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Biomedical subjects

J Ohta

Publications and source records attributed to J Ohta.

At least 19 recordsLinked to original sources

Connectivity matrix method for analyses of biological networks and its application to atom-level analysis of a model network of carbohydrate metabolism.

An approach for analysis of biological networks is proposed. In this approach, named the connectivity matrix (CM) method, all the connectivities of interest are expressed in a matrix. Then, a variety of analyses are performed on GNU Octave or Matlab. Each node in the network is expressed as a row vector or numeral that carries information defining or characterising the node itself. Information about connectivity itself is also expressed as a row vector or numeral. Thus, connection of node n1 to node n2 through edge e is expressed as [n1, n2, e], a row vector formed by the combination of three row vectors or numerals, where n1, n2 and e indicate two different nodes and one connectivity, respectively. All the connectivities in any given network are expressed as a matrix, CM, each row of which corresponds to one connectivity. Using this CM method, intermetabolite atom-level connectivity is investigated in a model metabolic network composed of the reactions for glycolysis, oxidative decarboxylation of pyruvate, citric acid cycle, pentose phosphate pathway and gluconeogenesis.

Adaptation, Physiological↗

Well-differentiated biphasic synovial sarcoma in the atlanto-occipital joint of a Holstein cow.

A 7-year-old Holstein cow developed a large cystic mass in the region between the atlantoaxis and larynx. The mass extended to the synovium in the atlanto-occipital joint. Many villous projections were present on the inner surface of the tumor tissue, and irregular clefts were formed in the inside. Two cell types, epithelioid-like synovioblasts and spindle cells, were present. Immunohistochemical analysis showed that the cells stained positively for cytokeratin (AE1/AE3) and vimentin. Both cells had similar fine structures ultra-structurally. Vacuoles present in the cytoplasm were full of an acid mucous substance. The tumor was diagnosed as a well-differentiated biphasic synovial sarcoma. This is the first report of a rare case of synovial sarcoma, from the viewpoint of its origin.

Animals↗

[A case report of ross operation and ventricular septal defect closure following correction of type A interruption by modified Blalock-Park, pulmonary artery banding and patent ductus arteriosus division].

A 2-year-old boy who had undergone a correction of a type A interruption using a modified Blalock-Park operation, pulmonary artery banding and the division of a patent ductus arteriosus, underwent a Ross operation and closure of ventricular septal defect (VSD). Although a pre-operative echo cardiogram revealed a bicuspid aortic valve, and a Doppler echocardiogram showed only 10 mmHg of pressure gradient across the aortic valve, Ross procedure was performed as a procedure accompanying the closure of a total conus VSD. The total conus VSD was closed with a Dacron patch using pledget mattress sutures. In addition, a running suture was applied over the denuded aortic root and the cranial margin to achieve water tight closure. An aortic root replacement procedure was our first choice for the Ross operation. After both coronary buttons were re-implanted into pulmonary sinuses, a pulmonary artery autograft was wrapped around by the remaining aortic wall for reinforcement to prevent future dilatation. The main pulmonary artery was reconstructed using a bicuspid pericardial valve conduit with a diameter of 24 mm. A post-operative echocardiogram showed no neoaortic valve regurgitation, good coaptation of tri-leaflets, mild regurgitation of pericardial valve and good cardiac performance.

Abnormalities, Multiple↗

Gene expression and in situ localization of diacylglycerol kinase isozymes in normal and infarcted rat hearts: effects of captopril treatment.

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attenuator of the PKC activity. In rats, five DGK isozymes have been cloned, but little is known about their role in the heart. In this study, the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybridization histochemistry and immunohistochemistry. In normal left ventricular myocardium, DGKalpha, DGKepsilon, and DGKzeta mRNAs were expressed evenly throughout the myocardium, although the DGKalpha expression was very low. In infarcted hearts, the expression of DGKzeta was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKzeta expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKepsilon in the infarcted and border areas was lower than that in the viable left ventricle (LV) throughout the postoperation period. Furthermore, DGKepsilon expression in the viable myocardium 21 days after MI decreased significantly compared with left ventricular myocardium in the sham-operated rats and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.

