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Biomedical subjects

K Isono

Publications and source records attributed to K Isono.

At least 415 records · Page 23Linked to original sources

Studies on binding of toromycin, an antitumor antibiotic, to DNA.

Toromycin, an antitumor, bactericidal and antiviral compound, was found to bind to DNA in such a way as to interfere with the dissociation of double helix at an elevated temperature. The antibiotic did not introduce strand scission into DNA. Single-strand-specific nuclease S1-susceptibility of negatively supercoiled DNA was not influenced by its binding. The antibiotic was shown to bind to both of the alternating purine-pyrimidine copolymers, poly(dG-dC):poly(dG-dC) and poly(dA-dT):poly(dA-dT). The unique C-glycoside molecule of toromycin interacted with single-stranded DNA, but was found to have no affinity for RNA.

Aminoglycosides↗

Purification and characterization of ascamycin-hydrolysing aminopeptidase from Xanthomonas citri.

A nucleoside antibiotic, ascamycin (9-beta-[5'-0-(N-L-alanyl) sulphamoyl-D-ribofuranosyl]-2-chloroadenine), has a selective antibacterial activity against Xanthomonas species. When ascamycin was dealanylated, dealanylascamycin showed a broad antibacterial activity against various Gram-negative and Gram-positive bacteria. Xanthomonas citri is susceptible to ascamycin by virtue of the ascamycin-dealanylating enzyme on the cell surface [Osada & Isono (1985) Antimicrob. Agents Chemother. 27, 230-233]. The enzyme (Xc aminopeptidase) was purified from X. citri cells by successive DEAE-cellulose, chromatofocusing and Sephadex G-100 column chromatography to a homogeneous state. The purified enzyme exhibited a single band with an Mr of 38 000 in SDS/polyacrylamide-gel electrophoresis. Gel filtration on a calibrated column indicated a similar Mr value. The isoelectric point of the enzyme was 5.7. The enzyme catalysed the hydrolysis of the alanyl group of ascamycin and liberated alanine from the sulphamoyl nucleoside. The enzyme also catalysed the hydrolysis of L-proline beta-naphthylamide and L-alanine beta-naphthylamide. The optimal pH and temperature for enzyme activity were pH 7.5-8.0 and 35-40 degrees C respectively. The enzyme was inhibited by thiol-enzyme inhibitors (i.e. rho-chloromercuribenzoate and N-ethylmaleimide), but was not affected by various naturally occurring aminopeptidase inhibitors (i.e. amastatin, bestatin, pepstatin and leupeptin). Mn2+ and Mg2+ activated the enzyme, whereas Cu2+, Zn2+ and Cd2+ were inhibitory.

2-Chloroadenosine↗

The nucleotide sequence of an Escherichia coli chromosomal region containing the genes for ribosomal proteins S6, S18, L9 and an open reading frame.

The DNA sequence of a cluster of genes for ribosomal proteins S6 (rpsF), S18 (rpsR) and L9 (rplI), and of their surrounding regions was determined. The order of the genes was established as promoter-rpsF-rpsR-rplI. There is a 315 bp open reading frame that begins seven nucleotides after the end of rpsF and ends immediately before rpsR. Based on the data of insertional mutagenesis experiments with transposon gamma delta, we concluded that these genes probably form an operon. The amino acid sequence deduced from the nucleotide sequence of the genes agrees completely with the published amino acid sequence data for protein S6, but there are discrepancies in the case of proteins S18 and L9. The C-terminus of protein S6 was deduced to end with two Glu residues, suggesting that the other Glu residues previously found in this protein are added post-translationally as has been predicted (Reeh and Pedersen 1979). A possible secondary structure in the leader sequence as well as a possible transcriptional terminator after rplI were noticed in the sequence.

Amino Acid Sequence↗

The synergism of nucleoside antibiotics combined with guanine 7-N-oxide against a rhabdovirus, infectious hematopoietic necrosis virus (IHNV).

Guanine 7-N-oxide was shown to have synergistic activity in combination with neplanocin A against a rhabdovirus, infectious hematopoietic necrosis virus (IHNV), as reported previously. We examined further the antiviral activity of guanine 7-N-oxide in combination with other nucleoside antibiotics against IHNV. Synergism was seen between guanine 7-N-oxide and D-eritadenine or cordycepin. It is considered that compounds inhibiting RNA methylation show synergism with guanine 7-N-oxide.

