Biomedical subjects

S Maeda

Publications and source records attributed to S Maeda.

At least 55 records · Page 3Linked to original sources

PubMed2002

The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.

Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.

Journal Article↗

PubMed2002

Thermotactile threshold testing for the evaluation of sensory nerve function in vibration-exposed patients and workers.

OBJECTIVES: The aim of the present study was to ascertain the usefulness of thermotactile testing under the measuring conditions clarified by our previous study in the evaluation of vibration-induced neuropathy. METHOD: Thermal (warm and cold) thresholds were examined on the index fingers of both hands of ten patients with hand-arm vibration syndrome, 36 workers exposed to hand-transmitted vibration, and ten healthy controls, using an aesthesiometer under the following measuring conditions: change rate of the applicator temperature was fixed at a rate of 1 degrees C/s; finger contact force on the applicator was kept at 0.5 N; and forearm was positioned on a support. Vibrotactile thresholds at 125 Hz and pain thresholds were also measured on the index fingers. RESULTS: Both warm and cold thresholds had more severely deteriorated in the patients than in the controls. Vibrotactile and pain thresholds were also increased in the patients. In the vibration-exposed workers, the neutral zone between the warm and cold threshold differed from in the controls. Thermotactile thresholds were likely to have deteriorated with advanced nerve impairment. Likelihood ratios of thermotactile testing were significantly high between the patients and the controls. For vibration-exposed workers with elevated vibrotactile and pain thresholds, the ratios were also significantly high, particularly in the neutral zone, though the accuracy tended to be lower than in the patients. Thermotactile thresholds appeared to be more closely correlated with pain thresholds than vibrotactile thresholds. CONCLUSIONS: Thermotactile threshold testing under the present measuring conditions can be useful for evaluating small sensory nerve fibre dysfunction in vibration-exposed subjects, and the neutral zone may be a sensitive indicator in vibration-exposed workers who may have slight or mild nerve impairments.

Adult↗

PubMed2002

Variation in MT expression in early-stage depressed-type and polypoid-type colorectal tumours.

Metallothionein (MT) expression is observed in various carcinomas, but its role is not fully understood. To clarify the clinicopathological significance of MT, 87 colorectal adenomas and 128 early-stage carcinomas were immunohistochemically analysed for MT expression. The degree of MT immunostaining of a specimen was graded according to the proportion of MT-positive cells; negative (<5%) and positive (focally 5-50%, diffusely >50%). MT expression significantly decreased with tumour development. For carcinomas, MT-positivity was significantly associated with depth of invasion (T1 60% versus T2 33%; P<0.01), vascular involvement (positive 35% versus negative 61%; P<0.01) and morphology (polypoid 62% versus depressed 26%; P<0.01). Regarding MT-positive distribution, the diffuse-positive rate in MT-positive polypoid lesions was 28%, while MT-positive depressed lesions were all diffusely stained (P<0.01). In conclusion, our results suggested that decreasing MT expression is an early event in colorectal carcinogenesis and may reflect local invasion. Furthermore, MT-positive distribution may reflect genetic differences between the polypoid and depressed-type.

Adult↗

PubMed2002

Prognostic implications of histological features in patients with chromophobe cell renal carcinoma.

OBJECTIVE: To assess the relationship between the histological features of renal chromophobe cell carcinoma (CCC) and clinical outcome in patients with renal cell carcinoma. PATIENTS AND METHODS: From 1957 to 1996, 41 patients with CCC of the kidney (4.9% of all kidney carcinomas) were treated at our university hospitals. Of these histologically defined cases, four who died from other types of cancer and two who were lost to follow-up were excluded, leaving 35 patients in the study; the carcinoma was classified as the typical variant in 26 and the eosinophilic variant in nine. Based on the differences of the variants, the histological features affecting prognosis were analysed. RESULTS: The overall survival rates at 1, 3, 5, 10, 15 and 20 years were 97%, 82%, 82%, 70%, 62% and 47%, respectively. The prognosis was more favourable in those with the eosinophilic than for the typical variant (there were no cancer-related deaths in the former). Of those with the typical variant, five died within 2 years of surgery; of these, three with high-stage disease had various degrees of sarcomatoid change. Conversely, two patients had a recurrence > 10 years after surgery (late recurrence). Both these patients and the others who later died from cancer had no sarcomatoid change in the tumour areas examined. CONCLUSION: The eosinophilic variant of CCC has a better prognosis; on the contrary, during long-term surveillance, early recurrence was detected especially in those with sarcomatoid change and late recurrence only in two typical variant. These prognostic implications of the histological differences are important for understanding the outcome of renal CCC.

