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Biomedical subjects

M Kaku

Publications and source records attributed to M Kaku.

At least 163 records · Page 9Linked to original sources

Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice.

We induced endogenous Pseudomonas aeruginosa bacteremia by administering cyclophosphamide and ampicillin to specific pathogen-free mice fed P. aeruginosa. Using this model, we evaluated the efficacy of erythromycin lactobionate (EML) in treating P. aeruginosa bacteremia. Treatment with EML at 50 and 100 mg/kg of body weight per day twice a day for 14 days significantly increased the survival rate. The most effective dose was 100 mg/kg/day, with a survival rate of 80% compared with a 20% survival rate in the control. However, the administration of EML at 500 mg/kg/day rather decreased the survival rate. In a model of intravenous infection, treatment with EML at 100 mg/kg/day twice a day for 7 days before the bacterial challenge also enhanced the survival rate. EML levels in serum, liver, and stool were apparently lower than the MIC (512 micrograms/ml). These observations suggest that EML is effective against P. aeruginosa bacteremia despite a lack of specific activity for this pathogen. Although the protective mechanism is still unclear, it is possible that a subinhibitory level of EML may affect the virulence of P. aeruginosa and enhance the host defense system.

Animals↗

Potential effects of erythromycin on host defense systems and virulence of Pseudomonas aeruginosa.

We evaluated several potential effects of erythromycin (EM) on host defense systems and the virulence of Pseudomonas aeruginosa. Peritoneal macrophages obtained from mice given 250 mg of EM per kg of body weight for 7 days by the intraperitoneal, intravenous, subcutaneous, or oral route produced significantly greater amounts of thymocyte-activating factors. These data suggest that EM enhances the in vivo production of cytokines, such as interleukins 1 and 6. Treatment of P. aeruginosa D4 with subinhibitory concentrations of EM enhanced the association of bacteria with murine Kupffer cells in vitro and increased bacterial clearance from the blood in mice. EM suppressed the in vitro production of exotoxin A, total protease, elastase, and phospholipase C by P. aeruginosa D4; exotoxin A production by P. aeruginosa PA-103; and total protease production by P. aeruginosa B16 and PAO1 in a generally dose-dependent manner. These data demonstrate that EM produces various effects in addition to its direct antimicrobial activity, suggesting that it has potential as an immunomodulator or bacterial virulence-suppressing agent against P. aeruginosa and other infections.

Adjuvants, Immunologic↗

Prospective comparative study of ofloxacin or ethambutol for the treatment of pulmonary tuberculosis.

The efficacy of ofloxacin, rifampicin and isoniazid was prospectively compared with the regimen of ethambutol, rifampicin and isoniazid for the primary treatment of pulmonary tuberculosis in 124 patients. All drugs were given orally daily for nine months. Culture conversion rates three months after starting treatment were 98 percent in the ofloxacin group and 94 percent in the ethambutol group; by six months all patients in both groups were culture-negative. Significant radiological improvement of pulmonary infiltrates was observed in 83 percent of the ofloxacin group and 85 percent of the ethambutol group one year after starting treatment. No relapse in either group was observed during a two-year follow-up period after the cessation of chemotherapy. Ofloxacin appears to be as useful as ethambutol in the treatment of pulmonary tuberculosis when either drug is combined with isoniazid and rifampicin.

Adolescent↗

Prevalence of HTLV-I antibody in pulmonary cryptococcosis.

A retrospective study was done to determine the prevalence of anti-HTLV-I antibodies in patients with pulmonary cryptococcosis. None of the 19 patients with pulmonary cryptococcosis had underlying immunodeficiency. Anti-HTLV-I antibody was present in 6 (32%) of 19 patients with pulmonary cryptococcosis, a significantly higher prevalence than found in patients with bronchial asthma (4 (7%) of 58) (p less than 0.01, chi-square test). No statistical difference was noted when anti-HTLV-I antibody seropositivity was compared to that of patients with pulmonary tuberculosis (16% (17/105)), lung cancer (17% (22/129)) and pneumonia (9% (6/64)). A reduced cellular immunity as shown by lymphopenia, the CD4/CD8 ratio, and purified protein derivative skin test was found in only 1 (5%) of 19, 2 (12%) of 17, and 6 (33%) of 18 patients, respectively. These results do not explain the susceptibility to pulmonary cryptococcosis in HTLV-I carriers. This is the first report of high prevalence of pulmonary cryptococcosis in HTLV-I carriers and it raises the question whether HTLV-I carriers are more susceptible to opportunistic infections and other malignancies probably due to subtle immunological abnormalities.

Adolescent↗

Combination of conventional and endotoxin-specific limulus tests for measurement of polysaccharides in sera of rabbits with experimental systemic candidiasis.

