Biomedical subjects

K Hatano

Publications and source records attributed to K Hatano.

At least 109 records · Page 6Linked to original sources

PubMed1993

Animal pharmacokinetics of FK037, a novel parenteral broad-spectrum cephalosporin.

Single-dose pharmacokinetics of FK037 has been investigated in laboratory animals. After bolus intravenous dosing with 20 mg/kg, the elimination half-life of FK037 varied in the species; with values of 0.27, 0.30, 0.97, 1.29 and 1.76 hours in mice, rats, rabbits, dogs and monkeys, respectively. The volume of distribution ranged between 260 ml/kg in rats and 390 ml/kg in dogs. These parameters approximated those of ceftazidime and cefpirome used as reference drugs. The renal clearance of FK037 was almost equal to glomerular filtration rate (GFR) in rabbits. Probenecid did not affect the elimination half-life of FK037 and its clearance ratio to GFR. These findings suggest that FK037 is solely excreted by glomerular filtration. FK037 readily penetrated into the tissues and inflammatory exudate fluid in rats, and the tissue level was highest in the kidneys, and decreased in the following order; lungs > heart > liver > spleen. Penetration of FK037, cefpirome and ceftazidime into the cerebrospinal fluid were determined using induced staphylococcal meningitis in rabbits. The penetration percentage ranged from 14.2 to 16.0% for these drugs with no significant differences. The major route of excretion of FK037 was via the kidney, with more than 74% of the dose being excreted in the urine within 24 hours after dosing to each species. Biliary excretion was low, 0.79% in rats. Bioautograms showed only unchanged drug in the plasma, urine and bile. Serum protein binding was low (8.8 to 17.6%) in all the species studied.

Animals↗

PubMed1993

In vitro antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 is a new parenteral cephalosporin, which offers some advantages over the commercially available parenteral cephalosporins. It demonstrated potent broad-spectrum activity against clinical isolates of Gram-positive bacteria including methicillin-resistant staphylococci, and Gram-negative bacteria including Pseudomonas aeruginosa. Against clinical isolates of aerobic Gram-positive bacteria, FK037, like cefpirome, demonstrated more potent activity than ceftazidime, cefoperazone and ceftizoxime. It is noteworthy that FK037, on the basis of the MIC90s, was the most active of all the cephalosporins tested against methicillin-resistant Staphylococcus aureus (MRSA). It was similar in activity to cefpirome against methicillin-sensitive S. aureus (MSSA). Against clinical isolates of aerobic Gram-negative bacteria, FK037, like cefpirome, was superior to cefoperazone, similar to ceftazidime and inferior to ceftizoxime in activity. Against P. aeruginosa, FK037 was superior to cefoperazone, similar or slightly superior to cefpirome and inferior to ceftazidime in activity. However, FK037 exhibited significant activity against Citrobacter and Enterobacter which were highly resistant to ceftazidime, cefoperazone and ceftizoxime. FK037 had an advantage in that its bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa at sub-MICs (1/2 or 1/4 the MIC) was much stronger than those of cefpirome and ceftazidime. Moreover, it exhibited potent bactericidal activity against MSSA, MRSA and P. aeruginosa in a pharmacokinetic in vitro model simulating human plasma concentrations after intravenous dosage of 0.125, 1.0 and 1.0 g, respectively. FK037 inhibited essential penicillin-binding proteins (PBPs), 1, 2 and 3 of S. aureus with a 50% inhibitory concentration (I50) of 0.58 micrograms/ml or lower. Of essential PBPs 3, 1a and 1b of E. coli and P. aeruginosa, FK037 inhibited PBP 3 at the lowest I50 (0.03 and 0.04 micrograms/ml, respectively) and PBPs 1a and 1b with I50 values of 2.7 micrograms/ml or lower. FK037, like cefpirome, was highly stable to hydrolysis by various beta-lactamases except Ic cephalosporinase from Bacteroides fragilis, and had extremely low affinity for beta-lactamases. Therefore, FK037 was more potent than ceftazidime in activity against beta-lactamase-producing bacteria except P. aeruginosa and Serratia marcescens. The ability of FK037 to penetrate the outer membrane of E. coli was slightly higher than that of ceftazidime, but slightly lower than that of cefpirome.

