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Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 289 records · Page 16Linked to original sources

[Pharmacokinetic and clinical studies on aztreonam in neonates and premature infants].

Aztreonam (AZT) was studied for its pharmacokinetics, clinical effect and effect on intestinal bacterial flora in neonates, and the results obtained are summarized as follows: 1. Serum concentrations of AZT upon intravenous administration of 20 mg/kg were 38.6 micrograms/ml in 30 minutes, 30.6 micrograms/ml in 1 hour and 13.6 micrograms/ml in 6 hours. The T 1/2 was 3.73 hours. Ampicillin (ABPC) 25 mg/kg was concurrently used with AZT in 2 cases and serum concentrations of AZT in these 2 cases were 40.3 and 36.9 micrograms/ml in 30 minutes, 35.7 and 32.6 micrograms/ml in 1 hour, and 13.1 and 10.2 micrograms/ml in 6 hours, respectively. T 1/2's were 3.32 and 2.91 hours, respectively, and no interaction between the 2 drugs was observed. 2. AZT was administered to 21 neonates between 0 and 83 days of age and ABPC was concurrently administered to 18 of the cases. Clinical evaluation was made in 14 cases, where AZT was remarkably effective in 7 cases, effective in 6 cases and not effective in 1 case. Of the 21 cases, 1 case of diarrhea, 1 case each of eosinophilia, an increase in platelets, an increase in platelets and an elevation of GOT and a decrease in platelets were recorded. 3. With respect to effects of AZT on intestinal bacterial flora, fecal concentrations of AZT upon its single administration to 2 cases were low suggesting, there was little effect on the intestinal flora. Some effect on anaerobes, however, was recognized in 4 cases in which ABPC was concurrently used.

Ampicillin↗

[Laboratory and clinical studies on norfloxacin in pediatrics].

Norfloxacin (NFLX, AM-715) is a new quinolone antibacterial agent. In the present study, we carried out laboratory and clinical investigations on NFLX in the field of pediatrics. The obtained results are summarized as follows. 1. NFLX was very active against Escherichia coli, Salmonella sp., Klebsiella sp., Enterobacter sp. and Pseudomonas aeruginosa among Gram-negative rods. Antibacterial activities of NFLX against Gram-positive cocci were lower than those against Gram-negative rods but superior to activities of usual quinolone agents. MIC values of NFLX against Campylobacter jejuni were distributed in a range of less than or equal to 0.05-0.78 micrograms/ml. 2. A peak serum level of 0.49 micrograms/ml was observed in 2 subjects and its urinary recoveries were 13.7%, 21.5%, respectively. 3. Clinical efficacies to NFLX were excellent in 25 patients and good in 9 patients with a efficacy rate of 92%. In a bacteriological examination, causative organisms were eradicated with an eradication rate of 87%. 4. No side effects were observed except eosinophilia in 1 patient. These findings indicate that NFLX will be useful and safe drug against bacterial infections in pediatrics.

Adolescent↗

[The role of surgery in the management of small cell lung carcinoma].

Small cell lung carcinoma is responsive to chemotherapy and radiotherapy, but long-term survival of patients is rarely seen. We analyzed resected 19 patients with small cell lung carcinoma. The overall 5-year survival rate of resected patients was approximately 30% and mean survival time (MST) was 50 months. 2 patients of them survived more than 5 years. The survivors were received chemotherapy and radiotherapy several times after surgery. When we consider the role of resection in the treatment of small cell lung carcinoma, we can realize multimodality therapy including resection is important to obtain long-term survival. Moreover, the surgical resection can identify mixed type with non-small cell elements or residual tumors after chemotherapy and determine optimal treatment methods from their histopathologic findings.

Aged↗

Sequence and characteristics of the Bifidobacterium longum gene encoding L-lactate dehydrogenase and the primary structure of the enzyme: a new feature of the allosteric site.

