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Biomedical subjects

K Kohno

Publications and source records attributed to K Kohno.

At least 289 records · Page 16Linked to original sources

Localization of hyaluronic acid in human articular cartilage.

To demonstrate localization of hyaluronic acid (HA) in articular cartilage of the human femur, biotinylated HA-binding region, which specifically binds HA molecules, was applied to the tissue. In sections fixed by 2% paraformaldehyde-2% glutaraldehyde, HA staining was detected in lamina splendens and chondrocytes in the middle zone. By pretreatment with trypsin, intense HA staining appeared in the extracellular matrix of the deep zone and weak staining in the superficial and middle zones. Moreover, pre-treatment with chondroitinase ABC (CHase ABC) intensely enhanced the stainability for HA in the superficial and middle zones and weakly in the deeper zone. Combined pre-treatment of trypsin with CHase ABC abolished intra- and extracellular staining for HA in all zones. By microbiochemical study, the concentrations of HA and dermatan sulfate were high in the middle zone, whereas those of chondroitin sulfate and keratan sulfate were high in the deep zone. These results suggest that HA is abundantly synthesized in and secreted from the chondrocytes, particularly in the middle zone, whereas it is largely masked by proteoglycan constituents in the extracellular matrix.

Adult↗

Recurrence of primary intracranial germinomas after complete response with radiotherapy: recurrence patterns and therapy.

Nine germinoma patients are described who developed a recurrence after a complete response to radiation without adjuvant chemotherapy. Extraembryonic tumors producing alpha-fetoprotein and human chorionic gonadotropin were excluded from this study. Four patterns of recurrence are described with respect to mechanism and appropriate treatment. Type I germinoma recurrence, characterized by intracranial recurrence caused by an inadequate initial irradiation field was treated by total craniospinal irradiation. Type II recurrence, characterized by a benign teratoma caused by late growth of the teratoma component was treated by surgery alone. All patients with these patterns of recurrence are still alive. Type III local recurrence is characterized by human chorionic gonadotropin- or alpha-fetoprotein-producing tumors of extraembryonic origin. This pattern of recurrence should be treated by chemotherapy or radiosurgery, because all these patients died. Type IV germinoma recurrence consists of extraneural metastasis without evidence of intracranial recurrence. Two of these patients were treated with chemotherapy. In summary, four patients died after recurrence, whereas the remaining five patients survived. The classification of germinoma recurrence patterns should facilitate the selection of the most appropriate treatment. However, it has been difficult to identify the precise histopathology by biopsy or partial resection alone. Furthermore, chemotherapy is indicated in treating germinomas that have a ventriculoperitoneal shunt because of the risk of extraneural metastases.

Adolescent↗

[A study of preventive medicine in relation to mental health among middle-management employees (Part 1)--Relationship between lifestyles and working-life satisfaction].

This study examined the cross-sectional relationship between health practices and working-life satisfaction, which we used as a subjective index of Quality of Life (QOL), based on data obtained from a survey of 3,928 middle-management employees (1,026 department chiefs and 2,902 section chiefs) in 110 major companies in 1990. The results are summarized as follows. (1) The section chiefs had more poor health practices than the department chiefs. The section chiefs appeared to have significantly more poor habits in terms of cigarette smoking, eating breakfast, nutritional balance, working hours, snacking, salt consumption, obesity, enjoying hobbies and physical status than the department chiefs. Surprisingly, 66% of department chiefs and 77% of section chiefs worked more than 10 hours per day. (2) Both the Health Practice Index (HPI) and working-life satisfaction tended to be higher as their ages were higher. (3) The department chiefs who had a poor nutritional balance, did not maintain an adequate stress level, had poor eating habits, poor sleeping habits and physical inactivity appeared to have lower working-life satisfaction. (4) The working-life satisfaction of the management staff was significantly affected by health practices, occupational stress, physical health status and position after controlling simultaneously for the other potential confounders. From these results, it may be concluded that the behavioral lifestyle change of the middle-management employee is an important factor to promote mental health as evaluated by working-life satisfaction.

Adult↗

[Actual status of measurement of blood concentration of lead, urinary concentration of delta-aminolevulinic acid and urinary concentration of metabolites of organic solvents entrusted to occupational health organizations].

