Biomedical subjects

M Sato

Publications and source records attributed to M Sato.

At least 199 records · Page 11Linked to original sources

PubMed2001

Off-pump coronary artery bypass for a heparin-allergic patient.

A 46-year-old man with no history of drug allergy developed acute myocardial infarction. Coronary angiographic findings revealed triple vessel disease. Serum hepatic enzymes were elevated due to heparin administered to control infarction, and an allergic reaction developed exclusively due to heparin. To avoid heparin use, we adopted heparin-free off-pump coronary artery bypass grafting through median sternotomy. The systemic anticoagulant agent argatroban was administered to maintain active clotting time over 200 seconds. The left internal thoracic artery was anastomosed to the left anterior descending artery, the radial artery to the diagonal branch, and the right gastroepiploic artery to the right coronary artery. Patency was confirmed by postoperative coronary angiography. No complications were noted. For patients with heparin allergy, off-pump coronary artery bypass grafting is a useful maneuver, because it can be conducted using anticoagulant agents other than heparin.

Anticoagulants↗

PubMed2001

Th1-cytokine induction and anti-tumor effect of 55 kDa protein isolated from Aeginetia indica L., a parasitic plant.

We have isolated a 55 kDa protein from the seed extract of Aeginetia indica L. (AIL), a parasitic plant, by affinity chromatography on an N-hydroxysuccinimide-activated Sepharose High Performance column bound with F3, a monoclonal antibody that neutralizes the cytokine-inducing and anti-tumor effect of AIL. In the present study, we examined this protein (AILb-A) for cytokine induction and anti-tumor effects by animal study, using syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. AILb-A administration resulted in markedly increased levels of Th1 cytokines [interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12 and IL-18] in the sera derived from Meth-A-bearing mice. The in vitro re-stimulation with AILb-A of splenocytes derived from AILb-A-primed mice also selectively induced Th1-type cytokines and antigen-specific killer cell activity. The neutralizing test using cytokine-specific antibodies revealed that AILb-A-induced IL-18 plays a most significant role for and killer cell-inducing activities. Furthermore, IL-12 and IL-18 induced by AILb-A inhibited specifically IL-10 and IL-4 production, respectively. Finally, we examined the anti-tumor effect of AILb-A in both Meth-A-bearing BALB/c mice and Meth-A-bearing nude mice with BALB/c background. AILb-A exhibited a striking anti-tumor effect in normal BALB/c mice inoculated with Meth-A cells. In athymic nude mice, the anti-tumor effect of AILb-A was relatively weak. These findings strongly suggested that AILb-A is a potent Th1 inducer and may be a useful immunotherapeutic agent for patients with malignant diseases.

Animals↗

PubMed2001

Effects of citrate on renal stone formation and osteopontin expression in a rat urolithiasis model.

Previous studies have described the inhibitory effects of citrate on calcium oxalate crystallization in place of crystal growth, but the effects of citrate on matrix proteins of stones has not been studied in vivo. To examine the effect of citrate on the matrix, we investigated the effect of citrate on osteopontin (OPN) expression, which we had previously identified as an important stone matrix protein. Control rats were treated with saline while rats of the stone group were treated with ethylene glycol (EG) and vitamin D3, and the citrate groups (low-dose and high-dose groups) were treated with a citrate reagent compound of sodium citrate and potassium citrate, in addition to EG and vitamin D3. The rate of renal stone formation was lower in the citrate groups than in the stone group. This was associated with a low expression of OPN mRNA in citrate-treated rats relative to that in the stone group. Citrate was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that citrate prevents renal stone formation by acting against not only the crystal aggregation and growth of calcium oxalate but also OPN expression.

Animals↗

PubMed2001

Enhancement of anti-cancer immunity by a lipoteichoic-acid-related molecule isolated from a penicillin-killed group A Streptococcus.

