Biomedical subjects

M Hosokawa

Publications and source records attributed to M Hosokawa.

At least 37 records · Page 2Linked to original sources

PubMed2002

Murine leukemia virus in organs of senescence-prone and -resistant mouse strains.

A series of inbred strains of mice have been developed that are either prone (SAMP) or resistant (SAMR) to accelerated senescence. All of these strains originated from an inadvertent cross or crosses between the AKR/J mouse strain and an unknown strain(s). The characteristics of the nine senescence-prone lines differ, with all strains showing generalized aspects of accelerated aging but with each line having a specific aging-related change that is emphasized, e.g. learning and memory deficits, osteoporosis and senile amyloidosis. The senescence-resistant strains have normal patterns of aging and do not show the specific aging-related changes seen in SAMP strains. The fact that AKR mice have high levels of endogenous, ecotropic murine leukemia virus (MuLV) prompted an examination of the expression levels of MuLV in SAM strains. Analysis of brain, spleen and thymus samples revealed that seven of nine SAMP strains had high levels of MuLV and contained the Emv11 provirus (previously termed Akv1) that encodes the predominant MuLV found in AKR mice. In contrast, none of the SAMR strains had Emv11 or significant amounts of virus. The current findings represent an initial step in determining the role of MuLV in the accelerated senescence seen in SAMP strains.

Aging↗

PubMed2002

Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading.

The expression of glucose transporters (GLUTs) and its relationship to fluorodeoxyglucose accumulation in malignant tumours have been well investigated, while such a relation has not been studied in inflammatory lesions. The aim of the present study was to investigate the effects of insulin and glucose loading on the expression of GLUTs in inflammatory lesions and compare them with those in malignant tumours in relation to fluorodeoxyglucose accumulation. All tissue specimens used in this study were obtained in our previous study, in which rats were inoculated with allogenic hepatoma cells (KDH-8), Staphylococcus aureus, or turpentine oil into the left calf muscle and divided into three subgroups: insulin loaded, glucose loaded, and control groups. The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the lesions (n=5-6, for each group). In all control groups, the expression levels of GLUT-1 and GLUT-3 were significantly higher than those of GLUT-2, GLUT-4 and GLUT-5. Insulin loading did not significantly affect the expression levels of GLUT-1 and GLUT-3 in these lesions except for a significant but slight decrease in the GLUT-1 expression level in the inflammatory lesion of non-infectious origin (89% of the control value). Glucose loading significantly decreased the expression level of GLUT-1 in the inflammatory lesion of non-infectious origin (70% of the control value, P<0.01), and that of GLUT-3 in the inflammatory lesion of infectious origin (70% of the control value, P<0.05), while the expression levels of GLUT-1 and GLUT-3 in the tumour were not significantly affected. These results demonstrate the effects of insulin and glucose loading on the expression level of a molecule (GLUT proteins). The decreased GLUT-1 and GLUT-3 expression levels induced by glucose loading may partly explain the impaired FDG uptake observed in our previous study.

Animals↗

PubMed2001

Differential sensitivity of GLUT1- and GLUT2-expressing beta cells to streptozotocin.

Streptozotocin injection in animals destroys pancreatic beta cells, leading to insulinopenic diabetes. Here, we evaluated the toxic effect of streptozotocin (STZ) in GLUT2(-/-) mice reexpressing either GLUT1 or GLUT2 in their beta cells under the rat insulin promoter (RIPG1 x G2(-/-) and RIPG2 x G2(-/-) mice, respectively). We demonstrated that injection of STZ into RIPG2 x G2(-/-) mice induced hyperglycemia (>20 mM) and an approximately 80% reduction in pancreatic insulin content. In vitro, the viability of RIPG2 x G2(-/-) islets was also strongly reduced. In contrast, STZ did not induce hyperglycemia in RIPG1 x G2(-/-) mice and did not reduce pancreatic insulin content. The viability of in vitro cultured RIPG1 x G2(-/-) islets was also unaffected by STZ. As islets from each type of transgenic mice were functionally indistinguishable, these data strongly support the notion that STZ toxicity toward beta cells depends on the expression of GLUT2.

