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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 1,351 records · Page 75Linked to original sources

[Anticancer effect and side effect of arterial chemoembolization using cis-diamine-dichloroplatinum (II)/4-0-tetrahydropyranyl-adriamycin-lipiodol (CTL) suspension on hepatocellular carcinoma].

Seventeen patients with hepatocellular carcinoma were treated by intraarterial injection of CTL suspension. The doses of CTL suspension, CDDP and THP(mean +/- SD)/injection were 4.1 +/- 1.6 ml, 81.9 +/- 31.6 mg and 13.5 +/- 5.2 mg, respectively. The therapy was given once in 10 patients, twice in 6 and 4 times in one. Over 50 per cent reduction in tumor size was obtained in 5 patients (30%). Fifty or more % decrease in serum alpha-feto-protein (AFP) levels was observed in 3 of 7 patients (43%) with the initial serum AFP level of more than 200 ng/ml, Fever, abdominal pain, nausea and vomiting were noted in most cases. However, they disappeared within 2 weeks after therapy was completed. No severe complications were encountered except one case of a liver abscess which healed by administration of antibiotics. No severe changes in laboratory data were observed. This study suggests that a new method of intraarterial injection must be developed to enhance the therapeutic effect even more, in addition to an increased injection dose of CDDP/THP-LPD and higher concentration of CDDP and THP in LPD.

Adult↗

[A multicenter, fixed-flexible dose study of terazosin hydrochloride in the treatment of symptomatic benign prostatic hypertrophy].

In this study the multicenter, fixed-flexible dose regimen was taken to evaluate the effective dose range of Terazosin for the treatment of micturition disturbance in benign prostatic hypertrophy (BPH) and to clarify the characteristics of patients who are more responsive to Terazosin therapy. After a 1-week washout (placebo) the first two weeks 1 mg/day of Terazosin was administered, then depending on efficacy of subjective symptoms, Terazosin doses were increased up to 2 mg/day and 4 mg/day at intervals of two weeks. After six weeks the final efficacy and safety were assessed. The subjective symptom improvement rate was 18.5% by 1 mg/day, 55.6% by 2 mg/day and 65.4% by 4 mg/day cumulatively. The objective symptom improvement rate were 13.2% by 1 mg/day, 42.1% by 2 mg/day and 50.0% by 4 mg/day cumulatively. The global improvement rate was 14.5% by 1 mg/day, 50.0% by 2 mg/day and 61.8% by 4 mg/day cumulatively. The patients who had a higher subjective symptom score in the lead-in period were more improved rather than those who had a lower score. In objective symptoms, voided volume, maximum flow rate (MFR), MFR nomogram score and average flow rate improved and the ratio of residual urine volume decreased. There was no relationship between clinical improvement on either subjective or objective symptoms and prostatic weight. Adverse reactions, such as dizziness, vertigo, tinnitus, nausea and blurred vision; were seen in 10 cases. In conclusion Terazosin was effective and well tolerated for the treatment of patients who had micturition disturbance with BPH in the dose range of 2 to 4 mg/day.

Adrenergic alpha-Antagonists↗

[Contents of chemical mediators in sputum in a case of mycoplasma pneumoniae bronchiolitis resembling bronchial asthma].

A case of Mycoplasma pneumoniae bronchiolitis with hypoxemia is presented. A 41-year-old man was admitted to hospital because of fever, productive cough and dyspnea with wheezing of one month duration. On admission, bronchial asthma was suspected on the basis of reversible airflow obstruction and sputum eosinophilia. However, despite treatment with bronchodilators, his condition did not improve. Chest film and computed tomogram revealed small nodular shadows and tramlines in the bilateral lower lung fields, and pulmonary function tests indicated peripheral airway obstruction. Serologic titer for Mycoplasma pneumoniae was 1:160. A diagnosis of bronchiolitis due to Mycoplasma pneumoniae was made. Improvement of lung function and roentgenographic findings was observed following administration of erythromycin and doxycycline. The concentrations of prostanoids in sputum were markedly higher than in cases of bronchial asthma, and decreased as he improved. These observations suggest that Mycoplasma bronchiolitis should be considered in the differential diagnosis of wheezing, and that measurement of prostanoids in sputum may be useful in the differentiation of infective bronchiolitis and bronchial asthma.

Adult↗

[Therapeutic modality for esophago-gastric varices analyzed by endoscopic ultrasonography].

