Biomedical subjects

K Konno

Publications and source records attributed to K Konno.

At least 685 records · Page 38Linked to original sources

PubMedDate not supplied

Systematic studies on synthesis, structural elucidation, and biological evaluation of A-ring diastereomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) and 20-epi-2-methyl-1alpha,25-dihydroxyvitamin D(3).

All possible A-ring diastereomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) (2) and 20-epi-2-methyl-1alpha,25-dihydroxyvitamin D(3) (3) were synthesized by palladium-catalyzed coupling reaction of A-ring 'enyne' synthons with CD-ring portions. The A-ring synthons were rationally synthesized via a novel and practical route, starting with methyl (R)-(+)- and (S)-(-)-3-hydroxy-2-methyl-propionate, in good yields. X-ray crystallographic analysis of 2alpha-methyl-1alpha,25-dihydroxyvitamin D(3) (2b) and conformational analysis of the A-ring of 2alpha-methyl-(2b) and 2beta-methyl-1alpha,25-dihydroxyvitamin D(3) (2f) were carried out, and the results are described. All A-ring diastereomers (2 and 3), thus synthesized, were biologically evaluated both in vitro and in vivo. The biologic potency was highly dependent on the stereochemistry of the A-ring substituents. In particular, 2b showed 4-fold higher vitamin D receptor [VDR] binding activity than the natural hormone, and its 20-epimer (3b) exhibited exceptionally high activity, 12-fold more potent in VDR binding, 7-fold in calcium mobilization, and 590-fold in induction of human promyelocytic leukemia (HL-60) cell differentiation as compared with the natural hormone. Further, the 20-epi-2beta-Me-1beta, 3alpha(OH)(2) isomer (3g) had significant biologic potencies compared to the natural hormone despite having 1beta-OH configuration. The transcriptional activities on human osteocalcin gene promoter, including VDRE in transfected mammalian cells, were also evaluated. Finally, there was a clear contrast between the effects of the 2-methyl group on the HL-60 cell differentiation- and apoptosis-inducing activities of 2 and 3.

Animals↗

PubMedDate not supplied

Identity of differentiation inducing factor and tumour necrosis factor.

Human myelogenous leukaemic cells can be induced to differentiate into the monocyte/macrophage pathway by protein inducers called differentiation inducing factors (DIF) in conditioned media of mitogen-stimulated human peripheral blood leukocytes. However, human DIF has not yet been well characterized. DIF is known to be a T-cell lymphokine, as it can be obtained from the T-cell line HUT-102 and can be partially purified from medium conditioned by phytohaemagglutinin (PHA)-stimulated lymphocytes. We found that monocytes also produce factor(s) that induce differentiation of human myelogenous leukaemia cell lines to cells with macrophage-like characteristics. This factor(s) has activity different from that of colony-stimulating factor(s) or interferons. We have now purified a DIF to homogeneity from medium conditioned by PHA-stimulated leukocytes using a human myeloblastic leukemia cell line, ML-1, as target cells. The purified DIF has a relative molecular mass (Mr) of approximately 17,000, with an NH2-terminal sequence the same as that of human tumour necrosis factor (TNF). Recombinant human TNF (rHuTNF) induces differentiation of ML-1 cells and an anti-pDIF monoclonal antibody can neutralize both differentiation inducing activity and cytotoxic activity of DIF and rHuTNF. The findings indicate that one of the DIF(s) produced by leukocytes is probably TNF.

Amino Acid Sequence↗

PubMedDate not supplied

Osteosarcoma as a second malignancy after treatment for neuroblastoma.

