Dyke-Davidoff-Masson syndrome manifested by seizure in late childhood: a case report.

The patient was a 19-year-old woman who presented with hemiatrophy and diminished superficial sensation on the left side of her body including her face. She had a past history of tonic-clonic seizures accompanied by left hemiparesis in late childhood. Brain CT demonstrated dilatation of the frontal sinus, calvarial thickening, cerebral hemiatrophy and dilatation of the lateral ventricle on the right side. Brain MRI showed atrophy of the right cerebrum and midbrain and dilatation of the lateral ventricle on T1-weighted images, as well as a high signal intensity area from the parietal to the occipital lobe on T2-weighted images. These findings are suggestive of an episode that may have caused a transient ischemia through the right cerebral hemisphere after the intrauterine period.     

A case of spontaneous mesenteric hematoma and a review of 17 cases in Japan

A 47 year-old male was admitted to Miyazaki Medical college Hospital for further evaluation of an abdominal mass in the left upper quadrant. Abdominal ultrasound (US) and abdominal computed tomography (CT) showed two cystic masses in the mesenterium, which were suspected to be hematomas, but were not related to the pancreas, kidney or spleen. Superior mesenteric artery angiography and galluim (GA)-scintigraphy showed no definite findings. The patient underwent laparotomy on a suspicion of mesenteric hematoma. Two 4 × 3 × 3cm soft tumors were found in the small intestinal mesenterium. These masses were histopathologically hematomas and surrounded by thick collageneous granulation tissue. The patient had no recent history of abdominal trauma, taking drugs capable of producing bleeding tendency, and/or vascular disease. The case was diagnosed as spontaneous mesenteric hematoma.     

Effects of right stellate ganglion block on the autonomic nervous function of the heart: a study using the head-up tilt test.

The effect of peripheral sympathetic block on the autonomic nerve function of the heart was studied using the head-up tilt test (HUTT) and right stellate ganglion block (RSGB). Blood pressure (BP), heart rate (HR) and the parameters of power spectral analysis of HR variability recorded during the HUTT were measured in 8 patients with chronic pain syndrome before and after RSGB. In the control state, the mean HR and the LF/HF component recorded during HUTT significantly increased whereas the HF component markedly decreased. Conversely, the mean HR and LF/HF and HF components during HUTT did not significantly alter after the RSGB procedure. There were no significant differences between the BP values before and after RSGB. These results suggest that RSGB suppresses cardiac sympathetic function without significantly affecting BP and thus may be a safe and effective therapy for the chronic pain syndrome.     

Involvement of Na+/Ca2+ Exchanger in Inside-Out Signaling Through the Platelet Integrin alpha IIbbeta 3

The platelet integrin _IIb3 has becomea new target for the treatment of pathological thrombosis. It becomesapparent that the affinity of _IIb3 forits ligands is dynamically regulated by inside-out signaling. However,the components that couple diverse intracellular signals to thecytoplasmic domains of _IIb3 remain obscure. Employing a chymotrypsin-induced_IIb3 activation model, we previouslyproposed the hypothesis that Na⁺/Ca^{2 +}exchanger (NCX) may be involved in inside-out signaling (Shiraga et al:Blood 88:2594, 1996). In the present study, employing two unrelated Na⁺/Ca²⁺ exchange inhibitors,3,4-dichlorobenzamil (DCB) and bepridil, we investigatedthe role of NCX in platelet activation induced by various agonists indetail. Both inhibitors abolished platelet aggregation induced by allagonists examined via the inhibition of_IIb3 activation. Moreover, theseinhibitors abolished _IIb3 activationinduced by phorbol 12-myristate 13-acetate or A23187. On the otherhand, neither of these inhibitors showed apparent inhibitory effects onprotein phosphorylation of pleckstrin or myosin light chain, or anincrease in intracellular calcium ion concentrations evoked by 0.1 U/mLthrombin. These effects of the NCX inhibitors are in striking contrastto those of protein kinase C inhibitor, Ro31-8220. Biochemical andultrastructural analyses showed that NCX inhibitors, particularly DCB,made platelets "thrombasthenic". These findings suggest that theNCX is involved in the common steps of inside-out signaling throughintegrin _IIb3.     

A newly estimated glomerular filtration rate is independently associated with arterial stiffness in Japanese patients.

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease, and thus is a major worldwide public health problem. Recently, an estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation for Japanese patients was proposed by the Japanese Society of Nephrology. However, the role of eGFR in the assessment of atherosclerosis is not well understood in Japanese patients. We analyzed the relationship between eGFR and severity of arterial stiffness using brachial-ankle pulse wave velocity (baPWV) in 647 adult Japanese patients. baPWV correlated significantly and positively with age, hypertension, diabetes, prior cardiovascular disease, blood pressure, pulse pressure and heart rate, and negatively with eGFR (r=-0.405, p<0.0001). A multiple regression analysis revealed that baPWV correlated independently with eGFR. Furthermore, there was a stepwise increase in baPWV, corresponding to advances in CKD through stages 1 to 5. When CKD stage 3 was divided at eGFR 45 mL/min/1.73 m2, the baPWV of stage 3b (eGFR 30 to 44) was significantly higher than that of stage 3a (eGFR 45 to 59) independent of traditional risk factors, suggesting that an eGFR of 45 mL/min/1.73 m2 may be a critical cut off value to predict arterial stiffness in CKD. In conclusion, the newly proposed eGFR is significantly associated with arterial stiffness, independent of traditional risk factors for cardiovascular disease.     

Recovery of BMIPP uptake and regional wall motion in insulin resistant patients following angioplasty for acute myocardial infarction.

