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Biomedical subjects

S Takayama

Publications and source records attributed to S Takayama.

At least 109 records · Page 6Linked to original sources
PubMed1998

Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer.

BACKGROUND: It was observed in the early 1970s that saccharin produced bladder cancer in rats. However, it has been unclear whether sodium saccharin when consumed by humans poses a substantial carcinogenic hazard. Numerous epidemiologic studies have not shown any evidence of increased urothelial proliferation associated with ingestion of sodium saccharin. PURPOSE: Our purpose was to determine the effects of long-term feeding of sodium saccharin to three species of nonhuman primates. METHODS: Twenty monkeys of three species (six African green, seven rhesus, six cynomolgus, and one hybrid [of rhesus male and cynomolgus female parentage]) were treated with sodium saccharin (25 mg in the diet/kg body weight daily for 5 days a week) beginning within 24 hours after birth and continuing for up to 24 years. Sixteen monkeys (seven rhesus and nine cynomolgus) served as controls. During their last 2 years of life, urine was collected from selected treated and control animals and evaluated for various urinary chemistries and for the presence of calculi, microcrystalluria, and precipitate. Urinary bladders were examined by light microscopy and by scanning electron microscopy. RESULTS: Sodium saccharin treatment had no effect on the urine or urothelium in any of these monkeys. There was no evidence of increased urothelial cell proliferation, and there was no evidence of formation of solid material in the urine. CONCLUSION: Although the dose of sodium saccharin administered to these monkeys was only five to 10 times the allowable daily intake for humans, the results provide additional evidence that sodium saccharin is without a carcinogenic effect on the primate urinary tract.

Animals↗
PubMed1998

Molecular pathogenesis of interstitial pneumonitis with TNF-alpha transgenic mice.

Tumour necrosis factor alpha (TNF-alpha) transgenic mice, which overexpress TNF-alpha in the lungs, develop interstitial pneumonitis resembling idiopathic pulmonary fibrosis (IPF) in humans. Transgenic mice were used to study molecular pathogenesis of interstitial pneumonitis with regard to sequential histological changes and cytokine network induced by TNF-alpha. The authors divided the histological process of interstitial pneumonitis into three stages: early stage with lymphocytic infiltration in alveolar septa, middle stage with recruitment of macrophages, and late stage with hyperplasia of epithelial cells and mild fibrosis. As for cytokine network, prolonged overexpression of TNF-alpha along with increasing interleukin 6 (IL-6) were associated with the progression of interstitial pneumonitis. Increasing IL-1 was found only in the early stage, the beginning of lymphocyte proliferation. The mRNA level of an anti-inflammatory cytokine, IL-10, was constantly enhanced in the lungs of transgenic mice. However, transforming growth factor beta 1 (TGF-beta 1) protein decreased, which is closely associated with prolonged TNF-alpha synthesis, resulting in development of chronic inflammation and less severe fibrosis in the lungs of this animal model, analogous to inflammatory stage of human IPF. TNF-alpha transgenic mice enabled the analysis of the sequential process of interstitial pneumonitis as a model of IPF pathogenesis in humans, the results of which will give rise to new therapeutic measures for human IPF.

Animals↗
PubMed1998

Dual radionuclide single-photon emission computed tomography in the prediction of further ischemic risk after acute myocardial infarction.

To evaluate whether the findings of dual single-photon emission computed tomography (SPECT) with technetium-99m pyrophosphate (Tc-99m PPi) and thallium-201 were predictive of further cardiac events in their hospital course, we studied 130 patients recovering from acute myocardial infarction (AMI). Fifty-four patients showed overlapping of Tc-99m PPi and thallium-201 in the same location (overlap positive group), and 76 patients had no overlap (overlap negative group). Of the 130 patients, 36 (28%) had a cardiac event. In patients in the overlap positive group, the incidence of subsequent events was significantly higher than in patients in the overlap negative group (44% versus 16%; p < 0.001). In the overlap positive group, the Tc-99m PPi uptake score and the number of overlap segments in patients with further events was significantly higher than those in patients without further events (10.2 +/- 5.1 versus 6.4 +/- 4.1, p < 0.005 and 5.2 +/- 2.0 versus 3.3 +/- 1.3, p < 0.001, respectively). These results suggest that patients who have a Tc-99m PPi and thallium-201 overlap negative scan can be candidates for early hospital discharge. In contrast, patients who have a greater number of overlap segments may require early catheterization and revascularization, so that simultaneous SPECT imaging Tc-99m PPi and thallium-201 might be useful for identifying patients with further ischemic risk after AMI in their hospital course.

