Biomedical subjects

S Kitamura

Publications and source records attributed to S Kitamura.

At least 19 recordsLinked to original sources

PubMed2000

Metabolic activation of the proestrogens trans-stilbene and trans-stilbene oxide by rat liver microsomes.

A liver microsome-mediated activation of the proestrogens trans-stilbene and trans-stilbene oxide was found in this study. trans-Stilbene and trans-stilbene oxide were negative in estrogen reporter assay using estrogen-responsive human breast cancer cell line MCF-7 and growth assay in rat pituitary tumor cell line MtT/E-2. However, these compounds exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH. In contrast, cis-stilbene and cis-stilbene oxide did not show estrogenic activity after such incubation. When trans-stilbene was incubated with the liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH, two metabolites were detected by HPLC. They were identified unequivocally as trans-4-hydroxystilbene and trans-4, 4'-dihydroxystilbene by mass and UV spectral comparison with authentic samples. The oxidase activity of the liver microsomes toward trans-stilbene was inhibited by SKF 525-A and alpha -naphthoflavone. Minor activity was observed when liver microsomes of untreated or phenobarbital-treated rats were used instead of those from 3-methylcholanthrene-treated rats. trans-4-Hydroxystilbene and trans-4,4'-dihydroxystilbene exhibited significant estrogenic activities. These results suggest that the estrogenic activities of trans-stilbene and trans-stilbene oxide were due to formation of hydroxylated metabolites.

Animals↗

PubMed2000

Mutations of the bak gene in human gastric and colorectal cancers.

The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early-stage and 18 advanced-stage cancers) and 20 primary colorectal cancers (6 early-stage and 14 advanced-stage cancers). The data herein demonstrate, for the first time, the mutation of the bak gene in gastric and colorectal cancers. Missense bak gene mutations were observed in 3 of 24 (12.5%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Sequence alterations without amino acid alteration were observed 1 of 24 (4.2%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Mutations in the bak gene were observed only in advanced-stage gastrointestinal cancers but not in early-stage cancers. Our observations suggest that mutations in this gene predispose bearers to the development of gastrointestinal malignancies in at least a subset of the cases.

Colorectal Neoplasms↗

PubMed2000

Deficiency in mitochondrial aldehyde dehydrogenase increases the risk for late-onset Alzheimer's disease in the Japanese population.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) deficiency is caused by a mutant allele in the Mongoloids. To examine whether genetic constitutions affecting aldehyde metabolism influence the risk for late-onset Alzheimer's disease (LOAD), we performed a case-control study in the Japanese population on the deficiency in ALDH2 caused by the dominant-negative mutant allele of the ALDH2 gene (ALDH2*2). In a comparison of 447 patients with sex, age, and region matched nondemented controls, the genotype frequency carrying the ALDH2*2 allele was significantly higher in the patients than in the controls (48.1% vs 37.4%, P = 0.001). Logistic regression analysis indicates that carriage of the ALDH2*2 allele is an independent risk for LOAD of the epsilon4 allele of the apolipoprotein E gene (APOE-epsilon4) (P = 0.002). Moreover, the odds ratio for LOAD in carriers of the ALDH2*2 allele was almost twice that in noncarriers, irrespective of status with regard to the APOE-epsilon4 allele. Among patients homozygous for the APOE-epsilon4 allele, age at onset of LOAD was significantly lower in those with than without the ALDH2*2 allele. In addition, dosage of the ALDH2*2 allele significantly affected age at onset of patients homozygous for the APOE-epsilon4 allele. These results indicate that the ALDH2 deficiency is a risk for LOAD, synergistically acting with the APOE-epsilon4 allele.

Age of Onset↗

PubMed2000

Intrasubject correlation between static scan and distribution volume images for [11C]flumazenil PET.

Accumulation of [11C]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [11C]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [11C]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.

Adult↗

PubMed2000

Surgical considerations of occlusive lesions associated with Takayasu's arteritis.

