Preventive effects of oral combination therapy of Vitamins B2/B6/C and L-cysteine on the development of dry skin in a guinea pig irritation model.
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Administration, Oral↗
Biomedical subjects
M Nakamura
Publications and source records attributed to M Nakamura.
Carotid artery intima-media thickness and reactive oxygen species formation by monocytes in hypertensive patients.
Carotid artery intima-media thickness (IMT) is a widely accepted index for assessing atherosclerosis, and is known to be a risk indicator for cardiovascular and cerebrovascular events. Oxidative stress and inflammation are also known to play critical roles in the pathogenesis of vascular events. We studied the association between IMT and inflammatory markers, such as oxidative stress in polymorphonuclear leukocytes (PMNs) and mononuclear cells (MNCs) in 156 patients with essential hypertension. Reactive oxygen species (ROS) formation by PMNs and MNCs was measured by gated flow cytometry. CRP and traditional risk factors, such as age, gender, body mass index, hemoglobin A(1c), and total cholesterol were also measured. The subjects were divided into a plaque group (max-IMT>or=1.1 mm, n=40), and a nonplaque group (max-IMT<1.1 mm, n=116). ROS formation by MNCs was significantly increased in the plaque group when compared with the nonplaque group (P<0.0001). Multiple regression analysis revealed a significant correlation between IMT and ROS formation by MNCs (r=0.407, P<0.0001), or CRP (r=0.216, P=0.0029) or hemoglobinA1c (r=0.158, P=0.0270) or age (r=0.157, P=0.0447). No significant correlation was observed between IMT and ROS formation by PMNs. These results suggest that carotid artery IMT may be affected by increased ROS formation by MNCs, and that increased ROS formation by MNCs may be related to the development of atherosclerosis. We propose that ROS formation by MNCs is a marker for prediction of carotid atherosclerosis.
Atherosclerosis↗
Preliminary comparison of capsule endoscopy and double-balloon enteroscopy in patients with suspected small-bowel bleeding.
BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) have been introduced as modalities for examining the entire small bowel. The aim of the present study was to assess the clinical effects of CE and DBE to consider the roles of CE and DBE and the indications for the procedures in patients with suspected small-bowel bleeding. PATIENTS AND METHODS: Between June 2004 and January 2005, 32 patients in whom a site of bleeding in the gastrointestinal tract had not been identified were enrolled in the study. Twenty-eight patients were examined with both methods. Bleeding sources were categorized as either A1 lesions (immediate hemostatic procedures required) or A2 lesions (close observation required). CE and DBE were evaluated with regard to whether or not they were capable of accessing the entire small bowel and provided a diagnosis, and the access and diagnostic rates were calculated. RESULTS: On CE, 13 patients were diagnosed with A1 lesions and six with A2 lesions; on DBE, 11 had A1 lesions and one had an A2 lesion. The access rate for the entire small intestine on CE was 90.6 % (29 of 32), significantly higher than with DBE at 62.5 % (10 of 16; P < 0.05). The diagnostic rate on CE was 59.4 % (19 of 32), higher than with DBE at 42.9 % (12 of 28; P = 0.30), but not significantly different. Among patients with A1 lesions who were diagnosed with DBE, histological diagnoses were obtained in six of the 11, and three patients were treated. CONCLUSIONS: In many suspected small-bowel bleeding cases, CE should be selected for the initial diagnosis and DBE for treatment or histopathological diagnosis after detection of the bleeding site on CE.
Adult↗
Efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction.