Adult↗

PubMed2002

Endoscopic surveillance for gastric remnant cancer after early cancer surgery.

BACKGROUND AND STUDY AIMS: The aims of this article were to clarify the incidence of gastric remnant cancer after surgery for early gastric cancer, and to develop surveillance programs for patients who have undergone partial gastrectomy in order to detect such lesions at an early stage. PATIENTS AND METHODS: A total of 642 patients with partial gastrectomy for early gastric cancer were enrolled in a surveillance program for gastric remnant cancer between 1985 and 1996. In 509 patients, the interval between endoscopic examinations was no more than 2 years. RESULTS: Among the 509 patients examined periodically, 15 patients were diagnosed as having gastric remnant cancer; in 12 patients, the cancers were detected at an early stage. All gastric remnant cancers were found distant from the site of the anastomosis, and in eight patients the cancers were located on the lesser curvature. The cumulative 5-year prevalence rate was estimated as 2.4 % and the 10-year prevalence rate as 6.1 %. The initial tumors in the patients with gastric remnant cancer were of the microscopically intestinal type, without exception. The interval between the preceding examination and diagnosis was shorter in the patients with early cancer than in those with advanced cancer ( P < 0.01). CONCLUSIONS: Periodical surveillance endoscopy for gastric remnant cancer is recommended after surgery for early gastric cancer, particularly in patients whose cancers are of the intestinal type. The examinations can be repeated at 2 - 3-year intervals, and special attention should be given to the lesser curvature away from the anastomotic site.

Aged↗

PubMed2002

Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori.

BACKGROUND AND AIMS: Although it is reported that Helicobacter pylori induces apoptosis on gastric epithelial cells, the mechanism remains unknown. Antiapoptotic effects generated by H pylori have not yet been evaluated. METHODS: (1) H pylori strains (type 1 wild, TN2-DeltacagE, TN2-DeltavacA) were cocultured with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed by trypan blue exclusion and DNA laddering, respectively. (2) Activation of caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa B (NFkappaB) activation induced by cag pathogenicity island (PAI) positive H pylori affects antiapoptosis, MKN45 cells stably expressing super-repressor Ikappabetaalpha were cocultured with H pylori, and cell viability and caspase activation were evaluated. NFkappaB regulated gene expression was also evaluated by ribonuclease protection assay. RESULTS: (1) Wild-type and DeltavacA mutant H pylori induced apoptosis more potently than the DeltacagE mutant. Inhibition of cell contact between H pylori and cancer cells and heat killing H pylori diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently by H pylori as well as by the agonist anti-Fas. Cytochrome c release from mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates was not changed by H pylori, Bax was decreased from mitochondria free cytosol suggesting that Bax was translocated into mitochondria. (3) Cell death and the activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing super-repressor Ikappabetaalpha that inhibits NFkappaB activation. Antiapoptotic proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains. CONCLUSION: cag PAI positive H pylori is capable of inducing apoptotic effects mainly through the mitochondrial pathway. Antiapoptotic effects mediated by NFkappaB activation were also observed.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori.

BACKGROUND AND AIMS: Although it is reported that Helicobacter pylori induces apoptosis on gastric epithelial cells, the mechanism remains unknown. Antiapoptotic effects generated by H pylori have not yet been evaluated. METHODS: (1) H pylori strains (type 1 wild, TN2-deltacagE, TN2-deltavacA) were cocultured with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed by trypan blue exclusion and DNA laddering, respectively. (2) Activation of caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa B (NFkappaB) activation induced by cag pathogenicity island (PAI) positive H pylori affects antiapoptosis, MKN45 cells stably expressing super-repressor IkappaBalpha were cocultured with H pylori, and cell viability and caspase activation were evaluated. NFkappaB regulated gene expression was also evaluated by ribonuclease protection assay. RESULTS: (1) Wild-type and deltavacA mutant H pylori induced apoptosis more potently than the deltacagE mutant. Inhibition of cell contact between H pylori and cancer cells and heat killing H pylori diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently by H pylori as well as by the agonist anti-Fas. Cytochrome c release from mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates was not changed by H pylori, Bax was decreased from mitochondria free cytosol suggesting that Bax was translocated into mitochondria. (3) Cell death and the activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing super-repressor IkappaBalpha that inhibits NFkappaB activation. Antiapoptotic proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains. CONCLUSION: cag PAI positive H pylori is capable of inducing apoptotic effects mainly through the mitochondrial pathway. Antiapoptotic effects mediated by NFkappaB activation were also observed.

