Search PubMed⌕ Search

Biomedical subjects

A Shiotani

Publications and source records attributed to A Shiotani.

At least 37 records · Page 2Linked to original sources

Helicobacter pylori infection reduces intraluminal nitric oxide.

BACKGROUND: Nitric oxide (NO) plays an important role in gastrointestinal mucosal protection. We have previously shown that Helicobacter pylori infection is associated with a lower concentration of NO in the human stomach. The aim of this study is to explore the pathogenesis of this finding using an animal model. METHODS: Mongolian gerbils were divided into four groups: H. pylori-negative and -positive, each with and without the intraperitoneal addition of superoxide dismutase (SOD). Intraluminal NO and serum nitrate were measured by using a chemiluminescence system. Inducible nitric oxide synthase (iNOS) levels in gastric mucosa were measured by using the NOSdetect Assay Kit. RESULTS: iNOS levels in H. pylori-positive gerbils were significantly greater than in those without infection. Intraluminal NO levels in H. pylori-positive gerbils were significantly lower than those in H. pylori-negative ones and increased after SOD administration. Serum nitrate levels in H. pylori-positive gerbils were significantly greater than those in H. pylori negative ones and decreased after SOD administration. CONCLUSIONS: The low level of NO in the gastric lumen in H. pylori infection is likely a result of superoxide production related to H. pylori-induced inflammation.

Animals↗

IGF-1 gene transfer into denervated rat laryngeal muscle.

OBJECTIVES: To demonstrate gene transfer in rat laryngeal muscle using a reporter gene, beta-galactosidase, and a muscle-specific expression system containing the human IGF-1 (hIGF-1) gene sequence and to investigate the myotrophic and neurotrophic effects of hIGF-1 gene transfer in denervated rat laryngeal muscle. METHODS: In 8 adult rats, a polyvinyl-based formulation containing beta-galactosidase DNA was injected into denervated thyroarytenoid muscle. Twelve animals were similarly administered a polyvinyl-based formulation containing a muscle-specific expression system and hIGF-1 DNA. Twelve animals were injected with isotonic sodium chloride solution, and all animals survived for 1 month. The production of beta-galactosidase and hIGF-1 was detected using immunohistochemical techniques. The effects of hIGF-1 on motor endplates and nerve sprouting were assessed using cholinesterase or silver staining and immunostaining for growth-associated protein (GAP-43). mals by immunostaining, X-gal histochemical staining, or both. In frozen section specimens, hIGF-1 immunoreactivity was positive in 3 of 8 animals. In sequential sections, GAP-43 was localized to areas of hIGF-1 expression in 2 of the 3 hIGF-1-positive specimens. Increased nerve sprouting and motor endplate contact occurred in 2 of 4 animals treated with hIGF-1. CONCLUSIONS: Gene transfer into laryngeal muscle was demonstrated using a polyvinyl-based formulation containing a muscle-specific gene expression system. Preliminary findings indicate a positive effect on motor endplates, nerve sprouting, and the expression of GAP-43 in animals treated with the hIGF-1 vector. This study establishes a foundation for investigating hIGF-1 gene transfer as a novel treatment of laryngeal paralysis. Further studies are necessary to quantify myotrophic and neurotrophic effects and to establish therapeutic benefit.

Animals↗

Human insulinlike growth factor 1 gene transfer into paralyzed rat larynx: single vs multiple injection.

