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Biomedical subjects

M Konno

Publications and source records attributed to M Konno.

At least 37 records · Page 2Linked to original sources
PubMed2000

Management of severe neutropenia with cyclosporin during initial treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis.

Severe neutropenia (absolute neutrophil count <500/gl) is probably due to the combined effects of dysregulated cytokine production and chemotherapeutic agents, and is one of the risk factors in the initial treatment of patients with Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). We report here 9 cases of neutropenic HLH, of which 8 were treated with cyclosporin (CSA, 2-6 mg/kg/day; continuous infusion, or 6 mg/kg/day; per os, for periods ranging from 9 days to >8 weeks) in the initial neutropenic phase during induction treatment using corticosteroids and etoposide. Five of the 6 cases, in which CSA treatment was started early (before the second week of induction), survived the critical period with recovery of neutrophil counts within a week. The remaining 3 cases, in which CSA was introduced later or not at all, died of infection. Based on these results, we recommend a prompt short-term CSA infusion during neutropenic episodes in the most common treatment regimen of etoposide and corticosteroids in patients with HLH. Improved neutrophil recovery as a result of CSA treatment makes it possible to continue immunochemotherapy safely and obtain improved patient outcomes.

Adolescent↗
PubMed2000

[Comparison between leucyl aminopeptidase and pseudo leucine aminopeptidase activities in sera].

The highest activities of leucyl aminopeptidase(LAP, cytosol aminopeptidase, EC 3.4.11.1) in sera have been found in patients with acute hepatitis(Kanno et al., Am J Clin Path, 82: 700-705, 1984). I observed inpatients with very high activities of LAP and alcohol dehydrogenase(AD) in sera. However, only slight elevations of serum pseudo leucine aminopeptidase(PLA), that is, membrane alanyl aminopeptidase(MAA, microsomal aminopeptidase, EC 3.4.11.2) activities for hydrolysis of leucyl-4-nitroanilide were observed in these patients. They were patients in critical care unit with ischemia caused by a cardiopulmonary arrest, multiple trauma, acute myocardial infarction or operation. Therefore, we should measure LAP activities in sera rather than PLA(MAA) activities in these patients.

Acute Disease↗
PubMed1999

Crystal structure of Escherichia coli methionyl-tRNA synthetase highlights species-specific features.

The 3D structure of monomeric C-truncated Escherichia coli methionyl-tRNA synthetase, a class 1 aminoacyl-tRNA synthetase, has been solved at 2.0 A resolution. Remarkably, the polypeptide connecting the two halves of the Rossmann fold exposes two identical knuckles related by a 2-fold axis but with zinc in the distal knuckle only. Examination of available MetRS orthologs reveals four classes according to the number and zinc content of the putative knuckles. Extreme cases are exemplified by the MetRS of eucaryotic or archaeal origin, where two knuckles and two metal ions are expected, and by the mitochondrial enzymes, which are predicted to have one knuckle without metal ion.

Amino Acid Sequence↗
PubMed1999

Correlation between Generated Shear Stress and Generated Permittivity for the Electrorheological Response of Colloidal Silica Suspensions.

Electrorheological response was experimentally studied by the use of silicone oil suspensions containing submicrometer-sized and supermicrometer-sized silica particles with different amounts of adsorbed water. The simultaneous measurements of dielectric permittivity and shear stress of the suspensions were carried out after the application of alternating current voltage under steady shear in ranges of shear rate (150-1400 s(-1)), electric field strength (0-4 kV/mm), its frequency (30-1000 Hz), and particle volume fraction (0.1-0.3). For the particles with small amounts of adsorbed water, steady shear stress was attained within several minutes after the application of electric field. The steady-state data for both the particles at each electric field strength showed that the shear stress generated by the application of electric field, Deltatau, varied correlatively with the generated permittivity, Deltaepsilon(r) (= epsilon(r) - epsilon(r,oil)), where epsilon(r) and epsilon(r,oil) are the permittivities of the suspension and the silicon oil, respectively. Under a wide variety of experimental conditions, the steady-state data for both the particle sizes could be correlated with a simple relationship, Deltatau ~ (Deltaepsilon(r)E)(2), where E is electric field strength. For the particles with large amounts of adsorbed water, steady state was not attained, and the evolutions of shear stress and permittivity of the suspensions were measured after the application of electric field. Remarkably, the transient values of Deltatau varied with (Deltaepsilon(r)E)(2) and fell along the same correlation line as the steady-state data. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Crystal structure of the E166A mutant of extended-spectrum beta-lactamase Toho-1 at 1.8 A resolution.

