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Biomedical subjects

K Kohno

Publications and source records attributed to K Kohno.

At least 253 records · Page 14Linked to original sources
PubMed1995

[A study of preventive medicine in relation to mental health among middle-management employees (Part 2)--effects of long working hours on lifestyles, perceived stress and working-life satisfaction among white-collar middle-management employees].

Recently, we have introduced the holistic method into health care of workers and aimed at improvement of Quality of Life (QOL). It has been made clear that primary prevention of diseases needs lifestyle appraisal. Therefore, we studied the daily working hours and the effects of long working hours on lifestyles, perceived stress and working-life satisfaction, which we used as a subjective index of Quality of Life (QOL), based on data obtained from a survey of 1,026 department chiefs and 2,902 section chiefs in 110 large companies in Japan in 1990. The results are summarized as follows. (1) The percentage of those working 10 hours per day was 41.6% for department chiefs and 40.4% for section chiefs, and for 11 or more working hours it was 24.1% in department chiefs and 30.9% in section chiefs. The younger both department and section chiefs, the longer their working hours. (2) Both department and section chiefs had a significant relationship between long working hours and poor sleeping habits, poor physical exercise, feeling busy, irregularity of daily life and irregularity of daily meals. The department chiefs had a significant relationship between long working hours and unbalanced nutrition or no hobbies. The section chiefs had a significant relationship between long working hours and drinking many cups of tea or coffee, taking a lot of salt or ill physical condition during the past six months.

Female↗
PubMed1995

Sinusoidal and exponential decays of postextrasystolic transient alternans in excised blood-perfused canine hearts.

We have recently reported that the postextrasystolic contractile potentiation decays in alternans after a compensatory pause in canine left ventricles even under normal coronary and contractile conditions. The transient alternans appears to consist primarily of a small-magnitude exponential decay and a large-magnitude sinusoidal decay. We, therefore, hypothesized that the contractility (y) of the postextrasystolic alternans beats (beat number x) could be expressed as y = a x exp[-(x-1)/b] + c x exp[-(x-1)/d] x sin[pi(x-0.5)] + yo, where a and c are the normalized magnitudes (relative to the preceding regular beat) of the two exponential terms in the first postextrasystolic beat, b and d are their time constants, and yo is the normalized magnitude of the post-alternans regular beat (approximately 1). The first exponential term represents the monotonic decay. The sine term multiplied by the second exponential term represents the alternating decay. Mathematical curve-fitting indicated: 1) the above equation very closely fitted the alternans data with a squared correlation coefficient of 0.9996 on average, 2) c was 7 times on average greater than a, indicating dominance of the sine component, 3) b and d were 2.5 and 1.0 beats on average, indicating a faster decay of the sine component, and 4) this b was comparable to the time constant of the exponential decay of the postextrasystolic potentiation after no compensatory pause. This study suggests that myocardium has a mechanism to switch the postextrasystolic potentiation between the exponential and alternans decays depending on the first postextrasystolic interval.

Animals↗
PubMed1995

Primary spinal chondrosarcoma localized in the cervical spinal canal and intervertebral foramen--case report.

A 48-year-old male presented with a very rare case of spinal chondrosarcoma localized in the cervical spinal canal and intervertebral foramen, but without marked destruction of the vertebral column. Spinal chondrosarcoma is characterized by radiological evidence of destruction of the surrounding bone structure and mottled calcification. Magnetic resonance imaging was useful in the diagnosis and determination of the extent of this spinal chondrosarcoma. However, preoperative differential diagnosis of the tumor was not possible based on neuroimaging evidence.

Cervical Vertebrae↗
PubMed1995

[Analysis of familial aggregation of ovarian and breast cancer in patients with ovarian cancer].

