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K Yagami

Publications and source records attributed to K Yagami.

At least 37 records · Page 2Linked to original sources
PubMed1999

Male sterility in transgenic mice expressing activin betaA subunit gene in testis.

Activins and inhibins, which are endocrine regulators of anterior pituitary function, have also been reported to participate in the paracrine and autocrine regulation of reproductive function. To determine the in vivo effects of overexpressed activin/inhibin, we generated transgenic mice carrying the human activin/inhibin betaA subunit mini gene under the regulatory control of the mouse methallothionein promoter. In one of the transgenic line analyzed, the betaA subunit gene was preferentially expressed in the testis. Ectopic and allochronic expression of the betaA gene started at 3 weeks after birth and transgenic male mice became sterile in the ensuing several weeks. Histological analysis revealed testicular degeneration in these mice. The results from this transgenic line strongly support the in vivo activity of activin/inhibin in male reproductive functions.

Animals↗
PubMed1999

Developmental stage-specific involvement of angiotensin in murine nephrogenesis.

Angiotensinogen-deleted mice (Agt-KO) show phenotypes of hypotension and renal atrophy. To investigate whether an alternative pathway other than angiotensin II (AII), i.e., processed angiotensin fragments, may play a biological role in nephrogenesis, we analyzed a congenic line of Agt-KO fetuses and neonates derived from two sources: one (Agt-KO/He) from mating with heterozygous angiotensinogen-deleted mice and the other (Agt-KO/Ho) from mating homozygous angiotensinogen-deleted mice. Although Agt-KO/He did not show a typical phenotype at birth, these mice showed papillary atrophy 2 weeks later and thereafter, a marked increase in renal size, i.e., pelvic dilatation. In contrast, Agt-KO/Ho showed renal abnormalities at birth and subsequently died. TUNEL staining and electron microscopy revealed that accelerated papillary apoptosis was present at birth in Agt-KO/Ho and caused abnormal papillary development; however, apoptosis was not detected in Agt-KO/He, suggesting that different mechanisms for the abnormal renal development exist in Agt-KO/He and Agt-KO/Ho. Two-week administration of an angiotensin fragment (3-8), angiotensin IV (AIV), to Agt-KO/He markedly attenuated the renal atrophy, decreasing the incidence from 81% to 14%. However, administration of AIV to fetal Agt-KO/Ho through the mother did not decrease the incidence. This is marked contrast to AII, which prevented renal atrophy in both fetal and neonatal periods. It is therefore suggested that AIV is involved in nephrogenesis in a developmental stage-specific manner.

Angiotensin II↗
PubMed1999

Vascular remodeling in hypertensive transgenic mice.

We physiologically and histopathologically analyzed vascular damage due to hypertension and vascular remodeling in hypertensive transgenic mice (Tsukuba hypertensive mice; THM). Pubertal (6-week-old) THM already had hypertension similar to blood pressure in adult THM due to an enhanced renin angiotensin system (RAS). They progressively developed remarkable vascular hypertrophy composed of dedifferentiation of vascular smooth muscle cells (VSMCs) and extracellular matrix accumulation in the thoracic aorta, and VSMC hyperplasia was predominant in the abdominal aorta. THM are therefore a useful animal model for studying vascular remodeling mediated by enhanced RAS.

Aldosterone↗
PubMed1998

Impaired blood-brain barrier function in angiotensinogen-deficient mice.

Astrocytes in the central nervous system have physiologically important roles in the response to brain injury. Brain damage results in disruption of the blood-brain barrier (BBB), producing detachment of astrocyte endfeet from endothelial cells. The resultant leakage of serum proteins from loosened tight junctions between endothelial cells produces brain edema. At the same time, reactive astrocytes migrate to the injured area, where they proliferate and produce extracellular matrix, thereby reconstituting the BBB. As astrocytes are known to express angiotensinogen, which is the precursor of angiotensins (AI to AIV), we have investigated a possible functional contribution of angiotensinogen or one of its metabolites to BBB reconstitution. The astrocytes of angiotensinogen knockout mice had very attenuated expression of glial fibrially acidic protein and decreased laminin production in response to cold injury, and ultimately incomplete reconstitution of impaired BBB function. Although these abnormalities were rescued by administration of AII or AIV, the restoration of BBB function was not inhibited by AII type 1 and 2 receptor antagonists. These findings provide evidence that astrocytes with angiotensins are required for functional maintenance of the BBB.

