Correlated functional changes of the prefrontal cortex in twins induced by classroom education of second language

As the neural substrates of second language (L2) acquisition are largely unknown, they may or may not be similar to those of first language (L1) representation. We used functional imaging to examine whether training in the conjugation of English verbs from present to past tense alters brain activations in 13-year-old twins. A novel experimental design contrasted past tense verb identification and verb matching, which were tested in either English (L2) or Japanese (L1). After 2 month classroom training in the past tense using bingo games, the two individuals in each pair exhibited significantly correlated performances. When pre- and post-scanning sessions were compared with each other for L2, the left dorsal inferior frontal gyrus (IFG) exhibited significantly correlated activation increases within each pair of twins and the increases were positively correlated with individual performance improvements. Moreover, the cortical plasticity for L2 acquisition was guided toward the L1 specialization of the left dorsal IFG, in spite of notable differences between L1 and L2 in the students' linguistic knowledge and in their performance in making past tense forms. These findings suggest a cortical mechanism underlying L2 acquisition, which critically depends on shared genetic and environmental factors for each twin in a surprisingly predictive manner.     

Congenital laryngeal stridor

We reviewed the diagnosis, complications and treatment of congenital laryngeal stridor (CLS), in 97 patients who consulted our clinic between 1991 and 2001. The 97 patients were diagnosed with laryngeal malacia (32%), vocal cord paralysis and laryngeal stenosis (22%), a neoplastic disease like hemagioma and papilloma (11%), or cystic disease (7%). The cases with vocal cord paralysis, laryngeal stenosis or laryngeal cysts were usually diagnosed within 2 months of birth based on severe dyspnea. Two of the 31 cases of laryngeal malacia and 2 of the 22 cases of vocal cord paralysis were associated with neuromuscular disorders. Three patients suffered from vocal cord paralysis complicated by laryngeal stenosis. Thirty-three of the 97 cases required a tracheostomy; these 33 cases included the one case of laryngeal papilloma (100%), 9 of the 10 cases of hemangioma (90%), and 18 of the 24 cases of laryngeal stenosis (75%). Since any disorders of the upper airway can potentially induce stridor, establishing an accurate diagnosis is sometimes difficult when stridor is the only presenting symptom. Hence, information on associated symptoms and the past history of the subject is particularly important for an accurate diagnosis. In addition, decisions regarding the course of treatment course require adequate consideration of possible complications.     

Mondini dysplasia and recurrent bacterial meningitis in a girl with relapsing Langerhans cell histiocytosis

We report a case of a girl with Langerhans cell histiocytosis (LCH) of multifocal bone disease, who developed recurrent bacterial meningitis and unilateral sensorineural hearing loss during the relapsing course of the disease. Mondini dysplasia, a congenital inner ear anomaly, was suspected by high resolution computed tomographic scan and the dysplasia with cerebrospinal fluid leakage was confirmed by surgery in the ipsilateral ear showing hearing loss. Although rare, congenital inner ear anomalies such as Mondini dysplasia should be kept in mind in pediatric patients with hearing impairment and/or recurrent bacterial meningitis during chemotherapy for various types of neoplasms including LCH.     

The effects of carbon monoxide on respiratory chemoreflexes in humans

As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of approximately 1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide.     

Cardiac metastasis from Merkel cell skin carcinoma

A 54-year-old woman presented with cardiac metastasis of a Merkel cell carcinoma. Chemotherapy was not effective for the metastasis sites; therefore, radiotherapy was performed for the metastatic cardiac tumors, and it reduced the volume of the cardiac tumors. Cardiac metastasis from Merkel cell carcinoma is rare. Radiotherapy for metastatic cardiac tumors from Merkel cell carcinoma is useful as palliative treatment when the response to chemotherapy is poor.     

Atm heterozygous deficiency enhances development of mammary carcinomas in p53 heterozygous knockout mice

Introduction

Ataxia-telangiectasia is an autosomal-recessive disease that affects neuro-immunological functions, associated with increased susceptibility to malignancy, chromosomal instability and hypersensitivity to ionizing radiation. Although ataxia-telangiectasia mutated (ATM) heterozygous deficiency has been proposed to increase susceptibility to breast cancer, some studies have not found excess risk. In experimental animals, increased susceptibility to breast cancer is not observed in the Atm heterozygous deficient mice (Atm ^+/-) carrying a knockout null allele. In order to determine the effect of Atm heterozygous deficiency on mammary tumourigenesis, we generated a series of Atm ^+/- mice on the p53 ^+/- background with a certain predisposition to spontaneous development of mammary carcinomas, and we examined the development of the tumours after X-irradiation.

Methods

BALB/cHeA-p53 ^+/- mice were crossed with MSM/Ms-Atm ^+/- mice, and females of the F₁ progeny ([BALB/cHeA × MSM/Ms]F₁) with four genotypes were used in the experiments. The mice were exposed to X-rays (5 Gy; 0.5 Gy/min) at age 5 weeks.

Results

We tested the effect of haploinsufficiency of the Atm gene on mammary tumourigenesis after X-irradiation in the p53 ^+/- mice of the BALB/cHeA × MSM/Ms background. The singly heterozygous p53 ^+/- mice subjected to X-irradiation developed mammary carcinomas at around 25 weeks of age, and the final incidence of mammary carcinomas at 39 weeks was 31% (19 out of 61). The introduction of the heterozygous Atm knockout alleles into the background of the p53 ^+/- genotype significantly increased the incidence of mammary carcinoma to 58% (32 out of 55) and increased the average number of mammary carcinomas per mouse. However, introduction of Atm alleles did not change the latency of development of mammary carcinoma.

