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Biomedical subjects

H Koga

Publications and source records attributed to H Koga.

At least 307 records · Page 17Linked to original sources

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↗

Fatal pneumonia caused by Corynebacterium group JK after treatment of Staphylococcus aureus pneumonia.

A 76-year-old man who was admitted to the hospital because of chronic renal insufficiency and chronic hepatitis died of Corynebacterium group JK pneumonia, after showing a slight improvement by treatment of Staphylococcus aureus with sulbactam/cefoperazone and minocycline. Transtracheal aspiration (TTA) just before his death revealed numerous gram-positive bacilli phagocytized by many neutrophils and more than 10(8) colony forming units (CFU)/ml of Corynebacterium group JK. A drug susceptibility test showed Corynebacterium group JK was resistant to many antibiotics, with the exception of vancomycin and amikacin.

Aged↗

Analysis of retained ventricular shunt catheters.

To identify the causes of ventricular shunt catheter retention, 42 shunt removals in 28 patients in our neurosurgical clinic from 1982 to 1991 were analyzed. The mean patient age was 13.8 years (2 mos-78 yrs), and mean shunt duration was 20.1 months (0.5-94 mos). There were nine retained ventricular catheters, including five with obstruction of the ventricular catheter. Shunt duration was significantly longer compared with the unretained group. Three retained ventricular catheters were stained by HE for histological examination. Light microscopy showed the inner lumen of catheters filled with granulomatous connective tissue and reactive glial tissue, and giant cell reaction to silicone material. Scanning electron microscopy of two catheters found peeling on the inner surface of the catheter, evidence of aging of the material. Granulomatous connective tissue and glial tissue reaction to aged silicone are suggested as the cause of catheter retention.

Adolescent↗

[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↗

[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 and pathological investigation of opportunistic pulmonary mycoses in autopsy cases].

Clinical and pathological investigations were performed in 58 cases of opportunistic pulmonary mycoses diagnosed at autopsy during the 10 years between 1979 and 1988 at Sasebo General City Hospital. The following findings were obtained. 1) The incidence of opportunistic pulmonary mycoses during the 10 years was 7.7%, with a significant increase in the incidence of fungal infections during the last 5 years of the study. The incidence of pulmonary mycoses was higher in patients with blood dyscrasia than in those with solid tumor or benign disease (p less than 0.001). 2) Administration of steroid hormone and anticancer drugs were suspected to be causative factors in the development of pulmonary aspergillosis and cryptococcosis, but not in candidiasis. 3) Characteristic radiographic patterns and clinical symptoms were absent in cases of pulmonary candidiasis due to the small size of the lesions and the high incidence of other complicating pulmonary infections and edema. 4) The most common initial roentgenographic pattern in opportunistic pulmonary aspergillosis was localized infiltrate, subsequently progressing to either multifocal infiltrates or cavitation. 5) The initial symptom in opportunistic pulmonary aspergillosis was usually high fever, and the radiographic abnormalities appeared later. The median duration between onset and death in 19 patients with pulmonary aspergillosis was 23.1 days. 6) Pulmonary aspergillosis should be suspected in the compromised host with high fever refractory to antibiotics and pulmonary infiltrates. Empiric antifungal therapy should be initiated at an early stage for the best chance for survival.

Aged↗

[Epidemiology of HTLV-I carriers in Hirado Island and virological and immunological investigation of HTLV-I associated pulmonary disease].

Adult T-cell leukemia (ATL) is endemic in Kyushu. Our study at Hirado island in Nagasaki prefecture revealed a higher incidence (35.9%) of HTLV-I carriers in villages with fishing than in those without (16.5%). HTLV-I carriers showed a higher incidence of abnormal findings on chest roentgenogram (21.7%) than non-carriers (16.5%), but most were lesions of old pulmonary tuberculosis and pleural thickening. Virological and immunological investigations were performed for 10 HTLV-I carriers, 3 patients with HTLV-I associated myelopathy (HAM), and 3 patients with ATL to determine the presence of HTLV-I associated pulmonary disease. In HAM patients, there were high titers of anti HTLV-I antibody, positive IgA reaction to HTLV-I, and an increase in interleukin-2 receptor (IL-2)-positive T-cells in the peripheral blood; and lymphocytosis and an increase in IL-2-positive T-cells in the bronchoalveolar lavage fluid (BALF). Virological examination showed the presence of pX gene and tax1/rex1 mRNA in the peripheral blood and BALF. Similar immunological and virological findings in 2 of 10 carriers suggested the presence of HTLV-I associated pulmonary disease.

