Health effects of methyl tertiary butyl ether (MTBE) in gasoline in Alaska

OBJECTIVES: This ecologic study assessed whether there was a change in health status in Alaska in the winter of 1992-93 after the introduction of MTBE in gasoline. Methyl tertiary butyl ether(MTBE) is used as a fuel oxygenate in the United States and in Europe. In the winter of 1992-93 MTBE was added to gasoline in the cities of Fairbanks and Anchorage, Alaska. The program was discontinued in Fairbanks in December, 1992, but continued in Anchorage until February 28, 1993. METHODS: Outpatient visits for state employees and dependents (n = approximately 28,000) living in Alaska were compared over three winters by analyzing health insurance claims. RESULTS: Odds ratios were calculated. The odds ratios indicated that the winter of 92-93 was not statistically different from previous winters in numbers of claims for upper respiratory illness, bronchitis, headache, or asthma in either Anchorage or Fairbanks. CONCLUSION: There was no increase in claims for respiratory illness in either city after introduction of MTBE.     

Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX

VanX, one of the five proteins required for the vancomycin-resistant phenotype in clinically pathogenic Enterococci, is a zinc-containing d-Ala-d-Ala dipeptidase. To identify potential zinc ligands and begin defining the active site residues, we have mutated the 2 cysteine, 5 histidine, and 4 of the 28 aspartate and glutamate residues in the 202 residue VanX protein. Of 10 mutations, 3 cause inactivation and greater than 90% loss of zinc in purified enzyme samples, implicating His116, Asp123, and His184 as zinc-coordinating residues. Homology searches using the 10 amino acid sequence SxHxxGxAxD, in which histidine and aspartate residues are putative zinc ligands, identified the metal coordinating ligands in the N-terminal domain of the murine Sonic hedgehog protein, which also exhibits an architecture for metal coordination identical to that observed in thermolysin from Bacillus thermoproteolyticus. Furthermore, this 10 amino acid consensus sequence is found in the Streptomyces albus G zinc-dependent N-acyl-d-Ala-d-Ala carboxypeptidase, an enzyme catalyzing essentially the same d-Ala-d-Ala dipeptide bond cleavage as VanX, suggesting equivalent mechanisms and zinc catalytic site architectures. VanX residue Glu181 is analogous to the Glu143 catalytic base in B. thermoproteolyticus thermolysin, and the E181A VanX mutant has no detectable dipeptidase activity, yet maintains near-stoichiometric zinc content, a result consistent with the participation of the residue as a catalytic base.     

The intracellular mechanisms of glutaminergic and cholinergic signal transduction in the cerebral cortex

Stimulation of glytamate- and cholinoreceptors by the agonists induced a prolonged calcium and phosphoinositide responses to short-term anoxia or administration of an antioxidant agent in cortical structures. Processes of adaptation essentially modified these responses.     

Security of capsular fixation: small-versus large-hole plate-hepatic lenses

PURPOSE: To assess the effect of relatively large positioning holes on the security of capsular bag fixation of plate-haptic silicone intraocular lenses (IOLs). SETTING: Center for Research on Ocular Therapeutics and Biodevices, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: This study tested the hypothesis that larger holes allow ingrowth of lens material, fibrous tissue, or both through them, which helps fixate the lens more firmly in the capsular bag. Five rabbits had bilateral continuous curvilinear capsulorhexis, phacoemulsification, and implantation of a plate-haptic silicone IOL. An IOL with a small, round positioning hole (Staar AA-4203V) was implanted in the right eye in each rabbit, and a large-hole IOL (Staar AA-4203VF) was implanted in the left eye. After 2 months, all rabbits were killed. The force required to extract one haptic from the capsular bag was measured with a digital force meter. All eyes had histopathological analysis. RESULTS: It was slightly more difficult to extract a large-hole IOL from the capsular bag, although this trend was not statistically significant. However, histopathological analysis consistently showed 360 degree synechia formation through the holes, showing that the IOL could be securely fixed in position. CONCLUSIONS: Proliferation of lens epithelial cells through a large positioning hole in a plate-haptic silicone IOL may improve the long-term security of capsular bag fixation. This will help reduce the incidence of IOL decentration and dislocation.     

Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa

The RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%-15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis.     

Consistent improvement in sphincterotome orientation with manual grooming

AIMS: To determine the prevalence of lymphoid follicles in Helicobacter pylori positive and negative gastritis in antral and body type gastric mucosa in patients with non-ulcer dyspepsia (NUD), duodenal ulcer, or gastric ulcer; to correlate follicle presence with patient age; to evaluate the correlation between the prevalence of lymphoid follicles and active and inactive gastritis and its severity; and to assess the positive predictive value of lymphoid follicle prevalence with respect to H pylori infection. METHODS: Gastric biopsy specimens, graded according to the Sydney system, from 337 patients were studied. RESULTS: Lymphoid follicles occurred more often in antral mucosa (78%) than in body type mucosa (41%) and were observed in 85% of patients with H pylori positive gastritis. There was no significant difference between NUD and gastric and duodenal ulcer disease with regard to the presence of lymphoid follicles. The positive predictive value of the presence of lymphoid follicles in H pylori infection was 96%. Lymphoid follicles were more commonly observed in patients aged between 10 and 29 years. Lymphoid follicles were more frequently found in pangastritis of all subtypes than in antral gastritis and also in active gastritis than in inactive gastritis. The presence of lymphoid follicles correlated strongly with the degree and severity of gastritis. CONCLUSION: Lymphoid follicles are a constant morphological feature of H pylori associated gastritis.