Angiotensin II↗
PubMed1998

Induction of apoptosis in vitro and in vivo by H-1 parvovirus infection.

Apoptosis induced by H-1 parvovirus infection was investigated in C6 rat glioblastoma cells and in newborn rats. Apoptotic changes, such as chromatin condensation, the appearance of apoptotic nuclear bodies and oligonucleosomal DNA ladders, were observed in infected C6 cells 2 days after infection. Inhibitor assay results suggest that a caspase-3-dependent apoptosis activation pathway is induced by H-1 virus infection in C6 cells. Observations made in vivo revealed that the number of apoptotic cells increased in the infected cerebellum, coinciding with known virus infection sites.

Animals↗
PubMed1998

Prevalence of "orphan" parvovirus infections in mice and rats.

"Orphan" parvovirus (OPV) infection in laboratory mice and rats was serologically surveyed for 465 mouse sera and 271 rat sera collected from 1986 to 1987 and from 1993 to 1996 in Japan. The results suggest that parvovirus infection is rare in mice but common in rats (positive rate: 13-22%) and that most putative viruses were OPVs. OPV is therefore considered to already have been harbored for at least ten years in Japan.

Animals↗
PubMed1998

Salt-sensitive aortic aneurysm and rupture in hypertensive transgenic mice that overproduce angiotensin II.

We studied the effect of excessive salt intake on vascular lesion development in hypertensive transgenic mice that overproduce angiotensin II, ie, Tsukuba hypertensive mice (THM). At 6 weeks of age, THM and C57BL/6J (controls) were given either 1% sodium chloride ("salt-loaded") drinking water or tap water for 30 days. Salt-loaded THM, but not controls, suffered frequent thoracic or abdominal cavity hemorrhage. THM mortality after 7 days of salt loading was 23%; after 30 days of salt loading, it rose to 67%. Hemorrhaging occurred due to the development of aortic aneurysm and rupture at the aortic arch and aorta near the renal arteries. Vascular lesions progressed with structural degeneration of the aortic media. Electronmicroscopic analysis revealed that intact THM already exhibited vascular remodeling consisting of vascular smooth muscle cells (VSMCs) with developed organelles and an increased extracellular matrix. Salt-loaded THM suffered aggravated vascular hypertrophy and vascular structure destruction by plasma material invasion, necrosis of VSMCs possessing extremely swollen cytoplasm and abundant organelles, and interlamellar bleeding, resulting in aortic aneurysm and eventual rupture. Interestingly, blood pressure levels and heart rates in salt-loaded THM did not differ significantly from those of controls; plasma renin activity between drinking regimens was also comparable between the two groups. Drinking volume and the concentration of atrial natriuretic peptide (ANP) in plasma, however, were significantly higher in salt-loaded THM than in intact THM. In addition to aneurysm localization, the findings regarding drinking volume and plasma ANP suggest that aortic aneurysm and rupture in salt-loaded THM occurred as the result of an unknown mechanical stress, other than blood pressure, on the aortic wall. High salt ingestion is involved in the development of thoracic and abdominal aortic aneurysm in the presence of hypertension in the activated renin-angiotensin system. THM should therefore serve as a useful animal model for studying the pathogenesis of aortic aneurysm accompanied by hypertension.

Angiotensin II↗
PubMed1998

Prevalence of herpes B virus antibody in nonhuman primates reared at the National University of Japan.

