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Biomedical subjects

A Nagasawa

Publications and source records attributed to A Nagasawa.

At least 19 recordsLinked to original sources
PubMed2006

Effects of tetrabromobisphenol A, brominated flame retardant, in ICR mice after prenatal and postnatal exposure.

Tetrabromobisphenol A (TBBPA), brominated flame retardant, is produced in the largest amounts globally for use in plastics or building materials. TBBPA has been detected in sediment, air at the dismantling plant or human serum samples. In the present study, we examined the effects of prenatal and postnatal exposure to TBBPA in mice. TBBPA (99.1% pure) in diet was administered to pregnant ICR mice at doses of 0% (control), 0.01%, 0.1% or 1.0% from gestational day 0 to weaning at postnatal day 27. The average daily food intake and body weight of dams showed no significant differences between the control and treated groups. There were no dose-related effects on reproductive data. Serum concentrations of total-cholesterol and liver weights of treated dams and offspring were higher than those of the control mice. Histological findings in treated dams or offspring showed the increase of focal necrosis of hepatocytes and inflammatory cell infiltration in the liver, and increase of dilation or atrophy of renal tubules and cyst in the kidney. TBBPA was developed as a new, safe class of flame retardant and was not highly toxic. However, the present data suggested that TBBPA caused a lipid metabolic disorder and hepatic or kidney lesion, under these conditions.

Alanine Transaminase↗
PubMed2003

Suppression of TGF-beta signaling by conophylline via upregulation of c-Jun expression.

In the course of screening for inhibitors of transforming-growth factor-beta (TGF-beta) functions we found that conophylline, a vinca alkaloid, inhibited TGF-beta-induced apoptosis in rat hepatoma cells. Because conophylline also inhibited TGF-b-induced promoter activity in mink lung cells, we studied the mechanism of the inhibition in this cell line. Conophylline did not inhibit nuclear translocation of Smad2. Instead, we found that conophylline increased the expression of c-Jun, which had been earlier shown to interact with the corepressor TGIF to suppress the transcriptional activity dependent on Smad2. Conophylline attenuated the interaction between the Smad2 complex and p300 but enhanced that between the Smad2 complex and TGIF. In cells overexpressing c-Jun, suppression of promoter activity induced by TGF-beta and the enhancement of the association of the Smad2 complex with TGIF were also observed. Thus, our data suggest that inhibition of TGF-beta-induced promoter activity by conophylline can be attributed to its potency in modulating the interaction of downstream transcriptional factors via upregulation of c-Jun expression.

Animals↗
PubMed2002

Beneficial effects of tea catechins on diet-induced obesity: stimulation of lipid catabolism in the liver.

OBJECTIVE: Obesity has increased at an alarming rate in recent years and is now a worldwide health problem. We investigated the effects of long-term feeding with tea catechins, which are naturally occurring polyphenolic compounds widely consumed in Asian countries, on the development of obesity in C57BL/6J mice. DESIGN: We measured body weight, adipose tissue mass and liver fat content in mice fed diets containing either low-fat (5% triglyceride (TG)), high-fat (30% TG), or high-fat supplemented with 0.1-0.5% (w/w) tea catechins for 11 months. The beta-oxidation activities and related mRNA levels were measured after 1 month of feeding. RESULTS: Supplementation with tea catechins resulted in a significant reduction of high-fat diet-induced body weight gain, visceral and liver fat accumulation, and the development of hyperinsulinemia and hyperleptinemia. Feeding with tea catechins for 1 month significantly increased acyl-CoA oxidase and medium chain acyl-CoA dehydrogenase mRNA expression as well as beta-oxidation activity in the liver. CONCLUSION: The stimulation of hepatic lipid metabolism might be a factor responsible for the anti-obesity effects of tea catechins. The present results suggest that long-term consumption of tea catechins is beneficial for the suppression of diet-induced obesity, and it may reduce the risk of associated diseases including diabetes and coronary heart disease.

