Increased mucosal inflammatory cytokines in children with Helicobacter pylori-associated gastritis

The concentrations of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1-β in tissue homogenates of gastric mucosal biopsy specimens, and in gastric juice samples from Helicobacter pylori-positive and -negative children, were determined. The study population comprised 30 children with recurrent abdominal pain attending upper gastrointestinal endoscopy. Of these patients 18 were infected with H. pylori. Cytokine concentrations in gastric biopsy homogenate supernatants and in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). TNF-α levels in gastric juice and in gastric biopsy homogenate supernatants in patients with H. pylori-positive gastritis were found to be significantly higher than those in children without H. pylori infection. IL-6 levels were also higher in H. pylori -infected subjects, but the difference in IL-6 concentrations measured in gastric juice and biopsy homogenate supernatants did not reach statistical significance. IL-1-β concentrations in both specimens showed no significant difference between the two groups of children. It was suggested that increased levels of inflammatory cytokines, especially TNF-α and IL-6 generated locally within the gastric mucosa might be implicated in the pathogenesis of H. pylori-associated gastritis in childhood.     

A Technique for Enrichment of Motile Spermatozoa from Oligozoospermic and Asthenozoospermic Patients

Summary: A system for rapid selection of normal motile spermatozoa from poor semen samples is described. Analysis of the selected samples shows that there are significant improvements in the percentage motility, velocity and morphology. The final spermatozoa suspension of 0,5 ml is sufficient for the purpose of intrauterine AIH and IVF.     

Cytotoxic T-cell response to ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2(db) mutation

The T(c)-cell response to ectromelia virus infection was studied in BALB/c-H-2(db) mice which carry a loss mutation in the H-2D region that results in the absence from cell surfaces of a molecule (D’) bearing certain public H-2 specificities. When infected, these mice showed a poor response of T(c) cells that recognize H-2D(d) plus virus-specific determinants on infected macrophage targets, but gave a normal response to H-2K d plus virus-specific antigens. However, their own infected macrophages do display wild-type antigenic patterns involving virus and H-2D(d) since they were killed as efficiently as wild-type (BALB/c,H- 2(d))-infected cells by T(c) cells specific only for H-2D(d) plus viral antigens. When tested in vitro, infected BALB/c-H-2(db) cells stimulated a poor T(c)-cell response to H-2D plus virus-specific antigens, but stimulated a normal response (in comparison with infected BALB/c macrophages) to H-2K(d) plus viral antigens. Uninfected BALB/c-H-2(db) cells stimulated a normal T(c)-cell response to minor H antigens or trinitrophenyl in association with H-2D(d), thus suggesting that the defective response to infection may reside in a failure of the relevant H-2D(d) antigens of mutant cells to physically associate with viral antigens. Close association of viral and H-2D-coded molecules was also suggested by ability of specific anti-H-2K or -H-2D to partially block T(c)-cell-mediated lysis of infected targets. These results were interpreted to mean that H-2Dd-dependent, virus- immune T(c) cells recognized an antigenic pattern consisting of virus- specific and H-2D(d) determinants with the latter borne on an H-2D molecule carrying serologically-defined H-2D(d) private specificities. A second H-2D(d)-coded molecule (D’) was not required for recognition and lysis by activated T(c) cells, but was apparently necessary for efficient stimulation of precursor T(c) cells, perhaps by promoting appropriate physical association of viral and H-2D(d) molecules.     

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator ( AIRE ) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1–7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.     

Endosulfan Application to a Stream Mesocosm: Studies on Fate,Uptake into Passive Samplers and Caged Toxicity Test with the Fish <Emphasis Type="Italic">M. ambigua</Emphasis>

A model mesocosm system was used to simulate the effect of endosulfan entering a waterway from episodic events such as accidental overspray or in runoff water containing contaminated sediment following storm events. The fate of technical endosulfan applied to a 24-stream mesocosm was compared in experiments where the pesticide was applied either directly as water contamination or after being pre-bound to sediment. The flow of water through the streams was discontinued for a 10–12 h period following the pesticide application. Following the water application, only approximately 3% of endosulfan remained in the streams after 4 days and then was not detectable after 7 days. In contrast, after application pre-bound to sediment, approximately 33% of the endosulfan remained in the streams after 4 days and 14% after 7 days. Additionally, with the sediment-bound application, the proportion of endosulfan was higher in the substrate (11%) after 7 days than in the overlying water (3%), and approximately 1% was oxidised to the sulphate form. The dissipation of endosulfan in the water column of both experiments followed a two-parameter exponential decay model characterised by a relatively fast first-order single-phase process. In sediment of both experiments and the gravel of the sediment-dosing experiment, the dissipation of endosulfan followed more closely a four-parameter bi-exponential decay model characterised by first-order kinetics of two fractions: the first fraction dissipates quickly, and in the longer term the second fraction dominates the overall dissipation with a slower rate. In the gravel section of the water-dosing experiment, endosulfan dissipation was characterised by relatively very slow two-parameter exponential decay. The overall dissipation rates of the α- and β-endosulfan isomers were significantly higher in the water-dosing than in the sediment-dosing experiment, except in the gravel section of the mesocosm. The uptake of the endosulfan into passive samplers constructed from polyethylene membrane bags containing trimethylpentane solvent (TRIMPS) placed in the overlying water was linear. In contrast, TRIMPS buried in sediment failed to uptake endosulfan from the sediment substrate, indicating that short-term deployment of passive samplers can only be used to determine time-weighted average concentrations of bioavailable chemicals in the water column. A 34-h LC50 of 2.8 μg/l [95% confidence interval (CI) 1.5–4.2 μg/l] for juveniles of the native fish Macquaria ambigua was obtained when exposed during the water-dosing experiment. This study demonstrated that the pulse entry of sediment contaminated with endosulfan into a receiving waterway was more persistent compared with direct aqueous contamination and the endosulfan would be bioavailable to pelagic organisms following a gradual partitioning to the water column.