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Biomedical subjects

T Takashima

Publications and source records attributed to T Takashima.

At least 19 recordsLinked to original sources

Complete regression of low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the gastric stump after eradication of Helicobacter pylori.

Recent studies have suggested that Helicobacter pylori (H. pylori)-associated gastritis may play an important role in the pathogenesis of primary gastric lymphoma. Recently, triple therapy using proton pump inhibitor, amoxicillin, and clarithromycin, has been established for the eradication therapy of H. pylori infection, and is also recommended for the treatment of the superficial type of low-grade gastric MALT (mucosa-associated lymphoid tissue ) lymphoma. MALT lymphoma of the gastric stump is rare, and total resection or chemotherapy for MALT lymphoma of the gastric stump has been previously reported. Therefore, there is no evidence that eradication therapy is effective for low-grade MALT lymphoma of the gastric stump. Our case illustrates the remarkable efficacy of eradication of H. pylori for low-grade MALT lymphoma of the gastric stump without other modalities such as surgery and systemic chemotherapy.

Aged↗

Efficacy of epidermal growth factor receptor-targeted molecular therapy in anaplastic thyroid cancer cell lines.

Anaplastic thyroid cancer is one of the most aggressive human malignancies and the outcomes of conventional therapy have been far from satisfactory. Recently, epidermal growth factor receptor (EGFR)-targeted therapy has been introduced as an alternative therapeutic strategy for highly malignant cancers. This study was undertaken to investigate the expression of EGFR in anaplastic thyroid cancer cell lines, and to explore the potential of therapies targeting EGFR as a new therapeutic approach. EGFR was universally expressed in anaplastic cancer cell lines at a variety of levels. Specific EGFR stimulation with epidermal growth factor showed significant phosphorylation of ERK1/2 and Akt, and resulted in marked growth stimulation in an anaplastic thyroid cancer cell line, which highly expressed EGFR. This EGFR-transmitted proliferation effect of the cancer cell line was completely inhibited by gefitinib, an EGFR tyrosine kinase inhibitor. Moreover, growth of xenografts inoculated in mice was inhibited in a dose-dependent manner with 25-50 mg kg(-1) of gefitinib administrated orally. Inhibition of EGFR-transmitted growth stimulation by gefitinib was clearly observed in anaplastic thyroid cancer cell lines. Our results suggested that EGFR-targeted therapy, such as gefitinib, might be worth further investigation for the treatment of anaplastic thyroid cancer.

Animals↗

Effects of famotidine, mosapride and tandospirone for treatment of functional dyspepsia.

BACKGROUND: An effective therapeutic strategy for functional dyspepsia (FD) has not been well-established. AIM: We investigated and compared the therapeutic effects of famotidine, mosapride and tandospirone for the control of dyspeptic symptoms. METHODS: Fully examined FD patients of outpatient clinics at seven different medical centres were enrolled in the study. They were randomly assigned to three groups based on the type of drug administered: famotidine, mosapride and tandospirone. The effects of treatment over 4 weeks were assessed by visual analogue scales. RESULTS: All of the drugs showed beneficial effects, although famotidine was the most effective for symptom relief, which was significantly greater than tandospirone, while the effect of mosapride was similar to that of famotidine. No subtype of FD showed a better response to a particular type of drug. CONCLUSIONS: For the treatment of FD, famotidine demonstrated the best therapeutic effect, followed by mosapride, while that of tandospirone was significantly lower.

Anti-Anxiety Agents↗

Serum CYFRA 21-1 (cytokeratin-19 fragments) is a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer.

The usefulness of serum CYFRA 21-1 (cytokeratin-19 fragments) in monitoring the recurrence of breast cancer and in evaluating therapeutic effects was studied retrospectively. The sera from 173 patients with primary breast cancer or recurrent disease were measured for CYFRA 21-1, carcinoembryonic antigen (CEA), and carbohydrate antigen 15-3 (CA 15-3) levels. The positive rates of serum CYFRA 21-1 for stage IV (n=12) or recurrent disease (n=26) were 83.3 and 84.6%, respectively, while those of serum CEA were 41.7 and 26.9%, and those of serum CA 15-3 were 83.3 and 34.6%. The elevated preoperative levels of serum CYFRA 21-1 decreased to normal levels after curative operation, whereas the levels remained abnormally high after noncurative operation. There was a significantly high frequency of recurrence in patients with elevated levels of serum CYFRA 21-1 preoperatively compared to those with normal levels of the marker preoperatively. The serum CYFRA 21-1 levels were well correlated with response to chemotherapy. The positive rate of serum CYFRA 21-1 alone was higher than that of an assay combining CEA with CA 15-3, in both primary and recurrent cases (28.8 vs 18.8 and 84.6 vs 46.2%, respectively). These observations suggest that serum CYFRA 21-1 may be a reliable marker of recurrence or therapeutic efficacy.

