Absorption of cyclosporine (Neoral) from a microemulsion formulation in a living donor liver transplant recipient.
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Administration, Oral↗
Biomedical subjects
S Hayashi
Publications and source records attributed to S Hayashi.
Flocculation properties of pectin in various suspensions.
Pectin had a flocculating activity and its flocculating activities in various suspensions were investigated. Flocculating activity of pectin in a kaolin suspension was markedly stimulated by the addition of Al3+ and Fe3+ to the suspension. Optimum temperature for flocculating activity of pectin in the kaolin suspension was around 30 degrees C and high flocculating activity was obtained when 30 mg/l of pectin and 0.2 mM Fe3+ were added to the suspension. Other inorganic suspensions of activated carbon and acid clay were flocculated by pectin in the presence of Al3+ or Fe3+. Flocculation of organic suspensions such as cellulose and yeast by pectin occurred when 0.1-0.2 mM Fe3+ was present in the suspensions.
Aluminum↗
Interleukin-18 and interleukin-12 synergistically inhibit osteoclastic bone-resorbing activity.
The effect of interleukin (IL)-18 on osteoclastic bone-resorbing activity was investigated in vitro. Osteoclast-enriched cells, about 70% of which were tartrate-resistant acid phosphatase (TRAP)-positive, were cultured on dentine slices, and then the total volume of resorption pits on each dentine slice was measured as bone-resorbing activity. When the effects of IL-18 alone at 1, 10, 100, and 1000 ng/mL were examined, bone-resorbing activity was significantly reduced only at 1000 ng/mL, by about 50%. However, IL-18 plus IL-12 (10 ng/mL each) reduced bone-resorbing activity by about 70%, whereas IL-12 alone had no significant effect. When the concentration of interferon (IFN)-gamma in the medium was measured, IL-18 or IL-12 was found to increase it slightly, and the combination of these two cytokines synergistically increased it. The inhibitory effect of the combination of the two cytokines was completely abolished by the addition of an anti-IFN-gamma neutralizing antibody to the medium, but IFN-gamma by itself did not inhibit osteoclastic bone resorption. IL-18 alone or in combination with IL-12 did not affect the number of TRAP-positive cells in culture of osteoclast-enriched cells. Osteoclasts prepared from osteoclast-enriched cells expressed mRNAs of IL-18 receptor, MyD88, and cathepsin K. Furthermore, IL-18 receptor protein was detected on the cell surface of osteoclasts. The present results indicate that the combination of IL-18 and IL-12 synergistically inhibits osteoclastic bone-resorbing activity, suggesting that IFN-gamma participates in the mechanism underlying this inhibition.
Animals↗
Pyrazinamide resistance associated with pncA gene mutation in Mycobacterium tuberculosis in Japan.
Thirty Japanese clinical isolates of Mycobacterium tuberculosis were analysed by pyrazinamide susceptibility testing and pyrazinamidase assay, as well as polymerase chain reaction for single-strand conformational polymorphism and direct sequencing of the gene encoding pyrazinamidase (pncA). All sensitive isolates showed pyrazinamidase activity and a wild-type pncA gene, but three resistant isolates had pncA gene mutations and lacked pyrazinamidase activity. The latter isolates showed a minimum inhibitory concentration of at least 100 mg/l by the 7H10 agar proportion method and 400 mg/l by the 7H9 liquid medium method. Isolate 28 showed T-to-C change at position 11, leading to Leu4 --> Ser substitution; isolate 29 had an 8-bp deletion from position 382; and isolate 30 had A-to-C change at position 29, leading to Gln10 --> Pro substitution. The deletion has not been described previously. This is the first demonstration of pncA gene mutations in PZA-resistant M. tuberculosis strains isolated from Japanese patients.
Amidohydrolases↗
Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polymerase chain reaction.