Aged↗

Analysis of a variant form of platelet glycoprotein (GP) IIb: a second patient with abnormal molecular weight GPIIb.

In 1988, we reported a thrombasthenic patient whose platelets contained an abnormal molecular weight GPIIb (Blood, 71, 915, 1988). Here we describe another patient whose platelets contain a variant GPIIb with properties similar to the previously reported abnormal GPIIb. This patient has a small amount of the abnormal GPIIb and was suggested to be a heterozygote characterized by deficient and abnormal GPIIb genes. The abnormal GPIIb was suggested to be related to the precursor form of GPIIb because the molecular weights of both proteins are the same. The abnormal GPIIb may lack a peptide region around the cleavage site of the two chains, as suggested from its lack of reactivity towards antibodies against these epitopes.

Antibodies, Monoclonal↗

A selective uricosuric action of AA-193 in rats. Comparison with its effect on PAH secretion in vivo and in vitro.

We evaluated the uricosuric action of AA-193 by comparing it with the effect on PAH secretion in rats, using in vivo and in vitro techniques. The i.v. administration of AA-193 elevated the fractional excretion of urate (FEurate) significantly in a dose-dependent manner at doses from 0.1 to 10 mg/kg. Only at the highest dose of 10 mg/kg did AA-193 cause a momentary decrease in FEPAH. On the other hand, tienilic acid and probenecid reduced FEPAH at uricosuric effective doses. To compare the inhibitory effects of uricosurics on urate reabsorption and PAH secretion more directly, we investigated the effects of uricosurics on the OH- gradient-dependent urate uptake in brush border membrane vesicles and the net PAH accumulation in cortical slices. The relation between the affinity of uricosuric drug for urate and PAH transporters corresponds well with the difference between the effect on FEurate and that on FEPAH. The relative affinity of AA-193 for the urate uptake is 83-fold greater than that for the PAH accumulation. These results support the assumption that, in contrast with the other uricosurics, AA-193 has a much higher affinity for urate reabsorption system than that for the common pathway of weak organic acids in rats.

Animals↗

A possible clinical application of multicytokine-producing cytotoxic mononuclear cell (MCCM) therapy.

When peripheral blood mononuclear cells (PBMC) were incubated with a streptococcal preparation, OK-432, for 24 h, PBMC acquired cytolytic activity against cultured and fresh human tumor cells. Such PBMC were called OK-432-activated mononuclear cells (OK-MC). OK-MC produce several kinds of cytokines such as interferon alpha (IFN alpha), IFN gamma, and tumor growth inhibitory factor (TGIF) both in vitro and in vivo. OK-MC-produced cytokines also inhibited the growth of cultured and fresh human tumor cells. The growth inhibition was examined by human tumor clonogenic assay using a double-layer agar technique. The results indicate that two pathways of anti-tumor activity are induced in OK-MC, i.e., cell-mediated and cytokine-mediated.

Adenocarcinoma↗

Substrate specificity of urate transporter in rat renal brush border membranes.

To further demonstrate the substrate specificity of urate-anion exchanger in rat renal brush border membrane vesicles, the hydroxyl ion gradient-dependent [2-14C] urate uptake was studied by a rapid filtration technique. The [2-14C] urate uptake was more sensitive to unlabeled urate than to unlabeled xanthine and hypoxanthine. In addition, urate derivatives which are methylated at the positions 3 and 9 hardly inhibited the urate uptake. Because of the substrate specificity, the urate-anion exchanger in brush border membranes appears to selectively use urate as the endogenous substrate.

