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Biomedical subjects

R Irwin

Publications and source records attributed to R Irwin.

At least 19 recordsLinked to original sources
PubMed2007

Prolyl-hydroxylase inhibition and HIF activation in osteoblasts promotes an adipocytic phenotype.

Bone is a dynamic environment where cells sense and adapt to changes in nutrient and oxygen availability. Conditions associated with hypoxia in bone are also associated with bone loss. In vitro hypoxia (2% oxygen) alters gene expression in osteoblasts and osteocytes and induces cellular changes including the upregulation of hypoxia inducible factor (HIF) levels. Our studies show that osteoblasts respond to hypoxia (2% oxygen) by enhancing expression of genes associated with adipocyte/lipogenesis phenotype (C/EBPbeta, PPARgamma2, and aP2) and by suppressing expression of genes associated with osteoblast differentiation (alkaline phosphatase, AP). Hypoxia increased HIF protein levels, hypoxic response element (HRE) binding, and HRE-reporter activity. We also demonstrate that prolyl-hydroxylases 2 and 3 (PHD2, PHD3), one of the major factors coordinating HIF degradation under normoxic but not hypoxic conditions, are induced in osteoblasts under hypoxic conditions. To further determine the contribution of PHDs and upregulated HIF activity in modulating osteoblast phenotype, we treated osteoblasts with a PHD inhibitor, dimethyloxaloylglycine (DMOG), and maintained cells under normoxic conditions. Similar to hypoxic conditions, HRE reporter activity was increased and adipogenic gene expression was increased while osteoblastic genes were suppressed. Taken together, our findings indicate a role for PHDs and HIFs in the regulation of osteoblast phenotype.

3T3 Cells↗
PubMed2006

Epithelioid hemangioendothelioma mimicking a nerve sheath tumor clinically and on MR imaging.

Epithelioid hemangioendothelioma is a tumor of the soft tissues arising from the vascular endothelium. It is considered an intermediate grade malignancy. A 42-year-old female patient presented with pain and tingling down her right arm and a mass at the right medial upper extremity. MRI revealed an oblong mass along the course of the neurovascular bundle. Given the clinical and MR findings, a nerve sheath tumor was suspected. At surgery, the mass was adherent to both the brachial artery medially and the median nerve posteriorly. Pathology revealed epithelioid hemangioendothelioma. The imaging characteristics of epithelioid hemangioendothelioma on ultrasound, CT, and MRI are reviewed. Epithelioid hemangioendothelioma can mimic a nerve sheath tumor clinically and radiologically and should be considered in the differential diagnosis of tumors involving or adjacent to a neurovascular bundle.

Adult↗
PubMed2005

Hepatocyte growth factor (HGF) adsorption kinetics and enhancement of osteoblast differentiation on hydroxyapatite surfaces.

Hepatocyte growth factor (HGF) is a growth factor that promotes angiogenesis (tissue vascularization), cell motility, and cell differentiation, making it a potentially beneficial coating for bone implants. However, very little is known about maximizing HGF attachment to surfaces of tissue-engineered scaffolds. Here, we examine methods and kinetics of HGF adsorption onto a dense hydroxyapatite (HA) surface (used in bone implants) and determine the influence of HGF coating on osteoblast phenotype/differentiation. We demonstrate that incubating HA with HGF in solution (and not allowing the solution to dry) resulted in maximal surface adsorption that was not enhanced by extending incubation time beyond 2 days. Daily shaking of the coated HA surface did not remove adsorbed HGF. To further examine the effect of HA on osteoblast phenotype, MC3T3-E1 preosteoblasts were seeded onto HA or HGF-HA surfaces. Gene expression analyses indicate that HGF coating enhanced osteoblast differentiation as demonstrated by increased runx2 (a transcription factor important for osteoblast lineage and differentiation), alkaline phosphatase (marker of mid stage differentiation) and osteocalcin (marker of late stage differentiation) mRNA levels. Taken together, our results demonstrate that HGF can serve as an excellent bone implant coating based on its ability to readily adsorb to HA surfaces, maintain integrity over time, and enhance osteoblast differentiation.

3T3 Cells↗
PubMed2005

Reflections on uncertainty in risk assessment and risk management by the Society of Environmental Toxicology and Chemistry (SETAC) precautionary principle workgroup.

Quantitative uncertainty assessments and the distribution of risk are under scrutiny and significant criticism has been made of null hypothesis testing when careful consideration of Type I (false positive) and II (false negative) error rates have not been taken into account. An alternative method, equivalence testing, is discussed yielding more transparency and potentially more precaution in the quantifiable uncertainty assessments. With thousands of chemicals needing regulation in the near future and low public trust in the regulatory process, decision models are required with transparency and learning processes to manage this task. Adaptive, iterative, and learning decision making tools and processes can help decision makers evaluate the significance of Type I or Type II errors on decision alternatives and can reduce the risk of committing Type III errors (accurate answers to the wrong questions). Simplistic cost-benefit based decision-making tools do not incorporate the complex interconnectedness characterizing environmental risks, nor do they enhance learning, participation, or include social values and ambiguity. Hence, better decision-making tools are required, and MIRA is an attempt to include some of the critical aspects.