In Japan "the Regulation on the Prevention of Lead Poisoning" and "the Regulation on the Prevention of Organic Solvent Poisoning" were partially amended in 1989 to introduce biological monitoring in the special medical examinations of workers exposed to lead and 8 organic solvents (toluene, xylene, styrene, N,N-dimethylformamide, n-hexane, tetrachloroethylene, 1,1,1-trichloroethane, trichloroethylene). Since many companies entrust these medical examinations to the Occupational Health Organizations (OHOs), a survey of OHOs which collect blood and urine samples for biological monitoring was made in August 1992, to ascertain the actual status of their activities from April of 1991 to March of 1992. The following findings were obtained through this survey. 1) One hundred and eighty-six OHOs collected 129,996 blood samples to measure the concentration of lead, and the median number of samples collected per organization was 356. 2) Thirty-nine OHOs (21.0%; Group A) measured all samples in their own laboratories. The number of samples measured was 55,462 (42.7%). However, 133 OHOs (71.5%; Group B) entrusted the measurement of all samples to registered laboratories. 3) The median number of samples collected by OHOs in Group A was 1,121, and the median number of Group B was 211. 4) One hundred and eighty-three OHOs collected 126,915 urine samples to measure the concentration of delta-aminolevulinic acid and the median number of samples collected per organization was 358. 5) The blood samples as well as the urine samples were divided into three groups according to the levels of lead or delta-aminolevulinic acid concentration. The concentration is relatively low in Group 1 and relatively high in Group 3. The cut-off values for this classification are legally set in the Regulation on the Prevention of Lead Poisoning. The frequency of each group was as follows: lead (Group 1; 93.8%, Group 2; 4.9%, Group 3; 1.3%), delta-aminolevulinic acid (Group 1; 96.8%, Group 2; 3.1%, Group 3; 0.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗

Large cystic cavernous angioma of the cerebellum--case report.

A 40-year-old female presented with gait disturbance and dysarthria. Computed tomography revealed a large cystic tumor in the cerebellar vermis with a mural nodule located in the deepest portion of the cyst. The magnetic resonance (MR) imaging appearance suggested cavernous angioma. The solid nodule was completely removed through the suboccipital approach. The cyst was filled with transparent yellowish fluid which showed positive Froin's sign. The histological diagnosis of the mural nodule was cavernous angioma. The cyst wall consisted of gliosis and contained no angiomatous tissues. Postoperative MR imaging demonstrated that the nodule was totally removed and the cyst size was reduced. The neurological deficits improved postoperatively. The mechanism of formation of the large cyst was assumed to be repeated peritumoral hemorrhage.

Adult↗

Selective increase in expression of isoform PP1 gamma 1 of type-1 protein phosphatase in chondrosarcoma cells.

The expression of the two catalytic subunits of protein phosphatase (PP) type 1 PP1 gamma 1 and PP1 delta was examined in 4 cases of osteochondroma and 4 cases of enchondroma as a benign cartilaginous tumor, and 4 cases of chondrosarcoma as a malignant cartilaginous tumor using immunohistochemical analysis. The percentage of tumor cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 were significantly higher in chondrosarcoma than in osteochondroma and enchondroma. Furthermore, chondrosarcoma showed markedly high S-phase fraction in the cell cycle of tumor cells, as compared to osteochondroma and enchondroma. These results suggest that PP1 gamma 1 is involved in the accelerated growth of malignant cells in chondrosarcoma.

Adolescent↗

Enhanced expression of catalytic subunit isoform PP1 gamma 1 of protein phosphatase type 1 in malignant fibrous histiocytoma.

The expression of the three catalytic subunits of protein phosphatase (PP) type 1 and 2A, PP1 alpha, PP1 gamma 1, and PP2AC, was examined in malignant fibrous histiocytoma using immunohistochemical analysis. The percentage of cells stained positively with antiserum against PP1 catalytic subunit isoform PP1 gamma 1 was significantly higher in tumorous region than in non-tumorous region of malignant fibrous histiocytoma. Furthermore, tumorous region showed markedly high S-phase fraction in the cell cycle, as compared to non-tumorous region. These results suggest that PP1 gamma 1 is involved in the accelerated growth of tumor cells in malignant fibrous histiocytoma.

