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Biomedical subjects

M Kono

Publications and source records attributed to M Kono.

At least 163 records · Page 9Linked to original sources
PubMed1993

Disposition and metabolism of KW-2149, a novel anticancer agent.

KW-2149 is a new derivative of mitomycin C (MMC). The plasma concentrations, distribution, metabolism, and excretion of [3H]-KW-2149 in normal and tumor-bearing mice after i.v. administration of 16.6 mg/kg were investigated. The plasma radioactivity decreased biexponentially after i.v. administration in normal mice. However, the unchanged drug disappeared rapidly, showing a half-life (t1/2) of 9.7 min, which was shorter than MMC's (18 min). The radioactivity was excreted in mouse urine (33%) and feces (58%) within 144 h. High radioactivity was distributed in the gallbladder, liver, kidney, pancreas, and lung at 1 h after i.v. administration to normal mice. The tumor concentration was lower than the plasma or blood concentration. The lowest radioactivity was observed in the brain. The metabolic rate of KW-2149 was very rapid. The methyl sulfide form (M-16), the symmetrical disulfide dimer (M-18), and the albumin conjugate were detected in plasma, which possessed anticellular activity. The specific anticellular activity of these compounds against uterine carcinoma (HeLa S3) was 1/100, 1, and 1/20 respectively, as compared with that of KW-2149.

Animals↗
PubMed1993

Comparison of uptake of mitomycin C and KW-2149 by murine P388 leukemia cells sensitive or resistant to mitomycin C.

KW-2149, a new mitomycin C (MMC) derivative, inhibited the growth of murine P388 leukemia in vitro at 20-fold lower concentrations than those of MMC. KW-2149 was also effective in inhibiting the growth of MMC-resistant P388 (P388/MMC) cells. To elucidate these characteristics of KW-2149, its uptake and efflux were compared with those of MMC in MMC-sensitive and -resistant P388 cells. Both MMC and KW-2149 accumulated rapidly in P388 cells after incubation at the concentration of 0.47 and 0.024 microM, respectively, which were the IC50 values at 1-h exposure. Although this concentration of KW-2149 was 20 times lower than that of MMC, its intracellular concentration was little more than that of MMC, suggesting that KW-2149 accumulated in the cells quite efficiently. The accumulated KW-2149 in the cells after 1-h treatment remained for as long as 24 h after the incubation of the cells in drug-free medium, suggesting that most of the intracellular KW-2149 or MMC was bound to cellular components. The ratios of resistance of P388/MMC cells to MMC and KW-2149 were 34 and 8.8, respectively, at 1-h exposure, suggesting that P388/MMC cells were partially resistant to KW-2149 in vitro. P388/MMC cells also showed partial resistance to cisplatin, Adriamycin, m-AMSA, and etoposide. The accumulation of MMC in P388/MMC cells was lower than that in P388 cells, although the size of the former cells was almost equal to that of the latter. As a result, the amount of DNA-bound MMC was lower in P388/MMC cells than in P388 cells, suggesting its involvement in the mechanisms of MMC resistance in P388/MMC cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Studies on the incidence of hepatocellular carcinoma in heavy drinkers with liver cirrhosis.

The incidence of hepatocellular carcinoma (HCC) in heavy drinkers who drank more than 130 g per day for more than 10 years, and non-drinkers with cirrhosis who were positive or negative hepatitis C virus (HCV) markers, was analyzed in order to evaluate the effect of a large amount of alcohol on the development of HCC. A parallel study was also conducted in some patients from the aspect of HCV genotypes. Among 57 heavy drinkers with liver cirrhosis, HCV marker was positive in 36 patients (C+Al group) and negative in 21 patients (Al-alone group). Eighty-one patients with liver cirrhosis of non-drinkers were positive for HCV markers (C-alone group). HCV infection was involved in 63% of heavy drinkers with cirrhosis and 44% of patients with HCC. The majority of HCC patients in the C+Al group was infected with HCV through routes other than blood transfusion. HCC developed at a younger age in patients of the C+Al group than in patients of the C-alone group without relation to history of blood transfusion. In more than a third of patients who had tattoos or used stimulants in the C+Al group, HCC developed without a history of blood transfusion. These results suggest that heavy drinking enhances the development of HCC. The HCV genotypes in patients with HCC were all type II, except for one case of type III and one unclassified. The mixed type of HCV was often found in patients who had a blood transfusion or tattoo, suggesting that there may be some correlation between the routes of HCV infection and the diversity of genotypes.

Adult↗
PubMed1993

Detection of plasmid DNA in Erysipelothrix rhusiopathiae isolated from pigs with chronic swine erysipelas.

