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Biomedical subjects

K Isono

Publications and source records attributed to K Isono.

At least 343 records · Page 19Linked to original sources

[Immunotherapy and quality of life].

In order to examine the quality of life with immunotherapy, a survey was conducted on 17 advanced gastric or colon cancer patients receiving LAK immunotherapy and on 10 patients receiving EAP chemotherapy as a control. Performance status of patients at the time of treatment was similar between the groups. Many patients on EAP therapy complained of severe side effects, such as loss of hair, nausea and vomiting, and appetite loss. None of the patients on LAK therapy complained of such effects on the contrary, favorable effects were found. Appetite increased in some patients and tenderness of the liver disappeared in others. As for the continuance of the treatment, two thirds of EAP patients declined, and all LAK patients replied in the affirmative. The data suggest that LAK immunotherapy is better than EAP chemotherapy from the standpoint of the quality of life.

Antineoplastic Combined Chemotherapy Protocols↗

[Study of risk factors for postoperative pulmonary complications following esophageal cancer surgery--multivariate statistical analysis].

In 91 patients undergoing resection and reconstruction of the esophagus for esophageal cancer, risk factors for postoperative pulmonary complications were studied. In order to investigate these factors, multivariate statistical analysis was applied. The incidence of postoperative pulmonary complications was significantly higher in patients over 70 years of age who had poor renal function (PSP15' less than 25%) and had prolonged thoracotomy time (greater than 3 h) by Student's t test. In preoperative pulmonary functions, obstructive respiratory dysfunction (MMF, FEV1.0) correlated well with postoperative pulmonary complications. The analysis of each factor was, however, not enough to predict the risk of pulmonary complications following operation. Meanwhile, risk score (= 2.0 (age) + 1.0 (FVC) + 0.7 (MMF) + 1.5 (PSP15') + 1.8 (thoracotomy time) + 1.7 (postoperative RI] was obtained by multivariate statistical analysis. High incidence (greater than 80%) of pulmonary complications was observed in patients with risk score more than 5.0. It is suggested that using this risk score will be helpful for postoperative pulmonary care.

Esophageal Neoplasms↗

Recurrent pneumothoraces and mediastinal emphysema in systemic lupus erythematosus.

Neither pneumothorax or mediastinal emphysema are well recognized pulmonary manifestations of systemic lupus erythematosus (SLE). We describe a 41-year-old woman with severe lupus pneumonitis complicated by recurrent pneumothoraces and mediastinal emphysema. Other features of SLE were minimal. She died of progressive respiratory failure. Autopsy revealed innumerable blebs in both lungs responsible for the pneumothoraces and mediastinal emphysema. Both pneumothoraces and mediastinal emphysema occurred during a course of corticosteroid therapy. The course of her illness was unaffected by treatments that included high dose corticosteroids, immunosuppressives and plasmapheresis. Better medical treatment for these lupus complications should be sought in addition to surgery.

Adrenal Cortex Hormones↗

Elevation of c-myc transcript level in human liver during surgical resection of hepatocellular carcinoma: possible cause for underestimation of c-myc gene activation in the tumor.

It has been a matter of controversy as to whether c-myc gene expression is activated in human hepatocellular carcinoma (HCC). We observed that the c-myc mRNA level in HCC was similar to that of the adjacent non-cancerous portion, as determined in freshly obtained specimens after a partial liver resection. However, the c-myc transcript was at a low level in non-cancerous tissue which was biopsied prior to surgery, whereas it was still at a high level in HCC obtained without performing hepatectomy. These results suggest that the high transcript level observed in the non-cancerous tissue from the excised liver relates to liver resection itself, and that the c-myc gene expression is enhanced in the HCC.

Blotting, Northern↗

Expression of c-myc oncogene in colorectal polyps as a biological marker for monitoring malignant potential.