Apoptosis↗

PubMed2002

Expression of parathyroid hormone-related protein (PTHrP) in parathyroid tissue under normal and pathological conditions.

Parathyroid hormone-related protein (PTHrP), a factor responsible for malignancy associated hypercalcemia, plays a physiological roles such as bone development and placental calcium transport. The expression of PTHrP in adult human parathyroid tissues under normal and pathological conditions was analyzed. By immunohistochemistry, PTHrP expression was detected in 86% of normal parathyroid (12/14 cases), 74% of adenomas (14/19) and 89% of hyperplasia secondary to chronic renal failure (16/18). PTHrP protein was observed mainly in the cytoplasm of oxyphil cells, consistent with the localization of its mRNA demonstrated by in situ hybridization. The rate of PTHrP-positive cells was higher in areas consisting of oxyphil cells than in those of non-oxyphil cells, regardless of whether the parathyroid was normal or pathological. In the normal parathyroid, an age-related increase in PTHrP expression was observed with a relative increase in oxyphil cells, reflecting aging and deterioration of parathyroid tissue. In adenoma, cases with a predominance of oxyphil cells expressed PTHrP, whereas clear cell adenoma did not. In secondary hyperplasia, the rate of PTHrP-expressing cells was higher than in normal parathyroid or adenoma, with varying levels of expression among nodules. We speculate that PTHrP could act through the paracrine/autocrine mechanism to regulate proliferation and differentiation of normal and neoplastic parathyroid cells.

Adenoma↗

PubMed2002

Production of recombinant ovine interferon tau using a Bombyx mori nuclear polyhedrosis baculovirus expression system.

Ovine interferon tau (oIFN-tau) is an embryonic protein of critical importance in the establishment of pregnancy in the sheep. We have produced recombinant (r) oIFN-tau using a baculovirus expression system and demonstrated the biological activity of the protein produced. Bombyx mori larvae were infected with B. mori nuclear polyhedrosis virus (BmNPV), modified by inserting a cDNA coding for oIFN-tau downstream of the strong polyhedron promoter. Following infection, antiviral activity of the haemolymph rose to a maximum of 3.6 x 10(8) u/mL (equivalent to 3 mg roIFN-tau/mL) by day 5, when haemolymph was collected and stored frozen. Control haemolymph, collected from uninfected insects at an equivalent time, contained no antiviral activity. The roIFN-tau was partially purified by gel filtration column chromatography and the presence of roIFN-tau confirmed by western blotting. The biological activity of the partially purified roIFN-tau was tested in ewes. Treatment with roIFN-tau caused a significant delay in luteolysis confirming biological potency. The results demonstrate that this system can be successfully used to produce large quantities of roIFN-tau.

Animals↗

PubMed2002

[Intelligibility of French consonants after partial supra-cricoid laryngectomy].

INTRODUCTION: The purpose of this study was to determine what patterns of perceptual confusions characterize the voice of patients after supracricoïd partial laryngectomy (SCPL) by the identification tests of French consonants. We evaluated the voicing distinction. METHODS: Ten male patients were recorded 18 months after SCPL. Audio recordings of the 16 French consonants in a syllabic context (CV) produced by each talker with three repetitions were presented to three expert listeners. The listeners transcribed their responses using an open-response paradigm. Listeners' pooled responses were converted to confusion matrices. RESULTS: Voicing features were altered with a shift of voiced consonants towards voiceless consonants (24%), predominantly for stop consonants. CONCLUSION: Consonant articulation appears to impose certain constraints on voicing ability of SCPL patients, since voiced consonants are predominantly perceived as voiceless consonants. Presumably, this poor voicing ability is the direct consequence of the mechanical properties of the neoglottis that are far different from those of the vocal folds. Moreover, assessing consonant identification and intelligibility should help to improve voice therapy and efficiency of speech.

Aged↗

PubMed2001

The first stage of transforming growth factor beta1 activation is release of the large latent complex from the extracellular matrix of growth plate chondrocytes by matrix vesicle stromelysin-1 (MMP-3).

