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Biomedical subjects

H Yamamoto

Publications and source records attributed to H Yamamoto.

At least 73 records · Page 4Linked to original sources

Comparison of hemostatic effects by route of H2 receptor antagonist administration following endoscopic mucosal resection in patients with neoplastic gastric lesions.

BACKGROUND: To date, there has not been an in-depth investigation to identify differences in the effects of bleeding prevention among different routes of administration of H2 receptor antagonists to treat gastric ulcers following endoscopic mucosal resection (EMR). AIM: To prospectively compare the frequency of bleeding following EMR between patients treated with intravenous (IV) famotidine and those with oral famotidine. METHODS: Fifty-three patients with neoplastic gastric lesions (33 carcinoma and 20 adenoma) treated by EMR were included. Subjects underwent EMR with circumferential mucosal incision assisted by submucosal injection of sodium hyaluronate (EMRSH), followed by IV or oral (PO) administration of famotidine at a dosage of 40 mg/day for 2 days. Patients with odd ID numbers were assigned to IV therapy (30 cases) while even numbers were given PO therapy (23 cases). Frequencies and endoscopic findings of bleeding during the first 2 days after EMR were examined. RESULTS: Frequency of bleeding within 2 days after EMR was 3 and 4% in IV and PO patients, respectively, showing no significant difference. No significant difference was seen in the endoscopic findings of bleeding and therapy, either, with respective IV and PO findings at 23 and 26%. CONCLUSIONS: No significant difference was observed in frequency of bleeding within 2 days after gastric EMR between IV and oral administrations of famotidine.

Adenocarcinoma↗

Influence of viral infection on the development of nasal hypersensitivity.

BACKGROUND: The underlying relationship between viral infections and allergic diseases of the upper respiratory tract has not been well clarified. METHODS: In order to clarify the relationship between viral infection and nasal hypersensitivity, mice were sensitized with ovalbumin (OVA) and then infected intranasally with respiratory syncytial virus (RSV), after which their nasal sensitivity to histamine or antigen was examined. RESULTS: Non-sensitized mice showed transient mild nasal hypersensitivity following nasal administration of histamine after intranasal RSV inoculation. In mice sensitized with OVA, RSV infection significantly exaggerated their nasal hypersensitivity to histamine and OVA. Treatment of these mice with a neurokinin (NK)-1/NK-2 receptor antagonist, but not with anti-IL-5 antibodies, reduced their hypersensitivity. The infiltration of nasal mucosa with eosinophils was temporarily associated with accelerated rate of RSV elimination in these animals. CONCLUSION: RSV infection induced transient nasal hypersensitivity. Several mechanisms, including impairment of nasal epithelial cells are thought to mediate this effect. In allergen-sensitized mice, RSV inoculation strongly enhanced nasal hypersensitivity.

Administration, Intranasal↗

Accumulation of plasma cells expressing CXCR3 in the synovial sublining regions of early rheumatoid arthritis in association with production of Mig/CXCL9 by synovial fibroblasts.

Accumulation of plasma cells in the synovium is one of the diagnostic hallmarks in the histopathological manifestations of rheumatoid arthritis (RA). This seems to be prominent even prior to significant B cell infiltration and/or formation of lymphoid follicles in the synovium. To clarify the mechanism of early plasma cell accumulation, we examined in situ expression of chemokines and their receptors using synovial targeting biopsy specimens, which were obtained under arthroscopy from early RA patients. By immunohistochemical staining, plasma cells were found to express a chemokine receptor CXCR3, while synovial fibroblasts in the synovial sublining regions expressed its ligand, Mig/CXCL9. By reverse transcription-polymerase chain reaction (RT-PCR), using targeted lesions of synovial tissues obtained by laser capture microdissection, expression levels of Mig/CXCL9 in the synovial sublining regions were remarkably high and were likely to be associated with interferon (IFN)-gamma expression. Furthermore, cultured synovial fibroblasts were confirmed to produce Mig/CXCL9 upon stimulation with IFN-gamma. Our results indicate that in the early stage of RA, plasma cells expressing CXCR3 may be recruited directly from the circulation into the synovial sublining regions by its ligand, Mig/CXCL9, produced by synovial fibroblasts.