Aged↗
PubMed1998

Expression of platelet-derived growth factor after transient forebrain ischemia in the gerbil hippocampus.

The present study was conducted to clarify the role of platelet-derived growth factor-B chain (PDGF-B) in neuronal death after ischemia. Transient forebrain ischemia was induced in Mongolian gerbils by occluding the bilateral carotid arteries for 5 min. We investigated PDGF-B expression in the hippocampus after ischemia by immunohistochemistry, Northern blotting and in situ hybridization histochemistry. The results showed that PDGF-B is expressed in control CAI and CA3 neurons. In CA1, the amount of the PDGF-B transcript immediately increased, then disappeared 2 days after ischemia. Delayed neuronal death followed 1 day later. However, PDGF-B immunoreactivity in CA1 rapidly decreased and disappeared 12 h after transient forebrain ischemia, proceeding to delayed neuronal death. In contrast, the expression of both PDGF-B protein and the transcript was well preserved throughout the study in CA3, which remained viable even after ischemia. Accordingly, the selective neuronal susceptibility in the CA1 to ischemia corresponded with rapid disappearance of PDGF-B. PDGF-B expression may contribute to neuroprotective effect after ischemia.

Actins↗
PubMed1998

Shinrin-yoku (forest-air bathing and walking) effectively decreases blood glucose levels in diabetic patients.

The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.

Baths↗
PubMed1998

Balance of interleukin-1 beta and interleukin-1 receptor antagonist in human periapical lesions.

Interleukin-1 beta (IL-1 beta) has been considered as a major potent mediator of bone resorption and implicated in the development of human periapical lesions. Among naturally occurring interleukin-1 (IL-1) inhibitors, IL-1 receptor antagonist (IL-1ra) is a 22 kDa protein that shares homology with IL-1 beta and IL-1 alpha, binds to IL-1 receptor with similar affinity to IL-1, and has no known agonist properties. In this study, we measured the periapical exudate (PE) levels of IL-1 beta and IL-1ra from human periapical lesions. PE samples were collected from root canals during routine endodontic treatments, and the enzyme-linked immunosorbent assay was used to measure PE-IL-1 beta and IL-1ra. Detectable levels of both IL-1 beta and IL-1ra were found in 25 of 29 clinical samples. Relatively high levels of IL-1ra compared with IL-1 beta (mean IL-1ra:IL-1 beta ratio = 128:7; range: 0.9 to 495.4), and significantly positive correlation between IL-1ra and IL-1 beta levels was found. The PE-IL-1ra:IL-1 beta ratios obtained from symptomatic lesions were significantly lower than those from asymptomatic lesions. These results suggest that IL-1ra-mediated IL-1 antagonism occurred to block locally produced IL-1 activity, and the balance of IL-1 to IL-1ra production may be crucial in the development of periapical lesions.

Analysis of Variance↗
PubMed1998

Erythrocyte aldose reductase protein: a clue to elucidate risk factors for diabetic neuropathies independent of glycemic control.

Prolonged hyperglycemia has been thought to be the primary cause of diabetic complications, however, some diabetic patients develop severe complications early in duration of diabetes, while some patients have no or mild complications even after prolonged hyperglycemia. To investigate the risk factors for diabetic severe neuropathy independent of glycemic control and duration of diabetes, erythrocyte aldose reductase was determined in 43 non-insulin-dependent diabetic patients by a two-site ELISA using recombinant human aldose reductase. Among 20 patients with severe neuropathy which was developed within 5 years of diagnosis, the level of erythrocyte aldose reductase protein was significantly higher than that of 23 patients with no or mild neuropathy who had more than 8 years duration of diabetes and prolonged hyperglycemia (11.9+/-5.7 vs. 8.3+/-1.3 ng/mgHb, P < 0.0001). There was a significant stability of the erythrocyte aldose reductase (AR) in the 40 diabetic patients during 1-4 years. The logistic regression analysis revealed that the maximum body mass index (BMI) in the past minus present BMI and the level of erythrocyte aldose reductase protein were the independent risk factors for diabetic severe neuropathy. The measurement of erythrocyte AR level may be useful for predicting severe neuropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients.