Forty-three strains of Erysipelothrix rhusiopathiae, isolated from pigs with chronic swine erysipelas, were examined for the presence of plasmid DNA by agarose gel electrophoresis and electron microscopy. Seven of these strains were found to contain plasmids of which number were varied from 1 to 6. The plasmids ranged from 1.4 to 86 kb in size. This is the first reported evidence for plasmid DNA in E. rhusiopathiae. The functions of the plasmids are unknown at present.

Animals↗
PubMed1993

Synthesis and structure-activity relationships of new dimeric mitomycin derivatives; 7-N,7'-N'-bis(omega-thioalkyl)dimitomycins.

The reaction between mitomycin A (1) and cysteamine afforded 7-N,7'-N'-bis(2-thioethyl)dimitomycin C (7), 7-N-[2-[(2-aminoethyl)dithio]ethyl]mitomycin C (8), and 7-methoxy mitosenes (10, 11). The structures of 7 and 8 were elucidated on the basis of spectroscopy and reactions between 1 and 8, and 1 and cystamine. The observation of the time course for the reaction revealed the mechanism of the formation of 7 and 8. The rapid oxidation of cysteamine by the quinone of 1 gave cystamine, which was trapped by 1 to give 8, and 8 was additionally reacted with 1 to give 7. Since 7 showed significant antitumor activities, related 7-N,7'-N'-bis(omega-thioalkyl)dimitomycins were synthesized. They also showed remarkable antitumor activities against HeLa-S3 in vitro, sarcoma 180 (sc-ip), leukemia P388 (ip-ip) in vivo. In these evaluations, compound 7 demonstrated unique potency.

Animals↗
PubMed1993

New development of integrated CT simulation system for radiation therapy planning.

In order to put more accurate radiotherapy into practice, a radiotherapy planning system using CT, which is named CT simulation system, has been developed and introduced at Kobe University Hospital. The CT simulation system consists of a CT scanner, an image processing work-station, and a laser marking system. The target area of radiation is determined on each CT axial image or scout view in the work-station. Three-dimensional treatment planning is feasible on the basis of the two-dimensional tumor information in CT axial images. After setting treatment parameters, the contour of the radiation field on beam's eye view and the iso-center position are calculated by computer. This system makes it possible to choose an appropriate irradiation method and an optimal dose distribution. In the present study we examined the fundamental capability of this system. The laser marking system proved to have a very high degree of accuracy. The outcome of a phantom test raised the strong possibility that this system may be applied clinically. In addition to these basic findings, this paper describes preliminary clinical observations that support the good reproducibility of the radiation field projected with the CT simulator. In conclusion, this system is of high value for radiation therapy planning.

Humans↗
PubMed1993

Survival ability of clinical isolates of methicillin-resistant Staphylococcus aureus.

The survival abilities of methicillin-resistant strains of Staphylococcus aureus were compared with those of sensitive strains. Absorbent cotton was inoculated with 10(8) cells of each strain tested and stored at 30% humidity at 25 degrees C. The numbers of cells of sensitive strains decreased significantly to well below those of resistant strains after 4 weeks, while cells of resistant strains remained above 10(3) after 14 weeks.

Anti-Bacterial Agents↗
PubMed1993

Clinical utility of Gd-DTPA-enhanced magnetic resonance imaging in lung cancer.

Magnetic resonance (MR) imaging has both advantages and disadvantages in its application in lung cancer staging. Because of its ability to provide superior contrast resolution and to display structures in many planes, MR imaging is better than computed tomography (CT) for the detection of mediastinal and chest wall invasion. MR imaging also is more sensitive than CT for detection of hilar and mediastinal lymph node enlargement. Multiplanar T1- and T2-weighted images are optimal for differentiating lymph nodes from large vessels without the need for contrast enhancement; in these cases administration of Gd-DTPA provides no more information than plain MR images. MR studies should be used for examining patients with suspected mediastinal or chest wall invasion and those who have equivocal hilar or mediastinal adenopathy. The shortening effect of Gd-DTPA on the T1 value results in a high signal. This effect is dependent upon both the perfusion and diffusion of the contrast agent and the amount of extracellular fluid. The distribution of Gd-DTPA is similar to that of iodinated water-soluble contrast media. Gd-DTPA examination should be tailored to provide information regarding blood flow, vascularity, and permeability, none of which is easily appreciated on CT or plain MR images. Applications for which Gd-DTPA enhancement may be helpful include differentiating between malignant and benign pulmonary masses, differentiating between hilar lung cancer and peripheral postobstructive atlectasis or pneumonia, determining therapeutic effect after radiation therapy, and differentiating between recurrent or residual tumor and radiation pneumonitis.