BACKGROUND AND STUDY AIMS: The esophagogastric junction (EGJ) has been considered a difficult location for endoscopic treatment of tumors, due to its narrow lumen and sharp angle. Endoscopic submucosal dissection (ESD) is a method of endoscopic resection, capable of removing large tumors in an en bloc fashion. The aim of this study was to evaluate the efficacy and safety of ESD for EGJ tumors. PATIENTS AND METHODS: For 30 lesions of EGJ tumors treated by ESD, the size of the lesions and resected specimens, the en bloc resection rate, complications, and local recurrence were assessed. RESULTS: The average maximum diameters of the lesions and resected specimens were 22.4 mm and 40.6 mm respectively. The complete en bloc resection (R0) rate was 97% (29/30). Histological evaluation of the resected specimens revealed five cases of angiolymphatic invasion and five cases of submucosal invasion deeper than 500 microm. Perforation occurred in one case but was safely managed by rotatable clips and administration of antibiotics for 3 days. Local recurrence was not observed in any patient during follow-up (mean 14.6 months, range 6-31 months). CONCLUSIONS: ESD can be safely performed for EGJ tumors, with a high en bloc resection rate. For lesions with no apparent submucosal invasion findings, ESD is a curative and diagnostic treatment option that may be considered before open surgery.
Adenocarcinoma↗
Endoscopic submucosal dissection for rectal epithelial neoplasia.
BACKGROUND AND STUDY AIMS: The technique of endoscopic submucosal dissection (ESD) has recently been developed for en-bloc resection of gastric tumors. For oncological reasons and in order to improve the patients' quality of life, it may be desirable to use the same technique for rectal neoplasia. PATIENTS AND METHODS: Thirty-five consecutive patients with rectal neoplasia who had a preoperative diagnosis of large intraepithelial neoplasias with submucosal fibrosis or located on the rectal folds were enrolled. ESD was carried out with the same technique previously described for the stomach, with some modifications. The efficacy, complications, and follow-up results of the treatment were assessed. RESULTS: The rates of en-bloc resection and en-bloc plus R0 resection were 88.6 % (31 of 35) and 62.9 % (22 of 35), respectively. Hemoglobin levels did not drop by more than 2 g/dl in any of the patients after ESD. None of the patients had to receive blood transfusions or undergo emergency colonoscopy due to bleeding during ESD or hematochezia after ESD. Perforation during ESD occurred in two patients (5.7 %), who were managed with conservative medical treatment after endoscopic closure of the perforation. Excluding three patients in whom additional surgery was carried out, all but one of 32 patients were free of recurrence during a mean follow-up period of 36 months (range 12 - 60 months). The exception was a patient in whom a multiple-piece resection was required; the recurrent (residual) tumor, found 2 months after ESD, was a small adenoma that was again treated endoscopically. CONCLUSIONS: ESD is applicable in the rectum with promising results, but the technique is still at a developmental stage and patients should be informed of the potential risks.
Chi-Square Distribution↗
Static bone cavity of the mandible: Computed tomography findings with histopathologic correlation.
PURPOSE: To review computed tomography (CT) findings of histopathologically examined static bone cavities in order to determine whether an additional pathogenesis may play a role in this disease. MATERIAL AND METHODS: Four patients with histopathologically examined static bone cavities were included in this retrospective study. Location, appearance of bone remodeling, tissue characteristics, and contrast enhancement of the cavity were assessed on CT images. CT findings were then compared with the histopathological findings. RESULTS: Static bone cavity was found in the lingual molar region in three patients and in the lingual cuspid region of the mandible in one patient. Both fatty and soft tissues were present in the cavities of all four patients. Attenuation of the soft tissue in the cavities was found to be different from that of the submandibular gland. The soft tissue showed enhancement with contrast-enhanced CT in three patients. For all patients, the histopathologic content of the static bone cavity included fat, soft tissue, and abnormal vasculature. The thickened vein wall in the abnormal vasculature was observed. Aberrant tissue of the submandibular gland was not found in any of the static bone cavities. CONCLUSION: Contrast enhancement of the soft tissue on the contrast-enhanced CT images suggests the presence of vasculature in the cavities. Histopathological examination confirmed the presence of fatty tissue and dilated abnormal vessels, and the absence of salivary gland tissue in the cavities. These findings show that vascular structures are prominent in tissues found in static bone cavities.
