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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 91 records · Page 5Linked to original sources

[The importance of pain control with morphine for terminally ill patient care for at home].

From April 1987 to June 1994, 81 patients of terminally ill had been care at home. In these home care, 38 patients received pain control with morphine. In 29 patients, pain control had been started before home care but in 9 patients pain control had been started under home care. Routes of morphine administration were oral in 24 cases and rectal in 14 cases. In cases of oral routes, finally 2 cases converted to rectal routes and 2 cases converted to subcutaneous routes. Duration of treatment were from 2 days to 741 days (average 72 days). Dosage of morphine were 7.5 mg to 480 mg (average 116 mg). Two patients lived but 24 patients died at home and 12 patients died at hospital. We concluded that palliative care especially pain control with morphine was very important care for patients of terminally ill who wanted care at home and ultimately die at home. We had to make ourself master of method pain control with morphine.

Administration, Oral

Effect of reconstituted basement membrane on growth and secretory function in pancreatic acinar AR42J cells.

This study investigated the influence of extracellular matrix on growth and secretory function associated with cholecystokinin (CCK) receptors in pancreatic acinar AR42J cells, using reconstituted basement membrane derived from Engelbreth-Holm-Swarm (EHS) tumor. The cells were cultured with basement membranes of two different thickness, 1 mg/ml protein equivalent (thick RBM) and 50 micrograms/ml protein equivalent (thin RBM). In cells cultured with thin RBM, the secretory function and the number of CCK receptors increased, but cell growth did not increase significantly. Cells cultured with thick RBM showed remarkable cell growth, but secretory function and the number of CCK receptors were reduced. There was little change in CCK receptor affinity. It was concluded that the extracellular matrix plays a crucial role in the proliferation and differentiation of AR42J cells and further, the quantitative difference of matrix components strongly influenced the up- and down-regulation of CCK receptor in the cells via cell-matrix interaction.

Amylases

Pure yolk-sac tumor of the lung.

The first case of a pure primary yolk-sac tumor of the lung is presented. The tumor developed in the right upper lobe of a 31-year-old man; preoperatively, the serum alpha-fetoprotein concentration was elevated. Treatment consisted of pulmonary segmentectomy with postoperative combination chemotherapy. The patient is alive and well 13 months after surgery with a normal serum alpha-fetoprotein concentration.

Adult

Antifibrillatory effects of class III antiarrhythmic drugs: comparative study with flecainide.

The antifibrillatory effects of flecainide 1 mg/kg + 0.05 mg/kg/min intravenously (i.v.), bretylium 6 mg/kg i.v., D-sotalol 2 mg/kg + 0.1 mg/kg/min i.v., and E-4031, a new class III drug, 50 micrograms/kg + 5 micrograms/kg/min i.v. were compared with three different methods of determining ventricular fibrillation threshold (VFT) in anesthetized open-chest dogs. In protocol 1, VFT was determined with 2-S, 50-Hz continuous pulses. Flecainide (n = 7) prolonged intraventricular conduction time (CT) and ventricular effective refractory period (ERP) and increased VFT significantly. Bretylium (n = 6) prolonged ERP slightly, but did not increase VFT significantly. Both D-sotalol (n = 6) and E-4031 (n = 6) prolonged ERP and increased VFT. In protocol 2, VFT was determined with the extrastimulus technique in dogs, with localized ventricular necrosis produced with protease. Flecainide (n = 10), D-sotalol (n = 8), and E-4031 (n = 8) restored VFT, which had been decreased by protease injection, to the baseline level, whereas bretylium (n = 8) did not. In protocol 3, the train pulse method with 100-Hz train pulses covering the vulnerable period was used in the same dogs used for protocol 2. Flecainide, bretylium, and D-sotalol increased VFT, but E-4031 did not. The antifibrillatory effects of class III drugs differ depending on the method of VFT determination. The present data suggest that the antifibrillatory effects of antiarrhythmic drugs should be assessed by different methods of VFT determination.

Analysis of Variance

Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.

