Anticancer and some biological activities of thiazinotrienomycin B.
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Biomedical subjects
Publications and source records attributed to T Takeuchi.
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A new compound, MK800-62F1, was isolated from a cultured broth of Streptomyces diastatochromogenes MK800-62F1. It inhibited H2O2-induced apoptosis in human small cell lung carcinoma Ms-1 cells as well as in human T-cell leukemia Jurkat cells. In addition, MK800-62F1 also inhibited camptothecin-induced apoptosis in Jurkat cells, which was mediated by intracellular H2O2 generation. MK800-62F1 did not exhibit antioxidative activity in vitro, suggesting that inhibition of apoptosis by MK800-62F1 was not due to the scavenging of H2O2, rather it was due to the modulation of the downstream event of H2O2 generation.
A new compound, MK800-62F1, was isolated from a cultured broth of Streptomyces diastatochromogenes MK800-62F1. The structure was determined by NMR analysis and degradation experiments.
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15-Deoxyspergualin (DSG) inhibited growth of mouse EL-4 lymphoma cells with an IC50 0.02 microg/ml. Even though the cells were treated with DSG for only 4 hours and then washed, the antiproliferative effect lasted long with an IC50 0.4 microg/ml. DSG has spermidine and guanidine moieties in its structure. One decomposed element containing guanidine moiety inhibited the growth at higher doses than DSG, but the effect did not last long unlike DSG. While another element containing spermidine moiety did not affect the growth, it diminished the long-lasting antiproliferative effect of DSG by pretreatment of the cells. Pretreatment with polyamines such as putrescine, spermidine, and spermine also diminished the effect of DSG. Furthermore, N-alkylation of spermidine moiety in DSG abolished the antiproliferative effect. These results suggested that DSG binds to the cells through its spermidine moiety and exerts its long-lasting antiproliferative effect.
New triene-ansamycins designated thiazinotrienomycins F (TT-F) and G (TT-G) and a new diene-ansamycin, benzoxazomycin, were isolated from a culture broth of Streptomyces sp. MJ672-m3 and their structures were elucidated by spectroscopic analyses. The Mean Graphs of TT-G suggests that the tumor growth inhibitory activities are almost as strong as TT-B, in respect of GI50 and TGI against several human cancer cell lines.
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Purpose: The purpose of this study was to elucidate the clinical features of hepatocellular carcinoma (HCC) fed by the internal thoracic artery (ITA). Methods: In seven patients HCC fed by the ITA was confirmed by digital subtraction angiography. The number of previous transcatheter arterial embolization (TAE), the period from the first TAE to TAE of the ITA, tumor location, tumor size, and occlusion of the hepatic artery (HA) and other collateral vessels were explored in each case. Results: The HCCs were located in S4 of the liver (n = 5) and in S8 (n = 1) and were fed by the right ITA and one nodule in S2-3 was fed by the left ITA. Tumor size was 3-10 cm. The number of previous TAE of the HA ranged from 2 to 12. The period from the first TAE to TAE of the ITA was 3-53 months. Angiography of these patients showed occlusion of the HA in six cases, and of the extrahepatic collaterals including the inferior phrenic artery (IPA) in five cases, intercostal artery (ICA) in one case, and epicholedocal artery (EPA) in one case. Conclusion: The ITA often supplies HCC located in the anterior superior region of the liver under the diaphragm; there can be long-term survival with repeated TAE and occlusion of HA.
Functional defects in DNA mismatch repair genes have been shown to be associated mainly with hereditary human malignancies. We examined genomic DNA from 88 sporadic transitional cell carcinomas (TCCs) of the urinary tract for mutations in hMSH6 gene by polymerase chain reaction and direct sequencing analysis. Mutational status of p53 gene was also studied as a potential target of genetic instability secondary to hMSH6 dysfunction. A total of 5 cases (5.7%: 5/88) displayed hMSH6 mutations all consisted of transition and located in exon 4, including three cases with missense mutation and two without change of corresponding amino acid. These three tumors with hMSH6 missense mutation had no microsatellite instability with five microsatellite markers tested. p53 gene mutations were detected in 22 cases (25.0%: 22/88). No tumors with p53 mutation had any hMSH6 missense mutations. Compared to the cases without hMSH6 alterations, the three patients with hMSH6 alterations had more frequent additional primary cancer (P<0.05). These findings provide the first in vivo evidence for the type of alterations and frequency of possible involvement of the hMSH6 mutations in sporadic type urothelial TCCs.
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The patient was a 69-year-old female. Right hemiparesis occurred on April 25, 1996, and then was relieved a day later. Because headache (dull pain in the left) persisted subsequently, she consulted our department on April 26. Head CT showed, without enhancement effect, osseous high density on the surface of the left frontal area. MRI showed high intensity on T1 and low intensity on T2 with flow-void like findings. Cerebral angiography showed a pooling of contrast medium in the same region. 123I-IMP-SPECT revealed reduced cerebral blood flow in the left frontal and parietal lobes just under the same region. On June 11, the patient underwent surgery during which a tumor with arachnoid hypertrophy was extracted en block. Histopathologically, there were abnormal blood vessels with elastic fibers, expanding to an ossified site, and AVM accompanying ossification was thus diagnosed. Postoperative 123I-IMP-SPECT showed improved cerebral blood flow in the left frontal and parietal lobes. The patient was discharged on June 22. The TIA pathologic condition, a symptom of its onset, was considered attributable to cerebral blood flow steal due to AVM.
