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Biomedical subjects

N Araki

Publications and source records attributed to N Araki.

At least 145 records · Page 8Linked to original sources
PubMed1992

Relaxant effect of C-type natriuretic peptide on guinea-pig tracheal smooth muscle.

The relaxant effects of the C-type natriuretic peptide (CNP) on guinea-pig tracheal smooth muscle were investigated. CNP (10(-8)-10(-5) mol/l) induced dose-dependent relaxant effects on the resting tone of tracheal smooth muscle with EC50 of 3.6 +/- 0.8 x 10(-6) mol/l (mean +/- SE). CNP caused a dose dependent increase in the tissue cyclic GMP level in tracheal smooth muscle (191 +/- 10 fmol/mg protein in control, 583 +/- 33 fmol/mg protein at 10(-7) mol/l, 688 +/- 56 fmol/mg protein at 10(-6) mol/l, 1091 +/- 167 fmol/mg protein at 10(-5) mol/l). Tissue cyclic GMP levels showed a peak at 1 min. Relaxation of the tracheal smooth muscle began at 1 min, reaching peak value at 5 min after the perfusion of CNP (10(-5) mol/l). Elevations in cyclic GMP preceded the relaxation of tracheal smooth muscle. These results suggest that CNP may be a novel potent relaxant in tracheal smooth muscle and that its relaxant effect may be mediated by cyclic GMP levels.

Animals↗
PubMed1991

Immunochemical approach to characterize advanced glycation end products of the Maillard reaction. Evidence for the presence of a common structure.

Reaction of protein amino groups with glucose (the Maillard reaction) leads from early stage products such as Schiff base and Amadori products to advanced glycation end products (AGE), structures implicated in diabetic complications and the aging process. We have prepared the polyclonal anti-AGE antibody and the monoclonal anti-AGE antibody against AGE-bovine serum albumin and made an immunochemical approach to characterize AGE structures. Both polyclonal and monoclonal antibodies reacted with AGE-proteins such as AGE-bovine serum albumin, AGE-human serum albumin, and AGE-hemoglobin but not with unmodified counterparts. Treatments of these AGE-proteins with borohydride had no effect on the immunoreactivity. Moreover, fructosyl-epsilon-caproic acid, a synthetic Amadori compound, did not serve as an antigen, indicating that these antibodies were specific for AGE products but not for early stage products of the Maillard reaction. In addition, these antibodies were also able to recognize AGE products prepared either from alpha-tosyl-1-lysine, alpha-tosyl-1-lysine methyl ester, monoaminocarboxylic acid such as epsilon-aminocaproic acid, gamma-amino-n-butyric acid, and beta-alanine. Thus, these results strongly suggest the presence of a common structure in AGE preparations, regardless of whether AGE products are generated from proteins, amino acids, or monoaminocarboxylic acids.

Antibodies, Monoclonal↗
PubMed1991

Mechanism underlying protective effect of MK-801 against NMDA-induced neuronal injury in vivo.

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 microns in depth by superfusion with the membrane-permeant indo-1 acetoxy-methyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 microM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18-22 Hz polyspikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.

Animals↗
PubMed1991

Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage.

Calcium ion can enter ischemic neurons through both receptor-operated and voltage-sensitive Ca2+ channels. To attenuate this Ca2+ entry and Ca2(+)-induced neuronal injury, we tried a combined treatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and the dihydropyridine calcium antagonist, nimodipine, in a cat middle cerebral artery occlusion (1 hour) and reperfusion (3 hours) model. We measured changes in cytosolic free calcium, nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox state, and blood flow in the cat cortex using a newly developed fluorometric technique with indo-1, a fluorescent intracellular Ca2+ indicator. The combined treatment, starting 5 minutes into ischemia, was effective in reducing both Ca2+ entry and histologic damage and in enhancing recovery of the electroencephalogram following reperfusion. MK-801 alone was also effective, but to a lesser extent. These data suggest that the dual blockade of Ca2+ entry using MK-801 and nimodipine may be a useful tool for protection against ischemic brain damage.

Animals↗
PubMed1991

[Application of a slow release system of anti-cancer drug retained in calcium hydroxyapatite ceramic against experimental bone and soft tissue sarcoma].