Aldehyde Reductase↗
PubMed1998

Expression of multiple apoptosis-regulatory genes in human breast cancer cell lines and primary tumors.

The expression of several apoptosis-regulating genes was evaluated in 9 human breast cancer cell lines, 2 immortalized human mammary epithelial lines, 1 normal breast tissue biopsy, and 3 primary breast tumors, using a multiple antigen detection (MAD) immunoblotting method. The anti-apoptotic proteins Bcl-2, Bcl-X(L), Mcl-1, and BAG-1 were present at immunodetectable levels in 7, 10, 10, and 9 of the 11 lines. Comparing these 11 cell lines among themselves revealed that steady-state levels of Bcl-2, Bcl-X(L), Mcl-1, and BAG-1 were present at relatively higher levels in 4, 6, 5, and 5 of the lines, respectively. In contrast, the pro-apoptotic proteins Bax and Bak were detected in all 11 cell lines, and were present at relatively higher levels in 10 and 5 of the 11 lines, respectively. The Interleukin-1beta converting enzyme (ICE) homolog CPP32 (Caspase-3) was expressed in 10/11 breast cell lines. High levels of p53 protein, indicative of mutant p53, were found in 8 of the 11 lines and correlated inversely with Bax expression (p = 0.01). Bcl-2 and BAG-1 protein levels were positively correlated (p = 0.03). Immunoblot analysis of primary adenocarcinomas revealed expression of the anti-apoptotic proteins Bcl-2, Bcl-X(L), Mcl-1, and BAG-1, as well as the pro-apoptotic proteins Bax, Bak, and CPP32, in at least 2 of the 3 tumors examined. Immunohistochemical analysis was also performed for all of these proteins using 20 paraffin-embedded breast cancer biopsy specimens that all contained residual normal mammary epithelium in combination with both invasive cancer and carcinoma in situ. All of these apoptosis-regulating proteins were detected in primary breast cancers, though the percentage of immunopositive tumor cells varied widely in some cases. Comparisons of the intensity of immunostaining in normal mammary epithelium and invasive carcinoma suggested that Bcl-2 immunointensity tends to be lower in cancers than normal breast epithelium (p = 0.03), whereas CPP32 immunointensity was generally higher in invasive cancers (p < 0.0001). Taken together, the results demonstrate expression of multiple apoptosis-modulating proteins in breast cancer cell lines and primary tumors, suggesting complexity in the regulation of apoptosis in these neoplasms of mammary epithelial origin.

Apoptosis↗
PubMed1998

Effect of insulin therapy on body fat distribution in NIDDM patients with secondary sulfonylurea failure: a preliminary report.

OBJECTIVE: To clarify the influence of insulin therapy on body weight and fat distribution, we compared these parameters in five non-insulin dependent diabetes mellitus (NIDDM) patients, with secondary sulfonylurea failure, before and after insulin therapy. Body weight increased significantly after instituting insulin treatment. However, the visceral to subcutaneous fat (V/S) ratio decreased significantly due to a marked increase in S-fat without a change in V-fat. Insulin therapy necessitated by sulfonylurea failure does not appear to accelerate the atherogenic process in NIDDM patients as there is no increase in visceral fat.

Adipose Tissue↗
PubMed1998

Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells.

Bcl-2 and a Bcl-2-binding protein BAG-1 function in protection from apoptosis induced by a variety of stimuli. Deregulated expression of Bcl-2 leads to inhibition of apoptosis and is correlated with development of various cancers. Here, we provide evidence that prolonged cell survival introduced by overproduction of Bcl-2 or BAG-1 strongly enhances peritoneal dissemination of human gastric cancer MKN74 cells. Gene transfer-mediated overexpression of Bcl-2 or BAG-1 led to prolonged cell survival of MKN74 cells against serum-starved apoptosis and anoikis. When the viable transfectants were inoculated into the intraperitoneal cavity of BALB/c nude mice, the Bcl-2-expressing MKN74 cells and the BAG-1-expressing MKN74 cells exhibited strongly enhanced peritoneal dissemination in BALB/c nude mice and whole disseminated tumor weights were increased by 4-fold and 3.3-fold, respectively, compared with the control transfectants. The enhanced peritoneal dissemination of MKN74-Bcl-2 and MKN74-BAG-1 transfectants correlated well with resistance to cell death induced by serum-starvation and anoikis. However, the overexpression of Bcl-2 or BAG-1 caused no significant difference among the transfectants in cell growth rates, either in vitro or in vivo. Taken together, these studies demonstrate that resistance to apoptosis is a crucial factor for development of peritoneal dissemination of human gastric cancer cells.

