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Biomedical subjects

K Ogawa

Publications and source records attributed to K Ogawa.

At least 37 records · Page 2Linked to original sources

Long-term follow-up of chronic hepatitis B after the emergence of mutations in the hepatitis B virus polymerase region.

Treatment of chronic hepatitis B has been greatly improved by the use of lamivudine, but mutations occur in the polymerase region of hepatitis B virus (HBV) and lamivudine-resistant mutants frequently develop. The emergence of lamivudine-resistant strains of HBV is a problem for treating chronic hepatitis B using lamivudine. We observed biochemical and virological changes in 15 patients with chronic hepatitis B for a median period of 29 months (range: 4-42 months) after the emergence of lamivudine-resistant mutants of HBV. Patterns of mutation of the polymerase gene were examined by sequencing the LLAQ motif in domain B and the YMDD motif in domain C. Exacerbation of liver dysfunction occurred in 14 (93.3%) of the 15 patients at a median of 4 months after the emergence of mutations. However, exacerbation of liver dysfunction was observed only in four patients (26.7%) at the time of appearance of the first mutations and in 80.0% of the patients at the time of appearance of the second mutations. Increase in serum alanine aminotransferase (ALT) levels was significantly greater at the time of appearance of second mutations (P = 0.0096). In most cases, wild-type HBV was mutated with the substitution of only rtM204I at first, and rtL180M/M204I mutations and then rtL180M/M204V mutations subsequently appeared. Further mutations of the polymerase region caused clinical deterioration. Thus as mutations emerge in the polymerase region, the clinical outcome deteriorates. Thus, monitoring the patterns of mutation of the polymerase gene is useful when using lamivudine for treating HBV.

Adult↗

Comparison of the effects of isoflurane and sevoflurane on protein tyrosine phosphorylation-mediated vascular contraction.

BACKGROUND: Isoflurane induces greater effects on vasodilation and decreasing blood pressure than sevoflurane. Tyrosine kinase-catalyzed protein tyrosine phosphorylation plays an important role in regulating vascular smooth muscle contraction. The aim of the present study was to compare the effects of isoflurane and sevoflurane on tyrosine phosphorylation-mediated vascular constriction, by assessing the degree of sodium orthovanadate (Na(3)VO(4), tyrosine phosphatase inhibitor)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle. METHODS: Na(3)VO(4)-induced contraction and protein tyrosine phosphorylation of rat aortic smooth muscle were measured in the presence of genistein, a tyrosine kinase inhibitor, and different concentrations of isoflurane and sevoflurane, using isometric force measurement and Western blot, respectively. RESULTS: Na(3)VO(4) (10(-4) M) induced sustained contraction and tyrosine phosphorylation of substrates that were both markedly attenuated in the presence of genistein (5 x 10(-5) M). Isoflurane and sevoflurane dose-dependently (1, 2, 3 MAC) attenuated the Na(3)VO(4)-induced contraction (P < 0.05-0.005, n = 8), with a greater degree of inhibition by isoflurane than sevoflurane at 2 MAC (P < 0.01) and 3 MAC (P < 0.05). Both anesthetics also attenuated the total band density of the Na(3)VO(4)-induced, tyrosine-phosphorylated substrates in a concentration-dependent manner (P < 0.05-0.005, n = 4), with much greater attenuation by isoflurane than sevoflurane at 1 and 2 MAC (P < 0.05), respectively. CONCLUSION: The results of the present study demonstrate that isoflurane exhibits a greater degree of inhibition on the Na(3)VO(4)-stimulated contraction and protein tyrosine phosphorylation of rat aortic smooth muscle compared with sevoflurane. These findings suggest that isoflurane depresses the protein tyrosine phosphorylation-mediated contraction of vascular smooth muscle to a greater degree than sevoflurane.

Anesthetics, Inhalation↗

Expression of a CD44 variant and VEGF-C and the implications for lymphatic metastasis and long-term prognosis of human breast cancer.

