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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 631 records · Page 35Linked to original sources

The other mediator for adherence of Haemophilus influenzae organisms without involvement of fimbriae.

The number of the nontypeable Haemophilus influenzae (HiN) organisms that adhered to the primary mouse fetal lung cells was significantly more than type b Haemophilus influenzae (Hib) organisms. The average number of HiN organisms adherent to host cells was 2,291/100 host cells (range, 1,654-3,182), but that of Hib was markedly reduced to 147/100 host cells (range, 102-238). In this case, P value was less than 0.05 by using a paired Student t-test. The sonicated extract from HiN TMS11 organisms inhibited adherence of H. influenzae TMS11 organisms to monolayer at 76.3% and it inhibited adherence of Hib TMS24 organisms at 92.3%. This result indicates that a mediator existing on the surface of HiN organisms may be the same as that on type b organisms. The number of detected organisms in broncho and lung tissues 3 days after intranasal infection with HiN strains was significantly greater than that in infection with Hib strains. Therefore, in vitro adhesive capacity of H. influenzae organisms was correlative to infectivity by intranasal injection.

Animals↗

Further evaluation of the pregnancy-linked down-regulation of the paternal antigen-specific splenic cytotoxic T lymphocyte activity in allogeneically pregnant mice.

Cytotoxic T lymphocyte (CTL) activity directed against paternal alloantigen was examined in allogeneically pregnant mice using various allogeneic combinations. The spleen cells from pregnant C57BL/6 (H-2b) mice mated with BALB/c (H-2d) male mice generated less anti-H-2d CTL after in vitro sensitization than those from unpregnant or syngeneically mated C57BL/6 mice. Different allogeneic combinations including the incompatibility at only D region of H-2 or minor histocompatibility loci were effective for downregulating the anti-paternal CTL activity in pregnancy. The downregulation of anti-paternal CTL activity induced by allogeneic pregnancy occurred at day 10 to day 18 of pregnancy, most extensively at day 14. The allogeneic pregnancy also downregulated the allogeneic CTL activities that had been amplified by injecting alloantigens before mating.

Animals↗

Co-existence of colonies with different serotypes and other biological characteristics in clinical isolates of Pseudomonas aeruginosa.

The biological characteristics of individual colonies of Pseudomonas aeruginosa from 138 specimens were investigated. Of these isolates, 90 (65.2%) formed colonies of similar appearance and morphology, and 48 (34.8%) formed colonies which differed either in appearance or morphology. The individual colonies of 138 isolates were tested for serotype. The former 90 isolates formed only the colonies with one kind of serotype, whereas 17 of the latter 48 isolates formed the colonies with more than one kind of serotype. All the 9 isolates tested also differed in other biochemical characteristics: acid productions from xylose, mannitol and maltose, urease production and gelatin liquefaction. beta-Lactamase activity was investigated in 7 isolates forming colonies with more than one serotype. There were no marked differences in beta-lactamase activity among the different colonies in 5 isolates but marked differences among those in the other 2 isolates.

Gelatin↗

[Role of capsular polysaccharide and lipopolysaccharide of Klebsiella pneumoniae in experimental mice pneumonia model].

In this study, role of capsular polysaccharide (CPS) and lipopolysaccharide (LPS) of Klebsiella pneumoniae was investigated in experimental mice pneumonia model. Inoculation with K. pneumoniae mucoid strain DT-S into mice lung induced expansive, voluminous lethal pneumonia characterized with thickening of the alveolar septa caused by infiltration of inflammatory cell and packing of bacteria within alveolar spaces. On the other hand, mice lung inoculated with K. pneumoniae DT-X, which was non-mucoid mutant isolated from DT-S during natural passage, showed infiltration of inflammatory cell into alveolar spaces but there was no death of mice during the course of this pneumonia. Inoculation of CPS 100 micrograms of DT-S strain into mice lung induced lesser extent of accumulation of inflammatory cell than that of LPS 4 micrograms of this strain. Stimulation of alveolar and peritoneal macrophage with CPS, even at a concentration of 100 micrograms/ml, induced weaker Interleukin-1 (IL-1) activity than stimulation with LPS 4 micrograms/ml. These results suggest that since CPS of K. pneumoniae DT-S encapsulate bacteria including LPS, CPS may inhibit chemotaxis of inflammatory cell and IL-1 production of macrophage to be induced by LPS during course of pneumonia. It is speculated that existence of CPS have important role in modulating host response to bacterial LPS, and this effect of CPS may be related with difference of pathological findings of lung and lethality between K. pneumoniae DT-S and DT-X.

