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Article ; Online: Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease.

Ishii, Satoshi / Taguchi, Atsumi / Okino, Nozomu / Ito, Makoto / Maruyama, Hiroki

2020 Volume 295, Issue 17, Page(s) 5577–5587

Abstract: Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, ... ...

Abstract	Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide
MeSH term(s)	Acylation ; Animals ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Fabry Disease/pathology ; Humans ; Kidney/pathology ; Liver/pathology ; Male ; Mice ; Myocardium/pathology ; Spleen/pathology ; Tandem Mass Spectrometry ; Trihexosylceramides/analysis
Chemical Substances	Trihexosylceramides ; globotriaosylceramide (71965-57-6)
Language	English
Publishing date	2020-03-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA120.012665
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Article ; Online: Delivery of a BET protein degrader via a CEACAM6-targeted antibody-drug conjugate inhibits tumour growth in pancreatic cancer models.

Nakazawa, Youya / Miyano, Masayuki / Tsukamoto, Shuntaro / Kogai, Hiroyuki / Yamamoto, Akihiko / Iso, Kentaro / Inoue, Satoshi / Yamane, Yoshinobu / Yabe, Yuki / Umihara, Hirotatsu / Taguchi, Junichi / Akagi, Tsuyoshi / Yamaguchi, Atsumi / Koga, Minaho / Toshimitsu, Kohta / Hirayama, Toshifumi / Mukai, Yohei / Machinaga, Akihito

Nature communications

2024 Volume 15, Issue 1, Page(s) 2192

Abstract: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all cancers. To improve PDAC therapy, we establish screening systems based on organoid and co-culture technologies and find a payload of antibody-drug conjugate (ADC), a bromodomain and ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all cancers. To improve PDAC therapy, we establish screening systems based on organoid and co-culture technologies and find a payload of antibody-drug conjugate (ADC), a bromodomain and extra-terminal (BET) protein degrader named EBET. We select CEACAM6/CD66c as an ADC target and developed an antibody, #84.7, with minimal reactivity to CEACAM6-expressing normal cells. EBET-conjugated #84.7 (84-EBET) has lethal effects on various PDAC organoids and bystander efficacy on CEACAM6-negative PDAC cells and cancer-associated fibroblasts. In mouse studies, a single injection of 84-EBET induces marked tumor regression in various PDAC-patient-derived xenografts, with a decrease in the inflammatory phenotype of stromal cells and without significant body weight loss. Combination with standard chemotherapy or PD-1 antibody induces more profound and sustained regression without toxicity enhancement. Our preclinical evidence demonstrates potential efficacy by delivering BET protein degrader to PDAC and its microenvironment via CEACAM6-targeted ADC.
MeSH term(s)	Humans ; Mice ; Animals ; Immunoconjugates/pharmacology ; Immunoconjugates/therapeutic use ; Pancreatic Neoplasms/genetics ; Carcinoma, Pancreatic Ductal/genetics ; Cell Line, Tumor ; Tumor Microenvironment ; Antigens, CD ; Cell Adhesion Molecules ; GPI-Linked Proteins
Chemical Substances	Immunoconjugates ; CEACAM6 protein, human ; Antigens, CD ; Cell Adhesion Molecules ; GPI-Linked Proteins
Language	English
Publishing date	2024-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46167-1
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Article ; Online: Discovery of 7-Azanorbornane-Based Dual Agonists for the Delta and Kappa Opioid Receptors through an In Situ Screening Protocol.

Karaki, Fumika / Takamori, Taro / Kawakami, Koumei / Sakurai, Sae / Hidaka, Kyoko / Ishii, Kei / Oki, Tomoya / Sato, Noriko / Atsumi, Nao / Ashizawa, Karin / Taguchi, Ai / Ura, Asuka / Naruse, Toko / Hirayama, Shigeto / Nonaka, Miki / Miyano, Kanako / Uezono, Yasuhito / Fujii, Hideaki

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 19

Abstract: In medicinal chemistry, the copper-catalyzed click reaction is used to prepare ligand candidates. This reaction is so clean that the bioactivities of the products can be determined without purification. Despite the advantages of this in situ screening ... ...

