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Biomedical subjects

H Osada

Publications and source records attributed to H Osada.

At least 109 records · Page 6Linked to original sources
PubMed1998

Molecular cloning of human TAK1 and its mutational analysis in human lung cancer.

In previous reports, we described that DPC4/Smad4 and Smad2 are mutated in a fraction of human lung cancers and suggested possible roles of the downstream mediators of transforming growth factor-beta (TGF-beta)-elicited signals in the pathogenesis of this most common cancer. In the present study, we investigated whether another downstream mediator, human TGF-beta-activated kinase 1 (hTAK1), also is altered in lung cancer. For this purpose, the hTAK1 gene was cloned with the aid of an expression sequence tag database search and cDNA library screening, and hTAK1 was found to be expressed ubiquitously in 2 distinct isoforms regulated in a tissue-specific manner in fetal and adult normal tissues. Interestingly, hTAK1 was assigned to the chromosome region 6q14-21, which is deleted frequently in various human malignancies, including lung cancer. Despite our extensive search for alterations in 39 lung cancer specimens as well as in 16 lung cancer cell lines, somatic mutations of hTAK1 were not identified, indicating that hTAK1 itself is not a frequent target for genetic alterations in lung cancer.

Amino Acid Sequence↗
PubMed1998

Primary mediastinal seminoma. Efficacy of chemo-radiotherapy alone.

A treatment policy must be established for primary mediastinal seminoma. We have treated five patients with this entity during 18 years. All our patients presented with a bulky mass as is usual for this disease. Our first patient was treated surgically and then with radiation, but developed recurrences and died 11 years after the initial diagnosis. Three subsequent patients, one with multiple lymph node metastases, were treated with radiation followed by cisplatin. Our most recent patient received two courses of adriamycin-reinforced PVB, and then radiation for consolidation, followed by another course of chemotherapy. For these five patients, the 5- and 10-year survival rates were both 100%. A review of the literature emphasized the fact that either radiation or surgery has recently been replaced by chemotherapy as the front-line treatment of this rare tumor in light of a better response to the latter form of treatment. We fully agree with this policy. Based on the favorable long-term results of our patients we conclude that chemo-radiotherapy can cure primary mediastinal seminoma, even in its extended form, without surgery. An initial three courses of cisplatin-based chemotherapy like adriamycin-reinforced PVB or BEP should be followed by radiation of up to 4,000 cGy for consolidation. Surgery may play a limited role for tumors that are small at presentation, or for any possible viable residue seen on roentgenograms following chemo-radiotherapy.

Adult↗
PubMed1998

Pure yolk sac tumor of the ovary with mosaic 45X/46X + mar Turner's syndrome with a Y-chromosomal fragment.

A pure yolk sac tumor (endodermal sinus tumor) of the dysgenetic gonad developed in a 23-year-old woman whose karyotype was mosaic 45X/46X + mar Turner's syndrome is reported. Molecular biological studies showed that the patient's DNA contained a fragment of Y chromosome. This case seems to be extremely rare case of developing a pure yolk sac tumor in a patient with mosaic Turner syndrome with a Y-chromosomal fragment.

Adult↗
PubMed1998

Tissue factor is associated with the nonbacterial thrombotic endocarditis induced by a hypobaric hypoxic environment in rats.

