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Biomedical subjects

T Hidaka

Publications and source records attributed to T Hidaka.

At least 145 records · Page 8Linked to original sources
PubMed1993

A deletion of mitochondrial DNA in murine doxorubicin-induced cardiotoxicity.

A deletion of about 4 kb has been determined in the mutated mitochondrial DNA (mtDNA) in cardiomyocytes with chronic doxorubicin (DOX)-induced cardiotoxicity in mouse. The incidence of the mtDNA deletion increased with the dosage and with the duration of the DOX administration. Coenzyme Q10 administration prevented the mtDNA deletion and decreased the thiobarbituric acid reactive substance content in the heart mitochondria, suggesting some free radical involvement in this mtDNA deletion. This mtDNA deletion may be involved in cardiomyopathy, which is known to be dosage-dependently induced by DOX administration.

Animals↗
PubMed1993

[A case of liver abscess associated with endophthalmitis caused by Klebsiella pneumoniae].

A 54-year-old female was admitted to our hospital because of a spiking fever, right hypochondriac pain, right orbital pain and visual disturbance. Before admission she was treated with systemic antibiotics infusion for a diagnosis of liver abscess at the other hospital and the liver abscess almost diminished for a while. With the diagnosis of liver abscess and endophthalmitis, liver drainage and evisceration were carried out. The culture of pus from the eye and liver yielded K. pneumoniae. After liver drainage, evisceration, and direct injection of antibiotics into the eye, inflammatory findings tended to improve. Seven cases of metastatic K. pneumoniae endophthalmitis have been reported so far in Japan. The cases had liver abscess as the primary disease and 3 cases had bilateral endophthalmitis. Five cases with liver abscess survived except one who died of sepsis, but unfortunately, all cases became blind in the affected eyes. The prognosis of bacterial endophthalmitis, especially associated with K. pneumoniae liver abscess, is poor and as the outcome could appear to depend on time when treatment is started, a more aggressive diagnostic approach is required. Moreover systemic antibiotic infusion alone is inadequate for treatment of liver abscess and endophthalmitis, and liver drainage, evisceration and intravitreal injection of antibiotics must be given in early stage.

Endophthalmitis↗
PubMed1993

In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method.

MICs of a newly developed benzoxazinorifamycin derivative, KRM-1648, for Mycobacterium avium complex (MAC) were determined by the BACTEC 460 TB system and compared with those of other known antimicrobial agents. The radiometric method gave a fast, accurate, and reproducible MIC for each antimicrobial agent. MICs of KRM-1648 for 30 strains of MAC (10 strains each of M. avium isolated from AIDS and non-AIDS patients and of Mycobacterium intracellulare isolated from non-AIDS patients) were measured. The MICs, ranging from 0.004 to 0.0625 microgram/ml, were the lowest of all tested drugs, including rifampin, rifabutin, streptomycin, kanamycin, isoniazid, ethambutol, ofloxacin, ciprofloxacin, sparfloxacin, and clarithromycin. The MICs were 2 to 512 and 1 to 32 times lower than those of rifampin and rifabutin, respectively. With rifampin and ethambutol, there were some differences between the MICs for M. avium isolated from AIDS patients (American) and those for M. avium from non-AIDS patients (Japanese). Moreover, appreciable differences between the MICs of some drugs against M. avium and M. intracellulare isolated from non-AIDS patients were found. Many strains of M. avium were more susceptible to ofloxacin than M. intracellulare, but, conversely, M. avium was more resistant to rifampin, streptomycin, ethambutol, and clarithromycin than M. intracellulare.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.

The therapeutic efficacy of the benzoxazinorifamycin KRM-1648 was studied in an experimental rabbit infection system with avian Mycobacterium avium. The infected rabbits died from Yersin type infections, a peculiar type of experimental bovine tuberculosis characterized by a very rapid course, enlargement of the spleen and liver, and septic infection, 14 to 20 days after bacterial challenge, as evidenced by bacteremia and severe bacterial loads in the visceral organs. Histopathologic studies of the visceral organs of the infected rabbits revealed the development of numerous typical granulomatous lesions. This experimental rabbit infection system, features of which resemble certain features of disseminated M. avium complex infections in AIDS patients, was used to evaluate the therapeutic efficacy of KRM-1648, a newly synthesized benzoxazinorifamycin. KRM-1648 given orally at 25 and 50 mg/kg of body weight reduced the incidence and degree of bacteremia in infected rabbits and protected against subsequent death. Moreover, the drug allowed almost complete recovery of infected rabbits by week 7. KRM-1648 cleared infections in the lungs, liver, spleen, and kidneys and restored histopathologic features of healthy tissue in the visceral organs. KRM-1648 exhibited a more potent therapeutic effect against M. avium infection than rifampin and clarithromycin.

