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Biomedical subjects

T Iwanaga

Publications and source records attributed to T Iwanaga.

At least 73 records · Page 4Linked to original sources
PubMed2000

Air leak syndrome as one of the manifestations of bronchiolitis obliterans organizing pneumonia.

A 46-year-old man developed respiratory distress with air leak syndrome (ALS), including pneumothorax, pneumomediastinum, and subcutaneous emphysema. Open lung biopsy was performed and revealed the histopathologic evidence of bronchiolitis obliterans organizing pneumonia (BOOP), which responded well to steroid treatment. As far as we know, this appears to be the first case of BOOP presenting with ALS as one of its major complications.

Biopsy↗
PubMed2000

Diverse roles of K(ATP) channels learned from Kir6.2 genetically engineered mice.

The regulation of insulin secretion from pancreatic beta-cells depends critically on the activities of their plasma membrane ion channels. ATP-sensitive K+ channels (K(ATP) channels) are present in many cells and regulate a variety of cellular functions by coupling cell metabolism with membrane potential. The activity of the K(ATP) channels in pancreatic beta-cells is regulated by changes in the ATP and ADP concentrations (ATP/ADP ratio) caused by glucose metabolism. Thus, the K(ATP) channels are the ATP and ADP sensors in the regulation of glucose-induced insulin secretion. K(ATP) channels are also the target of sulfonylureas, which are widely used in the treatment of type 2 diabetes. Molecular cloning of the two subunits of the pancreatic beta-cell K(ATP) channel, Kir6.2 (an inward rectifier K+ channel member) and SUR1 (a receptor for sulfonylureas), has provided great insight into its structure and function. Kir6.2 subunits form the K+ ion-permeable pore and primarily confer inhibition of the channels by ATP, while SUR1 subunits confer activation of the channels by MgADP and K+ channel openers, such as diazoxide, as well as inhibition by sulfonylureas. The SUR1 subunits also enhance the sensitivity of the channels to ATP. To determine the physiological roles of K(ATP) channels directly, we have generated two kinds of genetically engineered mice: mice expressing a dominant-negative form of Kir6.2 specifically in the pancreatic beta-cells (Kir6.2G132S Tg mice) and mice lacking Kir6.2 (Kir6.2 knockout mice). Studies of these mice elucidated various roles of the K(ATP) channels in endocrine pancreatic function: 1) the K(ATP) channels are the major determinant of the resting membrane potential of pancreatic beta-cells, 2) both glucose- and sulfonylurea-induced membrane depolarization of beta-cells require closure of the K(ATP) channels, 3) both glucose- and sulfonylurea-induced rises in intracellular calcium concentration in beta-cells require closure of the K(ATP) channels, 4) both glucose- and sulfonylurea-induced insulin secretions are mediated principally by the K(ATP) channel-dependent pathway, 5) the K(ATP) channels are important for beta-cell survival and architecture of the islets, 6) the K(ATP) channels are important in the differentiation of islet cells, and 7) the K(ATP) channels in glucose-responsive cells generally participate in coupling glucose sensing with cell excitability. Interestingly, despite the severe defect in glucose-induced insulin secretion, Kir6.2 knockout mice show only a very mild impairment in glucose tolerance. However, when the knockout mice become obese with age, they develop fasting hyperglycemia and glucose intolerance, while neither fasting hyperglycemia nor glucose intolerance is evident in the aged knockout mice without obesity, suggesting that both the genetic defect in glucose-induced insulin secretion and the acquired insulin resistance due to environmental factors are necessary to develop diabetes in Kir6.2 knockout mice. Thus, Kir6.2G132S Tg mice and Kir6.2 knockout mice provide a model of type 2 diabetes and clarify the various roles of K(ATP) channels in endocrine pancreatic function.

Adenosine Triphosphate↗
PubMed2000

[Subcutaneous sarcoidosis of the extremities].

