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Biomedical subjects

S Tomita

Publications and source records attributed to S Tomita.

At least 19 recordsLinked to original sources

Electron paramagnetic resonance investigation of cytochrome P-450c21 from bovine adrenocortical microsomes: a new enzymatic activity.

Cytochrome P-450c21 (CYP21A1) purified from bovine adrenocortical microsomes was investigated by electron paramagnetic resonance (EPR) spectroscopy to clarify the interactions among heme active center, protein surroundings, water molecules and bound substrates or analogues. The low-spin EPR signals of the oxidized enzyme (as purified) consisted of two species; one at gz = 2.39, gy = 2.23, and gx = 1.925 (component A) and the other at gz = 2.42, gy = 2.23, and gx = 1.916 (component B). The component A is probably representing a product-bound form, whereas the component B indicates either occupation of the substrate-binding site with a substrate analogue or absence of steroid at the site. Upon addition of progesterone, the component A signal completely disappeared and the intensity of high-spin signal (g = 8.06, 3.54) increased. Addition of 17 alpha-hydroxyprogesterone caused a development of a new low-spin signal at gz = 2.42, gy = 2.21, and gx = 1.966 (component C) and a further increase in intensity of the high-spin signal (g = 8.06, 3.54). Addition of 20 beta-hydroxyprogesterone caused an increase in intensity of the component C signal (and the g = 8 high-spin signal) even stronger than did 17 alpha-hydroxyprogesterone. These observations suggest that 20 beta-hydroxyprogesterone binds to the cytochrome P-450c21 active center in a very similar manner as 17 alpha-hydroxyprogesterone does and, therefore, may be a metabolizable substrate. A new enzymatic pathway catalyzed by cytochrome P-450c21 was confirmed with a reconstituted enzymatic system consisting of cytochrome P-450c21, NADPH-cytochrome P-450 reductase and an NADPH-generating system. 20 beta-Hydroxyprogesterone was converted to progesterone via a putative 20 beta-oxidase reaction in a comparable turnover number to that of the 21-hydroxylation of 17 alpha-hydroxyprogesterone.

Adrenal Cortex

Isolation of p10 gene from Bombyx mori nuclear polyhedrosis virus and study of its promoter activity in recombinant baculovirus vector system.

A homologue of Autographa californica NPV (AcNPV) p10 gene was identified and cloned from Bombyx mori NPV (BmNPV). BmNPV p10 gene encodes truncated protein of 70 amino acid residues that lacks carboxyl terminus comparing with the p10 protein encoded by AcNPV. The putative TATA box sequence and the ATAAG motif which is the consensus sequence of baculovirus very late promoter were conserved. A transfer vector, pBNT1, which includes the p10 promoter region of BmNPV for foreign gene expression was constructed. By using pBNT1, a recombinant BmNPV, Bmp10-Luc, in which the p10 gene was replaced by the firefly luciferase gene, was obtained. We also obtained another recombinant virus, BmPH-Luc, in which the polyhedrin gene was replaced by the luciferase gene. The luciferase activity detected in BoMo-15AIIc insect cells infected with Bmp10-Luc was approximately 50% of that infected with BmPH-Luc, suggesting that although both the p10 and polyhedrin promoters of BrnNPV are effective in high-level expression of foreign genes, the p10 promoter is not so strong as the polyhedrin promoter.

Amino Acid Sequence

Anti-neutrophil cytoplasmic antibody for proteinase 3 in a child with polyarteritis nodosa.

We report a case of a 15 year old boy with polyarteritis nodosa associated with antineutrophil cytoplasmic antibody (ANCA) against proteinase 3 (PR3). After months of steroid and immunosuppressant therapy, the symptoms subsided and the polyaneurysms almost disappeared. The levels of anti-PR3 antibody and of cytokines also decreased. The results indicate that ANCA is a good indicator of this disease activity, and may play some pathogenic role in the disease.

Adolescent

Resection of deep-seated gliomas using neuroimaging for stereotactic placement of guidance catheters.

