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Biomedical subjects

J Okada

Publications and source records attributed to J Okada.

At least 19 recordsLinked to original sources
PubMed1999

Mechanism of drug release from poly(L-lactic acid) matrix containing acidic or neutral drugs.

The release profiles of acidic and neutral drugs from poly(L-lactic acid) [P(L)LA] matrices were investigated to reveal their release mechanism. Cylindrical matrices (rods; 10 mmx1 mm diameter) were prepared by the heat compression method. The acidic and neutral drugs investigated were dissolved in the P(L)LA rods. It was found that the release profiles consisted of two sequential stages. At the first release stage, P(L)LA remained in an amorphous state and the drugs diffused through the hydrated matrices. At the second release stage, P(L)LA transformed to a semicrystalline state and the drugs diffused through water-filled micropores developed by polymer crystallization. In addition, the drugs were also found to precipitate out as crystals in the rods, resulting in a transformation of the rods into drug-dispersed matrices. On the basis of these findings, we derived a modified diffusion equation for the drug release at the second stage. This equation showed good fits to the release profiles of these drugs. Furthermore, the availability of the derived equation was supported by the acceleration in the fractional drug release rate noted both with decreases in the drug content in the rod and increases in the pH of the medium.

Biodegradation, Environmental↗
PubMed1999

67Ga planar imaging with a low-energy collimator and scatter correction using the triple energy window method.

To improve the spatial resolution and contrast of 67Ga planar imaging, we used a low-energy collimator and two lower-energy windows with a triple-energy-window (TEW) scatter compensation method. The spatial resolution is better than with a medium-energy collimator, and the TEW method can correct for scattered photons and reduce the background counts. In a phantom study and a clinical study involving 44 patients, the images obtained by the proposed method were compared with the images obtained with a medium-energy collimator and three energy windows without scatter compensation (the conventional method). The spatial resolution and the counts were measured. Two nuclear medicine physicians interpreted the images and clinical usefulness was evaluated. The spatial resolution and contrast were improved by our proposed method. It enabled the detection of lesions in five locations in the clinical study. The counts were reduced but misreadings were not seen. We conclude that our proposed method shows a clinical advantage over the conventional method. It can be used easily and quickly with commercially available equipment and is useful in clinical practice.

Adult↗
PubMed1999

Multineuronal spike classification based on multisite electrode recording, whole-waveform analysis, and hierarchical clustering.

We proposed here a method of multineuronal spike classification based on multisite electrode recording, whole-waveform analysis, and hierarchical clustering for studying correlated activities of adjacent neurons in nervous systems. Multineuronal spikes were recorded with a multisite electrode placed in the hippocampal pyramidal cell layer of anesthetized rats. If the impedance of each electrode site is relatively low and the distance between electrode sites is sufficiently small, a spike generated by a neuron is simultaneously recorded at multielectrode sites with different amplitudes. The covariance between the spike waveform at each electrode site and a template was calculated as a damping factor due to the volume conduction of the spike from the neuron to the electrode site. Calculated damping factors were vectorized and analyzed by hierarchical clustering using a multidimensional statistical test. Since a cluster of damping vectors was shown to correspond to an antidromically identified neuron, spikes of different neurons are classified by referring to the distributions of damping vectors. Errors in damping vector calculation due to partially overlapping spikes were minimized by successively subtracting preceding spikes from raw data. Clustering errors due to complex spike bursts (i.e., spikes with variable amplitudes) were avoided by detecting such bursts and then using only the first spike of a burst for clustering. These special procedures produced better cluster separation than conventional methods, and enabled multiple neuronal spikes to be classified automatically. Waveforms of classified spikes were well superimposed. We concluded that this method is particularly useful for separating the activities of adjacent neurons that fire partially overlapping spikes and/or complex spike bursts.

Action Potentials↗
PubMed1999

[Immunosuppressive treatment strategy in connective tissue diseases].

In this review, we summarized important articles published about immunosuppressive agents in connective tissue diseases. Intravenous cyclophosphamide therapy for lupus nephritis and oral cyclophosphamide therapy for Wegener's granulomatosis are major progress in past one decade. Newer immunosuppressive agents such as cyclosporin, tacrorimus are also introduced in steroid refractory organ involvements. And we discussed also the monitoring and prevention of adverse effects of immunosuppressive agents. This review will focus on immunosuppressive treatment strategy of connective tissue diseases.

