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Biomedical subjects

J Deguchi

Publications and source records attributed to J Deguchi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Stimulated activation of platelet-derived growth factor receptor in vivo in balloon-injured arteries: a link between angiotensin II and intimal thickening.

BACKGROUND: Growth factors such as platelet-derived growth factor (PDGF) have been postulated to be important mediators of neointimal formation in balloon-injured artery. Binding of growth factors to their receptors activates intrinsic receptor tyrosine kinase, resulting in tyrosine phosphorylation of receptors themselves and cellular substrate proteins. We investigated in vivo activities of growth factors by determining the extent of tyrosine phosphorylation of growth factor receptors and substrate proteins in injured artery. METHODS AND RESULTS: Rat balloon-injured carotid artery was analyzed for phosphotyrosine content of PDGF alpha- and beta-receptors, epidermal growth factor (EGF) receptors, and insulin receptor substrate-1 (IRS-1) by immunoprecipitation and anti-phosphotyrosine Western blot. The development of intimal thickening after deendothelializing balloon catheterization of rat carotid artery was accompanied by transient twofold to threefold increases in the extent of tyrosyl phosphorylation of PDGF alpha- and beta-receptors but not EGF receptor or IRS-1. The AT1 angiotensin II (Ang II) receptor antagonist TCV-116 markedly inhibited both tyrosyl phosphorylation of PDGF alpha- and beta-receptors and intimal thickening. The AT1 antagonist reduced mRNA levels of both PDGF-A and -B chains in injured arteries. CONCLUSIONS: The present study provides direct evidence for increased PDGF activities in injured artery in situ and the involvement of Ang II in stimulated activation of PDGF receptors. These results are consistent with the pathogenetic role for PDGF in intimal thickening.

Amlodipine↗
PubMed1997

Topographic anatomy of paraclinoid carotid artery aneurysms: usefulness of MR angiographic source images.

We evaluated the usefulness of magnetic resonance angiography (MRA) for showing the topography of paraclinoid carotid artery aneurysms in 27 patients with 30 paraclinoid aneurysms undergoing conventional angiography, three-dimensional time-of-flight MRA and surgery. The anatomy shown on the axial MRA source images was consistent with that found at surgery. The neck of the aneurysm could always be identified on the source images, while it could not be analysed exactly on conventional angiography in 3 cases (10%). The optic nerves, including those displaced by the aneurysm, were recognised in all patients. The anterior clinoid process was shown as a low-intensity rim or area contiguous with the cortical bone. The source images were of great value in understanding the topography of paraclinoid carotid artery aneurysms.

Adult↗
PubMed1997

Adenovirus-mediated transfer of tissue-type plasminogen activator gene to human endothelial cells.

BACKGROUND: Seeding of vascular grafts with genetically engineered human endothelial cells (hECs) secreting antithrombogenic or fibrinolytic agents has considerable clinical potential. METHODS: An adenoviral vector was used to transfer the human tissue-type plasminogen activator (htPA) gene to hECs, and the ability of the transduced hECs to secrete htPA was examined. Cultured hECs on plates were incubated with various concentrations of recombinant adenoviruses containing the htPA or LacZ gene for various times to determine the optimal transfer conditions. Transduced hECs were seeded onto fibronectin-coated expanded polytetrafluoroethylene grafts (4 mm in diameter), some of which were exposed to pulsatile flow in vitro. RESULTS: Effective transduction of the htPA gene into hECs (htPAhECs) was achieved with viral soup at a multiplicity of infection of 30 after incubation for 1 day, which yielded 4.8 +/- 0.20 x 10(3) ng/10(6) cells/6 hr htPA antigen on plates (n = 3), 2.2 +/- 2.0 x 10(3) ng/10(6) cells/6 hr on grafts (n = 6), and 6.8 +/- 1.7 x 10(2) ng/10(6) cells/6 hr on perfused grafts (n = 6). The retention of htPAhECs by perfused grafts was 84.0% +/- 3.0%, comparable with the noninfected (82.1% +/- 8.0%) and mock-infected (94.2% +/- 0.4%) hEC values. CONCLUSIONS: By adenoviral vector-mediated gene transfer, 10(2-3)-fold enhancement of htPA secretion was demonstrated, which did not affect cell retention by grafts.

