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Biomedical subjects

Y Ozeki

Publications and source records attributed to Y Ozeki.

At least 19 recordsLinked to original sources

Genomic organization of the genes encoding dihydroflavonol 4-reductase for flower pigmentation in the Japanese and common morning glories.

Genomic DNA segments (approximately 17kb) containing three DFR genes in the Japanese and common morning glories were sequenced. The three DFR genes in both plants were found to be arranged in a tandem array, and all of them comprised six exons with identical intron positions. Their DFR-B genes carrying longer introns than the DFR-A and DFR-C genes were expressed extensively in the young buds of pigmented flowers, and the transcription starting site for the DFR-B mRNA of the Japanese morning glory was determined. The DFR-B gene of the common morning glory was expressed considerably in stems, moderately in sepals and leaves, whereas the DFR-A and DFR-C genes of the same plant were expressed scarcely but significantly in the young flower buds and stems. Several novel mobile element-like sequences of around 200bp were found in the genomic DFR regions. A phylogenetic tree indicated that each DFR gene in the Japanese morning glory is most closely related to the corresponding DFR gene in the common morning glory, and that the DFR-B gene is the most diversified gene among the three DFR genes. These structural and functional features of the DFR genes and their evolutionary implications are discussed.

Alcohol Oxidoreductases

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer.

Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(-)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(-)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+)/VEGF-189(-) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189.

Analysis of Variance

Minimum light intensity required to suppress nocturnal melatonin concentration in human saliva.

We set out to determine the minimum intensity of light able to suppress nocturnal melatonin levels as measured in normal human saliva. Five healthy male volunteers were exposed to light at different intensities (<10, 500, 1000, 2500, and 5000 lux) in a repeated measure design. Suppression of melatonin was dependent on both light intensity and duration of light exposure. Minimum intensities of light suppressing nocturnal melatonin levels were calculated as 393, 366, 339, and 285 lux for exposure durations of 30, 60, 90, and 120 min, respectively. Minimum effective intensity and duration of light exposure showed a linear inverse relationship. These results suggest that less intensity of light than previously reported suffices to suppress melatonin in humans, and that caution is required in interpreting studies using long exposure to dim light as a background condition.

Adult

Focal, high dose, and fractionated modified stereotactic radiation therapy for lung carcinoma patients: a preliminary experience.

BACKGROUND: Stereotactic radiation therapy is highly effective in the treatment of small brain metastases, regardless of the histology. This suggests that small extracranial malignancies may be curable with similar radiation therapy. The authors developed a novel treatment unit for administering such therapy. METHODS: The unit consisted of a linear accelerator (linac), an X-ray simulator (X-S), computed tomography (CT), and a table. The gantry axes of the three machines were coaxial and could be matched by rotating the table. Patients were instructed to perform shallow respiration with oxygen. The motion of the tumor was monitored with the X-S. When the motion was slight enough, the table was rotated to the CT. To include all geometric movement on the CT images, each scan was made while the patient was performing shallow respiration. After the CT positioning, the table was rotated to the linac, and non-coplanar treatment was given. Beginning in October 1994, 45 patients with 23 primary or 43 metastatic lung carcinomas were treated. Radiation doses at the 80% isodose line were 30-75 gray in 5-15 fractions over 1-3 weeks with or without conventional radiation therapy. RESULTS: The treatment was performed with no or minimal adverse acute symptoms. The daily treatment time was short. During a median follow-up of 11 months, local progression occurred in 2 of 66 lesions. Interstitial changes in the lung were limited. CONCLUSIONS: With this unit and procedure, focal radiation therapy similar to stereotactic radiation therapy is possible for extracranial sites. The preliminary experience appeared safe and promising, and further exploration of this approach is warranted.

Adenocarcinoma

Purification and cell attachment activity of a D-galactose-binding lectin from the skin of sea hare, Aplysia kurodai.

A D-galactose-binding lectin which does not require Ca2+ or reducing reagents to induce activity was purified from skin of sea hare, Aplysia kurodai, by affinity chromatography. Skin lectin was confirmed to be a disulfide-bonded heteromultimer with molecular mass of 200 kDa, consisting of 28 kDa and 26 kDa subunits by SDS-PAGE and two-dimensional SDS-PAGE. Human rhabdomyosarcoma cells attached to and spread on plastic plates coated with lectin. Cell adhesion induced by lectin was completely inhibited by the addition of lactose.

