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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 343 records · Page 19Linked to original sources
PubMed1996

Formation of focal adhesion and spreading of polarized human colon cancer cells in association with tyrosine phosphorylation of paxillin in response to phorbol ester.

Regulation of cell adhesion systems is involved in both normal development and the invasive behavior of carcinomas. We examined alterations of cell morphology and adhesion molecules in response to phorbol ester treatment of the SW1116 colon cancer cell line, which forms well-organized dome-like tubular structures in culture. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced rapid spreading of cancer-cell colonies through formation of focal adhesion and disappearance of adherens junctions. Immunologic analyses demonstrated that tyrosine-phosphorylated proteins were concentrated at focal adhesions, and that tyrosine phosphorylation of two proteins, paxillin and an unidentified 130-kd protein, was significantly increased. Tyrosine phosphorylation of paxillin was detectable within 15 min after TPA treatment, when only lamellipodia had extended from the colony, and in cells treated with blocking antibodies against integrins beta 1 and beta 5, which strongly inhibited spreading and disorganization while preserving adherens junctions. The level of paxillin phosphorylation correlated well with the degree of morphologic change induced by low-dose TPA, and the dephosphorylation occurred before reversion of morphology upon removal of TPA. These findings suggest that the TPA signal was transduced to the tyrosine phosphorylation of paxillin strongly associated with formation of focal adhesion, and that this in turn induced dysfunction of the cadherin system and caused spreading and disorganization of the tubular structure. The mechanism responsible for disruption of the cadherin system at adherens junctions was not clear, but the transition of beta-catenin into nuclei corresponded to the disappearance of its signal along areas of cell-cell contact. This SW1116 model provides a good system for studying the molecules involved in transient regulation and crosstalk between the cell-cell and cell-substratum adhesion systems, which may explain the mechanism of invasion of well-differentiated human carcinomas.

Antibodies, Monoclonal↗
PubMed1996

[A comparative study on the efficacies of ritipenem acoxil and cefotiam hexetil in bacterial pneumonia by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against bacterial pneumonia, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as the control drug. Both RIPM-AC and CTM-HE were orally administered at 200 mg t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 208, of which 152 cases (RIPM-AC group: 73, CTM-HE group: 79) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent + good) were 91.8% (67/73) in the RIPM-AC group and 94.9% (75/79) in the CMT-HE group. There was no significant difference between the two groups, and the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 84.6% (22/26) in the RIPM-AC group and 91.7% (22/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 9 cases (9.6%) of the RIPM-AC group and 5 cases (4.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 23 cases (26.7%) of the RIPM-AC group and 15 cases (15.6%) of the CTM-HE group. There was no significant differences between the two groups in the incidence of side effects nor of abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 64 cases (68.1%) and CTM-HE in 82 cases (80.4%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 86.5% (64/74) in the RIPM-AC group and 92.5% (74/80) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of bacterial pneumonia.

Adolescent↗
PubMed1996

Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

Adolescent↗
PubMed1996

[CGH (comparative genomic hybridization)].

Comparative Genomic Hybridization (CGH) is a powerful new method which allows genome-wide mapping of regions with DNA sequence copy number changes (both increases and decreases) in a single experiment without previous knowledge of the locations of the regions of abnormality. CGH is based on in situ hybridization of differentially labeled total genomic tumor DNA and normal DNA to normal human metaphase chromosomes. After hybridization copy number variations among the sequences in the tumor DNA are detected by measuring the tumor/normal fluorescence intensity ratio for each locus in the target chromosomes. Many previously unknown chromosomal regions with relative copy number changes have been detected in various tumors by CGH. Some changes have been identified as genetic markers associated with biological and clinico-pathological characteristics (i.e., histopathological grade, and clinical outcome). We review the published CGH articles and discuss briefly on current progress in CGH analysis to ovarian and uterine cervical cancer in our laboratory.

DNA, Neoplasm↗
PubMed1996

[Comparative study on the efficacy of ritipenem acoxil and cefotiam hexetil in chronic lower respiratory tract infections by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infections.

Adult↗
PubMed1996

[Erythropoietin improved anemia in a case of multicentric Castleman's disease].

Severe anemia A 37 year-old male with therapy resistant multicentric Castleman's disease (MCD) anemia was treated by subcutaneous injection of erythropoietin. Although immunoglobulin and CRP concentration increased, anemia obviously improved with hemoglobin levels increasing from 4.8 g/dl to 8.5 g/dl without any side effects. Colony assay revealed that the bone marrow mononuclear cells responded to erythropoietin in a dose dependent manner. The mechanism of anemia of MCD is not clearly understood, and treatment is sometimes very difficult. There is no other previous report concerning erythropoietin as a treatment for anemia in MCD.

Adult↗
PubMed1995

Variability of brain lesions in rats administered methylmercury at various postnatal development phases.