Animals↗

PubMed2001

Dietary effects of bitter gourd oil on blood and liver lipids of rats.

Bitter gourd is widely used as an edible plant in Asia. In this study, we evaluated the effects of bitter gourd oil (BGO) on the blood and liver lipids of rats. Three groups of rats were given a basal diet (AIN-93G) containing 7% fat by weight. The dietary fat consisted of soybean oil (control), soybean oil + BGO (6.5:0.5, w/w; 0.5% BGO), or soybean oil + BGO (5:2, w/w; 2.0% BGO). This fat treatment gave 3.4 and 15.4% of cis(c)9,trans(t)11,t13-18:3 in the dietary fat of 0.5 and 2.0% BGO, respectively. Fatty acid analysis showed the occurrence of c9,t11-18:2 in the liver of rats fed BGO diets, whereas this conjugated linoleic acid (CLA) isomer was not detected in the liver of rats fed the control diet. Furthermore, dietary BGO decreased the concentration of 18:2n-6 and increased the concentration of 22:6n-3. The formation of the CLA isomer in the liver lipids of rats fed BGO diets could be explained by either of the following two metabolic pathways, namely, enzymatic biohydrogenation of c9,t11,t13-18:3 or enzymatic isomerization of c9,c12-18:2. The BGO diets had significantly reduced free cholesterol levels with a trend toward an increase in HDL cholesterol, but there was no significant change in the total cholesterol. The dietary BGO also affected the level of plasma hydroperoxides. A slight but significant increase in hydroperoxides was found in the rats fed 2.0% BGO. This may be attributed to the lower oxidative stability of c9,t11,t13-18:3 in BGO.

Animal Nutritional Physiological Phenomena↗

PubMed2001

Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation.

Hypovasculature is an outstanding characteristic of pancreatic cancers in imaging diagnosis, suggesting that blood supply is poor in pancreatic cancer tissues. Despite poor blood supply, pancreatic cancer cells survive and proliferate in severe hypoxia and nutrient deprivation. To demonstrate how pancreatic cancer cells adapt themselves to hypoxia and nutrient deprivation, we investigated the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and HIF-1-inducible genes in human pancreatic cancer cell lines in comparison with other cancer cell lines. We found that HIF-1alpha protein was constitutively expressed in 15 of 20 pancreatic cancer cell lines (75%) but in none of other cancer cell lines tested in this study. The cells with constitutive expression of HIF-1alpha were more resistant to apoptosis induced by hypoxia and glucose deprivation than those without constitutive expression of HIF-1alpha. Transfection with HIF-1alpha transformed the latter cells resistant to apoptosis and increased in vivo tumorigenicity. Furthermore, anaerobic metabolism-associated genes, Glut1 and aldolase A, were more highly expressed in the cells with constitutive expression of HIF-1alpha than in the cells without it. These results suggest that constitutive expression of HIF-1alpha contributes to the survival and proliferation of pancreatic cancer cells in hypoxia and glucose deprivation through the activation of anaerobic metabolism.

Animals↗

PubMed2001

Purification, molecular cloning, and functional expression of dog liver microsomal acyl-CoA hydrolase: a member of the carboxylesterase multigene family.

To clarify the reason for the high acyl-CoA hydrolase (ACH) activity found in dog liver microsomes, the ACH was purified to homogeneity using column chromatography. The purified enzyme, named ACH D1, exhibited a subunit molecular weight of 60 KDa. The amino terminal amino acid sequence showed a striking homology with rat liver carboxylesterase (CES) isozymes. ACH D1 possessed hydrolytic activities toward esters containing xenobiotics in addition to acyl-CoA thioesters, and these activities were inhibited by a specific inhibitor of CES or by CES RH1 antibodies. These findings suggest that this protein is a member of the CES multigene family. Since ACH D1 appears to be a protein belonging to the CES family, we cloned the cDNA from a dog liver lambdagt10 library with a CES-specific probe. The clone obtained, designated CES D1, possessed several motifs characterizing CES isozymes, and the deduced amino acid sequences were 100% identical with those of ACH D1 in the first 18 amino acid residues. When it was expressed in V79 cells, it showed high catalytic activities toward acyl-CoA thioesters. In addition, the characteristics of the expressed protein were identical with those of ACH D1 in many cases, suggesting that CES D1 encodes liver microsomal ACH D1.

