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Biomedical subjects

Y Sasaki

Publications and source records attributed to Y Sasaki.

At least 127 records · Page 7Linked to original sources

Absence of PTEN/MMAC1 gene mutations in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats.

Mutations of the phosphatase and tensin homolog deleted on chromosome ten/mutated in multiple advanced cancers 1 (PTEN/MMAC1) gene were investigated in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats (6 weeks old) were given 2000 ppm BHP in their drinking water for 12 weeks and maintained without further treatment until they were killed at week 25. Total RNA was extracted from 15 adenocarcinomas and mutations of the PTEN/MMAC1 gene were investigated by reverse transcription-polymerase chain reaction-restriction-single-strand conformation polymorphism analysis. No mutations were detected, and loss or decrease of expression of PTEN/MMAC1 mRNA was also not found in any of the cases. These results suggest that alterations of the PTEN/MMAC1 gene may not be involved in the development of adenocarcinomas induced by BHP in rats.

Adenocarcinoma↗

Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system.

The rat zitter (zi) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis. By positional cloning, we found a marked decrease in Attractin (Atrn) mRNA in the brain of the zi/zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. Atrn has been known to play multiple roles in regulating physiological processes that are involved in monocyte-T cell interaction, agouti-related hair pigmentation, and control of energy homeostasis. Rat Atrn gene encoded two isoforms, a secreted and a membrane form, as a result of alternative splicing. The zi mutation at the Atrn locus darkened coat color when introduced into agouti rats, as also described in mahogany (mg) mice, carrying the homozygous mutation at the Atrn locus. Transgenic rescue experiments showed that the membrane-type Atrn complemented both neurological alteration and abnormal pigmentation in zi/zi rats, but that the secreted-type Atrn complemented neither mutant phenotype. Furthermore, we discovered that mg mice exhibited hypomyelination and vacuolation in the CNS associated with body tremor. We conclude from these results that the membrane Atrn has a critical role in normal myelination in the CNS and would provide insights into the physiology of myelination as well as the etiology of myelin diseases.

Agouti Signaling Protein↗

Degradation of the cyanobacterial hepatotoxin microcystin by a new bacterium isolated from a hypertrophic lake.

A bacterium capable of degrading microcystins-RR, -YR, and -LR was isolated from a hypertrophic lake. The bacterium, designated Y2 and classified phenotypically as a member of the genus Sphingomonas, was shown to be distinct phylogenetically from any established species of Sphingomonas on the basis of 16S rDNA sequencing. The bacterium was tentatively identified as Sphingomonas by manual chemotaxonomy, but 16S rRNA sequencing analysis suggests that it is in fact a new species or even a new genus. When the Y2 bacterium was added to microcystins present in culture medium, the microcystins were degraded thoroughly in 4 days. The highest degradation rates of microcystins-RR and -LR were 13 and 5.4 mg L-1 day-1, respectively. The degradation rates were strongly dependent on temperature and the maximum rate was at 30 degrees C.

Biodegradation, Environmental↗

IGF-I-induced apoptosis in LM2d6 cultured at a low concentration of fetal bovine serum.

We examined the effects of IGF-I (1-1000 ng/ml) on cell proliferation in LM2d6 mouse fibroblast cells at 0.1, 1.0 and 5.0% fetal bovine serum (FBS). In medium containing 0.1% FBS, treatment of LM2d6 cells with IGF-I significantly reduced the cell number in a dose- and time-dependent manner, whereas no effects were seen at 1 or 5% FBS. Treatment of the cells with 0.1% FBS for 72 h caused DNA laddering and nuclear condensation. However, Scatchard analysis for IGF-I binding sites on the cells revealed that both the number and the affinity of IGF-I receptors were not greater than that of Balb/3T3 cells. Furthermore, the apoptotic action of Long (R(3))-IGF-I, an analogue of IGF-I that has a reduced affinity for IGF binding proteins, was not greater than that of IGF-I. Taken together, we conclude that IGF-I reduces cell proliferation at low levels of FBS due to the induction of apoptosis. This effect is probably not caused by an excess production of IGF binding proteins in LM2d6 cells.

Animals↗

Mitral valve replacement in a patient with a collapsed lung.

