Micrometastasis of prostate cancer to lymph nodes: detection by means of reverse transcription-polymerase chain reaction.
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Humans↗
Biomedical subjects
Y Kawada
Publications and source records attributed to Y Kawada.
Mutations in the gyrA and parC genes associated with fluoroquinolone resistance in clinical isolates of Citrobacter freundii.
We determined partial sequences of the gyrA and parC genes of Citrobacter freundii type strain, and then examined 38 C. freundii clinical strains isolated from patients with urinary tract infections for the association of alterations in GyrA and ParC with susceptibility to fluoroquinolones. Our results suggest that in C. freundii DNA gyrase may be a primary target of quinolones, that an amino acid change at Thr-83 or Asp-87 in GyrA is sufficient to decrease susceptibility to fluoroquinolones, and that accumulation of changes in GyrA with the simultaneous presence of an alteration at Ser-80 or Glu-84 in ParC may be associated with the development of high-level fluoroquinolone resistance in C. freundii clinical isolates.
Amino Acid Sequence↗
Increased plasma cholesteryl ester transfer activity in obese children.
To determine whether enhanced activity of cholesteryl ester transfer protein (CETP) contributes to the development of atherogenic lipoprotein profiles in obese children, plasma CETP activity was assayed according to a micro-method, by co-incubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. The study subjects were 31 obese children (14 males and 17 females). Serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC:high-density lipoprotein (HDL)-C, LDL-C:HDL-C, apolipoprotein (apo) B, and apo B:apo Al were increased in obese children. Thus they appeared to exhibit an atherogenic lipoprotein profile, with a relative decrease in cholesterol carried by HDL compared with the cholesterol in the other lipoprotein fractions. The mean fasting plasma insulin level was also increased. CETP activity was significantly higher in the obese children than in nonobese control children, and was correlated with LDL-C, TC:HDL-C, LDL-C:HDL-C, and apo B:apo Al. These results suggest that an increase in plasma CETP activity results in atherogenic change in lipoprotein metabolism in obese children. The increase in CETP may be due to the adiposity or insulin resistance. Alternatively, dyslipidemia per se, physical inactivity or excessive fat intake, that are commonly found in obese children, may contribute to the increase in CETP activity.
Adolescent↗
Correlation of expression levels of P-glycoprotein with resistance to adriamycin in a renal adenocarcinoma cell line.
We have demonstrated that low-level expression of P-glycoprotein (PGP), detectable by reverse transcriptase polymerase chain reaction (RT-PCR) assay and flow cytometric assay, is an important factor in multidrug resistance (MDR) in ACHN cancer cells. In this study, we established a subline highly resistant to adriamycin (ACHN/ADM) from ACHN cells, and determined the correlation between PGP levels and MDR levels using ACHN/ADM cells and their parent ACHN cells. The ACHN/ADM cells showed overexpression of PGP, and sensitivity to antitumor agents was lower than that found in ACHN cells. Intracellular accumulation of ADM in ACHN/ADM cells was approximately half the amount of its accumulation in ACHN cells. Sensitivity to ADM in ACHN/ADM cells was enhanced by chemosensitizers with an increase in intracellular ADM accumulation. These results indicate that PGP levels correlate with MDR levels and suggest that chemotherapy using chemosensitizers might be effective in the treatment of renal cancers with overexpression of PGP.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Significance of AgNOR counts for distinguishing carcinoma from adenoma and hyperplasia in parathyroid gland.
Nucleolar organizer region proteins, which can be stained and visualized by an argyrophil technique (AgNORs), are markers of cell activities, such as DNA transcription and proliferation, and they are useful for differential diagnosis between benign and malignant tumors. We counted both AgNOR numbers in 25 parathyroid lesions (three carcinomas, 11 adenomas, 10 hyperplasias, and one hyperplasia with carcinoma) to determine if the AgNOR number could be useful as a diagnostic aid in parathyroid neoplasms and hyperplasias, because it is often difficult to histopathologically distinguish among these lesions. The AgNOR numbers were significantly higher in carcinomas (3.18 +/- 0.05) than in adenomas (1.67 +/- 0.30, P < .001) or hyperplasias (1.85 +/- 0.16, P < .001), but there was no significant difference between adenomas and hyperplasias. These results suggest that AgNORs may be useful as an adjunct to discriminating carcinomas from adenomas or hyperplasias in the parathyroid gland.
Adenoma↗
Prostate cancer micrometastases to lymph nodes.
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Humans↗
Detection of micrometastatic prostate cancer cells in the bone marrow of patients with prostate cancer.