In 118 patients with common epithelial ovarian tumors (carcinomas and tumors of borderline malignancy) treated at Tsukuba University Hospital and Tsukuba-Gakuen Hospital, family histories of ovarian and breast cancer were obtained from medical records or in interviews, and familial aggregation of these cancers was examined. 1. A positive family history was found in 10 patients (8.5%). The high incidences of familial ovarian cancer and ovarian cancer in patients who were previously affected with breast cancer were statistically significant. 2. Patients with serous adenocarcinoma showed a significantly greater rate of positive family history than those with mucinous adenocarcinoma. 3. No significant correlation was seen between the clinical stage and a positive family history. 4. Every patient except one with a positive family history had onset of ovarian cancer after menopause. The age at onset for familial ovarian cancer cases was younger than that for the patients' relatives who were affected previously. 5. There were 14 healthy women considered to be at high risk for ovarian cancer among 5 familial ovarian and 2 familial ovarian and breast cancer aggregations. These preliminary findings suggest that screening for early ovarian cancer should be conducted in high risk relatives of familial cancer patients and women affected with breast cancer previously. More detailed studies are needed to define the occurrence of familial or hereditary ovarian and breast cancers in Japan.

Adenocarcinoma, Mucinous↗
PubMed1995

[MRI of the pituitary adenomas with reference to the hormonal activity].

Many studies in Magnetic Resonance Imaging (MRI) of pituitary adenomas are already performed. However, few reports exist about MRI findings of pituitary adenomas with reference to the hormonal activity, therefore, we evaluated this problem on the viewpoint of the signal intensity in MRI and pathological features. Fifteen patients with growth hormone producing adenoma (GH-group), 6 patients with prolactin producing adenoma (PRL-group), 15 patients with endocrinologically non-functioning adenoma (Null-group) and 9 cases with normal pituitary gland (normal control group) were examined. Signal intensity values in adenoma (or anterior lobe in normal control group) and in pons as standard value were measured in each cases, then their rates were calculated as signal intensity ratio (SIR). In 24 cases (14 in GH-group, 3 in PRL-group, 7 in Null-group), cellular density were examined with surgically resected specimens. In the T1-weighted images (T1 WIs), PRL-group and Null-group presented more hypointense tendency than normal control group. In the T2-weighted images (T2 WIs), only Null-group presented more hyperintense tendency than other groups. But significant correlation was not observed between SIR and cellular density.

Adenoma↗
PubMed1995

[Serum cardiac troponin-T in coronary artery bypass graft and mitral valve replacement].

Serum cardiac troponin-T was measured to evaluate perioperative myocardial injury in heart surgery. Twelve patients of coronary artery bypass graft (CABG) and nine of mitral valve replacement (MVR) were selected and the measurements were performed at 3 points-before, as well as after the surgery and on the first postoperative day. Elevated serum levels of troponin-T were observed in postoperative measurement in both groups (CABG 2.98 +/- 1.44, MVR 2.57 +/- 0.52 ng.ml-1), where all the preoperative values were less than 0.1 ng.ml-1. On the first postoperative day, CABG group showed a higher serum level of troponin-T than MVR group (6.05 +/- 4.16 vs. 2.57 +/- 2.12 ng.ml-1, P < 0.05 respectively). Taking another myocardial marker, such as CK-MB or myosin light chain I, into consideration, these data indicate that myocardial injury occurs during heart surgery and the grade of injury is severer in CABG than in MVR.

Aged↗
PubMed1994

Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins.

The immunosuppressant rapamycin (RAP) has been demonstrated to specifically inhibit the activity of p70 S6 kinase (p70s6k) and subsequent phosphorylation of ribosomal S6 protein in mammalian cells. Addition of RAP to proliferating lymphoid cells resulted in inhibition of protein synthesis before any changes in the rate of cell proliferation. When the cellular composition of proteins was examined by gel electrophoresis, RAP dramatically inhibited synthesis of selective proteins, particularly elongation factor 2 (eEF-2). The inhibition of eEF-2 synthesis by RAP was at the translational level. Further, RAP inhibited the polysomal association of mRNAs encoding not only eEF-2 but also elongation factor 1-alpha and ribosomal proteins without affecting mRNA translation of any of a number of nonribosomal proteins. Since levels of activity of p70s6k are correlated with the rate of biosynthesis of eEF-2, p70s6k might be involved in coordinate translational regulation of ribosomal protein mRNAs in higher eukaryotes, which have a conserved sequence at their 5' end. Specific inhibition of ribosomal protein synthesis likely explains the differential antiproliferative effect of RAP on proliferating and mitogen-activated quiescent cells.

