Erythropoietin Receptor Signaling Mitigates Renal Dysfunction-Associated Heart Failure by Mechanisms Unrelated to Relief of Anemia

ObjectivesWe examined the effect of asialoerythropoietin (asialoEPO), a nonerythrogenic derivative of erythropoietin (EPO), on renal dysfunction-associated heart failure.BackgroundAlthough EPO is known to exert beneficial effects on cardiac function, the clinical benefits in patients with chronic kidney disease are controversial. It remains to be addressed whether previously reported outcomes were the result of relief of the anemia, adverse effects of EPO, or direct cardiovascular effects.MethodsMice underwent 5/6 nephrectomy to cause renal dysfunction. Eight weeks later, when renal dysfunction was established, anemia and cardiac dysfunction and remodeling were apparent. Mice were then assigned to receive saline (control), recombinant human erythropoietin (rhEPO) at 5,000 IU (714 pmol)/kg, or asialoEPO at 714 pmol/kg, twice/week for 4 weeks.ResultsAlthough only rhEPO relieved the nephrectomy-induced anemia, both rhEPO and asialoEPO significantly and similarly mitigated left ventricular dilation and dysfunction. The hearts of rhEPO- or asialoEPO-treated mice showed less hypertrophy, reflecting decreases in cardiomyocyte hypertrophy and degenerative subcellular changes, as well as significant attenuation of fibrosis, leukocyte infiltration, and oxidative deoxyribonucleic acid damage. These phenotypes were accompanied by restored expression of GATA-4, sarcomeric proteins, and vascular endothelial growth factor and decreased inflammatory cytokines and lipid peroxidation. Finally, myocardial activation was observed of extracellular signal-regulated protein kinase and signal transducer and activator of transcription pathways in the treated mice.ConclusionsEPO receptor signaling exerts direct cardioprotection in an animal model of renal dysfunction-associated heart failure, probably by mitigating degenerative, pro-fibrosis, inflammatory, and oxidative processes but not through relief of anemia

Comparison between Integrated Backscatter Intravascular Ultrasound and 64-Slice Multi-Detector Row Computed Tomography for Tissue Characterization and Volumetric Assessment of Coronary Plaques

Background: The purpose of this study was to determine the cut-off values of Hounsfield units (HU) for the discrimination of plaque components and to evaluate the feasibility of measurement of the volume of plaque components using multi-detector row computed tomography (MDCT). Methods: Coronary lesions (125 lesions in 125 patients) were visualized by both integrated backscatter intravascular ultrasound (IB-IVUS) and 64-slice MDCT at the same site. The IB values were used as a gold standard to determine the cut off values of HU for the discrimination of plaque components. Results: Plaques were classified as lipid pool (n =50), fibrosis (n =65) or calcification (n =35) by IB-IVUS. The HU of lipid pool, fibrosis and calcification were 18 ± 18 HU (−19 to 58 HU), 95 ± 24 HU (46 to 154 HU) and 378 ± 99 HU (188 to 605 HU), respectively. Using receiver operating characteristic curve analysis, a threshold of 50 HU was the optimal cutoff values to discriminate lipid pool from fibrosis. Lipid volume measured by MDCT was correlated with that measured by IB-IVUS (r =0.66, p <0.001), whereas fibrous volume was not (r =0.21, p =0.059). Conclusion: Lipid volume measured by MDCT was moderately correlated with that measured by IB-IVUS. MDCT may be useful for volumetric assessment of the lipid volume of coronary plaques, whereas the assessment of fibrosis volume was unstable

A 100%-complete sequence reveals unusually simple genomic features in the hot-spring red alga Cyanidioschyzon merolae