The expression of oncogenes (c-myc, c-fos, c-Ki-ras, c-Ha-ras, and p53) was examined by Northern blot analysis using freshly isolated human colorectal and gastric cancers and noncancerous portions as the controls. Remarkably high levels of c-myc expression were found in colorectal cancers (eight of 11), but not in gastric cancers. High levels of c-myc expression were also detected in colorectal polyps and in metastatic liver tumors. In colorectal polyps, the transcript levels significantly correlated with the histologic malignancy and the size. In contrast, neither c-fos nor c-Ki-ras was overexpressed in colorectal and gastric cancers, and transcripts of c-Ha-ras and p53 were not evident in any tissue examined. In light of these observations the c-myc expression may be specifically associated with the evolution of colorectal cancer as well as progression and maintenance stages, hence may prove to be a useful marker to evaluate the malignant potential of colorectal polyps.

Adenocarcinoma↗

Complete primary structure of calcium-dependent serine proteinase capable of degrading extracellular matrix proteins.

A novel calcium-dependent serine proteinase (CASP) secreted from malignant hamster embryo fibroblast Ni 12C2 degrades extracellular matrix proteins. A complementary DNA encoding CASP has been isolated with the use of oligonucleotide probes synthesized based on partial amino acid sequences of CASP. The complete amino acid sequences of CASP revealed that it has a active site at the C-terminal side. Glu rich and proEGF homologous sites are found at the N-terminal site suggesting that it is structurally similar to blood coagulation factors such as IX, X and an anticoagulation factor, protein C.

Amino Acid Sequence↗

Ultrasonographic evaluation of cervical lymph node metastases in esophageal cancer with special reference to the relationship between the short to long axis ratio (S/L) and the cancer content.

Cervical lymph node metastasis was evaluated sonographically in 58 esophageal cancer patients. The short to long axis ratio (S/L) is a useful way to detect lymph node metastasis as opposed to the long axis alone. In other words, the lymph node exceeding 10 mm in long axis and with S/L over 0.5 showed a much higher incidence of metastasis than S/L under 0.5 in the analysis of the 126 detected lymph nodes. The cancer content was calculated with a microcomputer in each of the total 77 metastatic lymph nodes by enlarging the microscopic specimen 8 or 16 times using a magnifying apparatus. The average cancer content in the metastatic lymph nodes with S/L under 0.5 and over 0.5 was 26.0% and 59.1%, respectively, revealing a statistically significant difference (p less than 0.01). Thus, cancer proliferation in the metastatic lymph nodes of esophageal cancer is closely related to the increase in S/L.

Esophageal Neoplasms↗

Cloning and analysis of the nuclear genes for two mitochondrial ribosomal proteins in yeast.

Two mitochondrial ribosomal proteins of yeast (Saccharomyces cerevisiae) were purified and their N-terminal amino acid sequences determined. The sequence data were used for the synthesis of oligonucleotide probes to clone the corresponding genes. Thus, the genes for two proteins, termed YMR-31 and YMR-44, were cloned and their nucleotide sequences determined. From the nucleotide sequence data, the coding region of the gene for protein YMR-31 was found to be composed of 369 nucleotide pairs. Comparison of the amino acid sequence of protein YMR-31 and the one deduced from the nucleotide sequence of its gene suggests that it contains an octapeptide leader sequence. The calculated molecular weight of protein YMR-31 without the leader sequence is 12,792 dalton. The gene for protein YMR-44 was found to contain a 147 bp intron which contains two sequences conserved among yeast introns. The length of the two exons flanking the intron totals 294 nucleotide pairs which can encode a protein with a calculated molecular weight of 11,476 dalton. The gene for protein YMR-31 is located on chromosome VI, while the gene for protein YMR-44 is located on either chromosome XIII or XVI.

Amino Acid Sequence↗

Characterization of the gene rimK responsible for the addition of glutamic acid residues to the C-terminus of ribosomal protein S6 in Escherichia coli K12.

