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Biomedical subjects

Y Ogata

Publications and source records attributed to Y Ogata.

At least 127 records · Page 7Linked to original sources

Morgagni hernia diagnosed by MRI.

We herein present a patient with Morgagni hernia which was diagnosed by magnetic resonance imaging (MRI). The patient had a progressively enlarging mass in the right cardiophrenic angle on chest roentgenogram. On computed tomography (CT) scans, the mass was revealed to have fat density and therefore was suspected to be either a lipoma or liposarcoma. MRI clearly demonstrated that the mass shadow was composed of omental fat herniating into the right thorax through the diaphragmatic hiatus. MRI is thus considered to be a useful noninvasive modality for the evaluation of lower anterior mediastinal masses demonstrating fat density on CT.

Adipose Tissue↗

Effects of traditional herbal medicine on gastric mucin against ethanol-induced gastric injury in rats.

The effect of the traditional herbal medicine, Rikkunshi-to and its component crude drugs, Zingiberis Rhizoma and Glycyrrhizae Radix, on the gastric mucin was studied using a method developed to separate and quantify the mucin localized in the different layers of rat gastric mucosa. The oral administration of spray-dried extract to Rikkunshi-to (1000 mg/kg), Zingiberis Rhizoma (500 mg/kg) and Glycyrrhizae Radix (500 mg/kg) significantly prevented gastric mucosal damage induced by 70% ethanol in rats. In ethanol-treated rats the mucin content of the deep mucosa was reduced, and the reduction of the deep corpus mucin content was significantly inhibited by pretreatment of Rikkunshi-to and Zingiberis Rhizoma. Rikkunshi-to and Glycyrrhizae Radix pretreatment increased the surface mucin content by 140 and 146%, respectively. The effect on the gastric mucin by each drug differed in the different layers of the gastric mucosa.

Administration, Oral↗

AP-1 regulation of the rat bone sialoprotein gene transcription is mediated through a TPA response element within a glucocorticoid response unit in the gene promoter.

Bone sialoprotein (BSP), a protein which has been implicated in the initial mineralization of newly-formed bone, provides an early phenotypic marker for differentiated osteoblasts. BSP expression is induced by glucocorticoids in association with osteoblast differentiation, and a glucocorticoid response element (GRE) overlapping a putative TRE (TPA, 12-O-tetradecanoyl-phorbol 13-acetate, response element) site has been identified in the rat BSP promoter (Ogata et al., 1995). Since AP-1 and the glucocorticoid receptor have a central role in regulating cell proliferation and differentiation, we have studied AP-1 activity, stimulated by 100 ng/ml TPA in normal fetal rat calvarial cells and in transformed rat osteosarcoma cells (ROS 17/2.8). A transient induction of both c-fos and c-jun mRNAs by TPA was observed in both cell populations, together with an associated suppression of BSP mRNA in the fetal rat calvarial cells. Rat BSP promoter constructs, transiently transfected into ROS 17/2.8 cells, were used to show that TPA suppressed transcription of a luciferase construct (-938/+60; pLUC6) that included the GRE/TRE, but not transcription of shorter contructs lacking this element. Notably, suppression of pLUC6 transcription by TPA was abrogated in the presence of the synthetic glucocorticoid, dexamethasone. Gel mobility shift analyses were performed using two double-stranded synthetic oligonucleotides. These encompassed the TRE and either the distal pair of GRE half-sites (-936/ -910; GRE3) or the proximal pair of GRE half-sites (-925/-899; GRE 4) that comprise the GRE/AP-1 element. The assay showed binding of both AP-1 complexes and recombinant c-Jun homodimers. Additionally, either the c-Jun or glucocorticoid receptor could displace its counterpart from the GRE/TRE but not from consensus GRE and TRE oligonucleotides, indicating that the abrogation of AP-1-mediated gene suppression by glucocorticoids could involve competitive binding. These studies, therefore, have identified a glucocorticoid response unit through which c-Fos and c-Jun can suppress the expression of BSP in proliferating pre-osteoblastic cells and through which glucocorticoids can ameliorate the effects of AP-1 and promote osteoblast differentiation and the associated expression of BSP.

Animals↗

Histamine H1 receptor-stimulated Ca2+ signaling pathway in human periodontal ligament cells.

