The advanced lung cancer inflammation index predicts outcomes in patients with Crohn's disease after surgical resection.

AIM: Precise biomarkers for predicting prognosis could help to identify high-risk Crohn's disease (CD) patients to facilitate better follow-up during the postoperative course. In this study, the primary aim is the identification of the most reliable nutrition marker that predicts surgical relapse in CD patients. METHOD: We first evaluated the predictive value of various nutrition markers for postoperative surgical relapse in CD patients and identified the advanced lung cancer inflammation index (ALI) as a promising biomarker. Then, we assessed the clinical significance of preoperative ALI in CD patients using two cohorts. RESULTS: Preoperative ALI showed the highest correlation with reoperation rate compared with other nutritional parameters in CD patients receiving surgical resection (sensitivity 53%, specificity 86%, area under the curve 0.71). Lower levels of preoperative ALI were significantly correlated with the presence of perianal disease. A lower level of preoperative ALI was an independent prognostic factor for reoperation rate after an intestinal resection (hazard ratio 3.37, 95% CI 1.38-10.12, P = 0.006), and the prognostic impact of preoperative ALI was successfully validated in an independent cohort using the same cut-off value. CONCLUSION: Preoperative ALI might be useful for postoperative management of CD patients.

CCAT1 and CCAT2 long noncoding RNAs, located within the 8q.24.21 'gene desert', serve as important prognostic biomarkers in colorectal cancer.

BACKGROUND: 8q24.21 is a frequently amplified genomic region in colorectal cancer (CRC). This region is often referred to as a 'gene desert' due to lack of any important protein-coding genes, highlighting the potential role of noncoding RNAs, including long noncoding RNAs (lncRNAs) located around the proto-oncogene MYC. In this study, we have firstly evaluated the clinical significance of altered expression of lncRNAs mapped to this genomic locus in CRC. PATIENTS AND METHODS: A total of 300 tissues, including 280 CRC and 20 adjacent normal mucosa specimens were evaluated for the expression of 12 lncRNAs using qRT-PCR assays. We analyzed the associations between lncRNA expression and various clinicopathological features, as well as with recurrence free survival (RFS) and overall survival (OS) in two independent cohorts. RESULTS: The expression of CCAT1, CCAT1-L, CCAT2, PVT1, and CASC19 were elevated in cancer tissues (P = 0.039, <0.001, 0.018, <0.001, 0.002, respectively). Among these, high expression of CCAT1 and CCAT2 was significantly associated with poor RFS (P = 0.049 and 0.022, respectively) and OS (P = 0.028 and 0.015, respectively). These results were validated in an independent patient cohort, in which combined expression of CCAT1 and CCAT2 expression was significantly associated with a poor RFS (HR:2.60, 95% confidence interval [CI]: 1.04-6.06, P = 0.042) and a poor OS (HR:8.38, 95%CI: 2.68-37.0, P < 0.001). We established a RFS prediction model which revealed that combined expression of CCAT1, CCAT2, and carcinoembryonic antigen was a significant determinant for efficiently predicting RFS in stage II (P = 0.034) and stage III (P = 0.001) CRC patients. CONCLUSIONS: Several lncRNAs located in 8q24.21 locus are highly over-expressed in CRC. High expression of CCAT1 and CCAT2 significantly associates with poor RFS and OS. The expression of these two lncRNAs independently, or in combination, serves as important prognostic biomarkers in CRC.

Randomized clinical trial of 24 versus 72 h antimicrobial prophylaxis in patients undergoing open total gastrectomy for gastric cancer.

BACKGROUND: Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy. METHODS: An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of ß-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection. RESULTS: A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference -2·2 (90 per cent c.i. -6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group. CONCLUSION: Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 ( http://www.umin.ac.jp).

Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer.