A 65-year-old man was referred to our hospital due to abnormal chest roentgenograms showing bilateral hilar enlargement with diffuse micronodular opacities. He presented with uveitis and elevated serum ACE and tested negative for tuberculin response. Transbronchial lung biopsies as well as bronchoalveolar lavage were performed and yielded a diagnosis of sarcoidosis. Several months later, the patient showed multiple subcutaneous nodules around the knee joints and elbow joints with exacerbation of intrapulmonary lesions. A skin biopsy revealed multiple foci of typical non-caseating epithelioid cell granulomata. These pulmonary and subcutaneous lesions rapidly resolved in response to the systemic administration of corticosteroids. Subcutaneous sarcoidosis may be a subacute variant of sarcoidosis associated with systemic involvement.

Aged↗
PubMed2000

Parasitic forms of a myxosporean in the kidney of the arctic lamprey, Lampetra japonica: an ultrastructural study.

We found frequent and unique parasitism by an unidentified myxosporean in the kidney of the arctic lamprey, Lampetra japonica, living in Japan. Trophozoites (pseudoplasmodia with or without sporoblasts) existed predominantly in the lumina of proximal urinary tubules, but were rarely found in any other regions of the kidney. Since no mature spores were produced in the trophozoites, exact identification of the species was impossible. Two parasitic forms were recognized in proximal urinary tubules: one adhering to the epithelial cells of renal tubules, and the other free-floating in the lumina of tubules. Ultrastructurally, the attaching trophozoites developed microvilli-like projections towards the apical surface of epithelial cells and vigorously interdigitated with microvilli of the brush border. In contrast, the whole surface of the floating trophozoite was smooth without any cell projections. The developed projections in the former type of trophozoite may contribute to their firm attachment to the epithelial cells and/or to absorption of nutrients via the epithelial cells. Against the myxosporean infection, the lamprey as the host exhibited a local immune reaction by disposition of numerous lymphocytes and macrophages into the epithelium of urinary tubules.

Animals↗
PubMed1999

Kinetic studies on the successive reaction of neuronal nitric oxide synthase from L-arginine to nitric oxide and L-citrulline.

Rat neuronal nitric oxide synthase (nNOS) was heterologously expressed in Escherichia coliand purified. The conversion of L-arginine to N(omega)-hydroxy-L-arginine and further to L-citrulline in one cycle of the reaction of the purified nNOS was measured with the reaction rapid quenching method using (3)H-L-arginine as the substrate. It was found that most of the produced (3)H-N(omega)-hydroxy-L-arginine was successively hydroxylated to (3)H-L-citrulline without leaving the enzyme. From the analysis of time courses, the rate constants for each reaction step, and also for the dissociation of the intermediate, were estimated at various temperature in which the rates for the first and the second reactions were not much different each other but the rate for the dissociation of (3)H-N(omega)-hydroxy-L-arginine from the enzyme was significantly slow. Under the steady-state reaction condition, almost all of the nNOS was estimated to be active from the amount of burst formation of L-citrulline in the pre-steady state. The rate constant for the dissociation of the product L-citrulline from nNOS was calculated from the combination of results of the rapid quenching experiments and the metabolism of L-arginine in the presence of an excess amount of substrate, which was the smallest among all the rate constants in one cycle of the nNOS reaction. The activation energies for all the reaction steps were determined from the temperature dependence of the rate constants, which revealed that the rate-determining step of the nNOS reaction in the steady state was the dissociation of the product L-citrulline from the enzyme.

Animals↗
PubMed1999

Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial. Gastric Cancer Surgical Study Group.

