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Biomedical subjects

Y Ueda

Publications and source records attributed to Y Ueda.

At least 163 records · Page 9Linked to original sources
PubMed2000

Different role of IL-4 in the onset of hapten-induced contact hypersensitivity in BALB/c and C57BL/6 mice.

1. To study the role of interleukin (IL)-4 in the onset of contact hypersensitivity (CH) in mice, the effect of IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment on dinitrofluorobenzene (DNFB)-induced CH was examined. Simultaneously, to clarify the effect of background gene, DNFB-induced CH in BALB/c and C57BL/6 mice was compared. 2. Five repeated topical applications of DNFB to the ears of mice resulted in CH of the ears in terms of increases in ear thickness and histopathological changes. The magnitude of ear thickness increase in BALB/c mice was almost three times greater than that in C57BL/6 mice. 3. The CH in BALB/c mice was significantly suppressed by IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment. In contrast, the symptoms of dermatitis in C57BL/6 mice were slightly affected by the same treatment. These changes corresponded well to the production of specific IgE antibody. 4. Total IgE antibody production and the expression of productive Cepsilon mRNA were dramatically suppressed by IL-4 gene-depletion and anti-IL-4 treatment in BALB/c and C57BL/6 mice. Neither total IgG nor IgM levels in either strain of mice was altered by depletion of IL-4. 5. The expression of IFN-gamma in the skin lesion was dramatically suppressed by IL-4 gene-depletion in BALB/c mice, but not in C57BL/6 mice. 6. These findings indicate that IL-4 plays an important role in the onset of DNFB-induced CH in BALB/c mice, but not in C57BL/6 mice.

Animals↗
PubMed2000

Fulminant hepatitis B following bone marrow transplantation in an HBsAg-negative, HBsAb-positive recipient; reactivation of dormant virus during the immunosuppressive period.

It is widely accepted that seroconversion of HBsAg to HBsAb indicates clearance of hepatitis B virus. We describe a 50-year-old man with chronic myelocytic leukemia who developed lethal hepatitis B 22 months after allo-BMT. He had been negative for HBsAg and positive for HBsAb before BMT. Hepatitis B virus latently existing in the liver cells before BMT proliferated during the immunosuppressed period causing fatal hepatitis. Recipients with positive HBsAb should be considered to have the potential for active hepatitis B to emerge after BMT. Bone Marrow Transplantation (2000) 25, 105-108.

Bone Marrow Transplantation↗
PubMed2000

Long-term tracking of murine hematopoietic cells transduced with a bicistronic retrovirus containing CD24 and EGFP genes.

Hematopoietic stem cells (HSCs) are attractive targets for gene therapy, but current gene transfer methodologies are inadequate for efficient HSC transduction and perpetual transgene expression. To improve gene transfer vectors and transduction protocols, it is vital to establish a system to evaluate transgene expression and the long-term behavior of transduced cells in vivo. For this purpose, we constructed a bicistronic retrovirus encoding the human CD24 (as the first cistron) and the enhanced green fluorescent protein (EGFP; as the second cistron). Murine bone marrow cells were transduced with this vector and the transgene expression was monitored along with hematopoietic reconstitution. Stable expression of CD24 and EGFP was demonstrated in the long-term repopulating cells for at least 6 months, and multi-parameter flow cytometry illustrated expression of both markers in all the lymphohematopoietic lineages examined (B and T lymphoid, erythroid and myeloid). Sustained expression was also shown in the secondary transplants for 6 months, suggesting that self-renewing HSCs were transduced by this vector. Overall, EGFP-tagged bicistronic retroviruses would provide powerful tools for detailed in vivo analysis of transduced hematopoietic cells, such as transgene expression in conjunction with lineage differentiation. Gene Therapy (2000) 7, 1193-1199.

Animals↗
PubMed2000

Analysis of K-ras codon 12 mutations and p53 overexpression in colorectal nodule-aggregating tumors.