Adult↗
Mastopathic fibroadenoma of the breast: a pitfall of aspiration cytology.
OBJECTIVE: To assess the correlation between cytological diagnoses and histological subtypes of fibroadenoma (FA) and to clarify the cytological features of a specific group of FA displaying variable features similar to fibrocystic disease (mastopathic type, MFA), and to evaluate the significance of this subtype in cytological diagnosis. METHODS: A review of 141 cases of histologically proven FA was performed. We re-classified them into four subtypes according to Kinoshita's criteria [Jpn J Breast Cancer6 (1991) 377] and further selected 92 cases for which both fine needle aspiration (FNA) smears and histological specimens were available. Among them, 18 cases of MFA and their cytological smears were selected for the present study. RESULTS: There was significant correlation between MFA and cytological diagnosis of 'indeterminate' or 'suspicious for malignancy' (P < 0.01). Although no false-positive diagnosis was experienced in our series, 56% of the MFAs (10/18) had cytological diagnoses of indeterminate or were included in the category 'suspicious for malignancy'. Smears from MFA revealed high cellularity (9/18 smears had more than 10 epithelial clusters each composed of more than 50 cells), presence of cellular discohesiveness (13/18, 72.2%), but only mild nuclear atypia (5/18, 27.8%). Anisonucleosis was present in fewer than half the cases and no apparent condensed chromatin was identified. CONCLUSION: We highlight the significance of subclassification of MFA in aspiration cytology of breast. MFA had a significantly higher chance of falling into the 'suspicious for malignancy' or 'indeterminate' diagnostic category in aspiration cytology. It might be a diagnostic challenge for cytopathologist to identify this subtype of FA in FNA smears.
Adolescent↗
Eplerenone inhibits tumour necrosis factor alpha shedding process by tumour necrosis factor alpha converting enzyme in monocytes from patients with congestive heart failure.
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ADAM Proteins↗
Molecular roles of MAP kinases and FADD phosphorylation in prostate cancer.
Mitogen activated protein (MAP) kinases are well known serine threonine kinases that modulate gene expression, mitosis, cell proliferation and programmed cell death or 'apoptosis' in response to various stresses. Extracellular stress regulated kinase (ERK), c-jun NH2 terminal kinase and p38 are major members of the MAP kinases, and there is now a body of evidence of their involvement in genesis or sensitivity to chemotherapy of human prostate cancers. In this review, we focus on the molecular roles of MAP kinases and their pathological correlations, with particular attention to novel downstream signals through phosphorylation of the Fas-associated death domain protein that effectively regulates not only apoptosis but also the cell cycle in prostate neoplastic cells.
Adaptor Proteins, Signal Transducing↗
Distribution of dioxins in surface soils and river-mouth sediments and their relevance to watershed properties.
The dioxins toxic equivalent (TEQ) concentration in surface soils, river sediments and river-mouth sediments was measured by the CALUX assay in the Yasu and Ado River basins around Lake Biwa, Japan. In order to examine the distribution of dioxins in each watershed, we evaluated and compared the correlation between the dioxins TEQ concentration and the solid characteristics (i.e. organic carbon content and particle size distribution) of all samples. In both basins, the dioxins TEQ concentration in forest soil correspondingly showed a very good linear relationship to organic carbon content. On the other hand, the dioxins TEQ concentration in paddy field was significantly high, although organic carbon content was relatively low. Generally, the smaller particles have the higher dioxins TEQ concentrations in surface soils, and river sediments were composed of very coarse particles and had relatively low dioxins TEQ concentration. Therefore, we expected high dioxins TEQ concentration in river-mouth sediment, which was, however, not the case. Although the dioxins TEQ concentration in river-mouth sediments is low, the degree of dioxins pollution was different in each basin. The difference was considered to come from the difference of watershed properties including land use, river-slope, dam construction as well as the surface soil pollution.
Carbon↗
Correlation of serum pepsinogens and gross appearances combined with histology in early gastric cancer.