Base Sequence↗
PubMed1994

NBQX reduces threshold of protein synthesis inhibition in focal ischaemia in rats.

The effect of the AMPA antagonist NBQX on peri-infarct inhibition of cerebral protein synthesis (CPS) was studied in rats subjected to 3 h occlusion of the left middle cerebral artery (MCA). Cerebral blood flow and CPS were measured with double tracer autoradiography and local ATP content was monitored by bioluminescence imaging. In untreated MCA-occluded animals the perfusion threshold of ATP depletion in cerebral cortex was 17 +/- 5 ml 100 g-1 min-1 and that of CPS inhibition was 49 +/- 13 ml 100 g-1 min-1. NBQX treatment (2 x 30 mg kg-1 after vascular occlusion) reduced the perfusion threshold of CPS inhibition to 16 +/- 6 ml 100 g-1 min-1 (p < 0.05) whereas that of ATP depletion was not affected (11 +/- 6 ml 100 g-1 min-1). The NBQX-induced pharmacological improvement of peri-infarct CPS is similar to the previously described amelioration of peri-infarct CPS by MK-801 and may contribute to the reduction of infarct size by this treatment.

Adenosine Triphosphate↗
PubMed1994

Inhibition of tubular morphogenesis in human microvascular endothelial cells by co-culture with chondrocytes and involvement of transforming growth factor beta: a model for avascularity in human cartilage.

Tube formation in collagen gel was induced in human omental microvascular endothelial (HOME) cells in the presence of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). TGF-alpha enhanced the expression of the tissue type plasminogen activator (t-PA) gene, whereas TGF-beta increased the expression of the PA inhibitor-1 (PAI-1) gene and inhibited that of the t-PA gene. TGF-beta inhibited the tube formation of HOME cells in type I collagen gel that was enhanced in response to TGF-alpha. We have recently established an angiogenesis model in vitro in which vascular endothelial cells on type I collagen gel in an inner chamber are co-cultured with other types of cells in an outer chamber. Here we examined whether the EGF/TGF-alpha-induced tube formation in HOME cells was modulated by human chondrocytes co-culture in the outer chamber. TGF-alpha-dependent tube formation of HOME cells was inhibited when human chondrocytes were co-cultured in the outer chamber. This chondrocyte-induced inhibition of tube formation was partly abrogated by co-administration of anti-TGF-beta antibody. These findings suggest that TGF-beta is partly involved in the human chondrocyte-dependent inhibition of tube formation by human microvascular endothelial cells. This is the first model system demonstrating that avascularity of human chondrocytes is partly due to TGF-beta family produced from them.

Cartilage↗
PubMed1994

Possible involvement of multidrug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine, etoposide and adriamycin in human glioma cells.

The multidrug-resistance phenotype in human tumors is partly associated with over-expression of the 170 kDa-P-glycoprotein encoded by the multidrug-resistance-1 (MDR1) gene. Another related, but non-P-glycoprotein, multidrug-resistance-associated protein (MRP) gene encodes a 190 kDa-membrane ATP-binding protein. Glioblastoma multiforme is a highly malignant primary neoplasm of the central nervous system which is refractory to anti-cancer chemotherapy, but the mechanism underlying this drug resistance is unknown. Out of glioma cell lines, 2, namely IN500 and T98G, which had elevated MRP mRNA levels, showed the highest resistance to multiple anti-cancer agents such as etoposide, vincristine and adriamycin, and decreased intracellular accumulation of etoposide. In the remaining 5 cell lines, various degrees of sensitivity to adriamycin and etoposide appeared to correlate with their respective MRP mRNA levels. Our study proposes that MRP may be involved in spontaneous multidrug resistance in human gliomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Cellular control of human multidrug resistance 1 (mdr-1) gene expression in absence and presence of gene amplification in human cancer cells.

