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Biomedical subjects

M Yamamoto

Publications and source records attributed to M Yamamoto.

At least 55 records · Page 3Linked to original sources
PubMed2005

Protective effect of a radical scavenger, MCI-186 on islet cell damages induced by oxidative stress.

Oxidative stress generated during islet isolation and transplantation causes islet cell damage. These oxidative injuries are mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). MCI-186 is an antioxidant used for clinical treatment of cerebral infarction in Japan. We examined a possible protective effect of MCI-186 on islet cells against oxidative stress. Islets isolated from Sprague-Dawley rats by collagenase P digestion were purified by density gradient centrifugation with Ficoll. Islets were treated with hydrogen peroxide (H(2)O(2); 5 to 250 micromol) in the presence or absence of MCI-186. Cell death was measured by an LDH release assay. Maximum islet cell death was observed at 250 micromol of H(2)O(2). MCI-186 inhibited islet cell death in a dose-dependent manner with significant reduction above 30 micromol. From the results observed we suggest that the antioxidant effects of MCI-186 may prove beneficial to improve the preservation of islet cells.

Animals↗
PubMed2005

Evaluation of tumor-specific promoter activities in melanoma.

Gene therapy is a novel therapy for melanoma. To date, however, there is still no powerful tumor specific promoter (TSP) to restrict the transgene expression in melanoma cells. In order to define a useful TSP for targeting in the context of melanoma gene therapy, four promoters, the cyclooxygenase-2 (Cox-2), alpha-chemokine SDF-1 receptor (CXCR4), epithelial glycoprotein 2 (EGP-2), and survivin, were tested in both established melanoma cell lines and primary melanoma cells. We employed recombinant adenoviral vectors (reAds) each with a candidate TSP (the Cox-2, CXCR4, EGP-2, or survivin), a reporter luciferase gene, and a poly-A signal, all of which were inserted into the E1-deleted region. A reAdGL3Bcytomegalovirus (CMV), containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity. Luciferase activity was measured in multiple tumor cell lines and two primary melanoma cell cultures after infection with reAds. Human epithelial melanocytes, HEM, were used as normal control. In contrast to three other promoters, the survivin promoter exhibited the highest activities within both melanoma cell lines and primary melanoma cells, but not in HEMs. Additionally, the survivin promoter exhibited very low activities in major mouse organs including the liver, in vivo. EGP-2 is not active in melanoma; messenger RNA expressions were correlated to promoter activities both in melanoma cell lines and primary cell cultures. Thus, these data suggest that the survivin promoter achieved a 'tumor-on/liver-off' profile, and thus represents a potentially useful tumor-specific promoter with applications for transcriptional targeting of Ad vector-based cancer gene therapy or oncolysis to melanoma.

Adenoviridae↗
PubMed2005

Sodium reduction for hypertension prevention in overweight adults: further results from the Trials of Hypertension Prevention Phase II.

Sodium reduction is efficacious for primary prevention of hypertension, but the feasibility of achieving this effect is unclear. The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention, Phase II. Sodium reduction (comprehensive education and counselling about how to reduce sodium intake) was tested vs no dietary intervention (usual care) for 36-48 months. A total of 956 white and 203 black adults, ages 30-54 years, with diastolic blood pressure 83-89 mmHg, systolic blood pressure (SBP) <140 mmHg, and body weight 110-165% of gender-specific standard weight were included in the study. At 36 months, urinary sodium excretion was 40.4 mmol/24 h (24.4%) lower in sodium reduction compared to usual care participants (P<0.0001), but only 21% of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts. Net decreases in SBP at 6, 18, and 36 months of 2.9 (P<0.001), 2.0 (P<0.001), and 1.3 (P=0.02) mmHg in sodium reduction vs usual care were associated with an overall 18% lower incidence of hypertension (P=0.048); were relatively unchanged by adjustment for ethnicity, gender, age, and baseline blood pressure, BMI, and sodium excretion; and were observed in both black and white men and women. From these beneficial but modest results with highly motivated and extensively counselled individuals, sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes.

