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Biomedical subjects

F Kuze

Publications and source records attributed to F Kuze.

At least 73 records · Page 4Linked to original sources

[Effect of cytokines on anti-Mycobacterium avium complex (MAC) activities of human alveolar macrophages].

The macrophage is an essential component of the host defense against intracellular pathogens including MAC. Especially alveolar macrophages act as a first line defense in the lungs against MAC infection. Some cytokines were reported to activate mouse peritoneal macrophages and human monocyte-derived macrophages to inhibit growth or kill MAC. But we could find only one report describing the effect of cytokines on anti-MAC activities of human alveolar macrophages (PAM). Thus, we investigated the effect of several cytokines on anti-MAC activities of PAM. PAM were recovered from 12 healthy subjects by bronchoalveolar lavage and cells were cultured in RPMI 1640 with 10% heat-inactivated human AB serum. After 2 hours incubation nonadherent cells were discarded by vigorous washing to from monolayers of PAM (2 x 10(5) PAM in each 11-mm diameter tissue culture dish). Then we added 2 x 10(6) viable MAC bacteria (31F093T) and each cytokine to the wells simultaneously. We prepared the well without cytokines as control. After 96 hours incubation, PAM were disrupted by sonication, then all bacteria that had located inside and outside of the cells were plated onto 7H10 agar. The results are reported as mean colony forming units per each well. We had determined the optimal dose of each cytokine to prime PAM for enhanced O2- release and we used that optimal dose in this experiment. PAM with TNF-alpha pretreatment, and PAM with IFN-gamma pretreatment could release increased amount of O2- significantly, compared with control. PAM with IL-2 pretreatment and PAM with GM-CSF pretreatment also released somewhat increased amount of O2-.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗

[A clinical study on coexistence of active pulmonary tuberculosis and lung cancer].

Twenty-two patients were diagnosed as coexisting active pulmonary tuberculosis and lung cancer during last ten years until 1989. They were nineteen men and three women and their age ranged from 61 to 84 years with a mean age of 71.3. Six patients had history of tuberculosis, three had undergone gastrectomy and four patients were complicated with diabetes mellitus. Histological types of lung cancer were epidermoid cell carcinoma in 13, adenocarcinoma in 3, large cell carcinoma in 2, and small cell carcinoma in 4 and clinical stages were "stage I" in 2, "stage II" in 2, "stage IIIA" in 5, "stage IIIB" in 4 and "stage IV" in 7, except 2 patients after surgical treatment. Localizations of lesions of cancer and tuberculosis were in the same lobes in 6, in ipsilateral lung in 6, and in contralateral lung in 6, except 4 cases, whose lesion of tuberculosis was not detectable roentgenologically and all cancers of "same lobe" cases were peripheral origins. Although, the prognosis was poor, which reflects the prognosis of lung cancer as a whole, the efficacy of anti-tuberculous chemotherapy was as good as patients without lung cancer. We mainly discussed the diagnostic points to detect the coexistence of lung cancer and pulmonary tuberculosis at early stage.

Aged↗

[Evaluation of the tracheobronchial clearance in patients with chronic bronchial infections by an integrated system using radioactive aerosol inhalation scintigraphy].