Cytomegalovirus (CMV) antigenemia and quantitative real-time polymerase chain reaction (PCR) were compared for monitoring of CMV reactivation after allogeneic stem cell transplantation. The number of CMV antigen-positive cells by the antigenemia assay and the level of CMV DNA by real-time PCR correlated well. The sensitivity and specificity of the antigenemia assay was 55.4% and 95.5%, respectively, using real-time PCR as the reference standard. The probability of positive antigenemia at day 100 was 76.5%, with a median of first detection at day 37 in 51 patients, compared with a positive PCR of 84.3% and day 33, respectively. When HLA-identical sibling donor transplant recipients and other donor transplant recipients were analyzed separately, there was no difference between the two tests. However, temporal patterns of first detection of CMV antigen-positive cells and CMV DNA differed between HLA-identical and alternative recipients; patients without CMV (29%) or with sporadic positive PCR results (14%) were more common in HLA-identical sibling transplants, whereas patients with simultaneous antigenemia and positive PCR occurred more in alternative transplants (48%). Two of 51 patients (4%) developed CMV colitis despite antigenemia-guided prophylaxis, but both were successfully treated with ganciclovir. Although PCR is more sensitive than antigenemia, both tests are useful in the early detection of CMV after allogeneic stem cell transplantation.
Adolescent↗
Injury to the skin induces p53- and Fas-dependent bystander keratinocyte apoptosis in vivo.
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Animals↗
Bilateral maxillary fused primary incisors accompanied by succedaneous supernumerary teeth: report of a case.
A rare case of fusion between maxillary primary central incisors and supplemental teeth occurring bilaterally, accompanied by succedaneous supernumerary teeth, is presented. The patient was an 8.5-year-old Japanese boy. Intraoral examination revealed fusion of left and right maxillary primary central incisors to supplemental teeth, which had labial and lingual grooves. The maxillary primary lateral incisors were present. Radiographs showed that the fused teeth had separate roots, pulp chambers and root canals. There were two impacted supernumerary teeth and eruption of the permanent maxillary central incisors was delayed. Treatment was performed and the fused primary teeth and the impacted supernumerary teeth were extracted. After 6 months observation, surgical exposure of the two crowns of the permanent maxillary central incisors was performed. The teeth began to erupt and have since been kept under observation.
Child↗
Bcl-2 expression and frequency of apoptosis correlate with morphogenesis of colorectal neoplasia.
AIM: To investigate whether the expression of apoptosis and cell proliferation related proteins is related to the macroscopic form of colorectal neoplasia. METHODS: The extent of apoptosis, using the 3' end DNA labelling method, and the immunohistochemical expression of cell proliferation (Ki-67) and apoptosis related proteins (Bcl-2, Bak, and p53) were investigated in 64 colorectal adenomas and 22 early carcinomas extending no further than the upper submucosal region. The specimens were classified into three types of macroscopic form (polypoid, flat, and depressed). RESULTS: The Ki-67 labelling index and the Bak score did not differ significantly among each macroscopic form. In contrast, the apoptotic index and the Bcl-2 score changed significantly according to the macroscopic forms. Compared with polypoid and flat tumours, depressed tumours had a significantly lower apoptotic index (2.84, 2.28, and 1.44, respectively) and a significantly lower Bcl-2 score (3.18, 2.70, and 1.64, respectively). The proliferation/apoptosis ratio was significantly lower in polypoid tumours than in the other two macroscopic forms. The Bcl-2 score became significantly lower as the tumours flattened or took on a depressed form. Immunohistochemical p53 overexpression did not correlate with the macroscopic forms. CONCLUSIONS: These results suggest that differences in both Bcl-2 expression and apoptosis may play an important role in the morphogenesis of colorectal neoplasia.
Adenoma↗
Embryonic stem cells as a model for studying melanocyte development.
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Animals↗
Embryonic stem cells as a model for studying osteoclast lineage development.
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Animals↗
Development of cDNA microarray for expression profiling of estrogen-responsive genes.
Estrogen plays an important role in many physiological events including carcinogenesis and the development of human breast cancer. However, the molecular mechanisms of estrogen signaling in cancers have not been clarified hitherto and accurate therapeutic prediction of breast cancer is earnestly desired. We first carried out estrogen-responsive expression profiling of approximately 9000 genes in estrogen receptor-positive human MCF-7 breast cancer cells. Based on the results, estrogen-responsive genes were selected for production of a custom-made cDNA microarray. Using a microarray consisting of the narrowed-down gene subset, we first analyzed the time course of the estrogen-responsive gene expression profiles in MCF-7 cells, resulting in subdivision of the genes up-regulated by estrogen into early-responsive and late-responsive genes. The expression patterns of several genes were confirmed by Northern blot analysis. We also analyzed the effects of the estrogen antagonists ICI 182780 and 4-hydroxytamoxifen (OHT) on the estrogen-responsive gene expression profiles in MCF-7 cells. While the regulation of most of the genes by estrogen was completely abolished by ICI 182780, some genes were partially regulated by estrogen even in the presence of OHT. Furthermore, the estrogen-responsive gene expression profiles of twelve cancer cell lines derived from the breast, ovary, stomach and other tissues were obtained and analyzed by hierarchical clustering including the profiles in MCF-7 cells. Several genes also showed up-regulation or down-regulation by estrogen in cell lines other than MCF-7 cells. The significance of the estrogen-responsive genes identified in these analyses concerning the nature of cancer is discussed.