Animals↗
PubMed1993

Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.

As a part of our studies on the syntheses of benzoxazinorifamycin derivatives, 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives were synthesized, and tested for their antimicrobial activities. The antimicrobial activities of these compounds against gram-positive and gram-negative bacteria were almost identical to those of rifampicin (RFP) and rifabutain (RFB), however, antimicrobial activities against Mycobacterium tuberculosis were superior to RFP, while being similar to RFB. 3'-Hydroxy-5'-(4-alkyl-1-piperazinyl)benzoxazinorifamycin derivatives also had in vitro potent activities against Mycobacterium avium complex (MAC). Their minimal inhibitory concentration values against MAC were 2-256 times greater than RFP and RFB. Their in vivo efficacies against M. tuberculosis and MAC, after oral administration to mice, were superior to RFP and RFB, except for RFB against M. tuberculosis activity in vivo. Although they were absorbed from the gastrointestinal tract, their plasma levels were lower than that of RFP. Among these 5'-(4-alkyl-1-piperazinyl) derivatives, 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin, compound 19 (KRM-1648), was selected as the most promising and its preliminary pharmacokinetic characteristics in mice were investigated. Compound 19 was distributed much more in tissues, especially in spleen and lung, than in plasma and had a long elimination time from tissues.

Animals↗
PubMed1993

[Effects of carperitide (alpha-human atrial natriuretic peptide) on acute congestive heart failure in dogs].

Effects of carperitide (alpha-human atrial natriuretic peptide) on hemodynamics and renal function in dogs with congestive heart failure (CHF) produced by volume expansion and ligation of the left anterior descending coronary artery were compared with those of various anti-heart failure agents (cardiotonic, vasodilator and diuretic). Carperitide (0.1-1 microgram/kg/min) dose-dependently decreased the elevated left ventricular end-diastolic pressure (LVEDP). No significant changes in cardiac contractility (LV dP/dtmax) and heart rate (HR) were noted, although cardiac output (CO) tended to reduce during the infusion of carperitide. Nitroglycerin (NG; 3 micrograms/kg/min) and furosemide (1 mg/kg) also decreased LVEDP, but the potency was less than that of carperitide. Sodium nitroprusside (SNP; 10 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) caused a reduction in LVEDP and increased CO with an increase in HR. Hydralazine (H; 100 micrograms/kg/min) increased CO without reduction in LVEDP and induced a pronounced increase in HR. Double product (systolic blood pressure x HR), an index of myocardial oxygen consumption, was significantly reduced by carperitide, but significantly increased by DB and H. Carperitide, unlike NG, SNP, H and DB, increased urine volume and urinary electrolyte excretion. These results suggest that carperitide will be an useful therapeutic agent for the treatment of CHF.

Animals↗
PubMed1993

[Effect of carperitide (alpha-human atrial natriuretic polypeptide) on the cardiovascular system in experimental animals].

The cardiovascular and diuretic actions of carperitide were studied in experimental animals. Carperitide relaxed various canine arteries and veins that were contracted by high K+ or norepinephrine. Carperitide stimulated particulate guanylate cyclase from rat thoracic aortas. Carperitide had almost no effect on coronary perfusion pressure or heart rate, but caused a slight decrease in contractile force in isolated guinea pig hearts. Carperitide tended to decrease isoproterenol-induced renin release from isolated rat kidney slices and elicited decreases in angiotensin II-induced aldosterone release from bovine zona glomerulosa cells. Intravenous injection of carperitide elicited decreases in arterial blood pressure and total peripheral resistance in the anesthetized and conscious dogs. Carperitide also elicited transient increases in cardiac output and coronary blood flow followed by slight decreases in them. Intravenous infusion of carperitide elicited decreases in pulmonary capillary wedge pressure, pulmonary pressure and right atrial pressure in association with elevating plasma carperitide (ANP like immuno-reactivity) level in dogs with heart failure induced by coronary artery occlusion and saline loading. These results suggest that carperitide decreases both preload and afterload and can improve the untoward hemodynamic alterations in animals with acute experimental heart failure.

