Research Topics
Genomes and Genes | I ShimokawaSummaryAffiliation: Nagasaki University Country: Japan Publications
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Publications
Advanced glycosylation end products in adrenal lipofuscinI Shimokawa
Department of Pathology, Nagasaki University School of Medicine, Japan
J Gerontol A Biol Sci Med Sci 53:B49-51. 1998..Therefore, our results suggest that glycosylation-related processes are involved in lipofuscinogenesis, at least in its early stage, in the adrenal zona reticularis...
Effects of aging and dietary restriction on mRNA levels of receptors for growth hormone-releasing hormone and somatostatin in the rat pituitaryI Shimokawa
Department of Pathology, Nagasaki University School of Medicine, Nagasaki City, Japan
J Gerontol A Biol Sci Med Sci 55:B274-9. 2000..Although DR could slightly enhance the pituitary sensitivity to GHRH, the antiaging action may be minor at the level of gene expression...
Leptin signaling and aging: insight from caloric restrictionI Shimokawa
Department of Pathology, Nagasaki University School of Medicine, 1 12 4 Sakamoto, 852 8523, Nagasaki, Japan
Mech Ageing Dev 122:1511-9. 2001..Molecular dissection of the mechanisms underlying the effects of CR will contribute to a better understanding of the aging process, leading to the extension of a healthy lifespan in humans...
A role for leptin in the antiaging action of dietary restriction: a hypothesisI Shimokawa
Department of Pathology, Nagasaki University School of Medicine, Nagasaki City, Japan
Aging (Milano) 11:380-2. 1999..In this article, we advance that a reduction in plasma leptin levels in DR rodents might be a critical neuroendocrine modulator in the antiaging action of dietary restriction...
Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat modelIsao Shimokawa
Department of Respiratory and Digestive Medicine, Division of Experimental Medicine, Pathology, and Gerontology, Nagasaki University School of Medicine, Nagasaki City, Japan
Am J Pathol 160:2259-65. 2002..The results of the present study support the hypothesis, but suggest that there is an optimal level of the GH-IGF-1 axis to maximize survival in mammals...
Life span extension by reduction of the growth hormone-insulin-like growth factor-1 axis: relation to caloric restrictionIsao Shimokawa
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City 852 8523, Japan
FASEB J 17:1108-9. 2003..The present study suggests that CR affects aging and longevity by mechanisms other than suppression of the GH-IGF-1 axis, although CR might exhibit its effects partly through the reduced GH-IGF-1 axis...
Effects of caloric restriction on gene expression in the arcuate nucleusIsao Shimokawa
Department of Respiratory and Digestive Medicine, Nagasaki University School of Medicine, 1 12 4 Sakamoto, Nagasaki City 852 8523, Japan
Neurobiol Aging 24:117-23. 2003..The SRIH level was not significantly affected by CR. The present results support the neuroendocrine hypothesis of CR...
Leptin and anti-aging action of caloric restrictionI Shimokawa
Department of Pathology, Nagasaki University School of Medicine, 1 12 4 Sakamoto, Nagasaki City 852 8523, Japan
J Nutr Health Aging 5:43-8. 2001..Research on neuroendocrine mechanisms of CR is warranted, because such efforts might provide clues to the regulation of the aging process in humans...
Dietary restriction reduces hepatocyte proliferation and enhances p53 expression but does not increase apoptosis in normal rats during developmentY Higami
Department of Pathology, Nagasaki University School of Medicine, Japan
Cell Tissue Res 299:363-9. 2000..This process may be mediated by overexpression of p53 suppressor gene. While DR accelerates the expression of Fas antigen, this result does not influence the rate of apoptosis of hepatocytes under physiological conditions...
Modulation by dietary restriction in gene expression related to insulin-like growth factor-1 in rat muscleM Tomita
Department of Pathology, Nagasaki University School of Medicine, Japan
Aging (Milano) 13:273-81. 2001..The present results suggest that dietary restriction could modulate IGF-1 signaling by augmenting local tissue response to IGF-1 and by maintaining the local production of the peptide, even though plasma IGF-1 is reduced...