For 64 cases with portal hypertensive disease, we investigated the intramural and extramural structure of the stomach and esophagus by endoscopic ultrasonography (EUS). Variously developed intra- or extra-mural vascular structures had a relationship to the endoscopic variceal form, and the communicating (inflow) vessels to varices were found in 35 of 50 primary treated cases (70%). We classified the esophago-gastric varices into three types according to the vascular structure, such as the esophageal type, the esophago-gastric type and the solitary gastric type. From the analyses of these collateral structures, we should select a treatment as follows. In the esophageal type which has a few inflow vessels, it is easy to eliminate the varices by obturating the inflow vessels by endoscopic injection sclerotherapy (EIS). In the esophago-gastric type, which has many enlarged inflow vessels, the Hassab operation is effective to devascularize extramural inflow vessels, and the combination of EIS is necessary to sclerous the intramural varices. In the solitary gastric type which is a part of the downward porto-systemic shunt, Hassab operation is recommended to prevent the rupture of varices for the subtype with intramural running vessels, but conservative therapy is enough for the subtype without intramural running vessel.

Collateral Circulation↗

[The inhibitory effects of platelet activating factor (PAF) on ciliary activity of human paranasal sinus mucosa].

The effect of platelet activating factor (PAF) on human paranasal ciliated cells was investigated in vitro. Normal human paranasal sinus mucosa was obtained by surgical procedure and incubated with Eagle's MEM containing 10% FCS in the form of tissue culture. Ciliary activity was viewed at 37 degrees C under an inverted microscope equipped with a thermoregulator and a humidified CO2 chamber, recorded on video tapes and photoelectrically measured. Ciliary inhibition was observed by the treatment with PAF, in a dose dependent manner, at concentrations from 10(-10) M to 10(-6) M. The inhibitory effect of 10(-8) M PAF on ciliary activity was completely blocked when the mucosa was treated with 10(-6) M CV-3988 or 10(-6) M CV-6209 (specific PAF receptor antagonists). By the radioimmunoassay, the concentration of PAF in tissue culture was reduced by half within 12.5 min, and within 60 min it was only 5% of the initial concentration. There was no significant difference in ciliary inhibition between irrigation after a 60 min incubation with 10(-8) M PAF and non-irrigation. These results indicate that PAF inhibited ciliary activity directly and specifically, and induced irreversible damage primarily within the first 60 min after the challenge.

Cilia↗

[Sclerosing lipogranuloma of the male genitalia: report of 2 cases--review of 72 cases reported in Japan].

Two cases of male patients (49 and 36 y.o.) with sclerosing lipogranuloma of the genitalia are reported. They denied having received any injection of exogenous substances or having suffered from any trauma. We discuss the clinical features and review previously published papers reporting similar cases. We would like to propose that sclerosing lipogranuloma that is not caused by the injection of exogenous substances should be dealt with as a new disease entity.

Adult↗

[Operation of pleural dissemination of thymoma].

Nine patients underwent operation for pleural dissemination of thymoma and received radiotherapy postoperatively. In 5 patients dissemination was resected along with the invasive thymoma at the initial operation. In 6 patients resection of a part of the diaphragm was needed. In 4 patients recurrent dissemination of thymoma appeared in the phrenico-costal sinus, where not only the location of dissemination but also postoperative radiotherapy had not been performed properly at the time of the previous operation. Seven are alive 2 months to 7 years 10 months after the first operation for dissemination. Two died respectively 7 years and 3 years 5 months after the first operation for dissemination.

Adult↗

[Clinical significance of alpha(1----3)-L-fucosyltransferase activities in sera from patients with malignant diseases with a special reference to a potential tumor marker].

We measured alpha(1----3)-L-fucosyltransferase (alpha 13FT) activity in human plasma samples obtained from a group of 111 patients with malignant diseases, 86 patients with benign diseases, and 58 healthy controls using a newly developed assay method (Clin. Chem., 37: 2081-2086, 1991). The cutoff value was arbitrarily set at 73 units/ml (mean +/- 3SD of results for healthy controls). Forty-one of the 111 (36.9) plasma samples from patients with cancer showed high enzyme activity, and twelve of the 86 (13.6%) samples from patients with benign diseases were above the cutoff value. The levels of alpha 13FT were considerably high in samples obtained from the patients with esophagus, lung, liver and pancreatic and biliary cancer, and corresponding positive rates were 66.7, 64.7, 62.5 and 62.5%, respectively. The elevation of the enzyme activity was found in many samples from advanced cancer, whereas samples from patients with gastric and colon cancer in the clinical stage I showed high positive rates. No correlation was observed between the level of alpha 13FT and tumor--associated antigens such as carcinoembryonic antigen, CA19-9, and sialyl Tn (STN). These results suggest that alpha 13FT activity measured by the present assay method could have a potentiality for a new type of tumor marker.

