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81.
Dihydropyrimidine dehydrogenase activity in 150 healthy Japanese volunteers and identification of novel mutations. 总被引:4,自引:0,他引:4
82.
Gender difference in alcoholic liver injury] 总被引:1,自引:0,他引:1
Nobuyuki Enomoto Yoshiyuki Takei Shunhei Yamashina Kenichi Ikejima Satoko Suzuki Tsuneo Kitamura Nobuhiro Sato 《Nihon Arukōru Yakubutsu Igakkai zasshi》2004,39(3):163-167
Gender differences of alcoholic liver injury have been described previously, but mechanisms have only partially characterized. For example, it is known that females develop alcoholic liver injury more rapidly and to a greater extent than males. It now appears that estrogen participates in several aspects of this phenomenon. On the other hand, attention has been directed towards the effect of ethanol ingestion on Kupffer cell function, which is stimulated by gut-derived endotoxins via mechanisms dependent on increased gut permeability and the possible relationship between Kupffer cell and alcohol-induced liver injury. 相似文献
83.
Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients
Na Cha Naoki Oshima Kenichi Kishimoto Satoshi Kotani Eiko Okimoto Tomotaka Yazaki Hiroki Sonoyama Akihiko Oka Yoshiyuki Mishima Kotaro Shibagaki Hiroshi Tobita Kousaku Kawashima Norihisa Ishimura Shunji Ishihara 《Journal of Clinical Biochemistry and Nutrition》2022,70(3):297
Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation. 相似文献
84.
Taiichi Wakiya Taizen Urahashi Yoshiyuki Ihara Yukihiro Sanada Naoya Yamada Noriki Okada Kenichi Hakamada Koichi Mizuta 《Pediatrics international》2013,55(5):e119-e122
Abnormalities of liver function tests are frequently documented in patients with Kawasaki disease, but the mechanism responsible for this has not yet been established. Described herein is the case of a 1‐year‐10‐month‐old girl who underwent liver transplantation at 11 months of age. Eleven months after transplantation the patient was diagnosed with Kawasaki disease, which was associated with some portal flow reduction, and received i.v. immunoglobulin, after which fever abated with improvement of portal flow to its pre‐fever level. Abnormalities of liver function tests in Kawasaki disease patients may occur as a result of inflammation of both the biliary and portal systems. There are no reports on the potential relationship between Kawasaki disease and the portal vein, and accumulation of further data is necessary to better examine this relationship. 相似文献
85.
Sato H Kato Y Hayasi E Tabata T Suzuki M Takahara Y Sugiyama Y 《Pharmaceutical research》2002,19(11):1736-1744
Purpose. To demonstrate the utilities of a synthetic low-affinity ligand ((Gal)3) for the asialoglycoprotein receptor (ASGP-R) as a hepatic targeting device for therapeutic cytokines.
Methods. The site-specific incorporation of (Gal)3 or a typical high-affinity ligand (GalNAc)3 into IL-2 was catalyzed by microbial transglutaminase. The anti-tumor activities, pharmacokinetic profiles and receptor-mediated endocytosis in hepatocytes of the ligand-IL-2 conjugates were examined in mouse.
Results. The (Gal)3 has approximately 50 times lower affinity to ASGP-R than (GalNAc)3. Nevertheless, the antitumor effects were in the order of (Gal)3—IL-2 > unmodified IL-2 > (GalNAc)3—IL-2. The systemic elimination and the hepatic uptake of (GalNAc)3—IL-2 were more rapid than (Gal)3—IL-2. The ratio of the rate constant representing dissociation from the cell-surface receptor (koff) to that representing endocytosis of the ligand (kint) was greater for (Gal)3—IL-2 than (GalNAc)3—IL-2, suggesting that (Gal)3—IL-2 preferably avoids internalization due to its lower affinity to the receptor. The simulation studies demonstrated that (Gal)3—IL-2 was present in the hepatic extracellular space for a longer period than (GalNAc)3 IL-2.
Conclusions. The (Gal)3 ligand increases the therapeutic efficacy of IL-2 by enhancing its exposure to the cell-surface. The koff/kint affects the targeting efficacy of the conjugates to ASGP-R. 相似文献
86.
PURPOSE: To develop paclitaxel carried by injectable PEGylated emulsions, an artificial neural network (ANN) was used to optimize the formulation--which has a small particle size, high entrapment efficiency, and good stability--and to investigate the role of each ingredient in the emulsion. METHODS: Paclitaxel emulsions were prepared by a modified ethanol injection method. A computer optimization technique based on a spherical experimental design for three-level, three factors [soybean oil (X1), PEG-DSPE (X2) and polysorbate 80 (X3)] were used to optimize the formulation. The entrapment efficiency of paclitaxel (Y1) was quantified by HPLC; the particle size of the emulsions (Y2) was measured by dynamic laser light scattering and the stability of paclitaxel emulsions was monitored by the changes in drug concentration (Y3) and particle size (Y4) after storage at 4 degrees C. RESULTS: The entrapment efficiency, particle size and stability of paclitaxel emulsions were influenced by PEG-DSPE, polysorbate 80, and soybean oil. Paclitaxel emulsions of small size (262 nm), high entrapment efficiency (96.7%), and good stability were obtained by the optimization. CONCLUSIONS: A novel formulation for paclitaxel emulsions was optimized with ANN and prepared. The contribution indices of each component suggested that PEG-DSPE mainly contributes to the entrapment efficiency and particle size of paclitaxel emulsions, while polysorbate 80 contributes to stability. 相似文献
87.