Animals↗

[Effect of azithromycin on human serum sensitivity of Pseudomonas aeruginosa].

We examined the effect of azithromycin (AZM), a 15-membered azalide newly synthesized from erythromycin (EM), on serum sensitivity of 6 strains of Pseudomonas aeruginosa. Incubation for 48 h on agar with EM 12 micrograms/ml or AZM 1.6 micrograms/ml induced increased serum sensitivity in 2 of 6 strains (S-6, PA-103), but there were no changes in any strains with josamycin (JM) 12 micrograms/ml. Although EM 12 micrograms/ml induced increased serum sensitivity of S-6 after more than 36 h incubation, AZM 1.6 micrograms/ml induced increased serum sensitivity of this strain at 12 h incubation. AZM 0.8 microgram/ml (1/62.5 MIC) showed more potent activity to enhance serum sensitivity of S-6 than that of EM 12 micrograms/ml (1/8 MIC) after 48 h incubation. P. aeruginosa S-6 incubated with EM 12 micrograms/ml or AZM 1.6 micrograms/ml for 48 h was less hydrophobic than that of control bacteria, but there was little change in the hydrophobicity of the strain incubated with JM 12 micrograms/ml. These results show that AZM has more potent activity to enhance serum sensitivity of P. aeruginosa than that of EM. Since decrease of cell surface hydrophobicity of P. aeruginosa S-6 was correlated with increased serum sensitivity, EM and AZM may induce enhanced serum sensitivity by changing cell surface structure of P. aeruginosa.

Azithromycin↗

[Changes in serotypes of clinical isolates of Pseudomonas aeruginosa by anti-pseudomonal drugs].

Forty-two isolates of P. aeruginosa from various infections were each incubated in Mueller-Hinton broth including piperacillin, cefsulodin, ceftazidime, imipenem, gentamicin or norfloxacin (1MIC-4MIC) at 35 degrees C for 18 hours, and serotyped using monoclonal antibodies. Serotypes of 4 (9.5%)-8 (19.0%) of the 42 isolates each changed to different groups after incubation. No relationship was found between serotypes of the formed variants and anti-pseudomonal drugs used. When P. aeruginosa TA-2 was exposed to cefsulodin at different concentrations (1MIC and 2MIC) under the above conditions, the distinct variants different in serotypes were formed according to the drug concentrations. Furthermore, P. aeruginosa TA-2 and TA-13 were incubated in Mueller-Hinton broth including cefsulodin (1/2 or 2MIC) and gentamicin (1/2MIC), respectively, and the growth curves of parent and variant cells were determined. In the experiments, the variants appeared 6 hours after onset of the incubation and grew with the parents. The present results may explain our findings previously reported; coexistence of colonies different in serotype of P. aeruginosa isolated from some individual patients. The results indicate the possibility that alteration in bacterial surfaces in association with changes in serotypes might occur in vivo in these patients infected with P. aeruginosa and treated with anti-pseudomonal drugs.

Anti-Bacterial Agents↗

[The study of pathogenic mechanisms of chronic Pseudomonas aeruginosa lung infections by mucoid strains].