Angiotensin-Converting Enzyme Inhibitors↗

Determination of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione, a novel metabolite of L-histidine, in tissue extracts from sunlight-irradiated rat by capillary electrophoresis.

Exposure of the skin to sunlight results in an increase in the content of epidermal urocanic acid, a key metabolite of L-histidine, and some portions of the metabolite penetrate into the body fluid. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (GS(CIE)), an adduct of glutathione and urocanic acid, was proposed to be an origin of a urinary compound, S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). Various catabolites of Cys(CIE) were also isolated from human urine previously. However, no direct evidence to show the existence of GS(CIE) as a biological material had been found. By using capillary electrophoresis, the glutathione adduct has now been found in the extracts of rat tissues from the kidney, liver, skin and blood when the rat was kept under conditions of sunlight irradiation after the fur on the dorsal skin had been clipped. On the other hand, no or a trace of GS(CIE) was determined in rat tissue extracts when the animal was kept indoor in usual manner. The glutathione adduct was isolated from the kidney extract of the sunlight-irradiated rat using ion-exchangers and high-voltage paper electrophoresis, and determined by fast-atom-bombardment mass spectrometry. These results indicate that GS(CIE) formation actually occurs in the body and that the formation is accelerated by exposing the rat to sunlight irradiation. From these findings, we propose an alternative pathway of histidine metabolism which is initiated by the adduction of urocanic acid to glutathione to form GS(CIE) and terminates with the formation of the urinary compounds via Cys(CIE).

Animals↗

[Diagnosis of prostate capsular invasion by pelvic magnetic resonance imaging and serum level of prostate specific antigen].

Transrectal ultrasonography (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) are employed to diagnose the clinical stage of prostate cancer. However, several cases are diagnosed as pathological stage pT3 after total prostatectomy. We investigated the accuracy of the evaluation of pathologic capsular penetration by preoperative pelvic MRI and preoperative serum PSA level and capsular penetration. The diagnostic accuracy of capsular penetration by MRI was 63.3%. On the other hand, the diagnostic accuracy of capsular penetration by preoperative PSA was 89.7% when its cut off value was 17 ng/ml. We conclude that preoperative serum PSA level could be more useful to diagnose accurately stage of prostate cancer than pelvic MRI.

Aged↗

GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies.

GATA-1 germline mutation in mice results in embryonic lethality due to defective erythroid cell maturation, and thus other hematopoietic GATA factors do not compensate for the loss of GATA-1. To determine whether the obligate presence of GATA-1 in erythroid cells is due to its distinct biochemical properties or spatiotemporal patterning, we attempted to rescue GATA-1 mutant mice with hematopoietic GATA factor complementary DNAs (cDNAs) placed under the transcriptional control of the GATA-1 gene. We found that transgenic expression of a GATA-1 cDNA fully abrogated the GATA-1-deficient phenotype. Surprisingly, GATA-2 and GATA-3 factors expressed from the same regulatory cassette also rescued the embryonic lethal phenotype of the GATA-1 mutation. However, adult mice rescued with the latter transgenes developed anemia, while GATA-1 transgenic mice did not. These results demonstrate that the transcriptional control dictating proper GATA-1 accumulation is the most critical determinant of GATA-1 activity during erythropoiesis. The results also show that there are biochemical distinctions among the hematopoietic GATA proteins and that during adult hematopoiesis the hematopoietic GATA factors are not functionally equivalent.

Animals↗

Effect of surgical stress on endogenous morphine and cytokine levels in the plasma after laparoscopoic or open cholecystectomy.