Antigens, Neoplasm↗

A new diglycosyl megastigmane from Carallia brachiata.

A new megastigmane diglycoside was isolated from the leaves of Carallia brachiata. The structure was determined by spectroscopic methods as 3-hydroxy-5,6-epoxy-beta-ionol -3-O-beta-apiofuranosyl-(1-->6)-beta-glucopyranoside (1). Additionally, 29 known compounds consisting of two megastigmanes, one 1,2-dithiolane derivative, seven aromatic compounds, five condensed tannins, 12 flavonoids, and two glyceroglycolipids were isolated and identified.

Cyclohexanones↗

Ice-water interface migration by temperature controlling for stretching of DNA molecules.

This report shows a new DNA stretching method using migration of an ice-water interface. DNA molecules were stretched accompanying the migration of the solid-liquid interface and immobilized in frozen area. This simple method needs no chemical modification to keep DNA in the stretched form. For full stretching of DNA molecules, one terminus of the DNA molecules were anchored on silanized substrate. The anchored DNA molecules were stretched by freezing the DNA solution. The stretched DNA molecules were observed after sublimation of the frozen solution keeping its stretched form on silanized surface which had no attractive interaction with DNA molecules except for the SH-modified terminus in solution. An infrared (IR) laser beam was introduced to a frozen DNA solution through an objective lens for local area melting of the solution. Scanning of the laser irradiation caused stretching and enclosing of DNA molecules in the frozen area followed by migration of the solid-liquid interface.

Biophysical Phenomena↗

Indomethacin, but not Helicobacter pylori, inhibits adaptive relaxation in isolated guinea-pig stomach.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) are major factors in gastritis and peptic ulcer However, the role of NSAIDs and H. pylori infection in dyspepsia remains unclear. Gastric adaptive relaxation may be related to the pathogenesis of functional dyspepsia because the response is often disturbed in dyspeptic patients. In this study, we investigated the effects of indomethacin or H. pylori water extracts on gastric adaptive relaxation. This experiment was performed using the modified method of Desai et al. Isolated guinea-pig stomach in an organ bath was monitored for intragastric pressure and volume. Adaptive relaxation was induced by gastric luminal distention. The effects of indomethacin and H. pylori on gastric relaxation were tested in this system. Indomethacin (> 1 x 10(-5) M) significantly inhibited adaptive relaxation. Indomethacin (> 3 x 10(-6) M) induced gastric relaxation in a dose-dependent fashion. However, aspirin at a concentration sufficient for cyclooxygenase (COX)-1 inhibition did not induce gastric relaxation. Preincubation with N-nitro-L-arginine methyl ester, a nitric oxide (NO)-synthase inhibitor, inhibited indomethacin-induced gastric relaxation. Adaptive relaxation was not affected by H. pylori water extracts. In conclusion, indomethacin inhibited adaptive relaxation via prior gastric relaxation. NO production, but not COX-1 inhibition, may be involved in this effect of indomethacin. H. pylori water extracts may not have direct effects on adaptive relaxation. Inhibition of adaptive relaxation may be one of the major mechanisms underlying NSAID-induced dyspepsia.

Animals↗

Comparison of the effects of rebamipide with those of cimetidine on chronic gastritis associated with Helicobacter pylori in Mongolian gerbils.

