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Biomedical subjects

M Kono

Publications and source records attributed to M Kono.

At least 109 records · Page 6Linked to original sources

Subtle pulmonary disease: detection with computed radiography versus conventional chest radiography.

PURPOSE: To determine the diagnostic efficacy of hard- and soft-copy computed radiographic (CR) images versus conventional screen-film images of the chest in the detection of subtle pulmonary abnormalities. MATERIALS AND METHODS: Twenty observes compared 87 hard-copy and soft-copy CR images with hard-copy screen-film images. Of 87 test images, 45 (including two identical sets of 12 images to test intra-observer variability) were abnormal and 42 (including two identical sets of 12 images) were normal. Of the 45 abnormal images, 15 (including two sets of four identical images) showed subtle abnormalities, 15 (including two sets of four identical images) showed mild abnormalities, and 15 (including two sets of four identical images) showed obvious abnormalities. Soft-copy viewing provided three differently processed images of every radiograph. RESULTS: No statistically significant differences in receiver operating characteristic analyses were found among hard-copy screen-film images, hard-copy CR images, and soft-copy CR images, even in the group with subtle interstitial abnormalities. CONCLUSION: Hard-copy and soft-copy chest CR images are acceptable and available in place of screen-film images for primary interpretation of subtle interstitial lung diseases.

Adult↗

Inhibitors of acyl-CoA: cholesterol acyltransferase. II. Preparation and hypocholesterolemic activity of optically active dibenz[b,e]oxepin-11-carboxanilides.

In a previous paper, we reported a novel inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), 2-bromo-N-(2,6-diisopropylphenyl)-6,11- dihydrodibenz[b,e]oxepin-11-carboxamide (1). In this work, we prepared both enantiomers and tested them for ability to inhibit ACAT (liver microsomes from cholesterol-fed rabbits) in vitro and to decrease serum total cholesterol in cholesterol-fed golden hamsters in vivo. The precursor carboxylic acid 4 was optically resolved with cinchonidine. The obtained (-)- and (+)-4 were converted to (-)- and (+)-1 without racemization, respectively. The enantiomer (-)-1 showed potent ACAT inhibitory activity in vitro with an IC50 value of 8 nM and was approximately 10-fold more active than (+)-1. Furthermore, (-)-1 showed strong hypocholesterolemic activity in vivo, whereas (+)-1 was inactive. A molecular modeling study showed that the difference of ACAT inhibitory activity between the enantiomers was derived from the spatial alignment of the bromine. Compound (-)-1 was selected for further evaluation as KW-3033.

Animals↗

Purification and characterization of beta-N-acetylhexosaminidase from the liver of a prawn, Penaeus japonicus.

Beta-N-Acetylhexosaminidase (EC 3.2.1.52) was purified from the liver of a prawn, Penaeus japonicus, by ammonium sulfate fractionation and chromatography with Sephadex G-100, hydroxylapatite, DEAE-Cellulofine, and Cellulofine GCL-2000-m. The purified enzyme showed a single band keeping the potential activity on both native PAGE and SDS-PAGE. The apparent molecular weight was 64,000 and 110,000 by SDS-PAGE and gel filtration, respectively. The pI was less than 3.2 by chromatofocusing. The amino-terminal amino acid sequence was NH2-Thr-Leu-Pro-Pro-Pro-Trp-Gly-Trp-Ala-?-Asp-Gln-Gly-Val-?-Val-Lys-Gly- Glu-Pro-. The optimum pH and temperature were 5.0 to 5.5 and 50 degrees C, respectively. The enzyme was stable from pH 4 to 11, and below 55 degrees C. It was 39% inhibited by 10 mM HgCl2. Steady-state kinetic analysis was done with the purified enzyme using N-acetylchitooligosaccharides (GlcNAcn, n = 2 to 6) and p-nitrophenyl N-acetylchitooligosaccharides (pNp-beta-GlcNAcn, n = 1 to 3) as the substrates. The enzyme hydrolyzed all of these substrates to release monomeric GlcNAc from the non-reducing end of the substrate. The parameters of Km and kcat at 25 degrees C and pH 5.5 were 0.137 mM and 598 s-1 for pNp-beta-GlcNAc, 0.117 mM and 298 s-1 for GlcNAc2, 0.055 mM and 96.4 s-1 for GlcNAc3, 0.044 mM and 30.1 s-1 for GlcNAc4, 0.045 mM and 14.7 s-1 for GlcNAc5, and 0.047 mM and 8.3 s-1 for GlcNAc6, respectively. These results suggest that this beta-N-acetylhexosaminidase is an exo-type hydrolytic enzyme involved in chitin degradation, and prefers the shorter substrates.

