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Biomedical subjects

Kei Ito

Publications and source records attributed to Kei Ito.

At least 19 recordsLinked to original sources

Endoscopic biliary drainage for patients with unresectable pancreatic cancer with obstructive jaundice who are to undergo gemcitabine chemotherapy.

AIM: To assess optimum endoscopic biliary drainage (EBD) in cases with unresectable pancreatic cancer in the era of gemcitabine (GEM). METHODS: Thirty patients with unresectable pancreatic cancer, who presented with jaundice and underwent chemotherapy using GEM after EBD were included in this study (GEM group). Fifteen cases with the same clinical manifestation and stage of pancreatic cancer treated with EBD alone were also included as controls. A covered metallic stent (CMS) or a plastic stent (PS) was used for EBD. The mean survival time (MST) in each group, risk factors of survival time, type of stent used and associated survival time, occlusion rate of stent, patency period of stent, and risk factors of stent occlusion were evaluated. RESULTS: MST in the GEM group was longer than that in the control (9.9 mo vs 6.2 mo). In the GEM group, the survival time was not different between those who underwent metallic stenting and those who underwent plastic stenting. Stent occlusion occurred in 60% of the PS group and 7% of the CMS group. The median stent patency in the PS-GEM group and the CMS-GEM group was 5 mo and 7.5 mo, respectively. Use of a PS was the only risk factor of stent occlusion. CONCLUSION: A CMS is recommended in cases presenting with jaundice due to unresectable pancreatic cancer, since the use of a CMS makes it possible to continue chemotherapy using GEM without repetition of stent replacement.

Antimetabolites, Antineoplastic↗

Comprehensive classification of the auditory sensory projections in the brain of the fruit fly Drosophila melanogaster.

We established a comprehensive projection map of the auditory receptor cells (Johnston's organ neurons: JONs) from the antennae to the primary auditory center of the Drosophila brain. We found 477 +/- 24 cell bodies of JONs, which are arranged like a "bottomless bowl" within the auditory organ. The target of the JONs in the brain comprises five spatially segregated zones, each of which is contributed by bundles of JON axons that gradually branch out from the antennal nerve. Four zones are confined in the antennal mechanosensory and motor center, whereas one zone further extends over parts of the ventrolateral protocerebrum and the subesophageal ganglion. Single-cell labeling with the FLP-out technique revealed that most JONs innervate only a single zone, indicating that JONs can be categorized into five groups according to their target zones. Within each zone, JONs innervate various combinations of subareas. We classified these five zones into 19 subareas according to the branching patterns and terminal distributions of single JON axons. The groups of JONs that innervate particular zones or subareas of the primary auditory center have their cell bodies in characteristic locations of the Johnston's organ in the antenna, e.g., in concentric rings or in paired clusters. Such structural organization suggests that each JON group, and hence each zone of the primary auditory center, might sense different aspects of sensory signals.

Animals↗

Roles for Drosophila mushroom body neurons in olfactory learning and memory.

Olfactory learning assays in Drosophila have revealed that distinct brain structures known as mushroom bodies (MBs) are critical for the associative learning and memory of olfactory stimuli. However, the precise roles of the different neurons comprising the MBs are still under debate. The confusion surrounding the roles of the different neurons may be due, in part, to the use of different odors as conditioned stimuli in previous studies. We investigated the requirements for the different MB neurons, specifically the alpha/beta versus the gamma neurons, and whether olfactory learning is supported by different subsets of MB neurons irrespective of the odors used as conditioned stimuli. We expressed the rutabaga (rut)-encoded adenylyl cyclase in either the gamma or alpha/beta neurons and examined the effects on restoring olfactory associative learning and memory of rut mutant flies. We also expressed a temperature-sensitive shibire (shi) transgene in these neuron sets and examined the effects of disrupting synaptic vesicle recycling on Drosophila olfactory learning. Our results indicate that although we did not detect odor-pair-specific learning using GAL4 drivers that primarily express in gamma neurons, expression of the transgenes in a subset of alpha/beta neurons resulted in both odor-pair-specific rescue of the rut defect as well as odor-pair-specific disruption of learning using shi(ts1).