Adipose Tissue↗
PubMed2001

Chronic toxicity of thiabendazole (TBZ) in CD-1 mice.

Male and female CD-1 mice (50 mice per group) were administered thiabendazole (TBZ) in diet at levels of 0 (control), 0.031, 0.125 and 0.5% for 78 weeks. A life time study was terminated after 78 weeks due to enhanced strain specific mortality. There were no significant differences in mortality between the control and treated groups. Mean body weights of high-dose groups showed significant decreases compared with the controls. The bladder weights of male and female mice of the 0.5% group were significantly higher than those of the control mice. Gross findings in treated mice included the renal atrophy, hydronephrosis, calculi in renal pelvis and/or bladder and ovarian atrophy. Microscopic findings in the kidneys of treated mice included the nephrosis, hydronephrosis or hyperplasia of transitional epithelium of renal pelvis or papilla. In the bladder of treated mice, hyperplasia or squamous metaplasia of transitional epithelium and one transitional cell papilloma were observed. Dose-dependent decreases in the incidence of spontaneous lesion in the male or female reproductive system were recognized. It is concluded that TBZ is not carcinogenic to CD-1 mice of both sexes. However, caution should be exercised in the long-term application of high TBZ doses.

Administration, Oral↗
PubMed2001

Thiabendazole induces urinary tract toxicity in male ICR mice.

Male ICR mice were administered thiabendazole (TBZ) in the diet at concentration of 0 (control), 0.8, 1.2 and 1.6% for 44 weeks. The mortality was 10, 6, 40 or 90% in control, 0.8, 1.2 or 1.6% TBZ group, respectively. In dead mice, the gross findings included the abnormalities of kidney such as atrophy, hydronephrosis or swelling in 2, 67, 95 or 96% of the 0, 0.8, 1.2 or 1.6% TBZ group, respectively. In surviving mice at the end of study, the right kidney weight of treated groups was significantly lower than that of control group. The urinary bladder weight of treated groups was significantly higher than that of control group. Gross findings in treated mice included the renal atrophy, hydronephrosis, calculi in renal pelvis or urinary bladder and thickening of the bladder wall. Microscopic findings in the kidneys of treated mice included nephrosis, hydronephrosis and hyperplasia of transitional epithelium of renal pelvis and/or papilla. In the urinary bladder, hyperplasia or squamous metaplasia of transitional epithelium were found in treated mice. Administration of TBZ in the diet for 44 weeks results in nephrosis and calculus formation in the renal pelvis and urinary bladder of male ICR mice, and is associated with hyperplasia of transitional epithelium of renal pelvis or urinary bladder.

Animals↗
PubMed2001

Goitrogenic effects of green tea extract catechins by dietary administration in rats.

The effects of green tea extract catechins on the rat thyroid were examined in a 13-week feeding study and subsequent 2-,4- and 8-week studies. Commercially available polyphenon-60 (P-60) which contains green tea extract catechins at 66.2% was used as a source of catechins. A basic diet containing different concentrations of P-60 was used for experiments. In the 13-week study, 10 rats of each sex were administered diets containing P-60 at 0 (control), 0.625, 1.25, 2.5 and 5.0%. Goiters were observed in the 13-week test. The mean thyroid weight of rats fed a diet containing 5.0% of P-60 (5.0% group) significantly increased to 444% of the control in males and to 304% of the control in females. Histological examinations of the thyroid of the 5.0% group revealed marked hypertrophy and/or hyperplasia of the follicles, some with depletion of colloid and some with rich colloid, and formation of a fibrous capsule. Slight hypertrophy of follicular cells was observed in male rats fed a diet containing 1.25% of P-60 (1.25% group) and female rats fed a diet containing 2.5% of P-60 (2.5% group). Degree and incidence of thyroid lesions were higher in males than in females in the 1.25, 2.5 and 5.0% groups. In the 2-8-week studies, five rats of each sex were given diets containing 0 (control) and 5.0% of P-60. In the 5.0% group, the mean thyroid weight in males significantly increased to 161% of the control as early as 2 weeks and increased to 357% of the control at 8 weeks. Histologically, these goiters were also associated with follicular cell hypertrophy/hyperplasia as in the 13-week study. The degree and incidence of thyroid lesions were higher in males than in females. These results indicate that dietary administration of the green tea extract catechins at high doses induced goiters in rats, and this may be due to antithyroid effects of catechins. In the 13-week study, the no-observed effect level (NOEL) of green tea extract catechins for F344 rats based on histological changes of the thyroid was considered to be 0.625% in males and 1.25% in females in the diet, respectively.