A simple computed tomography- (CT) or magnetic resonance (MR) imaging-guided stereotactic method for guided microsurgical resection of either deep-seated gliomas or tumors adjacent to an eloquent area is described. The technique employs the Brown-Roberts-Wells stereotactic system and twist drills, 2.7 mm in diameter, for the stereotactic placement of 2.4 mm diameter scaled guidance catheters through the calvaria. In a patient with a deep-seated small glioma, less than 2 cm diameter, one catheter was implanted into the center of the enhanced mass through the cerebral cortex. In the other 14 patients, three to six catheters were used which made the tumor border clearer. After implantation of the guidance catheters, the stereotactic frame was removed and a standard open craniotomy performed. Target localization is not affected by brain movement, which is inevitable during open surgery. The tumor involved the frontal lobe in eight patients, the parietal lobe in two, and the thalamus in five. In all cases the lesion was quickly localized and radical removal was achieved. Neurological complications occurred in only one patient who suffered transient hemiparesis after the resection of a lesion in the pyramidal tract. The results demonstrate that microsurgery combined with CT- or MR imaging-guided stereotactic placement of guidance catheters is a new option for surgery of deep-seated gliomas or tumors adjacent to an eloquent area.

Adult

Meningiomas arising from the falcotentorial junction. Clinical features, neuroimaging studies, and surgical treatment.

Meningiomas arising from the falcotentorial junction are extremely rare. The authors describe the clinical features, neuroimaging studies, and results of surgical treatment of meningiomas of the falcotentorial junction and clarify the characteristics of this lesion based on a review of the literature and seven patients treated at their institution. The most common symptoms resulted from intracranial hypertension. Upward-gaze palsy appeared in only one patient. Computerized tomography (CT) showed no specific findings, but there was no evidence of edema around the tumor. Magnetic resonance (MR) imaging revealed a round, smooth-bordered mass with a peritumoral rim, without edema, and showing marked contrast enhancement. The multiplanar capability of MR imaging delineated the relationship between the tumor and adjacent structures better than did CT. Detailed knowledge of the vascular structures, especially evidence of occlusion of the galenic venous system and the development of collateral venous channels, is critical for successful surgery; stereoscopic cerebral angiography is necessary to achieve this aim. The seven patients described developed five types of collateral venous channels: through the basal vein of Rosenthal to the petrosal vein, through the veins on the medial surface of the parietal and occipital lobes to the superior sagittal sinus, through superficial anastomotic veins, through veins of the posterior fossa to the transverse or straight sinus, and through the falcian veins to the superior sagittal sinus. The first three types mainly developed after occlusion of the galenic system. The tumors were removed through the occipital transtentorial approach with a large window at the posterior part of the falx. A favorable prognosis for patients undergoing surgical treatment of falcotentorial junction meningiomas can be expected if detailed neuroimaging studies and microsurgical techniques are used.

Adult

[Image guided stereotactic biopsy for brain tumors: experience of 71 cases].

Despite advances in the neuroimaging of the brain, an accurate diagnosis of intrinsic lesion of the brain requires tissue sampling and histological verification. Seventy-one patients with intraparenchymal lesion of the brain underwent CT or MRI-directed stereotactic biopsy at Okayama University Hospital between June, 1987 and March, 1995. There were 32 men and 39 women whose ages ranged between 7 and 78 years (mean 46.1 years). All patients underwent preoperative cerebral angiography, high resolution contrast enhanced CT and MRI. The lesions were located in the hemisphere in 40 cases, the thalamus or basal ganglia in 14, the midline (corpus callosum or ventricle) in 11, the pineal region in 4, the suprasellar in one and multiple sites in one. A Brown-Roberts-Wells (BRW) CT-directed stereotactic system was used for biopsy under CT guidance. For MRI-directed biopsies a prototype modification of the BRW frame was employed. Target localization was performed using either CT or MRI. Usually one or two targets within the lesion were chosen and target coordinates were calculated using the CT or MRI scan soft ware. Positive diagnosis was obtained in 67 cases and the accuracy of the histological diagnosis was 94.4%. There were 53 gliomas, 4 metastasis, 5 germinomas, 3 malignant lymphomas, one pineoblastoma, one infarction and 4 negative biopsies. Bleeding as a complication due to stereotactic intervention occurred in one patient (1.4%). To patients with potentially inoperable lesions or lesions which might be best treated by chemotherapy or irradiation, modern techniques of neurosurgery now offer the option of precise stereotactic biopsy through small twist-drill burr holes as opposed to open biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

[Clinical study on the ideal temperature of blood cardioplegic solution in coronary artery bypass graft surgery].