Animals

Development of primary leiomyosarcoma of the sternum postirradiation: report of a case.

We report herein the case of a 30-year-old man who developed a primary leiomyosarcoma (LMS) 11 years after undergoing a median sternotomy for mediastinal seminoma followed by 50 Gy radiotherapy. He was given two courses of chemotherapy, resulting in 90% tumor regression, after which resection of the tumor with adjacent chest wall structures was carried out. Reconstruction was performed using a methylmethacrylate prosthesis prepared preoperatively. Postoperatively, he received two additional courses of chemotherapy and has had no sign of recurrence for 45 months.

Adult

A comparison of biopsy through a parasternal anterior mediastinotomy under local anesthesia and percutaneous needle biopsy for malignant anterior mediastinal tumors.

The various methods of treating the numerous types of anterior mediastinal neoplasms are undergoing refinements; however, prior to the commencement of any treatment, an accurate histologic diagnosis must be established. We conducted a retrospective analysis of biopsies performed through a parasternal anterior mediastinotomy (PAM) on 21 patients with an anterior mediastial mass suspected of being malignant by computed tomography (CT) and other clinical information. Patients with possible localized thymomas were excluded. Mediastinotomy, which enables relatively large tissue samples to be taken, was performed through the bed of the second or third costal cartilage under local anesthesia. In 19 of the 21 patients (90%), the histologic diagnosis made from the mediastinotomy biopsy was identical to the final diagnosis. Conversely, although the tissue obtained from needle biopsy was sufficient for a histologic diagnosis in 11 of 12 patients, the histologic diagnosis made from the needle biopsy was the same as the final diagnosis in only 5 of 10 patients (50%). Thus, diagnostic accuracy was significantly higher in the mediastinotomy biopsies than in the needle biopsies (P = 0.0318). Moreover, the mediastinotomy biopsy specimens revealed subtypes of lymphomas and germ cell tumors. All of the patients from whom a mediastinotomy biopsy had been taken began appropriate therapy without delay according to the histologic diagnosis. These results suggest that the PAM approach should be chosen as the preferred method of biopsy for suspected malignant anterior mediastinal tumors.

Adolescent

Echocardiography of a right atrial mass in hepatocellular carcinoma.

Antemortem diagnosis of hepatocellular carcinoma with a tumor thrombus extending into the right atrium has been rarely observed. Although echocardiography allows easy detection of the intracardiac mass, reports of echocardiographic descriptions of a right atrial mass associated with hepatocellular carcinoma are few. Herein, we describe two cases of hepatocellular carcinoma with a tumor thrombus in the right atrium detected by transthoracic echocardiography. In one of the patients we also performed transesophageal echocardiography. Neither patient had cardiac symptoms or signs. Thus, echocardiographic examination is very important in patients with hepatocellular carcinoma, with or without cardiac symptoms and signs.

Aged

Cartilage folding method for main bronchial stapling.

Bronchopleural fistula is one of the most severe complications of lung operations. To prevent bronchopleural fistula, we modified the stapling technique to include folding of both sides of the cartilaginous main bronchus. This reduces the tension at the center of the membranous portion of the airway. From 1991 to 1994, this technique was performed in 7 patients. Despite the fact that 4 of these patients received adjuvant therapy, none had development of a bronchopleural fistula.

Bronchi

Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer.

Vascular endothelial growth factor (VEGF) is a well known factor that induces angiogenesis. Four isoforms, i.e. VEGF206, 189, 165, and 121, have been identified. We examined the isoform patterns of VEGF mRNA using reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. All the colon cancers examined expressed VEGF121. The isoform patterns were classified into three groups: type 1, VEGF121; type 2, VEGF121 + VEGF165; type 3, VEGF121 + VEGF165 + VEGF189. Three of the 61 colon cancers examined showed type 1 expression, 26 showed type 2 expression and 32 showed the type 3 pattern. The patients with liver metastases showed the type 3 isoform expression pattern at a significantly higher incidence (12 of 16, 75%) than those without liver metastasis (20 of 45, 44%) (P=0.036). The type 3 isoform pattern was significantly associated with M1 stage (P=0.019). The patients with colon cancer and the type 3 isoform pattern showed significantly poor prognosis (P < 0.01, Cox-Mantel). The colon cancers with the type 3 pattern showed a significantly higher involvement of veins (P=0.006). These observations suggest that the aberrant type 3 expression pattern of VEGF189 mRNA isoforms is correlated with liver metastasis, M stage, and poor prognosis in colon cancer.

