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Biomedical subjects

J E Harrison

Publications and source records attributed to J E Harrison.

At least 55 records · Page 3Linked to original sources
PubMed1995

Construction and adhesive properties of a soluble MadCAM-1-Fc chimera expressed in a baculovirus system: phylogenetic conservation of receptor-ligand interaction.

MAdCAM-1 is a high endothelial venule adhesion molecule composed of immunoglobulin and mucin-like domains which binds the leucocyte integrin LPAM-1 (alpha 4 beta 7), and is largely responsible for the selective homing of lymphocytes to mucosal tissues. A novel soluble form of mouse MAdCAM-1 which is normally membrane bound has been produced by joining the extracellular region of the receptor to the Fc domain of human IgG1. The MAdCAM-1-Fc cDNA was inserted into the genome of Autographa californica nuclear polyhedrosis virus (AcNPV). Spodoptera frugiperda insect cells infected with the recombinant virus produced MAdCAM-1-Fc as a disulfide-linked homodimer of 82 kDa polypeptides, which was secreted into the culture medium at > 1 microgram/ml. The product purified by Protein G-Sepharose was identified as authentic MAdCAM-1-Fc by the anti-MAdCAM-1 monoclonal antibody (MoAb) MECA-367 using Western blot and ELISA analysis. When immobilized on glass it was fully functional in supporting the binding of mouse alpha 4 beta 1+ alpha 4 beta 7+ mesenteric lymph node lymphocytes, and the alpha 4 beta 1- alpha 4 beta 7+ TK1 T cell lymphoma. Binding was enhanced by Mn(++)-induced integrin activation, and specifically blocked by anti-integrin alpha 4 subunit and anti-MAdCAM-1 MoAbs. Binding was blocked by pretreatment of cells with sodium azide, and EDTA, indicating that binding is an energy-dependent process which requires divalent cations. Thus the mouse MAdCAM-1-Fc chimera produced in insect cells retains certain functional properties that typify the native receptor, and should be valuable in analysing the role of MAdCAM-1 in lymphocyte recirculation and emigration. However it was not sialylated despite being post-translational modified with N- and O-linked carbohydrate moieties, suggesting that the ability of MAdCAM-1 to support cell adhesion under static conditions is sialylation-independent. A rabbit polyclonal antibody raised against the entire cytoplasmic domain of the human integrin beta 7 subunit recognized LPAM-1-like molecules in human, rat, and mouse cells, suggesting a high degree of conservation of the MAdCAM-1 receptor across species. In agreement with this notion MAdCAM-1-Fc immobilized on glass was fully functional in supporting the cation-dependent binding of peripheral blood or spleen cells from a range of other species including human, rat, and guinea pig; and for human myeloid HL60 cells, binding was mediated by alpha 4 integrins.

Amino Acid Sequence↗
PubMed1994

Cloning of a gene encoding a human leukocyte protein characterised by extensive heptad repeats.

Complementary DNA (cDNA) clones, encoding a fusion protein that was recognised by an antiserum raised against a purified polypeptide fragment of a 180-kDa human leukocyte protein, were isolated from a lambda gt11 expressed library. The clones encoded a unique amino acid (aa) sequence interspersed with heptad repeats that typify coiled-coil proteins, and hybridised to a 5-kb transcript universally expressed in a panel of eight human tissues. Comparatively high levels of RNA expression were seen in testis, ovary and mitogen-activated peripheral blood leukocytes (PBLs). The deduced 1300-aa sequence reveals a protein with a typical signal peptide, a hydrophilic domain containing an N-terminal globular head with a nuclear localization signal sequence, a C-terminal region of coiled-coil structure, a candidate transmembrane domain, and a short 10-aa C-terminal domain. Rabbit polyclonal antisera raised against a truncated lambda gt11 fusion protein recognized a 150-170-kDa protein (non-reduced) in mitogen-activated PBLs. The protein designated here as CG-1 may exist as a homodimer destined for translocation to the nucleus, with a role in leukocyte differentiation and/or effector function.