Adult↗

[Atypical MDR].

Multiple drug resistance(MDR) is a major clinical obstacle in cancer chemotherapy. Acquirement of MDR phenotype in cancer cells is often associated with enhanced expression of human MDR-1 gene: MDR-1 gene codes membranous P-glycoprotein which catalyses energy-dependent outward transport of anticancer agents. By contrast, MDR cancer cell lines without overexpression of P-glycoprotein are called as atypical MDR (at MDR) cells. The acquirement of at MDR has been shown to be partly associated with altered DNA topoisomerase II. Furthermore, a new ATP binding cassette (ABC) family, MRP gene has just recently shown to involve in acquirement of at-MDR in cancer cell lines, which do not express both altered topoisomerase II and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Sevoflurane anesthesia in a patient with multiple sclerosis].

Multiple sclerosis (MS) is a disorder of the nervous system in which myelin breakdown is a prominent feature. We report a 65-yr-old woman scheduled for femoral neck prosthetic replacement under sevoflurane anesthesia, who had been suffering from a progressive type of MS for 27 years. Previously she had a history of exacerbation of symptoms after caudal block done for sciatic neuralgia. Stress such as surgery, anesthesia, emotional distress and variable body temperature can exacerbate the disease. Spinal and epidural block are relatively contraindicated in MS. Thiopental was reported to worsen MS. But there is no evidence that any of the volatile anesthetic agents has a deleterious effect on MS. Sevoflurane can be used to induce anesthesia quickly. To avoid thiopental, we chose slow induction with sevoflurane (GOS). Anesthesia was maintained with GOS. It seems that intraoperative hypotension which resists to ephedrine administration is partly due to autonomic abnormality. Yet, there is no report of sevoflurane anesthesia in MS patient. We consider that in this case sevoflurane is a safe anesthetic because of its less effect on postopreative neurological symptoms than that of epidural block.

Aged↗

[Multidrug resistance (MDR)].

Multiple drug resistance (MDR) is a major problem of current chemotherapy. Establishment of multiple drug resistant cell lines in culture and isolation of P-glycoprotein-coding MDR genes have promoted understanding of the molecular mechanisms underlying drug resistance in tumors. Another gene, MRP, has been recently isolated from a multiple drug resistant cell line which did not express P-glycoprotein. Both genes have DNA sequence homology for each other and have been identified as members of ATP binding cassette (ABC) transporter superfamily. This review refers to recent progress in MDR and MRP study, and focuses on involvement of these two drug-resistance-related genes in acquiring drug resistance and their physiological functions.

Animals↗

[Enzyme-linked immunosorbent assay for the quantification of Cry j I and Cry j II].

Enzyme-linked immunosorbent assays (ELISA) were developed to specifically quantify the two major allergens from Japanese cedar pollen, Cry j I and Cry j II. Polystyrene microplates coated with antibodies specific for Cry j I or Cry j II were incubated with an allergen and then with biotinylated anti-Cry j I or Cry j II antibody. The bound allergen-biotin Ab complexes were detected with HRPO-conjugated streptavidin and an enzyme substrate. The working ranges of Cry j I ELISA and Cry j II ELISA were 0.3-20 ng/ml and 0.6-20 ng/ml, respectively. Intra- and inter-assay coefficients of variation for reproducibility were 1.5-10.3% and 0.9-12.9%. These ELISA systems showed no cross-reactivity between Cry j I and Cry j II and showed little cross-reactivity with pollen allergens of plants botanically related to the Japanese cedar. Using the Cry j I ELISA and the Cry j II ELISA, it was possible to quantify Cry j I and Cry j II easily and accurately. These ELISA systems will be useful in various fields, especially for the analysis and standardization of the allergens necessary for diagnosis and treatment of Japanese cedar pollinosis.

Allergens↗

Anti-angiogenic activity of arachidonic acid metabolism inhibitors in angiogenesis model systems involving human microvascular endothelial cells and neovascularization in mice.

