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51.
Yukiya Hashimoto Toshiko Koue Yuko Otsuki Masato Yasuhara Ryohei Hori Ken-ichi Inui 《Journal of pharmacokinetics and pharmacodynamics》1995,23(2):205-216
A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady
state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten
model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal
elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE)
requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional
estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment
model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method,
ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological
half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully
for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction
with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL
is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological
half-life of a drug.
This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, and Culture of Japan. 相似文献
52.
Hidehito Matsuoka Wataru Nishio Toshihiko Sakamoto Hiroaki Harada Noriaki Tsubota 《European journal of cardio-thoracic surgery》2004,26(3):480-482
OBJECTIVE: To predict accurate morbidity after lung resection using treadmill exercise test. METHODS: A total of 130 patients (108 men and 22 women, with mean age 67.1+/-11.4 years (range, 34-78 years)) of 1129 patients underwent standard lobectomy were performed both treadmill exercise test and spirometry preoperatively. We measured maximum oxygen uptake/body weight (VO2max/BW) and change in arterial blood oxygen pressure from rest to symptom-limited maximum loading (delta aPaO2) and calculated exercise-induced hypoxemia (delta PaO2/delta VO2/BW), and retrospectively compared these parameters for patients with and without complications. RESULTS: There were five patients with severe postoperative complications, including three requiring use of a respirator, two with home oxygen therapy. %Vital capacity, VC (%, 80.2+/-13.2 vs. 92.5+/-20.9, P=0.026), delta PaO2 (Torr, -29.3+/-4.3 vs. -13.2+/-10.8, P=0.0004), VO2max/BW (ml/min/kg, 16.5+/-2.9 vs. 20.6+/-5.1, P=0.018) and delta PaO2/delta VO2/BW (Torr/ml/min/kg, -1.98+/-0.26 vs. -0.57+/-0.47) were significantly associated with worse outcome. All the five patients with complications had delta PaO2/delta VO2/BW<-1.7. CONCLUSIONS: Treadmill exercise testing is a good method for assessment of cardiopulmonary reserve. Limited resection must be performed if delta PaO2/delta VO2/BW is under -1.7. 相似文献
53.
Traumatic dislocation of the testes 总被引:1,自引:0,他引:1
Traumatic dislocation of the testis is an unusual disorder. A case of bilateral traumatic dislocation of the testes is presented. Ultrasound examination is very useful for determination of the preoperative diagnosis and management of the dislocated testis. 相似文献
54.
Masato Sakamoto Koichiro Takeshige Hisataka Yasui Kouichi Tokunaga 《Surgery today》1998,28(5):522-528
(Received for publication on Sept. 12, 1996; accepted on May 12, 1997) 相似文献
55.
Development of new immunoradiometric assay for CA 125 antigen using two monoclonal antibodies produced by immunizing lung cancer cells 总被引:4,自引:0,他引:4
Mihoko Kunimatsu Keigo Endo Tetsuo Nakashima Toshikazu Awaji Tsuneo Saga Yuji Watanabe Yasutaka Kawamura Hitoya Ohta Mitsuru Koizumi Harumi Sakahara Junji Konishi Shingo Fujii Takahide Mori Kanji Torizuka Yoichiro Matsuoka Tsuyoshi Nakagawa Nobuo Yamaguchi 《Annals of nuclear medicine》1988,2(2):73-79
CA 125 is an antigen associated with non-mucinous epithelial ovarian cancer, which is defined by OC 125 antibody developed by immunizing ovarian cancer cells. We have produced two monoclonal antibodies, 130-22 and 145-9, by using the human lung adenocarcinoma cell line PC-9. Both 130-22 and 145-9 antibodies recognized CA 125 antigen. However, the binding sites seemed to be separate from those of OC 125. Testing by 9 immunoradiometric assays (IRMA), using different combinations of the 3 monoclonal antibodies 130-22, 145-9 and OC 125 demonstrated that the best standard curve for detecting CA 125 could be obtained by a "simultaneous sandwich" assay based on a mixture of 125I-labeled OC 125 and 130-22 or 145-9 coated beads. One-step IRMA, using 130-22 as a tracer and 145-9 as an immunoadsorbent, also showed good reproducibility and sensitivity for measuring CA 125. Antigens were detectable in the culture supernatants of PC-9 cells and 5 of 6 ovarian cancer and endometrial adenocarcinoma cells. These results indicate that one-step IRMA using 130-22 and 145-9 is useful for detecting CA 125 antigen. 相似文献
56.
Ichiro Ikegaki Yoshio Suzuki Shin-ichi Satoh Toshio Asano Masato Shibuya Kenichiro Sugita 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(4):431-436
Summary The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 (PGF2). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1–29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone. 相似文献
57.
Y. Hirata K. Fukui Y. Dan H. Matsuoka T. Sugimoto M. Ishii 《European journal of clinical pharmacology》1989,36(6):575-578
Summary The renal and hormonal effects of the 1-adrenoceptor blocker bunazosin were examined in 6 patients with essential hypertension. Oral bunazosin for 4 to 12 weeks significantly decreased mean blood pressure by 10%, increased effective renal blood flow and creatinine clearance by 34% and 37%, respectively, the plasma norepinephrine concentration was elevated by 60%, and the plasma atrial natriuretic peptide level was lowered by 22%. The plasma renin activity and aldosterone concentration were unchanged. Thus, a moderate reduction in blood pressure was produced by bunazosin treatment while maintaining renal perfusion. 相似文献
58.
Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis 总被引:1,自引:0,他引:1
Azuma Y Nishinaka T Ushijima S Soh J Katsuyama M Lu HP Kawata M Yabe-Nishimura C Miki T 《Molecular human reproduction》2004,10(7):527-533
In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5alpha-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals. 相似文献
59.
Tanaka G Kanaji S Hirano A Arima K Shinagawa A Goda C Yasunaga S Ikizawa K Yanagihara Y Kubo M Kuriyama-Fujii Y Sugita Y Inokuchi A Izuhara K 《International immunology》2005,17(6):797-805
It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells. 相似文献
60.
Takeda H Matsumura Y Kuwata S Nakano H Shanmai J Qiyan Z Yufen C Kusuoka H Matsuoka M 《International journal of medical informatics》2004,73(3):311-316
To enhance medical cooperation between the hospitals and clinics around Osaka local area, the healthcare network system, named Osaka Community Healthcare Information System (OCHIS), was established with support of a supplementary budget from the Japanese government in fiscal year 2002. Although the system has been based on healthcare public key infrastructure (PKI), there remain security issues to be solved technically and operationally. An experimental study was conducted to elucidate the central and the local function in terms of a registration authority and a time stamp authority in contract with the Japanese Medical Information Systems Organization (MEDIS) in 2003. This paper describes the experimental design and the results of the study concerning message security. 相似文献