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Biomedical subjects

K Konno

Publications and source records attributed to K Konno.

At least 271 records · Page 15Linked to original sources

Inhibition of influenza virus infection by pine cone antitumor substances.

The anti-influenza virus activity of polysaccharides and other high molecular weight fractions from pine cone extract (PCE) of Pinus parviflora Sieb. et Zucc. was investigated. None of the fractions affected the growth of MDCK cells. The acidic PCE substances markedly suppressed the growth of the influenza virus in MDCK cells. Significant inhibition of both the viral protein synthesis in infected cells and virion-associated RNA-dependent RNA polymerase activity was observed with these acidic fractions. Although amantadine inhibited virus plaque formation as effectively as PCE fractions, it was less effective in inhibiting the RNA polymerase activity. These results suggest that PCE, which has been shown to contain antitumor substance(s), also contains anti-influenza virus substance(s).

Amantadine↗

Structural stability of fish myosin subfragment-1.

1. Tryptic cleavage of fish myosin subfragment-1 (S-1) revealed its similar substructure of heavy chain to that of rabbit S-1. 2. The structural stability of fish S-1 was studied by thermal denaturation method, and a rapid polymerization of inactivated fish S-1, detected by turbidity increase, was characteristic. 3. The light-chain release and tryptic susceptibility increase upon heating were significant with fish S-1.

Animals↗

Modification of human immunodeficiency viral replication by pine cone extracts.

We have shown previously that two fractions (PC6 and PC7) extracted from cones of the Japanese white pine Pinus parvifloria Sieb. et Zucc have potent immunopotentiating effects. Here, we show that PC6 and PC7 inhibited HIV-1 replication (greater than 95%), in a dose-dependent manner, in chronically infected CR10/HIV-1 cells and in acute cytolytic HIV-1 infection of CEM cells. Treatment of CEM cells, prior to or after acute infection with HIV-1, reduced subsequent viral production, but the best inhibitory effect was obtained with treatment before and after infection: an 80% inhibition was achieved with as little as 3 micrograms/ml of PC6. Comparable results were also obtained when PC6 was used to inhibit HIV-1 replication in the U937 human histiocytic lymphoma cell line. Both PC6 and PC7 were relatively nontoxic to cells. The anti-HIV-1 effect of PC6 and PC7 we observed in this report, coupled with earlier reports of their immunopotentiating properties suggest their potential as ideal therapeutic agents for the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗

Enhancement of interferon-gamma-induced differentiation of human monoblastic leukemia U-937 cells by cAMP-inducing agents.

The effects of combinations of interferons (IFNs) and cAMP-inducing agents on the induction of differentiation of human monocytic leukemia U-937 cells were examined. IFN-gamma induced nitro blue tetrazolium (NBT) reducing activity of U-937 cells in a dose-dependent manner, while cAMP-inducing agents such as cholera toxin, prostaglandin E1, forskolin, and isoproterenol only marginally induced NBT reducing activity. However, they all synergistically increased IFN-gamma induction of NBT reducing activity. Cholera toxin was the most potent of the cAMP-inducing agents. Combination effects of IFN-gamma and cholera toxin on other differentiation-associated markers of alpha-naphthyl acetate esterase activity, morphological maturation, Fc receptors, and surface phenotype were also observed. IFN-alpha and -beta, either alone or in combination with cAMP-inducing agents, did not induce NBT reducing activity. IFN-gamma and cholera toxin also synergistically induced differentiation-associated markers in another human monocytic leukemia cell line, THP-1, and a human myeloblastic leukemia cell line, ML-1. These results suggest that cAMP/A-kinase may be an important but insufficient signal for the maturation process of myelogenous leukemia cells.

Alprostadil↗

Biochemical and immunological studies on two distinct ganglioside-hydrolyzing sialidases from the particulate fraction of rat brain.