BACKGROUND: To study the survival benefit of adjuvant chemotherapy in gastric cancer, seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer. METHODS: 579 patients were enrolled in the study, stratified by disease stage (T1, n=188; T2, n=323), and allocated randomly adjuvant chemotherapy or no further treatment. 285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible. Six cases were excluded because they did not fulfill the entry criteria. The treatment group had intravenous mitomycin (1.4 mg/m2) and fluorouracil (166.7 mg/m2) twice weekly for 3 weeks after surgery, and oral UFT (uracil plus tegafur, 300 mg daily) for 18 months. Analyses were by intention to treat. FINDINGS: No serious toxic effects were observed in the treatment group. At median follow-up of 72 months, 59 patients in the control group and 47 in the treatment group had died. There was no significant difference in survival between the groups (5-year survival 82.9% control vs 85.8% treated; hazard ratio 0.738 [95% CI 0.498-1.093]). 5-year survival of patients with T1 (mucosal or submucosal) cancer in the control and treatment groups was 94.9% versus 92.0%, and that of patients with T2 (muscularis propria or subserosa) cancer was 76.9% versus 83.0%. However, a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response. INTERPRETATION: There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer (T1 and T2) after curative gastrectomy. Patients with T1 cancer can be excluded from future trials, because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy.

Adenocarcinoma↗
PubMed1999

Partial nuclear localization of a bovine phosphoprotein, BCNT, that includes a region derived from a LINE repetitive sequence in Ruminantia.

BCNT, named after Bucentaur, is a protein that contains a 324-amino-acid region derived from part of a long interspersed DNA sequence element (LINE) in Ruminantia. However, the unique portion is completely missing in human and mouse BCNTs. Since no significant information on their function has been obtained by homology search, we at first examined cellular localization and biochemical characteristics of bovine BCNT to get a hint on its function. Subcellular fractionation and immunohistochemical analyses using a normal bovine epithelial cell line and bovine brain revealed that a significant amount of bovine BCNT is localized in the nuclei, while the major portion is present in the cytosol. Furthermore, it was shown that bovine BCNT is a phosphoprotein and that both bovine and human BCNTs are phosphorylated by casein kinase II in vitro. These results show that BCNTs consist of a unique family, probably a substrate of casein kinase II, which may contribute further to the understanding of gene evolution.

Amino Acid Sequence↗
PubMed1999

Expression of protein gene product 9.5, a neuronal ubiquitin C-terminal hydrolase, and its developing change in sertoli cells of mouse testis.

Protein gene product 9.5 (PGP9.5), originally isolated as a neuron-specific protein, belongs to a family of ubiquitin carboxyl-terminal hydrolases that play important roles in the nonlysosomal proteolytic pathway. Antibodies against PGP9.5 have been used for immunohistochemical detection of neural elements, although some non-neuronal cells are also immunoreactive for PGP9.5. In the present study, developing testes of the mouse were immunostained after autoclave pretreatment of sections. In the testes of days 8 and 16, PGP9.5 was only localized on the spermatogonia, whereas on day 30 and in adults it appeared not only on spermatogonia, but also on Sertoli cells. In the testis of the male sterile W/W(v) mutant, very little, but strong, immunoreactivity was detected at some Sertoli cells, which were phagocytizing Sertoli cell aggregations that had fallen from the basal membrane. Additionally, it was confirmed that the nucleotide sequence of PGP9.5 in mice was highly conserved, like that in other mammals. These results suggest that PGP9.5 is a useful marker for activated Sertoli cells, playing an important role in degradation of abnormal proteins.

Animals↗
PubMed1999

Fast tissue segmentation based on a 4D feature map in characterization of intracranial lesions.