Amino Acid Sequence↗

PubMed2001

Spontaneous loss-of-function mutations of the 8-oxoguanine DNA glycosylase gene in mice and exploration of the possible implication of the gene in senescence.

8-Oxoguanine is one of the major premutagenic oxidative base legions in vivo and is suspected to play a crucial role in various pathophysiological processes, such as cancer and aging. Mammalian 8-oxoguanine DNA glycosylase (OGG1) is thought to play a major role in the removal of 8-oxoguanine adducts in vivo. We have identified several inbred mouse strains with a spontaneous mutation, OGG1-R336H or double mutations, OGG1-R304W/R336H. R304W mutation caused a complete loss of OGG1 activity, while the R336H mutation led to disruption of nuclear localization of the enzyme although the activity remained normal. Among the double mutants was SAMP1, which exhibits accelerated senescence and short lifespan. We assessed the possible implication of the mutant OGG1 and 8-oxoguanine in aging utilizing SAMP1 mice. SAMP1 retained 1.5- to 1.9-fold increase in 8-oxoguanine level of hepatic nuclear DNA as compared with normal mice, until at least 12 months of age. A genetic association study, however, indicated that the mutant Ogg1 gene per se is not responsible for the accelerated senescence and short lifespan of SAMP1. Mutant OGG1 may be associated with pathologic conditions in other mouse strains.

Aging↗

PubMed2001

Ultrastructural and permeability features of microvessels in the periventricular area of senescence-accelerated mice (SAM).

Brain transfer of intravenously injected horseradish peroxidase (HRP) and the ultrastructural features of the vessels were examined in periventricular areas in senescence-accelerated mice (SAMP8), which show age-related deficits in learning and memory, and senescence-accelerated resistant mice (SAMR1), which do not show age-related deficits. In all mice examined with light microscopy, staining reaction for HRP was seen in the periventricular area adjacent to the medial side of the lateral ventricle. Electron microscopic examination in the periventricular area of young and old mice of both strains showed that the staining reaction for HRP appeared in the vesicular profiles of the endothelial cytoplasm, the cytoplasm of the perivascular cells, the basal lamina, and the adjoining extracellular spaces of the white matter, suggesting an incomplete blood-brain barrier (BBB) in the periventricular white matter. In addition, irregularly thickened endothelial cell cytoplasm, membranous inclusions within the basal lamina, and electron-dense endothelial cell cytoplasm were occasionally seen in aged SAMP8 mice. These findings were not observed in 3-month-old SAMP8 mice and 3- and 13-month-old SAMR1 mice. Perivascular collagen deposits were also frequently seen in aged SAMP8 mice. These findings indicate that the endothelial cells and pericytes in the periventricular white matter in aged SAMP8 mice have an ultrastructure with damaged BBB function. Intravascular substances can easily penetrate the periventricular white matter and the BBB of the vessels in the area can be deteriorated with aging in SAMP8 mice.

Aging↗

PubMed2001

Association of trypsin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma.

