Biomedical subjects

N Furuya

Publications and source records attributed to N Furuya.

At least 55 records · Page 3Linked to original sources

PubMed1998

In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic.

The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against experimental murine septicemia caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli and against murine respiratory infections caused by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection by penicillin-susceptible and penicillin-resistant S. pneumoniae, sanfetrinem cilexetil was more effective than amoxicillin in reducing the number of bacteria in infected lungs. These results were reflected in its potent in vitro activity and high levels in plasma.

Animals↗

PubMed1998

Serum cytokines in patients with Legionella pneumonia: relative predominance of Th1-type cytokines.

Serum samples from 14 patients with Legionella pneumonia were examined for the presence of cytokines. In spite of high levels of serum C-reactive protein in all patients during the acute phase in only four cases (one involving interleukin-1beta [IL-1beta], three involving IL-6, and none involving tumor necrosis factor alpha) was the concentration of cytokines more than 100 pg/ml. Th2 cytokines IL-4 and IL-10 were detected in only one patient each. In contrast, significant increases of serum gamma interferon (IFN-gamma) and IL-12 levels were observed during the acute phase in 6 and 11 cases, respectively. Interestingly, although serum IFN-gamma levels diminished thereafter, in seven cases IL-12 levels remained high or increased further during the convalescent phase. In an additional 22 cases clinically suspected to be but not diagnosed as Legionella pneumonia, increases of serum IL-12 levels were observed in 16 cases, whereas the remaining 6 cases showed no detectable IL-12. Our results demonstrate the relative predominance of Th1 cytokine production in Legionella pneumonia. Although the role and significance of prolonged increases in IL-12 levels in Legionella disease are unknown, our results should prompt further investigation of the host immune response in terms of Th1 and Th2 balance in legionellosis.

Cytokines↗

PubMed1998

Adherence to and penetration of human intestinal Caco-2 epithelial cell monolayers by Pseudomonas aeruginosa.

Clinical isolates of Pseudomonas aeruginosa from blood adhered to and penetrated intestinal Caco-2 cell monolayers to a greater degree than did isolates from sputum, with a concomitant drastic decrease in transepithelial electrical resistance. PAO-PR1, an avirulent exotoxin A mutant of PAO1, did not cause a decrease in the resistance. The Caco-2 monolayer system may be useful for the evaluation of certain P. aeruginosa virulence factor activities.

Bacterial Adhesion↗

PubMed1998

Purification and characterization of thin pili of IncI1 plasmids ColIb-P9 and R64: formation of PilV-specific cell aggregates by type IV pili.

Thin pili of the closely related IncI1 plasmids ColIb-P9 and R64 are required only for liquid mating and belong to the type IV family of pili. They were sedimented by ultracentrifugation from culture medium in which Escherichia coli cells harboring ColIb-P9- or R64-derived plasmids had been grown, and then the pili were purified by CsCl density gradient centrifugation. In negatively stained thin pilus samples, long rods with a diameter of 6 nm, characteristic of type IV pili, were observed under an electron microscope. Gel electrophoretic analysis of purified ColIb-P9 thin pili indicated that thin pili consist of two kinds of proteins, pilin and the PilV protein. Pilin was demonstrated to be the product of the pilS gene. Pilin was first synthesized as a 22-kDa prepilin from the pilS gene and subsequently processed to a 19-kDa protein by the function of the pilU product. The N-terminal amino group of the processed protein was shown to be modified. The C-terminal segments of the pilV products vary among six or seven different types, as a result of shufflon DNA rearrangements of the pilV gene. These PilV proteins were revealed to comprise a minor component of thin pili. Formation of PilV-specific cell aggregates by ColIb-P9 and R64 thin pili was demonstrated and may play an important role in liquid mating.

Amino Acid Sequence↗

PubMed1998

Characterization and determination of human urinary keratan sulfate.

Keratan sulfate was isolated from normal human urine and was characterized by sugar compositional analysis and H-NMR spectroscopy. It was found that KS from human urine is classified as skeletal type (KS-II type chain) with an O-glycosidic linkage between galactosamine and serine (or threonine). H-NMR studies revealed that urinary KS is not a proteoglycan but a polysaccharide (molecular weight is about 5 kDa). The quantitation of human urinary KS by HPLC showed that urinary KS is excreted at constant levels (0.07 +/- 0.015 microgram/mg creatinine).

Carbohydrates↗

PubMed1997

Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis.

To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.

Animals↗

PubMed1997

Requirement of a limited segment of the sog gene for plasmid R64 conjugation.

