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Biomedical subjects

M Kono

Publications and source records attributed to M Kono.

At least 145 records · Page 8Linked to original sources
PubMed1994

trans activation by the full-length E2 proteins of human papillomavirus type 16 and bovine papillomavirus type 1 in vitro and in vivo: cooperation with activation domains of cellular transcription factors.

Papillomaviral E2 genes encode proteins that regulate viral transcription. While the full-length bovine papillomavirus type 1 (BPV-1) E2 peptide is a strong trans activator, the homologous full-length E2 product of human papillomavirus type 16 (HPV-16) appeared to vary in function in previous studies. Here we show that when expressed from comparable constructs, the full-length E2 products of HPV-16 and BPV-1 trans activate a simple E2- and Sp1-dependent promoter up to approximately 100-fold in human keratinocytes and other epithelial cells as well as human and animal fibroblasts. Vaccinia virus-expressed, purified full-length HPV-16 and BPV-1 E2 proteins bound a consensus E2 site with high specific affinities (Kd = approximately 10(-9) M) and stimulated in vitro transcription up to six- to eightfold. In vivo and in vitro trans activation by either E2 protein required cooperation with another activator, such as Sp1, or other factors that interact with papillomavirus promoters, such as AP-1, Oct-1, nuclear factor 1/CTF, transcriptional enhancer factor 1, or USF. The glutamine-rich domain B of Sp1 or the mutually unrelated activation domains of other transcription factors were necessary and sufficient for cooperation with either E2 factor. We conclude that like BPV-1 E2, the HPV-16 E2 protein has the potential to function as a strong activator of viral gene expression in cooperation with cellular transcription factors.

Base Sequence↗
PubMed1994

The effects of intravenous clonidine on regional myocardial function in a canine model of regional myocardial ischemia.

This study was performed to investigate the effects of clonidine on regional myocardial function in a canine model of regional myocardial ischemia. Myocardial systolic shortening (%SS) was used as an index of regional myocardial function. In eight dogs after thoracotomy, the left circumflex coronary artery (LCX) was occluded by screw clamp until regional myocardial function became impaired. After partial occlusion of the LCX, cumulative doses of clonidine (1.25, 2.5, and 5.0 micrograms/kg) were administered intravenously. After administration of clonidine, heart rate, mean arterial blood pressure (MAP), and norepinephrine concentration decreased in a dose-dependent manner. At a dose of 5.0 micrograms/kg of clonidine, the LCX flow and systolic shortening of the LCX area decreased to 76% and 81% of the poststenotic values (P < 0.05, respectively), whereas no significant changes were observed at a dose of 1.25 and 2.5 micrograms/kg. These results suggest that clonidine administration and an associated decrease in arterial blood pressure deteriorates regional myocardial function of the ischemic myocardium.

Animals↗
PubMed1994

Evaluation of antiseptics by the modified phenol coefficient method: sensitivity of methicillin-resistant Staphylococcus aureus.

The relationship between an effective concentration and the duration of exposure to antiseptics was evaluated in strains of Staphylococcus aureus with a known genetic background, which include methicillin-resistant strains, using a modified version of the phenol coefficient method as part of an effort to investigate the antiseptic resistance of S. aureus. Chlorhexidine digluconate killed an antiseptic-sensitive strain within 1.5 min at 22 degrees C at a standard concentration (0.1%), whereas resistant strains still survived after 1.5 min. Povidone-iodine killed the sensitive strain within 1.5 min at a concentration of 0.1%, whereas it took this agent 3.0 and 4.5 min to kill low- and high-level resistant strains, respectively, at a concentration of 0.8%. These results indicate that the modified phenol coefficient method used is suitable for the evaluation of the sensitivity of microorganisms to antiseptics. An antiseptic-resistant chain that was associated with the ebr gene exhibited cross-resistance to povidone-iodine.

Anti-Infective Agents, Local↗
PubMed1994

Substrates and inhibitors of antiseptic resistance in Staphylococcus aureus.

The range of substrates of antiseptic resistance associated with the ebr gene is very wide and includes antiseptics, DNA-intercalating drugs and preservatives which have no quaternary ammonium group in methicillin-resistant Staphylococcus aureus. Antiseptic resistance was inhibited by calcium channel blockers and calmodulin inhibitors similarly to the resistance to multiple antitumor agents encoded by the mdr gene in human cells. These results show that the common properties of the mdr gene and the ebr gene may be shared by the mechanisms that are involved in the removal of toxic substances from the cell.

Anti-Infective Agents, Local↗
PubMed1994

Expression in Escherichia coli of a TetK determinant from Staphylococcus aureus.