Thirty-five patients with prostate cancer were examined for micrometastases to the bone marrow using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for the prostate-specific antigen (PSA) gene. Of nine patients with bone metastases detectable by bone scan imaging, five patients had PSA mRNA expression in the bone marrow detectable by RT-PCR. Of 26 patients with negative bone scan findings, seven patients had PSA mRNA expression detectable in the bone marrow. RT-PCR could detect micrometastatic prostate cancer cells in the bone marrow that were not detectable by bone scan imaging. Of 16 patients with a serum PSA concentration of 25 ng ml(-1) or greater, only nine (56.3%) had bone metastases detected by bone scans. Of the remaining seven patients, five had micrometastases to the bone marrow detected by RT-PCR. Overall, 14 of 16 patients (87.5%) with a serum PSA concentration of 25 ng ml(-1) or greater had metastatic bone diseases including bone marrow micrometastases. Of 19 patients with a serum PSA concentration of less than 25 ng ml(-1), two (10.5%) had only micrometastatic disease detected by RT-PCR. A significant correlation was observed between the incidence of bone involvement and the serum PSA concentration. This study suggests that RT-PCR will potentially develop into a relevant tool to assess bone involvement including bone marrow micrometastases and establish a precise correlation between serum PSA concentration and metastatic bone disease in patients with prostate cancer.
Bone Marrow↗
New age-adjusted measure of body fat distribution in children and adolescents: standardization of waist-hip ratio using multivariate analysis.
OBJECTIVE: To explore a new anthropometric index of body fat distribution adjusted for ages ranging from 6-15 y in both boys and girls. DESIGN: Sex, age, and 11 anthropometric variables were subjected to principal component analysis. Based on these results, we developed a new anthropometric index, namely an age-adjusted measure of body-fat distribution. This index was evaluated statistically for suitability of use in epidemiological surveys. SUBJECTS: Japanese children, including obese and nonobese subjects, in one elementary and one junior high school in Yamanashi Prefecture, Japan: 508 boys and 549 girls whos ages ranged from 6 y 1 mon-15 y. MEASUREMENTS: Measurements included the height (Ht), body weight, circumference of the waist, hip and thigh. Body mass index, the ratios of the waist, hip or thigh to the Ht, waist-hip ratio (WHR) and waist-thigh ration were calculated. RESULTS: The first principal component (PC 1) accounted for 49.8% of the total variation, and was interpreted as an indicator of the general size on an individual. PC 2 accounted for 25.9%, and was interpreted as a shape measure that indicates body fat distribution. Calculation of WHR/Ht, a parameter that represented PC 2 adjusted by PC 1, gave an highly robust linear regression equation for age by gender. The residuals from the regression line for WHR/Ht deviated from normal distribution only in the boys, whereas the mean residual was nearly zero and distribution of the residuals was similar in three age subgroups by gender, supporting the use of the common standard deviation score in all age groups as an indicator of body fat distribution. CONCLUSION: The common standard deviation score of WHR/Ht can serve as an epidemiological index of body fat distribution adjusted for ages between 6 and 15 y.
Adipose Tissue↗
Antimicrobial activity of a new fluoroquinolone, DU-6859a, against quinolone-resistant clinical isolates of Neisseria gonorrhoeae with genetic alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV.
The in-vitro antimicrobial activity of DU-6859a, a new fluoroquinolone, was tested against 55 clinical isolates of Neisseria gonorrhoeae. The MIC of DU-6859a inhibiting 90% (MIC90) of the isolates with genetic alterations of both the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV was 0.125 mg/L. The MIC90 for isolates with alterations of GyrA alone or without alterations of GyrA or ParC was 0.03 mg/L and 0.004 mg/L, respectively. The potency of DU-6859a against clinical isolates bearing genetic alterations associated with quinolone resistance was significantly greater than that of currently available fluoroquinolones.
Anti-Infective Agents↗
In-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, against clinical isolates of Neisseria gonorrhoeae with quinolone resistance-associated alterations in GyrA and ParC.
The in-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, was tested against 51 clinical Neisseria gonorrhoeae isolates in comparison with ciprofloxacin, levofloxacin and sparfloxacin. The MICs of HSR-903 for 11 isolates with alterations in both GyrA and ParC, for 19 isolates with alterations only in GyrA and for 21 isolates without alterations in either GyrA or ParC ranged from 0.03 mg/L to 1.0 mg/L (MIC90 = 0.25 mg/L), from 0.03 mg/L to 0.5 mg/L (MIC90 = 0.125 mg/L) and from < or = 0.001 mg/L to 0.008 mg/L (MIC90 = 0.004 mg/L), respectively. Levofloxacin and ciprofloxacin were the least active of the four quinolones tested, particularly against the mutant strains. Sparfloxacin was more active, but HSR-903 exhibited the most potent in-vitro activity against the clinical N. gonorrhoeae isolates, including those harbouring quinolone-resistance-associated alterations in GyrA and ParC.
