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Biomedical subjects

K Totsuka

Publications and source records attributed to K Totsuka.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular cloning and expression of cynomolgus monkey interleukin-1beta cDNA.

The cynomolgus monkey cDNA encoding interleukin-1beta (IL-1beta) was molecularly cloned by the reverse transcription polymerase chain reaction from a cDNA library of adherent splenocytes stimulated with lipopolysaccharides. The sequence analysis showed that the monkey IL-1beta cDNA encodes a protein of 268 amino acids and displays a high degree (90%) of homology with the human counterpart. Substitution of amino acids resides mainly in the leader sequences of IL-1beta when compared with those of human IL-1beta. This cloned monkey IL-1beta cDNA was used to express in Escherichia coli as a fusion protein with thioredoxin and in insect cells infected with a recombinant baculovirus after molecular modification where monkey IL-1beta signal sequences were placed prior to the mature sequences of IL-1beta for efficient secretion in insect cells. Recombinant monkey IL-1beta expressed in both systems was shown to react with rabbit antihuman IL-1beta antiserum by Western blot analysis and to have the biological activity of IL-1beta in a bioassay.

Amino Acid Sequence↗
PubMed1998

[3D-CT cystography with perspective volume-rendering].

We evaluated the clinical utility of 3D-CT cystography using the perspective volume rendering technique in 5 patients with disorders of the urinary bladder and prostate. Unlike the conventional orthostatic volume-rendering technique, the capability of optional visual point settlement in the urinary bladder precluded cutting a subset of acquired data for luminal inspection, and permitted observation closer to lesions. Consequently, the technique enabled the evaluation of the accurate size, shape, and relation to adjoining mucosa and the region shaded by bulky tumor. 3D-CT cystography using the perspective volume-rendering technique facilitated 3-D inspection of the bladder lumen.

Aged↗
PubMed1996

[A fulminating case of Edwardsiella tarda septicemia with necrotizing fasciitis].

A 67-year-old Japanese male, suffering from liver cirrhosis with hepatoma, was admitted to the Yokohama National Hospital because of ascites retention. On physical examination, his abdomen was massively distended with ascites and his lower extremities were edematous. Laboratory findings on admission revealed hypoalbuminemia, moderate icterus, pancytopenia and hepatitis C virus antibody positivity. After admission, abdominal distention and edema were improved with the use of diuretics. On the 15th day of hospitalization, the patient noted diarrhea and bowel movements that occurred 10 times a day. On the following day, his body temperature rose to over 39 degrees C. On the morning of the 17th day, he complained of severe pain in the right lower extremity. Swelling and erythema over his right lower leg were evident. The skin lesion spread rapidly over the knee and became necrotic. His right leg became increasingly swollen with the development of edema and hemorrhagic bullae. About 4 hrs after the emergence of the skin lesion, his blood pressure fell to less than 60 mmHg. Laboratory findings suggested disseminated intravascular coagulation and multiple organ failure due to serious bacterial infection. In spite of vigorous treatment including administration of antibiotics, dopamine, gabexate mesilate and plasma, he did not recover from the state of shock and died about 14 hrs after the appearance of leg pain. Bacterial culture of the blood and contents of the bullae grew a gram negative rod identified as Edwardsiella tarda (E. tarda). Histological findings showed necrotizing fasciitis. E. tarda has recently become recognized as a pathogenic bacteria, particularly in patients with an underlying illness. This is the first reported case of E. tarda septicemia with necrotizing fasciitis.

Acute Disease↗
PubMed1995

Purification of canine alpha-fetoprotein and alpha- fetoprotein values in dogs.

Canine alpha-fetoprotein (AFP) was purified by a two step method. Anti-dog AFP antiserum was produced by immunizing rabbits with canine fetal serum proteins that failed to bind to an anti-dog whole adult serum affinity column. Canine AFP was then purified from amniotic fluid using affinity chromatography with anti-dog AFP antiserum. The bound protein was then eluted and further purified by passage through an anti-dog whole adult serum column. The non-binding protein's purity and specificity was confirmed by immunoelectrophoresis, double-diffusion, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and cross-reactivity with anti-human AFP. The molecular weight of canine AFP was approximately 66,000 by SDS-PAGE. Normal adult dogs had serum AFP levels of 7-63 ng ml-1. Levels of AFP were not altered by pregnancy but did show a small peak 2 days following parturition. Newborn puppies had serum AFP levels of 14.08 +/- 5.94 mg ml-1 at birth. By 1 week of age, serum AFP had fallen to 0.766 +/- 0.758 mg ml-1. AFP values in newborn puppies are thus considerably higher than those previously reported in humans, pigs and cattle.

