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Biomedical subjects

Y Kawaguchi

Publications and source records attributed to Y Kawaguchi.

At least 73 records · Page 4Linked to original sources
PubMed2001

[A case of recurrent hemophagocytic syndrome complicated with systemic sclerosis: relationship between disease activity and serum level of IL-18].

Hemophagocytic syndrome (HPS) is characterized by the activation of the mononuclear phagocytic system with prominent hemophagocytosis in the bone marrow and reticuloendothelial systems, and its occurrence is usually associated with variable disorders such as viral infections and malignant lymphoma. Recently, it was reported that HPS also occurred in association with underlying connective tissue disease, especially systemic lupus erythematosus. We report here a case of recurrent HPS complicated with systemic sclerosis. A 32-year-old woman had been diagnosed as systemic sclerosis since 1994. She was admitted due to unknown high fever and severe pancytopenia in 1997, and the diagnosis of HPS was determined because of hemophagocytosis in bone marrow and hyperferritinemia. Her symptoms were improved by immunosuppressive therapies including steroid pulse therapy and oral prednisolone (60 mg/day). She was followed by the treatment of oral prednisolone which was gradually tapered in our out-patient clinic. In August of 1999 high fever and severe anemia were recurred, and she was admitted again to our hospital because of the diagnosis as recurrent HPS. She had been treated with 40 mg/day of oral prednisolone and fever was immediately disappeared and hemoglobin was gradually increased. HPS is considered to be a rare complication with systemic sclerosis, and the etiology has been unknown. IL-18 is a novel cytokine which is a potent inducer of interferon-gamma, and its properties may be a proinflammatory regulation and activation of monocyte/macrophage and histiocyte through the expression of interferon-gamma. Therefore, the significance of IL-18 in the pathophysiology of HPS was recently reported. In this case, we investigated the significance of IL-18 and revealed the levels of serum IL-18 were well correlated with disease activity of HPS.

Adult↗
PubMed2001

Tumor necrosis factor-alpha (TNF-alpha) converting enzyme contributes to production of TNF-alpha in synovial tissues from patients with rheumatoid arthritis.

OBJECTIVE: Expression and function of tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in synovia of patients with rheumatoid arthritis (RA) were examined to investigate posttranslational regulation of TNF-alpha production by TACE in RA. METHODS: Expression of TACE protein was evaluated by immunohistochemistry. Cytokines and soluble cytokine receptors were measured by ELISA. TACE mRNA was detected by RT-PCR. The enzymatic activity of TACE was measured using TACE-specific fluorogenic substrate. RESULTS: Expression of TACE at protein level in synovial tissue (ST) of patients with RA was significantly stronger than that of patients with osteoarthritis (OA). In RA, TACE was mainly expressed in CD68+ macrophage-like synovial cells. ST from 9 of 9 RA and 3 of 8 OA patients expressed TACE mRNA. RA ST cells possessed significantly higher TACE-like enzymatic activity than OA ST. A synthetic TACE inhibitor significantly reduced the release of TNF-alpha and p75 TNF receptor from RA ST cells. CONCLUSION: TACE is an important regulator of the secretion of TNF-alpha from synovia of patients with RA.

ADAM Proteins↗
PubMed2001

Mature form of interleukin 18 is expressed in rheumatoid arthritis synovial tissue and contributes to interferon-gamma production by synovial T cells.