Factor G, the coagulation enzyme from limulus amebocytes, is activated by (1-->3)-beta-D-glucan but not by endotoxin. The endotoxin-specific limulus test, which is devoid of factor G, reacts only with endotoxin. However, the conventional limulus test which includes factors G and C, reacts with not only endotoxin but also with (1-->3)-beta-D-glucan. In this study, the culture supernatant of Candida albicans in RPMI medium activated the conventional limulus test, but not the endotoxin-specific limulus test. All five rabbits inoculated intravenously with Candida albicans (1.0 x 10(7) CFU/rabbit) showed increased levels of reactivity with the conventional limulus test, whereas no elevation in the levels of the endotoxin-specific limulus test was observed in the sera of any infected rabbits. Only one serum sample from rabbit No. 5 on day 8 showed a positive Cand-tectest. The difference in the titers of the two limulus tests was suggestive of a diagnosis of Candida infection.

Amino Acid Sequence↗

An adult case of severe chronic active Epstein-Barr virus infection syndrome.

A 23-year-old man with persisting high fever developed hepatosplenomegaly, lymphadenopathy and massive pericardial effusion. Immunological examination revealed a marked elevation of anti-Epstein-Barr virus antibodies (anti-viral capsid antigens IgG-antibody 1:10,240, anti-early antigens-DR IgG-antibody 1:5,120), decreased activities of Epstein-Barr virus specific cytotoxic T lymphocytes, natural killer cells and lymphokine activated killer cells. A liver biopsy showed moderate sinusoidal lymphocytosis with punched-out lesions. These findings suggested severe chronic active Epstein-Barr virus infection syndrome. The patient was treated with recombinant human interleukin-2, but it was discontinued because of an adverse reaction. Twelve months later, he died of suspected pulmonary infection.

Adult↗

An outbreak of Legionnaires' pneumonia in a nursing home.

An outbreak of Legionnaires' pneumonia occurred at a nursing home in December 1990. A 79-year-old female and a 73-year-old male clerk who were staying at the nursing home developed pneumonia with only a 5-day interval. Legionella pneumophila serogroup I was isolated from transtracheal aspirate of the former and sputum of the latter. After treatment with a combination of erythromycin and rifampicin both patients improved. Serological surveillance of inpatients and staff of the nursing home was performed in February 1991. Seven out of 51 samples (14.0%) showed a titer higher than 1:128 of anti-Legionella pneumophila serogroup I antibody determined by indirect immunofluorescence; two of these seven complained of respiratory symptoms. Molecular epidemiology analyzed by restriction endonuclease digestion of isolated L. pneumophila showed an identical pattern which suggested a common origin.

Aged↗

Superinfection of chronic necrotizing pulmonary aspergillosis by Mycobacterium tuberculosis.

A 63-year-old woman with chronic necrotizing pulmonary aspergillosis complicated by active pulmonary tuberculosis is reported. A small infiltrative shadow appeared, but no definite diagnosis was made. Six years later the shadow was found to have increased in size; chest CT revealed a fungus ball, while a transbronchial lung biopsy revealed aspergillus hyphae. The intrabronchial inoculation of amphotericin B proved ineffective, and a lobectomy was performed. Histopathologic findings showed necrotic granulomas containing aspergillus and some acid-fast bacilli. While the superinfection of healed tuberculous lesions by Mycobacteria or Aspergillus species is well documented, their coexistence is rare.

Aspergillosis↗

[DNA probe and polymerase chain reaction for detection and identification of mycobacteria].

The DNA probe and polymerase chain reaction (PCR) technique for detection and identification of mycobacteria were compared with the conventional smear and culture method. The results of identification by DNA probe agreed well with those of the biochemical method. Moreover, six percent of Mycobacterium avium complex (MAC) were revealed to be mycobacteria other than MAC by DNA probe. The nested PCR for detection of gene coding protein antigen b of Mycobacterium tuberculosis complex showed excellent specificity and sensitivity. Then we applied this technique to rapid detection of M. tuberculosis in 222 clinical samples. The agreement between nested PCR and the biochemical method was excellent, and 17 cases were diagnosed by only nested PCR in spite of negative results by smear and culture. These cases were unlikely to have yielded false positive results since their clinical features were compatible to tuberculosis. From these data, it was considered that the DNA probe and PCR technique were extremely useful strategies and would contribute to rapid diagnosis of mycobacterial infectious diseases.

Base Sequence↗

Mechanism of cell swelling of HeLa cells in an isosmotic Na(+)-free, high-K+ medium: study on the K+ transport pathways.

