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Adenovirus-mediated gene transfer of pancreatic duodenal homeobox transcription factor PDX-1, especially its super-active version (PDX-1/VP16), induces the expression of pancreatic hormones in murine liver and reverses streptozotocin-induced hyperglycemia. Histological analyses suggest that hepatocytes are the major source of insulinproducing cells by PDX-1 gene transfer, although the conversion of cultured hepatocytes into insulin-producing cells remains to be elucidated. The present study wasdoi:10.1507/endocrj.k06-116 pmid:16983179 fatcat:5r7ljqvyv5ab3kp33g4h4so2yq
more »... conducted to address this issue. Hepatocytes were isolated from adult rats. Then, PDX-1 or PDX-1/VP16 gene was introduced by using adenovirus vector. Two days later, the expression of insulin was detected at mRNA and protein levels. Transfection of PDX-1/VP16 was more efficient in converting hepatocytes to insulin-producing cells. Immunoreactivity of albumin was downregulated in transdifferentiated cells and some of them almost completely lost albumin expression. During the course of transdifferentiation, upregulation of mRNA for CK19 and α-fetoprotein was observed. When cultured in collagen-1 gel sandwich configuration, hepatocytes maintained their mature phenotype and did not proliferate. In this condition, transfer of PDX-1/VP16 also induced the expression of insulin. These results clearly indicate that hepatocytes possess a potential to transdifferentiate into insulinproducing cells in vitro.
We measured T-cell intracellular antigen-1 (TIA-1) expression in neoplastic cells from patients with hairy cell leukemia. Five of nine cases were positive for cytoplasmic TIA-1, with a small, dot-like, granular expression pattern. However, neoplastic cells were granzyme B-and perforin-negative in all cases. Other positive markers were CD20 in 9/9 cases, CD19 in 9/9 cases, DBA44 in 8/9 cases, LeuM5(CD11C) in 8/9 cases, IL-2R(CD25) in 7/9 cases, CD103 in 7/9 cases, FMC7 in 6/9 cases, anddoi:10.1038/modpathol.3800129 pmid:15073603 fatcat:2xip6b2owzdbdenkyxdxcoq2hm
more »... resistant acid phosphatase in 5/7 cases. We also analyzed TIA-1 expression in 94 B cell lymphomas, including 19 diffuse, large cell lymphomas, 19 mantle cell lymphomas, six follicular lymphomas, two extranodal marginal zone B-cell lymphomas, 13 nodal marginal zone B-cell lymphomas, one mediastinal large-cell lymphoma, 19 diffuse small-cell lymphomas, 14 myelomas, and one splenic lymphoma with villous lymphocytes. All cases were negative for TIA-1 expression. Based on these findings, TIA-1 expression in neoplastic cells of low-grade B-cell lymphomas may be a good diagnostic marker for hairy cell leukemia. Moreover, TIA-1 reactivity in lymphomas does not necessarily indicate a T-or NK-cell derivation.
Protein acylation in glucose stimulation of insulin secretion in the β cells has been implicated. Accordingly, we attempted to identify the target(s) of acylation in the pancreatic islets. Rat pancreatic islets were labeled with [ 3 H]palmitic acid for 1 h at 37°C and the whole cell lysate was analyzed by SDS-PAGE and 2 dimensional gel electrophoresis. The labeling of the proteins by [ 3 H]palmitic acid was shown to be palmitoylation by chemical analyses. Palmitoylation of 4 distinct bands wasdoi:10.1210/en.2003-0719 pmid:12960032 fatcat:4en4izucnrashfswbwvgcgvi7a
more »... ecognized, and the palmitoylation was significantly reduced in all of them when the labeling was performed with high glucose. Quite interestingly, the degree of attenuation was particularly dominant for a 24 kDa doublet. Palmitoylation of the 24 kDa doublet was preferentially attenuated also by the mitochondrial fuels and an acylation inhibitor, cerulenin. The half life of the labeling of the doublet was apparently shorter (approximately 45 min) than that of other bands upon pulsechasing of the islets, irrespective of the presence or absence of high glucose. High glucose attenuation of the palmitoylation of the 24 kDa doublet was partially blocked by 20 mM mannnoheptulose, a glucokinase inhibitor. Two dimensional gel electrophoresis revealed that the doublet was composed of acidic peptides and, by immunoprecipitaion, it was shown not to be SNAP-25. We identified rapidly turning over palmitoylated 24 kDa acidic proteins distinct from SNAP-25 in the pancreatic islets, which are preferentially modulated by fuel secretagogues. The data suggested a functional role of the palmitoylated 24 kDa doublet in nutrient stimulation of insulin secretion.