Decision Support Techniques↗
PubMed2002

Subcutaneous emphysema of the neck and colonic perforation.

Subcutaneous emphysema may result from pathological changes in the thorax or lung, as a result of localised infection with gas producing organisms, after abdominal procedures, or herald an intestinal perforation. The location and spread of extraperitoneal gas is determined by the anatomical barriers and fixed fascial layers surrounding the region of pathological change. The case highlights the extent of extraperitoneal gas after colonic perforation despite minimal clinical features and the importance of intra-abdominal causes of cervical subcutaneous emphysema.

Colonic Diseases↗
PubMed2001

Parathyroid hormone stimulates fra-2 expression in osteoblastic cells in vitro and in vivo.

PTH and PTH-related protein (PTHrP) are key mediators of skeletal development and homeostasis through their activation of the PTH-1 receptor. Previous studies have found that several AP-1 family members are regulated by PTH, such as c-fos, fra-1, and c-jun. There are numerous genes in the bone microenvironment that contain AP-1 sites, and different Fos family members are reported to have opposing transcriptional activities at AP-1 sites. The purpose of this study was to identify the effects of PTH on expression of the AP-1 protein complex member, fra-2, to extend our understanding of transcriptional regulators of PTH action. PTH induction of fra-2 messenger RNA (mRNA) levels in MC3T3-E1 preosteoblastic cells was maximal with 0.1 microM PTH (1-34). The expression in vitro was greatest 1 h after treatment and was present with N-terminal PTH but not PTH (7-34) or (53-84). Cycloheximide treatment induced fra-2 expression, and actinomycin D inhibited basal and PTHrP-induced expression. AP-1 protein in nuclear extracts of MC3T3-E1 cells was increased with PTH treatment at 3 h and consisted of high levels of Fra-2 protein, as evidenced by a supershift in an electrophoretic mobility shift assay and Western blot analysis. Up-regulation of steady-state fra-2 mRNA was also noted in vivo, where injection of PTH (1-34) (20 microgram) resulted in a more-than-7-fold maximal increase in fra-2 mRNA expression in the calvaria of mice, after 1 h of treatment. These data add to the transcriptional mediators induced by PTH and suggest that the interplay of AP-1 family members will provide insight into regulatory pathways of PTH and PTHrP for their anabolic and catabolic actions in bone.

Animals↗
PubMed2000

Extracellular glucose influences osteoblast differentiation and c-Jun expression.

Insulin dependent diabetes mellitus, marked by high blood glucose levels and no insulin secretion, is associated with decreased bone mass and increased fracture rates. Analysis of bone histology suggests that osteoblast phenotype and function are influenced by diabetes. To determine if elevated extracellular glucose levels could directly influence osteoblast phenotype we treated mouse osteoblasts, MC3T3-E1 cells, with 22 mM glucose and analyzed osteoblast gene expression. Collagen I mRNA levels significantly increased while osteocalcin mRNA levels decreased 24 h after the addition of glucose. Expression of other genes, actin, osteopontin, and histone H4, was unaffected. Effects on collagen I expression were seen as early as 1 h after treatment. c-Jun, an AP-1 transcription factor involved in the regulation of osteoblast gene expression and growth, was also modulated by glucose. Specifically, an increase in c-jun expression was found at 1 h and maintained for 24 h following glucose treatment. Treatment of osteoblasts with an equal concentration of mannitol completely mimicked glucose treatment effects on collagen I and c-jun expression, demonstrating that osmotic stress rather than glucose metabolism is responsible for the effects on osteoblast gene expression and phenotype. Additional studies using staurosporine and Ro-31-8220 demonstrate that protein kinase C is required for the glucose up regulation of collagen I and c-jun. Taken together, our results demonstrate that osteoblasts respond to increasing extracellular glucose concentration through an osmotic response pathway that is dependent upon protein kinase C activity and results in upregulation of c-jun and modulation of collagen I and osteocalcin expression.

3T3 Cells↗
PubMed2000

Lecture 5: erectile dysfunction in the HIV-positive male: a review of medical, legal and ethical considerations in the age of oral pharmacotherapy.

Urologists and health care professionals treating erectile dysfunction face a significant challenge in caring for the HIV-positive patient who seeks restoration of normal sexual function. The encounter between the health care provider and the patient in this setting requires knowledge of HIV disease and potential drug interactions specific to this population, as well as thorough counseling on strategies aimed at reducing the infectiousness of HIV-1. The interaction extends beyond the immediate boundaries of the doctor-patient relationship and their respective rights, to include careful consideration of the rights of the partner/s and the society as a whole. This paper is a summary and analysis of presentations and discussions by medical, legal, nursing and bioethics specialists in an interactive seminar on this topic.