Ribosomal protein S6 of wild-type strains of Escherichia coli contains up to six glutamic acid residues at its C-terminus. The first two residues are encoded by the structural gene for this protein (rpsF) and the rest are added post-translationally. Mutants deficient in this modification were isolated and characterized genetically and biochemically. The S6 protein in these mutants appeared to contain only two glutamic acid residues at the C-terminus as expected. The mutated gene was termed rimK and was mapped at 18.7 min between cmlA and aroA. The rimK gene was cloned into a cosmid vector and its nucleotide sequence determined. Analysis of the transcriptional and translational products of this gene indicates that it encodes a protein with an Mr of 31.5 kDa and that it forms an operon with a gene encoding a 24 kDa protein. An rpsF mutant containing a Glu to Lys replacement in the second residue from the C-terminus of protein S6 was isolated. The S6 protein of this mutant was apparently inaccessible to the RimK modification system. This indicates that the RimK modification system requires the wild-type amino acid sequence at least in the C-terminal region of ribosomal protein S6.

Amino Acid Sequence↗

Cloning and molecular characterization of the gene rimL which encodes an enzyme acetylating ribosomal protein L12 of Escherichia coli K12.

The rimL gene of Escherichia coli K12 encodes an enzyme catalyzing the acetylation of the N-terminal serine of ribosomal protein L12, thereby converting it into L7. Using a mutant strain defective in this acetylation reaction, we cloned the rimL gene into cosmid pHC79 and characterized it at the molecular level. From analysis by SDS-polyacrylamide gel electrophoresis of the proteins synthesized in maxi-cells containing derivatives of the rimL-harboring plasmid into which transposon gamma delta had been inserted at various sites, the product of this gene was identified as a protein with an apparent molecular weight of 20.3 kDa. The nucleotide sequence of the gene and the amino acid sequence deduced from the nucleotide sequence were compared with those of two other ribosomal protein acetylases encoded by the rimI and rimJ genes (Yoshikawa et al. 1987). A considerable degree of overall similarity was seen between rimL and rimJ, but the degree of similarity between rimL and rimI was very low. In addition, a short stretch of similar amino acid sequence was found in all three rim acetylases. The significance of these results with respect to other acetylating enzymes, in particular those involved in the acetylation of aminoglycoside antibiotics is discussed.

Acetylation↗

Optimal serum trough levels of FK506 in renal allotransplantation of the beagle dog.

The present study was performed to estimate the optimal serum trough levels of FK506 (FK) for prophylactic use and for the treatment of acute rejection in renal allotransplantation of the beagle dog. The serum trough levels of an immunosuppressive dose of FK 1.0 mg/kg p.o. ranged from 0.1 to 0.4 ng/ml. The data indicate that the effective serum trough level is about 100 times lower than that of cyclosporine, as was already observed in previous in vitro studies. Combining treatment with a nonimmunosuppressive dose of cyclosporine of 2.5 mg/kg could lower the effective trough levels of FK. By the combining treatment, 2 out of 5 renal recipient dogs survived with well-functioning grafts as long as 60 days with the trough levels between 0.04 and 0.07 ng/ml. High-dose 5-day i.m. FK treatment of 0.5 or 1.0 mg/kg was effective in the reversal of acute rejection, with peak serum trough levels during successful rejection therapy ranging between 0.28 and 3.7 ng/ml. Two dogs died of malaise or pneumonia with peak trough levels of 2.25 and 2.78 ng/ml. Among the wide range of the effective trough levels for successful acute rejection therapy, those above 2.0 ng/ml seem to be toxic in some renal-transplanted dogs.

Administration, Oral↗

Cloning and analysis of an Escherichia coli operon containing the rpmF gene for ribosomal protein L32 and the gene for a 30-kilodalton protein.

