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Biomedical subjects

T Chiba

Publications and source records attributed to T Chiba.

At least 271 records · Page 15Linked to original sources

Downregulation of gastric mucin gene expression and its biosynthesis by dexamethasone in the human.

The effect of corticosteroids on the release and biosynthesis of gastric mucin remains unclear. We studied the effects of dexamethasone on biosynthesis of mucin and MUC1 gene expression in the human stomach in vitro. Gastric mucosal specimens, obtained from six subjects at gastrectomy, were cultured with various concentrations of dexamethasone. Biosynthesis of mucin was studied by labeling gastric mucosa for 2 h with [3H]-glucosamine. After purification of mucin by CsCl gradient centrifugation, radioactivity of intra- and extracellular samples was counted. MUC1 gene expression was studied by Northern and dot-blot analysis using a cDNA encoding human gastric mucin gene MUC1. The dexamethasone treatment decreased mucin secretion from the isolated mucosa in a time- and concentration-dependent manner, with maximal inhibition of secretion (32+/-6%) observed after 8 h and 10(-5) M. Dexamethasone treatment also decreased MUC1 levels (28+/-9%). The inhibitory effect was also observed in carbachol-evoked secretion. These findings suggest that a decrease in mucin biosynthesis by corticosteroids may be involved in steroid-induced gastric mucosal damage.

Adult↗

Geranylgeranylacetone, an anti-ulcer drug, stimulates hexosamine production in a rat gastric mucosal cell line through binding to a specific cytosolic protein.

An anti-ulcer drug, geranylgeranylacetone (GGA), stimulates hexosamine production in a rat gastric mucosal cell line (RGM-1). The aim of this study was to elucidate the mechanism of this action. The role of protein kinase A, inositol phospholipid turnover and tyrosine kinase in the stimulatory action of GGA on hexosamine production in RGM-1 was determined by observing cAMP production, [3H]-inositol phosphate turnover and western blotting of tyrosine phosphorylation, respectively. Any trophic effect of GGA on RGM-1 was also checked by [3H]-thymidine incorporation. Our experiments showed that GGA has no effect on cAMP production, inositol phospholipid turnover, tyrosine phosphorylation or DNA synthesis in RGM-1. Finally, a [14C]-GGA competitive receptor binding assay was performed on RGM-1 and we found that [14C]-GGA specifically bound to RGM-1 cytosolic protein. Although retinoic acid (RA), another polyisoprenoid compound significantly stimulated hexosamine production in RGM-1, we confirmed that the [14C]-GGA binding site in RGM-1 is different from the RA binding site. In summary, GGA stimulates hexosamine production in RGM-1 and this action is probably mediated through its binding to a specific cytosolic protein in RGM-1.

Animals↗

Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan.

Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.

Adult↗

Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding gastric ulcers.

OBJECTIVE: Although physical stresses are known to induce peptic ulcers in the upper gastrointestinal tract, it remains controversial whether emotional stress can cause peptic ulcers. Therefore, we examined retrospectively the influence of the Hanshin-Awaji earthquake that occurred in Japan in January 1995 on the occurrence of peptic ulcer disease among noninjured residents. METHODS: Sixty-one hospitals, covering 70% of all endoscopy examinations performed in this area, joined the study and were divided into three areas according to the severity of the damage. A comparison was made between a group of 10,831 patients who underwent upper gastrointestinal endoscopy within 2 months after the earthquake and 16,100 who did so in the same hospitals during the corresponding period in 1994. RESULTS: In the most devastated area, in spite of a dramatic decrease in the total number of endoscopies (50.0%), patients with gastric ulcer (GU) were increased in 1995, whereas those with duodenal ulcer were decreased, resulting in a higher ratio of gastric to duodenal ulcers than in 1994 (3.07 vs 1.88). In particular, there was a marked increase in bleeding GU. The mean age of patients with GU was significantly higher in 1995 than in 1994. CONCLUSION: The Hanshin-Awaji earthquake-induced life event stress not only triggered but also exacerbated GU, particularly in the elderly.

