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Biomedical subjects

M Satoh

Publications and source records attributed to M Satoh.

At least 595 records · Page 33Linked to original sources

Assembly and DNA binding of recombinant Ku (p70/p80) autoantigen defined by a novel monoclonal antibody specific for p70/p80 heterodimers.

The Ku autoantigen is a heterodimer of 70 kDa (p70) and -80 kDa (p80) subunits that is the DNA-binding component of a DNA-dependent protein kinase (DNA-PK). The 350 kDa (p350) catalytic subunit of DNA-PK phosphorylates Sp-1, Oct-1, p53 and RNA polymerase II in vitro, but the precise cellular role of DNA-PK remains unclear. In the present studies, the assembly of p70/p80 heterodimers and the interaction of Ku with DNA was investigated using recombinant vaccinia viruses directing the synthesis of human p70 (p70-vacc) and p80 (p80-vacc), and monoclonal antibodies (mAbs). Expression of human Ku antigens in rabbit kidney (RK13) cells could be demonstrated by immunofluorescent staining because this cell line contains little endogenous Ku. A novel mAb designated 162 stained the nuclei of RK13 cells coinfected with p70-vacc and p80-vacc, but not cells that were infected with either virus alone, suggesting that it recognized the p70/p80 heterodimer but not monomeric p70 or p80. In agreement with the immunofluorescence data, 162 immunoprecipitated both p70 and p80 from extracts of coinfected cells, but did not immunoprecipitate either subunit by itself from extracts of cells infected with p70-vacc or p80-vacc, respectively. Conversely, the binding of 162 to Ku isolated from human K562 cells stabilized the p70/p80 heterodimer under conditions that normally dissociate p70 from p80. The nuclei of cells infected with p70-vacc alone could be stained with mAb N3H10 (anti-p70) and cells infected with p80-vacc alone could be stained with mAb 111 (anti-p80), indicating that the formation of p70/p80 heterodimers was not required for nuclear transport. Finally, free recombinant and cellular p70 both bound to DNA efficiently in vitro, suggesting that free p70, like the p70/p80 heterodimer, serves as a DNA-binding factor. Moreover, free human p70 could be released from the nuclei of p70-vacc-infected RK13 cells by deoxyribonuclease I treatment, suggesting that it was associated with chromatin in vivo. The nuclear transport of free p70 and the association of free p70 with chromatin in vivo raise the possibility that newly synthesized cellular p70 might undergo nuclear transport and DNA-binding prior to dimerization with p80 or assembly with p350.

Animals↗

Cellular polarity correlates with vimentin distribution, but not to keratin, in human renal cell carcinoma cells in vitro.

To investigate the relationships among vimentin, keratin and cellular polarity, reorganized glands composed of renal cell carcinoma cells were investigated in vitro. We employed two different three-dimensional collagen gel culture methods, the "floating sandwich method (FSM)" and the "dispersed embedding method (DEM)." The cells composed of reorganized glands formed by FSM culture showed distinct polarity. In contrast, the cellular polarity of the cells formed by DEM culture was less distinct. Keratin was evenly distributed throughout the cytoplasm regardless of the culture method. In contrast, in reorganized glands obtained by FSM culture, vimentin was distinctly polarized at the basal pole while glands obtained by DEM culture showed random distribution of vimentin. These results suggest that there is a close relationship between cell polarity and intracellular localization of vimentin, and that there may be different mechanisms controlling the organization of the two intermediate filament (IF) networks.

Carcinoma, Renal Cell↗

Potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor function by a nootropic drug, idebenone.

Effect of idebenone on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor was evaluated using Xenopus oocytes injected with RNAs encoding mouse alpha 1 and alpha 2 AMPA receptors. Concanavalin A augmented current responses of the RNA-injected oocytes to glutamate, kainate, and AMPA and these responses were further potentiated by 100 microM idebenone. The minimum concentration of idebenone that gave a significant potentiation was 10 microM for glutamate. These results suggest that idebenone acts on AMPA-selective glutamate receptor channels composed of alpha 1 and alpha 2 subunits.

Animals↗

Effect of vinconate on long-term potentiation in a mossy fiber-CA3 system of guinea pig hippocampal slices.

We investigated the effect of vinconate on the long-term potentiation of population spikes following the stimulation of mossy fibers in the CA3 pyramidal layer of hippocampal slices from guinea pig brain. Vinconate (10(-7) and 10(-6) M) dose-dependently augmented the long-term potentiation in the mossy fiber-CA3 system. This effect was reduced by treatment with scopolamine at a concentration of 10(-6) M, which showed no significant change in the long-term potentiation in a mossy fiber-CA3 system. These results suggest that vinconate may augment long-term potentiation in the mossy fiber-CA3 system partly via activation of the cholinergic system.