High-altitude hypoxia causes a hypercoagulable state. In our previous study on the blood coagulation system in rats, nonbacterial thrombotic endocarditis (NBTE) developed after 4-12 weeks' exposure to the equivalent of 5500 m in altitude. We hypothesized that TF (tissue factor)-producing cells in the cardiac valves might be induced by the hypobaric hypoxic environment (HHE) and then trigger NBTE. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m altitude for 1-12 weeks. We measured TF activity in the plasma and studied morphological changes in the mitral valves using immunohistochemical and immunoelectrical methods for TF protein and in situ hybridization for TF mRNA. After 4 weeks or more of exposure to HHE, 28 of the 56 surviving rats had developed NBTE. After 4-8 weeks' exposure to HHE, the plasma TF activity level was significantly higher than in control rats. There was a significant correlation between plasma TF activity and the incidence of NBTE. After 1 weeks' exposure to HHE, immunoreactivity for TF protein was detected in foamy macrophages and stromal cells in the cardiac valves. In rats with NBTE, TF protein was present in foamy macrophages and spindle stromal cells and focally present in the extracellular matrix. TF mRNA was detected in some foamy macrophages within the thrombus, TF protein was localized to the rough endoplasmic reticulum and plasma membrane of many macrophages, some fibroblasts, and a few endocardial cells. TF is associated with the pathogenesis of the NBTE induced by exposure to HHE. The accumulation of TF-producing macrophages during exposure to HHE may be responsible for initiating thrombus formation.

Animals↗
PubMed1998

Genetic differentiation of complete hydatidiform moles coexisting with normal fetuses by short tandem repeat-derived deoxyribonucleic acid polymorphism analysis.

OBJECTIVE: We applied deoxyribonucleic acid polymorphism analysis on the basis of differences in the number of short tandem repeat sequences to genetically differentiate dizygotic twins with complete hydatidiform moles and normal fetuses from partial moles presenting a similar appearance. STUDY DESIGN: Six pregnant women exhibiting apparent moles and coexisting fetuses were the subjects of this study. Eight polymorphic loci including short tandem repeat sequences were amplified by polymerase chain reaction from deoxyribonucleic acid of peripheral leukocytes of parents, umbilical cord, grossly normal placenta-villi, and molar tissue. The segregation of alleles among samples were determined by comparing band patterns on polyacrylamide gels. RESULTS: In all 6 cases amplifications of polymorphic loci provided sufficient information to determine the parental origin. At informative loci the alleles of cord and placenta-villi were transmitted from both patients and husbands whereas molar tissue had only paternal alleles. These allele segregations indicated 2 different genetic origins, namely, normal parental for a fetus and androgenetic for molar tissue, and thus the diagnosis of dizygotic twins with a complete hydatidiform mole and a normal fetus was made. Additionally, the molar component was defined as a heterozygous mole in 2 cases. CONCLUSION: Short tandem repeat-derived deoxyribonucleic acid polymorphism analysis was demonstrated to be a useful and precise procedure for the differential diagnosis of a complete hydatidiform coexisting with a normal fetus and the determination of its zygosity as well.

Adult↗
PubMed1998

Intraoperative TEE during mitral valve repair: does it predict early and late postoperative mitral valve dysfunction?

BACKGROUND: Intraoperative transesophageal echocardiography (TEE) using color Doppler flow mapping can accurately measure residual mitral regurgitation (MR), but it is unknown to what extent such measurements correlate with those obtained with postoperative transthoracic echocardiography (TTE). METHODS: We used intraoperative TEE (based on direct planimetry of the maximal regurgitant jet area) to measure residual MR in 42 patients who underwent mitral valve reconstruction for MR and compared these measurements with those obtained with early and late postoperative TTE. RESULTS: Residual MR as measured by intraoperative TEE correlated significantly with values obtained with both early (r = 0.66; p < 0.0001) and late (r = 0.71; p < 0.0001) postoperative TTE. Forty patients with no or trivial MR (< or =2 cm2) as measured by intraoperative TEE also had no or trivial MR as measured by early (probability of 87.5%) and late (probability of 80.0%) postoperative TEE. Of the 40 patients, 6 had clinically insignificant mild MR (< or =4 cm2) when measured by late postoperative TTE. Two other patients in whom intraoperative TEE showed mild MR developed moderate regurgitation about 3 months later. CONCLUSIONS: Intraoperative TEE correlates with early and late postoperative TTE in measurement of residual MR, suggesting it can reliably predict early and late postoperative mitral valve dysfunction.

Echocardiography, Doppler, Color↗
PubMed1998

Effect of maternal hydration on oligohydramnios: a comparison of three volume expansion methods.