BACKGROUND: Overexpression of the matrix serine proteinase (MSP) trypsin has been implicated in tumor growth, invasion, and metastasis. The objective of this study was to clarify the clinicopathologic and prognostic significance of trypsin expression in esophageal squamous cell carcinomas (SCC). METHODS: Production of trypsin in tissue extracts was analyzed by immunoblotting and gelatin zymography. The authors analyzed the association between immunohistochemically detected trypsin expression in esophageal SCC and clinicopathologic characteristics, and they investigated whether trypsin is a predictor of recurrence and/or survival. RESULTS: Overproduction and activation of trypsin was observed in 6 of 10 tumor extracts. The trypsin immunoreactivities at the invasive front were more intense than those at the superficial layer. Sections with immunostaining signals in greater than 30% of carcinoma cells at the invasive front, which were observed in 52 (52%) cases, were judged to be positive for trypsin. Trypsin positivity was significantly correlated with the depth of invasion (P < 0.0001), lymph node metastasis (P = 0.0048), advanced pTNM classification (P = 0.0006), recurrence (P = 0.0003), and recurrence within the first postoperative year (P = 0.0005). Patients with trypsin positive carcinoma had significantly shorter disease free and overall survival times than did those with trypsin negative carcinoma (P < 0.0001 and P < 0.0001, respectively). Trypsin retained its significant predictive value for disease free and overall survival in multivariate analysis that included conventional clinicopathologic factors (P = 0.0029 and P = 0.0006, respectively). Patients with concomitant overexpression of trypsin and matrilysin at the invasive front, in which they often were colocalized, had the worst prognosis. CONCLUSIONS: The authors' results suggest that trypsin plays a key role in the progression of esophageal carcinoma. Detection of trypsin expression as well as matrilysin is useful for the prediction of recurrence and poor prognosis.

Carcinoma, Squamous Cell↗

PubMed2001

Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats.

The biological role of the peroxisome proliferator-activated receptors (PPARs) in various diseases, including inflammation and cancer, has been highlighted recently. Although PPARgamma ligands have been found to inhibit mammary carcinogenesis in rodents, the effects on colon tumorigenesis are controversial. In the present study, three different experiments were conducted to investigate the modifying effects of PPARs ligands (PPARalpha and PPARgamma) on colitis and an early phase of colitis-related colon carcinogenesis in male F344 rats. In the first experiment, gastric gavage of troglitazone (PPARgamma ligand, 10 or 100 mg/kg body weight) or bezafibrate (PPARalpha ligand, 10 or 100 mg/kg body weight) inhibited colitis induced by dextran sodium sulfate (DSS) and lowered trefoil factor-2 content in colonic mucosa. In the second experiment, dietary administration (0.01 or 0.05% in diet) of troglitazone and bezafibrate for 4 weeks significantly reduced azoxymethane (AOM, two weekly s.c. injections, 20 mg/kg body weight)-induced formation of aberrant crypts foci, which are precursor lesions for colon carcinoma. In the third experiment, dietary administration (0.01% in diet for 6 weeks) of pioglitazone (PPARgamma ligand), troglitazone, and bezafibrate effectively suppressed DSS/AOM-induced ACF. Administration of both ligands significantly reduced cell proliferation activity in colonic mucosa exposed to DSS and AOM. Our results suggest that synthetic PPARs ligands (PPARalpha and PPARgamma) can inhibit the early stages of colon tumorigenesis with or without colitis.

Animals↗

PubMed2001

Increased oxidative DNA damage in mammary tumor cells by continuous epidermal growth factor stimulation.

BACKGROUND: Growth factors can enhance the malignant potential of tumor cells. To examine the relationship between growth factors and tumor progression, we previously established a weakly malignant cell line, ER-1. We found that a 24-hour exposure of ER-1 cells to epidermal growth factor (EGF) induced malignant properties (tumor progression) that were reversible but that, after a 1-month exposure, these changes were irreversible. In this study, we investigated the irreversible changes induced in ER-1 cells by a 1-month exposure to EGF and the possible involvement of oxidative stress. METHODS: ER-1 cells were treated with EGF (100 ng/mL) for 1 month in the presence or absence of an antioxidant, N-acetylcysteine or selenium, and compared with untreated control ER-1 cells. We assessed tumor progression by measuring intracellular peroxide levels, 8-hydroxydeoxyguanosine (a marker for oxidative DNA damage) levels, in vitro invasiveness, and in vivo tumorigenicity and metastatic ability. All statistical tests are two-sided. RESULTS: After ER-1 cells were treated for 1 month with EGF, levels of intracellular peroxide and 8-hydroxyguanosine in the DNA of treated cells were higher than those in the DNA of control cells, and treated ER-1 cells were more tumorigenic and metastatic in vivo and more invasive in vitro than untreated control cells (all P<.001). Levels of 8-hydroxyguanosine in DNA increased as the length of the EGF treatment increased (P<.001). However, when N-acetylcysteine or selenium was added with EGF for 1 month, levels of intracellular peroxide and 8-hydroxyguanosine in DNA were comparable to those in control cells (r =.795). Both tumorigenicity (P =.008) and metastatic ability (P<.001) decreased after addition of N-acetylcysteine or selenium. CONCLUSION: The irreversible changes caused by continuous EGF stimulation of ER-1 cells result from increased oxidative damage in the DNA, which generates tumor cells with more malignant characteristics.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