Administration, Oral↗
PubMed1999

Human and mouse ISLR (immunoglobulin superfamily containing leucine-rich repeat) genes: genomic structure and tissue expression.

We have previously reported a transcript of the novel gene for human immunoglobulin superfamily containing leucine-rich repeat (ISLR). By additional screening of a human retina cDNA library, we isolated another type of transcript with a 5' UTR different from that of the previously reported type. Genomic sequencing of the ISLR gene revealed that these two types of transcripts, ISLR-1 and ISLR-2, originated from the same gene but are composed of different first exons. Because the entire open reading frame is contained in the second exon, these two transcripts produce the same protein. Radiation hybrid mapping linked the ISLR gene to AFM248yh1, which is in the critical region of Bardet-Biedl syndrome type 4 (BBS4) on chromosome 15. Sequence analysis of the ISLR gene in five BBS4 patients, however, showed no mutations, although a few polymorphic changes were detected. Cloning of the mouse homolog of ISLR (Islr) revealed that the predicted protein consists of 428 amino acids, 86% of which are identical to those of ISLR. The Islr gene was expressed in various mouse tissues, including retina, in which Islr mRNA was detected in the ganglion cell layer, the inner nuclear layer, and the inner segment of the photoreceptor.

Animals↗
PubMed1999

Plastic surgical reconstruction of left main coronary artery.

OBJECTIVE(S): To report the early and mid-term results of surgical plasty of the left main coronary artery in 12 patients operated upon between 1993 and 1997. METHODS: The anterior approach was used in all patients. Saphenous vein (n = 4) of glutaraldehyde treated autologous pericardium (n = 8) were used as patch material. Additional coronary artery bypass grafting was performed in 7 patients, the first 3 as a safety back up, and for coexisting stenosis of other coronary branches not revascularized by the plastic procedure in the remaining 4. RESULTS: Pathologic specimens of the left main coronary artery in 5 revealed atheroma in 3 and myxomatous intimal thickening in 2. The left main coronary artery was widely patent angiographically in all patients prior to discharge. Six patients consented to angiographic restudy 5-40 months after the procedure and revealed excellent results in 5. One patient upon whom autologous pericardial patch had been used underwent percutaneous coronary angioplasty for restenosis of the left main coronary artery and a new lesion of the proximal left anterior descending branch 5 months after the operation. There were no late deaths nor other cardiac events. All patients were in CCS class 1 at their last follow-up. CONCLUSIONS: Surgical angioplasty of the left main coronary artery could be used to revascularize the left heart safely in patients with a discrete localized lesion of the left main coronary artery and is particularly useful in the face of unavailability of other conduits.

Aged↗
PubMed1999

Teratogenicity of thujaplicin in ICR mice.

Beta-thujaplicin (TP) was studied by in vitro and in vivo tests for teratogenicity using ICR mice. In the in vitro study, TP (0, 3.125, 6.25, 12.5 microg/ml medium) dissolved in dimethyl sulfoxide (DMSO) was administered to cultured embryos on 9 day of gestation. After 24 hr of exposure to TP, the embryos were examined for developmental parameters and external anomalies. Growth retardation and embryos with facial dysplasia or hydrocyst of the tail tip were observed among the embryos given 12.5 microg/ml. In the in vivo study, TP (0, 420, 560, 750 or 1000 mg/kg) dissolved in olive oil was administered orally to pregnant mice on day 9 of gestation. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. Various types of malformations were observed in the mice given 560 mg/kg or more. The number of litters having foetuses with external or skeletal anomalies increased in proportion to the dose of TP. The regression lines of Y (probit response) on X (log dose) for external anomalies was Y = 4.87X-8.43 . The 1% effective dose (ED1) for the malformation was 190 mg/kg. The present study shows that TP has teratogenic effects on mice.