Diagnosis, Differential↗
PubMed1993

Interstitial lung disease in rheumatoid arthritis: assessment with high-resolution computed tomography.

Interstitial lung disease (ILD) is a frequent manifestation of rheumatoid arthritis (RA), and it has a close bearing on the prognosis of RA patients. Computed tomography (CT) has been shown to be excellent for the diagnosis of diffuse lung disease. In this study chest radiographs and high-resolution CT (HRCT) scans were obtained in 91 patients with RA to evaluate their ILD precisely. By HRCT 43 patients could be diagnosed as having interstitial pneumonitis (IP), and 5 could be diagnosed as having bronchiolitis. The remaining 43 patients were normal by HRCT. Chest radiographic findings were consistent with the HRCT findings in approximately 50% of patients with IP. HRCT was superior to chest radiographs for the detection of early interstitial changes. The histogram of HRCT values might be a useful adjunct to HRCT diagnosis by adding some degree of objectivity. HRCT is useful for the diagnosis of ILD in patients with RA.

Adult↗
PubMed1993

Multiple primary lung cancers: radiographic and bronchoscopic diagnosis.

The article reports a review of 1140 cases of primary lung cancer diagnosed between 1974 and 1987 (13-year period) to examine the clinicopathologic features of multiple primary lung cancer. The following criteria were used: There were no malignant tumors in other organs; the tumors were separate or located in different lobes; the tumors were of different histologic types; if the histologic types were similar, there was no carcinoma in the common lymphatics of any tumors and no extrapulmonary metastases at the time of diagnosis. The following results were obtained. The incidence was 1.2% (14 of 1140 cases); 11 patients were heavy smokers; the most common histologic type was squamous cell carcinoma, and the combination of two squamous cell carcinomas was most common; 12 cases were bilateral, and 11 cases were synchronous; 19 tumors were diagnosed by bronchoscopic biopsy; 9 patients with bilateral tumors received chemotherapy and radiation therapy.

Aged↗
PubMed1993

Evaluation of structural change in diffuse liver disease with frequency domain analysis of ultrasound.

To evaluate structural changes in diffuse liver disease, frequency domain analysis was applied to ultrasonic signals from the liver. We assumed that liver tissue is a collection of semiregularly arrayed small scatterers of ultrasound. We applied cepstral analysis to the ultrasonic waveforms and evaluated the periodicity of scalloping of the power spectrum caused by an interference effect among liver scatterers of a given spacing. Patients with liver conditions involving nonspecific change (n = 6), chronic hepatitis (n = 11), cirrhosis (n = 7) or fatty liver (n = 6) were examined. One hundred ultrasonic signals were obtained noninvasively with a 3.5-MHz transducer, and the space among scatterers was calculated for each signal using cepstrum analysis. Two statistical parameters, mode and kurtosis, were determined from the distribution of the space among scatterers for each patient; these parameters were compared with the histological findings in the liver. Space among scatterers kurtosis decreased with progress of liver fibrosis, and space among scatterers mode increased in cirrhosis. Neither space among scatterers kurtosis nor space among scatterers mode was affected by pathological fat in the liver. These results suggest that we can evaluate fibrotic changes in diffuse liver disease and that we can also noninvasively discriminate diffuse fibrotic liver disease from fatty liver.

Chronic Disease↗
PubMed1992

5-HT3 receptor antagonists. 1. New quinoline derivatives.

A series of esters and amides of 1-alkyl-2-oxo-1,2-dihydroquinoline-4- carboxylic acid or 2-alkoxy-quinoline-4-carboxylic acid containing a basic azabicycloalkyl moiety has been synthesized and evaluated for affinity for the [3H]quipazine-labeled 5-HT3 receptors. Most of the esters exhibited 10-fold more potent activity than that of ondansetron (1; Ki = 7.6 nM). Lipophilic substituents at the 1- or 2-position of the quinoline ring enhanced affinity for the receptors. Compounds 21 and 37 showed the highest affinity (Ki = 0.32 and 0.31 nM, respectively) among them. On the other hand, most of the amides showed 100-fold lower affinity than that of the esters. Molecular modeling studies indicated that the carbonyl moiety in 19 (ester) or 31 (amide) was not coplanar to the plane of an aromatic ring (over 20 degrees deviation). Although some of the selected compounds exhibited potent activity in the Bezold-Jarisch (B-J) reflex test, good correlation was not observed between the affinity for the 5-HT3 receptors and the activity in the B-J reflex test (in vivo). From these data, it was suggested that our quinoline derivatives might interact with the 5-HT3 receptors in a different way from that of the reported 5-HT3 receptor antagonists presumably due to the presence of the heterogeneity of the 5-HT3 receptors between brain and heart.