OBJECTIVE: To compare the biological effects of single vs multiple treatment of rat denervated laryngeal muscle with human insulinlike growth factor 1 (hIGF1) gene therapy. EXPERIMENTAL METHODS OR DESIGN: A muscle-specific nonviral vector containing the alpha-actin promoter and hIGF1 gene formulated with polyvinyl polymers was injected into denervated adult rat thyroarytenoid muscle. The effects on animals given a single injection (n = 16) vs those given multiple injections (n = 14) vs control groups (n = 18) were evaluated. Twenty-eight days after the first injection, gene expression, muscle fiber size, motor endplate length, and nerve-to-motor endplate contact were evaluated. RESULTS: Gene expression, detected by reverse transcriptase polymerase chain reaction for hIGF1 messenger RNA, occurred in 13 (81%) of 16 animals receiving single injections and 14 (100%) of 14 animals receiving multiple injections. Compared with controls, hIGF1-transfected animals in both single- and multiple-injection groups had a significant increase in the lesser diameter of muscle fiber, a significant decrease in motor endplate length, and a significant increase in the percentage of endplates with nerve contact (P <.05 for all). There was no statistical difference between single- and multiple-injection groups. CONCLUSIONS: Applied to laryngeal paralysis, hIGF1 gene therapy provides an opportunity to augment surgical treatment modalities by the prevention or reversal of muscle atrophy, and enhancement of nerve sprouting and muscle reinnervation. Although the percentage of denervated muscles demonstrating hIGF1 expression was increased following multiple injections, no difference was observed in the biological response compared with that in the single-injection treatment groups. Further investigation will be conducted to assess long-term benefits and physiological responses and to define the limitations of this potentially valuable therapeutic strategy.

Animals↗

Helicobacter pylori infection reduces intraluminal nitric oxide in humans.

It has recently been demonstrated that nitric oxide (NO) is highly concentrated in the gastric lumen and plays an important role in defending against pathogenic microorganisms in the stomach. NO in the gastric lumen is mainly delivered by extrinsic sources from saliva. We studied whether Helicobacter pylori infection affected intraluminal NO levels in humans. H. pylori infection was diagnosed on the basis of histology and culture or (13C)-urea breath test. Air and gastric juice in the gastric lumen were collected endoscopically. The concentration of intraluminal NO was measured by a chemiluminescence system, using an NO analyzer. The concentration of nitrite in gastric juice was measured by the Griess reaction. The intraluminal concentration of NO in H. pylori-positive patients (198.2 +/- 41 parts per billion [ppb] mean +/- SE; n = 70) was significantly lower than that in H. pylori-negative patients (353.0 +/-57.9ppb; n = 43; P < 0.05). In contrast, the concentration of nitrite in gastric juice in H. pylori-positive patients (57.7 +/- 12.3 RM; n = 70) was significantly higher than that in H. pylori-negative patients (25.9 +/- 6.4 microM; n = 43, P < 0.01). The intraluminal concentration of NO in H. pylori-positive patients was markedly increased and the concentration of nitrite in H. pylori-positive patients was markedly decreased following the completion of eradication therapy. Based on these results, we propose that a decrease in NO and excess nitrite production in the gastric lumen are associated with H. pylori infection and may play an important role in the pathogenesis of H. pylori-related abnormalities.

Female↗

Hereditary angioedema with gastrointestinal involvement: endoscopic appearance.

We present the first reported case of hereditary angioedema (HAE) with gastric involvement to be successfully evaluated by endoscopy both during and after an attack. A 31-year-old man who had a family history of angioedema was admitted to our hospital with complaints of abdominal pain and swelling of extremities. Computed tomography scan and endoscopy carried out during this attack revealed transient gastrointestinal wall edema which, along with decreased levels of serum C4 and C1 inhibitor, confirmed the diagnosis of HAE with gastrointestinal involvement. During the attack, the gastric mucosa was erythematous and edematous, and parts of its surface bulged into the gastric lumen, resembling a submucosal tumor, as a result of massive submucosal edema. During the healing process, a number of small nodules and raised erosions developed over the entire gastric mucosal surface after healing of prominent gastric edema. Within 55 days, the gastric mucosa had returned to normal. The endoscopic findings for the stomach in HAE have not, to our knowledge, been previously described.

Adult↗

Myosin heavy chain composition in human laryngeal muscles.

