Biomedical subjects

T Toyota

Publications and source records attributed to T Toyota.

At least 109 records · Page 6Linked to original sources

PubMed1998

Anti-angiogenic effect of TGFbeta in aqueous humor.

Neovascularization is mediated by various factors in ocular tissues. Recent studies have emphasized the role of vascular endothelial growth factor in the induction of angiogenesis. We have previously reported that aqueous humor (AH) suppressed vascular endothelial cell growth and angiogenesis. We speculated that the anti-angiogenic effect of AH is mediated by transforming growth factor beta (TGFbeta). In order to clarify the presence of TGFbeta in bovine AH, we applied it on the heparin-sepharose affinity column and prepared two fractions (bound and unbound fractions). We measured TGFbeta concentration in each fraction and examined how the anti-TGFbeta antibody decreased the inhibitory effect of AH on human umbilical vein endothelial cell growth and on in vitro angiogenesis. We found the presence of TGFbeta2, but not TGFbeta1, in the heparin bound fraction, and the inhibitory effect was detected in the heparin-bound fraction. Anti-TGFbeta antibody completely and dose-dependently extinguished the inhibitory effect of AH. We propose that the inhibitory effect of AH on endothelial cell growth and in vitro angiogenesis are both mediated by TGFbeta2. Our results indicate TGFbeta2 is normally present in AH and protects the eye tissue against abnormal neovascularization.

Animals↗

PubMed1998

Gliclazide inhibits diabetic neuropathy irrespective of blood glucose levels in streptozotocin-induced diabetic rats.

N-acetylcysteine and pentoxifylline, free radical scavengers and inhibitors of tumor necrosis factor-alpha (TNF-alpha) production, inhibit the development of peripheral neuropathy in streptozotocin (STZ)-induced diabetic rats. This study was designed to elucidate the effect of gliclazide, an oral hypoglycemic sulfonylurea, on diabetic neuropathy, because it has been indicated to be a free radical scavenger and TNF-alpha inhibitor. Rats were fed with powder chow mixed with gliclazide or glibenclamide as a control ad libitum. Blood glucose levels and body weight were remarkably higher and lower in diabetic than in nondiabetic rats, respectively, while gliclazide and glibenclamide had no effect on these in both diabetic and nondiabetic rats throughout a 24-week experiment. Serum lipoperoxide levels and lipopolysaccharide (LPS)-induced serum TNF-alpha activities were significantly increased in diabetic rats, whereas these were significantly inhibited in gliclazide-treated rats. Motor nerve conduction velocity (MNCV) of the tibial nerve significantly slowed in diabetic rats compared with nondiabetic rats. On the other hand, the slowed MNCV was significantly inhibited in gliclazide-treated diabetic rats after 16 experimental weeks. Morphometric analysis showed that gliclazide prevented decreased myelinated fiber area (P < .05), increased fiber density (P < .001), and decreased axon/myelin ratio (P < .05) in diabetic rats. Glibenclamide treatment did not affect serum lipoperoxide, TNF-alpha, MNCV, or nerve morphology in this experiment. These results indicate that gliclazide has a beneficial effect on peripheral neuropathy in STZ-induced diabetic rats, irrespective of blood glucose levels.

Animals↗

PubMed1998

Adrenocortical tumor in a patient with familial adenomatous polyposis: a case associated with a complete inactivating mutation of the APC gene and unusual histological features.

Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disorder caused by a germline inactivating mutation of the adenomatous polyposis coli (APC) gene. Patients with FAP sometimes develop various extracolonic manifestations including adrenocortical neoplasms. We present a 14-year-old boy with FAP who had an adrenocortical tumor with atypical histopathologic features, ie, sex-cord-like differentiation. Immunohistochemical studies of adrenal 4 binding protein (Ad4BP) and steroidogenic enzymes showed the capacity of these tumor cells to produce steroids. Genetic analysis of the tumor disclosed a two-hit mutation in APC: a germline 5-base pair deletion accompanied by a loss of the normal allele. Because there were no reports of genetic alterations in adrenocortical tumors developed in FAP patients, we examined 10 sporadic adrenal tumors (four carcinomas and six adenomas) for mutations in APC. However, no mutations were found in these 10 sporadic adrenal tumors. These results suggest that mutation of APC is also responsible for some fraction of the adrenocortical tumors: the tumor in this case is included.

Adenoma↗

PubMed1998

Strain differences in histamine release from peritoneal mast cells in rats.

