Investigating endophenotype of endogeneous psychotic disorders]

Accumulated evidence from a number of previous structural MRI studies have revealed 1) the existence of abnormalities even at the brain structural level in subjects at an early stage of endogeneous psychotic illness, including schizophrenia and bipolar disorder, and 2) the existence of similar brain structural abnormalities to the patients even in individuals at high-risk of endogeneous psychotic illness. Recently, an increasing number of studies have investigated the associations between the functional polymorphism of candidate genes for susceptibility to schizophrenia and regional brain volume, a highly heritable trait marker, to uncover the linkage between the candidate genes and endophenotype of schizophrenia. Firstly, this review article overviewed recent literature examining the relationship between the candidate genes for susceptibility to schizophrenia and indices obtained from neuroimaging modalities. In contrast, a relatively limited number of previous studies examined associations between candidate genes for susceptibility to bipolar disorder and regional brain volume, although the high heritability of bipolar disorder has been reported as comparable to that of schizophrenia. Then, we discussed the possibility of endophenotyping of bipolar disorder and introduced our preliminary study. Finally, methodological considerations and future directions of endophenotyping of endogeneous psychosis were suggested.     

Anaplastic Ependymoma of the Spinal Cord in Childhood A Case Report

We report a 6-year-old girl with anaplastic ependymoma probably originating in the region of the conus medullaris and probably spreading retrogradely to the region of the interventricular foramen (Monro) through the cere-brospinal fluid (CSF). Since ependymoma of the spinal cord rarely occurs in children, and retrograde spreading is extremely rare, the histological features and mechanism of metastasis of the tumor are discussed.     

WS009 A and B, new endothelin receptor antagonists isolated from Streptomyces sp. no. 89009. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS009 A and B novel endothelin receptor antagonists, have been isolated from the fermentation broth of Streptomyces sp. No. 89009. These antagonists were purified from the culture filtrate followed by Diaion SP-207, DEAE Toyopearl column chromatography and HPLC. WS009 A and B showed selective activity in an endothelin receptor binding assay with IC50 of 5.8 x 10(-6) M and 6.7 x 10(-7) M, respectively. On the basis of spectroscopic and chemical evidence, the structures of WS009 A and B have been established as 1 and 3, and are highly hydroxylated benz[a]anthraquinone chromophores.     

WS-7528, a new isoflavanone with estrogen activity isolated from Streptomyces sp. No. 7528. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities

WS-7528, produced by Streptomyces sp. No. 7528, was extracted from cultured broth, purified by solvent extraction followed by chromatography on silica gel and then isolated as pale yellow powder (C16H14O5, mp 95-98 degrees C). WS-7528 inhibited estrogen binding to its receptor protein in rat uterine cytosol. The IC50 value of WS-7528 for partially purified rat uterine cytosol receptor was 5.7 x 10(-8) M. This compound was found to induce the growth of the estrogen dependent cell line MCF-7. WS-7528 was tested orally and subcutaneously in immature rats to confirm its effect on the growth of the uterus. WS-7528 has also weak anti-inflammatory activity on the carrageenin paw edema of the rat model.     

Application of a Machine Learning Algorithm for Structural Brain Images in Chronic Schizophrenia to Earlier Clinical Stages of Psychosis and Autism Spectrum Disorder: A Multiprotocol Imaging Dataset Study

Background and HypothesisMachine learning approaches using structural magnetic resonance imaging (MRI) can be informative for disease classification; however, their applicability to earlier clinical stages of psychosis and other disease spectra is unknown. We evaluated whether a model differentiating patients with chronic schizophrenia (ChSZ) from healthy controls (HCs) could be applied to earlier clinical stages such as first-episode psychosis (FEP), ultra-high risk for psychosis (UHR), and autism spectrum disorders (ASDs).Study DesignTotal 359 T1-weighted MRI scans, including 154 individuals with schizophrenia spectrum (UHR, n = 37; FEP, n = 24; and ChSZ, n = 93), 64 with ASD, and 141 HCs, were obtained using three acquisition protocols. Of these, data regarding ChSZ (n = 75) and HC (n = 101) from two protocols were used to build a classifier (training dataset). The remainder was used to evaluate the classifier (test, independent confirmatory, and independent group datasets). Scanner and protocol effects were diminished using ComBat.Study ResultsThe accuracy of the classifier for the test and independent confirmatory datasets were 75% and 76%, respectively. The bilateral pallidum and inferior frontal gyrus pars triangularis strongly contributed to classifying ChSZ. Schizophrenia spectrum individuals were more likely to be classified as ChSZ compared to ASD (classification rate to ChSZ: UHR, 41%; FEP, 54%; ChSZ, 70%; ASD, 19%; HC, 21%).ConclusionWe built a classifier from multiple protocol structural brain images applicable to independent samples from different clinical stages and spectra. The predictive information of the classifier could be useful for applying neuroimaging techniques to clinical differential diagnosis and predicting disease onset earlier.     

