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Biomedical subjects

S Kodama

Publications and source records attributed to S Kodama.

At least 181 records · Page 10Linked to original sources

Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells.

Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state.

Animals↗

Carbohydrate structures of human interleukin 5 expressed in Chinese hamster ovary cells.

The asparagine-linked sugar chains of recombinant human interleukin 5 produced by Chinese hamster ovary cells were released quantitatively as oligosaccharides by hydrazinolysis. After N-acetylation followed by NaB3H4 reduction, each oligosaccharide was isolated by paper electrophoresis and serial lectin column chromatography. Study of their structures by sequential exoglycosidase digestion in combination with methylation analysis, revealed that they are bi-, tri-, and tetraantennary complex-type with fucosylated and non-fucosylated trimannosyl cores and high mannose type sugar chains. More than 80% of the sugar chains occur as biantennary complex-type sugar chains. Although acidic oligosaccharides amount to only 14% of the total oligosaccharides, their sialic acid residues occur exclusively as the Sia alpha 2----3Gal group. Removal of the sugar moiety from intact recombinant human interleukin 5 produced a 2.5-fold increase of its activity to induce IgM secretion.

Animals↗

1H-NMR studies of urine in propionic acidemia and methylmalonic acidemia.

The present study deals with the usefulness of 1H-NMR spectroscopy in the chemical diagnosis of propionic acidemia and methylmalonic acidemia. A Varian VXR-500 spectrometer was used. 1H-NMR spectra of urine from a patient with propionic acidemia show peaks of 3-hydroxy-n-valerate, methylcitrate, propionyl glycine, 3-hydroxy-n-butyrate, lactate, 3-hydroxypropionate, tiglylglycine and hippurate. The assignment was made possible by the use of 2D COSY. The spectra from a patient with methylmalonic acidemia show methylmalonate and glycine. 1H-NMR spectroscopy has the advantages of requiring a short time for analysis, relatively small amounts of urine and no preliminary extraction.

Amino Acid Metabolism, Inborn Errors↗

[Measurement of serum eosinophil cationic protein levels in patients with bronchial asthma--analysis according to various clinical backgrounds].

To evaluate the clinical relevance of serum eosinophil cationic protein (ECP) levels, we measured serum ECP levels in 126 asthmatic children, and investigated its relationship with some of the clinical backgrounds. Serum was separated at 1 hour after blood was drawn, and ECP was measured by radioimmunoassay. Serum ECP levels were significantly higher in the patients who had asthma attack within 24 hours than those who did not, and were higher in the patients who had asthma attack almost everyday for the past two weeks than those who had not. In addition, serum ECP levels were correlated with severity of asthma in the previous year, and the patients who had longer history of asthma showed higher levels of ECP. Among the patients who had asthma attacks at the time of blood sampling, serum ECP levels were higher in the patients in whom the attack lasted less than 12 hours than those more than 12 hours. However, no significant correlations were observed between serum ECP levels and the severities of attacks, between serum ECP levels and eosinophil counts. These results suggest that serum ECP level increases during the asthma attack, especially in its chronic active status. Serum ECP may reflect eosinophil activation in vivo and may be a better parameter than eosinophil counts. It is suggested that the measurement of serum ECP level may be useful to evaluate the clinical status of bronchial asthma.

Asthma↗

[Pulmonary edema caused by cardiac ischemic attacks in cases with or without minimal myocardial infarction].

We report cases of angina pectoris or minimal acute myocardial infarction accompanied by pulmonary edema, which were retrospectively studied with regard to their clinical characteristics, prognosis and treatment. Sixteen patients, 5 males and 11 females with a mean age of 72.6 years, admitted to the Cardiovascular Center of Sendai between January 1986 and June 1989, were studied. Ten had previous myocardial infarction. Hypertension, chronic renal failure and diabetes mellitus were found in 10, 7 and 7 patients, respectively. Electrocardiograms during cardiac ischemic attacks showed ST elevation in 8 and ST depression in the other 8 patients. Coronary arteriography which was performed in 6 patients revealed three-vessel disease in 5, and two-vessel disease in one. Mechanical ventilation was indicative of 7, and intraaortic balloon counterpulsation in 2 patients. Coronary artery bypass graft surgery was performed for 3 patients. All patients recovered from pulmonary edema and were discharged. During the mean 15-month-follow-up period, 8 patients died. The causes of death were sudden cardiac death in 3, acute myocardial infarction in one, congestive heart failure in one, post-surgical death in one, and non-cardiac death in 2.

