Negative motor networks: Electric cortical stimulation and diffusion tensor imaging.

INTRODUCTION: This study investigated the networks of Negative motor areas (NMAs) using electric cortical stimulation and diffusion tensor imaging (DTI). METHODS: Twelve patients with intractable focal epilepsy, in which NMAs were identified by electrical cortical stimulation, were enrolled in this study. Electric stimulation at 50Hz was applied to the electrodes during motor tasks to identify the NMAs. DTI was used to identify the subcortical fibers originating from the NMAs found by electrical stimulation. RESULTS: NMAs were found in lateral frontal areas (premotor area (PM) and precentral gyrus) in all 12 patients, in pre-supplementary motor areas (pre-SMAs) in four patients, and in posterior parietal cortices (PPCs) in four. DTI detected fibers connecting to the ipsilateral PMs, PPCs and temporal regions via U-fibers, superior longitudinal fasciculus (SLF), and arcuate fasciculus (AF) from the lateral frontal NMAs. Pre-SMA-NMAs had connections with ipsilateral PMs and contralateral pre-SMAs via the frontal aslant tract and transcallosal commissural fibers, and PPC-NMAs with ipsilateral PMs via SLF and AF. CONCLUSION: This study found the characteristic cortical network of each NMA, and especially revealed new insight of pre-SMA-NMA and PPC NMA. These NMAs might be associated with different mechanism of negative motor response.

Japanese multicenter experience of endoscopic necrosectomy for infected walled-off pancreatic necrosis: The JENIPaN study.

BACKGROUND AND STUDY AIMS: Only a few large cohort studies have evaluated the efficacy and safety of endoscopic necrosectomy for infected walled-off pancreatic necrosis (WOPN). Therefore, a multicenter, large cohort study was conducted to evaluate the efficacy and safety of endoscopic necrosectomy and to examine the procedural details and follow-up after successful endoscopic necrosectomy. PATIENTS AND METHODS: A retrospective review was conducted in 16 leading Japanese institutions for patients who underwent endoscopic necrosectomy for infected WOPN between August 2005 and July 2011. The follow-up data were also reviewed to determine the long-term outcomes of the procedures. RESULTS: Of 57 patients, 43 (75 %) experienced successful resolution after a median of 5 sessions of endoscopic necrosectomy and 21 days of treatment. Complications occurred in 19 patients (33 %) during the treatment period. Six patients died (11 %): two due to multiple organ failure and one patient each from air embolism, splenic aneurysm, hemorrhage from a Mallory - Weiss tear, and an unknown cause. Of 43 patients with successful endoscopic necrosectomy, recurrent cavity formation was observed in three patients during a median follow-up period of 27 months. CONCLUSIONS: Endoscopic necrosectomy can be an effective technique for infected WOPN and requires a relatively short treatment period. However, serious complications can arise, including death. Therefore, patients should be carefully selected, and knowledgeable, skilled, and experienced operators should perform the procedure. Further research into safer technologies is required in order to reduce the associated morbidity and mortality.

Visual perceptual strengths and weaknesses in adults with intellectual disabilities compared with a birth year-matched norm.

BACKGROUND: The ventral and dorsal streams are considered to be the brain substrates of vision for perception and action, respectively. Using the Developmental Test of Visual Perception (DTVP), the current study examined whether visual perceptual strengths and weaknesses in adults with intellectual disabilities (ID) were attributable to the dichotomy of the visual streams. METHOD: In study 1, DTVP performance was compared among mild, moderate and severe adult ID groups; study 2 contrasted adult ID groups with and without Down syndrome (DS). To prevent possible contamination by the Flynn effect, participants were matched by birth year with the norm of the DTVP original edition. RESULTS: Independent of the extent of ID among the three groups in study 1 and the aetiological group difference in study 2, relative strength was found for two DTVP tasks: eye-hand coordination and distinguishing target figures from interference background. Relative weakness was obtained in identifying a figural category. Participants with DS demonstrated exceptional weakness in discerning a target from either mirror-imaged or rotated alternatives, in addition to figural-category detection. CONCLUSIONS: Visual perceptual strengths and weaknesses in persons with ID were difficult to explain on the basis of two visual streams. An interpretation originating in a different research context (e.g. frontal-lobe dysfunction) appears to be required for explaining visual perceptual weaknesses in persons with ID. For persons with DS, strong frontal-lobe dysfunction with atypical lateralisation might be the pathological determinant of visual perceptual weaknesses.