The effect of methylmercury chloride (MMC) on the developing rat nervous system was studied by light microscopy. Rats on postnatal day 2 (P2), P15 and P60 were administered 10 mg/kg/day MMC orally for 10 days. In newborn (after P2) rats, there was no abnormal activity or body weight loss. Young (after P15) rats showed weight loss on the 9th day after starting MMC, and subsequently unsteadiness, gait disturbance and paroxysmal convulsions appeared. In adult rats, weight loss began on the 6th day after starting MMC, and the hind-limb crossing phenomenon was induced on the 13th day. Histopathologically, minimal damage was found in the hippocampus and brainstem in newborn rats. In young rats, widespread neuronal degeneration was observed in the cerebral neocortex, CA3 and CA4 regions of the hippocampus, neostriatum, red nucleus, and various brainstem nuclei. In adult rats, neuronal damage was most extensive in the cerebellum and spinal dorsal nerve roots. These findings indicate that neuronal vulnerability to MMC exposure differs depending on the postnatal developmental stage and the brain region in the rat.

Age Factors↗
PubMed1995

Genetic analysis of benign, low-grade, and high-grade ovarian tumors.

Genetic abnormalities were assessed in 56 benign, low-, and high-grade ovarian tumors using comparative genomic hybridization (CGH) and analysis of loss of heterozygosity (LOH). In addition, 95 epithelial tumors were analyzed for microsatellite repeat instability. DNA sequence copy number abnormalities (CNAs) were not detected in the benign tumors, and more were detected in high-grade than in low-grade cancers. Almost no microsatellite repeat instability was detected in these cancers. CNAs occurring in more than 30% of the cancers included increased copy number on 3q25-26 and 8q24 and reduced copy number on 16q and 17pter-q21. Another 14 CNAs occurred in more than 20% of the cancers. Increased copy number at 3q25-26 and 20q13 was the most frequent CNA in low-grade tumors, and increased copy number at 8q24 occurred preferentially in high-grade tumors. The presence of a large number of CNAs per tumor was significantly correlated with reduced patient survival duration. Reduced copy number on 17pter-q21 was most strongly associated with accumulation of a large number of CNAs. The overall concordance between LOH and reduced copy number detected by CGH was 84%, but only 31% of the LOH was associated with reduced copy number detected using CGH.

Chromosome Aberrations↗
PubMed1995

Serotonergic cells in nucleus raphe pallidus provide tonic drive to posterior cricoarytenoid motoneurons via 5-hydroxytryptamine2 receptors in cats.

Microinjection of serotonin and 5-hydroxytryptamine2 (5-HT2) agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in nucleus ambiguus caused excitation of posterior cricoarytenoid (PCA) muscles of the larynx in anesthetized, spontaneously breathing cats. Intravenous administration of 5-HT2 antagonist ketanserin produced complete block of excitatory effect of DOM injection. Electrical stimulation of nucleus raphe pallidus caused excitation of PCA activity, that was blocked by pretreatment of ketanserin. These results indicate that serotonergic cells in the raphe pallidus provide tonic drive to medullary PCA motoneurons through 5-HT2 receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

Stimulatory effect of lead on the proliferation of cultured vascular smooth-muscle cells.

The effect of lead nitrate on the DNA synthesis of cultured bovine aortic smooth-muscle cells has been studied. Lead at 0.5-10 microM stimulated the incorporation of [3H]thymidine into the acid-insoluble fraction of the cells in a dose-dependent manner. However, other heavy metals including zinc, copper, manganese and nickel did not show such a stimulatory effect. Stimulation of [3H]thymidine incorporation by basic fibroblast growth factor was additive to that by lead. However, stimulation by either platelet-derived growth factor or acidic fibroblast growth factor was reduced by the metal. The leakage of lactate dehydrogenase into the medium from smooth-muscle cells, a marker of cell death, was not changed by the metal. Calcium ionophore A23187 inhibited [3H]thymidine incorporation in vascular endothelial cells but stimulated it in vascular smooth-muscle cells. These results suggest that lead may stimulate the proliferation of cultured vascular smooth-muscle cells probably via a calcium-dependent pathway; the metal may mimic calcium within the cells.

Animals↗
PubMed1995

Postcentral neurons of alert monkeys activated by the contact of the hand with objects other than the monkey's own body.

In the caudal postcentral finger region near or in the anterior bank of the intraparietal sulcus of alert monkeys, we found neurons that were activated selectively by the contact of the hand to certain common objects such as bottle brushes, acrylic plates, parts of the stabilized monkey's chair, etc. All of these neurons were not activated when the monkey's hand was contacted with the monkey's own body. We concluded that these neurons are concerned with the haptic discrimination of common objects with the selectivity to one of various material variables of objects, and that the process involves differentiation of the object from the animal's own body.

Animals↗
PubMed1995

Intratumoral DNA heterogeneity of small hepatocellular carcinoma.