Aged↗

In vitro effects of interleukin 1 on the synthesis of metalloproteases, TIMP, plasminogen activators and inhibitors in human articular cartilage.

Degradation of cartilage matrix macromolecules depends on the increase of metalloprotease activity. It has been suggested that interleukin 1 (IL-1) contributes to cartilage break-down by modulating the synthesis of the elements favoring an activation of these metalloenzymes. We analyzed the effect of IL-1 on the synthesis of collagenase, stromelysin, and tissue inhibitor of metalloproteases (TIMP) in human cartilage explants and culture chondrocytes, as well as its effect on the secretion of plasminogen activators (t-PA, u-PA) and inhibitors (PAI-1, PAI-2) in cartilage explants. Messenger RNA levels of collagenase and TIMP were also analyzed following chondrocyte incubation in the presence or absence of IL-1. We demonstrate that IL-1 stimulates the secretion of metalloproteases and t-PA in a dose dependent manner. At a relatively low concentration (5 pg/ml), IL-1 induced collagenase and stromelysin synthesis in parallel with a decline in TIMP secretion. While IL-1 induced collagenase gene expression, no change in the TIMP mRNA level was noted. The increase in t-PA synthesis was accompanied by a decreased PAI-1 level, while the PAI-2 level remained unchanged. u-PA could not be detected in the culture medium. This study gives insight into the ways that the synthesis, activation and inhibition of metalloproteases are modulated by IL-1. These results support the importance of IL-1 in the etiology of cartilage degeneration.

Blotting, Northern↗

One-step sandwich enzyme immunoassay for soluble human thrombomodulin using monoclonal antibodies.

Six monoclonal antibodies for human thrombomodulin (TM) were prepared. All of them recognized an elastase-digested fragment of TM which contains 6 epidermal growth factor (EGF)-like structural domains. We developed a one-step sandwich enzyme immunoassay for soluble TM by using 2 antibodies; one of them, which inhibited thrombin-binding to TM, was fixed to polystyrene balls, and the other, which did not inhibit the thrombin-binding, but inhibited the protein C-activating cofactor activity of TM, was used as peroxidase-labeled conjugate. The sensitivity of this assay was 1 microgram/l for soluble TM. The level of soluble TM was found to be significantly increased in sera of patients with systemic lupus erythematosus in comparison to the level in sera of healthy subjects.

Adult↗

[Examination of the effects of age on prognostic factors of squamous cell carcinoma of the uterine cervix].

The presence or absence of an association between age and prognostic factors of squamous cell carcinoma of the uterine cervix, including histologic cell type, depth of invasion, stromal reaction, CPL classification, and lymph node metastasis, was examined in 380 patients who had undergone radical hysterectomy. Age affected the rate of lymph node metastasis according to depth of invasion, and the metastasis rates in patients with invasion of 2/3 of the lateral side of the muscular layer (gamma type) in groups of patients in their 30s, 40s, 50s, and 60s were 40.0% (4/10), 59.3% (16/27), 36.7% (18/49), and 21.6% (8/37), respectively. Similarly, the metastasis rates in patients with invasion of the parametrium (delta type) in the above age groups were 100% (1/1), 72.7% (8/11), 46.4% (13/28), and 36.7% (11/30). Lymph node metastasis was significantly less in patients in their 60s than those in their 40s (gamma: p less than 0.01, delta: p less than 0.05). Moreover, 5-year survival rates of patients with lymph node metastasis (tested by Kaplan-Meier method) were 33.3% (N = 4), 65.0% (N = 15), 81.9% (N = 17), and 100% (N = 8) in groups of patients in their 30s, 40s, 50s, and 60s respectively, in the gamma type, and 45.0% (N = 8), 45.7% (N = 10), and 79.6% (N = 11) in groups of patients in their 40s, 50s, and 60s respectively, in the delta type. A significant difference was noted between the group of patients in their 60s and other age groups (gamma: p less than 0.01, delta: p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma von Willebrand factor and thrombomodulin as markers of vascular disorders in patients undergoing regular hemodialysis therapy.

Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are regarded as reflecting the release reaction by vascular endothelial cells and/or endothelial cell injury, and increased levels of thrombomodulin (TM) antigen as reflecting damage to endothelial cells. We investigated changes in plasma vWF:Ag and TM antigen levels during the course of regular hemodialysis treatment (RDT) in 14 patients undergoing RDT in order to evaluate the effect of hemodialysis (HD) on endothelial cells. vWF:Ag and TM were both measured by the sandwich EIA method. Predialysis levels of vWF:Ag and TM in RDT patients were both significantly higher than normal control values. Neither patient age nor blood pressure was not correlated with predialysis vWF:Ag and TM levels. Both vWF:Ag and TM levels significantly increased during a single HD session. There was a positive correlation between predialysis TM levels and duration of HD and an inverse correlation between the amount of vWF:Ag released during HD and duration of HD. It appears that HD procedures induce stimulation and damage of endothelial cells and that long-term, recurrent HD treatment may predispose to vascular disorders.

Adult↗

Rapid one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases. An application for rheumatoid arthritis serum and plasma.

A 1 h, one-step sandwich enzyme immunoassay was set up with a pair of monoclonal antibodies prepared against bovine tissue inhibitor of metalloproteinases (TIMP). TIMP in samples was allowed to react simultaneously with both solid-phase antibody and peroxidase-labeled Fab' of another antibody. Minimum sensitivity was 1 pg/well for bovine TIMP and 1.5 pg/well for human TIMP. The TIMP level in the sera of 38 rheumatoid arthritis (RA) patients (241 +/- 53 ng/ml, mean +/- SD) was significantly higher (P less than 0.001) than the level in the sera of 81 healthy subjects (175 +/- 39). A similar significant difference (P less than 0.001) was observed between the TIMP level in platelet-poor plasma of normal subjects (64 +/- 10) and that of RA patients (84 +/- 23), suggesting that the increase in TIMP seen in RA sera can not be ascribed merely to an increase in platelet-derived TIMP.

Arthritis, Rheumatoid↗

Karyotypic changes with neoplastic conversion in morphologically transformed golden hamster embryo cells induced by X-rays.

Chromosomes from nine morphologically transformed (MT) cell lines (designated MT14 to MT22) of Golden hamster embryo cells induced by X-rays and from tumor-derived cell lines (MT14T to MT22T), obtained after injection of MT cells, were analyzed by the Giemsa banding method. MT cell lines showed a variety of numerical abnormalities. All of the MT cell lines involved trisomy of chromosomes 11 (80 to 100% of cells in each cell line) and 3 (8% of MT22 cells and 100% in other cell lines). Although the latent period for tumor growth differed greatly, eight of nine MT cell lines (MT14 to MT21) produced tumors at the site of injection. All tumor-derived cell lines involved trisomy of chromosome 3 at a 100% rate of incidence. Seven of nine tumor-derived cell lines (MT15T to MT18T, MT20T to MT22T) lost one chromosome 11 from the trisomic condition, resulting in disomy of chromosome 11. These results suggest that trisomies of chromosomes 11 and 3 may play a role in X-ray-induced neoplastic progression.

Aneuploidy↗

Interaction of interleukin-5 with its receptors on murine leukemic BCL1 cells and its implication in biological activity.

Interaction of interleukin (IL)-5 with its receptors on murine leukemic cell line, BCL1 cells was examined. 125I-labeled recombinant murine IL-5(rmIL-5) bound specifically to high-affinity receptors on BCL1 cells. rmIL-5, which was about 2500-fold more active than recombinant human IL-5(rhIL-5) in IgM-inducing activity on BCL1 cells, also showed about 5000-fold higher affinity to receptors. These results suggest that the bioactivity of IL-5 correlates with its receptor-binding activity. When disulfide bond formation was blocked, rmIL-5 dissociated into a monomer and lost its biological activity. This monomeric form of rmIL-5 also lost its ability to bind to cells, suggesting that dimer formation is essential for the biological activity of IL-5.

Animals↗

Restoration of radiation resistance in ataxia telangiectasia cells by the introduction of normal human chromosome 11.