OBJECTIVES: Myosin heavy chain (MHC) composition of human thyroarytenoid (TA), lateral cricoarytenoid (LCA), interarytenoid (IA), vocalis, posterior cricoarytenoid (PCA), and cricothyroid muscles were examined using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western bolt techniques. The presence of superfast MHC was also assessed using antibodies directed against the extraocular MHC. STUDY DESIGN: MHC protein was analyzed using fresh human laryngeal muscles. METHODS: Laryngeal muscles excised from cadavers were processed for SDS-PAGE. The composition of MHC isoforms was determined by densitometry. Western blot was carried out to identify specific bands. RESULTS: MHC types IIA and IIB are the predominant MHC components in human laryngeal muscles. The adductor muscles--TA, LCA, and IA--have a higher percentage of type IIB MHC and a lower percentage of type I when compared with the abductor--PCA. The rank file order for type IIB MHC composition (TA > LCA > or = IA > PCA) is the same in all specimens. A band migrating between type IIA and type I was observed in several specimens. Although similar to type IIL in rats, this atypical band did not react with anti-extraocular MHC antibody on Western blot. CONCLUSION: Characterization of laryngeal muscles determined by the composition of MHC is correlated with function and neural input. Human laryngeal muscle is characterized by a predominance of fast-type MHCs in laryngeal closing muscle and mixed fast-slow type MHCs in respiratory and phonatory muscle groups. Although an atypical myosin band similar to type IIL (superfast) MHC in rat was identified, it did not react with anti-extraocular MHC antibody.

Aged↗

Postnatal development of myosin heavy chain isoforms in rat laryngeal muscles.

The developmental transitions of myosin heavy chain (MHC) isoforms of rat posterior cricoarytenoid (PCA), thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid (LCA) muscles were examined by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot techniques. The muscles were microscopically dissected from animals on postnatal days 0, 3, 7, 10, 14, 21, 28, 35, 45, and 55 and from adult animals. Silver-stained SDS-PAGE gels of each muscle were analyzed densitometrically to measure the composition of MHC isoforms, and Western blot was carried out to identify specific bands. Characterizations of the internal laryngeal muscles determined by the composition of MHCs were correlated with their function in the adult. Temporally, differentiation reflects onset of function. Differentiation of isoforms and transition to adult forms occur first in the TA muscle, followed by the PCA, LCA, and CT muscles. Expression of type IIL was observed only in muscles innervated by the recurrent laryngeal nerve. Postnatally observed developmental differences of myosin phenotypes suggest that regulation of MHC expression is influenced by neural activity or other environmental factors.

Aging↗

[Esophagitis, gastritis and duodenitis provoked by cure of Helicobacter pylori infection].

It has been recently reported that curing Helicobacter pylori (H. pylori) infection may provoke reflux esophagitis. We studied the effect of cure of H. pylori infection on the development of disorders of the upper gastrointestinal (UGI) tract. The estimated incidence of reflux esophagitis, gastric erosions and duodenal erosions after cure of infection was 8.9%, 32.8% and 8.9%. The incidences of reflux esophagitis, gastric erosions and duodenal erosions were 10.0%, 30.0% and 6.7% in patients with gastric ulcer, 2.8%, 36.1% and 27.8% in those with duodenal ulcer and 9.2%, 30.3% and 1.3% in those with atrophic gastritis. Therefore, patients whose H. pylori infection has been cured should carefully be investigated by endoscopy for H. pylori-associated disease.

Duodenitis↗

Expression of extraocular-superfast-myosin heavy chain in rat laryngeal muscles.

Superfast myosin heavy chain (MHC), which is found in jaw-closing muscle and extraocular muscle (EOM), may also be found in rat laryngeal muscles. Immunostaining and Western blot using anti-EOM antibody were performed to identify and localize EOM MHC in laryngeal muscles. Specific reactivity of laryngeal IIL MHC was confirmed by Western blot and on immunostaining, all fibers in the lateral part of thyroarytenoid muscle reacted with EOM antibody. A scattered pattern of positive fibers was observed in the medial part of the thyroarytenoid, the posterior cricoarytenoid and the lateral cricoarytenoid muscles. EOM MHC was not detected in the cricothyroid muscle. The expression of EOM MHC in rat laryngeal muscle is consistent with the functional demands of the airway protection reflex.

Animals↗

Reinnervation of motor endplates and increased muscle fiber size after human insulin-like growth factor I gene transfer into the paralyzed larynx.