The aim of the present study was to determine whether expression of the CD44 variant v7-v8 (CD44v7-v8) or vascular endothelial growth factor-C (VEGF-C) is associated with long-term prognosis in breast cancer patients. A 10-year follow-up of 91 patients with primary breast cancer who were previously assessed for CD44 expression was undertaken. Immunohistochemical evaluation of VEGF-C expression was performed in 87 of these patients and their long-term prognosis was assessed. The disease-free and overall survival rates were significantly poorer for the CD44v7-v8-positive patients than for the patients negative for this marker. VEGF-C expression was detected in 38 out of the 87 patients (43.7%) with primary human breast cancer. There were no significant differences in tumor size, histological type, axillary lymph node status, presence of lymphatic or venous invasion, or presence of estrogen receptors and progesterone receptors between the VEGF-C-positive and -negative patients. There were also no significant differences in the disease-free or overall survival rates in these patient groups. In conclusion after the 10-year follow-up, expression of CD44v7-v8 was associated with poor prognosis for breast cancer patients. However, there was no association between VEGF-C expression and the clinicopathological factors or prognosis of breast cancer patients.

Breast Neoplasms↗

Clinical significance of elongation factor-1 delta mRNA expression in oesophageal carcinoma.

Elongation factor-1 (EF-1) delta is a subunit of EF-1, which is a protein complex that participates in the elongation step of mRNA translation and has recently been considered to correlate with oncogenic transformation. However, there has been no information regarding the clinical significance of EF-1 delta mRNA expression in malignant tumours, including oesophageal carcinoma. Thus, we quantitated the expression of EF-1 delta in malignant and benign oesophageal tissues and associated these levels with clinicopathologic parameters of oesophageal carcinoma. Paired oesophageal tissue samples from cancerous and corresponding noncancerous parts were obtained from 52 patients who underwent curative oesophagectomy. Quantitative analyses of EF-1 delta expression were performed using real-time quantitative reverse transcription-polymerase chain reaction. Elongation factor-1 delta mRNA overexpression in cancerous tissues compared to normal counterparts was observed in 38 of 52 (73%) patients. The mean expression level of EF-1 delta mRNA in cancerous tissues was significantly higher than that in noncancerous tissues (P<0.01). A higher expression of EF-1 delta was significantly correlated with lymph node metastases (P<0.05) and advanced stages (P<0.05). Furthermore, the cause-specific survival of patients with a higher expression of EF-1 delta was significantly poorer than those with a lower expression (5-year cause-specific survival rates; 23 and 54%, respectively, P<0.05). The results of this study indicated that EF-1 delta mRNA expression was significantly higher in cancerous compared to noncancerous oesophageal tissues, and a higher expression of EF-1 delta mRNA was correlated with lymph node metastases, advanced disease stages and poorer prognosis for patients with oesophageal carcinoma.

Adenocarcinoma↗

Does eradication of Helicobacter pylori reduce the risk of carcinogenesis in the residual stomach after gastrectomy for early gastric cancer? Comparison of mucosal lesions in the residual stomach before and after Helicobacter pylori eradication.

BACKGROUND AND AIMS: After partial gastrectomy, the mucosa of the residual stomach usually undergoes severe changes, and these lesions are known to be pre-cancerous. Recently, Helicobacter pylori has been highlighted as an agent that induces such mucosal alterations. In the present study, we evaluated whether eradication of H. pylori reduced the risk of carcinogenesis. PATIENTS AND METHODS: The subjects were 12 patients who underwent distal gastrectomy with Billroth I anastomosis for early gastric cancer and were positive for H. pylori. We performed endoscopy and biopsy both before and after H. pylori eradication therapy to assess changes in the gastric mucosa. RESULTS: After eradication therapy, no mucosal edema or erythema was detected. On histological examination, mononuclear cell infiltration had decreased and there was complete absence of neutrophil infiltration. The Ki-67 labeling index and the tissue IL-8 level had also decreased significantly, compared with before eradication. CONCLUSION: Before H. pylori eradication, the mucosa of the residual stomach may be at high risk of carcinogenesis due to induction of mucosal damage and active gastritis by H. pylori. Such changes were almost completely normalized by eradication therapy, so the eradication of H. pylori may reduce the risk of H. pylori-associated carcinogenesis in patients who have undergone gastrectomy for early gastric cancer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Assessment of tissue-engineered stomach derived from isolated epithelium organoid units.