BACKGROUND AND AIMS: Morphologically, colorectal nodule-aggregating tumors are quite different from polypoid-type colorectal tumors that develop via the adenoma-carcinoma sequence. Although polypoid-type colorectal tumors are well known to have a high incidence of K-ras gene mutation and p53 overexpression, colorectal nodule-aggregating tumors have not been examined in terms of genetic changes and clinicopathological features. In the present study, therefore, we analysed the clinicopathological features, genetic changes in K-ras codon 12, and p53 overexpression in colorectal nodule-aggregating tumors. METHODS: A total of 18 colorectal nodule-aggregating tumors were surgically resected and then analysed clinicopathologically. Immunohistochemistry and polymerase chain reaction-single stranded conformational polymorphism were performed to analyse p53 abnormalities in the tumors. K-ras codon 12 mutations were screened out by the polymerase chain reaction-restriction fragment length polymorphism method and analysed by fluorescence direct sequencing. RESULTS: p53 overexpression was observed in six lesions (33%). p53-overexpressing cells were observed in parts of carcinoma or adenoma showing high-grade atypia. Four of the 10 (40%) samples had a p53 gene mutation. Nine of the 18 (50%) samples had a K-ras codon 12 point mutation. In eight cases (89%), the mutations of the K-ras codon 12 were of the same type: GGT (glycine) to GTT (valine). CONCLUSIONS: The colorectal nodule-aggregating tumor has distinctive characteristics showing a morphological phenotype of the superficial-type tumors and genotype of the polypoid tumors in terms of K-ras gene mutation and p53 overexpression.

Adenoma↗
PubMed2000

A case report of refractory obsessive-compulsive disorder improved by risperidone augmentation of clomipramine treatment.

A male patient aged 43 years, suffering from symptoms of obsessive-compulsive disorder (OCD), such as washing hands and feet frequently and checking documents compulsively, had received intensive pharmacotherapeutic and behavior therapy. Although the administration of anxiolytic drugs and/or clomipramine did not show curative effects, a combination of clomipramine and risperidone showed much greater effect in improving these symptoms.

Adult↗
PubMed2000

Incidence of P53 and K-ras alterations in ovarian mucinous and serous tumors.

Clarification of the pathogenic relationships existing among ovarian cystadenomas, tumors of low malignant potential (LMP) and various adenocarcinoma types, a series of 29 mucinous and 19 serous ovarian tumors including adenomas, LMP tumors and adenocarcinomas were examined. P53 protein was detected by the streptavidin-biotin method and point mutation of K-ras codon 12 was detected by polymerase chain reaction-restriction fragment length polymorphism analysis. P53 overexpression was observed more frequently in serous adenocarcinomas (5/8, 63%) than in mucinous adenocarcinomas (2/9, 22%) and was correlated with the malignant potential of serous tumors. Furthermore, the proportion of P53-positive cells was significantly higher in serous adenocarcinomas than in mucinous adenocarcinomas. P53 overexpression may therefore be closely related to the early events of carcinogenesis in serous tumors. Although mutation of the K-ras oncogene appears to be an important event in the early tumorigenesis of mucinous tumors, mutation of the K-ras oncogene in serous tumors may be dependent on morphology. Different complex pathways of oncogene and/or tumor suppressor gene abnormalities may be involved in the development of mucinous and serous adenocarcinomas.

Cell Transformation, Neoplastic↗
PubMed2000

Rotavirus infection in children in Japan.