BACKGROUND: Endogenous morphine in the brain leads to various biological responses after surgery. The aim of this study was to determine whether morphine levels in the plasma would be enhanced by open laparotomy rather than by laparoscopic procedures. METHODS: We compared 19 patients who underwent laparoscopic cholecystectomy with five patients who underwent resection of the gallbladder by open laparotomy. Morphine levels in the plasma were measured by an electrochemical detection system. RESULTS: Postoperative endogenous morphine levels were higher with open laparotomy than with the laparoscopic technique (three h after surgery: open, 200 +/- 52.6 fmol/ml vs laparoscopy, 17.6 +/- 3.7, p < 0.01). This morphine elevation accounted for higher levels of cytokine, greater pain scores, and longer duration of fasting in open laparotomized patients than in laparoscopic cholecystectomy patients. Stress hormone levels in the plasma were also higher with open laparotomy than with laparoscopy. CONCLUSION: Morphine synthesis was enhanced by open laparotomy, resulting in greater biological response postoperatively than that seen with laparoscopic cholecystectomy.

Adrenocorticotropic Hormone↗

Cysteine dioxygenase and gamma-glutamylcysteine synthetase activities in primary cultured hepatocytes respond to sulfur amino acid supplementation in a reciprocal manner.

Hepatocytes were cultured for 3 days as spheroids (aggregates) or as monolayers in basal medium and in sulfur amino acid-supplemented media. Cultured hepatocytes had low levels of cysteine dioxygenase (CDO) activity and normal levels of gamma-glutamylcysteine synthetase (GCS) and cysteine-sulfinate decarboxylase (CSDC) activities compared to freshly isolated cells. CDO activity increased and GCS activity decreased in a dose-response manner in cells cultured in either methionine- or cysteine-supplemented media. CSDC activity was not significantly affected by methionine supplementation. Changes in CDO and GCS were associated with changes in cysteine catabolism to taurine plus sulfate and in synthesis of glutathione, respectively. These responses are similar to those observed in liver of intact rats fed diets supplemented with sulfur amino acids. A near-maximal response of CDO or GCS activity was observed when the medium contained 1.O mmol/L of methionine plus cyst(e)ine. Changes in CDO and GCS activities did not appear to be mediated by changes in the intracellular glutathione concentration. Cultured hepatocytes offer a useful model for further studies of cysteine metabolism and its regulation in response to sulfur amino acid availability.

Animals↗

[Study of free to total prostate specific antigen ratio in the detection of patients with prostate cancer].

BACKGROUND: We investigated the clinical usefulness of free to total serum prostate specific antigen (PSA) ratio (F/T ratio) in order to improve the specificity of total PSA measurement for detecting prostate cancer. METHOD: In this study 129 patients with total PSA level 4-20 ng/ml underwent transrectal ultrasound guided sextant biopsy. Serum samples were assessed for total PSA, free PSA and the F/T ratio calculated. All patients were pathologically diagnosed as benign prostatic hyperplasia or prostate cancer. RESULTS: Of 129 patients 21 had prostate carcinoma (PCa) and 108 had benign prostatic hyperplasia (BPH) from the results of prostate biopsies. The mean of total PSA were not significantly different between men with PCa and with BPH. The mean of free PSA for PCa was significantly lower than that for BPH (p = 0.043). Furthermore, the mean of F/T ratio was significantly different between PCa and BPH group (p = 0.0014). The F/T ratio had a higher specificity than total PSA at all levels of sensitivity in detecting prostate cancers. Sensitivity, specificity and accuracy for cancer detection at a cut off 0.12 was 90.4%, 51.8% and 58.1%, respectively. Also, free PSA was as useful as F/T ratio for cancer detection when analyzed in receiver operating characteristic curves analysis. When determined the cut off number of free PSA at 0.78 ng/ml, the sensitivity, specificity and accuracy for cancer detection were 61.9%, 66.7% and 65.9%, respectively. CONCLUSION: This study indicated that the F/T ratio and free PSA could improve the specificity without impairing the sensitivity for detecting PCa in patients with 4-20 ng/ml of total PSA.

Aged↗

[Pulmonary outflow tract reconstruction with autologous tissue during the Ross procedure: right ventricular characteristics in mid-term follow-up].