Toxicity test using medaka (Oryzias latipes) early fry and concentrated sample water as an index of aquatic habitat condition.

The aim of the present study was to show a relationship between toxicity of 100-fold concentrated water and aquatic habitat conditions. Environmental waters are 100-fold concentrated with solid-phase extraction. Medaka early fry was exposed in these waters for 48 h. The number of death and disorder was counted at 1, 2, 3, 6, 12, 24, and 48 h; toxicity was expressed using inverse median effect time and median lethal time (ET (50)(-1), LT (50)(-1)). Average score per taxon (ASPT) for benthic animals and Index of Biotic Integrity (IBI) for fish were applied as indices of aquatic habitat conditions. The results of toxicity test were compared using ASPT and IBI. The different levels of toxicity were detected in the seawater of Japan. At the Husino River area, toxicity cannot be detected. In rivers, high toxicity appeared at urban districts without sewerage. By Spearman coefficient, the relationship between toxicity and high biochemical oxygen demand (BOD) were obtained. BOD household wastewater contains hydrophobic toxic matters; otherwise, seawater in industrial area does not show clear relationship between toxicity and chemical oxygen demand. Gas chromatography to mass spectrometry simultaneous analysis database may give an answer for the source of toxicity, but further test is required. Ratio of clear stream benthic animal sharply decreased over 0.25 of LT (50)(-1) or 0.5 of ET (50)(-1). Tolerant fish becomes dominant over 0.3 of LT (50)(-1) or 0.5-1.0 of ET (50)(-1). By Pearson product-moment correlation coefficient, correlation coefficient between toxicity and ASPT was obtained at -0.773 (ET (50)(-1)) and -0.742 (LT (50)(-1)) at 1 % level of significance with a high negative correlation. Toxicity (LT (50)(-1) ) has strong correlation with the ratio of tolerant species. By Pearson product-moment correlation coefficient, correlation coefficient between toxicity and IBI obtained were -0.155 (ET (50)(-1)) and -0.190 (LT (50)(-1)) at 1 % level of significance and has a low or no correlation between toxicity and IBI. Even with low toxic environmental waters, toxicity test using 100-fold concentrated and medaka early fly could detect acute toxicity. The detected toxicity seemed to limit the inhabiting aquatic species in the water body.

Standard steroid treatment for autoimmune pancreatitis.

OBJECTIVE: To establish an appropriate steroid treatment regimen for autoimmune pancreatitis (AIP). METHODS: A retrospective survey of AIP treatment was conducted in 17 centres in Japan. The main outcome measures were rate of remission and relapse. RESULTS: Of 563 patients with AIP, 459 (82%) received steroid treatment. The remission rate of steroid-treated AIP was 98%, which was significantly higher than that of patients without steroid treatment (74%, 77/104; p<0.001). Steroid treatment was given for obstructive jaundice (60%), abdominal pain (11%), associated extrapancreatic lesions except the biliary duct (11%), and diffuse enlargement of the pancreas (10%). There was no relationship between the period necessary to achieve remission and the initial dose (30 mg/day vs 40 mg/day) of prednisolone. Maintenance steroid treatment was given in 377 (82%) of 459 steroid-treated patients, and steroid treatment was stopped in 104 patients. The relapse rate of patients with AIP on maintenance treatment was 23% (63/273), which was significantly lower than that of patients who stopped maintenance treatment (34%, 35/104; p = 0.048). From the start of steroid treatment, 56% (55/99) relapsed within 1 year and 92% (91/99) relapsed within 3 years. Of the 89 relapsed patients, 83 (93%) received steroid re-treatment, and steroid re-treatment was effective in 97% of them. CONCLUSIONS: The major indication for steroid treatment in AIP is the presence of symptoms. An initial prednisolone dose of 0.6 mg/kg/day, is recommend, which is then reduced to a maintenance dose over a period of 3-6 months. Maintenance treatment with low-dose steroid reduces but dose not eliminate relapses.