Combined therapy after superselective arterial cisplatin infusion to treat maxillary squamous cell carcinoma

OBJECTIVE: We sought to assess the efficacy of combined therapy after superselective arterial cisplatin infusion (SACI) therapy to treat the maxillary squamous cell carcinoma. STUDY DESIGN: We conducted a retrospective chart review of 50 patients. After completion of two courses of SACI, 25 of the patients were successively treated by concurrent SACI and radiotherapy (AR), while the other 25 patients were treated by surgery with postoperative radiotherapy (ASR). RESULTS: Patients with surgery (ASR) had an 88% local control rate with 75% disease-free survival rate at 60 months by Kaplan-Meier analysis, compared with 62% disease-free survival rate for patients with AR treatment. A particularly good outcome was obtained in T4 cases of the ASR group (n=8) whose 5-year survival rate was 87% and local control rate was 100%. CONCLUSION/SIGNIFICANCE: Combined SACI therapy is very effective for the treatment of maxillary squamous cell carcinomas and contributes to the improving prognoses of patients and organ preservation rates.     

Contribution of color signals to ocular following responses

Ocular following responses (OFRs) are elicited at ultra‐short latencies (< 60 ms) by sudden movements of the visual scene. In this study, we investigated the roles of color signals in OFRs in monkeys. To make physiologically isoluminant sinusoidal color gratings, we estimated the physiologically isoluminant points using OFRs and found that the physiologically isoluminant points were nearly independent of the spatiotemporal frequency of the gratings. We recorded OFRs induced by the motion of physiologically isoluminant color gratings and found that OFRs elicited by the motion of color gratings had different spatiotemporal frequency tuning from those elicited by the motion of luminance gratings. Additionally, OFRs to isoluminant color gratings had smaller peak responses, suggesting that color signals weakly contribute to OFRs compared with luminance signals. OFRs to the motion of stimuli composed of luminance and color signals were also examined. We found that color signals largely contributed to OFRs under low luminance signals regardless of whether color signals moved in the same or opposite direction to luminance signals. These results provide evidence of the multichannel visual computations underlying motor responses. We conclude that, in everyday situations, color information contributes cooperatively with luminance information to the generation of ocular tracking behaviors.     

Changes of fiber type ratio and diameter in rabbit skeletal muscle during limb lengthening

 Changes in the fiber-type ratio and diameter during limb lengthening in 10 adult rabbits were studied using histochemical techniques. Changes in the ratio and diameter of muscle fibers (classified as type 1, 2A, or 2B fibers) in tibialis anterior muscles were examined after 20% gradual distraction of the tibia. There was an increase in the number of type 1 fibers and a decrease in type 2B fibers after tibial lengthening. Moreover, the average diameter of the type 1 fibers increased, whereas that of the type 2B fibers decreased. The diameters of muscle fibers measured immediately after completion of the lengthening showed a tendency to recover to normal levels within 1 month; however, the ratio profile of the muscle fibers changed both immediately and 1 month after lengthening. The above results demonstrate that stretched skeletal muscle adapts differently to bone lengthening according to the type of muscle fibers present, resulting in qualitative changes in the fiber-type profile. Received: February 1, 2002 / accepted: August 26, 2002 Acknowledgments. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan. Offprint requests to: H. Yamazaki, 4-21-2 Kurakuen, Nishi-nomiya 662-0088, Japan     

A comparative study of once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers

A randomized controlled study comparing once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers was carried out in 99 Japanese patients. Endoscopic examinations were performed at the baseline and repeated at 3-week intervals until healing was confirmed. Eighty-two patients fulfilled the evaluation criteria (38 in the morning group and 44 in the bedtime group). In 13 of these patients the antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring. The healing rates were 66% after 3 weeks and 95% after 6 weeks in the morning group, and 57% after 3 weeks and 80% after 6 weeks in the bedtime group. The differences were insignificant between the two groups, but there was a higher healing rate tendency after 6 weeks in the morning group (0.05<P<0.10). Regarding pain subsidence, there were no significant differences between the two groups. Both treatments were significantly superior to the controlgroup in increasing 24 h intragastric pH. The morning regimen was significantly superior to the bedtime regimen in suppression of daytime acidity. On the contrary, the bedtime regimen was significantly superior to the morning regimen in suppression of nocturnal acidity. These findings suggest that suppression of nocturnal acidity is important but not essential to promote duodenal ulcer healing and suppression of daytime acidity is equally important. Thus, once-a-day morning administration of 40 mg famotidine seems to be at least as effective as once-a-day bedtime administration of 40 mg famotidine in treating duodenal ulcers.     

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS: Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS: It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.