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.     

Binding, degradation and pressor activity of angiotensins II and III after aminopeptidase inhibition with amastatin and bestatin

In the metabolism of angiotensin peptides by tissue angiotensinases, aminopeptidases A, B, M and leucine aminopeptidase have been identified as being particularly effective. Because the inhibitory actions of amastatin (AM) and bestatin (BE) are relatively specific for these aminopeptidases, we have examined the effects of these inhibitors on the binding, degradation and pressor activity of angiotensin II (AII) and angiotensin III (AIII). Within 30 min at 37 degrees C, significant metabolism of 125I-AII and 125I-AIII by homogenates of a block of tissue containing hypothalamus, thalamus, septum and anteroventral third ventricle regions of the brain was observed. A majority of 125I-AIII metabolism was due to soluble peptidases, whereas that of 125I-AII primarily resulted from membrane-bound peptidases. AM, BE and reduced incubation temperatures significantly decreased the metabolism of 125I-AII and 125I-AIII. After appropriate adjustments to reflect the proportion of intact radioligand bound, temperature- or inhibitor-induced decreases in metabolism were matched by corresponding increases in specific binding. Heat-treated bovine serum albumin, as a nonspecific peptidase inhibitor, had no effect on either the metabolism or binding of the ligands used. In accordance with their actions in vitro, i.c.v. administration of AM and BE prolonged the pressor activity of subsequently applied AII and AIII. Unexpectedly, the amplitude of the pressor response to AIII was increased by BE, whereas that to AII was decreased by AM. The results of this study indicate that the metabolism of AII and AIII by aminopeptidases is relatively specific and acts to modulate the actions of these peptides.(ABSTRACT TRUNCATED AT 250 WORDS)