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Biomedical subjects

J Okada

Publications and source records attributed to J Okada.

At least 19 recordsLinked to original sources
PubMed2000

The skin permeation mechanism of ketotifen: evaluation of permeation pathways and barrier components in the stratum corneum.

To evaluate the pathways and barrier components in the stratum corneum (SC) for the permeation of ketotifen, the effect of delipidization on the permeation and partition was examined under several donor pHs. Assuming that ionized ketotifen (KTH+) and un-ionized ketotifen (KT) contribute independently in both permeation and partition, the intrinsic permeability coefficients and SC/water partition coefficients of both species were estimated. Delipidization enlarged the permeability of KTH+ 100 times. This suggested that the lipid phase functions as the barrier against KTH+. KT has an intrinsic permeability 100 times larger than that of KTH+. Delipidization did not result in a significant change in permeability of KT. This suggested that the permeability of KT through the lipid phase is comparable to that through the aqueous phase in delipidized SC; that is, the lipid phase functions as a highly permeable pathway for KT. On the other hand, the permeability coefficient of KT through delipidized SC was 1/34 of that through the pure aqueous layer, which had a thickness equivalent to SC. Since this suggests that the permeability of KT through the proteinaceous phase is much lower than that through the aqueous phase, the proteinaceous phase can be assumed to function as a barrier against the permeation of KT. From these results, it is concluded that the predominant permeation pathway for KT is through the lipid phase. The SC/water partition coefficient of KT was cut in half by delipidization, but the value was still more than 100. These results show that the proteinaceous phase functions not only as the barrier, but also as the depot for KT. The knowledge obtained here will be useful for formulation design and for the selection of enhancers in a transdermal therapeutic system of ketotifen.

Algorithms↗
PubMed2000

[Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) accompanied by hemophagocytosis and salivary gland swelling in a patient with systemic lupus erythematosus].

After 2 years of steroid therapy that had effectively controlled her systemic lupus erythematosus, a 37-year-old woman presented with fever, erythema (face, upper chest), and low CH50. Increased oral steroid (prednisolone from 15 mg to 40 mg) and intravenous methylprednisolone (mPSL) (80 mg for 3 days) alleviated these symptoms except for the fever. Subsequently, the patient's fever worsened and leukocytopenia, abnormal liver function, lymphadenopathy (neck, axilla), and salivary gland swelling developed. Lymph node histology revealed features characteristic of Kikuchi-Fujimoto's disease (KFD). Laboratory examinations showed WBC 600/microliter, Hb 9.5 g/dl, platelets 90,000/microliter, GOT 766 IU/l, GPT 646 IU/l, LDH 4,228 IU/l, TG 1,622 mg/dl, and ferritin 6,330 ng/ml. Serum interferon gamma was also elevated (673 U/ml). Because a bone marrow smear revealed hemophagocytosis, mPSL pulse therapy (1 g for 3 days) was started for treatment of hemophagocytic syndrome. The fever promptly disappeared, and the patient's clinical symptoms resolved within 2 weeks. The abnormal laboratory data related to KFD and hemophagocytosis returned to normal within 4 weeks after the initiation of mPSL pulse therapy. We speculated that the hemophagocytosis and salivary gland involvement in this patient were also symptoms of KFD. This case indicated that corticosteroid pulse therapy is effective for KFD with serious clinical symptoms.

Adult↗
PubMed1999

Effect of polymer/basic drug interactions on the two-stage diffusion-controlled release from a poly(L-lactic acid) matrix.

We investigated the effect of drug physico-chemical properties on the release of basic drugs from poly(L-lactic acid) (P(L)LA) cylindrical matrices (rods; 10 mmx1 mm diameter). All the rods were revealed to exhibit two-stage diffusion-controlled release profiles resulting from the transformation of P(L)LA from an amorphous to a semicrystalline state in aqueous medium. On the assumption that interactions between polymer carboxyl residues and basic drugs control the drug release rate, we evaluated the strength of these interactions by the drug partition between the polymer and the aqueous medium. In the first release stage, the drugs diffused through the swollen polymer matrix. The polymer-drug interactions shielded the polymer terminal carboxyl residues, thereby resulting in a less hydrated matrix and consequent diminishment of drug diffusion. In the second release stage, the drugs diffused through the water-filled micropores which had developed as a result of polymer crystallization. The stronger polymer-basic drug interactions reduced the drug diffusion rate by decreasing not only the porosity of the matrix, but also the drug partition to the water-filled micropores. It was also found that the fractional drug release rate in the second stage increased with drug content of the rod at the pH where both the polymer carboxyl residues and the drugs were ionized. Since the polymer-drug interactions must be close to saturation with increasing drug content, we believe this result to be due to an increase in the ratio of the drug partition to the water-filled micropores.

