Effect of long acting somatostatin-analogue, SMS 201 995, on gut hormone secretion in normal subjects

SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s.c. injection of 50 micrograms it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.     

Plasma enteroglucagon,peptide YY and gastrin in rats deprived of luminal nutrition,and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p<0.001) of=" intravenously=" fed=" (tpn)=" rats.=" urogastrone-epidermal=" growth=" factor,=" (uro-egf),=" reversed=" these=" changes.=" although=" plasma=" enteroglucagon=" and=" gastrin=" levels=" showed=" a=" small=" increase=" with=" uro-egf,=" this=" was=" far=" less=" than=" the=" gut=" tissue=" weight=" change,=" suggesting=" that=" it=" was=" unlikely=" that=" they=" were=" involved=" in=" modulating=" the=" proliferative=" response=" of=" the=" intestine=" to=" uro-egf.=" peptide=" tyrosine=" tyrosine=" (pyy)=" levels=" were=" however=" significantly=" increased=" by=" uro-egf,=" indicating=" that=" pyy=" may=" possibly=" have=" a=" role=" in=" the=" modulation=" of=" intestinal=" cell=">We thank the Cancer Research Campaign for their financial assistance and acknowledge the technical assistance of Mr W. Lenton.     

Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma

Interferon-gamma (IFN-gamma) is produced during the response to infection and participates in immunostimulatory events. We have previously reported the induction of diabetes in transgenic mice (ins-IFN-gamma) in which the expression of the lymphokine IFN-gamma is directed by the insulin promoter. This diabetes is a result of the progressive destruction of pancreatic islets that occurs with the influx of inflammatory cells. Here we demonstrate that this islet cell loss is mediated by lymphocytes, that engrafted histocompatible islets are destroyed, and that lymphocytes from the transgenic mice are cytotoxic to normal islets in vitro. These results indicate that the pancreatic expression of IFN-gamma can result in a loss of tolerance to normal islets, consistent with its role as an inducer of costimulatory activity, which is essential for lymphocyte activation during an immune response.     

High star formation rates as the origin of turbulence in early and modern disk galaxies

Observations of star formation and kinematics in early galaxies at high spatial and spectral resolution have shown that two-thirds are massive rotating disk galaxies, with the remainder being less massive non-rotating objects. The line-of-sight-averaged velocity dispersions are typically five times higher than in today's disk galaxies. This suggests that gravitationally unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos. These accreting flows, however, have not been observed, and cosmic accretion cannot power the observed level of turbulence. Here we report observations of a sample of rare, high-velocity-dispersion disk galaxies in the nearby Universe where cold accretion is unlikely to drive their high star formation rates. We find that their velocity dispersions are correlated with their star formation rates, but not their masses or gas fractions, which suggests that star formation is the energetic driver of galaxy disk turbulence at all cosmic epochs.     

T cells can present antigens such as HIV gp120 targeted to their own surface molecules

To trigger class II-restricted T cells, antigen presenting cells have to capture antigens, process them and display their fragments in association with class II molecules. In most species, activated T cells express class II molecules; however, no evidence has been found that these cells can present soluble antigens. This failure may be due to the inefficient capture, processing or display of antigens in a stimulatory form by T-cells. The capture of a soluble antigen, which is achieved by nonspecific mechanisms in macrophages and dendritic cells, can be up to 10(3) times more efficient in the presence of surface receptors, such as surface immunoglobulin on B cells that specifically bind antigen with high affinity. We asked whether T cells would be able to present soluble antigens that bind to their own surface molecules. Here we show that such antigens can be effectively processed and presented by both CD4+- and CD8+-bearing human T cells. This indicates that T cells are fully capable of processing and displaying antigens and are mainly limited in antigen presentation by their inefficiency at antigen capture.     

Extremely slow Drude relaxation of correlated electrons

The electrical conduction of metals is governed by how freely mobile electrons can move throughout the material. This movement is hampered by scattering with other electrons, as well as with impurities or thermal excitations (phonons). Experimentally, the scattering processes of single electrons are not observed, but rather the overall response of all mobile charge carriers within a sample. The ensemble dynamics can be described by the relaxation rates, which express how fast the system approaches equilibrium after an external perturbation. Here we measure the frequency-dependent microwave conductivity of the heavy-fermion metal UPd2Al3 (ref. 4), finding that it is accurately described by the prediction for a single relaxation rate (the so-called Drude response). This is notable, as UPd2Al3 has strong interactions among the electrons that might be expected to lead to more complex behaviour. Furthermore, the relaxation rate of just a few gigahertz is extremely low--this is several orders of magnitude below those of conventional metals (which are typically around 10 THz), and at least one order of magnitude lower than previous estimates for comparable metals. These observations are directly related to the high effective mass of the charge carriers in this material and reveal the dynamics of interacting electrons.     

Oncogenomics and the development of new cancer therapies

Scientists have sequenced the human genome and identified most of its genes. Now it is time to use these genomic data, and the high-throughput technology developed to generate them, to tackle major health problems such as cancer. To accelerate our understanding of this disease and to produce targeted therapies, further basic mutational and functional genomic information is required. A systematic and coordinated approach, with the results freely available, should speed up progress. This will best be accomplished through an international academic and pharmaceutical oncogenomics initiative.     

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.