High-performance liquid chromatographic analysis of the sulfation of 4-hydroxypropranolol enantiomers by monkey liver cytosol.

We developed a new high-performance liquid chromatographic method using an ODS column and a chiral column for the assay of racemic 4-OH-PL sulfate and enantiomeric 4-OH-PL sulfates, respectively. The method was successfully applied to measure phenolsulfotransferase (PST) activities for 4-OH-PL in cytosolic fractions from livers of Japanese monkeys (Macaca fuscata) and for comparison with its activity of cytosolic fractions from rat, rabbit, dog, and human livers and Hep G2 cells. The activity was ranked as Hep G2 cells > monkeys = humans = dogs = rats > rabbits. To evaluate the Japanese monkey as a nonhuman animal model in drug metabolism studies, we further characterized sulfation of 4-OH-PL as a further metabolic pathway in monkey livers to compare that with human livers. Inhibition studies in which cytosolic fractions were preincubated at 43 degrees C or 2,6-dichloro-4-nitrophenol (DCNP) used as a PST inhibitor indicated that two kinds of PSTs, thermolabile, low-Km and DCNP-resistant PST and thermostable, high-Km and DCNP-sensitive PST were involved in 4-OH-PL sulfation by monkey liver cytosol, which is very similar to the reported profile of 4-OH-PL sulfation by human liver cytosol. Sulfation kinetics in a low concentration range of 4-OH-PL enantiomers demonstrated that apparent Km values were similar between human and monkey liver cytosolic fractions, but the Vmax values were different, so that intrinsic clearance values (Vmax/Km, Clint) were higher in monkeys than in humans. Furthermore, enantiomer selectivity of [R(+)-4-OH-PL > S(-)-4-OH-PL] was observed in the Vmax and CLint values of monkey liver cytosol. These results indicate that the profile of sulfation of 4-OH-PL by liver cytosolic fractions is similar in humans and Japanese monkeys.

Adult↗

PubMed2001

Gelsolin functions as a metastasis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect.

Gelsolin, an actin-binding protein, is implicated as a critical regulator in cell motility. In addition, we have reported that cellular levels of gelsolin are decreased in various tumor cells, and overexpression of gelsolin by gene transfer suppresses tumorigenicity. We sought to assess the effects of gelsolin overexpression on metastasis and to determine the importance of a carboxyl-terminus that confers Ca(2+) dependency on gelsolin for effects of its overexpression. Expression vectors with cDNA encoding either full-length wild-type or His321 mutant form, isolated from a flat revertant of Ras-transformed cells and a carboxyl-terminal truncate, C-del of gelsolin, were transfected into a highly metastatic murine melanoma cell line, B16-BL6. Expression of introduced cDNA in transfectants was confirmed using Western blotting, 2-dimensional gel electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). We characterized phenotypes of transfectants, such as growth rate, colony formation in soft agar, cell motility and metastasis formation in vivo. Transfectants expressing the wild-type, His321 mutant and C-del gelsolin exhibited reduced growth ability in soft agar. Although expression of integrin beta1 or alpha4 on the cell surface of transfectants was not changed, wild-type and His321 mutant gelsolin, except for C-del gelsolin, exhibited retardation of cell spreading, reduced chemotatic migration to fibronectin and suppressed lung colonization in spontaneous metastasis assay. Gelsolin may function as a metastasis suppressor as well as a tumor suppressor gene. The carboxyl-terminus of gelsolin is important for retardation of cell spreading, reduced chemotasis and metastasis suppression.

