Comparison of methods for identifying transcription units and transcription map of the Werner syndrome gene region

OBJECTIVE: The audiologic presentation of vestibular schwannoma (VS) associated with neurofibromatosis type 2 (NF2) has not been well characterized. The goal of this study was to investigate the audiologic features of NF2-associated VS and to determine their relationship to the size of the tumor. STUDY DESIGN: A retrospective case review. SETTING: Quaternary governmental medical research institute evaluating patients fitting specific criteria for ongoing clinical studies. PATIENTS: Audiologic and magnetic resonance imaging data were available for 40 patients (25 males, 15 females), with an average age of 32 years, who had been recruited for ongoing clinical and genetic studies of NF2. MAIN OUTCOME MEASURES: The audiologic profile and magnetic resonance imaging characteristic of tumor were retrospectively reviewed. RESULTS: The average size of the tumor at presentation was 7.26 +/- 16.58 cm3 and measured 1.2, 1.6, and 1.1 cm in the anterior/posterior, lateral/medial, and superior/inferior dimensions, respectively. An increase in lateral/medial size of the tumor most significantly correlated with deterioration in mid- (1,000-2,000 Hz) and high- (4,000-8,000 Hz) frequency hearing levels, elevated speech reception threshold, and prolonged auditory brain stem response waves III and V latency. CONCLUSIONS: Patients with NF2 demonstrate a more predictable audiologic profile for a given size tumor than has been previously described with spontaneous or sporadic VS.     

Increased intraventricular velocities: an unrecognized cause of systolic murmur in adults

OBJECTIVES: The purpose of this study was to determine the frequency, clinical features and echocardiographic characteristics of increased intraventricular velocities (IIVs) in patients referred to the echocardiography laboratory for systolic murmur. BACKGROUND: A subset of patients referred to the echocardiography laboratory for evaluation of a systolic murmur have IIVs in the absence of other recognized causes of systolic murmur. METHODS: We prospectively studied echocardiograms from 108 consecutive patients referred for evaluation of a systolic murmur. Clinical data were obtained from patient examinations and medical records. RESULTS: The sole explanation for systolic murmur was IIVs in 16.7% of referred patients. Compared with those without IIVs, patients with IIVs had a higher ejection fraction (EF) (58.7+/-7.8% vs. 51.1+/-12.5%, p < 0.001), percent fractional shortening (42.3+/-9.7% vs. 31.0+/-11.4%, p < 0.0001), left ventricular (LV) mass index (181+/-70 vs. 152+/-48 g/m2, p=0.046) and prevalence of hypertension (73.3% vs. 51.7%, p=0.043) and a lower prevalence of segmental wall motion abnormalities (2.2% vs. 39.3%, p < 0.001). CONCLUSIONS: Increased intraventricular velocities are a common cause of systolic murmur in this group of patients and should be included in the differential diagnosis of systolic murmurs in adults. The association of IIVs with LV hypertrophy should be a clinical consideration when these murmurs are identified.     

Temporal prey distribution affects the competitive ability of parasitized sticklebacks

Parasitized animals are often reported to have a reduced competitive ability in experimental studies designed to examine foraging success under a specific type of competitive interaction; however, since animals compete under a range of competition regimes in natural situations, and because success is likely to require different foraging skills under each, it is unclear whether infected animals should be equally poor competitors under all competitive scenarios. We studied the foraging success of three-spined sticklebacks, Gasterosteus aculeatus, infected with plerocercoids of a cestode, Schistocephalus solidus, in competition with uninfected conspecifics. When pairs of differentially infected sticklebacks were presented with sequentially introduced items, the numbers of available prey taken by infected and uninfected competitors did not differ significantly, although nonparasitized fish were more successful at taking items over which there was direct competition. In contrast, when prey items were presented simultaneously in a locally dense patch, nonparasitized fish ingested significantly more of the available food than their infected counterparts: an apparent consequence of their greater ability to take items in rapid succession. Our results show that the type of competition conditions generated as a result of specific prey distribution patterns plays a role in determining the relative foraging success of parasitized sticklebacks, and suggest that this may have consequences for the distribution of different infection classes in natural, heterogeneous environments. (c) 1998 The Association for the Study of Animal Behaviour.     

Evidence for genetic anticipation in nodal osteoarthritis

OBJECTIVE: Evidence was sought for genetic anticipation (disease occurring at an earlier age in subsequent generations, with increasing severity) in nodal osteoarthritis (NOA). METHODS: Age at symptom onset and disease severity was compared within 30 parent/offspring pairs with NOA. Correlation between the offspring age of disease onset and the parental age at conception was also assessed. RESULTS: The age at onset of nodal symptoms was earlier in the offspring (43 years (95% confidence intervals (CI) 38 to 47) v 61 (CI 58 to 65); mean difference 18 years (CI 13 to 22): p < 0.001) as was larger joint symptom onset (48 years (CI 41 to 55) v 67 (CI 61 to 73); mean difference 20 years (CI 13 to 27): p < 0.01). A negative correlation existed between age of offspring symptom onset and parental age at conception. Fifteen (50%) offspring had similar or more extensive disease than their parents. CONCLUSIONS: These results suggest genetic anticipation occurs in NOA and if confirmed a search for trinucleotide repeats is warranted.     