BACKGROUND: Circulating microRNAs (miRNAs) are attracting major interest as potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients. PATIENTS AND METHODS: Comprehensive miRNA array analysis was carried out using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma, and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects. RESULTS: Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly up-regulated in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum miR-1290 levels could robustly distinguish adenoma [area under the curve (AUC) = 0.718] and CRC patients (AUC = 0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor [hazard ratio (HR) = 4.51; 95% confidence interval (CI) = 1.23-23.69; P = 0.0096] and an independent predictor for tumor recurrence (hazard ratio = 3.92; 95% confidence interval = 1.11-25.14; P = 0.032) in CRC. CONCLUSIONS: Serum miR-1290 is a novel biomarker for early detection, recurrence, and prognosis in CRC.

The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC.

BACKGROUND: The MYC oncogene has long been established as a central driver in many types of human cancers including colorectal cancer. However, the realization of MYC-targeting therapies remains elusive; as a result, synthetic lethal therapeutic approaches are alternatively being explored. A synthetic lethal therapeutic approach aims to kill MYC-driven tumors by targeting a certain co-regulator on the MYC pathway. PATIENTS AND METHODS: We analyzed copy number and expression profiles from 130 colorectal cancer tumors together with publicly available datasets to identify co-regulators on the MYC pathway. Candidates were functionally tested by in vitro assays using colorectal cancer and normal fibroblast cell lines. Additionally, survival analyses were carried out on another 159 colorectal cancer patients and public datasets. RESULTS: Our in silico screening identified two MYC co-regulator candidates, AURKA and TPX2, which are interacting mitotic regulators located on chromosome 20q. We found the two candidates showed frequent co-amplification with the MYC locus while expression levels of MYC and the two genes were positively correlated with those of MYC downstream target genes across multiple cancer types. In vitro, the aberrant expression of MYC, AURKA and TPX2 resulted in more aggressive anchorage-independent growth in normal fibroblast cells. Furthermore, knockdown of AURKA or TPX2, or treatment with an AURKA-specific inhibitor effectively suppressed the proliferation of MYC-expressing colorectal cancer cells. Additionally, combined high expression of MYC, AURKA and TPX2 proved to be a poor prognostic indicator of colorectal cancer patient survival. CONCLUSIONS: Through bioinformatic analyses and experiments, we proposed TPX2 and AURKA as novel co-regulators on the MYC pathway. Inhibiting the AURKA/TPX2 axis would be a novel synthetic lethal therapeutic approach for MYC-driven cancers.

Tropomyosin-related receptor kinase B at the invasive front and tumour cell dedifferentiation in gastric cancer.

BACKGROUND: Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding. METHODS: Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections. RESULTS: Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26-3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation. CONCLUSIONS: Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.

Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer.

BACKGROUND: Brain-derived neutrophic factor (BDNF) is a member of the neutrophin family that is known to activate the high-affinity tropomyosin-related receptor kinase B (TrkB). This study aimed to clarify the clinical and biological significance of the BDNF/TrkB pathway in gastric cancer. METHODS: We analysed BDNF and TrkB expression in gastric cancer samples by real-time reverse transcription PCR and immunohistochemistry. To investigate the biological role of BDNF/TrkB axis, recombinant human BDNF (rhBDNF) and the Trk antagonist K252a were used for in vitro and in vivo analysis. RESULTS: The BDNF expression at the invasive front of primary tumours was significantly elevated compared with that in the tumour core and adjacent normal mucosa. Increased BDNF expression at the invasive front was significantly correlated with factors reflecting disease progression, and poor prognosis. Increased co-expression of the BDNF/TrkB axis was significantly correlated with poor prognosis. Gastric cancer cells expressed BDNF, and administration of rhBDNF promoted proliferation, migration, invasion, and inhibition of anoikis. These effects were generally inhibited by K252a. In an in vivo assay, BDNF(+)/TrkB(+) gastric cancer cells injected into nude mice established peritoneal dissemination, whereas K252a inhibited tumour growth. CONCLUSION: The BDNF/TrkB pathway might be deeply involved in gastric cancer disease progression.

