Initial assessment of α-synuclein structure in platelets

Journal of Thrombosis and Thrombolysis - Over the last few years data from our group have indicated that α-synuclein is important in development of immune cells as well as potentially...     

The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.     

The influence of sleeping sickness on mortality in two districts of Northern Nigeria

The object of this enquiry was to obtain some idea of the mortality of untreated sleeping sickness in two non-adjacent districts in Northern Nigeria. The method employed was to obtain data, by methodical questioning of every householder, from which the crude death and other rates could be calculated over a preceding period, and be correlated with the known incidence of sleeping sickness. The figures were worked out village by village, and the villages then combined into groups of sufficient size to make the numbers significant.In the first district, Igabi, a close correlation was obtained, the death rate rising from 71.4 per 1,000 with a sleeping sickness incidence of 18.6 per cent., to 104 per 1,000 with a sleeping sickness incidence of 28.6 per cent. In other words an additional death occurred for approximately every additional three people infected. The infantile mortality rate also showed a close correlation with the sleeping sickness incidence. As infants were not found to be infected, this result was unexpected. The reasons for it are discussed. The birth rate showed no definite correlation.In the second district, Kankara, no correlation was found to exist, and the conclusion is drawn that, during the period under review, sleeping sickness was not fatal; the patients must either have harboured a mild chronic infection carrying no threat to life, or have been undergoing spontaneous cure.The clinical types of the cases found are described. They are similar in the two districts, and would not have been suspected of having so different a prognosis.It is pointed out that Igabi lies in the middle of a sleeping sickness belt, and it is suggested that the virulence of the disease in this district may be accounted for by the very free means of communication which exist, and by the movement in the past of large gangs of labour, tending to disseminate many different strains of trypanosome imported from outside. The infection in Kankara, on the other hand, was probably of later, though not very recent, introduction; and as the district is situated on the very edge of the belt and is traversed by no main roads or railways, the possibility of a multiplicity of strains existing is very much less. If this conclusion is correct, it emphasizes the necessity of careful sleeping sickness control measures in areas which may be opened up in the future.The mean birth rate found in Igabi was 64.7 per 1,000; and the mean death rate 84.2. The corresponding figures for Kankara were 44.1 and 23.6. The reliability of these figures is discussed.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.