Anti-Bacterial Agents↗

PubMed1993

In vivo antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 has potent therapeutic activity against lethal systemic infections and experimental local infections due to a wide variety of Gram-positive and Gram-negative bacteria such as staphylococci, Streptococcus pneumoniae, Enterobacteriaceae and Pseudomonas aeruginosa in mice. In murine systemic infections, FK037 was the most effective of the cephalosporins and imipenem tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA). It was more effective than ceftazidime against selected strains of S. aureus and Enterobacteriaceae, except Serratia marcescens and P. aeruginosa against which FK037 was as effective as ceftazidime and was as effective as cefpirome against all organisms tested, except MRSA and P. aeruginosa against which FK037 was more effective than cefpirome. These results correlated well with its in vitro activity. In murine local infections, with few exceptions, FK037 was more effective than ceftazidime and cefpirome against Klebsiella pneumonia in ED50 values and against methicillin-sensitive S. aureus (MSSA) subcutaneous abscess, pyelonephritis with Staphylococcus epidermidis, E. coli and P. aeruginosa, intrauterine infections with S. aureus and E. coli in reducing the number of viable bacteria in the abscess, kidneys and uterus. It is noteworthy that the therapeutic effects of FK037 were more potent than had been anticipated from its in vitro activity against local infections with staphylococci and P. aeruginosa when compared with ceftazidime or cefpirome. In addition, the therapeutic effects of FK037 were equipotent or superior to those of cefpirome and ceftazidime against pneumonia due to MSSA, K. pneumoniae and P. aeruginosa in reducing the number of viable bacteria in the lungs in mice using an in vivo pharmacokinetic model simulating human plasma concentrations after drip infusion of usual clinical doses (0.25 to 1.0 g for MSSA, 0.063 to 0.125 g for K. pneumoniae and 1.0 to 2.0 g for P. aeruginosa). FK037 induced an in vivo post-antibiotic effect (PAE) of 3.4 hours against a thigh infection with MSSA in neutropenic mice. These results strongly suggest that it has potential for clinical use against various infections due to bacteria which include staphylococci and P. aeruginosa.

Abscess↗

PubMed1993

Excellent activity of FK037, a novel parenteral broad-spectrum cephalosporin, against methicillin-resistant staphylococci.

FK037 exhibits potent in vitro and in vivo antibacterial activity against methicillin-resistant staphylococci. In in vitro studies, FK037 was the most active of the cephalosporins and imipenem tested against the highly methicillin-resistant staphylococci (MIC > 100 micrograms/ml). Only 2 of 57 strains of highly methicillin-resistant Staphylococcus aureus (H-MRSA) had a FK037 MIC value of 50 micrograms/ml. On the other hand, 55, 40 and 19 strains had MICs of 50 or > or = 100 micrograms/ml to cefpirome, flomoxef and imipenem, respectively. Against 13 strains of highly methicillin-resistant coagulase-negative staphylococci (H-MRCNS), FK037 inhibited all the strains at < or = 50 micrograms/ml, but there were many strains highly resistant to the reference drugs with MICs of > or = 100 micrograms/ml. The influence of culture conditions such as low temperature, high inoculum and supplementation with 4% NaCl on the anti-MRSA activity of FK037 was less than those with cefpirome, flomoxef and imipenem. The in vitro frequency of spontaneous mutant cells highly resistant to FK037 in MRSA was lower than that to cefpirome and flomoxef. These findings were supported by lack of colonies inside the inhibition zone demarcated by FK037 in a disk sensitivity test, although many colonies proliferated inside the inhibition zone demarcated by flomoxef and imipenem. The increase in MIC of FK037 against a MRSA strain during subculture in the presence of the drug was smaller than that noted with the reference drugs. FK037 had higher affinity and faster binding for the PBP 2a of MRSA than that of the reference drugs. Moreover, the capacity to induce PBP 2a was lower for FK037 than that of cefpirome but higher than that of flomoxef. In an in vitro pharmacokinetic model simulating human plasma concentrations, FK037 showed potent bactericidal activity against H-MRSA in the plasma concentrations after intravenous infusion dosing with 1.0 g. FK037 was synergistically active against H-MRSA in combination with either imipenem of fosfomycin. The in vitro post-antibiotic effect (PAE) of FK037 against H-MRSA ranged from 1.2 to 1.7 hours at one to four times the MIC. FK037 had potent therapeutic effects against lethal systemic infections and experimental local infections in mice such as pneumonia, endocarditis, subcutaneous abscess, intrauterine infection and granuloma pouch infection due to MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE). FK037 was about 4, 8 and 1.5 times more effective than cefpirome, flomoxef and imipenem, respectively, against lethal systemic infections with H-MRSA.(ABSTRACT TRUNCATED AT 400 WORDS)