BACKGROUND: Intratumoral DNA heterogeneity provides important information regarding biologic and clinical behavior. The purpose of this study was to evaluate the incidence of DNA heterogeneity in small hepatocellular carcinoma (HCC) nodules. METHODS: The DNA content of 28 surgically resected small HCC nodules (< or = 3.0 cm) was measured using flow cytometry of fresh or frozen samples taken from different parts of each nodule with reference to the macroscopic features. RESULTS: Of the 28 small HCC nodules, 14 (50.0%) had only DNA diploid stemline characteristics. Five nodules (17.9%) manifested DNA diploid and DNA aneuploidy within the same tumor. Of the remaining nine nodules (32.1%) that showed only DNA aneuploidy, two contained tumor tissues with apparently different DNA content. Thus, DNA heterogeneity was found in 7 (25.0%) of 28 nodules. DNA heterogeneity correlated well with macroscopic histologic features. All four early HCC were composed of only DNA diploid cells, whereas three of six nodule-in-nodule lesions were composed of DNA heterogeneous cells, in which the inner obviously cancerous nodule showed DNA aneuploidy and the outer well differentiated HCC portion demonstrated DNA diploid. Four of 18 overt HCC nodules showed DNA heterogeneity; 2 of these 4 nodules showed both diploid and aneuploid peaks, and the other 2 two showed different aneuploid peaks within the same nodule. CONCLUSIONS: DNA heterogeneity correlating with macroscopic features is found frequently even in small HCC nodules. Therefore, multiple sampling based on macroscopic features is required for the accurate assessment of DNA ploidy, particularly when the information about DNA ploidy is used as a prognostic indicator.

Aged↗
PubMed1995

Inhibitory effect of lead on the proliferation of cultured vascular endothelial cells.

We investigated the effect of lead nitrate (0.5, 1.0, 2.0 or 5.0 microM) on the proliferation of cultured bovine aortic endothelial cells. After exposure to lead, the number of cells and the incorporation of [3H]thymidine into the acid-insoluble fraction of the cells were reduced in parallel in a concentration-dependent manner. Histologically, lead treatment resulted in a decrease in the cell number accompanied by a change in the cell shape from polygonal to spindle; however, no degenerative change was observed except in 5.0 microM lead-treated cells. Furthermore, stimulation of [3H]thymidine incorporation by either basic or acidic fibroblast growth factor was significantly reduced by lead. However, the leakage of lactate dehydrogenase into the medium from the cells, a marker of nonspecific cell damage, was not changed by lead. From these results, it was revealed that lead inhibits the proliferation of cultured vascular endothelial cells without nonspecific cell damage. Although lead does not destroy the monolayer of endothelial cells, the metal may exhibit its noxious effect in the repair process of the vascular endothelium.

Animals↗
PubMed1995

Semiautomated DNA probe mapping using digital imaging microscopy: II. System performance.

This paper describes an evaluation of a semiautomated, multicolor image-analysis system to map cloned probes along metaphase chromosomes. Mapping with this system consists of fluorescence in situ hybridization (FISH) for probe localization, automatic acquisition of multicolor images showing total chromosomal DNA and probe location(s), and automatic determination of the fractional locations of the probes along the chromosomes relative to the short arm telomere (FLpter). The system was evaluated by mapping ten phage and ten cosmid probes previously mapped to chromosome 3 with other procedures. The standard deviations of FLpter measurements averaged 3.4 Mb and 2.6 Mb for phage and cosmid probes, respectively. With this variation, the order of two probes mapped in separate hybridizations could be determined with 95% confidence when their separation was greater than 2.5 Mb. In all cases, the probe locations and order were consistent with previous mapping data. FLpter values were converted to band locations using measurements of the band locations made using digital imaging microscopy. This proved superior to conversions made using ISCN ideograms.

Bacteriophages↗
PubMed1995

Intraoperative risk factors associated with hepatic resection.

Risk factors associated with complications following hepatic resection were investigated retrospectively in 121 patients between January 1987 and April 1992. Fifty-seven patients recovered uneventfully, but 64 suffered post-operative complications and 15 died within 3 months. All those who died had suffered from hyperbilirubinaemia or bleeding and/or coagulopathy, which were considered critical complications after hepatic resection. Risk factors following hepatic resection were investigated statistically. Stepwise logistic regression analysis showed that serum levels of cholinesterase, the histology of the remaining liver and the volume of intraoperative blood loss were significantly associated with major complications (odds ratio 0.02, 5.14 and 4.97 respectively). Coexisting liver cirrhosis, deterioration of liver protein synthesis and massive intraoperative blood loss are important risk factors following hepatic resection.

Aged↗
PubMed1995

Two distinct descending inputs to the cricothyroid motoneuron in the medulla originating from the amygdala and the lateral hypothalamic area.

1. The retrograde labelling study revealed that there are at least two independent descending pathways from the limbic system to the ventral medulla, i.e., the hypothalamo-medullary pathway and the amygdalo-medullary pathway. 2. The stimulation in the lateral hypothalamic area produced parasympathetic excitation and vocalization response: the recruited motor unit of CT muscle occurred in the late expiratory phase. By contrast, the stimulation at the medial part of the amygdala evoked sympathetic excitation and expiratory braking: the recruited motor unit of CT muscle occurred in the early expiratory phase or in the post-in-spiratory phase. 3. The present physiological study provided further important information on dual innervation of the cricothyroid muscle of the larynx: one motor unit with inspiratory firing is generated in the medulla, whereas the other motor unit with expiratory firing is evoked by a descending input from the limbic system.

Amygdala↗