Life-long caloric restriction suppresses age-associated Fas expression in the Fischer 344 rat kidneyM S Razzaque
Second Department of Pathology, Nagasaki University School of Medicine, Japan
Mol Cell Biol Res Commun 1:82-5. 1999..Our results suggest that increased expression of Fas is associated with age-related renal damage and that life-long diet-restricted alteration of its expression is associated with the modulation of age-associated renal structural damage...
Age-related nephropathy in the Fischer 344 rat is associated with overexpression of collagens and collagen-binding heat shock protein 47M S Razzaque
Second Department of Pathology, Nagasaki University School of Medicine, 1 12 4, Sakamoto, Nagasaki 852, Japan
Cell Tissue Res 293:471-8. 1998....
Intravenous injection of cycloheximide induces apoptosis and up-regulates p53 and Fas receptor expression in the rat liver in vivoY Higami
Department of Pathology, Nagasaki University School of Medicine, 1 12 4 Sakamoto, 852 8523, Nagasaki, Japan
Mutat Res 457:105-11. 2000....
Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern JapanK Arisawa
Department of Preventive Medicine and Health Promotion, Nagasaki University School of Medicine, Japan
Int J Cancer 85:319-24. 2000..The world age-standardized annual incidence rate of ATL per 100,000 persons aged 30 or older was estimated at 10.5 for men and 6.0 for women, which accounted for approximately 37 to 41% of the total NHL incidence...
Primary low-grade MALT lymphoma of the gallbladderT Tsuchiya
First Department of Pathology, Nagasaki University, Nagasaki, Japan
Pathol Int 51:965-9. 2001..Because autoimmune diseases, or chronic inflammatory disorders, seem to correlate with the occurrence of MALT lymphoma, Gram-negative bacterial infection could also be considered as a prodrome of MALT lymphoma of the gallbladder...
Apoptosis in the aging processY Higami
Department of Pathology, Nagasaki University School of Medicine, Japan
Cell Tissue Res 301:125-32. 2000..It is concluded that apoptosis plays an important role in the aging process and tumorigenesis in vivo probably as an inherent protective mechanism against age-associated tumorigenesis...
Hyperadiponectinemia protects against premature death in metabolic syndrome model mice by inhibiting AKT signaling and chronic inflammationS Otabe
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, Japan
J Endocrinol 213:67-76. 2012..The anti-inflammatory effects of adiponectin, achieved by inhibiting the AKT signaling pathway, may explain how adiponectin slows the accelerated aging process associated with the metabolic syndrome...
Life-long suppression of growth hormone-insulin-like growth factor I activity in genetically altered rats could prevent age-related renal damageYan Zha
Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan
Endocrinology 147:5690-8. 2006....
Primary hepatic lymphoma with spindle cell components: a case reportHiroko Hayashi
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Science, 1 12 4 Sakamoto, Nagasaki City, Nagasaki 852 8523, Japan
Virchows Arch 449:591-6. 2006..We emphasize that pathologists should be reminded of lymphoma as a differential diagnosis of spindle cell tumors...
Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf ratsOsami Sato
Division of Cardiovascular Medicine, Course of Medical and Dental Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
Int J Mol Med 19:23-7. 2007....
Hepatic gene expression profile of lipid metabolism in rats: Impact of caloric restriction and growth hormone/insulin-like growth factor-1 suppressionYoshikazu Higami
Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1 12 4 Sakamoto, Nagasaki 852 8523, Japan
J Gerontol A Biol Sci Med Sci 61:1099-110. 2006....
Involvement of insulin-like growth factor-1 in the effect of caloric restriction: regulation of plasma adiponectin and leptinHaruyoshi Yamaza
Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Sciences, 12 4 Sakamoto 1 Chome, Nagasaki City 852 8523, Japan
J Gerontol A Biol Sci Med Sci 62:27-33. 2007..The similarity of phenotypes and adipokine responses to rhIGF-1 between CR and Tg rats supports a role for reduced IGF-1 signaling in the CR effect...