A 67-year-old man, with a history of pulmonary tuberculosis since 18 years old, presented shortness of breath because of severe mitral regurgitation. Magnetic resonance imaging showed that the heart was displaced into the left thoracic cavity and rotated clockwise around its long axis. The forced expiratory volume per second was 1.06 l (46.7% of the predicted value) and the vital capacity was 2.48 l (72.1% of predicted value). Surgery was performed through a median sternotomy. An internal mammary artery harvest retractor was used to obtain operative exposure. Extensive pericardial suspension was used to push the over-inflated right lung across the midline. Extracorporeal circulation was established. The mitral valve was replaced with a mechanical prosthesis. The patient was weaned easily from extracorporeal circulation and was extubated on the day of surgery. If preoperative respiratory function is adequate, cardiac surgery can be performed safely in a patient with only one functional lung.

Aged↗

Secondary mitral valve replacement in antiphospholipid syndrome and chronic renal failure.

A 48-year-old woman admitted with progressive dyspnea had previously been diagnosed with systemic lupus erythematosus, antiphospholipid syndrome, and chronic renal failure, and had undergone mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis for mitral insufficiency 9 years before. She suffered a cerebral infarction 5 years earlier, despite appropriate anticoagulant therapy. On admission, echocardiography showed severe bioprosthetic stenosis. Repeat mitral valve replacement was conducted using a Mosaic bioprosthesis. On postoperative day 2, when heparinization was commenced, she suddenly had an epileptic fit. She also developed ischemic necrosis of the fingers and toes, considered secondary to microthrombosis. Aspirin was administered and heparin replaced by warfarin sodium. Necrosis gradually disappeared, and she was discharged 3 months after surgery. The original bioprosthesis showed degenerative changes with significant thrombus formation on cusps, thought to be mainly due to her hypercoagulable state. Considering the thrombophilic tendency in patients with antiphospholipid syndrome, strict management of anticoagulant therapy is required.

Adult↗

Early and late outcomes after reoperation for prosthetic valve endocarditis.

OBJECTIVE: Prosthetic valve endocarditis remains a challenging complication after heart valve replacement. To identify predictive risk factors, we have reviewed 30 patients who underwent surgery for prosthetic valve endocarditis between March 1986 and May 1999. METHODS: There were 15 men and 15 women (mean age 51 years). Prosthetic valve endocarditis was classified as early (< or = 1 year after operation) in 10 cases, and as late in the other 20 cases. The most common indication for surgery was moderate to severe congestive heart failure due to prosthetic valve dysfunction in 21 (70%) patients. The average follow-up period was 6.5 years, with a range of 0.3 to 14.1 years. RESULTS: The most common microorganism was Staphylococcus epidermidis in both patients with early (50%) and late prosthetic valve endocarditis (25%). The in-hospital mortality was 13.3% (4/30). There were six late deaths. The actuarial survival at 5 years was 78% and 66% at 10 years. An early onset of prosthetic valve endocarditis was the only significant determinant of both in-hospital mortality (p = 0.005) and overall mortality (p = 0.021). Emergency surgery had a statistically significant relationship with in-hospital mortality (p = 0.045). No significant influence on mortality after reoperation for prosthetic valve endocarditis was found in age, sex, valve position, antecedent native valve endocarditis, or in the type of pathological findings (ring abscess, valve dehiscence, and vegetation). CONCLUSION: Early onset of prosthetic valve endocarditis and emergency surgery were important risk factors for mortality due to prosthetic valve endocarditis.

Adult↗

Mitral insufficiency associated with primary antiphospholipid syndrome and chronic renal failure.

We report a case of 52-year-old woman with primary antiphospholipid syndrome who developed mitral insufficiency and chronic renal failure. Continuous ambulatory peritoneal dialysis was started preoperatively due to thrombocytopenia that was aggravated by hemodialysis. Mitral annuloplasty was performed since the mitral valve was not severely damaged. Her postoperative hemodynamics were stable, and anticoagulant therapy was controlled easily. She recovered from severe thrombocytopenia while on continuous ambulatory peritoneal dialysis. Valvular heart disease is a well known feature of primary antiphospholipid syndrome, and there have been several reports about valve replacement in patients who had antiphospholipid syndrome with or without systemic lupus erythematosus. However, valve repair has been reported in only a few such patients. We believe that valve repair is better than valve replacement in patients with antiphospholipid syndrome because of its hypercoagulable tendency. In addition, it seems that continuous ambulatory peritoneal dialysis is a suitable method for the perioperative management of patients with antiphospholipid syndrome who suffer from chronic renal failure as well as thrombocytopenia, and require cardiac surgery under cardiopulmonary bypass.

Antiphospholipid Syndrome↗

Re-treatment of relapsed indolent B-cell lymphoma with rituximab.