Animals↗

PubMed2001

Effects of insulin and glucose loading on FDG uptake in experimental malignant tumours and inflammatory lesions.

Fluorine-18 2-deoxy-2-fluoro-D-glucose (FDG) accumulation in tumours has been well investigated, but much less is known regarding FDG accumulation in inflammatory lesions. In this study, we determined the effects of hypo- and hyperglycaemia on FDG uptake in inflammatory lesions of infectious and non-infectious origin and compared them with those in malignant tumours in rats, to provide a biological basis for differentiating malignant lesions from benign lesions by means of FDG-PET. Rats were inoculated with a suspension of allogenic hepatoma cells (KDH-8) or Staphylococcus aureus, or with turpentine oil into the left calf muscle. Two weeks after KDH-8 inoculation and 1 week after S. aureus and turpentine oil inoculations, the rats were divided into three subgroups: insulin-loaded (2 U/kg body weight, i.p.), glucose-loaded (1.2 g/kg body weight, p.o.) and control groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. Intraperitoneal injection of insulin and oral administration of glucose induced hypoglycaemia and hyperglycaemia, respectively. In the control animals, tumours showed a level of FDG uptake which was 2.2 and 3.0 times higher than the levels in the inflammatory lesions induced by S. aureus and turpentine oil, respectively (P<0.0001). There was no significant difference in the level of FDG uptake between the two inflammatory lesions of infectious and non-infectious origin. Insulin loading significantly decreased the level of FDG uptake in tumours and in both types of inflammatory lesion to approximately one-half of the control values (P=0.001 in the tumour group and P<0.0001 in the two inflammatory lesion groups). In the glucose-loaded group, the level of FDG uptake in both types of inflammatory lesion decreased significantly to 50%-61% of the control value (P=0.0002 in the S. aureus group and P<0.0001 in the turpetine group), while the tumour uptake did not decrease significantly (86% of the control value) (P=NS). It is concluded that FDG uptake in both types of inflammatory lesion was significantly impaired in rats with hyperglycaemia induced by glucose loading, while tumour uptake of FDG was not significantly affected. These results indicate that glucose loading has greater effects on FDG uptake in inflammatory lesions than in tumours, providing a biological basis for differentiation of malignant lesions from benign lesions by FDG-PET in a clinical setting.

Animals↗

PubMed2001

Jejunal carcinoid tumor mimicking leiomyosarcoma: preoperative diagnosis by endoscopic biopsy.

Primary carcinoid tumor of the jejunum is rare, and is an unusual cause of massive gastrointestinal bleeding. A case of primary jejunal carcinoid tumor in a 39-year-old woman who presented with massive hematochezia is described. Both upper and lower gastrointestinal endoscopies showed no abnormalities. An abdominal computed tomographic scan, small-bowel barium contrast studies, and small-bowel endoscopy showed a subserosal mass, of 5 x 4 cm, with a cavity suggesting central necrosis, and a deep mucosal ulceration, located in the proximal jejunum. Although these clinical presentations were strongly suggestive of a leiomyosarcoma, histologic examination of biopsy samples obtained by enteroscopy confirmed the diagnosis of jejunal carcinoid tumor. The patient underwent radical jejunal resection and recovered uneventfully. In spite of the large size of the tumor, there was one solitary lymph node metastasis, but no evidence of liver metastases. This kind of jejunal carcinoid tumor, presenting with massive gastrointestinal bleeding and a subserosal bulky growth mimicking a leiomyosarcoma, has not been reported previously. Moreover, this is a rare case of a jejunal carcinoid which was diagnosed preoperatively by small bowel-endoscopic biopsy.

Adult↗

PubMed2001

Effects of aging and blood pressure on the structure of the thoracic aorta in SAM mice: a model of age-associated degenerative vascular changes.