Connective Tissue Diseases↗
PubMed1999

[In vitro activities of 23 antimicrobial agents against 4,993 gram-positive and gram-negative bacterial strains isolated from multicenter of Japan during 1994--in vitro susceptibility surveillance.Levofloxacin-Surveillance Group].

In a surveillance study conducted during 1994 at 24 medical institutes from different geographical areas of Japan, the susceptibility of clinical isolates to twenty three comparative agents, such as ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin, ampicillin, clavulanic acid/amoxicillin, oxacillin, piperacillin, cefaclor, cefotiam, cefdinir, cefclidin, ceftazidime, cefpirome, imipenem, aztreonam, vancomycin, minocycline, chloramphenicol, clarithromycin, sulfamethoxazole/trimethoprim, amikacin, and gentamicin, were tested by the standard broth micro-dilution method. A total of 4,993 isolates tested in this study included Streptococcus pneumoniae, methicillin susceptible Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), coagllase negative streptococci (CNS), Enterococcus faecalis, Enterococcus faecium, Enterobactericeae, Pseudomonas aeruginosa from patients with urinary tract infections or respiratory tract infections, and Haemophilus influenzae. For MSSA, S. pneumoniae, Enterobacteriaceae, and H. influenzae, more than 70% of the isolates was susceptible to fluoloquinolones. However, resistance occurred in more than 50% of MRSA and P. aeruginosa isolated from UTI. Fluoroquinolones were found to be effective against high level penicillin-resistant S. pneumoniae, the third generation cephem-resistant Enterobacteriaceae and ampicillin-resistant H. influenzae.

Anti-Bacterial Agents↗
PubMed1999

[Survey of the sensitivities of clinical isolates to antibacterial agents (annual report)].

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems, were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,241 strains of 11 bacterial species isolated at all institutions between October and December 1996. The results were as follows: Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae and showed low activities against MRSA. Their activities against Enterococcus faecalis were comparable to that of ampicillin and piperacillin. The carbapenems showed high activities against Haemophilis influenzae, Escherichia coli, Klebsiella pneumoniae. Enterobacter cloacae. Serratia marcescens and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents, but some resistant strains of Serratia marcescens were detected. The antibacterial activity of carbapenems against Pseudomonas aeruginosa was comparable to that of CAZ, and there were some resistant strains.

Carbapenems↗
PubMed1998

Factors influencing the diffusion-controlled release of papaverine from poly (L-lactic acid) matrix.

Effects of drug content and medium pH on the release of papaverine (PAP) from biodegradable poly(l-lactic acid) [P(L)LA] matrix were investigated to reveal the predominant factors affecting the two-stage diffusion-controlled release mechanism. A drug-dissolved cylindrical matrix (rod; 10 mmx1 mm diameter) was prepared by heat compression method. In the case of a PAP content below 10%, pH was found to have a strong effect on the release rate, and drug content was found to have no effect on the release profile. The release profile consisted of two sequential diffusion stages due to P(L)LA transformation from amorphous to the semicrystalline state prior to release. In the first release stage PAP diffused through the swollen matrix. The release accelerated with increasing medium pH due to an increase in water content in the acidic P(L)LA rod. In the second release stage PAP diffused through the water-filled micropores developed as a result of the polymer crystallization. On the assumption that the drug partition between the polymer and the medium in the micropores affects the diffusion and the partition is controlled by pH, we derived a modified diffusion kinetic equation. The observation that the release decelerated with increasing medium pH can be explained by the derived equation as resulting from the increase in the drug partition to the polymer. In the case where the rods contained more than 15% of PAP, the drug precipitated out as crystals during release. Accordingly, these rods showed a slower release.

Chemical Phenomena↗
PubMed1998

H+-sensitivity of cultured neurons from the dorsomedial and ventrolateral medulla of neonate rats.

The H+-sensitivity of neonate rat cultured neurons derived from the dorsomedial medulla (DMM) containing the nucleus tractus solitarii and the ventrolateral medulla (VLM) was determined by H+-sensitive fluorescent probe BCECF-AM and immunohistochemical methods. Against an extracellular pH as low as 7.2-7.3, H+-sensitivity was verified in 2.6% of the DMM neurons (46/ 1800) and 2.1% of the VLM neurons (38/1800). This H+-sensitive neurons of the DMM were immunoreactive to glutamate (52.4%) and glutamic acid decarboxylase (GAD) (28.6%), while those of the VLM were immunoreactive to glutamate (66.7%) and GAD (33.3%). There was no immunoreactivity to tyrosine hydroxylase, phenylethanolamine-N-methyltransferase or choline acetyltransferase in the H+-sensitive neurons are present in the DMM and VLM besides the ventral medullary surface, the site of the central chemoreceptors.