Abnormalities, Drug-Induced↗
PubMed1999

[Efficacy of mupirocin in eradicating methicillin-resistant Staphylococcus aureus from nasal discharge in carrying cardiovascular surgical patients].

Methicillin-resistant Staphylococcus aureus from nasal discharge was identified in 37 (2.5%) cardiovascular patients operated between 1995 and 1997; 25 male and 12 female, ranging from 1 to 83 years (mean 63); 2 were excluded because of Arbekacin or Isodine-gel treatment. The first 17 were treated with Vancomycin inhalation (V group) and eradication was considered to have been achieved when 3 consecutive negative cultures were obtained; the subsequent 18 were treated with Mupirocin (M group) and eradication was determined by 1 negative culture. In post-eradication electively operated 13 V and 15 M, postoperative MRSA infection was observed in one M (wound infection); the interval from the first nasal culture to the operation was 68 +/- 58 in V and 32 +/- 12 days in M, respectively (p < 0.05). In the remaining 7 who had to undergo emergency surgery while waiting for eradication because of progression of symptoms (2 V) or prior to instituting treatment (2 V, and 3 M), postoperative MRSA infection was observed in 2 M (both pneumonia). No deaths from infection were observed. Though the time required for conversion of the nasal culture was longer in V (13 +/- 20) than in M (7 +/- 1 days) differences were not significant. Mupirocin is easier to use, eradication can be achieved generally within a week.

Administration, Intranasal↗
PubMed1998

Mouse myocilin (Myoc) gene expression in ocular tissues.

Human myocilin is identical to TIGR (trabecular meshwork inducible glucocorticoid response) which is responsible for the pathogenesis of juvenile-onset primary open angle glaucoma (GLCIA). We have isolated cDNA for mouse myocilin (Myoc) and investigated mouse myocilin gene expression in ocular tissues with in situ RNA hybridization. Hybridization signals were observed in the iris, ciliary body, trabecular meshwork, sclera, and retina in the mouse eye. The marked signals were seen in trabecular meshwork cells and the anterior portion of sclera. These findings suggest that myocilin mutation could affect the capacity of aqueous outflow and cause elevation of the intraocular pressure which is involved in the pathogenesis of glaucoma.

Amino Acid Sequence↗
PubMed1998

Cyanoglycosylation products of 17-O-acetyl-testosterone.

17-O-Acetyl testosterone, which has no susceptible hydroxyl or carboxyl group for glycosylation, was glycosylated with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide in the presence of a mixed catalyst, Hg(CN)2 and HgBr2, in benzene-nitromethane. Reaction occurred on the alpha, beta-unsaturated ketone on the six-membered A-ring to give six 3-O-glycosides, each bearing a cyano group at the 3- or 5-position of the aglycon, and a 3-O-glycoside bearing a CONH2 group at the 3-position. Structural analyses of these products were carried out by various NMR (1H, 13C NMR, 1H-1H and 1H-13C COSY, HMBC, and DEPT), FABMS and X-ray analyses. The mechanisms of the formations of the products are discussed. It was determined that mercuric cyanide was essential as a catalyst for the progress of the cyanoglycosylation.

Bromides↗
PubMed1997

Cloning of the cDNA for a new member of the immunoglobulin superfamily (ISLR) containing leucine-rich repeat (LRR).