The Kst-6 cell line is a human KB carcinoma cell line that has a stably integrated chloramphenicol acetyl-transferase (CAT) reporter gene under the control of the human mdr-1 promoter. Using Kst-6 cells as the parental cell line, five vincristine-resistant sublines, designated Kst-V5, -V25, -V50, -V75, and -V100, were isolated by exposure to increasing concentrations of drug. These sublines showed increased resistance to vincristine when compared with parental Kst-6 cells. Two sublines, V25-1 and V25-2, were further isolated from Kst-V25 after culture in the presence of vincristine, and V100-1 and V100-2 were also isolated from Kst-V100. Southern analysis demonstrated mdr-1 gene amplification in Kst-50, Kst-V75, Kst-V100, V100-1, and V100-2 cells, respectively, but not in Kst-V5, Kst-V25, V25-1, and V25-2 cells. In contrast, increased mdr-1 expression was documented by Northern analysis in Kst-V25, V25-1, and V25-2 cells and five cell lines with mdr-1 amplification. Southern blot analysis utilizing a CAT probe demonstrated a stable copy number in all vincristine-resistant sublines. However, Northern analysis documented increased CAT expression in Kst-V5, Kst-V25, V25-1, and V25-2 cells but reduced mRNA levels in the cell line with amplification of the endogenous mdr-1 gene. Expression of the CAT gene was increased along with the endogenous mdr-1 gene in the early steps of the selection but decreased with the onset of gene amplification. There appeared almost similar mRNA levels of two trans-acting factor genes, SP-1 and MDR-NF1/YB-1, which are supposed to be involved in mdr-1 gene promoter activation, among all cell lines used in this study. These findings suggest that transcription of both the CAT gene fused to the mdr-1 promoter and the endogenous mdr-1 gene is enhanced through activation by trans-acting factors in the early steps of drug selection. However, the quantity of trans-activating factor is limiting, and with the onset of gene amplification, less is available for activation of the CAT gene, resulting in decreased expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Increased expression of DNA topoisomerase I gene and collateral sensitivity to camptothecin in human cisplatin-resistant bladder cancer cells.

We established three cis-diamminedichloroplatinum(II) (cisplatin)-resistant cell lines, T24/DDP5, T24/DDP7, and T24/DDP10, by the stepwise exposure of T24 human bladder cancer cells to increasing concentrations of cisplatin. The resistance to cisplatin of T24/DDP5, T24/DDP7, and T24/DDP10 cells was 2.2-, 5.2-, and 8.4-fold that of the parental T24 cells, respectively. The cisplatin-resistant cell lines also showed an increased resistance to vincristine, although their sensitivities to Adriamycin and etoposide resembled that of T24. In contrast, the cisplatin-resistant cells developed a collateral sensitivity to (4s)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)carbonyl oxy]dione hydrochloride trithydrate, a camptothecin derivative, and its active metabolite, 7-ethyl-10-hydroxy-camptothecin, that targets DNA topoisomerase I. Both a Northern blot analysis and an immunoblot analysis demonstrated increased cellular levels of DNA topoisomerase I mRNA in the resistant cell lines. However, the expression of DNA topoisomerase II in the three resistant cell lines did not differ significantly from that in the T24 cells. No significant differences in the glutathione S-transferase pi levels were observed, although the intracellular content of glutathione in the T24/DDP7 cells was slightly but significantly increased. In addition, the intracellular platinum concentration correlated negatively with the degree of cisplatin resistance and was found to be significantly decreased in T24/DDP10 at an external cisplatin concentration of 20 micrograms/ml. These results suggest that the increased levels of DNA topoisomerase I mRNA thus play an important role in cisplatin resistance and produce a collateral sensitivity to (4s)-4,11-diethyl-4-hydroxy-9[(4-piperidinopiperidino)carbonylo xy]dione hydrochloride trithydrate and 7-ethyl-10-hydroxycamptothecin in these cisplatin-resistant bladder cancer cell lines. In addition, the presence of decreased intracellular cisplatin accumulation may also contribute to the acquisition of resistance to cisplatin in these cell lines.

Blotting, Northern↗
PubMed1994

HPRT yeast artificial chromosome transfer into human cells by four methods and an involvement of homologous recombination.