Animals↗

Pleural multicystic mesothelial proliferation.

We report a rare case of pleural multicystic mesothelial proliferation occurring in a 62-year-old Japanese woman. Macroscopically, the lesion consisted of multiple thin wall cysts containing clear serous fluid. Histologic studies, including hematoxin-eosin stain, as well as the immunohistochemical method, revealed that the lesion was mesothelial in origin and consistent with a reactive change.

Antigens↗

Assessment of an ultrathin bronchoscope that allows cytodiagnosis of small airways.

We developed a new type of bronchoscope (BF-2.7T) and cytology brush (BC-0.7T) that permit collection of pulmonary cells during direct observation of the small airways. This kind of cell collection has been previously impossible. With our cytology brush, 3.58 +/- 2.76 x 10(4) cells were collected from small airways. The rate of living cells was 33.13 +/- 3.61 percent from the small airways. Analysis of endoscopic findings and investigation of pulmonary cells are very important for elucidating the pathophysiologic state of the small airways. The use of the BF-2.7T allowed collection of cancer cells under direct endoscopic vision in all five patients with peripheral lung cancer. They also contribute to our understanding of the relationship between exogenous factors and cells that compose the lung, and will provide means for treatment and prevention of diseases.

Adenocarcinoma↗

Inter-laboratory validation study of the Skin2 Dermal Model ZK1100 and MTT cytotoxicity assay kits.

An inter-laboratory validation study was conducted to evaluate the potential of 4 chemicals to cause irritation with utilizing the Skin2 Dermal Model ZK1100 kit developed by Advanced Tissue Sciences, Inc. (formerly Marrow-Tech, Inc., La Jolla, California, USA). The chemicals tested were sodium dodecyl sulfate (SDS), 1-n-hexadecyl-pyridinium chloride monohydrate (CC), ethanol (EtOH), and dimethyl sulfoxide (DMSO). Eleven Japanese institutions participated in this validation research to evaluate the usefulness of the Skin2 Model ZK1100 kit in accordance with an identical protocol. None of the participating laboratories had previously used the Skin2 Model ZK1100 kit. The MTT-50 value obtained in the individual institutions was 42 to 91 micrograms/ml for SDS, 2.7 to 8.6 micrograms/ml for CC, 2.0 to 9.3% for EtOH, and 11.5 to 21.9% for DMSO. Reproducibility was reasonably good as noted when one test chemical was repetitively tested by the same investigator. MTT-50 values obtained with the present method correlated with DS20 values obtained with Draize's method (r = 0.9881) in one of the participant institutions. The irritation study using the Skin2 Model ZK1100 kit was easy to perform and generated quantitative data. When the test was repeated, reproducibility was demonstrated with a variation of less than 2 sigma. These data suggested that this newly developed in vitro method would be useful in toxicity screening studies in terms of both time and cost, and would serve as a useful alternative to the conventional methods of the eye irritation study.

Animals↗

Clinical significance of growth hormone-binding protein measurements in children.

To investigate the role of growth hormone (GH) and its downstream axis in normal growth and growth disorders, we measured serum GH-binding protein (GHBP) levels in children by ligand-mediated immunofunctional assay (LIFA). Samples were taken from 512 healthy children of normal stature, 146 healthy neonates, 153 short but otherwise normal children, and 27 patients with GH deficiency. Serum GHBP showed no significant diurnal variation. Serum GHBP levels were low in neonates, acutely rose within 6 months, and gradually increased toward midpuberty in normal children (r = 0.2, P < 0.01, assessed among subjects over 1 year old). Neither significant sexual dimorphism nor rapid pubertal changes were observed. In normal short children and patients with GH deficiency, GHBP was lower than normal, but not significant. These data suggest that one of the etiologies for growth disorder in children could be resistance to, or low efficacy for, utilization of GH.

Adolescent↗

[Combination therapy of high energy under water shock waves and anticancer drugs for subcutaneous murine bladder cancer (MBT-2)].

The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5 mg/kg, i.p.) or carboplatin (CBDCA, 40 mg/kg, i.p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (< 10 mm3, n = 8) were suppressed more than that of larger tumors (10-35 mm3, n = 11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2 +/- 146.6 (mean +/- S.D.) in the control (n = 20), 116.3 +/- 98.9 in HESW alone (n = 11), 75.5 +/- 110.7 in THP alone (n = 8), 90.7 +/- 61.6 in CBDCA alone (n = 6), 75.8 +/- 72.2 in THP + HESW (n = 9), 3.2 +/- 4.5 in CBDCA + HESW (n = 8) and 0.8 +/- 1.3 in CBDCA + HESW 2 cycles (n = 9). Evident suppression on tumor growth was more often seen in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.01). The cumulative survival rates were higher in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA + HESW and 1/5 in CBDCA + HESW 2 cycles therapy, respectively.