OBJECTIVE: To determine the effect of maternal hydration with intravenous (i.v.) isotonic fluid, i.v. hypotonic fluid, and oral water on amniotic fluid index (AFI) in women with oligohydramnios. METHODS: Patients with low AFI and gestational age over 35 weeks without maternal complications were randomized into four groups (2 L/2 h i.v. isotonic fluid, 2 L/2 h i.v. hypotonic fluid, 2 L/2 h oral water, control). Maternal plasma osmolality, AFI, hematocrit, and hemoglobin concentration were measured before and after hydration. RESULTS: Eighty-four patients (n=21/group) completed the study without any maternal adverse effects. The mean increase in AFI after hydration was significantly greater in the i.v. hypotonic and oral water groups (2.8+/-1.9, P < .001; 3.8 +/-1.9, P < .001, respectively), but not in the i.v. isotonic group (0.5+/-1.1), compared with the control group (0.5+/-1.1). Significant decreases in maternal hematocrit and hemoglobin concentration were found only after i.v. isotonic hydration (32.0+/-2.9 to 29.5+/-2.3, P < .001; 11.0+/-1.6 to 10.1+/-1.4, P < .001, respectively). Changes in maternal osmolality correlated with the changes in AFI in both the i.v. hypotonic group (r=.58, P < .001) and oral water group (r =.63, P < .001). CONCLUSION: Maternal hydration with either i.v. hypotonic fluid or oral water increases AFI in oligohydramnios. Maternal osmotic change rather than maternal volume expansion had a more direct impact on increasing amniotic fluid volume with short-term acute hydration.

Adult↗
PubMed1998

p53 mutations in non-small-cell lung cancers occurring in individuals without a past history of active smoking.

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an association between the presence of p53 mutations and lifetime cigarette consumption. Although over 675 p53 mutations have been reported in lung cancers in the literature thus far, very little is known about the nature of such changes in lung cancers in the absence of a smoking background. In the present study, we therefore analysed 69 non-small-cell lung cancer specimens from individuals without any history of active smoking and identified p53 mutations in 26% of the cases. Statistical analysis of the present cohort of non-smokers also showed absence of significant relationship between p53 mutations and age, sex, histological type or disease stage. Comparison of mutational spectra between the present results in non-smokers and previously reported mutations in smokers clearly demonstrated G:C to T:A transversions to be significantly less frequent in non-smokers than in smokers (OR 5.35, 95% CI 1.77-16.12). Interestingly, G:C to C:G and G:C to A:T mutations were also observed in tumours of non-smokers at similar frequencies to G:C to T:A mutations, suggesting that these mutations can occur relatively frequently in the absence of active smoking. This study is, to our knowledge, the largest so far analysing a well-defined cohort of non-smokers in a single laboratory.

Adult↗
PubMed1998

Molecular analysis of a Myc antagonist, ROX/Mnt, at 17p13.3 in human lung cancers.

The chromosome region 17p13 is known to be frequently deleted in lung cancers. We recently showed the presence of an independent, commonly deleted region at 17p13.3, suggesting that in addition to p53 at 17p13.1 an as-yet-unidentified tumor suppressor gene may reside in this telomeric region. Interestingly, the chromosomal location of a recently isolated novel myc antagonist gene, termed ROX/Mnt, coincides exactly with the centromeric border of the commonly deleted region at 17p13.3 in lung cancers. In conjunction with the generally acknowledged roles of myc genes in the pathogenesis of lung cancers, these findings led us to investigate whether ROX/Mnt is altered in lung cancers. Despite an extensive search for alterations in 52 lung cancer specimens. somatic mutations of ROX/Mnt could not be identified. We conclude that ROX/Mnt itself is not a frequent target for 17p13.3 deletions in lung cancers and that further explorations are required to identify the putative tumor suppressor gene at 17p13.3.

Amino Acids↗
PubMed1998

Selective inhibition of the bacterial peptidoglycan biosynthesis by the new types of liposidomycins.