Adenylyl Cyclases↗

Systematic analysis of the visual projection neurons of Drosophila melanogaster. I. Lobula-specific pathways.

In insects, visual information is processed in the optic lobe and conveyed to the central brain. Although neural circuits within the optic lobe have been studied extensively, relatively little is known about the connection between the optic lobe and the central brain. To understand how visual information is read by the neurons of the central brain, and what kind of centrifugal neurons send the control signal from the central brain to the optic lobe, we performed a systematic analysis of the visual projection neurons that connect the optic lobe and the central brain of Drosophila melanogaster. By screening approximately 4,000 GAL4 enhancer-trap strains we identified 44 pathways. The overall morphology and the direction of information of each pathway were investigated by expressing cytoplasmic and presynapsis-targeted fluorescent reporters. A canonical nomenclature system was introduced to describe the area of projection in the central brain. As the first part of a series of articles, we here describe 14 visual projection neurons arising specifically from the lobula. Eight pathways form columnar arborization in the lobula, whereas the remaining six form tangential or tree-like arborization. Eleven are centripetal pathways, among which nine terminate in the ventrolateral protocerebrum. Terminals of each columnar pathway form glomerulus-like structures in different areas of the ventrolateral protocerebrum. The posterior lateral protocerebrum and the optic tubercle were each contributed by a single centripetal pathway. Another pathway connects the lobula on each side of the brain. Two centrifugal pathways convey signals from the posterior lateral protocerebrum to the lobula.

Animals↗

Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis.

Axon pruning is a common phenomenon in neural circuit development. Previous studies demonstrate that the engulfing action of glial cells is essential in this process. The underlying molecular mechanisms, however, remain unknown. We show that draper (drpr) and ced-6, which are essential for the clearance of apoptotic cells in C. elegans, function in the glial engulfment of larval axons during Drosophila metamorphosis. The drpr mutation and glia-specific knockdown of drpr and ced-6 by RNA interference suppress glial engulfment, resulting in the inhibition of axon pruning. drpr and ced-6 interact genetically in the glial action. Disruption of the microtubule cytoskeleton in the axons to be pruned occurs via ecdysone signaling, independent of glial engulfment. These findings suggest that glial cells engulf degenerating axons through drpr and ced-6. We propose that apoptotic cells and degenerating axons of living neurons are removed by a similar molecular mechanism.

Animals↗

Distinct memory traces for two visual features in the Drosophila brain.

The fly Drosophila melanogaster can discriminate and remember visual landmarks. It analyses selected parts of its visual environment according to a small number of pattern parameters such as size, colour or contour orientation, and stores particular parameter values. Like humans, flies recognize patterns independently of the retinal position during acquisition of the pattern (translation invariance). Here we show that the central-most part of the fly brain, the fan-shaped body, contains parts of a network mediating visual pattern recognition. We have identified short-term memory traces of two pattern parameters--elevation in the panorama and contour orientation. These can be localized to two groups of neurons extending branches as parallel, horizontal strata in the fan-shaped body. The central location of this memory store is well suited to mediate translational invariance.

Adenylyl Cyclases↗

Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is an inherited blistering skin disorder caused by mutations in the type VII collagen gene (COL7A1). Therapeutic introduction of COL7A1 into skin cells holds significant promise for the treatment of DEB. The purpose of this study was to establish an efficient retroviral transfer method for COL7A1 into DEB epidermal keratinocytes and dermal fibroblasts, and to determine which gene-transferred cells can most efficiently express collagen VII in the skin. We demonstrated that gene transfer using a combination of G protein of vesicular stomatitis virus-pseudotyped retroviral vector and retronectin introduced COL7A1 into keratinocytes and fibroblasts from a DEB patient with the lack of COL7A1 expression. Real-time polymerase chain reaction analysis of the normal human skin demonstrated that the quantity of COL7A1 expression in the epidermis was significantly higher than that in the dermis. Subsequently, we have produced skin grafts with the gene-transferred or untreated DEB keratinocytes and fibroblasts, and have transplanted them into nude rats. Interestingly, the series of skin graft experiments showed that the gene-transferred fibroblasts supplied higher amount of collagen VII to the new dermal-epidermal junction than the gene-transferred keratinocytes. An ultrastructural study revealed that collagen VII from gene-transferred cells formed proper anchoring fibrils. These results suggest that fibroblasts may be a better gene therapy target of DEB treatment than keratinocytes.