Conclusion

Our results indicate a strong enhancement in mammary carcinogenesis by Atm heterozygous deficiency in p53 ^+/- mice. Thus, doubly heterozygous mice represent a useful model system with which to analyze the interaction of heterozygous genotypes for p53, Atm and other genes, and their effects on mammary carcinogenesis.     

Mechanism of QT interval prolongation induced by sevoflurane in guinea-pig ventricular myocyte

BACKGROUND: Sevoflurane causes QT interval prolongation clinically, but its precise mechanism has not been clarified. We examined the mechanism of QT interval prolongation induced by sevoflurane by means of electrophysiological technique in guinea-pig ventricular myocyte. METHODS: Electrocardiogram was recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action potential (AP), delayed rectified potassium current (IKr), and L-type calcium channel current (ICa) were monitored as whole-cell current and by voltage clamp techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by bubbling into the bathing solution. RESULTS: Sevoflurane (1, 2, 4%) increased QTc value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%. IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher concentration (6%) did not show further inhibition. ICa was reduced only to 87% of control in the presence of 2% sevoflurane and the reduction was dose-dependent (4, 6%). CONCLUSIONS: Sevoflurane 2% inhibited IKr, but it showed only slight inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase) and IKr (repolarization), greater inhibition of IKr than ICa could result in prolongation of AP. It is suggested that this mechanism may play a role in QT interval prolongation under sevoflurane anesthesia.     

A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway

We identified IFI16 as a BRCA1-associated protein involved in p53-mediated apoptosis. IFI16 contains the Pyrin/PAAD/DAPIN domain, commonly found in cell death-associated proteins. BRCA1 (aa 502-802) interacted with the IFI16 Pyrin domain (aa 1-130). We found that IFI16 was localized in the nucleoplasm and nucleoli. Clear nucleolar IFI16 localization was not observed in HCC1937 BRCA1 mutant cells, but reintroduction of wild-type BRCA1 restored IFI16 nuclear relocalization following IR (ionizing radiation). Coexpression of IFI16 and BRCA1 enhanced DNA damage-induced apoptosis in mouse embryonic fibroblasts from BRCA1 mutant mice expressing wild-type p53, although mutant IFI16 deficient in binding to BRCA1 did not induce apoptosis. Furthermore, tetracycline-induced IFI16 collaborated in inducing apoptosis when adenovirus p53 was expressed in DNA-damaged p53-deficient EJ cells. These results indicate a BRCA1-IFI16 role in p53-mediated transmission of DNA damage signals and apoptosis.     

Ethnic difference in serology of Helicobacter pylori CagA between Japanese and non-Japanese Brazilians for non-cardia gastric cancer

The usefulness of serology against CagA of Helicobacter pylori as a biomarker to identify high-risk individuals for non-cardia gastric cancer (ncGC) remains unclear among several ethnic populations with a high prevalence of cagA-positive strains. We investigated ethnic differences of CagA serology in two sets of case-control subjects, Japanese-Brazilians (JB) and non-Japanese Brazilians (NJB). We performed a cross-sectional comparison of IgG antibody titers to CagA (CagA-Ab) and the combination of CagA-Ab with conventional surface antigen (Hp-Ab) in 80 JB and 178 NJB ncGC patients and their controls (160 JB and 178 NJB). The level of CagA-Ab titer in cancer cases was significantly higher in NJB than in JB. The strength of the association between CagA-Ab seropositivity (+) (>10 U/ml) and ncGC was almost 2-fold higher in NJB than in JB [odds ratio (OR) (95% confidence interval), 4.5 (2.6–7.8) and 2.1 (1.2–3.6), respectively]. However, in both JB and NJB, the OR was highest in CagA-Ab(+) subjects with low titer (10–29 U/ml), and decreased inversely with elevating CagA-Ab titer. In addition, the serological status of CagA-Ab(+) and Hp-Ab(-) showed a similar close association with ncGC between JB and NJB [5.4 (1.9–15.3) and 5.4 (2.0–15.0), respectively]. These results suggest that although the roles of CagA in the carcinogenic process of ncGC might be different between JB and NJB, the CagA-Ab could be a useful marker for ncGC, independently of ethnicity, particularly in high-risk individuals with the serological status of CagA-Ab(+) with low IgG titer or combined with Hp-Ab(-). (Cancer Sci 2003; 94: 64–69)     

Effects of ketamine on voltage-dependent calcium currents and membrane potentials in single bullfrog atrial cells

Purpose. This study was undertaken to assess the effect of ketamine on L-type calcium channel current (I_Ca) and membrane action potential in the bullfrog single atrial myocyte. Methods. Bullfrog single atrial myocytes were prepared by enzymatic dispersion. Whole-cell voltage-clamp technique and current clamp technique were used to monitor I_Ca, membrane resting potential, and action potential. Results. Ketamine (10⁻⁵–10⁻³ M) showed dose-dependent inhibition of I_Ca in a reversible manner. The 50% inhibitory concentration (IC₅₀) of ketamine on I_Ca was estimated to be 0.92 × 10⁻⁵ M. Use-dependent block of I_Ca was not observed. The resting membrane potential was depolarized at a high concentration (10⁻⁴ M) of ketamine. Reduction of the plateau phase and prolonged duration of the action potential were observed in the presence of a high concentration of ketamine (10⁻⁴ M). Conclusion. Ketamine has an inhibitory effect on I_Ca in the bullfrog single atrial myocyte, and a high dose (10⁻⁴ M) of ketamine prolonges the duration of the action potential. The mechanism of inhibition of I_Ca seems to be a direct effect on the L-type calcium channel, not like an open channel blocker. Received: October 2, 2000 / Accepted: February 19, 2001