OBJECTIVE: To investigate the expression and function of interleukin 18 (IL-18) in synovial tissue (ST) of patients with rheumatoid arthritis (RA). METHODS: The localization of IL-18 in ST was analyzed by immunohistochemistry. IL-18 and IL-18 receptor (IL-18R) mRNA were detected by RT-PCR. Expression of IL-18 at the protein level was analyzed by Western blotting. Cytokines in culture supernatants were measured by ELISA. RESULTS: From immunohistochemical analysis, IL-18-producing cells were localized in the lining layer and sublining region of RA ST. Most of them coexpressed CD68 antigen. In ST from patients with osteoarthritis (OA), IL-18-producing cells were localized only in the sublining region and the numbers of these cells were small. From RT-PCR, RA ST expressed mRNA of IL-18, as well as alpha- and beta-chains of IL-18R. OA ST did not express or very weakly expressed mRNA of alpha- and beta-chains of IL-18R. ST from RA patients produced significantly larger amounts of IL-18 in vitro than OA ST. Western blotting revealed that RA ST expressed mature IL-18 more abundantly than OA ST. IL-12 alone stimulates interferon-gamma (IFN-gamma) production by RA synovial tissue cells, but IL-18 alone could not. In the presence of IL-12, however, IL-18 could synergistically stimulate IFN-gamma production by RA synovial tissue cells. OA synovial tissue cells responded to neither IL-12 nor IL-12 + IL-18. IL-18 showed synergistic effects with IL-12 on promoting the ability of synovial T cells from RA patients to produce IFN-gamma. CONCLUSION: These findings suggest that mature IL-18 is expressed in RA synovia and contributes to the production of IFN-gamma by infiltrating T cells.

Arthritis, Rheumatoid↗
PubMed2001

[Therapeutic effect of multimodal therapy, such as cryosurgery, locoregional immunotherapy and systemic chemotherapy against far advanced breast cancer].

A total of 6 breast cancer patients, 5 with local recurrent tumors on their anterior chest wall and 1 with far advanced primary breast tumor, underwent multimodal therapy in which cryosurgery was performed in combination with local injection of the non-specific immunopotentiator OK-432. This multimodal therapy was repeated as many times as possible. In addition, 3 patients whose general condition was relatively good were treated with mild chemotherapy. In every patient who underwent cryosurgery combined with locoregional immunotherapy, eradication or reduction of tumor was observed for several months. Of 3 patients who underwent cryosurgery, locoregional immunotherapy and systemic chemotherapy, the tumor burden decreased markedly in 2 patients and rapid tumor growth was suppressed in 1 patient, even though the diameter of tumor was over 5 cm in all cases. There were no side effects caused by either cryosurgery or locoregional immunotherapy. Little toxicity was observed throughout the mild chemotherapy. These results indicated that cryosurgery in combination with local injection of OK-432 should be a feasible modality against unresectable breast cancer on the chest wall, and that this therapeutic effect might be augmented by mild chemotherapy.

Aged↗
PubMed2001

Lack of association between hepatocyte nuclear factor-1beta gene and common forms of type 2 diabetes in the Japanese population.

Mutations in the hepatocyte nuclear factor-1beta (HNF-1beta) gene have been shown to be a cause of maturity-onset diabetes of the young (MODY). We studied the contribution of the HNF-1beta gene to susceptibility to common forms of Type 2 diabetes in the genetically homogeneous Japanese population, by investigating the allelic association of Type 2 diabetes with two markers in the HNF-1beta region. The frequency of a nonsense mutation, R177X, which was previously reported in a Japanese family, was also studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using a mismatch primer. A total of 200 subjects were studied. There was no significant difference in allele frequencies of either of the two polymorphisms studied between patients with Type 2 diabetes and control subjects, or between subgroups of patients subdivided by the presence of mild or severe diabetic nephropathy. None of the subjects studied had R177X mutation, giving a frequency of less than 1.1% in common forms of Type 2 diabetes in Japan. These results suggest that mutations in the HNF-1beta gene derived from a limited number of founders are not a major cause of common forms of Type 2 diabetes, even in the genetically homogeneous Japanese population.

Adult↗
PubMed2001

[Perioperative management of a patient with systemic lupus erythematosus, myasthenia gravis, and pemphigus foliaceous].

A 38-year-old female with systemic lupus erythematosus (SLE), myasthenia gravis (MG), and pemphigus foliaceous (PF) was scheduled to undergo total hysterectomy and lymphadenectomy. Preanesthetic examination revealed anemia, a prolonged activated partial thromboplastin time, and a reduced percent vital capacity. Antiphospholipid antibody was not positive. After treating the bullous lesions of PF and the muscle weakness due to MG (noted on admission for surgery) with oral prednisolone, the patient was scheduled for surgery. To avoid the use of a muscle relaxant and the potential complications of the airway manipulation involved in using a laryngeal mask or endotracheal tube, since the patient had MG and PF, a regional anesthetic technique was selected. This involved continuous epidural anesthesia, achieved using 1% or 2% mepivacaine, with sedation by a combination of propofol infusion (3 mg.kg-1.hr-1) and nitrous oxide (60% in oxygen). The patient breathed spontaneously under the mask throughout the 3.5-hr operation. The intraoperative surgical and anesthetic course was uneventful. After a benign postoperative course, the patient was discharged on the 16th postoperative day.