Adult↗

Increased hepatocyte growth factor content in rat stomach during omeprazole treatment.

BACKGROUND AND AIMS: Hepatocyte growth factor (HGF) is a potent mitogen of gastric epithelial cells, and its production is stimulated during the healing of gastric mucosal lesions. In this study, the effect of a proton pump inhibitor, omeprazole, on the production and degradation of HGF in the stomach was examined to elucidate the mechanism of the omeprazole-induced acceleration of gastric mucosal healing. METHODS: Indomethacin-induced gastric mucosal lesions were induced in rats with or without omeprazole pretreatment. HGF gene expression and the content of HGF was investigated in the rat stomach. HGF degradation by gastric juice was also tested. RESULTS: In omeprazole-treated rats, the healing of gastric mucosal lesions was accelerated in comparison with those of untreated rats. Although omeprazole treatment did not enhance the indomethacin-induced increase in HGF gene expression, it significantly augmented the gastric HGF content. Furthermore, omeprazole increased the gastric content not only of the inactive but also of the active heterodimeric form of HGF, and this appeared to be due to the inhibition of the HGF degradation by gastric juice. CONCLUSION: Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.

Animals↗

Sensory nerve fibres from lumbar intervertebral discs pass through rami communicantes. A possible pathway for discogenic low back pain.

It has been thought that lumbar intervertebral discs were innervated segmentally. We have previously shown that the L5-L6 intervertebral disc in the rat is innervated bilaterally from the L1 and L2 dorsal root ganglia through the paravertebral sympathetic trunks, but the pathways between the disc and the paravertebral sympathetic trunks were unknown. We have now studied the spines of 17 rats to elucidate the exact pathways. We examined serial sections of the lumbar spine using immunohistochemistry for calcitonin gene-related peptide, a sensory nerve marker. We showed that these nerve fibres from the intervertebral disc ran through the sinuvertebral nerve into the rami communicantes, not into the corresponding segmental spinal nerve. In the rat, sensory information from the lumbar intervertebral discs is conducted through rami communicantes. If this innervation pattern applies to man, simple decompression of the corresponding nerve root will not relieve discogenic pain. Anterior interbody fusion, with the denervation of rami communicantes, may be effective for such low back pain.

Animals↗

Effect of pravastatin on plasma ketone bodies in diabetics with hypercholesterolemia.

Hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) is a common intermediate metabolite of cholesterol synthesis and ketone formation in the liver. In order to study the effect of HMG-CoA reductase inhibitor (pravastatin) on ketone formation, changes in the plasma levels of ketone bodies by treatment with pravastatin were studied in 18 non-insulin dependent diabetics with hypercholesterolemia. Body mass index, diabetic control, and plasma free fatty acid levels were not changed during the study, and the plasma levels of cholesterol decreased significantly from 250 +/- 25 to 211 +/- 34 mg/100 ml after 6 months of pravastatin treatment. The plasma levels of acetoacetic acid also significantly decreased from 37.7 +/- 22.6 to 28.4 +/- 13.4 mumol/l, and those of 3-hydroxybutyric acid and total ketone bodies also tended to decrease after pravastatin treatment. These results suggest that pravastatin decreases ketone formation in hepatic mitochondria besides cholesterol synthesis in hepatic microsome.

3-Hydroxybutyric Acid↗

Periosteal ganglion of the radius: a case report.

We report a case of 43-year-old female with a periosteal ganglion arising in the right radius. Plain radiographs showed thick and sparse spicula with shallow and irregular cortical erosion, which suggested periosteal ganglion. Magnetic resonance (MR) imaging revealed a well circumscribed homogeneous lesion with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. No apparent enhancement observed after gadolinium injection suggested that the lesion was cystic. At operation, gelatinous material was removed together with the spicula, the surface of the cortex and the overlying periosteum. There was no clinical evidence of recurrence after three years of surgical treatment. MR imaging was thought to be useful to confirm the diagnosis of periosteal ganglion.