OBJECTIVE: Isolated stomach epithelial organoid units developed on biodegradable polymers were transplanted to assess the feasibility of a tissue-engineered stomach. BACKGROUND: Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. An alternative treatment would be a tissue-engineered stomach, which replaces the mechanical and metabolic functions of a normal stomach. METHODS: Stomach epithelial organoid units isolated from neonatal rats were seeded onto biodegradable polymers. The constructs implanted into the omenta of adult rats were harvested for examination at designated times. Nine rats underwent a second operation for anastomosis. RESULTS: The constructs resulted in cyst-like formations showing vascularized tissue with neomucosa lining the lumen. The surface morphology as assessed using scanning electron microscopy was similar to that of a native stomach. Immunohistochemical staining for alpha-actin smooth muscle and gastric mucin indicated the presence of a smooth muscle layer and a well-developed gastric epithelium, respectively. The luminal surface of the anastomosed tissue-engineered stomach was well-covered with epithelium. CONCLUSIONS: Epithelium-derived stomach organoid units seeded on biodegradable polymers and transplanted into donor rats were shown to vascularize, survive, and regenerate into complex tissue resembling native stomach. Anastomosis between the units and native small intestine may have the potential to stimulate epithelial growth. This research may provide insight into new approaches to alleviate complications following total gastrectomy.

Animals↗

Prevention of hepatitis B virus recurrence after living donor liver transplantation.

The emergence of lamivudine-resistant hepatitis B mutations is a major complication during pretransplantation treatment. The proper time to begin Lamivudine before transplantation is not yet known. Twenty-six patients received preoperative lamivudine treatment followed by combined lamivudine and hepatitis B immunoglobulin after transplantation up to December 2002. The length of preoperative lamivudine treatment ranged from 13 to 200 days (mean, 52 +/- 37 days). Hepatitis B virus-DNA was positive in 22 of 26 (84.6%) patients before preoperative lamivudine prophylaxis and persistently positive among only 4 of 22 patients (18%) who at transplantation did not show a viral mutation. In all patients, hepatitis B virus-DNA became negative immediately after transplantation. At a median follow-up of 34 months, neither a hepatitis B recurrence nor a mutation had occurred in any patient. The ability to schedule the proper time for preoperative lamivudine prophylaxis is an advantage of living donor liver transplantation.

Antiviral Agents↗

Barium sulphate with a negative zeta potential accelerates skin permeability barrier recovery and prevents epidermal hyperplasia induced by barrier disruption.

BACKGROUND: Barium sulphate, a stable inorganic material, has been used in contrast media and cosmetic products because of its stability. As a negative external electric potential accelerates the skin barrier repair after barrier disruption, we hypothesized that topical application of barium sulphate may affect the skin barrier recovery rate depending on its zeta potential. OBJECTIVES: To investigate whether barium sulphate particles in aqueous solution have different zeta potentials depending on their surface structure, and to investigate the possible relation between zeta potential and skin barrier recovery rate. METHODS: Mice were subjected to tape stripping to disrupt barrier function, or were treated with acetone and kept in a dry environment to induce epidermal hyperplasia. They were then treated with different forms of barium sulphate, and barrier recovery was monitored by measurements of transepidermal water loss. RESULTS: There was a significant correlation between the barrier recovery rate and zeta potential of barium sulphate applied topically. Barium sulphate with a negative zeta potential significantly accelerated barrier recovery, but barium sulphate with a positive zeta potential did not accelerate or even delayed barrier repair. Barium sulphate with a negative zeta potential had an X-ray diffraction pattern different from that with a positive potential. The distribution of calcium in the epidermis was also influenced by the polarity of zeta potential. CONCLUSIONS: These findings suggest a new pharmacological approach towards altering barrier function or epidermal hyperplasia with inorganic particles in healthy and diseased skin.