A 4-month old girl was diagnosed as having stage IV neuroblastoma of the right adrenal gland. Preoperative chemotherapy was given, followed by local surgical excision. Postoperatively, irradiation of the tumor bed and adjuvant chemotherapy was given for 11 months. Nine years after cessation of chemotherapy, the patient developed left hip-joint pain. Biopsy of the ischium showed chondroblastic osteosarcoma. Limb salvage surgery was performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy was given for 14 months. Twenty-two months after treatment for the secondary osteosarcoma, the patient has been remained in disease-free condition without any evidence of relapse. A second osteosarcoma occurring outside the radiation field after treatment for neuroblastoma is quite rare. This unusual case emphasized the need for close monitoring for development of second malignant neoplasms in survivors of neuroblastoma even in the absence of a known predisposing factor, such as radiation therapy.

Combined Modality Therapy↗

PubMedDate not supplied

Unusual late extrapulmonary metastasis in osteosarcoma.

The major site of metastasis from osteosarcoma is the lung, and over 90% of fatalities in patients with this disease die from pulmonary metastases. Extrapulmonary disease is developing in an increasing proportion of patients, usually after pulmonary metastasis. This study reports three cases of patients with osteosarcoma that metastasized to the brain, mediastinum, intramuscular site, and pelvic cavity. The physician must be aware that extrapulmonary metastases may be present at the time a pulmonary metastasis becomes evident.

Adolescent↗

PubMedDate not supplied

Breed differences in allele frequency of the dopamine receptor D4 gene in dogs.

We previously reported that the dog dopamine receptor D4 (DRD4) gene is polymorphic as observed in humans, and four alleles were identified based on the number and/or order of the 12 and 39 bp sequences located in the homologous region of human DRD4. To assess the diversity of the DRD4 gene in dogs we examined the allelic variations in four breeds (beagle, golden retriever, Shetland sheepdog, and shiba) employing the polymerase chain reaction (PCR). As a result, we found three novel alleles and determined the DNA sequences of these alleles. The beagle shared four alleles, including 396, 435, 447a, and 447b, with the 435 (52.6%) and 447a (39.5%) alleles being common. The golden retriever had the 435 and 447a alleles, and the 435 allele was frequent (73.3%). In the Shetland sheepdog, the 435, 447a, and 498 alleles were observed, of which the 447a allele was most frequent (82.5%). The shiba had five alleles-447a, 447b, 486, 498, and 549-and the 447b allele was most common (55.4%). These findings suggest that the allele frequency varied among the four dog breeds, and analysis of the DRD4 polymorphism may therefore be useful for elucidating the relationships among dog breeds.

Alleles↗

PubMedDate not supplied

A severe hepatic disorder with myelodysplastic syndrome, treated with cytarabine ocfosfate, in a dog.

An 8-year-old female Shih Tzu was presented with weight loss and vomiting. Alanine aminotransferase was high and abdominal radiographs revealed hepato- and splenomegaly. Mild anaemia, neutrophilia with left shift, eosinophilia, a thrombocytosis with dysplastic features of eosinophils and platelets, were detected. The animal was initially considered to have hepatitis and was treated accordingly, but clinical signs persisted. Histological examination of liver biopsy samples showed disruption of the hepatic lobule, with extensive infiltration by haemopoietic cells. Further investigation of the bone marrow suggested a diagnosis of myelodysplastic syndrome. The animal was treated with cytarabine ocfosfate, a prodrug of cytosine arabinoside, and appeared to recover.

Animals↗

PubMedDate not supplied

Radioprotective and radiosensitizing effects of sulfur-containing amino acid derivatives on mice.

Both protection and sensitization of Mice C57Bl against 60Co gamma-rays by sulfur-containing amino acid derivatives--S-alkyl-L-cysteines, S-alkyl-2-methyl-DL-cysteines and their hydantoin derivatives, and sulfoxides of these compounds--were examined. DL-5 Allylthiomethyl-5-methylhydantoin (150 mg/kg body weight) had a remarkable radioprotective effect. The survival ratio was 4.3 or above two times as much as that of L-cysteine. On the other hand, its sulfoxide had a radiosensitizing effects; survival ratio, 0.333.

Amino Acids↗

PubMedDate not supplied

Administration of bromodeoxyuridine in early postnatal rats results in lung changes at maturity.

