Frequent mutations of genes encoding vacuolar H+‐ATPase components in granular cell tumors

Granular cell tumors (GCTs) are rare mesenchymal tumors that exhibit a characteristic morphology and a finely granular cytoplasm. The genetic alterations responsible for GCT tumorigenesis had been unknown until recently, when loss‐of‐function mutations of ATP6AP1 and ATP6AP2 were described. Thus, we performed whole‐exome sequencing, RNA sequencing, and targeted sequencing of 51 GCT samples. From these genomic analyses, we identified mutations in genes encoding vacuolar H⁺‐ATPase (V‐ATPase) components, including ATP6AP1 and ATP6AP2, in 33 (65%) GCTs. ATP6AP1 and ATP6AP2 mutations were found in 23 (45%) and 2 (4%) samples, respectively, and all were truncating or splice site mutations. In addition, seven other genes encoding V‐ATPase components were also mutated, and three mutations in ATP6V0C occurred on the same amino acid (isoleucine 136). These V‐ATPase component gene mutations were mutually exclusive, with one exception. These results suggest that V‐ATPase function is impaired in GCTs not only by loss‐of‐function mutations of ATP6AP1 and ATP6AP2 but also through mutations of other subunits. Our findings provide additional support for the hypothesis that V‐ATPase dysfunction promotes GCT tumorigenesis.     

Primary ovarian angiosarcoma: A case report and literature review

Primary ovarian angiosarcoma is extremely rare. Only 16 cases have histologicaliy been reported to date In the Ilterature. A case of angiosarcoma arising In the right ovary of a 46-year-old female is presented. Grossly, the resected right ovary was completely replaced by a solid tumor mass, which revealed multiple necrotic and/or hemorrhagic foci. This case revealed the typical histological features of angiosarcoma with sinusoldal and solid patterns of anaplastic tumor cells. Immunohlstochemically, tumor cells were strongly and diffusely positive for CD31 and CD34, in particular, along the cytoplasmic membrane of the tumor cells. Ultrastructurally, tumor cells possessed the intermediate junctions between tumor cells, discontinuous basal laminae attached to the irregularly shaped blood vessels and occasional cytoplasmic pinocytotlc vesicles. These findings confirmed the case as being one of angiosarcoma of the ovary. The patient died 9 months after surgery as a result of developed multlfocal brain metastases. A total of 17 cases reported as primary ovarian anglosarcoma, including this presented case, are clinicopathologically reviewed.     

Effects of estrogen on susceptibility to oxidation of low-density and high-density lipoprotein in postmenopausal women

Objective: To investigate the effects of estrogen on the susceptibility to oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in postmenopausal women. Methods: A total of 23 postmenopausal women were treated with 0.625 mg of conjugated equine estrogen daily for 3 months. Blood samples were obtained before and after therapy. Plasma levels of total cholesterol and triglyceride and the concentrations of cholesterol, triglyceride, phospholipid in LDL and HDL were determined enzymatically and the levels of apolipoprotein A-I, A-II in HDL and apolipoprotein B in LDL were measured by turbidimetric immunoassay. The isolated LDL and HDL were incubated at 37°C for 24 h with CuSO₄ 5 μmol/l and the lipid peroxide concentration of LDL and HDL was measured. Results: Estrogen significantly reduced the plasma level of total cholesterol and significantly increased the plasma level of triglyceride. The LDL concentrations of cholesterol, phospholipid and apolipoprotein B were significantly decreased following estrogen therapy. The triglyceride level of LDL did not change significantly. The HDL concentrations of cholesterol, triglyceride, phospholipid and apolipoprotein A-I and A-II were all significantly elevated after estrogen therapy. Estrogen significantly inhibited the peroxidation of LDL at 50–2000 μg of LDL protein (14.17±4.17–11.49±1.42 nmol/200 μg of LDL protein, P<0.001) and of HDL (4.49±1.74–3.37±1.24 nmol/200 μg of HDL protein, P<0.03) induced by their incubation in the presence of CuSO₄. Conclusions: Estrogen inhibited the susceptibility of LDL and HDL to oxidative modification and favorably affected lipid metabolism by reducing the number of LDL particles and increasing the number of HDL particles in plasma that were resistant to oxidation.     

