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H Shirafuji

Publications and source records attributed to H Shirafuji.

At least 19 recordsLinked to original sources
PubMed2005

Identification and characterization of cross-reactive antigens from Neospora caninum and Toxoplasma gondii.

Murine monoclonal antibodies (mAbs) against Neospora caninum tachyzoites were produced to identify the cross-reactive antigens between N. caninum and Toxoplasma gondii. Ten mAbs recognizing cross-reactive antigens of both parasites were obtained and tentatively classified into 6 different groups based on their reactivity patterns in an indirect fluorescent antibody test and Western blot analysis. Three mAbs in group 1 recognized antigens located on the surface of parasites with molecular masses ranging from 28 to 76 kDa; one mAb in group 2 recognized antigens located on interior organelles of parasites with a molecular mass of 50 kDa; one mAb in group 3 recognized antigens located on interior organelles of parasites with molecular masses of 35 kDa and 14 kDa; three mAbs in group 4 recognized antigens located on interior organelles with a molecular mass of 64 kDa; one mAb in group 5 recognized antigens located on the surface of parasites with an unknown molecular mass; one mAb in group 6 recognized antigens located on the apical end of parasites with an unknown molecular mass. The mAbs in groups 1, 2, 3, and 5 showed inhibitory effects on the growth of the two parasites in vitro in a dose-dependent manner. A cDNA expression library prepared from N. caninum tachyzoite mRNA was immunoscreened with the mAb panel. Three kinds of proteins, protein disulfide isomerase (PDI), heat-shock protein 70 (HSP70), and ribosomal protein 1 (RP1), were identified as cross-reactive antigens recognized by mAbs in groups 2, 3, and 4, respectively. Some of the proteins could be useful in developing vaccines or drugs for controlling the diseases caused by the two parasites.

Animals↗
PubMed2001

Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma.

Airway hyperresponsiveness (AHR), goblet cell metaplasia, and mucus overproduction are important features of bronchial asthma. To elucidate the molecular mechanisms behind these pulmonary pathologies, we examined for genes preferentially expressed in the lungs of a murine model of allergic asthma by using suppression subtractive hybridization (SSH). We identified a gene called gob-5 that had a selective expression pattern in the airway epithelium with AHR. Here, we show that gob-5, a member of the calcium-activated chloride channel family, is a key molecule in the induction of murine asthma. Intratracheal administration of adenovirus-expressing antisense gob-5 RNA into AHR-model mice efficiently suppressed the asthma phenotype, including AHR and mucus overproduction. In contrast, overexpression of gob-5 in airway epithelia by using an adenoviral vector exacerbated the asthma phenotype. Introduction of either gob-5 or hCLCA1, the human counterpart of gob-5, into the human mucoepidermoid cell line NCI-H292 induced mucus production as well as MUC5AC expression. Our results indicated that gob-5 may play a critical role in murine asthma, and its human counterpart hCLCA1 is therefore a potential target for asthma therapy.

Animals↗
PubMed1999

Cloning and expression of a novel lysophospholipase which structurally resembles lecithin cholesterol acyltransferase.

Lecithin cholesterol acyltransferase (LCAT) is the key enzyme in the esterification of plasma cholesterol and in the reverse cholesterol transport on high-density lipoprotein (HDL). We have found a novel LCAT-related gene among differentially expressed cDNA fragments between two types of foam cells derived from THP-1 cells, which are different in cholesterol efflux ability, using a subtractive PCR technique. The deduced 412-amino-acid sequence has 49% amino acid sequence similarity with human LCAT. In contrast to the liver-specific expression of LCAT, mRNA expression of the gene was observed mainly in peripheral tissues including kidney, placenta, pancreas, testis, spleen, heart, and skeletal muscle. The protein exists in human plasma and is probably associated with HDL. Moreover, we discovered that the recombinant protein hydrolyzed lysophosphatidylcholine (lysoPC), a proatherogenic lipid, to glycerophosphorylcholine and a free fatty acid. We have therefore named this novel enzyme LCAT-like lysophospholipase (LLPL), through which a new catabolic pathway for lysoPC on lipoproteins could be elucidated.

