TNF-R55-specific form of human tumor necrosis factor-alpha induces collagenase gene expression by human skin fibroblasts

Tumor necrosis factor-alpha (TNF-alpha) is a potent inhibitor of connective tissue formation. The cellular effects of TNF-alpha are mediated by two distinct cell-surface receptors, TNF-R55 and TNF-R75, both present on various types of cells, including fibroblasts. In this study we wanted to elucidate the role of TNF-R55 as a mediator of the connective tissue effects of TNF-alpha by using a mutant, TNF-R55-specific form of human TNF-alpha. This mutant TNF-alpha markedly induced collagenase and stromelysin-1 gene expression in dermal fibroblasts, the maximal activation (up to 42-fold) being 65%-89% of that noted with wild-type human TNF-alpha. In addition, TNF-R55-specific TNF-alpha suppressed type I collagen mRNA levels as potently as wild-type TNF-alpha (by 60%). The enhancement of collagenase gene expression by TNF-R55-specific TNF-alpha was augmented by simultaneous treatment of normal and scleroderma skin fibroblasts with interferon-gamma, indicating specific enhancement of TNF-R55 signaling pathway by interferon-gamma. These results show that stimulation of the TNF-R55 signaling pathway is sufficient for the inhibitory effects of TNF-alpha on extracellular matrix formation by dermal fibroblasts. It is conceivable that due to reduced systemic toxicity, TNF-R55-specific forms of human TNF-alpha may prove to be feasible in the therapy of fibrotic disorders.     

Antibodies to Bacillus megaterium H glycoprotein in patients with lung diseases

Enzyme immunoassay performed in patients with malignant and benign affections of the lungs determined antibodies (Abs) to glycoprotein isolated from saprophyte microorganism Bacilus megaterium H. In pulmonary tuberculosis and nonspecific pulmonary inflammation the above Abs occurred in patients with fibrous-proliferative changes and associated neoplastic conditions. In lung cancer the Abs were detected in well and moderately differentiated tumors. Nondifferentiated and poorly differentiated variants did not exhibit any rise in Abs to glycoprotein.     

Neck strain in car occupants. The influence of crash-related factors on initial severity

OBJECTIVE: To examine the relationship between the initial severity of neck strain in car occupants and crash-related factors, in particular, crash severity. DESIGN/PARTICIPANTS: Thirty-two individuals with neck strain after a car crash, drawn from physiotherapy and general practices in metropolitan Adelaide, were interviewed about their experience and examined by a manipulative physiotherapist. Crash severity was assessed by measurement of damage to the involved vehicles. MAIN OUTCOME MEASURES: Five measures of neck strain severity were obtained: number of body regions with symptoms, number of positive responses to palpation, cervical range of motion, subject's own rating on an analogue pain scale, and examiner's severity rating. Two measures of crash severity were used: maximum residual deformation, and velocity change of the subject's vehicle. RESULTS: Neck strain was observed in individuals who were involved in crashes of low severity. Maximum residual deformation of the vehicle was negatively associated with the subject's cervical range of motion and positively associated with the other measures of neck strain severity. For rear impacts, both measures of crash severity were associated with measures of neck strain severity. The group of subjects who were aware of the impending collision had a greater range of cervical spine movement and fewer positive responses to palpation than those who were unaware. CONCLUSIONS: Initial severity of neck strain is positively correlated with crash severity. Awareness of the impending collision may have a mitigating effect on injury severity.