We have established an in vitro angiogenesis model using human omental microvascular endothelial (HOME) cells, in which epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration and tube formation. In this study, we examined whether alpha-guaiaconic acid (GR-12) and its synthetic 20 derivatives showed inhibition of cell migration and tubular formation of HOME cells. We found that GR-12 inhibits arachidonic acid metabolism, while GR-12 and one derivative, GS-01, inhibit tubular formation of endothelial cells in our model system. Confluent monolayers of HOME cells were damaged with a razor blade and incubated with or without TGF-alpha; HOME cell migration was stimulated about 1.5-fold over control values in the presence of TGF-alpha. Treatment of HOME cells with GR-12 or GS-01 inhibited both spontaneous and TGF-alpha-stimulated migration. GR-12 or GS-01 inhibited TGF-alpha-induced HOME-cell tube formation in type-1 collagen gels. We examined whether these compounds could modulate tubular formation of HOME cells induced by human cancer cells. Enhanced tube formation of HOME cells by co-cultured esophageal cancer cells was almost completely inhibited by co-administration of GR-12 or GS-01. Both compounds also inhibited formation of tubular networks of HOME cells on Matrigels. We also examined anti-angiogenic activity of these compounds in an in vivo model system of tumor angiogenesis in mice. In this system, GS-01 inhibited development of capillary networks at a rate comparable to that of a well-known anti-angiogenic compound, fumagillin, but GR-12 did not. The inhibitor of arachidonic acid metabolism is thus expected to modulate tumor angiogenesis.

Animals↗

Neurotrophic action of gliostatin on cocultured neurons with glial cells.

Gliostatin is a polypeptide factor (apparent M(r) = 100 k with a homodimeric structure comprising two 50 kDa subunits) acting on cortical neurons (neurotrophic action) as well as astrocytic cells (growth inhibition). Under the coculture system of cerebral cortical neurons and astrocytes from fetal rats (E15 or E16), the neurotrophic action of gliostatin was examined immunocytochemically. Immunostaining by an anti-neurofilament (NF) monoclonal antibody visualized a marked neurite-outgrowth and interconnecting bundles of neuritic processes induced by gliostatin in the coculture system. Neurons stimulated by gliostatin formed dense aggregates in clumps, while neurons in control coculture spread out. Gliostatin has also shown survival-promoting effects on neurons. Furthermore, it was shown that gliostatin induced the differentiation of protoplasmic astrocytes to fibrous astrocytes. These results further support our previous contention that gliostatin plays physiological roles on neuronal and glial development.

Animals↗

Involvement of protein kinase in environmental stress-induced activation of human multidrug resistance 1 (MDR1) gene promoter.

The human MDR1 gene can be induced in response to various environmental stimuli. To examine whether such stress-induced activation of the MDR1 gene can be modulated by protein kinase, we employed a stable human cancer KB cell line which contained the bacterial chloramphenicol acetyltransferase (CAT) gene directed by the MDR1 gene promoter. H-7, a protein kinase C inhibitor, at more than 40 microM inhibited activation of the MDR1 promoter that was induced by ethylmethane sulfonate, 5-fluorouracil or UV irradiation. DNA binding activity of nuclear factors recognizing the MDR1 promoter was augmented in KB cells treated with UV, but decreased in cells treated concomitantly with H-7. Okadaic acid alone was able to induce the promoter activation, and this induction was dependent on specific promoter sequences. Okadaic acid also enhanced the DNA binding activity of nuclear factors recognizing the MDR1 promoter. The phosphorylation of transacting factors may modulate the MDR1 gene promoter activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

MK-801, a glutamate antagonist, lowers flow threshold for inhibition of protein synthesis after middle cerebral artery occlusion of rat.

The effect of the glutamate antagonist MK-801 on the ischemic threshold of energy metabolism and protein synthesis (CPS) was studied in rats submitted to 3 h occlusion of the left middle cerebral artery (MCA). Local blood flow and CPS were measured by double tracer autoradiography, and local ATP content by bioluminescence imaging. In untreated animals breakdown of energy metabolism occurred at flow values below 15 +/- 1 and CPS inhibition below 51 +/- 15 ml/100 g/min (means +/- S.D.). MK-801 treatment (3 mg/kg immediately after MCA occlusion) did not change the ischemic flow threshold of energy failure (16 +/- 3 ml/100 g/min) but lead to a highly significant decline of the perfusion threshold for the inhibition of CPS to 19 +/- 4 ml/100 g/min (P < 0.01). Our data demonstrate that MK-801 dramatically reduces the threshold for the suppression of protein synthesis which could explain previously reported therapeutical effects on the reduction of brain infarct size.

