Molecular and morphological analyses revealed a cryptic species of dojo loach Misgurnus anguillicaudatus (Cypriniformes: Cobitidae) in Japan.

Although it has been reported that populations of the Japanese dojo loach Misgurnus anguillicaudatus (Cypriniformes: Cobitidae) belong to two distinct mitochondrial (mt)DNA (Type I and Type II), the taxonomic status of the species remains unresolved. To address this question, nuclear DNA and morphological analyses were performed on M. anguillicaudatus population in the Nakaikemi Wetland, where Type I and Type II lineages are sympatric. Results suggest the existence of a cryptic species (Type I) within the Japanese dojo loach.

Effectiveness of third-line chemotherapy in recurrent ovarian cancer patients.

OBJECTIVE: Despite recent advances in the treatment of recurrent ovarian cancer, little evidence exists describing the benefit of third- line chemotherapy. The present authors previously reported that the treatment-free interval (TFI) after second-line chemotherapy may predict a survival benefit of third-line chemotherapy, however the length of TFI was uncertain due to limited cases. In this study, the authors evaluated the length of TFI, which is correlated with the effectiveness of third-line chemotherapy and a prognostic factor of third-line chemotherapy. MATERIALS AND METHODS: The authors reviewed the medical records of 85 women with recurrent ovarian cancer who received third-line chemotherapy after a paclitaxel/carboplatin (PC) regimen as first-line chemotherapy. RESULTS: The response rate [complete response (CR) + partial response (PR)] and clinical benefit rate [(CBR): CR + PR + stable disease (SD)] during the TFI after second-line chemotherapy for 0-3 months, 3-6 months, and 6-12 months and ≥ 12 months were 9.8%, 0%, 0%, 43.8% and 15.7%, 50%, 66.7%, and 93.8%, respectively. The median overall survival (OS) from the onset of third-line chemotherapy was longer for TFI ≥ 3 months than for TFI 0-3 months (795 days vs. 281 days, p < 0.001). Finally, according to univariate (HR = 0.256; p < 0.001) and multivariate (HR = 0.264; p < 0.001) analyses, TFI was the independent significant prognostic factor for OS. CONCLUSIONS: TFI less than three months after second-line chemotherapy may predict little survival benefit of third-line chemotherapy.

Admission hyperglycemia causes infarct volume expansion in patients with ICA or MCA occlusion: association of collateral grade on conventional angiography.

BACKGROUND AND PURPOSE: Hyperglycemia (HG) is associated with infarct volume expansion in acute ischaemic stroke patients. However, collateral circulation can sustain the ischaemic penumbra and limit the growth of infarct volume. The aim of this study was to determine whether the association between HG and infarct volume expansion is dependent on collateral circulation. METHODS: We performed a retrospective analysis of 93 acute ischaemic stroke patients with internal carotid artery or middle cerebral artery occlusion within 24 h of onset were retrospectively studied. HG was diagnosed in patients with an admitting blood glucose value ≥140 mg/dl. Angiographic collateral grade 0-1 was designated as poor collateral circulation and grade 2-4 as good collateral circulation. Infarct volume was measured at admission and at again within 7 days using diffusion-weighted magnetic resonance images. RESULTS: Among 34 patients with poor collateral grade, the change in infarct volume was significantly greater in the HG group than in the non-HG group (106.0 ml vs. 22.7 ml, P = 0.002). Among the 59 patients with good collateral circulation, the change in infarct volume was greater in the HG group than in the non-HG group (53.3 ml vs. 10.9 ml, P = 0.047). Multiple regression analysis indicated that admission HG (P = 0.004), baseline National Institutes of Health Stroke Scale score (P = 0.018), and poor collateral circulation (P = 0.040) were independently associated with infarct volume expansion. CONCLUSIONS: Infarct volume expansion was greater in individuals with HG on admission regardless of collateral circulation status.

Plasma brain natriuretic peptide predicts death during hospitalization in acute ischaemic stroke and transient ischaemic attack patients with atrial fibrillation.