OBJECTIVE: Takayasu's arteritis is an inflammatory vascular disease of unknown etiology that affects the aorta and its main branches, requiring surgical intervention due to occlusive lesions. We studied early and late surgical results. METHODS: Between 1979 and December 1998, 46 patients--1 man and 45 women aged 15 to 72 years (mean: 46 +/- 13 years)--with occlusive lesions caused by Takayasu's arteritis underwent surgery. Preoperative steroids were administered to 22 patients having inflammation. Diagnosis indicating surgery included obstructive cervical vessel disease in 13 patients, obstructive coronary artery disease in 19, aortic coarctation in 15, and abdominal branch stenosis in 3. Surgical procedures involved bypass grafting in 31 (cervical vessel bypass in 13, ascending-abdominal aortic bypass in 4, axillary artery-abdominal aortic bypass in 10, descending-abdominal aortic bypass in 1, abdominal branch bypass in 3), coronary artery bypass grafting in 10, and coronary ostial endarterectomy in 9. RESULTS: Four (8.7%) died during hospitalization. Follow-up ranged from 1 to 240 months (mean: 117 months). Eight suffered late deaths and 6 patients died of cardiovascular problems. The total actuarial survival rate was 76.2% at 5 years and 70.5% at 10 years. CONCLUSIONS: Steroid therapy before and after surgery appears to affect the overall prognosis positively in patients with Takayasu's arteritis.

Adolescent↗

PubMed2000

Results from coronary artery bypass surgery combined abdominal aortic aneurysm repair.

OBJECTIVE: Complication from coronary artery disease is a major cause of mortality and morbidity in patients undergoing abdominal aortic aneurysm repair. We report our results from coronary artery bypass surgery performed in combination with abdominal aortic aneurysm repair in patients with coronary artery disease and abdominal aortic aneurysm, each being an indication for an emergency operation. METHODS: Seventeen patients underwent combined coronary artery bypass surgery and abdominal aortic aneurysm repair. The mean age of the patients was 67.6 +/- 5.2 years. Four had left main disease, 8 patients had triple-vessel disease, and 12 had a prior myocardial infarction. The average left ventricular ejection fraction was 0.49 +/- 0.13. The average abdominal aortic aneurysm diameter was 6.2 +/- 1.0 cm (range 4.5-8.0 cm). Thirteen patients underwent coronary artery bypass surgery followed by abdominal aortic aneurysm repair after discontinuation of cardiopulmonary bypass. In the remaining four patients, including one patient with severe left ventricular dysfunction, cardiopulmonary bypass was continued as a circulatory assist until the abdominal aortic aneurysm repair was completed. The left internal thoracic artery was used in 14 patients, and the right internal thoracic artery in one patient. RESULTS: Postoperative surgical complications occurred in three patients (bleeding in one patient requiring reoperation, abdominal subcutaneous wound infection in another and transient neural disorder in the others). There were no surgical or in-hospital death. There was no late cardiac complication and no late cardiac death after a mean of 29 months follow-up. CONCLUSIONS: We concluded that combined surgery was reasonable for selected patients with combined coronary artery disease and abdominal aortic aneurysm, each of which is an indication for an urgent operation. The aortic aneurysm repair during cardiopulmonary bypass for patients with severe left ventricular dysfunction was safe and effective.

Aged↗

PubMed2000

Surgery in three-channeled aortic dissection. A 31-patient review.

OBJECTIVE: Three-channeled aortic dissection with 2 adjacent false lumens present is rare. METHODS: The 31 patients whose dissections we treated surgically accounted for 7.3% of the 426 patients with aortic dissection treated surgically between 1978 and May 1999. The 17 men and 14 women ranged in age from 24 to 77 years (mean: 45 +/- 12 years). Marfan syndrome was present in 18. Pain was observed at different times in 20. computed tomography scanning and magnetic resonance image proved useful in preoperative diagnosis. The morphology of the 1st and 2nd false lumens was Stanford type A + B in 13, type B + B in 15, type A + A in 2, and localized abdominal dissection in 1. RESULTS: Descending aortic replacement was done in 18 patients, thoracoabdominal aortic replacement in 7, ascending aortic replacement in 3, and others in 3. Five patients died in hospital and later during follow-up for 1-181 months (mean, 57 +/- 55 months). CONCLUSIONS: Pain recurring in patients with aortic dissection should alert the physician to the possibility of 3-channeled dissection and the necessity of surgery. The incidence of such dissection is high in patients with Marfan syndrome.

Adult↗

PubMed2000

A staged Fontan approach in patients initially unsuitable for the primary Fontan procedure.