A serological investigation by means of an enzyme immuno assay test for herpes B virus (cercopithecine herpesvirus 1) was performed on 961 sera of healthy nonhuman primates reared in laboratory animal facilities which belong to the Association of Laboratory Animal Facilities of the National University of Japan. An antibody prevalence of 40% (384/ 961) was demonstrated. The antibody titer was shown to be higher among macaques (60% of cynomolgus monkeys, 53% of rhesus monkeys, and 34% of Japanese monkeys) than among non-macaque species (21%). These data indicate that nonhuman primates reared in animal facilities may present an occupational health problem and a potential zoonotic biohazard as demonstrated in limited cases in the United States.

Animals↗
PubMed1997

Epidemiological characterization of newly recognized rat parvovirus, "rat orphan parvovirus".

Newly recognized rat parvovirus (rat orphan parvovirus: ROPV) was examined for viral excretion and persistence in infected rats, and also for infectivity to mice and hamsters. The virus appeared to replicate mainly in lymphoid or hematopoietic tissues, and was detected in feces, urine and oropharynx of the infected rats at 1 to 4 weeks postinfection. The infective virus was also detected in peripheral leukocytes and various tissues at an acute phase of infection, and decreased in every tissue at 8 weeks postinfection. Viral DNA, however, was persistent in lymphoid tissues at least up to 24 weeks postinfection. When the virus was inoculated to mice and hamsters, no evidence of viral production and antibody response was demonstrated. ROPV is assumed to be a variant of the known rat parvovirus which resulted to alter cell tropism and persist in lymphoid or hematopoietic tissues, in order to escape from host immune system.

Animals↗
PubMed1997

Acceleration of atherosclerotic lesions in transgenic mice with hypertension by the activated renin-angiotensin system.

The present study was designed to investigate the development of atherosclerotic lesions in hypertensive transgenic mice carrying both the human renin and angiotensinogen genes (Tsukuba hypertensive mice; THM). THM and C57BL/6J control mice 2 to 3 months of age were fed with either an atherogenic or a normal diet for 14 weeks. Although the systolic blood pressure of either strain remained the same regardless of diet, it was significantly higher in THM than in C57BL/6J on both diets. Total plasma cholesterol concentrations in mice on the atherogenic diet were significantly higher than those in mice fed the normal diet. Lipoprotein profiles of cholesterol in THM were fundamentally similar to those in C57BL/6J on either the atherogenic or normal diet. Compared with controls, however, microscopic analyses revealed accelerated damage of cellular structure in the aortic root in THM fed with the atherogenic diet. Remarkably, the surface area of atherosclerotic lesion in THM was shown by quantitative image analysis to be 4 times larger than that in C57BL/6J on the same atherogenic diet. These findings suggested that hypertension induced by the activated renin-angiotensin system is involved in the development of atherosclerotic lesions. Therefore, THM should be a useful animal model for the study on the pathogenesis of atherosclerosis.

Angiotensinogen↗
PubMed1997

[Genetically engineered mice for study of human hypertension].

Human essential hypertension is generally recognized as a multifactorial disease based on genetic diathesis. Despite the usefulness of SHR and Dahl rats as laboratory tools, the genetic diathesis including the development of hypertension in these rats remains unclear. Rapid advances in embryonic engineering and molecular biological techniques may make it possible to develop transgenic mice and gene-targeted mice and open new avenues for the molecular investigation of human disease. This report introduces genetically engineered mice with hypertension and hypotension.

Animals↗
PubMed1996

Detection and in vivo transmission of rat orphan parvovirus (ROPV).

Antibodies to rodent parvovirus were detected by the immunofluorescent antibody (IFA) test but not by haemagglutination inhibition (HAI) in a commercial rat breeding colony. These antibodies were considered to be a response to so-called 'orphan parvovirus'. The virus was transmissible by intraperitoneal inoculation of infected materials (spleen cell or lymphoid tissue homogenate), and direct contact with infected rats or contaminated bedding. Furthermore, parvoviral-specific DNA sequence coded non-structural (NS) protein was detected by the polymerase chain reaction (PCR) in spleen cells and peripheral lymphocytes of experimentally infected rats.

Animals↗
PubMed1996

Vertical transmission to embryo and fetus in maternal infection with rat virus (RV).