Adult↗
PubMed2000

Histochemistry and morphology of the multifidus muscle in lumbar disc herniation: comparative study between diseased and normal sides.

STUDY DESIGN: This comparative study was conducted on 19 patients (13 men and 6 women) with lumbar disc herniation (LDH). The histologic and histochemical differences and changes in the back muscles of the diseased and normal sides were evaluated. OBJECTIVES: To determine the histologic differences in the back muscles between the diseased and normal sides in lumbar disc herniation. SUMMARY OF BACKGROUND DATA: The morphologic changes of back muscles between the diseased and normal sides in lumbar disc herniation were examined using histologic and histochemical methods. Few studies have reported the difference in these changes based on quantitative analyses. METHODS: All samples were harvested bilaterally from the multifidus muscle at the level of L4-L5 or L5-S1 in patients with lumbar disc herniation and then were examined by histologic and histochemical methods (hematoxylin-eosin, Gomori trichrome, NADH-TR, and ATPase stains). The percentage, cross-sectional area (CSA), and lesser diameter (LD) of muscle fibers were measured using computerized image analysis. The Wilcoxon, paired t, Kruskal Wallis, and Fisher tests were used for statistical analysis. RESULTS: Both Type I and II fibers in the diseased side were significantly smaller than those from the normal side. In the diseased side, the potential strength of Type II fibers was weakened. Some pathologic changes (fiber type grouping, small angulated fibers, group atrophy, moth-eaten appearance, and internal nuclei, etc.) in the diseased side were more obvious than those in the normal side. When the straight leg raising test results were abnormal, both Type I and II fibers in the diseased side were smaller than those in the normal side. The Type I fibers of the diseased side were significantly smaller when the patients had symptoms of central low back pain. The size of the Type I fibers as well as of the Type II fibers did not differ between the diseased and normal sides in patients with unilateral and bilateral low back pain. CONCLUSIONS: The present study indicated that there were differences in the characteristics of the multifidus muscle between the diseased and normal sides in patients with lumbar disc herniation. The changes in muscle characteristics primarily were related to the disc protrusion. In addition, different locations of the low back pain seemed to cause different secondary effects on the muscle characteristics.

Adult↗
PubMed2000

Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: role of CD40-CD40 ligand interaction in IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 production.

In polymyositis (PM)/dermatomyositis (DM), T cells infiltrate the muscle tissues and interact with muscle cells via cell surface molecules. Recently, myoblasts have been reported to express CD40, but little is known about the role of CD40 in myoblasts. In the present study we examined the expression and involvement of CD40 and CD40 ligand (CD40L) in the interaction between muscle cells and T cells in PM/DM. Immunohistochemical staining revealed that CD40 was expressed on muscle cells in five of five PM and four of five DM patients, and that infiltrating mononuclear cells (MNCs) expressed CD40L in all cases of PM/DM. These CD40L-expressing MNCs were primarily CD4+ T cells. IFN-gamma, which is known to induce CD40 expression on various types of cells, was also expressed on the MNCs in four of the PM and four of the DM patients. Although cultured human myoblasts (SkMC 2859) did not express CD40 constitutively, IFN-gamma induced CD40 expression in a dose-dependent manner. To clarify the functional roles of CD40-mediated signals, the effects of a trimeric form of recombinant human CD40L on cytokine production were studied in SkMC 2859 that were prestimulated with IFN-gamma to express CD40. Recombinant human CD40L markedly increased the production of IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 of SkMC 2859. The expression of these humoral factors in muscle cells of PM and DM was demonstrated by immunohistochemistry. These results suggest that interaction between T cells and muscle cells via the CD40-CD40L system contributes to the immunopathogenesis of PM/DM by augmenting inflammation via cytokine production by the muscle cells.