Discrimination of Frailty Phenotype by KinectTM-Based Stepping Parameters.

Background: Frailty increases the risk of falling, hospitalization, and premature death, necessitating practical early-detection tools. Objectives: To examine the discriminative ability of KinectTM-based stepping parameters for identifying frailty phenotype. Design: Population-based cross-sectional study. Setting: Eighteen neighborhoods near Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi, Tokyo, Japan. Participants: In total, 563 community-dwelling older adults aged ≥75 years without mobility limitations, neurological disease, or dementia were included. Measurements: Step number (SN) and knee total movement distance (KMD) during a 20-s stepping test were evaluated using the KinectTM infrared depth sensor. Results: The number (%) of participants with frailty were 51 (9.1). The area under the receiver operating characteristic curves (95% confidence interval) of a parameter consisting of SN and KMD for frailty was 0.72 (0.64, 0.79). Conclusions: Stepping parameters evaluated using KinectTM provided acceptable ability in identifying frailty phenotype, making it a practical screening tool in primary care and home settings.

Macrophage migration inhibitory factor and DJ-1 in gastric cancer: differences between high-incidence and low-incidence areas.

BACKGROUND: There is a need for sensitive and specific blood-borne markers for the detection of gastric cancer. Raised serum macrophage inhibitory factor (MIF) levels have been proposed as a marker for gastric cancer diagnosis but, to date, studies have only encompassed patients from high-incidence areas. METHODS: We have compared the serum concentration of MIF in a large cohort of UK and Japanese gastric cancer patients, together with appropriate control subjects (age and gender matched). Carcinoembryonic antigen and H. pylori IgG were also measured, as was DJ-1, a novel candidate protein biomarker identified by analysis of gastric cancer cell line secretomes. RESULTS: Marked elevations of the serum concentration of MIF and DJ-1 were seen in Japanese patients with gastric cancer compared with Japanese controls, a trend not seen in the UK cohort. These results could not be accounted for by differences in age, disease stage or H. pylori status. CONCLUSION: In regions of high, but not low incidence of gastric cancer, both MIF and DJ-1 have elevated serum concentrations in gastric cancer patients, compared with controls. This suggests that differing mechanisms of disease pathogenesis may be at play in high- and low-incidence regions.

Loss of tumoral expression of soluble IL-6 receptor is associated with disease progression in colorectal cancer.

BACKGROUND: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients. METHODS: We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis. RESULTS: Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio <1.0 was significantly associated with factors reflecting disease progression, and was an independent prognostic factor not only in all the patients in this study, but also in the patients with curative intent. Colon cancer cell lines produced sIL-6R in vitro, and the production of sIL-6R in cancer cell lines was stimulated by cytokine stimulation. Immunohistochemistry revealed that loss of tumour expression of sIL-6R was significantly inversely correlated with intense IL-6 expression in the cytoplasm of cancer cells. In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression. CONCLUSION: Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression.

Identification of macrophage migration inhibitory factor and human neutrophil peptides 1-3 as potential biomarkers for gastric cancer.

BACKGROUND: Proteomic methods have the potential to meet the urgent need for better cancer biomarkers. We have used a range of proteomic analyses of serum and tissue from gastric cancer patients and relevant controls to discover biomarkers for gastric cancer. METHODS: Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI) and antibody arrays were used to compare protein expression in 21 pairs of gastric cancer tissue and adjacent normal mucosa and serum from 51 gastric cancer patients and 29 patients with benign gastric diseases. Expression differences were confirmed by enzyme-linked immunosorbent assay. RESULTS: Tissue analysis shows human neutrophil peptides 1-3 (HNPs 1-3) elevated 10-fold (P=0.001) in gastric cancer relative to adjacent normal mucosa. Macrophage migration inhibitory factor (MIF) was increased five-fold (P=1.84 x 10(-7)) in the serum of gastric cancer patients relative to individuals with benign gastric disease. The large increase in MIF concentration in serum gives an area under the receiver operating characteristic curve of 0.85. CONCLUSIONS: Proteomic analyses of serum and tissue indicate that HNPs 1-3 and MIF have potential as biomarkers for gastric cancer. In particular MIF may be useful, either alone or in combination with other markers, for diagnosing and monitoring gastric cancer.