We isolated the lipoteichoic-acid-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by affinity chromatography on CNBr-activated Sepharose-4B-bound monoclonal antibody TS-2, which neutralizes the interferon (IFN)-gamma-inducing activity of OK-432. We have previously reported that OK-PSA is a potent inducer of Th1-type cytokines in human peripheral blood mononuclear cells in vitro. In this study, we conducted an animal experiment to examine whether OK-PSA exhibits an anti-tumor effect in vivo by acting as a Th1 inducer in syngeneic Meth-A tumor-bearing BALB/c mice, in which the Th2 response is genetically dominant. It was found that OK-PSA induced Th1-type cytokines [IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12 and IL-18] in BALB/c mice bearing Meth-A tumor and caused a marked anti-tumor effect. Although it was suggested by an in vitro study. using spleen cells derived from the animals, that IL-18 plays the greatest role in the induction of the Th1-dominant state and tumor cell killing induced by OK-PSA, the in vivo experiments demonstrated that both IL-12 and IL-18 are essential in the anti-tumor effect exhibited by OK-PSA. These findings strongly suggest that OK-PSA is a major effector molecule of OK-432 and may be a useful immunotherapeutic agent, as a potent Th1 inducer, for cancer patients with a Th2-dominant state.

Adjuvants, Immunologic↗

PubMed2001

Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer.

PURPOSE: To determine the maximum tolerated dose (MTD) of irinotecan combined with carboplatin, to evaluate its efficacy and toxicity for patients with lung cancer, and to examine its pharmacokinetics and pharmacodynamics. METHODS: The dose of irinotecan was escalated from 40 mg/m2 per week in increments of 10 mg/m2. Carboplatin was fixed at 300 mg/m2. Multivariate regression models with an interaction term were used to evaluate synergistic pharmacodynamic interactions. RESULTS: The MTD and recommended dose of irinotecan were 60 and 50 mg/m2, respectively. Dose-limiting toxicities were grade 4 neutropenia and grade 3 or 4 diarrhea. In phase II studies, response rates were 81.3% (95% confidence interval 61.8-100%) in 16 patients with small-cell lung cancer and 22.2% (2.7-41.8%) in 18 patients with non-small-cell lung cancer. Two patients (6%) experienced grade 4 neutropenia, thrombocytopenia, and grade 3 diarrhea. The area under the plasma concentration versus time curve (AUC) of carboplatin ranged from 2.87 to 9.31 mg x min/ml, with a median of 4.66 mg x min/ml. In pharmacodynamic analyses, the log-transformed surviving fraction in platelet count (SFp) showed a significant association with the AUC of carboplatin (P=0.010), while that in neutrophil count (SFn) was not significantly correlated with any pharmacokinetic parameter. The interaction term was not significant in either case. CONCLUSIONS: These results indicate that AUC-based dosing of carboplatin is still rational in combination chemotherapy. A more sensitive method for predicting life-threatening toxicities is needed, however, because traditional pharmacokinetic parameters were not adequate tools for identifying patients at high risk of severe neutropenia and diarrhea. This combination regimen has only modest activity, and further studies are necessary to evaluate a different dose schedule.

Adult↗

PubMed2001

Carcinoma of the cystic duct associated with pancreaticobiliary maljunction.

We report a rare case of carcinoma of the cystic duct (CCD) associated with pancreaticobiliary maljunction (PBM). A 63-year-old man had presented with relapsing cholecystitis of 4 months, duration. Computed tomography showed a distended gallbladder: however, small mass in the cystic duct was overlooked. Endoscopic retrograde cholangiopancreatography demonstrated a long common channel (20-mm-long) and fusiform dilatation of the common bile duct, findings, which were consistent with PBM. At laparotomy, we found a papillary tumor, 20 mm in diameter, that obstructed the cystic duct. The patient underwent resection of the gallbladder and the common bile duct, lymph node dissection in the hepatoduodenal ligament, and hepaticojejunostomy. Histologic study revealed a papillary adenocarcinoma confined within the subserosal space. There was no lymphatic or perineural invasion of cancer cells. The surrounding cystic ductal mucosa showed dysplasia and hyperplasia, and the gallbladder and common bile duct showed severe inflammation. The patient has been doing well for 16 months after surgery, without tumor recurrence. This case suggests a relationship between CCD and chronic biliary inflammation caused by PBM, as in cases of gallbladder carcinoma.