Bacterial resistance to beta-lactams is mainly due to the production of beta-lactamase. Especially through the production of extended-spectrum beta-lactamases (ESBLs), bacteria have acquired resistance not only to penicillins, but also to expanded-spectrum cephems. Here, we describe the crystal structure of the E166A mutant of class A beta-lactamase Toho-1 at 1.8 A resolution, the first reported tertiary structure of an ESBL. Instead of the wild-type enzyme, a mutant Toho-1, in which Glu166 was replaced with alanine, was used for this study, because of the strong tendency of the wild-type enzyme to form twinned crystals. The overall structure of Toho-1 is similar to the crystal structures of non-ESBLs, with no pronounced backbone rearrangement of the framework. However, there are some notable local changes. First, a difference in the disposition of an arginine residue, which is at position 244 in non-ESBLs but at position 276 in Toho-1 and other ESBLs, was revealed and the role of this arginine residue is discussed. Moreover, changes in the hydrogen-bonding pattern and in the formation of the hydrophobic core were also observed near the Omega loop. In particular, the lack of hydrogen bonds in the vicinity of the Omega loop could be a cause of the extended substrate specificity of Toho-1. Through the generation of a model for the enzyme-substrate complex, a conformational change of Toho-1 occurring on complex formation is discussed based on the active-site cleft structure and the substrate profile.

Amino Acid Sequence↗
PubMed1999

[Assessment of left ventricular function by electrocardiogram-gated myocardial single photon emission computed tomography using quantitative gated single photon emission computed tomography software].

Electrocardiogram (ECG)-gated myocardial single photon emission computed tomography (SPECT) can assess left ventricular (LV) perfusion and function easily using quantitative gated SPECT (QGS) software. ECG-gated SPECT was performed in 44 patients with coronary artery disease under post-stress and resting conditions to assess the values of LV functional parameters, by comparison to LV ejection fraction derived from gated blood pool scan and myocardial characteristics. A good correlation was obtained between ejection fraction using QGS and that using cardiac blood pool scan (r = 0.812). Some patients with myocardial ischemia had lower ejection fraction under post-stress compared to resting conditions, indicating post-stress LV dysfunction. LV wall motion and wall thickening were significantly impaired in ischemic and infarcted myocardium, and the degree of abnormality in the infarcted areas was greater than in the ischemic area. LV functional parameters derived using QGS were useful to assess post-stress LV dysfunction and myocardial viability. In conclusion, ECG-gated myocardial SPECT permits simultaneous quantitative assessment of myocardial perfusion and function.

Electrocardiography↗
PubMed1999

[The effects of propofol anesthesia with or without the use of nitrous oxide on the intraoperative involuntary movement, the postoperative awareness and vomiting].

The authors investigated the effect of anesthesia with nitrous oxide and propofol on intraoperative involuntary movement, muscle relaxant usage, postoperative nausea and vomiting, the total amount of propofol used, and recovery time from anesthesia. Eighty-eight patients for gynecological surgery were randomly divided into group PE: propofol/epidural (n = 44), and group PEG: propofol/epidural/nitrous oxide (n = 44). The frequency of postoperative nausea and vomiting were assessed at 24-h postoperatively by blinded observers. There were significant decreases of the mean amounts of propofol and muscle relaxant used between group PEG and group PE. The authors found no correlation between the use of nitrous oxide and intraoperative involuntary movement, subsequent development of postoperative quality of awareness, recovery time, nausea and vomiting. We recommend PEG method for gynecological surgery rather than PE from an economical viewpoint because it is associated with the reduction of mean propofol and muscle relaxant used.

Adult↗
PubMed1998

Preparation of Monodisperse, Micron-Sized Polystyrene Particles with Single-Stage Polymerization in Aqueous Media.

A single-stage polymerization technique, proposed for producing micron-sized polymer particles in aqueous media by Gu and Konno, was examined. Styrene was used for the monomer, potassium persulfate for the initiator, and cetyltrimethylammonium bromide and sodium dodecyl sulfate were used for the ionic surfactants to control the aggregation of the particles during the reaction. Particle-size distributions and monomer-to-polymer conversions were measured over a range of initiator concentration (2-8 mmol/dm3 H2O), stirring speed (200-400 rpm), surfactant addition time and monomer concentration (1.1-2.2 mol/dm3 H2O). Changes in the initiator concentration and stirring speed did not bring about significant effect on the particle-size distributions. On the other hand, the addition of time affected the coefficient of variation of the particle-size distribution, but it had no significant effect on the average diameter of the particles. An increase in the monomer concentration enlarged the average size without lowering the coefficient of variation of particle-size distribution. Monodisperse polystyrene particles with an average diameter of 3.3 µm and a coefficient of variation of particle size distribution 7% could be prepared with the present technique. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Enzyme structure with two catalytic sites for double-sieve selection of substrate.