Transforming growth factor beta-1 (TGF-beta1) is secreted in a biologically inactive form and stored in the extracellular matrix as a 290 kDa complex consisting of the mature TGF-beta1 homodimer (Mr 25 kDa), the latency-associated peptide (LAP; Mr 75 kDa), and the latent TGF-beta1 binding protein-1 (LTBP1; Mr 190 kDa). Latent TGF-beta1, composed of these three components, is known as the "large latent TGF-beta1 complex." In contrast, latent TGF-beta1 without LTBP1 is known as "small latent TGF-beta1." For all latent forms, dissociation of the TGF-beta1 homodimer from LAP is necessary for growth factor activation and acquisition of biological activity. Matrix vesicles produced by growth plate chondrocytes contain matrix metalloproteinases that can activate small latent TGF-beta1. The enzyme responsible for this is matrix metalloproteinase-3 (MMP-3), although matrix vesicles also contain MMP-2 and plasminogen activator. The present study tested the hypothesis that matrix vesicle enzymes are also involved in the release of the large latent TGF-beta1 complex stored in the extracellular matrix. Matrix vesicles were isolated from cultures of resting zone and growth zone chondrocytes and metalloproteinases present in the matrix vesicles extracted with guanidine-HCl. Chondrocyte extracellular matrices were prepared by lysing confluent cultures and removing the lysed cells. The matrices were incubated with matrix vesicle extracts and the release of total and active TGF-beta1 was determined. To determine if MMP-2 or MMP-3 was involved in the release, matrix vesicle extracts were preincubated with anti-MMP-2 antibody or anti-MMP-3 antibody to selectively deplete the enzyme activity. Matrices were also treated with rhMMP-2 or rhMMP-3. To determine the identity of the released protein(s), digests were separated on SDS-polyacrylamide gels and Western blotting analysis was performed using a specific antibody to LTBP1. Matrix vesicle extracts released both active and total (=latent + active) TGF-beta1 in a time-dependent manner, with peak release after 1 hour of incubation. The amount of total TGF-beta1 released was 10 times higher than the release of active TGF-beta1. The effect of the matrix vesicle extracts was dose-dependent; in addition, the amount and ratio of active to total TGF-b1 released was very similar, irrespective of the source of matrix or matrix vesicle extracts. Pre-incubation of matrix vesicle extracts with anti-MMP-3 antibody blocked the release of active and total TGF-beta1, whereas pre-incubation with pre-immune IgG or anti-MMP-2 antibody had no effect. The addition of rhMMP-3, but not rhMMP-2, caused a dose-dependent increase in the release of total, but not active, TGF-beta1. Western analysis confirmed that both matrix vesicle extracts and rhMMP-3 released the large latent TGF-beta1 complex from the matrix. In addition to the expected 290, 230, and 190 kDa bands, samples run without reduction also contained proteins of molecular weights 110 and 50 kDa that reacted with the anti-LTBP1 antibody. When these same samples were electrophoresed after reduction, the high molecular weight immunoreactive bands disappeared and three bands of molecular weight 75, 32, and 25 kDa were observed. These results indicate that matrix vesicles contain enzymes, especially MMP-3, which are responsible for the release of TGF-beta1 from the matrix, most of which is in latent form. Further, the data suggest that release of the large complex occurs via cleavage at several novel sites in the 130 kDa LTBP1 molecule. Since matrix vesicle MMP-3 is also able to activate small latent TGF-beta1, these results suggest that the large latent TGF-beta1 complex protects against activation of the small latent TGF-beta1. Thus, the data suggest that release of the large latent TGF-bl complex from the matrix and activation of the latent growth factor are only two steps of what must be at least a three-step process.

Animals↗

PubMed2001

Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide.

Midazolam, a benzodiazepine, has an hypnotic effect via benzodiazepine receptors and is widely used as an anaesthetic. Recently, it has been suggested that benzodiazepines modulate cytokine responses. The purpose of the present study was to evaluate the effect of midazolam on interleukin-6 (IL-6) response by observing mRNA expression levels in human peripheral blood mononuclear cells (PBMCs) in the absence of lipopolysaccharide (LPS). PBMCs were isolated from healthy volunteers in endotoxin-free 0.9% sodium chloride solution. The cells were incubated for 2 h at 37 degrees C immediately after isolation. IL-6 mRNA expression levels in the cells were quantified using reverse transcription and competitive polymerase chain reaction. It was found that midazolam time-dependently inhibited the IL-6 mRNA expression in PBMCs in the absence of LPS, and significantly inhibited the IL-6 mRNA expression at 1 microg/ml (P<0.05) or 10 microg/ml (P<0.01) in the absence of LPS. However, neither a specific agonist of peripheral-type benzodiazepine receptors, Ro5-4864, nor a specific agonist of central-type benzodiazepine receptors, clonazepam, inhibited IL-6 mRNA expression. These findings indicated a suppression of the IL-6 response in human PBMCs by midazolam in the absence of LPS, and suggests that midazolam has its effect not via benzodiazepine receptors, but by another mechanism.

