Serum and plasma levels of Ba, but not those of soluble C5b-9, might be affected by renal function in chronic kidney disease patients.

BACKGROUND: During the last few decades, pathogenic mechanisms associated with uncontrolled activation of the complement (C) system and development of anti-C agents have been closely investigated in the field of nephrology. The usefulness of some C products such as C5a and sC5b-9 for diagnostic and prognostic purposes remains controversial. On the other hand, decreased renal function is being observed in many patients with or without nephritis as a background factor in progressively aging societies. We therefore investigated whether renal function influenced the evaluation of various complement components and activation products. METHODS: To investigate the influence of renal function on evaluations of C3, C4, CH50, Ba, C5a and sC5b-9, 40 patients were retrospectively chosen from among 844 patients without active glomerulonephritis from 2009 to 2016. We measured plasma and serum levels of C3, C4, CH50, Ba, C5a and sC5b-9 using enzyme-linked immunosorbent assays and compared the findings with inulin clearance (Cin) as a marker of preserved renal function. RESULTS: Both plasma and serum levels of Ba correlated significantly with Cin, but other values did not. Compared with patients with Cin ≥ 60 or ≥ 30 mL/min/1.73 m2, plasma and serum levels of Ba were increased in patients with Cin decreased to < 60 or < 30 mL/min/1.73 m2, but levels of C5a and sC5b-9 were not. CONCLUSION: The influence of renal function might need to be considered when evaluating Ba, but not C5a and sC5b-9, in plasma and serum samples from chronic kidney disease patients.

[Bilateral Internal Carotid Artery Dissection Caused by Elongated Styloid Processes:A Case Report].

We report a case of bilateral internal carotid artery(ICA)dissection associated with bilateral elongated styloid processes(ESPs). A 46-year-old man presented with transient aphasia and left visual disturbance at a business meeting. He complained of a foreign body sensation in his throat during swallowing for two years. Magnetic resonance imaging(MRI)demonstrated fresh small infarcts in the left corona radiata. Magnetic resonance angiography(MRA)revealed string signs bilaterally in the cervical ICAs. The patient was diagnosed with bilateral idiopathic ICA dissection and was treated with ozagrel and clopidogrel. Three-dimensional computed tomographic angiogram(3DCTA)indicated bilateral ESPs and bilateral ICA stenosis. 3DCTA with the patient's head tilting and neck extension revealed that each ICA was compressed by the ipsilateral ESP. A follow-up MRA showed complete normalization of bilateral ICAs after neck rest and anti-platelet therapy, following which, clopidogrel was stopped. The patient wore a soft cervical collar until the operation, to avoid contact between the ESPs and ICAs due to changes in head position. Bilateral ESP resection was performed to prevent recurrence of cerebral ischemic events caused by ICA dissection. The patient was discharged one week after the surgery without any neurological deficit. There was no recurrence of symptoms during the next eight months after the operation.

Mutation screening of the PCDH15 gene in Spanish patients with Usher syndrome type I.

PURPOSE: PCDH15 codes for protocadherin-15, a cell-cell adhesion protein essential in the morphogenesis and cohesion of stereocilia bundles and in the function or preservation of photoreceptor cells. Mutations in the PCDH15 gene are responsible for Usher syndrome type I (USH1F) and non-syndromic hearing loss (DFNB23). The purpose of this work was to perform PCDH15 mutation screening to identify the genetic cause of the disease in a cohort of Spanish patients with Usher syndrome type I and establish phenotype-genotype correlation. METHODS: Mutation analysis of PCDH15 included additional exons recently identified and was performed by direct sequencing. The screening was performed in 19 probands with USH already screened for mutations in the most prevalent USH1 genes, myosin VIIA (MYO7A) and cadherin-23 (CDH23), and for copy number variants in PCDH15. RESULTS: Seven different point mutations, five novel, were detected. Including the large PCDH15 rearrangements previously reported in our cohort of patients, a total of seven of 19 patients (36.8%) were carriers of at least one pathogenic allele. Thirteen out of the 38 screened alleles carried pathogenic PCDH15 variants (34.2%). CONCLUSIONS: Five out of the seven point mutations reported in the present study are novel, supporting the idea that most PCDH15 mutations are private. Furthermore, no mutational hotspots have been identified. In most patients, detected mutations led to a truncated protein, reinforcing the hypothesis that severe mutations cause the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.

Hybrid carcinoma of the parotid gland: report of a case (epithelial-myoepithelial carcinoma and salivary duct carcinoma) and review of the literature.

Hybrid tumors of salivary glands are rare neoplasms. We describe a case of a 74-year-old male with a hybrid carcinoma composed of epithelial-myoepithelial and salivary duct carcinomas of the right parotid gland. The presence of two components was verified by differential immunohistochemical staining. The tumor was surgically resected. There has been no evidence of recurrence to date. To our knowledge, this is the first report of a hybrid carcinoma composed of epithelial-myoepithelial and salivary duct carcinomas of the parotid gland in Japan.

Clinical characteristics and genotype-phenotype correlation of hearing loss patients with SLC26A4 mutations.

