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Biomedical subjects

T Otani

Publications and source records attributed to T Otani.

At least 73 records · Page 4Linked to original sources

New Cdc25B tyrosine phosphatase inhibitors, nocardiones A and B, produced by Nocardia sp. TP-A0248: taxonomy, fermentation, isolation, structural elucidation and biological properties.

Strain TP-A0248 which produces two new Cdc25B tyrosine phosphatase inhibitors and also possessing antifungal activity, designated nocardiones A (1) and B (2), was considered to belong to the genus Nocardia on the basis of literature comparison of chemotaxonomic properties. The nocardiones were isolated by solvent extraction of fermentation broth of Nocardia sp. TP-A0248 and purified by the conventional column chromatography. Spectroscopic studies led to determination that 1 and 2 belong to a class compound of naphtho[1,2-b]furan-4,5-diones. Compound 1 inhibited the activity of Cdc25B, PTP1B and FAP-1 protein tyrosine phosphatases at a concentration of 10 microM. It also showed moderate in vitro antifungal and cytotoxic activity.

Antifungal Agents↗

Measurement of carcinoembryonic antigen in colonic effluent as a high-risk marker for colorectal carcinoma.

We evaluated the usefulness of carcinoembryonic antigen (CEA) concentrations in colonic effluent as a high-risk marker for colorectal carcinoma (CRC). After 213 patients ingested 1,800 ml of a 5% isotonic solution of magnesium citrate, colonic effluent was collected from them before routine colonoscopy from February through June 1992. Of these patients, 27 who had undergone colonoscopy after a mean of 2.6 years were selected as subjects. The relationship between the CEA concentration in the colonic effluent and the occurrence of new colorectal tumors was examined. The CEA concentration in colonic effluent was adjusted on the basis of alkaline phosphatase activity. New colorectal tumors were noted significantly more frequently (P = .006) in patients with a high CEA level in colonic effluent (5 of 5; 100%) than in those with low a CEA level (6 of 22; 27%). The CEA concentration in colonic effluent is a simple and practical biomarker for identification of patients at high risk for CRC.

Age Factors↗

[A case of psoas cold abscess in a young tuberculosis patient].

A 28-year-old man was referred to our hospital with a complaint of painful induration of right epididymis accompanied with right back pain and persistent low-grade fever. He was finally diagnosed with tuberculosis by sputum culture. Abdominal computed tomography (CT) revealed right psoas abscess and vertebral caries. He underwent a percutaneous drainage of the abscess followed by multidrug (streptomycin, pyrazinamide, refanpicin, isoniazide) combination therapy. Immediately after the drainage, symptoms began to improve with these therapies. However, four months later, abdominal CT showed a worsening of the abscess. Recently there is a stagnation in the decline of incidence of tuberculosis. It is still necessary to examine young people carefully bearing urogenital tuberculosis in mind. The pathogenesis and management of this rare condition are discussed.

Adult↗

Reconstructive treatment of posterolateral rotatory instability of the knee: a biomechanical study.

Twelve cadaveric knees were tested to determine effective reconstructive treatment for severe chronic posterolateral rotatory knee instability accompanied by excessive varus and posterior laxity. Posterolateral, varus, and posterior laxity were measured, first with the ligaments intact, then after complete sectioning of the posterior cruciate ligament (PCL) and posterolateral structures, and finally after reconstruction of these structures in different orders. The increases in those laxities were produced following the sectioning of all of the structures and disappeared throughout the flexion range after combined reconstruction of the PCL, lateral collateral ligament (LCL), and popliteus tendon. However, some residual increase in the laxity was always observed if any of the three structures were excluded from reconstruction. Therefore, combined reconstruction of the PCL, LCL, and popliteus tendon is essential and adequate for treating severe chronic posterolateral rotatory instability.

Biomechanical Phenomena↗

Identification of IFN-gamma-producing cells in IL-12/IL-18-treated mice.