It is widely accepted that the impairment of tracheobronchial clearance (TBC) are closely related to the development and the progression of chronic bronchial infections. We investigated TBC in patients with chronic bronchial infections (bronchiectasis; 11 cases, diffuse panbronchiolitis; 9 cases and primary ciliary dyskinesia; 3 cases) and also in 6 healthy subjects by a radioactive aerosol (99mTc-human serum albumin, 4.4 +/- 1.4 microns in diameter) inhalation scintigraphy with cough control in order to elucidate the relationships between impaired TBC and chronic bronchial infections. All subjects were not current smokers. After 4-minutes inhalation of radioactive aerosols (tidal volume: 500 ml x 20/min.), radioactivities in whole right lung were measured every 20 seconds for 2 hours serially and then measured at the time of 6 and 24 hours after inhalation. Immediately after the serial recording for 2 hours, single photon emission computed tomography (SPECT) was performed to assess the deposition pattern of radioactive aerosols. During the first 2 hours, all the subjects were instructed to avoid coughing as much as possible to evaluate the mucociliary clearance without cough effect. And then the subjects were allowed to cough between 2 and 24 hours after inhalation. All radiation counts were corrected for background radiation and physical decay of 99mTc. Because it is considered that the deposited aerosols are eliminated much more slowly in alveoli (biological half life: several months) than in airways (biological half life: several hours), the radioactivity remaining at the time of 24 hours was defined as alveolar deposition (ALV). Initial bronchial deposition (Br0) was defined as initial whole lung deposition (L0) minus ALV. We evaluated the TBC with following parameters; 1) Br0/L0 (%):ratio of initial bronchial deposition to initial lung (bronchial and alveolar) deposition. 2) Br2/Br0 (%), Br6/Br0 (%):bronchial retention ratio; the ratio of bronchial deposition at the time of 2 and 6 hours after inhalation to initial bronchial deposition, respectively. 3) TMV (mm/min.):tracheal mucus velocity (rate of shift of radioactive bolus on tracheal mucosa), which was measured during the period of first 2 hours under prohibition of cough. The patients (23 cases) were divided into two groups with regards to cough control for the first two hours of the scintigraphy:cough-controlled group (19 cases) and cough-uncontrolled group (4 cases). The cough-controlled group was subdivided into two subgroups (group A and group B) according to Br0/L0:group A less than 47.9% (mean + SD of Br0/L0 in healthy control) less than or equal to group B.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗

[Antimycobacterial activities of rifamycin derivatives].

The Standard Initial Chemotherapy, chemotherapeutic activity of which depends mostly on the two potent bactericidal drugs, INH and RFP, has made a remarkable progress in the treatment of tuberculosis. However, certain difficult situations still remain in the treatment of resistant diseases, mostly in retreatment cases especially resistant to INH and/or RFP, and of the patients who are not able to continue the Standard Regimens because of side effects and/or severe complications with various organ dysfunctions. It is evident that presently available antituberculosis drugs are not potent enough to deal satisfactorily with the above situations, and besides, there has been unsatisfactory chemotherapeutic efficacy against infections caused by Mycobacterium avium complex. The above matters strongly urge our effort to develop new antimycobacterial agents. In the present review, in vitro and in vivo activities of newly synthesized rifamycin derivatives (3'-hydroxy-5'-alkylpiperazinyl-benzoxazinorifamycins, KRMs) were discussed. Of a total of 158 newly synthesized compounds, five (KRM-1648, KRM-1657, KRM-1668, KRM-1674, KRM-2312) were selected due to significantly lower MICs than those of RFP against M. tuberculosis H37Rv and M. intracellulare 31F093T. The MIC90s of these compounds were 16 to 32 times lower than MIC90 of RFP against RFP-susceptible clinical isolates (20 strains) of M. tuberculosis, and 100 times or more lower than MIC90s of RFP against 20 disease-associated M. avium complex strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbial Sensitivity Tests↗

[In vivo activities of new rifamycin derivatives against mycobacteria].

Therapeutic effects of new rifamycin derivatives, 3'-hydroxy-5'-(4-alkylpiperazinyl) benzoxazinorifamycins, KRM 1648, 1657, 1668, 1674 and 2312 (kindly supplied by Kanegafuchi Chem. Ind. Co. Japan), were evaluated on experimental tuberculosis and Mycobacterium avium complex infection in mice. I. Experimental tuberculosis in mice Male ddY mice were inoculated via tail vein with ca. 1 x 10(9) CFU of M. tuberculosis H37Rv suspended in 0.2 ml medium. Treatment of the mice with the new rifamycin derivatives or rifampicin (RFP: as a control drug) was performed by daily oral administration of 10 mg/kg of the drugs, starting at the 24th hour of infection and continuing until the 40th day of infection. Therapeutic effect of each drug was assessed by mortality of the treated mice. All control mice which did not receive any drug died within the 20th day (in Exp. 1) and the 22nd day (in Exp. 2) of infection, while 25% (in Exp. 1) and 40% (in Exp. 2) of RFP-treated mice and 100% (in Exp. 1 and 2) of mice treated with any of the KRMs survived on the 40th day of infection. II. Experimental M. avium complex infection in mice Female beige mice (8-12 weeks old) were inoculated via tail vein with ca. 1 x 10(8) CFU of M. avium complex strain 31F093T, a mouse-virulent strain, suspended in 0.2 ml medium. Treatment of the mice with each drug (daily oral administration of 20 mg/kg) was started 24 hours after the inoculation, and was continued throughout 12 weeks of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[In vitro activities of new rifamycin derivatives against Mycobacterium tuberculosis and M. avium complex].