Abscess↗

PubMed1993

Chemistry of oxidative DNA strand scission.

In order to investigate the reactivity of uracilyl-5-yl radical in fixed DNA structure, photoreaction of 5-halouracil-containing oligonucleotides was investigated. It was found that photoirradiation of BrU-containing duplex DNA provided C1' oxidation product selectively at adenine residue of ABrU sequence. In contrast, photoirradiation of IU-containing DNA gave C1' and C2' oxidation products with almost no sequence preference. Sequence specific electron transfer in duplex DNA is proposed in the photoreaction of ABrU.

Adenine↗

PubMed1993

[A case of 46XX male].

A 24-year-old man consulted our hospital with a complaint of male infertility. Semen analysis revealed azoospermia. Endocrinological examination showed elevated serum luteinizing hormone and follicle stimulating hormone levels, and low normal level of serum testosterone. Testicular biopsy disclosed atrophic seminiferous tubules. Abdominal computed tomography revealed no ovaries or uterus. The chromosomal analysis revealed a karyotype of 46XX. This cases was diagnosed as a case of 46XX male. Forty six cases of this syndrome have been cited in the Japanese literature. We discussed the genesis of this syndrome.

Adult↗

PubMed1992

Cloning and surface expression of Pseudomonas aeruginosa O antigen in Escherichia coli.

As a step toward developing recombinant oral vaccines, we have explored the feasibility of expression of O polysaccharide antigens from Pseudomonas aeruginosa by Escherichia coli. We cloned in E. coli HB101 a 26.2-kilobase DNA fragment from P. aeruginosa strain PA103 that specifies the production of the O polysaccharide of Fisher immunotype 2 (IT-2) strains. The recombinant organism incorporated the P. aeruginosa IT-2 O polysaccharide onto the core of the E. coli lipopolysaccharide (LPS). Transfer of the recombinant plasmid to three LPS-rough strains of P. aeruginosa resulted in synthesis of IT-2 O antigen, and two of these transconjugant strains also synthesized a second O polysaccharide, presumably representing expression of a repressed, or an incomplete, set of genes for an endogenous O polysaccharide. Rabbits injected with the purified recombinant LPS made antibody specific for P. aeruginosa IT-2 O side chains, as did mice fed the recombinant E. coli strain. Expression of P. aeruginosa O antigens by enteric bacteria makes it possible to study these recombinant strains as oral vaccines to prevent P. aeruginosa infections.

Animals↗

PubMed1992

[Results of radiation therapy of extrahepatic bile duct carcinoma].