Interferon-gamma is produced by CD8 T cells in response to HLA-A24-restricted hepatitis C virus epitopes after sustained virus loss.

Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8(+) T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/beta2-microglobulin/peptide complexes using two epitopes. Production of interferon-gamma by CD8(+) T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) (n = 13) against all the peptides, NS31296-1304 (the percentage of responding patients, 61.5%) and core 129-137 (53.8%), while no interferon-gamma production was observed in non-responders (NR) (n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8(+) T cells specific for all the peptides except NS31296-1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296-1304 (3/4) and core 129-137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-gamma production by CD8(+) T lymphocytes against HCV NS31296-1304 and core 129-137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8(+) T cell response in controlling HCV infection.

Non-transcallosal ipsilateral area 3b responses to median nerve stimulus.

We report two patients with left hemisphere lesions who had no normal left hemispheric responses to right median nerve stimulus on magnetoencephalography but displayed right area 3b responses. One patient had suffered a severe left hemispheric contusion and the other left hemispheric infarction. Equivalent current dipoles of these ipsilateral responses were detected on the central sulcus adjacent to the location of the N20m response to left median nerve stimulus. The somatosensory afferent pathway from the hand may extend directly to the ipsilateral area 3b without following the transcallosal pathway in at least part of the population.

Somatosensory-evoked fields for gingiva, lip, and tongue.

To localize the oral primary somatosensory cortex, we measured somatosensory-evoked fields for the lip, gingiva, and tongue in six healthy subjects. The latency of the first peak of the posterior-oriented current in the contralateral hemisphere was 50.9 +/- 8.3 ms for the gingiva, significantly shorter than those for the lip and tongue peaks. The equivalent current dipole was localized on the central sulcus. The gingival dipole was localized significantly inferior to the lip dipole but not different from the tongue dipole. The moment of the gingival dipole was significantly smaller than that of the lip dipole but not different from that of the tongue dipole. Differences in the above parameters were negligible between the left and right, anterior and posterior, and upper and lower locations within the same organ, except that the dipole location for the anterior upper tongue was significantly inferior to that for the lower tongue.

Expression of AODEF, a B-functional MADS-box gene, in stamens and inner tepals of the dioecious species Asparagus officinalis L.

Garden asparagus (Asparagus officinalis L.) is a dioecious species with male and female flowers on separate unisexual individuals. Since B- and C-functional MADS-box genes specify male and female reproductive organs, it is important to characterize these genes to clarify the mechanism of sex determination in monoecious and dioecious species. In this study, we isolated and characterized AODEF gene, a B-functional gene in the development of male and female flowers of A. officinalis. Southern hybridization identified a single copy of AODEF gene in asparagus genome. Northern blot analysis showed that this gene was specifically expressed in flower buds and not in vegetative tissues. In situ hybridization showed that during early hermaphrodite stages, AODEF gene was expressed in the inner tepal and stamen whorls (whorls 2 and 3, respectively), but not in the outer tepals (whorl 1), in both male and female flowers. In late unisexual developmental stages, the expression of AODEF gene was still detected in the inner tepals and stamens of male flowers, but the expression was reduced in whorls 2 and 3 of female flowers. Our results suggest that AODEF gene is probably not involved in tepal development in asparagus and that the expression of AODEF gene is probably controlled directly or indirectly by sex determination gene in the late developmental stages.

[A case of multiple liver metastases from sigmoid colon cancer effectively treated by hepatic intra-arterial administration of levoforinate and 5-fluorouracil].