Chronic Pseudomonas aeruginosa lung infection with mucoid strains is the predominant cause of death in cystic fibrosis (CF) or diffuse panbronchiolitis (DPB). This infection is characterized by a chronic course without spread of the bacteria to the blood when compared with other infections due to the non-mucoid strains. However, the mechanism of P. aeruginosa lung infection with the mucoid strains remains obscure. Intra-tracheal and systemic infection in mice, susceptibility to the bactericidal activity of fresh human and mouse serum, and adherent activity to mouse fetal lung cell were examined for mucoid and non-mucoid strains of P. aeruginosa. After intra-tracheal infection, the mucoid strains were distributed to other organs anormously but not the non-mucoid stains, and the bacterial number of the mucoid strains in the blood were significantly lower than that of the non-mucoid strains. On the other hand, when these strains were inoculated into the tail vein of mouse, the mucoid strain was eliminated more rapidly from blood as compared with the non-mucoid strain. The mucoid strains showed reduced bacteremic virulence when compared with non-mucoid strains with a 50% lethal dose (LD50) of 1.5 x 10(7) CFU/mouse as the mean value in a systemic infection. In contrast to the non-mucoid strains, the mucoid strains were sensitive to human fresh serum but were resistant to mouse fresh serum. The mucoid strains adhered to the monolayer of the mouse fetal lung cell 7-fold better than did non-mucoid strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of protein binding in serum on therapeutic efficacy of cephem antibiotics.

The effect of protein binding in serum of eight cephem antibiotics (ceftazidime, ceftizoxime, cefotiam, cefmetazole, cefpiramide, cefazolin, cefuzonam, ceftriaxone) on their therapeutic efficacies was examined in mice with experimentally induced intraperitoneal infections or pneumonia. The relationship among therapeutic activity, in vitro antibacterial activity, total or free (unbound) levels in serum, and homogenized whole lung levels was investigated. In the intraperitoneal infection caused by Staphylococcus aureus or Klebsiella pneumoniae, the 50% effective doses (ED50s) of the cephem antibiotics correlated with the area under the concentration-time curve (AUC) values of free levels in serum and the MICs but not with those of total levels in serum. A linear relationship was seen between 1/ED50 values and AUC of free levels in serum/MIC values. On the other hand, in mice with pneumonia caused by K. pneumoniae, the number of bacteria in the lung closely correlated with the AUC of the antibiotic concentration in lung tissue. There was a direct correlation between the levels in lung tissue and total levels in serum but not free levels in serum. The cephem antibiotics tested in this study were bound only slightly to homogenates of mouse lung. These results indicate that the effect of protein binding in serum on therapeutic efficacy against intraperitoneal infection differs from that against pulmonary infection.

Animals↗

In vitro and in vivo antibacterial activities of a new quinolone, OPC-17116.

The in vitro and in vivo antibacterial activities of OPC-17116 were compared with those of ofloxacin, enoxacin, ciprofloxacin, and tosufloxacin. The MICs of OPC-17116 for 90% of the strains tested were 0.125 to 8 micrograms/ml against gram-positive bacteria such as members of the genera Staphylococcus, Streptococcus, and Enterococcus: less than or equal to 0.063 to 16 micrograms/ml against members of the family Enterobacteriaceae; and less than or equal to 0.063 to 16 micrograms/ml against glucose-nonfermentative bacilli such as Pseudomonas aeruginosa. The activity of OPC-17116 against gram-positive organisms was comparable to that of tosufloxacin and higher than those of other reference drugs. The in vitro activity of OPC-17116 against gram-negative bacteria was similar to those of the reference drugs. In experimental systemic infections in mice with various organisms, the efficacy of OPC-17116 was similar to that of tosufloxacin and greater than those of ofloxacin, enoxacin, and ciprofloxacin. In a pyelonephritic model in mice with P. aeruginosa KU-1, OPC-17116 was as active as ciprofloxacin and more active than ofloxacin, enoxacin, and tosufloxacin. In respiratory tract infections in mice with Staphylococcus aureus Smith, Streptococcus pneumoniae TMS 3, and Klebsiella pneumoniae 3K25, the efficacy of OPC-17116 was generally greater than that of tosufloxacin. The peak level of OPC-17116 in the lungs of mice was 10 times higher than that in serum and was significantly greater than levels in lung achieved with an equivalent dose of the other quinolones. The therapeutic efficacy of OPC-17116 may depend not only on its in vitro activity but also on its high concentration in tissue.

Administration, Oral↗

Augmented plasma protein C activity after coronary thrombolysis with urokinase in patients with acute myocardial infarction.