Amino Acid Sequence↗
PubMed1994

Critical assessment of body-composition measurements in malnourished subjects with Crohn's disease: the role of bioelectric impedance analysis.

Bioelectric impedance analysis (BIA) has been widely used for assessment of body composition in healthy subjects but has not been validated in malnourished patients. This study compared calculation of fat-free mass (FFM) by five methods to determine whether the currently used equations for total body water (TBW) as assessed by BIA were applicable to 19 malnourished patients with Crohn's disease. When compared with TBW assessed by H2(18)O dilution, BIA was higher by 5.9 +/- 1.1% (P < 0.005). A stepwise-multiple-regression equation was derived to validate BIA: TBW (kg) = 0.25 (ht2/resistance) + 0.29 (wt) + 3.63 (r = 0.97, SEE = 0.28). Comparison of the hydration of FFM (TBW by 18O dilution/FFM) between methods showed that total body potassium (TBK) gave a significantly higher value when compared with the reference method of body protein, mineral, and 18O analysis. Dual-energy x-ray absorptiometry (DXA) provided a value for TBW/FFM in close agreement with the reference method. We conclude that BIA overestimates TBW, and TBK underestimates FFM in malnourished patients. DXA provides an accurate measurement of body fat in malnutrition.

Absorptiometry, Photon↗
PubMed1994

Traumatic work related fatalities in commercial fishermen in Australia.

OBJECTIVES: To describe the types and circumstances of traumatic work related fatalities in Australian commercial fishermen. METHODS: Work related traumatic fishing fatalities were studied as part of a larger study of all work related traumatic fatalities in Australia from 1982 to 1984. Data on 47 cases were obtained from inspection of coroners' files. RESULTS: The incidence of fatality of 143/100,000 person-years was 18 times higher than the incidence of fatality for the entire workforce, and considerably higher than that of the mining and agricultural workforces. 68% of decedents drowned and 13% died from physical trauma. Rough weather, non-seaworthy vessels, inadequate use of personal flotation devices, and inexperience were associated with many of the fatal incidents. DISCUSSION: Improved vessel and equipment maintenance, better training of workers, greater use of personal flotation devices, and development of improved clothing and personal flotation devices are recommended.

Accidents, Occupational↗
PubMed1994

Nutritional assessment.

Measurements of body composition are made to assess nutritional status. The measurements used for these studies should be selected on the basis of reliability, as well as simplicity and costs, and reliability depends on the information required. In normal adults simple estimates of fat and lean tissue (LBM), i.e. the anthropometric measurements of weight, height and skin fold thickness, should be sufficient since the proportions, in LBM, of water, protein and bone mineral are relatively constant. Measurements of body water (by isotope dilution or bioelectrical impedance) allow indirect estimates of fat and LBM that are reliable, provided that water is a constant proportion of LBM. In disease states, however, including renal disease, it is well established that the proportion of water in LBM varies from significant water overload to dehydration. In disease, it is important to determine not only total LBM but also the quality of LBM, determining essential body protein as well as body water. Body protein can be measured directly by nuclear techniques. This procedure should be more readily available for the clinical investigation of nutritional status.

Adipose Tissue↗
PubMed1994

Role of migrant factors in work-related fatalities in Australia.

OBJECTIVES: The importance of workers' language and migration characteristics to safety in the work environment has been debated but remains unclear. This study examined the role of these factors in the occurrence of work-related fatalities in Australia. METHODS: The study was based on an investigation of all work-related fatalities occurring in Australia during 1982-1984. Denominators for each year were obtained according to gender and country-of-birth census data from the 1981 and 1986 national censuses, interpolated and adjusted according to annual labor force survey estimates for the period 1981 to 1986 to indicate the true movement of the employed civilian labor force over the study period. RESULTS: Of 1211 decedents identified with known country of birth, 333 were born outside of Australia. The overall fatality incidence per 100,000 person-years in the employed civilian labor force was 7.12 [95% confidence interval (95% CI) 6.36-7.88], which is similar to that of Australian-born persons, 6.56 (95% CI 6.12-6.99). However, fatality incidences in rural and mining occupations were significantly increased among overseas-born persons when they were compared with Australian-born persons. Mortality ratios standardized separately for occupation and age showed significantly elevated mortality for duration of residence of less than five years, particularly for persons of non-English speaking background. These values converged to the Australian rate with increasing duration of residence. CONCLUSION: This study suggests that factors related to country of birth (eg, language) and duration of residence of overseas-born workers are important determinants of safety at work in Australia.

