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Biomedical subjects

K Hiramatsu

Publications and source records attributed to K Hiramatsu.

At least 19 recordsLinked to original sources
PubMed1997

Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin.

BACKGROUND: Since the discovery of the vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50 (minimum inhibitory concentration [MIC] 8 mg/L), there has been concern about the potential spread of such strains throughout Japanese hospitals. Two important questions need to be answered: (1) what is the prevalence of VRSA, and (2) by what mechanism does vancomycin resistance occur. METHODS: The vancomycin susceptibilities of three methicillin-resistant S aureus (MRSA) strains (Mu50, Mu3, and H1) and the methicillin-susceptible S aureus type strain FDA209P were compared by MIC determinations and population analysis. Mu3 (MIC 3 mg/L) was isolated from the sputum of a patient with pneumonia after surgery who had failed vancomycin therapy. H1 (MIC 2 mg/L), which is a representative vancomycin-susceptible MRSA strain, was isolated from a patient with pneumonia who responded favourably to vancomycin therapy. Subclones of Mu3 with increased resistance against vancomycin were selected with serial concentrations of vancomycin and their MICs were determined. The prevalence of VRSA and Mu3-like strains in Japanese hospitals was estimated by population analysis from 1149 clinical MRSA isolates obtained from 203 hospitals throughout Japan. The genetic traits of the Mu3 and Mu50 strains were compared with clonotypes of MRSA from around the world. FINDINGS: Mu3 and Mu50 had an identical pulsed-field gel electrophoresis banding pattern. When grown in a drug-free medium, Mu3 produced subpopulation of cells with varying degrees of vancomycin resistance, thus demonstrating natural heterogeneity, or variability, in susceptibility to vancomycin. In the presence of vancomycin, Mu3 produced subclones with resistance roughly proportional to the concentrations of vancomycin used. Selection of Mu3 with 8 mg/L or more of vancomycin gave rise to subclones with vancomycin resistance equal to that of Mu50 (MIC 8 mg/L) at a frequency of 1/1,000,000. During screening of Japanese MRSA strains, no strain of VRSA additional to Mu50 was found. The prevalence of MRSA isolates heterogeneously resistant to vancomycin was 20% in Juntendo University Hospital, 9.3% in the other seven university hospitals, and 1.3% in non-university hospitals or clinics. INTERPRETATION: Heterogeneously resistant VRSA is a preliminary stage that allows development into VRSA upon exposure to vancomycin. Heterogeneously resistant VRSA was found in hospitals throughout Japan. This finding could explain, at least partly, the frequent therapeutic failure of MRSA infection with vancomycin in Japan.

Aged↗
PubMed1997

A genetic animal model of human neocortical heterotopia associated with seizures.

Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a "rim-to-core" neurogenetic pattern rather than the characteristic "inside-out" pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the tish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures. The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.

Animals↗
PubMed1997

Effects of endocrine therapy on the primary lesion in patients with prostate carcinoma as evaluated by endorectal magnetic resonance imaging.

BACKGROUND: Little effort has been made at the quantitative and qualitative evaluation of patients with prostate carcinoma, including downsizing and downstaging of the primary lesion, after conservative therapy. The current study was undertaken to investigate the qualitative and quantitative effects of endocrine therapy on the primary prostate carcinoma using magnetic resonance imaging (MRI). METHODS: The primary prostate carcinoma was evaluated by endorectal MRI approximately 4 months after the initiation of endocrine therapy in 48 patients with histologically confirmed prostate carcinoma detected by endorectal MRI before therapy. RESULTS: The volumes of the prostate gland, the carcinoma, and the noncarcinomatous components were reduced to 60.2 +/- 2.7%, 25.5 +/- 2.9%, and 83.2 +/- 6.3% of their pretreatment volumes respectively after endocrine therapy, indicating that the tumors are more susceptible to endocrine therapy than the nontumorous components. The number of prostate carcinomas that demonstrated low signal intensity compared with the normal peripheral zone on T2-weighted images decreased after endocrine therapy and the number of carcinomas with enhancement of T1-weighted contrast-enhanced images increased after therapy. Seven of the 48 patients underwent downstaging after endocrine therapy, based on the endorectal MRI evaluation. CONCLUSIONS: The results of the current study suggest that downsizing and occasionally downstaging of the carcinoma may occur after endocrine therapy in patients with prostate carcinoma. In addition, the androgen sensitivity of the prostate carcinoma tissue is relatively high compared with the residual noncancerous prostate gland.

