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Biomedical subjects

N Sano

Publications and source records attributed to N Sano.

At least 37 records · Page 2Linked to original sources

Localization and roles of CD44, hyaluronic acid and osteopontin in IgA nephropathy.

An important function of CD44 is to act as a cellular receptor for hyaluronic acid and osteopontin. Cell-matrix interactions mediated by the CD44/hyaluronic acid receptor-ligand pair are involved in the regulation of leukocyte migration and activation. Osteopontin is a molecule associated with cell adhesion and migration and functions through binding to CD44. This study examined whether CD44, hyaluronic acid and osteopontin participate in the progression of IgA nephropathy. CD44 was expressed in mesangial cells, crescents, tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. Hyaluronic acid was deposited in the capillary tuft of adhesion, crescents and the periglomerular area, and around damaged tubules. Osteopontin was expressed in tubular cells and interstitial infiltrating cells in areas of tubulointerstitial injury. The glomerular and interstitial deposition of hyaluronic acid correlated with the glomerular and interstitial expression of CD44. The interstitial expression of CD44 correlated with the interstitial expression of osteopontin. The expression of both CD44 and osteopontin in the interstitium correlated with the extent of tubulointerstitial damage. The expression of CD44 in the interstitium correlated with the severity of chronic glomerular lesions. The glomerular and interstitial CD44 and hyaluronic acid expression correlated with proteinuria, and interstitial CD44 and hyaluronic acid expression correlated with creatinine clearance rate. In summary, this study suggests that CD44 participates in the progression of IgA nephropathy by binding hyaluronic acid and osteopontin.

Adolescent↗

Estrogen therapy in a male patient with chronic hepatitis C and irradiation-induced testicular dysfunction.

We report an 18-year-old male patient who developed chronic hepatitis C after blood transfusion and had testicular dysfunction after irradiation for a testicular relapse of childhood acute lymphocytic leukemia after cessation of maintenance therapy, and the initiation of testosterone replacement therapy at puberty. Concomitant administration of estradiol resulted in a reduction in serum alanine aminotransferase and ferritin levels and hepatic iron concentration and staining after 2 years of estrogen therapy, although interferon therapy was withdrawn because of adverse effects. This observation suggests that endogenous estradiol may play a beneficial role in male patients with chronic hepatitis C.

Adolescent↗

High trough levels of oral FK506 induced by loss of small intestine.

To establish a safe and effective usage of oral tacrolimus (FK506) in small bowel transplantation (SBTx) recipients, trough levels and area under the curve (AUC) values of FK506 were assessed using swine models of SBTx and short bowel. Thirty-eight Landrace male piglets were divided into four groups as follows: Group 1, controls (n=13); Group 2, a one-third small bowel model (n=5); Group 3, a short bowel model (n=10); and Group 4, a one-third small bowel allograft model (n=10; five donors and five recipients). Piglets of Groups 1 and 3 were further divided into two sub-groups, according to the route of drug administration: Groups 1a (n=10) and 3a (n=7) received FK506 orally, and Groups 1b (n=3) and 3b (n=3) received FK506 intravenously. Oral or intravenous FK506 was started on post-operative day 3 and continued until day 7 in each group. On day 7, trough levels and AUC values were measured. In Groups 1a, 2, 3a and 4, trough levels of FK506 were 2.1+/-1.2 (p<0.01 vs. Group 2, 3a or 4), 11.2+/-2.1, 23.3+/-4.8 (p<0.05 vs. Group 2 or 4) and 14.6+/-3.0 ng/mL, and AUC values were 101+/-90 (p<0.01 vs. Group 3a or 4), 319&+/-155, 808+/-200, and 531+/-113 ng.h/mL, respectively. Both trough levels and AUC values were lowest in Group 1a and highest in Group 3a. Between Groups 1b and 3b, there was no significant difference in the blood levels of intravenous FK506. The shorter the functioning residual small intestine was, the higher the trough level of oral FK506 was, while the presence or absence of small intestine did not affect blood levels of intravenous FK506. These results suggest that oral FK506 is metabolized in the functioning small intestine during its absorption. Therefore, events which cause intestinal malfunction, such as graft rejection in SBTx, inflammation and loss of small intestine, may adversely raise the trough level of oral FK506.