the liver mass is controlled strictly and maintained constant in normal and pathological situations. an exception is observed after an administration of follistatin, which induces proliferation in intact liver. In the present study, we identified genes differentially expressed in proliferating liver caused by overexpression of follistatin-288. Adenovirus vector encoding follistatin-288 (Ad-FS) or green fluorescent protein was injected intraperitoneally in rats. Changes in the liver weight,doi:10.1507/endocrj.k09e-224 pmid:19734694 fatcat:7aecenjfnvfmrg4jo7n24o3wve
more »... ssion of follistatin and nuclear bromodeoxyuridine labeling were measured. Samples taken on day 5 and day 7 were used to prepare RNA for microarray analysis. The expression of the genes was confirmed by quantitative reverse transcriptase PCR. After the injection of Ad-FS follistatin mRNA peaked on day 3, which was followed by progressive increase in the protein expression. a peak in bromodeoxyuridine labeling was observed on day 7. Microarray data from day 5 and day 7 samples showed that follistatin modified the expression of 907 genes, of which 575 were overexpressed and 332 were downregulated taking into consideration a two fold change reference compared to control rats. In particular, significant increases and time related changes in gene expression after the Ad-FS injection were found in nine genes including growth differentiation factor 15 and fibroblast growth factor 21. This study confirmed that follistatin induced proliferation in intact liver, and identified candidate genes involved in follistatin-induced liver cell growth.
Regeneration therapy for diabetes mellitus using somatic stem cell systems
Regeneration therapy for diabetes mellitus using somatic stem cell systems
和 町3-39-15 TEL:027-220-8835;FAX:027-220-8893 E-mail:email@example.com 2004年3月22日 受 付 Ferberら は,STZ糖 尿 病 マ ウ ス に ア デ ノ ウ イ ル ス ベ ク タ ー を 用 い てPdx-1を18), ま た 最 近Kojimaら は,新 し い ア デ ノ ウ イ ル スベ ...doi:10.11410/kenbikyo2004.39.91 fatcat:x7xcd6ualzhiboocyqzjwatn7i
A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml.doi:10.3892/ol.2017.7628 pmid:29434990 pmcid:PMC5777279 fatcat:y6aonmhihfen3aho2vgptsn2mu
more »... e was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to <1.0 ng/ml after AA discontinuation. His PSA remained <1.0 ng/ml without clinical or radiological progression for 1 year after AA withdrawal. Recently, it was reported that cessation of AA is associated with AA withdrawal syndrome in metastatic castration-resistant prostate cancer, defined as a PSA decrease after AA discontinuation, mimicking anti-androgen withdrawal syndrome. In the present study, explanations of the mechanisms underlying this phenomenon were explored, including mutant AR activation by alternative ligands.
Yonago acta medica
Acute transfusion reactions (ATRs) are significantly relevant to the morbidity and mortality of patients. ATRs are mostly not severe and rarely cause severe conditions, including anaphylactic shock. The aim of this study was to clarify the frequency of ATRs and the time of event occurrence. A total of 18,745 transfusions were administered to 11,718 patients during a 3-year period. Adverse reactions including at least one sign or symptom were collected through a report system in 143 of 2,478doi:10.33160/yam.2018.03.013 fatcat:oba4ngcn6jdi3iipj7siiyutpu
more »... %) platelet concentrate transfusions, 105 of 6,629 (1.6%) red blood cell component transfusions and 51 of 2,307 (2.2%) fresh frozen plasma transfusions. Allergic signs and symptoms accounted for 70% of all adverse events. Severe signs and symptoms were observed in 7.1% of patients. These events appeared significantly earlier than those of non-severe signs and symptoms (median time 20 min vs 100 min, P < 0.05). For patients who have had repetitive transfusion-associated adverse events, preventive treatments for adverse events should be proactively promoted.