High-fidelity transfers of genetic information in the central dogma can be achieved by a reaction called editing. The crystal structure of an enzyme with editing activity in translation is presented here at 2.5 angstroms resolution. The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the synthetase itself rapidly hydrolyzes only the valylated products. For this two-step substrate selection, a "double-sieve" mechanism has already been proposed. The present crystal structures of the synthetase in complexes with L-isoleucine and L-valine demonstrate that the first sieve is on the aminoacylation domain containing the Rossmann fold, whereas the second, editing sieve exists on a globular beta-barrel domain that protrudes from the aminoacylation domain.

Adenosine Monophosphate↗
PubMed1998

Crystallographic and mutational analyses of an extremely acidophilic and acid-stable xylanase: biased distribution of acidic residues and importance of Asp37 for catalysis at low pH.

Xylanase C from Aspergillus kawachii has an optimum pH of 2.0 and is stable at pH 1.0. The crystal structure of xylanase C was determined at 2.0 A resolution (R-factor = 19.4%). The overall structure was similar to those of other family 11 xylanases. Asp37 and an acid-base catalyst, Glu170, are located at a hydrogen-bonding distance (2.8 A), as in other xylanases with low pH optima. Asp37 of xylanase C was replaced with asparagine and other residues by site-directed mutagenesis. Analyses of the wild-type and mutant enzymes showed that Asp37 is important for high enzyme activity at low pH. In the case of the asparagine mutant, the optimum pH shifted to 5.0 and the maximum specific activity decreased to about 15% of that of the wild-type enzyme. On structural comparison with xylanases with higher pH optima, another striking feature of the xylanase C structure was found; the enzyme has numerous acidic residues concentrated on the surface (so-called 'Ser/Thr surface' in most family 11 xylanases). The relationship of the stability against extreme pH conditions and high salt concentrations with the spatially biased distribution of charged residues on the proteins is discussed.

Aspartic Acid↗
PubMed1998

Regional cerebral blood flow abnormalities in late-life depression: relation to refractoriness and chronification.

We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-refractory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression.

Aged↗
PubMed1998

A lasting change in trazodone response after non-convulsive electroshock therapy for medication-resistant senile depression.

A senile patient showed a dramatic recovery from medication-resistant depression after non-convulsive electroshock therapy (nc-EST), with a lasting change in response to trazodone, which mainly acts as a serotonin re-uptake inhibitor. This result suggests that a change in the serotonin reuptake mechanism may be involved in the effect of nc-EST on depression.

Aged↗
PubMed1998

[Identification of penicillin-resistant Streptococcus pneumoniae in nasopharynx of patient with acute otitis media by PCR].

Streptococcus Pneumoniae is a leading cause of acute otitis media (AOM). For most AOM caused by S. pneumoniae, penicillin is the antibiotic of choice. However, there are some recent reports of clinical resistance to penicillin by S. pneumoniae. The sequences of penicillin binding protein, pbpla, pbp2b and pbp2x, genes of penicillin-resistant S. pneumoniae (PRSP) were more highly divergent than those of penicillin-succeptible S. pneumoniae (PSSP). The polymerase chain reaction (PCR) can easily determine whether an S. pheumoniae isolate is susceptible or resistant to penicillin by amplifying the target gene by using a combination of primers. In this study, clinical isolates (n = 12) were obtained from the nasopharynx of patients with AOM. PCR was used to confirm the identification of an isolate as S. pneumoniae by amplifying the autolysin gene and to detect three PBP genes by amplifying parts of pbp1a, pbp2x and pbp2b. The resistance of S. pneumoniae to penicillin and other beta-lactams has been shown to be associated with mosaic mutations in the pbp1a, pbp2b and pbp2x genes. These findings suggest that rapid identification of PSSP and PISP/PRSP by PCR is possible and very useful for proper treatment of acute otitis media.

Acute Disease↗
PubMed1997

Trisubstituted benzene leukotriene B4 receptor antagonists: synthesis and structure-activity relationships.

A series of trisubstituted benzenes which demonstrate leukotriene B4 (LTB4, 1) receptor affinity was prepared. Previous trisubstituted benzenes from our laboratory showed high affinity to the LTB4 receptor but demonstrated agonist activity in functional assays. Compound 3a, the initial lead compound of this new series, showed only modest affinity (IC50 = 0.20 microM). However, 3a was a receptor antagonist with no demonstrable agonist activity up to 30 microM. Further modification of the lipid tail and aryl head groups region led to the discovery of 3b (ONO-4057). This compound, free of agonist activity, possesses high affinity to the LTB4 receptor (Ki = 3.7 +/- 0.9 nM).