Animals↗

[Respiratory function tests--current and future perspective].

The apparatus for the respiratory function test have recently made a great progress and become very easy to handle owing to the development of computer technology and medical ordering system. However, the respiratory function tests depend its result on the cooperation of patients. Thus, it is important for the medical technician to obtain the maximum efforts and cooperation of the patients in the testing. In the sense, the standardization of the testing should be done urgently regarding procedures, softwares, hardwares and maintenance of apparatus. In the future perspectives, we would like to emphasize following 3 points. First, more noninvasive and sophisticated testing methods and instruments should be developed, since the patients' age will become more and more old and vigorous active cooperation may not be possible for the assessment of respiratory function. The testing for the transplantation of lung should also be developed. Second, the development of screening test and its performance for the routine medical check for the local inhabitants have been important for the early detection, treatment, and follow up of respiratory diseases. Finally, the medical technician should be prepared so that the testing is available when it is needed.

Forced Expiratory Flow Rates↗

So-called mesothelial/monocytic incidental cardiac excrescences obtained during valve replacement surgery: report of three cases and literature review.

We present three cases of so-called mesothelial/monocytic incidental cardiac excrescences (MICE) of the heart and a brief review of related literature. Case 1 was a 51-year-old woman who underwent mitral- and aortic-valve replacement. A tissue sample was submitted as a thrombus attached to the left atrial endocardium. Case 2 was a 69-year-old woman who underwent mitral-valve replacement. The sample was incidentally obtained as whitish clot-like fragments, but its exact origin was not known. Case 3 was a 68-year-old woman who underwent mitral-valve replacement for suspected infective endocarditis. The sample adherent to the pericardium was removed after valvular surgery. Histologically, these lesions were composed of a mixture of plump histiocytoid cells, a papillary arrangement of cuboidal cells, various sized vacuoles, and fibrin. The nests of cuboidal cells resembled cancer cells but showed features of mesothelial cells and no proliferative activity, immunohistochemically or ultrastructurally. In all cases, a suction tube placed in the left atrium was occasionally used to remove overflowing intrapericardial fluid during the surgery. The tip of the suction tube was covered with spiral wire, which is likely to transfer the stripped pericardial mesothelial cells to the left atrium. The significance of MICE is their possibility of being misdiagnosed as metastatic carcinoma by pathologists and a risk of arterial embolization by mesothelial debris clinically.

Aged↗

A case of resectable lung adenocarcinoma associated with sarcoidosis.

A 71-year-old woman with uveitis was referred to our hospital for further examination of the possible underlying diseases. In roentgenological examination with plain X-ray and CT scan, hilar and mediastinal lymphadenopathy and a mass shadow in the right upper lung field was observed, whereas fibrotic changes were not obvious in both lung fields. Transbronchial lung biopsy with fiberoptic bronchoscope revealed granulomatous interstitial pneumonia. CD4-positive lymphocytes were increased in bronchoalveolar lavage. The patient was diagnosed as having sarcoidosis. Subsequently, right upper lobectomy was performed, and Stage I lung adenocarcinoma was diagnosed. The patient is under follow up without medication and the disease has been stable for two years. A relationship between epithelioid granulomatosis and malignant diseases is discussed and a review of the literature is given. Since it is still controversial as to the incidence of malignant diseases in sarcoidosis patients, it is important to accumulate data on these associations.

Adenocarcinoma↗

Antimicrobial susceptibilities and serogroups of clinical strains of Clostridium difficile isolated in France in 1991 and 1997.