Amino Acid Sequence↗
PubMed1995

Novel, potent, and orally active substance P antagonists: synthesis and antagonist activity of N-benzylcarboxamide derivatives of pyrido[3,4-b]pyridine.

A series of 4-phenylisoquinolone derivatives were synthesized and evaluated for NK1 (substance P) antagonist activity. Highly potent antagonists, 4-phenyl-3-isoquinolone-N-benzylcarboxamides (11), were discovered from the structure-activity relationship studies on the isoquinolone-urea lead 1a. Optimization of the activity in this series resulted in the development of 5-phenyl-6-pyrido[3,4-b]pyridine-N-benzylcarboxamides (30) which are highly potent orally active NK1 antagonists. Among the compounds synthesized, N-[3,5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N,7-dimethyl-8-oxo-5- (substituted phenyl)-6-pyrido[3,4-b]pyridinecarboxamides (30a,f,g) showed excellent antagonist activities with IC50 values (in vitro inhibition of [125I]-BH-SP binding in human IM-9 cells) of 0.21-0.34 nM and ED50 values (in vivo inhibition of capsaicin-induced plasma extravasation in guinea-pig trachea, iv) of 0.017-0.030 mg/kg. These compounds exhibited significantly potent activity upon oral administration with ED50 values of 0.068-0.17 mg/kg. Conformational studies on 30g indicated that the two stable conformers of 30g are quite similar to those of CP-99,994.

Administration, Oral↗
PubMed1988

[A study on ceftriaxone in the perinatal period].

Ceftriaxone (CTRX), a new cephem antibiotic with high activity against Gram-positive and Gram-negative bacteria, was investigated pharmacokinetically in 30 mothers in the perinatal period. The obtained results are summarized below. 1. The maximum CTRX level in the maternal serum was 135 micrograms/ml between 20 and 25 minutes after an intravenous administration of 1 g of CTRX. 2. The transfer of CTRX into the umbilical cord serum and the amniotic fluid was very good. CTRX levels in these fluids were about 20% and 10% of the maternal serum level, respectively. 3. No side effect was observed in mothers or neonates. 4. CTRX is a useful antibiotic for perinatal infections.

Abortion, Induced↗
PubMed1986

[Study on cefotiam in the perinatal period].

Cefotiam (CTM), a new cephem antibiotic with high activity against Gram-positive and Gram-negative bacteria, has been investigated for use in 60 mothers in perinatal period, and following results were obtained. The concentration of CTM in maternal serum was 38 micrograms/ml at 0.5 hour after an intravenous administration of 1 g. A good transport of CTM into umbilical cord serum and amniotic fluid was observed after the intravenous administration into the mother. No adverse effect appeared in the neonates. The CTM is highly useful antibiotic in perinatal infections, and the safe dose of CTM to the mother in perinatal period is considered to be 1-2 g per day.

Abortion, Induced↗
PubMed1986

[A study on ceftazidime in the perinatal period].

Ceftazidime (CAZ), a new cephem antibiotic with high activity against Gram-negative bacteria, has been investigated for use in mothers in perinatal period, and the results obtained are summarized below. Into maternal serum, umbilical cord serum and amniotic fluid, CAZ showed good transfer after intravenous administration of 1 g or 2 g into mothers, and no adverse effect appeared in their neonates. The CAZ is a very useful antibiotic for the prophylaxis and the treatment of perinatal infections at a dose level of 1-2 g per day.

Bacterial Infections↗
PubMed1985

[Fundamental studies on aspoxicillin in the field of gynecology. Penetration of the drug into the genital organs and the dead space fluid. Antibacterial activity of the drug against various strains of clinical isolates].