It is difficult to detect pancreatic cancer or biliary-tract cancer at an early stage using current diagnostic technology. Utilizing microRNA (miRNA) markers that are stably present in peripheral blood, we aimed to identify pancreatic and biliary-tract cancers in patients. With "3D-Gene", a highly sensitive microarray, we examined comprehensive miRNA expression PLOS ONE |doi:10.1371/journal.pone.0118220 pmid:25706130 pmcid:PMC4338196 fatcat:dqwex3ivffh7pe3k527swatqjm
The cases were presented at ICCN2010 (Kobe) in Japan. Highlights Two cases with unilateral asterixis caused by an infarction in the lateral thalamus were studied by using electrophysiological and neuroimaging methods. Averaging of EEG time-locked to the asterixis revealed rhythmic oscillations of beta band at the central area contralateral to the affected hand. The present study for the first time demonstrated that the asterixis due to thalamic lesion is mediated by the sensorimotor cortex which is rendered in an excessive inhibition.doi:10.1016/j.clinph.2012.01.021 pmid:22425586 fatcat:o57elgqvevhkxeyu4l2gihkz44
Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD). Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli. Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the setting ofdoi:10.1186/1465-9921-14-30 pmid:23497247 pmcid:PMC3599155 fatcat:sff4n3anovbjzmck5ftjudsae4
more »... garette smoke extract (CSE) exposure. Methods: Immunohistochemical evaluations of AIM were performed. Immunostaining was assessed by counting total and positively staining AM numbers in each case (n = 5 in control, n = 5 in non-COPD smoker, n = 5 in COPD). AM were isolated from bronchoalveolar lavage fluid (BALF). The changes of AIM expression levels in response to CSE exposure in AM were evaluated. Knock-down of anti-apoptotic Bcl-xL was mediated by siRNA transfection. U937 monocyte-macrophage cell line was used to explore the anti-apoptotic properties of AIM. Results: The numbers of AM and AIM-positive AM were significantly increased in COPD lungs. AIM expression was demonstrated at both mRNA and protein levels in isolated AM, which was enhanced in response to CSE exposure. AIM significantly increased Bcl-xL expression levels in AM and Bcl-xL was involved in a part of anti-apoptotic mechanisms of AIM in U937 cells in the setting of CSE exposure. Conclusions: These results suggest that AIM expression in association with cigarette smoking may be involved in accumulation of AM in COPD.
