Atypical soft tissue perineurioma in the tongue of a young girl

Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, reticular, and intraneural variants. Soft tissue perineuriomas arise in a wide anatomic distribution and mostly in patients older than 20 years of age. We report an atypical perineurioma in a 7-year-old girl. The tumor, located in the tongue, was uniformly hypercellular. The tumor cells were spindle-shaped with a slender, elongated, bipolar, wavy cytoplasmic process formation and wavy elongated nuclei, and the architecture was composed of predominantly short fascicles with areas exhibiting a vague storiform pattern. Although the tumor cells generally appeared bland, the tumor showed worrisome features including an infiltrative pattern and occasional mitotic figures. Psammoma bodies were observed in the periphery of the tumor. Immunohistochemically, the cells were positive for epithelial membrane antigen, vimentin, claudin-1, and GLUT-1, but negative for S-100 protein, CD34, and type IV collagen. The authors document a case of soft tissue perineurioma with atypical histological features that occurred in the tongue of a child.     

Immortalization of Epstein-Barr virus-negative human B lymphocytes with minimal chromosomal instability

The genes required for immortalization of human B cells infected by Epstein-Barr virus are multiple, and the precise mechanism of this process remains to be elucidated. In the present study HPV16 E6 and E7 were retrovirally transduced into human primary B cells stimulated by CD40-CD40L interaction, thereby establishing an Epstein-Barr virus negative immortalized human B cell line, which continued to proliferate for more than 2 years (100 population doublings). The established cell line had a high telomerase activity from the beginning of the culture period, and no shortening of the telomere length was observed. A chromosomal analysis revealed that a large portion of the HPV16E6E7 transduced cells had retained a normal karyotype. Similar to human epithelial cells, human B lymphocytes seem to require two steps for immortalization, namely, the inactivation of the p16/Rb pathway and the activation of telomerase, the latter that can be induced by the CD40-CD40L interaction. Furthermore, using this system, it is possible to analyze the role of individual genes in human B lymphocyte immortalization without the influence of a pre-existing Epstein-Barr virus genome.     

Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes

In order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study. A total of 27 FBN1 mutations (22 novel) in 27 patients (55%, 27/49), 1 novel TGFBR1 mutation in 1 (2%, 1/49), and 2 recurrent TGFBR2 mutations in 2 (4%, 2/49) were identified. No FBN2 mutation was found. Three patients with either TGFBR1 or TGFBR2 abnormality did not fulfill the Ghent criteria, but expressed some overlapping features of MFS and Loeys-Dietz syndrome (LDS). In the remaining 19 patients, either of the genes did not show any abnormalities. This study indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5-10% of patients with the syndrome.     

Modulation of voltage-dependent potassium currents by opiates in facial motoneurons of neonatal rats

We examined the modulation of rat facial motoneurons (FMNs) by opiates in a slice preparation (7-15 days old) using whole-cell patch clamp techniques. Although application of methionine enkephalin (ME) did not change the peak value of the transient outward current (A-current, IA), it reduced the persistent voltage-dependent K(+) currents (IKs) in a dose-dependent manner. The reduction was antagonized by naloxone (40 microM). IKs were reduced only by mu-selective agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO, 2-121.6 microM). This reduction was antagonized by naloxone (40 microM) or the mu-selective antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2) (CTOP, 1 microM). Agonists for other opiate receptors (delta- and kappa-opiate receptor) showed no effect on IKs. In accord with the effects on IKs, DAMGO (100 microM) prolonged the duration of the action potential evoked in Ca(2+)-free external solution containing 4-aminopiridine (1mM). These results suggest that the activation of mu-opiate receptors contributes to signal transduction in FMNs primarily by modulating action potential duration.     

Phosphorylation status of epidermal growth factor receptor is closely associated with responsiveness to gefitinib in pulmonary adenocarcinoma

Twenty-one cases of primary lung carcinoma were analyzed for correlations between the presence of somatic mutations of the epidermal growth factor receptor (EGFR) gene and the phosphorylation status of EGFR, which was analyzed by immunohistochemistry with antibodies recognizing the phosphorylated form of EGFR. Somatic mutations were detected in 11 (52.4%) of the 21 cases. Immunohistochemistry with an antibody recognizing EGFR phosphorylated at tyrosine (pEGFR-tyr) 992 and an antibody recognizing EGFR phosphorylated at tyrosine 1173 (pEGFR-tyr1173) revealed that 12 (57.1%) and 21 (100%) of the 21 cases were positive, respectively. Interestingly, the mutation status of the EGFR gene was strongly correlated with immunoreactivity for pEGFR-tyr992 (P = .0019). pEGFR-tyr992 immunoreactivity was significantly correlated with clinical responsiveness to gefitinib (P = .0011). These findings suggest that immunohistochemical evaluation with anti-pEGFR-tyr992 antibody is useful for prediction of responsiveness to gefitinib.     