BACKGROUND: The Ross procedure requires the interposition of prosthetic or homograft extracardiac conduits to establish ventricle-pulmonary artery connection (RV-PA). These materials usually require multiple reoperations because of conduit failure. To avoid the re-replacement of currently available conduits, usage of autologous tissue may be preferable to reconstruct RV-PA connection during the Ross procedure, especially in the pediatric age group. METHOD: Ten patients (mean age 8.7 years, range 2-23) with congenital aortic valve disease underwent the Ross procedure between June, 1996 and July, 1998. To establish RV-PA continuity, autologous aortic wall including aortic valve with a gusset of pericardial tissue was used in six patients, rolled pericardial conduit with fresh pericardial bicuspid valve in three and one direct anastomosis of pulmonary posterior wall onto the right ventricle with a fresh pericardial monocusp valved patch. All patient's postoperative courses were uneventful. All patients were followed up (mean follow-up period: 21.6 +/- 6.6 months) and postoperative right ventricular characteristics, cardio-thoracic ratio (CTR) on chest X-ray and pulmonary valve function were evaluated. RESULTS: Postoperative right ventricular end-diastolic volume, right ventricular ejection fraction and right ventricular end-diastolic pressure did not change significantly (RVEDV: 128 to 113% of normal, RVEF: 56.4 to 51.5%, RVEDP: 5.9 to 10.1 mmHg). Pulmonary regurgitation during follow-up was mild in six patients and moderate in four. However, CTR decreased significantly over time (preop.: 56.5% postop.: 58.5%, late period: 53.4%). CONCLUSION: Our results support the concept of the reconstruction of pulmonary outflow tract without foreign materials during the Ross procedure. Longer follow-up are necessary to define the possible limitation of this technique.

Adult↗

The mouse GATA-2 gene is expressed in the para-aortic splanchnopleura and aorta-gonads and mesonephros region.

We previously reported that the mouse GATA-2 gene is regulated by two alternative promoters (Minegishi et al, J Biol Chem, 273:3625, 1998). Although the more proximal IG (general) promoter is active in almost all GATA-2-expressing cells, the distal IS (specific) promoter activity was selectively detected in hematopoietic tissues but not in other mesodermal tissues. We report here in vivo analysis of the GATA-2 locus and its regulatory characteristics in hematopoietic tissues of transgenic mice. Transgenes containing 6 or 7 kbp of sequence flanking the 5' end of the IS first exon direct expression of beta-galactosidase or green fluorescent protein (GFP) reporter genes specifically to the para-aortic splanchnopleura, aorta-gonads, and mesonephros (AGM) region, and in the neural tissues. In situ hybridization analysis showed that reporter gene expression specifically recapitulates the endogenous expression profile of GATA-2 in these tissues. The flk-1, CD34, c-kit, and CD45 antigens were identified in the GFP-positive cells from the AGM region and fetal liver, indicating that GATA-2 is expressed in immature hematopoietic cells. Deletion of 3.5 kbp from the 5' end of the 6.0 kbp IS promoter construct, including one of the DNase I hypersensitive sites, completely abolished hematopoietic expression. These experiments describe an early developmental GATA-2 hematopoietic enhancer located between 6.0 and 2.5 kbp 5' to the IS exon.

Animals↗

Clinicopathological study of canine oral epulides.

To clarify the clinicopathological features of canine epulides, 189 epulides were reviewed retrospectively. The incidence of the fibromatous, ossifying, acanthomatous and giant cell epulides were 56.6% (107/189), 23.3% (44/189), 18.0% (34/189) and 2.1% (4/189), respectively. The average ages of dogs with fibromatous, ossifying, acanthomatous and giant cell epulides were 8.8, 8.4, 7.8 and 8.7 years, respectively. The male/female ratio of dogs with the acanthomatous epulis (0.8) was lower than those of dogs with the fibromatous (1.9), ossifying (1.4) and giant cell epulis (3.0). There were slight breed differences among the types of epulides. The most noticeable result was that 38.2% of the acanthomatous epulis occurred in Shetland sheepdogs. 43.9% of the fibromatous epulis and 52% of the ossifying epulides arose around maxillary premolars, while 58.8% of the acanthomatous epulis arose around the mandibular canines. Dogs with the fibromatous and ossifying epulides had more severe dental plaque deposition than those with the acanthomatous epulides. Few of the fibromatous (6/104) or ossifying epulides (4/44) showed recurrence after excision, while the majority (21/23) of the acanthomatous epulides showed rapid and repeated recurrences after surgical excision. Epulides treated with hemimandibulectomy or bleomycin chemotherapy did not recur. Giant cell epulides showed no recurrence after surgical removal. These results indicate that the acanthomatous epulis differed from other types of epulides in biological and morphological features and poor prognosis.