Biomarkers, Tumor↗

[Nonadrenergic noncholinergic inhibitory nervous system in guinea pig airway].

It has been reported that tracheal smooth muscle of guinea pig is innervated by both the adrenergic and nonadrenergic noncholinergic (NANC) inhibitory nervous system. However, NANC inhibitory nerve supply to the lower airway of guinea pig has not yet been demonstrated in in vivo experiments. We performed the present study to evaluate the physiological role of NANC inhibitory nerves in tracheal smooth muscle of guinea pig in vitro, and in anesthetized guinea pigs in vivo. Innervation of NANC inhibitory nerves to tracheal smooth muscle was much greater than that of adrenergic nerves (77.8 +/- 3.8%, 22.2 +/- 3.8%, respectively, p less than 0.01). Neither decrease in RL nor increase in CL, however, was observed with vagal stimulation during serotonin infusion after the administration of propranolol. The role of NANC inhibitory nerves in histamine-induced bronchoconstriction (HIB) was investigated. HIB was enhanced by vagotomy in guinea pig pretreated with propranolol (p less than 0.01). These results suggest the role of the NANC inhibitory nervous system in the attenuation of HIB in vivo in the guinea pig.

Animals↗

[Clinical study of paragangliomas in the thorax].

Four cases of paraganglioma in the thorax, consisted of 3 cases originating from the mediastinum and a case of pulmonary metastasis from the posterior peritoneum, were clinically investigated. Three were malignant and one was benign with noradrenaline secretion. On surgical excision, preoperative arterial embolization was assumed to be useful for reducing hemorrhage during procedure. Pre and intra-operative circulatory management was also mandatory in case of functioning paraganglioma. Of the 3 malignant cases, 2 survived for more than 10 years with radiotherapy alone or surgical resection of multiple metastatic nodules in the bilateral lungs. The other one, though inoperable due to extensive invasion to right and left atria, showed highly sensitivity to intra-arterial infusion chemotherapy of CDDP. These results suggested that long term survival might be expected even in metastatic or inoperable cases. There were no reliable histologic features distinguishing malignant from benign tumors, however 2 malignant cases with local invasion showed aneuploid patterns in the DNA histograms, which might offer a adjunct possibility in the assessment of malignancy.

Adult↗

Purification of rat megakaryocyte colony-forming cells using a monoclonal antibody against rat platelet glycoprotein IIb/IIIa.

We recently reported the production and characterization of four monoclonal antibodies (MoAbs) against rat platelet glycoprotein IIb/IIIa (GPIIb/IIIa). In this study we developed a simple and efficient three-step procedure, based on positive selection by immunoadsorption (panning) using one MoAb, P55, to purify rat megakaryocyte colony-forming cells (megakaryocyte colony-forming units, CFU-MK) from normal bone marrow. Cells obtained after each step were assayed for their ability to form megakaryocyte colonies in the presence of Concanavalin A (Con A)-stimulated rat spleen cell-conditioned medium in soft agar cultures. Marrow cells were first separated on discontinuous Percoll gradients. Cells sedimented at densities between 1.063 and 1.082 g/ml were depleted of cells adherent to plastic tissue culture dishes. The nonadherent cells were further incubated on dishes coated with P55 MoAb. CFU-MK were enriched about 50-fold in the adsorbed cell fraction. This sequential fractionation procedure resulted in a 345-fold (range 276 to 412-fold) enrichment of rat CFU-MK over whole bone marrow cells. The average cloning efficiency of CFU-MK in the final fraction was about 7% (range 5%-9.2%) of the nucleated cells. The overall recovery of CFU-MK averaged 20% (range 9%-29%). The panning step provided a 46-fold enrichment of megakaryocyte burst-forming cells (megakaryocyte burst-forming units, BFU-MK), whose average cloning efficiency in the post-panning fraction was 0.14% (range 0.07%-0.2%). In addition, erythroid burst-forming cells (erythroid burst-forming units, BFU-E) were also significantly enriched by panning, but to a lesser degree than BFU-MK and CFU-MK. By contrast, granulocyte-macrophage colony-forming cells (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid colony-forming cells (erythroid colony-forming units, CFU-E) were not enriched by panning. CFU-MK obtained after panning formed megakaryocyte colonies in the presence of recombinant rat interleukin 3 (rIL-3), mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF), or human erythropoietin (hEPO), as has been reported for murine CFU-MK in whole marrow cells. The highly enriched populations of rat CFU-MK should thus provide a basis for the further study of the regulation of megakaryocytopoiesis.