The purpose of this study was to examine how lungs in early postnatal animals that are administered bromodeoxyuridine (BrdU), a thymidine analog known to be a cytogenetically toxic agent, change in adult life. BrdU was injected (1 mg/g body weight) intraperitoneally in suckling rats on day 6 after birth. Immunohistochemical studies revealed that BrdU was incorporated in alveolar cells, and infrequently in the mesothelium, endothelium, and bronchiolar epithelium. The number (per high-power field) of alveolar cells incorporating BrdU was 8.76 +/- 0.50 in the interstitium and 1.66 +/- 0.25 in the epithelium. The animals were sacrificed at 2 and 8 weeks and 12 months of age. Control animals were treated the same as the BrdU-treated animals except for the injection of BrdU. Body weight, body size (nose-tail length), and lung weight were identical between BrdU-treated animals and control animals at all experimental periods. The histopathology and physiology of these lungs were studied. At 2 weeks of age, the BrdU-treated animals appeared morphologically and functionally similar to control animals. At 8 weeks and 12 months of age, the lungs in the BrdU-treated animals showed abnormal enlargement of the airspace, few alveoli, and less complexity in pulmonary architecture with or without increased lung compliance. These findings suggest that lung injured cytogenetically in early postnatal life may develop functional and structural abnormalities in later life.

Animals↗

PubMedDate not supplied

Effects of nicotinamide and niacin on bleomycin-induced acute injury and subsequent fibrosis in hamster lungs.

Nicotinamide (500 or 250 mg/kg body wt) or niacin (100 or 50 mg/kg body wt) was administered to hamsters given an intratracheal injection of bleomycin (BLM). At 7 days after the BLM injection, when compared with BLM-control animals, both nicotinamide- and niacin-treated animals showed similar acute lung injury, recognized as increases in the wet-to-dry lung weight ratio, intraalveolar albumin concentration, inflammatory cell number, and elastase activity. At 30 days after the BLM injection, both nicotinamide and niacin attenuated the development of pulmonary fibrosis, as indicated by fewer fibrotic changes and a decreased amount of lung hydroxyproline. Histologic examination revealed that, compared with nicotinamide, niacin had more potent antifibrotic effects. Lung nicotinamide-adenine-dinucleotide (NAD) was less depleted in nicotinamide-treated animals than in BLM-control animals. Nicotinamide- and niacin-treated animals had more intraalveolar cells than the BLM-control animals. These findings suggest that the development of pulmonary fibrosis induced by BLM was prevented through maintaining NAD by the administration of nicotinamide or niacin. Since neither nicotinamide nor niacin attenuated the inflammatory response to acute lung injury, the amelioration of fibrosis by these treatments appears to be independent of the early events.

Animals↗

PubMedDate not supplied

Regulation of airway cholinergic neurotransmission by Ca(2+)-activated K+ channel and Na(+)-K+ adenosinetriphosphatase.

Stimulation of Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may play an important role in the relaxant responses of airway smooth muscle to certain bronchodilators. To test whether cholinergic neuroeffector transmission can be modulated by Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase, canine airway smooth muscle was studied under isometric conditions in vitro. Addition of charybdotoxin (10(-7) M) did not alter the contractile responses to acetylcholine but augmented electrical field stimulation-induced contractions at 1-10 Hz (p < .01), whereas apamin and glibenclamide were without effect. This effect of charybdotoxin was dose dependent, with the maximal increase being 36.8 +/- 5.3% (p < .001). Ouabain (10(-7) M) increased contractions induced by both electrical field stimulation and acetylcholine. The magnitude of the increase in contractile responses to electrical field stimulation was similar to that of acetylcholine at an ouabain concentration of up to 3 x 10(-7) M, but the former was significantly greater at 10(-6) M ouabain (p < .05). These results suggest that both Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may be operative in the regulation of cholinergic neurotransmission by inhibiting the exocytotic release of acetylcholine from the vagal nerve terminals.