The effects of aging and blood pressure on the structural alterations of the thoracic aorta were examined using male, accelerated senescence-prone, short-lived SAMP11 mice or accelerated senescence-resistant, long-lived SAMR1 mice. The aortic wall thickness increased significantly by 34% in SAMR1 and by 62% in SAMP11 with advanced age. We observed branching, breakage and disorganization of the elastic lamellae, an increase in thin collagen fibrils between the medial smooth muscle cells and hypertrophy but a significant decrease in the number of medial smooth muscle cells with aging in both strains. These alterations observed in SAMP11 occurred earlier and were more exaggerated with advanced age than in SAMR1. The aortic lumen dilated gradually in SAMR1, but narrowed significantly in SAMP11 with aging. The systolic blood pressure did not differ significantly among SAMP11s aged 3-9months, or among all ages of SAMR1. However, it was elevated in SAMP11 at the terminal stage of their life. Our results suggest that the aorta in SAMR1 might reflect the physiological process of aging, whereas SAMP11 showed earlier changes due to the senescence acceleration of the vascular cells, which were exaggerated by the elevated blood pressure.

Aging↗

PubMed2001

Transmission of mouse senile amyloidosis.

SUMMARY: In mouse senile amyloidosis, apolipoprotein A-II polymerizes into amyloid fibrils (AApoAII) and deposits systemically. Peripheral injection of AApoAII fibrils into young mice induces systemic amyloidosis (Higuchi et al, 1998). We isolated AApoAII amyloid fibrils from the livers of old R1.P1-Apoa2(c) mice and injected them with feeding needles into the stomachs of young R1.P1-Apoa2(c) mice for 5 consecutive days. After 2 months, all mice had AApoAII deposits in the lamina propria of the small intestine. Amyloid deposition extended to the tongue, stomach, heart, and liver at 3 and 4 months after feeding. AApoAII suspended in drinking water also induced amyloidosis. Amyloid deposition was induced in young mice reared in the same cage for 3 months with old mice who had severe amyloidosis. Detection of AApoAII in feces of old mice and induction of amyloidosis by the injection of an amyloid fraction of feces suggested the propagation of amyloidosis by eating feces. Here, we substantiate the transmissibility of AApoAII amyloidosis and present a possible pathogenesis of amyloidosis, ie, oral transmission of amyloid fibril conformation, where we assert that exogenous amyloid fibrils act as templates and change the conformation of endogenous amyloid protein to polymerize into amyloid fibrils.

Amyloid↗

PubMed2001

Effects of carbamazepine on the first ovulation in gonadotropin-primed immature female rats.

1. The effects of carbamazepine (CBZ) and its possible mechanisms on the first ovulation were investigated in immature female rats. The first ovulation was induced by administration of equine chorionic gonadotropin (eCG) at 0800 h at 26 days of age. 2. A single s.c. injection of 360 mg x kg(-1) CBZ at 1300 h on the first pro-oestrus (day 28) completely inhibited the first ovulation on the morning of day 29. A marked elevation in 13, 14-dihydro-prostaglandin F2alpha (13, 14H2-PGF2alpha) forming capacity, a sensitive indicator of luteinizing hormone (LH) surge, was not detected in the CBZ-treated group at 0800 h on day 29 (72 h after eCG treatment). The elevation in serum LH levels at 57 h after eCG treatment was not observed in the CBZ-treated group, either. The blocking of the first ovulation and 13, 14H2-PGF2alpha forming capacity were recovered by an i.p. injection of human CG on day 28 in all animals. 3. However, the first ovulation was not blocked by repeated injections of 360 mg x kg(-1) CBZ at 1300 h once daily for 3 days (days 26 - 28). The repeated injections of CBZ caused a great fall (64% decrease) in the serum levels of CBZ at 4 h after the final CBZ injection as compared with the case of a single injection of CBZ and resulted in a delay for 5 h the occurrence of LH surge, which is normally observed around 57 h after eCG injection. 4. A significant increase in the activity of microsomal CBZ catabolism by the repeated injections of CBZ was quantitatively verified by the HPLC analysis. But, the activity of CBZ metabolism in the single injected-animals showed almost similar levels to that in the control. 5. The present results demonstrated that a single injection of CBZ blocks the ovulation by inhibiting LH surge but that the failure of the inhibition of ovulation by repeated injections of CBZ is due to a decrease in serum CBZ levels mediated through CBZ-induced hepatic enzyme induction.

Animals↗