The K+ content and the free Ca2+ concentration ([Ca2+]c) in HeLa cells began to increase after a latent period following medium change to an isosmotic Na(+)-free, high-K+ medium in the presence of 10-100 microM ouabain. These increases were accompanied by cell swelling, and stimulated by the addition of 1 microM ionomycin, whereas treatment with 1 mM quinine significantly inhibited the net K+ uptake. [Ca2+]c was slightly decreased, but the K+ uptake was unaffected in the Ca(2+)-free, high-K+ medium. However, when [Ca2+]c was extremely reduced by preloading 5 microM BAPTA-AM, the K+ uptake decreased to a level attained in the presence of quinine. Addition of DIDS and substitution with NO3- or SCN- for medium Cl- inhibited the K+ uptake to similar extents, and their effects were less strong than that of quinine. Substitution of medium Cl- with an impermeable anion gluconate completely inhibited the K+ uptake. Therefore, we conclude that cell swelling in the high-K+ medium is associated with K+ uptake mediated in greater part by quinine-sensitive and in smaller part by -insensitive pathway. The former pathway depends on cellular Ca2+ and its major component is Cl(-)-dependent, whereas the latter is independent of the Ca2+ and unselective for anions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

[A clinical study of tuberculous pleurisy].

Forty-eight cases of tuberculous pleurisy were examined and the following results were obtained. (1) Most of the patients were male, and there was no significant age and underlying diseases. (2) Fever and chest pain were observed mainly in younger patients, and sputum and dyspnea in older patients. (3) All of the cases examined had exudative pleural effusion, and increased ADA activity was frequently observed. (4) Mycobacterium tuberculosis was detected in the sputum of 65%, and also in the pleural effusion of 28% of the patients. The pathological diagnosis of tuberculosis was made by pleural biopsy in 83% of the patients, suggesting that pleural biopsy is very useful in the diagnosis of tuberculosis pleurisy. (5) The prognosis of the patients with tuberculosis pleurisy was good. Steroid therapy was generally ineffective.

Adolescent↗

[Laboratory and clinical studies on levofloxacin].

A newly developed broad-spectrum fluoroquinolone, levofloxacin (LVFX, DR-3355), was evaluated in vitro and in vivo in comparison with ciprofloxacin (CPFX), ofloxacin (OFLX) and norfloxacin (NFLX). The results were as follows. 1. Antimicrobial activity Minimal inhibitory concentrations (MICs) against 480 clinical isolates including 16 different species were determined using the microbroth dilution method. LVFX showed excellent antimicrobial activities against Gram-positive and -negative bacteria. The MIC values of LVFX for Gram-positive bacteria were superior to those of the other quinolones tested. The MIC values of LVFX for Gram-negative bacteria were comparable to those of CPFX and superior to those of OFLX and NFLX. 2. LVFX concentrations in serum and sputum LVFX was orally administered in a single dose of 200 mg to 2 patients with chronic lower respiratory tract infections, and its concentrations in serum and sputum were measured at intervals using bioassay. The peak concentrations of LVFX in serum were 1.52 and 1.24 micrograms/ml, and 84-95% of serum level were detected in sputum. From these data, it appeared that LVFX penetrate well into the lung. 3. Clinical efficacy and adverse reactions Fifteen patients with respiratory tract infections were treated with LVFX, and the overall efficacy rate was 78.6% (excellent in 3 cases, good in 8, fair in 3, poor in 0). As adverse reactions, anorexia was observed in 2 cases, diarrhea in 1 case and tremor of finger in 1 case. Although an elevation of total bilirubin in serum was observed in a case as an abnormal laboratory finding, it was mild, transient and improved rapidly after the completion of LVFX treatment.

Adult↗

[Clinical evaluation of serological antigen detection tests for candidemia].

The new serological tests for candidemia were evaluated. In nine cases of candidemia, fungal index (Endotoxin D-Endospecy) was 146.8 +/- 116.8 pg/ml and D-arabinitol/creatinine 1.10 +/- 1.04 mumol/mg. Fungal index was significantly (p less than 0.01) higher in candidemia than suspected infections. All candidemia were positive for Cand-Tec latex agglutination, but twelve of the sixteen cases of suspected infections were also positive. Mannan latex agglutination was very specific for candidemia. Four cases of candidemia was positive for Mannan latex agglutination and only one case was positive in suspected infections. Fungal index and D-arabinitol/creatinine was decreased after treatment of antifungal agents. In poor clinical efficacy case, these titer remained high even after treatment. These data suggested the usefulness of these serological tests for candidemia.

Adolescent↗

[Early diagnosis of Mycoplasma pneumoniae pneumonia by antigen detection using immunobinding assay].