Massive cystic lymphangiomas of a fetus

We present a fetus with progressive massive subcutaneous lymphangiomas leading to intrauterine death. A 28-year-old woman was referred to our hospital because of a precordial cystic mass of the fetus. An ultrasound revealed lymphangiomas extending from bilateral axillae to the anterior chest wall. At 18 weeks' gestation, amniocentesis was performed and the karyotype of the fetus was found to be normal 46, XY. Thereafter the lesions increased in size gradually and spread over the body. Amniotic fluid decreased, pericardial, and pleural effusion appeared, and cardiomegaly became evident. The fetus died in utero at 25 weeks' gestation. Postmortem examination revealed a male fetus surrounded with multicystic soft masses spreading over the body, and syndactyly (left third and fourth fingers) was present. Histologically, a number of irregularly dilated lymphatics extended through subcutaneous tissues to the skeletal muscles. No communications between the cysts and the thoracic or abdominal cavity existed, and no lymphatic dilations in the viscera were confirmed. As far as we know, such conditions have rarely been reported. Considering that in previous literature, a favorable prognosis of a fetus with an atypically located (lateral cervical or non-cervical) lymphangioma with a normal karyotype has been reported, our case may be included in a distinct pathological entity. When we find a lymphangioma in a fetus, careful follow-up by ultrasound is mandatory.     

Cortical functional abnormality assessed by auditory-evoked magnetic fields and therapeutic approach in patients with chronic dizziness

A long-lasting dizzy sensation is a common complaint in elderly subjects. The pathogenesis and effective treatment of such chronic dizziness (CD), however, have not yet been fully elucidated because of lack of methods for evaluating this sensation. On the basis of assumption that CD may be attributable partly to cortical functional abnormality, we attempted to estimate the function of auditory cortex by measurements of auditory-evoked magnetic fields (AEFs). Magnetic field signals in the parieto-temporal cortex were evoked by 1000-Hz tone-burst with 90-dB normal hearing level sounds, and the highest-amplitude magnetic waveforms at approximately 100-ms (N100m) were analyzed as electrical current arrows in normal subjects (n=11), patients with CD (n=27) and patients with cerebral infarction but no dizzy sensation (n=9). In the normal subjects, the current arrows pointed to a nearly straight line with small directional distortion as indicated by a rotation-degree parameter, dI(rot) of 1.59+/-0.46. In 17 of 27 CD patients, the directions of current arrows were markedly distorted showing abnormally high dI(rot) values greater than 2.50 (the mean plus two standard deviations of normal values) and disclosed a clockwise or counter-clockwise rotation in either side or both sides of parieto-temporal cortex. In all the patients with cerebral infarction, the current arrows exhibited the similar pattern as the normal subjects. None of them exhibited abnormally high dI(rot) values. We hypothesized that the rotational abnormality may be caused by abnormal neuronal excitation, since non-evoked magnetic fields in temporal lobe epilepsy demonstrated the similar current rotational abnormality as reported previously. Seven CD patients were treated with anticonvulsants, and four showed remarkable amelioration of dizzy sensation. In all the four patients with symptomatic amelioration, the disappearance of rotational abnormality in AEFs or the tendency towards disappearance was observed following symptomatic amelioration. The results of the present study suggest that the auditory center may contribute to the maintenance of equilibrium, and its dysfunction may lead to the development of CD. AEFs measurements may make it possible to evaluate the functional abnormality of auditory center and may be useful for studying the pathophysiology and treatment of CD.     

Oral administration of leucine stimulates phosphorylation of 4E-bP1 and S6K 1 in skeletal muscle but not in liver of diabetic rats