[Release of gamma-aminobutyric acid from cat colon].

The release of gamma-aminobutyric acid was confirmed in isolated cat colon loaded with tritiated gamma-aminobutyric acid. Thirty to 180 minutes after loading the spontaneous efflux of tritium appeared to fit a single exponential curve with an efflux rate coefficient of 0.002 per minute. Electrical stimulation produced frequency-dependent increases in the tritium efflux and in the contractions. Even 120 minutes later over 91 percent of the total radioactivity in the superfusates was attributable to tritiated gamma-aminobutyric acid. The acid release and the contractions induced by electrical transmural stimulation were inhibited by tetrodotoxin and by a calcium-free medium. Release of the acid was not significant during contractions elicited by nicotine and acetylcholine. These findings indicate that gamma-aminobutyric acid is released from the terminals of neurons in the myenteric plexus of the colon.

X-ray Detection of the Period-Four Cycling of the Manganese Cluster in Photosynthetic Water Oxidizing Enzyme.

X-ray absorption near-edge structure spectra of the manganese (Mn) cluster in physiologically native intermediate states of photosynthetic water oxidation induced by short laser flash were measured with a compact heat-insulated chamber equipped with an x-ray detector near the sample surface. The half-height energy of the Mn Kedge showed a period-four oscillation dependent on cycling of the Joliot-Kok's oxygen clock. The flash number-dependent shift in the Mn K-edge suggests that the Mn cluster is oxidized by one electron upon the S(0)-to-S(1), S(1)-to-S(2), and S(2)-to-S(3) transitions and then reduced upon the S(3)-to-S(0) transition that releases molecular oxygen.

Duodenogastric reflux induced by endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) may cause excessive duodenogastric reflux (DGR) in a similar manner to distal gastrectomy, particularly after antral resections. We aimed to examine the occurrence of DGR after ESD. PATIENTS AND METHODS: Patients with gastric neoplasm for whom ESD was indicated were categorized according to lesion site: the antral group (lower [L] stomach, n = 46) and the nonantral group (upper or middle [U or M] stomach, n = 49). Endoscopy was performed before ESD, the day after ESD, and 3 months after ESD, and the fasting bile acid concentration (BAC) in the gastric juice was analyzed. RESULTS: BAC values showed significant interaction between time point and group, although this association differed in the antral and nonantral groups. BACs on the day after ESD were higher in the antral group than in the nonantral group, but not the pre-ESD and 3 months post-ESD levels. In the antral group only, fasting BACs increased significantly the day after ESD and decreased to baseline levels 3 months post-ESD. There was also a correlation between BAC and lesion location in the antral subgroups, with significantly higher BACs found the day after ESD in patients with lesser curvature lesions. CONCLUSIONS: ESD of lesions in the antral lesser curvature may lead to a transient early increase in DGR. However, ESD does not result in long-term DGR, a factor that is known to increase the risk of carcinogenesis following gastrectomy.

Development of Simple, Objective Chair-Standing Assessment of Physical Function in Older Individuals Using a KinectTM Sensor.