The gene ldh, encoding L-lactate dehydrogenase (LDH; EC 1.1.1.27) of Bifidobacterium longum aM101-2, was cloned in Escherichia coli using an oligodeoxyribonucleotide hybridization probe. The amino acid (aa) sequence, deduced from the sequence of the cloned DNA, was consistent with the results of protein chemical analysis of B. longum LDH. The transcription start points (tsp) in B. longum were identified by S1 nuclease mapping. A sequence, GTAGCAA-(14 bp)-TTATAGA, which is located a few bp upstream from the tsp, was assigned as the promoter of this ldh gene. In the 3'-noncoding region, there were two structures that strongly resembled the Rho-independent transcriptional termination signal of E. coli. Therefore, the B. longum ldh gene might form a monocistronic unit. The deduced primary structure of B. longum LDH had 40% identity with LDHs from Thermus caldophilus, Bacillus stearothermophilus, Lactobacillus casei and dogfish muscle. Most bacterial LDHs are allosterically regulated by fructose 1,6-bisphosphate (FBP), while the vertebrate LDHs are not. The anion-binding site of vertebrate LDHs has been thought to correspond to the FBP-binding site of bacterial LDHs. Although the B. longum LDH was regulated by FBP, the charge properties of aa residues in the putative FBP-binding site of the LDH were closer to those of the vertebrate LDHs than to those of bacterial LDHs.

Allosteric Site↗

Effects of repeated testing on the incidence of haloperidol-induced catalepsy in mice.

Effects of repeated testing on the incidence of haloperidol-induced catalepsy were investigated in mice. The incidence of catalepsy, evaluated with the forelimbs or hindlimbs placed on a standard horizontal bar, increased in three successive tests in mice injected with haloperidol. Catalepsy was not provoked by repeated testing in animals with saline. In a subsequent study, mice were examined for catalepsy in the forelimbs in the first two trials and then in the hindlimbs. In this procedure, the incidence of catalepsy did not increase with repeated testing. These results suggest that repeated testing increases the incidence of haloperidol-induced catalepsy but does not influence the cataleptogenic potency of the drug.

Animals↗

Human respiratory airflow through an artificial nasal model: pressure/flow relationship.

Nasal airflow and differential pressure at peak flow were measured by Rhinorheograph MPR-1100 made by Nihon Kohden Co., Ltd. with human resting respiratory airflow through an artificial nasal model. In the healthy nasal model, it was assumed that nasal resistance was produced mainly in the vicinity of the pyriform aperture. Reduction of air space in the nasal model due to various simulated diseases led to decrease airflow and increased differential pressure with consequent increase of nasal resistance. Severe diffuse swelling of the inferior turbinate was the most important cause of marked elevation of resistance, nasal secretion also was an important factor which increased nasal resistance.

Airway Resistance↗

A fundamental study of rhinomanometry and its clinical application to objective evaluation.

We measured differential pressure and airflow at constant flow through a cylinder which had a variable aperture in its central portion, by means of a Rhinorheograph MPR-1100 in order to obtain a turbulent coefficient "n" experimentally in the equation R = delta P/Vn. Between of 1.0-5.0 cm H2O (not equal to 100-500 Pa) pressure, the coefficient "n" was distributed between 1.01-2.80 with a mean value of 2.02 (+/- 0.36), and resistances calculated from the equation R = delta P/Vn were almost the same value at each differential pressure. We applied this coefficient to 95 adult patients referred to our nasal airflow laboratory in Toronto, and found the equation R = delta P/V2 to be quite suitable for clinical assessment.

Adolescent↗

Further development of experimental techniques for refilling the lens of animal eyes with a balloon.

Various techniques for experimental refilling of the lens of animal eyes are possible. We describe two new methods: Balloon insertion after endocapsular phacoemulsification and after phacoemulsification with circular capsulorhexis. The feasibility of these techniques was tested in both rabbit eyes and pig cadaver eyes. With organo-silicone gel as the balloon filling material, post-operative refractive changes of up to 4 diopters of residual hyperopia were achieved; accommodation changes were up to -1 diopter. The technique of refilling the lens with a balloon to avoid leakage of filling material warrants further study.

Animals↗

Evaluations on the usefulness of viscous agents in anterior segment surgery. II. Effect on intraocular pressure and clearance from the anterior chamber.