Anti-Bacterial Agents↗

Occurrence of an ascamycin dealanylating enzyme, Xc-aminopeptidase, in mammalian cell membranes and susceptibility to ascamycin.

An ascamycin dealanylating enzyme (Xc-aminopeptidase) has been isolated from Xanthomonas citri and characterized as a proline iminopeptidase of molecular weight of 38,000 (H. OSADA & K. ISONO, Biochem. J. 233: 459 approximately 463, 1986). Immunological studies have shown that all the mammalian cells tested possess a closely-related enzyme(s) on their cell membranes. This enzyme is more active in transformed cells than in nontransformed cells. A decreased ratio of ID50 (ascamycin/dealanylascamycin based on [35S]methionine uptake) in transformed cells compared with the nontransformed cell can be explained on the basis of the conversion of ascamycin to dealanylascamycin by the enzyme. It is suggested that ascamycin cannot be transported through mammalian cell membranes but dealanylascamycin can permeate; a similar situation exists in prokaryotic cells.

2-Chloroadenosine↗

[Endoscopic ultrasonic diagnosis of esophageal cancer].

Endoscopic Ultrasonography (EUS) has been developed rapidly and is becoming a new routine examination of the digestive diseases. In this thesis, the usefulness of EUS with reference to the diagnosis of the depth and the margins of the cancer invasion and the metastatic lymph nodes is described. Furthermore, the judgment of the efficacy of the combined therapy including radiotherapy, chemotherapy and immunotherapy will be possible with EUS. The information from EUS is useful to determine the treatment plan of esophageal cancer. Therefore, EUS is expected to become a preoperative necessary examination of cases with esophageal cancer.

Esophageal Neoplasms↗

[Application of NMR-CT in the staging of cancer of the digestive organs].

To assess the potential of NMR-CT for demonstrating cancer of the digestive organs, we examined a total of 232 patients (89 with esophageal cancer, 52 with liver cancer, 40 with colorectal cancer, 9 with pancreatic cancer, 9 with gastric cancer, and 33 with other diseases). NMR-CT has many features, but we use especially those features which it is possible to select not only in the transverse plane but also in the coronal and sagittal planes, and it has excellent soft tissue contrast resolution. Our machine is a Picker International NMR-CT using a superconducting magnet of 0.256 tesla. Diagnosis of lymph node involvement of esophageal cancer. Using only the coronal plane, each patient was scanned by the spin echo technique (TE = 40, TR = 400) from the plane of the descending aorta to the plane of the trachea 1 cm in thickness, at 1 cm intervals, continuously. All the vessels were clearly differentiated as no-signal regions, especially in coronal images, from areas of carcinomatous involvement. Lymph nodes were identified as intense grey masses in fat tissue of high intensity. Twenty cases were proved by surgery or autopsy, and it was possible to assess 160 lymph-node groups. A total of 25 patients were imaged as having positive lymph nodes, but 17 of them had metastasis-positive nodes. In other 135 nodes imaged as negative lymph nodes, only two had metastasis and 133 were negative for metastasis. Overall accuracy was 93.8%. Diagnosis of liver cancer. Intrahepatic vessels were clearly imaged without using contrast enhancement in NMR-CT, so it was easy to diagnose the segment containing the tumor and to detect tumor emboli in the portal vein. The capsule was imaged in 84% (16/19) using IR techniques, although only 37% (7/19) could be imaged by X-CT. Diagnosis of colorectal cancer. Using the sagittal plane, the sacrum, urinary bladder and other organs were imaged better parallel to their axis, so that the relationship between rectal cancer and surrounding organs could be clearly visualised with NMR-CT. With regard to lymphatic metastasis, coronal imaging was useful for picturing mesenteric and pelvic vessels, so that lymph nodes were imaged as low-intensity masses along the vessels. Lymph metastasis almost 1 cm size can be detected using coronal NMR-CT.

Digestive System Neoplasms↗

[Retroperitoneal liposarcoma with various histological figures].

