Publications

UNLABELLED

We have developed a novel model for depleting mouse hepatic stellate cells (HSCs) that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV). Effects of GCV were explored in primary HSCs and in vivo. Panlobular damage was provoked to maximize HSC depletion by combining CCl(4) (centrilobular injury) with allyl alcohol (AA) (periportal injury), as well as in a bile duct ligation (BDL) model. Cell depletion in situ was quantified using dual immunofluorescence (IF) for desmin and GFAP. In primary HSCs isolated from both untreated wild-type (WT) and Tg mice, GCV induced cell death in ≈ 50% of HSCs from Tg, but not WT, mice. In TG mice treated with CCl(4) +AA+GCV, there was a significant decrease in GFAP and desmin-positive cells, compared to WT mice (≈ 65% reduction; P < 0.01), which was accompanied by a decrease in the expression of HSC-activation markers (alpha smooth muscle actin, beta platelet-derived growth factor receptor, and collagen I). Similar results were observed after BDL. Associated with HSC depletion in both fibrosis models, there was marked attenuation of fibrosis and liver injury, as indicated by Sirius Red/Fast Green, hematoxylin and eosin quantification, and serum alanine/aspartate aminotransferase. Hepatic expression of interleukin-10 and interferon-gamma was increased after HSC depletion. No toxicity of GCV in either WT or Tg mice accounted for the differences in injury.

CONCLUSION

Activated HSCs significantly amplify the response to liver injury, further expanding this cell type's repertoire in orchestrating hepatic injury and repair.

OBJECTIVES

Although psychosocial stress can result in adverse health outcomes, little is known about how perceptions of neighborhood conditions, a measure of environment-derived stress, may impact obesity. The association between perceptions of neighborhood environment and obesity (defined as body mass index [BMI] ≥ 30 kg/m(2) ) among 5,907 participants in the Dallas Heart Study, a multi-ethnic, probability-based sample of Dallas County residents was examined.

DESIGN AND METHODS

Participants were asked to respond to 18 questions about perceptions of their neighborhood. Factor analysis was used to identify three factors associated with neighborhood perceptions: neighborhood violence, physical environment, and social cohesion. Logistic regression analyses were performed to determine the relationship between each factor (higher quintile = more unfavorable perceptions) and the odds of obesity.

RESULTS

Decreasing age, income, and education associated with unfavorable overall neighborhood perceptions and unfavorable perceptions about specific neighborhood factors (P trend <0.05 for all). Increasing BMI was associated with unfavorable perceptions about physical environment (P trend <0.05) but not violence or social cohesion. After adjustment for race, age, sex, income, education, and length of residence, physical environment perception score in the highest quintile remained associated with a 25% greater odds of obesity (OR 1.25, [95% CI 1.03-1.50]). Predictors of obesity related to environmental perceptions included heavy traffic (OR 1.39, [1.17-1.64]), trash/litter in neighborhood (OR 1.27, [1.01-1.46]), lack of recreational areas (OR 1.21, [1.01-1.46]), and lack of sidewalks (OR 1.25, [95% CI 1.04-1.51]).

CONCLUSIONS

Thus, unfavorable perceptions of environmental physical conditions are related to increased obesity. Efforts to improve the physical characteristics of neighborhoods, or the perceptions of those characteristics, may assist in the prevention of obesity in this community.

BACKGROUND

Nursing is known as an occupation with high risk of musculoskeletal injury. Nurses' perceptions about the risk of injury may have a role in preventing such injury.

OBJECTIVES

The aim of this study was to investigate how nurses perceived the risk of musculoskeletal injury from work and identify factors associated with their risk perception.

METHODS

In a cross-sectional study using a postal survey, 361 critical care nurses reported on risk perception, physical workload, psychosocial job factors, safety climate, musculoskeletal symptoms, and safe work behavior.

RESULTS

Of all critical care nurse respondents, 83% perceived that they were more likely than not to have a musculoskeletal injury within 1 year. On average, nurses perceived the risk of musculoskeletal injury as lower to themselves than to coworkers. This more positive perception of risk to self had stronger correlations with symptom experiences. Multiple linear regression analysis revealed that higher risk perception of injury was associated with greater job strain, greater physical workload, lack of availability of lifting devices or lifting teams, and more symptoms.

DISCUSSION

Study findings indicated that most critical care nurses were concerned about their ergonomic job risks. Their risk perceptions about musculoskeletal injury risk were affected by physical work exposures, psychosocial job stressors, and experience with musculoskeletal symptoms, but not by perceived workplace safety climate. The findings underscore the need for management efforts to improve physical and psychosocial working conditions and create a safe work environment.

OBJECTIVE

To investigate the association between occupational risk factors and the incidence of knee disorders in a young adult population.

METHODS

Israeli recruits to the Israel Defense Forces go through a rigorous medical investigation. Study participants were classified by prior knee condition status and divided into 5 categories of prospective occupational exposure to physical activity according to their assigned military duties, and were then followed for 30 months for the development of severe knee disorders (SKD). Logistic regression analysis was used to estimate the occupational risks for incident SKD, adjusted for any previous mild or moderate disorder, body mass index, and body height at induction.

RESULTS

The study population consisted of 76,491 males. SKD developed in 615 (0.8%). Compared to administrative workers as referents, a higher risk of developing SKD was manifest among high intensity combat occupations, (odds ratios [OR] 2.15), those in moderate intensity combat occupations (OR 2.57) and maintenance (OR 1.59). Drivers did not demonstrate increased risk of knee disorders compared to referents.