Acetylcholine↗

PubMedDate not supplied

Zizyphi fructus, a constituent of antiasthmatic herbal medicine, stimulates airway epithelial ciliary motility through nitric oxide generation.

The effects of Zizyphi fructus, a major constituent of Chinese anti-asthmatic herbal medicine, on ciliary motility and nitric oxide (NO) generation in canine cultured tracheal epithelium were studied by the microphoto-oscillation method and the specific amperometric method, respectively. Addition of Zizyphi fructus at 100 micrograms/mL rapidly increased ciliary beat frequency (CBF), an effect that was inhibited by NG-nitro-L-arginine methylester (L-NAME) but not by NG-nitro-D-arginine methylester (D-NAME), and this inhibition was reversed by L-arginine but not by D-arginine. Immersion of the NO-selective electrode in the medium bathing tracheal epithelial cells showed a baseline current of 21.3-60.4 pA, which corresponded to NO concentration ([NO]) at 34.4 +/- 7.8 nM. Zizyphi fructus caused a concentration-dependent increase in [NO], the maximal increase from the baseline [NO] level and the concentration of Zizyphi fructus required to produce a half-maximal effect (EC50) being 107 +/- 14 nM (p < .001) and 7.2 +/- 2.9 micrograms/mL, respectively. These results suggest that Zizyphi fructus enhances airway ciliary motility and that this effect is exerted through the stimulation of epithelial NO generation.

Animals↗

PubMedDate not supplied

Antitumor, antiviral and immunopotentiating activities of pine cone extracts: potential medicinal efficacy of natural and synthetic lignin-related materials (review).

Several antitumor substances that effectively inhibited the growth of ascites and solid tumor cells transplanted in mice were isolated from pine cone NaOH extract by acid- and ethanol-precipitation. These antitumor substances were also potent antiviral agents against human immunodeficiency virus, herpes simplex virus and influenza virus; they induced antimicrobial activity against Staphylococcal aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and induced antiparasite activity against Hymenolepis nana in mice. Chemical analysis of these substances by IR, UV, NMR, ESR and partition chromatography on cellulose-TLC plate disclosed that they had lignin-related structures complexed with sugars or polysaccharides. Chlorinated decomposition of the lignin portion significantly reduced their antiviral activity. In agreement with this, the antiviral activity of synthesized lignins prepared by polymerization of phenylpropanoid precursors was comparable to that of the undecomposed counterparts of the pine cone extract. Acid hydrolysis of the polysaccharide portion significantly reduced the ability of the substances to induce antitumor and antimicrobial activities in mice. With an appropriate eliciting agent, intravenous administration of natural lignified substances transiently induced endogenous production of a cytotoxic factor (possibly tumor necrosis factor) in normal mice. Their priming activity was significantly higher than that of their component units or degradation products. These data suggest the importance of conjugating lignins with polysaccharides for in vivo expression of various kinds of immunopotentiating activity. As possible explanations for their induction of a variety of immunopotentiating activities, these natural and synthetic lignins stimulated macrophage NBT-reducing activity, polymorphonuclear cell (PMN) iodination and splenocyte DNA synthesis and inhibited poly (ADP-ribose) glycohydrolase, RNA-dependent DNA polymerase (reverse transcriptase) and RNA-dependent RNA polymerase activities.

Adjuvants, Immunologic↗

PubMedDate not supplied

Purification and characterization of human fibroblast derived differentiation inducing factor for human monoblastic leukemia cells identical to interleukin-6.

A differentiation inducing factor for human monocytic leukemia cells was purified to homogeneity from conditioned medium of WI-26VA4, a human fibroblast cell line. The purification scheme consisted of micro bead silica gel chromatography, hydroxyapatite chromatography, gel filtration chromatography, chromatofocusing and reverse phase high performance liquid chromatography. The purified protein was almost homogeneous when determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and N-terminal sequence analysis. The protein has a molecular weight of approximately 27,000 and an isoelectric point of 5.4. The sequence of the first 13 N-terminal amino acid residues was consistent with that of B-cell stimulatory factor 2 (interleukin-6) except for the absence of the N-terminal proline. The purified factor induced differentiation of human monocytic leukemia U-937 cells into a monocyte/macrophage pathway.