The purpose of this study was to investigate the toxicity and the efficacy of re-treatment with rituximab, a chimeric mouse human anti-CD20 monoclonal antibody, in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (NHL) who responded to rituximab in the previous phase I or phase II study. Thirteen patients with relapsed B-cell NHL, each of whom was confirmed to have Revised European-American Lymphoma Classification type II, 1-6 histology (indolent B-NHL), enrolled in this re-treatment study. All were re-treated with rituximab at 375 mg/m2 weekly for 4 consecutive weeks. Rituximab re-treatment was well tolerated with no grade 3/4 nonhematological toxicities, similar to that of the initial treatment. No patients developed detectable human anti-chimeric antibody. Partial responses were observed in 5 of 13 patients (38%; 95% confidence interval [CI], 14% to 68%); 6 patients showed stable disease and 2 showed progressive disease. Overall survival rate was 93% at 19 months of median follow-up after rituximab re-treatment. Median progression-free survival (PFS) after the re-treatment was 5.1 months (95% CI, 4.1 to 5.6 months), and the median PFS after the initial treatment was 8.2 months (95%CI, 5.9 to 11.3 months). Although rituximab re-treatment induced prolonged depletion of normal peripheral blood B cells in all patients, no significant decrease in serum immunoglobulin or complement level was observed. In conclusion, rituximab re-treatment was well tolerated, and it may produce a prolonged PFS in some patients with indolent B-cell NHL who showed initial response to rituximab.

Adult↗

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↗

Use of oolong tea extract staining of soft-tissue specimens in low-vacuum scanning electron microscope with a cooling stage.

For direct observation of the surface structures of soft-tissue specimens, we examined rat tracheal tissue in a low-vacuum scanning electron microscope (SEM) equipped with a cooling stage. In specimens fixed with glutaraldehyde and osmium tetroxide, back-scattered electron images of the surface structure could not be clearly observed in the low-vacuum SEM because of the disruption of fine structures and a low signal-to-noise (S/N) ratio. Processing of the specimens in 70% ethanol resulted in marked shrinkage, in contrast to results when processing in 30% ethanol. To overcome these problems, the trachea was initially fixed in 2.5% glutaraldehyde (0.1 M phosphate buffer pH 7.4), treated with a mixture of 0.2% oolong tea extract (OTE) and 2.5% glutaraldehyde, and postfixed in 1% osmium tetroxide. The sample was immersed in 30% ethanol and examined in a chilled SEM at -10 degrees C. The luminal coutour of the tracheal epithelial cells was clearly observed because of the decrease in shrinkage. Cilia of ciliated cells and microvilli of nonciliated cells were also clearly observed. These specimens also showed a high S/N ratio, thus allowing the observation of samples without the need for complete dehydration, critical-point drying, or metal coating. This OTE-incorporated conductive staining method is simple and rapid, and should prove to be highly useful for rapid SEM analyses of biological specimens.

Animals↗

A new procedure for chronic atrial fibrillation: bilateral appendage-preserving maze procedure.

BACKGROUND: Atrial transport and atrial natriuretic peptide secretion is severely reduced from normal after the maze III procedure. To improve these factors, we developed a bilateral appendage-preserving maze procedure (BAP-maze). METHODS: Forty-six patients with chronic atrial fibrillation who underwent the BAP-maze procedure were compared with 40 patients who underwent the maze III procedure. The ratio of the peak velocity of the A and E waves of transmitral flow (transthoracic pulsed Doppler echocardiography), the left atrial appendage ejection fraction (transesophageal echocardiography), and the atrial natriuretic peptide secretory reserve during treadmill exercise test were measured at 6 months postoperatively. RESULTS: Sinus rhythm was restored in 44 patients (95.7%) by the BAP-maze procedure and in 39 patients (97.5%) by the maze III procedure. The ratio of the peak velocity of the A and E waves was 0.52 +/- 0.22 in the BAP-maze group and 0.25 +/- 0.19 in the maze III group (p < 0.0001). The left atrial appendage ejection fraction was 44.7% +/- 11.5%, and the atrial natriuretic peptide secretory reserve was greater in the BAP maze group (p = 0.037). CONCLUSIONS: The BAP-maze procedure improved atrial transport and atrial natriuretic peptide secretion as well as simplifying the maze operation, without decreasing its effectiveness against atrial fibrillation.

Aged↗

Severe hypertriglyceridemia with plasma inhibitory factor(s) on lipoprotein lipase activity in a patient with a common Ser(447)-Ter LPL mutation.