BACKGROUND AND PURPOSE: atrial fibrillation (AF) is the most powerful predictor of early death in patients with acute ischaemic stroke. We investigated whether the plasma brain natriuretic peptide (BNP) level on admission can serve as a biological marker of in-hospital death in acute ischaemic stroke and transient ischaemic attack (TIA) patients with AF. METHODS: we prospectively enrolled ischaemic stroke and TIA patients with AF within 24 h of onset and measured plasma BNP on admission. Patients were divided into two groups: the deceased group, who died during hospitalization, and the survival group. The factors associated with in-hospital death were investigated by multivariate logistic regression analysis. RESULTS: a total of 221 patients with AF were enrolled. Death occurred in 24 (10.9%) patients. The mean ± SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group (714.1 ± 716.3 vs. 320.0 ± 380.7 pg/ml, P < 0.0001). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the deceased group from the survival group were 320 pg/ml, 79.2, and 69.0%, respectively. Multivariate logistic regression analysis demonstrated that age per 10 years increase (OR, 3.56; 95% CI, 1.728-7.346, P = 0.0006), internal carotid artery occlusion (OR, 10.20; 95% CI, 2.525-41.177, P = 0.0011), NIHSS score of >17 (OR, 4.68; 95% CI, 1.137-19.286, P = 0.0325), and plasma BNP level of > 320 pg/ml (OR, 4.74; 95% CI, 1.260-17.800, P = 0.0213) were independent factors associated with in-hospital death. CONCLUSION: the plasma BNP level on admission can predict in-hospital death in acute ischaemic stroke and TIA patients with AF.

Brain natriuretic peptide as a predictor of delayed atrial fibrillation after ischaemic stroke and transient ischaemic attack.

BACKGROUND AND PURPOSE: We investigated whether the brain natriuretic peptide (BNP) level can serve as a predictive biological marker of delayed atrial fibrillation (AF). METHODS: Two hundred and thirty seven consecutive patients admitted to our institution with acute ischaemic stroke or transient ischaemic attack (TIA) within 24 h of onset were enrolled. The patients were classified according to the presence or absence of AF upon admission [AF and sinus rhythm (SR) groups]. The SR group was subdivided based on the development of AF after admission (new- and non-AF groups). We compared the characteristics between the AF and SR groups, and between the new- and non-AF groups. The factors associated with new-AF were investigated by multivariate logistic regression analysis. RESULTS: Amongst the enrolled patients, 72 (30.4%) had AF upon admission (AF group), and 13 (5.5%) developed AF thereafter (new-AF group). The plasma BNP level was significantly higher in the AF, than in the SR group (401.7 vs. 92.1 pg/ml, P < 0.001). Moreover, the plasma BNP level was significantly higher in the new-, than in the non-AF group (184.7 vs. 84.1 pg/ml, P < 0.001). The optimal cutoff BNP level required to distinguish new-, from non-AF groups was 85.0 pg/ml, and the sensitivity and specificity was 83.3% and 76.2%, respectively. On multivariate logistic regression analysis, plasma BNP level >85.0 pg/ml (odds ratio, 7.20; 95% confidence interval, 1.71 to 30.43, P = 0.007) was an independent factor associated with new-AF. CONCLUSION: High plasma BNP level should be a strong predictor of delayed AF after ischaemic stroke or TIA.

Microembolic signals at 48 hours after stroke onset contribute to new ischaemia within a week.