Adenoviridae↗
PubMed1997

Surgical results of abdominal aortic aneurysm repair in patients with chronic renal dysfunction.

The purpose of this study was to determine the influence of preoperative renal dysfunction on the outcome of patients undergoing elective, infrarenal abdominal aortic aneurysm (AAA) repair. Patients undergoing AAA repair from 1984 to 1996 (n = 250) were divided into 2 groups, according to their preoperative serum creatinine levels: > or = 1.5 mg/dl (group A, n = 33) and < 1.5 mg/dl (group B, n = 217). There was no apparent difference in the incidences of preoperative risk factors, excluding ischemic heart disease, between the groups. The mortality rates of the 2 groups did not differ (9.9% vs 3.2% in groups A and B, respectively, p = 0.13), but the morbidity rate of group A (30.3%) was significantly higher than that of group B (12.9%, p = 0.0095). The 5-year cumulative survival rate of group A patients was 60%, which was significantly lower (p < 0.0001) than that of group B patients (84%). Five group A patients underwent simultaneous renal artery reconstruction, which relieved postoperative renal deterioration in 4, although 2 of them developed chronic renal failure requiring hemodialysis over 5 years after the operation. These findings suggest that morbidity and long-term survival in patients with renal dysfunction can be severe after AAA repair and that simultaneous renal artery reconstruction may delay renal function decline.

Aged↗
PubMed1997

Fourteen-day oral combination dose toxicity study of CGS 16949 A (aromatase inhibitor) with 5-fluorouracil or tamoxifen in rats.

CGS 16949A, an aromatase inhibitor, was administered orally to female rats at doses of 1 and 10 mg/kg/day alone and in combination with tamoxifen (0.5 or 5 mg/kg/day) or 5-fluorouracil (20 mg/kg/day) for 14 days. CGS 16949A and tamoxifen combination: Increased food intake and body weight noted after CGS 16949A treatment were also observed following combination treatment, though to a lesser degree. Most of the clinical pathological features noted following combination treatment were similar to those induced by single compound treatment. Gross pathological and histopathological changes ascribed to the antiestrogenic action of CGS 16949A, such as increased ovarian weight, decreased uterine weight, cystic follicles and atrophied uterus and vaginal epithelium, were alleviated by combination treatment, and were comparable in severity to those caused by tamoxifen alone. No severe toxic changes were induced by combination treatment. CGS 16949A and 5-fluorouracil combination: Increased body weight noted after CGS 16949A treatment was also observed following combination treatment, though to a lesser degree. Most of the changes caused by single compound treatment, including the aforementioned effects of CGS 16949A on the genital organs, were also noted following combination treatment. There was no evidence of enhancement of the effects by combination treatment.

Administration, Oral↗
PubMed1996

[Tumor necrosis factor alpha regulates the proliferative activity and differentiated function of granulosa cells: in vitro study with a porcine model].

Ovarian folliculogenesis is a dynamic process during which follicles undergo growth and differentiation. It is now evident that various growth factors interact with FSH to modify follicular growth and function. In the present study, the effects of tumor necrosis factor alpha (TNF alpha) on the proliferative potential and steroidogenic ability of granulosa cells were examined in vitro as a function of follicular growth by using a porcine model. Porcine granulosa cells obtained from small (1-2mm), medium (3-5mm) and large (6-12 mm) follicles were cultured under serum-free conditions in the presence or absence of FSH (100 ng/ml) and IGF-1 (100 ng/ml), with or without various concentrations of TNF alpha. The proliferative activity of cultured granulosa cells was assessed by immunocytochemical techniques with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) and by [3H]-thymidine uptake, while differentiated functions of granulosa cells were assessed by determining the ability to secrete progesterone and 17 beta-estradiol. The addition of FSH and IGF-I augmented the proliferative activity and steroidogenic ability of cultured granulosa cells. The increases in proliferative activity and steroidogenic ability caused by treatment with FSH and IGF-I were significantly reduced by the concomitant treatment with TNF alpha in culture of granulosa cells. The inhibitory effect of TNF alpha on the proliferative activity was prominent in small follicle granulosa cells, whereas the inhibitory effect of TNF alpha on estradiol secretion was very strong in large follicle granulosa cells. The inhibitory effect of TNF alpha on progesterone secretion was apparent regardless of the stage of follicular growth. These results suggest TNF alpha participation in regulating the proliferation and differentiation of granulosa cells. In appears that the biological action of TNF alpha on granulosa cells may shift from the inhibition of proliferative activity in immature follicles to the inhibition of differentiated function in mature follicles during the course of follicular growth.