The in vitro anti-M. tuberculosis and anti-M. avium complex activities of five new rifamycin derivatives, KRM1648, KRM1657, KRM1668, KRM1674 and KRM2312, provided by Kanegafuchi Chem. Ind. Co. Japan were evaluated and compared with those of rifampicin (RFP) and rifabutin (RBU). Antimycobacterial activity was tested by broth dilution method using Kirchner's liquid medium supplemented with 10% bovine serum. The MICs 90 (micrograms/ml) of all five KRMs and RBU for 20 clinical isolates of M. tuberculosis were 0.035-0.07, whereas that of RFP was 1.25. The new rifamycin derivatives showed 16 to 32 times lower MICs than those of RFP against M. tuberculosis. All five KRMs inhibited 100% of 20 clinical isolates of M. avium complex at a concentration of 1.25 micrograms/ml, while only 35% and 10% of the strains were inhibited by the same concentration of RBU and RFP, respectively. The MICs 90 (micrograms/ml) for the strains tested were 0.07-0.3 for all five KRMs, and 5 and 40-80 for RBU and RFP, respectively. The new rifamycin derivatives were 16 times more active than RBU, which was 8 times more active than RFP. The new rifamycin derivatives were far more effective against M. tuberculosis in vitro than RFP, and their superiority to RBU which showed the effect superior to RFP was notable in in vitro anti-M. avium complex activities.

Humans↗

[Oxygen radical generation of murine alveolar macrophages].

The respiratory burst of murine alveolar macrophages (AM) was compared with that of peritoneal macrophages (PM). Superoxide anion (O2-) released from resident AM was similar to that of resident PM. That is, resident AM or PM exposed to phorbol myristate acetate (PMA) released only a small amount of O2-, whereas both macrophages released a large amount of O2- when stimulated with zymosan particles. AM as well as PM obtained from mice injected with Mycobacterium bovis BCG 3 weeks previously (abbreviated to BCG-AM and BCG-PM, respectively) showed an enhanced killing activity to Candida parapsilosis. O2- release of BCG-AM stimulated with zymosan was similar to that of BCG-PM. In both BCG-AM and BCG-PM, maximal O2- response was obtained by stimulation with a lower concentration of zymosan than the concentration which required for resident macrophages to release maximal amount of O2-. There was however, a remarkable difference between the ability of BCG-AM and BCG-PM to release O2- when stimulated with PMA. Markedly enhanced O2- release of BCG-PM was observed. In contrast, O2- release of BCG-AM exposed to PMA was almost the same as that of resident AM. Hydrogen peroxide release of BCG-AM, when stimulated with PMA or zymosan, was compatible with O2- release. Isoquinolinylsulfonyl piperadine (H-7), an inhibitor of protein kinase C, inhibited O2- release of PMA-stimulated BCG-AM and BCG-PM in a dose-dependent manner and the extent of inhibition was greater in O2- release of PM than that of AM. Superoxide anion release in response to zymosan was slightly inhibited by H-7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical and ultrastructural study on primary ciliary dyskinesia].

We evaluated laboratory and radiological findings and examined tracheobronchial cilia by transmission electron microscopy in 9 patients with primary ciliary dyskinesia (PCD), in order to elucidate the clinical pictures of PCD and the relationship between PCD and diffuse panbronchiolitis (DPB) which was proposed as a new disease entity in Japan in 1969. The clinical pictures of our PCD patients were almost the same as that already described in several articles in Europe and North America; early onset of respiratory symptoms, high incidence of chronic sinusitis and otitis media exudative as well as infertility, continuous infections in the lower respiratory tracts (Hemophilus influenzae, Pseudomonas aeruginosa etc.). Tracheobronchial cilia obtained by brushing technique were immotile (6 out of 8 patients) or dyskinetic (2 out of 8 patients). Ultrastructural study of cilia revealed the lack of dynein arms in all patients: the lack of both outer and inner arms (4 patients), the lack of outer arms (2 patients), the lack of inner arms (2 patients). Chest X-ray films revealed situs inversus in six out of nine patients. According to the radiological findings (chest X-ray film, CT-scan, bronchogram), the patients were divided into three groups; I: localized bronchiectasis (5 patients), II: diffuse micronodular lesions without definite bronchiectasis (3 patients), III: diffuse micronodular lesions with bronchiectasis (1 patient). Two patients of the second group satisfied the clinical diagnostic criteria for DPB (Chest 83:63, 1983). In conclusion, PCD can cause a variety of respiratory tract lesions such as bronchiectasis, DPB and other types of peripheral airway disorders.

