A Mouse Model for Degeneration of the Spiral Ligament

Previous studies have indicated the importance of the spiral ligament (SL) in the pathogenesis of sensorineural hearing loss. The aim of this study was to establish a mouse model for SL degeneration as the basis for the development of new strategies for SL regeneration. We injected 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, at various concentrations into the posterior semicircular canal of adult C57BL/6 mice. Saline-injected animals were used as controls. Auditory function was monitored by measurements of auditory brain stem responses (ABRs). On postoperative day 14, cochlear specimens were obtained after the measurement of the endocochlear potential (EP). Animals that were injected with 5 or 10 mM 3-NP showed a massive elevation of ABR thresholds along with extensive degeneration of the cochleae. Cochleae injected with 1 mM 3-NP exhibited selective degeneration of the SL fibrocytes but alterations in EP levels and ABR thresholds were not of sufficient magnitude to allow for testing functional recovery after therapeutic interventions. Animals injected with 3 mM 3-NP showed a reduction of around 50% in the EP along with a significant loss of SL fibrocytes, although degeneration of spiral ganglion neurons and hair cells was still present in certain regions. These findings indicate that cochleae injected with 3 mM 3-NP may be useful in investigations designed to test the feasibility of new therapeutic manipulations for functional SL regeneration.     

PRRT2 mutation in Japanese children with benign infantile epilepsy

Mutations in PRRT2 genes have been identified as a major cause of benign infantile epilepsy and/or paroxysmal kinesigenic dyskinesia. We explored mutations in PRRT2 in Japanese patients with BIE as well as its related conditions including convulsion with mild gastroenteritis and benign early infantile epilepsy. We explored PRRT2 mutations in Japanese children who had had unprovoked infantile seizures or convulsion with mild gastroenteritis. The probands included 16 children with benign infantile epilepsy, 6 children with convulsions with mild gastroenteritis, and 2 siblings with benign early infantile epilepsy. In addition, we recruited samples from family members when PRRT2 mutation was identified in the proband. Statistical analyses were performed to identify differences in probands with benign infantile epilepsy according to the presence or absence of PRRT2 mutation. Among a total of 24 probands, PRRT2 mutations was identified only in 6 probands with benign infantile epilepsy. A common insertion mutation, c.649_650insC, was found in 5 families and a novel missense mutation, c.981C>G (I327M), in one. The family history of paroxysmal kinesigenic dyskinesia was more common in probands with PRRT2 mutations than in those without mutations. Our study revealed that PRRT2 mutations are common in Japanese patients with benign infantile epilepsy, especially in patients with a family history of paroxysmal kinesigenic dyskinesia.     

Actin and Vimentin proteins with N‐terminal deletion detected in tumor‐bearing rat livers induced by intraportal‐vein injection of Ha‐ras‐transfected rat liver cells

The introduction of the tumorigenic v‐Ha‐ras oncogene‐transformed rat liver epithelial cells (WBras), which is deficient in gap junctional intercellular communication (GJIC), into F344 rats, induces significant formation of hepatocellular tumors. GJIC plays a major role in maintaining tissue homeostasis. Using this in vivo tumor model system, we used 2‐dimensional electrophoresis with isoelectric focusing in the first dimension and SDS‐PAGE in the second dimension to globally identify proteins that are uniquely expressed in the livers of WBras‐treated rats as compared to the sham control. Immunoblotting was used to identify Ras and Connexin43, which were the positive and negative marker proteins, respectively, of the introduced WBras cells. As predicted, immunoblotting indicated that the whole liver of tumor‐bearing animals exhibited a decreased level of Connexin43 and an increased level of Ras. Connexin43 and GJIC were expressed and functional in normal liver, but not in the tumor. In addition to these 2 markers, an additional 4 proteins exhibited decreased levels and 2 proteins exhibited increased levels in the livers of tumor‐bearing animals. N‐Terminal sequencing analysis was used to identify these proteins, which were glucose‐regulated protein 78, 2 isoforms of heat shock protein 60, and the β‐chain of ATP synthase for the down regulated proteins, and β‐Actin with a 46 amino acid deletion from its N‐terminus and Vimentin with a 71 amino acid deletion from its N‐terminus for the up regulated proteins. These data offer potentially new markers of liver tumorigenicity, particularly, Vimentin. © 2008 Wiley‐Liss, Inc.     

Effect of basic fibroblast growth factor (FGF2) gene polymorphisms on SSRIs treatment response and side effects

Antidepressant response usually appears in 2 to 4 weeks and 30–40% of patients do not show a significant response although biochemical changes of monoaminergic system occur within hours after administration. Genetic factors could play a role in this process and genes involved in synaptic plasticity and neurogenesis are possible candidates. In fact, antidepressants and electroconvulsive therapy increase basic fibroblast growth factor (FGF2) and the rs1449683C/T polymorphism within this gene has been found to be a predictor for both an elevated mRNA and protein level of FGF2. Therefore we examined the possible association of rs1449683C/T and a panel of tagging SNPs in SSRI efficacy and side effects in 144 Japanese major depressive subjects followed for 6 weeks. We observed a significant association of rs1449683T (p = 0.010) and rs308393C (p = 0.029) variant carriers toward a better response to SSRI and of rs1048201 with higher frequency of drop out due to side effects (p = 0.010), independently from clinical variables. Furthermore the rs308447T–rs308393C–rs1449683T haplotype was associated with higher response rate (p = 0.012) while the rs1048201T–rs3747676T haplotype was significantly associated with higher dropped out rate (p = 0.015). In conclusion, this is the first study investigating the association of antidepressant response and intolerance with FGF2 variants. This finding adds an important piece of information for the pathway of detecting the genetics of antidepressant response.     

Concurrent lung adenocarcinoma hidden among multiple shadows of COVID‐19 pneumonia: A rare and instructive case report

A 40‐year‐old man was admitted with a diagnosis of COVID‐19 pneumonia. Although most of multiple ground‐glass opacities and consolidations on computed tomography improved, a round ground‐glass opacity with consolidation remained unchanged and was suspected to be a part‐solid nodule of lung adenocarcinoma. Pathologic diagnosis of resected tumor was papillary adenocarcinoma.