Animals↗
PubMed1996

Completion arteriography in paramalleolar bypasses: effect of configurational changes, with special reference to spasm, on long-term outcome.

PURPOSE: The purpose of this study was to ascertain the durability of paramalleolar bypasses and elucidate the effect of configurational changes, especially spasm, seen on the completion arteriography upon the outcome. DESIGN: Retrospective study. SETTING: University hospital experience. PATIENTS AND METHODS: Nineteen paramalleolar bypass operations in sixteen patients performed between April 1988 and March 1995 were studied retrospectively. Reversed saphenous vein grafts were used in all cases. One patient required an additional microvascular free flap transfer to cover a foot amputation stump. Seventeen completion arteriograms were obtained. Patients were followed for an average of 37 months. RESULTS: One patient died in hospital, giving a hospital death rate of 5.9%. Two grafts failed immediately and could not be salvaged. Inadvertent perforation of one graft required partial replacement with a polytetrafluoroethylene graft; it eventually failed after 42 months. There were no other graft failures during follow-up. Nine completion arteriograms showed spastic change of the run-off artery, but this change had disappeared on repeat angiograms obtained before discharge. CONCLUSION: Spasm of run-off artery is a frequent finding in distal bypass surgery and adversely affects the immediate outcome. Heparinization during the first 24 hours after surgery may reduce the consequences of spasm, and long-term patency can be expected providing that the whole graft consists of autogenous vein.

Adult↗
PubMed1995

Renal cysts and associated renal tumours in male ddY mice injected with ferric nitrilotriacetate.

In experiments using ferric nitrilotriacetate (Fe-NTA) as a renal carcinogen, multiple renal cysts are often observed in addition to renal tumours. In the present study, we used 3-week-old male ddY mice and examined the relation between renal cysts and cancer development. Four months after the start of Fe-NTA administration, we observed cysts in the renal cortex in all Fe-NTA-treated mice, but not in Fe-free NTA-treated mice. Three types of cysts were observed, but only those which originated from the renal proximal tubules showed multilayered or papillary growth of cyst epithelial cells. Using histochemical staining, we found a cyst formation-tumour induction sequence, and the supposed cystic-papillary tumour induced by Fe-NTA was of proximal tubular cell origin. We also found that the minimum dose of Fe-NTA capable of inducing renal tumours in ddY mice was 10 mg of iron/kg/day, four times in 2 weeks.

Animals↗
PubMed1995

Sex hormone-dependent renal cell carcinogenesis induced by ferric nitrilotriacetate in Wistar rats.

Ferric nitrilotriacetate (Fe-NTA), an iron chelate, induces necrosis of renal proximal convoluted tubules as a consequence of lipid peroxidation, and a high incidence of renal cell carcinoma (RCC) is also observed in rats and mice. The incidence of RCC and the extent of lipid peroxidation are greater in males than females. In the present study, the effects of castration or ovariectomy, and sex hormone treatment on Fe-NTA-induced renal carcinogenesis in rats were examined. Male and female Wistar rats were each divided into 5 groups. In group 1, rats were sham-operated and treated intraperitoneally (i.p.) with nitrilotriacetate (NTA). In group 2, sham-operated rats were treated with Fe-NTA (5-10 mg iron/kg/day, i.p.). Castrated or ovariectomized rats treated with Fe-NTA served as group 3. Group 4 or 5 was treated in the same way as group 3, but in addition received either testosterone (group 4) or estradiol (group 5). NTA, Fe-NTA or sex hormone treatments were initiated 4 weeks after the operation. NTA or Fe-NTA treatments were conducted for 12 weeks, and sex hormones were administered for 10 months. After 10 months of treatment, all rats were autopsied and both kidneys were examined histopathologically. In NTA-treated groups, there was no pathological change in the kidneys. In Fe-NTA-treated groups (groups 2-5), testosterone treatment or ovariectomy increased the incidence of RCC, and estradiol treatment or castration decreased the incidence of RCC (male: sham operation, castration and testosterone treatment > castration > castration and estradiol treatment, female: ovariectomy and testosterone treatment > ovariectomy > sham operation, ovariectomy and estradiol treatment). These results indicate that sex differences observed in the incidence of RCC induced by Fe-NTA are dependent upon sex hormones.