Adenocarcinoma, Papillary↗

PubMed2001

Three-dimensional simulation of the Blalock-Taussig shunt using computational fluid dynamics.

To examine blood flow after the placement of a Blalock-Taussig shunt, three complex T-figure models were developed according to shunt size and the degree of pulmonary artery hypoplasia. With the use of computational fluid dynamics, the net energy loss and wall shear stress were calculated under pulsatile conditions. We calculated that the 5-mm shunt carried the least energy loss, but the most wall shear stress. In this simulation, the 5-mm shunt was thought to be superior to the 4-mm and 3-mm shunts in terms of energy loss and smooth flow, but it produced high wall shear stress.

Anastomosis, Surgical↗

PubMed2001

Molecular cause of the severe functional deficiency in osteoclasts by an arginine deletion in the basic domain of Mi transcription factor.

Severe osteopetrosis was observed in mi/mi mutant mice. However, the bone of VGA9/VGA9 mutant mice, in which Mi gene expression is undetectable, showed normal histology. No osteopetrosis was found in mi/+ mice, but was observed in VGA9/mi mice. Biochemical analysis revealed that the gene product encoded with the mi mutant allele (mi-Mi) has impaired DNA binding activity and nuclear translocation ability. Furthermore, inhibitory effects of mi-Mi were shown not only on the DNA binding activity of wild-type Mi, but also on the nuclear translocation ability of Mi, PU.1 and cFOS. The present results suggest the presence of a target gene for Mi that is essential for the proliferation/differentiation of osteoclasts.

Active Transport, Cell Nucleus↗

PubMed2001

Cloning, sequencing, and phylogenetic analysis of complementary DNA of novel cytochrome P-450 CYP1A in Japanese eel (Anguilla japonica).

Complementary DNA of cytochrome P-450 CYP1A, in addition to CYP1A1, has been isolated from Japanese eel (Anguilla japonica) liver treated with 3-methylcholanthrene. The cDNA contained a 5' untranslated region of 66 bp, an open reading frame of 1554 bp coding for 517 amino acids and a stop codon, and a 3' untranslated region of 1166 bp. The predicted molecular weight of the Japanese eel CYP1A was approximately 58.5 kDa. The nucleotide sequence exhibited identities with the reported CYP1A1 sequences of 77% for Japanese eel, 75% for rainbow trout, 72% for scup, plaice, and butterfly fish, and 71% for toadfish. The deduced amino acid sequence exhibited identities with the reported CYP1A1 sequences of 78% for Japanese eel, 77% for rainbow trout, 75% for scup, 74% for toadfish, 73% for plaice, and 72% for butterfly fish. The novel eel CYP1A obtained had less similarity to the other teleost CYP1A1 proteins (72%-78%) than that of the eel CYP1A1 (74%-80%). When compared with mammalian CYP proteins, the novel eel CYP1A was more similar to the CYP1A1 proteins (54%-56%) than to the CYP1A2 proteins (50%-53%). The phylogenetic tree of the teleost CYP1A genes constructed using the maximum likelihood method suggested that the novel eel CYP1A is ubiquitous among the Anguilliformes.

Journal Article↗

PubMed2001

Molecular characterization of a mitochondrial DNA segment from the Japanese scallop (Patinopecten yessoensis): demonstration of a region showing sequence polymorphism in the population.