Glycopeptides (vancomycin and teicoplanin) and metronidazole are the drugs of choice for the treatment of Clostridium difficile infections, but trends in susceptibility patterns have not been assessed in the past few years. The objective was to study the MICs of glycopeptides and metronidazole for unrelated C. difficile strains isolated in 1991 (n = 100) and in 1997 (n = 98) by the agar macrodilution, the E-test, and the disk diffusion methods. Strain susceptibilities to erythromycin, clindamycin, tetracycline, rifampin, and chloramphenicol were also determined by the ATB ANA gallery (bioMérieux, La Balme-les-Grottes, France). The MICs at which 50% of isolates are inhibited (MIC(50)s) and MIC(90)s of glycopeptides and metronidazole remained stable between 1991 and 1997. All the strains were inhibited by concentrations that did not exceed 2 microgram/ml for vancomycin and 1 microg/ml for teicoplanin. Comparison of MICs determined by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards and the E test showed correlations (+/-2 dilutions) of 86. 6, 95.9, and 99% for metronidazole, vancomycin, and teicoplanin, respectively. The E test always underestimated the MICs. Strains with decreased susceptibility to metronidazole (MICs, >/=8 microgram/ml) were isolated from six patients (n = 4 in 1991 and n = 2 in 1997). These strains were also detected by the disk diffusion method (zone inhibition diameter, </=21 mm); they belonged to nontoxigenic serogroup D (n = 5) and toxigenic serogroup H (n = 1). Decreased susceptibility to erythromycin (MICs, >/=1 microgram/ml), clindamycin (MICs, >/=2 microgram/ml), tetracycline (MICs, >/=8 microgram/ml), rifampin (MICs, >/=4 microgram/ml), and chloramphenicol (MICs, >/=16 microgram/ml) was observed in 64.2, 80.3, 23.7, 22.7, and 14.6% of strains, respectively. Strains isolated in 1997 were more susceptible than those isolated in 1991, and this trend was correlated to a major change in serogroup distribution. Periodic studies are needed in order to detect changes in serogroups and the emergence of strains with decreased susceptibility to therapeutic drugs.

Adult↗

Comparative tumorigenicity of 1- and 3-nitrobenzo[a]pyrenes, and 3,6- and 1,6-dinitrobenzo[a]pyrenes in F344/DuCrj rats.

Our earlier study revealed that 1- and 3-nitrobenzo[a]pyrene (NBP), 1,6- and 3,6-dinitrobenzo[a]pyrene (DNBP), nitrated derivatives of benzo[a]BP (BP), are present in the environment. These derivatives are potent mutagens for Salmonella tester strains and we have preliminarily reported them to be carcinogenic in F344/DuCrj rats. In this study, the tumorigenic action of 1- and 3-NBP, 1.6- and 3,6-DNBP, and BP induced by subcutaneous injection into rats was found to differ according to the NO2-substitution in the BP structure. The chemicals were suspended in equal volumes of beeswax and tricaprylin, and rats were subcutaneously injected with single doses of 500, 1000, and 2000 microg for 1- and 3-NBP, and of 8, 40, 200, and 1000 microg for 3,6- and 1,6-DNBP, and BP as a positive control. 3,6-DNBP and BP induced tumors in a dose-dependent manner at the injection site. Rats given 1000 microg of 3,6-DNBP (2924 nmol) and BP (3968 nmol) developed subcutaneous tumors at the rate of 70 and 80%, respectively, and those given a minimum dose of 23 nmol for 3.6-DNBP and 32 nmol for BP per rat developed tumors at a rate of 4.8 and 18.2%, respectively. However, rats given 500 and 1000 microg of 1- and 3-NBP did not develop any tumors while those given a high dose, 2000 microg, of each chemical developed tumors at only one of ten animals used. It was concluded, therefore, that these chemicals are weak carcinogens. Histologically, most of the tumors were malignant fibrous histiocytomas. Rats given various doses of 1,6-DNBP did not develop any tumors at the injection site. The failure of 1,6-DNBP to induce tumors may involve its metabolites because of the lower mutagenicity of its reduction products, 1-nitroso-6-NBP and 1-amino-6-NBP. It is suggested, therefore, that tumorigenicities of NBPs and DNBPs differ according to the NO2-substitution on the chemical structure, which may be due to the possible nitroreduction of the chemicals.

