Biomedical subjects

T Fujioka

Publications and source records attributed to T Fujioka.

At least 145 records · Page 8Linked to original sources

PubMed1998

[Helicobacter pylori infection].

Since Helicobacter pylori was first isolated by Warren and Marshall in 1983, many investigators have reported that it is closely associated with gastro-duodenal diseases. Several diagnostic methods, C-urea breath tests, rapid urea test, histological exam and culture, are used for detecting H. pylori. Japanese monkey and Mongolian gerbils is the animal model that can sustain persistent colonization with H. pylori. Japanese monkeys persistently infected with H. pylori can develop histological gastritis quite similar to that in humans. Eradicating H. pylori markedly reduces the recurrence of peptic ulcers. The new triple therapy regimen consisting of proton pump inhibitor (PPI) plus two antibiotics is effective for eradicating H. pylori. This therapy has shown high rates of H. pylori eradication (90%) with few side effects. An increase in the prevalence of antibiotic-resistant H. pylori strains has been reported worldwide. Failed attempts to eradicate the bacteria resulted in an increased number of H. pylori resistant strains. The relationship between H. pylori infection and gastric cancer has been recently investigated.

Anti-Bacterial Agents↗

PubMed1998

[Metastatic renal tumor originating from esophageal carcinoma: a case report].

We report a case of renal metastasis from esophageal carcinoma. The patient was a 74-year-old man, who had undergone an operation for esophageal carcinoma thirteen months previously. He was admitted to our clinic for examination of a right renal mass. Computed tomography (CT) revealed an irregular low density area in the right kidney and angiography showed a hypovascular tumor. Partial nephrectomy was performed. Histological examination revealed squamous cell carcinoma and the diagnosis was metastasis of esophageal carcinoma. Metastatic renal tumors are rarely encountered clinically and, to our knowledge, the present case is only the 16th clinical report of the renal metastasis of esophageal carcinoma in Japan. However, metastasis to the kidney is relatively common at autopsy. It is the fifth most common site of metastasis following the lungs, liver, bones and adrenals. Consequently, patients with malignancy should be followed up while keeping renal metastasis in mind.

Aged↗

PubMed1998

[Studies on the conditions of blood sampling and storage for the liposome-based CH50 assay].

The CH50 values in the serum and plasma, especially those from chronic hepatitis caused by hepatitis C virus (HCV), are strongly affected and reduced through a process known as cold activation. We attempted to optimize the conditions of blood sampling and storage for the CH50 assay with a recently developed liposome-based assay kit. The bloods were obtained from HCV hepatitis patients as well as healthy donors. Regardless of the temperature (room temperature, 4 degrees C or 37 degrees C) at which samples were kept until the assay, higher values were always obtained in the serum than in the plasma. The plasma samples could either be heparinized or given any of the other anticoagulants, EDTA-2K and sodium citrate, at the time of sampling. We also attempted to optimize the temperature at which the fresh specimens were left during the period from sampling to assay and the temperatures to freeze them for storage and to thaw for assays. In the assays immediately after sampling, higher values were obtained when the specimens were left at 37 degrees C than at room temperature or 4 degrees C. To store at -80 degrees C rather than at -20 degrees C and to thaw rapidly at 37 degrees C rather than slowly at room temperature were found to be advantageous.

Blood Preservation↗

PubMed1998

Toxigenicity of Helicobacter pylori isolates possessing cagA gene and vacuolating cytotoxin.

Inflammatory cells in the gastric epithelium and direct cell damage are important effects of H. pylori infection in causing gastroduodenal diseases. The aim of this study was to determine whether H. Pylori possessing the cagA gene and vacuolating cytotoxin activity (cagA+/tox+) has these toxigenicities. The detection of cagA was performed by the polymerase chain reaction method. Culture supernatants of H. pylori were tested on rabbit gastric epithelial cell culture for intracellular vacuolation. H. pylori isolates were divided into two major types, cagA+/tox+ and cagA-/tox- strains. Ten Japanese monkeys were allocated to two groups, with six animals inoculated with the cagA+/tox+ strain and four animals inoculated with the cagA-/tox- strain. Five other Japanese monkeys served as controls. They were observed endoscopically every week and the severity of gastritis was evaluated in biopsy specimens obtained from the antral mucosa. Histopathological examination of the gastric mucosa revealed a more severe neutrophil infiltration caused by the cagA+/tox+ strain than that caused by the cagA-/tox- strain for 3 months after inoculation. These findings indicate that cagA and vacuolating cytotoxin may be important factors in causing the severe damage of the human gastric mucosa produced by H. pylori.

Animals↗

PubMed1997

Induction of fatty acid synthesis by pravastatin sodium in rat liver and primary hepatocytes.