BACKGROUND AND AIMS: We investigated whether new ischaemic lesions (NIL) on follow-up diffusion weighted magnetic resonance imaging (DWI) are associated with microembolic signals (MES) within 24 h or at 48 h after stroke onset. METHODS: Patients had acute ischaemic stroke and were studied within 24 h of onset. Transcranial Doppler ultrasonography (TCD) was prospectively examined twice, within 24 h and at 48 h after onset. DWI was conducted twice, on admission and on day 7. NIL were defined as the presence of hyperintense lesions undetected on initial DWI. RESULTS: 125 patients were consecutively enrolled from November 2004 to March 2006. TCD detected MES in 49% within 24 h and in 29% at 48 h after onset. In 27 patients with small vessel disease, MES were found in 8 (30%) patients within 24 h and in 5 (19%) patients at 48 h after stroke onset. In contrast, in 20 patients with large vessel disease, 11 (55%) patients within 24 h and 7 (35%) at 48 h had MES. Follow-up DWI detected NIL in 28 of 125 patients (22%) and NIL were significantly more frequent in MES positive patients (42%) than in MES negative patients at 48 h (15%; p = 0.002). MES at 48 h (OR 3.9; 95% CI 1.5 to 10; p = 0.005), atrial fibrillation (OR 3.6; 95% CI 1.3 to 11; p = 0.013) and arterial lesions (OR 4.3; 95% CI 1.5 to 12; p = 0.007) represented independent factors for NIL. CONCLUSION: The presence of MES at 48 h, atrial fibrillation and arterial lesions were associated with recurrence of cerebral ischaemia on DWI.

Magnetoelectrical control of nonreciprocal microwave response in a multiferroic helimagnet.

The control of physical properties by external fields is essential in many contemporary technologies. For example, conductance can be controlled by a gate electric field in a field effect transistor, which is a main component of integrated circuits. Optical phenomena induced by an electric field such as electroluminescence and electrochromism are useful for display and other technologies. Control of microwave propagation is also important for future wireless communication technology. Microwave properties in solids are dominated mostly by magnetic excitations, which cannot be easily controlled by an electric field. One solution to this problem is to use magnetically induced ferroelectrics (multiferroics). Here we show that microwave nonreciprocity, that is, different refractive indices for microwaves propagating in opposite directions, could be reversed by an external electric field in a multiferroic helimagnet Ba2Mg2Fe12O22. This approach offers an avenue for the electrical control of microwave properties.

Ischaemic stroke with malignancy may often be caused by paradoxical embolism.

BACKGROUND: Although ischaemic stroke with malignancy occasionally occurs, the mechanisms of stroke in such cases have not been investigated in detail. OBJECTIVE: To examine the mechanisms of ischaemic stroke with malignancy, particularly in relation to right-to-left shunt (RLS). METHODS: Consecutive patients with ischaemic stroke within 24 h of stroke onset were prospectively studied. Contrast saline transcranial Doppler examination was carried out for all patients, to investigate the presence of RLS. When patients with stroke had RLS, deep venous thrombosis (DVT) or pulmonary embolism was assessed to diagnose paradoxical brain embolism. RESULTS: Participants comprised 184 consecutive patients (115 men and 69 women) with a mean (standard deviation (SD)) age of 73 (11.8) years and mean (SD) National Institutes of Health Stroke Scale (NIHSS) score of 8 (7.4). RLS was detected in 32 of 184 (18%) patients. Malignancy was present in 11 (5%) patients. RLS was more frequent in patients with malignancy than in patients without malignancy (55% v 15%, respectively; p = 0.001). All six patients with RLS and malignancy displayed DVT or pulmonary embolism with severe disability (modified Rankin Scale 4-5) before stroke onset. CONCLUSION: Paradoxical brain embolism should be considered to be an important mechanism in patients with stroke and malignancy.

Seasonal variations of acute massive submacular haemorrhage associated with age-related macular degeneration.

AIMS: To determine whether there is a seasonal variation in the onset of acute, massive submacular haemorrhage associated with age-related macular degeneration. METHODS: Sixty eyes of 59 patients diagnosed between April 1998 and March 2005, were studied retrospectively. For each patient, the month and season of onset of the submacular haemorrhage and the mean monthly ambient temperature in Nagoya were analysed. Any history of systemic hypertension was also recorded, and the seasonal variations were also investigated in hypertensive and non-hypertensive groups. RESULTS: The number of cases peaked in winter with a trough in summer, and this seasonal variation was significant (Roger's R = 12.03, p<0.01). The monthly incidence was inversely correlated with the temperature (Spearman's rank correlation coefficient r = 0.89, p<0.01). The seasonal variations were significant in the hypertensive group but not in the non-hypertensive group. CONCLUSION: The considerable seasonal variations suggests that the mechanism for the haemorrhage is strongly correlated with the systemic blood pressure.