Animals↗

Effects of applying povidone-iodine just before skin closure.

Many surgeons apply povidone-iodine (PVP-I) to the skin around an incision before closing a wound to reduce wound infection rates. However, the effectiveness of this procedure has not been proven. Forty-seven cases of gastric surgery and 60 cases of colorectal surgery performed at Kanto Medical Center between July 2004 and December 2004 were randomly assigned to the group with PVP-I or the group without PVP-I. Wound infection and surgical site infection (SSI) rates were compared between these two groups. Applying PVP-I was effective in eliminating skin contamination, as cultures became negative in all cases after applying PVP-I. However, this study could not demonstrate the reduction of wound infection or SSI in the group with PVP-I, possibly because the number of cases in this study was too small to make a difference. Subcutaneous tissue contamination was considered a more important factor than skin contamination in causing wound infection.

Administration, Topical↗

[Solid-pseudopapillary tumor with an elderly woman, showing an increase in size over a four-year follow-up period: report of a case].

Solid-pseudopapillary tumor (SPT) is considered to be a tumor showing an essentially benign biological behavior based on the results of histological examination of resected specimens and postsurgical follow-up. Little is known regarding the growing speed and pattern, and the process of cystic structure formation of this tumor due to a lack of reports describing its natural history. We herein report a case of SPT showing an increase in size in a four-year follow-up period, which underwent resection thereafter.

Aged, 80 and over↗

[An autopsied case of schizophrenic patient who died from heat stroke].

A male residual schizophrenic out-patient of 65 years old had presented "heat stroke" and died in progressive course of 7 months. His mental condition had been stable and he had kept good drug compliance. In some summer day, he presented high fever and confusion, followed by convulsion. He showed over 40 degrees C high temperature (max 42 degrees C) for about 6 hours. After 10 day's high serum CPK, he gradually presented severe muscle atrophy (proximal dominant), flaccid quadriplegia and brain atrophy (especially in cerebellum). He died from pneumonia. His brain weight was 1,350g. Neuropathological study showed severe loss of Purkinje cell with gliosis. Neurons in dentate nucleus ware entirely lost and a great amount of fatty macrophages were present around the dentate nucleus. Fatty macrophages were observed from cerebellum to red nucleus through superior cerebellar peduncle. These findings have been known as findings of heat stroke. Addition to these findings, this case presented a neuronal loss in the substantita nigra and in the anterior horn of spinal cord and the degeneration of bilateral pyramidal tract. These findings have not been thus far reported, so this case is thought to be the valuable case on considering the variation of neuropathology of "heat stroke".

Aged↗

Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa.

Dystrophic EB (DEB) is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy, and is caused by mutations in the COL7A1 gene encoding type VII collagen. DEB is inherited in either an autosomal dominant (DDEB) or recessive (RDEB) fashion. DDEB basically results from a glycine substitution mutation within the collagenous domain on one COL7A1 allele, while a combination of mutations such as premature stop codon, missense, and splice-site mutations on both alleles causes RDEB. In this study, mutation analysis was performed in 20 distinct Japanese DEB families (16 RDEB and four DDEB). The result demonstrated 30 pathogenic COL7A1 mutations with 16 novel mutations, which included four missense, five nonsense, one deletion, two insertion, one indel, and three splice-site mutations. We confirmed that Japanese COL7A1 mutations were basically family specific, although three mutations, 5818delC, 6573 + 1G > C, and E2857X, were recurrent based on previous reports. Furthermore, the Q2827X mutation found in two unrelated families would be regarded as a candidate recurrent Japanese COL7A1 mutation. The study furthers our understanding of both the clinical and allelic heterogeneity displayed in Japanese DEB patients.