The sog gene of the IncI1 plasmid R64 was sequenced and characterized. The sog gene was shown to express two acidic proteins, SogL and SogS, with 1255 and 844 amino acid residues, respectively. The SogS protein was expressed by translational reinitiation within the SogL reading frame. Analysis of dnaG-suppression activity using the Escherichia coli dnaG strain indicated that the domain for this activity was located within the N-terminal one-third segment of the SogL protein. A Deltasog mutation was constructed by replacing most of the sog coding sequence with a DNA fragment encoding a tetracycline resistance gene. Introduction of the Deltasog mutation into an R64 derivative resulted in approximately a 50-fold reduction in transfer frequency. It was observed that only a limited portion of the SogL or SogS protein corresponding to an internal 0.94-kb EcoRV-SnaBI segment of the sog gene was required for the conjugal transfer of R64.

Amino Acid Sequence↗

PubMed1997

Long-term follow-up of patients with chronic pancreatitis and K-ras gene mutation detected in pancreatic juice.

BACKGROUND & AIMS: Conflicting reports have raised the question whether K-ras gene mutations in chronic pancreatitis are related to the development of pancreatic neoplasm. The aim of the present study was to clarify this issue by surveying patients with chronic pancreatitis and K-ras gene mutation over 4 years. METHODS: K-ras point mutations at codon 12 in duodenal juices obtained during exocrine function tests were examined by enriched polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis, and long-term follow-up of these patients was performed. RESULTS: K-ras gene mutation was found in 20 of 54 patients (37%) with chronic pancreatitis. The types of mutation were GAT in 7, GTT in 11, and TGT in 2 patients. Pancreatic neoplasm occurred in none of the mutation-positive patients over a mean follow-up period of 78 months. CONCLUSIONS: K-ras gene mutation in patients with chronic pencreatitis did not seem to be related to the development of pancreatic neoplasm during the follow-up period, and analysis of K-ras gene mutation seems of little use for diagnosing pancreatic neoplasm in patients with chronic pancreatitis.

Adult↗

PubMed1997

[Isolation frequency and biological characteristics of the multiple-antibiotic resistant Pseudomonas aeruginosa isolated from clinical specimens].

Isolation frequency of multiple-antibiotic resistant Pseudomonas aeruginosa (MARPA) was 11.9% (fifty six strains) of a total of four-hundred seventy-one strains of P. aeruginosa isolated from clinical specimens at the Kyorin University Hospital from October 1994 to December 1996. Eighteen strains of MARPA and thirteen strains of antibiotic sensitive P. aeruginosa (ASPA) isolated from clinical specimens in internal medicine ward A were determined O serotype, and characterized with production of pyocyanin, pyoverdin, hemolysin, elastase, and caseinase. Sixteen strains (88.9%) of MARPA were identified as serotype C. The ability to produce pyocyanin, hemolysin, elastase, and caseinase was not detected in all MARPA. One side, thirteen strains of ASPA showed various serotypes, i.e., B: 5 strains (38.4%), G: 4 strains (30.8%), C: 2 strains (15.4%), E: 1 strain (7.7%) and unknown type: 1 strain (7.7%), and the production of both hemolysin and pyoverdin was observed in 13 strains (100%), pyocyanin in 8 strains (61.5%), elastase and caseinase in 9 strains (69.2%) of ASPAs, which suggests that ASPAs do maintain the synthetic ability of pathogenic factors and pigments, but MARPAs do not. These results indicate that from epidemiological points of view the current strains of MARPA spread from one clone within the internal medicine ward A with nosocomial outbreak by serotype C.

Ampicillin Resistance↗

PubMed1997

[Properties of extracellular products produced by group A streptococci isolated from patients with streptococcal toxic shock syndrome].

Extracellular products of group A streptococci isolated from patients with streptococcal toxic shock syndrome (STSS) were examined. The outline of the discussion of the 3 products are as follows; streptolysin O (SLO), proteinase and erythrogenic toxin. SLO and proteinase showed a relatively large amount of products more than erythrogenic toxin. SLO produced by group A streptococci isolated from the patient with STSS had an isoelectric point (pI) of 6.0 and a molecular weight of 64,000 and showed hemolytic activity in the presence of 2-mercaptoethanol (2-ME). Furthermore, the hemolytic activities of all components were inhibited by gamma-globulin and cholesterol. Proteinase had pIs of 8.7 and 8.9, and a molecular weight of 21,000. These data suggest that STSS clinical criteria probably reflects a characteristic of a large amount of products of individual S. pyogenes isolates.