Animals↗
PubMed1995

[Usefulness of thin axial images of computerized tomography angiography for surgery on paraclinoidal carotid artery aneurysms].

A number of surgical experiences with paraclinoidal carotid artery aneurysms have been reported recently. However, neuroradiological examinations can not sufficiently visualize the topographic relations around the aneurysms due to variations in the size of the anterior clinoid process (ACP) or course of the carotid artery in individual cases. Although three-dimensional computerized tomography angiography (3-D-CT-A) is known to be useful for the surgical management of cerebral aneurysms in common locations, its usefulness for paraclinoidal carotid artery aneurysms has not been investigated. Ten cases involving a total of 13 aneurysms located in the clinoid portion of the carotid artery were included in this study according to Al-Radham's classification (Table). The CT scan used was an X Force system manufactured by Toshiba Electric Co, Japan. Non-ionic, iodinated contrast solution, a total of 2ml/kg, was intravenously infused at a rate of 2ml/sec. Helical scanning was begun 30 seconds after initiating the infusion, 1mm pitch/1.5 second/rotation. 3-D images and original images of axial slices were compared to conventional angiography, DSA and surgical findings. The 3-D images of 3-D-CT-A was able to demonstrate both aneurysms located in the C2 segment of the carotid artery (groups I and II), and five of nine carotid cave aneurysms (group III). The aneurysms located more proximally (group IV or V) could not be visualized.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Immunocytochemical analyses of distributions of Na, K-ATPase and GLUT1, insulin and transferrin receptors in the developing retinal pigment epithelial cells.

The retinal pigment epithelium (RPE) is unique in that Na,K-ATPase is predominantly localized on its apical surface. We studied the distributions of Na,K-ATPase and glucose transporter GLUT1, insulin and transferrin receptors in developing rat RPE cells immunocytochemically. Na,K-ATPase, first detected in 17-day-old embryonic eyes, was already distributed predominantly on the apical surface. This reversed distribution of Na,K-ATPase was maintained throughout their life. Insulin receptor and transferrin receptor were distributed exclusively on the basolateral surface. By quantitative immunogold electron microscopic technique we found that glucose transporter GLUT1 is distributed almost equal in amount on both the apical and basolateral surfaces of RPE cells, thus presumably constructing an efficient pathway for glucose transport from the choriocapillaries to the neural retina through the blood-retinal barrier. These results suggest that in the RPE cells the intrinsic basolateral plasma membrane proteins are sorted out at least in three different ways.

Animals↗
PubMed1994

[Immunohistological study in Bruch's membrane of senescence accelerated mouse].

Age-related macular degeneration is one of the major causes of severe visual loss is elderly individuals. However, relatively little is known about its etiology. The disease may be associated with senescence. Ultrastructural and immunohistochemical studies on SAM (senescence accelerated mouse) eyes were carried out to learn details of aging changes in the retinal pigment epithelium (RPE) and Bruch's membrane. SAM P 1 mice aged 2, 10, 14 months were examined in this study. The eyes were analysed for type IV collagen and heparan sulfate proteoglycan (HSPG) by the avidin-biotin-peroxidase complexes (ABC) method and post-embeddig immunolocalization with colloidal gold. With the ABC method, the basement membranes of both the RPE and the choriocapillaris showed markedly positive staining when treated with anti-type IV collagen antibody and moderately positive staining when treated with anti-HSPG antibody. In ultrastructural immunolocalization, both basement membranes showed fairly heavy labeling in response to the antibodies to type IV collagen, and moderate labeling in response to the antibodies to HSPG. With aging, the thickness of the basement membrane of the choriocapillaris and gold particle labeling by the antibodies to type IV collagen increased. The gold particle labeling by the antibodies to HSPG increased slightly, but was distributed sparsely. These results showed the advancing process of senescence changes in Bruch's membrane.