From January 1975 to August 1988, 40 patients with extrahepatic bile duct carcinoma were treated by external irradiation at Chiba University Hospital and the National Medical Center Hospital. Thirty-four patients (male: 20, female: 14) were evaluable. Eighteen patients were postoperative cases because the surgical margin was positive for tumor cells in the postoperative pathological examination; the other 16 were inoperable cases. Survival in postoperative and inoperable cases was not significantly different, with median survival times of 13.8 and 8.1 months, respectively. Survival in the recanalization-positive and negative-groups was significantly different (p less than 0.05) after irradiation, with median survival times of 13.5 and 6.0 months, respectively. Complications of therapy were recognized in 68% of all cases. They were mainly gastrointestinal symptoms such as nausea, vomiting, erosive gastritis and loss of appetite, but they were not severe. Distant metastasis was recognized in only 4 patients (10%): three had bony metastasis and one had supraclavicular and pulmonary hilar lymph node metastasis. Ninety percent of all cases died from hepatic failure or peritonitis carcinomatosa due to failure to obtain local control by external irradiation. A more effective modality of treatment is necessary to cure these patients.

Aged↗

PubMed1992

Radiation therapy in patients with unresectable hepatocellular carcinoma.

From April 1978 through December 1989, a total of 17 patients with unresectable hepatocellular carcinoma (HCC) were treated with radiation therapy alone or radiation therapy in conjunction with percutaneous ethanol injection (PEI), transarterial infusion chemotherapy (TAI), or transarterial embolization (TAE) at the National Medical Center Hospital. The median survival of all patients was 13.8 months. The survival values determined at 1, 2, and 3 years were 58.8%, 26.1%, and 9.8%, respectively. Only the pretreatment liver function affected the survival value. Between patients who did not have liver cirrhosis (LC) as well as those who had LC of Child's class A and patients who had LC of Child's class B or C, the differences observed in the 1-year survival value and the median duration of survival were statistically significant (P < 0.05). The serum cholinesterase (ChE) level seemed to be a good indicator of liver function during the radiation therapy. A field size of 150 cm2 and a total dose of 5000 cGy (TDF 82) seemed to be well tolerated by patients who did not have LC and those who had LC of Child's class A. The field size determined whether patients with poor liver function such as LC of Child's class B or C would develop severe hepatic deterioration after undergoing radiation therapy.

Aged↗

PubMed1991

Structure of (cyano)(2,3,7,8,12,13,17,18-octaethylporphinato)(pyridine)iron(III) chloroform solvate.

[Fe(C36H44N4)(CN)(C5H5N)].CHCl3, Mr = 813.12, monoclinic, P2(1)/n, a = 10.345 (2), b = 14.748 (2), c = 27.302 (3) A, beta = 92.12 (3) degrees, V = 4162.6 A3, Z = 4, D chi = 1.30, Dm = 1.29 g cm-3, Mo K alpha, lambda = 0.71073 A, mu = 5.92 cm-1, F(000) = 1708, T = 293 K, R = 0.046 for 5193 unique observed [F greater than 3 sigma(F)] reflections. The iron(III) atom is six-coordinate with an average Fe-N(p) distance of 1.980 (4) A and axial Fe-C and Fe-N distances of 1.934 (4) and 2.087 (3) A, respectively.

Chemical Phenomena↗

PubMed1991

Characterization of benzodiazepinooxazoles: crystal and molecular structure of trans and cis isomers of oxazolam.

The stereochemistry of the trans and cis isomers of 2(S)- and 2(R)-oxazolam is described. A total of four molecular structures of the 11b(R) and 11b(S) diastereomers of 2(S)- and 2(R)-oxazolam have been revealed by X-ray diffraction techniques. 2(S)-Oxazolam crystallizes in space group P2(1)/c, with cell dimensions a = 16.180(2) A, b = 8.791(2) A, c = 13.574(2) A, and beta = 102.07(1) degrees. The molecule in an asymmetric unit exhibited disorder at the 2-carbon (C2) atom, and the structures for trans and cis isomers have been resolved crystallographically. 2(S)-Oxazolam forms polymeric chains with intermediation of ethanol through hydrogen bonding. 2(R)-Oxazolam crystallizes in space group P1, with cell dimensions a = 7.754(1) A, b = 8.654(1) A, c = 15.795(2) A, alpha = 104.09(1) degrees, beta = 91.19(1) degrees, and gamma = 114.00(1) degrees. A similar disorder at the C2 position has been elucidated by a mixture of trans- and cis-2(R)-oxazolams. The two 2(R)-oxazolam molecules form a dimer with a hydrogen bond net. The structural details, focusing on the conformation and molecular complex formation of both oxazolams, have been discussed in connection with the oxazolidine ring stability and the crystal polymorph.