The correlation between serum pepsinogen (PG) levels and the gross types was investigated in 128 consecutive patients with early gastric cancer. Although there was no significant difference in age, gender, cancer location, or cancer depth among gross appearances, the distribution of histological type was significantly different between polypoid and depressed cancers: all polypoid cancers except one were intestinal type, whereas nearly a third of depressed cancers were diffuse type. All the patients in whom Helicobacter pylori status was investigated had Helicobacterpylori infection. Combination of gross appearances and histology (polypoid cancer with intestinal type, depressed cancer with intestinal type and depressed cancer with diffuse type) showed a clear difference in distribution of serum PG levels and a ratio between levels of PG I and PG II (I/II ratio). In polypoid cancer with intestinal type, a PG I level and a I/II ratio were significantly lower than those of the others. In depressed cancer with diffuse type, PG I and PG II levels were significantly higher. These findings revealed that backgrounds such as intragastric acidity and extent of gastric atrophy might differ among early gastric cancers with different morphology and histology.
Adult↗
Roles of pedunculopontine tegmental cholinergic receptors in brain stimulation reward in the rat.
RATIONALE: The brainstem pedunculopontine tegmental nucleus (PPTg) is proposed to mediate hypothalamic self-stimulation reward via cholinergic activation of the ventral tegmental area (VTA). However, to date there is little direct evidence to support this hypothesis. OBJECTIVES: To further study the role of PPTg in hypothalamic self-stimulation reward. METHODS: By using in vivo microdialysis, the levels of extracellular acetylcholine (ACh) in the PPTg and VTA were detected during lateral hypothalamic (LH) self-stimulation in rats. Rate-frequency curve shift procedure was used to evaluate the effects of nonselective muscarinic antagonist scopolamine (1 approximately 100 microg/microl) and nicotinic antagonist mecamylamine (5 approximately 100 microg/microl) microinjected into the PPTg on the rewarding efficacy of LH self-stimulation. Subsequently, the drugs were injected into the PPTg, and the extracellular ACh in the VTA was measured. RESULTS: LH self-stimulation produced a concurrent ACh release in the PPTg and VTA. Intra-PPTg injection of scopolamine (100 microg/microl) significantly reduced the frequency threshold for LH self-stimulation reward, but nicotinic antagonist mecamylamine did not shift the threshold. However, mecamylamine (10, 25 microg/microl) injected into the PPTg robustly diminished the nicotine-potentiated LH self-stimulation reward. The extracellular ACh in the VTA was dramatically increased by intra-PPTg scopolamine (10, 100 microg/microl), but not by mecamylamine. CONCLUSIONS: Results confirm that PPTg plays an important role in brain stimulation reward by modulating the cholinergic activity of the VTA. The PPTg muscarinic receptors contribute to an inhibitory modulation of reward effects by self-stimulation, whereas nicotinic receptors seem to be more involved in nicotine potentiation of brain stimulation reward.
Acetylcholine↗
Presynaptic GABAA receptors facilitate spontaneous glutamate release from presynaptic terminals on mechanically dissociated rat CA3 pyramidal neurons.