Benzene Derivatives↗
PubMed1997

Synthesis of structural analogues of leukotriene B4 and their receptor binding activity.

Structural analogues of leukotriene B4 (LTB4) were designed based on the plausible conformation of LTB4 (1). Joining C-7-C-9 of the conformer A or B into an aromatic ring system led to the discovery of benzene analogues 2, 4 and 6a. Joining C-4-C-9 of the conformer C or D into an aromatic ring system led to the discovery of analogues 3, 5 and 7. The compounds examined in this study were evaluated as to their inhibition of [3H] LTB4 binding to human neutrophils, and by a secondary intact human neutrophil functional assay for agonist/antagonist activity. The first analogues prepared, compounds 2-7, demonstrated moderate potency in the LTB4 receptor binding assay. The modification of these compounds by the introduction of another substituent into the aromatic ring produced a marked increase in receptor binding (28c, IC50 = 0.020 microM; 38c, IC50 = 0.020 microM; 52a, IC50 = 0.020 microM; 52b, IC50 = 0.018 microM). Most of these structural analogues of LTB4 demonstrated agonist activity. Of the analogues prepared in this study, only compound 57 demonstrated weak LTB4 receptor antagonist activity, at 10 microM.

Cell Aggregation↗
PubMed1997

Decreased serum apolipoprotein A-I concentrations in cows infected with Salmonella typhimurium.

Serum apolipoprotein A-I concentrations in cows infected with Salmonella Typhimurium were evaluated to assess its relevance in salmonellosis. Apolipoprotein A-I has been shown in rats to be secreted by the intestine as well as the liver. Clinical symptoms such as diarrhea revealed an outbreak of salmonellosis in 22 cows on a farm, and sera were obtained at 6 (acute phase), 16, 28 (convalescent period) and 42 d (postconvalescent period) after the outbreak. Apolipoprotein A-I concentrations (mean +/- SD, mg/mL), determined by ELISA, were 0.598 +/- 0.497 (day 6), 0.111 +/- 0.060 (day 16), 0.432 +/- 0.311 (day 28) and 0.727 +/- 0.516 (day 42). Compared with the concentration at day 42, those at 16 and 28 d were significantly (P < 0.01, P < 0.05) lower, but that at day 6 was not. The serum concentration of apolipoprotein B-100 (of liver origin in cattle) was unaltered during the course of salmonellosis. The concentration of apolipoprotein A-I was positively correlated with those of serum total cholesterol (r = 0.589, P < 0.01) and phospholipids (r = 0.590, P < 0.01). These results suggest that apolipoprotein A-I in cattle is in part of intestinal origin, and also that its decreased serum concentration in salmonellosis can be attributed to the reduced intestinal synthesis or secretion of this apolipoprotein. Moreover, as a potential carrier for dietary lipids such as cholesterol, determination of serum apolipoprotein A-I concentration is suggested to be useful when assessing the nutritional status of the affected cows.

Animals↗
PubMed1996

The substrate-binding site in Escherichia coli cyclophilin A preferably recognizes a cis-proline isomer or a highly distorted form of the trans isomer.

The three-dimensional structure of Escherichia coli cytosolic cyclophilin A (CyPA) complexed with a tripeptide (succinyl-Ala-Pro-Ala-p-nitroanilide) was refined at 1.8 A resolution by the multiple isomorphous replacement method to a crystallographic R-factor of 17.6%. As in human CyPA, the peptide binding site in E. coli enzyme is in a cleft created on the surface of the upper sheet of two orthogonal beta-sheets. In this cleft, the walls of the hydrophobic pocket are formed by the side-chains of five non-polar residues, Phe48, Met49, Phe107, Leu108, and Try120, with Phe99 at the bottom. When the cis isomer of the tripeptide binds to the enzyme, a cis-proline ring is inserted into the hydrophobic pocket. Since the binding pocket of CyPAs are largely hydrophobic, the cis isomer of a peptide can be bound more firmly than the trans isomer. Distortion of the trans isomer could lead to better binding, but at an energetic cost of the distortion energy. At the periphery of the upper beta-sheet in E. coli CyPA, conformations of loops L1, L3, and L4 and the segment connecting alpha1 and beta3 with deletions or insertions against human CyPA differ significantly from those in human CyPA. The refined model also shows that steric hindrance to attachment of cyclosporin A (CsA) prevents E. coli CyPA forming a complex with CsA. Thus, the extra amino acid residue of E. coli CyPA, polar Gln89, lies along the pathway to the hydrophobic pocket of CyPA and seems to prevent the access hydrophobic part of CsA to the cleft of CyPA.

Amino Acid Isomerases↗