The effect of myocardial protection in coronary artery bypass graft surgery was evaluated from enzymatic examination and cardiac function to clarify the ideal temperature of blood cardioplegic perfusate (BCP). The surgical cases were divided into two groups from the temperature of BCP; 8 degrees C BCP in 64 cases (Group I) and 20 degrees C BCP in 64 cases (Group II). Peak total creatine-Kinase (CK) and CK-MB fraction were significantly elevated in Group I than in Group II. The value of CK-MB was 79 +/- 79 IU/L in Group I and 37 +/- 26 IU/L in Group II (p < 0.01). The parameters of cardiac function were measured from radio-isotope (RI) ventriculography in the 35 cases with depressed ejection fraction and elevated left ventricular end-diastolic pressure (17 cases in Group I and 18 cases in Group II). Postoperative parameters such as ejection fraction, first third ejection fraction, peak ejection rate and early diastolic peak filling rate improved more significantly than preoperative values in Group II, although these parameters did not improve in Group I. From these results, 20 degrees C BCP provided excellent myocardial protection to arrested heart during coronary artery bypass surgery probably because of decreased viscosity of BCP and adequate oxygen carrying capacity to myocardium.

Blood

Characteristic properties of retinal oxidase (retinoic acid synthase) from rabbit hepatocytes.

Retinal oxidase (retinoic acid synthase) (EC 1.2.3.11) was purified electrophoretically, as a single protein band, from rabbit liver cytosol. The characteristic properties, enzymatic reaction mechanism, substrate specificity and kinetic parameters for retinals and molecular oxygen of the retinal oxidase were investigated. The Km values for all-trans-retinal of the retinal oxidase was the lowest than those for the other retinal derivatives. The retinal oxidase is a metalloflavoenzyme containing 2 FADs as the coenzyme, and 8 irons, 2 molybdenums, 2 disulfide bonds and 8 inorganic sulfurs. Its relative molecular mass was determined to be 270 kDa by gel filtration HPLC on a TSKgel G3000swXL column. Its minimum molecular mass was estimated to be 135 kDa by SDS-PAGE. The optical spectrum of the retinal oxidase showed absorption peaks at 275, 340 and 450 nm, and shoulders at 420 and 473 nm, in the oxidized form. The molecular extinction coefficients of the oxidase at selected wavelengths were determined. Circular dichroism spectra of the retinal oxidase were measured in the ultraviolet and visible regions. These spectra showed positive absorption in the visible region. The amino-acid composition was determined. The activity of the oxidase was not affected by any cofactors, such as NADP+, NAD+, NADPH and NADH, and it did not occur under anaerobic conditions. The oxidase was not inhibited by BOF-4272, a potent inhibitor of xanthine dehydrogenase, or rat anti-xanthine dehydrogenase IgG. Experiments on retinoic acid formation under 18O2 or H2(18)O demonstrated that the oxygen of water was incorporated into retinoic acid by the retinal oxidase, but not molecular oxygen.

Aldehyde Oxidoreductases

Immunochemical detection of human lactoferrin in feces as a new marker for inflammatory gastrointestinal disorders and colon cancer.

We have developed a new immunochemical test for fecal lactoferrin (LF) utilizing an enzyme-linked immunosorbent assay (ELISA). The ELISA had a sensitivity of about 10 micrograms/L of lactoferrin and the measurable range was 10.0-1000.0 micrograms/L (1.0-100.0 micrograms LF/g feces). The stability of lactoferrin in feces was greater than that of myeloperoxidase and leucocyte elastase. The fecal concentration of lactoferrin (mean +/- SD) in 35 normal subjects was 0.75 +/- 0.83 microgram/g feces, whereas that in 24 patients with colon cancer was 74.4 +/- 88.3 micrograms/g feces. The fecal lactoferrin concentration of 38 patient with active ulcerative colitis was 307.4 +/- 233.9 micrograms/g feces, and that in 36 patients with active Crohn's disease was 191.7 +/- 231.1 micrograms/g feces. The ELISA for human fecal lactoferrin might be useful in the diagnosis of colon disease.