OBJECTIVE: To determine the efficacy of the Glenn procedure in terms of establishing the Fontan procedure. METHODS: Surgical results were investigated in 248 patients undergoing either the total or partial right heart bypass. Of these, the conventional and the bidirectional Glenn procedures were employed in 27 and 58 patients, respectively. RESULTS: Conversion to the Fontan circulation was attempted in 32 of 58 patients initially considered unsuitable for the Fontan circulation and undergoing the bidirectional Glenn procedure, with 2 operative deaths. Of the 27 undergoing the conventional Glenn procedure, 13 have undergone conversion with 2 deaths. Actuarial survival rate after the staged Fontan approach did not statistically differ from that after the primary Fontan procedure. Catheterization in 130 patients with the established Fontan circulation showed no significant differences in ejection fraction, end diastolic volume, and end diastolic pressure of the systemic ventricle, as well as in Cardiac Index, between the group of patients treated with the primary Fontan procedure and the group treated with the staged Fontan procedure. When achieving the bidirectional Glenn procedure, the size of the additional channel from the ventricles to the pulmonary arteries was correlated with the postoperative change in pulmonary arterial size, but such additional forward flow produced insufficient ventricular offloading in 9 of 16 patients with significant atrioventricular valvar regurgitation. CONCLUSION: The staged Fontan strategy has an advantage in patients with complicated circumstances. Whether the primary or the staged Fontan procedure was used, however, did not affect the Fontan circulation itself when once the Fontan circulation was established. The additional forward flow in the bidirectional Glenn physiology, if employed, should be appropriately adjusted, considering both the advantages and the disadvantages of the option.

Child, Preschool↗

PubMed2000

Mitral valve plasty in systemic lupus erythematosus in the setting of antiphospholipid syndrome.

The first case was of a 27-year-old female, who was diagnosed as having mitral valve stenosis with regurgitation, systemic lupus erythematosus and antiphospholipid syndrome at her previous pregnancy. We performed mitral valve plasty, which included open mitral commissurotomy and Kay's annulo plasty. The second case was of a 53-year-old female, who was diagnosed as old myocardial infarction, mitral regurgitation, systemic lupus erythematosus and antiphospholipid syndrome. She underwent mitral valve plasty and coronary artery bypass grafting. Both cases were treated by administration of methylpredonisolone and heparin perioperatively to avoid thrombosis and aggravation of systemic lupus erythematosus. Both patients showed good postoperative outcome without complications. We consider that it is important to perform the plasty as far as possible, and to administer effective anticoagulation treatment to prevent complications for patients in the setting of systemic lupus erythematosus and antiphospholipid syndrome.

Adult↗

PubMed2000

Valved conduit operation for aortic regurgitation associated with Behçet's disease.

OBJECTIVES: Aortic regurgitation associated with Behçet's disease is rare, and prosthetic valve detachment after aortic valve replacement is one of the most serious complications reported. We have investigated the surgical results of valved conduit operation in 8 patients. METHODS: Between 1987 and April 1999, 8 patients underwent surgery. There were 7 males and 1 female, and their ages ranged from 33 to 60 years (mean, 48 +/- 10 years). The valved conduit procedure was a modified Bentall operation. RESULTS: One patient died of arrhythmia during the hospital stay. The follow-up period in the other 7 patients ranged from 1 to 138 months after surgery (mean, 74 months). None of these 7 patients died during the follow-up period. Valve detachment needing redo-operation occurred in 1 patient, and he underwent a valved conduit operation again. CONCLUSIONS: Valved conduit reconstruction is indicated in patients with aortic regurgitation caused by Behçet's disease, in whom prevention of valve detachment is difficult even by current valve fixation methods.

Adult↗

PubMed2000

Expression of hepatocyte growth factor and c-met in ulcerative colitis.

OBJECTIVE AND DESIGN: This study was designed to determine if the hepatocyte growth factor (HGF)-Met system is involved in the repair process of inflamed mucosa of ulcerative colitis (UC) and in the development of UC-associated colorectal cancer. MATERIALS AND METHODS: HGF and c-met gene expressions were quantified in colonic mucosal specimens from healthy control subjects, patients with UC and patients with UC-associated colorectal cancer, using the competitive reverse transcription-polymerase chain reaction. Expression of HGF protein was determined by immunoblot analysis. Expression of c-Met protein was analyzed immunohistochemically. RESULTS: HGF and c-met gene expressions were increased in inflamed mucosa of UC, compared with control subjects. Gene expression of HGF was also increased in the surrounding inflamed mucosa of UC-associated cancers. In cases in which the HGF gene expression was increased, an apparent increase in protein levels of HGF in inflamed mucosa of UC were observed by immunoblot analysis. The c-met gene was overexpressed in UC-associated cancers and a high level of immunoreactivity of the c-Met protein was immunohistochemically detected within the cancer cells. CONCLUSION: We showed that HGF and c-met expression is increased in the inflamed mucosa of UC and that c-met is overexpressed in UC-associated colorectal cancers. These observations suggest HGF-Met system is involved in the repair process of the inflamed mucosa of UC and provide further support for the view that the inappropriate expressions of both HGF and c-met genes predispose to the development of colorectal cancer in patients with UC.