1. Peritoneal mast cells from Brown-Norway (BN) rats were compared with those from Wistar and Sprague-Dawley (SD) rats. 2. Peritoneal mast cells from BN rats showed the smallest values in number, cell diameter and histamine contents compared with those from Wistar and SD rats. 3. BN rat peritoneal mast cells were more sensitive to compound 48/80 and anti-IgE than were those from Wistar and SD rats, and they showed a higher response to A23187 than did cells from Wistar rats. 4. The histamine release from passively sensitized peritoneal mast cells was weaker in BN rats than was that from Wistar and SD rats.

Animals↗

PubMed1998

The UBiT-100 13CO2 infrared analyzer: comparison between infrared spectrometric analysis and mass spectrometric analysis.

BACKGROUND: Although the 13C-urea breath test is the most accurate noninvasive method for detecting the presence of H. pylori infection, the requirement for an expensive mass spectrometer to analyze breath samples has prevented physicians from providing rapid results near the patient. Recently, a new type of infrared spectrometric analyzer, the UBiT-100, was developed for analyzing 13CO2 in breath. The purpose of this study is to compare results analyzed by the UBiT-100 to those analyzed by the mass spectrometric method. METHODS: Four hundred and fifty-three subjects participated in this study. Breath samples were collected before administration of 100 mg of 13C-urea and at 10, 20, 30, 45 and 60 min after administration. Subjects were asked to hold their breath for 10 sec and then exhale in order to collect breath samples containing more than a 2% concentration of CO2. Samples were then analyzed by both methods. RESULTS: The correlation analysis using values at 20 min after the administration of the study drug (433 points) was excellent with the regression equation of Y = 1.034x - 0.203; r = .996. The results of the UBiT-100 were available in 6 min, making the entire testing procedure less than 30 min. CONCLUSIONS: The UBiT-100 infrared analyzer provides a simple and accurate method of performing the urea breath test while the patient is still in the doctor's office.

Breath Tests↗

PubMed1998

Hepatocellular carcinomas supplied by inferior phrenic arteries.

PURPOSE: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). MATERIAL AND METHODS: A total of 126 consecutive cases of HCC were studied by contract-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. RESULTS: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 1, 1, and 4. CONCLUSION: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography.

Aged↗

PubMed1998

Pancreatic diabetes in Japan.

Pancreatic diabetes is usually a complication of other pancreatic disorders. Diabetes was a complication in 55.5% of 2,774 patients with chronic pancreatitis (CP) in Japan. More than half of alcoholic patients with CP in our clinic showed diabetes, and approximately 50% of those patients with diabetes were treated with insulin injections. On the other hand, cases of nonalcoholic CP showed mild endocrine dysfunction in terms of diabetic frequency and severity. Epidemiologic studies suggest that diabetes resulting from chronic pancreatitis accounts for <0.8% of all Japanese patients with diabetes. In patients with CP, B-cell dysfunction occurred first, followed by disturbances in A-cell function. Decreased insulin secretion during postprandial periods plays an important role in pancreatic diabetes. The fasting level of blood glucose is not useful for the diagnosis of the early stage of pancreatic diabetes. The glucose-tolerance test should be performed to diagnose early-stage diabetes in patients with CP with normal fasting blood glucose levels. For control of blood glucose in diabetic patients with CP, multiple injections of short-acting effective insulin before the meal are necessary. The incidence of long-term diabetic complications, diabetic retinopathy, nephropathy and neuropathy, in patients with CP with diabetes are not less than those in patients with primary diabetes.

Chronic Disease↗

PubMed1998

Expression of transforming growth factor beta1 (TGFbeta1) and its receptors in pancreatic duct cell carcinoma and in chronic pancreatitis.

Transforming growth factor beta1 (TGF beta1) is a multifunctional factor that regulates many aspects of cellular functions such as epithelial cell growth and synthesis of extracellular matrices. TGFbeta transduces signaling through a heterodimeric complex of type I and type II TGFbeta receptors (TbetaRI and TbetaRII). Recently, it has been shown that enhanced expression of TGFbeta1 is associated with the progress of pancreatic duct cell carcinoma (PDC) and chronic pancreatitis (CP). In this study, the expression of TGFbeta1 and its receptors, TbetaRI and TbetaRII, is examined in 21 cases of PDC by immunohistochemistry using specific antibodies, and the results are compared with those for 13 cases of CP. In the epithelial cells of PDC and CP, there are no significant differences in the expression of TGFbeta1, TbetaRI, and TbetaRII. In contrast, stromal expression of this cytokine and its receptors tends to be stronger in PDC than in CP; especially, the expression of TbetaRII is significantly stronger in PDC (p < 0.05). These findings suggest that there are some pathological differences in the properties of stromal reactions between PDC and CP, although the morphologies of their stroma resemble each other.