Both IL-12 and IL-18 have been characterized as effective IFN-gamma-inducing cytokines. Concomitant treatment with IL-12 and IL-18 has been shown to synergistically induce IFN-gamma and may be an effective therapy for treating cancer, allergy, and infectious diseases. To understand the mechanisms underlying the strong induction of IFN-gamma by IL-12/IL-18 in mice, we focused our studies on the IFN-gamma-producing cells in various lymphoid organs and tissues and utilized the intracellular cytokine staining method to detect such cells in situ. After combined treatment with IL-12 and IL-18, IFN-gamma-positive cells in C57BL/6 mice were detected in the liver (12.18%), spleen (0.68%), bone marrow (1.80%), and peritoneum (2.12%), but not in the thymus or lymph nodes (<0.05 and <0.08%, respectively). A two-color staining method revealed that the majority of IFN-gamma-producing cells in the liver were NK1.1(+) cells, while those in the spleen were mostly CD3(+) cells, and to a lesser degree NK1.1(+) cells. Both CD4(+) and CD8(+) cells in the liver and in the spleen produced IFN-gamma. The CD19(+) B cell population was not definitely shown to produce IFN-gamma in our induction experiments. NKT cells, which are a subpopulation of NK1. 1(+) CD3(+) cells, were diminished in the liver and did not seem to contribute to IFN-gamma production arising from IL-12/IL-18 treatment. Further in vitro experiments confirmed the responsiveness of hepatic mononuclear cells to IL-12/IL-18 stimulation. This study is the first to show the IFN-gamma-producing mechanisms of IL-12/IL-18 treatment at the phenotypic level.

Animals↗

Transient increases of apoptosis and Bax expression occurring during radiotherapy in patients with invasive cervical carcinoma.

BACKGROUND: Apoptosis plays a crucial role in radiation therapy (RT) in various carcinomas. This study was designed to investigate the relation between apoptosis and RT in invasive squamous cell carcinoma (ISCC) of the uterine cervix METHODS: Thirty-five specimens were obtained from 7 patients with ISCC before and during a fractionated RT. The occurrence of apoptosis was examined by end labeling of DNA gel fractionation and in situ 3' end labeling of DNA. The expression of Bax and Bcl-2 proteins was investigated by immunohistochemical staining. RESULTS: Autoradiographic analysis revealed that high molecular weight DNA was predominant in the untreated ISCC specimens. However, a ladder-like pattern, characteristic of the apoptotic breakdown of DNA, was identified at doses of 900 cGy and 1980 cGy. At doses >1980 cGy, DNA laddering disappeared without any extensive smearing. Quantitative analysis of low molecular weight fragments of DNA revealed significant increases at doses of 900 cGy and 1980 cGy compared with those before RT and at doses of >1980 cGy. Labeling of DNA in situ indicated that cells undergoing apoptosis increased dramatically at a dose of 900 cGy. However, apoptotic cells decreased at a dose of 3960 cGy. In addition, a large fraction of tumor cells was immunonegative for Bcl-2 before and during RT. By contrast, immunoreactive Bax was observed intensely in many neoplastic cells at doses of 900 cGy and 1980 cGy. CONCLUSIONS: The current investigation indicates that low doses of RT result in apoptotic cell death in ISCC in association with the increased expression of Bax but not with increased Bcl-2 expression.

Aged↗

Apoptosis and the expression of Bax and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the uterine cervix.

BACKGROUND: Apoptosis plays a crucial role in the suicide and turnover of cells in various tumors. This study was designed to investigate the relation between apoptosis and the histologic types of cell in invasive cervical carcinoma. METHODS: Cervical tissues were obtained from 19 patients with invasive squamous cell carcinoma (ISCC), 9 patients with invasive endocervical adenocarcinoma (IEAC), and 15 patients with myoma uteri (which were used as controls). Each tissue was rapidly frozen and/or fixed in Bouin's solution. The occurrence of apoptosis was examined by end labeling of DNA with (alpha-32P)dideoxyATP and electrophoretic fractionation and by end labeling of DNA in situ with digoxigenin-dideoxyUTP. The expression of Bcl-2 and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. RESULTS: Autoradiographic analysis revealed that high molecular weight DNA was predominant in the normal cervical epithelium (NCE) and in ISCC. However, a ladder-like pattern of DNA fragments, characteristic of the apoptotic breakdown of DNA, was identified in IEAC. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in IEAC but not in ISCC compared with NCE. Labeling of DNA in situ indicated that cells undergoing apoptosis were predominant among the neoplastic cells of IEAC. However, no apoptotic cells were noted in ISCC, with the exception of cells in some tumor nests. A large fraction of IEAC and ISCC was immunonegative for Bcl-2. Although the expression of Bax was detected weakly in a small fraction of ISCC, strong expression of Bax was observed in all cases of IEAC. CONCLUSIONS: Apoptosis appears to occur in the cancerous cells of invasive adenocarcinoma of the uterine cervix in association with a high level of expression of Bax but not of bcl-2.