Antineoplastic Agents, Hormonal↗
PubMed1997

Behavioral and P3 amplitude enhancement in schizophrenia following feedback training.

In order to clarify the remediability of behavioral and electrophysiological abnormalities in schizophrenia, hit rate, reaction time, and P3 amplitude from auditory event-related potentials were evaluated before and after feedback training of a task in 14 schizophrenics and 12 age-matched normal controls. Although mean changes in the three indices due to the training were nonsignificant in both schizophrenic and normal control groups as a whole, the changes in hit rate and reaction time correlated significantly with the P3 amplitude change in the schizophrenic (r = 0.60 and -0.58, respectively) but not in the normal control group. The P3 amplitude change also correlated with the P3 amplitude before the training only in the schizophrenic group (r = -0.68), suggesting that the training was more effective for the schizophrenic patients with marked P3 amplitude reduction. The observed P3 amplitude increase due to training may represent an electrophysiological correlate of a remediable aspect of behavioral deficits in schizophrenics, which may underlie the effectiveness of nonpharmacological treatments.

Adult↗
PubMed1997

Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor. Competitive binding to the response element.

Peroxisome proliferators (e.g. clofibric acid) and thyroid hormone play an important role in the metabolism of lipids. These effectors display their action through their own nuclear receptors, peroxisome proliferator-activated receptor (PPAR) and thyroid hormone receptor (TR). PPAR and TR are ligand-dependent, DNA binding, trans-acting transcriptional factors belonging to the erbA-related nuclear receptor superfamily. The present study focused on the convergence of the effectors on the peroxisome proliferator response element (PPRE). Transcriptional activation induced by PPAR through a PPRE was significantly suppressed by cotransfection of TR in transient transfection assays. The inhibition, however, was not affected by adding 3,5,3'-triiodo-L-thyronine (T3). Furthermore, the inhibition was not observed in cells cotransfected with retinoic acid receptor or vitamin D3 receptor. The inhibitory action by TR was lost by introducing a mutation in the DNA binding domain of TR, indicating that competition for DNA binding is involved in the molecular basis of this functional interaction. Gel shift assays revealed that TRs, expressed in insect cells, specifically bound to the 32P-labeled PPRE as heterodimers with the retinoid X receptor (RXR). Both PPAR and TR bind to PPRE, although only PPAR mediates transcriptional activation via PPRE. TR.RXR heterodimers are potential competitors with PPAR.RXR for binding to PPREs. It is concluded that PPAR-mediated gene expression is negatively controlled by TR at the level of PPAR binding to PPRE. We report here the novel action of thyroid hormone receptor in controlling gene expression through PPREs.

Animals↗
PubMed1997

Microvascular changes associated with postischaemic hypoperfusion in rats.

The present study was undertaken to explore the cause of postischaemic hypoperfusion through morphological observations of the microstructure of brain cortex capillaries in rats with postischaemic hypoperfusion. Sixteen rats were used. The left middle cerebral artery of each animal was occluded for one hour (n = 8) or 2 hours (n = 8) and was followed by reperfusion for 2 hours. The regional cerebral blood flow (rCBF) of the ischaemia induced brain cortex was monitored continuously during the experiment and the microstructure of the brain cortex capillaries was then observed under electron microscope. Postischaemic hypoperfusion was observed in both ischaemia groups. The rCBF after (1.5 hours of reperfusion was significantly lower in the 2-hour ischaemia group than in the one-hour ischaemia group. The number of endothelial microvilli (MV) per capillary in the one-hour ischaemia group did not differ significantly from the control (the right cortex capillaries), whereas it was significantly higher in the 2-hour ischaemia group (p < 0.05). The ratio of the inner diameter to the outer diameter of capillaries decreased significantly in both ischaemia groups, and the ratio in the 2-hour ischaemia group was significantly lower than that in the one-hour ischaemia group (p < 0.05). Thus the present study statistically revealed that as postischaemic perfusion of the brains decreases, the number of MV increases, and endothelial cells swell more markedly. These microvascular changes seem to represent morphological factors associated with postischaemic hypoperfusion.

Animals↗
PubMed1997

Intrapleural instillation of interferon gamma in patients with malignant pleurisy due to lung cancer.