Animals↗
PubMed1998

Double column-switching high-performance liquid chromatographic method for the determination of TAK-603 and its metabolites in human serum.

A double column-switching high-performance liquid chromatographic (HPLC) method for the determination of concentrations for TAK-603 (T) and its metabolites, T-72258 (M-I) and T-72294 (M-III), in human serum was developed. The analytes were extracted with ethyl acetate from human serum samples treated with triethylamine and injected into the HPLC system. Separation of the analytes was performed on the HPLC system with double column-switching technique. The mobile phases A and B for the first column and the mobile phase C for the second column used were a mixture of methanol-10 mM aqueous ammonium acetate solution (1:1, v/v), methanol and a mixture of methanol-10 mM aqueous ammonium acetate solution (11:9, v/v), respectively. The eluate was monitored with a UV detector at a wavelength of 253 nm. The work-up procedure was reproducible and more than 90% of the analytes could be recovered from human serum. The lower limits of quantitation were all 1 ng/ml for the analytes when 0.5 ml of human serum was used. Standard curves were linear with a correlation coefficient (R) of more than 0.999 in the range of 1-500 ng/ml for T, M-I and M-III in human serum. The intra- and inter-day precision of the method for the various analytes were below 4.8%. The accuracy was good with the deviations between spiked and calculated concentrations of the analytes being within 11.0%. The method was successfully applied to analyze serum samples after an oral administration of T to healthy male volunteers.

Administration, Oral↗
PubMed1998

Pharmacological properties of the CO2/H+-sensitive area in the ventral medullary surface assessed by the effects of chemical stimulation on respiration.

We recently discovered that CO2/H+-sensitive neurons in the ventral medullary surface (VMS) are immunoreactive to glutamate, glutamic acid decarboxylase (GAD), calcineurin and cAMP. We then tested the hypothesis that glutamate, GABA, calcineurin and cAMP affect the activity of CO2/H+-sensitive neurons in the VMS. Using male Wistar rats anesthetized with urethane and pentobarbital, we checked for changes in relative tidal volume (VT) and respiratory frequency (f) in response to injecting the VMS with a variety of test agents dissolved in mock CSF. Respiratory changes occurred immediately and were dose-dependent. (1) 200-1600 pmol Glutamate increased VT but decreased f. The glutamate effect was never abolished by concomitant injection of AP5, a NMDA receptor antagonist, but was abolished by CNQX, an AMPA receptor antagonist, indicating predominance of AMPA receptors in the CO2/H+-sensitive neurons in the VMS. (2) 200-1600 pmol GABA decreased both VT and f. The GABA effect was never abolished by concomitant injection of saclofen, a GABA(B) receptor antagonist, but was abolished by bicuculline, a GABA(A) receptor antagonist, indicating predominance of GABA(A) receptors in the CO2/H+-sensitive neurons in the VMS. (3) 4-32 microg Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase 2B, and 200-1600 pmol FK506, selective inhibitor of calcineurin, had no effect on respiration when they were applied extracellularly, but 400-3200 pmol BAPTA-AM, an intracellular Ca2+-chelating agent, decreased both VT and f, indicating involvement of intracellular Ca2+ in the excitatory mechanisms of respiration. (4) 100-800 pmol IBMX, an enhancer of intracellular cAMP, decreased both VT and f, indicating involvement of cAMP in the inhibitory mechanisms of respiration. These results indicate that the CO2/H+-sensitive neurons in the VMS contain glutamate and/or GABA in cytoplasma, possess AMPA and/or GABA(A) receptors on surface of plasma membrane, and compose the internal circuit, and that their activities are regulated by Ca2+ and cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Difference in topology and numbers of barosensitive catecholaminergic and cholinergic neurons in the medulla between SHR and WKY rats.