We examined the effect of pravastatin sodium (pravastatin), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on fatty acid synthesis in rat liver. The repeated administration of pravastatin to rats at 250 mg/kg for 7 days led to a 2.8-fold increase in fatty acid synthesis in the liver. The diurnal change of fatty acid synthesis was not affected by the treatment. Hepatic fatty acid synthase activity was increased 3.2-fold, while acetyl-CoA carboxylase activity was not changed by the repeated administration of pravastatin. In rat hepatocytes, the incubation with 2 microg/ml pravastatin for 24 h increased fatty acid synthase activity 1.5-fold, as well as HMG-CoA reductase activity 2.8-fold. These results suggest that HMG-CoA reductase inhibitors might increase fatty acid synthesis in vivo through the induction of hepatic fatty acid synthase.

Acetyl-CoA Carboxylase↗

PubMed1997

The hupC gene product is a component of the electron transport system for hydrogen oxidation in Pseudomonas hydrogenovora.

The hydrogenase gene cluster containing nine genes (hupSLCDFGHIJ) was identified by sequencing of an 8.8-kb DNA region from Pseudomonas hydrogenovora. To investigate the function of the hupC gene product, we isolated a hupC-null mutant (HID3) of P. hydrogenovora by introducing an in-frame deletion into the hupC. The mutant, HID3, could not grow autotrophically but retained half the level of hydrogenase activity of the wild-type strain. Results of the oxygen consumption test and Western blot analysis revealed that the hupC gene product is a b-type cytochrome but not involved in the hydrogenase maturation process.

Amino Acid Sequence↗

PubMed1997

Effects of single administration of pravastatin sodium on hepatic cholesterol metabolism in rats.

Pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was administered to rats at 500 mg/kg, and the changes in several parameters concerning the metabolism of cholesterol in the liver were determined over 12 h. HMG-CoA reductase activity began to be induced 6 h after pravastatin dosage and continued to increase for an additional 6 h. A significant reduction of serum and liver microsomal cholesterol was observed only at 9 h. At this time point, the protein mass and activity of cholesterol 7 alpha-hydroxylase were significantly decreased by 31% and 34%, respectively. Hepatic low density lipoprotein (LDL) receptor expression was not affected by pravastatin throughout the experimental period. These results suggest that, in rats, the compensatory mechanism to restore the cholesterol balance after depletion of liver cholesterol produced by a single administration of pravastatin might primarily depend on the induction of HMG-CoA reductase and might be facilitated by a reduction in cholesterol 7 alpha-hydroxylase, without the induction of hepatic LDL receptor.

Animals↗

PubMed1997

Helicobacter pylori infection accelerates human gastric mucosal cell proliferation.

Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation in H. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whom H. pylori) recurred. H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation in H. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whom H. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P < 0.01, P < 0.001), and 6 months later, it had markedly decreased (P < 0.05, P < 0.05) and returned to normal. In patients in whom H. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but when H. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest that H. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.

Amoxicillin↗

PubMed1997

Metachronous development of malignant Leydig cell tumor.

Leydig cell tumor (LCT), a rare testicular tumor, is malignant in only about 10% of the cases. We report the case of a patient with bilateral malignant LCTs that developed metachronously. After undergoing a right inguinal orchiectomy for a malignant LCT at the age of 43 years, the patient was given cisplatin-based chemotherapy for suspected para-aortic lymph node metastasis. Eighteen months after the right orchiectomy, examination of a left testicular biopsy specimen showed a malignant LCT and a left inguinal orchiectomy was performed. Histologically, the initial malignant LCT exhibited a highly pleomorphic appearance with mitotic figures (58/10 HPF), whereas the second malignant LCT showed fewer mitoses (2/10 HPF). The proliferating cell nuclear antigen (PCNA)-labelling index in these tumors also differed (right-sided tumor, 50%; left-sided tumor, 28%). These findings suggest that the malignant LCT in the left testis developed as a second primary rather than as a metastatic tumor. There have been no known similar cases, although three cases of malignant LCT with contralateral metastasis have been reported.

Adult↗

PubMed1997

Antitumor agents. 180. Chemical Studies and cytotoxic evaluation of cumingianosides and cumindysoside A, antileukemic triterpene glucosides with a 14,18-cycloapotirucallane skeleton.