Blotting, Northern↗
[Contralateral pneumothorax after pneumonectomy for bronchogenic carcinoma; report of a case].
A case of contralateral pneumothorax after pneumonectomy was reported. Intrathoracic drainage was performed and pneumothorax was healed. Recurrent pneumothorax was occurred in this patient and intrathoracic drainage was performed again and pneumothorax was healed. We suspected that bulla was the cause of pneumothorax and thought that contralateral pneumothorax after pneumonectomy must be carefully follow-up.
Aged↗
[Multiple lung cancer with cavity; report of a case].
A case of multiple lung cancer with cavity was reported. Chest X-ray and chest computed tomography (CT) showed two abnormal shadows with consolidation in the right S1 and S2b. The shadow in S2b had a cavity. Right upper lobectomy and right middle lobe partial resection was performed and the histopathological examination revealed adenocarcinoma. This case deserves attention of difficulty in differentially diagnosis on the chest X-ray and chest CT from pulmonary tuberculosis.
Adenocarcinoma↗
Fatal pulmonary hypertension associated with an atypical case of Hunchinson-Gilford progeria.
We report the first autopsied case of an incomplete type of Hunchinson-Gilford progeria associated with fatal pulmonary hypertension. Histopathologic findings revealed abnormal deposition of collagen and elastic fibers, as well as cellular proliferation, at intima of the coronary arteries, pulmonary small arteries, and arterioles. These changes could be underlying conditions of the association of the two diseases.
Child↗
Neuronal nuclear alterations in dentatorubral-pallidoluysian atrophy: ultrastructural and morphometric studies of the cerebellar granule cells.
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion, resulting in ubiquitinated inclusions and diffuse accumulation of mutant atrophin-1 in the neuronal nuclei in many regions of the central nervous system. In the cerebellar cortex, such nuclear abnormalities occur in the granule cells. In the present study, we performed ultrastructural and morphometric analyses on the nuclei of the cerebellar granule cells from eight patients with DRPLA (four with juvenile-onset disease and four with adult-onset disease) in an attempt to obtain further insight into the neuronal nuclear alterations that occur in CAG-repeat diseases. Ultrastructurally, all patients had intranuclear filamentous inclusions (NIIs, neuronal intranuclear inclusions) and nuclear membrane indentations (NMIs) in some of their granule cells, and chromatin tended to be sparse in the nucleoplasm of the affected nuclei. No such changes were observed in the granule cells of four control subjects. In all patients there was an association between NIIs and NMIs, and nuclei with NIIs and/or NMIs were larger than those without such changes. However, the nuclear enlargement was not due solely to the NIIs - even nuclei without NIIs or NMIs were larger in the patients than in the controls. In the DRPLA patients, there was a significant inverse correlation between the cross-sectional area of the nuclei and the disease duration. These findings indicate that NIIs and NMIs are features in the disease and occur in association with each other, and that nuclear enlargement - the degree of which may decrease with time after onset of the illness - is a more prevalent abnormality than the formation of NIIs or NMIs.
Adolescent↗
Gene therapy utilizing the Cre/loxP system selectively suppresses tumor growth of disseminated carcinoembryonic antigen-producing cancer cells.