Adolescent

[Study of pulmonary function after CABG with pleurotomy].

We studied the influence of pleurotomy during harvesting IMA for CABG on postoperative pulmonary function. Ninety nine cases underwent CABG surgery from January 1991 to July 1992, were divided into three subgroups, 45 patients (subgroup AY 2) having bilateral IMAs graft with pleurotomy, 45 patients (subgroup AY 1) having unilateral IMA graft with pleurotomy, 9 patients (subgroup AN) having unilateral IMA graft or vein grafts without pleurotomy. Frequencies of chest X-rays abnormality such as elevation of diaphragm and accumulation of pleural effusion before discharge around 2 weeks after surgery, were not significantly different among three subgroups. 58 cases without chest X-rays abnormalities were divided into three subgroups in the same way. There was no case with late extubation or with postoperative pulmonary complication. At first we compared pre-with postoperative pulmonary function in each subgroups. Pulmonary function (VC, FEV1.0, peak flow, MMF, V50, V25) was significantly deteriorated in the patients with pleurotomy, while VC, FEV1.0, peak flow significantly decreased, and MMF, V50 and V25 tended to decrease in the patients without pleurotomy. Moreover, magnitude of change of pulmonary function from pre- to postoperative period were not different significantly among three subgroups. In conclusions pleurotomy itself didn't appear to influence postoperative morbidity.

Coronary Artery Bypass

[A case of pineal region germinoma treated by interstitial brachytherapy].

Although radiation therapy has been universally accepted as treatment for primary intracranial germinomas, the optimal technique for both diagnosis and treatment continues to be a matter of controversy. We report a case of germinoma in the pineal region treated by interstitial brachytherapy. A 23-year-old female was admitted with diplopia and consciousness disturbance. Magnetic resonance imagings (MRI) revealed an enhanced tumor of the pineal region and hydrocephalus. No serum and CSF tumor markers such as alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) or placental alkaline phosphatase (PLAP) were detectable. Stereotactic needle biopsy was performed using BRW MRI-guided stereotactic apparatus. After the histological diagnosis confirmed the presence of germinoma, three catheters for interstitial brachytherapy were implanted into the tumor through the biopsy tract, and iridium-192 seeds were inserted into the catheters and kept there for 5 days to give 35 Gy of irradiation at the tumor periphery. Subsequent MRI showed marked tumor regression and the clinical symptoms were gradually improved, and Gd-enhanced tumor on MRI completely disappeared 2 months after brachytherapy. Histological diagnosis is essential before initiation of treatment because a germinoma is commonly thought to be radiosensitive. However, pineal region tumor is dangerous to remove surgically because of high morbidity and mortality rates. Image-guided stereotactic technique provides a safe method to obtain an accurate diagnosis, and subsequent interstitial brachytherapy enables selective irradiation of the tumor, and does not give rise to complications caused by external irradiation such as mental disturbance, hypopituitarism, visual disturbance and brain necrosis. Interstitial brachytherapy following image-guided biopsy can be a useful tool for patients with germinoma.

Adult

[Small nodular lesions of the pancreas: differential diagnosis with ultrasound angiography].

Ultrasound angiography (USAG), sonographic imaging of the blood flow in an organ or tissue obtained by carbon dioxide infusion into the supplying artery, was performed on 28 pancreatic nodular lesions less than 3 cm in diameter. The hemodynamics of tumors observed with USAG were divided into three groups: hypovascular, isovascular, and hypervascular, compared with the adjacent pancreatic tissue. Most of hypovascular nodules were duct cell carcinoma (sensitivity 94.1%, specificity 90.4%), while isovascular lesion was the characteristic of inflammatory masses (sensitivity 100%, specificity 95.8%). Hypervascular cases included all of the mucin producing tumors and islet cell tumors but only one case of duct cell carcinoma. So you can almost exclude duct cell carcinoma as an diagnosis in vascular rich tumors (negative predictive value 83.6%). These results were compared with those on conventional x-ray angiograms and incremental CT scans. Ultrasound angiography enabled us to detect more slight differences of tumor vascularity than the other modalities. Thus we conclude that USAG can be a useful diagnostic aid in small mass lesions of the pancreas.

