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Biomedical subjects

T Igawa

Publications and source records attributed to T Igawa.

At least 37 records · Page 2Linked to original sources

[A case of retroperitoneal abscess and disseminated intravascular coagulation as a complication of upper ureteral rupture caused by ureteral calculus].

A 38-year-old man visited our hospital complaining of severe right flank pain with hematoemesis. Imaging studies including computerized tomographic (CT) scan demonstrated a right ureter stone and retroperitoneal abscess. His septic condition and presence of disseminated intravescular coagulation (DIC) necessitated percutaneous nephrostomy and drainage of the abscess. The patient recovered from DIC and infection within a week. To our knowledge, 5 similar cases of retroperitoneal abscess secondary to ureteral rupture have been reported in the Japanese literature.

Abscess↗

Stenosis enhances role of platelets in growth of regional thrombus and intimal wall thickening in rat carotid arteries.

The authors present the results of a study in which stenosis was induced, resulting in either thrombus or intimal wall thickening, in rat carotid arteries. At > or = 75% stenosis in mildly denuded arteries, an acute and occlusive thrombus formation was induced, but the thrombus was significantly reduced in thrombocytopenia. Thrombus formation near the site of stenosis decreased with decreasing degree of stenosis, whereas the percent formation in the distal region (percent total thrombus) increased. Numerous mural platelet microthrombi were noted at the distal region of the stenosed arteries. After chronic 50% stenosis of the carotid artery for 2 weeks, significant intimal thickening was observed, without any occlusive thrombus formation. The combination with mild denudation was critical in eliciting the effect of stenosis. The magnitude of intimal growth in the stenosed artery was marked by day 6 and plateaued thereafter, whereas it was slight in nonstenosed arteries. The 5-bromodeoxyuridine index of the cells of the medial layer at day 3 was significantly increased by the stenosis, and the effect was reversed in thrombocytopenia. Complete reendothelialization of the intimal surface was observed by 7 to 10 days after surgery in the stenosed arteries. These findings suggest that the introduction of stenosis in these arteries enhances the interaction of platelets with the damaged arterial walls under abnormal fluid shear and that this enhancement leads to acute and occlusive thrombus formation associated with more marked stenosis as well as to sustained increase of intimal wall thickness in less marked stenosis.

Animals↗

Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets.

A search for potent inhibitors of release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE), which plays an important role in the pathogenesis of various circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5-tetrazolyl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)-quinolinone derivatives having an azole group in the side chain. Many 2(1H)-quinolinone derivatives were synthesized and tested in vitro for the inhibitory activity in human platelets. 3,4-Dihydro-6-[3-(1-o-tolylimidazol-2-yl)sulfinylpropoxy]-2( 1H)-quinolinone (5k) was found to be one of the most potent inhibitors of 12-HETE release, being more potent than esculetin. In addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet adhesion in rats. Since 5k is racemic, the enantiomers were prepared and their potencies were compared in vitro and in vivo. (S)-(+)-5k had the best pharmacological profile and was selected as a candidate drug for further development. The structure-activity relationships are discussed.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

The response of serum and hepatic lipids and the aortic wall to different levels of dietary cholesterol: a comparative study between hyperlipidemia-and- atherosclerosis-prone quail and commercially available quail.

A hyperlipidemia-and-atherosclerosis-prone (LAP) quail model was developed by dietary cholesterol feeding through genetic selection of commercially available (CA) Japanese quail. The response of serum lipids and the aortic wall to dietary cholesterol feeding was compared in CA and LAP quails. Ten groups were fed a combination diet with different levels of cholesterol and corn oil for 12 weeks. In CA quail, dietary feeding of cholesterol only failed to induce significant hypercholesterolemia or atherosclerotic lesion. The respective optimal dietary levels of cholesterol and corn oil to induce hyperlipidemia and atherosclerotic lesion, were 2% and 15%, respectively. Ad-libitum feeding of only 0.5% cholesterol without corn oil induced significant hypercholesterolemia and aortic atherosclerosis in LAP quail. The main proliferating cellular component of the aortic atherosclerotic lesion was phenotypically transformed fibroblasts from medial fibroblasts. These results suggest that the LAP quail is a useful animal model for the study of atherosclerosis.