Recent clinical trials of cancer gene therapy have shown encouraging results for controlling localized tumors. However, to control metastatic or disseminated tumor cells, further modification of vectors is required to enhance specificity and infectivity against targets. We investigated whether utilization of the Cre recombinase(Cre)/loxP system contributes to enhanced antitumor effects together with minimal adverse reactions in specific gene therapy against disseminated carcinoembryonic antigen (CEA)-producing cancer cells in the peritoneal cavity of mice. CEA-producing cancer would be a good therapeutic target because it is found in lung, stomach and colon sites, which account for most cancers. We constructed a pair of recombinant adenoviral vectors (Ads), one of which expresses the Cre gene under the control of the CEA promoter (Ad.CEA-Cre); the other expresses the herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.lox-TK), or the beta-galactosidase gene (beta-gal) by Cre (Ad.lox-beta-gal). Intraperitoneal coinjection of Ad.CEA-Cre and Ad.lox-beta-gal into mice with peritonitis carcinomatosa by CEA-producing tumor cells showed selective expression of the beta-gal gene in tumor foci. Coinfection of Ad.CEA-Cre and Ad.lox-TK followed by ganciclovir (GCV) administration significantly suppressed the total tumor weight in the peritoneal cavity of the mice to 13% of that of the untreated mice and 22% of that of the mice treated with Ad.CEA-TK/GCV, an Ad that expressed the HSV-TK gene driven by the CEA promoter alone. Moreover, treatment with Ad.CEA-Cre and Ad.lox-TK/GCV completely suppressed tumors in 4 of 10 (40%) mice without significant weight loss, although 2 of 10 mice treated with Ad.CAG-TK/GCV, an adenovirus vector that strongly but nonspecifically expressed the TK gene, died due to severe side effects including diarrhea, weight loss and liver dysfunction. These findings suggest that cell type-specific gene therapy using the Cre/loxP system is effective against disseminated cancer cells without significant side effects.
Adenoviridae↗
The relationship between UVB screening and cytoprotection by microcorpuscular ZnO or ascorbate against DNA photodamage and membrane injuries in keratinocytes by oxidative stress.
Decreased cell viability and increased formation of cyclobutane-type pyrimidine dimers (CPDs) in DNA of UVB-irradiated keratinocytes were shown to be appreciably restored by the addition of w/o emulsion of microcorpuscular zinc oxide (mcZnO) with a corpuscle diameter of 0.15 microm. The cytoprotection was exerted only by 20 wt/wt% mcZnO at levels equivalent to 40- to 100-microm-thick emulsion layers, which screened 90-92% of the incident UVB. However, protection was not seen by mcZnO below 20-microm thickness, which, unexpectedly, screened 79% of the incident radiation. This suggests that thorough UVB screening is necessary for cytoprotection. This may be attributable to involvement of intracellular reactive oxygen species (ROS) secondarily generated from UVB-irradiated mcZnO. Intracellular ROS was increased in mcZnO-added cells in a time-dependent manner even after UVB irradiation, contrasting with reduction of intracellular ROS in ascorbic acid-added cells. UVB-induced disruption of cell membrane integrity was reduced by mcZnO at 100-microm thickness, equivalent to the addition of ascorbic acid of 50 microM. Thus, mcZnO was thought to be cytoprotective through reductions of intracellular ROS generation, CPD formation and cell membrane disintegration when added so abundantly so as to achieve UVB-screening more than 90%.
Animals↗
Regulation of mammalian phospholipase D2: interaction with and stimulation by G(M2) activator.
We have previously reported that a heat-stable activator for ganglioside metabolism, G(M2) activator, potently stimulates ADP-ribosylation factor (ARF)-dependent phospholipase D (PLD) activity (presumably PLD1) in an in vitro system [Nakamura, Akisue, Jinnai, Hitomi, Sarkar, Miwa, Okada, Yoshida, Kuroda, Kikkawa and Nishizuka (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 12249-12253]. However, little is known about the regulation of PLD2. In the present studies we have investigated the regulation of PLD2 by G(M2) activator and various other regulators including ARF. PLD2 was potently stimulated in vitro by G(M2) activator in a time- and dose-dependent manner. Neither ARF nor protein kinase C caused any significant changes in PLD2 activity. Importantly, PLD2 responsiveness to ARF was greatly enhanced by G(M2) activator, suggesting a possible role for G(M2) activator as a coupling factor. G(M2) activator was also demonstrated to physically associate with PLD2 in a stoichiometric manner. Further, PMA stimulation of COS-7 cells overexpressing both G(M2) activator and PLD2 resulted in a marked increase in the association of the two molecules. Interestingly, ARF association with PLD2 was greatly increased by G(M2) activator. Moreover, G(M2) activator enhanced PMA-induced PLD activity in a synergistic manner with ARF in streptolysin-O-permeabilized, cytosol-depleted HL-60 cells, suggesting that G(M2) activator may regulate PLD in a concerted manner with other factors, including ARF, inside the cells.
Amino Acid Sequence↗