Current surgical strategies for the treatment of laryngeal paralysis are limited by the muscle atrophy associated with denervation. Moreover, attempts at reinnervation have not effected significant change in surgical outcome. To address this clinical problem, we have developed a rat laryngeal paralysis model to study novel gene transfer strategies. Using this model, the human insulin-like growth factor I (hIGF-I) gene was introduced into paralyzed rat laryngeal muscle to assess the benefit of sustained local hIGF-I production. A muscle-specific nonviral vector containing the alpha-actin promoter and hIGF-I gene was used in formulation with a polyvinyl-based delivery system and injected into paralyzed adult rat laryngeal muscle. Twenty-eight days after a single injection, gene transfer efficiency, muscle fiber size, motor endplate length, and nerve-to-motor endplate contact were evaluated. Gene transfer was detected in 100% of injected animals by PCR. Gene transfer with expression, as measured by RT-PCR for hIGF-I mRNA, occurred in 81.3 % of injected animals. When compared with controls, hIGF-I-transfected animals presented a significant increase in muscle fiber diameter [17.56 (+/-0.97 SD) microm versus 14.70 (+/-1.43 SD) microm; p = 0.0002], a significant decrease in motor endplate length [20.88 (+/-1.42 SD) microm versus 25.41 (+/-3.19 SD) microm; p = 0.0025], and a significant increase in percentage of endplates with nerve contact (20.3% (+/-13.9 SD) versus 4.4% (+/-4.2 SD); p = 0.0079). In the context of laryngeal paralysis, gene therapy represents a tremendous opportunity to augment current surgical treatment modalities by preventing or reversing muscle atrophy, and by enhancing nerve sprouting and reinnervation.

Actins↗

Myosin heavy chain composition in rat laryngeal muscles after denervation.

OBJECTIVES: The effects of denervation on myosin heavy chain (MHC) expression in specific laryngeal muscles are characterized using gel electrophoresis. Observed temporal changes in MHC composition will then be used as a biologic marker in studies designed to develop strategies for laryngeal reinnervation and gene therapy. STUDY DESIGN: Animal study using an adult rat model for laryngeal paralysis. METHODS: In anesthetized rats the left recurrent and superior laryngeal nerve were divided. Animals were survived for 7, 14, 28, 90, and 180 days. Animals were euthanized and the thyroarytenoid (TA), vocalis (VOC), posterior cricoarytenoid (PCA), lateral cricoarytenoid (LCA), and cricothyroid (CT) muscle excised. Each muscle was processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and densitometric measurements were obtained to determine composition of MHC fiber types. RESULTS: The changes in relative MHC composition are described for each specific laryngeal muscle. In general, a decrease in type IIB and an increase in IIA and IIX are seen after denervation. Expression of IIL in the denervated condition is variable and the relative change in type I is minimal. CONCLUSION: This study supports previous work using rat soleus muscle in which IIA/IIX expression is favored in conditions with decreased neuromuscular activity, and conversely, IIB expression is activity dependent. Expression of type I appears to be independent of neural activity. Further study will be undertaken to quantify expression of MHC components and to study factors modulating expression.

Animals↗

Lubrication mechanism of the larynx during phonation: an experiment in excised canine larynges.

To evaluate how the viscosity of the laryngeal mucus influences vocal fold vibration, two fluids of differing viscosity were applied separately to excised canine larynges and experimental phonation was induced. Vibration of the vocal folds was measured by use of a laryngostroboscope and an X-ray stroboscope. With the high viscosity fluid, the amplitude of vibration of the free edge and the peak glottal area was decreased while the open quotient was increased. Because the viscosity of this fluid affected the wave motion of the vocal fold mucosa, changes in viscosity of the mucus may be involved in causing such disorders as hoarseness, in the absence of apparent changes in the vocal folds themselves.

Animals↗

Epidermal growth factor and okadaic acid stimulate Sp1 proteolysis.

