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Biomedical subjects

A Tada

Publications and source records attributed to A Tada.

At least 55 records · Page 3Linked to original sources
PubMed1996

Presence of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (dG-C8-MeIQx) in human tissues.

One of the mutagenic and carcinogenic heterocyclic amines (HCAs), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), is present in cooked foods and we are chronically exposed to this compound in our daily life. To study the role of HCAs in human carcinogenesis, we analyzed MeIQx-DNA adducts in 38 DNA samples obtained from surgical and autopsy specimens by the 32P-postlabeling method under adduct-intensification conditions with the modification of additional digestion with nuclease P1 and phosphodiesterase I after 32P-labeling at 5'-hydroxyl termini. This modified 32P-postlabeling method can detect N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo- [4,5-f]quinoxaline 5'-monophosphate (5'-pdG-C8-MeIQx) at levels down to 1/10(10) nucleotides. The DNA samples from colon and rectum surgical specimens and a kidney taken at autopsy were found to contain an adduct spot corresponding to that of standard 5'-pdG-C8-MeIQx on TLC at levels of 14,18 and 1.8 per 10(10) nucleotides, respectively. Each adduct spot was extracted from TLC and identified to be 5'-pdG-C8-MeIQx by HPLC. Thus, MeIQx-DNA adducts actually exist in human tissues and this adduct formation may be involved in human cancer development.

Aged↗
PubMed1996

[Home oxygen therapy (HOT) in patients with pulmonary tuberculosis sequelae--comparison between patients medically treated and those surgically treated].

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups. The study included 1537 patients with TBS under HOT followed at National Hospitals and Sanatoriums nationwide in Japan. In 819 patients the treatments were specified and of those 354 were in Group 1, 29 in Group 2, and 436 in Group 3, so that the proportion of surgically treated patients in PTS was estimated between 28.4% (436/ 1537) to 53.2% (436/819). The ages at the onset of tuberculosis, at the start of HOT and the intervals in between were 36.6, 66.2 and 29.8 in Group 1, and 26.8, 65.5, and 38.1 in Group 3 respectively. Though the ages at the start of HOT were the same, those at the onset of tuberculosis were about ten years younger in Group 3 than in Group 1. Comparing Group 1 and 3, the survival rates after the initiation of HOT (Kaplan-Meier method) was better in Group 2 (surgically treated) than in Group 1 (medically treated). It is speculated that the reason could be a better preservation of the function of the remaining lung in the surgically treated and a higher incidence of obstructive impairments in the medically treated patients.

Adolescent↗
PubMed1995

[Interferon production in peripheral blood cells of patients with pulmonary mycobacterial disease].

Production of interferon (IFN)-alpha and IFN-gamma were examined in 31 patients with acute tuberculosis, 12 patients with atypical mycobacterial disease. IFN production was examined in cultures of unseparated fresh whole blood. Production of IFN-alpha was induced by hemagglutinating virus of Japan and production of IFN-gamma was induced by PHA. Patients with mycobacterial disease produced significantly less IFN-alpha than healthy subjects. In patients with acute tuberculosis, effective chemotherapy for 2 months restored IFN-alpha production. Patients produced less IFN-gamma than healthy subjects, but the difference was not significant. Patients with high serum CRP levels tended to produce little IFN-alpha. These results suggest that measurement of IFN production is useful for immunological evaluation of patients with mycobacterial disease.

Acute Disease↗
PubMed1995

Identification of new mutagenic heterocyclic amines and quantification of known heterocyclic amines.