Identification of differentially expressed genes in senescence-accelerated mouse testes by suppression subtractive hybridization analysisTakuya Chiba
Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852 8523, Japan
Mamm Genome 18:105-12. 2007..These gene expression profiles might explain the findings of early testicular maturation and rapid decline in the ability to produce spermatozoa with advancing age in SAMP1 mice...
Down-regulation of AMP-activated protein kinase by calorie restriction in rat liverKazuo To
Department of Investigative Pathology, Unit of Basic Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 12 4 Sakamoto 1 Chome, Nagasaki City 852 8523, Japan
Exp Gerontol 42:1063-71. 2007..The phosphorylated-ACC levels did not alter in parallel with the p-AMPKalpha level, particularly in the liver. The present results suggest that CR down-regulates the AMPK activity in the liver on a long-term basis...
Identification of fasting-induced genes in the rat hypothalamus: relationship with neuroprotectionTakuya Chiba
Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1 12 4 Sakamoto, Nagasaki 852 8523, Japan
Ann N Y Acad Sci 1119:216-26. 2007..Thus, the increased expressions of the genes identified in the present study may have protective effects against neural damage that could otherwise result in cell death...
Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8Toshimitsu Komatsu
Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan
Exp Gerontol 43:339-46. 2008..These results suggest restriction of calorie intake is important for the prevention of learning and memory deficits, and that the simulation of serum changes induced by CR is not sufficient to prevent the cognitive defects of SAMP8 mice...
Genetic suppression of GH-IGF-1 activity, combined with lifelong caloric restriction, prevents age-related renal damage and prolongs the life span in ratsYan Zha
Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Am J Nephrol 28:755-64. 2008....
Effect of leptin on hypothalamic gene expression in calorie-restricted ratsToshimitsu Komatsu
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan
J Gerontol A Biol Sci Med Sci 61:890-8. 2006..The results indicated that leptin administration reversed the upregulated expression of neuropeptide Y and agouti-related protein genes in CR rats, suggesting the possibility of a role for the leptin-ARH pathway in the effect of CR...
Calorie restriction initiated at middle age improved glucose tolerance without affecting age-related impairments of insulin signaling in rat skeletal muscleSeongjoon Park
Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan
Exp Gerontol 41:837-45. 2006..The present results emphasized the possibilities of CR activation of an insulin-independent mechanism in skeletal muscle and also of the involvement of non-muscle tissues in glucose uptake...
Laboratory findings of caloric restriction in rodents and primatesYoshikazu Higami
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8523, Japan
Adv Clin Chem 39:211-37. 2005
Acute stress response in calorie-restricted rats to lipopolysaccharide-induced inflammationTomoshi Tsuchiya
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan
Mech Ageing Dev 126:568-79. 2005..The present results suggest that CR attenuates liver injury without suppression of the proinflammatory response, and that the protective effect emerges from constitutively, rather than inductively, expressed gene products...
Lifespan extension by caloric restriction: an aspect of energy metabolismHaruyoshi Yamaza
Department of Respiratory and Digestive Medicine, Nagasaki University School of Medicine, Nagasaki City 852 8523, Japan
Microsc Res Tech 59:325-30. 2002..Future studies on metabolic adaptation and gene silencing with regard to lower caloric intake will be warranted to understand the mechanisms of the anti-aging and life-prolonging effects of CR...
Effects of aging and caloric restriction on the gene expression of Foxo1, 3, and 4 (FKHR, FKHRL1, and AFX) in the rat skeletal musclesTatsuo Furuyama
Department of Molecular Genetics, National Institute for Longevity Sciences NILS, Aichi, Japan
Microsc Res Tech 59:331-4. 2002..This suggests that caloric restriction may increase the expression of FKHR-family genes and prevent the aging process in the skeletal muscles...
