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71.
Hydroxyamino, nitroso and nitro derivatives of 3-amino-1-methyl-5H-pyrido[4,3-b]indole(Trp-P-2) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole(Glu-P-1), mutagens-carcinogens produced on pyrolysis of aminoacids, were synthesized from Trp-P-2 and Glu-P-1. 3-Hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole(N-OH-Trp-P-2) and 2-hydroxyamino-6-methyldipyrido[l,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) were obtained with good yieldsby controlled catalytic reduction of 3-nitro-l-methyl-5H-pyrido[4,3-b]indoleand 2-nitro-6-methyldipyrido[1,2-a:3',2'-d]imidazole. Subsequentoxidation of N-OH-Trp-P-2 and N-OH-Glu-P-1 with -manganese dioxideyielded 3-nitroso-1-methyl-5H-pyrido[4,3-b]indole and 2-nitroso-6-methyldipyrido[1,2-a:3',2'-d]imidazole.All six synthesized compounds were mutagenic to Salmonella typhimuriumTA98 without mammalian activation systems. The mutagenic activitiesof hydroxyamino and nitroso derivatives were identical for bothS. typhimurium TA98 and TA98NR, the nitroreductase deficientstrain. However, nitro derivatives were essentially mutageniconly towards S. typhimurium TA98. 相似文献
72.
73.
Toshihiko Iizasa Hao Chang Makoto Suzuki Mizuto Otsuji Sana Yokoi Masako Chiyo Shinichiro Motohashi Kazuhiro Yasufuku Yasuo Sekine Akira Iyoda Kiyoshi Shibuya Kenzo Hiroshima Takehiko Fujisawa 《Clinical cancer research》2004,10(16):5361-5366
PURPOSE: The aim of this study was to determine whether collagen XVIII expression is correlated with circulating serum endostatin and whether this has any prognostic value in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Serum endostatin levels were measured quantitatively by a competitive enzyme immunoassay, and collagen XVIII expression in tumor tissue was investigated with an immunohistochemical method in a series of 94 patients who underwent surgery for NSCLC. RESULTS: Sixty cases (63.8%) had positive immunohistochemical staining with anticollagen XVIII polyclonal antibodies, including strongly positive staining in 11 (11.7%) cases. The mean (+/- SD) serum endostatin level was 41.6 +/- 34.4 ng/ml in the patient group and 16.3 +/- 10.3 ng/ml in the control group (P < 0.0001). The 11 cases who were strongly collagen XVIII-positive had significantly higher serum endostatin levels than the cases who were negative or weakly positive (P = 0.0297). The 5-year survival rates of negative, weakly positive, and strongly positive patients were 77.8%, 56.9%, and 43.8%, respectively. The cases with strongly positive collagen XVIII expression had a significantly poorer outcome than cases with negative expression (P = 0.0027). A multivariate analysis with Cox proportional hazards model for disease-specific survival revealed that expression of collagen XVIII (strongly positive versus negative; weakly positive versus negative), tumor classification, and regional lymph node classification were independent prognostic factors. CONCLUSIONS: Our results suggest that expression of collagen XVIII in tumor tissue is strongly associated with a poorer outcome in NSCLC and correlates with elevated levels of circulating serum endostatin. 相似文献
74.
Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney 总被引:5,自引:0,他引:5
Nakajima N Sekine T Cha SH Tojo A Hosoyamada M Kanai Y Yan K Awa S Endou H 《Kidney international》2000,57(4):1608-1616
BACKGROUND: The cDNA of the multispecific organic anion transporter 1 (OAT1) responsible for the tubular secretion of organic anions was recently isolated. In the current study, we investigated the developmental changes in OAT1 expression in the rat kidney. METHODS: Ontogenic expression of rat OAT1 was investigated by Northern blot, in situ hybridization, Western blot, and immunohistochemical analysis. In addition, para-aminohippurate (PAH) accumulation was measured using fetal, neonatal, and adult rat kidney slices. RESULTS: In Northern blot analysis, OAT1 was detected as early as on embryonic day 18 in the fetal kidney. The expression level of OAT1 mRNA increased remarkably just after birth (postnatal day 0). In situ hybridization revealed OAT1 expression on embryonic day 19. In both the fetal and neonatal kidneys, OAT1 mRNA was localized in a relatively deep region in the cortex. Western blot analysis detected OAT1 protein on embryonic day 20, and the expression level increased after birth. Immunohistochemical analysis did not reveal OAT1 staining in the fetal kidneys. A faint signal of OAT1 protein was detected on postnatal day 0; thereafter, the expression level increased. In the functional study using kidney slices, low but definite probenecid-sensitive PAH accumulation was noted in fetal rat kidney on embryonic day 20. After birth, probenecid-sensitive PAH uptake was increased. CONCLUSIONS: The present study consistently demonstrates the remarkable increase of OAT1 expression after birth, and the immature excretory capacity of the proximal tubules of the neonatal kidney can be attributed, at least in part, to the low expression level of OAT1. 相似文献
75.
Hitoshi Kotanagi Toshiaki Yoshioka Osamu Muto Hiroshi Kon Ryuichi Yanagida Masanao Ito Toshiki Kikuchi Kenji Koyama 《International journal of clinical oncology / Japan Society of Clinical Oncology》1997,2(3):133-137
Background Japanese surgeons have to macroscopically assess nodal metastasis from colon cancer according to the general rules established
in Japan. Adjuvant therapy is sometimes started after macroscopic assessment of nodal metastasis. Macroscopic assessment,
however, is difficult in many cases.