2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine (4'-OH-PhIP) was mutagenic, inducing 180 revertants of Salmonella typhimurium TA98 per 100 micrograms with S9 mix and was formed by heating a mixture of creatine, tyrosine and glucose. It was detected in broiled beef at a level of 21.0 ng per g of broiled beef, which is comparable to the level of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Two new mutagens were isolated from bacteriological-grade beef extract using a new Salmonella tester strain, YG1024, which has a much higher O-acetyltransferase level than TA98. These mutagens were identified as 2-amino-4-hydroxymethyl-3,8-dimethylimidazo[4,5-g]quinoxaline (4-CH2OH-8-MeIQx) and 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline(7,9-DiMeIgQx++ +). The amounts of these mutagenic heterocyclic amines (HCAs) in beef extract were 6.0 ng and 53 ng per g of beef extract, respectively. 4-CH2OH-8-MeIQx induced 326,000 revertants of YG1024 and 99,000 revertants of TA98 per microgram with S9 mix, while 7,9-DiMeIgQx induced 13,800 and 670 revertants of YG1024 and TA98, respectively, per microgram in the presence of S9 mix. The levels of nine previously reported HCAs in cooked meats and fish and in beef extract were determined quantitatively. The level of PhIP was highest (0.56 approximately 69.2 ng/g), followed by that of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (0.64 approximately 6.44 ng/g), and those of other HCAs were 0.03 approximately 2.50 ng/g. Mainstream smoke condensates of five Japanese brands of cigarettes contained four HCAs, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C), at levels of 0.02 approximately 13.5 ng per cigarette and sidestream smoke condensates of two brands of cigarettes contained these HCAs at levels of 0.14 approximately 2.72 ng per cigarette. PhIP was not detected in any sample of mainstream or sidestream smoke condensate.

Amines↗
PubMed1994

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary.

The correlation between histological subtype [endodermal sinus (ES), polyvesicular vitelline (PV), glandular (G) and hepatoid (H) subtypes] and the prognosis of pure yolk sac tumours (YSTs) of the ovary was investigated. From 1964 to 1989, 35 patients with YSTs were treated with primary surgery and adjuvant chemotherapy. The prevalence of histological subtypes was as follows: 14 patients had a single subtype, either ES (12) or G (2); 12 patients had two subtypes, ES+G (4), ES+PV (3), ES+H (4) or G+H (1); six patients had three subtypes, ES+P+H (4) or ES+G+H (2); and three patients had all four subtypes. Multivariate analysis showed that important predictors were FIGO stage, chemotherapeutic regimen and residual tumour size. However, for stage I, multivariate analysis showed that the histological subtype was a superior predictor to the subclassification of FIGO stage I, age or chemotherapeutic regimen (P = 0.03). Kaplan-Meier analysis showed that YSTs composed of an admixture of three or four subtypes was associated with a better prognosis than those composed of one or two subtypes (P < 0.01), other variables being constant.

Adolescent↗
PubMed1994

Isolation and identification of a new mutagen, 2-amino-4-hydroxy-methyl-3,8-dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx), from beef extract.

By monitoring the mutagenicity to a new Salmonella tester strain, YG1024, which has a much higher level of O-acetyltransferase activity than S.typhimurium TA98, we found two new mutagenic compounds in bacteriological-grade beef extract. One of them (compound I), which had a similar UV spectrum to that of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), was isolated and shown to account for approximately 2% of the total mutagenicity of the materials adsorbed to blue cotton, and its concentration was estimated to be 6.0 ng/g beef extract. This amount of compound in beef extract was insufficient to allow measurements of various spectra, but its level was increased approximately 9-fold by heating beef extract with creatine and threonine at 200 degrees C for 5 h. From UV and mass spectra of the compound obtained from beef extract heated with creatine plus threonine, it was deduced to be a hydroxymethyl derivative of aminodimethylimidazo-quinoxaline. Compound I was isolated from the urine of rats given 4,8-DiMeIQx and identified as 2-amino-4-hydroxymethyl-3,8-dimethylimidazo[4,5-f]quinoxaline (4-CH2OH-8-MeIQx) by 1H-NMR analysis. 4-CH2OH-8-MeIQx induced 326,000 revertants of YG1024 and 99,000 revertants of TA98 per micrograms in the presence of S9 mix.

Animals↗
PubMed1994

Identification of N-(deoxyguanosin-8-yl)-2-amino-3,4-dimethylimidazo[4,5-f]quinoline (dG-C8-MeIQ) as a major adduct formed by MeIQ with nucleotides in vitro with DNA in vivo.

