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Biomedical subjects

J Leigh

Publications and source records attributed to J Leigh.

At least 19 recordsLinked to original sources
PubMed2001

Potential role for a carbohydrate moiety in anti-Candida activity of human oral epithelial cells.

Candida albicans is both a commensal and a pathogen at the oral mucosa. Although an intricate network of host defense mechanisms are expected for protection against oropharyngeal candidiasis, anti-Candida host defense mechanisms at the oral mucosa are poorly understood. Our laboratory recently showed that primary epithelial cells from human oral mucosa, as well as an oral epithelial cell line, inhibit the growth of blastoconidia and/or hyphal phases of several Candida species in vitro with a requirement for cell contact and with no demonstrable role for soluble factors. In the present study, we show that oral epithelial cell-mediated anti-Candida activity is resistant to gamma-irradiation and is not mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide oxidative inhibitory pathways or by nonoxidative components such as soluble defensin and calprotectin peptides. In contrast, epithelial cell-mediated anti-Candida activity was sensitive to heat, paraformaldehyde fixation, and detergents, but these treatments were accompanied by a significant loss in epithelial cell viability. Treatments that removed existing membrane protein or lipid moieties in the presence or absence of protein synthesis inhibitors had no effect on epithelial cell inhibitory activity. In contrast, the epithelial cell-mediated anti-Candida activity was abrogated after treatment of the epithelial cells with periodic acid, suggesting a role for carbohydrates. Adherence of C. albicans to oral epithelial cells was unaffected, indicating that the carbohydrate moiety is exclusively associated with the growth inhibition activity. Subsequent studies that evaluated specific membrane carbohydrate moieties, however, showed no role for sulfated polysaccharides, sialic acid residues, or glucose- and mannose-containing carbohydrates. These results suggest that oral epithelial cell-mediated anti-Candida activity occurs exclusively with viable epithelial cells through contact with C. albicans by an as-yet-undefined carbohydrate moiety.

Adult↗
PubMed2001

Generation and characterization of a defined mutant of Streptococcus suis lacking suilysin.

A defined allelic-replacement mutant of the sly gene, encoding a thiol-activated cytolysin, from a European isolate of Streptococcus suis serotype 2 was generated and characterized. Unlike the parental strain, it is nonhemolytic, noncytotoxic for cultured macrophage-like cells, avirulent in a mouse infection model, yet only slightly attenuated in a porcine model of systemic infection.

Animals↗
PubMed2000

Growth inhibition of Candida by human oral epithelial cells.

Oropharyngeal candidiasis (OPC) caused by Candida albicans is a significant problem in human immunodeficiency virus (HIV)-infected persons. Recognizing the paucity of information on innate and/or adaptive mucosal host defenses against C. albicans, we recently reported that human and nonhuman primate and mouse vaginal epithelial cells inhibit the growth of C. albicans in vitro. In the present study, oral epithelial cells collected from saliva of healthy volunteers and a purified oral epithelial cell line were found to inhibit blastoconidia and/or hyphal growth of several Candida species. Cell contact was a strict requirement for the epithelial cell anti-Candida activity; neither saliva nor culture supernatants alone inhibited Candida growth, and addition of saliva to the coculture did not modulate the epithelial cell activity. Finally, epithelial cell anti-Candida activity was significantly lower in HIV-infected persons with OPC. Together, these results suggest that oral epithelial cells may play a role in innate resistance against OPC.

Adult↗
PubMed1999

Global burden of disease and injury due to occupational factors.

We made estimates of absolute morbidity and mortality due to occupational factors for the world using all available published data as of 1994, and, where no data were available, applying the most appropriate (in terms of similar economy, race, and environment) age-/sex-/diagnosis-specific incidence and mortality rates to known working population distributions. We report results according to economic groupings determined by the World Bank (World Development Report, 1993) and disease and injury groupings according to The Global Burden of Disease project (1997). This was part of a larger study that estimated the total global disease burden. We present aggregate results and analyses by region and disease. We estimate that approximately 100,000,000 occupational injuries (100,000 deaths) and 11,000,000 occupational diseases (700,000 deaths) occur in the world each year. We regard these as very conservative estimates which, although unavoidably crude, can nevertheless provide a basis for health priority planning at global level.