In order to identify the human chromosome which carries a mutated gene in cells from a patient with the hereditary disorder ataxia telangiectasia belonging to complementation group D (AT-D), we performed chromosome transfer experiments via microcell fusion. A single, pSV2neo-tagged chromosome, either 11 or 12, derived from normal human fibroblasts was introduced into AT-D cells by microcell fusion, and clones which were resistant to the antibiotic G418 were isolated. All 3 hybrid clones containing an additional copy number of chromosome 11 showed a restoration of the resistance of wild-type cells to killing by X-irradiation, whereas all 3 hybrid clones containing an additional copy number of chromosome 12 remained hyper-radiosensitive, like the parental AT cells. The results indicate that a defective gene of AT-D cells is also located on chromosome 11, since a genetic linkage analysis has previously suggested that a defective gene of its complementation group A is located on this chromosome.

Ataxia Telangiectasia↗

Beta-glucosidase activity in liver, spleen and brain in acute neuropathic Gaucher disease.

We examined the property of beta-D-glucosidase in normal child liver, spleen and brain tissues and in tissues affected by Gaucher disease using two different kinds of synthetic substrates, 2-hexadecanoylamino-4-nitrophenyl-beta-D-glucopyranoside (HN Glc) and 4-methylumbelliferyl-beta-D-glucopyranoside (MU Glc). HN glucosidase activity was noted only in the particulate fraction of each organ tissues of the normal child, and it was deficient in the tissue affected by Gaucher disease. MU glucosidase activity in the whole homogenate and the soluble fraction showed normal levels for the liver and brain tissue of the Gaucher patient. However, MU glucosidase activity in the particulate fraction, at the vicinity of pH 4.5, for the liver, spleen and brain tissue was deficient in the affected patient. HN Glc was a very easy and useful substrate for the diagnosis of Gaucher disease, but it was not very sensitive. While MU Glc was very sensitive, it was necessary to remove the non-specific beta-D-glucosidase for the diagnosis of Gaucher disease.

Brain↗

Structure of recombinant human interleukin 5 produced by Chinese hamster ovary cells.

The complete peptide map of purified recombinant human interleukin 5 (rhIL-5) was determined to verify its primary structure, glycosylation sites, and disulfide bonding structure. Each peptide fragment generated by Achromobacter protease I (API) digestion was purified and characterized by amino acid analysis and amino acid sequence analysis. After digestion with API, we could identify all the peptides which were expected from human IL-5 cDNA sequence. The analyses of sulfhydryl content in rhIL-5 molecule and disulfide-containing peptide obtained from API digestion indicated that active form of rhIL-5 existed as an antiparallel dimer linked by two pairs of Cys-44 and Cys-86. In addition, we concluded that Thr-3 and Asn-28 were glycosylated. The results indicate that primary structure of rhIL-5 is highly homogeneous and observed heterogeneity is due to the difference in the content of carbohydrate.

Amino Acid Sequence↗

Urinary dicarboxylic acids in X-linked adrenoleukodystrophy.

The urinary excretion of dicarboxylic acids in X-linked adrenoleukodystrophy (X-ALD) was studied. The dicarboxylic acid profile in X-ALD did not show any specific pattern, unlike Zellweger syndrome and neonatal adrenoleukodystrophy. Medium-chain dicarboxylic acids with an even number of carbon atoms (adipic, suberic, sebacic) and an odd number of carbon atoms (pimelic, azelaic) were excreted within the normal ranges. Dicarboxylic acids with more than 10 carbon atoms were not found. These findings may be due to the normal beta-oxidation system of dicarboxylic acids in X-ALD.

Adolescent↗

Unusual intra- and extracranial arteriovenous communication--case report.

The authors report an unusual case of arteriovenous communication between extracranial and intracranial vessels, accompanied by incidentally detected bilateral arachnoid cysts of the middle cranial fossa. A 52-year-old male was admitted with a sudden onset of headache, vomiting, and conjunctival hyperemia of the right eye followed by progressive chemosis and proptosis. He had undergone a craniotomy for hypertensive right putaminal hemorrhage 4 months previously. Angiography showed the main feeding artery to be the superficial temporal artery and the draining veins to be the superficial Sylvian veins and the basal vein of Rosenthal. Partial obstruction of the right cavernous sinus was also shown. At surgery, granulation tissue continued to the dura mater through the skull aperture of previous craniotomy and adhered to the underlying damaged cerebrum. The extremely unusual nature of the communication, the operative findings, and the atypical fistulous figures suggested that communication had occurred postoperatively via newly generated vessels in granulation tissue.

Arachnoid Cysts↗