The N-hydroxylamine of a carcinogenic heterocyclic amine, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), was reacted with four 2'-deoxynucleoside 3'-monophosphates after O-acetylation. 32P-Postlabeling analysis demonstrated that the adduct was formed with only the guanine nucleotide, and the structure of the compound in the obtained adduct spot was determined to be N-(deoxyguanosin-8-yl)-MeIQ 3',5'-diphosphate (3',5'-pdGp-C8-MeIQ). DNA samples from livers of mice fed MeIQ were also 32P labeled under standard conditions and additionally treated with nuclease P1 and phosphodiesterase I. A single adduct spot was obtained and the structure of the adduct was identified as 5'-pdG-C8-MeIQ. Thus, MeIQ binds at the C-8 position of guanine in vitro and in vivo, like other heterocyclic amines.

Animals↗
PubMed1994

[Therapeutic potential of sparfloxacin for preventing mycobacterial infections].

We studied the therapeutic potential of utilizing sparfloxacin (SPFX), a newly developed quinolone, to prevent various mycobacterial infections. The in vitro activity of SPFX as a preventive agent for various mycobacteria was determined using the actual count method on Ogawa egg medium. The minimal inhibitory concentrations (MICs) of SPFX were as follows: ofloxacin-sensitive M. tuberculosis, 0.16-0.32 microgram/ml; ofloxacin-resistant M. tuberculosis, 0.63-2.5 micrograms/ml; M. avium; 0.63-10 micrograms/ml (MICs were equal or less than 1.25 micrograms/ml in seven out of 11 strains); M. intracellulare, 2.5-10 micrograms/ml (MICs were equal or more than 10 micrograms/ml in 17 out of 23 strains); M. kansasii, < or = 0.08-0.16 microgram/ml; M. fortuitum, < or = 0.08 microgram/ml; M. chelonae subsp. abscessus, > 10 micrograms/ml; M. chelonae subsp. chelonae, 0.63 microgram/ml; M. scrofulaceum, < or = 0.08 microgram/ml; M. nonchromogenicum, 1.25 micrograms/ml; M. xenopi, < or = 0.08 microgram/ml; M. gordonae, < or = 0.08 microgram/ml. The average serum concentrations of SPFX during the period of multiple oral administration (200 mg once a day) were 0.35 +/- 0.16 microgram/ml before administration, 0.67 +/- 0.32 microgram/ml after one hour, 1.13 +/- 0.21 microgram/ml after two hours, 1.27 +/- 0.32 microgram/ml after four hours and 1.31 +/- 0.34 micrograms/ml after six hours. These results indicate that SPFX has a strong therapeutic potential to prevent infections due to M. tuberculosis, M. kansasii, M. fortuitum, M. chelonae subsp. chelonae, M. scrofulaceum, M. xenopi and M. gordonae. Moreover, it may be expected to be a promising agent against infections due to ofloxacin-resistant M. tuberculosis, M. avium and M. nonchromogenicum.

Anti-Infective Agents↗
PubMed1994

[Henoch-Schönlein purpura associated with pulmonary tuberculosis].

A 34-year-old man was admitted to our hospital because of cough and fever. Chest radiograph showed multiple cavities mainly on the right lung. His sputum was positive for acid-fast bacilli on smear, and he was treated with daily isoniazide, rifampicin and streptomycin. Antituberculous treatment was successfully performed, so acid-fast bacilli of his sputa disappeared on smear and culture. Five months later, he developed a purpuric lesions over both legs accompanied by low grade fever and arthralgia, but proteinuria and abdominal pain could not be observed. Laboratory findings showed a normal platelet count and a normal bleeding time. High levels of serum IgG, IgA, C3 and C4 were evident. ASLO and ASK titer were elevated and they markedly increased within two weeks. A direct invasion of the vessel wall by tubercle bacilli is deniable because antituberculous treatment was successfully continued. Henoch-Schönlein purpura was diagnosed judging from these findings. High levels of ASLO and ASK suggest a preceding streptococcal infection for developing purpura but a possible infectious focus could not be identified. He was treated with 15 mg of prednisolone daily for two weeks and the lesion was subsided. The effect of prednisolone suggests that a subsequent antigen-antibody interaction caused by a streptococcal infection may participate in the formation of the purpura.