Adolescent↗
PubMed1997

Silica-induced apoptosis in alveolar and granulomatous cells in vivo.

Silica is a toxicant that can stimulate cells to produce various cellular products such as free radicals, cytokines, and growth factors. Silica and its induced substances may induce apoptosis to regulate the evolution of silica-induced inflammation and fibrosis. To examine this hypothesis, groups of Wistar male rats were intratracheally instilled with different doses of Min-U-Sil 5 silica (Silica, Berkeley Springs, WV). Ten days after the instillation, we obtained cells by bronchoalveolar lavage and placed them on slides by cytospin preparation. The slides were stained with Diff-Quik (Lab Aids, Sydney, NSW, Australia) and examined under oil immersion. A substantial number of cells with apoptotic features were identified in all silica-instilled rats and the apoptosis was confirmed by agarose gel electrophoresis. The number of apoptotic cells was clearly related to silica dosage. Engulfment of apoptotic cells by macrophages was also noted. Neutrophil influx in silica-instilled rats could be saturated with the increase of silica dosage and the number of macrophages in different dose groups changed in parallel with the proportion of apoptotic cells. Fifty-six days after instillation, morphologically apoptotic cells could be identified in granulomatous cells of lung tissue from silica-instilled rats. We conclude that intratracheal instillation of silica could induce apoptosis in both alveolar and granulomatous cells, and the apoptotic change and subsequent engulfment by macrophages might play a role in the evolution of silica-induced effects.

Administration, Inhalation↗
PubMed1995

Health status and exposure of workers at a pilot brown coal liquefaction plant in Australia, 1985-1991.

In 1985, Brown Coal Liquefaction (Victoria) Pty Ltd (BCLV) commenced operation of a pilot plant that investigated the feasibility of producing oil from brown coal. The plant operated for five years. This study aimed to use exposure and health information routinely collected by the company to characterize various health parameters of the workforce and to investigate whether any adverse health measures were exposure-related. About 1680 persons were employed at some time or other by BCLV, and the primary study population consisted of 408 workers who had a medical examination at the end of employment and who consented to being in an epidemiological study. Reported photosensitivity was associated with higher cumulative skin exposure (RR = 1.85; 95% CI = 1.22-2.78), with an exposure-response relationship of increasing risk with increasing skin exposure being suggested. There was no consistent evidence that chemical exposure at BCLV had any negative effect on the haematological, biochemical, endocrine or lung function of workers at the plant. However, the maximum follow-up period of less than eight years limits the ability of the study to detect any emerging chronic effects.

Adult↗
PubMed1994

Quantitative relation between emphysema and lung mineral content in coalworkers.

The relation between quantified emphysema and measured lung content of coal and silica was investigated in the lungs of 264 deceased underground coalworkers who had been exposed to mixed coal and silica dust. Lung specimens obtained at postmortem and inflated and fixed under standard conditions were used to quantify the extent of emphysema and then to measure the amount of coal and silica present in the lungs at the time of death. These data were combined with clinical and other pathological information from the subjects. Multiple regression analysis showed that the extent of emphysema (E score) had a strong positive quantitative relation with coal content of the lungs (p < 0.0003), age (p < 0.0001), and smoking (p < 0.0001). There was a significant negative interaction of uncertain biological importance between coal content of the lungs and smoking (p < 0.004; E score = -1.79 + 0.62 coal + 0.06 age + 0.21 smoking -0.17 coal x smoking; adjusted R2 = 0.25). In lifelong non-smokers emphysema was particularly strongly related to coal content and age (coal: p < 0.001; age: p < 0.002; E score = -1.56 + 0.78 coal + 0.06 age; adjusted R2 = 0.66). The relation was basically unchanged by adding a lung silica content term. Emphysema score was highly negatively correlated with forced expiratory volume in one second (FEV1; % predicted, obtained within five years of death) (r = -0.44, p < 0.0001). Degree of lung fibrosis was highly positively associated with lung silica content (chi 2(1) = 12.9, p < 0.0003). These results provide strong evidence that emphysema in coalworkers is actually related to lung coal content. The role silica in development of emphysema, however remains unclear.