Treatment of cumingianosides and cumindysoside A, which possess a 14,18-cycloapotirucallane skeleton, with p-toluenesulfonic acid in CH2Cl2 yielded new triterpene glucosides. Cumingianoside A (1) gave 10 and 11, along with cumingianoside Q (5). The structures of 10 and 11 were determined on the basis of spectral examination and contained a dammar-13(17)-ene and a 17(R),23(R)-epoxydammarane skeleton, respectively. Cumingianoside C (2) afforded, together with cumingianoside P (6), products 12 and 13, which were similar to 10 and 11, respectively. With a short reaction time at room temperature, cumingianoside E (3) yielded cumingianoside D (4). In contrast, when 3 was treated with p-toluenesulfonic acid in CH2Cl2 overnight at 5 degrees C, it gave two products, 9 and 14. Extensive spectroscopic examination revealed that 9 possessed a dammar-12-ene skeleton, while 14 was a pentacyclic tetranortriterpene glucoside with a novel skeleton. Cumindysoside A (8) gave a product (15) similar to 14. The cytotoxicities of 9-15 were evaluated against a panel of 58 human tumor cell lines. Compounds 11-15 exhibited potent cytotoxicity with log GI50 values ranging from -7.11 to -4.94, especially against leukemia and colon-tumor cell lines.

Antineoplastic Agents, Phytogenic↗

PubMed1997

A new semi-solid agar dilution method for determining amoxycillin, clarithromycin and azithromycin MICs for Helicobacter pylori isolates.

The MICs of amoxycillin, clarithromycin and azithromycin for 26 strains of Helicobacter pylori were determined using Mueller-Hinton semi-solid agar (SSA) without CO2 incubation, as in the conventional agar dilution method. The tested H. pylori strains grew satisfactorily in the SSA method within 48 h of incubation. Reasonable values of MICs of three antibiotics for these strains were obtained by this method, avoiding the inactivation of macrolides due to acidification of the medium. By this method, the MICs of the antibiotics for the reference strains were within the acceptable NCCLS ranges for quality control.

Amoxicillin↗

PubMed1997

Long-term sequelae of experimental gastritis with Helicobacter pylori: a 5-year follow-up study.

To investigate the long-term effects of Helicobacter pylori gastritis on the gastric mucosa, 13 wild Japanese monkeys (six H. pylori-infected and seven controls) were monitored for 5 years. Colonization with H. pylori, the presence of macroscopic and histological gastritis, pyloric glandular height, and epithelial cell kinetics were investigated, using Ki-67 immunostaining in the gastric mucosa. In the infected group, persistent colonization with H. pylori was demonstrated by culture and histopathologic examination. In this group, the gastritis scores were significantly higher than in controls. Simultaneously, a significant decrease in the height of antral glands and a significant increase in the length of Ki-67-positive cells between the highest and lowest cells were also demonstrated in the infected animals. These experimental results directly demonstrate the effect of H. pylori infection on the gastric mucosa and may explain the potential mechanism for its causal role in the chain of events leading to gastric carcinoma.

Animals↗

PubMed1997

Virulence-associated genes as markers of strain diversity in Helicobacter pylori infection.

To establish a marker of strain diversity of Helicobacter pylori, a genetic examination was performed based on the detection rates by PCR of cagA and vacA, which are known to be virulence-associated genes. The test strains were obtained from 70 patients suffering from gastric ulcer (GU), 82 patients with duodenal ulcer (DU) and 48 patients with gastritis (GS). Fragments located in the three different regions of vacA were amplified; V1 being the upstream portion, V2 the mid-portion and V3 the downstream portion. For cagA, the detection rates were 70% for GU, 79% for DU and 50% for GS, showing a significantly higher rate for DU than for GS (P = 0.0005). With V1, the detection rates were 90% for GU, 90% for DU and 69% for GS, giving a significantly higher rate for GU than for GS (P = 0.0036) and also giving a significantly higher rate for DU than for GS (P = 0.0019). With V2, the detection rates were 60% for GU, 70% for DU and 44% for GS, giving a significantly higher rate for DU than for GS (P = 0.0024). The differences in vacA gene polymorphism were closely related to the evidence of gastroduodenal ulcers in H. pylori infection. Furthermore, the detection rates of cagA and polymorphisms of vacA by PCR could be used as markers of strain diversity in H. pylori-induced gastroduodenal ulcer.

Adult↗

PubMed1997

Characterization of sphingosine 1-phosphate-induced actions and its signaling pathways in rat hepatocytes.

Sphingosine 1-phosphate (S-1-P) and lysophosphatidic acid (LPA) stimulated glycogen phosphorylase, a rate-limiting enzyme responsible for glycogenolysis, in association with Ca2+ mobilization and phospholipase C (PLC) activation in rat hepatocytes. S-1-P, but not LPA, also inhibited adenosine 3',5'-cyclic monophosphate accumulation reflecting adenylyl cyclase inhibition. S-1-P-induced PLC activation, Ca2+ mobilization, and phosphorylase activation were markedly enhanced by primary culture of the cells for 24 h, whereas the inhibitory adenosine 3',5'-cyclic monophosphate response was unchanged by increasing culture time. Activation of the PLC-Ca2+ system during primary culture was specific to the lysosphingolipid; PLC and Ca2+ responses to LPA and NaF were unchanged or slightly attenuated by increasing culture time. Pertussis toxin treatment almost completely suppressed the S-1-P-induced inhibition of adenylyl cyclase but hardly influenced the lipid-induced activation of PLC and its cascade reactions. We conclude that S-1-P, through an LPA receptor-independent mechanism, stimulates two signaling pathways, i.e., activation of the PLC-Ca2+ system and inhibition of adenylyl cyclase, through distinct S-1-P receptor-transducer systems, resulting in the modulation of glycogenolysis in rat hepatocytes.