We studied histamine-induced Ca2+ mobilization in human periodontal ligament (HPDL) cells. Histamine induced a transient rise in intracellular Ca2+ ([Ca2+]i) and maintained a sustained phase in the presence of extracellular Ca2+. In the absence of extracellular Ca2+, the transient peak was slightly reduced and the sustained phase was decreased to the basal level. The initial rise in [Ca2+]i was attributed to two components: intracellular Ca2+ release and Ca2+ influx, whereas the sustained phase was due to Ca2+ influx. After depletion of intracellular Ca2+ stores with thapsigargin, a known Ca(2+)-ATPase inhibitor, histamine-induced increase in [Ca2+]i was significantly reduced, suggesting histamine induces Ca2+ release from inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]- and thapsigargin-sensitive Ca2+ stores. Histamine-induced peak in [Ca2+]i was increased dose-dependently in the presence and absence of extracellular Ca2+. The histamine-mediated response in [Ca2+]i was specifically attenuated by chlorpheniramine (H1 antagonist) but not by cimetidine (H2 antagonist), clearly indicating that activation of H1 receptor mediates histamine-induced Ca2+ mobilization. We next examined the effect of histamine on inositol phosphates formation. Histamine stimulated the formation of inositol phosphates which changed time-dependently. In particular, the formation of Ins(1,4,5)P3 was increased significantly for 10 s. The histamine-induced Ca2+ mobilization caused an increase of prostaglandin E2 (PGE2) release which was reduced in excluding extracellular Ca2+. These results indicate that activation of histamine H1 receptor induces the accumulation of Ins(1,4,5)P3 and the following transient increase in [Ca2+]i, and elicits the release of PGE2 which may be coupled with Ca2+ influx.

Calcium↗

The fractional inhibitory concentration index of antimicrobial agents for bacteria and Mycoplasma isolated from the nasal swabs of cattle with respiratory diseases.

We investigated the effect of thiamphenicol plus lincomycin (TP + LCM) and thiamphenicol plus tylosin (TP + TS) combinations using checker board method on the growth of Pasteurella (P.) multocida, P. haemolytica and Mycoplasma (M.) bovis by calculating the fractional inhibitory concentration index (FIC index). The results showed that the FIC indexes of the TP + LCM combination for P. multocida, P. haemolytica and M. bovis were 0.36 +/- 0.10, 0.72 +/- 0.09 and 0.81 +/- 0.18, respectively. The FIC indexes of the TP + TS combination for P. multocida, P. haemolytica, and M. bovis were 0.79 +/- 0.20, 0.66 +/- 0.11 and 0.32 +/- 0.14, respectively. Thus, these combinations are assumed to have a more synergistic or additive effect on bacteria growth than a single antimicrobial agent.

Animals↗

Effect of a combination of antimicrobial agents for the treatment of respiratory disease in cattle.

Clinical effect of the administration of thiamphenicol (TP) and tylosin (TS) on bovine respiratory disease was investigated. Group I (n = 64) were administered TP (10 mg/kg) and TS (4 mg/kg), group II (n = 26) were given TP (5 mg/kg) and TS (2 mg/kg). For the control, TP group (n = 25) were given 20 mg/kg of TP and ampicillin group (n = 23) were given 10 mg/kg of ampicillin. As a result, improvement of clinical findings was more rapid and the cure rate was significantly higher in group I compared to those in the other 3 groups. These results showed that a combination therapy with minimal basic doses of TP and TS is very effective for some respiratory diseases in cattle.

Animals↗

Immunohistochemical localization of vascular endothelial growth factor in esophageal cancer.

We have studied the expression of vascular endothelial growth factor (VEGF) in esophageal cancer using immunohistochemistry. A total of 101 specimens of esophageal cancer tissue were fixed by formalin, embeded in paraffin wax, and examined in 3 microns sections by avidin-biotin peroxidase complex method. VEGF was noted in the cytoplasm of normal esophageal glandular cells, monocyte-macrophages, squamous carcinoma cells and of the vascular endothelial cells themselves. VEGF expression by monocyte-macrophages was observed in all cases, in contrast the incidence of VEGF expression in the tumor cells was relatively low at 26.7% of all specimens. However, in the cases where the tumor cells were positive for VEGF, it was discovered that the main source of the VEGF production was the tumor cells themselves. In the cases with proper mucosal invasion the incidence of VEGF expression by the tumor cells was quite low at 7.6%. However, when the tumor invaded the submucosal layer the expression increased to 33.3%. There was also a significant correlation in those with the submucosal invasion between the expression of VEGF in the tumor cells and that VEGF may play an important role in tumor progression and in the angiogenesis via auto-crine and para-crine mechanisms in esophageal cancer.

Endothelial Growth Factors↗

Hepatic arterial chemotherapy for liver metastases from colorectal cancer.