A 62-year-old female patient, who was diagnosed with sigmoid colon cancer with multiple liver metastases, was admitted to our hospital. She underwent sigmoidectomy with D3 lymph node dissection on January 31, 2000. In addition to that, she received hepatic intra-arterial infusion of levoforinate (l-LV) 250 mg and 5-fluorouracil (5-FU) 500 mg for combined multiple hepatic metastases starting on postoperative day 14, and these medications were administered over 48 hours once weekly by infuser pump. The tumor diminished by 59% 2 months after the start of administration and further diminished at 4 months. PR was achieved. Cancer metastasis to the cerebellum and metastasis to the lung were detected at month 9 and month 11, respectively, but the liver metastatic tumor continued to diminish in size, ultimately becoming undetectable by CT scan at month 10. Surgery and radiotherapy were performed for the cerebellar metastasis, and intravenous administration of a combination of l-LV and 5-FU was performed systemically for the pulmonary metastatic tumor. At present, the patient receives regular outpatient treatment continuously. To our knowledge, there has been no report on the combination therapy with l-LV and 5-FU through the hepatic artery. Since good antitumor efficacy was demonstrated in the present patient, this case is described in this report together with four other cases of hepatic metastasis from colorectal cancer.

Movement-related magnetic fields to tongue protrusion.

Movement-related magnetic fields (MRFs) associated with tongue protrusion were measured in five normal subjects using a helmet-shaped magnetoencephalography system. Bihemispherical two-dipolar patterns appeared from approximately -2000 or -1000 to 0 ms to the trigger signal indicating when protrusion of the tongue tip reached the frontal part of the palate. Equivalent current dipoles (ECDs) for the MRFs were localized on the central sulcus, 14.4 +/- 6.1 mm inferior (P < 0.0001) and 7.6 +/- 6.9 mm anterior (P < 0.01) to the ECD for the N20m in the somatosensory evoked fields for median nerve stimuli. The ECD orientations of MRFs were anterior and perpendicular to the central sulcus. These results correspond to the movement-related potentials for tongue protrusion previously recorded from subdural electrodes in patients with epilepsy. Magnetoencephalography can be applied to analyze cortical functions related to tongue movement with high resolution in time and space in normal subjects.

Judging semantic and episodic incongruity: a magnetoencephalographic study.

Evoked magnetic fields over the entire head were measured during a semantic judgment task, in which conditions of the pre-test learning session were manipulated. Subjects learnt related and unrelated category-noun pairs, and were then asked to judge the relationship between category and noun. Unrelated pairs evoked activation around 400 ms in the left temporal area. In addition, newly presented related pairs, of which the categories were used to learn unrelated pairs, also evoked similar activities. Our findings suggest that these activities are not only related to the semantic incongruity between a pair of words as in previous studies, but also to the episodic incongruity between the learning and measurement sessions.

Neuromagnetic localization of N15, the initial cortical response to lip stimulus.

The initial cortical response of the trigeminal somatosensory evoked magnetic fields was measured for electrical stimulation of the lower lip in eleven subjects. The stimulus frequency was 0.7 Hz and stimulus intensity was nine times sensory threshold. The initial contralateral response was detected in 20 hemispheres at a latency of 14.6+/-1.3 ms and was named N15m. The equivalent current dipole of N15m was localized at the posterior bank of the central sulcus with anterior-superior orientation, and inferior to the dipole of N20m for median nerve stimulation.

Somatosensory evoked fields in comatose survivors after severe traumatic brain injury.

OBJECTIVE: To evaluate the cortical function quantitatively in patients in the chronic phase of severe traumatic brain injury. METHODS: Thirteen patients with severe traumatic brain injury due to traffic accident followed by persistent consciousness disturbance and disability were studied. Somatosensory evoked magnetic fields (SEFs) for unilateral median nerve stimulation were measured using a whole-head magnetoencephalography system. The latency and electrical current dipole (ECD) moment for the N20m, P30m, N45m and P60m components were calculated and compared with those of 14 age-matched healthy adults. RESULTS: The peak latency of N20m was longer (P<0.05) and those of P30m and N45m were shorter (P<0.01) in the patients than in normal adults. The ECD moment of N20m and P30m was smaller and that of N45m and P60m was larger in the patients than in normal adults (P<0.01). CONCLUSIONS: These results can be explained by the hypothesis that diffuse brain injury induces decreased and delayed input of the somatosensory afferent and compensational amplification of the response in the primary somatosensory cortex. Middle-latency SEFs may be applicable as a cortical functional measure for patients with severe traumatic brain injury.