We examined the inhibitory activity against bacterial peptidoglycan biosynthesis, mammalian glycoprotein biosynthesis and growth of BALB/3T3 cells of four different types of liposidomycins which have the structure with or without sulfate and/or 3-methylglutaric acid moieties. Liposidomycins inhibited peptidoglycan biosynthesis about 30 to 500 times more effectively than tunicamycin, whereas liposidomycins inhibited mammalian glycoprotein biosynthesis about 30 to 300 times less effectively than tunicamycin. When the cytotoxic effect of liposidomycins and tunicamycin on the growth of mammalian cells were compared, liposidomycins did not show toxicity against BALB/3T3 cell at 25 microg/ml, though tunicamycin inhibited cell growth by 50% at 0.05 microg/ml. On the basis of these results, it is concluded that liposidomycins are selective antibiotics showing highly specific inhibition toward bacterial peptidoglycan biosynthesis.

3T3 Cells↗
PubMed1998

New types of liposidomycins that inhibit bacterial peptidoglycan synthesis and are produced by Streptomyces. I. Producing organism and medium components.

Liposidomycins are atypical lipid-bearing nucleoside antibiotics that inhibit bacterial peptidoglycan synthesis. A producing strain was identified as a Streptomyces sp. from its cultural characteristics and physiological properties. It produced new types of liposidomycins that lacked sulfate and/or 3-methylglutaric acid moieties present in known liposidomycins by changing medium components. Sucrose and malt extract were particularly suitable sources for specific production of the new types of liposidomycins.

Aminoglycosides↗
PubMed1998

New types of liposidomycins that inhibit bacterial peptidoglycan synthesis and are produced by Streptomyces. II. Isolation and structure elucidation.

Various new liposidomycins were isolated from a culture of the strain Streptomyces sp. SN-1061M by changing medium components and they were classified into four types (I-IV) based on their structures. They were purified by butanol extraction, silica gel and LH-20 column chromatographies, and high performance liquid chromatography on ODS columns. Type (I) has the original structure which has sulfate and 3-methylglutaric acid moieties. Type (II) has no 3-methylglutaric acid moiety and type (III) has no sulfate moiety. Type (IV) has neither moiety. Type (III) and (IV) compounds, which have no sulfate moiety, exhibited more potent antimicrobial activity.

Aminoglycosides↗
PubMed1998

Bioprobes for investigating mammalian cell cycle control.

Bioprobes are low molecular weight compounds which are useful for investigating mammalian cell functions. The use of bioprobes has substantially assisted the investigation of complex biochemical processes of the mammalian cell cycle. In this review, cell cycle inhibitors mainly isolated from the microorganism are described and their possibility as an antitumor agents is considered. Most cancer cells have some abnormality in the control mechanism of cell cycle progression. Cyclin-dependent kinases (Cdk), which are activated by the binding with the cyclin and simultaneously by the phosphorylation/dephosphorylation of itself, play important roles as engines in the cell cycle. Tubulins are considered to be one of the most important proteins of the cell division machinery. Therefore, Cdk inhibitors and tubulin binders are possible anticancer drugs. Since the function of proteins controlling the cell cycle is also regulated by phosphorylation and dephosphorylation, inhibitors of protein kinases and phosphatases are considered as possible an antitumor agents. We expect that some bioprobes will be developed for clinical use.

Animals↗
PubMed1998

Inhibition of human telomerase activity by alterperylenol.

Human telomerase is a ribonucleoprotein that maintains telomeres by adding TTAGGG tandem repeat sequences using RNA template of the enzyme. Telomerase activity is highly expressed in immortalized cells but not in most somatic cells, except for some renewal tissues, such as hematopoietic stem cells. Therefore, telomerase can be a target for anticancer drugs. Here we show that a fungus metabolite, alterperylenol, inhibits human telomerase activity. Alterperylenol inhibited telomerase activity (IC50 = 30 microM), but altertoxin I, a structurally related compound, did not affect it at 1 mM. Moreover, alterperylenol did not affect the activity of viral reverse transcriptase at 1 mM.

Benz(a)Anthracenes↗