Adult↗

In vitro antagonism between cisplatin and vinca alkaloids.

The effects of the combination of cisplatin and other cytotoxic agents were studied in vitro. When A549 lung cancer cells were treated simultaneously with cisplatin and other cytotoxic agents, cisplatin additively increased the cytotoxic effects of etoposide, mitomycin C, adriamycin, 5-fluorouracil and 1-beta-D-arabinofuranosylcytosine, but antagonised those of vincristine, vindesine, vinblastine and podophyllotoxin. The antagonism between cisplatin and vincristine was also observed with HT29 colon cancer cells. NC65 renal carcinoma cells and A431 epidermoid carcinoma cells when these cells were simultaneously exposed to both agents. When A549 cells were exposed to cisplatin and vincristine sequentially, the antagonism between them was evident when cells were pretreated with cisplatin but not when treated in the opposite sequence. Therefore, when combination chemotherapy including cisplatin and vinca alkaloids is given, possible antagonism between them should be considered, especially in determining the schedule of drug administration.

Cell Line↗

Plasmid profiles of Mycobacterium avium complex isolated from swine.

Twenty strains of Mycobacterium avium complex (MAC) isolated from swine and five strains from humans were examined for drug susceptibility and plasmid content. Four strains of swine origin and two strains of human origin harbored plasmid DNAs differing in molecular weights. No relationship between plasmid contents and drug resistance was observed. Southern DNA-DNA hybridization showed that small plasmids from swine MAC strains were homologous to those from human origin at the nucleotide level.

Animals↗

Identification and partial characterization of Mycobacterium avium and Mycobacterium intracellulare by using DNA probes.

We attempted to identify the Mycobacterium avium complex (MAC) isolated in Japan by using DNA probes specific for M. avium or Mycobacterium intracellulare (Gen-Probe Rapid Diagnostic System for MAC; Gen-Probe, Inc., San Diego, Calif.). The source and drug susceptibility distributions were examined. This assay system proved to be rapid, sensitive, specific, and reliable for identification of MAC and of the species as either M. avium or M. intracellulare. The DNA probe test showed that of the generally accepted MAC serovars, serovars 1 to 6, 8 to 11, and 21 belonged to M. avium and 7 and 12 to 20 belonged to M. intracellulare. Moreover, with the DNA probe test we found that the distribution patterns of M. avium and M. intracellulare isolates in Japan differed depending on the district in which MAC was isolated. The ratio of M. avium was much higher in eastern Japan. In Tokai and Shimane districts, the ratio of M. avium and M. intracellulare isolates significant in human disease was related to that of isolates from soil and house dust (natural sources). In M. avium, human disease-associated isolates were more resistant to rifampin, streptomycin, and kanamycin than were isolates from natural sources. However, this source dependence was not evident for M. intracellulare. In human disease-associated MAC, M. avium isolates were more resistant to most agents, except for quinolones, than were M. intracellulare isolates.

Animals↗

Isolation and partial characterization of human low molecular weight protein associated with pulmonary surfactant.

A low molecular weight (MW) protein was isolated from the bronchoalveolar lavage fluid of a patient with alveolar proteinosis. The protein was isolated on DEAE-cellulose and CM-cellulose columns by a cross-reaction with the monoclonal antibody against pig low MW protein (15 kDa) used as a marker. Acidic ethanol-soluble proteins obtained from the fractions eluted by 0.09 to 0.16 M NaCl concentration from the CM-cellulose column migrated mainly as a 15-kDa band in the SDS-PAGE system without urea but mainly as a 5-kDa band in a system with 8 M urea. The isoelectric point of the protein was pH 10 to 11, and it contained a large proportion of hydrophobic amino acids (72%), especially leucine (17%). The arginine content was also high (9%). Two monoclonal antibodies were raised against this low MW protein, and immunohistochemical studies revealed that the antigen was located in the inclusions of alveolar wall cells in normal lungs and in lungs from a patient with alveolar proteinosis. These results indicate that the low MW protein originates from lamellar inclusions of alveolar wall cells (possibly type II epithelial cells) and is secreted into alveolar spaces.

Amino Acids↗