Adenocarcinoma↗

Inhibition by D-limonene of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of prolonged oral administration of D-limonene on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the labeling and apoptotic indices of gastric cancers were investigated in Wistar rats. After 25 weeks of the carcinogen treatment, rats were given chow pellets containing 1% or 2% limonene. In week 52, long-term oral administration of 2%, but not 1%, limonene significantly decreased the incidence of gastric cancers. Limonene also significantly decreased the labeling index and significantly increased the apoptotic index of gastric cancers. No K-ras mutations were detected in gastric cancers induced by MNNG in either group. These findings indicate that limonene inhibits the development of gastric cancers through increased apoptosis and decreased DNA synthesis of gastric cancers, but not through ras oncoprotein plasma membrane association.

Adenocarcinoma↗

Anterior cruciate ligament reconstruction and physiological joint laxity: earliest changes in joint stability and stiffness after reconstruction.

Physiological joint laxity is an important element of normal knee joint function, providing smooth joint movement. However, the objective evaluation of post-operative results after knee ligament surgery is usually based primarily on stability and range of motion, and joint laxity has been ignored. In this study, we measured the joint stiffness of 82 knees undergoing anterior cruciate ligament (ACL) reconstruction with the Leeds-Keio artificial ligament, before the operation, immediately after the operation, and finally when the full range of motion was achieved postoperatively; changes in joint laxity after the ACL reconstruction were investigated. Before the operation, joint laxity was greater than that of the normal side (P < 0.01), but immediately after the operation it diminished compared not only with that observed preoperatively, but also with that of the normal side. When the full range of motion was achieved, joint laxity was lower than that observed immediately after the operation (P < 0.01), but still remained higher than that of the normal side (P < 0.01). In other words, stability was achieved, but joint laxity was diminished through the operation. In this series, a stiffer artificial ligament than the natural ACL was used, and maximum tension was applied during the operation, aiming at better stability, but this may cause diminution of joint laxity.

Adolescent↗

Patterns of diabetic macular edema with optical coherence tomography.

PURPOSE: We report cross-sectional images of diabetic macular edema and correlation between tomographic features and visual acuity with best correction by means of optical coherence tomography. METHOD: In a prospective study, optical coherence tomography was performed in 59 eyes of 42 patients with diabetic macular edema and in 10 eyes of 10 normal control subjects. RESULTS: Optical coherence tomography showed three patterns of structural changes in diabetic macular edema: sponge-like retinal swelling (52 [88%] of 59 eyes), cystoid macular edema (28 [47%] of 59 eyes), and serous retinal detachment (9 [15%] of 59 eyes). Some eyes had more than one pathologic change. Retinal swelling was more pronounced in the outer rather than the inner retinal layers. Cystoid macular edema was located mainly in the outer retinal layers. In eyes with long-standing cystoid macular edema, cystoid spaces had fused, resulting in a large cystoid cavity involving almost the entire retinal layer. Hard exudates were seen as highly reflective areas located in the outer retinal layers. The retinal thickness at the central fovea and the visual acuity with best correction showed an intermediate negative correlation in eyes without cystoid macular edema (correlation coefficient: -0.61, P < .01). CONCLUSIONS: Diabetic macular edema involved three structural changes, including sponge-like retinal swelling (88%), cystoid macular edema (47%), and serous retinal detachment (15%). Visual acuity with best correction moderately correlated with retinal thickness regardless of the different tomographic features.