Adult↗
PubMed2005

Nasal exposure to Staphylococcal enterotoxin enhances the development of allergic rhinitis in mice.

BACKGROUND: Staphylococcal enterotoxins (SEs) appear to play a role in the pathogenesis of allergic disease. However, little is known whether the nasal exposure to SE affects the development of allergic rhinitis (AR). OBJECTIVE: We sought to determine the in vivo effect of nasal exposure to SE on the development of AR using mouse model. METHODS: BALB/c mice were intranasally sensitized with Schistosoma mansoni egg antigen (SmEA) in the presence or absence of staphylococcal enterotoxin B (SEB). Control mice were intranasally sensitized with either SEB or SmEA alone. The production of antigen-specific antibodies including IgE, nasal eosinoplilia and cytokines by nasal mononuclear cells was compared among mice that had or had not received SEB treatment. RESULTS: Nasal exposure to SEB enhanced the development of AR in SmEA-sensitized mice, as manifested by SmEA-specific IgE production, nasal eosinophilia, and IL-4 and IL-5 production by nasal mononuclear cells after Ag challenge. This treatment also elicited IFN-gamma production by SmEA-primed cells. In addition, these mice produced SEB-specific IgE whereas mice treated with SEB without SmEA sensitization did not produce SEB-specific IgE or demonstrate nasal eosinophilia. CONCLUSION: These results suggest that the nasal exposure to SEB enhances susceptibility to AR although the exposure to SE solely does not induce AR.

Allergens↗
PubMed2005

Age associated axonal features in HNPP with 17p11.2 deletion in Japan.

OBJECTIVE: To clarify age related changes in the clinicopathological features of hereditary neuropathy with liability to pressure palsy (HNPP) in Japanese patients with deletion of 17p11.2, particularly concerning axonal abnormalities. METHODS: Forty eight proband patients from 48 HNPP families were assessed as to clinical, electrophysiological, and histopathological features, including age associated changes beyond those in controls. RESULTS: Motor conduction studies showed age associated deterioration of compound muscle action potentials in nerves vulnerable to repetitive compression (median, ulnar, and peroneal nerves), but not in others such as the tibial nerve. Sensory conduction studies revealed more profound reduction of action potentials than motor studies with little age related change. Large myelinated fibre loss was seen in the sural nerve irrespective of age at examination. CONCLUSIONS: Irreversible axonal damage may occur at entrapment sites in motor nerves in HNPP patients, progressing with aging. Sensory nerves may show more profound axonal abnormality, but without age association. The electrophysiological features of HNPP are presumed to be a mixture of abnormalities occurring from early in life and acquired features caused by repetitive insults at entrapment sites. Unlike Charcot-Marie-Tooth disease type 1A, age associated axonal damage may not occur unless the nerves are subjected to compression.

Action Potentials↗
PubMed2005

High-resolution physical mapping of the secalin-1 locus of rye on extended DNA fibers.

High-resolution mapping of secalin-1 (Sec-1) locus has been performed by fluorescence in situ hybridization to extended DNA fibers of rye (Secale cereale, 2n = 14), employing DNA probes of lambda phage clones containing the omega-secalin gene. The fluorescent signals to rye extended DNA fibers revealed continuous strings of 45 microm, corresponding to the size of 147 kb DNA. To determine the copy number of Sec-1 locus on DNA fibers, a 1.2-kb fragment including the entire coding region of the omega-secalin gene and a 1.0-kb fragment of the promoter region were amplified by PCR as probes for another fiber FISH. The physical position of these sequences was visualized as alternating fluorescent spots by multicolor in situ hybridization. Alternating signals of two DNA probes reflected the tandem repeated organization of the Sec-1 locus having 15 copies of the gene. The present findings based on fiber FISH analysis support the contention that the omega-secalin genes are arranged in a head-to-tail fashion separated by 8 kb of spacer sequences with a total length of 145 kb.

Base Sequence↗
PubMed2005

Role of the nrf-2 gene in protection and repair of gastric mucosa against oxidative stress.