Coronary thrombolysis reduces morbidity and mortality in patients with acute myocardial infarction, however, the exact effects of thrombolytic agents on the status of intrinsic hemostases are not fully understood. In the present study, we examined serial changes in plasma thrombin and protein C activities of 6 patients with acute myocardial infarction treated with urokinase. Fibrinolysis occurred immediately after urokinase injection with an increase in the plasma thrombin-antithrombin III complex, suggesting a subsequent procoagulant state due to thrombin generation. Correspondent increases in plasma protein C activity were observed, however, protein S levels did not change at all. Our findings suggest that urokinase administration for coronary thrombolysis not only causes fibrinolysis, but also induces thrombin activity, which may be antagonized by augmented intrinsic protein C activity.

Aged↗

Progression of systolic dysfunction correlated with the ultrasonographically assessed myocardial tissue damage in patients with dilated cardiomyopathy.

An echocardiographic follow-up study was performed in 59 patients with dilated cardiomyopathy to characterize the relationship between left ventricular systolic dysfunction and the myocardial tissue character assessed by echocardiographic myocardial gray level distributions. All the selected patients were divided into two groups; those with (group A) and those without (group B) progressive systolic dysfunction. In group A, the ejection fraction decreased from 47 +/- 5 to 23 +/- 4% (p < 0.05) during the follow-up period. The histogram of the myocardial gray level distribution became wider, less peaked and more right-sided in those patients. The relative echo intensity of the myocardium increased from 1.29 +/- 0.19 to 1.60 +/- 0.18 (p < 0.01). In group B, however, neither the shape of the gray level distribution nor ejection fraction changed during the same follow-up period. The relative echo intensity did also not change. Our present results suggested that some of the patients with dilated cardiomyopathy showed progressive systolic dysfunction with extensive myocardial tissue damage.

Adult↗

Pseudo-adrenal incidentaloma: magnetic resonance imaging in a patient with para-adrenal Castleman's disease.

We report a case of para-adrenal angiofollicular lymph node hyperplasia (Castleman's disease) of the hyaline-vascular type. The mass could not be differentiated from an adrenal tumor by ultrasonography and computed axial tomography (CT). However, magnetic resonance imaging (MRI) suggested the possibility of an extra-adrenal origin of the mass. The intensity of the mass by MRI was homogeneous and of a higher intensity in the T2-weighted image than in the T1-weighted image, a finding similar to lymphadenopathy, lymphatic tumorous mass or metastatic tumor of the lymph node. Ultrasonography, CT and MRI may not be useful in characterizing Castleman's disease, but MRI was useful to distinguish asymptomatic para-adrenal masses from those of adrenal origin.

Adrenal Gland Neoplasms↗

Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation.

BACKGROUND: Shear-induced platelet aggregation (SIPA) is an important mechanism in thrombogenesis. von Willebrand factor (vWF) binding to platelet glycoprotein Ib (GP Ib) has been found to be crucial for platelet aggregation under the high shear force probably generated in stenosed coronary artery. The physiological significance of vWF-dependent SIPA has not been clarified. METHODS AND RESULTS: Blood samples were collected from 23 normal volunteers. SIPA was continuously monitored using a modified cone-plate viscometer adapted for measuring the transmitted light intensity of the material. The effects of low concentrations of epinephrine, ADP, and collagen on SIPA under both low shear (12 dyne/cm2) and high shear (108 dyne/cm2) force were investigated. All agonists tested enhanced SIPA under low shear force, whereas only epinephrine augmented SIPA under high shear force. The maximum extents of SIPA under high shear force in the absence and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/- 13.9%, respectively. The antagonist of the alpha 2-adrenergic receptor yohimbine (1 microgram/ml) antagonized the effects of epinephrine. The monoclonal antibody NMC-4 against vWF, which was shown to inhibit its binding to GP Ib, completely abolished SIPA under high shear force, even in the presence of epinephrine. However, this antibody only partially inhibited SIPA under low shear force. CONCLUSIONS: Our findings suggest that epinephrine is the agonist that enhances SIPA mediated by vWF through its specific receptor. This may be clinically important because occlusion of the coronary artery often occurs in stenosed atherosclerotic vessels under sympathetic stimulation.

Adrenergic alpha-Antagonists↗

A simple enhancement method for the silver-gold-intensified diaminobenzidine reaction in the light microscopic immunoperoxidase technique.