Adult↗

DPP signaling controls development of the lamina glia required for retinal axon targeting in the visual system of Drosophila.

The Drosophila visual system consists of the compound eyes and the optic ganglia in the brain. Among the eight photoreceptor (R) neurons, axons from the R1-R6 neurons stop between two layers of glial cells in the lamina, the most superficial ganglion in the optic lobe. Although it has been suggested that the lamina glia serve as intermediate targets of R axons, little is known about the mechanisms by which these cells develop. We show that DPP signaling plays a key role in this process. dpp is expressed at the margin of the lamina target region, where glial precursors reside. The generation of clones mutant for Medea, the DPP signal transducer, or inhibition of DPP signaling in this region resulted in defects in R neuron projection patterns and in the lamina morphology, which was caused by defects in the differentiation of the lamina glial cells. glial cells missing/glial cells deficient (gcm; also known as glide) is expressed shortly after glia precursors start to differentiate and migrate. Its expression depends on DPP; gcm is reduced or absent in dpp mutants or Medea clones, and ectopic activation of DPP signaling induces ectopic expression of gcm and REPO. In addition, R axon projections and lamina glia development were impaired by the expression of a dominant-negative form of gcm, suggesting that gcm indeed controls the differentiation of lamina glial cells. These results suggest that DPP signaling mediates the maturation of the lamina glia required for the correct R axon projection pattern by controlling the expression of gcm.

Animals↗

Developmentally programmed remodeling of the Drosophila olfactory circuit.

Neural circuits are often remodeled after initial connections are established. The mechanisms by which remodeling occurs, in particular whether and how synaptically connected neurons coordinate their reorganization, are poorly understood. In Drosophila, olfactory projection neurons (PNs) receive input by synapsing with olfactory receptor neurons in the antennal lobe and relay information to the mushroom body (MB) calyx and lateral horn. Here we show that embryonic-born PNs participate in both the larval and adult olfactory circuits. In the larva, these neurons generally innervate a single glomerulus in the antennal lobe and one or two glomerulus-like substructures in the MB calyx. They persist in the adult olfactory circuit and are prespecified by birth order to innervate a subset of glomeruli distinct from larval-born PNs. Developmental studies indicate that these neurons undergo stereotyped pruning of their dendrites and axon terminal branches locally during early metamorphosis. Electron microscopy analysis reveals that these PNs synapse with MB gamma neurons in the larval calyx and that these synaptic profiles are engulfed by glia during early metamorphosis. As with MB gamma neurons, PN pruning requires cell-autonomous reception of the nuclear hormone ecdysone. Thus, these synaptic partners are independently programmed to prune their dendrites and axons.

Animals↗

Clinical study of choledochocele: is it a risk factor for biliary malignancies?

BACKGROUND: We aimed to clarify the clinical characteristics of choledochocele and to evaluate the possibility of choledochocele as a risk factor for biliary malignancies. METHODS: The clinical feature, the configuration of the pancreatobiliary ductal system, coexistent pancreatobiliary lesions, and amylase level in bile in 21 patients with choledochocele were reviewed. The correlation between the configuration, comorbid diseases, and amylase level in the bile was investigated. RESULTS: There was a female predominance, and 57% of the patients showed abdominal pain. Quite a few patients showed elevation of the levels of hepatobiliary enzymes. The configuration of the pancreatobiliary ductal system and choledochocele was classified into two categories: type I, where the choledochocele and pancreatic duct were visualized independently or simultaneously (90.5%); and type II, where the pancreatic duct was visualized after filling of the choledochocele (9.5%). Among coexistent bilio-pancreatic diseases, biliary stone diseases were the most frequent. Biliary malignancy was seen in 3 patients (14.3%). The amylase level in the bile was high in 50% (4/8) of the patients examined. The rate of abnormal elevation of amylase level in the bile in the two types of pancreatobiliary ductal system and choledochocele was 3/7 and 1/1, respectively. CONCLUSIONS: The prevalence of organic abnormal arrangement of the pancreatobiliary ductal system in which the choledochocele serves as a common channel is low. However, there are patients with suspected functional abnormal arrangement of the pancreatobiliary ductal system, who may possibly be a high-risk group for biliary malignancy.