<p>Abstract</p> <p>Background</p> <p>All previously reported eukaryotic nuclear genome sequences have been incomplete, especially in highly repeated units and chromosomal ends. Because repetitive DNA is important for many aspects of biology, complete chromosomal structures are fundamental for understanding eukaryotic cells. Our earlier, nearly complete genome sequence of the hot-spring red alga <it>Cyanidioschyzon merolae </it>revealed several unique features, including just three ribosomal DNA copies, very few introns, and a small total number of genes. However, because the exact structures of certain functionally important repeated elements remained ambiguous, that sequence was not complete. Obviously, those ambiguities needed to be resolved before the unique features of the <it>C. merolae </it>genome could be summarized, and the ambiguities could only be resolved by completing the sequence. Therefore, we aimed to complete all previous gaps and sequence all remaining chromosomal ends, and now report the first nuclear-genome sequence for any eukaryote that is 100% complete.</p> <p>Results</p> <p>Our present complete sequence consists of 16546747 nucleotides covering 100% of the 20 linear chromosomes from telomere to telomere, representing the simple and unique chromosomal structures of the eukaryotic cell. We have unambiguously established that the <it>C. merolae </it>genome contains the smallest known histone-gene cluster, a unique telomeric repeat for all chromosomal ends, and an extremely low number of transposons.</p> <p>Conclusion</p> <p>By virtue of these attributes and others that we had discovered previously, <it>C. merolae </it>appears to have the simplest nuclear genome of the non-symbiotic eukaryotes. These unusually simple genomic features in the 100% complete genome sequence of <it>C. merolae </it>are extremely useful for further studies of eukaryotic cells.</p

教室における肺癌症例の検討 : 病期分類,切除率,生存率からみた肺癌手術例の検分

昭和50年1月から昭和61年1月までの約11年間に当科に入院した原発性肺癌症例は121例で,これらの症例について病期分類,切除率,生存率等について検討を加えた.内訳は,男性88例,女性33例,年齢は22歳から83歳,平均67.0歳で,70歳代は24例(19.8%),80歳代は2例(0.2%)であった.病期分類はIa期32例(26.4%),Ib期8例(6.6%),II期5例(4.1%),III期45例(37.2%),IV期28例(23.1%)で,III・IV期を合わせると60%以上を占めていた.このうち切除例は78例(64.5%)で,治癒切除例は57例(73.1%)であり,II期症例までは全例治癒切除可能であったが,III期症例は45例のうち治癒切除は11例のみであった.121症例の組織型は,腺癌は59例(48.8%),類表皮癌は37例(30.6%),小細胞癌は10例(8.3%),大細胞癌は4例(3.3%)であった.全切除例の50%生存期間は36.4カ月であったが,病期別に比較するとla期の5年生存率は約71%であったのに対して,Ib期,II期,III期の50%生存期間はそれぞれ27.5カ月,31.4カ月,24.4カ月と,Ia期の生存率は有意に良好で(p<0.05),治癒切除,非治癒切除に分けて比較すると,50%生存期間はそれぞれ46.6カ月,20.4カ月で治癒切除可能例において有意に良好であった(p<0.05).また,当院呼吸器内科で非観血的療法をうけた切除不能94例の50%生存期間は約7.5カ月であり,切除例の36.4カ月と比べ明らかに不良であった.このように生存率は早期症例ほど良好で,肺癌予後を決定する因子としては病期分類が最も重要であり,さらに小細胞癌,III期肺癌に対しても積極的な拡大根治手術により生存率の向上が期待できるものと考えられる.One hundred and twenty-one patients with lung cancer were admitted to our division during the 11 years between January, 1975 and January, 1986. There were 88 men and 33 women, whose ages ranged from 22 to 83 years. Thirty-two patients were in Clinical Stage Ia of the disease (24.6%), 8 in Stage Ib (6.6%), 5 in Stage II (4.1%), 45 in Stage III (37.2%) and 28 in Stage IV (23.1%). Fifty-five patients had adenocarcinoma (48.8%), 37 epidermoid cell carcinoma (30.6%), 10 small cell carcinoma (8.3%), 4 large cell carcinoma (3.3%) and 11 had other forms of the disease. Of these, 78 patients underwent surgical resection. That group of patients was analyzed for long-term survival by clinical stage, and a survival curve was drawn according to the methods of KAPLAN & MEIER. The 50% survival period was at 36.4 months for all resected cases, at 27.5 months in patients with Stage Ib, at 31.4 months in those with Stage II, at 24.4 months in those with Stage III and at 7.5 months in non resected cases. On the other hand, the five-year survival rate was 71% in patients with Stage Ia. There was a significant difference in prognosis between Stage Ia and the other stages of the disease. In conclusion, the clinical stage is most important for prognosis in patients with lung cancer, and it can be effectively treated with prolonged survival to operated extensively for Stage III of the disease and for small cell carcinoma of the early stage

Studies on Experimental Leukemia in Mice. Ⅲ. Homologous Transplantation of C 58 Mouse Leukemia