Adenosine Triphosphate↗

Irsogladine is a potent inhibitor of angiogenesis.

We describe a novel inhibitor of angiogenesis, Irsogladine, an anti-ulcer drug. Irsogladine inhibited plasminogen activator synthesis of, and tube formation by, human microvascular endothelial cells in type 1 collagen gel treated with an angiogenic growth factor, EGF. Furthermore, Irsogladine administered orally significantly inhibited in vivo angiogenesis in mice. Irsogladine may be useful in the treatment of diseases associated with angiogenesis.

Animals↗

Expression of non-ADP-ribosylatable, diphtheria toxin-resistant elongation factor 2 in Saccharomyces cerevisiae.

Eucaryotic elongation factor 2 (EF-2) contains a post-translationally modified histidine residue termed diphthamide that is specifically ADP-ribosylated by diphtheria toxin (DT) or Pseudomonas exotoxin A. To analyze the potential physiological role of ADP-ribosylation of EF-2 by cellular ADP-ribosyl transferase, we constructed DT-resistant, non-ADP-ribosylatable Saccharomyces cerevisiae EF-2 by site-directed mutagenesis and expressed the mutant EF-2 in yeast. Substitution of Arg for Gly(701) in yeast EF-2 conferred complete resistance to DT in vivo and in vitro. However, when only non-ribosylatable EF-2 was expressed in cells using genetic manipulation, the mutated EF-2 did not affect vegetative cell growth, mating, sporulation and germination of ascospores.

Adenosine Diphosphate Ribose↗

Enhanced expression of the DNA topoisomerase II gene in response to heat shock stress in human epidermoid cancer KB cells.

Type II DNA topoisomerase breaks both DNA strands, and many anticancer agents including etoposide (VP-16) and teniposide (VM-26) have been developed by targeting topoisomerase II molecules. In this study we examined whether expression of the topoisomerase II gene is regulated in response to heat shock stress in human epidermoid cancer KB cells. Exposure of KB cells to 42 degrees C for 3 to 24 h permitted cell growth at a slightly reduced rate but still at an exponential rate, in comparison with that at 37 degrees C, whereas exposure to 45 degrees C for 15 to 120 min caused the almost complete cessation of exponential growth. There appeared 5-fold or higher increases in mRNA levels of both topoisomerase II and a heat shock protein, hsp-70, after exposure to 42 degrees C for 3 h, but only a slight, if any, increase in topoisomerase I mRNA. Nuclear run-on assays showed increased transcription of topoisomerase II and the hsp-70 gene after exposure to 42 degrees C. By contrast, KB cells induced a rapid and transient increase of topoisomerase II mRNA after exposure to 45 degrees C for 15 to 30 min, whereas the cellular level of hsp-70 mRNA was dramatically enhanced 60 min after exposure to 45 degrees C. The immunoblot assay also demonstrated increased expression of topoisomerase II in KB cells exposed to 42 degrees C. Decatenation activity of the nuclear extracts from KB cells was increased 1.5-fold by exposure to 42 degrees C, but there appeared no increase in topoisomerase I activity. Prior exposure of KB cells to 42 degrees C enhanced the cytotoxicity of VP-16, but not that of a topoisomerase I-targeting agent, a camptothecin analogue, CPT-11. However, exposure of KB cells to 42 degrees C after treatment with VP-16 did not enhance the cytotoxicity induced by the drug. The formation of cleavable DNA-topoisomerase II-VP-16 complexes was also greatly increased by prior exposure to 42 degrees C. Our present study proposes the hypothesis that the topoisomerase II gene might be one of the heat-shock-inducible genes and that hyperthermic anticancer therapy with topoisomerase II-targeting antitumor agents can be improved.

Camptothecin↗