Adjuvants, Immunologic↗
PubMed2000

A cyclodextrin-based molecular shuttle containing energetically favored and disfavored portions in its dumbbell component

A molecular shuttle containing dodecamethylene units, 4, 4'-bipyridinium units, and alpha-cyclodextrin (alpha-CD) has been prepared. Shuttling behavior is solvent- and temperature-sensitive and could be controlled by double interactions: hydrophobic interaction between a CD ring and a station and a repulsive interaction between a CD ring and a linker. This is a novel method to control the mobility of a bead in a molecular shuttle.

Journal Article↗
PubMed2000

Magnetic resonance imaging and histologic evidence of postoperative back muscle injury in rats.

STUDY DESIGN: Postoperative back muscle injury was evaluated in rats by magnetic resonance imaging and histologic analyses. OBJECTIVE: To compare the magnetic resonance imaging manifestation of back muscle injury with the histologic findings in rats and to subsequently clarify the histopathologic appearance of the high intensity regions on T2-weighted images in human postoperative back muscles. SUMMARY OF BACKGROUND DATA: In a previous study, it was found that the signal intensity on T2-weighted images of the postoperative back muscles was increased in patients who had postsurgical lumbar muscle impairment, especially in those with a prolonged surgery duration. However, the specific histopathologic changes that cause the high signal intensity on T2-weighted images remain unclear. METHODS: Rats were divided into three groups: sham operation group, 1-hour retraction group, and 2-hour retraction group. Magnetic resonance imaging and histology of the multifidus muscles were examined before surgery and at 2, 7, and 21 days after surgery. RESULTS: T2-weighted imaging was more useful than T1-weighted imaging to estimate back muscle injury. The high signal intensity of the multifidus muscles on T2-weighted images remained 21 days after surgery only in the 2-hour retraction group. Histologically, the regeneration of the multifidus muscles was complete at 21 days after surgery in the 1-hour retraction group, but the regenerated muscle fibers in the 2-hour retraction group had a small diameter, and the extracellular fluid space remained large. CONCLUSION: The high signal intensity on T2-weighted images of the postoperative multifidus muscles in the regenerative phase may be due to an increased extracellular space and incomplete muscle fiber regeneration.

Animals↗
PubMed2000

Surgical outcome of cervical expansive laminoplasty in patients with diabetes mellitus.

STUDY DESIGN: The results from cervical laminoplasty in 18 patients with diabetes mellitus were compared with results from the same procedure in 34 nondiabetic patients matched for age, gender, and disease. OBJECTIVE: To analyze the effects of diabetes mellitus on the surgical outcome after cervical laminoplasty. SUMMARY OF BACKGROUND DATA: There have been no reports on the results of cervical laminoplasty patients with diabetes. METHODS: A retrospective analysis of 18 patients with diabetes mellitus who underwent cervical laminoplasty and 34 nondiabetic patients who underwent the same surgical procedure was undertaken. The postoperative score, intra- and postoperative findings, complications, and radiologic factors were compared between the two groups. In the group with diabetes, the correlation between the recovery rate of the Japanese Orthopedic Association score and the factors indicating the severity of diabetes was assessed. RESULTS: There was no statistical difference between the total Japanese Orthopedic Association scores of the two groups. However, the group with diabetes mellitus showed a poor recovery of sensory function of the lower extremities. Three patients in the group with diabetes had superficial wound complication after surgery. In contrast, none of the patients in the control group had a wound problem. Furthermore, a negative correlation was observed between the recovery rate and the preoperative HbA1 level in the group with diabetes. CONCLUSIONS: Although patients with diabetes mellitus who had cervical myelopathy experienced benefits from cervical laminoplasty similar to those of nondiabetic patients, the patients with diabetes were more likely to have wound complication. Furthermore, the negative correlation between the recovery rate and the preoperative HbA1 value might suggest that long-term diabetes control of more than 2 to 3 months before surgery at least is recommended for a favorable surgical outcome.

Aged↗
PubMed2000

Dependence of GABAergic synaptic areas on the interneuron type and target size.

