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.

title: Bioactive natural compounds for the treatment of gastrointestinal disorders.
abstract: 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.

title: Management of Crohn’s disease from efficacy, quality of life and health economic perspectives
abstract: 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.

title: Mobilization of cytoplasmic CE droplets by overexpression of human macrophage cholesteryl ester hydrolase Published, JLR Papers in Press, July 1, 2003. DOI 10.1194/jlr.M300162-JLR200
abstract: The obligatory first step in the removal of cholesterol from foam cells is the hydrolysis of stored cholesteryl esters (CEs) to release free cholesterol (FC). Neutral cholesteryl ester hydrolase (CEH) catalyzes this hydrolysis, and limiting levels of CEH could play a role in determining the susceptibility to atherosclerosis. We have recently reported the first identification and cloning of cDNA for human macrophage CEH. In the present study, we tested the hypothesis that systematically varied levels of overexpression of human macrophage CEH results in a proportional degree of reduction in cellular CE content in a cell system with known and reproducible amounts of CE accumulation. CEH expression was confirmed by demonstrating the presence of CEH mRNA and protein with an increase in CEH activity. A significant reduction in intracellular lipid droplets was observed in CEH-expressing cells, together with a decrease in cellular CE mass and a 2-fold increase in FC efflux. These results demonstrate that when human macrophage CEH is expressed in lipid-laden cells, hydrolysis and mobilization of CE (stored as lipid droplets) occur. These data establish the possibility that increased CE hydrolysis, mediated by CEH up-regulation, could represent an important mechanism to reduce the cholesterol burden of foam cells.

title: In vitro and in vivo efficacy of Acorus calamus extract against Rhipicephalus (Boophilus) microplus
abstract: To develop a environment friendly control measure against cattle tick, Rhipicephalus (Boophilus) microplus, medicinally important plants were identified and extracts were prepared. Twelve 95% ethanolic, thirteen 50% hydroethanolic and nine hot water extracts were prepared and tested against laboratory reared homogenous colony of R. (B.) microplus. Amongst the 34 extracts, 26 extracts showed no mortality within 72 h of application while 12.0 ± 4.9% to 35.0 ± 9.6% mortality of treated ticks was recorded in other extracts. Of the effective extracts, the extract prepared from rhizome of Acorus calamus proved highly efficacious and 100% final mortality within 14 DPT was recorded. The LC85 value of the extract was determined as 11.26. In vivo experiments confirmed the efficacy of the extract up to 42%, and repeat application was required after 7 DPT. The extract was found safe and no reaction was observed when animals were treated with 50% of the concentration, which was five times of the concentration used for in vivo studies. The possibility of using the extract for the control of cattle tick is discussed.

title: Report of a new syndrome: focus on differential diagnosis and review of Ellis-van Creveld, Curry-Hall, acrofacial dysostosis, and orofacial digital syndromes.
abstract: Ellis-van Creveld (EvC) and Curry-Hall (CH) syndromes are rare syndromes that occur due to mutations of genes mapped to the chromosome 4p16 region. Hence, they both have few features that are common. The dental literature describing the oral manifestations and etiology of both syndromes is scarce. We report a case of a 7-year-old girl who appeared with features that are common to both syndromes, as well as with other features such as reduced cranial base flexure and toes of equal length with skeletal changes that have not been mentioned or described in earlier reports. The patient possibly represents a new syndromic entity that has not been reported until now. Further, we present a review of various other similar syndromes, such as various types of orofacial digital (OFD) syndrome and acrofacial dysostosis.

title: Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal.
abstract: 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.

title: Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA.
abstract: The sensitive technique of RT-PCR was used to identify cholesteryl ester hydrolase (CEH) expressed in human macrophages. This enzyme is thought to regulate the availability of intracellular free cholesterol for efflux. The expected 667-bp product was obtained starting with RNA from human peripheral blood and THP-1 monocytes and macrophages. The cDNA for human macrophage CEH was then cloned by PCR-based screening of a lambda-gt11 cDNA library. The full-length cDNA was sequenced and found to exhibit 76% homology (at the nucleotide and conceptually translated protein level) to hepatic CEH, an enzyme shown to be involved in hepatic cholesterol homeostasis and regulated by cholesterol at the transcription level via sterol response elements in the proximal promoter. Identification of the conserved catalytic triad (Ser(221, His(468), and Glu354)) and the SEDCLY motif places human macrophage CEH in the family of carboxylesterases. A greater than 20-fold increase in CEH activity was observed when COS-1 and COS-7 cells were transiently transfected with an eukaryotic expression vector, pcDNA3.1/V5/His-TOPO, containing the cDNA for human macrophage CEH. Using this full-length cDNA as a probe, a 2.2-kb transcript was identified by Northern blot analysis of total RNA from human peripheral blood and THP -1 macrophages. Overexpression of human macrophage CEH resulted in an impairment of upregulation of low-density lipoprotein (LDL) receptor mRNA in Chinese hamster ovary (CHO-K1) cells grown in cholesterol-deficient environment. These data identify the human macrophage CEH, demonstrate its expression in human peripheral blood macrophage and human macrophage cell line, THP-1, and suggest its role in the intracellular cholesteryl ester metabolism.