Various viscous agents in anterior segment surgery were replaced with the aqueous humor of rabbit eyes. The effects of these agents on intraocular pressure (IOP) and their clearance from the anterior chamber were studied. Furthermore, the degradation of these agents in ocular and hepatic tissues was investigated. The IOP after the injection of a 1% solution of sodium hyaluronate with a molecular weight of 790 x 10(3) (Na-HA (790 x 10(3), 1%], fell to the normal level after 12 hours; however, after a 1% solution of sodium hyaluronate with a molecular weight of 2160 x 10(3) (Na-HA (2160 x 10(3), 1%], a 2% solution of methylcellulose with a molecular weight of 86 x 10(3) (MC (86 x 10(3), 2%] or a 30% solution of sodium chondroitin sulfate with a molecular weight of 30 x 10(3) (Na-Chs (30 x 10(3), 30%], the return of IOP to normal level required 24 hours. Six hours after the injection of MC (86 x 10(3), 2%), the IOP was significantly higher than those of other agents. Na-Chs (30 x 10(3), 30%) and Na-HA (790 x 10(3), 1%) were eliminated from the anterior chamber within 12 and 24 hours, respectively. Na-HA (2160 x 10(3), 1%) and MC (86 x 10(3), 2%) required 72 hours to be eliminated from the anterior chamber. The degradation of Na-HA was detected in extracts of the iris, corneo-scleral junction, and liver. The degradation of Na-Chs was also detected in the liver extract, but the degradation of MC was not detected. On the basis of these findings, and the results in our previous report with respect to the efficacy of the viscous agents, it is concluded that Na-HA is the best viscous agent to be used in anterior segment surgery.

Animals↗

Crystallization of and preliminary crystallographic data for allosteric L-lactate dehydrogenase from Bifidobacterium longum.

L-Lactate dehydrogenase from Bifidobacterium longum aM101-2 was overexpressed in Escherichia coli and then purified. The enzyme was crystallized from a polyethylene glycol 6000 solution by the hanging drop vapor diffusion method. Crystals grown in the presence of NADH (type II), both NADH and oxamate (type III), and NADH, oxamate, and FBP (type IV) were analyzed. All three crystal forms belong to the orthorhombic system, space group P2(1)2(1)2. The cell dimensions of the type II crystals were a = 106.2 A, b = 131.6 A, and c = 63.8 A. Those of the type III and type IV crystals were a = 106.4 A, b = 131.4 A, and c = 63.8 A. The type III crystals diffract X-rays to beyond 2.5 A spacing. The type II and type III crystals were stable as to X-ray irradiation.

Allosteric Site↗

Turnover of proteoglycans by chick lens epithelial cells in cell culture and intact lens.

Chick lens epithelial cells were cultured on plastic and type IV collagen substrata, and the confluent cultures were labeled continuously with [35S]sulfate for 20 h. Intact lenses were also labeled in the same way. 35S-Proteoglycans isolated from those cultures were compared for their molecular sizes and glycosaminoglycan compositions. The results have shown that: 1) Proteoglycans synthesized by cells on type IV collagen were significantly smaller than those by cells on plastic. 2) Proteoglycans of intact lens showed a broad distribution of molecular size and contained a high proportion of chondroitin sulfate in the medium fraction compared to those of the two cell cultures. In order to explain such differences between proteoglycans from cultures, label-chase experiments with [35S]sulfate were done for proteoglycans synthesized. 35S-Proteoglycans isolated at each chase time 0, 2.5, and 17 h) were compared and the following results were found: 1) The cell layers of both "plastic" and "type IV collagen" cultures contained glycosaminoglycan species predominantly at each chase time rather than proteoglycans. 2) Changes in the glycosaminoglycan compositions of medium fractions of cell cultures were observed during the chase period; in medium of the "plastic" culture, proteoheparan sulfate increased with chase time, whereas in medium of the "type IV collagen" culture, chondroitin sulfate glycosaminoglycan (not proteoglycan) increased with chase time. 3) In intact lens culture, lens capsule fraction at every chase time contained a proteoglycan unique in molecular size, which was not found in cell culture fractions. 4) All fractions from intact lens cultures contained a higher content of chondroitin sulfate at every chase time than the respective fractions from cell cultures. These results suggest that adhesion of the cells to type IV collagen or lens capsule influences the degradation and secretion of proteoglycans. In addition, they can account partially for the above-described differences in molecular sizes and glycosaminoglycan compositions between 35S-proteoglycans from various cultures continuously labeled with [35S]sulfate.