Animals↗
PubMed1993

Double filtration plasmapheresis in a patient with autoimmune hepatitis-systemic lupus erythematosus overlap.

Double filtration plasmapheresis (DFPP) therapy was administered to a patient with autoimmune hepatitis (AIH)-systemic lupus erythematosus overlap. The patient had suffered from recurrent AIH attacks with an interval of 3-4 months despite massive corticosteroid administration. After vigorous removal of immunoglobulins by DFPP procedures combined with immunosuppressive therapies, clinical and laboratory findings of AIH were remarkably improved. DFPP might be an optional modality in the treatment of AIH patients, especially for those who are resistant to and/or cannot tolerate massive corticosteroid or immunosuppressive therapies.

Adult↗
PubMed1993

[Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, administered at the different periods of infection in Mycobacterium intracellulare--infected mice].

Therapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, administered at the different periods of infection in Mycobacterium intracellulare-infected mice was studied. Mice were infected intravenously with M. intracellulare (9.8 x 10(6) CFU/mouse) and then were given 0.4 mg of KRM-1648 emulsified in 2.5% gum arabic-0.2% Tween 80 by gavage, once daily six times per week, from day 1 to week 4, week 2 to week 6, week 4 to week 8, and week 8 to the end of experiment (week 12). Judgement of the therapeutic efficacy of the drug against the infection was done on the basis of incidence and degree of gross lung lesions, % organ weight (organ weight/body weight x 100), and bacterial loads in the lungs and spleen. The lung lesions were not observed in the control and KRM-treated mice at 4 weeks after infection (KRM treatment: day 1 to week 4). At 6 weeks after infection (KRM treatment: week 2 to week 6), the lung lesions were observed in all control mice, whereas 3 of the 5 mice given KRM-1648 did not show the lesions. At 8 weeks after infection (KRM treatment: week 4 to week 8), the lung lesions were observed in all control and KRM-1648-treated mice, but the degree of the lung lesions was much more slight in mice given KRM-1648 than in control mice. The incidence and the degree of the lung lesions at 12 weeks after infection (KRM treatment: week 8 to week 12) was not different in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, administered in various frequencies per week in Mycobacterium intracellulare-infected mice].

Mice were infected intravenously with M. intracellulare (5.2 x 10(6) CFU/mouse) and then were given 0.4 mg of KRM-1648 emulsified in 2.5% gum arabic-0.2% Tween 80 by gavage, once daily 1, 3 or 6 times per week, from 24h after infection to the end of experiment (week 8). Evaluation of the therapeutic efficacy of the drug against the infection was done on the basis of incidence and degree of gross lung lesions, organ weight (square root of organ (mg)/body (g) x 10), and bacterial loads in the lungs and spleen. The lung lesions were not observed in all experimental groups at 4 weeks after infection. At 8 weeks after infection, the lung lesions observed in all control and solute (2.5% gum arabic-0.2% Tween 80) control mice, whereas 3 of the 5 mice given KRM-1648, 3 times per week and all of 5 mice given KRM-1648, 6 times per week showed no lung lesions. Although lung lesions were observed in all mice given KRM-1648 only once per week, the degree of the lesions was much more milder in KRM-1648-treated mice than in solute control mice. The spleen weight of solute control mice and KRM-treated mice differed from each other 4 and 8 weeks after infection, especially in mice administered 6 times per week. The CFUs of organisms in the lungs and spleen were lower in mice treated with the agent than in mice given solute at 4 and 8 weeks after infection, in orders of administration of 6, 3 and 1 times per week.

Animals↗
PubMed1993

[Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, combined with a immunopotentiator, LC9018, in Mycobacterium intracellulare infection induced in beige mice].