PURPOSE: To characterize lacrimal gland function and lymphocyte infiltration in patients with Mikulicz's disease (MD) and Sjögren's syndrome (SS). METHODS: Four patients with MD and 5 with SS were recruited, on whom were performed Schirmer test I (Schirmer test without anesthesia), Schirmer test with nasal stimulation, and vital staining of the ocular surface. The lacrimal gland was then biopsied and the tissues stained with CD3, CD4, CD8, B220, APO2.7, Fas, and Fas ligand (Fas-L) antibodies. RESULTS: Although regular Schirmer test results in the MD group were less than 10 mm, those with nasal stimulation, 38.1 +/- 3.4 mm, were significantly greater than the SS group. There were minimal ocular surface changes in MD. Morphologic staining with hematoxylin and eosin was identical in both groups, but the acinar cells were stained with APO2.7 only in the SS group. There was strong Fas and Fas-L staining in SS patients but not in those with MD. CONCLUSIONS: Lacrimal gland acinar cells in those with MD maintained their function and were not programmed for cell death. The sicca syndrome was not observed in MD patients. Although the pathology is similar for MD and SS, the difference in acinar cell apoptosis and function can explain clinical differences.
A technique to identify and isolate live fish primordial germ cells (PGCs) has not been established, in spite of the importance of purified germ cells for molecular and cellular studies. In rainbow trout, the distribution of vasa transcripts is restricted to the germ cell lineage, making this transcript a useful indicator of PGCs. Therefore, in this study, we cloned and characterized the rainbow trout vasa-like gene (RtVLG) regulatory regions and produced transgenic trout carrying the green fluorescent protein (GFP) gene driven by the RtVLG regulatory regions (p vasa-GFP) in order to identify live PGCs in vivo. In transgenic trout carrying the p vasa-GFP construct, cells showing green fluorescence were first observed at the mid-blastula stage; however, no cell-type-specific expression was observed at this stage. At the eyed stage, about 30% of the transgenic embryos showed specific GFP expression in PGCs, and at the hatching stage, about 70% of the transgenic embryos did so. An immunohistochemical study of hatching stage embryos revealed that the GFP-expressing cells are located in genital ridges. This transgenic trout, having visualizable PGCs, will make it possible to isolate live PGCs for in vitro studies and to study the ontogeny of PGCs including sex differentiation in live embryos.
PURPOSE: To clarify clinical characteristics of atypical idiopathic normal pressure hydrocephalus (AINPH) and indications for shunt operations. SUBJECTS AND METHODS: Subjects examined in the present study included 65 patients who satisfied the following 4 diagnostic criteria of AINPH and underwent V.P shunt with Medos type shunt system; set pressure: epidural standard pressure x 13.6 - 20 mmH2O (omission of a figure in the first place). The diagnostic criteria were: 1) no apparent history of intra- or extra-cranial disease; 2) dementia was present as a main complaint; 3) the presence of moderate to severe cerebral atrophy and ventricular enlargement and PVL around the anterior horn on CT scans; 4) normal cerebrospinal pressure and filling of ventricles or subarachnoid space with contrast medium at 24 hours on cisternography. The patients were aged 49-83 with the mean age of 62.9 years; the ratio of male to female was 37:28. They were categorized as shunt-effective (group E: 36 cases) or non-shunt-effective (group NE: 29 cases), and the following parameters in both groups were compared: 1. clinical characteristics: 2. the presence or absence of pressure wave (PW) during preoperative continuous epidural pressure measurement (EDPM) 3. CSF outflow resistance (Ro) 4. preoperative serum alpha-1-antichymotrpsin (alpha-1-ACT) 5. cerebral arteriovenous difference of oxygen content (c-AVDO2) before and after surgery 6. mean cerebral blood flow (mCBF; 99mTc-HMPAO-SPECT) before and after surgery. RESULTS AND CONCLUSIONS: 1. Group E had a shorter duration between symptom onset and hospital visit (within 16 months and showed hyporoluntary and hyporeactivity as their main complaints associated with gait disturbance; the time course of symptoms was classified as suddenly progressing and fluctuating in many cases. Group NE had a relatively longer duration between symptom onset and hospital visit and showed activeness, wandering, nervousness and quick temper as their main complaints; the time course of symptoms was classified as progressing in many cases. 2. PW-positive cases were all included in group E. but some PW-negative cases were also observed in group E. 3. Ro was significantly higher in group E (p < 0.01), and cases with a Ro value over 20 mmHg/ml/min. were all included in group E. 4. alpha-1-ACT was significantly lower in group E (p < 0.05), and cases with an alpha-1-ACT value over 55 mg/dl were all included in group NE. 5. Although preoperative c-AVDO2 was significantly higher in group E (p < 0.05), cases with a c-AVDO2 value over 8.5 ml% were all included in group NE. c-AVDO2 values were within 5-8.5 ml% in all cases of group E. 6. mCBF significantly increased after surgery in group E (p < 0.001). 7. It was confirmed that cerebral atrophy in group E on AINPH is caused by a cerebral circulation disturbance defined as a cerebral blood flow of penumbra or more due to cerebral arteriosclerosis, etc. 8. A flowchart of indications for shunt surgery for AINPH was prepared based on the results of the present study.