The expression in Escherichia coli of a tet(K) gene, which originated in Staphylococcus aureus, was studied. The minimum inhibitory concentration (MIC) of tetracycline (TC) for E. coli cells that carried the tet(K) gene was only slightly higher than that for the recipient cells. This result indicated that the level of expression of the tet(K) gene in E. coli was very low. Insertion of a lac promoter into the upstream region of the tet(K) gene resulted in a slight increase in the MIC, from 12.5 to 50 micrograms/ml in the presence of isopropyl-beta-D-thiogalactopyronoside. An altered tet(K) gene, in which the initiation codon and the ribosome-binding site (RBS) were changed from TTG to ATG and from GAGG to GGAGG, respectively, and in which the distance between the RBS and the initiation codon was increased from 4 to 11 bases, was associated with high-level resistance to TC, with a MIC of 200 micrograms/ml. The MIC resembles that associated with expression of the tetA(B) gene of E. coli. These results indicate that the barrier to expression of the tet(K) gene in E. coli is located at the initiation of translation.

Base Sequence↗
PubMed1994

Mitomycin derivatives having unique condensed-ring structures. Their synthesis and antitumor activity.

A series of mitomycin derivatives 1-3 having unique condensed-ring structures was synthesized and evaluated for their anticellular and antitumor activity. These compounds were synthesized by the Michael addition of 1.3-dicarbonyl compounds to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylenemitosanes (4-6, and 14) and the subsequent cyclization. For the preparation of 1. the allyloxycarbonyl (Aloc) group was employable for the protection of the aziridine (1a-N-H), since the deprotection proceeded without decomposition of the substrates under the mild conditions with Pd(0) and HCO2H-NEt3. Among these structurally unique derivatives, compounds 1a, 1b, 1d and 1e were quite potent against HeLa S3 human tumor cells and sarcoma 180 solid tumor in mice.

Animals↗
PubMed1994

[Clinical evaluation of dynamic MRI in the re-diagnosis of therapeutic effect and recurrence after transcatheter arterial embolization for hepatocellular carcinoma].

We evaluated re-diagnostic ability of dynamic MRI as compared with T2 weighted image in the diagnosis of primary therapeutic effect and tumor recurrence after transcatheter arterial embolization (TAE) for hepatocellular carcinoma. Thirty-four nodules in 30 patients with hepatocellular carcinoma were estimated based on operative and angiographic findings. According to the time when dynamic MRI was taken, nodules were classified as a short-term observation group consisting of 15 nodules obtained within a month after TAE, or as a long-term observation group consisting of 19 nodules obtained over a month after TAE. In the short-term observation group, sensitivity, specificity, accuracy was 89%, 100%, 93% on dynamic MRI and 78%, 67%, 73% on T2WI, respectively. In the long-term observation group, these were 94%, 100%, 95% on dynamic MRI and 100%, 33%, 89% on T2WI and 94%, 67%, 89% on Lipiodol-CT, respectively. In both groups, dynamic MRI was superior in accuracy. Conclusively, we consider that dynamic MRI is a most accurate diagnostic method that should be added to routine MRI after TAE. Especially in the case diagnosed positive on T2WI, the usefulness of dynamic MRI should be emphasized to determine the schedule of the therapy, because the cases that were false positive on T2WI were accurately diagnosed on dynamic MRI.

Aged↗
PubMed1994

Effect of beta-lactamase on minimum inhibitory concentrations of methicillin in methicillin-resistant Staphylococcus aureus.

A study was undertaken to determine whether the production of penicillin-binding protein-2' (PBP-2') and the production of beta-lactamase were related to the minimum inhibitory concentrations of methicillin (DMPPC) in various strains of methicillin-resistant Staphylococcus aureus. The amount of PBP-2' produced by the low-level resistant strain L20A was small and the strain became resistant to DMPPC as a result of inactivation of DMPPC by beta-lactamase. The largest amount of PBP-2' produced was in a moderately resistant strain L21A but the MIC was not high since the strain was not capable of producing beta-lactamase and the population of cells was heterogeneous. The amount of PBP-2' produced in the high-level resistant strain L457A was lower than that in strain L21A but the MIC was high as a result of the production of beta-lactamase. Production of PBP-2' was essential for resistance to methicillin but production of beta-lactamase had a major effect on the MIC.

Bacterial Proteins↗
PubMed1993

Genetic mapping in Bacillus subtilis 168 of the aadK gene which encodes aminoglycoside 6-adenylyltransferase.