The aim of this work was to develop a fast and accurate method for tissue segmentation in magnetic resonance imaging (MRI) based on a four-dimensional (4D) feature map and compare it with that derived from a 3D feature map. High-resolution MRI was performed in 5 normal individuals, in 12 patients with brain multiple sclerosis (MS), and 9 patients with malignant brain tumors. Three inputs (proton-density, T2-weighted fast spin-echo, and T1-weighted spin-echo MR images) were routinely utilized. As a fourth input, either magnetization transfer MRT was used or T1-weighted post-contrast MRI (in patients only). A modified k-nearest neighbor segmentation algorithm was optimized for maximum computation speed and high-quality segmentation. In that regard, we a) discarded the redundant seed points; b) discarded the points within 0.5 standard deviation from the cluster center that were non-overlapping with other tissue; and c) removed outlying seed points outside 5 times the standard deviation from the cluster center of each tissue class. After segmentation, a stack of color-coded segmented images was created. Our new technique utilizing all four MRI inputs provided better segmentation than that based on three inputs (P < 0.001 for MS and P < 0.001 for tumors). The tissues were smoother due to the reduction of statistical noise, and the delineation of the tissues became sharper. Details that were previously blurred or invisible now became apparent. In normal persons a detailed depiction of deep gray matter nuclei was obtained. In malignant tumors, up to five abnormal tissue types were identified: 1) solid tumor core, 2) cyst, 3) edema in white matter 4) edema in gray matter, and 5) necrosis. Delineation of MS plaque in different stages of demyelination became much sharper. In conclusion, the proposed methodology warrants further development and clinical evaluation.

Brain↗
PubMed1999

Optimization of tissue segmentation of brain MR images based on multispectral 3D feature maps.

The purpose of this work was to optimize and increase the accuracy of tissue segmentation of the brain magnetic resonance (MR) images based on multispectral 3D feature maps. We used three sets of MR images as input to the in-house developed semi-automated 3D tissue segmentation algorithm: proton density (PD) and T2-weighted fast spin echo and, T1-weighted spin echo. First, to eliminate the random noise, non-linear anisotropic diffusion type filtering was applied to all the images. Second, to reduce the nonuniformity of the images, we devised and applied a correction algorithm based on uniform phantoms. Following these steps, the qualified observer "seeded" (identified training points) the tissue of interest. To reduce the operator dependent errors, cluster optimization was also used; this clustering algorithm identifies the densest clusters pertaining to the tissues. Finally, the images were segmented using k-NN (k-Nearest Neighborhood) algorithm and a stack of color-coded segmented images were created along with the connectivity algorithm to generate the entire surface of the brain. The application of pre-processing optimization steps substantially improved the 3D tissue segmentation methodology.

Anisotropy↗
PubMed1999

Perioperative allogenic blood transfusion and serum levels of immunosuppressive acidic protein in patients undergoing resection of colorectal carcinoma.

Serum levels of immunosuppressive acidic protein (IAP) were determined in 68 patients undergoing resection of colorectal cancer and 21 healthy subjects. Eighteen patients had perioperative transfusion of allogeneic blood (transfused patients) and 50 patients had no blood transfusion (nontransfused patients). Transfused patients had a higher incidence of nodal involvement, advanced disease, and noncurative surgery compared to nontransfused patients, but the difference did not reach a statistical significance. Hemoglobin concentration and serum albumin level were lower in transfused patients, although there was no statistically significant difference. Preoperative serum IAP level was higher in the patients with nodal involvement and advanced disease and those with moderately or poorly differentiated tumor, though this was not statistically significant. The preoperative serum IAP level was higher in patients than in controls, but the difference did not reach statistical significance. Serum IAP level rose immediately after the operation. In nontransfused patients, the serum IAP level returned to the preoperative value by three months after the operation. In contrast, the serum IAP level of transfused patients remained significantly higher than the preoperative value (P < 0.05) at three months after the operation. These findings indicated that perioperative transfusion of allogeneic blood elevated the serum IAP level for a considerable period after the operation.

Adult↗
PubMed1999

Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons.

