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Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 649 records · Page 36Linked to original sources

Early gastric stump cancer following distal gastrectomy.

BACKGROUND: Gastric stump cancer (GSC) is usually diagnosed at an advanced stage, and consequently the prognosis is poor. AIMS: To investigate the clinicopathological characteristics of GSC at an early stage to assist in its identification, and thereby improve its prognosis. METHODS: Forty three patients with resected early GSC were compared with 156 patients with resected primary early cancer in the upper third of the stomach. RESULTS: Sixty five per cent (28/43) of the early GSC patients showed the elevated type endoscopically, although the frequency of the depressed type in GSC has tended to increase in the past five years. This occurred in less than 26% (40/156) of the primary early cancers. Half of the early GSCs were located on the lesser curvature (47%), and revealed differentiated adenocarcinoma (81%) histologically. The male:female ratio of early GSC cases was about 6:1, which was much higher than that in patients with primary early cancer. The five year survival rates of patients with early GSCs and early primary cancers were 84% and 95%, respectively. GSC had a favourable prognosis, if it was detected at an early stage. CONCLUSION: To detect early GSC, our results suggest that special attention should be given to elevated as well as depressed lesions on the lesser curvature of the stomach, particularly in men, during endoscopic examinations.

Adenocarcinoma↗

Effect of fentanyl on morphine levels in the brain in rats receiving intracerebroventricular injection of TNF-alpha.

Fentanyl citrate analgesia attenuates the excess nitrogen excretion in the urine and glucose production induced by trauma. On the other hand, intracerebroventricular injection of morphine stimulates excretion of stress hormones, such as catecholamines and corticosterone. Furthermore, morphine levels in the brain are increased during fasting and sepsis. The aims of this study were to determine whether intracerebroventricular injection of tumor necrosis factor-alpha (TNF-alpha) elevates morphine levels in the rat brain and whether prophylactic administration of fentanyl blocks metabolic responses induced by intracerebroventricular injection of TNF-alpha because of a reduction of morphine levels in the brain. Morphine levels in the brain were increased from 648 to 1,134 fmol/g at 30 min after intracerebroventricular injection of TNF-alpha (P < 0.05 vs. control). This increase was associated with an increase in stress hormones (corticosterone: 416.1 +/- 69.1 ng/ml, P < 0.05 vs. control; epinephrine: 3,778.3 +/- 681.3 pg/ml, P < 0.01 vs. control) and an enhancement of proteolysis (254.2 +/- 45.7 micromol Leu . kg-1 . h-1, P < 0.01 vs. control) and glucose production (7.5 +/- 0. 7 mg . kg-1 . min-1, P < 0.05 vs. control). Fentanyl reduced morphine levels in the brain to 624 fmol/g (not significant vs. control), resulting in a reduction of stress hormone levels in the plasma and blunted metabolic responses. In conclusion, prophylactic administration of fentanyl prevented an increase in morphine levels in the brain induced by intracerebroventricular injection of TNF-alpha, leading to a reduction in stress hormone levels and subsequent metabolic responses.

Animals↗

Endoscopic diagnosis and treatment of early cancer in the alimentary tract.

Due to the recent widespread use of detailed endoscopy together with careful scrutiny of the mucosa using dye-spraying techniques, there has been a general acceptance in Japan that early malignancies in the alimentary tract may not appear polypoid or ulcerative. Regardless of organ, superficial early cancers have been reported. These lesions appear as faint mucosal irregularities or discolorations, which may be difficult to distinguish from nonspecific inflammation or trauma. The recognition of these malignancies has prompted the development of new techniques for their treatment. Endoscopic mucosal resection (EMR) which can resect lesions as completely as specimens removed at open surgery, has become the first choice of treatment for early digestive cancer. The lesions that can be removed by EMR should be those which hardly ever carry lymph node metastases. Endoscopically, they are shown to be flat esophageal cancers, gastritis-like cancers and colorectal cancers less than 2 cm in flat elevated type or less than 1 cm in depressed type. In spite of the advances in characterizing early cancers and an emerging consensus on indications and contraindications for EMR, much work remains to be done. New techniques will continue to push the limits of what can be achieved via an endoscope.