Adult↗
PubMed1993

Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma.

Previous studies have demonstrated that some human endometrial carcinomas contain an activating point mutation in codon 12 of the Ki-ras protooncogene. To examine the hypothesis that this mutation may occur at an earlier stage of neoplastic progression in the endometrium, we analyzed 89 samples of premalignant endometrial hyperplasia and an additional 84 samples of endometrial carcinoma for point mutations of Ki-ras codon 12. Mutations were found in all three types of endometrial hyperplasia, simple, complex, and atypical, with no clear evidence of a differential distribution in any particular type. Furthermore, the overall incidence of Ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%), indicating that ras mutation may represent an early event in a subset of endometrial carcinomas. When the tissue samples were segregated as to country of origin, the frequency of this mutation was approximately 2-fold higher in hyperplasia and carcinoma samples from Japan than from the United States, where the incidence, clinicopathological characteristics, and risk factors for endometrial carcinoma differ dramatically. There was no apparent correlation, however, between ras mutation and any pathological, histological, or clinical parameter examined, except survival. The presence of a ras mutation was inversely associated with death from disease, suggesting that this molecular feature may characterize a subset of endometrial carcinomas with a good prognosis.

Adult↗
PubMed1993

Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells.

Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided.

Aromatase↗
PubMed1993

Aromatase activity and the effect of estradiol and testosterone on DNA synthesis in endometrial carcinoma cell lines.

Human endometrial and breast carcinoma cell lines were examined for aromatase activity and the effects of sex steroids (estradiol and testosterone) on DNA synthesis. Aromatase activity was high (greater than 500 fmol/10(7) cells/24 h) in the cell lines MCF-7 and OMC-2, moderate (100-499 fmol/10(7) cells/24 h) in the cell lines HEC-59 and Ishikawa, and low (less than 100 fmol/10(7) cells/24 h) in the HHUA cell line. A substantial stimulation of DNA synthesis by estradiol (10(-9)M) was observed in cell lines HEC-59, OMC-2, and MCF-7, with an increase in [3H]thymidine uptake of over 250%. The Ishikawa cell line was stimulated moderately (115-249%). No estradiol-induced increase in DNA synthesis was observed in HHUA. Responsiveness of DNA synthesis to testosterone was observed in cell lines that showed the greatest response to estradiol, namely HEC-59, OMC-2, and MCF-7. Otherwise, estrogen-responsiveness did not always correlated with a significant aromatase activity. These data suggest that some but not all endometrial carcinomas may possess an aromatase-dependent growth stimulating system.

Aromatase↗
PubMed1993

Identification of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethyl-imidazo[4,5- f]quinoxaline 3',5'-diphosphate, a major DNA adduct, detected by nuclease P1 modification of the 32P-postlabeling method, in the liver of rats fed MeIQx.

The carcinogenic heterocyclic amine 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) is widely distributed in cooked foods. The nuclease P1 method increased the sensitivity of the standard 32P-postlabeling analysis about 1000-fold for detection of MeIQx-DNA adducts. The recovery of MeIQx-DNA adducts by the nuclease P1 method was determined to be about 50% using liver DNA of a rat treated with [14C]MeIQx intragastrically. By the nuclease P1 method five adducts were detected in the liver DNA of rats fed MeIQx and two of them, including the most abundant one, were identified as MeIQx-deoxyguanosine adducts by comparison with the adducts formed in in vitro reactions of N-acetoxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with the four 2'-deoxyribonucleotides. The most abundant adduct in vivo was identified as N2-(deoxyguanosin-8-yl)-MeIQx 3',5'-diphosphate (3',5'-pdGp-C8-MeIQx). MeIQx-DNA adduct levels in human tissues could be determined by the nuclease P1 modification of the 32P-postlabeling method in combination with HPLC, and thus provide information on the roles of MeIQx in human carcinogenesis.