Leucine performs a signaling role to enhance protein synthesis by phosphorylating eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and 70-kDa ribosomal protein S6 kinase (S6K1), two key regulatory proteins involved in the initiation of mRNA translation. The purpose of the current study was to assess whether the phosphorylation of 4E-BP1 and S6K1 was increased in skeletal muscle and liver by an oral administration of leucine to diabetic rats and to determine the in vivo contribution of insulin to a leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation. Food-deprived (18 h) normal and diabetic rats were orally administered 135 mg/ 100 g body weight L-leucine and sacrificed at 1 h after administration. Leucine administration resulted in enhanced phosphorylation of 4E-BP1 and S6K1 in skeletal muscle and in liver of nondiabetic rats. The stimulatory action of leucine on the phosphorylation of 4E-BP1 and S6K1 in skeletal muscle was not abolished in rats with streptozotocin-induced diabetes. In contrast, leucine administration did not stimulate the phosphorylation of 4E-BP1 and S6K1 in the liver of diabetic rats. These findings suggest that in skeletal muscle, leucine functions as a nutritional signaling molecule that independently regulates the phosphorylation states of 4E-BP1 and S6K1. In contrast to skeletal muscle, insulin is essential in mediating the leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation in liver. leucine, 4E-BP1, S6K1, translation initiation, diabetes     

The relationships among self-identity,self-esteem and attitude towards sexual behavior in university students

PURPOSE: It has been reported that the young people of today tend to engage in sexual behavior at an early age and the abortion rate is high. The purpose of this study was to investigate the attitudes of post-adolescents with regard to sexual behaviors and the relationship to self-identity and self-esteem. METHODS: The subjects were 234 males (mean +/- SD 20.2 +/- 1.1 years) and 460 females (mean +/- SD 19.5 +/- 1.1 years) 4-year university students aged 18 to 23 years in Aichi Prefecture. An anonymous, self-report questionnaire was used to survey the subjects with regard to self-identity ("Establishment of Self" scale), self-esteem (Rosenberg Self-Esteem Scale), and sexual attitude and behavior. The scores on both scales and subscales of the "Establishment of Self" scale, "Foundation of Identity (Foundation)" and "Establishment of Identity (Establishment)", were calculated and intercompared, along with sexual attitude and behavior, controlled for age and school type. RESULTS: The mean total score of the "Establishment of Self" scale for males was 55.3 (SD9.2) and for females 52.2 (SD9.3), while those for the Rosenberg Self-Esteem Scale were 27.2 (SD5.5) and 25.7 (SD5.2), respectively. There was significant positive correlation all scales in both sexes. Both male and female students had positive attitude towards sex and a negative view of "traditional gender roles" particularly females. Of the subjects, 82.4% of males and 69.5% of females were thinking of accepting a request for sexual intercourse from their partners. Many students understood the "need for contraception", that is a component of contraceptive behavior. Most of them, however, didn't acquire the other components. A total of 68.3% of males and 48.2% of females had experienced sexual intercourse during the last year. Of these, 50.6% of males and 58.2% of females consistently used contraception. The score on the "Establishment of Self" scale was higher among both the male and female students who responded positively to having "communication ability," "learning ability," and "acquisition ability." Significant differences were found in total and "Establishment" scales among males, and all scales among females. The score on the Rosenberg Self-Esteem Scale was significantly higher with "learning ability" among males, and with "communication ability" and "learning ability" among females. However, no significant relationship was found between actual contraceptive behavior and any of the scales. CONCLUSION: In dealing with contraception, a gap exists between university students' attitudes and actual behavior. The scores on the "Establishment of Self" scale and the Rosenberg Self-Esteem Scale were found to be significantly higher for those who exhibited higher values for components of contraceptive behavior.     

Severe hypotony after macular translocation surgery with 360-degree retinotomy

PURPOSE: To report a case of severe hypotony after macular translocation with 360-degree retinotomy. DESIGN: Interventional case report. METHODS: A 50-year-old woman with myopic neovascular maculopathy underwent macular translocation with 360-degree retinotomy in her left eye. RESULTS: After the second procedure of silicone oil removal, severe hypotony developed. No clear sign of leakage was found. Pure perfluoropropane gas tamponade was then performed, which resulted in temporal resolution of severe hypotony, but the hypotony recurred as the gas bubble was absorbed. Ten weeks after the second surgery, the hypotonous eye was refilled with silicone oil. No apparent cyclitic membrane was observed intraoperatively. After this procedure, the choroidal and retinal folds regressed; intraocular pressure has been between 5 and 7 mm Hg for more than 4 months thereafter. CONCLUSION: Severe hypotony can occur as a complication of otherwise uneventful macular translocation with 360-degree retinotomy.