Biopsy↗

Effect of multidisciplinary treatment with high dose rate intraluminal brachytherapy on survival in patients with unresectable esophageal cancer.

BACKGROUND: Since carcinoma of the esophagus is usually diagnosed at an advanced stage, many cases of esophageal cancer are beyond possible radical resection and only palliative treatment can be performed in such cases. Therefore, a great deal of discussion has taken place concerning indications for treatment modality, and various procedures have been performed to palliate such patients. The prognosis for such patients is still poor, even though many kinds of palliation have already been developed and applied. To improve the prognosis of such patients we developed a multidisciplinary treatment which includes high dose rate intraluminal brachytherapy (HDR-ILBRT) and evaluated its effectiveness, especially the HDR-ILBRT component. PATIENTS AND TREATMENT METHODS: Sixty-six patients with unresectable esophageal cancer enrolled in this study. Twenty-seven patients underwent bypass operations. Seven of the 27 patients received external irradiation only (group BE), 11 received external irradiation and HDR-ILBRT (group BEH), while the remaining 9 did not receive radiotherapy (group B). Another 39 patients without bypass operations were all treated with radiotherapy, 22 with external irradiation only (group E) and 17 were treated with external irradiation and HDR-ILBRT (group EH). After completion of radiotherapy, all patients received chemotherapy with 5-FU (2,500 mg/body) and CDDP (100 mg/body). RESULTS: Mean survival time and the 5-year survival rate of group BEH (13.3 +/- 1.5 months and 20%) were significantly improved compared with group BE + B (p < 0.05). In the patients without bypass operations, there were significant differences in the mean survival time and the 3-year survival rate in groups EH and E (group EH 16.5 +/- 2.5 months, 21.8%, group E 9.0 +/- 1.3 months, 0%, p < 0.05). The bypass operation itself and chemotherapy did not significantly affect the prognosis of patients with unresectable esophageal cancer. CONCLUSION: These results strongly suggest the use of HDR-ILBRT, as a component of multidisciplinary treatment for unresectable esophageal cancer, was significantly effective and HDR-ILBRT contributed to improve outcomes in patients with advanced esophageal cancer. HDR-ILBRT should be established as a component of treatments for unresectable esophageal cancer.

Aged↗

Bronchial hyperresponsiveness, hypersensitivity to analgesics and urinary leukotriene E4 excretion in patients with aspirin-intolerant asthma.

This study was designed to investigate the protective effect of cromolyn sodium on airway sensitivity to sulpyrine, and bronchial responsiveness to methacholine, and to investigate whether this protective activity is associated with reduction in aspirin-induced excretion of urinary leukotriene E4 (u-LTE4), a marker of the cysteinyl LT overproduction that participates in the pathogenesis of aspirin-induced asthma. We assessed the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to a sulpyrine provocation test were included in this study. A double-blind, randomized, crossover design was used. u-LTE4 was measured using combined reverse-phase high-performance liquid chromatography enzyme immunoassay. Cromolyn sodium protected against analgesic-induced bronchoconstriction through mechanisms that are not related to its bronchodilator property, but to the improvement of both bronchial hyperresponsiveness and hypersensitivity to analgesics (p<0.01 and p<0.001). Although excretion of u-LTE4 did not increase after the methacholine provocation test, it significantly increased after sulpyrine provocation (p<0.01). Furthermore, after pretreatment with cromolyn sodium, the maximum level of u-LTE4 after the sulpyrine provocation test was significantly lower than in controls (p<0.01). These results support the hypothesis that cysteinyl LT is one of the most important components in the pathogenesis of aspirin-intolerant asthma. Cromolyn sodium improves both hypersensitivity to analgesics, and bronchial hyperresponsiveness in aspirin-intolerant asthma.

