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21.
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
22.
23.
Shirai Y Hashimoto M Kato R Kawamura YI Kirikae T Yano H Takashima J Kirihara Y Saito Y Fujino MA Dohi T 《Journal of clinical immunology》2004,24(1):42-52
Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis. 相似文献
24.
Nishio J Iwasaki H Ohjimi Y Ishiguro M Isayama T Naito M Okabayashi H Kaneko Y Kikuchi M 《Cancer Genetics and Cytogenetics》2002,133(2):124-128
Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently described, rare but morphologically distinctive soft tissue tumor. The histogenesis of this lesion remains uncertain, although several immunohistochemical and ultrastructural features suggest that it is an unusual neural tumor, possibly of Schwann cell origin. We report here a case of a malignant variant of OFMT that occurred in the foot of a 52-year-old man. The karyotype of a pulmonary metastasis exhibited the following complex numeric and structural aberrations:72 approximately 74,XXY,-5,+6,+del(8)(p21),del(9)(p22),+10,der(11)t(3;11)(p21;p15),del(12) (q13),der(13)t(5;13)(q13;q34),+18,+19,+20,-22 [cp10]. A kidney metastasis exhibited the following karyotypic abnormalities: 46,XY,add(3)(p11),+der(3)t(3;?;11)(3qter-->3p11::?::11q13-->11qter), -5,del(8)(p21),add(9)(q22),del(9)(p22),der(11)t(3;11)(p21;p15),del(12)(q13),+der(13)t(5;13) (q13;q34),-22. To our knowledge, this is the first reported case of OFMT in which clonal chromosomal aberrations have been shown. 相似文献
25.
Toshio Takeuchi Hiroshi Iwasaki Yuko Ohjimi Yasuhiko Kaneko Masako Ishiguro Chikako Fujita Yasusi Mlura Yoshiharu Hiratsuka Kimitaka Sakamoto Masahiro Kikuchi 《Pathology international》1996,46(4):292-297
The cytogenetic and morphologic characteristics of a case with a primitive neuroectodermal tumor (PNET) arising from the left kidney in a 22 year old man are presented. The patient was detected as having a left renal mass with a tumor embolus In the inferior vena cava and multiple pulmonary metastases. A radical nephrectomy with tumor embolectomy of the Inferior vena cava, along with a resection of the pulmonary nodules were performed. Histologic examination revealed a dense proliferation of small round cells with many Homer-Wright type rosettes and perlvascular pseudo-rosettes. Immunohlstochemically, the tumor cells stained strongly positive for HBA71(p30/32M IC2 ), a surface glycopro-teln specific to PNET and Ewlng's sarcoma. In addition, the tumor cells expressed several neural markers (neuron specific enolase, neurofilament, synaptophysin, and Leu-7) and vimentin, while the epithelial, muscular, and lymphocytlc markers were negative in the tumor cells. Cytogenetic analysis of cultured tumor cells showed a reciprocal translocation t(11; 22)(q24; q12) that is considered to be specific to PNET and Ewing's sarcoma. In conclusion, this case suggested that a karyotyping analysis is a useful diagnostic tool for renal PNET, and it may therefore be utilized to help distinguish between difficult cases of small round cell tumors and Wilms' tumor of the kidney. 相似文献
26.
27.
28.
Kojima M Nakamura S Shimizu K Yamane Y Itoh H Masawa N 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(12):1133-1136
A completely infarcted lymph node is an unusual event. However, lymph node infarction should alert the pathologist to the considerable likelihood of malignant lymphoma. We report two unusual cases of acute myeloid leukemia presenting with granulocytic sarcoma at disease onset with a lymph node lesion exhibiting extensive lymph node infarction. The infarcted tissue contained numerous eosinophilic cell ghosts. There were some islands of degenerated, pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+, CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation of granulocytic sarcoma from malignant lymphomas is important for adequate therapy. The present cases indicate that granulocytic sarcoma should be added to the list of differential diagnoses for lymph node infarction. 相似文献
29.
Yuko Ikeda Masato Tabuchi Yasuhiro Sekiguchi Yoshikazu Miyake Shinzo Kohjiya 《Macromolecular chemistry and physics.》1994,195(11):3615-3628
A useful instrument for polymer film preparation by solution casting was employed in this study. It enabled us to control the solvent evaporation rate of the polymer solution. By using this instrument, the aggregation of hard segments in segmented poly(urethane-urea) (SPUU) was investigated. SPUU was prepared from poly(tetramethy1ene oxide), 4,4′-diphenylmethane diisocyanate and ethylenediamine. The effect of solvent evaporation rate on the microphase-separated structure of SPUU was elucidated by dynamic mechanical analysis, tensile test, differential scanning calorimetry analysis, small-angle X-ray scattering measurement, IR and IR dichroism analyses. The aggregation of hard segments in SPUU was observed to be affected considerably by the solvent evaporation rate of the cast film during the preparation. It was found that the slower the solvent evaporation rate, the higher the aggregation of hard segments to form rigid hard segment domains in SPUU. Nine months after casting, this casting effect still remained on the aggregation state of hard segments of SPUU films, although the interdomain spacing was not influenced by its rate. 相似文献
30.
Takeki Tsutsui Yuriko Tanaka Yuko Matsudo J. Carl Barrett 《Methods in Cell Science》1995,17(2):155-160
Immortalization of normal human fibroblasts is a very rare event. Multiple genes such as p53 and cellular senescence genes are possibly involved in immortalization of human fibroblasts, suggesting that multiple treatments with carcinogens are required for the immortalization. We describe here the procedure for immortalization of human fibroblasts (MDAH 087) from Li-Fraumeni cancer syndrome with a germ-line p53 mutation. The cells were subjected to multiple treatments with aflatoxin B1 (AFB1) in the presence of exogenous metabolic activation with rat liver post-mitochondrial supernatant (PMS), and 3 of 9 MDAH 087 cell cultures treated 1–3 times with 0.1–1 µg/ml AFB1 became immortal, defined as continuous growth for over 300 population doublings after the first treatment. However, cultures of human fibroblasts from a normal embryo treated under the same conditions failed to escape senescence. The results indicate that the model of human fibroblasts with a mutated p53 allele exposed to AFB1 is potentially useful for studying mechanisms of chemically induced immortalization. 相似文献