BACKGROUND AND AIMS: The effects of rebamipide on chronic gastritis associated with Helicobacter pylori have not been well-defined. We compared these effects of rebamipide with those of cimetidine in Mongolian gerbils infected with H. pylori. METHODS: Mongolian gerbils with or without H. pylori were divided into 10 groups 6 weeks after inoculation and fed diets containing a drug (rebamipide or cimetidine) or control diet. All animals were sacrificed 4 weeks after grouping. Their stomachs were examined for histology, colonization by H. pylori, myeloperoxidase activity (myeloperoxidase), production of neutrophil chemokine (CINC/KC) and tumour necrosis factor-alpha (TNF-alpha), and serum gastrin levels. RESULTS: H. pylori colonized all of the inoculated animals. Neither rebamipide nor cimetidine decreased myeloperoxidase activity, but each reduced wet stomach weight in H. pylori-infected animals. The amount of increase in CINC/KC and TNF-alpha in gastric tissue caused by H. pylori infection was decreased by treatment with rebamipide or cimetidine. H. pylori infection increased serum gastrin levels, and this increase was significantly enhanced by cimetidine but not rebamipide. CONCLUSIONS: Rebamipide may improve H. pylori-infected chronic gastritis by preventing the production of inflammatory cytokines and chemokines, as does cimetidine, but may be preferable to cimetidine for long-term administration for treatment of H. pylori-infected chronic gastritis due to its effect on serum gastrin levels.

Alanine↗

Thoracoscopic internal mammary sentinel node biopsy for breast cancer.

Sentinel node (SN) biopsy has changed the management of breast cancer. This pilot study assessed the utility of lymphatic mapping and thoracoscopic SN biopsy for internal mammary node (IMN) staging. Forty-nine breast cancer patients underwent lymphatic mapping using 99mTc-tin colloid. Patients with IMSNs underwent thoracoscopic biopsy. Lymphoscintigraphy showed IMSNs in 15 of 49 cases (31%). The incidence of IMN drainage was relationed to age and tumor location; 50% of patients younger than age 40 and 43% with tumors located in inner quadrants had IMN drainage. The thoracoscopic procedure was performed in 11 of 15 patients, and 18 IMSNs were removed; the time of the procedure ranged from 20 to 60 min. No patients had complications from the procedure. Two of 11 patients (18%) had IMSN metastasis, and one of them had only IMN metastasis. Lymphatic mapping and the thoracoscopic approach were useful for IMSN biopsy. They may enable the physician to make an appropriate treatment decision for breast cancer.

Adult↗

High molecular protein of Helicobacter pylori responsible for inhibition of ornithine decarboxylase activity of human gastric cultured cells.

BACKGROUND: Ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, mediates epithelial cell proliferation and plays a critical role in the optimal repair of gastric mucosal damage. Several studies have shown that Helicobacter pylori inhibits the growth and proliferation of gastric cells in vitro. AIM: To test whether H. pylori extract affects ODC mRNA expression and its enzyme activity in gastric cells and to examine the partial characterization of the molecule responsible for this effect. METHODS: Human gastric cells (MKN-45) were used. Bacterial extracts from various E. coli or H. pylori strains, namely (1) cagA+, vacA+, CagA+, VacA+; (2) cagA+, vacA+, CagA+ VacA-; or (3) cagA-, vacA+, CagA-, VacA- were added to the cells. Cell proliferation was assessed by [3H]-thymidine incorporation, viability by MTT assay and LDH release test, ODC enzyme activity by 14CO2 counts from L-[1(14)C]ornithine, and ODC mRNA by Northern blotting. RESULTS: H. pylori and E. coli extract did not affect viability of gastric cells. H. pylori extract, especially extracts containing a protein greater than 50 kDa, significantly inhibited proliferation and ODC activity of gastric cells while E. coli extract had no effect. Inhibition of ODC activity was found in extracts of all H. pylori strains, irrespective of CagA and VacA protein expression. Serum stimulation induces an increase in ODC mRNA while H. pylori extract did not affect ODC mRNA expression. CONCLUSION: High molecular weight (greater than 50 kDa) proteins of H. pylori extract without CagA or VacA protein inhibited proliferation and ODC activity of human gastric cells, but did not affect ODC mRNA expression, suggesting that inhibition of ODC activity is regulated at the post-transcriptional level.

Antigens, Bacterial↗

Increased expression of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats.