Cis-platinum enclosed into porous calcium hydroxyapatite ceramics (CDDP-CHA) has already been reported to be an excellent slow releasing drug preparation in vivo and in vitro study. In this paper, CDDP-CHA tried to apply for experimental bone and soft tissue sarcoma. When CDDP-CHA were implanted into solid tumors (Dunn osteosarcoma cells) transplanted subcutaneously in mice, high concentration of CDDP was found and a prolonged retention of the drug in the tumor as same pattern as in normal muscle. In contrast, CDDP concentration in other organs such as liver, kidney were significantly lower than in the tumor. Tumor growth was markedly inhibited at 30 days after CDDP-CHA implantation into the tumor compared to that after intraperitoneal administration. CDDP-CHA showed a similar effect to experimental bone tumor (mammary carcinoma) as that of soft tissue tumor. These result suggests that this delivery system will be able to apply clinically for bone and soft tissue sarcoma.

Animals↗
PubMed1991

Intracellular calcium and pathophysiological changes in cerebral ischemia.

The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link included studies in cell cultures, measurements of calcium accumulation in the mitochondria during ischemia as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since high concentrations of intracellular free calcium have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. The studies outlined demonstrate that changes in intracellular free calcium occur in focal ischemia and describe the time course of these changes. They indicate that cellular damage can be attenuated by the use of agents that block calcium channels (both voltage-sensitive and receptor-operated) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium.

Animals↗
PubMed1991

Involvement of the retinoblastoma gene in primary osteosarcomas and other bone and soft-tissue tumors.

The retinoblastoma (Rb) gene, thought by some to be associated with tumor formation of retinoblastoma as a recessive human oncogene, was investigated in 57 cases using DNA and RNA from primary osteosarcomas and other bone and soft-tissue tumors. Eight of 23 osteosarcoma cases (35%) showed structural alterations of the Rb gene. Three of the eight demonstrated homozygous deletions, and the remaining five cases showed heterozygous deletions. Seven out of eight cases represented deletion of a 7.5-kb HindIII fragment. Northern blot analysis of five cases of osteosarcoma showed that four demonstrated no detectable Rb gene transcription, and one case had a truncated 3.5-kb fragment with a faint 4.7-kb band. In the other 34 cases of bone and soft-tissue tumors, two cases of three malignant fibrous histiocytomas showed an Rb gene abnormality by Southern blot analysis. These results strongly suggest that Rb gene alteration is pertinent to the tumorigenesis of most osteosarcoma cases and some other bone and soft-tissue tumors.

Adolescent↗
PubMed1991

[A case of gastric cancer of Borrmann type IV complicated with carcinomatous peritonitis responding well to chemotherapy of tegafur only].

A 46-year-old-male was admitted to our hospital with an unresectable stage of gastric cancer of Borrmann type IV with carcinomatous peritonitis. He was treated only with tegafur 900 mg/day. After 2 months' treatment, computed tomography showed ascites disappeared and a remarkable improvement was observed by barium meal study and endoscopic examination. The patient has survived for 12 months without any abdominal complaints and ascites since the beginning of treatment. Thus, this is a rare case responding well to chemotherapy of tegafur only.

Adenocarcinoma↗
PubMed1990

Cytochemical demonstration of NPPase activity for detecting proton-translocating ATPase of Golgi complex in rat pancreatic acinar cells.

An attempt at cytochemical demonstration of acidification proton-translocating ATPase (H(+)-ATPase) of Golgi complex in rat pancreatic acinar cells has been made by using p-nitrophenylphosphatase (NPPase) cytochemistry which is used for detecting of Na(+)-K(+)-ATPase (Mayahara et al. 1980) and gastric H(+)-K(+)-ATPase (Fujimoto et al. 1986). K(+)-independent NPPase activity was observed on the membrane of the trans cisternae of Golgi complex, but not inside of cisternae. The localization of NPPase activity is different from that of acid phosphatase activity where reaction products were seen on the inside of the trans Golgi cisternae. Since this activity was insensitive to vanadate, ouabain and independent of potassium ions, it was distinct from plasma membranous ATPases such as Na(+)-K(+)-ATPase and Ca2(+)-ATPase. The K(+)-independent NPPase activity was diminished by the inhibitors of H(+)-ATPase such as N-ethylmaleimide (NEM) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The NPPase reaction products were also seen on the membranes of other acidic organelles, i.e., lysosomes, endosomes, autophagosomes and coated vesicles. These results suggest that NPPase activity on the membrane of the Golgi complex and other acidic organelles corresponds with H(+)-ATPase which plays a role in acidification.

Animals↗
PubMed1990

Microquantification of cholesterol and cholesteryl esters in rat peritoneal macrophages by reverse-phase high-performance liquid chromatography.