Animals↗

[Trans-urethral whole layer core biopsy of invasive bladder tumor].

We have developed a percutaneous whole layer core biopsy (WLCB) of bladder tumor and applied it successfully to stage invasive bladder tumor since April, 1985. We report here a modified method, trans-urethral WLCB (TU-WLCB) and present its clinical results. The patient was placed in the lithotomy position under caudal anesthesia, and a 20 F rigid nephroscope was introduced transurethrally. A newly developed 18-gauge (1.2 mm), 350 mm-long biopsy needle (Crown Core Cut Biopsy Needle) was advanced to the tumor through the nephroscope. A longitudinal transabdominal US was used to measure the distance between the needle tip and the outer layer of the bladder tumor. Because the needle advances 2.5 cm when fired by spring-loaded BIP Biopsy Gun (BIP, Germany), biopsy is performed by advancing the needle tip until the outer layer of tumor is slightly pierced under US guidance. Specimens of all 11 trans-urethral WLCB cases included the muscle layer and adipose tissue, and pathological staging were possible. TU-WLCB could be applied safely to tumors located at posterior wall and covered with the peritoneum. Serious complications were not observed so far. Thus, TU-WLCB may become a reliable technique to stage and evaluate neoadjuvant therapy for invasive bladder cancer.

Adult↗

Endothelins stimulate cyclic AMP accumulation in the isolated rat anterior pituitary gland: possible involvement of ETA receptor activation and prostaglandin E2 production.

Effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on cyclic AMP (cAMP) levels were studied in the isolated rat anterior and intermediate-posterior pituitary slices. In the anterior pituitary, ET-1 increased cAMP levels in a concentration-dependent manner (10(-7)-10(-5) M). ET-3 also increased the levels at the same concentration range, but ET-1 was more potent than ET-3 at an approximate ED50, 10(-6) M. The stimulatory effects of ET-1 and ET-3 (10(-6) M) on cAMP levels were antagonized by the ETA receptor antagonist BQ 123, 2 x 10(-6) M, and the ETB receptor agonist IRL 1620 evoked only a weak increase in cAMP levels. Moreover, the effects of ET-1 and ET-3 were completely abolished by the cyclooxygenase inhibitor indomethacin, 2 x 10(-5) M. On the other hand, among prostaglandins, prostaglandin E2 (PGE2) increased cAMP levels in a concentration-dependent manner (10(-7)-10(-5) M), whereas prostaglandin D2 and prostaglandin I2 did not exhibit such effects. PGE2 levels were increased by application of ET-1 (10(-8)-10(-5) M). The ET-1-induced PGE2 accumulation was strongly inhibited by indomethacin and BQ 123, but not by treatment with pertussis toxin (100 ng/ml, 6 hr). Treatment with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also elevated the cAMP level by approximately 9-fold above the basal cAMP level. After 3-isobutyl-1-methylxanthine, ET-1 failed to increase PGE2 and cAMP levels. In the intermediate-posterior pituitary, ET-1 and ET-3 did not affect cAMP levels. The results suggest that endothelins increase cAMP levels via ETA receptor activation interacting with the pertussis toxin-insensitive G-protein, in which PGE2 production is involved in the rat anterior pituitary, whereas endothelins lack these effects in the intermediate-posterior pituitary.

1-Methyl-3-isobutylxanthine↗

[Transcranial Doppler measurement of middle cerebral artery blood flow during continuous retrograde cerebral perfusion].

This is the first report of cerebral blood flow measurement with transcranial Doppler (TCD) during aortic arch reconstruction using continuous retrograde cerebral perfusion (CRCP) with deep hypothermia. Cerebral blood flow velocity was measured in 6 patients. CRCP was performed via the superior vena cava (SVC) at 30 cmH2O of internal juglar vein pressure and at 18 degrees C or lower of minimum bladder temperature. During the operation, the flow velocity of the middle cerebral artery (MCA) was continuously measured with TCD fixed on the temple. The cerebral blood flow during CRCP was different in each of the 6 patient. The retrograde MCA flow could be measured during CRCP in 3 patients, and the flow velocity was 11-60% of the MCA flow velocity before cardiopulmonary bypass. In the other 3 patients, retrograde MCA flow could not be detected during CRCP, but antegrade MCA flow could be found after antegrade perfusion was resumed. The antegrade flow velocity right after CRCP became more than the MCA flow before CRCP, which was regarded as a reaction due to cerebral ischemia. All the patients awoke within several (2-9) hours after operations and had no permanent neurological complications. But 2 patients developed drowsiness for several days after the operations; their CRCP times were 127 and 131 minutes. It is concluded that CRCP is a simple technique for brain protection, but the cerebral blood flow during CRCP is a simple technique for brain protection, but the cerebral blood flow during CRCP is different in each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Malignant T cell lymphoma associated with sarcoidosis.

