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Biomedical subjects

T Ogata

Publications and source records attributed to T Ogata.

At least 217 records · Page 12Linked to original sources

Enzymatic 2'-N-acetylation of arbekacin and antibiotic activity of its product.

Aminoglycoside antibiotics (AGs) with a free 2'-amino group were subjected to enzymatic N-acetylation using a cell free extract that contained an aminoglycoside 2'-N-acetyltransferase, AAC (2'), derived from a kasugamycin-producing strain of Streptomyces kasugaensis. TLC and antibiotic assay of the incubated reaction mixtures revealed that a modified compound retaining substantial antibiotic activity was formed from arbekacin (ABK), while modification of the other AGs resulted in the marked decrease in antibiotic activity. Structure determination following isolation from a large scale reaction mixture showed the modified ABK to be 2'-N-acetyl ABK. In addition, 2',6'-di-N-acetyl ABK was formed as a minor product. The same conversion also occurred with dibekacin (DKB) resulting in the formation of 2'-N-acetyl DKB and 2',6'-di-N-acetyl DKB. MIC determination showed antibacterial activity (1.56 approximately 3.13 micrograms/ml) of 2'-N-acetyl ABK against a variety of organisms. By contrast, 2'-N-acetyl DKB showed no substantial antibiotic activity. We believe 2'-N-acetyl ABK has the highest and broadest antibacterial activity, compared with known N-acetylated AGs.

Acetylation↗

Mechanism of multiple aminoglycoside resistance of kasugamycin-producing Streptomyces kasugaensis MB273: involvement of two types of acetyltransferases in resistance to astromicin group antibiotics.

The biochemical basis for the multiple resistance to aminoglycoside antibiotics (AGs) of kasugamycin-producing Streptomyces kasugaensis MB273 was studied. The strain was resistant to a wide range of deoxystreptamine (DOS)-containing AGs as well as astromicin (ASTM) group antibiotics. These AGs strongly inhibited in vitro polyU-directed polyphenylalanine-synthesis using ribosomes from the strain, while they were acetylated and inactivated by the MB273 cell free extract supplemented with acetyl-CoA. It seemed thus likely that the acetyltransferase activity played a critical role for the multiple AG resistance. The acetylation was selective to AGs with 2'-NH2, suggesting the involvement of aminoglycoside 2'-N-acetyltransferase, AAC (2'). Interestingly, the acetylation of istamycin B (ISM-B; an ASTM group AG) resulted in the formation of two different products (1-N-acetyl ISM-B and 2"-N-acetyl ISM-B) at a similar ratio. In this context, an AAC (2') gene cloned as an ISM-B resistance gene from the strain MB273 directed the conversion of ISM-B to only 1-N-acetyl ISM-B. It seemed likely that two types of AACs [AAC(2') and a novel one] were involved in the mechanism of resistance to ASTM group AGs.

Acetylation↗

[A histopathological study of corneal amyloidosis secondary to trichiasis].

We present a case of secondary corneal amyloidosis whose etiological mechanism was investigated by immunohistochemistry and electron microscopy. A 48-year-old woman had suffered from trichiasis in the right eye for 35 years, and developed secondary corneal amyloidosis, a phenomenon previously described but whose etiological mechanism has not been explained. Slitlamp examination of the cornea revealed a white excrescence with a diameter of 2 mm. The lesion was excised and examined by light and electron microscopy. Large deposits of an amorphous eosinophilic material were observed beneath the atrophic epithelium. Amyloid was detected in these deposits using Congo red stain, polarized light, and electron microscopy. Neither vascularization nor infiltration of inflammatory cells was observed. Immunohistochemical tests for protein AL, protein AA, prealbumin, beta 2-microglobulin and cytokeratin in paraffin sections were all negative. Characteristic findings were observed in the border zone between the basal cells and the deposits. Numerous digitiform cell processes and membrane-bound globular fragments of basal cells were seen in the superficial region of the deposits. The cell membrane of some globules was interrupted and the contents appeared to have been discharged into the stroma. These findings suggest that basal cells of the corneal epithelium provide an amyloid precursor on the stroma.

Amyloidosis↗

[Cavernous hemangioma of urinary bladder: a case report and review of the literature].