Aged↗

PubMed1998

Lipopolysaccharide-induced desensitization to pancreatic edema formation in rat cerulein pancreatitis.

Previously we reported that prior administration of lipopolysaccharide (LPS) mitigates subsequently produced cerulein (Cn) pancreatitis. To clarify the mechanism further, the pathological features of Cn pancreatitis were examined in detail after treating rats with very low doses of LPS. LPS pretreatment reduced the formation of pancreatic edema during Cn pancreatitis in a dose- and time-dependent manner. In contrast, the elevation of serum amylase and the histological findings, including acinar cell vacuolization and infiltration of inflammatory cells, were not affected. The lowest dose of LPS, 500 ng/kg, was sufficient to inhibit pancreatic edema formation completely. LPS at a dose of 5 microg/kg was fully effective when it was given from 30 min to 12 h before the induction of pancreatitis. Pretreatment with tumor necrosis factor-alpha (TNF-alpha) inhibited the pancreatic edema in a manner similar to that of LPS. Moreover, the inhibitory effect of LPS was partially attenuated by the administration of anti-TNF-alpha antibody before the injection of LPS. Actinomycin D (0.5 mg/kg) abolished the effect of LPS, whereas cycloheximide (0.5 mg/kg) given alone reduced pancreatic edema formation during pancreatitis. From these results, it was concluded that very low doses of LPS can induce, partially via TNF-alpha, a state refractory to pancreatic edema formation during Cn pancreatitis, and this phenomenon seems to be regulated at the transcriptional level.

Animals↗

PubMed1998

Low doses of lipopolysaccharide upregulate acinar cell apoptosis in cerulein pancreatitis.

We have reported previously that administration of a sublethal low dose of lipopolysaccharide (LPS; 50 microg/kg) prior to the induction of cerulein (Cn) pancreatitis mitigates the pathological course. To clarify the mechanism, we examined apoptosis in the pancreas using the same model. Apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) and transitional electron microscopy. LPS pretreatment at a dose of 50 microg/kg increased remarkably the incidence of acinar cell apoptosis in Cn pancreatitis rats compared with LPS-untreated Cn pancreatitis rats. Apoptosis was observed selectively in acinar cells but was not shown in endocrine cells or ductal epithelial cells. Infiltration of inflammatory cells was scarcely observed. These acinar cells showed the characteristic morphological features of apoptosis by electron microscopy. Administration of LPS at a dose of 50 microg/kg alone caused acinar cell apoptosis but the incidence was much lower than that in the LPS-pretreated Cn pancreatitis rats. The TUNEL labeling was significantly increased depending on the dose of LPS and on the interval between the administration of LPS and that of Cn. These results suggest that the pathological features of acute pancreatitis might be modified by the presence of nonfatal endotoxemia through the induction of acinar cell apoptosis.

Animals↗

PubMed1998

Nitric oxide is overproduced by peritoneal macrophages in rat taurocholate pancreatitis: the mechanism of inducible nitric oxide synthase expression.

To investigate the pathobiology of severe acute pancreatitis, we studied the expression of inducible nitric oxide synthase (iNOS) in peritoneal macrophages of experimental pancreatitis. Taurocholate (TCA) pancreatitis and cerulein (CE) pancreatitis were used as models of lethal and self-limited pancreatitis, respectively, and the mechanism of iNOS expression in peritoneal macrophages was studied. Serum nitrate and nitrite (NOx) concentrations increased during the course of TCA pancreatitis, and iNOS-immunoreactivity was detected in the peritoneal macrophages 12 h after the induction of TCA pancreatitis, but these phenomena were not observed in CE pancreatitis. Despite the difference in the iNOS expression, the iNOS messenger RNA (mRNA) and the activation of nuclear factor-kappa B (NF-kappa B) were detected in the peritoneal macrophages of both pancreatitis models. The supernatant of TCA pancreatitis ascites could induce iNOS in the peritoneal macrophages of normal rats in vitro, but the peritoneal lavage fluid of CE pancreatitis rats could not. The results indicated that there may be qualitative or quantitative differences in the macrophage activation between the two types of experimental pancreatitis and suggested that the ascites of rats with lethal acute pancreatitis contains some soluble factors that activate the macrophage/monocyte system and cause an overproduction of NO by the iNOS expression.

Acute Disease↗

PubMed1998

A new endoscopic method of gastric acid secretory testing.