Anti-aging effects of caloric restriction: Involvement of neuroendocrine adaptation by peripheral signalingTakuya Chiba
Department of Respiratory and Digestive Medicine, Nagasaki University School of Medicine, Nagasaki City 852 8523, Japan
Microsc Res Tech 59:317-24. 2002..In this review, we discuss the potential involvement of neuroendocrine modulators in longevity and the anti-aging effects of caloric restriction...
Involvement of DNase gamma in apoptotic DNA fragmentation in histiocytic necrotizing lymphadenitisYoshikazu Higami
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Science, 1 12 4 Sakamoto, 852 8523 Nagasaki, Japan
Virchows Arch 443:170-4. 2003....
EPO-producing gastric carcinoma in a hemodialysis patientManabu Matsuo
Department of Urology, Nagasaki University School of Medicine, Nagasaki City, Japan
Am J Kidney Dis 42:E3-4. 2003..The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis...
A solitary Peutz-Jeghers-type hamartomatous polyp in the duodenum. A case report including results of mutation analysisFumio Kitaoka
Department of Surgery, Nagasaki Memorial Hospital, Japan
Digestion 69:79-82. 2004..We report a case of solitary Peutz-Jeghers-type hamartomatous polyp of the duodenum in a 22-year-old Japanese woman along with the results of genomic analysis...
Aging increases DNase gamma, an apoptosis-related endonuclease, in rat liver nuclei: effect of dietary restrictionKenji Tanaka
Pathology and Gerontology, Department of Respiratory and Digestive Medicine, Nagasaki University School of Medicine, Sakamoto 1-12-4, Nagasaki 852-8523, Japan
Exp Gerontol 39:195-202. 2004....
A transgenic dwarf rat model as a tool for the study of calorie restriction and agingHaruyoshi Yamaza
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki City 852-8523, Japan
Exp Gerontol 39:269-72. 2004..The transgenic rat model is, therefore, a useful one for studies of CR and aging...
Expression of DNase gamma during Fas-independent apoptotic DNA fragmentation in rodent hepatocytesYoshikazu Higami
Department of Pathology and Gerontology, Nagasaki University Graduate School of Biomedical Science, 1 12 4 Sakamoto, Nagasaki, 852 8523, Japan
Cell Tissue Res 316:403-7. 2004..In contrast, it was evident during CHX-induced, but not Fas-induced, apoptotic DNA fragmentation. These findings suggest that DNase gamma plays an important role in Fas-independent apoptotic DNA fragmentation in hepatocytes...
Impact of aging and life-long calorie restriction on expression of apoptosis-related genes in male F344 rat liverKohei Ando
Department of Surgery II, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan
Microsc Res Tech 59:293-300. 2002..Hepatocytes that were immunoreactive for p53 had slightly increased with aging, suggesting that p53 may mediate the age-enhanced up-regulation of Fas receptor in hepatocytes...
Preoperative irradiation combined with chemotherapy impairs healing of bronchial anastomosis during the early postoperative period in ratsMasao Inoue
Division of Surgical Oncology, Department of Translational Medical Sciences, Nagasaki University School Graduate School of Biomedical Sciences, Nagasaki 852 8501, Japan
Tohoku J Exp Med 199:1-12. 2003..In conclusion, this study demonstrated that the healing of bronchial anastomosis was markedly delayed in early postoperative days in the rats receiving irradiation and combined therapy...
Effects of caloric restriction on development of the proximal growth plate and metaphysis of the caput femoris in spontaneously hypertensive rats: microscopic and computer-assisted image analysesToshio Kawahara
Department of Respiratory and Digestive Medicine, Nagasaki University School of Medicine, Nagasaki City 852 8102, Japan
Microsc Res Tech 59:306-12. 2002..The CR paradigm might give insight into the pathogenesis of, and a therapeutic strategy for, human Perthes' disease...