Accidents, Occupational↗
PubMed1994

Missing anterior teeth: treatment options and their orthodontic implications.

Recent advances in restorative and surgical materials and techniques have increased the treatment options available for patients who are missing an anterior tooth. The factors influencing the management of such patients and the orthodontic implications of these treatment options are discussed in this paper.

Anodontia↗
PubMed1994

Effect of PAF-antagonists on aeroallergen-induced bronchial eosinophilia in guinea pigs: a therapeutic approach.

Aeroallergen-induced eosinophilia in actively sensitized guinea pigs was used as a marker of bronchial inflammation in this study. Drugs were administered p.o. therapeutically, i.e., four hours after aeroallergen challenge. Allergic bronchial eosinophilia in guinea pigs was sensitive to dexamethasone. Thus, the therapeutic approach appears to be a reliable, predictable, and sensitive for the evaluation and selection of potential bronchial anti-inflammatory compounds. PAF-antagonists (WEB-2086, WEB-2170, and E-6123) and a 5-lipoxygenase inhibitor (E-6080) did not influence allergen-induced eosinophil infiltration in the bronchoalveolar lavage fluid. These observations seem to suggest that therapeutic administration of PAF antagonists and leukotriene synthesis inhibitors exert little or no inhibitory effect on the progression of late-phase allergic bronchial inflammation in this model.

Administration, Oral↗
PubMed1993

Evaluation of a program for rehabilitation of osteoporotic patients (PRO): 4-year follow-up. The Bone and Mineral Group of the University of Toronto.

The value of a program for the rehabilitation of osteoporotic patients (PRO) was assessed from a 4-year follow up of 139 patients referred to the program over its initial 2 years of operation. The program consisted of educational seminars, social activities and regular exercise supervision. Patients had annual clinical assessments, and bone mass measurements by neutron activation analysis (reported as CaBI). Fitness was assessed by performance on a treadmill (reported in terms of VO2max, ml/kg/min). Seventy-eight of the 139 patients remained in the program over the 4-year follow-up. This unusually high level of commitment to the program is indicative of the psychological value that patients have derived from it. The effect of the program on the osteoporosis process was inconclusive. Group 2, the 37 patients who obtained the greatest improvement in fitness (VO2max > 6 ml/kg/min), had a significantly greater reduction in back pain than did group 1, the 36 with less significant improvement (VO2max < or = 6 ml/kg/min). The bone mass and incidence of vertebral fractures on entry into the program were not significantly different between the two groups. Group 2 had on average a greater increase in bone mass over the 4 years; mean increases in CaBI, (+/- SD) were 0.09 +/- 0.09 and 0.05 +/- 0.10 for groups 2 and 1 respectively. Group 2 had on average fewer new vertebral fractures (0.08 +/- 0.36 and 0.28 +/- 0.75 for groups 2 and 1 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Mucolytic activity of azelastine in mice and rats.

The mucolytic activity of azelastine, an antiallergic/antiasthmatic drug, in mice and rats was investigated. The oral administration of test compounds 30 min before phenol red i.p. injection stimulated dye secretion in the trachea of mice. The resulting oral ED50's (mg/kg) were: azelastine, 0.16; salbutamol, 2.5; N-acetylcysteine, 61.8; S-Carboxymethyl-l-cysteine, < 100; bromhexine, > 100; and potassium iodide, approximately 200. In rats, several drugs stimulated secretion of fluorescein sodium (FINa) in the tracheobronchial lumen. The resulting oral ED50's (mg/kg) were: azelastine, 0.33; terbutaline, 0.3; salbutamol, 0.89; and S-carboxymethyl-l-cysteine, 56.8. Terfenadine and diphenhydramine (1-10 mg/kg, p.o.) did not stimulate tracheal secretion in rats and mice. The mucolytic activity of azelastine may contribute to its overall effectiveness, including antitussive activity in asthmatics. Finally, this activity seems to be dissociated from its H1-histamine receptor blocking activity.