Animals↗

[Hypertrophy and hyperplasia of renal tubular interstitial cells--regulatory factors].

Renal tubular cells do not proliferate under normal intact conditions, whereas a marked regeneration is evident when tubular cells are injured by renal toxins or by ischemia. In case of compensatory renal growth too, hyperplasia of renal proximal tubular cells is observed. Various growth factors, including epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) seem to be involved in renal regeneration, however, the physiological role of these growth factors for the natural course of the renal regeneration have yet to be established. Hepatocyte growth factor (HGF), a potent mitogen for cultured renal tubular cells, may function as a renotropic factor, which enhances regeneration of the kidney. Once renal tubular cells are damaged by some agents, HGF mRNA, HGF activity and DNA synthesis of renal tubular cells are sequentially increased. Since both HGF mRMA and HGF protein are localized in renal interstitial cells, HGF seems to act on the tubular cells as a paracrine mediator. In addition to these results, HGF has multiple biological functions. This suggests that HGF possesses biological activities essential for renal regeneration.

Animals↗

[Clinical examination and therapies of hydronephrosis after radical hysterectomy].

We investigated postoperative hydronephrosis in 50 patients (100 ureter) undergoing radical hysterectomy for uterine cervical cancer from Jan. 1989 to Dec. 1991 at Department of Obstetrics and Gynecology in Nagasaki University Hospital. The incidence of hydronephrosis was 68.1% of patients, and hydronephrosis was seen significantly more frequently and was of a higher grade on the right kidney than the left. After one year, hydronephrosis disappeared in 59.1% of patients (65.1% of right kidney, 88.2% of left kidney), and only 2 of 93 kidney have worsened. In cases without hydronephrosis, hydronephrosis developed in only 3 of 31 kidney after one year due to local recurrence or nodule metastasis of the original disease. We compared therapeutic effects of 3 methods (ureteral stent, PNS, no treatment). But there was no significant difference between these methods, we could not determine which was the best treatment. And we observed that indwelling ureteral stent might interrupt spontaneous healing of ureter. Radiotherapy didn't significant influence hydronephrosis after radical hysterectomy; Therefore, we suggest that, in patients with hydronephrosis without other severe urological complications after radical hysterectomy, clinical course should be observed for at least one year, first and them some treatments should be applied if cases worsen gradually than before.

Adult↗

Effects of low concentration of vinblastine on the anchorage-independent growth and in vitro invasion of human renal carcinoma cell lines.

A study was conducted on the effect of vinblastine (VBL), an anti-mitotic drug that is commonly employed in the treatment of human renal cell carcinoma. When VBL was added to serum-free cultures of the ACHN and NT cell lines (both lines are of human renal carcinoma origin), a concentration of 1 microgram/ml resulted in death of most of the cells of both cell types. However, at a concentration of 10 ng/ml or less, although the cells detached from the culture dish, many viable cells were observed. In addition, in an in vitro invasion assay, the invasiveness of these detached cells was demonstrated to be accelerated in comparison with the parent monolayed cells. This increase of invasion was observed in the treatment of TN-16 which is known to have a metaphase-arresting effect, not to have an anti-cancer effect. When detached cells by VBL were inoculated into soft agar, their colony-forming ability was clearly increased in comparison with the parent cells or TN-16 treated cells. These results indicate that low concentration of VBL appears to increase the malignant potential of human renal carcinoma cells in culture.

Aprotinin↗

Hepatocyte growth factor may function as a renotropic factor for regeneration in rats with acute renal injury.