Amino Acid Sequence↗

[Effect of wall thickness of left ventricle on 201Tl myocardial SPECT images: myocardial phantom study].

201Tl myocardial SPECT is known for better sensitivity, specificity, and accuracy than planar images in detecting coronary artery disease and diagnosing myocardial viability. SPECT images are also superior to planar images in diagnostic sensitivity and anatomical orientation. However, as limitation of the spatial resolution of the machine, we often encounter poor SPECT plower image quality in patients with decreased wall thickness. To test the accuracy of SPECT images in patients with marked thinning of the left ventricular wall, as occurs in dilated cardiomyopathy, we performed a experimental study using myocardial phantom with 7 mm wall thickness. Tomographic image of the phantom images were rather heterogeneous, though no artificial defect was located. Dilated cardiomyopathy is thought to be characterized by patchy defects in the left ventricle. Careful attention should be given to elucidating myocardial perfusion in patients with a thin left ventricle wall, as there are technical limitations in addition to clinical features.

Aged↗

[Three-dimensional reconstruction images of central airway using spiral CT: experimental and clinical studies in the demonstrability of tracheobronchial lesions].

The purpose of this study was to evaluate the role of three dimensional reconstruction image using spiral CT (3D image) for demonstrating the tracheobronchial lesions. In the experimental study using originally developed phantom, 3D images of simulated endobronchial protrusions were evaluated at combinations of detector collimation (1, 3 and 5 mm), table speed (1, 2, 3 and 5 mm/sec) and reconstruction pitch (1 and 3 mm). 3D images with 1 mm collimation, 1 mm/sec table speed, and 1 mm reconstruction pitch (1/1/1) could provide the best demonstrability of simulated endobronchial protrusions. But the condition (1/2/1) is not so inferior to 1/1/1. The stair-step artifacts were caused by the effects of rotation and aliasing, which could be reduced with slow table speed and fine reconstruction pitch. In clinical study, 3D images (1/2/1) were applied in 34 patients with hilar lung cancer and these images were compared with bronchoscopic findings. 3D images demonstrated irregular obstructions or stenoses in 15 of 16 cases with mucosal lesions, 5 of 7 cases with submucosal lesions with mucosal invasion. On the other hand, in 4 cases with submucosal lesions without mucosal invasion and 6 of 7 cases with intramural or extramural lesions, smooth stenoses were demonstrated on 3D images. In 30 of 34 cases (88.2%), 3D images corresponded to bronchoscopic findings. In conclusion, 3D images proved useful in demonstrating not only the obstructions or stenoses of central airway, but also mucosal irregularity. 3D-CT could be helpful for determining indication for transbronchial biopsy of hilar lung cancer.

Adult↗

Decreased medial temporal oxygen metabolism in Alzheimer's disease shown by PET.

UNLABELLED: In mild-to-moderate Alzheimer's disease, previous PET studies failed to reveal significant involvement in the medial temporal lobe having pathologically neurodegenerative changes. The purpose of this study was to clarify the medial temporal perfusion and functional changes in mild-to-moderate Alzheimer's disease using PET. METHODS: Sixteen patients with probable mild-to-moderate Alzheimer's disease (age 62.9 +/- 6.0 yr, MMSE 17.7 +/- 3.7) and 14 normal volunteers (age (60.9 +/- 5.9 yr) were studied. Regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) were measured using 15O steady-state method and PET. By rendering magnetic resonance volumetry of the medial temporal structures, the significance of partial volume effects on PET study measurements was examined. RESULTS: The mean CMRO2 in the medial temporal, as well as in the parietal and lateral temporal cortices were significantly lower in the patient group than in the control group. The mean CBF in the parietal and lateral temporal cortices also significantly decreased in the patient group. The OEF in the medial temporal was also decreased in the Alzheimer's disease group, while the OEF in the other cortical regions in Alzheimer's disease group were similar to that of control group. Decline of medial temporal oxygen consumption was the most distinctive feature of Alzheimer's disease. Those measurements were independent from volume of medial temporal structures. In Alzheimer's disease, medial temporal CMRO2 and CBF correlated with some of the nonverbal memory test scores and cognitive impairment scales, when normalized for individual difference. CONCLUSION: Medial temporal oxygen metabolism was markedly affected in patients with mild-to-moderate Alzheimer's disease. This measure substantiated the functional impairment of the medial temporal region in Alzheimer's disease.