Adult↗

Mechanisms of intracellular zymogen activation.

The pancreatic acinar cell is potentially the initial site of injury that begins the series of events leading to acute pancreatitis. Pathological intrapancreatic zymogen activation occurs in experimental pancreatitis in animals and in human pancreatitis. Intracellular activation has been clearly linked to aberrant zymogen processing in one form of hereditary pancreatitis; in this genetic disease a mutation in cationic trypsinogen may eliminate the degradation of any trypsin activated in the acinar cell. Recent studies have also provided the first direct evidence that trypsinogen activation takes place early in the course of caerulein-induced pancreatitis; parallel studies have used isolated pancreatic acini and conditions that simulate those that cause pancreatitis in vivo to demonstrate that zymogens can be pathologically activated in isolated cells. A unique acinar cell pathway regulates the intracellular proteinase processing of zymogens to their active forms. Stimulating the acinar cell with supramaximal concentrations of cholecystokinin (CCK) or carbamylcholine can activate this pathway. The activation depends on a low pH compartment within the acinar cell and activation of an intracellular serine protease. A marker of trypsinogen processing, the trypsinogen activation peptide (TAP), is generated in acinar cell compartments that do not overlap with secretory granules. This compartment overlaps with a marker of recycling endosomes and lysosomes. Thus, zymogen processing within the acinar cell proceeds in a distinct subcellular compartment and is dependent on a low pH environment and activation of serine proteases.

Acute Disease↗

Facilitated expansion of pneumococcal colonization from the nose to the lower respiratory tract in mice preinfected with influenza virus.

A strain of Streptococcus pneumoniae, when inoculated intranasally in 2 microl of suspension into BALB/c mice preinfected with influenza virus, colonized first in the nose, and several days thereafter also colonized significantly in the trachea and lungs with purulent inflammation. Pneumoccocal colonization was also observed in the noses of normal mice after the same bacterial inoculation, but not apparently in the lower respiratory tract. These results suggest that pneumococcal infection may develop from the upper to the lower respiratory tract as a possible sequence preferentially in influenza virus-infected subjects.

Animals↗

The vascular endothelial growth factor/fms-like tyrosine kinase system in human ovary during the menstrual cycle and early pregnancy.

In human ovaries, angiogenesis is known to be associated with the development of follicles and the formation of the corpus luteum (CL). A complex vascular network is formed within the thecal cell layer during follicular growth, and rapid neovascularization occurs toward the granulosa cell layer after ovulation. Vascular endothelial growth factor (VEGF) is a multifunctional cytokine, stimulating endothelial cell growth and enhancing microvascular permeability. A specific receptor for VEGF, fms-like tyrosine kinase (Flt-1), is expressed in vascular endothelial cells that mediates the action of VEGF. We examined the localization and expression of VEGF and Flt-1, using an immunohistochemical technique and RT-PCR analysis, in human follicles and corpora lutea during the normal menstrual cycle and early pregnancy. We measured concentrations of VEGF in extracts of human CL using an enzyme-linked immunosorbent assay during the luteal phase and early pregnancy. Immunostaining for VEGF was observed in granulosa cells from small antral follicles to preovulatory follicles. The staining was detected in thecal cells from medium-sized to preovulatory follicles. The intensity of the staining was gradually increased as a follicle grew. Flt-1 was localized in granulosa and thecal cells of preovulatory follicles as well as in endothelial cells. In the human CL, the intense staining for VEGF was observed in granulosa and thecal lutein cells, especially in the midluteal phase. The immunostaining for Flt-1 was faint in endothelial cells in the CL, whereas it was distinct in granulosa and thecal lutein cells. The concentrations of VEGF in lutein extracts were high in the early and midluteal phases and tended to decrease toward the late luteal phase. During early pregnancy, a measurable amount of VEGF was detected. RT-PCR analysis demonstrated that messenger ribonucleic acids encoding VEGF121, VEGF165, and Flt-1 were expressed in the CL. These results suggest that VEGF might have an autocrine role in the ovulatory process and luteal function as well as a paracrine role in angiogenesis.

Adult↗