Bacillus subtilis 168 has an aadK gene, which encodes aminoglycoside 6-adenylyltransferase, a streptomycin-modifying enzyme, on its chromosome. To characterize the aadK gene, we constructed a B. subtilis 168 strain that carried the chloramphenicol resistance gene near the aadK on the chromosome and an aadK deletion mutant using an integration technique. The aadK gene was mapped between azlB and pheA on the chromosome of B. subtilis 168. The aadK deletion mutant was slightly more susceptible to streptomycin than the original strain. The result indicates that the aadK gene contributes low-level resistance to streptomycin in B. subtilis 168.

Bacillus subtilis↗
PubMed1993

Effect of the arginine-82 to alanine mutation in bacteriorhodopsin on dark adaptation, proton release, and the photochemical cycle.

The pH dependence of the rate constant of dark adaptation (thermal isomerization from all-trans- to 13-cis-bR) drastically changes when Arg82 of bacteriorhodopsin is replaced by an alanine. In the wild type (WT) the rate decreases sharply between pH 2.5 and pH 5. In R82A the sharp decrease is shifted to pH > 7. This correlates with the shift in the pK of the purple-to-blue transition from pH 2.6 in the wild type to pH 7.2 in the mutant (in 150 mM KCl). We propose that the same group that controls the purple-to-blue transition, namely, Asp85, catalyzes dark adaptation. The rate of dark adaptation in the R82A mutant is proportional to the fraction of protonated Asp85, indicating that dark adaptation occurs when Asp85 is transiently protonated. Thermal isomerization is at least 2 x 10(3) times more likely when Asp85 is protonated (blue membrane) than when it is deprotonated (purple membrane). The pH dependence of dark adaptation in the WT can be explained by a model in which the rate of dark adaptation in the WT is also proportional to the fraction of protonated Asp85 and that the pK of Asp85 depends on some other group, X, which deprotonates (or moves away from Asp85) with pK9 and causes the shift in the pK of Asp85 from 2.6 to 7.2. The quantum yield of light adaptation is at least an order of magnitude less in R82A as compared to the WT. The rise time of M formation is very fast in R82A and, unlike the WT, pH independent (1 microsecond versus 85 and 6 microseconds in the WT at pH 7 and 10, respectively). The activation energy of the L to M transition is 6.9 kcal/mol versus 13.5 kcal/mol in the WT. Thus the loss of a positive charge in the active site greatly increases the rate of light-induced deprotonation of the Schiff base. In the R82A mutant, the M decay at pH > 8.8 is much faster than the recovery of initial bR, which suggests a decrease in the rate of back-reaction from N to M. In a suspension of R82A membranes the rate of proton release as measured by the pH-sensitive dye pyranine is delayed by at least 20-fold (in 2 M KCl), while the uptake of protons did not change much (12 ms in the WT versus 8 ms in R82A).(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗
PubMed1993

pH dependence of light-induced proton release by bacteriorhodopsin.

We have measured the current generated by light-activated proton release from bacteriorhodopsin into solution as a function of both pH and ionic strength. We find that proton release into solution decreases with increasing pH with an intrinsic pKa of 8.2 +/- 0.2. This pH dependence indicates that the deprotonation of a certain group inhibits or abolishes proton release. Under physiological conditions, this group either releases a proton directly into solution or interacts with the site of proton release. The most immediate candidates for this protonatable species are tyrosine-57, tyrosine-185, arginine-82, and water; acting individually or cooperatively. The salt dependence of the apparent pKa of this group also allows us to calculate the surface charge density of about -5 charges per bacteriorhodopsin, compatible with previous estimates.

Bacteriorhodopsins↗
PubMed1993

[Clinical utility of computed radiography (CR) for the diagnosis of lung cancer].

To clarify the clinical utility of computed radiography (CR) for the diagnosis of lung cancer, several kinds of image-processed CR images were compared with conventional radiographs (CXR). The images in the three patients with peripheral lung cancer were processed by the following six types: 1) processing close to CXR (plain CR), 2) wide latitude and high frequency emphasis (wide CR), 3) advanced high frequency emphasis (HE-CR), 4) lower frequency emphasis (LE-CR), 5) single exposure dual energy subtraction (ES) and 6) ES with lower frequency emphasis (LE-ES). In the two cases of hilar lung cancer, 1) plain CR, 2) wide CR, 3) CR tomographs similar to CXR tomographs (plain CR-TOMO) and 4) high frequency emphasized CR tomographs (HE-CR-TOMO) were processed. Twenty-six radiologists rated the image-processed CR images using a 5 point rating scale method. The following results were found for the evaluation of lung anatomy: almost all image-processed CR images were equal or superior to CXR; especially scores for plain CR were better than those for CXR in all anatomical structures studied; scores for ES were superior to those for plain CR in the bilateral main bronchi, left upper lobe bronchus and right paratracheal stripe; and scores for CR tomographs were better than those for CXR tomographs. In peripheral lung cancer, plain CR and ES were superior to CXR. Especially ES had the best scores. In hilar lung cancer, plain CR and CR tomographs were judged better than CXR and CXR tomographs. These findings indicate the usefulness of CR images for the diagnosis of lung cancer.