Ganglioside-hydrolyzing sialidase activity was solubilized from rat brain particulate fraction by using Triton X-100 plus sodium deoxycholate. When chromatographed on AH-Sepharose 4B, the solubilized activity was resolved into two peaks, which were designated sialidases I and II in order of elution. The two sialidases were purified by using sequential chromatographies on Octyl-Sepharose CL-4B, Phenyl-Sepharose CL-4B, and Sephadex G-200. Sialidase II was purified further by Mono Q-FPLC. Overall purification was 450- and 2,150-fold, for sialidases I and II, respectively. Purified sialidases I and II were maximally active at near pH 5.0 and exhibited M = 70,000 by gel filtration. Sialidase I hydrolyzed gangliosides but scarcely other substrates including 4-methylumbelliferyl-NeuAc (4MU-NeuAc). Sialidase II hydrolyzed oligosaccharides, glycoproteins, and 4MU-NeuAc although gangliosides appeared to be preferential substrates. Sialidase II cleaved GM2 much faster than sialidase I. An antibody raised in rabbits against sialidase I reacted with only sialidase I and an antibody against sialidase II reacted with only sialidase II. A subcellular distribution study suggested sialidase I in the synaptosomal membrane and sialidase II in the synaptosomal and lysosomal membranes, and this was verified by using the above antibodies.

Animals↗

Immunological discrimination of intralysosomal, cytosolic, and two membrane sialidases present in rat tissues.

Cytosolic sialidase was purified from rat skeletal muscle, and the purified enzyme migrated as a single band of Mr 43,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A polyclonal antibody raised against the enzyme inhibited and immunoprecipitated rat liver cytosolic sialidase as well as the muscle enzyme but failed to cross-react with the intralysosomal sialidase of rat liver and membrane sialidases I (synaptosomal) and II (lysosomal) of rat brain. The antibody against brain membrane sialidase I (anti-I) and that against sialidase II (anti-II), which could be useful to discriminate the two enzymes, did not cross-react with the intralysosomal and cytosolic sialidases of liver. Although more than 90% of liver plasma membrane sialidase was immunoprecipitated with anti-I, only 60% of liver lysosomal membrane sialidase was immunoprecipitated with anti-II, the remainder being immunoprecipitated with anti-I. In confirmation of these data, liver lysosomal membrane exhibited two peaks of ganglioside sialidase corresponding to the membrane sialidases I and II on Aminohexyl-Sepharose chromatography while only one peak of ganglioside sialidase corresponding to sialidase I was observed for liver plasma membrane. These results indicate that the four types of rat sialidase are proteins distinct from one another and that the three kinds of antisera described above are useful for discriminating these sialidases qualitatively and probably quantitatively.

Animals↗

Combination effects of interferon-gamma and cholera toxin on induction of differentiation of an insensitive U-937 clone.

We examined the combination effect of interferon-gamma (IFN-gamma) and cholera toxin and the role of cAMP in the induction of differentiation of a differentiation-insensitive U-937 clone, in which the reactivity to differentiation-inducers was decreased. IFN-gamma (100 units/ml) or cholera toxin (10(-9) M) alone only marginally induced various differentiation-associated characteristics such as NBT-reducing activity, phagocytic activity, a-naphthyl acetate esterase activity and surface markers. However, when combined with each other, they significantly induced these markers. Other cAMP-inducing agents such as prostaglandin E2, forskolin, epinephrine and isoproterenol did not induce NBT-reducing activity, either alone or in combination with IFN-gamma. However, all these cAMP-inducing agents significantly increased intracellular cAMP levels. Tumor necrosis factor, interleukin 6 or granulocyte/macrophage colony-stimulating factor alone did not induce NBT-reducing activity, but they could induce activity when combined with cholera toxin. These results suggest that enhancement of induction of differentiation by cholera toxin in combination with IFN-gamma or other cytokines may not be merely due to increased cAMP levels. There seems to be a transduction signal other than cAMP coupling with cholera toxin to stimulate induction of differentiation of an insensitive U-937 clone.

Cell Differentiation↗

Neoplastic alteration of a membrane-associated sialidase of rat liver.