We isolated cDNAs for a novel protein with a calculated molecular mass of 46 kDa, containing a leucine-rich repeat (LRR) with conserved flanking sequences and a C2-type immunoglobulin (Ig)-like domain. This novel protein was considered to be a new member of the Ig superfamily and was named ISLR (immunoglobulin superfamily containing LRR). These domains are known to be important for protein-protein interaction or cell adhesion, and therefore it is possible that the novel protein ISLR may also interact with other proteins or cells. Northern blot analysis showed the presence of a 2.4-kb transcript in various human tissues including retina, heart, skeletal muscle, prostate, ovary, small intestine, thyroid, adrenal cortex, testis, stomach, and spinal cord as well as fetal lung and fetal kidney. The ISLR gene was mapped on human chromosome 15q23-q24 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1997

[Coronary artery bypass surgery in aged patients].

From January 1993 through December 1996, 749 patients underwent isolated coronary artery bypass grafting. Of these patients, 578 patients were older than 60 years old. We classified them into three groups; Group A were the 60 to 69 year age group (337 patients), Group B were the 70 to 79 year age group (224 patients) and Group C were over 80 years age group (17 patients). Emergency cases and preoperative LV dysfunction cases were more frequently in Group C, but mortality did not differ among three groups. Duration of intubation, ICU stay and hospital stay were longer in Group C than other groups and complications (PMI, arrhythmia and reoperation for bleeding) were more frequently in Group C. Coronary artery bypass surgery can be performed in aged patients, especially for patients over 80 years old, with acceptably low mortality and significant functional benefit but a high incidence of complications necessitates careful postoperative management in aged patients.

Age Factors↗
PubMed1997

[Emergent operation after percutaneous transluminal coronary rotational atherectomy (ROTABLATOR)].

Emergent operations were performed in seven patients after percutaneous transluminal coronary rotational atherectomy (PTCRA). The causes of the emergent operations were coronary rupture in three patients, acute coronary occlusion in two patients, perforation of the ascending aorta in one patient and impossible weaning from IABP in one patient. IABP was used preoperatively in all patients. Coronary artery bypass grafting was performed in all patients. Ruptured sites of the coronary arteries were closed and perforated site of the ascending aorta was repaired. Two patients died due to cardiac failure but five patients were recovered. Coronary artery rupture was main complication after PTCRA. It is important to recognize the difference between the complication after PTCRA and that after conventional PTCA.

Adult↗
PubMed1994

A case of vascular leiomyoma of the larynx.

We present a 68-year-old woman with a vascular leiomyoma of the larynx, a benign tumour that rarely involves that organ. Chief complaints were a feeling of a narrowing of the pharynx and difficulty in breathing in the supine position. A spherical tumour measuring 1.5 cm and covered with normal mucosa was found at the margin of her epiglottis. The patient was administered a general anaesthetic and the tumour was successfully removed via direct laryngoscopy. Histological examination revealed that the tumour lay beneath a layer of stratified squamous epithelium and was encased in a well-defined fibrous capsule. The tumour parenchyma was composed of proliferated fibres that consisted of elongated cells, surrounded by an abundance of blood vessels. Its complete removal is the treatment of choice with care taken to avoid profuse bleeding. Recurrence is rare.

Aged↗
PubMed1994

Herbicide-resistant tobacco plants expressing the fused enzyme between rat cytochrome P4501A1 (CYP1A1) and yeast NADPH-cytochrome P450 oxidoreductase.

Transgenic tobacco (Nicotiana tabacum cv Xanthi) plants expressing a genetically engineered fused enzyme between rat cytochrome P4501A1 (CYP1A1) and yeast NADPH-cytochrome P450 oxidoreductase were produced. The expression plasmid pGFC2 for the fused enzyme was constructed by insertion of the corresponding cDNA into the expression vector pNG01 under the control of the cauliflower mosaic virus 35S promoter and nopaline synthase gene terminator. The fused enzyme cDNA was integrated into tobacco genomes by Agrobacterium infection techniques. In transgenic tobacco plants, the fused enzyme protein was localized primarily in the microsomal fraction. The microsomal monooxygenase activities were approximately 10 times higher toward both 7-ethoxycoumarin and benzo[a]pyrene than in the control plant. The transgenic plants also showed resistance to the herbicide chlortoluron.

Animals↗