A simple and rapid method for the microquantification of cholesterol and cholesteryl esters by reverse-phase high performance liquid chromatography has been established. Comparison of elution patterns of authentic cholesterol and cholesteryl esters revealed that a mu Bondasphere reverse-phase C8 (300-A) column was more suitable than a corresponding reverse-phase C4 or C18 column in terms of rapidity and sensitivity. Recovery of cholesterol and cholesteryl esters from a C8 column was greater than 98% when determined either by radioactive cholesterol and cholesteryl oleate or by cholesteryl heptadecanoate. The sensitivity of the quantification ranged from 5 ng to 50 micrograms for both cholesterol and cholesteryl esters. This method was applied to determination of cellular cholesterol and cholesteryl esters of rat peritoneal macrophages. Lipid extracts of these cells were found to contain 38.01 +/- 2.60 micrograms of cholesterol and 3.18 +/- 0.36 micrograms of cholesteryl esters per milligram of cell protein. When the cells were loaded with cholesteryl esters by incubation for 24 h with various concentrations of acetylated low-density lipoprotein, a cellular level of cholesteryl esters showed a dose-dependent increase and reached a maximal level of 106.60 +/- 3.05 micrograms/mg cell protein. Thus, the present method is useful for the microquantification of cholesterol and cholesteryl esters from lipid extracts of biological samples.

Animals↗
PubMed1990

Alterations in cytosolic free calcium in the cat cortex during bicuculline-induced epilepsy.

Influx of calcium ion (Ca++) into the neurons has recently been implicated in the generation of seizure activity. Utilizing indo-1, a fluorescent Ca++ indicator, changes in cytosolic free calcium ([Ca++]i), NAD/NADH redox state and hemodynamics were simultaneously measured in vivo from the cat cortex during bicuculline-induced seizure activity. A ratio of indo-1-Ca++ fluorescence at 400 and 506 nm during ultraviolet excitation (340 nm) was utilized as a measure of changes in [Ca++]i. Alterations in the NAD/NADH redox state and local cortical blood volume (1CBV) were assessed at 464 nm and 340 nm, respectively. Local cortical blood flow (1CBF) was calculated from 1CBV and mean transit time determined from cortical hemodilution curves. Electroencephalogram (EEG) was monitored from the same cortical region as the optical measurements. The [Ca++]i signal ratio started to increase 19 +/- 2 sec prior to the onset of seizure activity on the EEG and remained elevated until the activity was suppressed by an intravenous administration of diazepam (2 mg/kg). The early increase in [Ca++]i is presumably due to a synaptic Ca++ entry associated with facilitated excitatory neurotransmission. The NAD/NADH redox state became oxidized during the seizure activity and started to recover as the EEG activity was suppressed. The 1CBV and 1CBF increased by 17 +/- 8% and 68 +/- 16%, respectively, 10 min into the seizure activity. This study provides direct in vivo evidence suggesting a possible role of calcium entry into the neurons in the epileptogenesis.

Animals↗
PubMed1990

The use of calcium hydroxyapatite ceramic in bone tumour surgery.

We report 60 benign bone tumours treated by resection and curettage followed by the implantation of calcium hydroxyapatite ceramic (CHA). After follow-up of six to 60 months (average 36), no patient had local recurrence of the tumour or any adverse effects from the implants. In almost all cases radiography showed that the CHA was well-incorporated into the host bone, with new bone formation in and around the CHA. Corrective remodelling of deformed bone and normal fracture healing suggested that there was normal bone turnover in the presence of the CHA. Histology of biopsies from seven patients showed bone ingrowth into the pore structure of CHA in the central zone of some defects by one year after implantation. CHA appears to be a useful substitute for bone graft in the treatment of some benign tumours.

Adolescent↗
PubMed1990

[A leiomyosarcoma of the jejunum diagnosed by an ultrasonically guided percutaneous biopsy].

Reported is a leiomyosarcoma of jejunum that was found in a 61-year-old man who was admitted to our clinic because of an abdominal distension. A CT scan and an ultrasonic examination revealed a giant tumor with a central necrosis in the abdominal cavity. A study of barium that was ingested revealed an elevated lesion without a fistel formation in the jejunum about 25 cm distant from the Treitz ligament. An ultrasonic the guided percutaneous biopsy was done and pathological diagnosis indicated a leiomyosaroma. Surgery was performed on June 16 1989 and the tumor weighing 4,934 g and 30 x 25 x 18 cm in size, was completely resected.

Biopsy, Needle↗
PubMed1990

Cytosolic free calcium during focal cerebral ischemia and the effects of nimodipine on calcium and histologic damage.