Adult↗

PubMed2000

Osteophyte of the femoral head after transtrochanteric rotational osteotomy.

The relationship between change in the shape of the femoral head and the clinical results after transtrochanteric rotational osteotomy for osteonecrosis of the femoral head was investigated. Fifty-six hips in 50 patients, followed for at least 2 years, showed no progressive collapse and no osteoarthrotic change during that time. The growth of a superolateral osteophyte of the femoral head was observed postoperatively at a higher rate with progression of the preoperative stage. Excessive restoration of the rotated necrotic lesion of the femoral head was observed at a higher rate in hips with the growth of the superolateral osteophyte. The total Japanese Orthopaedic Association score at final follow-up in hips with these shape changes of the femoral head was significantly inferior to the score in hips without these changes. There was a tendency for hips with a low ratio of intact articular surface of the femoral head in the weight-bearing area to the acetabulum just after surgery to manifest these shape changes. Although such changes of the femoral head were considered to represent remodeling to stabilize the hip joint, excessive remodeling could worsen the clinical results.

Adolescent↗

PubMed2000

Transmural necrosis of the esophagus secondary to acute aortic dissection.

A case of transmural ischemic necrosis of the esophagus secondary to aortic dissection is presented. A 66-year-old woman with acute type A aortic dissection underwent total arch replacement with a technique of deep hypothermic arrest and retrograde cerebral perfusion. Postoperatively she had hematemesis, and endoscopic examination revealed circumferential mucosal necrosis and desquamation of the lower esophagus. She died of multiple organ failure on postoperative day 74. Autopsy demonstrated transmural necrosis of the esophagus secondary to ischemia. Ischemia of the esophagus secondary to aortic dissection is extremely rare.

Acute Disease↗

PubMed2000

Preservation of the right atrial appendage improves reduced plasma atrial natriuretic peptide levels after the maze procedure.

OBJECTIVES: The present study was conducted to determine whether preservation of the right atrial appendage lessens the decrease of plasma atrial natriuretic peptide levels after the maze procedure and whether the increase of plasma atrial natriuretic peptides improves the ability of the kidneys to excrete the fluid load after the operation. METHODS: We evaluated 42 patients who underwent the maze procedure. The right atrial appendage was preserved in 22 patients but not in 20. Blood samples were obtained before and after the operation for measurement of atrial natriuretic peptides. To evaluate the influence of atrial natriuretic peptides on the ability of the kidneys, we also measured body weight, fluid balance, and the doses of furosemide and dopamine administered after the operation. RESULTS: The restoration to sinus rhythm at 1 month after was comparable in the two groups. Plasma atrial natriuretic peptide levels significantly increased after the operation in patients in whom the right atrial appendage was preserved (1 day after: 23.4 +/- 17.8 vs 3 days after: 42.7 +/- 23.6 and 7 days after: 36.3 +/- 23.7 pg/mL, P <.05) but not in patients in whom the right atrial appendage was not preserved (1 day after: 20.0 +/- 19.6, 3 days after: 28.5 +/- 19.3, and 7 days after: 23.0 +/- 16.1 pg/mL). Furthermore, plasma atrial natriuretic peptide levels were significantly lower in patients in whom the right atrial appendage was not preserved than in patients in whom the right atrial appendage was preserved at 3 and 7 days after the operation. The fluid balance during the first 7 days of the postoperative period was comparable in the two groups, although the total dose of dopamine used in the same period was significantly smaller in patients in whom the right atrial appendage was preserved than in patients in whom the right atrial appendage was not preserved (155.3 +/- 119.0 vs 244.9 +/- 129.0 microg/kg, P <.05). CONCLUSIONS: The present study showed that preservation of the right atrial appendage lessens the decrease of plasma atrial natriuretic peptide levels after the maze procedure and that increased plasma atrial natriuretic peptides may improve the ability of the kidneys to excrete the fluid load after the operation.

Atrial Appendage↗

PubMed2000

Acidification severely suppresses spawning of hime salmon (land-locked sockeye salmon, Oncorhynchus nerka).