Coal Mining↗
PubMed1994

Simultaneous in vivo measurements of HbO2 saturation and PCr kinetics after exercise in normal humans.

Simultaneous measurements of phosphocreatine (PCr) and oxyhemoglobin (HbO2) saturation were made during recovery from exercise in calf muscles of five male subjects. PCr was measured using magnetic resonance spectroscopy in a 2.0-T 78-cm-bore magnet with a 9-cm-diam surface coil. Relative HbO2 saturation was measured as the difference in absorption of 750- and 850-nm light with use of near-infrared spectroscopy. The light source and detectors were 3 cm apart. Exercise consisted of isokinetic plantar flexion in a supine position. Two 5-min submaximal protocols were performed with PCr depletion to 60% of resting values and with pH values of > 7.0. Then two 1-min protocols of rapid plantar flexion were performed to deplete PCr values to 5-20% of resting values with pH values of < 6.8. Areas of PCr peaks (every 8 s) and HbO2 saturation (every 1 s) were fit to a monoexponential function, and a time constant was calculated. The PCr time constant was larger after maximal exercise (68.3 +/- 10.5 s) than after submaximal exercise (36.0 +/- 6.5 s), which is consistent with the effects of low pH on PCr recovery. HbO2 resaturation approximated submaximal PCr recovery and was not different between maximal (29.4 +/- 5.5 s) and submaximal (27.6 +/- 6.0 s) exercise. We conclude that magnetic resonance spectroscopy measurements of PCr recovery and near-infrared spectroscopy measurements of recovery of HbO2 saturation provide similar information as long as muscle pH remains near 7.0.

Adult↗
PubMed1993

The role of alcohol in work-related fatal accidents in Australia 1982-1984.

This paper describes the role of detectable blood alcohol in fatal work injuries. An attempt was made to identify all work-related fatalities that occurred throughout Australia in the period 1982-1984. A research team examined coroners' records and classified 1737 fatal injury cases as being work-related according to study definitions. The following were also extracted from data in coroners' records: (i) whether or not the description of the fatal event indicated that inebriation was likely to have been a factor; (ii) whether or not there was documentation of blood alcohol concentration (BAC), and if so, what it was. The likelihood of inebriation was assessed without knowledge of the victim's BAC. In 1030 (59 per cent) of the 1737 fatal work injury cases, a BAC determination was documented. Zero levels were detected in 867 fatalities (84 per cent), and 163 cases (16 per cent) had non-zero BAC. In the latter group the median BAC was 104 mg%. Sixty-five per cent of measurable BAC cases had BAC greater than 50 mg%. Fatality risk in the non-zero BAC group relative to that of the zero BAC group was elevated for the following factors: marital status--single (risk ratio (RR) = 1.7, 95 per cent confidence interval (CI) 1.1-2.8) or separated/divorced (RR = 2.4, CI 1.5-3.8); occupation as manager, executive or administrator (RR = 2.5, CI 1.5-5.8); and commuting (RR = 1.6, CI 1.2-2.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗
PubMed1993

Clinical aspects of malignant mesothelioma in Australia.

Australia is currently experiencing an epidemic of malignant mesothelioma. The clinical aspects of malignant mesothelioma were investigated in 295 Australian patients as part of a national study of the disease. Most patients were male (91%), with the mean age at diagnosis being 64 years. The predominant cell type was epithelial (38%) and the majority of primary tumours arose from the pleura (94%). Mean survival was poor (17.6 months from first symptom; 11.8 months from diagnosis). Patients with a pleural primary tumour were more likely to present with dyspnoea, chest pain and cough; to have a pleural effusion diagnosed radiologically; and to have metastatic spread. Patients with a peritoneal primary tumour were more likely to present with weight loss, loss of appetite, abdominal pain and ascites; to have radiologic evidence of asbestos exposure; and to have spread along a needle track created during a diagnostic tap. A minority of patients had past thoracic conditions, or radiologic findings, specifically related to previous asbestos exposure. About one fifth of patients had no known asbestos exposure. Forty-one per cent of subjects received some form of chemotherapy, radiotherapy and/or surgery, but no formal disease staging had been documented for any patient. Proper controlled trials of secondary and tertiary treatments in malignant mesothelioma are now needed.

Aged↗
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↗