Mapping of α- and β-globin genes on Antarctic fish chromosomes by fluorescence in-situ hybridization

The pathways and mechanisms of genomic change that have led to the peculiar haemoglobinless phenotype of the white-blooded Antarctic icefishes (16 species in the family Channichthyidae) constitute an important model for understanding the rapid diversification of the Antarctic notothenioid fish flock. To provide complementary structural information on genomic change at globin-gene loci in Antarctic fish species, cytogenetic studies and in-situ chromosomal mapping have been undertaken. Using a DNA probe containing one α- and one β-globin gene from the embryonic/juvenile globin gene cluster of the red-blooded species Notothenia coriiceps, we mapped the cluster on the chromosomes of Antarctic teleosts by fluorescence in-situ hybridization. As anticipated on the basis of its molecular organization, the cluster was located on a single chromosome pair in all of the red-blooded fish species probed (N. coriiceps, N. angustata, Trematomus hansoni, T. pennellii). In contrast, the α/β-globin probe did not recognize complementary sequences on the chromosomes of the white-blooded species Chionodraco hamatus and Channichthys rhinoceratus. These results represent the first example of chromosomal mapping of embryonic/juvenile globin genes in teleostean fishes. Beyond its relevance to the evolutionary history of Antarctic notothenioids, this work contributes to our understanding of the evolution of the chromosomal loci of globin genes in fishes and other vertebrates. This revised version was published online in July 2006 with corrections to the Cover Date.     

A method to remove artifacts in attenuation-corrected myocardial perfusion SPECT Introduced by misalignment between emission scan and CT-derived attenuation maps.

Nonuniform soft-tissue attenuation affects the diagnostic accuracy of SPECT in myocardial perfusion imaging. The attenuation map required for attenuation correction can be acquired using x-ray tomography (CT). Frequent findings in attenuation-corrected images are defects in the apical and anterior myocardial wall. We assume that these are artifacts produced by misalignment of SPECT images and the attenuation map. METHODS: One hundred forty patients underwent myocardial perfusion imaging with 99mTc-methoxyisobutylisonitrile. Twenty-seven of 140 showed pronounced defects in the apical or anterior wall only after CT-based attenuation correction. SPECT and corresponding CT slices were examined for misalignment in the ventrodorsal direction (y-direction) visually and by threshold-based delineation of the body surface. Mismatched studies were realigned and image reconstruction and analysis were redone. The effect of the correction was assessed visually and by semiquantitative analysis based on a 20-segment model using 4D-MSPECT. RESULTS: In 15 of 27 patients, the improved coregistration led to smaller and less-pronounced defects in the regions mentioned. In 6 of 27 patients, former defects were judged as normal. No improvement was seen in only 4 patients. In these 4 subjects, the mismatch in the y-direction was <1 pixel (7 mm), and visual inspection suggested a coincident mismatch in the craniocaudal direction. In 2 cases, coregistration was not possible because the body outline extended beyond the CT field of view. Semiquantitative analysis revealed a significant increase of the relative uptake in the apex; in the apical segments of the anterior, septal, and inferior wall; and in the mid-anterior and mid-anteroseptal segment. Basal segments of the anterolateral, lateral, and inferolateral wall and the middle inferolateral segment showed a significant decrease of relative uptake. CONCLUSION: Misalignment in the y-direction between SPECT and the attenuation map can lead to artifacts in the apical, septal, and anterior wall, which will appear as defects. It also can cause overcorrection in the basal inferior and lateral segments. There is evidence that mismatches along the other directions may have a similar effect. The coregistration of SPECT and the attenuation map needs to be verified for every patient, even when using integrated dual-modality imaging devices.     

The relationship between interviewers' characteristics and ratings assigned during a multiple mini-interview.

PURPOSE: To assess the consistency of ratings assigned by health sciences faculty members relative to community members during an innovative admissions protocol called the Multiple Mini-Interview (MMI). METHOD: A nine-station MMI was created and 54 candidates to an undergraduate MD program participated in the exercise in Spring 2003. Three stations were staffed with a pair of faculty members, three with a pair of community members, and three with one member of each group. Raters completed a four-item evaluation form. All participants completed post-MMI questionnaires. Generalizability Theory was used to examine the consistency of the ratings provided within each of these three subgroups. RESULTS: The overall test reliability was found to be .78 and a Decision Study suggested that admissions committees should distribute their resources by increasing the number of interviews to which candidates are exposed rather than increasing the number of interviewers within each interview. Divergence of ratings was greater within the pairing of community member to faculty member and least for pairings of community members. Participants responded positively to the MMI. CONCLUSION: The MMI provides a reliable protocol for assessing the personal qualities of candidates by accounting for context specificity with a multiple sampling approach. Increasing the heterogeneity of interviewers may increase the heterogeneity of the accepted group of candidates. Further work will determine the extent to which different groups of raters provide equally valid (albeit different) judgments.     

Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

The dbl oncogene was initially isolated from a human diffuse B-cell lymphoma. Antisera from mice bearing tumors induced by this oncogene specifically detected a protein of about 66 kDa (p66) in dbl transformants. dbl cDNA-selected poly(A)+ RNA isolated from a transfectant clone expressing p66 directed the in vitro synthesis of this protein, establishing that it is encoded by dbl. Subcellular localization studies revealed that p66 is a cytoplasmic protein distributed between cytosol and crude membrane fractions. Moreover, p66 was shown to be a phosphoprotein, with phosphorylation specific to serine residues. Our characterization of the dbl-encoded protein appears to distinguish this transforming gene product from those of other known oncogenes.     

Olfaction in essential tremor patients with and without isolated rest tremor.

An olfactory deficit is present in patients with essential tremor (ET), but it is often milder than that in patients with Parkinson's disease (PD). In both, the deficit occurs early in the disease. Isolated rest tremor without other signs of parkinsonism can occur in patients with ET. If the rest tremor in these patients represents a manifestation of ET rather than early PD, we hypothesized that their University of Pennsylvania Smell Identification Test (UPSIT) scores would be similar to those of ET patients without rest tremor. The mean UPSIT score in 13 ET patients with isolated rest tremor did not differ from that of 58 ET patients without rest tremor (29.3 +/- 4.3 vs. 29.4 +/- 6.4; P = 0.69). Several ET patients with rest tremor had UPSIT scores that fell outside of the range that is seen in 95% of patients with PD. These data raise the possibility that some ET patients with isolated rest tremor may not have early PD and that the pathological process that is responsible for their ET is also involving the basal ganglia.     

Treatment of scleromyxoedema with hydroxychloroquine

Background: Scleromyxoedema is a rare disease of unknown aetiology that is characterized by deposition of mucin and sclerotic induration of the skin; it is associated with paraproteinaemia. Patients suffer from progressive disability due to immobilization and cosmetic disfigurement. Treatment of scleromyxoedema is a therapeutic challenge. The antimalarial hydroxychloroquine has a rapid and reliable effect in reticular erythematous mucinosis. Patients and methods: Four consecutive patients (two women, two men; median age: 50 years) with scleromyxoedema, three of them with IgG λ paraprotein, were treated with hydroxychloroquine. Treatment was initiated with 600 mg p. o. for 10 days, followed by 400 mg for at least 4 weeks, and 200 mg thereafter. Results: Complete remission of skin manifestations was achieved in one patient, whereas three patients achieved a partial remission of 61+, 5 and 25 months' duration. Notably, three patients felt increased mobility and reduced firmness of skin during the first week of treatment, which was reflected in a rapid reduction in dermal thickness. In one patient, dysphagia was reverted as evidenced by normalization of oesophageal clearance. Paraproteinaemia was not influenced at all. Side effects included one case of electroretinogram abnormalities after 19 months of therapy and one case of leucopenia after 3 months. Conclusion: Hydroxychloroquine is an effective form of therapy for scleromyxoedema, leading to rapid and prolonged alleviation of symptoms.     

Increased sensitization in urban vs. rural environment – Rural protection or an urban living effect?

In a population-based longitudinal cohort study, we tested the hypothesis that children growing up in a high-traffic polluted urban area (UA) in the Athens' basin have higher prevalence of allergies and sensitization when compared with those growing up in a Greek provincial rural area (RA). We recruited 478 and 342 children aged 8-10 living in the UA and the RA, respectively. Respiratory health was assessed by a parent-completed questionnaire in three phases: 1995-96 (phase 1), 1999-2000 (phase 2), 2003-04 (phase 3) and skin-prick testing to common indoor and outdoor aeroallergens was performed at phases 1 and 2. Reported asthma and eczema did not differ between the two areas, whereas reported hay fever was persistently more prevalent in the UA than in the RA (16.5%, 17.0%, 18.2% vs. 7.0%, 8.3%, 9.6%, respectively). Sensitization was more prevalent in the UA at both phases (19.0% vs. 12.1% in phase 1, 20.0% vs. 14.1% in phase 2). Residential area contributed independently to sensitization to >or=1 aeroallergens (OR: 0.29; 95% CI: 0.13-0.66; p = 0.003) and to polysensitization (OR: 0.28; 95% CI: 0.10-0.82; p = 0.020) in phase 1. These associations were independent of farming practices. No significant contributions were found in phase 2. Our results suggest that long-term exposure to urban environment is associated with a higher prevalence of hay fever but not of asthma or eczema. The negative association between rural living and the risk of atopy during childhood, which is independent of farming practices, implies that it is mainly driven by an urban living effect.     

Effects of oral N-acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women.

Oral N-acetylcysteine supplementation in nine young healthy females induced a quick and highly significant decrease in plasma homocysteine levels and an increase in whole blood concentration of the antioxidant glutathione. N-acetylcysteine impresses as an efficient drug in lowering homocysteine concentration and might be beneficial for individuals with hyperhomocysteinemia who are at increased risk of cardiovascular disease.