Helicobacter pylori infection, as well as NSAIDs induce oxidative stress on gastric mucosa, thereby causing mucosal damage and retarding mucosal repair. Cells can survive against chronic oxidative stress by enhancing activities of anti-oxidant enzymes, thereby protecting cells from DNA damage. Recent studies have clearly shown that the gene encoding Nrf-2 (NF-E2 p45-related factor-2) plays an important role in the induction of antioxidant enzymes against oxidative stress. In this paper, we will describe the cellular mechanisms by which the nrf-2 gene stimulates anti-oxidant enzyme activities during exposure to oxidative stress. Secondly, we will also mention the beneficial effects of sulforaphane, an isothiocyanate family which is abundantly included in broccoli sprouts, on gastric mucosa. Sulforaphane stimulates nrf-2 gene-dependent anti-oxidant enzyme activities, thereby protecting cells from oxidative injury. Finally, we will state our perspective on the efficacy of sulforaphane in protection and repair of gastric mucosa against oxidative stress during H. pylori infection.

Animals↗
PubMed2005

Effect of uncertainties in agricultural working schedules and Monte-Carlo evaluation of the model input in basin-scale runoff model analysis of herbicides.

In the prediction of time-series concentrations of herbicides in river water with diffuse-pollution hydrological models, farming schedules (the dates of herbicide application and drainage of irrigation water from rice paddies) greatly affect the runoff behavior of the herbicides. For large catchments, obtaining precise data on farming schedules is impractical, and so the model input inevitably includes substantial uncertainty. This paper evaluates the effectiveness of using the Monte-Carlo method to generate sets of estimated farming schedules to use as input to a GIS-based basin-scale runoff model to predict the concentrations of paddy-farming herbicides in river water. The effects of using the Monte-Carlo method to compensate for uncertainty in the evaluated parameters for herbicide decomposition and sorption were also evaluated.

Acetanilides↗
PubMed2004

Attenuation of brain derived neurotrophic factor (BDNF) by ethanol and cytoprotective effect of exogenous BDNF against ethanol damage in neuronal cells.

Ethanol-induced cell damage was investigated using human neuroblastomas SH-SY5Y cells, which can be differentiated by retinoic acid. With 100 mM or more of ethanol, cytotoxicity was significantly higher in undifferentiated cells than in differentiated cells. Thus, a severer effect of ethanol was observed in undifferentiated cells. In differentiated cells it was shown that the secreted amount of brain derived neurotrophic factor (BDNF) and the cyclic AMP responsive element binding protein (CREB) activity were significantly reduced by ethanol. These effects may be involved in ethanol-induced cell damage in differentiated cells. It was reported that neurotrophic factors have protective effects and that the hippocampus exclusively was damaged by ethanol. Since SH-SY5Y cell is a cell line (a neuronal cell model) and similar cytotoxic effect of ethanol was observed in both SH-SY5Y and primary culture neuronal cells, it will be favorable to use primary culture cells to test a protective effect of BDNF. Exogenous BDNF was shown to have a protective effect against ethanol-induced damage in primary culture neurons from rat hippocampi.

Alcohol-Induced Disorders, Nervous System↗
PubMed2004

SAM(g2) analysis for detecting spike localization: a comparison with clinical symptoms and ECD analysis in an epileptic patient.

SAM(g2) analysis, a combination of synthetic aperture magnetometry (SAM) and excess kurtosis (g2) method, is a novel epilepsy analysis procedure based on a spatial filtering technique. By producing a three-dimensional image of the g2 values and superimposing them onto a patient's MR images, this analysis can automatically estimate spike localization from raw MEG epilepsy signals including spikes. The aim of this study is to examine SAM(g2) analysis using MEG signals of an epileptic patient, whose clinical symptoms of colored elementary visual auras had ceased in accordance with the changes of the estimated localizations of the equivalent current dipoles (ECDs) of the interictal spikes. His visual auras were experienced in 1997, while they ceased in 1999 with effective medication. The patient provided written informed consent for the experimental procedures. The MEG signals were recorded in 1997 and 1999, and were analyzed using both ECD and SAM(g2) analyses. For the MEG signals of 1997, ECD analysis estimated most of the interictal spikes in the right fusiform and inferior temporal gyri, which subserve human color processing. SAM(g2) analysis also estimated them in the same areas. For those of 1999, both ECD and SAM(g2) analyses estimated them in the right transverse gyrus of Heschl. As well as ECD analysis, SAM(g2) analysis successfully estimated the changes of the localizations of the interictal spikes in accordance with the changes of the patient's clinical symptoms, indicating that SAM(g2) analysis is useful for detection of interictal spike localization in epileptic patients.

