Prolonging survival in vascularized bone allograft transplantation: developing specific immune unresponsiveness

Vascularized bone allografts (VBAs) could be useful adjuncts to the clinical reconstructive surgeon's arsenal. These grafts are known experimentally to be subject to host rejection. One way to control the rejection problem would be to develop specific immune unresponsiveness via host conditioning. Using a proven reliable model in inbred rats for studying heterotopic VBA transplantation, recipient animals were conditioned preoperatively with third-party unrelated blood, donor-specific blood (DSB) alone and with cyclosporine, and ultraviolet irradiated donor-specific blood. The combination of DSB plus cyclosporine delayed rejection of grafts across a strong histocompatibility barrier for three to four weeks. However, rejection was delayed across a weak histocompatibility barrier for five to six weeks using this same host pretreatment. The implications are that specific immunosuppression, although possible, is difficult to achieve in VBA transplantation, and that such techniques will rely on tissue-matching to minimize the genetic disparity between graft and host.     

Congenital rubella in babies of south Asian women in England and Wales: an excess and its causes

The incidence of congenital rubella was found to be 2.3 times higher in Asian than non-Asian births in England and Wales. This was attributed in part to higher susceptibility to rubella in Asian than non-Asian women, as shown by antenatal serological data from public health laboratories in Leeds, Luton, and Manchester. Examination of the ethnic origin of pregnant women requesting laboratory testing after contact with rubella or rash and of women with laboratory confirmed rubella in pregnancy also suggested that the disease was being underdiagnosed in pregnant Asian women. Failure to prevent congenital rubella by termination of infected pregnancies may therefore contribute to the increased incidence of the syndrome in Asians. Health education programmes about the dangers of rubella in pregnancy and of the need for vaccination can readily be promoted in the Asian community through existing ethnic organisations. Protection of other ethnic minorities likely to be at similar increased risk may require a vaccination programme aimed at national elimination of rubella.     

Mathematical modeling of nicotine and cotinine as biological markers of environmental tobacco smoke exposure

Computer software developed in our laboratory (CMATRIX) was used to design a physiological pharmacokinetic model of nicotine absorption, distribution, metabolism and excretion in man. The model accommodates inhalation of nicotine from various environmental settings and physiological conditions in man. It was also used to predict pharmacokinetic behavior of cotinine arising from nicotine metabolism. Model-predicted variations in body-fluid nicotine levels confirm that nicotine is not an acceptable quantitative marker of environmental tobacco smoke (ETS) exposure. Though cotinine provides a more stable pattern, predicted interindividual variation suggests the need for specific strict sampling and monitoring guidelines for cotinine to be a reliable quantitative marker.     

Cell biology of smooth muscle in culture: implications for atherogenesis

Smooth muscle cells are one of the most important, if not the most important component of atheromatous plaque. Smooth muscle cells from developing and regenerating arteries, as well as atheromatous plaques, show similar morphological and biochemical characteristics which differ from adult tissue. During primary culture, adult smooth muscle cells alter their morphology to resemble those of the developing, regenerating and atheromatous material. We propose that primary cell culture of smooth muscle cells provides a model for the study of smooth muscle cell changes during atheroma formation.     

The state of sulphydryl groups in proteins isolated from normal and cataractous human lenses

Individual crystallins, urea-soluble and urea-insoluble proteins were isolated from the nucleus and cortex of types I-IV cataractous lenses and normal lenses. The levels of protein sulphydryls (P-SH), disulphides (S-S), as well as surface (F-SH) and buried (S-SH) in these proteins were determined by reaction with 5, 5'-dithiotris- (2-nitrobenzoic acid) or performic acid oxidation followed by amino acid analysis. During nuclear colour development there is a progressive decrease in the sulphydryl content of the crystallins. In the nuclei of advanced cataractous lenses, the P-SH decreases to 10% of the levels found in the normal nucleus. Similar but smaller changes take place in the cortex. No specific changes were found between the crystallins, with the exception of beta S crystallin. The cysteine remains constant in all lens types suggesting no higher oxidation products are formed. There is a significant shift in the distribution of cysteine in the nucleus of type III and IV lenses. Urea-insoluble proteins are the predominant species, accounting for about 70% of the total cysteine pool. This is consistent with the accumulation of modified insoluble polypeptides during senile nuclear cataract formation.     

The development of neurons in the cat perigeniculate nucleus and reticular nucleus of the thalamus

The postnatal development of soma size and cytochrome oxidase activity was examined in the perigeniculate nucleus (PGN) and reticular nucleus of the thalamus (RNT). Neurons in the PGN and RNT exhibited a rapid increase in soma size between 2 and 4 weeks of age. During this period of cell growth there is an increase in the intensity of cytochrome oxidase staining within the cell body. Cells in both the PGN and RNT decrease in size after 4 weeks of age, and become very fusiform in shape. During this postnatal period, there is also a shift in cytochrome oxidase staining from the cell body to the dendrites.     

Activating effect of substance P on nerve tissue in culture

The effect of substance P on organotypic culture of rat sympathetic ganglia and spinal cord was studied. Substance P was able to stimulate the fibre outgrowth from explant, to increase the numbers of glial and fibroblasttypic cells in ganglia growth zone. The effect was observed in the range from 10(-5) to 10(-12) M (for sympathetic ganglia) and from 10(-5) to 10(-14) M (for spinal cord culture). It is suggested that substance P can be used as a nonspecific growth factor for peripheral and central nervous tissue.     

Increased prevalence of apolipoprotein E2 in patients with retinitis pigmentosa

Apolipoprotein E isoforms were determined in 139 unrelated patients with retinitis pigmentosa (RP). When compared to prevalence rates for the general population in Germany, an increased prevalence was observed for phenotypes E2/E2: 10.1 vs. 1.0% (p less than 0.001), E2/E3: 19.4 vs. 12.0% (p less than 0.05), and E2/E4: 5.8 vs. 1.5% (n.s.), while the prevalence appeared to be reduced for phenotypes E3/E3: 48.9 vs. 59.8% (n.s.) E3/E4: 13.7 vs. 22.9% (p less than 0.05), and E4/E4: 2.2 vs. 2.8% (n.s.). These findings suggest that genetically determined abnormalities of plasma lipoprotein metabolism may be associated with some forms of RP.