Reward-predicting activity of dopamine and caudate neurons--a possible mechanism of motivational control of saccadic eye movement

Recent studies have suggested that the basal ganglia are related to motivational control of behavior. To study how motivational signals modulate motor signals in the basal ganglia, we examined activity of midbrain dopamine (DA) neurons and caudate (CD) projection neurons while monkeys were performing a one-direction-rewarded version (1DR) of memory-guided saccade task. The cue stimulus indicated the goal position for an upcoming saccade and the presence or absence of reward after the trial. Among four monkeys we studied, three were sensitive to reward such that saccade velocity was significantly higher in the rewarded trials than in the nonrewarded trials; one monkey was insensitive to reward. In the reward-sensitive monkeys, both DA and CD neurons responded differentially to reward-indicating and no-reward-indicating cues. Thus DA neurons responded with excitation to a reward-indicating cue and with inhibition to a no-reward-indicating cue. A group of CD neurons responded to the cue in their response fields (mostly contralateral) and the cue response was usually enhanced when it indicated reward. In the reward-insensitive monkey, DA neurons showed no response to the cue, while the cue responses of CD neurons were not modulated by reward. Many CD neurons in the reward-sensitive monkeys, but not the reward-insensitive monkey, showed precue activity. These results suggest that DA neurons, with their connection to CD neurons, modulate the spatially selective signals in CD neurons in the reward-predicting manner and CD neurons in turn modulate saccade parameters with their polysynaptic connections to the oculomotor brain stem.     

Analysis of daily energy,protein, fat,and carbohydrate intake in citrin-deficient patients: Towards prevention of adult-onset type II citrullinemia

Patients with citrin deficiency during the adaptation/compensation period exhibit diverse clinical features and have characteristic diet of high protein, high fat, and low carbohydrate. Japanese cuisine typically contains high carbohydrate but evaluation of diet of citrin-deficient patients in 2008 showed a low energy intake and a protein:fat:carbohydrate (PFC) ratio of 19:44:37, which indicates low carbohydrate consumption rate. These findings prompted the need for diet intervention to prevent the adult onset of type II citrullinemia (CTLN2). Since the publication of the report about 10 years ago, patients are generally advised to eat what they wish under active dietary consultation and intervention. In this study, citrin-deficient patients and control subjects living in the same household provided answers to a questionnaire, filled-up a maximum 6-day food diary, and supplied physical data and information on medications if any. To study the effects of the current diet, the survey collected data from 62 patients and 45 controls comparing daily intakes of energy, protein, fat, and carbohydrate. Food analysis showed that patient's energy intake was 115% compared to the Japanese standard. The confidence interval of the PFC ratio of patients was 20–22:47–51:28–32, indicating higher protein, higher fat and lower carbohydrate relative to previous reports. The mean PFC ratio of female patients (22:53:25) was significantly different from that of male patients (20:46:34), which may explain the lower frequency of CTLN2 in females. Comparison of the present data to those published 10 years ago, energy, protein, and fat intakes were significantly higher but the amount of carbohydrate consumption remained the same. Regardless of age, most patients (except for adolescents) consumed 100–200 g/day of carbohydrates, which met the estimated average requirement of 100 g/day for healthy individuals. Finally, patients were generally not overweight and some CTLN2 patients were underweight although their energy intake was higher compared with the control subjects. We speculate that high-energy of a low carbohydrate diet under dietary intervention may help citrin-deficient patients attain normal growth and prevent the onset of CTLN2.     

Impact of the one-carbon metabolism on oocyte maturation,fertilization, embryo quality,and subsequent pregnancy

PurposeTo investigate impact of the one‐carbon metabolism (OCM) on oocyte maturity and embryo development.MethodsThis prospective study analyzed 18 women who agreed to participate. We measured the OCM biomarkers’ concentrations including Vitamin B12 (VB12), folic acid (FA), and homocysteine (Hcy) in serum and follicular fluid (FF), and assessed their correlation. We also evaluated the influence of such OCM biomarker concentrations in mono‐FF on oocyte maturation, fertilization, embryo quality, and consequent pregnancy after embryo transfers.ResultsAll biomarkers showed a high concentration variability in different follicles of each woman, but their mean levels correlated with the serum levels. Among the 106 collected oocytes, 92 were mature, 59 were fertilized, and 16 yielded good‐quality embryos. We performed 26 single embryo transfers, and 7 patients achieved clinical pregnancies. VB12 concentration (FF) was significantly lower in fertilized than unfertilized oocytes by univariate analysis. In multivariate logistic analysis, a significant correlation was found between FA concentration (FF) <14.25 ng/mL and good‐quality embryos and between Hcy concentration (FF) <4.9 nmol/mL and clinical pregnancy.ConclusionOCM in FF may affect fertilization, embryo quality, and clinical pregnancy.