We report an unusual case of non-Hodgkin T cell lymphoma associated with sarcoidosis. A 44-year-old woman was histologically diagnosed as having sarcoidosis in 1966. Diffuse interstitial lung disease and erythematous skin nodules disappeared following steroid therapy. Twenty years after sarcoidosis onset erythematous nodosum recurred and biopsy specimens revealed non caseating epithelioid granuloma. Thirty-seven months later a malignant T cell lymphoma developed in the skin portion where sarcoid lesions recurred. We discuss the possible relationship between the sarcoid inflammatory process and the development of a malignant T cell clone as origin of the T cell lymphoma.

Adult↗

[A case of Jordans' anomaly].

A 35-years old female with Jordans' anomaly was reported. She had been treated for diabetes mellitus and hypertension at another hospital. She was admitted to our hospital for operation for diabetic retinopathy on July 9, 1992. Wright-Giemsa stained peripheral blood smear revealed multiple vacuoles in the cytoplasm of the granulocytes and monocytes. Histochemical studies of these vacuoles showed positive for Sudan III but negative for peroxidase, alkaline phosphatase and PAS staining. Electron microscopic examination revealed that lipid containing vacuoles had no clear membrane and were not associated with cell organelles. Laboratory findings of the serum showed hyperglycemia (FBS 188mg/dl), high HbA1c level (9.4%) and mild type IIa hyperlipidemia. Abdominal sonogram and abdominal CT showed no remarkable abnormalities except for mild fatty liver. Her elder sister and daughter had similar morphological findings in granulocytes, monocytes and lymphocytes.

Adult↗

Efficacy of a novel injectable cephalosporin, Cefclidin, on the experimental complicated urinary tract infections with urinary stones caused by Pseudomonas aeruginosa and Proteus mirabilis.

We evaluated the effects of a novel cephalosporin, cefclidin (CFCL) and imipenem (IPM), on the eradication of bacteria from the urine, bladder stones and the kidneys, and also on the prevention of the infection stone formations, in our polymicrobial urinary tract infection model of rats associated with bladder stones using IMP-sensitive or IPM-resistant Pseudomonas aeruginosa and Proteus mirabilis as a causative pathogen. CFCL completely eradicated P. mirabilis from the urine and the stone in the short-term regimen (5 days). CFCL completely eradicated both IPM-sensitive P. aeruginosa and P. mirabilis from the urine, the stones and the kidneys as compared to IPM in the long-term regimen (11 days), reflecting the superior antibacterial activity of CFCL. CFCL also significantly prevented the development of infection stones as compared to IPM in the long-term regimen. There was no significant difference in the blood urea nitrogen (BUN) values between the CFCL or IPM-treated and the non-treated groups. The cumulative recovery rate of unchanged CFCL reached 47.3% of the total dosage (20 mg/kg) within 8 hours.

Animals↗

[Survey of activities of daily living in non-institutionalized elderly residents].

To investigate the states of activities of daily living (ADLs) in the elderly, non-institutionalized residents-aged 65 and over living in Azuchi (population of approximately 12,000) were interviewed. Data was collected from 1,287 subjects (509 men and 778 women; 92.1%) for the 3 years, 1990 to 1992. Differences in difficulties with the 6 basic ADLs (BADLs) and the 7 instrumental ADLs (IADLs) were analyzed according to gender and age. For the BADLs (eating, dressing, bathing, using the toilet, mobility, and incontinence), only the percentage of incontinence was significantly higher in women than in men (p < 0.01). The percentage of those fully independent in the 6 BADLs in men was 87%, which was higher than that in women (77%), but except for incontinence there were no significant differences between the sexes. The percentages of disability in the BADLs for women and for both sexes combined were higher according to age (p < 0.01), but for men, only those of dressing (p < 0.05) and of incontinence (p < 0.01) were related with age. The disability percentage for cooking was the only activity among the IADLs (cooking, using the telephone, cleaning house, walking, shopping, going up and down steps, and using transportation) which was significantly higher in men (p < 0.01), but those for walking, going up and down steps, and using transportation were higher in women (p < 0.01). The percentage of those who were fully independent was 74% in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