Adult↗

Mode of progression of intraductal papillary-mucinous tumor of the pancreas: analysis of patients with follow-up by EUS.

BACKGROUND: We investigated the mode of progression of intraductal papillary-mucinous neoplasm of the pancreas (IPMN) in patients who underwent follow-up in order to elucidate the characteristics of malignancy and to establish an effective treatment strategy. METHODS: Fifty-one patients with IPMN (branch-duct type, 47; main-duct type, 4) who had undergone follow-up study by endoscopic ultrasonography (EUS) were included (mean follow-up duration, 41.0+/-32.3 months; average number of EUS examinations performed during follow-up, 4.4). Chronological changes in EUS findings and histological findings of resected specimens were evaluated. RESULTS: Of the patients with the branch-duct type, only 2% showed enlargement of the dilated branches. In the main-duct-type group, an increase in size of the main pancreatic duct (MPD) was observed in 75% of the patients. In 14 patients with papillary protrusions, an increase in size and lateral spread was observed in 71% and 43%, respectively. No patients developed invasive cancer. In 15 patients who had thick septum-like structures (TSS), the development of papillary protrusions and that of invasive cancer were observed in 53% and 13%, respectively. Twenty-nine patients who had thin septum-like structures showed no change. Two patients with dense multilocular large cysts and TSS developed invasive cancer without change in the cystic lesions. One patient developed carcinoma with multifocal stromal invasion. CONCLUSIONS: Patients with branch-duct type IPMNs without papillary protrusions or TSS are not immediate candidates for surgery. Those who have small papillary protrusions have a benign course. It is recommended that patients with the large branch-duct type with TSS should undergo surgery. Attention should be paid to the entire pancreas when performing follow-up examinations in patients with branch-duct type IPMN, as invasive ductal adenocarcinoma can develop at a site in the pancreas different from that of the IPMN.

Adenocarcinoma, Mucinous↗

Periampullary tumors: high-spatial-resolution MR imaging and histopathologic findings in ampullary region specimens.

PURPOSE: To prospectively determine the magnetic resonance (MR) signal intensity characteristics of structures of the ampullary region and to assess the potential use of MR imaging in evaluation of the extent of periampullary tumors in resected specimens. MATERIALS AND METHODS: Twenty-five specimens from the ampullary region obtained in four autopsy cases without periampullary tumors and in 21 patients with periampullary tumors were examined with a 1.5-T MR system and a circular surface coil with 5-inch (12.7-cm) diameter. High-spatial-resolution MR images were obtained with field of view of 100 x 100 mm, matrix of 256 x 256 or 512 x 256, and section thickness of 2 mm. MR imaging findings were compared with histopathologic findings. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of high-spatial-resolution MR imaging for assessment of tumor invasion into surrounding tissues were evaluated by two radiologists. RESULTS: T1- and T2-weighted MR images clearly depicted normal structures in the ampullary region that included Oddi muscle, duodenal wall, common bile duct, and pancreas; these findings corresponded well with histologic findings. In 20 (95%) of 21 tumors, high-spatial-resolution MR imaging depicted location and extension of periampullary tumors precisely. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of high-spatial-resolution MR imaging for assessment of tumor invasion into surrounding tissue were 88%, 100%, 96%, 100%, and 94%, respectively. CONCLUSION: In this study, MR imaging correctly depicted location, extension, and origin of tumor. High-spatial-resolution MR imaging has potential for presurgical staging of tumors in this region.

Aged↗