Rat liver particulate fraction contains two types of membrane-associated and gangliosides-hydrolyzing sialidase, which have been shown to be identical to two membrane-associated sialidases of rat brain (I and II) chromatographically, immunologically and in substrate specificity. Chromatography on AH-Sepharose 4B of the membrane sialidases of rat primary hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (MeDAB) further revealed that hepatocarcinogenesis induces a marked decrease in sialidase II but no decrease in sialidase I. Using antisera against sialidases I and II of rat brain, immunoprecipitation studies of the solubilized particulate fractions of rat liver and MeDAB-hepatoma gave results similar to those obtained chromatographically. Using the same immunological technique, sialidase II but not sialidase I was found to be decreased in AH109 A hepatoma and in regenerating and fetal liver.

Animals↗

Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro.

Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibitory effects on the synthesis of DHBV core antigen in primary duck hepatocytes. (S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine, 2',3'-dideoxyadenosine, and 2',3'-dideoxycytidine inhibited DHBV core antigen synthesis at concentrations that were significantly lower than those found to be toxic to the primary hepatocytes. Of all the compounds tested, (S)-HPMPA showed the lowest 50% effective concentration (0.5 micrograms/ml). The selectivity index or ratio of the 50% cytotoxic concentration to the 50% effective concentration of (S)-HPMPA was greater than 300. (S)-HPMPA not only inhibited DHBV core antigen but also DHBV DNA synthesis in DHBV-infected hepatocytes.

Animals↗

Does a beta 2-stimulator really facilitate mucociliary transport in the human lungs in vivo? A study with procaterol.

The purpose was to study whether procaterol, a beta 2-stimulator, facilitated mucociliary transport on the ciliated airways in the human lungs. From immediately after inhalation of [99mTc]albumin aerosol, radioactivity of the thorax was continuously measured anteriorly by a gamma camera with the examinee in the supine position; the data were sequentially stored in a computer in 10-s frame mode. Three puffs (30 micrograms) of procaterol were inhaled from a metered dose inhaler at 60 min in the same supine position, and measurement of radioactivity was continued for 30 min more. Spirometry was performed before and after the measurement of radioactivity. A group of 8 normal subjects and 34 patients with various lung diseases, including 6 with bronchial asthma in remission, were studied. In addition to observation of mucus transport on the large airways by radioaerosol inhalation lung cinescintigraphy, the time-activity curve from the right lung was evaluated and the quantitative parameters for evaluating mucociliary clearance were calculated for the right lung. Following inhalation of procaterol, there were neither significant acceleration in mucus transport on the large airways by cinescintigraphy nor significant changes in the slope of time-activity curves. Quantitative parameters did not show any significant changes either, although spirometry indicated significant bronchodilation. We conclude that three puffs of inhaled procaterol neither necessarily accelerate mucus transport nor facilitate mucociliary clearance in the human lung.

Administration, Inhalation↗

Development and clinical application of a portable oxygen concentrator.

We have produced a compact, lightweight oxygen concentrator, using a newly-developed polymer of poly [1-(trimethylsilyl)-1-propyne] with a performance, i.e. oxygen permeability, of 61 x 10 cm3 (STP) cm/cm2 s cmHg, which is 17 times higher than that of the membrane material of conventional concentrators. The oxygen and nitrogen selectivity was 1.80. The dimensions of the apparatus are 325 x 180 x 150 mm and it weighs about 4.0 kg. It is actuated by a battery (DC 12 V, 5.6 Ah), with a 100 V AC source and a car battery (12 V) source also available. The power consumption is 70 W. The generated oxygen concentration is about 30%, and the maximum flow rate is 41/min. Applying 10 samples of various chronic pulmonary diseases to the subject, the suction of oxygen from the apparatus in the patients' rest state was conducted. An increase in the PaO2, from an average of 59.1 Torr before the suction to an average of 68.5 Torr after the suction, together with easing of breathing, was indicated. The usefulness of this apparatus for supplying portable oxygen-treatment to patients with chronic respiratory disease is shown.

Berylliosis↗

Phosphonylmethoxyalkyl derivatives of purine as inhibitors of human hepatitis B virus DNA synthesis.