Neuroinflammation involving CC chemokines such as monocyte chemoattractant protein-1 (MCP-1) has been demonstrated in the pathological process of retinitis pigmentosa (RP), an inherited degenerative retinal disease. However, the mechanism of MCP-1 and its receptor CCR2 involvement in the disease remains unclear. To investigate the role of MCP1/CCR2 in RP pathogenesis, ccr2 mutant RP mice (ccr2−/− rd10) were created and analyzed. The expression of MCP-1, RANTES, stromal cell-derived factordoi:10.1016/j.exer.2012.08.013 pmid:23022404 fatcat:5lwyhe2325ccxpl5if25nbhjx4
more »... ), and tumor necrosis factor-α (TNF-α) in the retinas of wild-type, rd10, and ccr2−/− rd10 mice was analyzed using quantitative RT-PCR. Photoreceptor apoptosis (TUNEL staining) and the number of microglia (positive for the F4/80 antibody) in the retina were examined. Retinal function was assessed using electroretinograms, and the structure of the whole retina was analyzed from images obtained using optical coherence tomography (OCT) and by histological examination. The expression levels of MCP-1, RANTES, and SDF-1 increased with time in the rd10 mice but not in the wild-type mice. Rearing the mice in the dark prevented degeneration and resulted in thicker photoreceptor layers at each time point. In those mice, the peaks of chemokine expression shifted to a later time with degeneration, suggesting that the expression of these chemokines was induced during the progression of degeneration. Although the difference was not so obvious, the retina in the ccr2−/− rd10 mice was consistently and significantly thicker than that in the 2 rd10 (ccr2+/+ rd10) mice at all time points. Rhodopsin gene expression was also higher in the ccr2−/− rd10 mice than in rd10 (ccr2+/+ rd10) mice, suggesting photoreceptor survival in the former. Retinal function was also better preserved in the ccr2−/− rd10 mice than in the rd10 mice. The number of microglia in the retinas of the ccr2−/− rd10 mice was significantly lower than that in the retinas of the rd10 mice. Interestingly, the MCP-1 induction that was observed in the retinas of the rd10 mice was diminished in the retinas of the ccr2−/− rd10 mice. Our results suggest that the MCP-1/CCR2 system plays a role in retinal degeneration in rd mouse retinas. Retinal MCP-1 expression in the rd mouse retina may be partially controlled by ccr2-positive circulating cells.
Malignant peripheral nerve sheath tumorの再発例
Malignant peripheral nerve sheath tumorの再発例
Municipal Hospital *4 Kurosawa Clinic A 68-year-old Japanese man was referred to our hospital to have a tumor on his left shoulder treated, which had been operated on several times and had recurred. When he came to us, there was a red, lobulated, and scar-like fibrous tumor on the previously operated site. Histologically, the tumor consisted of two kinds of cells: one with wound nuclei, forming nests, the other, fibrous cells with spindle shaped nuclei. Both atypical cells were stained withdoi:10.5227/skincancer.18.266 fatcat:jdkcsfsrwrfybe3fqtmfahirse
more »... 0, vimentin, desmin, and NSE, while negative with SMA, CD68, EMA, CD34, myoglobin, and cytokeratin. It is well known that malignant peripheral nerve sheath tumors (MPNST) are usually associated with patients with von Recklinghausen's disease, arising from the deep soft tissue, and growing even into the spinal and pelvic space. Our case seems to be a rare case, since the patient has no history of von Recklinghausen's disease, and the tumor is originated on the skin. The tumor cells had characteristics of nerve origin by immuno-histochemical staining patterns with an exception of positive staining by desmin. We should take great care of the local metastasis and the metastasis to the other organ as well since this tumor easily recurs and metastasizes, especially to the lung. [Skin Cancer (Japan) 2003; 18: 266-269]
Bietti crystalline retinopathy (BCR) is a distinct retinal degenerative disease characterised by retinal degeneration with many yellowewhite crystals located mainly at the posterior pole area. Using spectral domain-optical coherence tomography (SD-OCT), the structural change in retina was investigated. Methods Patients diagnosed with BCR (n¼12), retinitis pigmentosa (RP, n¼292) and cone dystrophy (n¼16) were included in this study. The authors mainly examined fundus photographs and SD-OCT,doi:10.1136/bjo.2010.199356 pmid:21803923 fatcat:7rwgagwvtfayxpwmw6umn2mwxm
more »... red and fundus autofluorescence images of these patients. Results Crystalline deposits were detected in portions of the retinal pigment epithelium that lacked patchy degenerated lesions. SD-OCT revealed that most of the observed crystalline deposits were located adjacent to the inner side of retinal pigment epithelium layer. The change most frequently observed was circular hyperrefractive structures in the outer nuclear layer. Although the structures were considered to be previously reported "tubular formation" or "tubular degeneration", we determined that many of these circular structures were slices of spherical structures and were typically noted in areas suspected of ongoing active degeneration. Conclusion BCR has characteristic structures in the outer nuclear layer. Although the incidence of the structure varies, it may be characteristic of retinal degeneration and can be found in many retinal degenerative diseases.
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