A laboratory study was conducted to investigate the effects of an acidic environment on the female sexual behavior of hime salmon (land-locked sockeye salmon, Oncorhynchus nerka). Spawning hime salmon were extremely sensitive to the acidity of ambient water. Nest-digging behavior was severely inhibited (P<0.05) by very slight acidification (pH below 6.4) of the water. Below pH 6.0, females showed almost no diggings. When the ambient water was returned to nearly neutral (pH 6.6), diggings reappeared in four of the six fish tested, whereas in two individuals, none was observed. Avoidance of slightly acidic water in selection of spawning site or cessation of spawning behavior in weakly acidic environments may be the most potent cause of the reduction of salmonid populations in the early stages of acidification.

Animals↗

PubMed2000

Delapril versus manidipine in hypertensive therapy to halt the type-2-diabetes-mellitus-associated nephropathy.

Thirty-nine hypertensive patients with type 2 diabetes mellitus were followed under long-term treatment (mean, 20.7 months) with manidipine hydrochloride, a Ca antagonist, or delapril hydrochloride, an ACE inhibitor, at nine institutions. Both the treatments showed similar antihypertensive effects, although slight but significantly larger decreases were observed in systolic and mean blood pressures at months 12 and 24 in the patients treated with manidipine (P < 0.02). The urinary albumin excretion index (AEI) tended to increase throughout the study in both treatment groups, but no significant difference in AEI was observed between the two treatment groups at any time point. Overt albuminuria developed in four patients on manidipine but did not appear in any of the patients on delapril. The risk of progression to overt albuminuria was significantly different between manidipine and delapril groups (P = 0.011). No increase in serum creatinine (Cr) was observed with delapril. The average excretion indexes of tubular markers such as beta2-microglobulin, alpha1-microglobulin, and NAG tended to be higher in the patients on manidipine than in those on delapril. Taken in sum, these findings suggest that the ACE inhibitor delapril is more beneficial than the Ca antagonist manidipine in the treatment of diabetic renal diseases via mechanisms other than the blood pressure regulation, partly through their different effects on tubular function. In conclusion, delapril was significantly more effective than manidipine in inhibiting progression to overt albuminuria in hypertensive type 2 diabetes mellitus patients.

Adult↗

PubMed2000

Cynomolgus monkey liver aldehyde oxidase: extremely high oxidase activity and an attempt at purification.

Aldehyde oxidase (EC 1.2.3.1) in monkey (Macaca fascicularis) liver was characterized. Liver cytosol exhibited extremely high benzaldehyde and phthalazine oxidase activities based on aldehyde oxidase, compared with those of rabbits, rats, mice and guinea pigs. Monkey liver aldehyde oxidase showed broad substrate specificity distinct from that of the enzyme from other mammals. Purified aldehyde oxidase from monkey liver cytosol showed two major bands and two minor bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These bands were also observed in Western blotting analysis using anti-rat aldehyde oxidase. The molecular mass of the enzyme was estimated to be 130-151 kDa by SDS-PAGE, and to be about 285 kDa by HPLC gel filtration. The results suggest that isoforms of aldehyde oxidase exist in monkey livers.

Aldehyde Oxidase↗

PubMed2000

Whole-body metabolism of the organophosphorus pesticide, fenthion, in goldfish, Carassius auratus.

The in vivo metabolism of fenthion, an organophosphorus pesticide, and its sulfoxide (fenthion sulfoxide) was examined in goldfish (Carassius auratus). When goldfish were administered fenthion i.p. at a dose of 100 mg/kg, two metabolites were isolated from the tank water. They were identified as fenthion sulfoxide and fenthion oxon, in which > P = S of fenthion is transformed to > P = O, by comparing their mass and UV spectra, and their behavior in HPLC and TLC, with those of authentic standards. However, fenthion sulfone was not detected as a metabolite. The amounts of fenthion, fenthion sulfoxide and fenthion oxon excreted within 4 days were 2.7, 3.4 and 2.5%, of the initial dose of fenthion, respectively. Unchanged fenthion was detected in the body of the fish to the extent of 42-50% of the dose after 10 days, but fenthion sulfoxide and fenthion oxon showed very low concentrations. When fenthion sulfoxide was administered to the fish, about 70% of the dose was excreted unchanged into the tank water within 24 h, but little of the reduced compound, fenthion, was found. In contrast, fenthion was detected at 2.1% of dose in the body of goldfish as a metabolite of fenthion sulfoxide. The fact that fenthion is metabolized to the toxic oxon form in fish presumably has environmental and health implication for its use as a pesticide.

Animals↗