Middle and long latency peak sources in auditory evoked magnetic fields for tone bursts in humans.

The relative position of the P50m and the N100m sources of the auditory evoked magnetic field remains unclear. Magnetoencephalography was performed in 24 normal subjects. Contralateral P50m to left and right ear stimulus was observed in 21 and 19hemispheres, respectively. Ipsilateral P50m to left and right ear stimulus was observed in 17 and 16hemispheres, respectively. N100m was observed in all subjects for all stimuli. Relative position of the equivalent current dipole of the P50m was 1.0+/-7.6 (mean+/-SD) mm posterior, 2.0+/-5.8mm inferior and 1.8+/-8.0mm medial to the N100m dipole position considering all observations. We suggest that the P50m and N100m sources are colocated in an extended area of the cortex.

Marked therapeutic effect of dimyristoylphosphatidylcholine liposomes on carcinoma mice model in vivo.

Significantly prolonged survival rate was obtained for the first time using carcinoma mice models after the administration of single-component liposomes of dimyristoylphosphatidylcholine (DMPC) without any drug. An increase in lymphocytes under optical microscope was observed without any increase in the neutrophils count, suggesting that the DMPC liposomes might inhibit the tumor growth as well as increase in lymphocytes in vivo.

[A patient with multiple pulmonary metastases from colonic cancer who survived for 5 years by effectual administration of 5'-DFUR].

The patient was a 69-year-old woman who had been diagnosed with a bowel obstruction due to colonic cancer, with simultaneous multiple pulmonary metastases. The primary lesion was resected and 5'-DFUR was administered for 2 years at an out-patient clinic. During those 2 years, there was no change in CEA value and the pulmonary lesions were fading on the roentogenograms. It then became doubtful whether the pulmonary shadows were real metastases or not, and 5'-DFUR administration was discontinued. After stopping the medication, her CEA value rose and the tumor shadows increased in intensity. 5'-DFUR was therefore re-administrated and her CEA value declined. Afterwards, a re-elevation in CEA value was seen, and low-dose FP therapy was added on an out-patient basis. Anti-cancer chemotherapy of 5'-DFUR (oral) and low-dose FP (i.v.) was contributed to her 5-year survival.

A short history of MADS-box genes in plants.

Evolutionary developmental genetics (evodevotics) is a novel scientific endeavor which assumes that changes in developmental control genes are a major aspect of evolutionary changes in morphology. Understanding the phylogeny of developmental control genes may thus help us to understand the evolution of plant and animal form. The principles of evodevotics are exemplified by outlining the role of MADS-box genes in the evolution of plant reproductive structures. In extant eudicotyledonous flowering plants, MADS-box genes act as homeotic selector genes determining floral organ identity and as floral meristem identity genes. By reviewing current knowledge about MADS-box genes in ferns, gymnosperms and different types of angiosperms, we demonstrate that the phylogeny of MADS-box genes was strongly correlated with the origin and evolution of plant reproductive structures such as ovules and flowers. It seems likely, therefore, that changes in MADS-box gene structure, expression and function have been a major cause for innovations in reproductive development during land plant evolution, such as seed, flower and fruit formation.

[Home anti-cancer therapy with a venous port].

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.

Automatic auditory processing and event-related brain potentials in persons with mental retardation.

Measuring event-related brain potentials, this study examined automatic auditory processing in adults with and without mental retardation. Using an auditory oddball paradigm under an inattentive condition, we anticipated that an enhanced negative potential would be followed by a relatively small positive potential. The former was considered as the mismatch negativity and the latter as the P3a. Retarded adults (1 woman, 6 men, defined as a range of moderate to profound retardation) and 8 nonretarded (2 women, 6 men) adults participated. The mismatch negativity showed smaller amplitudes and greater latencies for retarded persons than those for nonretarded adults, whereas the P3a for the groups was comparable. The results may suggest malfunction of automatic auditory change-detection of the brain in mentally retarded persons.