Adult↗

Clinical usefulness of oral granisetron hydrochloride for alleviation of delayed nausea and vomiting induced by CPT-11.

This open label pilot study evaluated the safety and efficacy of the oral 5-HT3 receptor antagonist granisetron for prophylaxis of delayed chemotherapy-induced nausea and vomiting (CINV) in 30 patients with advanced or recurrent colorectal cancer. Patients were studied during two cycles of a 5-week regimen with irinotecan (CPT-11) and UFT. Patients received prophylactic anti-emetic therapy that included intravenous granisetron. If Grade 1 or higher severity gastrointestinal symptoms occurred during 6 days after CPT-11 administration in Cycle 1, then oral granisetron was administered daily for the following 5 days of CPT-11 in Cycle 2. Sixteen patients (53.3%) experienced delayed CINV in Cycle 1. The incidence of Grade 2 or higher vomiting was 32.1% and 27.7% in Cycles 1 and 2 in males (P = 0.554) respectively, and 54.6% and 32.4% in females (P = 0.001) respectively. Granisetron is effective against delayed Grade 2 or higher vomiting induced by CPT-11/UFT in female patients, although granisetron alone may not sufficiently control nausea induced by this regimen.

Administration, Oral↗

Pericryptal fibroblast sheath in intestinal metaplasia and gastric carcinoma.

BACKGROUND AND AIMS: In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype which is closely related to gastric carcinoma. However, to date, it has not been elucidated whether the intestinal metaplasia is merely a change in the epithelium or whether the underlying mesenchyme also changes from gastric type to intestinal type. We have investigated the relationship between intestinal metaplasia and the pericryptal fibroblast sheath (PCFS) in the mesenchyme. In addition, we also examined PCFS in gastric carcinoma. METHODS: We determined the existence of PCFS in the intestinal metaplastic mucosa and carcinoma of both human and Cdx2 transgenic mouse stomach. PCFS was determined using the antibody against alpha-smooth muscle actin and electron microscopic observations. RESULTS: PCFS formed an almost complete layer around the small and large intestinal crypts while it did not exist around the normal gastric glands in both mice and humans. PCFS was seen around the glands of intestinal metaplastic mucosa in both Cdx2 transgenic mouse and human stomachs. However, PCFS was virtually absent in the intestinal-type gastric adenocarcinoma area. CONCLUSION: We successfully demonstrated that the epithelium as well as the mesenchyme changed from the gastric type to the intestinal type in intestinal metaplasia and that PCFS disappeared in intestinal-type gastric carcinoma.

Actins↗

Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts.

BACKGROUND AND AIMS: Insulin-like growth factor (IGF) I receptor (IGF-Ir) signalling is required for carcinogenicity and proliferation of many tumours but this pathway has not been studied in detail in gastric cancer. We have previously shown successful therapy for colorectal, pancreatic, and lung cancer using recombinant adenoviruses expressing dominant negative (dn) IGF-Ir. In this study, we sought to better dissect the role of IGF-Ir on progression of gastric cancer and determine whether IGF-Ir targeted adenoviruses represent potentially effective therapeutics for human gastric cancer. METHODS: We assessed the effect of IGF-Ir ligands on proliferation and survival in gastric cancer cells in culture. Then, recombinant adenoviruses expressing truncated IGF-Ir (482 and 950 amino acids long, IGF-Ir/dn) that function as dn inhibitors were studied in the treatment of human gastric cancer xenografts. We characterised the effects of IGF-Ir/dn on signalling blockade, growth, apoptosis induction, and in vivo therapeutic efficacy. RESULTS: IGF-Ir signalling promoted tumour growth and survival in gastric cancer. IGF-Ir/dn expression suppressed tumorigenicity both in vitro and in vivo and upregulated stressor induced apoptosis. IGF-Ir/dn blocked Akt-1 activation induced by IGF-I, IGF-II, and des(1-3)IGF-I, but not by insulin. IGF-Ir/dn expression increased radiation and chemotherapy induced apoptosis and the combination of IGF-Ir/dn and chemotherapy was very effective against tumours in mice. In an intraperitoneal model, IGF-Ir/dn therapy also suppressed peritoneal dissemination. CONCLUSIONS: IGF-Ir is involved in the regulation of survival and cell growth in human gastric cancer and may be a good molecular therapeutic target. Adenovirus-IGF-Ir/dn may thus have therapeutic use in gastric cancer.

