The Molecular Pathogenesis and Clinical Implications of Hepatocellular Carcinoma

The prognosis of hepatocellular carcinoma (HCC) is affected by tumoral factors and liver functions; therefore it is often difficult to select the appropriate therapeutic methods for HCC. Recently, two global phase III trials showed that sorafenib, which is a tyrosine kinase inhibitor, improved the prognosis of patients with advanced HCC. As a new therapeutic strategy for HCC, sorafenib is expected to expand the indication for HCC in the future. However, it alone is insufficient for the molecular-targeted treatment of HCC because the signaling pathway exists not only in cancer cells but also in normal cells. Recently, cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for HCC. There is now much evidence that stem cell properties such as self-renewal, unlimited proliferation, and differentiation are highly relevant to cancer recurrence and the drug resistance of HCC. In this review, we describe the molecular pathogenesis and the current state and future development of molecular- and CSC-therapeutic targeted agents for HCC, citing various reports

Transient Automatic Writing Behavior following a Left Inferior Capsular Genu Infarction

A 79-year-old, right-handed woman was admitted to the hospital with decreased spontaneity. Brain magnetic resonance imaging showed a left inferior capsular genu infarction. 99m TC-ECD single-photon emission computed tomography revealed a left-dominant diffuse hypoperfusionin the basal ganglia and frontal lobe. The patient showed abulia and increased writing activity without motor or sensory deficit. The writing was mainly perseverative, and words written along lines were legible and without spatial distortions. This augmented writing behavior disappeared on day 21. The writing characteristic was more similar to automatic writing behavior than hypergraphia. Dissociation between speech and writing behavior was present in our patient. We suggest that a disconnection within the frontal-subcortical circuit contributed to the development of motor perseveration in writing

Idiopathic REM Sleep Behavior Disorder: Implications for the Pathogenesis of Lewy Body Diseases

Objectives. Both results of the odor identification and cardiac 123I-metaiodobenzylguanidine accumulation have been investigated for their potential to enhance the detection of pathogenesis resembling that of Lewy body-related α-synucleinopathies in patients clinically diagnosed as having idiopathic REM sleep behavior disorder. Methods. We performed both the Odor Stick Identification Test for Japanese and 123I-metaiodobenzylguanidine scintigraphy in 30 patients with idiopathic REM sleep behavior disorder, 38 patients with Parkinson's disease, and 20 control subjects. Results. In idiopathic REM sleep behavior disorder, reduced odor identification score and an early or delayed heart to mediastinum ratio on 123I-metaiodobenzylguanidine were almost as severe as in Parkinson's disease patients. Delayed cardiac 123I-metaiodobenzylguanidine uptake was even more severe in the idiopathic REM sleep behavior disorder group than in the Parkinson's disease group. Conclusions. Reduced cardiac 123I-metaiodobenzylguanidine uptake, which is independent of parkinsonism, may be more closely associated with idiopathic REM sleep behavior disorder than olfactory impairment

Utility of Plain Chest Computed Tomography in Diagnosing Cardioembolic Stroke due to Paroxysmal Atrial Fibrillation

Background：Diagnosing cardioembolic stroke due to paroxysmal atrial fibrillation（PAF）is difficult, mainly due to low detection rate. We evaluated whether left atrial volume, which can be simply measured using non-contrast chest computed tomography（CT-LAV）, can contribute to the diagnosis of cardioembolic stroke due to PAF（PAF-CE）.Methods：Fifty-one consecutive patients with acute ischemic stroke within 24 h of onset were included in this study. Upon admission, we measured the left atrial diameter using transthoracic echocardiography（TTE-LAD）and CT-LAV. Patient background factors such as sex, age, and stroke risk factors were noted as well as brain natriuretic peptide（BNP）value and QTc interval were evaluated on admission. Utilities of BNP value, CT-ALV, and TTE-LAD in PAF-CE diagnosis were compared.Results：Patients were classified into three groups：cerebral thrombosis（CTB）group including large-artery atherosclerosis and small-vessel occlusion（n＝16）, cardioembolic stroke due to non-valvular atrial fibrillation（AF-CE）group（n＝20）, and cardioembolic stroke due to paroxysmal atrial fibrillation（PAF-CE）group（n＝15）. BNP value was highest in the AF-CE group（240.5 pg/mL）, followed by the PAF-CE（187.9 pg/mL）and CTB groups（35.0 pg/mL）（p＜0.001）. There was a significant difference in TTE-LAD among the groups（AF-CE group, 43.8 mm；PAF-CE group, 38.3 mm；CTB group, 34.1 mm）（p＜0.001）. CT-LAV was higher in the AF-CE group（142 mm3）than in the PAF-CE（95.8 mm3）and CTB groups（95.8 mm3）（p＜0.001）. In differentiating PAF-CE, the area under the receiver operating characteristic curve was 0.867, 0.742, and 0.845 for BNP value, TTE-LAD, and CT-LAV, respectively. A cut-off CT-LAV value of ≥ 69.6 mm3 had a high diagnostic rate（＞80％ of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy）.Conclusion：CT-LAV can be useful in diagnosing PAF-CE. Further studies with larger sample size are required to confirm our findings and determine better cut-off value for CT-LAV

Conduction block in acute motor axonal neuropathy

Guillain-Barré syndrome is divided into two major subtypes, acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. The characteristic electrophysiological features of acute motor axonal neuropathy are reduced amplitude or absence of distal compound muscle action potentials indicating axonal degeneration. In contrast, autopsy study results show early nodal changes in acute motor axonal neuropathy that may produce motor nerve conduction block. Because the presence of conduction block in acute motor axonal neuropathy has yet to be fully recognized, we reviewed how often conduction block occurred and how frequently it either reversed or was followed by axonal degeneration. Based on Ho's criteria, acute motor axonal neuropathy was electrodiagnosed in 18 patients, and repeated motor nerve conduction studies were carried out on their median and ulnar nerves. Forearm segments of these nerves and the across-elbow segments of the ulnar nerve were examined to evaluate conduction block based on the consensus criteria of the American Association of Electrodiagnostic Medicine. Twelve (67%) of the 18 patients with acute motor axonal neuropathy had definite (n = 7) or probable (n = 5) conduction blocks. Definite conduction block was detected for one patient (6%) in the forearm segments of both nerves and probable conduction block was detected for five patients (28%). Definite conduction block was present across the elbow segment of the ulnar nerve in seven patients (39%) and probable conduction block in two patients (11%). Conduction block was reversible in seven of 12 patients and was followed by axonal degeneration in six. All conduction blocks had disappeared or begun to resolve within three weeks with no electrophysiological evidence of remyelination. One patient showed both reversible conduction block and conduction block followed by axonal degeneration. Clinical features and anti-ganglioside antibody profiles were similar in the patients with (n = 12) and without (n = 6) conduction block as well as in those with (n = 7) and without (n = 5) reversible conduction block, indicating that both conditions form a continuum; a pathophysiological spectrum ranging from reversible conduction failure to axonal degeneration, possibly mediated by antibody attack on gangliosides at the axolemma of the nodes of Ranvier, indicating that reversible conduction block and conduction block followed by axonal degeneration and axonal degeneration without conduction block constitute continuous electrophysiological conditions in acute motor axonal neuropath

1,10-Phenanthroline- or Electron-Promoted Cyanation of Aryl Iodides

A 1,10-phenanthroline-promoted cyanation of aryl iodides has been developed. 1,10-Phenanthroline worked as an organocatalyst for the reaction of aryl iodides with tetraalkylammonium cyanide to afford aryl cyanides. A similar reaction occurred through an electroreductive process