (or risk) in relative versus absolute terms may have a major influence on patient preference.

Adolescent↗
PubMed1992

Endoscopic detection and therapy of colonic actinomycosis.

Abdominal actinomycosis is a disease that is difficult to diagnose nonoperatively. Usual manifestations are abscesses and draining sinus tracts. Treatment is typically surgical and requires prolonged intravenous antibiotics. Presented is a patient who underwent surveillance colonoscopy after resection for colon carcinoma. Diagnosis of colonic actinomycosis and subsequent resolution was demonstrated endoscopically after lengthy oral penicillin therapy (2 g/day for 1 yr). This case documents that resection may not be necessary to effect cure of abdominal actinomycosis.

Actinomycosis↗
PubMed1991

Primary squamous cell carcinoma of a gastric remnant.

A 77-yr-old male developed primary gastric squamous cell carcinoma 33 yr after gastric resection for peptic ulcer disease. At the time of diagnosis, he was being endoscopically followed for large irregular stomal polyps. Infiltrating squamous cell carcinoma with focal keratinization and stomal polypoid hypertrophic gastritis was found. Previous reports describe adenocarcinoma and adenosquamous carcinoma in gastric remnants. There are various theories as to how such a tumor may arise in this setting.

Aged↗