Amniotic Fluid↗
PubMed1995

Effects of combination of benzylpenicillin and fosfomycin on penicillin-resistant Streptococcus pneumoniae.

The in vitro activity of benzylpenicillin in combination with fosfomycin against 51 clinical isolates of penicillin-resistant Streptococcus pneumoniae [minimal inhibitory concentrations (MICs) of benzylpenicillin > or = 0.5 mg/liter] was investigated. The fractional inhibitory concentration (FIC) index using the checkerboard method ranged from 0.38 to 0.75 (mean: 0.63). A synergy was also demonstrated in the killing curve on S. pneumoniae TW-1303 (MIC of benzylpenicillin, 2 mg/liter; MIC of fosfomycin, 32 mg/liter: FIC index, 0.38). Fosfomycin inhibited the production of all penicillin-binding proteins (PBP) except PBP 2B of S. pneumoniae TW-1303 and it decreased that of PBP 2B when it was combined with benzylpenicillin. These results suggest that the combination of benzylpenicillin and fosfomycin could be considered as the alternative treatment of penicillin-resistant pneumococcal infections.

Bacterial Proteins↗
PubMed1995

Comparison of phenotypic characteristics, DNA-DNA hybridization results, and results with a commercial rapid biochemical and enzymatic reaction system for identification of viridans group streptococci.

The rapid ID 32 Strep system (bioMérieux, Marcy l'Etoile, France) was evaluated for its ability to identify 21 species of viridans group streptococci; results were compared with DNA-DNA hybridization results and results of conventional physiological tests. A total of 171 strains of the 21 species including 147 clinical strains was analyzed. Of the 156 strains of species included in the database of this system, 136 strains (87%) were correctly identified. Incorrect identification occurred for 13 strains (8%), and no identification was given for 7 strains (5%). It was difficult to differentiate S. mitis and S. oralis accurately with this system. Of the 17 strains identified as S. mitis by the rapid ID 32 Strep system, the results of DNA-DNA hybridization were in agreement for only 3 strains. S. crista and S. parasanguis, which are not included in the database, were identified as S. mitis or S. sanguis or were not identified, but S. parasanguis could probably be identified by using the rapid ID 32 Strep system because the biochemical profile is well characterized for this species. The rapid ID 32 Strep system can be used to differentiate most species for which phenotypic characteristics have been described if the database is revised according to recently reported amended criteria for the identification of viridans group streptococci. However, identification of a few species such as S. mitis and S. oralis is problematic with this system.

Bacterial Typing Techniques↗
PubMed1994

Postantibiotic effects and postantibiotic sub-MIC effects of benzylpenicillin on viridans streptococci isolated from patients with infective endocarditis.

We investigated the postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects of benzylpenicillin on three strains of viridans streptococci isolated from infective endocarditis patients. The PAEs of benzylpenicillin on penicillin tolerant Streptococcus sanguis TW-70 (0.4-3.9 h), penicillin tolerant S. sanguis TW-80 (0.3-6.3 h) and nontolerant Streptococcus oralis TW-186 (0.5-3.1 h) were dependent on exposure time. The PAEs were not concentration dependent for S. sanguis TW-70 and S. sanguis TW-80 above the MIC, and for S. oralis TW-186 above 16 x MIC. The antimicrobial effects of benzylpenicillin at sub-MIC concentrations were examined in bacteria pretreated with benzylpenicillin (8 x MIC) for 2 h and compared with untreated bacteria. At the sub-MICs tested, the regrowth of pretreated S. oralis TW-186 cells was more prolonged than that of untreated cells and bactericidal action was seen only in pretreated cells. These effects (so-called 'postantibiotic' sub-MIC effects') were not observed in penicillin tolerant S. sanguis TW-70. The presence of the postantibiotic sub-MIC effect may be an important factor in determining the dosing regimen for infective endocarditis.

Endocarditis, Bacterial↗
PubMed1994

[Microbiological and clinical studies of vancomycin resistant Leuconostoc spp. and Pediococcus spp. isolated from septicemia patients].

