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Biomedical subjects

T Noda

Publications and source records attributed to T Noda.

At least 307 records · Page 17Linked to original sources

[Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents].

We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Usefulness of intraperitoneal carboplatin administration-- pharmacokinetic analysis].

A bolus of carboplatin (CBDCA) 200-450mg/body (148-292mg/m2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (Pt) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those in blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboplatin↗

[Urinary trypsin inhibitor as an acute phase reactant].

Early in this century, trypsin inhibiting activity has already been recognized in patients with acute infection or renal disease. In addition to these, conditions such as coronary thrombosis, surgical operation, artificial fever by heat-killed bacilli, malignancy, leukemia, later stage of normal pregnancy, etc. have been known to cause the elevated excretion of UTI in urine. Typically, maximal excretion of UTI has been observed within one or two days after the onset. It appears that recent studies have overcome the complexity of UTI molecule. Automated measurement of urinary trypsin inhibitor (UTI) in urine sample was carried out by either enzymic or immunologic method. UTI as well as erythrocyte sedimentation rate and C-reactive protein enables us to monitor acute phase response, being confirmed in cases of abdominal surgery.

Abdomen↗

Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by introduction of rat OTC gene.

We introduced rat ornithine transcarbamylase (OTC) gene into OTC-deficient spf-ash mice by mating spf-ash heterozygotes with transgenic mice which carried recombinant DNA composed of 1.3 kb of the 5' flanking region of the gene fused onto rat OTC cDNA. The liver OTC activity of hemizygous spf-ash mice which carried the transgene was about twice that of nontransgenic spf-ash mice, and the small intestinal OTC activity was 6 times higher; the values being 12% and 27% of the control levels, respectively. The transgenic spf-ash mice showed normal hair growth without sparse fur, nearly normalized urinary orotic acid excretion and normalized serum citrulline concentration.

Animals↗

L-argininosuccinate modulates L-glutamate response in acutely isolated cerebellar neurons of immature rat.

Fura-2 microfluorometry revealed that as little as 10(-13) M L-argininosuccinate, an intermediate of the L-arginine synthesizing pathway, is sufficient to reduce the increase in intracellular free calcium produced by L-glutamate in the acutely isolated cerebellar neurons of immature rats. In these neurons L-argininosuccinate also reduced the response to quisqualate, but not the response to kainate or N-methyl-D-aspartate. The results suggest that L-argininosuccinate may function as a transmitter or modulator in the brain.

Animals↗

Structure-activity relationships in calcitonin gene-related peptide: cyclic AMP response in a preosteoblast cell line (KS-4).

Synthetic analogs of chicken and human CGRP were used to define structure-function relationships in a murine osteoblast precursor cell line, KS-4, that exhibits a substantial cyclic AMP response to CGRP but no response to calcitonin. Human CGRP had 40% of the activity of chicken CGRP, but [Asp-14]-human CGRP was equipotent with chicken CGRP. Similar observations were made previously for calcium- and phosphate-lowering effects. Des-1-Ala,deamino CGRP compounds of both human and chicken origin were three-fold more potent than the respective native CGRPs. The [4-F-Phe)-37]-chicken CGRP analog had a four-fold enhanced activity. In all of the 13 analogs either truncated amino-terminally or missing the (2-7)-disulfide bridge, biologic activity was greatly reduced (0.1% of chicken CGRP), as it was in chicken CGRP-(1-36)-OH, which lacks the C-terminal amino acid. The same analog has been shown to retain a hypocalcemic effect, which is most likely mediated through calcitonin receptors. In confirmation of their antagonistic effect reported in liver, analogs that lack the N-terminal ring structure exhibited significant antagonistic activity. The data illustrate the specificity of CGRP receptors in promoting cyclic AMP formation in osteoblast-like cells. Such CGRP analogs will be useful in investigating structure-function relationships of CGRP.

Animals↗

Teratogenicity study of tri-n-butyltin acetate in rats by oral administration.

A teratological test was carried out on tri-n-butyltin acetate (TBTA) used as a biocide and anti-fouling agent. Pregnant Wistar rats were treated orally with TBTA at dose levels of 0, 1, 2, 4, 8, and 16 mg/kg from days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. In pregnant rats, salivation and depression of body weight gain and food intake were observed at a late stage of pregnancy at the highest dose level of TBTA. Atrophy of the thymus was also observed in a dose-dependent manner on day 20 of gestation. In the fetuses, treatment with the highest dose level increased embryonic and fetal deaths, increased the incidence of fetuses with cleft palate, cervical rib and/or rudimentary lumbar rib, and decreased the body weights of fetuses.