Adult↗
PubMed2000

Bacteriological and histological profile of turkeys condemned for cyanosis.

Canadian Food Inspection Agency (CFIA) has adopted the term cyanosis to describe a category of condemnation for poultry that is dark but has no other condemnable lesions. Two case-control studies (n = 30 pairs; n = 65 pairs) of 18-wk-old tom turkeys were conducted. A case was defined as a carcass condemned by the veterinary inspector for cyanosis, and a control carcass was one that passed inspection. Microbiological tests were conducted on samples of Pectoralis major and Gastrocnemius lacteralis. A modified Rappaport Vassiliadis medium was used for Salmonella, and a Petrifilm method was used to assess aerobic counts, coliform counts, and Escherichia coli. The Salmonella (qualitative) test was negative for all cases and controls, and there were no significant differences between the aerobic counts, coliform counts, and E. coli counts of case and control carcasses. Two pathologists conducted a blind histopathological study: there were no lesions compatible with those of septicemia-toxemia, as defined by CFIA and the USDA, nor any significant histopathological differences between the skin, P. major, G. lateralis, kidney, liver, spleen, small intestine, pancreas, lung, and heart of cases and controls. The inter-rater agreement between pathologists ranged from good to excellent (Kappa = 0.7 to 1.0). In the absence of important lesions and microbial contamination, carcasses with this color change alone should be suitable for human consumption.

Animals↗
PubMed2000

Treatments for patients with sexual problems.

Nurses need to be aware of psychosexual issues in patient care. If necessary, nurses must be able to direct the patient to sources of specialist help. Sex therapy and psychosexual medicine both offer approaches to sexual dysfunction.

Female↗
PubMed1998

The work of clinical nurse specialists (HIV/AIDS) in areas with a low prevalence of HIV infection.

The role of the clinical nurse specialists (HIV/AIDS) who work in areas with a low known prevalence of HIV is considered and their contribution to patient care, either directly or indirectly through the education and support of other health care workers, is discussed. Attention is given to the implications for nursing practice and the role of the clinical nurse specialist associated with the relative infrequency of contact with patients who have HIV disease; and some of the issues for people living with HIV/AIDS in rural areas are alluded to. Finally, some of the limitations of the clinical nurse specialist role are delineated and some consideration is given to the future role of clinical nurse specialists for HIV and AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Sexual health promotion and nursing.

The HIV epidemic provides continued impetus for effective sexual health promotion. Sexual health promotion in nursing practice has traditionally been equated to prevention at primary, secondary and tertiary levels. Increasing demands on practitioners to address the psycho-social aspects of sexual health, together with a greater emphasis on primary prevention, is leading to the adoption of theoretical paradigms from the behavioural sciences and the increasing use of counselling skills. The limitations of individualist interventions for primary prevention are explored, and the assumption that health care professionals are effective promoters of sexual health is questioned. The importance of placing sexual health and nursing practice within a wider social, political and cultural context is emphasized.

HIV Infections↗
PubMed1997

Prevention of rhinovirus infection in chimpanzees by soluble intercellular adhesion molecule-1.

Intercellular adhesion molecule-1 (ICAM-1) is the cell surface receptor for the major class of human rhinoviruses, and tICAM453, a truncated, soluble form of ICAM-1, has been shown previously to be a potent in vitro inhibitor of rhinovirus. In this report, we have investigated the in vivo efficacy of tICAM453 for the prophylaxis of rhinovirus serotype 16 infection in the chimpanzee. Because chimpanzees do not show clinical symptoms of infection after rhinovirus challenge, infection was followed by measuring antirhinovirus serum antibody responses and detection of virus shedding. By both of these measures, intranasal application of tICAM453 was efficacious in preventing rhinovirus infection in chimpanzees subsequently challenged with infectious doses of virus. These results suggest that the use of soluble rhinovirus receptor to inhibit virus binding to host cells should be feasible in humans.

Administration, Intranasal↗
PubMed1997

Psychosis following acute alteration of thyroid status.

OBJECTIVE: Mania with psychotic features presenting following abrupt normalisation of thyroid function from severe Graves's disease is reported. CLINICAL PICTURE: A 33-year-old man with severe, untreated Graves's disease was treated aggressively, with rapid restoration of normal serum thyroid hormone levels. Symptoms of mania and psychosis then developed. TREATMENT: Time limited antipsychotic medication and continuing medical treatment. OUTCOME: There was resolution of psychiatric symptoms. CONCLUSIONS: The association of mania and psychosis with thyroid disease is rare, but aggressive medical treatment and rapid restoration of normal serum thyroid levels may increase the risk of the emergence of such symptoms.

Adult↗