BACKGROUND: Epidermal growth factor (EGF), which binds to EGF receptors (EGF-R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF-R expression is present and confined to the basal layer. AIM: To examine histological changes in and dynamics of EGF-R expression during healing after acid reflux oesophagitis in a rat model. METHODS: Gastric acid reflux oesophagitis was induced in Wistar rats by ligation of the pylorus and the transitional region between the forestomach and the grandular portion for 5 h, followed by release of both ligations. Rats were killed 7 and 14 days after production of oesophagitis to examine macroscopic and histological changes as well as dynamics of EGF-R expression. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of EGF-R mRNA and protein by RT-PCR and Western blotting or immunohistochemistry. RESULTS: Gastric acid reflux induced erosive and ulcerative mucosal lesions in the lower and middle part of the oesophagus. These lesions were healed by 14 days and histologically showed thickening of the oesophageal epithelium from 41.11 +/- 3.09 microm in controls to 142.73 +/- 11.59 microm (P < 0.001) in ligated rats, as well as elongation of papillae and basal cell hyperplasia. The number of BrdU-positive cells among basal cells on day 14 was significantly increased from 7.1 +/- 0.8/field in controls to 30.9 +/- 3.0/field in ligated rats. Expression of EGF-R mRNA and protein was significantly increased on day 14 and most basal cells were immunohistochemically positive in both BrdU and EGF-R staining. CONCLUSION: Acid reflux-induced oesophageal injury caused basal cell hyperplasia with an increase in cell proliferation and EGF-R expression. Activation of EGF-R gene and protein in response to acid reflux-induced injury may facilitate mucosal healing. These results suggest that epidermal growth factor receptors play a crucial role in healing after acid reflux oesophagitis in rats.

Amino Acid Sequence↗

Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma.

BACKGROUND: Since endoscopic treatment was first evaluated and established as a treatment for patients with early stage gastric carcinoma, metachronous disease recurrence at other sites in the stomach after endoscopic treatment has become a major problem. METHODS: A retrospective case-control study was conducted on 10 patients with metachronous recurrence of gastric carcinoma after undergoing successful endoscopic mucosal resection (EMR) therapy for early stage gastric carcinoma and on 14 patients without recurrence. Gastric mucosal tissues obtained during the initial EMR were dissected, and DNA samples from the tumor tissue and surrounding nonneoplastic mucosa were extracted separately. Microsatellite instability (MSI) was tested in five microsatellite markers (D2S137, D3S1067, TP53, TGFbetaRII, and BAX). The authors also looked for K-ras codon 12 point mutations in the tumor tissues. In addition, immunohistochemical staining was done to test for the presence of proliferating cell nuclear antigen (PCNA), p53, hMSH2, and hMLH1 in the mucosal tissues. Finally, the correlation between the presence or absence of metachronous recurrence and the characteristics of the primary tumor (MSI, K-ras, p53, etc.) were investigated. RESULTS: Three of 10 patients with recurrent disease showed MSI in more than two microsatellite markers among 3-5 investigated site (MSI-H), whereas none of the patients with nonrecurrent disease did so. There was no significant correlation between metachronous recurrence after EMR and immunohistochemical staining reactions, including those for PCNA, p53, hMSH2, and hMLH1. None of the patients showed K-ras mutations. CONCLUSIONS: Thirty percent of patients with recurrent disease showed MSI-H, whereas none of the patients with nonrecurrent disease did so.

Adaptor Proteins, Signal Transducing↗

Characterization of the amino acid transport of new immortalized choroid plexus epithelial cell lines: a novel in vitro system for investigating transport functions at the blood-cerebrospinal fluid barrier.

PURPOSE: To establish and characterize a choroid plexus epithelial cell line (TR-CSFB) from a new type of transgenic rat harboring the temperature-sensitive simian virus 40 (ts SV 40) large T-antigen gene (Tg rat). METHODS: Choroid plexus epithelial cells were isolated from the Tg rat and cultured on a collagen-coated dish at 37 degrees C during the first period of 3 days. Cells were subsequently cultured at 33 degrees C to activate large T-antigen. At the third passage, cells were cloned by colony formation and isolated from other cells using a penicillin cup. RESULTS: Five immortalized cell lines of choroid plexus epithelial cells (TR-CSFB 1 approximately 5) were obtained from two Tg rats. These cell lines had a polygonal cell morphology, expressed the typical choroid plexus epithelial cell marker, transthyretin, and possessed Na+, K+-ATPase on their apical side. TR-CSFBs cells expressed a large T-antigen and grew well at 33 degrees C with a doubling-time of 35 approximately 40 hr. [3H]-L-Proline uptake by TR-CSFB cells took place in an Na+-dependent, ouabain-sensitive, energy-dependent, and concentration-dependent manner. It was also inhibited by alpha-methylaminoisobutylic acid, suggesting that system A for amino acids operates in TR-CSFB cells. When [3H]-L-proline uptake was measured using the Transwell device, the L-proline uptake rate following application to the apical side was five-fold greater than that following application to the basal side. In addition, both Na+-dependent and Na+-independent L-glutamic acid (L-Glu) uptake processes were present in TR-CSFB cells. CONCLUSIONS: Immortalized choroid plexus epithelial cell lines were successfully established from Tg rats and have the properties of choroid plexus epithelial cells, and amino acid transport activity was observed in vivo.