Aging↗
PubMed1994

Acidification of phagosomes and degradation of rod outer segments in rat retinal pigment epithelium.

PURPOSE: The authors investigated the phagocytic processes of the rod outer segments (ROS) in rat retinal pigment epithelium (RPE) cells, and the appearance of lysosomal enzymes, acidification, and degradation of the contents in the phagolysosomes. In particular, they examined the effect of bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, on the degradation of ROS in the RPE cells in vivo. METHODS: A lysosomal enzyme (cathepsin D), a lysosomal membrane protein (LGP107), and opsin were localized in the RPE cells by the immunogold electron microscopic technique. Bafilomycin A1 was injected into the vitreous, and acidification of the phagosomes was measured in vivo by injecting 3-[2,4-dinitroanilino]3'amino-N-methyldipropylamine (DAMP) in the vitreous and detecting the accumulation of DAMP in the phagolysosomes using anti-dinitrophenol antibody. RESULTS: Opsin was abundantly detected in phagosomes that did not contain cathepsin D, but the immunolabeling of opsin rapidly disappeared soon after the appearance of cathepsin D. By double staining with cathepsin D and DAMP, it was shown that the pH of the phagosomes dramatically decreased after fusion with lysosomes. When bafilomycin A1 was injected into the vitreous, many large phagolysosomes containing cathepsin D appeared in the RPE cells, in which the immunoreactivity of opsin was well preserved. CONCLUSIONS: Degradation of opsin and acidification proceeded almost parallel with the appearance of cathepsin D in the phagolysosomes. Bafilomycin A1 did not inhibit the fusion of phagosomes with lysosomes, but it increased intraphagosomal pH and markedly inhibited the degradation of ROS in the phagolysosomes. This result indicates that vacuolar-type H(+)-ATPase is essential for acidifying the lumen of phagolysosomes and subsequent protein degradation of ROS in the RPE cells.

Animals↗
PubMed1993

Transforming growth factor-alpha expression of renal proximal tubules in Wistar rats treated with ferric and aluminum nitrilotriacetate.

A high incidence of renal adenocarcinoma has been observed in rats treated with ferric nitrilotriacetate (Fe-NTA) but not in rats treated with aluminum nitrilotriacetate (Al-NTA). Transforming growth factor (TGF)-alpha is one of the several cytokines that is known to be expressed in human and rat renal adenocarcinomas. However, its role in neoplastic transformation is still questionable. Therefore, we investigated the effect of repeated Fe-NTA and Al-NTA administration on renal TGF-alpha expression. Male Wistar rats were given Fe-NTA (n = 16, 5-10 mg Fe/kg) and Al-NTA (n = 19, 1-2 mg Al/kg) i.p., three times a week for 3 or 12 weeks. Another group of rats (n = 4) was given Fe-NTA (5-10 mg Fe/kg) three times a week for 12 weeks and then left untreated for one year. Immunoreactivity for TGF-alpha was positive in the collecting ducts and on the apical surface of proximal tubules in the outer stripe of the outer medulla in all the animals including NTA-injected control animals. However, TGF-alpha immunoreactivity in the regenerative proximal tubular epithelium was observed only in the animals treated with Fe-NTA for 12 weeks. Northern blot analysis also showed expression of TGF-alpha mRNA only in animals treated with Fe-NTA for 12 weeks. The expression of TGF-alpha mRNA in the kidney was stronger than that in the liver or brain. TGF-alpha was also positive in renal cell carcinoma found in animals treated with Fe-NTA for 12 weeks and left untreated for one year. These results suggest that TGF-alpha expression may play an important role in renal carcinogenesis and that it may be a sensitive marker during the induction stage of renal cell carcinoma.

Animals↗
PubMed1993

Insulin receptor expression in follicular and stromal compartments of the human ovary over the course of follicular growth, regression and atresia.