Isologous transplantation experiments of two transplautable lines of C58 mouse leukemia, OHS-LL (lymphocytic) and OHS-ML (myelogenous) were reported in the Part Ι and Ⅱ. The present communication deals with the results of homologous transplantation of these two strains of leukemia in C58 mice. Mice used were strains C3H, Zb, AKR, ddN, C57B1, Db, Strong A, Cb, Rf, D103, and R'Ⅱ. When transplanted intraperitoneally, OHS-ML grew in 67% of C3H, 90% of Zb, and 30% of ddN, while OHS-LL grew in 30% of Zb, and 17% of AKR. All the other mice rejected the homotransplants. When injncted intravenously, OHS-ML grew in only a AKR mouse with negative takes in all the other cases. No positive takes resulted following subcutaneous, intracerebral, and intratesticular transplantation. Temporary tumor formation was seen at the site of subcutaneous implantation of OHS-LL, which was not the case of OHS-ML. The pathological changes in mice showing positive takes of OHS-ML was similar to those of isologous transplantation, but mice bearing homografts of OHS-LL were atypical in that the latency was prologned with marked emaciation or without hepatosplenomegaly or lymphadenopathy. Some mice showed accumulation of ascites. OHS-ML could be serially passaged through Zb and C3H mice, and OHS-LL through Zb mice for 2 to 3 generations

Studies on Experimental Leukemia in Mice. Ⅱ. Preservation and Resistance of C58 Mouse Leukemic Cells

Two strains of transplantable leukemia in C58 mice described in the Part I, OHS-LL (lymphocytic) and OHS-ML (myelogenous), were compared as to the resistance and preservation of leukemic cells by means of bioassay experiments. Both leukemic cell lines were not viable beyond 24 hours at room temperature, and rapidly lost transplantability at 65℃. For the preservation of leukemic cells it was more appropriate to keep them as frozen spleens or animals than to keep them as cell suspensions. OHS ML withstood for 60 days and OHS-LL for 47 days at -80℃., and it would be possible to preserve them for a longer period. OHS-ML was not transplantable below pH 5 and OHS LL below pH 3, indicating inferior resistance of the former to an acid solution. Both leukemic strains became negative for transplantation in NaCl solutions at 0% and over 10% , and showed no difference in osmotic fragility. Both cell stains proved to be cell-graftable after 5 times of freezing and thawing at -30℃. for 15 minutes, but not after 5 times of the same procedure at -30℃. for 60 minutes. Both cell lines were not transplantable after lyophilization. The lethal X-ray irradiation dose was 8,000r against OHS-ML and 3,000r against OHS-LL. OHS-ML became inactivated by formalin, trichloroacetic acid and marsonin at the concentration of over 10(-1)%, 10(-2)%, and 10(-3)%, and similarly OHS-LL at the concentration of over 10(-2)%, 10(-1)%, and 10(-2)%, respectively

カワサキビョウヒフネンマクリンパセツショウコウグンマタワMLNSニオケルシンゾウノビョウリ

京都大学0048新制・課程博士医学博士甲第2013号医博第497号新制||医||238(附属図書館)5221UT51-53-C156京都大学大学院医学研究科内科系専攻(主査)教授 濱島 義博, 教授 河合 忠一, 教授 日笠 頼則学位規則第5条第1項該当Kyoto UniversityDA

Studies on Experimental Leukemia in Mice. Ι. Isologous Transplantation of C58 Mouse Leukemia

In 1961 two strains of transplantable leukemia in C58 mice were established in the Department of Internal Medicine, Okayama University Medical School. One is a lymphocytic leukemia (OHS-LL) of spontaneous origin and the other a myelogenous leukemia (OHS-ML) developing in a mouse inoculated with a cell-free extract from the lymphocytic leukemia. The present paper concerns transplantation experiments of both strains of leukemia into isologous mice. Both strains of leukemia were transplantable in 100% , and the age or sex of the recipient mice did not considerably influence the survival days of the animals. The number of the inoculated leukemic cells and life span of the recipient mice showed an inverse relation, and even a single leukemic cell, when transplanted intraperitoneally, killed animals in 18 days. Transplantation of different organs indicated that the number of leukemic cells contained in the organs determined the survival pericds of the inoculated mice, and it was possible to assess the degree of leukemic infiltration in a given organ from the life span of the animals. The site of cell-graft influenced the survival days but very slightly the manifestation of the disease. However, the local changes following intracerebral, intratesticular and subcutaneous transplantation were more pronounced in OHS-LL in comparison with OHS-ML