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Biomedical subjects

M Nakamura

Publications and source records attributed to M Nakamura.

At least 109 records · Page 6Linked to original sources
PubMed2004

Reflux esophagitis after eradication of Helicobacter pylori is associated with the degree of hiatal hernia.

BACKGROUND: Several studies have shown that reflux esophagitis (RE) occurs after eradication of Helicobacter pylori. However, endoscopic findings do not allow prediction of the development of RE after successful treatment. In this study, we evaluated the relationship between the prevalence of RE after eradication therapy and the degree of hiatal hernia. METHODS: The study comprised 148 patients who had undergone H. pylori eradication therapy over the past 5 years. The degree of RE and hiatal hernia was evaluated based on endoscopic findings. Hiatal hernia was graded according to Hill's gastroesophageal flap valve (GEFV; grades I-IV) classification. RE after eradication therapy was graded according to the Los Angeles classification system. H. pylori infection was confirmed in all patients by culture, urease test and histological examination of antral and fundic biopsy specimens. RESULTS: Among 148 patients, there were 122 patients (82.4%) with successful and 26 (17.6%) with failed eradication therapy. RE was diagnosed in 25 (20.5%) out of 122 patients with successful therapy but only in 1 (3.8%) out of 26 patients with failed therapy (P < 0.05). After successful eradication, 25 patients had mild RE (12 with grade A, 13 with grade B). Among patients of the successful eradication group (n = 122), RE was diagnosed in 2 (5.3%) out of 38 patients without hiatal hernia and in 23 (27.4%) out of 84 patients with hiatal hernia (P = 0.0051). Furthermore, RE was diagnosed in 2 (5.3%) out of 38 patients with GEFV grade I, 13 (24.1%) out of 54 with grade II, 7 (30.4%) among 23 with grade III, and 3 (42.9%) out of 7 patients with grade IV. The pH level of gastric juice after eradication therapy was lower in the group with successful eradication than in the group with failed therapy regardless of the incidence and degree of RE. CONCLUSIONS: There is a high incidence of RE after successful H. pylori eradication therapy. This incidence of RE was closely associated with the presence and degree of hiatal hernia and with the decrease in gastric juice pH. These findings suggest that the presence of hiatal hernia together with increase in gastric acidity are important determinant factors for the development of RE after successful H. pylori eradication therapy.

Endoscopy, Gastrointestinal↗
PubMed2004

Prediction of differences in in vivo oral clearance of N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl] ethylamine monohydrochloride (NE-100) between extensive and poor metabolizers from in vitro metabolic data in human liver microsomes lacking CYP2D6 activity and recombinant CYPs.

1. It has previously been reported that N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) was predominantly metabolized by cytochrome P450 (CYP) 2D6 in human liver microsomes (HLM). In the present study, the contribution of CYP forms involved in the formation of the major metabolites of NE-100 in human liver lacking CYP2D6 activity (PM-HLM) has been predicted by use of in vitro kinetic data on recombinant CYPs microsomes (rCYPs). 2. In PM-HLM, NE-100 is predicted to be metabolized to N-despropyl-NE-100 (NE-098), p-hydroxy-NE-100 (NE-152) and m-hydroxyl-NE-100 (NE-163), but not to O-demethy-NE-100 (NE-125), which is a major metabolite in pooled human liver microsomes (EM-HLM). The relative activity factor approach assumed that NE-098 formation is predominantly catalysed by CYP3A4 and CYP2C9 and the NE-152+163mix (a mixture of two hydroxylated metabolites, NE-152 and NE-163) formation is only catalysed by CYP3A4. 3. The predicted contribution rates of CYP3A4 and CYP2C9 for NE-098 formation were 58.1 and 34.6%, respectively, in PM-HLM. These predicted results were strongly supported by kinetic and inhibition studies using PM-HLM. The intrinsic clearance of NE-100 predicted from rCYPs (the predicted CLint-HLM-total) corresponded to those observed from EM- and PM-HLM (the observed CLint-HLM). 4. The in vivo oral clearance (CLoral) of NE-100 in extensive metabolizers and poor metabolizers of CYP2D6 was predicted to be 50times higher in extensive metabolizers than poor metabolizers using in vitro-in vivo scaling method based on the dispersion model. These data suggest that polymorphism of CYP2D6 might greatly affect NE-100 metabolism in vivo.