Hepatocyte growth factor (HGF), a potent mitogen for mature hepatocytes, possesses mitogenic and morphogenic activities for renal epithelial cells. To examine the renotropic function of HGF, we investigated the expression of HGF mRNA and HGF activity in the rat kidney after acute renal failure. When acute renal failure was induced by ischemia or by HgCl2 administration, a DNA synthesis occurred predominantly in the renal tubular cells located in the outer medulla with a peak at 48 h after the treatments. In both renal injuries, HGF mRNA in the kidney increased markedly, reaching a maximum 6 to 12 h after the treatments. HGF activity in the kidney also increased to three- to fourfold higher level than the normal level at 12 h after ischemic treatment or HgCl2 administration. In situ hybridization and immunohistochemical analysis indicated that both HGF mRNA and HGF protein were expressed in renal interstitial cells, presumably endothelial cells and macrophages, but not in tubular epithelial cells. In addition, HGF activity in the plasma of rats with renal ischemia or HgCl2 administration rapidly increased, reaching a maximum at 6 h after the treatment. One week after these injuries, HGF mRNA and HGF activity reverted to normal levels, and renal tubular cell regeneration ceased. Moreover, intravenous injection of human recombinant HGF into mice with acute renal failure caused by HgCl2 administration stimulated DNA synthesis of renal tubular cells in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Peritubular endothelial cell proliferation in mice during compensatory renal growth after unilateral nephrectomy.

The proliferation of peritubular endothelial cells during compensatory renal growth (CRG) following unilateral nephrectomy in mice was investigated using a labeling index. The labeling index of peritubular endothelial cells increased 6 h after uninephrectomy and decreased to the normal level within 72 h. Immunohistochemical study revealed that c-myc protein was expressed in the nuclei of both cortical tubular cells and peritubular endothelial cells. Furthermore, intravenous injection of anti-basic fibroblast growth factor (bFGF) neutralizing antibody just after uninephrectomy led to significant inhibition of proliferation of peritubular endothelial cells, but not tubular cells. These results indicate that peritubular endothelial cells proliferate transiently during CRG and that bFGF plays an important role for the growth regulation of that cell in the kidney.

Animals↗

Transforming growth factor-beta in rat kidney during compensatory renal growth.

Transforming growth factor-beta (TGF-beta) inhibits the DNA synthesis and stimulates the alkaline phosphatase activity of cultured renal cortical tubular cells. When unilateral nephrectomy was performed, TGF-beta activity content gradually decreased in the remaining kidney. An immunohistochemical study of the remaining kidney after uninephrectomy, however, showed that the expression of TGF-beta increased by the third day after uninephrectomy in the proximal tubular cells and an autoradiographic study revealed that TGF-beta expressing tubular cells were different from proliferating cells during compensatory renal growth. These results indicate that the total renal TGF-beta content decreases after uninephrectomy, while the expression of TGF-beta in the proximal tubular cells may increase and act as a brake for compensatory renal hyperplasia.

Adaptation, Physiological↗

Anti-epidermal growth factor antibody inhibits compensatory renal hyperplasia but not hypertrophy after unilateral nephrectomy in mice.

The effect of anti-epidermal growth factor (EGF) antibody on the compensatory renal growth including hyperplasia and hypertrophy was investigated. The antibody used in this study blocked the stimulatory effect of EGF on the DNA synthesis of cultured rat hepatocytes. When this antibody was injected into mice intravenously after unilateral nephrectomy, the labeling index of the renal cortical tubular cells decreased significantly at the second day after uninephrectomy, but the antibody caused no decrease in remaining kidney weight. Immunohistochemical study revealed that injected anti-mouse EGF rabbit IgG was positively stained at the renal cortical tubular cells. EGF would thus appear importantly essential to compensatory renal hyperplasia.

Animals↗

Gene expression and immunohistochemical localization of basic fibroblast growth factor in renal cell carcinoma.

Renal cell carcinoma is known as a neoplastic condition of renal tubular cells and usually shows a hypervascular tumor in angiographic examination. We examined the presence of basic fibroblast growth factor (bFGF) in human renal cell carcinoma. To determine if alterations in bFGF gene expression are present in human renal cell carcinoma, paired samples of normal and neoplastic renal tissue from 6 patients were analyzed for bFGF mRNA content by Northern blot hybridization. In 4 out of 6 patients, tumor tissue expressed bFGF mRNA 2 to 4 times greater than corresponding normal tissue. Two patients showed minimal elevation of tumor bFGF mRNA. The localization of bFGF in the renal cell carcinoma tissue was also examined using immunohistochemical staining, and it was found that bFGF was positively stained at the nuclei of tumor cells and the cell surface. These results suggest that increased expression of bFGF may be associated with neoplastic growth in renal tubular epithelial cells and neovascularization.