Animals↗

Non-carcinogenicity of capsaicinoids in B6C3F1 mice.

The carcinogenicity of a mixture of capsaicinoids (64.5% capsaicin and 32.6% dihydrocapsaicin) was examined in B6C3F1 mice. In a 13-week toxicity study, renal toxicity was observed in 1% capsaicinoid-treated males. Next, groups of 50 mice of each sex were given 0, 0.025, 0.083 or 0.25% capsaicinoids in powdered diet for 79 weeks and killed in week 83. Food intake was reduced in mice of all capsaicinoid-treated groups, especially females, because of the pungency of capsaicinoids, and inhibition of body weight gain was apparent in females. The numbers of tumour-bearing females in the high-dose groups were significantly lower than that in the controls, and the incidences of hepatocellular neoplasms in both sexes were negatively correlated with the dose of capsaicinoids (Cochran-Armitage trend test). Renal cell adenomas developed in one mouse each of 0.025 and 0.25% capsaicinoid-treated males. The incidences of other tumours were similar in the treated and control groups. Thus, the present study indicated that a mixture of capsaicinoids is not carcinogenic in B6C3F1 mice.

Animals↗

Enhanced biliary excretion of lithocholate-3-sulfate by ursodeoxycholate-3,7-disulfate infusion in Eisai hyperbilirubinemic rat (EHBR).

Biliary excretion of lithocholate-3-sulfate and ursodeoxycholate 3,7-disulfate is markedly impaired in EHBR. In the present study, the effects of ursodeoxycholate 3,7-disulfate infusion on lithocholate-3-sulfate excretion were studied in EHBR and Sprague-Dawley rats. Although in control rats, ursodeoxycholate 3,7-disulfate infusion had no effect on biliary lithocholate-3-sulfate excretion, in EHBR it enhanced biliary lithocholate-3-sulfate excretion. Although ursodeoxycholate 3,7-disulfate dose-dependently inhibited lithocholate-3-sulfate binding by rat serum albumin and rat liver cytosol, it did not affect the serum clearance of lithocholate-3-sulfate in EHBR in vivo. These findings indicate that in EHBR, in which the major ATP-dependent organic anion transporter is impaired, the excretory pathway for ursodeoxycholate 3,7-disulfate may interact to that for lithocholate-3-sulfate.

Animals↗

Changes in biliary excretory mechanisms in rats with ethinyloestradiol-induced cholestasis.

Several excretory pathways for cholephilic compounds have been known. To examine the changes in excretory pathways in cholestasis induced by ethinyloestradiol, various bile acids, organic anions and organic cations were intravenously administered to ethinyloestradiol-treated rats and their biliary excretion was studied. Biliary excretion of taurocholate was slightly delayed, but its excretory maximum was markedly decreased. Biliary excretion of lithocholate-3-O-glucuronide, leukotriene C4, sulphobromophthalein and pravastatin was markedly impaired to a similar extent. Biliary excretion of vinblastine, a P-glycoprotein substrate, was increased, suggesting increased expression of P-glycoprotein. In contrast, biliary excretion of erythromycin, a cationic antibiotic, was markedly impaired. In conclusion, ethinyloestradiol treatment altered the biliary excretion of organic compounds, which may partly be related to changes of the canalicular transporters.

Animals↗

Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats.