Adult↗

Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix.

Expression of squamous cell carcinoma (SCC) antigen emerged concurrently with squamous formation of the uterine cervix and increased during the neoplastic transformation of the cervical squamous epithelium. SCC antigen expression differed considerably among the histomorphologic cell types of cervical carcinoma. Large cell nonkeratinizing carcinoma contained high levels of the antigen. In contrast, no appreciable expression of SCC antigen was observed in small cell nonkeratinizing carcinoma. The pattern of SCC antigen expression closely coincided with EGF receptor (EGF-R) expression in cervical squamous neoplasia. This suggests that the expression of SCC and EGF-R in cervical carcinoma is related to the differentiation or dedifferentiation processes of the tumor cells. SCC production by CaSki cervical epidermoid carcinoma cells was stimulated by EGF. It seems likely that an autocrine system, in which EGF serves as the signal, may exist in cervical squamous carcinoma. 17beta-estradiol and L-triiodothyronine were found to upregulate EGF-R expression, proliferative potential and SCC production in the CaSki cervical carcinoma cells.

Antigens, Neoplasm↗

Entry and intracellular growth of Legionella dumoffii in alveolar epithelial cells.

We have found that Legionella dumoffii strain Tex-KL (ATCC 33343) invades into and proliferates in the human lung alveolar epithelial-cell line A549 in vitro. The organism associated with the A549 cells at a 10-fold greater magnitude than L. pneumophila Philadelphia-1 during in vitro coculture for 1 h. Thereafter, L. dumoffii Tex-KL invaded the cells at a significantly higher rate (100- to 1,000-fold) than did L. pneumophila Philadelphia-1. After internalization, however, both bacteria proliferated at the same rate. This in vitro finding led us to examine the bacterial localization in lungs in a fatal case of L. dumoffii pneumonia. Double immunostaining revealed the bacteria in surfactant apoprotein A-positive cells (i.e., type II alveolar epithelial cells). Next, we infected guinea pigs intratracheally with L. dumoffii Tex-KL. The animals became sick with a fever from 24 h to 48 h after infection with 10(4) to 10(9) cfu of L. dumoffii Tex-KL. The lung tissues were examined through electron microscopy at definite intervals. Many bacteria were found not only inside phagocytic cells in the alveolar space, but also in type I and type II alveolar epithelial cells. These findings strongly suggest that L. dumoffii has an ability to invade into and proliferate in human alveolar epithelial cells, which may explain the rapid and fulminant progress of pneumonia caused by L. dumoffii.

Animals↗

Expression of neuropsin mRNA in the mouse embryo and the pregnant uterus.

Neuropsin is a novel serine protease whose mRNA is expressed in the mouse central nervous system. We examined the expression of neuropsin mRNA during embryonic development using Northern and in situ hybridization in non-neural tissues. The pregnant uterus showed strong expression of neuropsin mRNA, whereas the nonpregnant uterus did not express this mRNA. Expression was first detected in the primary decidual zone at 5.5 days post coitum and was maximized at 10 days post coitum, decreasing remarkably thereafter. During mouse organogenesis, neuropsin expression was observed in the developing heart, lung, thymus, pituitary, choroid plexus, and epithelial linings of the skin, oral cavity, tongue, esophagus, and forestomach. In adult mouse organs, neuropsin mRNA was expressed in epithelial tissues covered by keratinocytes with moderate density, whereas low expression was observed in lung, thymus, and spleen. Neuropsin mRNA expression in developing organs and adult keratinocytes suggests that neuropsin is associated with extracellular matrix modifications and cell migrations.

Animals↗

The role of NF-kappaB in retinal neovascularization in the rat. Possible involvement of cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 family.