Currently, a high morbidity of rotavirus diarrhea has been seen in children in developed and developing countries. Improvement of the vaccines is necessary in order to reduce the burden of diarrhea caused by rotavirus. A survey of rotavirus infection from diarrheal stool specimens in children of seven regions in Japan was conducted from 1984 to 1999. The present study discusses the survey results and reviews the national and international data of more than 23 papers and congress proceedings about rotavirus infection in Japan. We analyze the prevalence of rotavirus infection in acute diarrheal in- and outpatients, the distribution of rotavirus G-serotypes and surveillance data for seasonality and age groups in Japan. The data indicated that rotavirus is the most important cause of diarrhea in Japan among young children, with the prevalence ranging from approximately 9.7 to 88%. The most common rotavirus strains belonged to serotype G1, specifically since 1993. Serotypes G2, G3 and G4 had also been documented to be predominantly based in the area and year before 1992. However, untypeable rotavirus strains had been found each year, with a prevalence up to 56.7% which suggests that rare serotypes (except G1-4) or new serotypes might exist. Unexpectedly, in Tokyo and Sapporo from 1998 to 1999, G9 was found to be the first most prevailing serotype with a high prevalence of 52.9 and 71.4%, respectively. Despite these data from different geographic areas, the year under investigation was relatively clear in respect to seasonality, with a peak of rotavirus activity in late winter (February) through early spring (March). Age distribution had also characterized that the infection was predominant among children aged 1-2 years of age, although it was also common in children of 2-3 years. In addition, mixed infection with bacteria was documented.

Adolescent↗
PubMed2000

Advanced glycation and lipidoxidation of the peritoneal membrane: respective roles of serum and peritoneal fluid reactive carbonyl compounds.

BACKGROUND: Advanced glycation of proteins has been incriminated in the progressive alteration of the peritoneal membrane during chronic peritoneal dialysis (PD). Advanced glycation end products (AGEs) result from a modification of proteins by reactive carbonyl compounds (RCOs). RCOs resulting from glucose breakdown are present in commercial PD fluid. They also accumulate in uremic plasma. The present study was undertaken to evaluate the respective contribution of these two sources of RCOs in the genesis of peritoneal AGEs. METHODS: Three major RCOs formed during heat sterilization of PD fluid, that is, glyoxal, methylglyoxal, and 3-deoxyglucosone, and total RCOs were measured in commercial PD fluid and in PD effluent. The generation of pentosidine, used as a surrogate marker for AGEs, during one-week incubations of PD fluid and effluent samples fortified with bovine serum albumin (BSA) was measured by high-performance liquid chromatography. Peritoneal samples were stained with antibodies specific for two AGEs derived from carbohydrate-dependent RCOs, Nepsilon-(carboxymethyl)lysine (CML) and pentosidine, or for two advanced lipoxidation end products (ALEs) derived from lipid-dependent RCOs, malondialdehyde (MDA)-lysine and 4-hydroxynonenal (HNE)-protein adduct. RESULTS: Glyoxal, methylglyoxal, and 3-deoxyglucosone were identified in commercial PD fluid. Their levels in PD effluents decreased with dwell time probably by diffusion into blood circulation. In contrast, the levels of total RCOs were initially low in commercial PD fluid, increased in PD effluent with dwell time probably by diffusion from circulation into the peritoneal cavity, and after 12 hours, reached values observed in uremic serum. The relevance of the rise in total RCOs for AGE formation is demonstrated by a parallel increase in the generation of pentosidine during incubations of PD effluents. In contrast with RCOs present in glucose-rich PD fluid, RCOs diffusing from uremic circulation originate from both carbohydrates and lipids. Their role in the modification of peritoneal proteins is demonstrated by the immunohistochemical study of peritoneal tissue. Two AGEs and two ALEs increase in parallel in the mesothelial layers and in vascular wall of small arteries in the peritoneum. CONCLUSIONS: Protein modification of the peritoneum is determined not only by RCOs originating in PD fluid, but also by RCOs originating from the uremic circulation. The present data might be relevant to current attempts to improve PD fluid toxicity by lowering its glucose content.

Adult↗
PubMed2000

Effect of dwell time on carbonyl stress using icodextrin and amino acid peritoneal dialysis fluids.