We have investigated the complications, toxicities, tumor response and survival rate with hepatic arterial (HA) chemotherapy for liver metastases from colorectal cancer. Forty-three patients with measurable liver metastases and 10 patients after the resection of liver metastases were treated with HA bolus mitomycin C (MMC) or continuous fluorouracil (5-FU) infusion between 1986 and 1994. The catheter- or reservoir-related complications such as catheter induced infection, subcutaneous reservoir pocket infection, or catheter or hepatic artery occlusion occurred in 14 patients (26%) mainly in our early cases. Severe gastritis or a gastroduodenal ulcer developed in 12 patients (23%), in particular after treatment with continuous infusion of 5-FU and when the catheter was placed into the gastroduodenal artery during laparotomy. An ulcer often caused a serious complication such as a duodeno-biliary fistula, penetration into the hepatic artery or duodenal perforation. Also noted were upper gastrointestinal symptoms in 26 patients, hepatic toxicities in 3 patients, and bone marrow depression in 4 patients. Because of these complications and toxicities, HA therapy was discontinued in more than 60% of the cases. The overall tumor response rate was 17%. However, in the cases which were treated by 5-FU continuous infusion for longer than 3 months, the response rate was higher than 60%. There was no significant difference in survival rate between HA therapy and systemic palliative chemotherapy. These results suggest that it is important to prevent gastrointestinal toxicities in order to allow continuation of HA continuous 5-FU infusion therapy which could provide a higher response rate and a better survival for colorectal cancer patients with liver metastases.

Colorectal Neoplasms↗

Characterization of the bone sialoprotein (BSP) gene promoter.

Bone sialoprotein is a 34 kDa phosphorylated and sulphated glycoprotein that is essentially unique to mineralizing connective tissues. Recent studies on the developmental expression of BSP mRNA and the temporo-spatial appearance of the protein during bone formation in vivo and in vitro have demonstrated that BSP is expressed by differentiated osteoblasts and that it may function in the initial nucleation of hydroxyapatite crystals in de novo bone formation. To study the cell-specific regulation of BSP we have isolated genomic clones that encompass the BSP promoter regions of both the human and rat genes. These promoters are characterized by a highly conserved region (BSP Box) that extends upstream from the transcription start site to nt -370. Within this region the immediate promoter is further characterized by a unique inverted TATA box and an inverted CCAAT box, both of which are required for basal transcriptional activity. The TATA box is overlapped by a vitamin D3 response element (VDRE) which appears to mediate vitamin D suppression of BSP gene transcription by competing with the TATA-binding protein (TBP) for occupancy of the site of the pre-initiation complex formation. Mutation of the inverted TATA box into a normal TATA sequence increases transcription slightly but does not affect the functionality of the VDRE indicating that the orientation of the TATA box is not critical for these functions. Further upstream an AP-1 site, overlapped by a steroid hormone response-like sequence, mediates down-regulation of BSP transcription induced by TPA that is abrogated by a complex interaction between Jun and the glucocorticoid receptor protein induced by dexamethasone. Thus, the characterization of approximately 3 kb of the BSP promoter and approximately 2 kb of the first intron has revealed several sites of transcriptional regulation that are important in regulating BSP expression and, consequently, bone formation.

Animals↗

[Immunohistochemical labeling of inner ear tissues embedded in polyethylene glycol 4000--comparative study with araldite and unicryl embedded sections].

An improved method for embedding specimens in polyethylene glycol (PEG) 4000, a water soluble polymer, was used to prepare the vestibular end-organs of the inner ear. Staining of the tissue sections of PEG embedded specimens with antibodies to alpha-tubulin and to calmodulin was compared with staining of tissue sections of Araldite and Unicryl embedded specimens. PEG embedded sections revealed sensitive immunocytochemical labeling with excellent morphological resolution. The problems of embedding and orienting small specimens of the inner ear in PEG are described and the methods used to solve them are described.

Acrylic Resins↗

[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.

Adult↗

[Analysis of contributing factors with high renal uptake of 99mTc-MDP after anti-cancer chemotherapy including cisplatin].

We studied the effect of anti-cancer chemotherapy including cis-platin (CDDP) on renal high uptake of 99mTc-MDP using renal accumulation index (RAI) which was defined as a ratio of the densities between kidneys and lumbar bodies. We analyzed 21 cases who received bone scintigraphy within 30 days after chemotherapy. High RAIs were observed in 15 cases (71.4%). We compared the relationship between the RAI and time interval of CDDP administration and bone scintigraphy, total dose of CDDP, BUN and age. High RAIs were inversely related to the time interval and no patient showed high RAI when bone scintigraphy were studied later than 17 days after chemotherapy. BUN level were related to RAI. But, dose of CDDP and ages were unlikely responsible for the RAI values in this study. We summarized that high renal uptake of 99mTc-MDP was likely to be due to short time interval after chemotherapy.