Anti-Infective Agents↗
Detection of mutations in the gyrA and parC genes in quinolone-resistant clinical isolates of Enterobacter cloacae.
We have determined partial sequences of the gyrA and parC genes of Enterobacter cloacae type strain including the regions analogous to the quinolone resistance-determining region of the Escherichia coli gyrA gene. The deduced 65- and 49-amino acid sequences of the determined regions of the E. cloacae gyrA and parC genes were identical to the corresponding regions of the E. coli GyrA and ParC proteins, respectively. We examined 40 clinical strains of E. cloacae isolated from patients with urinary tract infection for susceptibilities to nalidixic acid and ciprofloxacin. Based on the nalidixic acid and ciprofloxacin MICs, these isolates were divided into 19 quinolone-susceptible strains (MICs of nalidixic acid, 3.13-25 mg/L; MICs of ciprofloxacin, < or = 0.025 mg/L) and 21 quinolone-resistant strains (MICs of nalidixic acid, 400 to > 800 mg/L; MICs of ciprofloxacin, 0.39-100 mg/L). We analysed five quinolone-susceptible and 21 quinolone-resistant strains for alterations in GyrA and ParC. The five quinolone-susceptible strains had amino acid sequences in GyrA and ParC identical to those of type strain. Of the 21 quinolone-resistant isolates, three (MICs of nalidixic acid, 400 to > 800 mg/L; MICs of ciprofloxacin, 0.39-3.13 mg/L) had a single amino acid change at the position equivalent to Ser-83 in the E. coli GyrA protein and no alterations in ParC; one (MIC of nalidixic acid, > 800 mg/L; MIC of ciprofloxacin, 3.13 mg/L) had a single amino acid change at Ser-83 in GyrA and a single amino acid change at the position equivalent to Glu-84 in the E. coli ParC protein; two (MIC of nalidixic acid, > 800 mg/L; MIC of ciprofloxacin, 25 mg/L) had double amino acid changes at Ser-83 and Asp-87 in GyrA and no alterations in ParC; and 15 (MICs of nalidixic acid, > 800 mg/L; MICs of ciprofloxacin, 25-100 mg/L) had double amino acid changes at Ser-83 and Asp-87 in GyrA and a single amino acid change at Ser-80 or Glu-84 in ParC. This study suggests, that in clinical isolates of E. cloacae, DNA gyrase is a primary target of quinolones, that only a single amino acid change at Ser-83 in GyrA is sufficient to generate high-level resistance to nalidixic acid and to decrease susceptibility to ciprofloxacin, and that the accumulation of amino acid changes in GyrA and the simultaneous presence of the ParC alterations play a central role in developing high-level resistance to ciprofloxacin.
Amino Acid Sequence↗
In-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, against clinical isolates of Klebsiella pneumoniae and Enterobacter cloacae with fluoroquinolone resistance-associated amino acid alterations in GyrA and ParC.
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Anti-Infective Agents↗
Fluoroquinolone treatment failure in gonorrhea. Emergence of a Neisseria gonorrhoeae strain with enhanced resistance to fluoroquinolones.
BACKGROUND AND OBJECTIVES: Although emergence of clinical isolates of Neisseria gonorrhoeae with decreased susceptibilities to fluoroquinolones and treatment failures in gonorrhea have been reported, there have been no clinical reports that fluoroquinolone treatments actually select quinolone-resistant strains, nor have isolates that exhibited clinically significant resistance been analyzed for resistance mechanisms. GOALS: To report a case of fluoroquinolone treatment failure in gonorrhea and emergence of a posttreatment isolate with enhanced resistance to fluoroquinolones; and to study mechanisms of quinolone resistance in the isolates from this patient. STUDY DESIGN: A patient with gonococcal urethritis treated with ofloxacin, 200 mg, three times daily for 5 days is described. Pretreatment and posttreatment isolates were tested for minimum inhibitory concentrations (MICs) of antimicrobial agents and analyzed for alterations in DNA gyrase and topoisomerase IV. They were also examined for ofloxacin uptake. RESULTS: Treatment failure with multiple doses of ofloxacin was observed in this case of gonorrhea. The pretreatment isolate showed decreased susceptibilities to fluoroquinolones (MIC of ofloxacin, 1.0 mg/l; MIC of ciprofloxacin, 0.25 mg/l), and had amino acid changes of Ser-91-->Phe in GyrA and Ser-87-->Ile in ParC. The posttreatment isolate exhibited an increase in resistance to fluoroquinolones (MIC of ofloxacin, 8.0 mg/l; MIC of ciprofloxacin, 1.0 mg/l). This isolate had identical alterations in GyrA and ParC, but exhibited significantly reduced uptake of ofloxacin. This isolate also showed a small decrease in susceptibilities to cephalosporins. CONCLUSIONS: Alterations in DNA gyrase and topoisomerase IV confer clinically significant resistance to fluoroquinolones in N. gonorrhoeae strains. Treatment with multiple doses of fluoroquinolones is likely to bring about selection of more fluoroquinolone-resistant strains of N. gonorrhoeae and to influence susceptibilities to cephalosporins.