OBJECTIVE: To date, the effect of Helicobacter pylori on acid secretion remains controversial. To evaluate changes in the gastric acid secretory response before and after H. pylori eradication in a large number of patients, we devised a new endoscopic method of gastric acid secretory testing, the endoscopic gastrin test (EGT). METHODS: In EGT, endoscopy was begun 15 min after intramuscular injection of 4 microg/kg tetragastrin. Gastric fluid secreted between 20 and 30 min after gastrin injection was aspirated and collected during endoscopic examination. The amount of acid in the sample collected over this 10-min period was estimated by titration and expressed in H+ mEq/10 min. Fifteen subjects underwent a conventional secretory test using a nasogastric tube (conventional method) and EGT on different days to assess the correlation between results obtained with the two methods. In 10 of these subjects, EGT was repeated under the same conditions to assess its reproducibility. RESULTS: EGT values correlated very well with peak acid output determined by the conventional method (n = 15, r = 0.92) and had high reproducibility (n = 10, CV = 5.6). We noted that EGT takes just a little longer to perform than a routine endoscopic examination, and the influence of an endoscope in the stomach on acid secretion was not present. CONCLUSION: The EGT should be very useful as a rapid, simple substitute for conventional secretory testing when repeated gastric secretory tests are required, especially in investigating the effect of H. pylori on acid secretion in a larger population.

Adult↗

PubMed1998

Stromal expression of urokinase-type plasminogen activator receptor (uPAR) is associated with invasive growth in primary liver cancer.

AIMS/BACKGROUND: Expression of urokinase-type plasminogen activator receptor (uPAR) was studied in 25 hepatocellular carcinomas (HCCs) and seven cholangiocellular carcinomas (CCCs) by immunohistochemistry. METHODS AND RESULTS: uPAR was expressed mostly by host cells distributed along the tumour-host interface in all cases of HCC and CCC, and its expression was higher in CCC. These uPAR-positive cells were identified as macrophages by observation of serial sections stained for CD68, a marker for macrophages. Cancer cells were positive for uPAR in only one case of poorly differentiated HCC with sarcomatous changes and in three cases of CCC. Hepatocellular carcinomas were classified into two types: those with a fibrous capsule (expansive type) and those without a fibrous capsule (invasive type). Invasive-type HCCs showed more prominent expression of uPAR by macrophages than expansive HCCs (p<0.001), to approximately the same degree as that of CCC. Extrahepatic metastasis was observed in two of 16 expansive HCCs, five of nine invasive HCCs and six of seven CCCs. CONCLUSIONS: Our findings suggest that uPAR expression mainly by macrophages is associated with invasive growth of cancer cells into the surrounding tissue in primary carcinoma of the liver.

Animals↗

PubMed1998

Leukocyte removal filter-passed lymphocytes produce large amounts of interleukin-4 in immunotherapy for inflammatory bowel disease: role of bystander suppression.

To determine immunosuppression by leukocytapheresis, we studied the immune profiles of filter-passed lymphocytes (FPLs) in patients with ulcerative colitis. These patients were treated with a leukocytapheresis (LCAP) filter of granulocyte apheresis (GCAP) column. Cytokine profiles or FPLs and peripheral blood mononuclear cells (PBMCs) were examined using interleukin (IL)-4 and interferon-gamma (IFN-gamma) immunoassay with lectin stimulation. The IL-4 production of LCAP FPLs was significantly higher than in prefilter PBMCs and GCAP column-passed lymphocytes (median: 540 pg/ml x 10(6) cells versus 4.7 and 2.9, respectively, p = 0.001). IL-4 production in PBMCs was increased after LCAP. IFN-gamma production was not increased in the FPLs. The IL-4 immune deviation was not shown in the patients treated with GCAP. LCAP FPLs showed increased CD4+DR- cells and decreases CD4+DR+ cells in comparison to PBMCs. LCAP FPLs could produce IL-4 and may lead to bystander suppression.

Adult↗

PubMed1998

Secretion imbalance between tumour necrosis factor and its inhibitor in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF) alpha and TNF-beta are soluble ligands binding to TNF receptors with similar activities; soluble TNF receptors neutralise TNF activity by acting as inhibitors. Little is known about the cytokine/soluble receptor role in inflammatory bowel disease (IBD). AIMS: To test the hypothesis that an imbalance in secretion between TNF and TNF inhibitors plays a role in gut inflammation in patients with IBD. METHODS: The secretion of TNF-alpha, TNF-beta, and soluble TNF receptors was compared in the culture supernatants of colonic biopsy specimens and isolated lamina propria mononuclear cells from patients with active colonic IBD. RESULTS: Spontaneous secretion of TNF-alpha in involved IBD mucosa was higher than in normal control and self limited colitis mucosa. Secretion of TNF-beta was higher in patients with Crohn's disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was increased in active inflammation; release from lamina propria cells was not increased. Mucosal TNF-alpha production correlated with severity of disease. CONCLUSIONS: Results showed enhanced secretion of TNF-alpha but failure to release enhanced amounts of soluble TNF receptor in lamina propria mononuclear cells of patients with IBD. An imbalance in secretion between TNF and TNF inhibitor may be implicated in the pathogenesis of IBD.