The chromosomal DNA fragments of Escherichia coli K-12 were cloned into a mini-F cosmid, pRE435, after partial digestion with restriction endonuclease Sau3AI. The clones were first screened for PyrC+ and then for other genes, including rpmF encoding ribosomal protein L32 that had been mapped near pyrC (I. Janda, M. Kitakawa, and K. Isono, Mol. Gen. Genet. 201:443-436, 1985). Thus, we obtained a total of five rpmF-containing clones. The rpmF gene was located on the chromosomal segment in one of the clones (pAY2-5) by insertional mutagenesis with transposon gamma delta, followed by analysis of the gene products by the maxicell method. Hybridization analysis of clone pAY2-5 with the ordered clone bank (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987) indicates that a gap at the 1,510-kilobase coordinates in the physical map of E. coli can be bridged by this clone. The nucleotide sequence of the region containing rpmF was accordingly established. In addition, the RNA transcripts from the chromosomal region containing rpmF were analyzed, and the transcriptional initiation sites were determined. The results suggest that rpmF forms an operon with the gene termed g30k which codes for a 30-kilodalton protein of unknown function. At least four transcripts were found to code for ribosomal protein L32.

Amino Acid Sequence↗

Parameters linked to ten-year survival in Japan of resected esophageal carcinoma. Japanese Committee for Registration of Esophageal Carcinoma Cases.

From January 1969 to December 1980, 8,948 patients with esophageal carcinoma were registered in Japan. Among these patients, 5,506 underwent resection. The ten-year survival rate was 12.3 percent for all registered patients and 18.7 percent for resected cases. Female patients had significantly better survival rates than male patients. Depth of invasion correlated better with ten-year survival than the superficial extent of the tumor. The TNM classification revised in 1987 was examined in relation to the survival, and it was found to have good prognostic value.

Carcinoma, Squamous Cell↗

A new biological role of sangivamycin; inhibition of protein kinases.

During the screening for the inhibitors of protein kinase C (PKC), we found that a streptomycete produced an inhibitor in our bleb-forming assay (Osada et al., J. Antibiotics 41: 925, 1988). The inhibitor was isolated and identified as sangivamycin (4-amino-5-carboxamide-7-(D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine). Biological activity of sangivamycin was compared with that of other 7-deazaadenosine group antibiotics, tubercidin and toyocamycin. Sangivamycin showed a strong inhibitory activity against bleb-formation of K562 cells and PKC. On the other hand, tubercidin and toyocamycin had only weak activities in both assays. This paper deals with a new biological activity of sangivamycin, that of an inhibitor of protein kinases, especially PKC.

Anti-Bacterial Agents↗

Comparison of the effect of tautomycin and phorbol ester on protein kinase C in a cell-free system.

The effect of tautomycin (TM) on protein kinase C (PKC) was studied in a cell-free system. TM, like phorbol dibutyrate (PDBu), enhanced both base-line and Ca2+/phospholipids-dependent protein kinase activity. However, PDBu but not TM increased the affinity of the enzyme for calcium ions (Ca2+), suggesting that TM is a new activator of PKC, distinct from PDBu. In the presence of 10 micrograms/ml phosphatidyl inositol, the activity of PKC reached maximum at 10(-3) M Ca2+ concentration when the other co-factors were absent. Both TM and PDBu increased the maximum level of PKC activity at the optimum concentration of Ca2+, suggesting that they interacted with the site of PKC which is distinct from the site where Ca2+ interacts. TM and PDBu did not activate the enzyme when protamine sulfate in place of histone III-S was used as a substrate, indicating that they activate PKC by affecting the regulatory domain of the enzyme.

Antifungal Agents↗

Epiderstatin, a new inhibitor of the mitogenic activity induced by epidermal growth factor. I. Taxonomy, fermentation, isolation and characterization.

Inhibitors of mitogenic activity induced by epidermal growth factor (EGF) were screened from culture broths of soil microorganisms. A strain of actinomycetes has been found to produce a new glutarimide antibiotic named epiderstatin which inhibits the incorporation of [3H]thymidine into quiescent animal cells stimulated by EGF. Taxonomic studies have revealed that the producing strain belongs to a subspecies of Streptomyces pulveraceus, thus the name, Streptomyces pulveraceus subsp. epiderstagenes was given to this strain. The molecular formula (C15H20N2O4) and UV profile (lambda max 295 nm) of the antibiotic are distinct from other known antibiotics. It inhibited the incorporation of [3H]thymidine into quiescent cells stronger than into growing cells.

Animals↗