BACKGROUND: Deterioration of the peritoneal membrane limits the technical survival of peritoneal dialysis (PD). Advanced glycation of the membrane has been incriminated in this evolution. Advanced glycation end products (AGEs) develop under the influence of glucose and of its degradation products, mainly reactive carbonyl compounds (RCOs) such as glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3-DG). The present study was undertaken to evaluate the impact of recently developed glucose-free PD fluids on AGE generation. METHODS: Recently developed glucose-free PD fluids containing either icodextrin or amino acids were investigated. GO, MGO, and 3-DG [high-performance liquid chromatography (HPLC)] and total RCOs (spectrophotometry) were measured in fresh solutions and in effluents after various dwell duration. The AGE formation potential of PD fluids and effluents was assessed by incubation at 37 degrees C, for one week, with bovine serum albumin and by the eventual measurement of pentosidine (HPLC) and Nepsilon-carboxymethyllysine (CML; gas chromatography/mass spectrometry). RESULTS: GO, MGO, and 3-DG (P < 0. 001) as well as total RCOs levels (P < 0.01) were significantly lower in icodextrin and amino acid PD fluid than in commercial, heat-sterilized, 1.36% glucose PD fluid. Pentosidine and CML generation were also significantly lower (P < 0.001) in icodextrin and amino acid PD fluid than in conventional 1.36% glucose PD fluid. The levels of total RCOs, however, increased in icodextrin and amino acid PD fluid effluents with dwell time. AGE formation potential rose accordingly, as demonstrated by a parallel increase in the generation of pentosidine and CML during incubation of PD effluents. CONCLUSION: The present data demonstrate lower RCO contents and AGE formation potential in fresh icodextrin and amino acid PD fluids than in fresh heat-sterilized glucose PD fluids. However, this difference decreases progressively during dwell time, mainly as a result of the influx of total RCOs.

Aged↗
PubMed2000

Treadmill training with body weight support: its effect on Parkinson's disease.

OBJECTIVE: To test whether body weight-supported treadmill training (BWSTT) is effective in improving functional outcome of patients with Parkinson's disease. DESIGN: Prospective crossover trial. Patients were randomized to receive either a 4-week program of BWSTT with up to 20% of their body weight supported followed by 4 weeks of conventional physical therapy (PT), or the same treatments in the opposite order. Medications for parkinsonism were not modified throughout the study. SETTING: Inpatient rehabilitation unit for neurologic diseases. SUBJECTS: Ten patients (5 men, 5 women) with Hoehn and Yahr stage 2.5 or 3 parkinsonism; mean age 67.6 years, mean duration of Parkinson's disease 4.2 years. MAIN OUTCOME MEASURES: The Unified Parkinson's Disease Rating Scale (UPDRS), ambulation endurance and speed (sec/10 m), and number of steps for 10-meter walk. RESULTS: The mean total UPDRS before/after BWSTT was 31.6/25.6, and before/after PT was 29.1/28.0. Analysis of covariance for improvement of UPDRS demonstrated a significant effect of type of therapy (F(1, 16) = 42.779, p < .0001) but not order of therapy (F(1, 16) = 0.157, p = .697 1). Patients also had significantly greater improvement with BWSTT than with PT in ambulation speed (BWSTT, before/after = 10.0/8.3; PT, 9.5/8.9), and number of steps (BWSTT, 22.3/19.6; PT, 21.5/20.8). CONCLUSIONS: In persons with Parkinson's disease, treadmill training with body weight support produces greater improvement in activities of daily living, motor performance, and ambulation than does physical therapy.

Aged↗
PubMed2000

Circulating bronchoepithelial cells expressing mRNA for surfactant protein A in patients with pulmonary fibrosis.

There are several unsolved clinical findings in patients with idiopathic pulmonary fibrosis (IPF); (i) predominance of fibrosis in the lower lung fields, (ii) digital clubbing, and (iii) patchy distribution of pulmonary fibrosis. To explain these unsolved problems, we hypothesized that regenerated or premature bronchoepithelial cells may circulate in the blood in patients with IPF. To prove this, we performed the reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19) and pulmonary surfactant protein A (SPA) in peripheral blood in patients with IPF and pulmonary fibrosis associated with collagen vascular disorders. In addition, 20 patients with chronic pulmonary emphysema as a disease control and 19 normal volunteers were also evaluated for the existence of circulating bronchoepithelial cells. RT-PCR analysis showed that CK19 was expressed in 12 of 38 blood samples (31.6%) of IPF and pulmonary fibrosis associated with collagen vascular disorders, seven of 20 (35.0%) blood samples of chronic pulmonary emphysema, and four of 19 (21.1%) blood samples of normal volunteers. mRNA for SPA was positive in eight of 38 (21.1%) blood samples of IPF. In contrast, SPA expressing cells were not detected in any blood samples obtained from patients with chronic pulmonary emphysema or normal volunteers. This evidence suggests that there were some circulating bronchoepithelial cells expressing mRNA for SPA in peripheral blood of patients with IPF and pulmonary fibrosis associated with collagen vascular disorders.