Abstract	In medicinal chemistry, the copper-catalyzed click reaction is used to prepare ligand candidates. This reaction is so clean that the bioactivities of the products can be determined without purification. Despite the advantages of this in situ screening protocol, the applicability of this method for transmembrane proteins has not been validated due to the incompatibility with copper catalysts. To address this point, we performed ligand screening for the µ, δ, and κ opioid receptors using this protocol. As we had previously reported the 7-azanorbornane skeleton as a privileged scaffold for the G protein-coupled receptors, we performed the click reactions between various 7-substituted 2-ethynyl-7-azanorbornanes and azides. Screening assays were performed without purification using the CellKey
MeSH term(s)	Receptors, Opioid, kappa/metabolism ; Ligands ; Copper ; Membrane Proteins ; Receptors, Opioid, mu/metabolism ; Analgesics, Opioid/chemistry
Chemical Substances	Receptors, Opioid, kappa ; Ligands ; Copper (789U1901C5) ; Membrane Proteins ; Receptors, Opioid, mu ; Analgesics, Opioid
Language	English
Publishing date	2023-10-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28196925
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Article ; Online: Low bone mineral density due to secondary hyperparathyroidism in the

Maruyama, Hiroki / Taguchi, Atsumi / Mikame, Mariko / Lu, Hongmei / Tada, Norihiro / Ishijima, Muneaki / Kaneko, Haruka / Kawai, Mariko / Goto, Sawako / Saito, Akihiko / Ohashi, Riuko / Nishikawa, Yuji / Ishii, Satoshi

FASEB bioAdvances

2020 Volume 2, Issue 6, Page(s) 365–381

Abstract: Low bone mineral density (BMD)-diagnosed as osteoporosis or osteopenia-has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model ... ...

Abstract	Low bone mineral density (BMD)-diagnosed as osteoporosis or osteopenia-has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [
Language	English
Publishing date	2020-06-10
Publishing country	United States
Document type	Journal Article
ISSN	2573-9832
ISSN (online)	2573-9832
DOI	10.1096/fba.2019-00080
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Article ; Online: Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort.

Maruyama, Hiroki / Taguchi, Atsumi / Mikame, Mariko / Izawa, Atsushi / Morito, Naoki / Izaki, Kazufumi / Seto, Toshiyuki / Onishi, Akifumi / Sugiyama, Hitoshi / Sakai, Norio / Yamabe, Kenji / Yokoyama, Yukio / Yamashita, Satoshi / Satoh, Hiroshi / Toyoda, Shigeru / Hosojima, Michihiro / Ito, Yumi / Tazawa, Ryushi / Ishii, Satoshi

Current issues in molecular biology

2021 Volume 43, Issue 1, Page(s) 389–404

Abstract: Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. ... ...

Abstract	Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and
MeSH term(s)	Adolescent ; Adult ; Aged ; Asians ; Biomarkers/blood ; Child ; Cohort Studies ; Fabry Disease/blood ; Fabry Disease/diagnosis ; Fabry Disease/ethnology ; Female ; Glycolipids/blood ; Humans ; Japan ; Male ; Mass Screening/methods ; Middle Aged ; Sensitivity and Specificity ; Sphingolipids/blood ; alpha-Galactosidase/blood ; alpha-Galactosidase/metabolism
Chemical Substances	Biomarkers ; Glycolipids ; Sphingolipids ; globotriaosyl lysosphingolipid (126550-86-5) ; alpha-Galactosidase (EC 3.2.1.22)
Language	English
Publishing date	2021-06-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2000024-8
ISSN	1467-3045 ; 1467-3037
ISSN (online)	1467-3045
ISSN	1467-3037
DOI	10.3390/cimb43010032
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Article ; Online: Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort

Hiroki Maruyama / Atsumi Taguchi / Mariko Mikame / Atsushi Izawa / Naoki Morito / Kazufumi Izaki / Toshiyuki Seto / Akifumi Onishi / Hitoshi Sugiyama / Norio Sakai / Kenji Yamabe / Yukio Yokoyama / Satoshi Yamashita / Hiroshi Satoh / Shigeru Toyoda / Michihiro Hosojima / Yumi Ito / Ryushi Tazawa / Satoshi Ishii

Current Issues in Molecular Biology, Vol 43, Iss 32, Pp 389-

2021 Volume 404

Abstract	Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.
Keywords	globotriaosylsphingosine ; late-onset biopsy-proven Fabry disease ; saposin ; gene analysis ; aberrant splicing transcript ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Low bone mineral density due to secondary hyperparathyroidism in the GlatmTg(CAG‐A4GALT) mouse model of Fabry disease

Hiroki Maruyama / Atsumi Taguchi / Mariko Mikame / Hongmei Lu / Norihiro Tada / Muneaki Ishijima / Haruka Kaneko / Mariko Kawai / Sawako Goto / Akihiko Saito / Riuko Ohashi / Yuji Nishikawa / Satoshi Ishii

FASEB BioAdvances, Vol 2, Iss 6, Pp 365-

2020 Volume 381

Abstract: Abstract Low bone mineral density (BMD)—diagnosed as osteoporosis or osteopenia—has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a ... ...

Abstract	Abstract Low bone mineral density (BMD)—diagnosed as osteoporosis or osteopenia—has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [GlatmTg(CAG‐A4GALT)] exhibits impaired functioning of medullary thick ascending limb (mTAL), leading to insufficient Ca2+ reabsorption and hypercalciuria. Here, we investigated bone metabolism in GlatmTg(CAG‐A4GALT) mice without marked glomerular or proximal tubular damage. Low BMD was detected by 20 weeks of age via micro‐X‐ray‐computed tomography. Bone histomorphometry revealed that low BMD results by accelerated bone resorption and osteomalacia. Plasma parathyroid hormone levels increased in response to low blood Ca2+—not plasma fibroblast growth factor 23 (FGF‐23) elevation—by 5 weeks of age and showed progressively increased phosphaturic action. Secondary hyperparathyroidism developed by 20 weeks of age and caused hyperphosphatemia, which increased plasma FGF‐23 levels with phosphaturic action. The expression of 1α‐hydroxylase [synthesis of 1α,25(OH)2D3] in the kidney did not decrease, but that of 24‐hydroxylase [degradation of 1α,25(OH)2D3] decreased. Vitamin D deficiency was ruled out as the cause of osteomalacia, as plasma 1α,25(OH)2D3 and 25(OH)D3 levels were maintained. Results demonstrate that secondary hyperparathyroidism due to mTAL impairment causes accelerated bone resorption and osteomalacia due to hyperphosphaturia and hypercalciuria, leading to low BMD in Fabry model mice.
Keywords	24‐hydroxylase ; bone histomorphometry ; osteomalacia ; parathyroid hormone ; renal phosphate wasting ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article ; Online: Medullary thick ascending limb impairment in the Gla

Maruyama, Hiroki / Taguchi, Atsumi / Nishikawa, Yuji / Guili, Chu / Mikame, Mariko / Nameta, Masaaki / Yamaguchi, Yutaka / Ueno, Mitsuhiro / Imai, Naofumi / Ito, Yumi / Nakagawa, Takahiko / Narita, Ichiei / Ishii, Satoshi

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2018 Volume 32, Issue 8, Page(s) 4544–4559

Abstract: A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic ... ...