Biocompatible Materials↗
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

Analysis on reassortment of rotavirus NSP1 genes lacking coding region for cysteine-rich zinc finger motif.

Rotavirus clones A5-10 and A5-16 isolated from a bovine rotavirus strain A5 possess NSP1 gene which has a point mutation generating a nonsense codon and a 500 base-deletion, respectively. As a result, the two A5 clones encode truncated NSP1 product which lacks cysteine-rich region forming zinc finger motif. In order to analyze reassortment of these mutated NSP1 gene with RNA segments from heterologous strains, we investigated a number of reassortant clones derived from coinfection with either A5-10, A5-16 or a reference strain A5-13 (possessing intact NSP1 gene) and either simian rotavirus SA11 or human rotavirus KU. In coinfection with SA11 and A5-13, selection rates of A5-13 segments in reassortants ranged approximately from 20 to 70% (46% for NSP1 gene). In contrast, in the reassortment between SA11 and A5-10 or between SA11 and A5-16, selection rates of NSP1 gene from A5-10 and A5-16 were only 1% (one clone) and 0%, respectively. In reassortants from crosses KU x A5-clones, selection rate of A5-13 NSP1 gene decreased to 15%, while 11 reassortants with A5-10 NSP1 gene (31%) and one reassortant with A5-16 NSP1 gene (2%) were isolated. Reassortants with A5-10 NSP1 possessed a single gene (segment 9 or 11) from KU in the genetic background of A5-10. One reassortant clone (cl-55) with A5-16 NSP1 gene possessed KU gene segments 3, 4, and 8-11. When single-step growth curves were compared, the reassortant cl-55 showed almost identical growth curve to that of KU, while KU showed a better replication than A5-16. These results indicated that although A5-10 or A5-16 NSP1 gene encoding the truncated NSP1 is selected into reassortants much less efficiently than normal NSP1 gene, the reassortants with the mutated NSP1 gene and RNA segments from heterologous strains normally replicated in cultured cells. Thus, cysteine-rich region of NSP1 was not considered essential for genome segment reassortment with heterologous virus.

Animals↗
PubMed1999

Functional analysis of the heterologous NSP1 genes in the genetic background of simian rotavirus SA11.

Function of rotavirus NSP1 was analyzed by using single-NSP1 gene-substitution reassortants, SKF, SDF, and SNF which have the NSP1 gene derived from human rotaviruses KU, DS-1, and canine rotavirus K9, respectively, in the genetic background of simian rotavirus SA11. The NSP1 genes from KU, DS-1, K9, and SA11 exhibited 58-76% nucleotide sequence identity to one another. No substantial difference in viral growth was observed among the reassortants and SA11. However, production of NSP1 was not detected in SNF when viral proteins were labelled with 35S-methionine during replication in MA104 cells, in contrast to SA11, SKF and SDF which exhibited evident expression of NSP1. Difference in reassortant formation was examined among the reassortant clones generated between human rotavirus strain 69M and either of SA11, SKF or SNF. Although reassortant formation rate was significantly lower in the cross 69M x SNF than the other crosses, selection rates of RNA segments from parent strain 69M in the resultant reassortants was similar among the crosses. Selectivity of homologous and heterologous NSP1 genes in SA11 background was also analyzed by mixed infection and multiple passages among the single-NSP1 gene-reassortants and/or SA11, KU NSP1 gene was selected most frequently, whereas homologous (SA11) NSP1 gene was least efficiently segregated. These results indicated that viral growth and genome segment reassortment with other viruses may not be influenced by the presence of heterologous NSP1 and its expression level, while genomic diversity of NSP1 genes might have been associated with the relative adaptability to the genetic background of SA11.

