Association between nasal allergy and a coding variant of the Fc epsilon RI beta gene Glu237Gly in a Japanese population.

The gene for the beta-chain of the high-affinity receptor for IgE (Fc epsilon RI beta) has been proposed as a candidate gene for atopy. A coding variant Glu237Gly has been studied in various populations with asthma and atopy, and the results were controversial for association of the variant with atopy/asthma. Because nasal allergy is a more common atopic disease and shows less remission than asthma, we analyzed whether the Glu237Gly variant is correlated with nasal allergy. The study enrolled 233 patients with nasal allergy and 100 control subjects. Further, three subgroups were selected: patients with perennial nasal allergy (n=149), Japanese cedar pollinosis (n=189), and allergy to multiple allergens (n=45). The allele frequency of Gly237 in the controls and patients was 0.14 and 0.20, and the frequency of Gly237-positive subjects was 0.23 and 0.356, respectively. There was a significant association between Gly237-positivity and nasal allergy, perennial nasal allergy, Japanese cedar pollinosis, and allergy to multiple allergens. Among all 333 subjects we observed a significant relationship between Gly237 and elevated levels of serum total IgE (>250 IU/ml) and very high IgE (>1000 IU/ml). Among patients positive for a specific IgE, Gly237 was significantly associated with high IgE for house dust, mite, and Japanese cedar pollen. These results suggest that the Glu237Gly variant of the Fc epsilon RI beta gene is involved in the development of nasal allergy through the process for the production of both specific and nonspecific IgE antibodies.

Frequency and clinical features of patients with sensorineural hearing loss associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic clinics.

The A3243G mutation of the mitochondrial gene is a cause of maternally inherited diabetes and deafness. The aim of this study was to evaluate the frequency and clinical features of this mutation in patients with sensorineural hearing loss (SNHL) in otorhinolaryngic clinics. The frequency of the A3243G mutation in 230 patients with SNHL was 1.74% (4/230). Three of the four patients had diabetes mellitus (DM) and were already aware that they had the mutation. The other had cardiomyopathy but not DM, and proved to have the mutation in this study. The frequency of the mutation was 12.9% (4/31) in patients with a family history of possible maternal inheritance of SNHL, 10.3% (3/29) in patients with DM, and 50% (3/6) in patients with both. The age of onset of SNHL in these patients and their families was between their teens and their forties. The chance of diagnosing the A3243G mutation in patients with SNHL in otorhinolaryngic clinics is probably less than 1%. Association of DM, cardiomyopathy, a family history of possible maternal inheritance of SNHL, and an onset of SNHL between the teens and the forties are signs suggesting the mutation. These signs provide us with a reason for genetic testing for the mutation.

Fast 3D dynamic MR imaging of the liver with MR SmartPrep: comparison with helical CT in detecting hypervascular hepatocellular carcinoma.

Dynamic magnetic resonance (MR) imaging with SmartPrep was compared with dynamic enhanced helical computed tomography (CT) for the detection of hepatocellular carcinoma (HCC). Thirty patients with 49 HCCs were studied. Arterial-phase MR images using with SmartPrep were significantly superior to arterial-phase CT in detecting small lesions (< or = 2 cm) (85.3% vs. 67.6%, P < .05). In addition, in six recurrent tumors after arterial chemoembolization, dynamic MR imaging with MR SmartPrep technique was superior to helical CT in detecting of recurrent tumors.

Assessment of coronary flow velocity reserve using fast velocity-encoded cine MRI for noninvasive detection of restenosis after coronary stent implantation.

PURPOSE: Serial change of the coronary flow velocity reserve was evaluated with fast velocity-encoded cine magnetic resonance imaging (MRI) for noninvasive detection of restenosis after coronary stent implantation. METHOD: In total, 60 MRI flow studies were performed in 10 patients with coronary artery disease who undersvent elective successful stent implantation to the lesion in the proximal left anterior descending artery. Flow velocities in the segment that was distal to the stent were measured before and after intravenous injection of dipyridamole. MRI measurements of coronary flow velocity reserve were repeated every 4 weeks for 6 months, and follow-up angiography was performed 6 months after the procedure. RESULTS: In patients without restenosis (n = 7, % diameter stenosis: 27.8%+/-7.1) at follow-up angiography, the coronary flow velocity reserve remained normal during the 6-month follow-up time. The flow velocity reserve was 2.31+/-0.30 at 1 month and 2.52+/-0.25 at 6 months after stent implantation (p = NS). In contrast, the coronary flow velocity reserve showed a significant decrease after 4 months in patients with restenosis (n = 3, % diameter stenosis: 66.3%+/-8.1) at follow-up angiography. The flow velocity reserve was 2.26+/-0.49 at 1 month and 1.52+/-0.09 at 6 months after stent implantation (p < 0.05). CONCLUSION: Fast velocity-encoded cine MRI is a technique that shows promise in providing non-invasive detection of restenosis of coronary stent implantation.