Alzheimer Disease↗

Isolation of cDNA encoding a putative chitinase precursor in the kuruma prawn Penaeus japonicus.

Amino acid sequences of chitinases have been determined in insects, plants, yeast, and bacteria, but not in crustaceans. We searched for chitinase-encoding cDNA in the kuruma prawn Penaeus japonicus by polymerase chain reaction (PCR) amplification of hepatopancreas cDNA using degenerate oligonucleotide primers derived from the two conserved regions of known chitinases. Using a PCR product as a probe, a cDNA clone was isolated. This clone contains an open reading frame for a protein (named Pjchi-1) of 572 amino acids that exhibits sequence similarities to known chitinases, especially to a chitinase from the tobacco hornworm Manduca sexta. Transcription of the mRNA was detected in the hepatopancreas but not in epidermal tissues.

Amino Acid Sequence↗

A general method for mapping tertiary contacts between amino acid residues in membrane-embedded proteins.

A general method for mapping tertiary interactions in membrane proteins using the visual pigment rhodopsin as a model is presented. In this approach, the protein is first assembled from two separately expressed gene fragments encoding nonoverlapping segments of the full-length polypeptide. Cys residues are then introduced into each of the two fragments such that juxtaposed residues are able to form disulfide cross-links in the protein either spontaneously or with the assistance of a Cu(2+)-(phenanthroline)3 oxidant. The cross-linked polypeptides are identified from a characteristic mobility shift on sodium dodecyl sulfate (SDS) gels as detected by Western blot analysis where the covalently bound heterodimer migrates with a mobility essentially identical to that of the native, full-length protein. Three different split rhodopsin mutants were prepared: one with a split in the loop connecting helices 3 and 4 (the 3/4 loop), one with a split in the 4/5 loop, and one with a split in the 5/6 loop. Each of these proteins when purified from transfected COS cells bound 11-cis-retinal, had a native absorption maximum at 500 nm, and activated transducin in a light-dependent manner. The cross-linking assay was tested with the rhodopsin mutant split in the 5/6 loop using the rho-1D4 antibody (which recognizes the carboxy terminal eight amino acids of rhodopsin) to detect the proteins on Western blots of SDS gels. Cys residues were substituted for Val-204 in the amino terminal fragment and Phe-276 in the carboxy terminal fragment of the rhodopsin mutant because Schwartz and co-workers [Elling et al.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Rapid identification of Streptococcus pneumoniae by PCR amplification of ribosomal DNA spacer region.

Streptococcus pneumoniae is one of the important human pathogens in clinical microbiology. A polymerase chain reaction assay was designed to detect and identify S. pneumoniae through amplification of the ribosomal DNA spacer regions between the pneumococcal 16S-23S ribosomal RNA genes. Thirty-two Streptococcus and non-Streptococcus strains were tested to verify the specificity of the assay, and only S. pneumoniae strains gave a positive reaction. This method is a powerful technique for the rapid identification of S. pneumoniae.

Bacteriological Techniques↗

Synthesis and antitumor activity of various 6-demethylmitomycins and 6-demethyl-6-halomitomycins.