Hypoxia precedes neovascularization in many retinal diseases that can lead to irreversible vision loss. The transcription factor NF-kappaB is activated by hypoxia and regulates the expression of many genes, including angiogenic factors. The relation between the NF-kappaB activation and the cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 (IL-8) family, was investigated by immunohistochemistry in a rat model of proliferative retinopathy presumably caused by relative hypoxia. Activated NF-kappaB and CINC immunoreactivity was detected in retinal glial cells in the nonperfused retina and in neovascular cells. Activated NF-kappaB was detected before the CINC staining, and both of these events occurred before the development of neovascularization. The intensity of both activated NF-kappaB and CINC staining remained increased during the development of neovascularization and then declined as neovascularization regressed. In rat retinal glial cells in vitro, dexamethasone, an inhibitor of NF-kappaB activation, prevented the hypoxia-induced increase in the amount of CINC mRNA. Furthermore, CINC induced neovascularization in a rat corneal pocket model. These results suggest that hypoxia-induced activation of NF-kappaB results in CINC production and participates in the induction of retinal neovascularization.

Actins↗

Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus.

OBJECTIVE: To examine the effect of diets with different polyunsaturated fatty acid contents, including linseed oil which contains 70% omega-3 fatty acids, on autoantibody production in idiotype induced mouse model of systemic lupus erythematosus (SLE). METHODS: Five different fats were fed to mice with induced SLE and antibody titers to anti-DNA and anti-cardiolipin were determined and histological examination of kidneys were carried out. RESULTS: SLE mice fed linseed oil showed lower titers of antibodies to DNA and to cardiolipin and less severe kidney damage than mice fed other diets, including fish oil. CONCLUSION: Use of linseed oil may attenuate the severity of SLE and this diet may be recommended for other auto-immune diseases as well.

Animals↗

Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates 'reserve cells'.

When a proliferating myoblast culture is induced to differentiate by deprivation of serum in the medium, a significant proportion of cells escape from terminal differentiation, while the rest of the cells differentiate. Using C2C12 mouse myoblast cells, this heterogeneity observed upon differentiation was investigated with an emphasis on the myogenic regulatory factors. The differentiating part of the cell population followed a series of well-described events, including expression of myogenin, p21(WAF1), and contractile proteins, permanent withdrawal from the cell cycle and cell fusion, whereas the rest of the cells did not initiate any of these events. Interestingly, the latter cells showed an undetectable or greatly reduced level of MyoD and Myf-5 expression, which had been originally expressed in the undifferentiated proliferating myoblasts. When these undifferentiated cells were isolated and returned to the growth conditions, they progressed through the cell cycle and regained MyoD expression. These cells demonstrated identical features with the original culture on the deprivation of serum. They produced both MyoD-positive differentiating and MyoD-negative undifferentiated populations once again. Thus the undifferentiated cells in the serum-deprived culture were designated 'reserve cells'. Upon serum deprivation, MyoD expression rapidly decreased as a result of down-regulation in approximately 50% of the cells. After this heterogenization, MyoD positive cells expressed myogenin, which is the earliest known event of terminal differentiation and marks irreversible commitment to this, while MyoD-negative cells did not differentiate and became the reserve cells. We also demonstrated that ectopic expression of MyoD converted the reserve cells to differentiating cells, indicating that down-regulation of MyoD is a causal event in the formation of reserve cells.

Animals↗

Cell cycle-associated accumulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) in the nuclei of human gingival fibroblasts.