The effect of intrapleural instillation of recombinant human interferon gamma (IFN gamma) at increasing doses of (1-12) x 10(6) U was examined in six patients with cytologically positive pleural effusion due to lung cancer. Intrapleural instillation was repeated up to three times. Clinically, no reaccumulation of pleural effusion was observed in one patient and disappearance of lung cancer cells from the pleural effusion was seen in two other patients. No severe side-effects were observed. Considerable levels of IFN gamma remained in the pleural effusion as well as in patients' serum up to 7 days after instillation of 2 x 10(6) U and higher doses. The total cell number showed a transient decrease on day 1 of therapy. Levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin(IL)-1 beta and IL-6, in the pleural effusion remained almost stable after IFN gamma instillation. On the other hand, intrapleural IL-1 receptor antagonist levels were remarkably elevated by the instillation of IFN gamma. IL-2- and IL-12-inducible killer activity of pleural mononuclear cells tended to increase slightly. Despite the inability of IFN gamma to control pleural effusion in this treatment schedule, IFN gamma instilled by an intrapleural route had a potential local antitumor activity. Moreover, since IFN gamma persists in pleural effusions for a long time after a single instillation, such a therapy in combination with other fibrogenic biological response modifiers can be promising.

Aged↗
PubMed1997

Diagnostic and prognostic usefulness of N1,N8-diacetylspermidine and N1,N12-diacetylspermine in urine as novel markers of malignancy.

Recently, we found N1,N8-diacetylspermidine (Ac2Spd) and N1,N12-diacetylspermine (Ac2Spm) in human urine, and noted that their amount increased significantly in patients with urogenital malignancies. Previous findings that simultaneous reference to these diacetylpolyamines is useful in distinguishing cancer patients from healthy persons were confirmed by more recent analytical data on urine samples from several cancer patients. Further examination revealed that urinary Ac2Spm and Ac2Spd tended to decrease when cancer patients were treated and entered partial remission. In cases where the Ac2Spm and Ac2Spd levels were normal or near-normal after treatments, the prognosis of the patients was generally good. In contrast, when their level remained far above the normal limits after apparently effective treatment, the prognosis of the patients was poor. When a patient is in remission for more than 3 years, urinary levels of both Ac2Spm and Ac2Spd are stabilized and stay below the normal limits, with rare exceptions. The recurrence of a cancer as well as the complication of a second one during the period of follow-up examination was accompanied by elevation of urinary diacetylpolyamines. These observations indicate that urinary Ac2Spm and Ac2Spd are useful as prognostic indicators after treatment and during follow-up examination of cancer patients.

Adult↗
PubMed1997

Echocardiographic diagnosis of subepicardial aneurysm ruptured into the right ventricle after inferior myocardial infarction.

A subepicardial aneurysm is a rare complication of myocardial infarction that sometimes causes a left to right shunt at the ventricular level. We report on echocardiographic observations in two recent cases of inferior myocardial infarction complicated by rupture of a subepicardial aneurysm into the right ventricle (RV). Two-dimensional and color flow Doppler images in several planes offered diagnostic characteristics of the lesion, including discontinuity of the myocardium at the neck of the aneurysm, a narrow neck relative to the diameter of the aneurysm, and a back and forth flow at the neck of the aneurysm. These techniques also provided new findings, such as a two-chambered structure of the aneurysm and a circular flow pattern within the inner aneurysmal cavity. In addition, color flow Doppler imaging showed multiple shunt flows from the aneurysm to the RV. Echocardiographically diagnosed abnormalities were verified by and successfully treated with surgery in both cases. In conclusion, echocardiography with color flow Doppler imaging may have the potential to diagnose the anatomic and hemodynamic condition of a subepicardial aneurysm.

Aneurysm, Ruptured↗
PubMed1997

Preparation of antibodies highly specific to N1,N8-diacetylspermidine, and development of an enzyme-linked immunosorbent assay (ELISA) system for its sensitive and specific detection.