The effect of insulin resistance (IR) on the fatty acid metabolism of myocardium, and therefore on the recovery of left ventricular (LV) wall motion, has not been established in patients with acute myocardial infarction (AMI). A total of consecutive 58 non-diabetic AMI patients who had successfully undergone emergency coronary angioplasty were analyzed retrospectively. They were categorized into 2 groups, normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), based on a 75-g oral glucose tolerance test (OGTT). The parameters of OGTT, myocardial scintigraphy (n=58) (thallium-201 (Tl) and iodine-123-beta-methyl-iodophenylpentadecanoic acid (BMIPP)) and left ventriculography (n=24) were compared in the 2 groups after reperfusion (acute phase) and 3-4 weeks after the AMI (chronic phase). The insulin resistance (IR), estimated by the serum concentration of insulin at 120 min (IRI 120') of the OGTT and by the HOMA (the homeostasis model assessment) index, was higher in the IGT group than in NGT group. An inverse correlation was found between the recovery of regional LV wall motion in the ischemic lesion and the IRI 120' and HOMA index. Although the recovery of BMIPP uptake from the acute to the chronic phase was higher in the IGT group, it was only correlated with the degree of IRI 120', not with the HOMA. IR accompanied by IGT can negatively influence the recovery of regional LV wall motion.     

Atrial Septal Aneurysm may Cause In-Hospital Recurrence of Cryptogenic Stroke

Aims: Awareness of potentially embologenic diseases is critical to determining the prognosis of cryptogenic stroke. The clinical significance of atrial septal aneurysm (ASA) in cryptogenic stroke has not been fully studied. Therefore, we explored clinical characteristics and in-hospital recurrence in patients with ASA in cryptogenic stroke. Methods: A multicenter observational registry of cryptogenic stroke patients was conducted. We obtained baseline characteristics, radiological and laboratory findings, and echocardiographic findings, especially of embolic sources on transesophageal echocardiography. The CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for embolic stroke of undetermined source/cryptogenic stroke) registry was recorded at http://www.umin.ac.jp/ctr/ (UMIN000032957). Patients’ clinical characteristics were compared according to the presence of ASA, and factors associated with in-hospital stroke recurrence were assessed. Results: The study included 671 patients (age, 68.7±12.7 years; 450 males; median National Institutes of Health Stroke Scale score, 2). ASA was detected in 92 patients (14%), displaying higher age (72.4±11.0 vs. 68.1 ±12.9 years, p =0.004), reduced frequency of diabetes mellitus (16% vs. 27%, p =0.030), higher frequency of right-to-left shunt (66% vs. 45%, p ＜0.001), and in-hospital stroke recurrence (8% vs. 3%, p =0.034). ASA was relatively associated with in-hospital recurrence (odds ratio 2.497, 95% confidence interval 0.959–6.500, p = 0.061). Conclusions: The CHALLENGE ESUS/CS registry indicated that ASA was not rare in cryptogenic stroke, and ASA’s clinical characteristics included higher age, reduced frequency of diabetes mellitus, and increased frequency of concomitant right-to-left shunt. ASA may be related to in-hospital stroke recurrence in cryptogenic stroke.     

NCL1, a highly selective lysine-specific demethylase 1 inhibitor,suppresses prostate cancer without adverse effect

Herein, we investigated therapeutic potential of a novel histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in prostate cancer. Hormone-sensitive prostate cancer cells, (LNCaP) and castration resistant cancer cells (PC3 and PCai1) were treated with NCL1, and LSD1 expression and cell viability were assessed. Prostate cancer cells showed strong LSD1 expression, and cell viability was decreased by NCL1. ChIP analysis showed that NCL1 induced H3K9me2 accumulation at the promoters of androgen-responsive genes. NCL1 also induced G1 cell cycle arrest and apoptosis. In addition, autophagosomes and autolysosomes were induced by NCL1 treatment in LNCaP. Furthermore, LC3-II expression was significantly increased by NCL1 and chloroquine. In mice injected subcutaneously with PCai1 and intraperitoneally with NCL1, tumor volume was reduced with no adverse effects in NCL1-treated mice. Finally, LSD1 expression in human cancer specimens was significantly higher than that in normal prostate glands. In conclusion, NCL1 effectively suppressed prostate cancer growth without adverse events. We suggest that NCL1 is a potential therapeutic agent for hormone-resistant prostate cancer.     

The hypoxia-related microRNA miR-199a-3p displays tumor suppressor functions in ovarian carcinoma

During the dissemination of ovarian cancer cells, the cells float in the peritoneal cavity without access to a vascular supply and so are exposed to hypoxic conditions, which may cause the ovarian cancer cells to acquire a more aggressive and malignant phenotype. In this study, we screened microRNAs (miRNAs) to identify those that displayed altered expression patterns under hypoxic conditions and then analyzed their functional roles in ovarian cancer progression. miRNA PCR arrays performed on cells from 2 ovarian cancer cell lines (CaOV3 and RMUG-S) revealed miR-199a-3p as one of the miRNAs that are downregulated under hypoxia. In silico analyses indicated that MET is one of the target genes for miR-199a-3p; subsequently, miR-199a-3p expression was found to be inversely correlated with c-Met expression in ovarian cancer. Transfection of precursor miR-199a-3p into ovarian cancer cells reduced c-Met expression and inhibited the phosphorylation of c-Met, extracellular signal-regulated kinase, and AKT; in addition, proliferation, adhesion, and invasiveness were inhibited. Moreover, overexpression of miR-199a-3p in cancer cells significantly suppressed peritoneal dissemination in a xenograft model. In summary, the hypoxia-related microRNA miR-199a-3p drastically inhibits ovarian cancer progression through the downregulation of c-Met expression. Therefore, miR-199a-3p is a potential target for treating ovarian cancer dissemination.