Adult↗
Mycoplasma genitalium in the cervices of Japanese women.
BACKGROUND: Mycoplasma genitalium is considered a cause of nongonococcal urethritis in men. This organism also is a cause of genital infections in women, and has been detected in women attending sexually transmitted disease clinics in the United Kingdom and Denmark, although its prevalence is unknown in Japanese women. GOALS: To determine the prevalence of M. genitalium in the cervices of women with cervicitis or adnexitis as well as in asymptomatic pregnant women in Japan. STUDY DESIGN: Two hundred women who attended obstetric and gynecologic clinics were recruited. Sixty-four women had cervicitis, 53 had adnexitis, and 3 had both. Eighty pregnant women were asymptomatic for infection. Cervical swab specimens were examined for M. genitalium using a polymerase chain reaction-based assay. RESULTS: Five (7.8%) of 64 women with cervicitis and 3 (5.7%) of 53 women with adnexitis were positive for M. genitalium. After exclusion of Chlamydia-positive women, 5 (8.8%) of 57 women with cervicitis, and 2 (4.1%) of 49 women with adnexitis were positive for M. genitalium. In none of 80 asymptomatic pregnant women, including a Chlamydia-positive woman, was M. genitalium detected. Overall, 7 (6.6%) of 106 women with Chlamydia-negative genital infections were positive for the M. genitalium. This prevalence was significantly greater than that in asymptomatic pregnant women (P < 0.05). CONCLUSIONS: A significantly greater prevalence of M. genitalium was demonstrated in Japanese women with Chlamydia-negative cervicitis or adnexitis, compared with that in asymptomatic pregnant women. This study suggests that M. genitalium may play a pathogenic role in a portion of cases with Chlamydia-negative genital infections.
Adult↗
Mutations in the gyrA and parC genes in fluoroquinolone-resistant clinical isolates of Pseudomonas aeruginosa.
We determined partial sequences of the gyrA and parC genes of the fluoroquinolone-susceptible strain ATCC 27853 and 22 clinical isolates of Pseudomonas aeruginosa. While a single amino acid change in GyrA with or without a change in ParC was found in 14 isolates with decreased susceptibility to fluoroquinolones, 3 higher-level fluoroquinolone-resistant isolates had a double amino acid change in GyrA and a single amino acid change in ParC.
Amino Acid Sequence↗
Improved antimicrobial activity of DU-6859a, a new fluoroquinolone, against quinolone-resistant Klebsiella pneumoniae and Enterobacter cloacae isolates with alterations in GyrA and ParC proteins.
MICs of DU-6859a, a novel fluoroquinolone, for 18 Klebsiella pneumoniae isolates and 21 Enterobacter cloacae isolates with altered GyrA or altered GyrA and ParC ranged from < or =0.025 to 6.25 microg/ml and from 0.1 to 3.13 microg/ml, respectively. Based on the MICs at which 90% of the isolates were inhibited for these strains of K. pneumoniae and E. cloacae, DU-6859a exhibited 16- to 256-fold-greater activity than currently available fluoroquinolones.
Anti-Infective Agents↗
Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in quinolone-resistant clinical isolates of Klebsiella pneumoniae.
We determined a partial sequence of the Klebsiella pneumoniae parC gene, including the region analogous to the quinolone resistance-determining region of the Escherichia coli gyrA gene, and examined 26 clinical strains of K. pneumoniae for an association of alterations in GyrA and ParC with susceptibilities to quinolones. The study suggests that in K. pneumoniae DNA gyrase is a primary target of quinolones and that ParC alterations play a complementary role in the development of higher-level fluoroquinolone resistance.
Amino Acid Sequence↗
In vivo selection of Klebsiella pneumoniae strains with enhanced quinolone resistance during fluoroquinolone treatment of urinary tract infections.
We report two cases of failure of fluoroquinolone treatment of urinary tract infections with Klebsiella pneumoniae strains harboring quinolone resistance-associated alterations in GyrA and ParC and in vivo selection of posttreatment isolates with enhanced fluoroquinolone resistance. Active efflux leading to decreased accumulation of a drug enhanced fluoroquinolone resistance in one posttreatment isolate, and an additional mutation in parC resulting in an additional amino acid change in ParC was associated with increased resistance in the other.
Aged↗