1. The aim of our study is to clarify the relationship between expression pattern of P2X receptors and the cell type of male adult rat (Wistar) dorsal root ganglion (DRG) neurons. We identified the nociceptive cells of acutely dissociated DRG neurons from adult rats type using capsaicin sensitivity. 2. Two types of ATP-activated currents, one with fast, the other with slow desensitization, were found under voltage-clamp conditions. In addition, cells with fast but not slow desensitization responded to capsaicin, indicating that there was a relationship between current kinetics and capsaicin-sensitivity. 3. Both types of neurons were responsive to ATP and alpha, beta methylene-ATP (alpha,betameATP). The concentration of alpha,(beta)meATP producing half-maximal activation (EC50) of neurons with fast desensitization was less (11 microM) than that of neurons with slow desensitization (63 microM), while the Hill coefficients were similar. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS) antagonized alpha,betameATP-induced currents in both types of neurons. 4. In situ hybridization revealed that small cells of the DRG predominantly expressed mRNAs of P2X3 and medium-sized cells expressed mRNAs of P2X2 and P2X3. In contrast, both of mRNAs were not detected in large cells of the DRG. 5. These results suggest that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X2 and P2X3.

Adenosine Triphosphate↗
PubMed1999

Butyrate from bacterial fermentation of germinated barley foodstuff preserves intestinal barrier function in experimental colitis in the rat model.

BACKGROUND AND AIMS: The consumption of germinated barley foodstuff (GBF) prevents inflammation and diarrhoea in a colitis model. In this study we investigated the mechanism of the preventative effect of GBF on experimental colitis in rats, in view of production of bacterial butyrate and preservation of intestinal barrier function. METHODS: Sprague-Dawley rats administered with diets supplemented with 3.5% dextran sodium sulphate were used as an experimental colitis model. Butyrate was given to rats orally or intracaecally. Intestinal barrier function was estimated by light microscopic observation of the mucosa, intestinal permeability and bacterial translocation. RESULTS: Mucosal damage was reduced by intracaecal administration of butyrate, but not by oral administration. Bacterial butyrate production and reduction of mucosal damage depended on the dose of GBF in diets. The action of endogenous bacterial butyrate, including the reduction of intestinal permeability and bacterial translocation, was inhibited by administration of an inhibitor of beta-oxidation of short-chain fatty acids. CONCLUSIONS: The feeding of GBF promotes bacterial butyrate production and improves intestinal barrier function in rats, resulting in mitigation of experimental colitis.

Animals↗
PubMed1999

Germinated barley foodstuffs attenuate colonic mucosal damage and mucosal nuclear factor kappa B activity in a spontaneous colitis model.

BACKGROUND: Germinated barley foodstuffs (GBF), which are derived from brewer's spent grain and are a highly safe food substance, increased butyrate production in the lower intestine and prevented mucosal damage and bloody diarrhoea in an acute experimental colitis model. As human histocompatibility leucocyte antigen (HLA)-B27 transgenic rats develop spontaneous and chronic intestinal inflammation resembling ulcerative colitis, we investigated the mechanisms underlying the preventive effects of GBF against a spontaneous and chronic colitis model. Specifically, the production of bacterial butyrate and the regulation of proinflammatory cytokine production were examined. METHODS: A GBF diet and a cellulose (CE) diet were fed to HLA-B27 transgenic rats for 13 weeks. The presence of faecal occult blood, colonic mucosal protein, DNA and RNA content, colonic myeloperoxidase activity, nuclear factor kappa B (NFkappaB) DNA binding activity, the depth of the crypts and serum inflammatory parameters were then evaluated. Butyrate production in the caecal contents was also determined. RESULTS: Feeding GBF significantly increased bacterial butyrate production and simultaneously attenuated the presence of faecal occult blood and colonic mucosal hyperplasia. Colonic mucosal NFkappaB-DNA binding activity and the production of interleukin-8 were also suppressed by the butyrate produced from GBF. CONCLUSIONS: Germinated barley foodstuffs feeding promotes bacterial butyrate production and attenuated inflammation in both spontaneous and chronic colitis in HLA-B27 transgenic rats.

Animals↗
PubMed1999

Unique localization of protein gene product 9.5 in type B synoviocytes in the joints of the horse.