BACKGROUND: With increasing interest in addressing quality of life of older individuals, tests such as the Functional Independence Measure (FIM) are widely used measures of infirmity and burden of care. However, these scales are largely qualitative and especially problematic when assessing movement-based tasks. While effective, reliable analysis of human movement is technically complicated and expensive; an infrared depth sensor is potentially a low-cost, portable devise which may provide a quantitative aspect to clinical testing. OBJECTIVE: to assess the utility of the KinectTM sensor in providing an objective evaluation of human movement using an oft measured ADL (chair stand). DESIGN: Cross-sectional study. SETTING: Community, geriatric day-care center in Japan. PARTICIPANTS: Men (n=136) and women (n=266) between 50 and 93 years of age, consisting of healthy (HE; n=312) and physically frail (FR; n= 90) individuals. MEASUREMENTS: Subjects completed two trials of the chair stand, conducted without assistance. Trials were timed and recorded with KinectTM v2. Coronal plane angle (CPA) was determined by a line transecting the shoulder-center and waist relative to the vertical axis and was used to assess quality of the chair stand movement pattern. RESULTS: Age, height, and body mass were not different between groups. CPA was significantly greater in FR (29.3 ± 8.3°) than HE (19.5 ± 6.5°). CPA and age were significantly related (r=0.148, p<0.01). An optimal threshold for CPA identifying frailty was determined by a receiver-operator characteristic curve with a CPA of 23.1° providing the greatest combination of sensitivity (79%) and specificity (73%). CONCLUSION: During the chair stand, frail older adults adopted a forward lean position (increased CPA) compared to healthy older adults. This compensatory posture appears to facilitate torso rotation while reducing lower-limb muscular effort during standing. As such, CPA serves as an indicator of reduced lower-body function in older, frail adults.

Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy.

AIMS: HsMAD2 and BubR1 are crucial components of a functional mitotic checkpoint. Recently, impaired mitotic checkpoints or decreased expression of mitotic checkpoint genes have been associated with sensitivity to certain anticancer drugs. The current study aimed to evaluate the association of hsMAD2 and BubR1 with sensitivity to various anticancer drugs in oesophageal squamous cell carcinoma (ESCC) cell lines. We also investigated responses to 5-fluorouracil and cisplatin-based radiochemotherapy in ESCC patients. MATERIALS AND METHODS: HsMAD2 and BubR1 mRNA levels in six ESCC cell lines and 21 ESCC patients were determined by real-time reverse transcription polymerase chain reaction. Responses to 5-fluorouracil, cisplatin, paclitaxel and docetaxel in human oesophageal cancer cell lines, TE1 and TE2, were evaluated by WST-8 colorimetric assay. HsMAD2 and BubR1 levels were compared with clinicopathological characteristics and responses to radiochemotherapy. RESULTS: TE1, with lower hsMAD2 and BubR1, showed greater sensitivity to paclitaxel and docetaxel compared with TE2, with higher hsMAD2 and BubR1. HsMAD2 and BubR1 were significantly higher in cancer tissue than in adjacent normal tissue (P < 0.01). Tumoral hsMAD2 and BubR1 were significantly decreased after radiochemotherapy (P < 0.01). There was a significantly strong positive association between hsMAD2 and BubR1 in cancer tissue (P < 0.01). Neither clinicopathological characteristics nor the response to radiochemotherapy was associated with hsMAD2 or BubR1. CONCLUSION: The mitotic checkpoint genes, hsMAD2 and BubR1, were co-ordinately overexpressed in ESCC. Low hsMAD2 and BubR1 was associated with sensitivity to paclitaxel and docetaxel. Decreased hsMAD2 and BubR1 after radiochemotherapy may indicate the potential efficacy of taxanes as second-line chemotherapy for recurrent and metastatic oesophageal cancer.

Schedule-dependent cytotoxicity of 5-fluorouracil and irinotecan in p53 mutant human colon cancer.