OBJECTIVE: In order to clarify relationship among physical growth, mental development of low-birth-weight (LBW) infants and child-rearing anxiety of mothers, a follow-up study was accomplished for LBW cases from birth to three years of age in a regional group. METHODS: A self-administered questionnaire survey was conducted for mothers whose premature infants were born from April 1992 through March 1993 and whose existence was confirmed from April 1995 through March 1996 in Fukui prefecture. A control group was selected from mature infants whose gestation was 37 weeks or more, who were born in the same year and in the same region. The questionnaire was focused on fetal and child growth, as well as child-rearing anxiety. RESULTS: Of the subjects, while including only 6% very LBW infants, the percentage of full-term LBW infants was 55.3% and that of pre-term LBW infants was 44.7%. In the former group, the mean birth weight (MBW) was 2,319 g, the percentage of females was 63.3%, firstborn children was 59.2%, and light-for-dates (LFD) infants due to intrauterine growth retardation 76.9%. In the latter group, the MBW was 1,983 g, the percentage of females was 52.9%, that of firstborn children was 44.5%, and LFD infants was 14.3%. The growth of the LBW infants through the age of three fell into the same category of growth as the upper portion (1,250-1,499 g) of the very LBW infants rather than that of the mature infants. While the growth of appropriate-for-dates (AFD) infants at full-term were normal, that of LFD infants and pre-term infants was insufficient, and the percentage of those demonstrating catch-up of mature infants was less than 80%. The group of pre-term infants was retarded in the gross motor skills, but not language understanding and pronunciation of two-word sentences. The child-rearing anxiety in mothers who delivered pre-term infants was extremely severe after child birth. As the child grew older, however, the feeling of uneasiness was reduced. Mothers who were delivered of full-term LBW infants did not exhibit any fluctuation in child-rearing anxiety during the first three years. CONCLUSION: Fetal size affects growth progress of children. The prognosis of LBW infants is not satisfactory and mothers who deliver full-term LBW infants continue to worry about their child's growth.
The development of sporocysts of Schistosoma mansoni was monitored in pigmented and albino Biomphalaria glabrata from Puerto Rico and Brazil. The snails were exposed individually to 20 miracidia, and sporocysts were allowed to develop for 3 to 12 weeks. Most of the immature sporocysts were found in the seminal receptacle sac and vas deferens during development. In contrast, mature daughter sporocysts were detected everywhere except in the foot at 12 weeks after exposure to the miracidia. It was found that mature daughter sporocysts formed more rapidly in the pigmented than in the albino snails, but no difference was observed in the formative time between the same types of Puerto Rican and Brazilian snails. It seems likely that there is a correlation between the infection rate and the time required for formation of mature daughter sporocysts in B. glabrata.
PURPOSE: The effects of functional training on physical Activities of Daily Living (ADL) based on the Health and Medical Service Law for the Elderly have been controversial. The aim of the present study was to explore its characteristics and influence with a large sample. SUBJECTS AND METHODS: 669 participants and 1,110 non-participants in functional training were recruited from 54 cities and villages in 1998. The effects of functional training on physical ADL were evaluated by comparing the baseline ADL and 1-year follow-up ADL in the "index of Activities of Daily Living for bedridden elderly (1993)". RESULTS: 1. The change in physical ADL in participants was significantly better than that in non-participants after adjusting for age. 2. Significant effects of functional training were observed in both sexes, in all three age groups, and in ranks J, A and B. 3. There was no significant difference between the sexes in terms of the influence of functional training. Functional training was more effective in the younger group, in stroke subjects, and individuals suffering from any disease within one year prior to the baseline. 4. A total of 16.4% of the participants demonstrated increased physical ADL, while 7.2% of the participants also had increased mobility. CONCLUSION: Functional training has a significant positive effect on increase of physical ADL. Functional training based on the Health and Medical Service Law for the Elderly is an effective program especially for homebound and/or frail people who are at risk of becoming bedridden. Further longitudinal studies are now needed to improve functional training for increasing ADL and QOL.
We report a successful case of post operative management by inhaling nitrogen gas for a one-month old infant with high pulmonary blood flow after Blalock-Taussig shunt and plasty of the pulmonary artery. The operation was performed under extracorporial circulation. Nitrogen gas inhalation was dramatically effective for this infant to stabilize his post operative hemodynamic state. This therapy appears to be a very useful and easy handling technique in postoperative management for a patient with high pulmonary blood flow.