A series of 6-demethylmitomycins and 6-demethyl-6-halomitomycins having various mitomycin skeletons were synthesized, taking into account the electronic effect toward the quinone moiety and the partition coefficients. Treatment of enones 15 and 16 with selenenamide or N-halosuccinimide-Et2NH afforded the 6-demethyl intermediates 17, 18, and 21-24 via the tandem Michael addition/retro-Mannich reaction sequence. Subsequent conversions into the mitomycin skeletons resulted in the formation of the desired derivatives 7a-c, 8a-c, 11a-c, and 12a,b. These mitomycin derivatives including 3a-c and 4a-c were evaluated for their anticellular activity against HeLa S3 cells and antitumor activity against Sarcoma 180 in mice. The anticellular activity of 1 and 3a-c depends on the substituent at the C-6 position and the order of increasing activity is H < CH3 < Br < Cl. A similar tendency was observed in their antitumor potency (ED50). The activities of 9 and 11a-c also follow a pattern similar to that of 1 and 3a-c. Compounds 4b,c, 8b,c, and 12b having both a halogen at the C-6 position and a methoxy group at the C-7 position did not show the activities because of the instability of the compounds. Interestingly, a correlation between the anticellular activity (IC50) and the partition coefficients (log kappa') determined by HPLC was observed within the compounds studied except the unstable compounds, while their antitumor activity (ED50 or T/C) did not correlate with the quinone reduction potential (E1/2). These results would indicate the importance of the C-6 substituents and the mitomycin skeletons for exhibiting both anticellular and antitumor activities.

Animals↗

Effects of substitution of tyrosine 57 with asparagine and phenylalanine on the properties of bacteriorhodopsin.

Tyrosine 57 is one of the residues present in the retinal binding pocket and is conserved in all the halophilic retinal proteins. We have studied mutants of bacteriorhodopsin, expressed in Halobacterium salinarium, in which tyrosine 57 is replaced by an asparagine (Y57N) or phenylalanine (Y57F). In Y57N the photocycle proceeds only up to the L intermediate; no M is formed at neutral pH. The lifetime of L intermediate is extremely long, ca. 500 ms. Proton release is severely affected in both the mutants which suggests that Y57 is associated with the proton release pathway. By comparing the pH-induced absorption changes in the UV in Y57N and Y57F with those in the wild-type (WT), we determined that the pKa of Y57 is 10.2. In Y57F, which shows M formation, the rate constant of the L-->M transition is pH dependent (pKa 8.7) suggesting that Y57 is probably not the residue that normally controls the transition into the alkaline photocycle. Y57 is either part of the counterion complex or in close proximity to D85 since its mutation influences the pKa of Asp85. In Y57F the pKa of D85 is approximately 4.9 (compared to approximately 2.9 in the WT). The Y57N mutant shows two pKa's in the purple to blue transition, approximately 3.8 and < 1. In the presence of hydroxylamine, at neutral pH, Y57N is stable in the dark but bleaches very rapidly upon illumination compared to the WT. Since the lifetime of L intermediate is long in Y57N, we suggest that the Schiff base becomes accessible to hydroxylamine in this state.

Asparagine↗

In vitro microsome-mediated aflatoxin B1-DNA binding and its inhibition by cytosol of various organs of the hamster and quail.

We studied the in vitro activation of aflatoxin B1 (B1) by microsomes and its inactivation by the cytosol of various quail and hamster organs, using B1-DNA binding as an index. The microsomal activity of the liver to bind B1 to DNA was not largely different between the two species and was higher than that of the other organs examined in either species. The microsomal activity of the kidney and lung was very low in the quail compared with the hamster, indicating the very small contribution of the lung and kidney microsomes to the activation of B1 in birds. Only the hamster liver cytosol showed strong inhibition of microsome-mediated B1-DNA binding.

Aflatoxin B1↗

Effects of alpha-adrenergic blockade on regional myocardial function in canine ischemic myocardium during beta-adrenergic blockade.