Age Factors↗

Proliferative potential of canine oral epulides and malignant neoplasms assessed by bromodeoxyuridine labeling.

The proliferative potential of canine oral lesions, including epulides, squamous cell carcinomas, a malignant melanoma, and a fibrosarcoma, was examined using a monoclonal antibody to bromodeoxyuridine (BrdU). Twenty-three dogs with oral masses were administered BrdU intravenously at a dose of 8 mg/kg 1 hour before surgery, and the BrdU labeling index (LI) of each lesion was determined immunohistochemically. The average BrdU LIs for the main proliferating elements in the fibromatous epulis (4 cases), ossifying epulis (2 cases), and acanthomatous epulis (10 cases) were 4.9, 3.0, and 8.8%, respectively. The squamous cell carcinomas (5 cases) had an average LI of 15.9%, and the LIs of the malignant melanoma and fibrosarcoma were 7.5 and 10.3%, respectively. All cases of acanthomatous epulides and squamous cell carcinoma treated with simple marginal surgical resection recurred within a short time. The higher LIs in the acanthomatous epulides, squamous cell carcinomas, and fibrosarcoma correlate well with their poor prognoses, reflected by rapid growth and frequent recurrence. Acanthomatous epulis is clearly distinguished from other epulides by its aggressive clinical behavior and high proliferative potential, which is equivalent to that of malignant tumors, despite a lack of cell atypia. The BrdU LI is a useful marker for evaluating the proliferative potential and prognosis of canine oral tumors.

Animals↗

Formation of gamma-glutamylpropargylglycylglycine from propargylglycine in human blood and erythrocytes.

Gamma-Glutamylpropargylglycylglycine (gamma-Glu-PPG-Gly) was isolated as a metabolite of propargylglycine (2-amino-4-pentynoic acid, a natural and synthetic inhibitor of cystathionine gamma-lyase) from human blood incubated with D,L-propargylglycine in the presence of L-glutamate and glycine, and identified by fast-atom-bombardment mass spectrometry, indicating that human blood can metabolize propargylglycine to gamma-Glu-PPG-Gly. When whole blood was incubated with 2 mM D,L-propargylglycine in the presence of 10 mM L-glutamate and 10 mM glycine at 37 degrees C for 16h, 0.094+/-0.013 micromol of gamma-Glu-PPG-Gly was formed per ml of whole blood. When erythrocytes were incubated under the same conditions for 16h, 0.323+/-0.060 micromol of gamma-Glu-PPG-Gly was formed per ml of erythrocytes, suggesting a large contribution of erythrocytes to gamma-Glu-PPG-Gly formation in whole blood. The apparent Km value of gamma-Glu-PPG-Gly formation in human erythrocytes for D,L-propargylglycine was 0.32 mM. The observed rate of gamma-Glu-PPG-Gly formation and the Km value for D,L-propargylglycine suggest that metabolism of propargylglycine to gamma-Glu-PPG-Gly can play a definite biological role in human subjects who are loaded with propargylglycine.

Adult↗

[A case of Bentall's operation for an 11-year-old patient with Marfan syndrome].

An 11-year-old girl who was diagnosed to have Marfan syndrome in her infancy, visited us with complaints of easy fatigability and chest discomfort. She was pointed out to have acute development of annuloaortic ectasia with severe aortic regurgitation and mild mitral regurgitation. She underwent replacement of the ascending aorta and aortic valve using composite graft with prosthetic valve (Bentall's operation) and circular annuloplasty of the mitral valve. Bentall's operation for infants and children is remarkably rare because in this generation, acute development of aortic dilatation leading rupture and dissection is quite infrequent while main death is caused by mitral regurgitation.

Aorta↗