Isolation and characterization of murine orthologue of PTP-BK.

We isolated and characterized a murine orthologue of PTP-BK, a receptor-type protein tyrosine phosphatase expressed in brain and kidney. The deduced amino acid sequences showed 89, 95, and 92% identities with human, rabbit, and chicken homologues of PTP-BK. Mouse PTP-BK encodes a polypeptide of 1,226 amino acids with calculated molecular weight of 138,598 Da. The mature form of PTP-BK constitutes of 3 domain structures including extracellular, transmembrane, and a single intracellular PTPase domain. Western blot analysis indicated that anti-PTP-BK antibody specifically immunoreacted to 2 distinct molecules of 200 kDa and 220 kDa in COS cells, possibly due to differential glycosylation. The recombinant PTP-BK showed the phosphatase activity specific for the phosphotyrosine, but not for the phosphoserine residue of phosphopeptides in vitro. Radiation hybrid panel assigned mouse PTP-BK gene to 5.02cR distal to from the marker D6Mit339 on chromosome 6. Mouse PTP-BK was classified in PTPRO family in novel nomenclature. We discuss here the diversity and physiological functions of PTPRO family of PTP.

Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains.

The UNC-51 serine/threonine kinase of C. elegans plays an essential role in axonal elongation, and unc-51 mutants exhibit uncoordinated movements. We have previously identified mouse and human cDNAs encoding UNC-51-like kinase (ULK1). Here we report the identification and characterization of the second murine member of this kinase family, ULK2. Mouse ULK2 cDNA encodes a putative polypeptide of 1033 aa which has an overall 52% and 33% amino acid identity to ULK1 and UNC-51, respectively. ULKs and UNC-51 share a typical domain structure of an amino-terminal kinase domain, a central proline/serine rich (PS) domain, and a carboxy-terminal (C) domain. Northern blot analysis showed that ULK2 mRNA is widely expressed in adult tissues. In situ hybridization analysis indicated that ULK2 mRNA is ubiquitously localized in premature as well as mature neurons in developing nervous system. ULK2 gene was mapped to mouse chromosome 11B1.3 and rat chromosome 10q23 by FISH. HA-tagged ULK2 expressed in COS7 cells had an apparent molecular size of approximately 150 kDa and was autophosphorylated in vitro. Truncation mutants suggested that the autophosphorylation occurs in the PS domain. Although expression of ULK2 failed to rescue unc-51 mutant of C. elegans, a series of ULK2/UNC-51 chimeric kinases revealed that function of the kinase and PS domains are conserved among species, while the C domain acts in a species-specific manner. These results suggest that ULK2 is involved in a previously uncharacterized signaling pathway in mammalian cells.

Mu1B, a novel adaptor medium chain expressed in polarized epithelial cells.

The apical and basolateral plasma membrane domains of polarized epithelial cells contain distinct sets of integral membrane proteins. Biosynthetic targeting of proteins to the basolateral plasma membrane is mediated by cytosolic tail determinants, many of which resemble signals involved in the rapid endocytosis or lysosomal targeting. Since these signals are recognized by adaptor proteins, we hypothesized that there could be epithelial-specific adaptors involved in polarized sorting. Here, we report the identification of a novel member of the adaptor medium chain family, named mu1B, which is closely related to the previously described mu1A (79% amino acid sequence identity). Northern blotting and in situ hybridization analyses reveal the specific expression of mu1B mRNA in a subset of polarized epithelial and exocrine cells. Yeast two-hybrid analyses show that mu1B is capable of interacting with generic tyrosine-based sorting signals. These observations suggest that mu1B may be involved in protein sorting events specific to polarized cells.

Analysis of T cell receptor beta chain repertoire in middle ear effusions.

In order to elucidate the immune response in otitis media with effusion (OME), the polymerase chain reaction was employed to examine T cells in middle ear effusions in patients with OME for utilization of T cell receptor (TCR) variable region genes. Specimens of RNA were extracted from 13 ears of 12 patients (9 children and 3 adults). Oligonucleotide primers specific for individual TCR Vbeta gene families were used to amplify TCR gene products in each sample. Although the number of Vbeta families utilized by each sample varied from 1 family to 21, a few significant trends emerged. Eleven ears out of 13 expressed Vbeta7, which was the most frequently utilized (84.6%) Vbeta family among the 24 Vbeta families. In 5 of the 13 samples, the number of Vbeta families utilized was restricted to 1, which was Vbeta7 in all 5 samples. This result indicates the possibility that Vbeta7-bearing T cells in the middle ear are responding to a certain common antigen in some cases of OME.