Adult↗

Ductectatic mucinous cystic neoplasms of the pancreas: evaluation with MR cholangiopancreatography.

OBJECTIVE: We performed this study to describe the advantages of MR cholangiopancreatography and its findings in revealing ductectatic mucinous cystic neoplasms of the pancreas. CONCLUSION: MR cholangiopancreatography using both projection and source images can reveal characteristic findings of a ductectatic mucinous cystic lesion of the pancreas and show the presence of the communicating duct between the cystic lesion and the main pancreatic duct.

Aged↗

[Contrast-enhanced power Doppler imaging of the liver--preliminary animal study].

PURPOSE: To evaluate efficacy of contrast-enhanced power Doppler imaging of the liver. MATERIALS AND METHODS: We administered two kinds of contrast agents, SHU-508 (Schering AG, Germany) and FS069 (MBI, USA), intravenously to woodchucks with hepatocellular carcinomas. Power Doppler imaging of the liver was performed. To obtain minute hemodynamic information of the liver, we tried continuous infusion of contrast agents and flash echo mode (intermittent scanning) on power Doppler imaging. RESULTS: When we administered continuously contrast agents, the enhancement increased gradually and lasted until the end of the infusion. To compare with bolus injection, we were able to detect blood flow of the liver more clearly and easily without saturation artifacts. On power Doppler flash echo imaging of three or five seconds suspension, signals from only arterial flow were obtained. In comparison on seven seconds suspension imaging, signals from both arterial and portal flow were obtained. With flash echo mode, we could acquire the information of blood perfusion to depict the signals from eliminated microbubbles. CONCLUSION: With continuous infusion and flash echo mode on contrast-enhanced power Doppler imaging, we could get more detailed information of blood flow and perfusion of the liver. This method is expected to be useful for the diagnosis of liver tumor in clinical settings.

Albumins↗

[CDDP-resistant early recurrent uterine cervical cancer successfully treated with low-dose oral etoposide: a case report].

A 36-year-old woman with early recurrence of uterine cervical cancer had received radiotherapy and a CDDP-containing chemotherapy regimen. She was treated with oral etoposide by administration of 50 mg/day for 21 consecutive days at 14-day intervals. After two courses, complete remission was demonstrated by disappearance of the cervical tumor mass and pelvic lymph node enlargement on MRI. Leukopenia (grade 3) occurred after five courses, as well as alopecia (grade 2) and gastrointestinal discomfort (grade 1) after two courses. The patient has shown no sign of recurrence for 1.5 years. This method might be quite effective for patients with recurrent cervical cancer as well as allowing outpatient treatment and improving the quality of life.

Administration, Oral↗

Fibrilization in mouse senile amyloidosis is fibril conformation-dependent.

Amyloidosis refers to a group of diseases characterized by tissue deposition of amyloid fibrils. A single intravenous injection of a very small amount of the native mouse senile amyloid fibrils (AApoAII) induced severe systemic amyloid deposition in young mice having the amyloidogenic apoA-II gene (Apoa2c). After AApoAII injection, amyloid deposition occurred rapidly and advanced in an accelerated manner, as observed in spontaneous senile amyloidosis in mice. However, the injection of denatured AApoAII, native apoA-II in high-density lipoprotein (HDL), and denatured apoA-II monomer, which have the same primary structure but without a fibril conformation, did not induce amyloidosis. No amyloid deposition was observed in mice having an amyloid-resistant apoA-II gene (Apoa2b) even 3 months after AApoAII injection. Significantly less amyloid deposition was observed in mice having both types of apoA-II genes heterozygously (Apoa2b/c). These findings suggest that the nucleation-dependent polymerization found in vitro also occurs in vivo, and that the fibril conformation is required for the injected amyloid fibrils to act as seeds in vivo. Fibril conformation-dependent fibrillization is proposed as a general model of the pathogenesis of various kinds of amyloidosis occurring in vivo; it may be useful in both elucidating the pathogenesis of amyloidosis and developing effective therapeutic modalities to treat this disease.