A new semisynthetic penicillin aspoxicillin (ASPC, TA-058) has been evaluated in regard to distribution into the genital organs and the dead space fluid and also in regard to antibiotic activity against various strains clinically isolated in the field of gynecology. The pharmacokinetic studies were made by using two-compartment model on the data of concentration in ovary, oviduct, endometrium, myometrium, cervix uteri and portio vaginalis of the genital organs and in dead space fluid. The following results were obtained. After one shot intravenous administration of 2.0 g ASPC, no marked difference was observed in concentration pattern between peripheral vein and uterine artery. Half-lives were 1.8 hours and 3.5 hours, respectively. The concentrations in various tissues of genital organs reached to the maximum at 36.2-73.6 micrograms/g during 0.07-0.44 hour with half-life varied from 0.53 to 1.3 hours. Area under the curves (AUC) of various tissues were reached to 30-65% of that uterine artery. After 2.0 g administration of ASPC drip intravenously (d.i.v.; for 30 or 60 minutes), there are no remarkable difference on simulation curve of concentration between peripheral vein and uterine artery. The peak level of various tissues attained to 22.5-40.3 micrograms/g during 0.53-0.56 hours and AUC of their concentration achieved about 20-40% of that of uterine artery after intravenous drip infusion for 30 minutes. After intravenous drip infusion for 60 minutes, tissue level reached to the maximum during 1.01-1.82 hours with half-life of 0.65-1.4 hours and AUC of tissue concentration achieved about 20-57% of that of uterine artery. The concentration of the drug in dead space fluid was reached to the maximum at 3.1 hours after the administration and its half-life was 5.3 hours. The in vitro activities of ASPC against clinical isolates were examined. The values of MIC70 and MIC80 were ranged 0.35-5.1 micrograms/ml against S. aureus, S. epidermidis, E. faecalis and P. mirabilis, respectively. Against E. coli, the value of MIC70 was attained 2.9 micrograms/ml, however, the value of MIC80 was more than 100 micrograms/ml due to the two-peaked activity of this drug against the bacteria. AUC and duration time of various tissue concentration were scrutinized regarding to the value of MIC80 of ASPC against S. aureus, S. epidermidis, E. faecalis and P. mirabilis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amoxicillin↗
PubMed1985

[Fundamental and clinical study on cefpiramide in obstetrics and gynecology. Obstetrics and Gynecology Study Group for Cefpiramide].

Fundamental and clinical studies on a new cephalosporin antibiotic, cefpiramide (CPM), was carried out under a joint study program, in order to evaluate the usefulness of the drug in treating infection of the female genital organs. The results obtained were as follows: CPM was readily transported to female genital organ tissues, and the concentrations of the drug exceeded 35 micrograms/g in various organ tissues in about 1 hour, following intravenous injection of 1 g. A level of more than 2 micrograms/g was maintained even 14 hours after the injection. The transport of CPM to various tissues was also studied following intravenous drip infusion of 1 g for 1 hour. The concentrations in tissues were slightly low but similar to those following intravenous injection. The peak concentration of the drug in the dead space exudate was 3.1-20.4 micrograms/ml, following intravenous injection and intravenous drip infusion of 1 g. The MIC80 of CPM were 3.13-12.5 micrograms/ml against S. aureus, Klebsiella sp., P. mirabilis and P. aeruginosa. Clinical effects of CPM were analyzed in 158 patients, including 56 cases with intrauterine infection, 37 cases with intrapelvic infection, 22 cases with external genital infection, 31 cases with adnexitis, 6 cases with postoperative wound infection and 6 cases with other infections. Excellent response was seen in 28 cases (17.7%), good response in 120 (75.9%) poor response in 10 (6.3%). The rate of response was calculated as 93.7%. Safety of the drug was analyzed in 258 patients, and side effects occurred in 4 (1.6%). Of these 4 patients, rash was in 1 patient, heat sensation in 1 patient, nausea in 1 patient and rash accompanying edema in 1 patient. Abnormal values in clinical laboratory findings were seen in 7 patients. Elevations of transaminase were seen in 5 patients and decrease of platelet was seen in a patient, and then elevations of transaminase with decrease of platelet was seen in a patient, and no other changes of particular note appeared.

Adult↗
PubMed1984

[Fundamental and clinical studies on latamoxef in the perinatal period].