Administration, Oral↗
PubMed2004

Expression of leptin in two-layered culture of gastric mucous cells and fibroblasts: effect of Helicobacter pylori attachment.

BACKGROUND: Our recent histochemical studies have revealed an increase in myofibroblasts and in leptin and its receptor in endothelial cells, and myofibroblasts in Helicobacter pylori-infected human and Mongolian gerbil fundic mucosa. AIM: The present study was undertaken to clarify the H. pylori-induced interaction between leptin in cultured gastric surface mucous cells and fibroblasts. METHODS: GSM06 cells were incubated with an air- liquid interface on a collagen gel layer containing mouse fibroblast cell line L929. Medium containing H. pylori bacilli (ATCC43504) at 10-100 times higher concentration than the GSM06 cells was added from the luminal side and the localization of leptin was observed by immunohistochemistry. The transformation of L929 cells to myofibroblasts was detected by electron microscopy and PR 2D3 immunoreactivity. RESULTS: L929 cells in the control group showed a spindle shape with scarce cytoplasm. In the H. pylori-treated group, L929 cells showed features characteristic of myofibroblasts, and most GSM06 and L929 cells showed leptin immunoreactivity. In contrast, L929 cells incubated with H. pylori alone did not undergo this differentiation. CONCLUSIONS: Attachment of H. pylori to surface epithelial cells caused conversion of fibroblasts to myofibroblasts. We suggest that leptin plays a role in this transformation.

Animals↗
PubMed2004

Vital role of the itch-scratch response in development of spontaneous dermatitis in NC/Nga mice.

BACKGROUND: The itch sensation and the resultant response, scratching, are important symptoms of atopic dermatitis (AD) and have a significant impact on the quality of life of affected patients. However, the influence of the itch-scratch response on the pathology of AD has not been precisely elucidated. OBJECTIVES: To investigate the role of scratching behaviour in the development of spontaneous dermatitis using conventionally raised NC/Nga mice (Conv-NC mice), which are known to be an animal model for human AD. METHODS: Capsaicin-sensitive sensory nerves of the mice were ablated by neonatal capsaicin treatment (Cap-NC mice), and the development of spontaneous dermatitis in the Cap-NC mice was compared chronologically with that in Conv-NC mice. RESULTS: Scratching behaviour was almost completely prevented in Cap-NC mice raised for 84 days under conventional conditions, and the development of dermatitis and elevation of the serum IgE level were significantly suppressed. Histological analysis revealed that the numbers of infiltrating eosinophils and mast cells in the lesional skin of Cap-NC mice were lower than those in Conv-NC mice. Immunological studies showed that the capability of spleen T cells to produce both T-helper (Th) 1 (interferon-gamma) and Th2 [interleukin (IL)-5 and IL-13] cytokines was diminished in Cap-NC mice. Furthermore, serum levels of IL-18 were approximately twice higher in Conv-NC mice than in Cap-NC mice. CONCLUSIONS: These observations suggest that scratching behaviour contributes to the development of dermatitis by enhancing various immunological responses in the murine AD model, implying that prevention of the itch sensation and/or itch-associated scratching behaviour is an effective treatment for AD.

Animals↗
PubMed2004

Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1beta stimulated rheumatoid synovial fibroblasts.

Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.

Aniline Compounds↗
PubMed2004

Neonatal alloimmune thrombocytopenia due to an antibody against a labile component of human platelet antigen-3b (Bak b).

We report the second case of neonatal alloimmune thrombocytopenia due to anti-human platelet antigen (HPA)-3b (Bak(b)) antibody. The infant was severely affected with intracranial haemorrhage. Most importantly, we were able to detect this antibody only by using fresh, unfixed platelets as antigen. This antibody was detectable neither by conventional mixed passive haemagglutination, platelet immunofluorescence test using fixed platelets, nor by monoclonal antigen immobilization of platelet antigen assay using solubilized platelets. We assume that this antibody reacts only with fresh platelets and that the antigen is a labile component of HPA-3b (Bak(b)).

Antigens, Human Platelet↗
PubMed2004

Effects of modification at the fifth residue of mu-conotoxin GIIIA with bulky tags on the electrically stimulated contraction of the rat diaphragm.