1. We have investigated the mechanism of capsaicin-induced mouse ear oedema compared with that of arachidonic acid (AA)-induced ear oedema, and evaluated the possible involvement of neuropeptides in the development of capsaicin-induced oedema. 2. Topical application of capsaicin (0.1-1.0 mg per ear) to the ear of mice produced immediate vasodilatation and erythema followed by the development of oedema which was maximal at 30 min after the treatment. This oedema was of shorter duration with less swelling than AA-induced oedema (2.0 mg per ear). 3. Capsaicin-induced ear oedema was unaffected when inhibitors of arachidonate metabolites including platelet activating factor (PAF) were administered before capsaicin (250 micrograms per ear) application, while these agents significantly prevented AA-induced oedema. Dexamethasone, histamine H1 and/or 5-hydroxytryptamine (5-HT) antagonists, and substance P (SP) antagonists were effective in inhibiting both models. Furthermore, a Ca(2+)-channel blocker and the capsaicin inhibitor, ruthenium red, were effective inhibitors of capsaicin oedema but had no effect on AA-induced oedema. 4. Phosphoramidon (50 micrograms kg-1, i.v.), an endopeptidase inhibitor, markedly (P < 0.001) enhanced only capsaicin-induced ear oedema, but bestatin (0.5 mg kg-1, i.v.), an aminopeptidase, failed to enhance oedema formation. 5. Neuropeptides (1-100 pmol per site) such as rat calcitonin gene-related peptide (CGRP), SP, neurokinin A (NKA), and vasoactive intestinal peptide (VIP), which are released from capsaicin-sensitive neurones, caused ear oedema by intradermal injection. Furthermore, a synergistic effect of CGRP (10 fmol per site) and SP (10 pmol per site) on oedema formation was observed. 6. The oedema induced by neuropeptides was significantly (P<0.05 or P<0.001) inhibited when cyproheptadine (20 mg kg-1, p.o.), a histamine H, and 5-HT antagonist, was administered before injection. In contrast, nifedipine (50 mg kg-1, p.o.), a Ca2+-channel blocker, and indomethacin(10 mg kg-1, p.o., except for NKA), a cyclo-oxygenase inhibitor, had little effect on neuropeptide induced oedema.7. These results suggest that the mechanism of capsaicin-induced ear oedema is different from that of AA-induced oedema and suggest that the development of capsaicin-induced ear oedema is primarily mediated by neuropeptides. The neuropeptides released after activation of sensory nerves cause an increase of vascular permeability by interactions with endothelial cells and by histamine (and 5-HT)release from mast cells.

Administration, Cutaneous

Neuropeptide Y inhibits neurogenic inflammation in guinea pig airways.

We examined the effect of neuropeptide Y (NPY) on neurogenic airway microvascular leakage. Male Dunkin-Hartley guinea pigs (250-350 g) were anesthetized with urethan (2 g/kg ip). The cervical artery and vein were cannulated for monitoring blood pressure and injecting drugs, respectively. Atropine and propranolol (each 1 mg/kg i.v.) were administered 30 min before the experiment. After pretreatment with saline (vehicle for NPY) or NPY (1-100 micrograms/kg i.v.), Evans blue dye (30 mg/kg iv) was administered. Then, bilateral vagal nerves were electrically stimulated (5 V, 7 Hz, 5-ms duration for 3 min) to induce airway plasma leakage. Airways were divided into four sections [trachea (Tr), main bronchi, central intrapulmonary airways (IPA), and peripheral IPA] and incubated in formamide (37 degrees C for 16 h). The concentration of Evans blue dye was measured by spectrophotometer. Furthermore, we examined the effect of NPY on exogenous substance P- (0.3 microgram/kg i.v.) induced plasma extravasation. Bilateral vagal stimulation significantly increased leakage of dye in Tr to peripheral IPA. NPY did not affect basal leakage but did significantly inhibit neurogenic plasma extravasation in a dose-dependent manner with maximal inhibitions of 42.3 (Tr), 67.7 (main bronchi), 38.2 (central IPA), and 26.3% (peripheral IPA) at 30 micrograms/kg. Exogenous substance P-induced plasma extravasation was not inhibited by NPY. We conclude that NPY inhibits neurogenic inflammation by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals.