The possibility of rapid diagnosis of Mycoplasma pneumoniae infection by immunobinding assay is described. Immunobinding assay which was developed by Kotani and McGarrity is a simple and rapid method for identification of mycoplasmas. Small amounts of antigen were spotted onto the nitrocellulose membrane. It was treated with a specific rabbit antisera against M. pneumoniae. The antigen-antibody complex was visualised with the avidin-biotin horseradish peroxidase method. Cross reaction was seen between M. pneumoniae and M. genitalium. Throat swabs from hamsters infected with M. pneumoniae were positive on 7th and 14th day after infection. Although the cross reaction was seen between M. pneumoniae and M. genitalium, this method could be useful for rapid diagnosis of M. pneumoniae infection.

Animals↗

[Laboratory and clinical investigation of lysis centrifugation blood culture method for fungemia].

We compared the lysis centrifugation blood culture system using Isolator (Du Pont) to the conventional blood culture bottle using BCB system (Roch), and the following results were obtained. In the investigation of experimental fungemia made by human blood and Candida albicans, the organism was detected 9/12 after 1 day and 11/12 after 3 days by Isolator, although the organism was detected 3/12 after 3 days and 11/12 after 6 days by the culture bottle system. In the experimental fungemia of Candida tropicalis, the organism was detected 12/12 after 2 days by Isolator, although it was detected 1/12 after 6 days and 4/12 after 10 days with the culture bottle system. Isolator showed faster and a more sensitive detection rate for fungemia. Clinical investigation of 94 cases (180 cultures) showed a 11.1% isolation rate with Isolator system and a 7.1% isolation rate with the culture bottle system. In 43 cases which were examined by the both systems, 7 cases were positive with Isolator, 3 positive with culture bottle. The culture bottle system isolated only Candida albicans and Candida parapsilosis, where as the Isolator isolated Candida albicans, Candida parapsilosis, Candida tropicalis, Candida krusei, and Candida spp. This investigation suggested that the Isolator system was an excellent method for the detection of fungemia.

Blood↗

Role of bacterial association with Kupffer cells in occurrence of endogenous systemic bacteremia.

Bacteremia in immunocompromised hosts often arises from their endogenous intestinal flora. We produced experimental endogenous bacteremia by administering cyclophosphamide and ampicillin to conventional and specific-pathogen-free mice. The frequencies of bacteremia and mortality in the conventional mice were significantly higher than for the specific-pathogen-free mice. Pseudomonas aeruginosa was the major pathogen causing systemic bacteremia in conventional mice and was associated with a high mortality rate. Morganella morganii caused systemic bacteremia in both conventional and specific-pathogen-free mice. In contrast, Escherichia coli, enterococci, or other species most often caused portal bacteremia only. To determine the mechanism of occurrence of systemic bacteremia, we investigated bacterial blood clearance in mice and association with murine Kupffer cells, using several bacterial strains isolated from mice with bacteremia. Blood clearance rates and the abilities of isolated Kupffer cells to associate with bacteria were significantly greater for the organisms causing portal bacteremia than for those causing systemic bacteremia. There were no significant differences between the blood clearance rates in carrageenan-treated mice and that in normal mice. Moreover, association at 4 degrees C was not different from that at 37 degrees C. The results suggest that blood clearance of bacteria reflects bacterial adherence to Kupffer cells and that the resistance of bacteria to association with Kupffer cells plays an important role in the occurrence of overwhelming systemic bacteremia in this animal model.

Agglutination↗

Effect of dietary protein depletion and ethanol on demethylation and denitrosation of N-nitrosodimethylamine by rabbit liver microsomes.

To study how the metabolism of N-nitrosodimethylamine (NDMA) is affected by dietary protein level and chronic ethanol feeding, 24 rabbits at 18 weeks of age, assigned to four groups, each with 6 rabbits, were fed for 8 weeks on the following 4 different diets; 21% protein content containing 21.1% casein and water, 21% protein content containing 21.1% casein and 7.5% ethanol, 7% protein content containing 4.8% casein and water, 7% protein content containing 4.8% casein and 7.5% ethanol. Body weights, liver weights and microsomal protein contents in the liver were significantly smaller in 7% protein diet groups than in 21% protein diet groups. Microsomal P-450 contents per protein content were less in 7% protein diet groups than in 21% protein diet groups. NDMA demethylation activity due to non-arachidonic acid stimulated system (NASS) and NDMA denitrosation activity were greater in 21% protein diet groups than in 7% diet groups. Chronic ethanol feeding increased NDMA denitrosation activity due to arachidonic acid stimulated system in both dietary protein levels. The ratio of NDMA demethylation activity (carcinogenic action) to NDMA denitrosation activity (detoxication action) was greater in 7% dietary protein groups than 21% dietary protein groups. The value of this ratio was decreased by chronic ethanol feeding in 7% dietary protein groups. Cytotoxic and carcinogenic actions of NDMA might be enhanced by low protein diet due to inhibition of denitrosation of NDMA in liver microsome and chronic 7.5% ethanol feeding alleviates metabolic activation of NDMA to carcinogenic compounds.

Animals↗