Administration, Cutaneous↗

Serum granulysin is a marker for Th1 type immunity in pre-eclampsia.

Recent studies suggest that pre-eclampsia is associated with a Th1 predominant state and may be considered a failure of tolerance. Granulysin is a cytotoxic granule protein of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Recently, we developed an enzyme-linked immunosorbent assay (ELISA) system for detecting serum granulysin, and reported that serum granulysin is a useful marker to evaluate the cell-mediated immunity. In this study, we show that the serum levels of granulysin were significantly elevated in pre-eclamptic patients compared with those in normal pregnancy subjects. In addition, the serum granulysin levels in pre-eclamptic patients were well associated with mean blood pressure, percentage of peripheral blood Th1 cells and Th1/Th2 ratios. The present results suggest that the serum granulysin levels would be a useful and novel serum marker to evaluate the Th1/Th2 balance, especially Th1 type immunity in pre-eclampsia.

Adult↗

Increase in Ksp37-positive peripheral blood lymphocytes in mild extrinsic asthma.

Killer-specific secretory protein of 37 kDa (Ksp37), identified as a Th1/Tc1 specific secretory protein is expressed preferentially in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells and might be involved in essential processes of CTL-mediated immunity. Although extrinsic asthma is linked currently to a Th2-dominated pathogenesis, there is increasing evidence for Th1/Tc1-mediated processes in the aetiopathology of asthma. CTL from patients with asthma have been shown to express cytokines and effector molecules which were different from healthy controls. We hypothesized that Ksp37 could indicate the involvement of CTL in the pathogenesis of extrinsic asthma. We therefore investigated Ksp37 expression in PBMC from patients with mild extrinsic asthma (n = 7) and healthy controls (n = 7). Flow cytometric analysis was used to quantify Ksp37+ cells and to investigate cellular Ksp37 expression as relative mean fluorescence intensities (MFI). We found a significantly (P = 0.016) higher percentage of Ksp37+ cells within the total lymphocyte population obtained from patients with mild extrinsic asthma compared with healthy controls. Subdifferentiation revealed a significant difference limited exclusively to the CD8+ subset (P = 0.010). In addition, Ksp37 secretion from cultured peripheral blood mononuclear cells (PBMC) and MFI of Ksp37+ lymphocytes were increased in patients with asthma compared with healthy controls. We conclude that mild extrinsic asthma appears to be associated with an increased expression of the Tc1 related protein Ksp37. The functional role of Ksp37 in the pathogenesis of asthma remains to be elucidated.

Adult↗

Modes of transmission of Glugea plecoglossi (Microspora) via the skin and digestive tract in an experimental infection model using rainbow trout, Oncorhynchus mykiss (Walbaum).

Glugea plecoglossi (Microspora) is a significant cause of economic loss in cultured ayu, Plecoglossus altivelis, in Japan, due to the unsightly appearance of infected fish harbouring xenomas in the body cavity. Modes of transmission of G. plecoglossi via the skin and digestive tract were studied in an experimental infection model using rainbow trout, Oncorhynchus mykiss. Combined with Uvitex 2B and in situ hybridization (ISH) assays, the early development of G. plecoglossi was successfully traced. Following a bath exposure of fish Uvitex 2B-labelled G. plecoglossi spores were observed to attach to microscopic injuries (trypan blue-positive sites) of fish skin, after which ISH-positive sporoplasms were found to invade the epidermis as early as 5 min post-infection (PI), migrating rapidly to the subdermis. It was also shown that G. plecoglossi entering via the skin does not spread into the internal organs but develops into subdermal xenomas. After rainbow trout were exposed to G. plecoglossi spores by oral intubation, spores germinated in the intestinal lumen, followed by penetration of sporoplasms into the gut mucosal epithelium 5 min PI. In vitro trials determining stimulation factors (fish mucus, changes in pH, digestive enzymes) for the extrusion of the polar tube were inconclusive. The present study indicates that skin wounds and the gut epithelium can be portals of entry of G. plecoglossi and that natural infection in fish seems to occur perorally rather than via the skin.