Methods We evaluated the reliability of macroscopic assessment of nodal metastasis in colon cancer by (1) comparing the number of
nodes picked up macroscopically with that of nodes recognized microscopically, and (2) by comparing the number of metastatic
nodes found between macroscopic and microscopic examination.
Results The number of nodes found during macroscopic examination was equal to that found in microscopic examination in only 52 of
206 cases (25%). Although 120 of 206 cases (58%) were judged macroscopically to have metastatic nodes, 61 had no metastatic
nodes found microscopically. Sensitivity and specificity for the recognition of cases with nodal metastasis was 85.5% and
55.5%, respectively. The number of metastatic nodes in macroscopic examination was equal to that in microscopic examination
in 90 cases (44%).
Conclusion Because macroscopic assessment of nodal metastasis is not reliable, physicians should not rely on macroscopic assessment to
indicate the need for further therapy, such as adjuvant chemotherapy. The recommendation for macroscopic assessment of nodal
metastasis should be eliminated from the general rules in Japan. 相似文献
76.
Seiji Kawakita Ryuichi Aibara Yuji Kawamura Eiji Yumoto Junzo Desaki 《The Laryngoscope》1998,108(3):398-402
The authors investigated the process of denervation and reinnervation of the interarytenoid (IA) muscle in the guinea pig using transmission electron microscopy and glycogen depletion technique after unilateral transection of the recurrent laryngeal nerve (RLN) and superior laryngeal nerve to clarify the innervation pattern of the unpaired IA muscle. Anastomosis between the bilateral arytenoid branches was confirmed in the belly of the IA muscle. Five weeks after transection, all of the IA muscle fibers appeared to have been reinnervated by the contralateral RLN. As the arytenoid branch of the RLN runs together with that of the contralateral RLN in a single intramuscular nerve funiculus, it is possible that collateral sprouting branches grow and extend into the adjacent denervated Schwann's sheaths. The authors conclude that the unpaired IA muscle, as a whole, receives specific motor nerve supply from the bilateral RLNs, although each muscle fiber is innervated unilaterally. 相似文献
77.
Kasai T; Ohe Y; Nishio K; Kunitoh H; Tamura T; Sekine I; Kubota K; Yamamoto N; Nakamura Y; Shinkai T; Kodama T; Saijo N 《Japanese journal of clinical oncology》1998,28(3):214-221
BACKGROUND: It is important to minimize the incidence of ineligible cases
to improve the quality of clinical trials. To determine factors which may
influence the incidence of ineligible cases, the incidence of and reasons
for ineligibility in clinical trials were retrospectively analyzed.
METHODS: We retrospectively examined the incidence of and reasons for
ineligibility for inclusion in eight clinical trials conducted by the Lung
Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group and
four trials financed by trust funds from a pharmaceutical company. RESULTS:
In these 12 clinical studies, the incidence of ineligibility was 4.2%
(32/762) (range 0-10.6%). Specific factors that might influence the
incidence of ineligible cases were then analyzed. There was a significant
difference in the incidence of ineligibility between the methods of
registration (P < 0.05). The incidences using a central registration and
without using a central registration system were 2.8% (9/322) and 5.2%
(23/440) respectively. We also analyzed ineligible cases in clinical
studies published in the Journal of Clinical Oncology. In clinical studies
published in the Journal of Clinical Oncology recently and 10 years ago,
the incidences of ineligible cases were 5.0% (942/18 878) and 4.1%
(206/4995) respectively. In clinical studies on lung cancer published in
the Journal of Clinical Oncology from 1984 to 1995, the incidence of
ineligible cases was 4.7% (900/19,116). There was no significant difference
in the incidence of ineligible cases between our 12 studies and the Journal
of Clinical Oncology clinical studies by the chi 2 test (P > 0.05).
CONCLUSIONS: We conclude that the incidence of ineligible cases in our
studies is similar to that in clinical trials published in the Journal of
Clinical Oncology. Central registration systems are useful for checking for
ineligibility, and to increase the quality of clinical trials.
相似文献
78.
79.
Kiyokazu Takebayashi Yoshimoto Sekine Nori Takei Yoshio Minabe Haruo Isoda Hiroyasu Takeda Katsuhiko Nishimura Kazuhiko Nakamura Katsuaki Suzuki Yasuhide Iwata Harumi Sakahara Norio Mori 《Neuropsychopharmacology》2004,29(5):1019-1026
Long-term toluene abuse causes a variety of psychiatric symptoms. However, little is known about abnormalities at the neurochemical level in the living human brain after long-term exposure to toluene. To detect neurochemical changes in the basal ganglia of subjects with a history of long-term toluene use, proton magnetic resonance spectroscopy (1H MRS) was performed in 12 abstinent toluene users and 13 healthy comparisons with no history of drug abuse. N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr + PCr), choline-containing compounds (Cho), and myo-inositol (MI) levels were measured in the left and right basal ganglia. The Cho/Cr + PCr ratio, a marker of membrane metabolism, was significantly increased in the basal ganglia of toluene users in comparison to that of the control subjects. Furthermore, the increase in the Cho/Cr + PCr ratio was significantly correlated with the severity of residual psychiatric symptoms. These findings suggest that long-term toluene use causes membrane disturbance in the basal ganglia, which is associated with residual psychiatric symptoms that persist even after long-term abstinence from toluene use. 相似文献