Adolescent↗

PubMed1998

Mitochondrial deoxyribonucleic acid 3256C-T mutation in a Japanese family with noninsulin-dependent diabetes mellitus.

Accumulating reports indicate a relationship between mitochondrial DNA mutation and impaired glucose-induced insulin secretion leading to a subtype of noninsulin-dependent diabetes mellitus. DNA from a 45-yr-old Japanese woman with noninsulin-dependent diabetes mellitus and muscle atrophy was isolated and studied for mitochondrial DNA mutations. We identified a mitochondrial DNA C-T heteroplasmic mutation at nucleotide position 3256. The mutation was located in the transfer ribonucleic acidLeu in a region conserved in evolution. Eight other members of her family were examined for the mutation. Six of them had the same mutation together with noninsulin-dependent diabetes mellitus, and one teenage boy had the mutation and impaired glucose tolerance. The other family member who did not have this mutation had normal glucose tolerance. The enzyme activity of the mitochondrial oxidative phosphorylation pathway in the muscle of the proband was measured. The enzyme activity was decreased in the proband, especially in complex I. This mutation might be responsible for the abnormal glucose metabolism.

Adolescent↗

PubMed1998

Effect of rabeprazole (E3810), a novel proton pump inhibitor, on intragastric pH in healthy volunteers.

In this study, we examined the effect of rabeprazole (E3810), a novel proton pump inhibitor, on gastric acidity under physiological conditions in healthy volunteers using 24-hour intragastric pH monitoring. Twenty-four-hour intragastric pH monitoring was performed three times to seven subjects randomly assigned in a cross over fashion to one of the following groups; without drug administration (basal), and with 10 mg or 20 mg of rabeprazole for four days. The median pH for 24 hours was 2.15 in the basal study, while the corresponding median pH were 5.05 and 5.90 after treatment with 10 mg and 20 mg of rabeprazole, respectively. Significant differences in the median pH were observed between the basal study and that after administration of the 10 mg and 20 mg doses of rabeprazole. The cumulative percentage of pH readings above the threshold pH 4 value, was 34.1% in the basal study, and 72.6% and 78.3% after treatment with 10 mg and 20 mg doses of rabeprazole, respectively. This result indicates that the efficacy of rabeprazole allows for substantial control of gastric acidity with once-daily dosing, and that both the 10 mg and 20 mg doses result in potent inhibition of gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

[Correlation between 13C-urea breath test and gastric histological findings in Helicobacter pylori positive patients].

13C-urea breath test (UBT), available for diagnosis of Helicobacter pylori (HP) in the stomach, measures the 13CO in the breath in which 13C urea is resolved in the stomach by urease derived from HP. Accordingly UBT is useful for a test of HP infection. This study is aimed at clarifying the relationship between the UBT and gastric histological findings. For this study we selected 63 patients with HP infection who showed both positive UBT and positive histological diagnosis. Briefly in the UBT procedure, the patients were given 13C-urea (100 mg dissolved 100 ml water) in a fasting state and kept in the left decubitus position for 5 minutes, and then the patients were asked to expire into testing bags before and 20 minutes after administration of the urea. Biopsy specimens were taken endscopically from the gastric antrum and the body. The specimens of all patients showed positive CLO test. HP organisms, inflammation, activity, and atrophy of the gastric specimens, were expressed in score from 0 to 3 according to the Update Sydney system. The UBT values were high correlated with the increase of HP organisms. The UBT was 11.8, 26.3, and 37/1000 in the groups with the scores of 0.1, and 2 in the number of HP organisms from the gastric body, respectively. The UBT was 19.2, 22.2, 36.1, 26.7/1000 in the groups with scores of 0, 1, 2, and 3 for the specimens from the antrum, respectively. The results show that there is a positive correlation between the UBT values and HP organisms. As a result, the UBT correlated with the activity score. Grade of gastric mucosal atrophy was expressed histologically in scores of 0,1,2, and 3. The UBT was 29.4, 19.1, 17.5, and 9.3/1000 in the groups with scores 0,1,2, and 3 in the grades of gastric atrophy from the gastric body, respectively. There was a negative correlation between the UBT values and the grade of gastric atrophy. We conclude that the UBT values which indicate the number of HP organisms can be used not only for diagnosis of HP infection but also the quantitative index of HP load.

Adult↗