Sp1 nuclear levels have been shown to directly correlate with the proliferative state of the cell. We therefore studied changes in the abundance of Sp1 in a rat pituitary cell line GH4 whose growth rate is regulated by epidermal growth factor (EGF). Nuclear extracts from GH4 cells treated with 10 nM EGF for at least 16 h showed a 50% decrease in Sp1 binding to a GC-rich element present in the gastrin promoter. The decrease in binding correlated with a decrease in cell proliferation, a loss of nuclear Sp1 protein and a 50-60% decrease in Sp1-mediated transactivation through an Sp1 enhancer element in transfection assays. Okadaic acid, a phosphatase inhibitor, was synergistic with the effect of EGF on Sp1 protein levels suggesting that the loss of Sp1 was mediated by phosphorylation events. This result was confirmed by showing a 2-fold increase in orthophosphate-labeled Sp1 with EGF and okadaic acid. Cycloheximide prevented the expected loss of Sp1 mediated by EGF and okadaic acid suggesting that the synthesis of a protease may mediate these events. This hypothesis was tested directly by showing that the cysteine protease inhibitor leupeptin prevented Sp1 degradation. Using the PEST-FIND computer program, the computed PEST score for human and rat Sp1 is 10.4 and 13.7, respectively, indicating that Sp1 has a domain with a high concentration of proline, glutamic acid, serine, and threonine residues as reported for a number of proteins with inducible rates of degradation. Collectively, these results indicate that sustained stimulation of GH4 cells by EGF initiates a cascade of phosphorylation events that promotes Sp1 proteolysis, decreased Sp1 nuclear levels and decreased cellular proliferation.

Amino Acid Sequence↗

[A case of the tuberculous abscess in the abdominal wall].

A case of the tuberculous abscess in the abdominal wall is reported. A 84-year-old female was admitted to our hospital with evaluation of soft tumor at the left lower abdomen. She has a mass in the abdominal wall measuring 4 cm in diameter, and abscess in the abdominal wall was detected by ultrasonogram and CT. The confirmed diagnosis of abdominal wall tuberculosis was made by means of bacterial culture and polymerase chain reaction (PCR method) of the aspirated fluid from a mass. Multiple calcified lesions on the abdominal X-ray were seen, which were thought to past history of tuberculous peritonitis. Antituberculosis therapy of three-drug regimens was not effective. Four month later, resection of the abscess was then performed. Adhesion was demonstrated between greater omentum and peritoneum, therefore the abscess in the abdominal wall was considered to arise and advance directly from the abdominal cavity.

Abdominal Muscles↗

Wegener's granulomatosis with dural involvement as the initial clinical manifestation.

We treated a patient with an atypical presentation of Wegener's granulomatosis (WG) with dural involvement as the initial clinical manifestation. A 37-year-old man had a dural lesion without lower respiratory tract or renal manifestations in the initial clinical course. His only initial symptom was headache, and at disease onset computed tomography (CT) and magnetic resonance imaging (MRI) of the head revealed bilateral abnormal subdural masses. The diagnosis of WG was made based on the results of needle biopsy of the nasal polyps and the finding of positive circulating antineutrophil cytoplasmic antibodies (c-ANCA). He achieved remission on daily prednisone and cyclophosphamide with the later addition of sulfamethoxazole-trimethoprim.

Adult↗

Vocal fold vibration in simulated head voice phonation in excised canine larynges.

In order to establish precise vibratory patterns and their clinical implication for phonation, the mode of vibration of the vocal folds around the time of register transition in excised canine larynges was analyzed multi-directionally according to various acoustic parameters. Phonation was simulated by artificially tensing the cricothyroid muscles. Vibration of the vocal folds around the time of register transition was filmed from above using ultra-high-speed cinematography and in a frontal plane using X-ray stroboscopy. Acoustic parameters included subglottic pressure, pitch, intensity and tension and were recorded simultaneously during register transition. The fundamental vibration patterns observed during vocal phonation were the same as that involved in chest voice phonation in excised canine larynges, with respect to the traveling wave of the vocal fold vibration. Changes in the physical properties of the vocal folds were considered to occur at register transition. These changes were probably strongly dependent upon changes in the structure of the lamina propria. Head voice phonation requires adaptability of the lamina propria and is less efficient than chest voice phonation. Hence, head voice phonation would be one method for assessing the condition of the vocal folds.

Animals↗