We first confirmed an earlier immunohistochemical study showing that immunoreactive TIMP-1-like protein accumulated in the nuclei of human gingival fibroblasts (Gin-1 cells), reaching a maximum in the S phase of the cell cycle (Li, H., Nishio, K., Yamashita, K., Hayakawa, T. and Hoshino, T. (1995). Nagoya J. Med. Sci. 58, 133-142). Then we isolated this protein from a nuclear extract of Gin-1 cells and demonstrated it to be identical to human recombinant TIMP-1 by western blotting, by a sandwich enzyme immunoassay for TIMP-1 and by an assay for matrix metalloproteinase inhibition. The amount of TIMP-1 in the cytosolic fraction of quiescent Gin-1 cells after stimulation by fetal calf serum increased continuously for 48 hours, whereas that in the nuclear extract showed a maximum at 24 hours (S phase) and significantly decreased thereafter. Gin-1 cells expressed mRNAs for both TIMP-2 and TIMP-3 together with mRNA for TIMP-1. However, neither TIMP-2 nor TIMP-3 proteins seemed to accumulate in the nuclei of Gin-1 cells. These facts strongly suggest that TIMP-1 accumulates specifically in the nuclei of Gin-1 cells in a cell cycle-dependent manner.

Cell Cycle↗

An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase beta.

As described previously (Mizushina Y., Tanaka N., Yagi H., Kurosawa T., Onoue M., Seto H., Horie T., Aoyagi N., Yamaoka M., Matsukage A., Yoshida S., and Sakaguchi K., Biochim. Biophys. Acta, 1308, 256-262, 1996), linoleic acid (LA) inhibits the activities of mammalian DNA polymerases. We found a natural product from a basidiomycete, Ganoderma lucidum, that enhances this effect of LA in a special manner. The structure was identified to be an ergosterol peroxide, 5,8-epidioxy-5alpha,8alpha-ergosta-6,22E-dien -3beta-ol by spectroscopic analyses. The ergosterol peroxide (EPO) itself scarcely inhibited the activities of calf thymus DNA polymerase alpha (pol. alpha) or rat DNA polymerase beta (pol. beta). However, when EPO at 0.25 mM was present, 10 microM or less of LA almost completely inhibited the pol. beta activity, while almost complete inhibition by LA itself was achieved at 80 microM or higher. Interestingly, under the same conditions, EPO did not affect the LA-effect on pol. alpha. The action mode of the EPO was discussed.

Animals↗

Sulfoquinovosyldiacylglycerol, KM043, a new potent inhibitor of eukaryotic DNA polymerases and HIV-reverse transcriptase type 1 from a marine red alga, Gigartina tenella.

A new sulfolipid, KM043, which belongs to the 6-sulfo-alpha-D-quinovopyranosyl-(1-->3')-1',2'-diacylglycerol (SQDG) class of compounds, has been isolated from a marine red alga, Gigartina tenella, as a potent inhibitor of eukaryotic DNA polymerases and HIV-reverse transcriptase type 1. Its structure was determined on the basis of spectroscopic and gas chromatographic analyses. The inhibition was dose-dependent, and complete (more than 90%) inhibition of DNA polymerase alpha (pol. alpha), DNA polymerase beta (pol. beta) and HIV-reverse transcriptase type 1 (HIV-RT) was observed at concentrations of 5, 10, and 30 microM, respectively.

Chromatography, Gas↗

Pathophysiological effects of dietary essential fatty acid balance on neural systems.

Dietary fatty acid balance has been revealed to affect neural functions as well as chronic diseases such as cancer, cerebro- and cardiovascular diseases, and allergic hyper-reactivity. In this review, we focused on the pathophysiological effects of n-6 and n-3 fatty acids on brain functions. Long-term n-3 fatty acid deficiency in the presence of n-6 fatty acids has been shown to affect learning behavior, drug sensitivity and retinal functions. Some membrane enzymes and ion channel functions have been shown in experimental animals to be regulated by membrane fatty acid modifications. We also summarized the effects of these fatty acids in diets on human psychotic aspects and brain diseases. Although biochemical mechanisms remain to be elucidated, investigations on the effect of dietary fatty acids on neural networks may provide an important clue to clarify complex brain functions.

Animals↗

Glutathione transport systems of the budding yeast Saccharomyces cerevisiae.