Amino Acid Sequence↗

PubMedDate not supplied

Lignified materials as potential medicinal resources. II. Prevention of pathogenic bacterial infections in mice.

Antibacterial activity was demonstrated when ddY mice were intraperitoneally infected with E. coli or P. aeruginosa two days after a single ip-injection of a hot-water or alkaline extract obtained from lignified materials, such as chips of slash pine, Douglas fir, tallow wood, and two shelf fungi. Lignified material is a promising medicinal resource for the prevention and/or treatment of pathogenic microbial infection.

Animals↗

PubMedDate not supplied

Stimulation of interferon-gamma-induced human myelogenous leukemic cell differentiation by high molecular weight PSK subfraction.

PSK, a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor (Fr.) Quel, stimulated tumor necrosis factor-induced cytotoxicity against mouse L-929 fibroblast. PSK also stimulated interferon-gamma-induced differentiation of human myelogenous leukemic U-937 and THP-1 cells. The differentiated cells had higher proportions of cells that expressed NBT-reducing activity and alpha-naphthyl acetate esterase activity. Among four PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) had the most potent stimulating activity. This is the first report regarding direct PSK modulation of cytokine action.

Animals↗

PubMedDate not supplied

Dependence of cytokine-induced human myelogenous leukemic cell differentiation on the type of serum in the medium.

Human myelogenous leukemic cell lines (ML-1, U-937, THP-1) were induced to differentiate by treatment with various cytokines such as tumor necrosis factor, interferon-gamma and interleukin-6. However, the extent of cell maturation depended upon the types and concentrations of sera included in the culture medium. The stimulating activity of human sera on the cytokine-induced differentiation significantly exceeded that of various lots of calf serum, horse serum, fetal calf serum and fetal bovine serum, and its stimulating effects were reproducibly observed irrespective of age and sex of normal volunteers. On Sephadex G-200 gel filtration chromatography, the stimulatory substance(s) present in human sera were separated from the inhibitory substance(s) eluted near the void volume.

Blood Proteins↗

PubMedDate not supplied

Antimicrobial spectrum of lignin-related pine cone extracts of Pinus parviflora Sieb. et Zucc.

Pine cones of Pinus parviflora Sieb., et Zucc, were extracted successively with 5% NaHCO3, 3% NH4OH, 1% NaOH and 4% NaOH, and the extracts were tested for ability to induce antimicrobial activity in mice infected with Staphylococcal aureus. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, or Salmonella enteritidis. These alkaline extracts were potent against the first 5 of these strains of microorganisms, and the activity was recovered mostly from their acid-precipitates at pH 5. After further fractionation on a Sephadex LH-60 column, the highest molecular weight fraction was most potent. Chemical structures in these bioactive fractions were assumed to be lignin-related structures, based on spectral data from UV, NMR and IR spectroscopy.

Anti-Bacterial Agents↗

PubMedDate not supplied

Stimulation of human peripheral blood polymorphonuclear cell iodination by PSK subfractions.

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN), human promyelocytic leukemic HL-60 cells and human myeloblastic leukemic ML-1 cells. In contrast, PSK did not significantly increase the iodination of other cultured cell lines (U-937, THP-1, L-929, T98G, BALB 3T3). The PSK stimulation of iodination of both PMN and HL-60 cells depended on incubation time and temperature, and was significantly suppressed by the presence of myeloperoxidase inhibitors. Among various PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD), or the fraction precipitated at pH 4.0-4.5, stimulated the iodination most. In contrast, natural and chemically modified glucans had little or no stimulation activity. The active PSK subfractions synergistically enhanced TNF stimulation of PMN iodination. The data suggest the presence of some unique components in PSK which directly stimulate the iodination of myeloperoxidase-positive cells.

Animals↗