Fibroblast-like (Type B) synoviocytes are cells in the synovial membrane that are responsible for production of both synovial fluid and the extracellular matrix in the synovial intima. Immunostaining of the horse synovial membrane for protein gene product (PGP) 9.5, which is a neuron-specific ubiquitin C-terminal hydrolase, demonstrated selective localization of the immunoreactivity in a synoviocyte population different from acid phosphatase-positive Type A synoviocytes. The immunoreactive cells were lined up in the synovial intima and extended dendritic processes towards the joint cavity to form a dense plexus on the surface. Electron microscopic examination clearly identified the PGP 9.5-immunoreactive cells as Type B synoviocytes characterized by developed rough endoplasmic reticulum and free ribosomes. Immunoreactivity for PGP 9.5 was diffusely distributed throughout the cytoplasm, including the tips of fine processes. Western and Northern blot analyses could not distinguish the corresponding protein and mRNA obtained from the brain and synovial membrane. The existence of the neuron-specific PGP 9.5 in Type B synoviocytes suggests a common mechanism regulating the protein metabolism between neurons and synoviocytes, and also provides a new cytochemical marker for identification of the cells.

Animals↗
PubMed1999

Scanning electron microscopic observation of apical sites of open-type paraneurons in the stomach, intestine and urethra.

The apical region of open-type paraneurons in tubular organs functions as a receptor site for chemical information in the lumen. Electron microscopic studies have demonstrated a tuft of microvilli on the luminal surface of cells, but failed to visualize it three-dimensionally. The present scanning electron microscope (SEM) observation succeeded in viewing, from the luminal side, open-type paraneurons distributed in epithelia of the stomach, intestine, and urethra. The pyloric antrum of avian species and the duodenum of human fetuses, the latter forming an endocrine cell colony at every villus tip, were chosen for SEM observation in order to eliminate visual obstruction by adjacent epithelial cells with developed microvilli. The luminal surface of gut endocrine cells was consistently covered with a tuft of 80-200 microvilli. Pyloric paraneurons possessed thick and stiff microvilli as compared with those of exocrine cells. The microvilli on intestinal paraneurons were more irregular in length and more loosely grouped than those composing the striated border of enterocytes. Urethral paraneurons containing serotonin were surrounded by three or four polygonal epithelial cells. Their narrow apical surface was provided with 30-100 microvilli which varied in length from cell to cell, and which were conspicuously projected above the luminal surface of the urethra. The microvillous crown of the gut and urethral paraneurons was so prominent and constant a structure on the apical surface as to allow easy identification of open-type paraneurons under the SEM.

Animals↗
PubMed1999

Three-dimensional ultrastructure of synoviocytes in the horse joint as revealed by the scanning electron microscope.

The synovial membrane displays a superficial cellular lining composed of two types of synoviocytes: "absorptive" macrophages (type A cells) and "secretory" fibroblast-like cells (type B cells). The types are intermingled and extend a variety of processes, rendering the cellular architecture of the synovial membrane difficult to visualize. Previous electron microscopic and histochemical studies failed to demonstrate the entire shape of synoviocytes, except our immunohistochemical study for protein gene product 9.5 in the horse joint. The present SEM study is the first to demonstrate the three-dimensional ultrastructure of synoviocytes as well as their distribution in the synovial membrane, using macerated samples from the horse carpal joints. The equine synovial membrane was largely covered by conspicuously developed synovial villi. Type A synoviocytes were closely similar to macrophages in regard to surface structure, and showed uneven distribution with the densest occurrence around the tips of the synovial villi. In the basal half of villi, type B synoviocytes, which were situated in close proximity to the synovial cavity, projected thick processes horizontally and intertwined to form a regular network of processes on the synovial surface. Those in the upper half of the villi were located in the abluminal layers and protruded an antenna-like process into the joint cavity with tips covered with long microvilli, in addition to forming the superficial plexus of processes. Type B cells were also provided with fine, membranous extensions that tended to cover the surface of synovial intima. The meshwork of horizontal processes, the antenna-like processes, and the membranous processes imply advantages in not only secretion but also sensation and regulation of the barrier function in the synovial membrane.

Animals↗