Mu-conotoxin GIIIA, a peptide toxin from the cone snail, blocks muscle-type sodium channels. Thr-5 of mu-conotoxin GIIIA, located on the opposite side of the active site in the globular molecule, was replaced by Cys to which the bulky tags were attached. The tagged mu-conotoxin GIIIA derivatives, except for the phospholipid-tagged one, exerted the biological activity with a potency slightly weaker than natural mu-conotoxin GIIIA. When the biotinylated tags of various lengths were added, the presence of avidin suppressed the action of the biotinylated toxins of <4 nm, but not with 5 nm. The bulky biotinylated tags are useful as a caliper to measure the depth of receptor sites in the channels.

Amino Acid Sequence↗
PubMed2004

The prognostic value of progesterone receptor status in meningiomas.

BACKGROUND: Meningiomas are known to recur frequently, and their longterm management remains controversial. Previous studies indicate that progesterone and its receptors can play a role in the recurrence of meningiomas, but the correlation between the presence of these receptors and patients' outcome is unclear. AIM: To conduct a retrospective analysis to investigate the prognostic relevance of progesterone receptor (PR) expression in meningiomas. METHODS: Five hundred and eighty eight meningiomas operated on over a period of 10 years were examined immunohistochemically to determine the PR status using monoclonal antibodies. Several factors including recurrence (mean follow up of 65 month), sex, tumour tissue consistency, location, vascularity, and en plaque appearance were analysed. RESULTS: PR status showed comparable values for men and women. World Health Organisation (WHO) grade II and III tumours had significantly fewer receptors than benign meningiomas. There was no significant correlation between PR status and recurrence rates in WHO grade I totally removed meningiomas. However, a combination of PR status and proliferation indices was shown to predict recurrence reliably. CONCLUSIONS: Together with routine histological evaluation, PR status can help to describe the biological behaviour of meningiomas. Only a combination of clinical and biological features can describe the behaviour of meningiomas, predict their recurrence, and help to devise more effective follow up strategies.

Adolescent↗
PubMed2004

MRI characteristics of sporadic CJD with valine homozygosity at codon 129 of the prion protein gene and PrPSc type 2 in Japan.

Two Japanese sporadic Creutzfeld-Jakob disease (sCJD) patients with valine homozygosity at codon 129 of the prion protein gene and protease-resistant prion protein (PrP(Sc)) type 2 (VV2) are described. In contrast with Western countries, this type of sCJD is very rare in Japan. In 123 sCJD cases, only two were recognised as VV2 by the Japanese CJD surveillance committee. The clinical symptoms and pathological findings of the patients were similar to those of European and US patients. The noteworthy finding of diffusion weighted MRI (DWI) was that an abnormal high intensity covered a wide range of the thalamus including the dorsomedial nucleus, the pulvinar, and the ventral anterior, lateral, and posterolateral nuclei. This thalamic pattern has not been recognised in sCJD with methionine homozygosity and PrP(Sc) type 1 (MM1) or methionine/valine heterozygosity and PrP(Sc) type 1 (MV1) which comprises the vast majority of sCJD. This finding may be characteristic to VV2 and may distinguish it from MM1, MV1, and variant CJD. DWI can provide a very important clue for the antemortem diagnosis of VV2 subjects.

Aged↗
PubMed2004

Histopathology, pathogenesis and molecular genetics in primary central nervous system lymphomas.

Recent increases in the incidence of primary central nervous system lymphoma (PCNSL), a rare non-Hodgkin's lymphoma arising in the brain, have been noted in both immunodeficient and immunocompetent patients. Compared with lymphomas originating outside the central nervous system, the biology of PCNSL at the molecular or cytogenetic level has not been well characterized, yet it is important to thoroughly understand the etiology of this rare malignant lymphoma if effective therapies are to be developed. This review will focus on the epidemiology, clinical aspects, histopathology, pathogenesis, and molecular genetics of this aggressive, extranodal lymphoma in immunocompetent patients.

Animals↗
PubMed2004

Effects of biotin supplementation on serum biotin levels and physical properties of samples of solar horn of Holstein cows.