Adenoviridae↗

Tumour matrilysin expression predicts metastatic potential of stage I (pT1) colon and rectal cancers.

BACKGROUND AND AIMS: Nodal metastases are indisputable determinants of prognosis for colon and rectal cancer. Using classical histological criteria, many attempts to predict nodal metastasis have failed, preventing the adequate management of stage I (pT1) cancer. We investigated the role of tumour matrilysin in predicting metastatic potential, and discuss its potential use in individualising treatment of pT1 colon and rectal cancer. METHODS: The gene signature associated with nodal metastasis was investigated by cDNA array in 24 colon and rectal cancers. We studied 494 colon and rectal cancer patients to identify risk factors for nodal metastasis and evaluated the potential to predict nodal metastasis by either the logistic regression model or the Bayesian neural network model with built-in matrilysin. We then inferred possible causality of nodal metastasis from structural equation modelling. RESULTS: cDNA array revealed that matrilysin was maximally upregulated in the metastasis signature identified. Tumour matrilysin expression emerged as a stage independent risk factor for nodal metastasis, resulting in a similar predictive performance in receiver operating characteristic curve analysis in the two models. A Bayesian approach called automatic relevance determination identified matrilysin as one of the most relevant predictors examined. Structural equation modelling suggested possible direct causality between matrilysin and nodal metastasis. CONCLUSIONS: We have provided evidence that tumour matrilysin expression is a promising biomarker predicting nodal metastasis of colon and rectal cancer. Analysis of tumour matrilysin expression would help clinicians achieve the goal of individualised cancer treatment based on the metastatic potential of pT1 colon and rectal cancer.

Adenocarcinoma↗

Anode glow discharge plasma treatment of titanium plates facilitates adsorption of extracellular matrix proteins to the plates.

Glow discharge plasma (GDP) supplied to an anode (GDP+) promotes calcium phosphate adsorption onto titanium better than that supplied to a cathode (GDP-). However, the adsorption of extracellular matrix (ECM) proteins is crucial for cell adhesion to titanium. Since GDP+ induced both inorganic adsorption and cell adhesion, we hypothesized that the inorganic adsorption in a culture medium might affect the adsorption of the ECM proteins. In this study, ECM proteins adsorbed on titanium with and without GDP were examined by x-ray photoelectron spectroscopy. After 1 hr of incubation, increasing sodium adsorption on GDP+ specimens induced adsorption of ECM proteins as shown by NH(+) and COO(-) signals without calcium adsorption. In contrast, since no specific adsorption of sodium on GDP-specimens was detected, GDP-did not contribute to the adsorption of ECM proteins. Thus, promotion of sodium adsorption of GDP+ was effective, at least in the initial ECM protein adsorption on a titanium surface.

Adsorption↗

Colloidal beta-tricalcium phosphate prepared by discharge in a modified body fluid facilitates synthesis of collagen composites.

The development of hydroxyapatite/collagen composites that are naturally synthesized and need no additional treatment is required for use in bone repair. Since reducing the diameter can increase the specific surface area of calcium phosphate particles that can conjugate collagen molecules, we expected colloidal calcium phosphates of submicron diameter obtained by discharge to be effective in formulating these composites. Additionally, since biodegradable beta-tricalcium phosphate has better osteoconductivity than hydroxyapatite, this study aimed to investigate the synthesis of colloidal hydroxyapatite and beta-tricalcium phosphate/collagen composites. Collagen molecules were tightly polymerized in the beta-tricalcium phosphate/collagen composite by catalysis of the generated -P-O-P- polyphosphate chain. Bonding strength between collagen NH+ amino groups and -P-O-P-, and cross-linking of the Ca++-RCOO- in the collagen were increased compared with those in the hydroxyapatite/collagen composite. These chemical reactions due to colloidal beta-tricalcium phosphate might play a key role in the synthesis of collagen composites.

Biocompatible Materials↗

[Successful removal of T4 lung cancer with left atrial invasion after induction chemotherapy].