Adult↗

[Infective endocarditis associated with vertebral osteomyelitis: report of two cases].

A 42-year-old man and a 65-year-old woman with infective endocarditis suffered onset of severe back pain. Magnetic resonance imaging and technetium-99 m bone scanning demonstrated osteomyelitis in the lumbar spine which is an unusual complication of infective endocarditis. The man was treated by antibiotics and finally aortic valve replacement and laminectomy with bone grafting. The woman had small patent ductus arteriosus and developed aortic regurgitation, but was treated by antibiotics and corset application with good result. The possibility of osteomyelitis in the lumbar spine should be considered in a patient with endocarditis complaining of severe back pain. The appropriate antibiotic therapy over a prolonged period is recommended.

Adult↗

Steps involved in activation of the pro-matrix metalloproteinase 9 (progelatinase B)-tissue inhibitor of metalloproteinases-1 complex by 4-aminophenylmercuric acetate and proteinases.

The precursor of matrix metalloproteinase 9 (pro-MMP-9, progelatinase B) noncovalently binds to tissue inhibitor of metalloproteinases (TIMP)-1 through the C-terminal domain of each molecule. We have isolated the proMMP-9.TIMP-1 complex from the medium of human fibrosarcoma HT-1080 cells and investigated the activation processes of the complex by 4-aminophenylmercuric acetate, trypsin, and matrix metalloproteinase 3 (MMP-3, stromelysin 1). The treatment of the proMMP-9.TIMP-1 complex with 4-aminophenylmercuric acetate or trypsin converts proMMP-9 to lower molecular weight species corresponding to active forms, but no gelatinolytic activity is detected. The lack of enzymic activity results from binding of TIMP-1 to the activated MMP-9. The treatment of the proMMP-9.TIMP-1 complex with a possible physiological proMMP-9 activator, MMP-3, does not reveal any gelatinolytic activity unless the molar ratio of MMP-3 to the complex exceeds 1. This is due to the inhibition of MMP-3 by TIMP-1 forming a ternary proMMP-9.TIMP-1.MMP-3 complex. The formation of the ternary complex weakens the interaction between proMMP-9 and TIMP-1, resulting in partial dissociation of the complex into proMMP-9 and the TIMP-1.MMP-3 complex. When MMP-3 is in excess, the propeptide is completely processed, and the full activity of MMP-9 is detected. Similarly, the proMMP-9.TIMP-1 complex inhibits MMP-1 (interstitial collagenase) and in turn renders the proMMP-9 activable by a catalytic amount of MMP-3. These results suggest that formation of the proMMP-9.TIMP-1 complex regulates extracellular matrix breakdown in tissue by switching the predominant MMP activity from one type to another.

Collagenases↗

Glucocorticoid regulation of bone sialoprotein (BSP) gene expression. Identification of a glucocorticoid response element in the bone sialoprotein gene promoter.

Glucocorticoids modulate the development and growth of many organs through interactions with a specific intracellular receptor (glucocorticoid receptor) that regulates gene transcription through a cognate element, the glucocorticoid response element (GRE), in the promoter of target genes. In bone formation glucocorticoids stimulate osteoblast differentiation and the formation of bone matrix. Recent studies have demonstrated that the induction of the bone sialoprotein (BSP) gene is associated with osteoblast differentiation and de novo bone formation. To determine the molecular pathways of glucocorticoid regulation of BSP expression, we have analyzed the effects of the synthetic glucocorticoid, dexamethasone, on the expression of the BSP by bone cells in vitro. At 10 nM, dexamethasone induced BSP expression in association with bone tissue formation by confluent fetal rat calvarial cells and adult rat marrow cells and also stimulated BSP expression up to sixfold in osteoblastic cells (UMR 106-6 and ROS 17/2.8 cells). Most of the stimulation was blocked by cycloheximide, indicating direct and indirect mechanisms of BSP gene regulation. Nuclear 'run-on' transcription analysis revealed an up to twofold increase in transcription corresponding to the increase in mRNA that was unaffected by cycloheximide. Analysis of BSP mRNA in the presence of a transcription inhibitor (5,6-dichloro-1-beta-D-ribofuanosyl benzimidazole) by Northern hybridization revealed that the stability of the BSP mRNA was not significantly altered by dexamethasone, indicating that the major, indirect, stimulation of BSP expression involves a nuclear post-transcriptional mechanism. To study the direct effects of dexamethasone, nucleotide sequence analysis of the rat BSP promoter was extended upstream to position -2992 and downstream to +2282 in the first intron. Transient transfection analyses, using various rat BSP promoter constructs linked to a luciferase reporter gene, and gel mobility shift assays were used to identify a putative glucocorticoid response unit comprising three GRE half-sites and a putative AP-1 site, located within positions -906 to -931 upstream from the translation start site of the BSP gene promoter. BSP transcription was stimulated approximately 1.5-fold by dexamethasone through this GRE, indicating that its direct effects are mediated by glucocorticoid receptor binding to this site. These studies, therefore, have identified both indirect and direct pathways of glucocorticoid regulation of BSP gene expression, the direct effects being mediated by a GRE in the rat BSP promoter through which the effects of glucocorticoids on BSP gene transcription appear to be regulated.