We report a case of cavernous hemangioma of the urinary bladder treated with transurethral resection (TUR). A 58-year-old woman was admitted to our department with the chief complaint of macroscopic hematuria. Cystoscopy revealed a red sessile tumor 2 cm in diameter, at the internal urethral orifice. The tumor had a mostly low signal intensity, partly high signal intensity, on T1-weighted, coronal magnetic resonance (MR) images. Computed tomography and T2-weighted MR images did not delineate the tumor. TUR was performed, and the specimen was pathologically diagnosed as cavernous hemangioma of the urinary bladder. A brief description of the case is provided and the literature is reviewed.

Female↗

Assessment and comparison of algorithms for in vivo ESR-CT imaging of bioradicals with L-band microwaves.

In ESR-CT imaging, it is much more difficult to obtain satisfactory images than in imaging with other modalities, since two inverse problems, i.e. deconvolution of observed data and reconstruction from projections, must be solved. In this work, suitable algorithms for ESR-CT are examined using simulations and experiments. The algorithms were applied to actual data from a rat's head and a satisfactory reconstructed image was obtained from the viewpoint of morphological imaging. Several properties of the algorithms are discussed: (1) which combination of deconvolution and reconstruction method is favorable, (2) whether or not a raw differential signal should be integrated before deconvolution and reconstruction procedures, and (3) how SIRT, which offers good performance in ESR-CT, depends on an initial value and a noise type.

Algorithms↗

Electron microscopic study of the morphological changes of gastric mucous cell induced by Helicobacter pylori in human gastric ulcers.

Specimens from 8 cases of human gastric ulcers infected with H. pylori, 3 cases of gastric ulcers without H. pylori infection and mucosal specimens infected with H. pylori from 3 cases of early gastric cancers obtained at surgery were studied by transmission electron microscopy. In the surrounding epithelium of the ulcer, when present, the bacteria were preferentially located at the luminal side of the apical junctional complexes. This was accompanied by dome-like bulging of the apical cytoplasm, but the epithelial continuity was maintained. A consistent finding was the apocrine-like release of the apical cytoplasm into the lumen. In addition, there were cells with marked apical protrusions and cells with dissolution of mucous granules. Degenerative changes, such as cellular edema, vacuole formation and disruption of cell membrane were also observed. The cells which had shed their apical mucous area appeared to degenerate causing massive cell exfoliation and formation of denuded lamina propria. Similar changes of the surface mucous cells were observed in the mucosal specimens infected with H. pylori obtained from early gastric cancers, but such cell pathology was scarce in samples of the gastric ulcers without H. pylori infection. In some ulcers infected with H. pylori, the bacteria were also observed on the surface of the regenerating epithelial cells at the ulcer base. These findings suggest that H. pylori infection is an important factor in the development of gastric ulcers and in the prevention or delay in ulcer healing.

Gastric Mucosa↗

Contrast-enhanced radiographic computed tomographic findings in patients with straight back syndrome.

UNLABELLED: Straight back syndrome (SBS) is usually diagnosed by physical and chest radiographic findings. Radiographic computed tomographic (CT) findings are very useful for the diagnosis and the evaluation of its severity. The purpose is to evaluate the relationship between chest X-ray film and CT findings. SUBJECTS: We evaluated 26 patients (SBS group) and 11 normal subjects (control group). SBS group consisted of 15 patients without structural heart disease (group I) and 11 patients with other heart disease (group II). METHODS: (1) On the chest X-ray film, antero-posterior diameter (APD) of the thorax, transthoracic diameter (TTD), and APD/TTD ratio were measured. (2) On the CT image, three parameters were calculated; APD of the left atrium (LA diameter), APD/transverse diameter ratio of the heart (flattening ratio) and left side shift ratio of the heart (shifting ratio). (3) CT parameters were compared with APD/TTD ratio in patients and control group. RESULTS: (1) APD/TTD ratio was smaller in group I and II than control group (30.0 +/- 5.4, 30.5 +/- 4.0 v 44.6 +/- 2.7%, p < .001). (2) LA diameter was smaller in group I and II than control group (23.2 +/- 4.1, 26.0 +/- 8.6 v 30.0 +/- 6.5 mm, p < .01). Flattening ratio was also smaller in group I and II than control group (59.2 +/- 9.4, 61.8 +/- 8.6 v 75.4 +/- 13.2%, p < .01). Shifting ratio was greater in group I and II than control group (10.9 +/- 5.0, 11.9 +/- 4.5 v 8.4 +/- 4.0%, p < .01). (3) APD/TTD ratio correlated with LA diameter (r = .39, p < .05) and flattening ratio (r = .53, p < .001). APD/TTD ratio did not correlate with shifting ratio (r = -.27, NS). CONCLUSIONS: APD/TTD ratio correlated with LA diameter and flattening ratio rather than shifting ratio. LA diameter and flattening ratio on the CT image were more useful for evaluating the severity.