In the neostriatum, several types of interneuron with distinct firing patterns and expression of neuroactive substances are known to exist. We found two types of neostriatal interneurons, parvalbumin-containing fast-spiking (FS) cells and somatostatin-containing low-threshold spike (LTS) cells to both be immunoreactive for GABA at their axon terminals in immersion-fixed brain slices from rat. To reveal the differences in synaptic connections between these two types of GABAergic interneurons, the postsynaptic target and their synaptic structure were compared by three-dimensional reconstructions from electron microscopic images of intracellularly stained axon terminals. FS cells made a greater proportion of synaptic contacts onto somata than LTS cells. Although terminal boutons of FS and LTS cells were similar in volume, their synaptic junctional areas differed in size distribution and relation to the dimensions of postsynaptic dendritic shafts or spines. Whereas the synaptic junctional areas of FS cells (0.024-0.435 microm(2); n = 28) sharply and linearly increased with the circumference of the postsynaptic dendrites or spines (0.939-5.146 microm), the slope for the junctional area of LTS cells (0.02-0.103 microm(2); n = 29) against circumference (0.844-4.252 microm) was less steep, and a much weaker correlation was seen. In addition to the differences in firing patterns, expressed molecules, axonal arborizations, and postsynaptic targets, this variation in dependency of the synaptic area on the target size suggests functional differentiation of GABAergic interneurons.

Action Potentials↗
PubMed2000

Age-dependent changes in phenotypes and candidate gene analysis in a polygenic animal model of Type II diabetes mellitus; NSY mouse.

AIMS/HYPOTHESIS: The Nagoya-Shibata-Yasuda (NSY) mouse closely mimics human Type II (non-insulin-dependent) diabetes mellitus in that the onset is age-dependent, the animals are not severely obese, and both insulin resistance and impaired insulin response to glucose contribute to disease development. The aim of this study was to clarify the influence of age on the pathogenesis of diabetes and to analyse a candidate gene for Type II diabetes in this strain. METHODS: Several phenotypic characteristics related to diabetes mellitus were monitored longitudinally in male NSY and control C3H/He mice. The nucleotide sequence of Glut4, a candidate gene for Nidd1nsy (a susceptibility gene for Type II diabetes) on Chromosome 11, encoding insulin-sensitive glucose transporter, was determined in NSY and C3H mice. RESULTS: Glucose intolerance worsened with age, and fasting blood glucose and fasting plasma insulin concentration increased with age in NSY mice. Pancreatic insulin content increased until 24 weeks of age but then decreased at 48 weeks of age in NSY mice. The hypoglycaemic response to insulin was statistically significantly smaller in NSY than in C3H/He mice. The nucleotide sequence of GLUT4 cDNA was identical in NSY and C3H/He mice, but both were different from the sequence reported previously. CONCLUSION/INTERPRETATION: Insulin secretion and insulin resistance, as well as ageing possibly play an important part in the disease development in NSY mice. A decline of pancreatic insulin content in older age might cause the relative insulin deficiency in this strain. Nucleotide sequencing suggests that Glut4 is unlikely to be a candidate gene for Nidd1nsy.

3T3 Cells↗
PubMed2000

CD40 expression on human lung cancer correlates with metastatic spread.

PURPOSE: The poor prognosis associated with lung cancer is related to the high incidence of regional and distant metastasis. There is a crucial need to identify parameters that can predict a tendancy to metastatic spread to allow better prognostic evaluation and therapeutic approach. METHODS: Using flow cytometry we evaluated 18 human lung cancer cell lines for the expression of different surface markers on lung cancers suggested to be possible prognostic parameters, including epidermal growth factor receptor (EGFR), intercellular adhesion molecule 1 (ICAM-1), Fas and CD40. RESULTS: No correlation was found between tumor prognosis and EGFR, ICAM-1 or Fas. However, a statistically significant correlation was found between the surface expression of CD40 and the metastatic spread of the tumor. In this study, 14 of 18 lung cancer cell lines (78%) expressed CD40 on their surface. All of the 4 tumors that were CD40-negative, were stage I tumors, without any evidence of regional or distant metastasis. Of the 14 tumors that expressed CD40, all but 1 (93%) had either nodal or systemic metastasis at the time of diagnosis. Patients whose tumors were CD40-negative showed a significantly better N stage, overall stage at presentation and survival than those patients with CD40-positive patients. No significant differences between the two groups were observed in tumor size, gender, age, histology, differentiation or preoperative therapy. CONCLUSIONS: These results suggest that CD40 expression on lung cancer may play a role in metastatic spread, and also may serve as a prognostic marker and an indicator of advanced disease.