Aged↗

Transforming growth factor-beta-like activity is secreted by rabbit renal cortical tubular cells in primary culture.

The activity of an autocrine growth factor in a medium conditioned by cultured rabbit renal cortical tubular cells was investigated. Little stimulatory growth activity for tubular cells was observed in the conditioned medium, and inhibitory activity was seen only in acidified conditioned medium. This factor stimulated the colony formation of NRK 49F cells in soft agar only with epidermal growth factor and inhibited the DNA synthesis of primary cultured rat hepatocytes, and its molecular weight was about 25 kDa. The factor was neutralized by the specific antibody to transforming growth factor (TGF)-beta 1. These results indicate that renal tubular epithelial cells can produce latent TGF-beta in primary culture.

Animals↗

[A case of prostatic carcinoma presenting as a metastatic orbital tumor].

A 66-year-old man presented with progressive proptosis of the left eye associated with ocular pain. A computed tomographic scan showed a high density mass in the posterolateral portion of the left orbit. The patient underwent surgical removal of the tumor and histopathological examination revealed adenocarcinoma of unknown origin. To find out the primary focus of the tumor the patient was referred to our department, where biopsy of the prostate revealed adenocarcinoma. Further, immunohistochemical examination of the orbital tumor was performed and prostatic acid phosphatase was identified. Finally, we made a diagnosis of orbital metastasis from prostatic carcinoma. This paper presents a rare case of prostatic carcinoma with orbital metastasis and reviews the literature of the subject.

Acid Phosphatase↗

Effects of cytokines on the growth of cultured rabbit renal cortical tubular cells.

The effects of various cytokines including interleukin-1 beta, -2, and -6, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor on the DNA synthesis of cultured rabbit renal cortical tubular cells were investigated. Among these cytokines, it was found that only interleukin-1 beta could stimulate the DNA synthesis of cultured renal tubular cells, while interleukin-6 mildly suppressed the DNA synthesis of such cells. Interleukin-1 beta and -6 are produced by mesangial cells. The above results suggest that these cytokines may regulate the growth of tubular cells via the urinary flow in the nephron.

Animals↗

Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells.

Hepatocyte growth factor (HGF), which is a potent growth factor of adult rat hepatocytes in primary culture, also strongly stimulated DNA synthesis of rabbit renal tubular epithelial cells in secondary culture. Its mitogenic activity was dose-dependent, being detectable at 3 ng/ml and maximal at 30 ng/ml. Over 20% of the cells were shifted to the S-phase by HGF alone, judging by the labeling index. HGF had additive effects with EGF, acidic fibroblast growth factor (a-FGF), and insulin. Transforming growth factor-beta 1 (TGF-beta 1) strongly inhibited DNA synthesis of renal tubular cells stimulated by HGF. The growth of renal tubular epithelial cells was also regulated by cell density: DNA synthesis stimulated by HGF was high at lower cell density and was strongly suppressed at high cell density. These results suggest that HGF may act as a renotropic factor in compensatory renal growth or renal regeneration in vivo.

Animals↗

Transient increase in renal epidermal growth factor content after unilateral nephrectomy in the mouse.

A sensitive enzyme-linked immunosorbent assay for mouse epidermal growth factor was established for measurement of the content of epidermal growth factor in the remaining kidney after uninephrectomy. In 5-week-old male mice, the renal epidermal growth factor content before uninephrectomy was 355 +/- 97 ng/g wet tissue with a 2.1-fold increase on the first day after uninephrectomy, whereafter it gradually decreased. In 15-week-old mature male mice, the renal epidermal growth factor content increased 1.7-fold on the first day after uninephrectomy. Immunohistochemical analysis showed that epidermal growth factor was present in the distal tubular cells and that the staining intensity was increased on the first day after uninephrectomy. During the course of compensatory renal growth, no significant alteration of epidermal growth factor content was observed in plasma or in the submaxillary gland. Our data suggest that the increase in renal epidermal growth factor content after uninephrectomy is due to an increased production of epidermal growth factor in the kidney itself. The significance of this phenomenon is discussed.

Animals↗