Animals↗
PubMed1993

[Cyclosporine disposition in living related donor partial liver transplant recipients].

We studied the disposition of cyclosporine (CyA) in 8 living related donor partial liver transplant recipients (patient A-H). CyA blood levels were determined by fluorescence polarization immunoassay with specific monoclonal antibody (m-FPIA) and fluorescence polarization immunoassay with non-specific polyclonal antibody (p-FPIA). The ratio of the blood levels of CyA determined by p-FPIA to those by m-FPIA varied significantly, because the levels determined by p-FPIA were influenced by the function of graft liver. Thus, the levels of CyA determined by p-FPIA could not be used for the adjustment of CyA dose. The CyA dose ratios [DR; CyA blood level (mg/l)/dose (mg/kg)] of 3 in 8 patients were relatively large in 1-4 d after the transplant operation, however, it decreased within 2-5 d after the operation. CyA DR gradually increased from 5-8 d after the transplantation, and it reached to a maximum in 10-13 d in 5 patients to whom CyA was administered intravenously over 12 d after transplantation. The average ratio of DR in oral administration to that in intravenous one was about 43%. CyA bioavailability in the patient of living related partial liver transplantation was as usual as that in other organ transplant patient except for cadaveric liver transplant patients. The average DR of intravenous CyA administration in liver transplant recipients was 1.5 times larger than that in bone marrow transplant patients. CyA disposition had large inter-individual and intra-individual variation, and CyA blood level and DR varied in clinical time course at least within 1.5 month after operation. Therefore, it is necessary to measure CyA blood level frequently and to adjust CyA dose.

Administration, Oral↗
PubMed1993

[Non-Hodgkin's lymphoma of the bone, with reference to MRI findings following treatment].

A 38-year-old man was admitted to our department on April, 1991 for a progressive mass in his right thigh. He had pain in the same area since April, 1990, but did not notice lymph node swelling until March, 1991. The biopsy specimen of the mass showed diffuse large cell non-Hodgkin's lymphoma (NHL) with an immunohistochemical feature of B cell. He achieved a complete remission (CR) by a doxorubicin-containing combination regimen and received involved field irradiation with a total dose of 35 Gy thereafter. He has been in CR since September, 1991. Primary NHL of the bone is rare and there have been few reports on MRI findings during the treatment. These findings and management of primary NHL of the bone were discussed.

Adult↗
PubMed1993

Alternating chemotherapy of CHOP-Bleo and POEM-Bleo for diffuse large-cell lymphoma: a single-institutional study with a long-term follow-up.

Diffuse large-cell lymphoma (DLCL) is a neoplasm that is curable with chemotherapy in an appreciable percentage of patients. However, not all patients are cured and the best drug combination and optimal dose intensity have not yet been established. In an attempt to improve complete response rate and survival with minimal toxicity, we devised an alternating combination chemotherapy consisting of CHOP-Bleo (cyclophosphamide, doxorubicin, vincristine, prednisolone, and bleomycin) and POEM-Bleo (prednisolone, vincristine, etoposide, mitoxantrone, and bleomycin). Between March 1986 and October 1990, 30 newly-diagnosed patients with advanced DLCL were treated with the regimen. Of these 30 patients, 14 (47%) were 61 years of age or more, 15 (50%) had stage IV disease, 14 (47%) presented with constitutional symptoms, and 7 (23%) had T-cell lymphoma. After the completion of therapy, 23 (77%) achieved a complete response and 6 (20%) had a partial response. The actuarial relapse-free survival at 5 years is 52% and the overall survival projected to 5 years is 47%. Toxicity was generally mild and well tolerated. Although this alternating regimen had substantial activity as front-line chemotherapy for advanced DLCL, we conclude that the observed response rate and survival do not essentially differ from those achieved with conventional regimens and further clinical trials are thus not warranted.

Adult↗