The budding yeast Saccharomyces cerevisiae was shown to have two kinetically distinguishable glutathione transport systems. While one with high affinity (GSH-P1; KT = 0.045 mM) was regulated, the other with low affinity (GSH-P2; KT > 2 mM) was not. GSH-P1 was highly specific to glutathione, and its activity was quickly lost by suspending the cells in buffer solutions. This activity loss was not observed if glucose-containing buffer was used. In addition, rho-isolates had only about one half of the glutathione transport activity of the original (rho+) strain. Therefore, it is concluded that GSH-P1 is an ATP-driven transport system. Strong and moderate inhibition of GSH-P1 by protonophores and ionophores, respectively, are attributed to competition for ATP between GSH-P1 and proton- and cation-pumps, respectively.

Adenosine Triphosphate↗

Effect of dibromochloropropane (DBCP) on the hormone receptors of the male rat reproductive system.

The effects of dibromochloropropane (DBCP), a pesticide, on the male rat reproductive system were examined at morphological and hormonal expression levels. Changes of Leydig cells and seminiferous tubules were examined in rats treated with one subcutaneous (s.c.) injection of DBCP at doses of 10, 50, 75 and 100 mg/kg of body weight. The Leydig cells degenerated and decreased in number in those rats with an s.c. injection of DBCP at a dose of 50 mg/kg of body weight. However, these morphological changes were not significant in those rats that were treated with four separate s.c. injections of DBCP at 10 mg/kg of body weight. The expression of luteinizing hormone receptor mRNA, which is specifically expressed in Leydig cells, was decreased significantly in the DBCP-treated rats as compared with the normal-control rats. The expression of follicle-stimulating hormone receptor mRNA was decreased to a mild degree in DBCP-treated rats. At a dose of 75 mg/kg of body weight, seminiferous tubules as well as Leydig cells were severely damaged morphologically and at hormonal receptor expression levels. Multinucleated giant cells appeared at a dose of 75 mg/kg of body weight. All the rats died at a dose of 100 mg/kg of body weight. Our data indicate that DBCP had a cytotoxic effect on the male rat reproductive system in a dose-dependent manner.

Animals↗

Cloning, sequence analysis, and expression in Escherichia coli of a gene coding for an enzyme from Bacillus circulans K-1 that degrades guar gum.

A 2,048-bp nucleotide sequence containing a gene coding for an enzyme that degraded guar gum from Bacillus circulans K-1 was identified by polymerase chain reaction walking. This G-gene consisted of 1,551 nucleotides coding for a protein with Mr 55,242. The enzyme was overexpressed in Escherichia coli JM109 cells by the cloning the G-gene downstream of the lac Z promoter of pUC19. The molecular mass of recombinant G-enzyme estimated by SDS-PAGE was 62 KDa, close to that from strain K-1. Analysis of the recombinant enzyme showed GalNAc, Xyl, GlcNAc, Man, Glc, and Gal to account for 1.7%, 14.4%, 6.1%, 3.2%, 54.2%, and 10.4%, respectively, of the total monosaccharides. Polyacrylamide gel electrophoresis of this enzyme with staining gave a red band. The results suggested that the sugars accounted for the differences in the molecular masses. The recombinant enzyme had two kinds of N-terminal sequences, Thr-Met-Ile-Thr-Pro-Ser-Phe-Ala-Ser-Gly-Phe-Tyr-Val-Ile and Ile-Thr-Pro-Ser-Phe-Ala-Ser-Gly-Phe-Tyr-Val-Ile-Gly-Thr. Comparison of these sequences with the deduced N-terminal sequence coded for the G-gene showed that the amino acid, first Met, of the lac Z gene or the next residues Thr-Met in the recombinant enzyme were absent in the native enzyme. Methionines near and at the N-terminus of the mature protein probably were digested by methionine aminopeptidases of E. coli after translation. The properties of recombinant G-enzyme were similar to those of the enzyme from K-1 cells.

Amino Acid Sequence↗