A 53-year-old man presented with cough, sputa and chest pain. The chest X-ray revealed a large mass shadow in the right lower lobe. Massive tumor extending into the left atrium was diagnosed by computed tomography (CT). The brushing cytology by broncoscopy was squamous cell carcinoma and its stage was IIIB. Chemothrapy using cisplatin, paclitaxel and gemcitabine hydrochloride was performed 8 courses during 6 months. The effect of the chemotherapy was complete response, enabling the surgical treatment. The right pneumonectomy with partial resection of the left atrium was performed by using vascular clamp. The defect of the left atrium could be sutured directly. Wide-spread necrotic change with very small amount of cancer cells in the atrial wall was confirmed by pathology. The patient has been well for 3 years and 6 months after surgery.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical and pathological differences between Mikulicz's disease and Sjögren's syndrome.

OBJECTIVE: Mikulicz's disease (MD) has been included within the diagnosis of primary Sjögren's syndrome (SS), but represents a unique condition involving enlargement of the lachrymal and salivary glands and characterized by few autoimmune reactions and good responsiveness to glucocorticoids. We have previously described elevated immunoglobulin (Ig) G4 in the serum of four patients with MD. In this paper, we accumulated more MD cases and undertook clinical and histopathological analysis of these patients to clarify differences between MD and SS. METHODS: We diagnosed seven patients with MD according to the following criteria: (i) visual confirmation of symmetrical and persistent swelling in more than two lachrymal and major salivary glands; (ii) prominent mononuclear infiltration of lachrymal and salivary glands; and (iii) exclusion of other diseases that present with glandular swelling, such as sarcoidosis and lymphoproliferative disease. We summarized the clinical and serological characteristics (IgG subclasses and IFN-gamma/IL-4 ratio) of seven patients with MD, compared with SS with glandular swelling (SSw) and without glandular swelling (SSo). After steroid administration, we analysed changes in IgG subclasses in MD. Labial salivary gland specimens in MD, SSw and SSo were stained with anti-IgG4 antibodies. RESULTS: The concentration (+/-s.d.) of IgG4 was 1169.7 +/- 892.2 mg/dl in MD, 24.4 +/- 7.0 mg/dl in SSw (P<0.005) and 82.6 +/- 189.7 mg/dl in SSo (P<0.005). The IFN-gamma/IL-4 ratio was 0.392 +/- 0.083 (0.78 +/- 0.23/2.14 +/- 0.31 IU/pg) in MD, 0.004 +/- 0.002 (0.20 +/- 0.07/57.02 +/- 14.05 IU/pg) in SSw (P<0.05) and 0.012 +/- 0.009 (0.58 +/- 0.86/116.24 +/- 207.65 IU/pg) in SSo (P<0.05). The concentration (+/-s.d.) of IgG4 in MD decreased to 254.0 +/- 50.3 mg/dl (P<0.05) after glucocorticoid treatment. Histopathologically, only MD was associated with prominent infiltration of IgG4-positive plasmacytes into lachrymal and salivary glands. CONCLUSION: Mikulicz's disease is quite different from SS clinically and histopathologically. MD is suggested to be an IgG4-related systemic disease.

Aged↗

Robust NADH-regenerator: improved alpha-haloketone-resistant formate dehydrogenase.

Formate dehydrogenases (FDH) are useful for the regeneration of NADH, which is required for asymmetric reduction by several dehydrogenases and reductases. FDHs have relatively low activity and are labile, especially to alpha-haloketones, thus FDH cannot be applied to the industrial manufacture of optically active alpha-haloalcohols. To stabilize a FDH from Mycobacterium vaccae (McFDH) against the alpha-haloketone ethyl 4-chloroacetoacetate (ECAA), a set of cysteine-mutant enzymes was constructed. Sensitivity to ECAA of mutant C6S was similar to that of the wild-type enzyme, and mutants C249S and C355S showed little activity. In contrast, mutant C256S exhibited remarkable tolerance to ECAA. Surprisingly, mutant C146S was activated by several organic compounds such as ethyl acetate. An optimized mutant, C6A/C146S/C256V (McFDH-26), was obtained by combining several effective mutations. Ethyl (S)-4-chloro-3-hydroxybutanoate [(S)-ECHB] was synthesized from ECAA to 49.9 g/l with an optical purity of more than 99% e.e. using recombinant Escherichia coli cells coexpressing McFDH-26 and a carbonyl reductase (KaCR1) from Kluyveromyces aestuarii.

Acetates↗