CONCLUSIONS: The present study confirmed the clinical characteristics of patients with SLC26A4 mutations: congenital, fluctuating, and progressive hearing loss usually associated with vertigo and/or goiter during long-term follow-up. This clarification should help to facilitate appropriate genetic counseling and proper medical management for patients with these mutations, but there was no particular genotype-phenotype correlation among them, suggesting that other factors may contribute to such variability. OBJECTIVES: Due to the wide range of phenotypes caused by SLC26A4 mutations, there is controversy with regard to genotype-phenotype correlation. The present study was performed: (1) to determine phenotypic range in patients with biallelic SLC26A4 mutations, and (2) to evaluate whether possible genotype-phenotype correlation exists. SUBJECTS AND METHODS: Phenotypes in 39 hearing loss patients with SLC26A4 mutations were summarized and genotype-phenotype correlation was analyzed. RESULTS: Hearing level varied in the individuals from mild to profound severity. Most of the patients had fluctuating and progressive hearing loss that may have been of prelingual onset. Twenty-four (70.6%) patients had episodes of vertigo, and 10 (27.8%) patients had goiter, which had appeared at age 12 or older. In contrast to such phenotypic variabilities, no apparent correlation was found between these phenotypes and their genotypes.

Immunocytochemical localization of ubiquitin A-52 protein in the mouse inner ear.

The ubiquitin A-52 residue ribosomal protein fusion product 1 (UbA52) is a gene highly expressed specifically in the inner ear. Through cellular localization we immunocytochemically investigated its function in the inner ear. In the adult mouse, UbA52 protein was distributed in the strial marginal cells and vestibular dark cells, which regulate the endolymphatic ion homeostasis. In the developing mouse cochlea, no significant staining was observed from birth to postnatal day 3, whereas after postnatal day 6, strong UbA52-immunoreactivities were observed in strial marginal cells. Endolymphatic K concentration is elevated between postnatal days 3-8: therefore, our results indicate that UbA52 may have a functional role in regulation of ion secretion in the inner ear.

micro-Crystallin as an intracellular 3,5,3'-triiodothyronine holder in vivo.

Previously, we identified reduced nicotinamide adenine dinucleotide phosphate-dependent cytosolic T(3) binding protein in rat cytosol. Cytosolic T(3)-binding protein is identical to mu-crystallin (CRYM). Recently, CRYM mutations were found in patients with nonsyndromic hereditary deafness. Although it has been established that CRYM plays pivotal roles in reserving and transporting T(3) into the nuclei in vitro and has a clinical impact on hearing ability, the precise functions of CRYM remain to be elucidated in vivo. To further investigate the in vivo functions of CRYM gene products, we have generated mice with targeted disruption of the CRYM gene, which abrogates the production of CRYM. CRYM knockout loses the reduced nicotinamide adenine dinucleotide phosphate-dependent T(3) binding activity in the cytosol of the brain, kidney, heart, and liver. At the euthyroid state, knockout significantly suppresses the serum concentration of T(3) and T(4) despite normal growth, heart rate, and hearing ability. The disruption of the gene does not alter the expression of TSHbeta mRNA in the pituitary gland or glutathione-S-transferase alpha2 and deiodinase 1 mRNAs in either the liver or kidney. When radiolabeled T(3) is injected intravenously, labeled T(3) rapidly enters into and then escapes from the tissues in CRYM-knockout mice. These data suggest that because of rapid T(3) turnover, disruption of the CRYM gene decreases T(3) concentrations in tissues and serum without alteration of peripheral T(3) action in vivo.

Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns.

Mutations in the GJB2 (connexin 26, Cx26) gene are the major cause of nonsyndromic hearing impairment in many populations. Genetic testing offers opportunities to determine the cause of deafness and predict the course of hearing, enabling the prognostication of language development. In the current study, we compared severity of hearing impairment in 60 patients associated with biallelic GJB2 mutations and assessed the correlation of genotypes and phenotypes. Within a spectrum of GJB2 mutations found in the Japanese population, the phenotype of the most prevalent mutation, 235delC, was found to show more severe hearing impairment than that of V37I, which is the second most frequent mutation. The results of the present study, taken together with phenotypes caused by other types of mutations, support the general rule that phenotypes caused by the truncating GJB2 mutations are more severe than those caused by missense mutations. The present in vitro study further confirmed that differences in phenotypes could be explained by the protein expression pattern.

Light Chain 3 associates with a Sos1 guanine nucleotide exchange factor: its significance in the Sos1-mediated Rac1 signaling leading to membrane ruffling.

A 19 kDa protein was identified to associate with the Dbl oncogene homology domain of Sos1 (Sos-DH) and was purified from rat brains by GST-Sos-DH affinity chromatography. Peptide sequencing revealed that the protein is identical to light chain 3 (LC3), a microtubule-associated protein. LC3 coimmunoprecipitated with Sos1, and GST-LC3 was capable of forming complexes with Sos1 in in vitro GST-pull down assay. Furthermore, LC3 was colocalized with Sos1 in cells, as determined by immunohistochemistry. While Sos1 stimulated the guanine nucleotide exchange reaction on Rac1, LC3 suppressed the ability of Sos1 to activate Rac1 in in vitro experiments using COS cell lysates. Consistent with this, overexpression of LC3 decreased the level of active GTP-bound Rac1 in COS cells. Sos1 expression induced membrane ruffling, a downstream target for Rac1, but LC3 expression inhibited this biological effect of Sos1. These findings suggest that LC3 interacts with Sos1 and thereby negatively regulates the Sos1-dependent Rac1 activation leading to membrane ruffling.