Animals↗

PubMed1997

Antitumor agents. 169 Dysoxylum cumingianum. V. Cumingianosides P and Q, new cytotoxic triterpene glucosides with an apotirucallane-type skeleton from Dysoxylum cumingianum.

Detailed chemical studies on the cytotoxic fraction from the leaves of Dysoxylum cumingianum have resulted in the isolation of two new triterpene glucosides, cumingianosides P (18) and Q (19), with an apotirucallane-type skeleton. The structures of 18 and 19 were determined by spectral examinations, and by conversion of cumingianosides C (3) and A (1) into 18 and 19, respectively. The cytotoxicities of cumingianosides P and Q against over 50 human cancer cell lines were evaluated. Cumingianoside P exhibited significant (EC50 < 4 microM) cytotoxicity against 37 human cancer cell lines. Among them, the UO-31 (renal cancer) cell line was the most sensitive to this compound (EC50 0.267 microM). In contrast, cumingianoside Q showed selective cytotoxicity against NCI-H522 (non-small cell lung cancer) cells with an EC50 value of 1.67 microM, and exhibited no cytotoxicity (EC50 > 10 microM) against most of the remaining cancer cell lines.

Antineoplastic Agents, Phytogenic↗

PubMed1997

Antitumor agents. 168. Dysoxylum cumingianum. IV. The structures of cumingianosides G-O, new triterpene glucosides with a 14,18-cycloapotirucallane-type skeleton from Dysoxylum cumingianum, and their cytotoxicity against human cancer cell lines.

Nine new triterpene glucosides, named cumingianosides G-O (4-7, 9, 12-15), containing a 14,18-cycloapotirucallane-type skeleton were isolated from a cytotoxic fraction of the leaves of Dysoxylum cumingianum. The structures of the new compounds were established on the basis of chemical and spectral examinations. Evaluation of the cytotoxic activity of cumingianosides G-O showed that cumingianoside M exhibited significant (< 4 microM) cytotoxicity, especially against leukemia and melanoma cell lines.

Antineoplastic Agents, Phytogenic↗

PubMed1997

[Inhibitory action of natural compounds of microbial origin on cholesterol metabolism].

1) Repeated administration of pravastatin significantly increased serum and liver cholesterol in rats. Hepatic LDL receptor activity was not changed and VLDL cholesterol secretion from the liver was increased. Net cholesterol synthesis in rat liver was increased after 7 days of repeated pravastatin administration. These results suggest that for rats, unlike other animals for which serum cholesterol is decreased, induced HMG-CoA reductase activity due to pravastatin treatment might overcome the inhibitory capability of pravastatin. 2) In the course of screening for squalene synthase inhibitors, novel zaragozic acids-F10863A, B, C and D-containing zaragozic acid D3 were isolated. F10863A was most potent and selectively inhibited cholesterol synthesis in freshly isolated rat hepatocytes among several cultured and isolated cells. It also showed in vivo serum cholesterol-lowering effects in hamsters and marmosets. However, the inhibition for squalene synthase proved to cause acidosis due to the accumulation of farnesol-derived dicarboxylic acids in urines. 3) A novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A, a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent, was isolated from the fermentation broth of Stachybotrys bisbyi. It inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.

Animals↗

PubMed1997

[Regression of atherosclerosis and centrally depressed lesions in rabbit aortas].

Atherosclerotic plaque with central depression (depressed lesion) has been hypothesized to be a morphological feature of atherosclerosis regression. We tested this hypothesis in New Zealand white rabbits. After the animals were fed a diet containing 1% cholesterol for three months, they were changed to a normal diet for 6 to 9 months. Several aortas had centrally depressed lesions similar to those found in elderly people, and the animals had low serum cholesterol levels. Immunohistochemical study showed that the depressed lesions contained more smooth muscle cells and collagen type IV, and fewer macrophage-derived foam cells than did common atherosclerotic elevated lesions found in rabbits. We know of no other report of depressed lesions in rabbits with atherosclerosis. Thus we believe that the centrally depressed lesion is a histological characteristic of regression of atherosclerosis.

Animals↗