A 1.3-kb mitochondrial DNA segment from the Japanese scallop Patinopecten yessoensis was cloned and sequenced. This segment contained the transfer RNA(Met) gene and partial sequences of 2 ribosomal RNA genes, together with 2 separate noncoding regions (designated NcR1 and NcR2). The NcR regions derived from 78 individuals cultured in Lake Saroma or Matsu Bay, were sequenced, and we found 15 loci with sequence alterations including 13 substitutions, 1 deletion, and 1 insertion (1 locus in NcR1, 14 loci in NcR2), and 17 haplotypes. Of the 17 haplotypes, 10 were found in the Saroma population only, 3 in the Mutsu population only, and 4 in both populations. The gene diversity and nucleotide diversity values were, respectively, 0.87 and 0.0069 for the Saroma population, 0.63 and 0.0040 for the Mutsu population, and 0.83 and 0.0203 overall. Thus the NcR segment was considered to have sufficient sequence variation for population genetic studies. The 16 variants of the NcR2 sequence were separated successfully by denaturing gradient gel electrophoresis, confirming the sequence variation in NcR2.

Journal Article↗

PubMed2001

Segmentectomy for roentgenographically occult bronchogenic squamous cell carcinoma.

BACKGROUND: Roentgenographically occult bronchogenic squamous cell carcinomas (ROSCCs) are early squamous cell lung cancers of central type. Some of them cannot be treated with intrabronchial therapy. Although surgical treatment was performed for such tumors, it was unknown whether lobectomy was indispensable or not. METHODS: The clinicopathologic information of the 58 patients who underwent segmentectomy for ROSCCs were collected from 16 hospitals and reviewed retrospectively, compared with 98 patients who underwent lobectomy for ROSCCs. RESULTS: Five-year survival rate of the 58 patients based on lung cancer deaths was 96.8%, and 82.6% including all causes of death. The duration of chest tube drainage in the segmentectomy group was slightly longer than in the lobectomy group. Operative mortality and the frequency of postoperative complications were not statistically different in both groups. Postoperative/preoperative vital capacity and forced expiratory volume in 1 second were higher in the segmentectomy group. CONCLUSIONS: These results suggest that segmentectomy may be an alternative for surgical therapy of carefully selected ROSCCs. More prospective studies are required to fully demonstrate clinical benefit.

Adult↗

PubMed2001

Secretory leukocyte protease inhibitor in ovarian endometriomas following GnRH agonist therapy.

OBJECTIVE: To determine whether expression of secretory leukocyte protease inhibitor is affected in tissue and peritoneal fluid of women with ovarian endometriomas treated with GnRH analogues. METHODS: In 32 women with endometriomas (17 untreated and 15 treated with GnRH analogue) and 21 with ovarian cystadenomas, we examined the expression of secretory leukocyte protease inhibitor messenger RNA (mRNA) by Northern blot analysis; protein distribution was measured immunohistochemically. Concentrations of secretory leukocyte protease inhibitor in peritoneal fluid were measured by enzyme-linked immunosorbent assay. Expression of secretory leukocyte protease inhibitor in endometrioma explants in vitro was also studied with and without the GnRH analogue treatment. RESULTS: Secretory leukocyte protease inhibitor mRNA expression was identified only in untreated endometriomas. In the GnRH agonist-treated endometriomas, the semiquantitative H-score for secretory leukocyte protease inhibitor immunostaining was significantly lower than that for untreated endometriomas (P <.001). The peritoneal fluid of the GnRH agonist-treated women also contained significantly lower concentrations of secretory leukocyte protease inhibitor (median 76 ng/mL, interquartile range 51-131 ng/mL; P <.001) than untreated women (124 ng/mL, 70-186 ng/mL). Secretory leukocyte protease inhibitor in endometrioma explants in vitro was significantly inhibited by the GnRH analogue (P <.05). CONCLUSION: Expression of secretory leukocyte protease inhibitor in tissue and peritoneal fluid of women with ovarian endometriomas was decreased by GnRH agonist treatment.