CD40 Antigens↗
PubMed2000

Reduction of 5-fluorouracil (5-FU) gastrointestinal (GI) toxicity resulting from the protection of thymidylate synthase (TS) in GI tissue by repeated simultaneous administration of potassium oxonate (Oxo) in rats.

PURPOSE: An important cytotoxic effect of 5-fluorouracil (5-FU) is the inactivation of thymidylate synthase (TS) (EC 2.1.1.45) activity by the formation of a ternary complex consisting of covalently bound 5-fluorodeoxyuridine 5'-monophosphate (FdUMP), TS and 5,10-methylenetetrahydrofolate (CH2FH4). The gastrointestinal (GI) toxicity of 5-FU is also caused by its phosphorylation in the GI tract. Potassium oxonate (O(XO)) competitively inhibits pyrimidine phosphoribosyltransferase (EC 2.4.2.10), which converts 5-FU to 5-fluorouridine 5'-monophosphate (FUMP) in vitro. In this study the benefits of combining Oxo and tegafur (FT), which is a masked compound of 5-FU, in reducing the GI toxicity of 5-FU and in protecting the activity of TS in the normal GI tissues were evaluated. METHODS: We administered orally a preparation of 1 M FT and 0.4 M 5-chloro-2,4-dihydroxypyridine (CDHP) with or without 1 M O(XO) (called S-1 and FT + CDHP, respectively) or vehicle only (control) to rats for ten consecutive days and compared the toxicity, the histopathological findings and the free TS activity in the GI tissues of the treated rats. RESULTS: During the experimental periods, the signs of toxicity, such as a decrease in body weight, diarrhea and death, were only observed in the rats treated with FT + CDHP. The histopathological findings in the ileum and colon samples from rats treated consecutively with S-1 on day 1, day 4, day 7 and day 10 were less frequent and more mild than in the samples from rats treated with FT + CDHP. Furthermore, the free TS activities in the ileum samples of rats given S-1 and FT + CDHP were significantly decreased compared with the activity in samples from the control rats throughout the experimental periods. The free TS activities in GI tissues of rats treated with S-1 were higher than the TS activities in tissues from rats treated with FT + CDHP daily from day 4 to day 10, although activities in S-1-treated rat were decreased to almost same low levels as in FT + CDHP-treated rats on day 1. CONCLUSIONS: Our results suggest that repeated simultaneous administration of Oxo and FT can effectively protect the activity of TS by decreasing FdUMP via FUMP from 5-FU in GI tissue, and may lead to a reduction in GI toxicity.

Animals↗
PubMed2000

Significance of K-ras mutation and CEA level in pancreatic juice in the diagnosis of pancreatic cancer.

The early diagnosis of pancreatic carcinoma is essential for increasing patient survival rates. In this study, 52 patients with suspected pancreatic diseases were examined to investigate the value of K-ras codon 12 point mutation, levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9), and cytology of pancreatic juice in the diagnosis of pancreatic carcinoma. Pancreatic juice was taken without secretin stimulation. K-ras mutation was detected by enriched polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). K-ras mutation in pancreatic juice was more frequent in carcinoma than in benign diseases (P = 0.0448). The positive predictive value of K-ras mutation for the diagnosis of neoplastic disease was 83%. The CEA level in pancreatic juice in carcinoma was significantly greater than that in benign disease (P< 0.0001). When the cutoff level of CEA was set at 50 ng/ml, its accuracy for the diagnosis of carcinoma was 85%. A multivariate analysis showed that K-ras mutation and CEA level in pancreatic juice, as well as serum CA19-9 level and age of the patient were independent variables for the diagnosis of carcinoma, and the accuracy of diagnosis by this analysis was increased to 90%. In conclusion, both K-ras mutation and CEA level in pancreatic juice may be valuable for the diagnosis of carcinoma. Better discrimination was possible with a multivariate analysis.

Adult↗