Action Potentials↗
PubMed2004

Water and enzyme secretion are tightly coupled in pancreatic secretion stimulated by food or CCK-58 but not by CCK-8.

Pancreatic secretion of protein, water, chloride, and bicarbonate under basal conditions and in response to intravenous and intraduodenal stimuli were studied in awake rats fully recovered from surgery. During the basal phase of pancreatic secretion, protein output and water output were weakly correlated or uncorrelated, consistent with separate regulation and distinct cellular origin of enzyme (acinar cells) and water (duct cells), referred to as the two-component paradigm of pancreatic secretion. When pancreatic secretion was stimulated physiologically, water and protein output abruptly became strongly and significantly correlated, suggesting that protein secretion and water secretion are tightly coupled or that protein secretion is dependent on water secretion. The apparent function of this coupling is to resist or prevent increases in protein concentration as protein output increases. This pattern of secretion was reproduced by intravenous infusion of the CCK-58 form of cholecystokinin, which strongly stimulates pancreatic water and chloride secretion, but not by CCK-8, which only weakly stimulates water and chloride secretion in a non-dose-dependent manner. The remarkably tight association of water and protein secretion in food-stimulated and CCK-58-stimulated pancreatic secretion is consistent with a single cell type as the origin of both water and enzyme secretion, i.e., the acinar cell, and is not consistent with the two-component paradigm of pancreatic secretion. Because CCK-58 is the only detectable endocrine form of cholecystokinin in the rat and its bioactivity pattern is markedly and qualitatively different from CCK-8, actions previously recorded for CCK-8 should be reexamined.

Animals↗
PubMed2004

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↗
PubMed2004

Carrier dependent cell differentiation of bone morphogenetic protein-2 induced osteogenesis and chondrogenesis during the early implantation stage in rats.

To evaluate the osteoinductive effects of recombinant human bone morphogenetic protein (rhBMP)-2 during the early stages of rat ectopic bone formation, we prepared two distinct carriers. Two carriers, insoluble bone matrix (IBM) and fibrous glass membrane (FGM) were combined with rhBMP-2 and implanted into the backs of rats to evaluate the osteoinductive effects of the two rhBMP-2 carrier systems. Insoluble bone matrix particle size was 320 to 620 microm. Fibrous glass membrane was constructed from unwoven glass fibers 1 microm in diameter. Alkaline phosphatase (ALP) activity and type II collagen were detected in IBM/rhBMP-2 at 5 days postimplantation. Calcium (Ca) was also detected in IBM/rhBMP-2 at 7 and 9 days postimplantation. In contrast, ALP and type II collagen were detected in FGM/rhBMP-2 at 7 days. Calcium was undetected, indicating that the bone formation in IBM/rhBMP-2 proceeded faster than in FGM/rhBMP-2 during the early stage of BMP-induced osteogenesis. In addition, mRNA expression level of KDR, a receptor for vascular endothelial growth factor, was also increased in IBM/rhBMP-2. To investigate the in vivo release profile of rhBMP-2, iodine 125 ((125)I)-labeled BMP-2-incorporating IBM and FGM implants were inserted into the back subcutis of mice. More than 60% of the rhBMP-2 was released from the IBM/rhBMP-2 carrier within 1 day after implantation, whereas 50% of the rhBMP-2 was released from the FGM/rhBMP-2 10 days postimplantation. These results indicated that osteo- and chondrogenesis depends highly upon the geometry of the carrier and the in situ retention of rhBMP-2 during the early stage of rhBMP-2 induced bone formation.