Animals↗

Three-dimensional structure-activity relationships and receptor mapping of N1-substituents of quinolone antibacterials.

Quantitative structure-activity relationships for quinolone antibacterials have been previously examined and a steric parameter L for the N1-substituents found to be important in QSAR equations. But some compounds for which previous QSAR equations could not predict the activity have appeared recently. In this study, conformations of a variety of N1-substituents of quinolone antibacterials were analyzed by a molecular modeling method. An active conformation of each of the compounds was estimated with information of the energy profile calculated by molecular orbital methods and of its biological activity. A model of a receptor corresponding to the N1-substituents was constructed by superposing van der Waals volumes of active conformer of highly active compounds. As a result of these conformational analyses and receptor mapping, it is proposed that there are two different optimum volumes for increasing the activity of quinolone antibacterials and two unfavorable regions for reducing the activity. It is suggested that the steric parameter L which appeared in previous QSAR equations corresponds to one of the optimum volumes of the proposed receptor model. With this receptor model, a relation between structure and activity of the compounds, including those mispredicted compounds in previous QSAR equations is able to be rationalized qualitatively and elegantly. We believe that this receptor model is useful for a prediction of the activity of compounds not yet synthesized as well as for designing new quinolone antibacterials.

4-Quinolones↗

Studies on uricosuric diuretics. 4. Three-dimensional structure-activity relationships and receptor mapping of (aryloxy)acetic acid diuretics.

Attempts to develop new (aryloxy)acetic acids with a better profile of diuretic and uricosuric activities as well as with fewer side effects have produced a series of compounds in which the ring system has been varied. Diuretic screening of these analogues in rats indicated that the great difference in the activity between these compounds might be ascribed to a difference in the ring system rather than that in the substituent effect and that the annulation hypothesis described before is not necessarily applicable to all of these compounds. This prompted us to study the relationship between the structure and the diuretic activity of the (aryloxy)acetic acids. An active model (receptor model) was created with the indanone moiety of R-(-)-3 and the dihydrobenzofuran-2-carboxylic acid moiety of S-(+)-4. The three-dimensional structure-activity study of known compounds 2-4, and 5a using the active model showed that the degree of fitting to the model is related to the diuretic activity of these compounds. This was also confirmed for compounds 6a, 6b, 9a, 10a, 11a, 12a, 13a, 14a, 15a, and 16a, and the relation between the structure and the diuretic activity was rationalized qualitatively. With these insights in mind, a modified receptor model was constructed. We believe that this model is useful for a prediction of the activity of compounds not yet synthesized as well as for designing new (aryloxy)acetic acid diuretics.

Acetates↗

Multiple proteolytic action of rat liver cathepsin B: specificities and pH-dependences of the endo- and exopeptidase activities.

Dipeptidylcarboxypeptidase, endopeptidase, and carboxypeptidase activities of rat liver cathepsin B were investigated using soluble denatured protein substrates, reduced and S-(3-trimethylammonio)propylated proteins and their derivatives. It was found that the soluble denatured proteins were degraded mainly by the dipeptidylcarboxypeptidase activity and in a few cases by the endopeptidase and carboxypeptidase activities. The eipeptidylcarboxypeptidase activity showed broad substrate specificity with broad pH optimum at 4-6. A peptide having the alpha-carboxyl group amidated with methylamine could also be a good substrate for this activity. These results suggest that this activity is dependent not upon the dissociated alpha-carboxyl group at the P2' site but upon the hydrogen-bonding abilities of the alpha-imino moiety and the protonated or amidated alpha-carboxyl moiety at P2'. On the other hand, the endopeptidase and carboxypeptidase activities were observed in a few cases, suggesting that special amino acid sequences in the substrates are responsible for these activities. These activities showed sharp pH optima at 6 and seemed to prefer basic amino acid residues at P1 site. Therefore, we suppose that cathepsin B has a carboxyl group with a pKa of about 5.5 at the S1 subsite which more effectively interacts with a positive charge at the P1 site of the substrate at pH 6 than at pH 5. Based on these results, a model of the binding subsites of this enzyme is proposed.

Amino Acid Sequence↗