Abnormalities, Drug-Induced↗

Effects of triphenyltin acetate on pregnancy in rats by oral administration.

A teratological test was carried out on triphenyltin acetate (TPTA) used as a fungicide and antifouling agent. Pregnant Wistar rats were treated orally with TPTA at dose levels of 0, 1.5, 3.0, 6.0, 9.0 and 12.0 mg/kg/d during days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. In the pregnant rats, 2 of 13 and 2 of 12 dams died at 9.0 and 12.0 mg/kg, respectively. Vaginal bleeding, bloody mouth and nose, somnolence and depression of body weight gain and food intake were observed at 9.0 and 12.0 mg/kg at late stages of pregnancy. No statistically significant reductions in maternal thymus and spleen weights were observed on day 20 of gestation. Increase in embryonic and fetal deaths and in dams with total resorption of fetuses were observed at doses of more than 6.0 mg/kg. The doses of TPTA in this experiment, however, induced no teratogenic effects in rats.

Abnormalities, Drug-Induced↗

Monoclonal antibodies against CA125-bearing antigenic molecule fragments; reactivity with mucinous ovarian tumours and lung cancers.

We first established a cell strain, SHIN-3, from human ovarian serous cystadenocarcinoma, and performed antigen analysis for CA125 which appeared to be massively secreted by the SHIN-3 cells. Protein digestion analysis revealed that a low molecular weight peptide of 49 kDa showed antigen activity. In the present study, we describe a mouse monoclonal antibody against this low molecular peptide, presumed to be part of the CA125-bearing antigenic molecule. Purified antigen prepared from culture supernatant was adsorbed to nitrocellulose membranes and injected intrasplenically in mice. Of the obtained 398 clones, 10 clones were selected by screening in an ELISA test. Of the 10, two were further selected, i.e. SH-9. This hybridoma produces IgG1 monoclonal antibodies. Immunoblotting analysis revealed that SH-9 recognizes the low molecular peptide used as the immunogen. Immunohistological examination with the SH-9 MAb revealed that the antigen reacted with the bronchial epithelium, cervical glands of the uterus and other various normal tissues. Of tumorous tissues, the antibody mainly reacted with ovarian tumours, but positive reactions were also observed with pulmonary adenocarcinomas or squamous cell carcinomas. Surprisingly the positive rate was high in mucinous tumour of the ovary, while no positive reaction was observed in serous tumours. Dot-blot assay using SH-9 revealed that 17/19 (90%) sera of lung cancer patients were positive for the titre suggesting that SH-9 may be useful to set up a serum test for lung cancers.

Animals↗

Inhibition spectra of solar urticaria: a case report and a review of the Japanese cases.

A 34-year-old Japanese female with solar urticaria is described, who had an episode of urticarial response when she was exposed to indoor fluorescent light first and sunlight later. The action spectrum was found to range from 480 to 520 nm with an inhibition spectrum above 650 nm in the visible light by both postirradiation and preirradiation. Injection of in vitro-irradiated serum did not produce an urticarial wheal on the patient. In the Japanese literature, 17 cases of solar urticaria with inhibition spectra have been reported. The wavelength of the inhibition spectrum was longer than that of the action spectrum in each case.

Adult↗

Complete atrioventricular block induced during left heart catheterization.

Complete atrioventricular block (CAVB) during cardiac catheterization is a rare complication. We describe a patient with preexisting complete right bundle branch block who developed CAVB during left-sided cardiac catheterization. CAVB was induced when a left-sided catheter was passed through the aortic valve. We speculate that the patient's His bundle was injured by mechanical compression. Physicians should always pay attention to the possibility of the development of CAVB during cardiac catheterization, particularly in patients with preexisting heart block.

Animals↗

[The importance of cervical muscles in responses of galvanic body sway test].

Body sway in normal subjects was analyzed by means of various methods to study a role of cervical muscles in galvanic body sway test. Galvanic stimulation through the retro-auricular electrode induced an initial response and a deviation response in body sway. When the anodal stimulation was given through the right retro-auricle during standing, a deviation response toward the right side was observed. While keeping a posture weighted on one foot, the stimulation induced a similar response. The stimulation during squatting produced also a deviation response toward the right side. When the head was rotated to the right, the stimulation produced backward responses. When rotated to the left, it produced forward responses. Even without galvanic stimulation, similar responses were also induced by some other method, for example, inclining the head to one side. Galvanic stimulation while sitting resulted in slight but apparent head inclination. The results suggested that cervical muscles played an important role in galvanic body sway test. Initial and deviation responses appeared to be secondarily produced by changes in the cervical muscular tension.

Adult↗

[Application of Y-chromosome specific DNA analysis for detection of mixed hematopoietic chimerism after allogeneic bone marrow transplantation].