Adult↗
PubMed2000

Prognostic value of vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinomas.

Vascular endothelial growth factor (VEGF) has been identified as the substance that increases the permeability and proliferation of vascular endothelial cells. We examined the clinical significance of VEGF expression in 60 head and neck squamous cell carcinomas using the methods of Western blot, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR), comparatively, and analysed the relationship between VEGF status in Western blot and tumour size, lymph-node status, histologic grade and disease-free survival (DFS) rate. Western blot analysis revealed high VEGF expressors (tumour/normal tissue density >/= 3-fold) in 26 patients (43%) and low VEGF expressors (< 3-fold) in 34 patients (57%). The results of the Western blot analysis correlated significantly with those of the RT-PCR (P = 0.00007) or immunohistochemistry (P = 0. 00006). High VEGF expressors are associated with the progression of lymph-node spread (P = 0.0009), which are correlated with poor DFS. The 2-year DFS rate of high VEGF expressors (30%) was significantly lower than that of low VEGF expressors (78%) (P = 0.0008). Multivariate analysis showed VEGF expression and stage were independent predictors for the DFS (P = 0.045 and 0.041, respectively). VEGF expression may play an important role in progression of HNSCC.

Adult↗
PubMed2000

Serum IgE response to orally ingested antigen: a novel IgE response model with allergen-specific T-cell receptor transgenic mice.

BACKGROUND: The mechanism by which orally ingested allergens elicit an IgE response remains unclear because there are few animal models available for investigation of this response. OBJECTIVE: We tried to develop a murine model suitable for investigation of the IgE response to orally ingested allergens, which would allow us to identify T cells that could promote IgE production. METHODS: Ovalbumin (OVA)-specific T-cell receptor transgenic mice were fed a diet containing OVA, and both the serum antibody response and cytokine production by splenocytes were examined. RESULTS: Oral administration of OVA to transgenic mice led to an increase in the levels of both antigen-specific IgE and total IgE in the sera. Subsequent intravenous challenge of OVA-fed transgenic mice with OVA resulted in anaphylactic shock. Analysis of cytokine production by splenocytes revealed that high IL-4-producing T cells appeared in the spleen 1 week after the start of feeding the OVA diet. T cells from these mice were found to promote IgE secretion by BALB/c B cells in vitro. This helper activity and the levels of IL-4 secretion were diminished after long-term feeding. These findings suggest the possibility that the orally ingested antigen elicited a response by a subpopulation of T cells that produce high levels of T(H2)-type cytokines and that promote IgE secretion, and these same T cells were tolerized by the orally ingested antigen. CONCLUSION: This experimental model with transgenic mice may be a useful tool for further studies of the cellular and molecular mechanisms of the T-cell and IgE responses to orally ingested antigens.

Administration, Oral↗
PubMed2000

Metabolism of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27-hexafluoro-1 alpha,23(S)25-trihydroxyvitamin D3 in ROS17/2.8 cells transfected with a plasmid expressing CYP24.