Abstract	A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Gla
MeSH term(s)	Animals ; Disease Models, Animal ; Fabry Disease/metabolism ; Fabry Disease/pathology ; Kidney Concentrating Ability/physiology ; Kidney Diseases/metabolism ; Kidney Diseases/pathology ; Kidney Medulla/metabolism ; Kidney Medulla/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Polyuria/metabolism ; Polyuria/pathology ; Sodium/metabolism ; Sodium-Potassium-Chloride Symporters/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism ; Trihexosylceramides/metabolism
Chemical Substances	Sodium-Potassium-Chloride Symporters ; Trihexosylceramides ; globotriaosylceramide (71965-57-6) ; Sodium (9NEZ333N27) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9)
Language	English
Publishing date	2018-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201701374R
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

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Article: Serum folate, total homocysteine levels and methylenetetrahydrofolate reductase 677C>T polymorphism in young healthy female Japanese.

Taguchi, Takashi / Mori, Hideki / Hamada, Atsumi / Yamori, Yukio / Mori, Mari

Asia Pacific journal of clinical nutrition

2012 Volume 21, Issue 2, Page(s) 291–295

Abstract: Environmental and genetic factors influence serum total homocysteine (tHcy), a risk factor for vascular diseases. The gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) is reported to be a genetic factor for influencing tHcy. However, it is ...

Abstract	Environmental and genetic factors influence serum total homocysteine (tHcy), a risk factor for vascular diseases. The gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) is reported to be a genetic factor for influencing tHcy. However, it is not clear whether MTHFR polymorphism influences tHcy in the younger generation. To investigate the influence of MTHFR polymorphism on vascular disease risks in young Japanese females, we determined dietary intakes, serum folate and tHcy, and examined the influence of MTHFR 677C>T polymorphism in healthy junior and high school students (n=192, 12-18y). The relationships between MTHFR polymorphism and folate intake, serum folate or tHcy were investigated by dividing participants into CC, CT and TT types. Among individuals with the TT genotype, folate and tHcy levels were significantly lower (p<0.05) or higher (p<0.0001), respectively, than in those with the other genotypes; although there were no significant differences in the intake of folate among genotypes. In addition, a significant inverse correlation between folate and tHcy (p<0.05) was noted in all genotypes, even in young females, so far not examined in Asian populations. Therefore, MTHFR genotypes were proven to be a significant determinant for folate and tHcy concentrations. However, the association of increased folate intake with lower tHcy concentration, even in cases of the mutation TT type, indicates the importance of folate intake in young Japanese females for early detection of risk, as well as the prevention of vascular diseases.
MeSH term(s)	Adolescent ; Amplified Fragment Length Polymorphism Analysis ; Child ; Diet/adverse effects ; Female ; Folic Acid/administration & dosage ; Folic Acid/blood ; Genetic Association Studies ; Genetic Predisposition to Disease/ethnology ; Health Surveys ; Homocysteine/blood ; Homozygote ; Humans ; Hyperhomocysteinemia/blood ; Hyperhomocysteinemia/ethnology ; Hyperhomocysteinemia/genetics ; Hyperhomocysteinemia/metabolism ; Japan ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Methylenetetrahydrofolate Reductase (NADPH2)/metabolism ; Polymorphism, Single Nucleotide ; Vascular Diseases/ethnology ; Vascular Diseases/genetics ; Vitamin B 12/administration & dosage ; Vitamin B 6/administration & dosage
Chemical Substances	Homocysteine (0LVT1QZ0BA) ; Vitamin B 6 (8059-24-3) ; Folic Acid (935E97BOY8) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20) ; Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2012
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1460012-2
ISSN	0964-7058
ISSN	0964-7058
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Zs.A 5285: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Possible Association of High Urinary Magnesium and Taurine to Creatinine Ratios with Metabolic Syndrome Risk Reduction in Australian Aboriginals

Atsumi Hamada / Takashi Taguchi / Hideki Mori / Marjorie Thorpe / Yukio Yamori / Mari Mori

Cardiology Research and Practice, Vol

2011 Volume 2011

Keywords	Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Cardiovascular ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
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