Animals↗
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

Efficacy of sulfamethoxazole-trimethoprim administration in the prevention of Pneumocystis carinii pneumonia in patients with connective tissue disease.

The efficacy and adverse effects of prophylactic administration of Sulfamethoxazole-Trimethoprim (ST) for Pneumocystis carinii Pneumonia (PCP) were assessed in patients with connective tissue diseases (CTD). Eighty-four patients who were receiving more than 40 mg/day of prednisolone were entried in the present study. Patients with at least one of the two PCP risk factors (interstitial pulmonary fibrosis and lymphopenia), were administered either one (11 patients) or two (26 patients) ST tablets/day. The remaining 47 patients who did not receive ST served as the controls. Although PCP was detected in 4.3% of the patients in the no-ST group, none of the patients who received ST developed PCP. Five of these 26 patients who received two tablets of ST/day, experienced adverse reactions. However, no adverse reactions were detected in the patients who received one tablet of ST/day (p < 0.05). Abnormal laboratory data were obtained for 10 (38.5%) of the patients who received two tablets of ST/day and for 4 (36.4%) of the 11 patients who received one tablet of ST/day. The results of the present study suggest that the prophylactic administration of one tablets of ST in patients with CTD that have at least one of the two PCP risk factors is effective in preventing PCP.

Adult↗
PubMed1999

Prevalence of soft tissue calcifications in patients with SLE and effects of alfacarcidol.

OBJECTIVE: To clarify the prevalence and etiology of ectopic calcification in patients with systemic lupus erythematosus (SLE), especially under the active vitamin D3 administrations and to reveal the risk factors of ectopic calcification. METHODS: Sixty patients with SLE, excluding the patients on dialysis were studied. We examined radiographs of hands, forearms, upper and lower extremities, and pelvises of all patients to evaluate ectopic calcification. RESULTS: The prevalence of ectopic calcification in SLE was 40% (24 out of 60 patients), found in 6.7% (4 patients) in peripheral arteries, 33.3% (20 patients) in periarticular area and 16.7% (10 patients) in other soft tissues. The incidence of lupus nephritis and nephrotic syndrome were significantly higher (respectively: P=0. 0144 and P=0.0348) in the calcification-positive than negative group. Total protein levels (7.04+/-0.6 g/dl) of patients in the calcification-positive group were decreased significantly (P=0.0056) compared with 7.48+/-0.55 g/dl in the negative group. However, other biochemical parameters were not significantly different between the two groups. Sixty-three percent of the SLE patients with ectopic calcification received alfacarcidol, which is significantly (P=0. 0007) higher than the 19% in patients without calcification. CONCLUSION: It is suggested that the alfacarcidol therapy and lupus nephritis could increase the risk of ectopic calcification in SLE patients.

Adult↗
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↗
PubMed1999

[Five cases of systemic sclerosis with associated with intestinal pseudo-obstruction].

OBJECTIVES: We experienced five cases of systemic sclerosis (SSc) associated with pseudo-obstruction, and evaluated their clinical characteristics and outcome. METHODS: Five patients with SSc were found to have intestinal pseudo-obstruction. We studied the clinical characteristics, treatments and outcome of these five case from medical records. RESULTS: The intestinal symptoms were free air in three and pneumatosis cystoides intestinalis (PCI) in two of the five patients. Cisapride was administered to all patients and octreotide and dinoprost to three patients, but the effects were not adequate and intravenous hyperalimentation (IVH) had to be introduced in four patients. Drug treatment was effective in patients in the early stage of intestinal symptoms, but IVH had to be introduced in patients with a long course. Septicemia occurred in two of the four patients on IVH and an infection occurred at the catheter insertion site in one patient. These two patients died of septicemia. Of five patients we experienced with SSc associated with intestinal pseudo-obstruction, two had PCI and four required IVH at home. Two of the four on home IVH developed septicemia. CONCLUSIONS: Intestinal pseudo-obstruction is one of the poor prognostic factors for SSc.

Aged↗
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↗