The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link includes studies in cell cultures and measurements of calcium accumulation in the mitochondria during ischemia, as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since it is dangerously high concentrations of the intracellular free calcium that have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. A technique for the measurement of intracellular free calcium is described, along with data from studies that dramatically demonstrate the time course of changes in intracellular free calcium induced by focal ischemia. Additional data are also presented that indicate that cellular damage can be attenuated by the use of agents that block calcium channels (nimodipine, which blocks voltage-sensitive calcium channels, and MK-801, which blocks receptor-operated channels) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium.

Animals↗
PubMed1989

Scavenger receptor of human monocytic leukemia cell line (THP-1) and murine macrophages for nonenzymatically glycosylated proteins.

Long-term incubation of proteins with glucose undergo a series of nonenzymatic reactions to form advanced glycosylation end product (AGE) with fluorescence and brown color. The receptor for AGE-proteins was demonstrated in murine macrophages (Vlassara et al. (1985) Proc. Natl. Acad. Sci. USA 82. 5588). Our recent study with rat macrophages revealed that the receptor also recognized proteins modified with aliphatic aldehydes such as formaldehyde or glycolaldehyde, indicating its close identity to a scavenger receptor for aldehyde-modified proteins (Takata, K. et al. (1988) J. Biol. Chem. 263. 14819). This notion was tested in the present study with human monocytic leukemia cell line (THP-1 cells), human monocyte macrophages and murine peritoneal macrophages. Endocytic uptake of AGE-proteins and aldehyde-modified proteins was inhibited in a cross-competitive fashion. The receptor activities of THP-1 cells for AGE-albumin and aldehyde-modified proteins were induced synchronously by phorbol 12-myristate 13-acetate. Furthermore, upon reduction by NaBH4 of the Schiff base formed between proteins and glucose or aldehydes, no ligand activity was generated. However, once the ligand activity was generated, NaBH4 was no longer effective for the ligand activity. Thus, a structure in common between AGE-proteins and aldehyde-modified proteins may be crucial for recognition by the human macrophage receptor.

Animals↗
PubMed1989

Intracellular accumulation of cholesteryl esters suppresses production of lipopolysaccharide-induced interleukin 1 by rat peritoneal macrophages.

Interleukin 1 (IL-1) is a major cytokine of macrophages secreted by several stimulants such as lipopolysaccharide (LPS). Macrophages are known to possess the scavenger receptor for acetylated low density lipoprotein (acetyl-LDL) and maleylated albumin. In the present study we determined effects of these ligands on LPS-induced IL-1 production by rat peritoneal macrophages. These ligands themselves did not induce IL-1 production. However, upon short incubation with acetyl-LDL, LPS-induced IL-1 production was significantly suppressed. The extent of the suppression was proportional to cellular cholesteryl esters. Thus, intracellular accumulation of cholesteryl esters might be responsible for suppression of LPS-induced IL-1 production.

Albumins↗
PubMed1989

Lysosomal movements during heterophagy and autophagy: with special reference to nematolysosome and wrapping lysosome.

Recent studies on lysosomal movements during heterophagy and autophagy performed in our laboratory for the past several years were reviewed; methods for the investigation of lysosomes and the cytoskeleton in these studies mainly involved electron microscopic cytochemistry. Lysosomal movements during heterophagy were observed in cultured rat alveolar macrophages taking up horseradish peroxidase (HRP) and rat peroxidase-antiperoxidase (PAP) by fluid-phase pinocytosis and adsorptive pinocytosis, respectively. A characteristic lysosomal change which was induced by the pinocytosis was the appearance of long, threadlike lysosomes (nematolysosomes) in the cytoplasm. The effects of actin filament destabilizer and antimicrotubular drug on lysosomal changes revealed that the appearance of nematolysosomes was dependent on the presence of both actin filaments and microtubules. The close morphological relationship between lysosomes and cytoskeletal elements, such as actin filaments and microtubules in the alveolar macrophages, supports the participation of the cytoskeletal system in the regulatory mechanism of lysosomal movements. In the study of the lysosomal wrapping mechanism (LWM), which is one type of lysosomal movement that occurs during autophagy, it was found that the occurrence of LWM was dependent on energy--namely, the supply of ATP--and on the presence of actin filaments. However, deconstruction of microtubules induced or favored the occurrence of LWM. It is conceivable that the LWM is also related to the cytoskeletal system. We conclude that intracellular dynamics of lysosomes during heterophagy and autophagy are largely a consequence of complicated modulation by the cytoskeletal system.

Animals↗