Adrenergic beta-Antagonists

[Anti-Hp antibody may vary with strain used as antigen possibly due to serological diversity].

Western blotting and ELISA techniques have been used to investigate antigen specificity of systemic responses. Immunoblotting studies demonstrate several major protein antigens that are detected most sera. H. pylori immunoblotting studies using rabbit hyperimmune sera identify several distinct strains. Seven monoclonal antibodies which are prepared in our laboratory recognize 33-35 kDa and 66 kDa of H. pylori. ELISA studies using the monoclonal antibody reveals considerable antigenic diversity among H. pylori strains. Serotyping of clinically isolated H. pylori Seems to be useful in clarifying the etiological roles of this bacteria. In spite of studies by several investigators, serotyping of H. pylori has not been established yet. Our studies suggest that H. pylori need to be further subdivided serologically.

Animals

Invasive human T lymphoma cells produce a novel factor that upregulates expression of adhesion molecules on endothelial cells.

The interaction between lymphoma cells and vascular endothelial cells (EC) is the first critical step in the invasion of lymphoma cells. We found that invasive human CCRF-CEM T lymphoma cells (CEM) released a factor that upregulates the expression of adhesion molecules on vascular EC. The supernatant of CEM (CEM-SUP) increased the expression of both ICAM-1 and ELAM-1 in time- and dose-dependent manners as shown by cell enzyme-linked immunoabsorbent assay (ELISA). In contrast, the induction of VCAM-1 on EC with CEM-SUP was relatively weak. No activity for interleukin-1 alpha (IL-1 alpha), IL-1 beta, interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha), which are known to augment ICAM-1 expression, was detected in CEM-SUP by ELISA. In reverse transcriptase polymerase chain reaction (RT-PCR) assay, CEM expressed a minimum amount of TNF-alpha mRNA, but absolutely no IL-1 beta or IFN-gamma mRNA. In addition, antibodies for cytokines did not inhibit the upregulatory effect of CEM-SUP. Semipurified CEM-SUP further increased the cellular binding between CEM cells and EC in vitro. This factor was stable to heat (65 degrees C, 30 minutes) and labile to acid (pH 2.0). Gel filtration and chromatofocusing estimated its molecular weight at 50 kd, with an isoelectric point of pH 7.2. Production of this factor might contribute to the invasive character of CEM through upregulation of adhesion molecules on EC.

Base Sequence

[Anticancer and side effect of arterial subsegmental chemoembolization using cisplatinum/pirarubicin lipiodol suspension (CTLS) for hepatocellular carcinoma].

Twenty patients with unresectable hepatocellular carcinoma were treated by intra-arterial subsegmental injection of Cisplatin/4-0-Tetrahydro-Pyranyl-adriamycin Lipiodol suspension (CTLS). The mean single doses of Lipiodol, cisplatin and THP were 2.3 ml, 85 mg and 8.9 mg, respectively. The therapy was given once in 10 patients, twice in 8 and 3 times in two. Over 25% reduction in tumor size was recognized in 12 patients (60%). Fifty or more % decrease of alfa-feto-protein (AFP) was observed in all of 7 patients (100%) with the initial serum AFP level of more than 200 ng/ml. Although transitional and mild symptoms, such as fever, abdominal pain and vomiting were recognized in some cases, no severe complications were encountered. This method is promising as an excellent procedure for unresectable hepatocellular carcinoma.

Aged

Hepatocyte growth factor is linked by O-glycosylated oligosaccharide on the alpha chain.

The glycosylation site and the structure of O-glycosylated oligosaccharide of recombinant human HGF were investigated. N-acetylgalactosamine (GalNAc) in the alpha chain suggested the presence of O-glycosylated oligosaccharide. Sugar analysis and amino acid sequence analysis of peptide fragments produced by limited degradation revealed that O-glycosylated oligosaccharide linked to Thr445 of the alpha chain. The molecular weight of the oligosaccharide was determined with ion spray mass spectrometry. From these studies, the structure of the O-glycosylated oligosaccharide on the alpha chain of HGF was concluded as [formula: see text].