Vesicular transport inhibitors have been reported to inhibit biliary excretion of some organic anions, suggesting that vesicular transport has a role in intracellular transport of these compounds. However, these inhibitors are substrates for P-glycoprotein. To examine whether P-glycoprotein has a role in canalicular transport of organic anions in addition to the canalicular multispecific organic anion transporter, we studied the effect of colchicine, a vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein expression on biliary excretion of various organic anions in rats. Colchicine treatment slightly but significantly inhibited biliary excretion of indocyanine green, dinitrophenyl-glutathione and pravastatin, and had no effect on biliary excretion of sulphobromophthalein and dibromosulphophthalein. Phenothiazine treatment did not affect biliary excretion of indocyanine green and pravastatin, but it increased biliary sulphobromophthalein-glutathione excretion. In conclusion, the present findings suggest that P-glycoprotein plays an additive role on biliary excretion of some organic anions in addition to the canalicular multispecific organic anion transporter.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Adenosarcoma of the uterine cervix presenting as a cervical polyp.

A case of adenosarcoma arising from the uterine cervix of a 55-year-old female who complained of vaginal discharge is reported. A polyp, 6 x 2 x 1.5 cm in size, identified in the cervical canal was clinically diagnosed as benign cervical polyp and resected. Histologically, the polyp was composed of benign epithelial components and sarcomatous stroma wherein periglandular hypercellularity and some mitoses including atypical ones were noted. Immunohistochemically, stromal cells were positive for muscle-type actins, desmin and estrogen receptor. Adenosarcoma is a rare, biphasic tumor of the uterus and usually presents as a polypoid mass in the endometrial cavity. When they arise from the cervix, adenosarcomas may be confused with benign cervical polyps clinically and pathologically. As the former often recurs, microscopic differentiation is crucial for further treatment.

Actins↗

Assessment of the biological malignancy of hepatocellular carcinoma: relationship to clinicopathological factors and prognosis.

It is difficult to determine the prognosis of patients with hepatocellular carcinoma (HCC). Assessment of the clinicopathological and biological malignancy of HCC may help in determining treatment strategies and predicting outcome. The tumor DNA content, p53 protein expression, proliferating cell nuclear antigen labeling index, and argyrophilic proteins of nuclear organizer regions were used as markers of biological malignancy. A correlation between these biological parameters and clinicopathological factors was sought. DNA aneuploidy was observed in 31 of 80 tumors (38.8%). Aneuploidy increased as differentiation decreased. The overall survival rate of patients with aneuploid tumors was significantly poorer than that of patients with diploid tumors. p53 overexpression was observed in 18 of 80 tumors (22.5%). The incidence of p53 positivity increased significantly with increasing tumor size and poorer differentiation. The overall survival rate of p53-positive patients was significantly worse than that of p53-negative patients. The proliferating cell nuclear antigen labeling index and the mean number of argyrophilic proteins of nuclear organizer regions were higher in more poorly differentiated lesions. We conclude that DNA ploidy and p53 expression are useful prognostic indicators in HCC. Cell proliferation increases as HCC progresses. With progression, tumors tend to become more poorly differentiated.

Adult↗

A case of sarcoidosis associated with chronic eosinophilic pneumonia.

A 38-year-old man was hospitalized in our university hospital because of pulmonary opacities with bilateral hilar and mediastinal lymphadenopathy seen on chest radiograph. Eosinophilia was observed in the circulation and bronchoalveolar lavage (BAL) fluid. Histological examination revealed noncaseating epithelioid granulomas and eosinophilic infiltration in the lung. Based on these findings, a diagnosis of sarcoidosis combined with chronic eosinophilic pneumonia was made. The infiltrates on chest radiograph and BAL eosinophilia were promptly reduced with corticosteroid therapy, but only mild reduction was observed in diffuse nodular shadows and hilar and mediastinal lymphadenopathy, and high amounts of lymphocytes in BAL fluid remained. Increased IFN-gamma, IL-4 and IL-5 were detected in the BAL fluid, and corticosteroid therapy reduced IL-4 and IL-5 (Th-2 cytokines) but not IFN-gamma (Th-1 cytokine). These cytokine levels in BAL fluid were intimately correlated with the clinical course of sarcoidosis and chronic eosinophilic pneumonia.

Adrenal Cortex Hormones↗