Animals↗

Hearing improvement after tumor removal in a vestibular schwannoma patient with severe hearing loss.

We herein report on the hearing improvement obtained after tumor removal in a vestibular schwannoma patient with preoperative severe hearing loss and good otoacoustic emission. Hearing recovery after tumor removal is an uncommon occurrence. As a result, hearing preservation surgery is usually not performed for patients with severe hearing loss. However, patients with a good OAE seem to have a better chance to recover their hearing than those with a poor OAE, even if they have severe hearing loss. As a result, the cochlear function should be evaluated, especially regarding the OAE, before determining the indications for hearing preservation surgery.

Adult↗

Monosegmental living donor liver transplantation.

BACKGROUND: Living donor liver transplant (LDLT) program has been started from 1990 in Japan, and is still major form of liver transplantation because of the scarcity of cadaveric donor organs. In small infants, implantation of left lateral segment grafts can be a problem because of a large-for-size graft. Until November 2002, we performed 867 transplants for 828 patients (561 children and 306 adults), and 14 cases received monosegment grafts from living donors. METHODS: Fifteen patients, median age 211 days, median weights 5.95 kg, received monosegmental LDLT. The indication for using this technique was infants with an estimated graft-to-recipient weight ratio of over 4.0%. RESULTS: Graft and patient survival is 85.7%. There were no differences in donor operation time and blood loss between monosegmentectomy and left lateral segmentectomy. Segment III grafts were indicated in 13 cases. Two vascular complications were observed (one hepatic artery thrombosis and one portal vein thrombosis). CONCLUSIONS: Monosegental living donor liver transplantation is a feasible option with satisfactory graft survival in small babies with liver failure.

Body Weight↗

Increased hepatocyte growth factor level in cerebrospinal fluid in Alzheimer's disease.

BACKGROUND & OBJECTIVE: Hepatocyte growth factor (HGF), also known as the scatter factor, is a potent mitogen for mature hepatocytes, and also has multifunctional effects on some cells in various organs. Recently, we have found expression and localization of HGF in white matter astrocytes in human brain tissues. Furthermore, immunohistochemistry using anti-HGF antibody revealed more intense immunolabeling in Alzheimer's disease (AD) than control brains. The aim of the study is to investigate the level of HGF in cerebrospinal fluid (CSF) from patients with AD. MATERIAL AND METHODS: We examined the level of HGF in CSF from 34 AD and 15 age-matched disease control patients by highly sensitive enzyme-linked immunoabsorbent assay (ELISA) system. RESULTS: Consistent with the immunohistochemical data, a significantly higher concentration of HGF in AD CSF was found as compared with controls. A significant correlation was also seen between CSF HGF levels and white matter high-signal foci determined on brain magnetic resonance imaging (MRI) in AD patients. CONCLUSION: These results indicate that CSF HGF levels correspond with the white matter damage in AD brain.

Aged↗

Analysis of gene expression in peripheral blood eosinophils from patients with atopic dermatitis and in vitro cytokine-stimulated blood eosinophils.