Adenocarcinoma

Midterm results of thoracoscopic surgery for pulmonary metastases especially from colorectal cancers.

Indications for thoracoscopic metastatectomy remain controversial because not all metastatic tumors may be detected without the manual palpation that is possible with thoracotomy. However, the accuracy (92%) of preoperative lung imaging in patients with one or two lesions led us to re-evaluate thoracoscopic metastatectomy with patient survival as the primary end point. Thoracoscopic wedge resection using an endoscopic stapling device or video-assisted thoracic surgery (VATS) lobectomy was performed in patients with one or two pulmonary metastases. Thoracoscopic resection was performed in 27 patients with 22 solitary lesions and 5 patients with two lesions. The primary tumors were colorectal cancer (15), testicular cancer (3), osteosarcoma (2), and seven other histologies. In 5 of 27 patients (18.5%) a thoracoscopic operation was converted to a VATS procedure, which requires minithoracotomy to identify metastasis primary by digital palpation. The 3-year survival rate for colorectal cancer patients who underwent thoracoscopic resection was 56.4%, in comparison to 48.6% in historical control thoracotomy patients (n = 16). There was no statistically significant difference between the two groups. Thoracoscopic resection of one or two colorectal cancer lung metastases results in a survival rate similar to standard thoracotomy, and thereby provides an acceptable alternative to this more invasive approach.

Adolescent

Production of granulocyte-macrophage colony-stimulating factor in a patient with metastatic chest wall large cell carcinoma.

Recent reports of cancers that produce colony-stimulating factors (CSF) and which are associated with leukocytosis indicate that most are granulocyte CSF-producing tumors. A 71-year-old man with metastatic chest wall tumors from large cell lung cancer with marked leukocytosis and eosinophilia was reported. His maximal leukocyte count was 48300/microliter with 37.5% eosinophils. Granulocyte-macrophage CSF (GM-CSF) activity detected by enzyme-linked immunosorbent assay (ELISA) in serum was 112 pg/ml (normal range < 2.0 pg/ml), but G-CSF was normal. Immunohistochemical detection of GM-CSF protein on a chest wall tumor sample was positive. Irradiation of the chest wall tumor was performed and the leukocyte count decreased temporally. However, he died of respiratory failure due to progressive tumor growth 56 days after admission. Based on these results it appears that autocrine production of GM-CSF is a possible cause of this leukemoid reaction.

Aged

Isolation and characterization of a cDNA clone of UDP-galactose: flavonoid 3-O-galactosyltransferase (UF3GaT) expressed in Vigna mungo seedlings.

Four cDNA clones were isolated from Vigna mungo seedlings by the screening with cDNA encoding UDP-glucose:flavonoid 3-O-glucosyltransferase (UF3GT) of Antirrhinum majus as a probe; the product of the gene corresponding to one cDNA was more highly expressed in the first simple leaves than in stems. Nucleotide sequence analysis revealed 1,691 bp (including 326 bp non-reading) containing an open reading frame of 455 amino acids. The deduced amino acid sequence showed 42% and 23% identity with those of A. majus UDP-glucose:flavonoid 3-O-glucosyltransferase (UF3GT) and Petunia hybrida UDP-rhamnose:anthocyanidin 3-O-glucoside rhamnosyltransferase (RT), respectively. One region of the cDNA (amino acids 325 to 387) showed similarity to ceramide UDP-galactosyltransferases of mice, rats and humans. A crude extract from Escherichia coli, in which the protein was expressed from the cDNA, showed high UF3GaT activity but low UF3GT activity, and was similar in K(m), optimal pH and substrate specificity to UF3GaT from V. mungo. We conclude that we have obtained UDP-galactose:flavonoid 3-O-galactosyltransferase (UF3GaT) cDNA from V. mungo.

Amino Acid Sequence

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na (1). Fertility study in rats].