Fundamental and clinical studies on latamoxef (LMOX) in the perinatal period were carried out, and following results were obtained. Concentration of LMOX was showed high peak levels in maternal serum, umbilical serum and amniotic fluid. LMOX seemed to be a very transferable compound to human tissues. LMOX was administered to 28 cases of various perinatal infections. Clinical responses were excellent in 13 cases, good in 15 cases and poor in none. And 140 cases of prophylactic use in the field of perinatal period were evaluated in good. No side effect was seen and an abnormal laboratory finding, the increase of GPT, was observed in only 1 case. LMOX was a highly useful antibiotic in perinatal infections, the safe dose range of LMOX into the perinatal mothers was estimated to be 2 g/day, with the maximum safe dose being 4 g/day.

Adult↗
PubMed1983

[Laboratory and clinical studies on latamoxef in the field of obstetrics and gynecology].

Latamoxef (LMOX) is a new antibiotic synthesized by Shionogi Research Laboratory. Chemically LMOX is especially unique with a sulfur atom replacing the oxygen atom in the 1 position of the conventional cephalosporin nucleus, and in addition, this antibiotic has a cephamycin-like structure. The antibacterial activity of LMOX shows high potency against Gram-negative bacteria, but tends to be weak against Gram-positive bacteria. The tissue levels of LMOX in humans after intravenous injection of 1 g were examined. The levels in uterine and adnexa uteri tissue at 1 hour after administration were 25.4 and 27.4 micrograms/g respectively. LMOX was administered to 147 cases in infections of obstetric and gynecological field. The clinical effect according to disease was 94.6% for intrauterine infections, 95.0% for adnexitis, 87.0% intrapelvic infections, and 100% for external genital organ infections, making a total of 92.5%. The rate of occurrence of side effects or abnormal laboratory findings was similar to or slightly less than that seen with other beta-lactam antibiotics.

Adult↗
PubMed1983

[Transfer of fosfomycin sodium into the pelvic organs].

To confirm efficacy and safety of fosfomysin sodium (FOM-Na) in the field of obstetrics and gynecology, hemodynamics and pelvic transference were analyzed using so-called three-compartment model in adult women treated with the drug at a dose of 2 g either as an one shot injection or an intravenous infusion over 1 hour. Following results were obtained. 1. Hemodynamics in these patients were similar to those obtained in healthy adult males, although there was a tendency that levels reached were lower and elimination was more rapid in cases of genital cancer. 2. As to drug concentration of dead cavity fluid, Tmax appeared at 1.75 hours after completion of administration irrespective of administration methods, with Cmax being 67.8 micrograms/ml and 50.5 micrograms/ml of intravenous injection and intravenous infusion, respectively. Thereafter, there was no difference between two administration methods. 3. Uterine tissue concentration reached to its Tmax at 15 to 30 minutes after intravenous injection and within 10 minutes after completion of intravenous infusion, Cmax being higher than 90 micrograms/g. Even at 5 hours, 15 to 25 micrograms/g of the drug was detected. From these results and from susceptibilities of clinical isolates to the drug, it was considered that FOM-Na at a dose level of 2 g is highly effective in the treatment of various infections in the field of obstetrics and gynecology including intrapelvic infections, uterine infections and adnexitis.

Anti-Bacterial Agents↗
PubMed1983

[Clinical evaluation of latamoxef in the perinatal period].

Latamoxef (LMOX), a new oxacephem antibiotic with high activity against Gram-negative bacteria has been investigated for use in No. of 58 mothers in perinatal period, and obtained following results. Concentration of LMOX in maternal serum was 43.4 micrograms/ml at the 1 hour after intravenous administration of 1 g. In umbilical cord serum and amniotic fluid, LMOX showed good translation after intravenous administration of 1 g into the mother, but no adverse effect appeared in the neonate. LMOX is highly useful antibiotic in perinatal infections, and the safe dose of LMOX to the mother in perinatal period is 1--2 g per day considerably.

Amniotic Fluid↗