Visualization of the stop of microtubule depolymerization that occurs at the high-density region of microtubule-associated protein 2 (MAP2).

Individual microtubules (MTs) repeat alternating phases of polymerization and depolymerization, a process known as dynamic instability. Microtubule-associated proteins (MAPs) regulate the dynamic instability by increasing the rescue frequency. To explore the influence of MAP2 on in vitro MT dynamics, we correlated the distribution of MAP2 on individual MTs with the dynamic phase changes of the same MTs. MAP2 was modified selectively on its projection region by X-rhodamine iodoacetamide without altering the MT-binding activity. When the labeled MAP2 was added to MTs, the fluorescence was distributed along almost the entire length of individual MTs. However, the inhomogeneity of the distribution gradually became obvious due to the fluorescence bleaching, and the MTs appeared to consist of rapidly bleached portions (RBPs) and slowly bleached portions (SBPs), which were distributed randomly along the MT. By measuring the duration of fluorescence bleaching, the density of MAP2 in SBP was estimated to be approximately 2.5 times higher than the RBP. The average tubulin:MAP2 ratio in SBP was calculated to be 16. When the MT dynamics were observed by dark-field microscopy after determining the MAP2 distribution, rescues were always found to occur only at the SBPs. MTs also displayed intermittent shortening by repeated depolymerization phases separated by pause phases. In these cases, depolymerization phases stopped only at the SBPs. Not every SBP stopped depolymerization, but depolymerization always stopped at an SBP. Taken together, we suggest that there is a minimum density of MAP2 that is necessary to stop depolymerization.

Hairy cell leukemia in Japanese patients: a study with monoclonal antibodies.

Using a panel of monoclonal antibodies and three anti-hairy cell sera (alpha HC1 and alpha HC2 of Posnett and 4B122 prepared by the authors), hairy cells were phenotyped on frozen sections of cell pellets from blood and spleen of 11 Japanese patients with hairy cell leukemia (HCL). The results were quite similar to those reported for HCL of non-Japanese patients inasmuch as hairy cells in the majority of these patients were B1+, B2-, FMC7+, and IL-2R1+. However, they were more often than not J5+, Leu-1+, alpha HC1-, alpha HC2-, and 4B122+ in contrast to the pattern reported for non-Japanese patients. In conclusion, HCL in the Japanese constitutes a special variant of HCL because of its rareness, unusual immunophenotype, and atypical clinicohematologic features.

Highly selective inhibitors of thromboxane synthetase. 2. Pyridine derivatives.

The enzyme thromboxane (TX) synthetase is inhibited by pyridine. The beta-substituted pyridine derivatives showed higher inhibitory potency than the gamma-substituted ones having the same side chain. Among the beta-substituted derivatives containing the omega-carboxyalkyl group, the compounds with 6-8 carbon atoms in the side chain were especially effective. The derivatives holding the phenylene group in the side chain exhibited much higher inhibitory activity than those of the alkylene type. Among them, (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid hydrochloride (5a) had the highest potency (IC50 = 3 x 10(-9) M). The beta-substituted pyridine derivatives and 1-substituted imidazole derivatives which had the same side chain showed almost the same potency. The beta-substituted pyridine derivatives do not inhibit arachidonic acid cyclooxygenase or prostaglandin I2 synthetase, two other enzymes of the arachidonic cascade.

Highly selective inhibitors of thromboxane synthetase. 1. Imidazole derivatives.