We hypothesized that there may be a significant difference in the neuronal composition of the baroreceptor reflex pathway between normotensive Wistar Kyoto (WKY) and spontaneously hypertensive SHR rats. Using the double-immunoreactive (IR) method, the topology and numbers of barosensitive neurons that contain glutamate (Glu), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT) and choline acetyltransferase (ChAT) were compared between the two strains. The control rats were sham-operated only for cannulation of the trachea and femoral artery/vein. The test rats were injected with the pressor agent phenylephrine to raise blood pressure and stimulate arterial baroreceptors. In both the control and test experiments, the c-Fos/Glu-, GAD-, TH- and PNMT-IR neurons were found in the nucleus tractus solitarii (NTS) and ventrolateral medulla (VLM), while the FosB/ChAT-IR neurons were found in the NTS, dorsal motor nucleus of the vagus (DMX) and nucleus ambiguus (AMB). In the control experiment, no significant difference in numbers was recognized in any of the double-IR neurons between the two strains. In the test experiment, the numbers of FosB/ChAT-IR neurons in the NTS, DMX and AMB were significantly smaller in SHR than in WKY. The numbers of c-Fos/TH-IR neurons in the caudal VLM were significantly larger in SHR than in WKY. These results suggest that a smaller number of barosensitive cholinergic neurons in the DMX and AMB in SHR causes the weaker baroreceptor-cardiac vagal reflex in SHR, and that a larger number of barosensitive catecholaminergic neurons in the caudal VLM in SHR are involved in the stronger baroreceptor-vasopressin reflex in SHR.

Animals↗
PubMed1998

Topology and immunohistochemistry of proton-sensitive neurons in the ventral medullary surface of rats.

We aimed to clarify the topology and immunohistochemistry of CO2/H+-sensitive neurons in the ventral medullary surface (VMS), the central chemoreceptor area in rats. Inhalation of 3 and 7% CO2 in air significantly decreased pH in arterial blood and increased paCO2, which caused hyperpneic and tachypneic responses. Following inhalation of 3 and 7% CO2 in air for 5 min, the density of c-Fos-immunoreactive (IR) neurons increased stepwise not only in the 3rd-5th divisions of the VMS (between the caudal end of the nucleus corporis trapezoidei and the caudal end of the area postrema), but also in the rostroventromedial medulla (RVMM). Following inhalation of 7% CO2 in air for 5 min, glutamate-, glutamic acid decarboxylase (GAD)-, calcineurin- and cAMP-IR neurons were found not only in the VMS, but also in the RVMM. The topology of these neurons was similar to that of the c-Fos-IR neurons. No immunoreactivity was found for serotonin, substance P, somatostatin, cholecystokinin-octapeptide, methionine-enkephalin, choline acetyltransferase, tyrosine hydroxylase, phenylethanolamine N-methyltransferase, NO-synthase, S-100, calbindin-D, calmodulin, or parvalbumin. The densities of c-Fos-, glutamate-, GAD-, calcineurin- and cAMP-IR neurons were almost zero in the 1st division of the VMS, but became higher along the 2nd-4th divisions of the VMS. Regression lines of the density against the 1st-4th divisions of the VMS were significantly linear. These results indicate that H+-sensitive neurons are common in the 4th-5th divisions of the VMS, and that they are glutamatergic, GABAergic, and containing calcineurin and cAMP.

Administration, Inhalation↗
PubMed1998

Preferential selection of heterologous G3-VP7 gene in the genetic background of simian rotavirus SA11 detected by using a homotypic single-VP7 gene-substitution reassortant.

Introduction of segmented genomes into virion is an important process in viral replication of rotavirus. We previously studied the assortment of the VP7 gene segment (encoding outer capsid protein VP7) in the genetic background of simian rotavirus SA11 (G serotype 3, G3) and found the preferential selection of homologous G3 VP7 gene over VP7 gene of heterologous G serotype (G1, G2 or G4). In the present study, in order to clarify whether or not VP7 gene derived from different G3 rotavirus (heterologous G3-VP7 gene) is also preferentially selected in the SA11 background, a single-VP7 gene-substitution reassortant was prepared from SA11 through multiple steps of coinfection with rotaviruses in vitro. The isolated reassortant, SNR1, possessed VP7 gene derived from canine G3 rotavirus K9 and all other gene segments of SA11 origin, and showed an identical growth characteristic to that of SA11. Amino acid sequence of K9 VP7 gene showed a high degree of identity (93.6%) to SA11 VP7 gene. In analysis by mixed infection and multiple passages of SNR1 and a single VP7 gene (with G1, G2 or G4 specificity) reassortant in the SA11 background, the G3-VP7 gene became predominant at early passage numbers. However, in mixed infection with SA11 and SNR1, homologous G3-VP7 gene (SA11-VP7 gene) was preferentially selected into progenies over heterologous one (K9-VP7 gene). These results together with our previous findings suggested that G3-VP7 gene, irrespective of origin of species, was functionally adapted to the genetic background of SA11, although the homologous gene had a better fit with other SA11 genes than did heterologous one, providing suggestions for efficaciousness of multivalent reassortant rotavirus vaccine.