Alkaline Phosphatase↗
PubMed2004

Pathology of early- vs late-onset TTR Met30 familial amyloid polyneuropathy.

BACKGROUND: Late-onset type I familial amyloid polyneuropathy (FAP TTR Met30) cases unrelated to endemic foci in Japan show clinical features setting them apart from early-onset cases in endemic foci. OBJECTIVE: To compare pathologic features between the early- and late-onset types. METHODS: Pathologic findings in FAP TTR Met30 with onset before age 50 in relation to endemic foci (11 cases) were compared with those in 11 later-onset cases unrelated to endemic foci. RESULTS: Sural nerve biopsy specimens showed predominantly small-fiber loss in early-onset cases; variable fiber size distribution, axonal sprouting, and relatively preserved unmyelinated fibers characterized late-onset cases. Autopsy cases representing both groups showed amyloid deposition throughout the length of nerves and in sympathetic and sensory ganglia, but amounts were greater in early-onset cases. Amyloid deposition and neuronal cell loss were greater in sympathetic than dorsal root ganglia in early-onset cases; the opposite was true in late-onset cases. Size assessment of remaining neurons in these ganglia suggested predominant loss of small neurons in early-onset cases but loss of neurons of all sizes in late-onset cases. Transthyretin-positive, Congo red-negative amorphous material was more conspicuous in nerves from late- than early-onset cases. In extraneural sites, amyloid was more conspicuous in thyroid and kidney from early-onset cases and in heart and hypophysis from late-onset cases. In early-onset cases, cardiac amyloid deposition was prominent in the atrium and subendocardium but was conspicuous throughout the myocardium in late-onset cases. CONCLUSION: The pathology of early- and late-onset FAP TTR Met30 correlated well with differences in clinical findings.

Adult↗
PubMed2004

A DNA microarray-based methylation-sensitive (MS)-AFLP hybridization method for genetic and epigenetic analyses.

We previously developed a PCR-based DNA fingerprinting technique named the Methylation Sensitive (MS)-AFLP method, which permits comparative genome-wide scanning of methylation status with a manageable number of fingerprinting experiments. The technique uses the methylation sensitive restriction enzyme NotI in the context of the existing Amplified Fragment Length Polymorphism (AFLP) method. Here we report the successful conversion of this gel electrophoresis-based DNA fingerprinting technique into a DNA microarray hybridization technique (DNA Microarray MS-AFLP). By performing a total of 30 (15 x 2 reciprocal labeling) DNA Microarray MS-AFLP hybridization experiments on genomic DNA from two breast and three prostate cancer cell lines in all pairwise combinations, and Southern hybridization experiments using more than 100 different probes, we have demonstrated that the DNA Microarray MS-AFLP is a reliable method for genetic and epigenetic analyses. No statistically significant differences were observed in the number of differences between the breast-prostate hybridization experiments and the breast-breast or prostate-prostate comparisons.

Blotting, Southern↗
PubMed2004

In vivo and in vitro constant expression of GATA-4 in mouse postnatal Sertoli cells.

In the mammalian postnatal testis, the biochemical and structural features of Sertoli cells change, depending on developmental stage and spermatogenic cycle, to support efficient spermatogenesis. Consequently, basic transcription factors that determine fundamental properties should be strictly maintained in postnatal Sertoli cells. We have confirmed that GATA-4 expression is kept at a constant level in mouse Sertoli cells during postnatal development, and is also maintained at a constant level in primary cultures, independent of treatment with hormones or the addition of germ cell fractions. In transient transfection assays with the testicular cell line TM3, established from Leydig cells, GATA-4 induced several Sertoli cell-specific genes. In the Sertoli cell line TM4, and in Sertoli cells in primary culture, GATA-4 slightly up-regulated these genes. These results suggest that GATA-4 plays an important role in the regulation of Sertoli cell function, and is exactly regulated in these cells.

Animals↗