Adult↗

PubMed2001

Synthesis of coenzyme A esters of 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oic acids for the study of beta-oxidation in bile acid biosynthesis.

3alpha,7alpha,12alpha-Trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl CoAs were chemically synthesized by the conventional method for the study of side chain cleavage in bile acid biosynthesis. 3alpha,7alpha,12alpha-Triformyloxy- and 3alpha,7alpha-diformyloxy-5beta-cholan-24-als were initially subjected to the Reformatsky reaction with methyl alpha-bromopropionate, and the products were then converted into methyl 3alpha,7alpha,12alpha-triformyloxy- and 3alpha,7alpha-diformyloxy-24-oxo-5beta-cholestan-26-oates. Protection by acetalization of the 24-oxo-group of these methyl esters with ethylene glycol, followed by alkaline hydrolysis, gave 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24,24-ethylenedioxy-5beta-cholestan-26-oic acids. These acids were condensed with coenzyme A by a mixed anhydride method, and the resulting CoA esters were treated with 4M-hydrocholic acid to remove the protecting group to give 24-oxo-5beta-cholestanoic acid CoA esters. The chromatographic behaviors of these CoA esters were also investigated.

Bile Acids and Salts↗

PubMed2001

Conjugation reactions catalyzed by bifunctional proteins related to beta-oxidation in bile acid biosynthesis.

The conjugation reactions of hydration and dehydrogenation catalyzed by the dehydratase and dehydrogenase activities of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (DBP) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein (LBP) in the side chain degradation step of bile acid biosynthesis were investigated using chemically synthesized C27-bile acid CoA esters as substrates. The hydration catalyzed by DBP showed high diastereoselectivity for (24E)-3alpha,7alpha,12alpha-trihydroxy- and (24E)-3alpha,7alpha-dihydroxy-5beta-cholest-24-en-26-oyl CoA to give (24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy- and (24R,25R)-3alpha,7alpha,24-trihydroxy-5beta-cholestan-26-oyl CoAs, respectively, and the dehydrogenation catalyzed by DBP also showed high stereospecificity for the above (24R,25R)-isomers to give 3alpha,7alpha,12alpha-trihydroxy- and 3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl CoAs, respectively. On the other hand, the dehydratase activity of LBP displayed a different diastereoselectivity producing the (24S,25S)-isomer, and dehydrogenase activity of LBP was stereospecific for the (24S,25R)-isomer to give the above 24-oxo-derivative. The hydration and dehydrogenation reactions catalyzed by DBP were effectively conjugated to convert (24E)-5beta-cholestenoyl CoA to 24-oxo-5beta-cholestanoyl CoA. However, the reactions catalyzed by LBP were not conjugated. These results indicate that DBP plays an important role in the biosynthesis of bile acid.

17-Hydroxysteroid Dehydrogenases↗

PubMed2001

Effects of disparity-perspective cue conflict on depth contrast.

The role of disparity-perspective cue conflict in depth contrast was examined. A central square and a surrounding frame were observed in a stereoscope. Five conditions were compared: (1) only disparity was introduced into either the centre or surround stimulus, (2) only perspective was introduced into the centre or surround, (3) concordant perspective and disparity were introduced into the centre or surround, (4) disparity was introduced into one stimulus and perspective into the other, and (5) only the centre stimulus was presented with horizontal shear disparity and perspective manipulated independently. The results show that individual differences in depth contrast were related to individual differences in the weighting of disparity and perspective in the single-stimulus conditions. We conclude that conflict between disparity and perspective contributes to depth contrast. However, significant depth contrast occurred when there was no disparity-perspective cue conflict, indicating that this cue conflict is not the sole mechanism producing depth contrast.

Adult↗

PubMed2001

Multifocal pupillary light response fields in normal subjects and patients with visual field defects.