Adenocarcinoma↗
PubMed1998

Molecular characterization of photomixotrophic tobacco cells resistant to protoporphyrinogen oxidase-inhibiting herbicides

Peroxidizing herbicides inhibit protoporphyrinogen oxidase (Protox), the last enzyme of the common branch of the chlorophyll- and heme-synthesis pathways. There are two isoenzymes of Protox, one of which is located in the plastid and the other in the mitochondria. Sequence analysis of the cloned Protox cDNAs showed that the deduced amino acid sequences of plastidial and mitochondrial Protox in wild-type cells and in herbicide-resistant YZI-1S cells are the same. The level of plastidial Protox mRNA was the same in both wild-type and YZI-1S cells, whereas the level of mitochondrial Protox mRNA YZI-1S cells was up to 10 times the level of wild-type cells. Wild-type cells were observed by fluorescence microscopy to emit strong autofluorescence from chlorophyll. Only a weak fluorescence signal was observed from chlorophyll in YZI-1S cells grown in the Protox inhibitor N-(4-chloro-2-fluoro-5-propagyloxy)-phenyl-3,4,5, 6-tetrahydrophthalimide. Staining with DiOC6 showed no visible difference in the number or strength of fluorescence between wild-type and YZI-1S mitochondria. Electron micrography of YZI-1S cells showed that, in contrast to wild-type cells, the chloroplasts of YZI-1S cells grown in the presence of N-(4-chloro-2-fluoro-5-propagyloxy)-phenyl-3,4,5, 6-tetrahydrophthalimide exhibited no grana stacking. These results suggest that the herbicide resistance of YZI-1S cells is due to the overproduction of mitochondrial Protox.

Journal Article↗
PubMed1998

Expression of receptors for basic fibroblast growth factor on human periodontal ligament cells.

Basic fibroblast growth factor (FGF-2; bFGF) is a major mitogen for connective tissue cells, and participates in the healing process. It has already been reported that FGF-2 could be applicable to enhance periodontal regeneration. In the present study, we examined FGF receptor (FGFR) expression on human periodontal ligament (PDL) cells. The binding of [125I]-labeled FGF-2 to human PDL cells was studied by radioreceptor assay. The binding of [125I]-FGF-2 to PDL cells reached a plateau after 2.5 h incubation at 4 degrees C and was inhibited by the addition of unlabeled FGF-2 and acidic FGF (FGF-1; aFGF), but not insulin-like growth factor-I, platelet-derived growth factor and transforming growth factor-beta 1. Scatchard analysis revealed the presence of approximately 1.0 x 10(5) FGF-2 binding sites per cell with an apparent Kd of 1.2 x 10(-10) M. Interestingly, the binding of [125I]-FGF-2 on PDL cells reached its maximum at d 6 of the culture and then gradually decreased. Scatchard analysis also demonstrated that the number of FGFRs on a PDL cell was altered during the course of the culture, while the affinity between FGF-2 and its receptor was not. The responsiveness of PDL cells to FGF-2, which was monitored by the inhibitory effect on alkaline phosphatase activity, was reduced in proportion to the decrease in the number of FGFRs on the PDL cells. The present study suggests that PDL cells alter the responsiveness to FGF-2 during the course of the culture by changing the density of its receptor, and that the density of FGFR expression might be a marker of the cytodifferentiation of PDL cells into mineralized tissue forming cells.

Alkaline Phosphatase↗
PubMed1998

BAG-1 and Bcl-2 in IL-2 signaling.

