Helicobacter pylori; histological and cultural correlation in chronic gastritis.

Seventy seven antral biopsies were collected from patients attending endoscopy clinic at King Khalid University Hospital, Riyadh, Saudi Arabia during a period of six months between December 1988 to May 1989. Of these 69 (89.6%) showed chronic gastritis as well as Helicobacter-like organisms (HLOs) in the biopsy specimens while 63 (81.8%) of biopsies grew Helicobacter pylori on culture. These findings indicate a good correlation between the histological diagnosis of chronic gastritis and isolation of H. pylori on culture.     

Identification of 6 new mutations in the iduronate sulfatase gene. Mutation in brief no. 233. Online

Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. We sequenced genomic DNA and RT-PCR products in the iduronate sulfatase (IDS) gene in 6 unrelated patients with Hunter syndrome to assess genotype/phenotype relationships and offer carrier testing where required. Six novel mutations were identified: four missense mutations, one four-base pair deletion (596-599delAACA) and a cryptic splice site mutation. Three of the missense mutations were significant amino acid substitutions (S143F, S491F, E341K) of which the latter two involve amino acids conserved amongst sulfatase enzymes. The patients identified with these mutations all had a severe clinical phenotype. One missense mutation with a minimal amino acid substitution (H342Y), in a non-conserved region of the gene, was associated with a mild clinical phenotype. We identified a novel cryptic splice site (IVS5+934G>A) with some normal (wild type) mRNA processing. We predict that the normal mRNA product confered some residual functional enzyme, resulting in a mild phenotype associated with the absence of overt central nervous system disease.     

Mutations underlying 3-Hydroxy-3-Methylglutaryl CoA Lyase deficiency in the Saudi population

Background  

3-Hydroxy-3-Methylglutaric aciduria (3HMG, McKusick: 246450) is an autosomal recessive branched chain organic aciduria caused by deficiency of the enzyme 3-Hydroxy-3-Methylglutaryl CoA lyase (HL, HMGCL, EC 4.1.3.4). HL is encoded by HMGCL gene and many mutations have been reported. 3HMG is commonly observed in Saudi Arabia.     

Alterations of mononuclear inflammatory cells, CD4/CD8+ T cells, interleukin 1beta, and tumour necrosis factor alpha in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a multisystem disease with underlying immune mechanisms. AIMS: To investigate the clinicopathological characteristics of the lesions; immunological alterations in the bronchoalveolar lavage fluid (BALF), peripheral blood, and skin; and correlations between the clinicopathological characteristics and immunological alterations in SSc. MATERIALS/METHODS: Skin biopsies, BALF, and peripheral blood samples were obtained from 19 patients (18 women, one man) with SSc and six age and sex matched healthy controls (HCs). Mononuclear inflammatory cells (MICs), CD4/CD8 cells, tumour necrosis factor alpha (TNFalpha), and interleukin 1beta (IL1-1beta) concentrations were examined in all samples using histological methods, enzyme linked immunosorbent assay, and immunoperoxidase staining. RESULTS: The mean (SD) age of the patients with SSc was 34.8 (2.6) years. Proteinuria, positive rheumatoid factor, and C reactive protein were seen in 15.8%, 26.3%, and 26.3% of patients, respectively. Compared with HCs, there were significantly higher: total MICs (macrophages, lymphocytes), neutrophils, and eosinophils in BALF, blood, and skin (all p<0.05); cytokine concentrations in BALF (TNFalpha, p<0.001; IL-1, p<0.01) and peripheral blood (p<0.01 and p<0.05); and CD8/CD4+ T cells in peripheral blood (p<0.05). Compared with HCs, lesional skin had significantly higher histiocyte cell counts (p<0.05), lower lymphocyte counts (p<0.05), and higher CD4/CD8 ratios (p<0.001). There were significant correlations between cytokine concentrations and CD8+ T cells and forced vital capacity (p<0.001 and p<0.01, respectively). CONCLUSIONS: MICs, CD4/CD8+ cells, and cytokines are altered in SSc. These alterations correlated with the underlying disease process and therefore may have pathogenic, modulatory, and potential prognostic roles in SSc.     

Application of Evidence-Based Treatment in Community Mental Health Settings: Examining EBT Delivery Duration and Client Discharge

The Journal of Behavioral Health Services & Research - Characterizing community mental health (CMH) treatment duration and discharge is an important step toward understanding how to better meet...     

Carbamoylation of peptides and proteins in vitro by S-(N-methylcarbamoyl)glutathione and S-(N-methylcarbamoyl)cysteine, two electrophilic S-linked conjugates of methyl isocyanate

The reactivity toward peptides and proteins of S-(N-methylcarbamoyl)glutathione (SMG), the glutathione conjugate of methyl isocyanate, and the corresponding cysteine adduct, S-(N-methylcarbamoyl)cysteine (SMC), was investigated with the aid of in vitro model systems. Incubation of SMC or a trideuteriomethyl analogue of SMC with either the reduced or oxidized forms of oxytocin afforded similar mixtures of mono-, bis- and tris-N-methylcarbamoylated peptides. Structure elucidation of the mono and bis adducts by fast atom bombardment tandem mass spectrometry indicated that carbamoylation of oxytocin occurred preferentially at Cys-6 and that Cys-1 and/or Tyr-2 were secondary sites of modification. Upon incubation of S-[N-([14C]methyl)carbamoyl]glutathione (14C-SMG) with native bovine serum albumin (BSA), radioactivity became bound covalently to the protein in a time- and concentration-dependent fashion. "Blocking" of the lone Cys-34 thiol group of BSA in the form of a disulfide prior to exposure of the protein to 14C-SMG failed to decrease significantly the extent or time course of this covalent binding. It is concluded that carbamate thioester conjugates of MIC are reactive, carbamoylating entities which can donate the elements of MIC to nucleophilic functionalities on peptides and proteins. Free thiols appear to be preferred sites for such carbamoylation processes, a phenomenon that may have important toxicological consequences in the pathology of tissue lesions induced by MIC and related isocyanates.     

Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity

Background:Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis.Results:Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease.Conclusions:HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.