The cytologic localization and cellular levels of insulin receptors in the human ovary during follicular growth, regression and atresia were examined by the avidin/biotin immunoperoxidase techniques with a monoclonal antibody to insulin receptor. In primordial follicles, only the oocyte showed a weak immunostaining for insulin receptor, whereas the stromal cells surrounding primordial follicles were moderately immunostained. The earliest stage of follicular growth at which immunostaining for insulin receptor in granulosa cells and theca interna cells became apparent was the preantral stage. With the increase in the size of the follicles, the immunostaining of the oocyte and follicular elements intensified, whereas the staining intensity of the stromal cells surrounding growing follicles was reduced compared to those surrounding primordial follicles. The immunostaining in granulosa and theca interna cells persisted in the corpus luteum, and further intensified during the midluteal phase. In the regressing corpus luteum, the immunostaining was present only in the peripheral lutein cells adjacent to the central scar tissue. The corpus albicans was negative for the immunostaining, but the surrounding stromal cells exhibited predominant staining. In atretic follicles, the theca interna cells exhibited intense staining for insulin receptor without appreciable staining in the scattered granulosa cells, whereas the surrounding stromal cells were moderately immunostained. This is the first study to demonstrate notable changes in insulin receptor expression in the oocyte, granulosa cells, theca cells, lutein cells and surrounding stromal cells during follicular growth, regression and atresia. The results obtained indicate insulin participation in oocyte maturation, follicular growth and stromal cell function. The increased expression of insulin receptors in theca interna cells of atretic follicles and in stromal cells surrounding the corpora albicans raises the intriguing possibility of insulin involvement in the transformation of theca interna cells into stromal cells. This implies that insulin may participate in remodelling ovarian local tissues following follicular atresia and luteolysis in the human ovary.

Adult↗
PubMed1992

Localization of nonspecific lipid transfer protein (nsLTP = sterol carrier protein 2) and acyl-CoA oxidase in peroxisomes of pigment epithelial cells of rat retina.

We investigated the localization of nonspecific lipid transfer protein (nsLTP) in rat retina, especially in the pigment epithelial (RPE) cells, by the avidin-biotin-peroxidase complex method on cryosections for light microscopy and by the cryoimmunogold method for electron microscopy. Light microscopic observation revealed that the RPE, inner segment layer, nerve fiber layer, and Müller cells contain nsLTP. In the RPE cells gold particles were exclusively concentrated in the small peroxisomes (microperoxisomes; 0.1-0.3 micron in diameter), which were identified by double staining using anti-nsLTP and anti-catalase antibodies. In the peroxisomes gold particles were distributed homogeneously in the matrices and no preferential binding to the limiting membrane was observed. Acyl-CoA oxidase was also localized in the matrices of the peroxisomes. We suggest that the peroxisomes in RPE cells play important roles in the metabolism of lipids of the outer segment disk membranes, especially in the beta-oxidation of polyunsaturated long-chain and very long-chain fatty acids, such as docosahexaenoic acid which is composed of approximately one third of fatty acids in the disk membranes.

Acyl-CoA Oxidase↗
PubMed1990

[Successful resection of mediastinal and abdominal recurrent tumors of esophageal leiomyosarcoma 12 years after surgery].

A 57-year-old woman admitted to our hospital in October, 1988 because of the tumor of the abdominal wall and abnormal shadows of right chest wall and right upper mediastinum. Her esophagus had been resected and reconstructed by the stomach roll because of the esophageal leiomyosarcoma in May, 1976. Clinical examinations revealed that the abdominal mass and chest shadows were the recurrence of the leiomyosarcoma. The abdominal tumor was resected on 17th October, 1988. On 14th December, 1988 right thoracotomy was performed. Chest wall tumor (40 x 30 x 20 mm) and mediastinal tumor (45 x 40 x 35 mm) were resected completely. The mediastinal tumor was adhered to the remnant esophageal muscle layer. Microscopic section of the tumor showed spindle cell sarcoma with fine calcification, and it was diagnosed as the metastatic leiomyosarcoma.

Abdominal Muscles↗