Adolescent↗

[Clinicopathological study of pulmonary hamartoma with special reference to 6 patients who also had another tumor].

We studied 22 patients in whom intrapulmonary hamartoma was diagnosed between 1975 and 1994. Twelve were men and 10 were women, and their ages ranged from 20 to 72 years (averaged: 52.5). The sizes of the hamartomas ranged from 5 mm to 3 cm. Five patients also had other types of cancer (ling 3, colon 1, thyroid 1) and one had a mediastinal tumor (1). In those 6 patients, the hamartomas had to be distinguished from intrapulmonary metastasis. In 2 of those 6, thoracoscopic surgery was useful for obtaining sufficient materials for diagnosis. In one patient immunohistochemical analysis with anti-PCNA (proliferative cell nuclear antigen) antibody was useful in distinguishing leiomyomatous hamartoma from benign metastatic leiomyoma.

Adult↗

The effect of TNP-470 on cell proliferation and urokinase-type plasminogen activator and its inhibitor in human lung cancer cell lines.

The plasminogen activator system has been found to modulate neoplastic spread and angiogenesis in tumors. An angiogenesis inhibitor, TNP-470, has been shown to possess potent antitumor activities in various types of cancer cells. We therefore investigated the inhibitory effect of TNP-470 on cancer cell proliferation, and the suppressive effect of TNP-470 on urokinase-type plasminogen activator (u-PA) and its inhibitor (PAI-1), in human lung cancer cell lines in vitro. TNP-470 inhibited cell proliferation in a dose-dependent manner in both cell lines. u-PA and PAI-1 in culture supernatants were suppressed with the concentrations of TNP-470, in association with a decrease in viable cancer cells. Unchanged serum levels of u-PA and PAI-1 would be of great advantage to the diseased patients, since the plasminogen activator system has a crucial function in the process of distant metastasis.

Antibiotics, Antineoplastic↗

Expression of the human cGMP-dependent protein kinase II gene is lost upon introduction of SV40 T antigen or immortalization in human cells.

We have cloned a human cGMP-dependent protein kinase type II cDNA to examine its gene expression in terms of cellular senescence and/or immortalization. The genetic locus was mapped to band 4q21 by FISH. Northern blot analysis revealed that expression of the type II gene was markedly decreased or lost in mortal or immortal human fibroblasts producing SV40 T antigen. Also in various immortalized cell lines tested, the gene was not expressed. In normal diploid fibroblasts, the gene was constitutively expressed during cell-cycle and population doubling levels (PDLs).

Amino Acid Sequence↗

Free radical imaging by electron spin resonance computed tomography in rat brain.

Images of nitroxide radicals were obtained from the brains of living rats following intracarotid injection of imaging agent, [2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinylox y] (16 DS) using L-band electron spin resonance computed tomography (ESR-CT). The image patterns obtained from the 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolinyloxy injected rats showed the agent in tissues of the cranium but not within the brain. The uptake of 16 DS was found in the cortex, hippocampus, striatum, midbrain, pons medulla oblongata and cerebellum, and nuclei, mitochondria, synaptosomes of the cerebrum after intracarotid injection of 16 DS using an x-band ESR spectrometer. These results suggest that 16 DS penetrates the blood brain barrier.

Animals↗

Successful treatment of invasive thoracopulmonary mucormycosis in a patient with acute lymphoblastic leukemia.

BACKGROUND: Pulmonary mucormycosis associated with hematologic malignancy is an uncommon, but important opportunistic fungal pneumonia that is usually a fatal infection. Only a few survivors of pulmonary mucormycosis have been reported. METHODS: A case report of invasive thoracopulmonary mucormycosis during remission-induction therapy for acute lymphoblastic leukemia and a review of the literature are presented. RESULTS: The fungal lesions extended to both lungs, the left ribs, and intercostal muscles. Percutaneous needle biopsy and immunostaining of the fungal hyphae established the diagnosis of thoracopulmonary mucormycosis. The patient was treated with granulocyte-colony stimulating factor (G-CSF) and intravenous amphotericin B for 9 weeks and the lesions in the right lung disappeared. Left pneumonectomy and partial resection of the chest wall were later performed. The left lung was grossly necrotic and contained a large cavity and bronchopulmonary fistula. Thereafter, antileukemic therapy was resumed and completed without recurrence of mucormycosis or leukemia. CONCLUSIONS: In the management of mucormycosis, the addition of G-CSF to the conventional treatment may substantially improve outcome.