Bacterial Proteins↗

PubMed1997

[Clinical and diagnostic characteristics of Legionella pneumonia].

We have characterized clinical and diagnostic features in 18 cases of Legionella pneumonia. Age average of patients was 62.0 years old (male:female = 14:4) and underlying diseases were observed in 12 patients. Legionella pneumonia were diagnosed in 3, 5, 8 and 9 cases by culture, serum antibody measurement, urinary antigen detection and PCR, respectively. Sixteen cases were caused by L. pneumophila, while the other 2 cases were L. bozemanii pneumonia and L. pneumophila or L. dumoffii pneumonia. Chest X-rays of those patients showed multiple pneumonia shadows in 14 cases, alveolar shadows in 10 cases, pleural effusion in 5 cases. Blood-gas analysis on admission indicated hypoxemia in all cases with abnormal A-a DO2. Laboratory findings showed abnormal data in WBC, CRP, LDH, CPK and liver function tests (ex. GOT, GPT) in most cases. Serum antibody testing showed positive by 5 weeks after onset of pneumonia, but 10 cases of Legionella pneumonia diagnosed by other techniques were judged to be negative. In urinary antigen detection test, 6 and 2 cases showed positive 1 and 4 weeks after onset of pneumonia, respectively. Macrolide antibiotics were administered in all cases during the episode, but delay of macrolide administration was observed in 3 of 4 cases of dead outcome. Serum antibody measurement, urinary antigen detection and PCR, in addition to culture to bacteria, may be required for exact diagnosis of Legionella infection.

Adult↗

PubMed1997

In vitro and in vivo antibacterial activities of CS-940, a new fluoroquinolone, against isolates from patients with respiratory infections.

We compared the in vivo and in vitro activities of CS-940, a new fluoroquinolone, with those of a group of other drugs. The activities of CS-940 against gram-positive cocci and gram-negative rods, including methicillin-susceptible Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, were comparable to those of tosufloxacin, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.5 microg/ml or less. Against methicillin-resistant S. aureus, CS-940 was as active as tosufloxacin, with a MIC90 of 16 microg/ml. The efficacy of CS-940 against murine respiratory infections due to S. pneumoniae or Haemophilus influenzae was better than those of tosufloxacin and sparfloxacin. The efficacy of oral doses of CS-940 reflected not only potent in vitro activity but also a high transmigration ratio from the bloodstream to lung tissues.

Animals↗

PubMed1997

Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.

Adjuvants, Immunologic↗

PubMed1997

Mutational analysis of the R64 oriT region: requirement for precise location of the NikA-binding sequence.

Conjugative DNA transfer of IncI1 plasmid R64 is initiated by the introduction of a site- and strand-specific nick into the origin of transfer (oriT). In R64 oriT, 17-bp (repeat A and B) and 8-bp inverted-repeat sequences with mismatches are located 8 bp away from the nick site. The nicking is mediated by R64 NikA and NikB proteins. To analyze the functional organization of the R64 oriT region, various deletion, insertion, and substitution mutations were introduced into a 92-bp minimal R64 oriT sequence and their effects on oriT function were investigated. This detailed analysis confirms our previous prediction that the R64 oriT region consists of an oriT core sequence and additional sequences necessary for full oriT activity. The oriT core sequence consists of the repeat A sequence, which is recognized by R64 NikA protein, and the nick region sequence, which is conserved among various origins of transfer and is most probably recognized by NikB protein. The oriT core sequence is sufficient for NikAB-mediated oriT-specific nicking. Furthermore, it was shown that the repeat A sequence is essential for localization to a precise position relative to the nick site for oriT function. This seems to be required for the formation of a functional ternary complex consisting of NikA and NikB proteins and oriT DNA. The repeat B sequence and 8-bp inverted repeat sequences are suggested to be required for the termination of DNA transfer.

Bacterial Proteins↗

PubMed1997

[Pulsatile diameter change of coronary artery lumen estimated by intravascular ultrasound].