Animals↗

Deletion of kringle domains or the N-terminal hairpin structure in hepatocyte growth factor results in marked decreases in related biological activities.

To determine the essential domain for biological activity in the hepatocyte growth factor (HGF) molecule, we prepared various mutated recombinant HGFs using site-directed mutagenesis, and examined the effects on DNA synthesis in hepatocytes, scattering of MDCK cells and the antiproliferative activity on HepG2 hepatoma cells. Native HGF and mutant HGFs, in which Gln534 and/or Tyr673 were respectively substituted for His and Ser to coincide with the catalytic triad amino acids in plasmin, markedly stimulated DNA synthesis of hepatocytes and scattering of MDCK cells but inhibited DNA synthesis of HepG2 cells. The mutant HGF deleted with the third or fourth kringle domain resulted in marked decrease of all three biological activities, while deletion of the N-terminal hairpin structure or the first or second kringle domain almost completely inactivated biological activities. We propose that the N-terminal hairpin structure and the first and second kringle domains are essential for biological activities of HGF and possibly for binding to its receptor.

Animals↗

Non-essentiality of cysteine and histidine residues for the activity of human class PI glutathione S-transferase.

In order to examine the roles of cysteine and histidine residues in the activity of human class Pi glutathione S-transferase (GST pi), site-directed mutagenesis was used to replace each of the four cysteine residues (at positions 14, 47, 101 and 169) with serine and each of the two histidine residues (at positions 71 and 162) with asparagine using a cDNA for the enzyme (Kano, T. et al. (1987) Cancer Res., 47, 5626-5630) and an E. coli expression system. The replacements of Cys101, Cys169, His71 and His162 did not affect the GSH-conjugating activity toward 1-chloro-2,4-dinitrobenzene and ethacrynic acid. On the other hand, the activities were partly decreased by the replacements of Cys47 and Cys14. These results indicated that the cysteine and histidine residues in GST pi are not essential for the catalytic activity, although Cys47 and Cys14 may contribute to some extent to the catalytic efficiency.

Base Sequence↗

How does RNase H recognize a DNA.RNA hybrid?

The mechanism of RNase H substrate recognition is proposed from a model of a chemically modified DNA.RNA hybrid Escherichia coli RNase H complex. Site-directed mutagenesis of the enzyme and substrate titration observed by heteronuclear two-dimensional NMR spectra have been carried out. A model complex has been built, based on free structures of the enzyme and the substrate independently determined by x-ray crystallography and NMR distance geometry, respectively. In addition to steric and electrostatic complementarities between the molecular surfaces of the enzyme and the minor groove of the hybrid in the model, putative hydrogen bonds between the polar groups in the enzyme and 2'-oxygens of the RNA strand of the hybrid fix the hybrid close to the active site of the enzyme. The enzymatic activities of the mutant proteins and the changes in NMR spectra during the course of substrate titration are consistent with the present model. Moreover, the specific cleavage of the RNA strand in DNA.RNA hybrids can be explained as well as cleavage modes in modified heteroduplexes. A mechanism of enzymatic action is proposed.

Amino Acid Sequence↗

The nucleotide and deduced amino acid sequences of porcine liver proline- beta-naphthylamidase. Evidence for the identity with carboxylesterase.

A cDNA clone for porcine liver proline-beta-naphthylamidase was isolated and sequenced. The deduced amino acid sequence of 567 residues was highly homologous with those of carboxylesterases (EC 3.1.1.1) previously reported for other species. In addition, proline-beta-naphthylamidase purified from porcine liver was shown to have strong activity towards p-nitrophenylacetate, a representative substrate for carboxylesterases. These results suggest that proline-beta-naphthylamidase is identical with carboxylesterase.

Amino Acid Sequence↗