Amino Acid Sequence

Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist.

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.

Administration, Inhalation

Putrescine-dependent invasive capacity of rat ascites hepatoma cells.

The effects of inhibitors of polyamine synthesis on the invasive capacity of rat ascites hepatoma (LC-AH) cells were examined by in vitro assay of penetration of the LC-AH cells through a monolayer of calf pulmonary arterial endothelial (CPAE) cells. Pretreatment of LC-AH cells with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, before seeding them onto a CPAE cell monolayer and culturing them for 24 h in the absence of DFMO decreased the number of penetrating tumor cells time and dose dependently (about 35% of the maximal inhibition) without affecting their viability or proliferative activity. DFMO treatment caused a marked decrease in the intracellular level of putrescine but not of spermidine or spermine. The DFMO-induced decreases in invasive capacity and putrescine level were almost completely reversed by the addition of putrescine to the medium during pretreatment with DFMO or invasion assay but were not affected by exogenous spermidine or spermine. No change in the invasive capacity was observed when the CPAE cells were treated with DFMO and the LC-AH cells with methylglyoxal-bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, which depressed the spermidine and spermine levels but increased the putrescine level in the LC-AH cells. These results suggest that intracellular putrescine modulates the in vitro invasive capacity of LC-AH cells.

Animals

[MR imaging during arterio-portography (MR-AP) in the detection of hepatic cancer].

Magnetic resonance imaging during arterio-portography (MR-AP) was performed in 2 patients of hepatic cancer. Low dose of meglumine gadopentetate (4 ml of a 0.5 mmol/L solution) was injected into a superior mesenteric artery during acquisition of a Turbo-FLASH sequence. An increase in liver to lesion contrast was obtained with MR-AP and it is also useful in the late phase to distinguish a flow defect lesion due to portal obstruction from the tumor.

Gadolinium DTPA

Induction of uterine cervical neoplasias in mice by human papillomavirus type 16 E6/E7 genes.

We constructed a recombinant retrovirus containing the E6/E7 genes of human papillomavirus (HPV) 16 (ZE67) and examined the morphological changes in the cervicovaginal epithelium induced by inoculation of this virus into the vagina of mice. The ZNeo virus without HPV genes was used as a negative control. Moreover, cotreatment with phorbo-13-myristate-12-acetate or N-methyl-N'-nitro-N-nitrosoguanidine and these viruses was carried out. At the end of the observation period (9 months for CD-1 nu/nu and 15 months for C57BL/6J), of 31 CD-1 nude mice treated with ZE67, 7 and 19 had low-grade and high-grade dysplasia, respectively, while 5 of 22 mice treated with ZNeo had low-grade dysplasia (rank sum test, P less than 0.001). Similarly, 4 and 3 of 8 C57BL mice treated with ZE67 had low-grade and high-grade dysplasias, respectively, whereas 3 of the 8 control mice had low-grade dysplasias (P = 0.049). ZE67 plus phorbol-13-myristate-12-acetate and ZE67 plus N-methyl-N'-nitro-N-nitrosoguanidine cotreatments induced cervical cancers in 2 of 13 CD-1 nude mice and 6 of 15 C57BL mice, respectively. On the contrary, none of 6 CD-1 and 2 of 10 C57BL mice had cancer in the control groups (P = 0.0142 for phorbol-13-myristate-12-acetate treatment; P = 0.0173 for N-methyl-N'-nitro-N-nitrosoguanidine treatment). In addition, the existence and expression of HPV 16 E6/E7 genes were detected in the lesions induced by ZE67 but not in the lesions of the control mice by analysis by polymerase chain reaction and mRNA in situ hybridization. The present results suggest that HPV 16 E6/E7 genes induce dysplastic changes but require additional promoting or mutagenic stimulation for the development of cancer.