We report a case involving mixed hematopoietic chimerism after an allogeneic bone marrow transplantation (BMT) from a sex mismatched donor. A 31 year-old-man who was diagnosed as having chronic myelogenous leukemia in the accelerated phase received an allogenic BMT from his HLA-identical sister in March, 1989. To determine the mixed chimerism we used the Y-chromosome specific repeated sequence of DNA using a specific probe (PHY 10). The donor's DNA 3.5 kb band appeared in 1-10% of male DNA by Southern blot hybridization in the peripheral blood 21 days after BMT. The Y-chromosome DNA band decreased day by day, and disappeared 110 days after BMT. The Y-chromosome DNA band could be detected, even though few metaphases were obtained immediately after BMT. Thus this method is very sensitive for determining which cells contain the Y-chromosome, and is therefore useful for detecting mixed chimerism after sex-mismatched BMT. Using this method the clinical significance of mixed chimerism can be assessed.

Adult↗

Transgenic mouse model of kidney disease: insertional inactivation of ubiquitously expressed gene leads to nephrotic syndrome.

Transgenic mouse strains carrying proviruses were generated by exposing mouse embryos to a recombinant retrovirus. Animals carrying a single provirus were intercrossed to derive mice homozygous for a given proviral insertion. Adult mice homozygous for the Mpv17 integration developed nephrotic syndrome and chronic renal failure. Histologically, affected kidneys showed progressive glomerular sclerosis. Similar lesions are seen in patients with progressive renal function deterioration. A probe to DNA sequences flanking the provirus detected a 1.7 kb RNA ubiquitously expressed during embryogenesis and in adults with high levels in kidney, brain, and heart. This RNA was not detected in tissues of homozygous animals, suggesting that the provirus interferes with RNA expression. Sequence analysis of the cDNA revealed that the gene encodes a 176 amino acid peptide containing hydrophobic regions, suggesting membrane association of the putative protein. The Mpv17 mutant is a potentially useful experimental system for studying mechanisms leading to renal disorders in man.

Amino Acid Sequence↗

Urea cycle disorder in C3H-H-2 degree mice with juvenile steatosis of viscera.

We determined the activities of urea cycle enzymes in the liver of C3H-H-2 degree-jsv mice. The activities of all urea cycle enzymes decreased in the latter period of lactation. The activities of carbamylphosphate synthetase and ornithine transcarbamylase in some affected mice were undetectable. On the other hand, the activities of enzymes other than urea cycle enzymes were normal. We consider that the decrease in the urea cycle enzymes is caused by an abnormality in the mechanism of gene expression.

Ammonia↗

Automated measurement of trypsin inhibitor in urine with a centrifugal analyzer: comparison with other acute phase reactants.

Automated measurement of trypsin inhibitor in urine was performed with good precision using the COBAS FARA. Elevated levels of both trypsin inhibitor in urine and acute phase proteins in serum were shown in most cases of major abdominal surgery. We suggest that the automated assay of urinary trypsin inhibitor might be useful for the clinical diagnosis of acute phase response.

Acute-Phase Proteins↗

Recovery of the slow inward current from Ca2(+)-mediated and voltage-dependent inactivation in the rabbit sinoatrial node.

The process of recovery from inactivation of the slow inward current (isi) in the rabbit sinoatrial (S-A) node was evaluated by voltage clamp experiments using double microelectrode method. Double pulse experiments were carried out on preparations loaded with Cs+ using nystatin. The rate of the rapid isi inactivation depended on the amplitude of isi rather than the membrane potential. After a 50 ms depolarizing prepulse isi rapidly recovered from inactivation at -40 mV with a time constant of 84 +/- 25 ms, whereas after a longer prepulse, an additional slow recovery phase with a time constant of 1 to 2 s was observed. The amount of isi during the fast recovery phase following a 300 ms prepulse to -20 mV was smaller than that following a prepulse to +20 mV, as predicted by a Ca2(+)-mediated inactivation mechanism. Conversely, a prepulse to +20 mV caused a greater inactivation in the slow recovery phase, suggesting a voltage-dependent mechanism. The inactivation curve obtained during the fast recovery phase using 50 ms prepulses was U-shaped, indicating a predominant role of the Ca2(+)-mediated mechanism, whereas that obtained during the slow recovery phase resembled previously reported voltage-dependent steady state inactivation (f infinity) curve. These results indicate that the fast and slow phases of recovery represent the removal of Ca2(+)-mediated and voltage-dependent isi inactivation, respectively. The presence of Ca2(+)-mediated inactivation via steady state Ca2+ inflows was also suggested.

Animals↗