23116607
Intestinal entry of prions.
Variant Creutzfeldt-Jakob disease is thought to be caused by infected prion protein via ingestion of contaminated beef. After ingestion of infected prion proteins, uptake by small intestine may be by either M-cell dependent or M-cell independent routes. A receptor for prion protein, laminin receptor precursor is expressed on the brush border of small intestinal epithelium in 40 % of subjects. The cellular prion protein expressed on the enteric nervous system might serve as the target for conversion to infectious prion protein and a route for spread to the central nervous system.
24936933
Mechanism of intestinal entry of infectious prion protein in the pathogenesis of variant Creutzfeldt-Jakob disease.
The pathogenesis of variant Creutzfeldt-Jakob disease (vCJD) is most likely to be dependent on intestinal entry of orally ingested infectious prion proteins, though tonsils or other oral portals of entry are possible. The exact route of entry of infectious prion proteins is uncertain but receptors for prion proteins such as laminin receptor precursor (LRP) may be expressed on intestinal brush border. Cellular prion protein (PrP(c)) is expressed on intestinal enteric nervous system and is separated by a single layer of epithelial cells from ingested infectious prion proteins. Intestinal M cells in the Peyer's patches may also transcytose prion proteins which may be transported to the lymphatic system by migrating dendritic cells underlying the M cells. The relative importance of the several potential portals of intestinal entry of infectious prion proteins is uncertain but may determine susceptibility of the population and also potential preventive strategies.
35121171
Bioactive natural compounds for the treatment of gastrointestinal disorders.
Many healthy subjects and patients are taking natural bioactive products for the prevention and treatment of multiple conditions, including gastrointestinal disorders. Based on current evidence, the scientific validity of the use of many of these commercial compounds by the general public is severely limited, with quality control and regulatory issues continuing to be a concern. Nevertheless, there is sufficient preliminary data to warrant further research of these products in order to identify novel compounds for potential clinical use in addition to performing formal randomized controlled clinical trials of the commercial preparations.
37212550
Management of Crohn’s disease from efficacy, quality of life and health economic perspectives
The expectations of the physician and patient in the modern management of Crohn’s disease have moved on from alleviation of symptoms whenever relapses occur, to sustained maintenance of remission and mucosal healing. The majority of treatment costs are as a consequence of hospitalizations and surgery. These heightened therapeutic goals are leading to expectations that management costs will decrease. Health-related quality of life can be measured by validated disease-specific tools in Crohn’s disease, and such measurements are now forming common outcome measures in clinical trials of new therapies in Crohn’s disease. This review gives an overview of patient-focused management of Crohn’s disease and the rapid evolution in therapy, with pharmacoeconomic analysis where available.
27300590
Identification of motor areas of the cat cerebral cortex based on studies of cortical stimulation and corticospinal connections.
The location and topography of motor areas in the cat cerebral cortex were studied by electrical stimulation of the cortex in five animals, and by the injection of retrograde tracers into the spinal cord of four animals. Movements evoked by intracortical microstimulation (ICMS) of the anterior, posterior and lateral sigmoid gyri, both banks of the cruciate sulcus and the dorsal bank of the presylvian sulcus were observed in anaesthetized cats. Fluorescent tracers (Fast Blue and/or Diamadino Yellow) were injected into the lateral funiculus in the second cervical segment, into the gray matter of cervical segments C3-T1 and/or into the gray matter of lumbar segments L2-S1. Contraction of the contralateral forelimb, hindlimb or facial muscles was observed following electrical stimulation of several cytoarchitectonic areas: 4 gamma, 4 delta, 6a alpha, 6a gamma, and 3a. These findings suggested representations of contralateral forelimb and hindlimb movements in areas 4 gamma and 4 delta, and of the contralateral forelimb muscles in areas 6a alpha and 6a gamma. Corticospinal neurons were located in all the above cytoarchitectonic areas as well as in areas 3b, 1, 2, 2pri, and 5. Large numbers of neurons were labeled in areas 4 gamma and 4 delta, and moderate labeling was observed in areas 6a gamma and 6a alpha. Corticospinal neurons projecting to cervical and lumbar segments were located in areas 4 gamma and 4 delta, while those projecting only to cervical segments were detected in areas 6a alpha and 6a gamma. Based on these findings it is proposed that within the motor cortex of the cat there are representations of limb movements in several cytoarchitectonic subdivisions. Many of these representations may be candidate secondary motor areas.