N8-Acetylspermidine was coupled to mercaptosuccinylated BSA using a bifunctional cross-linker, N-(4-maleimidobutyryloxy)succinimide, and the resulting conjugate was used to raise N1,N8-diacetylspermidine (DiAcSpd)-specific antibodies in rabbits. DiAcSpd-specific antibodies were enriched from crude sera through a series of affinity-based fractionations using ligands with structures mimicking those of DiAcSpd and monoacetylspermidines. With the N8-acetylspermidine-BSA conjugate as a solid phase antigen in a competitive ELISA system, the selectivity for DiAcSpd over other polyamine species was high, but competition by DiAcSpd added to the fluid phase was too weak for the system to be applicable to measurement of the concentration of DiAcSpd in human urine. In contrast, with the N1-acetylspermidine-BSA conjugate adsorbed on the ELISA plate, DiAcSpd efficiently competed for the same antibody, thus yielding a sensitive competitive ELISA system for measuring DiAcSpd. The Ki value for DiAcSpd with the latter competitive ELISA system was 54 nM, and the cross-reactivity with DiAcSpd, N1,N12-diacetylspermine, N8-acetylspermidine, N1-acetylspermidine, and acetylputrescine was 100, 1.2, 0.74, 0.12, and 0.08%, respectively. The DiAcSpd-specific antibodies and the competitive ELISA system developed in this study will prove to be useful for analyzing the urinary level of DiAcSpd, that was recently shown to be a promising diagnostic and prognostic indicator of malignant disorders.

Antibody Specificity↗
PubMed1997

Combined use of ribotyping, PFGE typing and IS431 typing in the discrimination of nosocomial strains of methicillin-resistant Staphylococcus aureus.

We have previously reported the phenotypic characterization of methicillin-resistant Staphylococcus aureus (MRSA) clinical strains isolated in Malaya University Hospital in the period 1987 to 1989 using antibiogram, coagulase typing, plasmid profiles, and phage typing. Here, we report the analysis of the same strains with three genotyping methods; ribotyping, pulsed-field gel electrophoresis (PFGE) typing, and IS431 typing (a restriction enzyme fragment length polymorphism analysis using an IS431 probe). Ribotyping could discriminate 46 clinical MRSA strains into 5 ribotypes, PFGE typing into 22 types, and IS431 typing into 15 types. Since the differences of the three genotyping patterns from strain to strain were quite independent from one another, the combined use of the three genotyping methods could discriminate 46 strains into 39 genotypes. Thus, the powerful discriminatory ability of the combination was demonstrated.

Bacterial Proteins↗
PubMed1997

[Evaluation of antibiotics used for enterohemorrhagic Escherichia coli O157 enteritis--effect of various antibiotics on extracellular release of verotoxin].

We tested antimicrobial activities of ten oral antibiotics; ampicillin (ABPC), cefdinir (CFDN), cefaclor (CCL), fosfomycin (FOM), norfloxacin (NFLX), nalidixic acid (NA), kanamycin (KM), minocycline (MINO), doxycycline (DOXY), and tetracycline (TC) against eleven enterohemorrhagic Esherichia coli (EHEC) O157 clinical strains. Two strains were resistant to ABPC and TC. Other strains were sensitive to all the ten antibiotics. To investigate the effect of antibiotics on extracellular release of verotoxin (VT), strain EHEC TT10 was grown in 10 ml of LB containing various concentrations of the antibiotics for 2 h. Number of viable cells were counted and the amounts of VT1 and VT2 released in the supernatants were measured with reverse passive latex agglutination (RPLA) using serially diluted sterilized culture supernatants. The amount of VT1 and VT2 was evidently increased with ABPC, CFDN, CCL, and FOM, the inhibitors of cell wall biosynthesis. In the case of quinolons, VT2 was markedly increased, but VT1 was not released to the supernatant. KM killed the bacteria efficiently, but no release of VT1 or VT2 was observed in the supernatant. Tetracyclines (MINO, DOXY, and TC) did not make the bacteria release either VT1 or VT2, but could not kill the bacteria appreciably. These results indicated that the inhibitors of protein synthesis (KM, MINO, DOXY, TC) are the safe antibiotics not causing the release of verotoxin from the cells and thus preventing development of hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpra (TTP), the important sequelae of the enteritis.

Ampicillin Resistance↗
PubMed1997

Angiomyolipoma: imaging findings in lesions with minimal fat.