Maintenance of remission of ulcerative colitis: a comparison between balsalazide 3 g daily and mesalazine 1.2 g daily over 12 months. ABACUS Investigator group

BACKGROUND: Despite widespread use of aminosalicylates as maintenance treatment for ulcerative colitis (UC), patients still report troublesome symptoms, often nocturnally. AIM: To compare the efficacy and safety of balsalazide (Colazide) with mesalazine (Asacol) in maintaining UC remission. METHODS: A randomized, double-blind comparison of balsalazide 3 g daily (1.04 g 5-ASA) and mesalazine 1.2 g daily for 12 months, in 99 (95 evaluable) patients in UC remission. RESULTS: Balsalazide patients experienced more asymptomatic nights (90% vs. 77%, P=0.0011) and days (58% vs. 50%, N.S.) during the first 3 months. Balsalazide patients experienced more symptom-free nights per week (6.4+/-1.7 vs. 4.7+/-2.8; P=0.0006) and fewer nights per week with blood on their stools or on the toilet paper, mucus with their stools or with sleep disturbance resulting from symptoms or lavatory visits (each P < 0.05). Fewer balsalazide patients relapsed within 3 months (10% vs. 28%; P=0.0354). Remission at 12 months was 58%, in both groups. Similar proportions of patients reported adverse events (61% balsalazide vs. 65% mesalazine). There were five serious adverse events (two balsalazide, three mesalazine) and four withdrawals due to unacceptable adverse events (three balsalazide, one mesalazine), of which one in each group was also a serious adverse event. CONCLUSIONS: Balsalazide 3 g/day and mesalazine 1.2 g/ day effectively maintain UC remission and are equally well tolerated over 12 months. At this dose balsalazide prevents more relapses during the first 3 months of treatment and controls nocturnal symptoms more effectively.     

Benzo[b]fluoranthene: tumorigenicity in strain A/J mouse lungs, DNA adducts and mutations in the Ki-ras oncogene

The polycyclic aromatic hydrocarbon benzo[b]fluoranthene (B[b]F) is a pervasive constituent of environmental combustion products. We sought to examine the lung tumorigenic activity of B[b]F in strain A/J mice, to study the relationship between formation and decay of B[b]F-DNA adducts and to examine mutations in the Ki-ras proto-oncogene in DNA from B[b]F-induced tumors. Mice were given i.p. injections of 0, 10, 50, 100 or 200 mg/kg body wt and lung adenomas were scored after 8 months. B[b]F induced significant numbers of mouse lung adenomas in a dose-related fashion, with the highest dose (200 mg/kg) yielding 6.95 adenomas/ mouse, with 100% of the mice exhibiting an adenoma. In mice given tricaprylin, the vehicle control, there were 0.60 adenomas/mouse, with 55% of the mice exhibiting an adenoma. Based on dose, B[b]F was less active than benzo[a]pyrene. DNA adducts were analyzed qualitatively and quantitatively by 32P-post-labeling in lungs of strain A/J mice 1, 3, 5, 7, 14 and 21 days after i.p. injection. Maximal levels of adduction occurred 5 days after treatment with the 200 mg/kg dose group, producing 1230 amol B[b]F-DNA adducts/microgram DNA. The major B[b]F-DNA adduct was identified by co-chromatography as trans-9, 10-dihydroxy-anti-11, 12-epoxy-5-hydroxy-9, 10, 11, 12-tetra-hydro-B[b]F-deoxyguanosine. Approximately 86% of the tumors had a mutation in codon 12 of the Ki-ras oncogene, as determined by direct DNA sequencing of PCR-amplified exon 1 and single-stranded conformation polymorphism analysis. Analysis of the Ki-ras mutation spectrum in 25 of 29 B[b]F-induced tumors revealed the predominant mutation to be a G-->T transversion in the first or second base of codon 12, congruous with the DNA adduct data. Our data are consistent with previous reports in mouse skin implicating a phenolic diol epoxide as the proximate carcinogenic form of B[b]F that binds to guanine.     

The WHO multicenter study on Listeria monocytogenes subtyping: random amplification of polymorphic DNA (RAPD)

As part of a WHO multicenter study on Listeria monocytogenes subtyping methods the random amplification of polymorphic DNA (RAPD)-technique was evaluated. Six participants were asked to use a standard protocol to analyse a set of 80 L. monocytogenes strains. This set contained 22 groups of epidemiologically linked isolates and 11 pairs of duplicate strains. Using three different 10-mer primers the median reproducibility of the RAPD-results obtained by the six participants was 86.5% (range 0-100%). Failure in reproducibility was mainly due to results obtained with one particular primer. The number of epidemiological groups found to be homogeneous varied from 1-22 (median 16). However, for some groups an inhomogeneity was found by the majority of participants. The overall correlation between the results from the different participants ranged from 32 to 85%.