We described three septicemia cases in which blood cultures yielded gram-positive cocci identified as Leuconostoc spp. and Pediococcus spp. Patients were three male adults aged 63 to 71 years with severe underlying diseases, pancreatic cancer, esophageal cancer and diabetes mellitus with chronic renal failure. They had fever and chills at the onsets of septicemia with acute obstructive suppurative cholangitis, acute pneumonia, and infection complicated with invasion sites of esophageal cancer contagious to bronchus and subcutaneous tissue. Blood cultures yielded catalase and oxidase negative highly vancomycin-resistant (MIC: 1024 micrograms/ml <) gram-positive cocci showing alpha or gamma hemolysis on blood agar plates. Two cases were polymicrobial infections. In one case with esophageal cancer, clinical symptoms persisted after the start of antimicrobial chemotherapy and the patient died 10 days later associated with complications of esophageal cancer. Leuconostoc lactis, Leuconostoc mesenteroides subsp. dextranicum, and Pediococcus acidilactici wee identified by physiological reactions. These strains were also highly resistant to teicoplanin and fosfomycin, and tolerant to all rested beta-lactams such as benzylpenicillin. This is the first report in Japan to our knowledge on the identification of Leuconostoc spp. and Pediococcus spp. isolated from human infectious diseases.

Aged↗
PubMed1994

[Microbiological and clinical studies of infective endocarditis due to nutritionally variant streptococci].

We report four cases of infective endocarditis due to nutritionally variant streptococci (NVS) that occurred between 1981 and 1991. Three female and one male patients had underlying heart diseases. Causative organisms showed satellitism to staphylococci. Two strains were identified as S. adjacens and the other two were identified as S. defectivus by DNA-DNA hybridization. All strains had tolerance and one strain had resistance to benzylpenicillin (MIC 4 micrograms/ml). This penicillin-resistant strain also had tolerance to gentamicin. There was no synergism of benzylpenicillin and gentamicin against this strain by a killing curve in vitro. A 11-year-old female patient with infective endocarditis due to this strain, who had a transposition of great arteries, had large vegetations in external conduits by the Rastelli's operation. Some intensive antimicrobial chemotherapies were unsuccessful and a surgical replacement of the conduits must be done in this case. Since infective endocarditis due to NVS is not rare in Japan, NVS should be considered for the causative organisms in culture negative endocarditis.

Adult↗
PubMed1994

[Evaluation of once-daily administration of arbekacin. Experimental study and determination of pharmacokinetic properties in man].

Experimental and phase I clinical studies were performed to evaluate the efficacy and safety of once-daily administration of arbekacin (ABK). The results obtained were as follows: 1. ABK displayed dose-dependent, excellent antibacterial activity and post-antibiotic effects (PAE) against MRSA. 2. No significant difference was found between once-daily and divided administration regimens in protection against an experimental MRSA infection in mice. 3. There was no significant difference between once-daily and twice-daily administration of ABK in ototoxicity in guinea pigs or in nephrotoxicity in rats. 4. In the phase I clinical study using 200 mg single daily administration of ABK, no abnormal laboratory test results or symptoms were observed. 5. In the phase I clinical study of 5-day repeated administration of 200 mg/day of ABK, headache and increase in WBC sediment in the urine was noted in 1 volunteer; however these were not confirmed to be attributable to ABK. No abnormal laboratory test results were obtained other than increases in beta 2-microglobulin, NAG and gamma-GTP levels, each of which returned to normal after the completion of ABK administration. No abnormality was observed in the audiometry examination. 6. Maximum serum concentration (Cmax), serum half-life (T1/2 beta) and urinary recovery rate (0-48 hours) after single administration of 200 mg of ABK, were 13.20 micrograms/ml, 2.30 hours and 86.75%, respectively. There were no significant differences in pharmacokinetic parameters or urinary recovery rates between day 1 and day 5 in the 5-day repeated administration study. These findings suggest that once-daily administration regimen of ABK may be as effective and safe as divided administration regimen for the treatment of MRSA infection. Further clinical evaluation is required, however.

Adult↗
PubMed1994

[Factors on antimicrobials].

Infections which are difficult to cure are mainly caused by resistant organisms or opportunistic pathogens. For the treatment of such infections, we should maximize drug's therapeutic potentials, and minimize its toxicity. Characteristics of pharmacodynamics and pharmacokinetics in antimicrobials should be taken into account to maximize the efficacy and to minimize the toxicity. Bactericidal activity and post-antibiotic effect of antimicrobials are the major factors to determine the optimal dosing. Infections caused by intra-phagocytic pathogens should be treated with drugs which penetrate cell well. Early treatment with antimicrobials is the corner-stone for the treatment of infections in immunocompromised host. It is very important to determine which of the two drugs should be given first to maximize the efficacy on combination therapy.