The structure--activity relationships of imidazole derivatives as inhibitors of thromboxane (TX) synthetase were investigated. Introduction of various substituents (e.g., one or two methyl groups, a halogen atom, a methylidene group, unsaturated bonds, or a phenylene group) into the alpha position or other positions in the carboxy-bearing side chain of 1-(7-carboxyheptyl)imidazole (15) was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum for the inhibitory potency on TX synthetase in the region of 8.5-9.0 A. Among the tested imidazole derivatives, 1-(7-carboxy-7-methyl-2-octynyl)imidazole (47), 4-[3-(1-imidazolyl)-propyl]benzoic acid (50), and (E)-4-(1-imidazolylmethyl)cinnamic acid (54) and its alpha-methyl analogue (57) showed the highest potency with an IC50 in the range of 10(-8) to 10(-9) M. Inhibition by these derivatives was highly selective for the TX synthetase, since other enzymes such as fatty acid cyclo-oxygenase and prostacyclin synthetase were not affected.

Synthesis and non-thrombogenicity of heparinoid polyurethaneureas.

Unsaturated polyurethaneureas were synthesized from 4,4'-diphenylmethane diisocyanate, 1,2-diaminopropane and polybutadiene containing hydroxyl groups at both ends of a chain. The polyurethaneureas were cast as a film and subsequently treated with N-chlorosulphonyl isocyanate to produce sulphamate and carboxylate groups on the film surface. The level of in vitro non-thrombogenicity increased with increasing degree of modification. The high blood compatibility is attributed to the low level of platelet stimulation and to heparinoid activity. It was observed that platelet stimulation depends on the surface structure of the original polyurethaneura, and that the heparinoid activity is related with the presence of sulphamate and carboxylate groups.

Solitary cystic dilatation of the intrahepatic bile duct.

A 31 year old man was hospitalised with general fatigue and epigastric pain. Abdominal ultrasonography, computed tomography, and magnetic resonance imaging showed a cystic lesion in the left lobe of the liver. Endoscopic retrograde cholangio-pancreatography and percutaneous trans-hepatic cholangiography revealed a localised dilatation of the intrahepatic bile duct without any obstruction. However, a large mass of mucinous material was noted in the saccular intrahepatic duct and the common bile duct. There was no evidence of a choledochal cyst, anomalous pancreaticobiliary ductal union, or congenital cystic change of the kidneys. A possible diagnosis of mucinous cystic neoplasm of the intrahepatic bile duct was made and a left hepatectomy performed. Cholangiography of the resected specimen showed a non-obstructive solitary cystic dilatation of the left hepatic duct. Histologically, the dilated duct was lined with columnar biliary epithelium without any papillary proliferation and/or atypia. Neither malignancy nor hepatic fibrosis was observed; the term "solitary cystic dilatation of the intrahepatic bile duct" perhaps is more descriptive and the concept easier to understand.

Selective spatial attention induces short-term plasticity in human somatosensory cortex.

Early cognitive process in the primary somatosensory cortex (SI) was studied by measuring somatosensory evoked magnetic fields during selective attention tasks. We used vibratory stimuli to the index or middle finger with a frequency of 100 or 400 Hz for selective discrimination of spatial finger and non-spatial frequency attribute of stimuli. An early M50 component from the SI cortex indicated that the SI regions for the fingers were specifically segregated in a finger discrimination task but not in a frequency discrimination task or in a control condition. The task-dependent and immediate switchover of cortical finger representation demonstrates a dynamic SI activation for spatial information processing.

Serial activation of distinct cytoarchitectonic areas of the human S1 cortex after posterior tibial nerve stimulation.