Animals↗

Inhibitory effect of a lichen polysaccharide sulfate, GE-3-S, on the replication of human immunodeficiency virus (HIV) in vitro.

A sulfate (GE-3-S) prepared by chlorosulfonic acid treatment of GE-3, a partially acetylated beta(1----6) glucan of the lichen Umbilicaria esculenta, inhibited the cytopathic effect of human immunodeficiency virus (HIV) and suppressed the HIV-antigen expression in Molt-4 (clone 8) cells. GE-3-S also suppressed the giant cell formation of HIV-infected Molt-4 cells, and inhibited HIV-induced plaque formation by 50% at the dose of 19.5 micrograms/ml and completely at 250 micrograms/ml in MT4 cells. GE-3-S had no direct effect on the reverse transcriptase of HIV.

Antiviral Agents↗

[Determinations of silicon and phosphorus in rice planted in a district of high incidence of amyotrophic lateral sclerosis by neutron activation and X-ray fluorescence analyses].

Silicon and phosphorus contents in polished and unpolished rice planted in a district of high incidence of amyotrophic lateral sclerosis (ALS) have been determined by neutron activation and X-ray fluorescence methods, and compared with those from control areas. In the neutron activation analysis, beta-ray spectra of 32P produced by the 31P(n, gamma)32P reaction on polished and unpolished rice were measured with a low background beta-ray spectrometer. In the X-ray fluorescence analysis, characteristic X-rays were analyzed with a wavelength dispersive X-ray fluorescence spectrometer. Silicon contents in polished and unpolished rice from the ALS area are 42 micrograms.g-1 and 370 micrograms.g-1, respectively, and the corresponding phosphorus contents are 1,210 micrograms.g-1, and 3,370 micrograms.g-1, respectively. The data for ALS area are equal to those for the control area within standard deviation.

Amyotrophic Lateral Sclerosis↗

[Serum concentration of laminin in renal cell carcinoma].

Serum concentration of laminin was measured radioimmunologically in 19 patients with renal cell carcinoma and 71 normal controls. The serum laminin levels of renal cell carcinoma patients were significantly higher than those of normal controls. After nephrectomy the elevated serum levels of laminin showed marked decreases in most of the patients without metastasis. By the immunofluorescent technique with LAM-1, a monoclonal antibody which is specific to laminin A and B chains , strong fluorescence was found in the extracellular matrix in renal cancer tissue. Taken all these facts together, renal cell carcinoma may be a laminin synthetic tumor. The average serum laminin level of the patients with a disseminated disease were significantly higher than that of the patients with a localized disease. The elevated serum level of laminin may play an important role in the process of tumor metastasis. Furthermore, our data suggest that elevated laminin levels may predict the subsequent course of a tumor condition. The monitoring of serum laminin level may be valuable for following-up of the course of renal cell carcinoma.

Adult↗

[Pharmacokinetics and clinical studies on cefsulodin in neonates].

Pharmacokinetics and clinical studies on cefsulodin (CFS) were conducted in neonates. 1. MIC's of CFS, sulbenicillin and gentamicin (GM) were determined using 7 strains of Pseudomonas aeruginosa clinically isolated from neonates and maintained as stock cultures. CFS was found to be nearly as active as GM. 2. When CFS 20 mg/kg was administered to a 12-day-old neonate by intravenous bolus injection, serum concentrations were 8.7 micrograms/ml before administration and 51.7 micrograms/ml at 30 minutes, 44.4 micrograms/ml at 1 hour, 38.6 micrograms/ml at 2 hours and 11.1 micrograms/ml at 6 hours after administration. The half-life was 2.5 hours. 3. CFS was administered alone or combination with other drugs to 3 neonates. The drug was clinically effective in 2 cases and slightly effective in another. Bacteriologically, one case was rated as decreased, another as replaced, and the remaining one as unchanged. 4. Neither side effects nor abnormal laboratory values attributable to CFS were found.