The optimal conditions for recording focal pupillary light responses with a multifocal stimulation technique were determined, and the technique was applied to normal subjects and patients with visual field defects. Thirty-seven hexagonal stimuli were presented on a TV monitor with a visual field of 40 degrees diameter under a constant background illumination. Using a slow (4.7 Hz) m-sequence, reliable focal responses were obtained in both normal subjects and patients. The pupillary field and visual field were well correlated in patients with retinal diseases, but the correlation was not strong in patients with optic-nerve diseases. Pupillary light responses were reduced in the blind hemifield in patients with post-geniculate lesions. These results indicate that the multifocal stimulation technique can be used clinically to obtain a pupillary field for objective visual field testing.

Adult↗

PubMed2001

Envelope size-tuning for transient disparity vergence.

Our prior studies have demonstrated that the transient-vergence system responds preferably to dichoptic stimulus pairs that contain the highest combined energy, regardless of dichoptic differences in spatial frequency, contrast, orientation, or luminance polarity (Edwards, M., Pope, D. R., & Schor, C. M. (1998), Vision Research 38, 705; Pope, D. R., Edwards, M., & Schor, C. M. (1999) Vision Research 39, 575). This broadband tuning for spatial frequency, orientation and contrast is indicative of a second order (non-linear) extraction system. The current study examined the potential size-tuning of binocular channels to the contrast envelope that is extracted by a non-linear process. Stimuli were size-scaled Gabor patches with parallel and orthogonal carrier orientations that subtended a large (3.8 degrees ) disparity. Results indicate that the transient-vergence system exhibits broad band-pass tuning to overall size of dichoptic targets, independent of interocular differences in carrier orientation, spatial frequency or contrast. Equal sizes elicited a higher proportion of vergence responses than unequal sizes, however responses to unequal size still occurred over a 2-octave range, illustrating broad band-pass tuning. Size tuning was found to be broader for small than large envelope sizes. The broad tuning for envelope size is likely to result from the overlapping extracted low-pass frequency spectra of the contrast envelopes. However, the transient-vergence system also responds to monocular, hemi-retinal stimuli over a larger (3-octave) range. Thus some of the observed "binocular tuning" may be due to these monocular responses.

Adult↗

PubMed2001

Envelope size tuning for stereo-depth perception of small and large disparities.

Stereopsis is the sense of depth derived from binocular disparities that are formed between targets that are matched between the two retinal images. Binocular matches for sustained stereopsis are based on similarity of orientation, spatial frequency and contrast of the two retinal images whereas matches for transient stereopsis depend on these parameters to a very limited extent. In this investigation we have tested the possibility that transient stereopsis forms matches between objects of similar overall size. The tuning of sustained and transient stereopsis to contrast-envelope size was investigated by presenting narrow-band Gabor targets of unequal size to the two eyes. Bandwidth for envelope-size tuning was estimated from the range of dichoptic size-differences over which stereo performance remained above chance level. An equal bandwidth of 2 octaves was found for the sustained and transient stereo systems when stimulated with parallel orientation Gabors that subtended a small disparity. Sustained-stereo performance with orthogonal carriers was reduced with large envelope sizes. Bandwidth of the transient stereo system increased to 3 octaves when tested with a larger disparity stimulus and it was independent of carrier orientation. Reducing the contrast of the larger-size Gabor improved transient-stereo performance from near chance (48-58%) to 85-95%. Thus the bandwidth for envelope-size tuning is much broader than indicated with equal physical contrast stimuli. The observed tuning to envelope size, while broad, is tighter than that observed for carrier spatial-frequency [Vis. Res. 38 (1998) 3057], carrier orientation [Vis. Res. 39 (1999) 2717] and contrast polarity [Vis. Res. 39 (1999) 4010] of the stimulus. Thus it would appear that envelope size and, to a greater extent, temporal synchrony of the dichoptic stimuli [Perception 24 (1995) 33] are the primary means for selecting matched binocular inputs for transient stereopsis.

Contrast Sensitivity↗