We describe a simple and sensitive method for enhancement of the silver-gold-intensified 3,3'-diaminobenzidine (DAB) reaction demonstrating peroxidase activity. After completing silver-gold intensification of the preparations immunostained by the avidin-biotin-peroxidase method with DAB as the chromogen, the preparations were immersed in a solution containing uranyl nitrate. This new method appeared to increase the sensitivity by at least one order of magnitude as compared with silver-gold intensification alone.

3,3'-Diaminobenzidine↗

Striosomal organization of substance P-like immunoreactivity in parkinsonian patients.

We designed this study to evaluate the expression of substance P (SP) in the striatum and the globus pallidus in normal controls, idiopathic Parkinson's disease (PD), and striatonigral degeneration (SND). We determined immunohistochemically the expression of SP in formalin-fixed, paraffin-embedded brain tissues using the free-floating method. In normal controls, we observed SP-like immunoreactivity in the internal segment of the globus pallidus, where the SP-positive fibers showed typical "woolly fiber" patterns. SP expression in the striatum had the characteristic patchwork of striosomes. Patients with PD showed the normal distribution pattern of SP. By comparison, in patients with SND, there was a striking diminution of SP in the putamen, while the SP-positive patches persisted in the caudate nucleus. This study represents the first unequivocal immunohistochemical demonstration of SP-positive striosomes in the human striatum.

Aged↗

Evaluation of enteric coated tablet sensitive to pancreatic lipase. I. In vitro disintegration test.

We designed a new enteric coated preparation which is pH independent and functions by pancreatic lipase activity in the duodenum. Triolein (TO) and trilaurin (TL) were selected as lipase sensitive components and ethylcellulose (EC) was used as the support film for TO and TL. Tablets (330 mg, d = 10 mm) containing a model drug, sulfamethizole (SMZ), were coated with 1% each of TO, TL and EC solution by the fluidized bed coating technique. Disintegration tests were carried out in the media including JPXI 1st fluid (pH 1.2, JP-1), 2nd fluid (pH 6.8, JP-2) and JP-2 with gall powder and pancreatic lipase (JP-2-GL). The lag time of disintegration of the tablet (TOTL-Tab) coated 5-7 mg/tab with TO, TL and EC was about 10 min and all of the tablets disintegrated completely within 30 min in JP-2-GL. However, in the other media, which did not contain lipase, TOTL-Tab did not disintegrate for at least 2 h. It was confirmed that TO and TL in the coating film were digested by lipase. In addition, the tensil strength of the film decreased quickly after incubation in JP-2-GL. These results suggest that the application of TO, TL and EC to tablet coating is useful for an enteric release preparation sensitive to pancreatic lipase, even if patients have low gastric acidity or are taking antacids.

Chemistry, Pharmaceutical↗

Preparation and evaluation of eudragit gels. V. Rectal gel preparations for sustained release and avoidance of first-pass metabolism of lidocaine.

The release of lidocaine from hydrogel and xerogel preparations was remarkably suppressed compared with polyethylene glycol (PEG) 2000 suppository. The release rate of lidocaine from hydrogel and xerogel increased with the increase in the amount of sodium hydroxide incorporated within the range of 3 to 7 milliequivalent (meq). After an oral administration of lidocaine HCl solution, the plasma concentration of lidocaine was considerably lower than that after intravenous administration for all time periods. The absolute bioavailability (F(oral)) was 5.63%. For the Witepsol S-55 and PEG 2000 suppositories, the plasma levels of lidocaine were higher than those for the oral preparation, and Cmax and area under the concentration-time curve (AUC) values significantly improved (p < 0.01). The absolute bioavailabilities were 21.3 and 29.6%, respectively. On the other hand, Eudispert hv-hydrogel and xerogel preparations showed the characteristics of a sustained-release preparation, especially the xerogel preparation with 5 meq NaOH. Absolute bioavailability for hydrogel and xerogel preparations increased significantly (p < 0.05) by approximately 1.7-3.4 folds compared with those of Witepsol S-55 and PEG 2000 suppositories.

Acrylic Resins↗