PURPOSE: To investigate a method of diagnosing angiomyolipoma that contains minimal fat. MATERIALS AND METHODS: In six cases of angiomyolipoma with minimal fat, the attenuation on contrast material-enhanced and unenhanced computed tomographic (CT) images, the echogenicity on sonograms, the signal intensity on T2-weighted magnetic resonance (MR) images, and the gross configuration of the lesion were retrospectively analyzed. In 100 cases of renal cell carcinoma, the same parameters were analyzed, and results were compared with those of angiomyolipoma. RESULTS: When compared with the surrounding renal parenchyma, all six angiomyolipomas showed homogeneously high attenuation on unenhanced CT images, homogeneous enhancement on contrast-enhanced CT images, and homogeneous isoechogenicity on sonograms. Of the five angiomyolipomas examined with MR imaging, four were hypointense and one was isointense on T2-weighted images. All six angiomyolipomas protruded from the renal margin. None of the 100 renal cell carcinomas showed homogeneously high attenuation on unenhanced CT images, homogeneous enhancement on contrast-enhanced CT images, or homogeneous isoechogenicity on sonograms. CONCLUSION: In the kidney, homogeneously high attenuation on unenhanced CT images, homogeneous enhancement on contrast-enhanced CT images, and homogeneous isoechogenicity on sonograms are suggestive of angiomyolipoma that contains abundant muscle and minimal fat.

Adipose Tissue↗
PubMed1997

Cyclic AMP-elevating agents inhibit mite-antigen-induced IL-4 and IL-13 release from basophil-enriched leukocyte preparation.

Human peripheral blood basophils are known to secrete interleukin (IL)-4 and IL-13 after cross-linking of cell surface IgE. However, little is known about the pharmacological regulation of allergic cytokine release from basophils. In the present study, we investigated the effects of cyclic 3',5'-adenosine monophosphate (cAMP)-elevating agents on antigen-induced IL-4 and IL-13 release from basophil-enriched leukocyte preparations. We obtained venous blood from 27 atopic asthmatic patients (mean age was 45.8+/-3.6 years, all patients were sensitive to mite antigen) and prepared basophil-enriched leukocyte preparations by double-Percoll gradients (basophil purity was 13.4+/-1.6%). The cell preparations were treated with phosphodiesterase (PDE) inhibitors, dexamethasone, forskolin or dibutyryl cAMP for 10 min and were challenged with mite antigen for 6 h. The released IL-4 and IL-13 in the supernatants were measured by enzyme-linked immunosorbent assay systems. No IL-4 or IL-13 was detected in the supernatant of the basophil-depleted preparation after the challenge with mite antigen, suggesting that basophils specifically produce these cytokines. A nonselective PDE inhibitor, theophylline, and a PDE IV-selective inhibitor, rolipram, significantly suppressed the release of IL-4 and IL-13 from the basophil-enriched preparation. Although several concentrations of cilostazol, a PDE III-selective inhibitor, had no effect on the release of both cytokines, cilostazol suppressed the release of IL-4 additively when applied with rolipram. Forskolin and dibutyril cAMP also significantly suppressed the release of both cytokines, suggesting that the suppressive effects by PDE inhibitors were accompanied by the elevations in cAMP levels. We conclude that basophil-enriched leukocyte preparations produce IL-4 and IL-13 in response to antigen and that the release of these cytokines could be regulated by cAMP-modulating agents.

Animals↗
PubMed1997

Effect of antimicrobial agents on the piliation of Pseudomonas aeruginosa and adherence to mouse tracheal epithelium.

The effect of subminimal inhibitory concentrations (sub-MICs) of antimicrobial agents on the adherence of Pseudomonas aeruginosa (pili+) to trachea mucosal cells, the first stage in the development of P. aeruginosa respiratory tract infections, was investigated. The adherence of P. aeruginosa to the cells of the lower respiratory tract using a model of acid-injured trachea in mice was observed by electron microscopy (transmission and scanning). When P. aeruginosa was cultured with 1/4 MIC of erythromycin, minocycline, clindamycin, ofloxacin or tobramycin at 37 degrees C for 4 hours, the number of pili was significantly reduced (P < 0.01), together with a significant reduction in the number of adherent bacteria at 1/4 MIC of erythromycin (P < 0.01). No suppressive effects of piperacillin or ceftazidime were obtained on the piliation and adhesion of P. aeruginosa. These findings indicate that sub-MICs of erythromycin reduce the adherence of P. aeruginosa to the tracheal mucosa, which may prevent the onset of P. aeruginosa respiratory tract infection.

Animals↗