A selected number of antiviral compounds which have been previously shown to inhibit the replication of DNA viruses or retroviruses were examined for their inhibitory effects on human hepatitis B virus (HBV) DNA synthesis. The assay system was based on the use of a human hepatoblastoma cell line (HB611) that continuously synthesizes HBV DNA. The following phosphonylmethoxyalkyl-purine derivatives were found to inhibit HBV DNA synthesis: 9-(2-phosphonyl-methoxyethyl)-2',6'-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA). PMEDAP, HPMPA and PMEA not only inhibit HBV DNA synthesis in HB611 cells but also duck hepatitis B virus (DHBV) DNA and core antigen synthesis in primary duck hepatocytes.

Adenine↗

[Case report and literature analysis of the clinical factors relating to the development of fibrotic changes in gold lung].

A 26-year-old female with gold lung induced by Shiosol (gold thiomalate) administered for her rheumatoid arthritis is presented. Chest X-ray films after treatment with prednisolone hardly improved and showed diffuse fibrotic shadow. We reviewed previously reported cases of gold lung and tried to determine the clinical factors which might affect the development of pulmonary fibrotic changes in gold lung. The cases reported in Japan were classified into two groups according to the improvement of X-ray films after steroid therapy: group A in which the chest X-ray film returned to almost normal, group B these with diffuse fibrotic shadow. No significant difference was observed in the values of %VC and PaO2 admission between the two groups. The total dose of gold received was greater (p less than 0.05) and the duration of gold received was longer (p less than 0.01) in group B than in group A. These findings suggest that the development of pulmonary fibrosis does not depend on the severity of the injury indicated by pulmonary function, but in part on the amount of gold which has been stored in pulmonary macrophages. No statistical difference was shown in the initial dose of steroids between these groups. The duration between the onset of gold lung and the start of steroid therapy were longer in group B than than group A (p less than 0.05). Thus, early diagnosis and treatment with steroids are highly recommended in the clinical management of patients with gold lung.

Adult↗

Structure-activity relationships of philanthotoxin analogs and polyamines on N-methyl-D-aspartate and nicotinic acetylcholine receptors.

The effects of varying the structure of philanthotoxin (PhTX) were investigated on binding of the channel blockers: [3H]perhydrohistrionicotoxin (H12-HTX) to the nicotinic acetylcholine receptor (nACh-R) of Torpedo electric organ and [3H]MK-801 [( 3H]-5-methyl-10,11-dihydro-5H-dibenzocyclo-hepten-5,10-imine maleate) to the N-methyl-D-aspartate receptor (NMDA-R) of rat brain cortex. The four moieties of PhTX (tyrosine, butyrate, spermine and the terminal amino group) were modified or conjugated resulting in 36 compounds. Although the potencies of the PhTX analogs on both receptors were higher with increasing lipophilicity and the polyamine chain length, there was considerable divergence between the two receptors' channels in the structural activity requirements for blockade by PhTX analogs. A major difference was the more critical role of the amine terminal for inhibition of the nACh-R than the NMDA-R, whereas the reverse might be true for the tyrosine moiety. The potency range of PhTX analogs on [3H]H12-HTX binding was 1070, but only 21 on [3H]MK-801 binding. Adding a lysine or arginine onto the spermine moiety increased the compound's potency on the nACh-R with little effect on the NMDA-R. Because spermine is a component of PhTX, the effects of five polyamines were also studied. Spermine and spermidine potentiated [3H]MK-801 binding, whereas putrescine, cadeverine and agmatine inhibited it. In presence of glutamate, higher concentrations of all polyamines inhibited [3H]MK-801 binding. On the nACh-R, spermine, spermidine and agmatine inhibited [125I]alpha-bungarotoxin and also [3H]H12-HTX binding in presence of carbamylcholine. The complex nature of PhTX interactions with the two receptors suggests that PhTX may bind to two sites: an external polyamine binding site and a channel binding site.

Animals↗

[A case of herpes simplex encephalitis with cerebral white matter lesion after acyclovir administration].