Cefsulodin↗

[Laboratory and clinical studies on clarithromycin in pediatrics].

Clarithromycin (TE-031, A-56268) is a new 14-membered ring macrolide antibiotic developed by Taisho Pharmaceutical Co., Ltd. TE-031 has a methoxy group at position 6 in its structure. In the present study, we carried out laboratory and clinical investigations on TE-031 in the field of pediatrics. The obtained results are summarized as follows. The antibacterial activity of TE-031 was investigated against 16 clinically isolated strains of Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, Bordetella pertussis and Campylobacter jejuni. TE-031 showed antibacterial activity comparable to erythromycin. The pattern of changes in TE-031 concentrations in the blood after administration was investigated. In subjects administered the granular preparation of TE-031, Cmax values were 0.64 micrograms/ml in 1 subject given a 5 mg/kg dosage, and 5.94 and 9.02 micrograms/ml in 2 subjects administered with 10 mg/kg. The tablet form of TE-031 was administered to 3 subjects at 5 mg/kg, and Cmax values were 2.09-3.92 micrograms/ml, while T 1/2 values were in a range of 2.9-3.8 hours. When drug concentrations in the urine were investigated, it was found that 6-hour recovery rates were 9.9% (dose: 5 mg/kg) and 53.4% (dose: 10 mg/kg) in the subjects administered the granular form, whereas recovery rates averaged 36.8% in the tablet-administered subjects. In the clinical trial, TE-031 was administered in 2-3 doses/day for 2-18 days. In cases given the granular form, dosages were 12-38 mg/kg/day, while tablets were administered at 12-29 mg/kg/day. The overall clinical efficacy rate was 92.8%, i.e., the drug was effective in 64 of 69 patients. TE-031 was ineffective in 1 case of otitis media, but efficacious in 10 of 10 (100%) cases of upper respiratory infection, 15 of 18 (83.3%) cases of bronchitis and pneumonia, 5 of 6 (83.3%) cases of pertussis, 13 of 13 (100%) cases of mycoplasmal pneumonia, 4 of 4 (100%) cases of Chlamydia psittaci pneumonia, 16 of 16 (100%) cases of gastroenteritis (including 15 cases of Campylobacter gastroenteritis), and 1 (100%) case of impetigo. In bacteriological studies conducted on the patients, the overall elimination rate was 93.1%, i.e., bacterial elimination was obtained in 27 of 29 cases. TE-031 showed especially good bacteriological efficacy (100%) against C. jejuni and B. pertussis, which were eliminated from all of 15 and 2 cases examined, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Aluminum deposition and Ca-hydroxyapatite formation in frontal cortex tissue of amyotrophic lateral sclerosis].

To investigate a possible participatory role of an environmental metals in a pathogenetic process of amyotrophic lateral sclerosis (ALS), elementary and structural analyses of calcified substance in frontal cortex (percental gyrus) tissues of ALS patients were conducted using particle-induced X-ray emission (PIXE) and X-ray diffraction methods, as compared with control subjects. In the results of PIXE analysis, aluminum (Al) and calcium (Ca) contents in the frontal cortex tissues of the ALS patients were significantly increased with a high calcium (Ca)/phosphorus (P) Ca-hydroxyapatite (Ca-HAp). Although the content of peak ratio, as compared with those of control subjects. Only the Al content in the ALS patients showed significantly negative correlations with age at onset and/or at death. X-ray diffraction patterns from the sample (ashed at low temperature) of the frontal cortex tissues of the ALS patients were very similar to those from a standard sample of Ca-hydroxyapatite (Ca-HAp). Although the content of Ca-HAp in the mixed sample of frontal cortex tissues from the ten control subjects were not detectable (less than 3ppm), those of the ALS patients were markedly high, i.e., 111ppm in the mixed sample of five young patients with age under 60 and 168ppm in that of five old patients with age over 60. These results strongly indicated that Al may induce a calcifying degeneration in the CNS tissue of ALS patients, consequently leading to Ca-HAp formation as the final chemical compound.

Adult↗