Anti-Anxiety Agents↗

PubMed1991

Prognostic factors for local control in nasopharyngeal cancer (NPC): analysis by multivariate proportional hazard models.

Despite the development of meticulous radiation therapy techniques, the local control of the nasopharyngeal cancer (NPC) remains unsatisfactory. We examined retrospectively the clinicopathologic factors which have impact upon local recurrence-free survival (LRFS) of the 67 patients with NPC who had been irradiated greater than or equal to 40 Gy with curative intent from 1975 through 1988. Three-year LRFS rate was 63%. T stage, histology, the presence of accompanying lymphocytic infiltration, and the properness of radiation therapy had influence upon LRFS with a statistical significance. Multivariate proportional hazard models showed that T stage and pathology retained significance. Radiation therapy properness emerged as a third factor when only the patients irradiated greater than or equal to 60 Gy were included in the analysis. From these results, three groups with low, moderate, and high risk of shortened LRFS could be separated. This risk classification could contribute to the stratification criteria of future study for the improvement of local control by new modalities.

Adult↗

PubMed1991

Purification and characterization of beta-N-acetylhexosaminidase from Trichoderma harzianum.

beta-N-Acetylhexosaminidase was produced by Trichoderma harzianum cultivated with chitin as the growth substrate. The enzyme was purified 13.2-fold to homogeneity by ultrafiltration and sequential chromatography on SP-Toyopearl and Sephacryl S-200. The molecular weight of the enzyme was estimated to be about 150,000 by gel filtration. The pH and temperature optima were 4.0-5.5 and 50 degrees C, respectively. The enzyme hydrolyzed N-acetylchitooligosaccharides at the non-reducing ends to release GlcNAc monomer. The enzyme showed a strict substrate specificity to the sugar chains in complex carbohydrates, hydrolyzing only the linkage of GlcNAc beta 1-3Gal, but not hydrolyzing the other linkages such as GalNAc beta 1-3Gal and GlcNAc beta 1-2Man.

Acetylgalactosamine↗

PubMed1991

Measurement of D2 dopamine receptor-specific carbon-11-YM-09151-2 binding in the canine brain by PET: importance of partial volume correction.

Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.

Animals↗

PubMed1991

[Evaluation of maintenance of cardiac output during DDD and VVI pacing by exercise Doppler echocardiography].

To evaluate the efficacy of DDD pacing for cardiac reserve, we assessed increases in the stroke volume and cardiac output during randomized treadmill exercise in 16 patients by DDD and fixed-rate ventricular (VVI) pacing. The stroke volume index and cardiac index were determined using suprasternal Doppler measurements. Ten patients who showed sinus rhythm during exercise were excluded from this study. Compared with the findings during VVI pacing, those during DDD pacing showed: 1) a greater exercise-induced positive chronotropic response (mean maximum heart rate 122 +/- 22 beats/min vs 70 beats/min, p < 0.01), 2) a lesser increase in the stroke volume index (34 +/- 7 to 39 +/- 9 ml/m2 vs 31 +/- 7 to 49 +/- 11 ml/m2, p < 0.05), 3) a greater increase in the cardiac index (2.43 +/- 0.45 to 4.48 +/- 1.36 L/min/m2 vs 2.22 +/- 0.47 to 3.43 +/- 0.45 L/min/m2, p < 0.05), and 4) prolongation of exercise duration (6.35 +/- 2.00 min vs 5.97 +/- 1.81 min, NS). These findings indicated that VVI pacing promoted a greater stroke volume than DDD pacing, which provides a compensatory increase in contractility and the preload in cases without an increase in heart rate during exercise, however, the increase in cardiac output was insufficient due to the absence of a chronotropic response. In conclusion, a DDD pacemaker could effectively increase heart rate, causing a significant increase in cardiac output and extending exercise duration.