Effects of dietary biotin supplementation on serum biotin levels and physical properties of sole horn of 40 Holstein cows were evaluated. The mean serum biotin level in biotin-supplemented cows after 10 mo of biotin supplementation (1163.2 +/- 76.2 pg/mL) was significantly higher (P = 0.007) than that in control cows (382.0 +/- 76.2 pg/mL). The sole horn of biotin-supplemented cows was significantly harder (P = 0.026) and had a significantly lower moisture content (P = 0.021) than that of control cows. No morphologic differences in horn tubules or intertubular horn were found between the biotin-supplemented and control cows. The total lipid content of sole horn was significantly higher (P = 0.030) in the biotin-supplemented cows than in the control cows. These results suggest that dietary biotin supplementation causes increases in serum biotin levels and changes in physical properties and fat content of sole horn.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Computational study on the evolution of an intraventricular vortical flow during early diastole for the interpretation of color M-mode Doppler echocardiograms.

A computational fluid dynamics study of intraventricular flow during early diastole was carried out using a 3D model of the human left ventricle (LV). It was found that a vortical flow formed under the aortic orifice and then grew in size and extended laterally along the ventricular wall towards the posterior side. With further expansion of the LV, it developed into an annular vortex asymmetrically enlarged on the side of the aortic orifice, narrowing the passage of blood inflow and thus causing a shift of the high-velocity portion of inflow towards the apex. This appeared as an elongation of the aliasing area when the velocity of the inflow was expressed as a spatiotemporal map in the same manner as a color M-mode Doppler (CMD) echocardiogram. Based on these findings, it was concluded that the shape of the aliasing area in a CMD echocardiogram shows the change in the velocity of blood inflow affected by the development of an annular vortex formed in the LV.

Blood Flow Velocity↗
PubMed2003

Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1.

AIMS/HYPOTHESIS: The healing of corneal epithelial wounds is often delayed in individuals with diabetes. The effect of the combination of a substance P-derived tetrapeptide (phenylalanine-glycine-leucine-methionine amide, or FGLM-NH(2)) and insulin-like growth factor-1 (IGF-1) on corneal epithelial wound healing was investigated in rats with streptozotocin-induced diabetes. METHODS: The corneal epithelium of diabetic and non-diabetic rats was removed, and the animals were treated by the application of eye drops containing FGLM-NH(2) and IGF-1, or vehicle alone as a control, six times a day for 3 days. The area of the corneal epithelial wound was measured at various times up to 72 h after removal of the corneal epithelium. RESULTS: The rate of corneal epithelial wound healing was slower in diabetic rats treated with vehicle than in non-diabetic rats. However, the rate of wound closure in diabetic rats treated with FGLM-NH(2) and IGF-1 was markedly increased compared with that in diabetic rats treated with vehicle. The wound healing process seemed similar in normal rats and in diabetic rats treated with FGLM-NH(2) and IGF-1. CONCLUSION/INTERPRETATION: The combination of FGLM-NH(2) and IGF-1 promotes corneal epithelial wound healing in diabetic rats, suggesting that such a treatment might prove effective in humans with diabetic keratopathy.

Animals↗
PubMed2003

Overexpression of leucocyte common antigen (LAR) P-subunit in thyroid carcinomas.

Protein tyrosine phosphatase (PTPase) dephosphorylation and protein tyrosine kinase (PTKs) phosphorylation of key signal transduction proteins may be regulated by extracellular signals, making PTPases important in the regulation of cell proliferation. Leucocyte common antigen (LAR), a receptor-like PTPase, consists of E-subunit, containing the cell adhesion molecule-like receptor region, and P-subunit specific for a short segment of the extracellular region, the transmembrane peptide, and two cytoplasmic PTPase domains. We produced a monoclonal antibody against the LAR P-subunit for immunohistochemical screening of LAR expression in normal and tumourous tissues. Gliomas and gastric, colorectal, lung, breast and prostate cancers showed weak and relatively infrequent expression. Intense and diffuse expression, however, was detected in 95% (227 out of 239) of thyroid carcinomas, but only 12% (22 out of 128) of adenomas and no cases of benign thyroid disease were immunopositive. In contrast to broad staining in carcinomas, LAR expression in thyroid adenomas was often found in small focal or locally invasive areas. Western blot analysis similarly detected LAR P-subunit protein in thyroid carcinomas, but not in normal tissues. We believe this to be the first demonstration of LAR overexpression in thyroid carcinoma and may help to elucidate the role of PTPases in the development of malignancy.

Antigens, CD↗