Adolescent↗

Inhibitors of cGMP-dependent protein kinase block senescence induced by inactivation of T antigen in SV40-transformed immortal human fibroblasts.

Immortal human fibroblasts isolated following transfection with thermolabile simian virus 40 T antigen lost division potential upon shift up in temperature due to heat inactivation of the antigen. Such cells showed a concomitant change in the distribution of a mortality marker, mortalin, from a juxtanuclear cap like distribution of immortal cells to a uniform cytosolic distribution of mortal cells. We made an attempt to modulate the above inducible system of cellular senescence using various protein kinase inhibitors. Among the indolocarbazole type inhibitors tested, only KT5823, defined as a specific inhibitor of cGMP-dependent protein kinase, blocked the loss of division potential as determined by cell growth and colony forming ability. This inhibitor also prevented the above change in mortalin distribution due to temperature shift. In addition, the isoquinoline sulfonamide derivatives H8, H9, H88 and H89, all shown to inhibit cGMP-dependent protein kinase, suppressed the senescence. Inhibitors specific to other types of protein kinases, protein phosphatases or tyrosine kinases tested had no effect. Since there was no difference between the effective and non-effective inhibitors in their effects on cell cycle progression, cell cycle arrest by itself cannot account for the above phenomenon. These results suggest that a signaling pathway possibly mediated by cGMP-dependent protein kinase is involved in the induction of cellular senescence.

Alkaloids↗

A 10-year experience of intraoperative radiotherapy for gastric carcinoma and a new surgical method of creating a wider irradiation field for cases of total gastrectomy patients.

PURPOSE: To improve the prognosis of gastric cancer, radical surgical resection with extensive lymph node dissection plus intraoperative radiation therapy (IORT) was tried in our clinic. In addition, a new operative procedure was created to obtain wider irradiation field for total gastrectomy patients. METHODS AND MATERIALS: A total of 183 gastric cancer patients who underwent radical gastrectomy with or without IORT from August 1983 to July 1992 were retrospectively evaluated. The patients were divided into two groups: group 1 consisted of 58 patients who underwent radical operation plus IORT. A single dose of 28 to 30 Gy was delivered around the celiac axis with an electron beam of 12 MeV. Group 2, our historical control group, which showed no difference in age, sex and stage, consisted of 120 patients who underwent only radical surgery. In addition, a new method of total gastrectomy with IORT after mobilization of the tail and body of the pancreas was devised to get wider irradiation field for advanced gastric cancer. RESULTS: Of the Stage II gastric cancer patients, all the 11 patients of group 1 are alive, whereas in group 2, the 4-year and the 8-year survival rates were 60% and 48%, respectively. In Stage III patients, the 8-year survival rate of group 1 was 55% vs. 35% in group 2. As for Stage IV patients, the 5-year survival rate of group 1 was 12% and that of group 2 was 13%. CONCLUSION: Using this combined treatment modality of radical surgical operation+IORT, improved survival rates were obtained for Stage II and III gastric cancer patients. However, the method was ineffective for more advanced, Stage IV, patients. The wider irradiation field method used for total gastrectomy patients was safe and no complications were encountered.

Adult↗

Heritable formation of neuroectodermal tumor in transgenic mice carrying the combined E1 region gene of adenovirus type 12 with the deregulated human renin promoter.

Adenovirus early 1 (E1) region gene products, including E1A and E1B, are required for transcriptional regulation of viral and cellular promoters in infected and transfected culture cells and for transformation of primary rodent cells. Here, we established a line of transgenic mice carrying the E1 region gene of human adenovirus type 12 under the control of the human renin promoter, in which a neuroectodermal tumor derived from retroperitoneal, olfactory, and/or pelvic regions was heritably developed with varying degrees of incidence and the phenotype was successfully passed through six generations. The transgenes were located in the region E2-E3 bands of chromosome 7 with which no genetic linkage to neuroectodermal tumors was previously demonstrated, and expressed only in the tumors but not in another tissue examined. Notably, in addition to the expression of a neural marker gene N-CAM, the three nuclear oncogenes, c-, L-, and N-myc, were coexpressed in the tumors. These results suggest that E1A and E1B are cooperatively involved in the heritable formation of neuroectodermal tumors associated with co-expression of the three sets of myc family genes.

Adenovirus E1 Proteins↗