Iida T Yasuda M Miyazawa M Fujita M Osamura RY Hirasawa T Muramatsu T Murakami M Saito K Mikami M 《Archives of gynecology and obstetrics》2008,277(6):539-546
Material and methods We analyzed the expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) by immunohistochemistry
in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy.
A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous
13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18).
Results The overall positive ratios were as follows: HIF-1α, 74% of
adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and
100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive
ratios of HIF-1α and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly
expressed in serous adenocarcinomas (HIF-1α, 3 + 100%; GLUT-1, 3 + 76%) than in mucinous adenocarcinomas (HIF-1α, 3 + 61%;
GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical
expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than
in mucinous adenocarcinomas.
Conclusion HIF-1α and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association
with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared
with mucinous tumors is related to the difference in their histological characteristics. 相似文献
88.
Tomotaka Yazaki Ichiro Moriyama Hiroshi Tobita Hiroki Sonoyama Eiko Okimoto Akihiko Oka Yoshiyuki Mishima Naoki Oshima Kotaro Shibagaki Kousaku Kawashima Norihisa Ishimura Taichi Nagami Riruke Maruyama Hiroaki Shiina Shunji Ishihara 《Internal medicine (Tokyo, Japan)》2022,61(10):1485
Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy. 相似文献
89.
Tsung-Che Chang Yoshiyuki Manabe Keita Ito Ryuku Yamamoto Kazuya Kabayama Shino Ohshima Yoshie Kametani Yukari Fujimoto Chun-Cheng Lin Koichi Fukase 《RSC advances》2022,12(29):18985
Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam3CSK4), and T-helper (Th) cell epitope, and found that this three-component self-adjuvanting vaccine effectively resulted in the production of anti-triSTn IgG antibodies. We herein analyzed immune responses induced by this self-adjuvanting vaccine in detail. We newly synthesized two-component vaccines, i.e., Pam3CSK4- or Th epitope-conjugated triSTn, as references to evaluate the immune-stimulating functions of Pam3CSK4 and Th epitope. Immunological evaluation of the synthesized vaccine candidates revealed that Pam3CSK4 was essential for antibody production, indicating that the uptake of triSTn antigen by antigen-presenting cells (APCs) was promoted by the recognition of Pam3CSK4 by TLR1/2. The function of the Th epitope was also confirmed. Th cell activation was important for boosting antibody production and IgG subclass switching. Furthermore, flow cytometric analyses of immune cells, including T cells, B cells, dendritic cells, and other monocytes, were first employed in the evaluation of self-adjuvanting vaccines and revealed that the three-component vaccine was able to induce antigen-specific immune responses for efficient antibody production without excessive inflammatory responses. Importantly, the co-administration of Freund''s adjuvants was suggested to cause excessive myeloid cell accumulation and decreased plasma cell differentiation. These results demonstrate that vaccines can be designed to achieve the desired immune responses via the bottom-up construction of each immune element.Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responses via bottom-up construction of the necessary immune elements. 相似文献
90.
N. Motoi Tsuyoshi Ishida Imaharu Nakano Nobu Akiyama Kinuko Mitani Hisamaru Hirai Yoshio Yazaki Rikuo Machinami 《Acta neuropathologica》1997,93(3):301-305
A 64-year-old man in a severely immunocompromised state due to acute myelogenous leukemia died, respirator-unaided, about
10 h after the abrupt onset of coma. An earlier blood culture had yielded Bacillus cereus. The autopsy, performed 2 h after death, demonstrated diffuse subarachnoid hemorrhage without berry aneurysms, and the formalin-fixed
brain was tinged with gray-brownish discoloration. The sections of the brain presented a whitish tint of the surface layer
of all portion of the cerebral cortices, even those in the sulci. Histological examination of the brain revealed leptomeningeal
B. cereus dissemination, and widespread necrosis of the leptomeninges and arachnoid vessels without inflammatory cell reaction. The
grossly recognizable whitish surface layer of the cerebral cortex showed overt hyperchromatism, and contained neurons more
degenerative than those located in the deeper cortical layer. The total absence of inflammatory reaction may be explained
by a combination of the immunocompromised state of the patient and the character of B. cereus infection, which in itself induces little inflammatory reaction. The prominent lesions were confined to the cerebral surface
layer and leptomeningeal tissue including the arachnoid vessels, which were all bathed in the cerebrospinal fluid, suggesting
that some necrotizing toxins had been secreted into the fluid by the B. cereus. The necrosis of arachnoid vessels is thought to have in turn caused diffuse subarachnoid hemorrhage and marked disturbance
of the cerebral blood flow, resulting in the terminal coma.
Received: 4 April 1996 / Revised, accepted: 8 September 1996 相似文献