Animals↗
PubMed1992

[Experimental study of indirect lymphography with iodinated starch].

Opacification of lymph nodes on CT was attempted by means of indirect lymphography with iodinated starch (IS). Sixty percent solutions of two different molecular weights of IS were prepared (5,000 mol wt and 70,000 mol wt in average). After subcutaneous injection of IS solutions to the pedal area of dogs, CT scans were performed to evaluate opacification of the popliteal lymph nodes. The lymph nodes began to be opacified from 10 min after the injection of each solution. The high molecular weight IS showed higher attenuation and longer duration of opacification than did the low molecular weight IS. Homogeneity of opacification was better with latter. The optimum molecular weight for this purpose is considered to be between 5,000 and 70,000 mol wt.

Animals↗
PubMed1992

Purification and characterization of macrolide 2'-phosphotransferase type II from a strain of Escherichia coli highly resistant to macrolide antibiotics.

The resistance mechanism of Escherichia coli BM2506 to macrolides was found to be due to inactivation. Inactivated oleandomycin was identified as oleandomycin 2'-phosphate by thin-layer chromatography. A new type of macrolide-phosphorylating enzyme, macrolide 2'-phosphotransferase type II (MPH(2')II), was detected, purified 95-fold and its enzymological properties investigated. MPH(2')II was a constitutive intracellular enzyme which showed high levels of activity with both 14-member-ring and 16-member-ring macrolides. The optimum pH for the inactivation of oleandomycin was 8.2 and the optimum temperature of the reaction was 40 degrees C. Enzyme activity was lost by heat treatment at 60 degrees C for 1 min. The isoelectric point and M(r) of the enzyme were 5.3 and 48,000, respectively. Purine nucleotides, such as ITP, GTP and ATP, were effective as cofactors in the inactivation of macrolides. An inhibitory effect of iodine, EDTA, or divalent cations on MPH(2')II activity was observed.

Anti-Bacterial Agents↗
PubMed1992

[Utility of helical CT for the secondary mass screening of lung cancer].

From December 1991 to 1992, helical CT scan was performed in 55 patients with having abnormal shadow in the chest X-ray on the secondary screening for lung cancer. In all patients with suspected pulmonary lesions at first screening, helical CT scan was performed with 10 mm slice thickness for 300 mm. The moving speed of the patients table is 20 mm/l rot./1.5 sec for 300 mm in a single breath-hold. Helical CT allowed shortening of examination time and providing both better data continuity and resolution than conventional CT. In conclusion, helical CT can be useful for secondary screening of lung cancer but it was considered that there are some problems such as method of final pathological diagnosis and treatment for small nodular lesion.

Female↗
PubMed1992

[Transcatheter embolization for huge pulmonary arteriovenous fistula using metallic "spider" and spring embolus--application of hand-made metallic "spider" using partial monorail technique].

We performed transcatheter embolization in two cases with huge pulmonary arteriovenous fistula (AVF) using a metallic "spider" and spring embolus. Conventional spring embolus or detachable balloon could not be used in these cases. Metallic spider was indicated for pulmonary AVF with a feeding artery diameter of more than 16 mm to prevent embolus passing through the AVF. In the first case, we used large handmade metallic spiders of 25 mm in diameter followed by embolization by numerous spring coils. At that time, a partial monorail technique was newly devised to carry the large metallic spider into the feeding artery, otherwise the spider could not pass into a 9F catheter. After embolization, symptoms and PaO2 in arterial blood improved remarkably in both cases. In the second case, a spring coil migrated into the normal pulmonary artery, but no infarction resulted. In conclusion, the metallic spider was very useful for embolization of hugee pulmonary AVF to avoid the embolus passing through and to tangle spring coils together with it. If commercially available "spiders" are too small, ones can be made easily.

Adult↗
PubMed1992

High-level resistance to ethidium bromide and antiseptics in Staphylococcus aureus.

A gene encoding high-level resistance to ethidium bromide (EB) and antiseptics was isolated from a transferable plasmid, pTZ22, in Staphylococcus aureus. DNA sequencing revealed that the plasmid has two copies of the ebr gene that normally mediates low-level resistance to EB and antiseptics. The efflux rate for EB of strains with duplicated ebr genes was twice the rate of strains with a single ebr gene. It was concluded that the duplication of ebr is responsible for the high-level resistance to EB and antiseptics.

Amino Acid Sequence↗