Herpes simplex virus (HSV) is regarded as an agent that selectively affects temporal and frontal lobes with necrosis and hemorrhage, and no case of herpes simplex encephalitis (HSE) with white matter lesion in a diffuse fashion has previously been reported. A 2-year-old boy developed high fever, right hemi-convulsions and lethargy. Computed tomography (CT) showed wedge-shaped areas of high density in the left frontal region, whereas, cerebral angiography disclosed no vascular abnormality. T1-weighted magnetic resonance imaging (MRI) demonstrated cortical changes which were similar to those illustrated by CT. However, T2-weighted images depicted further spread high intensities of the lesion. The patient's symptoms spontaneously disappeared before an antiviral drug, acyclovir, was administered. After the significant increase of HSV antibody titers in serum and cerebro-spinal fluid (CSF) established a definite diagnosis, acyclovir was intravenously given at a daily dosage of 30 mg/kg for a period of 6 days in order to prevent the recurrence of HSE. Two months later, T2-weighted MRI visualized a diffuse lesion of increased signal intensities involving the white matter of both hemispheres, while both CSF protein and myelin basic protein were significantly elevated. Despite of these changes of the white matter, our patient developed a few symptoms such as mild speech disturbance, slight weakness of the right upper limb and sialorrhea. Although the mechanism of these changes in the white matter remains obscure, it is postulated that a direct invasion of HSV to the white matter, an immunological disorder following HSV infection and a side effect of acyclovir could have triggered a reversible process of demyelination of the cerebral white matter.

Acyclovir↗

[Lung function measurement of small airway obstruction in idiopathic interstitial pneumonia].

Small airway obstruction in idiopathic interstitial pneumonia was studied in 54 cases of interstitial pneumonia accompanied by restrictive, but not obstructive impairment (%VC less than 80%, FEV1/FVC% greater than 70%). Correlation analysis of %VC showed that small airway obstruction seemed to play a role in the decrease in VC in these cases. Cases were then divided into two groups. In group A, restrictive impairment was caused by the decrease in TLC (%TLC less than 80% & %RV less than 120%) and in group B, it was caused by increase in RV (%TLC greater than 80% & %RV greater than 120). Cases of idiopathic interstitial pneumonia (IIP) were preferentially categorized into group A. Statistical comparison of the lung function measurements revealed that lung parenchyma was altered less severely whereas small airway obstruction was more advanced in group B than group A. Group B was divided into two subgroups, the subgroups of IIP cases and of the other disease cases, and the latter had a larger lung volume and more severely impaired small airway function. Furthermore, IIP cases from group A had less severely altered lung parenchyma than IIP cases from group B. Smoking habits did not seem to be related to these results. The results indicate that in most cases of interstitial pneumonia other than IIP, the lung function was characterized by small airway obstruction rather than decreased lung volume, and some cases of IIP also showed a similar trend. In addition, a long-term study of lung function was made in some cases of interstitial pneumonia and it was shown that small airway obstruction could change in severity after a time interval.

Aged↗

Mucociliary clearance and transport in bronchiectasis: global and regional assessment.

Global and regional mucociliary clearance and transport in the lungs was studied in 20 patients with bronchiectasis by radioaerosol inhalation lung cine-scintigraphy and the quantitative analysis following inhalation of ultrasonically-generated 99mTc-tagged human serum albumin aerosol (mass median diameter; 1.93 microns with geometric s.d. of 1.52). In bronchiectatic lung regions, deposition of inhaled aerosol was diminished or inhomogeneous. Transport of inhaled radioactivity from the bronchiectatic regions was deranged in 95% of the patients (19/20). The following abnormal mucous transport patterns were regionally observed; stasis in 12 of the 20 patients (12/20), regurgitation or reversed transport in 14/20, straying in 8/20, spiral or zigzag transport in 1/20, and/or various combinations of these four abnormal transport patterns. When coughs occurred, regurgitation and stray became more marked in the bronchiectatic regions. These regional abnormalities in mucociliary transport seem to be responsible for the development of infections and hemoptysis in the bronchiectatic regions.

Administration, Inhalation↗