Amino Acid Substitution↗
PubMed1998

Molecular discrimination of enterotoxin C subtype in clinical isolates of Staphylococcus aureus.

The subtype of staphylococcal enterotoxin C (SEC) of 33 S. aureus clinical isolates was determined by polymerase chain reaction and direct DNA sequencing of a portion of the SEC gene encoding the SEC subtype-specific region. With the exception of a single strain with the SEC2 gene, all other strains showing different biologic and genetic properties were proved to possess the SEC3 gene.

DNA Primers↗
PubMed1998

Glomerular thromboxane contributes to pressor response in deoxycorticosterone acetate-salt hypertension.

To assess the role of renal thromboxane in a salt sensitive pressor response in hypertension, urinary excretion of thromboxane and its release from isolated glomeruli and renal papillae were examined in deoxycorticosterone acetate treated rats with normal (0.6%, n = 12) and high (4%, n = 12) salt diets for 8 weeks. Mean blood pressure, measured directly by an implanted aortic catheter, was higher in the high salt diet group than in the normal salt diet group (146 +/- 2 vs 119 +/- 2 mmHg, P<0.01). Urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1alpha in the high salt group were significantly higher than those in the normal salt diet group, but there was no difference in urinary excretion of prostaglandin E2 between the two groups. Release of thromboxane B2, 6-keto-prostaglandin F1alpha, and prostaglandin E2 from isolated glomeruli in the high salt diet group increased significantly by 104%, 55%, and 74%, respectively, compared with the normal salt diet group. Stepwise multiple linear regression analysis showed that significant contributory factors for mean blood pressure in deoxycorticosterone acetate treated rats were urinary excretion of sodium (F=14.187, P<0.01) and release of thromboxane B2 from isolated glomeruli (F=4.135, P<0.05). The unstandardized coefficient (R) calculated from the regression function using these two factors was 0.875 and R2 was 0.765. The manifest synthesis of thromboxane in renal glomeruli has an important role on salt sensitive pressor response in deoxycorticosterone acetate-salt hypertension of rats.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Experience and clinical usefulness of BACTEC MGIT 960.

Recently, an automatic instrument for culturing acid-fast bacteria in liquid media has been introduced in Japan to accelerate and increase the detection of the bacteria as well as the work e ciency of test lab technicians. We compared the MGIT (Mycobacterium Growth Indicator Tube) method and the two conventional culture methods used in our lab by testing 176 specimens (130 cases) submitted for acid-fast testing between July 27 and September 18, 1998. BACTEC MGIT 960 (Nippon Becton Dickinson) was used in the MGIT method while Ogawa K medium and Kudo PD medium were used for our conventional culture methods. Of the 176 specimens, 26 specimens were MGIT positive, 22 specimens were Ogawa K medium positive, and 21 specimens were Kudo PD medium positive. Among these three culture methods, M. tuberculosis was found in 8 specimens, M. avium was found in 9 specimens, M. intracellulare was found in 4 specimens, and other acid-fast bacteria were found in 5 specimens. It took an average of 13.5 days to detect M. tuberculosis by the MGIT method, 23.0 days by the Ogawa K medium, and 24.3 days by the Kudo PD medium, suggesting that the MGIT method is signi cantly faster than the conventional methods (p < 0.05). The MGIT method took an average of 5.7 days to detect M. avium and M. intracellulare while the two conventional methods required more than 20 days, suggesting that the MGIT method is signi cantly faster than the conventional methods (p < 0.05). The BACTEC MGIT 960 was extremely useful for clinical diagnosis in some of the cases and our results indicated that the MGIT method led to more rapid diagnosis and earlier treatment than the conventional methods.

Adult↗
PubMed1998

[Survey of the sensitivities of clinical isolates to antibacterial agents (annual report)].

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,282 strains of 11 bacterial species isolated at all institutions between October and December 1995. The results were as follows: 1. Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae. Their activities against Enterococcus faecalis were comparable to that of ABPC. Carbapenems showed low activities against MRSA. 2. OFLX exhibited the greatest antibacterial activity against Haemophilus influenzae, followed by MEPM. The antibacterial activities of the other carbapenems were comparable to those of FMOX and CTM. 3. The carbapenems showed high activities against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents. The carbapenems also exhibited greater antibacterial activities against Serratia marcescens than the other beta-lactam antibacterial agents, but some resistant strains were detected. 4. The antibacterial activities of carbapenems against Pseudomonas aeruginosa were comparable to those of CAZ, AZT, AMK.

Carbapenems↗