Fertility study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. ONO-5046.Na was administered intravenously at doses of 18.75, 37.5 and 75 mg/kg/day to male rats from 64 prior to mating, through the mating period and until necropsy, and to female rats from 15 days prior to mating until Day 7 of gestation, in order to examine its effects on fertility and reproductive performance of males and females and the development of their fetuses. There were no changes attributable to ONO-5046.Na in general signs, body weight, food consumption or autopsy findings in males and females. No drug-related changes were observed in estrous cycles, copulation and fertility indices in males and females. Pituitary weight of dams was decreased in each of the ONO-5046.Na treated groups, but no histopathological changes were observed in the pituitary. In the cesarean section findings in dams, ONO-5046.Na had no effects on the number of corpola lutea, the number of live fetuses, the implantation ratio, the resorbed and dead fetus ratio, fetal or placental weight, or the incidences of external, skeletal or visceral anomalies of the fetuses. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for general and reproductive toxicity in males and females and for developmental toxicity in their fetuses.

Animals

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). Study for effects on pre- and postnatal development in rats, including maternal function].

Prenatal and postnatal toxicity of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied in Sprague-Dawley (SD) rats. ONO-5046.Na was injected intravenously at doses of 0, 18.75, 37.5 and 75 mg/kg/day to pregnant rats from day 7 of pregnancy to day 20 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. No adverse effects on dams were observed in clinical signs, body weight change, food consumption, pregnant, delivery or lactating performances. ONO-5046.Na did not affect the postnatal development of offspring, including birth index, survival index, physical and functional development, motor activity, emotionality, learning ability and reproductive performance. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for dams and their offspring.

Animals

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). Teratogenicity study in rabbits].

Teratogenicity of sodium N[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied. ONO-5046.Na was injected intravenously at doses of 0, 7.5, 15 and 30 mg/kg/day to pregnant Kbl: NZW rabbits from day 6 to day 18 of pregnancy. All female rabbits were sacrificed on day 29 of pregnancy and their fetuses were examined. There were no clinical signs or death attributable to ONO-5046.Na. One dam in the control group and 3 dams in the 30 mg/kg/day group aborted. Body weight gain in the 15 and 20 mg/kg/day groups and food intake in the 30 mg/kg/day group were decreased during the administration period. These changes had recovered by the end of the study. Kidney weight was increased in the 30 mg/kg/day group. There were no effects of ONO-5046.Na in necropsy findings at cesarean section in dams at any dose levels. Developmental toxicity of ONO-5046.Na was not found at any dose levels. From these results, it is considered that the NOAEL of ONO-5046.Na is 7.5 mg/kg/day for pregnant animals and 30 mg/kg/day for fetuses.

Animals

Expression of cell-associated isoform of vascular endothelial growth factor 189 and its prognostic relevance in non-small cell lung cancer.

Vascular endothelial growth factor (VEGF) has four isoforms (VEGF121, VEGF165, VEGF189, VEGF206). We examined the expression patterns of VEGF isoforms in non-small cell lung cancer (NSCLC) by RT-PCR. The cell-associated isoform VEGF189 was more frequently expressed in NSCLC (90.5%) than in extraneoplastic lung tissue (57.6%, p=0.00004). Immunohistochemical examination confirmed VEGF protein expression in 33 of 76 NSCLC expressing VEGF189 (V189p+ group). The V189p+ group showed significantly poorer prognosis than those without VEGF189 mRNA and protein (V189p- group, p=0.01722). These results suggest that expression of the cell-associated isoform VEGF189 is closely associated with progression of NSCLC.

Carcinoma, Non-Small-Cell Lung

[Clinicopathological study of six cases of primary pulmonary lymphoma diagnosed by gene rearrangement analysis].

We report six cases of primary pulmonary lymphoma in which a gene-rearranged band was shown by Southern blot analysis of transbronchial or surgical biopsy specimens. The cases were 3 mens and 4 women with an average age of 59.6, who had abnormal pulmonary shadows on chest X-ray. Two cases had Sjögren's syndrome and one case had monoclonal gammopathy (IgM-lambda type). Histopathologic and immunologic examination revealed diffuse infiltration of small lymphocytes (B-cell type) in all cases, and histological features of lymphoepithelial lesion or lympho-cytic interstitial pneumonia (LIP) in three cases. CT revealed an ill-defined margin, air-space consolidation, and air-bronchogram in all cases. A CT-angiogram sign was apparent in 2 cases. In all cases, Southern blot analysis of the tissue obtained from transbronchial or surgical biopsy revealed a gene re-arranged band, supporting the diagnosis of primary pulmonary lymphoma. We infer that an ill-defined margin, air-bronchogram and air space consolidation on CT were associated with the histopathological features of primary pulmonary lymphoma.

Aged