Adenocarcinoma, Mucinous

[A case of pulmonary cryptococcosis diagnosed by percutaneous lung biopsy].

A 53-year-old male was admitted with complaint of bloody sputum. The chest X-ray film revealed a solitary round mass with cavity formation in the left upper lung field. A diagnosis of pulmonary cryptococcosis was made by the percutaneous lung biopsy. As his chest X-ray film did not improve even by administration of antimycotic agents for 6 months, he underwent partial resection of left upper lobe. Thus, the percutaneous lung biopsy was a significant procedure for the definitive diagnosis of this case.

Biopsy, Needle

[A female case of adenocarcinoma of the lung producing human chorionic gonadotropin].

A 72-year-old female was admitted with complaints of cough and sputum. The chest X-ray film revealed a solitary round mass and pleural effusion in the left lower lung field. Laboratory tests demonstrated elevated levels of serum HCG and beta-HCG. Left lower lobectomy with parietal pleurectomy was performed under the diagnosis of primary lung cancer with malignant effusion. The serum HCG level decreased after the operation. Histologically, the tumor was diagnosed as moderately differentiated papillo-tubular adenocarcinoma of the lung. In the HCG staining using an immunohistochemical method, the tumor cells showed a positive reaction. Thus, this tumor was definitively diagnosed to be HCG-producing adenocarcinoma of the lung.

Adenocarcinoma

Retinal oxidase is identical to aldehyde oxidase.

Retinal oxidase (EC 1.2.3.11) and aldehyde oxidase (EC 1.2.3.1) were compared with respect to their enzymatic and physiochemical properties. It was found that the molecular weights, subunits, optical spectra, chemical and immunological properties, cellular localization and substrate specificities of the two oxidases are identical on almost all points. The physiological function of aldehyde oxidase appears to be the synthesis of retinoic acid from retinal.

Aldehyde Oxidase

Intratumoral heterogeneity of DNA ploidy and regional differences in epidermal growth factor and epidermal growth factor receptor of esophageal carcinoma.

Intratumoral regional differences in DNA ploidy patterns, and expression of epidermal growth factor (EGF) and EGF receptor (EGF-R) were studied to evaluate the biological and clinical significance of intratumoral DNA heterogeneity in 23 cases of esophageal carcinoma. Multiple specimens were subjected to histologic grading of carcinoma, DNA analysis and immunohistochemistry. DNA heterogeneity was found in 34.8% of the cases. Expression of EGF and EGF-R within a single tumor was observed in 69.6% and 73.9% of the lesions examined, respectively. A positive correlation was noted between the expression of EGF and that of the EGF-R. EGF expression showed positive correlation with the DNA index, but not with the proliferative index. There was no relationship between DNA heterogeneity and the degree of histopathological differentiation of carcinoma. Cases with DNA heterogeneity showed better prognosis than those with DNA homogeneity. The present study suggests that esophageal carcinoma consists of carcinoma cells with intratumoral regional polymorphism and variable types of clones. Furthermore, the autocrine mechanism of EGF and EGF-R could be one of the contributory factors on the development of DNA abnormalities during tumor proliferation.

Adult

In vitro correlates of the L. casei animal model of Kawasaki disease.

The induction of coronary arteritis in mice by Lactobacillus casei cell wall (CW) is thought to represent an animal model of Kawasaki disease. Treatment of vascular endothelial cells (EC) in vitro with supernatants from CW stimulated human mononuclear cells (MNC) enhanced adherence of human polymorphonuclear leukocyte (PMN) to human EC, and EC expression of intercellular adhesion molecule-1 (ICAM-1) but not HLA-DR. Supernatants contained high concentrations of tumor necrosis factor-alpha (TNF-alpha) and PMN adherence correlated directly with the concentration of TNF-alpha. Intravenous human gamma globulin (IVGG) preparations did not block the effect of cytokine containing MNC supernates upon EC, ICAM-1 expression by EC, or PMN adherence to prestimulated EC. However, both EC ICAM-1 expression and enhanced PMN adherence to EC by CW induced MNC supernatants were blocked by anti-TNF-alpha treatment. The initial coronary inflammatory reaction in the mouse model appears to involve PMN adherence to vascular EC that have been activated by TNF-alpha released by MNC after stimulation with CW.

Adult