The influence of maternal rat virus (RV) infection on rat embryogenesis and fetus was examined by viral reisolation, immunostaining and PCR analysis. Vertical transmission caused by the UT-1 strain of RV depended on the stage of gestation when maternal infection occurred. When females were infected at the pre-mating point, the number of fetuses was smaller than that normally obtained, possibly due to infection at the stage of the hatched blastocyst, but almost all of the fetuses obtained were free from infection and developed normally. The incidence of transplacental infection was the highest when pregnant females were infected in the middle of the gestation stage, and some of the fetuses died. In pregnant females which were infected late in the gestation stage, all fetuses developed normally. Some of them were infected transplacentally and harbored the infectious virus. Much attention should be paid to performing reliable rederivation of RV-infected rat colonies by hysterectomy and embryo transfer.

Animals↗
PubMed1996

Nephrogenesis and renovascular development in angiotensinogen-deficient mice.

Angiotensinogen-deficient mice provide a model to examine the roles of angiotensin II as a renal growth factor in vivo. We monitored nephrogenesis and renovascular development in angiotensinogen-deficient mice from Embryonic Day 13 (E13) to 4 weeks after birth. Northern analysis of homozygote (Atg-/-) mice confirmed the absence of angiotensinogen mRNA in the liver and the kidneys. Embryonic kidneys in Atg-/- mice from E13 to E18 exhibited active nephrogenesis, as also observed in Atg+/- mice and Atg+/+ mice. Furthermore, metanephroi harvested at E12 from Atg-/- embryos showed branching morphogenesis of ureteric bud and tubulogenesis similar to metanephrol from Atg-/- embryos grown with exogenous angiotensin II in serum-free culture. In newborn Atg-/- mice, we observed uniform dilation of the pelvis accompanied by a coarse medulla, which was not noted in Atg+/- or Atg+/+ mice. Hydronephrosis in Atg-/- mice continued, and renal papillae underwent atrophy for the 4 weeks after birth. Another characteristic aspect of the morphology of Atg-/- mice was the thickening of vascular walls as little as 2 weeks after birth. Immunohistochemistry revealed recruitment of renin in hyperplastic vascular smooth muscle cells (VSMC) in Atg-/- mice after 2 weeks. Electron microscopy confirmed that the majority of hyperplastic VSMC contained various sized renin granules with abundant endoplasmic reticulum. In situ hybridization demonstrated that expression of renin mRNA became prominent in parallel with hyperplasia of VSMC, as well as recruitment of renin protein. Furthermore, at 4 weeks, Atg-/- mice expressed alpha-smooth muscle actin in the mesangium, whereas none was ever found in that of Atg+/- mice and Atg+/+ mice. In conclusion, the renin-angiotensin system seems not be essential for nephrogenesis in vivo. Furthermore, hyperplasia of VSMC and expression of the smooth-muscle phenotype in the mesangium are inducible even in the absence of angiotensin II, with hypotension, in vivo.

Angiotensinogen↗
PubMed1995

Alterations of angiotensin II receptor contents in hypertrophied hearts.

Tsukuba hypertensive mice, which carry the human genes for renin and angiotensinogen, show cardiac hypertrophy as well as hypertension due to activation of the renin-angiotensin system (RAS). Here, we compared the cardiac angiotensin II (Ang II) receptor contents in these and normotensive control mice by means of ligand binding studies and competitive reverse transcription-polymerase chain reaction analyses. The content of the Ang II receptor type 1 (AT1) was significantly higher at both the protein (2.5-fold; p < 0.01) and mRNA (1.4-fold; p < 0.05) levels in the hypertensive mice than that in control mice. Almost identical levels of the Ang II receptor type 2 (AT2) expression were identified at the mRNA levels in the two types of mice, although the levels were less than 20% of those of AT1 mRNA in control mice. These results suggest that AT1 in the heart is upregulated in response to Ang II-induced hypertrophic change and that, in particular, the upregulation of AT1 in particular contributes to the development and/or maintenance of cardiac hypertrophy in conjunction with the increase in Ang II production, because AT1 is responsible for cardiac hypertrophy related to the RAS.

Animals↗