Adult↗

PubMed1990

Visualization of histamine H1 receptors in dog brain by positron emission tomography.

Histamine H1 receptors were visualized in the living dog brain using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The regional distribution of these carbon-11 labeled compounds in the brain corresponded well with that of the histamine H1 receptors separately determined by in vitro binding assay. The radioactivity in the brain was reduced by treatment with triprolidine (1 mg/kg), a histamine H1 antagonist. The results of our study indicate that it is feasible to visualize histamine H1 receptors in human brain using these 11C-labeled compounds and PET.

Animals↗

PubMed1990

[Therapeutic factors related to irradiation in primary and metastatic liver cancer using multivariate analysis].

Between December 1973 and August 1987, 21 patients with primary liver cancer and 41 patients with metastatic liver cancer were treated with external irradiation, intra-arterial infusion chemotherapy and/or trans-arterial embolization (TAE) at the National Medical Center Hospital, the National South Kyushu Central Hospital and the National Kure Hospital. They were all inoperable cases. We diagnosed the tumor site and the involved area with many imagings and we decided the target volume. 1. Primary liver cancer: the average survival period was 10.9 months, the 1-year survival rate was 28.6%, the 2-year survival rate was 14.3% and the 3-year survival rate was 4.7%. Using multivariate analysis, stage, cancer reduction rate, Child classification and field size were valuable factors of the prognosis in the arterial infusion group. In the TAE group, cancer reduction rate was the most valuable factor. 2. Metastatic liver cancer: The average survival period was 8.0 months, the 1-year survival rate was 19.5%, the 5-year survival rate was 2.4%. Using multivariate analysis, pre-treatment K.P.S, distant metastasis, H, Child classification were valuable factors and pre-treatment K.P.S. was most valuable factor. Although the indication of hepatic irradiation were generally thought to limit those cases which were Child A or B, H1 or H2 and the cases which have no distant metastasis, the case which have their main portal tumor thrombus were also the indication of this therapy.

Aged↗

PubMed1990

[Therapeutic efficacy of postoperative irradiation on carcinoma of the breast].

From July 1973 to October 1983, 77 patients received mastectomy followed by postoperative irradiation at National Medical Center Hospital. The patients were classified as follows: 9 cases as stage I, 30 cases as stage II, 28 cases as stage IIIa, 7 cases as stage IIIb and 2 cases as stage IV. Irradiation fields were the parasternal and supraclavicular region. The axis of the irradiation fields to parasternal and supraclavicular regions were set up at 3.5 cm from the surface of the body and they were irradiated separately. The irradiation fields were about 0.5 cm apart from each other. Parasternal region contained bilateral parasternal lymphnodes. In some cases, the centersplit was used to prevent the radiation myelopathy. Prophylactic irradiation to axilla was performed by electron beam from October 1974 to September 1977. Prophylactic irradiation to chest wall has not been done since 1973. The five and ten years survival rates of stage II were 93.2% and 86.3%, stage IIIa were 61.9% and 55. 7%, Stage IIIb were 71.4% and 35.7%. The rate of the local recurrence at the supraclavicular region was 0% as stage I, 6.7% as stage II, 0% as stage IIIa and 14.3% as stage IIIb. Among the cases with regional lymphnode involvement at the time of mastectomy, the rate of local recurrence at the supraclavicular region was 6.7% in prophylactic irradiation group and it was significantly lower than in non-prophylactic irradiation group (11.5%) (p less than 0.05). The rate of local recurrence to chest wall was 0% as stage I, 6.7% as stage II, 8.0% as stage IIIa and 42.9% as stage IIIb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