To analyze the pulsatile movement of coronary arterial walls, intravascular ultrasound was used to measure the diameter changes in the arterial lumen of 32 patients with coronary artery disease (CAD group) and five patients with chest pain but no CAD (control group). Measurements were performed on segments of the proximal left anterior descending coronary artery that were angiographically nonstenotic. Following identification of the peak systolic and end-diastolic phases using intra-coronary pressure tracings, the luminal diameters were measured around the center at 4 degrees intervals using a computer-assisted image analyzer. The pulsatile diameter change (dD) and end-diastolic diameter (DD) at each interval were analyzed and compared between the CAD and control groups. Mean DD did not differ significantly between the CAD group (4.53 +/- 0.69 mm) and the control group (4.52 +/- 0.51 mm). In contrast, the mean dD in the CAD group (0.05 +/- 0.18 mm) was significantly lower than that of the control group (0.13 +/- 0.12 mm). The mean maximum and minimum standardized percentage pulsatile diameter changes were -10.6 +/- 6.2% and 16.2 +/- 5.9%, respectively, in the CAD group, and -2.7 +/- 4.6% and 11.7 +/- 1.3%, respectively, in the control group. The mean standard deviation of dD was significantly greater in the CAD group (0.182 +/- 0.05 mm) than in the control group (0.116 +/- 0.04 mm), which indicated dD in CAD patients varied to a greater degree than in control patients. The ratio dD/dP (dP : pulse pressure) was used as an index of vascular compliance at the site of measurement. The mean dD/dP was significantly smaller in the CAD group (1.1 +/- 2.5 x 10(-3) mm/mmHg) than in the control group (4.0 +/- 3.3 x 10(-3) mm/mmHg). Aniso-diametric wall movement in the coronary artery (as indicated by a negative dD during systolic expansion) was enhanced in the CAD group compared to the control group. This was probably caused by the early stages of the arterial sclerotic process as it progressed heterogeneously along the vessel wall. Thus, aniso-diametric movement, which is a functional abnormality of the coronary arterial wall, appears to antedate detectable morphological changes.

Adult↗

PubMed1997

Effects of newly developed excitatory amino acid antagonists on vestibular type I neurons in the cat.

A newly synthesized compound NC-1200 (oxazolidinone) has been shown to have a powerful inhibitory action on the glutamate response at the neuromuscular junction in crayfish where glutamate is thought to be an excitatory neurotransmitter. However, the pharmacological function of NC-1200 in the CNS of mammals remains unknown. We examined the glutamate blocking action of NC-1200 on various glutamate receptors of cat's vestibular neurons. The effects of NC-1200 on secondary vestibular neurons were studied by intra-venous (3-5 mg/kg) and iontophoretic application using multi-barreled electrodes filled with NMDA, kainic acid and NC-1200 in decerebrated cats. After identification of type 1 neurons, the chemicals were applied to examine their effects on neuronal activity. The results were as follows; i) Systemic application of NC-1200 suppressed type 1 responses to yaw rotation; ii) both NMDA-mediated and kainate-mediated excitations on the vestibular neurons were abolished by application of NC-1200; iii) the suppression of various glutamic receptors was dose-dependent; and iv) the kainate receptor was more strongly suppressed than the NMDA receptor by NC-1200.

Animals↗

PubMed1997

[Serum soluble CD8 and soluble interleukin-2-receptor levels during interferon therapy in chronic hepatitis C].

We examined the relationship between the changes of serum soluble CD8 (sCD8) and soluble interleukin-2 receptor (sIL-2R) levels and effectiveness of interferon (IFN) in patients with chronic hepatitis (CH) C. Changes in sCD8 levels were parallel with fluctuations of alanine aminotransferase (ALT) in CH patients during IFN treatment but decreases of sCD8 levels were slower than those of ALT. In IFN effective and ALT decreased patients sCD8 levels is also decreased. sIL-2R levels was increased transiently during administration of IFN in most cases. It was suggested that decrease in sCD8 levels is indicative of the effectiveness of IFN therapy.

Adult↗

PubMed1996

Comparative study of CA242 and CA19-9 in chronic pancreatitis.

CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim of the present study was to clarify the mechanisms contributing to the high specificity of CA242 as compared with CA19-9 resulting from scarce serum elevation of this antigen in patients with chronic pancreatitis by correlating serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings and by immunohistochemical analysis. Serum CA19-9 levels were significantly elevated in patients with calcification and with main pancreatic duct (MPD) stenosis or obstruction. On the other hand, serum CA242 levels showed no significant elevation in patients with such factors. Even though such pathological conditions were considered to lead to the stagnation of pancreatic juice, serum CA242 levels seemed to be less affected than serum CA19-9 levels. Immunohistochemical studies of chronic pancreatitis tissues revealed that CA242 was expressed less frequently and less intensely than CA19-9, and the difference in expression was more prominent in the centroacinar cells and terminal ductules. From the results of the present study, it is conceivable that CA242 is less influenced by the stagnation of the pancreatic juice than CA19-9 because of the low levels of expression in ductal systems, which results in the release of this antigen into the circulation in lower amounts than that of CA19-9.

Antigens, Tumor-Associated, Carbohydrate↗