The transfer of a yeast artificial chromosome (YAC) into mouse and human cell lines was effected by four methods, and the efficiency and integrity of the incorporated YAC DNA were compared. A 500 kb YAC containing the human hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene was transferred more efficiently by polyethylene glycol-mediated fusion than by lipofection, electrofusion, or electroporation. Southern blot analysis demonstrated that PEG fusion lines yielded fragments of the size of the original YAC clone, whereas lipofection and electroporation did not. Two of 53 fusion lines showed 6-thioguanine resistance and confirmatory disruption of the HPRT gene in the YAC DNA, suggesting that the YAC DNA was integrated by homologous recombination with the endogenous HPRT gene region.

Animals↗
PubMed1994

Chimeric YACs were generated at unreduced rates in conditions that suppress coligation.

Chimerism is a major limitation of current YAC libraries. A method based on partially filled-in ends of restriction fragments was designed to avoid coligation as a possible source of chimeras. Model experiments using plasmid DNA as an insert showed that coligation was clearly avoided by this method. Pilot collections of YACs with an average insert size of 650kb were then constructed with and without the partial fill-in treatment. Starting from a mixture of a equal amounts of human and mouse DNA, none of 108 clones was positive by hybridization with both Alu and B2 probes, again suggesting that coligation was effectively blocked. However, 4 out of 10 clones still hybridized to 2 or more locations by FISH on chromosomes in human metaphase spreads, level similar to that in the clones made without the partial fill-in step. These results strongly suggest that chimeric clones generally arise by a mechanism independent of coligation, presumptively based on recombination.

Animals↗
PubMed1994

Elongation factor 2 mutants deficient in diphthamide formation show temperature-sensitive cell growth.

Protein synthesis elongation factor 2 (EF-2) from eukaryotes contains an unusual modified histidine residue, termed diphthamide. Diphthamide has been shown to be a site of ADP-ribosylation by bacterial toxins, but its function remains obscure. We expressed mutant genes of EF-2 with substitutions of 19 other amino acids for His-699, which is modified to diphthamide, in yeast cells and found that they can be classified into three groups. In the first group (Group 1), replacement of His-699 by the basic amino acid Arg or Lys showed not only loss of EF-2 activity but also inhibitory effects on the growth of cells co-expressing wild-type EF-2. In the second group (Group 2), replacement with Gly, Pro, Ser, or Asp resulted in nonfunctional EF-2, but it did not affect the growth of cells co-expressing wild-type EF-2. In the third group (Group 3), replacement by one of the other 13 amino acids resulted in a functional EF-2. In the Group 3 mutants, EF-2 was not ribosylated by diphtheria toxin, indicating that the mutant EF-2s did not form diphthamide. However, the viable cells grew more slowly than cells expressing wild-type EF-2 and showed temperature sensitivities. This result suggests that diphthamide may confer heat resistance on EF-2, although it still may be active without diphthamide at a normal temperature.

Amino Acids↗
PubMed1994

IHF supresses the inhibitory effect of H-NS on HU function in the hin inversion system.

In the hin-mediated DNA inversion system, HU facilitates formation of the synaptic complex composed of two recombination sites spaced 996 bp apart and of the enhancer situated between them, by looping the DNA as to promote interaction of Hin invertase with the Fis enhancer factor [Johnson et al., Nature 329 (1987) 462-465]. The HU requirement for the in vivo hin-mediated inversion was demonstrated previously [Wada et al., Gene 76 (1989) 345-352; Hillyard et al., J. Bacteriol. 172 (1990) 5402-5407; Haykinson and Johnson, EMBO J. 12 (1993) 2503-2512] and in the current experiments. This HU action, however, required IHF when H-NS was present in the cell; i.e., the inversion reaction of the hin-invertible DNA fragment carried by the pKK1202R plasmid proceeded efficiently in host cells either deficient in H-NS or in the presence of both H-NS and IHF, but not in the cells depleted for IHF alone. The level of hin mRNA in mutant cells lacking HU or IHF, in which hin inversion did not occur, was normal or slightly increased. When IHF was absent, the stimulating effect of HU on in vitro DNA circle formation of a 125-bp hin fragment between hixL and the enhancer where Fis binds was inhibited by H-NS. The present study provides an example of a multi-component interaction between HU, H-NS and IHF on the hin DNA region, which contains three characteristic sites, a d(A/T)4 stretch and bent DNA site, and two putative IHF-binding sites.

Bacterial Outer Membrane Proteins↗