Some cytokines can prolong cell survival in hematolymphoid cells and thus may be crucial for regulation of hematolymphoid cell numbers. It has been shown that mitogenic cytokines can induce not only cellular proliferation but also cellular survival by inhibiting apoptosis in hematolymphoid cells. The signals transduced by these cytokines eventually go to the nucleus and induce expression of their specific target genes. In this context, the induction of anti-apoptotic molecules such as Bcl-2 oncoprotein and BAG-1 protein seems to be a key event for the anti-apoptotic function of cytokines. In T lymphocytes, the interaction of interleukin-2 (IL-2) with its receptor (IL-2R) induces both cellular proliferation and cellular survival. The IL-2R consists of three subunits, i.e., IL-2Ralpha, IL-2R(beta)c, and IL-2R(gamma)c chains. Structure-function analysis of the IL-2R(beta)c chain has revealed that there are at least two functional domains within the subunit. The serine-rich (S) region but not the acidic (A) region within the (beta)c chain is responsible for the mitogenic signaling of IL-2R. The S region is also crucial for the cellular survival signaling, which include the induction of anti-apoptotic gene expressions bcl-2 and bag-l. However, the cellular survival signaling is segregated from the mitogenic signaling in independence from the Jak-family protein kinase activation and rapamycin sensitivity. Segregation of the two signaling pathways of a cytokine receptor has also been shown in receptors of the other mitogenic cytokines. Current topics regarding signal transductions of cytokine receptors responsible for the suppression of apoptosis are discussed in this review.

Animals↗
PubMed1998

[Asymptomatic pancreatic islet cell tumor (glucagonoma): case report].

A case of asymptomatic pancreatic islet cell tumor (glucagonoma) is reported. A 36-year-old woman undergoing a ultrasonic scan was found to have two masses in the body and tail of the pancreas measuring 5 cm and 4 cm in diameter, respectively. Investigations of serum peptide hormones revealed an elevated glucagon level of 27,500 pg/ml (normal < 100 pg/ml), suggesting the possibility of an islet cell tumor (glucagonoma). The patient, however, was asymptomatic although high levels of glucagon were present. The patient underwent distal pancreatectomy to remove the lesions in the body and tail of the pancreas. Histological findings revealed islet cell tumors of the pancreas, and immuno histochemical staining of the tumor cells demonstrated a positive reaction for chromogranin and glucagon.

Adult↗
PubMed1998

[Biochemical and immunohistological changes in the gastric mucosa of rats with long-term administration of histamine H2-receptor antagonist].

Effects of long term administration of Histamine H2-receptor Antagonist (H2-RA) in the treatment of peptic ulcer was studied for the influence to the risk of causing precancerous changes in gastric mucosa. Serum gastrin. ODC activities, polyamine and PCNA labeling index were biochemically and immunohistologically observed. Rat's mucosae with experimentally induced peptic ulcer treated with long term H2-RA, showed no morphological changes but at 30 weeks of H2-RA, had significantly higher value in PCNA labeling index and in polyamine (spermidine) quantity compared to control H2-RA alone and ulcer alone groups. These results suggest that long term administration of H2-RA, even after healing of the ulcer, may cause the gastric mucosa to possess a milieu in favour of precancerous changes, due to the increased proliferative activity of the cells.

Animals↗
PubMed1997

IFN-gamma upregulates anti-apoptotic gene expression and inhibits apoptosis in IL-3-dependent hematopoietic cells.

IFN-gamma is a cytokine which functions in a wide range of biological activities by inducing a number of early and delayed genes. In murine IL-3-dependent cell lines BAF-B03 and 32D, IFN-gamma upregulated bag-1 and bcl-xL gene expression. These cells revealed prolonged cell survival against IL-3-deprivation by IFN-gamma stimulation. In contrast, human myeloma cell line RPMI8226, despite expression of IFN-gamma receptor, showed neither induction of their expressions nor prolonged cell survival against serum starvation-induced apoptosis by IFN-gamma stimulation. Gene-transfer-mediated overexpression of BAG-1 protein in BAF-B03 cells led to prolonged cell survival against IL-3-deprived apoptosis compared with control BAF-B03 transfectants, indicating that levels of BAG-1 expression are crucial for cell survival in BAF-B03 cells. Taken together, these studies suggest that induction of anti-apoptotic gene expression is a crucial factor for the anti-apoptotic function of IFN-gamma in IL-3-dependent immature hematopoietic cells.

Animals↗