IFL [irinotecan (CPT-11), 5-fluorouracil (5-FU), and folinic acid] is one of the treatments for metastatic colorectal cancer. We evaluated cytotoxic effects of a sequentially administered a combination of 5-FU with CPT-11 in human p53 mutant colon cancer. Sequential combination of 5-FU and CPT-11 in human colon cancer SW480 cells using a WST-8 colorimetric assay was studied. Cytotoxicity and cell cycle distribution for each drug were evaluated using an apoptosis assay and flow cytometry. Potential mechanisms of sequence-dependent cytotoxic effects were investigated using microarrays. Cytotoxicity of 5-FU (10, 100, 1000 microM) combined with subsequent use of CPT-11 (1 microM) was significantly greater than the reverse sequence of CPT-11 followed by 5-FU (p < 0.05). Following 24 hrs treatment with 5-FU (0.1-100 microM), no significant apoptosis was observed. In contrast, apoptosis was significantly induced after 24 hrs treatment with CPT-11 (1 and 10 microM). Flow cytometric analysis showed no significant difference in cell cycle distribution between different drug concentrations. We demonstrated up-regulation of 85 genes and down-regulation of 21 genes correlating with sequence-dependent cytotoxicities of 5-FU and CPT-11. The superiority of 5-FU-CPT-11 sequence was proven for p53 mutant colon cancer, SW480. Treatment with 5-FU followed by CPT-11 administration may be the optimal sequence for IFL treatment of metastatic colon cancers.

Evaluation and treatment for spinal cord tethering in patients with anorectal malformations.

BACKGROUND: It has recently been recognized that there is a close relationship between spinal cord tethering (SCT) and congenital anorectal malformation (ARM). PATIENTS AND METHODS: We evaluated spinal MRI examinations of 28 patients with ARM (14 boys and 14 girls) aged 5 months to 9 years. All patients diagnosed with SCT subsequently underwent operation. Patients were divided into high and low type ARM groups. We reviewed the relationship between SCT and ARM, and evaluated the untethering surgery. RESULTS: We evaluated 14 boys (high, 9; low, 5) and 14 girls (high, 4; low, 10). Of these 28 patients, 13 had SCT on MRI. Five out of 13 patients with high type ARM and 8 out of 15 patients with low type ARM had SCT. Seven out of 10 girls with low type ARM had SCT. Ten of these 13 patients with SCT experienced bowel/urological/orthopedic symptoms. SCT symptoms progressed prior to operation in the 2 patients who underwent untethering surgery a few years after their initial MRI examination. Postoperatively, orthopedic symptoms disappeared completely in all patients, but other symptoms did not. CONCLUSIONS: Based on the results of this study, we recommend routine MRI examination of patients with ARM and early untethering surgery in cases with SCT.

The TINS Lecture. The parietal association cortex in depth perception and visual control of hand action.

Recent neurophysiological studies in alert monkeys have revealed that the parietal association cortex plays a crucial role in depth perception and visually guided hand movement. The following five classes of parietal neurons covering various aspects of these functions have been identified: (1) depth-selective visual-fixation (VF) neurons of the inferior parietal lobule (IPL), representing egocentric distance; (2) depth-movement sensitive (DMS) neurons of V5A and the ventral intraparietal (VIP) area representing direction of linear movement in 3-D space; (3) depth-rotation-sensitive (RS) neurons of V5A and the posterior parietal (PP) area representing direction of rotary movement in space; (4) visually responsive manipulation-related neurons (visual-dominant or visual-and-motor type) of the anterior intraparietal (AIP) area, representing 3-D shape or orientation (or both) of objects for manipulation; and (5) axis-orientation-selective (AOS) and surface-orientation-selective (SOS) neurons in the caudal intraparietal sulcus (cIPS) sensitive to binocular disparity and representing the 3-D orientation of the longitudinal axes and flat surfaces, respectively. Some AOS and SOS neurons are selective in both orientation and shape. Thus the dorsal visual pathway is divided into at least two subsystems, V5A, PP and VIP areas for motion vision and V6, LIP and cIPS areas for coding position and 3-D features. The cIPS sends the signals of 3-D features of objects to the AIP area, which is reciprocally connected to the ventral premotor (F5) area and plays an essential role in matching hand orientation and shaping with 3-D objects for manipulation.

Organization of space perception: neural representation of three-dimensional space in the posterior parietal cortex.

The representation of perceptual space in the posterior parietal cortex can be divided into at least two categories: far space, beyond arm's reach, and peripersonal space, within arm's reach. These are encoded by different groups of neurons that are closely related to the control of gaze and the guidance of arm and hand movement, respectively.