Amino Acids↗

Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese population.

AIM: To investigate the prevalence of functional dyspepsia and Helicobacter pylori infection and their relationship in a Japanese population. METHODS: Two thousand five hundred people who visited Shimane Institute of Health Science for their annual medical check-up from September 1998 to August 1999 were prospectively enrolled in the study. After routine medical examination, including an upper gastrointestinal study and an ultrasonographic examination, all subjects were asked standard questions to check for the presence of any symptoms that suggested dyspepsia. Helicobacter pylori infection was determined by using a serum IgG antibody concentration with an ELISA. RESULTS: Of the 2,500 persons investigated, 2,263 showed no abnormal finding in any medical examination. The presence or absence of symptoms and H. pylori infection was investigated in these 2,263 cases. Of these, 201 people (8.9%) experienced nausea, fullness and/or early satiety and were diagnosed as having dysmotility-like dyspepsia, while 118 people (5.2%) experienced pain localized to the epigastrium and were diagnosed as having ulcer-like dyspepsia. The frequency of these symptoms had a tendency to decline with age, although this was not statistically significant. In contrast, the rate of H. pylori infection increased with age. There was no significant relationship between H. pylori infection and any type of functional dyspepsia. CONCLUSIONS: Helicobacter pylori infection does not influence the prevalence of the dysmotility-like and ulcer-like dyspeptic symptoms.

Adult↗

EUS-guided one-step drainage of pancreatic pseudocysts: experience in 3 patients.

BACKGROUND: EUS-guided drainage has been recognized as a nonsurgical treatment for pancreatic pseudocysts. Bleeding at the puncture site is a known complication of this procedure. This is a report of the use of new equipment for one-step drainage without the use of an electrosurgical needle. METHODS: EUS-guided cystoenterostomy was performed in 3 patients. The mean size of the pseudocysts was 8 cm (head = 1, body = 2). A needle and drainage tube were inserted in a one-step procedure into the cyst through the accessory channel of an echoendoscope under EUS. The drainage tube was released immediately after insertion. OBSERVATIONS: All 3 patients were treated successfully without complication. A drainage tube was inserted through the duodenal bulb (n = l) and the body of the stomach (n = 2). The drain was removed after 1 month in all patients. Two of the 3 drains were obstructed by sludge. One pseudocyst recurrence was observed at a mean follow-up of 3.6 months (range 2-6 months). CONCLUSIONS: The EUS-guided one-step system is simple to use and suitable for drainage of pancreatic pseudocysts. It appears to minimize the risk of hemorrhage.

Adolescent↗

The effects of epidural block on the distribution of lymphocyte subsets and natural-killer cell activity in patients with and without pain.

Although epidural anesthesia prevents immune suppression during surgery, no reports have elucidated how epidural block affects immune response in nonsurgical patients. We examined changes in proportion of lymphocyte subsets and in natural-killer (NK) cell activity in patients with and without pain. Fifteen patients with pain (Pain group) and 15 preoperative patients without pain (Preoperative group) received three different treatments in random order: epidural block with 7 mL 1% lidocaine, epidural injection of an identical volume of normal saline, and IV injection of 1 mg/kg lidocaine. Blood samples were drawn before and after 30, 60, and 120 min of treatment. During epidural block at 30 and 60 min, both groups showed significantly decreased epinephrine, norepinephrine, and cortisol levels, and the proportion of NK cells decreased, whereas the CD4+/CD8+ ratio increased significantly. NK cell activity in both groups decreased significantly at 30 and 60 min. At 120 min, the variables had all returned to preblock values. During treatments with saline and IV lidocaine, neither group showed significant changes in any of the above variables. We conclude that epidural block causes a transient and significant alteration of lymphocyte subsets and NK cell activity regardless of pain status.

Adrenocorticotropic Hormone↗