Animals↗

Effects of bradykinin on Ca2+ mobilization and prostaglandin E2 release in human periodontal ligament cells.

In fura-2-loaded human periodontal ligament (HPDL) cells, bradykinin induced a rapidly transient increase and subsequently sustained increase in cytosolic Ca2+ ([Ca2+]i). When external Ca2+ was chelated by EGTA, the transient peak of [Ca2+]i was reduced and the sustained level was abolished, implying the Ca2+ mobilization consists of intracellular Ca2+ release and Ca2+ influx. Thapsigargin, a specific Ca(2+)-ATPase inhibitor for inositol 1,4,5-trisphosphate (1,4,5-IP3)-sensitive Ca2+ pool, induced an increased in [Ca2+]i in the absence of external Ca2+. After depletion of the intracellular Ca2+ pool by thapsigargin, the increase in [Ca2+]i induced by bradykinin was obviously reduced. Bradykinin also stimulated formation of inositol polyphosphates including 1,4,5-IP3. These results suggest that bradykinin stimulates intracellular Ca2+ release from the 1,4,5-IP3-sensitive Ca2+ pool. Bradykinin stimulated prostaglandin E2 (PGE2) release in the presence of external Ca2+, but not in the absence of external Ca2+. Ca2+ ionophore A23187 and thapsigargin evoked the release of PGE2 in the presence of external Ca2+ despite no activation of bradykinin receptors. These results indicate that bradykinin induces Ca2+ mobilization via activation of phospholipase C and PGE2 release caused by the Ca2+ influx in HPDL cells.

4-Nitrophenylphosphatase↗

Immunocytochemical comparison of posttranslationally modified forms of tubulin in the vestibular end-organs of the gerbil: tyrosinated, acetylated and polyglutamylated tubulin.

Specific antibodies against alpha-tubulin, acetylated alpha-tubulin, tyrosinated alpha-tubulin and polyglutamylated alpha- and beta-tubulin were used to compare the distribution of posttranslationally modified tubulin in the vestibular end-organs of the gerbil. Antibodies to acetylated tubulin labeled a dense network of microtubules in the hair cells and bundles of microtubule in the supporting cells. Nerve fibers within and below the epithelium were weakly labeled. This localization paralleled that seen with antibodies to alpha-tubulin which labeled all microtubules present in the cells. Antibodies to tyrosinated tubulin labeled networks and bundles of microtubules in both hair cells and supporting cells and in addition gave intense, diffuse labeling in the cytoplasm of both cell types. It also labeled the nerve fibers. Antibodies to polyglutamylated tubulin were localized mainly in nerve fibers, and in the calyces the labeled microtubules were found running circumferentially around the type I sensory hair cells. Thus, tyrosinated tubulin was found in the fine networks of microtubules in both the sensory and supporting cells. Acetylated tubulin was found in the dense networks and bundles of microtubules in the sensory and supporting cells, but did not colocalize with polyglutamylated tubulin, which was found predominantly in the nerve fibers. The labeling patterns for the tyrosinated tubulin and posttranslationally modified tubulins in the sensory and supporting cells of the vestibular end organs differ from that seen in the organ of Corti and may reflect differences in the stability of the microtubules and the mechanical properties of the sensory epithelium.

Acetylation↗

Automated smear counting and data processing using a notebook computer in a biomedical research facility.

An automated smear counting and data processing system for a life science laboratory was developed to facilitate routine surveys and eliminate human errors by using a notebook computer. This system was composed of a personal computer, a liquid scintillation counter and a well-type NaI(Tl) scintillation counter. The radioactivity of smear samples was automatically measured by these counters. The personal computer received raw signals from the counters through an interface of RS-232C. The software for the computer evaluated the surface density of each radioisotope and printed out that value along with other items as a report. The software was programmed in Pascal language. This system was successfully applied to routine surveys for contamination in our facility.

Computers↗