1. To clarify the possibility that the metabolism of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 [F6-1,25(OH)2D3] to 26,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3 [F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to 26,27-hexafluoro-23-oxo-1 alpha,25-dihydroxyvitamin D3 [F6-23-oxo-1,25(OH)2D3] are catalysed by 25-hydroxyvitamin D3 24-hydroxylase (CYP24), ROS17/2.8 cells transfected with a plasmid expressing CYP24 [pSVL-CYP24(+)] and a corresponding blank plasmid [pSLV-CYP24R(-)] were used. 2. Incubation of [1 beta-3H]-F6-1,25(OH)2D3 for 2 and 5 days with ROS17/2.8 cells transfected with pSVL-CYP24(+) generated a metabolite that co-migrated with authentic F6-1,23,25(OH)3D3 in both normal phase and reversed-phase HPLC systems. 3. Incubation of [1 beta-3H]-F6-1,23,25(OH)3D3 for 5 days with pSVL-CYP24(+)- transfected ROS 17/2.8 cells generated a metabolite that co-migrated with authentic F6-23-oxo-1,25(OH)2D3. In contrast, the metabolites F6-1,23,25(OH)3D3 or F6-23-oxo-1,25(OH)2D3 were not generated in the cells transfected with pSVL-CYP24R(-). 4. The results indicate that CYP24 catalyses the conversion of F6-1,25(OH)2D3 to F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to F6-23-oxo-1,25(OH)2D3.

Animals↗
PubMed2000

Transmission electron microscopic study of hepatocytes in bioartificial liver.

A bioartificial liver (BAL) was prepared by simple inoculation of hepatocytes into the inner space of hollow fibers of a hemodialyzer and it was maintained in a closed circuit for in vitro culture. Morphology of hepatocytes in the hollow fibers was studied in detail using transmission electron microscopy (TEM). The hepatocytes formed three-dimensional, rod-shaped aggregates of 200 microm in diameter throughout the whole dimension of the hollow fibers after 1 day of culture. Approximately five hepatocyte layers existed from the surface to the center of the aggregate. The hepatocytes in the aggregate displayed mostly polygonal shapes and were surrounded by five to six cells. Abundant bile canaliculi were formed between the hepatocytes and were sealed by tight junctions. The distance between the adjacent hepatocytes except the bile canaliculus domain was approximately 20 nm, and interdigitation was observed between some hepatocytes. These observations indicate that the hepatocytes formed functionally associated aggregates, that is, organoids. Although the cells facing the inner surface of the hollow fiber lost their polygonal shape and became flattened during the following several-day culture, no drastic change was observed in the morphology of the hepatocytes located inside the aggregate. After 14 days of culture, the number of living cells decreased and most of these had a deformed nucleus, few numbers of organelles, and intermittent lipid droplets.

Animals↗
PubMed2000

'Carbonyl stress' and dialysis-related amyloidosis.

Advanced glycation end products (AGEs) are formed by nonenzymatic glycation and oxidation (glycoxidation) reactions. As AGE formation is related to hyperglycaemia, they have been implicated in the pathogenesis of diabetic complications. They also increase in normoglycaemic uraemic patients: AGEs, such as pentosidine and carboxymethyllysine (CML), are elevated in both the plasma proteins and skin collagen of uraemic patients, being several times greater than in normal subjects and nonuraemic diabetic patients. However, AGE concentrations do not differ between diabetics and non-diabetics in uraemia. AGE accumulation in uraemia, therefore, cannot be attributed to hyperglycaemia, or simply to the decreased removal by glomerular filtration of AGE-modified proteins as over 90% of plasma pentosidine and CML are linked to albumin. Recently, evidence has suggested that, in uraemia, the increased carbonyl compounds, derived from both carbohydrates and lipids, modify proteins both by the glycoxidation reaction (leading to augmented AGE production) and also by the lipoxidation reaction (leading to the augmentation of the advanced lipoxidation end product, ALE, production). Thus, uraemia might be a state of carbonyl overload with potentially damaging proteins ('carbonyl stress'). Carbonyl stress in uraemia appears to be relevant to long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis. Immunohistochemical studies, with specific antibodies to AGEs and ALEs, identified carbonyl stress in long-lived beta2-microglobulin amyloid deposits. Furthermore, proteins modified with carbonyl stress exhibit several biological activities through interactions with several types of cell, e.g. monocytes/macrophages, synovial cells and osteoclasts/osteoblasts, which might partially account for dialysis arthropathies.

Amyloidosis↗