Animals

Photoaffinity labeling of T4 endonuclease V with a substrate containing a phenyldiazirine derivative.

T4 endonuclease V recognizes thymine photodimers in DNA duplexes and, in a two-step reaction, cleaves the glycosyl linkage of the 5'-side thymidine and the phosphodiester linkage. To determine the amino acid residues responsible for binding thymine photodimers, a photoaffinity reagent, 4-(1-azi-2,2,2-trifluoroethyl)-benzoate, was linked to the aminoalkylphosphonate of a thymine photodimer in a 14-mer duplex. The reactive substrate was treated with the enzyme under UV light (365 nm). The nascent enzyme and the modified enzyme were treated with lysyl endopeptidase, and the peptide maps were compared. Three peptides from the C terminus were found to interact with the reactive oligonucleotide to various extents. The three modified peptides were isolated and analyzed by Edman degradation. The amino acid residues Gly-133, Tyr-129, and Thr-89 were partially linked with the reactive substrate and may be involved in the binding of thymine photodimers.

Affinity Labels

Partial purification and characterization of membrane-associated diacylglycerol kinase of Drosophila heads.

A membrane-associated diacylglycerol kinase of Drosophila heads was purified to near homogeneity from the KCl extract of Drosophila heads. The purification procedure involved chromatography on Q-Sepharose, ammonium sulfate fractionation, Superose 12, hydroxyapatite and ATP-agarose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of fractions after the ATP-agarose column chromatography showed that only a 115 kDa protein correlated well with the enzyme activity. The apparent Km values of partially purified DG kinase were 220 microM for ATP and 540 microM for diolein, respectively. The activity of the DG kinase was inhibited by deoxycholate and was not activated by Ca2+.

Animals

[Complications of arterial infusion of CDDP in the treatment of malignant neoplasms].

Arterial infusion of cis-diamminedichloroplatinum (CDDP) is an effective therapy for malignant neoplasms. Severe complications after this therapy in 298 patients with malignant tumors were reviewed in our institute from March 1982 to August 1989. Arteries infused with CDDP and the number of infusions were as follows: bronchial artery (a.) 277, hepatic a. 153, internal iliac a. 51, femoral or popliteal a. 15, lumbar a. 6, pulmonary a. 5, esophageal a. 3 and intercostal a. 3. Eight cases of severe complications were encountered: 3 of esophageal ulcer, 3 of spinal paralysis, and one each of mediastinitis and toe necrosis. The arteries responsible for complications were the bronchial a. in 3 cases of esophageal ulcer and 2 of spinal paralysis, intercostal a. in one of spinal paralysis, esophageal a. in one of mediastinitis and popliteal a. in toe necrosis. Complication rates were 2.7% (8/298 cases) and 1.5% (8/518 infusions). Angiotensin II was infused in 6 of 8 of the cases with complications. The complication rate was 2.9% (6/209 infusions) in the group with CDDP and angiotensin II and 0.6% (2/309 infusions) in the group with CDDP only. Arterial infusion of CDDP, especially combined with angiotensin II, should be done in consideration of the arteries responsible for such complications.

Adenocarcinoma

An immunomodulatory protein, Ling Zhi-8, facilitates cellular interaction through modulation of adhesion molecules.

Ling Zhi-8 (LZ-8), a novel immunomodulatory protein, markedly enhanced the expression of CD11b, but not CD11a, CD13, CD14, CD18, CD33 or HLA-DR, on the U937 cell line in a dose-dependent fashion. It also induced ICAM-1 expression on vascular endothelial cells and significantly augmented gamma - interferon-induced cellular binding between vascular endothelial cells and U937. Furthermore, LZ-8 increased the expression of CD2, but not VLA4, VLA5 or LFA3, on MOLT4 and enhanced rosette formation between human T cells and sheep red blood cells. These data suggest that LZ-8 exerts its pharmacological effect by modulating adhesion molecules on immunocompetent cells.

Adjuvants, Immunologic