Anti-Anxiety Agents↗

PubMed2001

Distinct mechanism of Helicobacter pylori-mediated NF-kappa B activation between gastric cancer cells and monocytic cells.

NF-kappaB is a critical regulator of genes involved in inflammation. Gastric epithelial cells and macrophages are considered the main sources of pro-inflammatory cytokines. We investigated NF-kappaB activation by Helicobacter pylori in MKN45 gastric epithelial cells and THP-1 monocytic cells. Although, cag pathogenicity island (PAI)-positive H. pylori (wild type) activated NF-kappaB in both cells, isogenic mutant of cagE (DeltacagE) activated it only in THP-1 cells. Supernatant from the wild type culture could activate NF-kappaB in THP-1 cells but not in MKN45 cells. High density cDNA array analysis revealed that mRNA expression of NF-kappaB-regulated genes such as interleukin (IL)-8, tumor necrosis factor-alpha (TNFalpha), and IL-1beta was significantly up-regulated by the wild type in both cells, whereas it was up-regulated by DeltacagE only in THP-1 cells. Experiments using CD14-neutralizing antibody and IL-1 receptor-associated kinase (IRAK) assay showed that both wild type and DeltacagE H. pylori activated NF-kappaB through CD14 and IRAK in THP-1 cells but not in MKN45 cells. Macrophages from C3H/HeJ mice carrying point mutation in the Toll-like receptor 4 (TLR4) gene showed decreased NF-kappaB activation and TNFalpha secretion compared with C3H/HeN mouse macrophage when treated with H. pylori. In conclusion, H. pylori-induced NF-kappaB activation in epithelial cells is dependent on cag PAI and contact but does not involve CD14 and IRAK, whereas in macrophage/monocytic cells it is independent of cag PAI or contact but involves CD14 and TLR4.

Animals↗

PubMed2001

Mice lacking serum amyloid P component do not necessarily develop severe autoimmune disease.

Serum amyloid P component (SAP) is a major acute-phase reactant in mice. Recently, it was reported that SAP-deficient mice spontaneously developed anti-nuclear antibodies and severe glomerulonephritis. Because the SAP-deficient mice we generated display no obvious phenotypic abnormalities, we investigated whether our SAP-deficient mice would also spontaneously develop autoimmune responses. In accordance with the report, our mice produced high titers of anti-nuclear antibody but did not develop severe glomerulonephritis. On the other hand, it was recently reported that SAP bound to gram-negative bacteria via lipopolysaccharide (LPS) prevented LPS-mediated activation of a classical complement pathway. Thus, we asked if SAP-deficient mice would show altered responses to an intraperitoneal injection of LPS from Salmonella typhimirium. SAP-deficiency did afford resistance to lethality induced by high-dose LPS. Our experiments clearly showed that contrary to documented data, SAP-deficient mice do not develop serious autoimmune disease and we suggest that SAP has a critical role in LPS toxicity.

Animals↗

PubMed2001

Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans.