Aging↗

Pepsinogen C gene product is a possible growth factor during gastric mucosal healing.

We isolated, by the subtraction cloning method, a pepsinogen C (PGC) gene fragment (the sequence between the 968th and 1179th base pairs) from a rat gastric mucosal cDNA library as a cDNA clone encoding a substance that promotes growth of the normal rat gastric mucosal cell line RGM1. Northern blot analysis revealed that PGC gene expression was enhanced not only in acetic acid-induced chronic gastric ulcers but also in indomethacin-induced gastric mucosal lesions. PGC gene expression was also increased in the Helicobacter felis-infected stomachs. Thus, the PGC gene may play a role in gastric epithelial cell growth during gastric mucosal healing.

Acetic Acid↗

Immunohistochemical studies on glutamatergic, GABAergic and glycinergic axon varicosities presynaptic to parasympathetic preganglionic neurons in the superior salivatory nucleus of the rat.

After the superior salivatory nucleus (SSN) neurons were labeled by administration of cholera toxin B subunit (CTB) or wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) to the pterygopalatine ganglion, morphological interactions between SSN neurons and fibers afferent to SSN neurons were examined by light and electron microscopy with double-immunostaining techniques. Antibodies to either the neurotransmitters or its receptor were used to label glutamatergic, GABAergic and glycinergic synapses on these neurons. By light microscopy, SSN neurons were identified in the ipsilateral ventrolateral part of the rostral medulla oblongata, and rich distributions of glutamate- and GABA-immunoreactive (ir) axon varicosities were observed around SSN neurons. Electron microscopy revealed that dendrites of SSN neurons received asymmetric synapses from glutamate-ir axon varicosities. Somata as well as dendrites received symmetric synapses from GABA-ir varicosities, or showed immunoreactivity for glycine receptors. Quantitative analysis by electron microscopy showed that glutamate-ir axon varicosities comprised 45.3% of total axon profiles in the SSN region, while GABA-ir varicosities were 20.8% and varicosities presynaptic to glycine receptors were 19.9%. These findings suggest that glutamatergic, GABAergic and glycinergic inputs, originated from a variety of nuclei, directly affect the activity of SSN neurons, and play a role in the regulation of the pterygopalatine ganglion of the rat.

Animals↗

Accumulation of pro-apolipoprotein A-II in mouse senile amyloid fibrils.

Apolipoprotein A-II (apoA-II), the major apoprotein of serum high-density lipoprotein, is deposited as amyloid fibrils (AApoAII) in murine senile amyloidosis. We have identified and purified a more basic amyloid protein from old-mouse liver. N-terminal sequencing of the protein revealed that the pro-segment of five amino acid residues (Ala-Leu-Val-Lys-Arg) extended from the N-terminal glutamine residue of mature apoA-II protein. MS analysis revealed the deposit of intact pro-apoA-II protein (molecular mass 9319 Da). Antiserum was prepared for staining of the AApoAII amyloid deposition. The relative abundance of pro-apoA-II to mature apoA-II in the amyloid-fibril fraction isolated from livers of mice with severe amyloidosis was 14.1%. The similar abundance of pro-apoA-II in the amyloid fibril fraction from the spleen (16.3%) suggested that deposited pro-apoA-II originated from the blood. The concentration of pro-apoA-II was much lower in the serum (1.5% of mature apoA-II) than in the amyloid-fibril fraction. There was no difference in the content of pro-apoA-II between the amyloidogenetic R1.P1-Apoa2c and amyloid-resistant SAMR1 strains at the age of 3 months. The abundance of pro-apoA-II in the amyloid-fibril fraction compared with the serum suggested that it plays a key role in the initialization of mouse senile amyloidosis.

Amino Acid Sequence↗