Severe hypertriglyceridemia is a major risk for acute pancreatitis. So far, several mutations on the lipoprotein lipase (LPL) gene causing type I hyperlipidemia have been identified. However, the common mutation Ser(447)-Ter has been recently proposed to have a lowering effect on serum triglyceride concentrations in the general population. In this study, we analyzed blood from a patient suffering from severe hypertriglyceridemia and pancreatitis with the mutation on the lipoprotein lipase gene, Ser(447)-Ter. The patient's plasma showed inhibitory effects on the LPL activities from normal subjects. The bottom fraction separated by ultracentrifugation revealed enhanced effects as an inhibitory factor. The inhibitory effect observed in the bottom fraction was dose-dependent, stable at treatment of 65 degrees C for 30 min, and decreased significantly after being dialyzed using membranes with a cut-off molecular weight of 3500 or 6000 Da. The inhibitory effect was significantly higher when the post-heparin plasma was used from the patient or a subject with the same LPL mutation as an LPL source, compared to that from normal subjects. These results suggest that the patient has inhibitory factors in his plasma. Such inhibitory factors might cause severe hypertriglyceridemia in a case with the common mutation, which has been proposed to show the lowing effect on serum triglyceride concentrations in the general population.

Acute Disease↗

Isolation of virulent Rhodococcus equi from native Japanese horses.

R. equi was isolated from soil samples obtained from the environment of seven native Japanese horse breeds (Hokkaido, Kiso, Noma, Misaki, Tokara, Miyako and Yonaguni) and from fecal samples collected from three native horse breeds (Hokkaido, Kiso and Misaki). Virulent R. equi at various levels (ranging from 0.5 to 12.9%) was isolated from the feces or soil environment of Hokkaido, Kiso and Misaki horses. Isolates were investigated both for the presence of 15- to 17-kDa antigens (virulence-associated protein antigens; VapA) by colony blotting, using the monoclonal antibody 10G5, and the gene of VapA by PCR. Plasmid DNAs extracted from positive isolates were digested with restriction endonucleases, and the digestion patterns of the plasmids of virulent isolates were divided into three types. Two of the three types (87-kb type II and 90-kb type I) had already been reported in Japanese isolates, and a new type (tentatively designated as 90-kb type II) had been found in isolates from Kiso horses. Six virulent R. equi isolates from the Hokkaido horses contained an 87-kb type II plasmid. Eight of 24 isolates from the Kiso horses contained an 87-kb type II plasmid, and the remaining 16 contained a 90-kb type II (a new type) plasmid. Two isolates from the Misaki horses contained a 90-kb type I plasmid. These results demonstrate the geographic difference in the distribution of virulence plasmids in R. equi isolates among native Japanese horses.

Actinomycetales Infections↗

Serotonin-induced platelet intracellular calcium mobilization in various psychiatric disorders: is it specific to bipolar disorder?

BACKGROUND: Serotonin (5-HT)-stimulated platelet intracellular calcium (Ca) mobilization has been reported to be enhanced in unmedicated depressive patients compared to those of normal healthy subjects, which suggests increased 5-HT2A receptor function in these patients. It has not been ascertained whether this enhanced response is specific to some type of affective disorders among various mental disorders. METHODS: We examined 5-HT-induced platelet intracellular Ca response in 152 unmedicated outpatients with various psychiatric disorders including bipolar disorder (BD), major depressive disorder with melancholia (DM), major depressive disorder without melancholia (DN), schizophrenia (SCH), panic disorder (PD), obsessive-compulsive disorder (OCD), social phobia (SP) and bulimia nervosa (BN), and 30 normal controls. RESULTS: We observed no significant differences in basal intracellular Ca concentration among all patient subgroups and normal controls. While the 5-HT-induced Ca response was significantly and specifically higher in patients with BD than in normal controls, no significant differences were found in the Ca response to 5-HT between patients with DM, DN, SCH, PD, OCD, SP and BN, and normal controls. LIMITATIONS: The sample sizes of each group are still small. Therefore, they have to be enlarged in the continuation of the study so as to increase the power of the statistical tests. CONCLUSION: These results indicate the possibility that enhanced signal transduction, mediated by the 5-HT2A receptor, may be specific to bipolar disorder.

Adult↗

Vascular endothelial growth factor mRNA synthesis by peripheral blood mononuclear cells in patients with acute myocardial infarction.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.

Aged↗