Lung Transplant Metalloproteinase Levels Are Elevated Prior to Bronchiolitis Obliterans Syndrome

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.     

Cytokines and growth factors in keratinocytes and sweat glands in chronic venous leg ulcers. An immunohistochemical study

The role of growth factors and cytokines in the impaired healing of chronic leg ulcers remains uncertain. The aim of this study was to determine whether changes in the amount and location of cytokines and growth factors may be associated with impaired healing in chronic leg ulcers. Biopsies from leg ulcers of 21 patients and from normal skin of nine healthy volunteers were examined immunohistochemically for selected growth factors and cytokines. Greater staining intensity was found in keratinocytes at the edges of ulcers compared to normal skin, or skin adjacent to the ulcers. Staining at the ulcer edge was more intense in nonhealing ulcers for only vascular endothelial growth factor and platelet-derived growth factor, whereas staining in the adjacent skin was more intense for all factors in the nonhealing phase. For all factors staining was cytoplasmic, suggesting production in these areas. This study shows up-regulation of the production of cytokines and growth factors in keratinocytes of chronic leg ulcers that is greater when the ulcers are nonhealing.     

Trial of pyrethroid impregnated bednets in an area of Tanzania holoendemic for malaria. Part 2. Effects on the malaria vector population.

The malaria vector population consisted mainly of Anopheles gambiae s.s. with a small contribution from An. funestus and An. rivulorum. The mosquitoes coming to bite in bedrooms were monitored with light traps set beside untreated bednets. When impregnated bednets were provided for all the other beds in a village the Anopheles populations declined but the Culex quinquefasciatus populations were unaffected. The survival of An. gambiae (as measured by the mean number of ovarian dilatations) and the sporozoite rate declined following introduction of the nets and the estimated sporozoite inoculation rates into people not under their nets declined by more than 90%. The net introductions caused sharp declines in the number of mosquitoes resting indoors, but the evidence was inconclusive regarding diversion to outdoor resting, animal biting, earlier biting or outdoor biting. DDT spraying greatly reduced the Anopheles populations.     

Trial of pyrethroid impregnated bednets in an area of Tanzania holoendemic for malaria. Part 1. Operational methods and acceptability.

In five Tanzanian villages, nets impregnated with permethrin or lambdacyhalothrin were given out. The people received them enthusiastically and brought their nets for re-impregnation at six monthly intervals. Bioassays showed that the insecticidal power of permethrin impregnated nets remained adequate for six months unless the nets were washed. Nets with 30 mg lambdacyhalothrin/m2 retained high insecticidal power despite washing, but this dose caused temporary cold-like symptoms in those sleeping under freshly treated dry nets. Methods by which durable bednets might be made affordable by Tanzanian villagers are discussed.     

Lack of C-erbB-2 protein expression in pulmonary carcinoid tumours.

To determine if amplification of the C-erb-B2 proto-oncogene could be correlated with prognosis in carcinoid tumours, 49 pulmonary carcinoid tumours (26 typical, 23 atypical) were examined using a polyclonal antibody to the C-terminal peptide of the C-erb-B2 protein sequence. No C-erb-B2 gene product could be shown: the demonstration of C-erb-B2 does not seem to help, therefore, in determining diagnosis or prognosis in pulmonary carcinoid tumours.