OBJECTIVE: The contribution of alpha-adrenergic receptor subtypes in mediation of coronary vasoconstriction during ischemia remains controversial. This study investigated the effects of alpha-adrenergic subtypes blockade on regional myocardial function in a canine ischemic model. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental animal laboratory in a university medical center. PARTICIPANTS: Thirty-two adult dogs, weighing 13 to 22 kg. INTERVENTIONS: The animals were prepared with pentobarbital, oxygen, enflurane and pancuronium. Two selective alpha 1-adrenergic antagonists (bunazosin, 50 micrograms/kg/min, n = 8, and prazosin, 25 micrograms/kg/min, n = 8) and the alpha 2-adrenergic antagonist (yohimbine, 15 micrograms/kg/min, n = 8) were administered after the partial occlusion of the left circumflex coronary artery (LCX) during beta-adrenergic blockade (propranolol, 1 mg/kg). MEASUREMENTS AND MAIN RESULTS: Myocardial systolic segment shortening (%SS) and a myocardial lactate extraction ratio (LER) were used as indices of regional myocardial and metabolic function. Compared with poststenotic condition, coronary blood flow of the LCX was increased by 123% with bunazosin and 138% with prazosin (p < 0.05, respectively). Both %SS and LER in the ischemic myocardium were significantly improved after treatment with both alpha 1-adrenergic antagonists (in the bunazosin group, %SS, 8.3 +/- 1.9 to 10.4 +/- 2.2%, p < 0.05; LER, -12.8 +/- 12.3 to 6.2 +/- 15.9%, p < 0.01; in the prazosin group, %SS, 8.5 +/- 1.6 to 10.3 +/- 1.9%, p < 0.05; LER, -10.2 +/- 5.7 to 3.6 +/- 10.2%, p < 0.05). In contrast, coronary blood flow of the LCX, %SS and LER were not different from poststenotic condition during alpha 2-adrenergic receptor blockade with yohimbine. The salutary effect of bunazosin was also observed after mechanically controlling for the afterload reduction produced by alpha 1-adrenergic blockade (n = 8). Prazosin and yohimbine were found to produce a significant increase in plasma norepinephrine levels in contrast to bunazosin, which had no significant effect. CONCLUSIONS: These data indicate that alpha 1-adrenergic blockade increases coronary blood flow and improves regional myocardial function during myocardial ischemia.

Adrenergic alpha-Antagonists↗

Enhanced magnetic resonance imaging in monitoring of conservative treatment of cervical pregnancy.

We report on case of cervical pregnancy successfully treated by two 5-day courses of etoposide, embryocide with the injection of KCl, the injection of methotrexate into the placenta, and cervical curettage. We evaluated the effects of these treatments by measuring urinary human chorionic gonadotropin (hCG) titers and serial hCG beta-carboxy-terminal peptide (CTP) levels. Moreover, we used ultrasonography and magnetic resonance imaging (MRI) enhanced by gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) to diagnose and to evaluate the blood supply to the trophoblast. The beneficial outcomes suggest that Gd-DTPA-enhanced MRI is useful in detecting the blood supply to the trophoblast, in order to avoid the massive bleeding that results from conservation treatments. This is the first report of the usefulness of Gd-DTPA-enhanced MRI for the successful conservative treatment of cervical pregnancy.

Adult↗

Nucleotide sequence and characterization of erythromycin resistance determinant that encodes macrolide 2'-phosphotransferase I in Escherichia coli.

The DNA fragment (3.3 kb) containing the erythromycin resistance determinant was cloned from Escherichia coli Tf481A and sequenced. Deletion and complementation analyses indicated that the expression of high-level resistance to erythromycin requires two genes, mphA and mrx, which encode macrolide 2'-phosphotransferase I and an unidentified hydrophobic protein, respectively.

Amino Acid Sequence↗

[Interuncal distance measurements in normal controls and patients with dementia: MR imaging study].

To evaluate the utility of measuring interuncal distance (IUD) as a reflection of the limbic system, we compared the IUD of 60 dementia patients with that of 10 normal controls. We also measured the width of the intracranial compartment (W1 and W2) to correct for differences in individual brain size, and calculated the ratio of IUD/W1 and IUD/W2. IUD could not separate patients with dementia from normal controls, but there were significant differences in IUD/W1 and IUD/W2 between patients with dementia and normal controls. IUD, IUD/W1 and IUD/W2 did not correlate with Mini-Mental Examination score or ADAS score in patients with dementia. We conclude that IUD measurement is not helpful in distinguishing patients with mild stage dementia from normal aged people or as a scale for dementia. However, we suggest that IUD/W1 and IUD/W2 can discriminate between cases of mild dementia and normal aged people.

Aged↗

[Assessment by three-dimensional CT of pleural indentation or invasion by peripheral lung cancer].

We evaluated the effectiveness of three-dimensional (3D) CT for pleural indentation or invasion by peripheral lung cancer adjacent to pleura. Pleural indentation was shown in three of nine cases on conventional CT, and six cases were demonstrated three-dimensionally. 3D-CT was superior to conventional CT in demonstrating pleural indentation. Pleural invasion could not be assessed on 3D-CT because the pleura adjacent to the tumor was not visualized.

Humans↗