Anti-Bacterial Agents↗
PubMed1992

Metabolism of S-1108, a new oral cephem antibiotic, and metabolic profiles of its metabolites in humans.

The metabolism and pharmacokinetics of pivalic acid, a major metabolite of S-1108, were studied with three healthy volunteers. Concentrations of S-1006 (the active compound), pivalic acid, and pivaloylcarnitine in plasma and urine were measured after administration of S-1108. Recoveries in urine at the doses of S-1108 given (100 and 200 mg) were 33 to 41% for S-1006, 93% for total pivalic acid, and 89 to 94% for pivaloylcarnitine in 24 h, and maximum concentrations in plasma were 2 micrograms of S-1006 per ml, 1 micrograms of total pivalic acid per ml, and 2 micrograms of pivaloylcarnitine per ml after a 200-mg oral administration of S-1108. More than 90% of the pivalic acid was excreted as pivaloylcarnitine, and no measurable amount of free pivalic acid was present in urine samples, indicating that the pivalic acid liberated from S-1108 was almost quantitatively conjugated with carnitine in the human body. The level of free carnitine in plasma was unaffected by a single 200-mg administration of S-1108, whereas urinary excretion of free carnitine decreased as levels of acylcarnitine increased. The acylcarnitines were excreted primarily in the form of pivaloylcarnitine. This study clearly showed how the pivalic acid was metabolized and excreted in humans. The importance of monitoring carnitine, an essential cofactor in fatty acid metabolism, was also discussed in terms of its utilization by pivalic acid.

Administration, Oral↗
PubMed1989

Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models.

Animal studies that compare antibiotics have used only a limited number of doses administered at intervals chosen without regard for their pharmacodynamic effects of pharmacokinetic profiles. We compared the relative efficacy and potency of three beta-lactams and two aminoglycosides in lung and thigh-infection models in neutropenic mice by defining the maximum attainable antimicrobial effect at 24 h (Emax) and the total dose required to reach 50% of maximum effect (P50) at several dosing intervals. For beta-lactams, Emaxs were similar, whereas P50s increased 10- to 50-fold with longer intervals in both models. Aminoglycosides were significantly more bactericidal in the lung than in the thigh, and dosing interval had little impact on P50s in either model. Recognizing the variable impact of dosing interval on efficacy for different classes of antibiotics is mandatory for the proper design and interpretation of comparative trials.

Animals↗
PubMed1989

[Four cases of adult Listeria monocytogenes infection in the last 5 years--hepatic necrotic foci in the adult septic case].

We have reported on the clinical courses of 4 cases of adult Listeria monocytogenes (Lm) infection, and the autopsy findings of 2 cases, those we have observed over the past 5 years. They were 2 cases of meningitis, 1 case of meningitis and sepsis and 1 case of sepsis. These 4 cases had CML, neoplastic angioendotheliosis, SLE and post-renal transplant condition, as their underlying diseases, and all were receiving immunosuppressive therapy. One meningitis patient who recovered showed mild liver dysfunction during her clinical course. The other 3 patients who died had jaundice at the time of onset and severe liver dysfunction. The 2 cases those were autopsied were the sepsis cases. The one with an acute course and hepatic failure showed multiple miliary necrotic foci in the liver, where the presence of Lm in the cells could be verified. The other autopsy case, which had received adequate antibiotic therapy and the Lm infection had been cured, showed no necrotic foci in the liver. The case that had necrotic foci in the liver was the first such adult case in Japan. We have discussed the hepatic Lm infection in adult compromised hosts, which conventionally has not been considered a serious problem.

Aged↗
PubMed1987

Thyroxine-induced molting and gonadal function of laying hens.

Twenty laying hens, 238 days of age, were divided into four groups which received daily intramuscular injections of L-thyroxine (T4) (0, 20, 100, or 500 micrograms/kg body weight per day) for 4 weeks. There was no change in body weight or egg production rate of the control (0 microgram T4) or of 20 and 100-micrograms T4 groups over time. Body weight and egg production of the 500 micrograms T4 group decreased markedly and molting started 10 days after T4 injection. Circulating iodothyronine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) of the 500-micrograms T4 group increased markedly (30 to 150 times those of the control group) whereas serum luteinizing hormone and progesterone declined after one week and estradiol after two weeks. We concluded that a large dose of T4 (500 micrograms T4/kg, body weight per day) induced an increase in circulating iodothyronine levels, decreased secretion of gonadotropin and sex steroid hormones, and induced molting.

Animals↗