Mossy fiber-derived giant spontaneous miniature excitatory postsynaptic currents have been suggested to be large enough to generate action potentials in postsynaptic CA3 pyramidal neurons. Here we report on the functional roles of presynaptic GABA(A) receptors on excitatory terminals in contributing to spontaneous glutamatergic transmission to CA3 neurons. In mechanically dissociated rat hippocampal CA3 neurons with adherent presynaptic nerve terminals, spontaneous excitatory postsynaptic currents were recorded using conventional whole-cell patch clamp recordings. In most recordings, unusually large spontaneous excitatory postsynaptic currents up to 500 pA were observed. These large spontaneous excitatory postsynaptic currents were highly sensitive to group II metabotropic glutamate receptor activation, and were still observed even after the blockade of voltage-dependent Na(+) or Ca(2+) channels. Exogenously applied muscimol (0.1-3 microM) significantly increased the frequency of spontaneous excitatory postsynaptic currents including the large ones. This facilitatory effect of muscimol was completely inhibited in the presence of 10 microM 6-imino-3-(4-methoxyphenyl)-1(6H)-pyridazinebutanoic acid HBr, a specific GABA(A) receptor antagonist. Pharmacological data suggest that activation of presynaptic GABA(A) receptors directly depolarizes glutamatergic terminals resulting in the facilitation of spontaneous glutamate release. In the current-clamp condition, a subset of large spontaneous excitatory postsynaptic potentials triggered action potentials, and muscimol greatly increased the frequency of spontaneous excitatory postsynaptic potential-triggered action potentials in postsynaptic CA3 pyramidal neurons. The results suggest that presynaptic GABA(A) receptors on glutamatergic terminals play an important role in the excitability of CA3 neurons as well as in the presynaptic modulation of glutamatergic transmission onto hippocampal CA3 neurons.
Action Potentials↗
Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation.
BACKGROUND: Early events in the progression of 90% of sporadic colorectal cancers depend on constitutive activation of Wnt signalling. Recent data also indicate a close association between the Hedgehog (Hh) and Wnt pathways in colonic epithelial cell differentiation. AIMS: To investigate whether expression of Gli1, a transactivator of Hh signalling, can suppress Wnt signalling and inhibit proliferation of human colorectal cancer cells. METHODS: Gli1 and nuclear beta-catenin expression were examined in a series of 40 human colorectal cancers by immunohistochemistry. We quantified Gli1 and nuclear beta-catenin staining as markers of Hh and Wnt pathway activation, respectively. Two human colon cancer cell lines, SW480 and HCT116, with mutations in APC and beta-catenin, respectively, were used. The effects of Gli1 overexpression on Wnt transcriptional activity, beta-catenin subcellular distribution, and proliferation in these cells were analysed. RESULTS: Nuclear accumulation of beta-catenin and the Gli1 staining level were inversely associated in the 40 human colorectal cancers. Wnt transcriptional activity was reduced in Gli1 transfected cells. These effects were observed even in Gli1 transfected cells cotransfected with mutated beta-catenin. Furthermore, nuclear accumulation of beta-catenin was diminished compared with that in empty vector transfected cells, and downregulated transcription of c-Myc was observed in Gli1 transfected cells. Proliferation of Gli1 transfected cells was also significantly suppressed compared with that in empty vector transfected cells. CONCLUSIONS: Our data suggest that Gli1 plays an inhibitory role in the development of colorectal cancer involving Wnt signalling, even in cases with the stabilising mutation of beta-catenin.
Carrier Proteins↗
The potyvirus associated with the dappled fruit of Passiflora edulis in Kagoshima prefecture, Japan is the third strain of the proposed new species East Asian Passiflora virus (EAPV) phylogenetically distinguished from strains of Passion fruit woodiness virus.
A potyvirus (isolate IB) causing dappled or faded fruits and foliar mosaic symptoms of purple passionfruit, was found in the botanical garden of Kagoshima University, Japan. This isolate--differed in host range from isolates of Passion fruit woodiness virus (PWV)-AO, previously reported to cause "woodiness" in Japan. Isolates IB and AO had 83% amino acid identity in their coat proteins (CPs). In phylogenetic analysis, East Asian isolates IB, AO, and PWV-Taiwan clustered together, and were distinguishable from Australian PWV and Brazilian Cowpea aphid-borne mosaic virus isolates, which also cause "woodiness" in passionfruit. We propose the name "East Asian Passiflora virus (EAPV)" for the new potyvirus species.
Capsid Proteins↗
A ninety-day oral toxicity study of a new type of processed gum arabic, from Acacia tree (Acacia senegal) exudates, in F344 rats.