Acetylcysteine↗
PubMed1993

Work-related road fatalities in Australia, 1982-1984.

A study of work-related fatalities, based on coroners' records, has provided national data on work-related road fatalities. A total of 1,544 work-related fatalities were identified over 1982-1984. Of these, 600 (39%) resulted from injuries sustained in road vehicle accidents on public roads; 366 (24%) in the course of work, and 234 (15%) while commuting between home and work. These figures are likely to underestimate work-related road fatalities because the coroners' records often did not contain the required information. The incidence of road fatalities declined slightly over the three years, although the proportion amongst all work-related fatalities remained constant. The at-work victims tended to be older than victims of road death generally. Fifty-six percent of the at-work cases were in the occupational group "drivers, road transport". Articulated trucks accounted for 41% of the at-work cases. Drivers made up 79% of the at-work group. In contrast, drivers accounted for only 38% of all road deaths. Two-thirds of the at-work road fatalities occurred outside capital city districts, the proportion of nonmetropolitan cases being highest for deaths involving articulated trucks. This is striking, in view of Australia's highly urbanised population. Blood alcohol data were available for 76% of the at-work cases and 79% of the commuting fatalities. Of these, 15% and 13%, respectively, had a blood alcohol of 0.05 g/100mL or more. In contrast, 6% of other workplace fatalities for which blood alcohol data were available had such levels. This difference may reflect more assiduous blood-alcohol testing of road-accident victims.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗
PubMed1993

Allergic bronchial eosinophilia: a therapeutic approach for the selection of potential bronchial anti-inflammatory drugs.

Aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) in guinea pigs was used as a marker of bronchial inflammation. Drugs were administered orally 4 h after aeroallergen challenge. Allergic bronchial eosinophilia in guinea pigs was inhibited by orally administered dexamethasone and methylprednisolone. Terfenadine (a newer H1-receptor antagonist), theophylline (a nonspecific phosphodiesterase inhibitor), and salbutamol (a beta 2-agonist) did not influence allergic eosinophilic infiltration. Many of these agents, administered prophylactically, have been reported to suppress allergic eosinophilic infiltration in the BALF of guinea pigs. Methylprednisolone, a steroid, inhibits allergic bronchial eosinophilia regardless of the time of administration; that is, 2 h before or 4 h after aeroallergen challenge. The therapeutic approach used in this study may facilitate drug discovery for bronchial inflammation/asthma.

Albuterol↗
PubMed1993

Work-related agricultural fatalities in Australia, 1982-1984.

Work-related agricultural fatalities were examined as part of a larger population-based study of all work-related fatalities in Australia in the period 1982-1984. A total of 257 farm-related fatalities were identified, of which 223 were deaths of persons in the employed civilian labor force (19.4 deaths per 100,000 persons per year) and 34 were deaths of children less than 15 years of age. The fatality incidence was higher among men, older age groups, and nonmanagers in general and in certain occupations in particular. Mobile mechanical equipment (particularly tractors) was the main fatal agent, roll-overs accounting for many of the fatalities. Better provision of information to agricultural workers, improvements in compliance to and enforcement of legislation, and changes in farming work practices are recommended to improve the safety of farms and farm work.

Accidents, Occupational↗
PubMed1992

Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach.

In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependent fashion. The resulting ED50 was 10 (3.4-32.8) micrograms/kg. The clinical therapeutic usefulness of anti-IL-5 or anti-IL-5-producing cells in asthma/allergy treatment remains to be an intriguing possibility.

Animals↗