11853260
Evidence for interstate transmission and increase in prevalence of bovine group B rotavirus strains with a novel VP7 genotype among diarrhoeic calves in Eastern and Northern states of India.
During a surveillance study (2003-2005) in a cattle market in Kolkata city, state of West Bengal, Eastern India, 34 (13.0%) of 260 calves with diarrhoea were positive for group B rotaviruses (GBR) by RNA electrophoresis in polyacrylamide gels. Analysis of the partial VP7 gene sequence of 28 of the 34 GBR strains revealed maximum identities (97.7-99.5% at nucleotide level and 97.8-100% at amino-acid level) with the novel bovine GBR 'Kolkata strains' reported in an earlier surveillance study (1.5%, n=192, 2001-2002) from the same cattle market, and shared low identities of 73.7-78.9% and 80.8-89.6%; 62.6-66.2% and 59.8-65.4%; 58.9-62.2% and 48.6-54.9% at nucleotide and amino-acid level with other bovine, human, and murine GBR. The GBR-infected calves were traced to districts in neighbouring states of West Bengal. Therefore, the present study reports a rapid increase in prevalence (13.0% in 2003-2005 against 1.5% in 2001-2002) of novel GBR strains among calves with diarrhoea, and provides evidence for interstate transmission of GBR.
21127198
Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal.
The DNA binding subunit of the transcription factor NF-kappa B, p50, has been cloned. p50 appears to be synthesized as a larger protein that is then processed to its functional size. Sequence analysis reveals remarkable homology for over 300 amino acids at the amino-terminal end to the oncogene v-rel, its cellular homolog c-rel, and the Drosophila maternal effect gene dorsal. This establishes NF-kappa B as a member of the rel family of proteins, all of which display nuclear-cytosolic translocation. Protein sequence from the p65 polypeptide has established that it is not encoded in the same mRNA as p50. However, p65 appears homologous to c-rel, suggesting that c-rel may form heterodimers with p50 and rel may include a homodimerization motif.
38995657
Posthepatitis aplastic anaemia presenting only with bilateral vision loss.
Aplastic anaemia is pancytopenia with marrow hypocellularity. Hepatitis-associated aplastic anaemia is a varient or aplastic anaemia that follows an acute attack of seronegative hepatitis. Here a case of hepatitis-associated aplastic anaemia presenting with sudden onset of severe simultaneous bilateral vision loss and without any other usual presenting signs is reported. Partial recovery of blood cell count occurred following immunosuppressive therapy. Posterior hyalodotmy helped rapid resolution of premacular subhyaloid haemorrhage. Although bilateral vision loss may rarely be the initial presentation of aplastic anaemia, no such report is known in hepatitis-associated aplastic anaemia. Posthepatitis vision loss needs careful investigation to exclude an underlying haematological disorder.
20426294
Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B.
Nuclear factor kappa B (NF-kappa B), which was first detected by its binding to the kappa B site in the immunoglobulin kappa-gene enhancer, is important for the regulated expression of the kappa-gene and is partly responsible for the induction in appropriate cells of interleukin-2 (IL-2), IL-2 alpha receptor, beta-interferon and serum amyloid A protein. NF-kappa B is present as a nuclear DNA-binding protein in B lymphocytes and mature macrophages, but is found in the cytoplasm of many cells in a form unable to bind to DNA. The cytoplasmic form is bound to an inhibitor protein, I kappa B, from which it can be released in vitro by deoxycholate and other agents. Activation of cells by various agents, notably the phorbol esters that stimulate protein kinase C (PKC), leads to dissociation in vivo of the NF-kappa B/I kappa B complex and migration of NF-kappa B to the nucleus. Therefore, it acts as a second messenger system, transducing activation signals from the cytoplasm to the nucleus. To elucidate the mechanism of signal transfer, we have used an in vitro system in which addition of purified protein kinases to a partially purified NF-kappa B/I kappa B complex leads to the activation of the DNA-binding activity of NF-kappa B. Using gel retardation assays we found that PKC, cyclic AMP-dependent protein kinase (PKA) and a haem-regulated eIF-2 kinase (HRI) could activate NF-kappa B in vitro, whereas casein kinase II was ineffective. To determine the target for the protein kinases we purified and characterized both NF-kappa B and I kappa B and found that I kappa B is phosphorylated and inactivated in the presence of PKC and HRI but not PKA.