A study was performed on the therapeutic efficacy of KRM-1648 combined with LC9018 in beige mice infected with Mycobacterium intracellulare. Each mouse was intravenously infected with 3.9 x 10(6) CFU, and then given 0.2 mg of KRM-1648 emulsified in 2.5% gum arabic-0.2% Tween 80 by gavage once a day, six times per week, beginning 24 h after infection for up to eight weeks. A sc injection of 0.1 mg LC9018 in saline was given once or twice per week, beginning two weeks before infection to the end of experiment. An evaluation of the therapeutic efficacy of these drugs against the infection was performed on the basis of incidence and degree of gross lung lesions and bacterial loads in the lungs and spleen. Lung lesions were not observed in all experimental groups at four weeks after infection. However, at eight weeks after infection, although lung lesions were observed in all experimental groups, the degree of lesions was much milder in those mice receiving KRM-1648 than in the control mice. The degree of lesions in the mice receiving LC9018 was much the same as that in the control mice. Moreover, the degree of lung lesions in mice treated with KRM-1648 alone. The CFUs of organisms in the lungs and spleen of the mice treated with KRM-1648 were considerably lower than those of the control mice (P < 0.05), but the CFUs in the mice treated with KRM-1648 and LC9018 were nearly the same as those mice treated with KRM-1648.

Adjuvants, Immunologic↗
PubMed1992

An ultrasensitive system to detect IL-4: enzyme-linked immunosorbent assay (ELISA) combined with an avidin-biotin and enzyme amplification system.

We established an ultrasensitive interleukin-4 enzyme-linked immunosorbent assay by combining ELISA with an avidin-biotin and enzyme amplification system. The resultant system (AB-EA ELISA) was 250 times more sensitive than conventional ELISA and 2.5 times more sensitive than enhanced ELISA using an enzyme amplification system alone. The ultrasensitive assay was specific to IL-4 alone; there was no cross reaction with other cytokines. Using the ultrasensitive assay, we measured IL-4 synthesis in vitro by unstimulated and stimulated peripheral blood mononuclear cells (PBMC) from patients with allergic rhinitis. PBMC from patients spontaneously produced measurable amounts of IL-4, whereas IL-4 production from PBMC of normal controls, if any, was below detectable levels. Stimulation of the cultures with LPS significantly increased IL-4 production in two of six patient PBMC cultures but in none of the control cultures; stimulation with Con A markedly increased IL-4 production in all patient PBMC cultures but in only two of seven control cultures. These results suggest that the AB-EA ELISA is a useful method to study the mechanism of IL-4 synthesis in type-I allergic diseases.

Animals↗
PubMed1992

Increased interleukin 1 receptor, type I, at messenger RNA and protein level in skin fibroblasts from patients with systemic sclerosis.

Summary. To elucidate the mechanisms of the fibrosis in systemic sclerosis (SSc) through the action of a cytokine, interleukin 1 (IL-1), we studied the specific biologic and biochemical features of interleukin 1 receptor (IL-1R) as expressed on the surfaces of fibroblast cells in cultures from 3 SSc patients and 3 normal donors. 125I-IL-1 beta binding assays revealed a high density of IL-1R on the cell surfaces of SSc fibroblasts as compared to those of normal subjects. We also found an enhanced expression of IL-1R messenger RNA (mRNA) in SSc fibroblasts, using Northern blot or slot blot analysis. These findings indicate that the expression of IL-1R on SSc fibroblasts were spontaneously induced at the transcriptional level. It is suggested that SSc fibroblasts are more sensitive to IL-1, and that the signal transduction of IL-1 through IL-1R may be eventually involved in the fibrosis of SSc.

Cells, Cultured↗
PubMed1992

Nucleotide sequence of a carboxyphosphonoenolpyruvate phosphonomutase gene isolated from a bialaphos-producing organism, Streptomyces hygroscopicus, and its expression in Streptomyces lividans.

The carboxyphosphonoenolpyruvate (CPEP) phosphonomutase gene of bialaphos-producing Streptomyces hygroscopicus, which encodes a C-P bond forming enzyme was cloned into Streptomyces lividans and sequenced. The amino acid composition of the protein coded in an open reading frame of 295 codons and its calculated molecular mass, 32,800 Da, coincided well with those of the purified enzyme. Introduction of the CPEP phosphonomutase gene, the expression of which is controlled by the promoter of the aph gene, into S. lividans resulted in the production of this enzyme at a level almost equivalent to that in the parent strain.

Amino Acid Sequence↗