Vascular endothelial cells produce nitric oxide (NO), which is a potent vasodilator substance and has been proposed as having antiatherosclerotic property. Vascular endothelial cells also produce endothelin-1 (ET-1), which is a potent vasoconstrictor peptide and has potent proliferating activity on vascular smooth muscle cells. Therefore, ET-1 has been implicated in the progression of atheromatous vascular disease. Because exercise training has been reported to produce an alteration in the function of vascular endothelial cells in animals, we hypothesized that exercise training influences the production of NO and ET-1 in humans. The purpose of the present study was to examine whether chronic exercise could influence the plasma levels of NO (measured as the stable end product of NO, i.e., nitrite/nitrate [NOx]) and ET-1 in humans. Eight healthy young subjects (20.3 +/- 0.5 yr old) participated in the study and exercised by cycling on a leg ergometer (70% VO2max for 1 hour, 3-4 days/week) for 8 weeks. Venous plasma concentrations of NOx and ET-1 were measured before and after (immediately before the end of 8-week exercise training) the exercise training, and also after the 4th and 8th week after the cessation of training. The VO2max significantly increased after exercise training. After the exercise training, the plasma concentration of NOx significantly increased (30.69 +/- 3.20 vs. 48.64 +/- 8.16 micromol/L, p < 0.05), and the plasma concentration of ET-1 significantly decreased (1.65 +/- 0.14 vs. 1.23 +/- 0.12 pg/mL, p < 0.05). The increase in NOx level and the decrease in ET-1 level lasted to the 4th week after the cessation of exercise training and these levels (levels of NOx and ET-1) returned to the basal levels (the levels before the exercise training) in the 8th week after the cessation of exercise training. There was a significant negative correlation between plasma NOx concentration and plasma ET-1 concentration. The present study suggests that chronic exercise causes an increase in production of NO and a decrease in production of ET-1 in humans, which may produce beneficial effects (i.e., vasodilative and antiatherosclerotic) on the cardiovascular system.

Adult↗

PubMed2001

cDNA microarray analysis of Helicobacter pylori-mediated alteration of gene expression in gastric cancer cells.

Helicobacter pylori infection stimulates several intracellular signaling pathways and is accompanied by increased gene expression in gastric epithelial cells. High-density cDNA microarray was used to characterize the mRNA expression profile of genes in human gastric cancer cells (MKN45, AGS) cocultured with H. pylori. Coculture with cag pathogenicity island (PAI)-positive H. pylori (wild-type) significantly up-regulated mRNA expression in 8 of 2304 genes tested. In 6 (interleukin-8, I(kappaB)alpha, A20, ERF-1, keratin K7, glutathione peroxidase) of the 8 genes, up-regulation was confirmed by RT-PCR. In coculture with isogenic cagE-negative mutant ((Delta)cagE), which encodes a type IV secretion system with other genes in the cag PAI, no significant up-regulation was found. We further analyzed the role of A20. Transfection of expression vector encoding A20 resulted in an inhibition of H. pylori-mediated NF-kappaB activation, indicating that H. pylori-mediated A20 expression could be a negative regulator of NF-kappaB activation. Taken together, these results indicate the importance of microarray technology as a tool for analyzing the complex interplay between H. pylori and the host.

Adenocarcinoma↗

PubMed2001

The intrinsic origin of nitric oxide synthase immunoreactive nerve fibers in the right atrium of the guinea pig.

We previously reported three kinds of nitric oxide synthase-immunoreactive (NOS-ir) axons in the guinea pig heart: the sparse fiber network covering the right atrium, the basket-like endings around intracardiac neurons, and the axons in the septal region. The sparse NOS-ir nerve fiber network in the right atrium remained after vagotomy and has been suggested to be originated from intrinsic cardiac ganglia. Using Chorera toxin B as a retrograde tracer, we determined a part of them were derived from cardiac ganglionic neurons located in the area near the vena cavae.

Animals↗

PubMed2001

Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma.

Genetic alteration is considered a probable cause of malignant lymphoma. Folate and methionine metabolism play essential roles in DNA synthesis and DNA methylation, and their metabolic pathways might thus affect disease susceptibility. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms, MTHFR677 C-->T and MTHFR1298 A-->C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5,10-methylenetetrahydrofolate and results in a reduced incidence of DNA double-strand breakage. The MS2756 A-->G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA. To evaluate the association between malignant lymphoma susceptibility and these polymorphisms, hospital-based case-control study was conducted in Aichi Cancer Center. Ninety-eight patients with histologically confirmed lymphoma and 243 control subjects without cancer were evaluated. Unconditional logistic regression analyses revealed a higher susceptibility with the MTHFR677 CC and the MTHFR1298 AA genotypes (odds ratio, 2.26; 95% confidence interval, 1.26-4.02) when those harboring at least one variant allele in either polymorphism of MTHFR were defined as the reference. For the MS polymorphism, the MS2756 GG genotype also showed a higher susceptibility (odds ratio, 3.83; 95% CI, 1.21-12.1) than those with MS2756 AA or AG types. The significance was not altered when these 3 polymorphisms were evaluated in combination, and the results suggest that folate and methionine metabolism play important roles in the occurrence of malignant lymphomas. Further studies to confirm the association and detailed biologic mechanisms are now required.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