Aged↗
PubMed1993

5-HT3 receptor antagonists. 2. 4-Hydroxy-3-quinolinecarboxylic acid derivatives.

A series of 4-hydroxy-3-quinolinecarboxylic acid derivatives (6) and 4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid derivatives (7) were designed and synthesized as 5-HT3 receptor antagonists. Molecular modeling studies suggested that the 3-carbonyl moiety in 6 was almost coplanar to the plane of an aromatic ring, but in 7 there was a 30 degrees deviation. 4-Hydroxy substitution in quinoline derivatives enhanced affinity for the 5-HT3 receptors, and endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-4-hydroxy-3- quinolinecarboxamide (6f) exhibited the most potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.1 micrograms/kg, iv) among quinoline derivatives 6. Although 4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives (7a) exhibited higher affinity (e.g., 7d: Ki = 0.48 nM) for the 5-HT3 receptors than ondansetron (Ki = 7.6 nM) or granisetron (Ki = 2.1 nM), these amides showed less potent activity in the B-J reflex test than the reference compounds. Interestingly, the ester derivatives 7c, 7f, and 7h eliminated affinity for the 5-HT3 receptors. These unusual structure-activity relationships and the deviation of the 3-carbonyl moiety from the plane of an aromatic ring suggest that the active conformation of 7a might be different from the proposed one for the preceding 5-HT3 antagonists. Thus, 6f was chosen for further studies. No receptor binding for a variety of ligands was significantly antagonized by 6f. Comparing the ratios of the ED50 value in the B-J reflex test (rat, iv) with the LD50 value in acute lethal toxicity (mouse, iv), 6f was proved to have a 600-fold wider margin of safety than ondansetron. Compound 6f dose-dependently attenuated both the incidence and frequency of emetic episodes induced by cisplatin in the dog (ED50 = 14 micrograms/kg, iv) more potently than ondansetron (ED50 = 210 micrograms/kg, iv). Compound 6f (KF-20170) is now under further investigation as a drug for treating gastrointestinal disorder.

Animals↗
PubMed1993

[A study of the utility of the MR image for the diagnosis of thymic tumors--imaging and pathologic correlation].

MR imaging was performed in 25 patients with thymic tumors (five with non-invasive thymomas, 15 with invasive thymomas, and five with thymic carcinomas), and the MR imaging appearance was compared with the pathological findings. Non-invasive thymomas showed generally oval or round masses with well-defined margins and homogeneous intensity on T1- and T2-weighted images. Invasive thymomas showed a multinodular appearance in 79% (11/15) of cases, and an internodular difference in signal intensity (IDSI) in 64% (7/11) on T2-weighted images. It was considered that the IDSI on T2-weighted images correlated pathologically with the hemorrhagic and/or necrotic areas and hyalinization. The IDSI seemed to be a characteristic finding of invasive thymomas. The histological findings and MR imaging appearance of thymomas were compared. The predominantly epithelial type showed a low incidence of nodular appearance but showed marked IDSI on T2-weighted images. Therefore, it is more likely that the predominantly epithelial type induced more varied intratumoral changes than other types. Extension of thymic carcinomas was similar to that of invasive thymomas on MR imaging, but thymic carcinomas showed no definite nodular appearance. In conclusion, MR images in thymic tumors were useful for not only determining the morphology of the tumor but also the tissue characteristics. Therefore, MR imaging can be a useful modality to correlate with the histological findings and biological behavior of thymic tumors.

Adult↗
PubMed1993

A quantitative pathological investigation of the cervical cord, roots and ganglia after long-term amputation of the unilateral upper arm.

A pathological study was conducted on an autopsied patient who had undergone amputation of the right arm at the level of the shoulder 38 years prior to death. The numbers of anterior horn cell, spinal ganglion cells and myelinated fibers in the anterior and posterior spinal roots at the cervical segments were examined quantitatively and compared with those of age-matched control subjects. On the amputation side, anterior horn cells, spinal ganglion cells and large myelinated fibers of the anterior and posterior roots were decreased in number. In addition, on the spared side, the medium-sized neurons of Rexed's lamina IX were shrunken, or decreased in number, and the number of small- and medium-sized myelinated fibers in the anterior roots was decreased. These findings indicate that the long-term effects of axonal amputation induce retrograde degeneration of the anterior horn and spinal ganglion cells on the amputation side, resulting in atrophy and a decrease of medium-sized neurons in the anterior horn even on the contralateral, spared side.

Amputation, Traumatic↗