MEG recordings visualized non-invasively a dynamic anterior-posterior activation in the pyramidal cell population of the human primary somatosensory cortex (S1) after posterior tibial nerve stimulation. Somatosensory evoked fields (SEFs) were recorded over the foot area in response to right posterior tibial nerve stimulation at the ankle in six normal subjects. A newly developed MEG vector beamformer technique applied to the SEFs revealed two distinct sources in the mesial wall of the left hemisphere around the primary P37m response typically separated by 1.3 cm. The first source was located in area 3b and oriented toward the contralateral hemisphere. The second source was assumed to be in an area near the marginal sulcus and the source orientation was directed posteriorly. The first source began to be active during the initial slope of the P37m. The second source was active after the P37m peak and the signal intensities of the first and second sources were equal at a mean latency of 2.6 ms after the peak of P37m. Then the first source became inactive and the second source was dominant after about 5 ms post-P37m peak. These findings suggest that a single peaked posterior tibial nerve P37m consists of partially overlapping two subcomponents generated in area 3b and an area near the marginal sulcus.

Dynamic activation of distinct cytoarchitectonic areas of the human SI cortex after median nerve stimulation.

MEG recordings visualized non-invasively a serial mediolateral activation of the human somatosensory 3b area followed by a stationary activation of area 1 after median nerve stimulation. Somatosensory evoked fields (SEFs) were recorded over the hand area contralateral to the right median nerve stimulation at the wrist in six normal subjects. A newly developed MEG vector beamformer technique applied to the SEFs revealed two distinct sources (areas 3b and 1) in the primary somatosensory cortex (SI) during the primary N20m-P22m response in all subjects. The first source was located in area 3b, which started to move sequentially toward mediolateral direction 0.7 ms prior to the peak of N20m and ended its movement 1.4 ms after the peak with a total distance of 11.2 mm. We speculate that the movement reflects a sequential mediolateral activation of the pyramidal cells in area 3b, which is mediated by horizontal connections running parallel to the cortical surface. The second source in area 1, located 5.6 mm medial and 4.2 mm posterior to the first source, was active 1.0 ms after the N20m peak. Then, the first source became inactive and the second source was dominant. In sharp contrast with the first source, the second source was stationary. The different behavior of these two components (moving vs stationary) indicates independent parallel inputs to area 3b and area 1 from the thalamus.

Frequency representation in the human hand somatosensory cortex: a reappraisal.

Frequency organization in the human primary somatosensory cortex (SI) was re-examined. Somatosensory evoked magnetic fields (SEFs) were measured with a 37 channel first-order axial gradiometer system. Sensory stimuli comprising a 20ms vibration at frequencies of 50, 100, 200 and 400 Hz were delivered to the volar surface of the tip of the right index finger. Using a single dipole model, the sources of the first main peak (M50) of SEFs were estimated. All of the sources were located in the 3b area. There were no statistically significant differences between the locations of the dipoles evoked by different frequency stimulations. These results support our previous study using a 122 channel whole head planar gradiometer system that systematic frequency organization at the hand area of SI cortex may not be present in humans.

Sequential information processing during a mental arithmetic is reflected in the time course of event-related brain potentials.

OBJECTIVE: We hypothesized that mental arithmetic is a complex of sequential information processing. In order to test the hypothesis, event-related potentials (ERPs) were measured during 3 mental tasks. METHODS: Fifteen normal human subjects performed the following tasks; (1) subjects added up every digit delivered successively on a computer display, (2) subjects counted the number of presented digits, or (3) subjects counted the number of meaningless patterns. Spatiotemporal differences between ERP waveforms under the 3 tasks were studied within the period of 1200 ms post-stimulus. RESULTS: During the adding task, N120-P180-N220 complex advanced in latency in the left frontal, central and parietal regions. P300 increased in amplitude in the frontal and temporal regions during adding and counting digits, which was specific to the digit presentation. A positive slow potential depended on the adding task and showed two spatiotemporal distributions; one was a widespread brain activity over the frontal, central, temporal and parietal regions observed within 400-820 ms, and another was a brain activity restricted to the frontal region lasting up to 1150 ms. CONCLUSIONS: The results suggest that the early portion of ERPs reflects identification of physical attributes of stimuli and numeric meaning of digits, and that the positive slow potential reflects processes associated with calculation.