CONCLUSIONS

Occupational factors during military service are associated with incident SKD, even when taking into account previous knee disorders, body mass index, and height, which also had independent effects in our study population.

The aim of this study was to assess the effects of short exposures to experimentally aged cigarette smoke on the nose and upper airways. This crossover study compared the effects of 30-min exposures to (1) experimentally aged cigarette smoke at 1 mg/m³ particulate matter (PM)/14 ppm carbon monoxide (CO) and (2) conditioned filtered air on urinary metabolites of nicotine and tobacco-specific nitrosamines. Subjective nasal symptoms were assessed by questionnaire, objective nasal congestion was assessed by anterior rhinomanometry and nasal nitric oxide (NO) concentrations were determined. Experimentally aged cigarette smoke is a validated model for secondhand smoke (SHS). Twenty-six healthy nonsmokers (10 normal, 7 atopic/nonrhinitic, 7 atopic rhinitic, 2 nonatopic/rhinitic) were studied. A 30-min exposure to SHS increased nasal resistance in healthy nonsmokers. The rise in nasal resistance was most pronounced in rhinitic subjects. Significant increases were not noted when atopic subjects were considered independent of rhinitis status. Secondhand smoke exposure also elevated subjective nasal symptoms and urinary concentrations of metabolites of nicotine (cotinine and trans-3´-hydroxycotinine) and tobacco-specific nitrosamines [(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)] in all subgroups of subjects. Exposure-related, subjective nasal symptoms were significantly higher in rhinitic than in normal subjects. Significant changes in nasal NO concentrations were not detected. Data indicate a 30-min exposure to secondhand smoke at 1 mg/m³ PM increases subjective upper respiratory symptoms, increases urinary cotinine and NNAL, and produces objective nasal airflow obstruction in human subjects.

The Src and Syk families of kinases are two distinct sets of kinases that play critical roles in initiating membrane-proximal B cell receptor (BCR) signaling. However, unlike in other lymphocytes, such as T cells, the "division of labor" between Src family kinases (SFKs) and Syk in B cells is not well separated because both Syk and SFKs can phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) present in proteins comprising the BCR. To understand why B cells require both SFKs and Syk for activation, we investigated the roles of both families of kinases in BCR signaling with computational modeling and in vitro experiments. Our computational model suggested that positive feedback enabled Syk to substantially compensate for the absence of SFKs when spatial clustering of BCRs was induced by multimeric ligands. We confirmed this prediction experimentally. In contrast, when B cells were stimulated by monomeric ligands that failed to produce BCR clustering, both Syk and SFKs were required for complete and rapid BCR activation. Our data suggest that SFKs could play a pivotal role in increasing BCR sensitivity to monomeric antigens of pathogens and in mediating a rapid response to soluble multimeric antigens of pathogens that can induce spatial BCR clustering.

OBJECTIVE

To determine the prevalence of obesity and how accurately standard anthropometric measures identify obesity among men and women with rheumatoid arthritis (RA).

METHODS

Dual x-ray absorptiometry (DXA) was performed for 141 persons with RA (56 men and 85 women). Two anthropometric proxies of obesity (body mass index [BMI] and waist circumference [WC]) were compared to a DXA-based obesity criterion. Receiver operating characteristic curves determined optimal cut points for each anthropometric measure, relative to DXA. The association of body fat and anthropometric obesity measures with disease status and cardiovascular risk was assessed in multiple regression analyses, controlling for age and glucocorticoid use. All analyses were performed separately for men and women.

RESULTS

A total of 20%, 32%, and 44% of women and 41%, 36%, and 80% of men were classified as obese by BMI, WC, and DXA, respectively. Cut points were identified for anthropometric measures to better approximate DXA estimates of percent body fat (BMI ≥26.1 kg/m(2) for women and ≥24.7 kg/m(2) for men; WC ≥83 cm for women and ≥96 cm for men). For women and men, higher percent fat was associated with poorer RA status. Anthropometric measures were more closely linked to RA status for women, but identified cardiovascular risk for both women and men.

CONCLUSION

A large percentage of this RA sample was overfat; DXA-defined obesity was twice as common in men as in women. Utility of revised BMI and WC cut points compared to traditional cut points remains to be examined in prospective studies, but results suggest that lower, sex-specific cut points may be warranted to better identify individuals at risk for poor RA and/or cardiovascular outcomes.

PURPOSE OF REVIEW

Cocaine use is associated with several rheumatic syndromes. This review summarizes these clinical manifestations and highlights recent developments linked to levamisole-adulterated cocaine.

RECENT FINDINGS

Cocaine use has been linked to several distinctive syndromes that can be difficult to distinguish from idiopathic rheumatic diseases. These disorders can range in severity from purely cosmetic damage to organ and/or life-threatening disease that includes sinonasal destruction and vasculitis. Many of these illnesses are associated with antineutrophil cytoplasmic antibodies (cytoplasmic, perinuclear and atypical perinuclear patterns). With the recent introduction of levamisole as a cocaine adulterant, a newly reported syndrome has emerged that is associated with neutropenia, retiform purpura with cutaneous necrosis and autoantibodies consisting of high-titre perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) with specificities for 'atypical' antigens.

SUMMARY

Cocaine use is associated with clinical syndromes that closely mimic other primary rheumatic diseases. Given the high prevalence of cocaine use and its adulteration with levamisole, clinicians should be familiar with these rheumatic manifestations in order to avoid misdiagnosis and unnecessary treatment with potentially toxic therapies.