A case of retroperitoneal liposarcoma consisting of three large nodules with three different types of histologic findings is presented. A 69-year-old man was diagnosed as having a malignant tumor in the retroperitoneum and underwent successful tumor extirpation. The resected tumor had three different type of nodules, 18 X 15 X 7.0 cm, 8 X 15 X 4.0 cm, 15 X 10 X 2.5 cm in size, respectively. The histologic examination revealed myxoid, well-differentiated fibrosing and lipoma-like liposarcoma type, respectively. Chemotherapy was undertaken postoperatively, and there is no evidence of recurrence two years after surgery.

Aged↗

[Phase II study of cisplatin in esophageal carcinoma].

A multi-institutional cooperative phase II study of Cisplatin for esophageal carcinoma was conducted. Cisplatin was administered by i.v. infusion at 10-20 mg/m2 body surface area daily for 5 days and repeated every 3-4 weeks (method A) or at 50-100 mg/m2 body surface area once every 3-4 weeks (method B). Out of 78 cases entered, 47 were evaluable. No complete response (CR) was obtained and partial responses (PR) were observed in 10 cases, the overall response rate being 21.3%. Response rates by administration methods A and B were 12.5% and 25.8%, respectively. Responders to treatment exhibited significantly longer survival periods compared to non-responders (p less than 0.05, generalized Wilcoxon test). Major adverse reactions were gastrointestinal symptoms, generalized malaise, bone marrow suppression and renal disorders. One case of leukopenia leading to eventual death from pneumonia was observed.

Adult↗

[Combination of radiotherapy with cisplatin in esophageal cancer].

Combination of radiotherapy with Cisplatin was performed in order to improve the results obtained with radiotherapy alone in the treatment of esophageal cancer. The therapeutic effect of this regimen and administration of Cisplatin were analyzed in 7 primary and 8 recurrent esophageal cancer patients from April 1983 to February 1985 in N.I.R.S. Cisplatin 10 mg/m2, without hydration and diuresis, was given daily followed by radiotherapy of 2 Gy daily for five consecutive days. The course was performed for two consecutive weeks and repeated after a one-week withdrawal of Cisplatin alone. Total doses of Cisplatin were 200 mg and the total dosage of radiotherapy including fast neutrons was TDF 110 to 120. Cisplatin 30 to 50 mg/m2 was continued monthly for maintenance every four weeks after the second course. Response rates in primary and recurrent cases were 71.4% and 62.5% respectively. Administration of Cisplatin 10 mg/m2 daily was useful since nausea and vomiting rarely appeared and bone marrow toxicity and renal dysfunction as side effects were mild and reversible. In the combination of radiotherapy with Cisplatin, it seemed most effective to perform radiotherapy immediately after Cisplatin administration, considering the change in serum concentration.

Aged↗

[Problem of the general rules and the TNM classification].

According to the TNM classification stage of disease progression, intrathoracic and lower esophagus carcinoma without good prognosis were stage II by T3. On the other hand, cardiac and cervical lymph node metastases with good prognosis were categorised as M1 and correspond to stage IV, so that the meaning of stage grouping is disappeared each other. A new classification of esophagus carcinoma based on the depth of invasion is proposed by the Esophagus Carcinoma Registration Committee.

Esophageal Neoplasms↗

[Combined effect of the topical administration of OK-432 with radiation on the C3H mouse fibrosarcoma (NFSa)--TCD50 and the mechanism of action].

Optimal timing of topical administration of OK-432 and TCD50 were studied using weakly immunogenic and radioresistant C3H mouse fibrosarcoma (NFSa). The mechanism of action of this combined therapy was examined histologically and electron microscopically. Topical administration of OK-432 was performed from 2 days before irradiation to 7 days after irradiation and tumor volumes on the 20th day after irradiation were compared with a control group given radiation alone. Significant difference was observed only in the group which was given OK-432 just after irradiation. The TCD50 of the combined therapy of radiation with topical administration of OK-432, 4 KE which was given just after irradiation was 64.5 Gy and that of radiation alone was 83.5 Gy. Combined therapy shifted the TCD50 curve about 20Gy to the left. Histological examination of the tumor on the 6th day after combined therapy showed marked degeneration and necrosis of tumor cells with marked infiltration of lymphocytes. These lymphocytes were electron microscopically seen surrounding not only damaged cells, but also apparently active tumor cells. We postulate the latter cells had a tendency to be degenerative. This phenomenon suggests that lymphocytes recognize as foreign these tumor cells which are apparently active but some what damaged by radiation.

Administration, Topical↗