Investigation of differentially expressed genes in eosinophils of patients with allergic diseases such as atopic dermatitis (AD) will provide important information for elucidating possible mechanisms of pathology. To identify novel genes that are expressed in AD, we compared gene expression in samples of peripheral blood eosinophils from AD patients and healthy volunteers. RNA was extracted from peripheral blood eosinophils. The expression of various genes, such as those for cytokine receptors, eosinophil activation marker, platelet activating factor (PAF) receptor, eosinophil-specific granular proteins and apoptosis-related genes, was confirmed using real-time reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood eosinophils of healthy volunteers were also isolated and stimulated for introduction of various cytokines. RNA was extracted and gene expression was monitored. Several genes, such as those for cytokine receptors (granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha and beta chain and interleukin (IL)-3 receptor alpha chain), CD44 and PAF receptor were expressed at significantly higher levels in AD patients than in healthy volunteers. In addition, the anti-apoptotic genes, bcl-2 and bcl-xL, were expressed at increased levels in AD patients. No single gene expression correlated with clinical markers, such as eosinophil count or IgE levels. Expression of GM-CSF receptor beta chain and IL-3 receptor alpha chain in isolated blood eosinophils of healthy volunteers was stimulated by IL-5, IL-4, interferon (IFN)-gamma and GM-CSF. Expression of bcl-2 and bcl-xL was also increased after stimulation with IL-5, IL-4 or IFN-gamma. The in vitro enhancement of cytokine-stimulated gene expression correlated well with the enhancement observed in clinical samples of eosinophils, suggesting that cytokines may affect gene expression in vivo in eosinophils of patients with AD.

Adolescent↗

Factors involved in the susceptibility of spontaneously hypertensive rats to low K+-induced arrhythmias.

Disorders of intracellular Ca2+ homeostasis and intercellular coupling are thought to be crucial in the initiation and maintenance of malignant arrhythmias. The aim of this study was to investigate possible arrhythmogenic factors in spontaneously hypertensive rats (SHR) as well as their susceptibility to low K+-related arrhythmias. The experiments were performed on isolated hearts of 13 weeks-old SHR and age-matched Wistar Kyoto rats (WKY). Equilibration of the heart by Langendorff perfusion with oxygenated, 37 degrees C warm, standard Krebs solution at a constant pressure was followed by perfusion with low K+ solution for 60 min, unless sustained ventricular fibrillation occurred earlier. Electrocardiogram and epicardial monophasic action potentials (MAPs) were continuously monitored for incidence of arrhythmias and action potential changes. Myocardial tissue was taken for ultrastructural analysis and immunodetection of the main gap junction protein, connexin-43. The results showed that hypertrophic hearts of SHR exhibited prolongation of MAPs and a decrease in phosphorylation of connexin-43. Moreover, they were more prone to low K+-induced early after-depolarisations and ventricular premature beats as well as to connexin-43 and ultrastructural alterations than WKY rats. Consequently, the incidence of ventricular tachycardia (70% vs. 50%) and both transient (50% vs. 25%) and sustained (60% vs. 25%) ventricular fibrillation was higher in SHR than WKY rats. The results suggest that both prolongation of MAP and connexin-43 alterations are important arrhythmogenic factors facilitating arrhythmias in the setting of Ca2+ disorders due to hypokalaemia.

Animals↗

Studies of magnesium in congenital long QT syndrome.

We studied the role of magnesium (Mg) in congenital long QT syndrome (LQTS). Twenty-two congenital LQTS patients and 30 control subjects were included in this study. We measured serum Mg (SMg) level and Mg retention (MgR) level, and evaluated the role of Mg (a high MgR level reflects Mg deficiency in the body). The influence of intravenous Mg infusion on Mg level was evaluated. Relatively low SMg level and high MgR level (LQTS:control = 53:33%, p < 0.01) were recognized in congenital LQTS patients, but there was an overlap with controls. Mg supplementation did not shorten QT interval and there was no significant correlation between Mg levels and QTc interval. Patients with syncopal history showed a higher MgR level (syncope (+):syncope (-) = 70:46%, p < 0.01) and intravenous Mg infusion improved Mg deficiency. These results suggest that some (not all) congenital LQTS patients are in a Mg-deficient state, which may be associated with syncope, and Mg supplementation may prevent recurrent syncope in these patients. Because there are several subtypes of congenital LQTS, perhaps with genetic testing Mg deficiency may be identified as a significant cofactor in some forms, whereas in other forms it is not relevant.

Dietary Supplements↗