This study was designed to evaluate and characterize any subchronic toxicity of a new type of gum arabic (SUPER GUM [Acacia(sen)SUPER GUM]), a naturally processed polysaccharide exudate from gum acacia trees (Acacia senegal), when administered to both sexes of F344 rats at dietary levels of 0 (control), 1.25%, 2.5%, and 5.0% (10 rats/sex/group). During the study, the treatment had no effects on clinical signs, survival, body weights, and food and water consumption, or on findings of urinalysis, ophthalmology, hematology, or blood biochemistry. Gross pathology and histopathology exhibited no differences of toxicological significance between control and treated rats. Increased relative cecum (filled) weights, evident in both sexes of 5.0% group and females of 1.25% and 2.5% groups, were considered to be a physiological adaptation. Thus, the results indicated the toxic level of SUPER GUM to be more than 5.0%, and the no observed adverse effect level (NOAEL) was concluded to be 5.0% (3,117 mg/kg body weights/day for males, and 3,296 mg/kg body weights/day for males) from the present study.
Administration, Oral↗
Anti-inflammatory effect of activated protein C in gastric epithelial cells.
It has been previously demonstrated that activated protein C (APC) plays an important role in the inhibition of inflammation in the gastric mucosa from patients with Helicobacter pylori infection. However, the role of gastric epithelial cells in the anti-inflammatory activity of APC remains unknown. In the present study, we evaluated the anti-inflammatory activity of APC and the expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) in gastric epithelial cells. The gastric epithelial cell lines, MKN-1 and AGS, and gastric biopsy samples from patients with and without H. pylori infection were used in the experiments. Polymerase chain reaction showed that gastric epithelial cell lines express EPCR and TM. Flow cytometry analysis also showed EPCR expression in both cells. H. pylori infection significantly increased EPCR expression compared with non-infected cells. Similar results were observed in vivo when samples from patients with and without H. pylori infection were analyzed for EPCR protein expression. Significant TM activity was found on AGS and MKN-1 cells stimulated with LPS from Escherichia coli and VacA antigen. APC was able to significantly inhibit the secretion of MCP-1 and IL-1beta induced by H. pylori homogenate in AGS cells. APC also remarkably suppressed the mRNA expression and secretion of MCP-1 from AGS cells infected with H. pylori. These results demonstrated the expression of components of the protein C pathway on gastric epithelial cells and that APC may play a critical role in the protection against gastric mucosal inflammation.
Antigens↗
Neuroradiologic and clinicopathologic features of oculoleptomeningeal type amyloidosis.
OBJECTIVE: To clarify the pathogenesis of leptomeningeal amyloidosis in familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C (FAP ATTR Y114C). METHODS: The authors analyzed eight FAP ATTR Y114C patients. Six patients showed CNS symptoms associated with leptomeningeal amyloidosis. To examine the function of the blood-CSF barrier and blood-brain barrier (BBB), the authors performed CSF and MRI studies. The authors also performed a histopathologic study of autopsy specimens to examine the distribution of amyloid deposition in the CNS. RESULTS: CSF study showed high total protein concentrations and increased albumin CSF/serum concentration quotients (Qalb; an indication of blood-CSF barrier function). MRI with gadolinium (Gd) revealed enhancement from brainstem to spinal cord. Serial brain MRI studies with FLAIR images after Gd administration showed Gd leakage into the subarachnoid space (two patients). These findings suggested the blood-CSF barrier and BBB dysfunctions. Constructive interference in steady state (CISS) three-dimensional Fourier transformation (CISS-3DFT) sequence analysis demonstrated amyloid-induced funiculus structures joining the spinal cord and dura mater (one patient). Histopathologic study revealed intense amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. These distributions of amyloid deposition are unique compared to other TTR related leptomeningeal amyloidosis. CONCLUSIONS: Patients with familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C had CNS disorders related to amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. The pathogenesis of CNS disorders may reflect disruption of the blood-CSF barrier and blood-brain barrier by amyloid deposition.
Adult↗