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Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 217 records · Page 12Linked to original sources

Chemiluminescent response to PMA in isolated rat liver after in situ ischemia-reperfusion.

The median and left lateral lobes of rat liver in situ were rendered ischemic for 30 min, then blood flow reinstituted. After 1, 3, 6, 24, or 48 h, livers were removed and set up for isolated perfused organ study. Luminol enhanced chemiluminescence (LEC) was recorded from the surface of the median and left lateral lobes before and for 90 min following phorbol myristate acetate (PMA, 1.6 x 10(-8) M) perfusion. An increase in PMA induced LEC was evident at 1 h and continued to increase up to 6 h. By 24 h the magnitude of the PMA response had returned to within control values. This indicates that a large influx of inflammatory cells had occurred in the liver following the in vivo ischemia-reperfusion insult and that these cells were well fixed in the tissue and capable of mounting a very large and sustained burst of radical production on stimulation with PMA. This combined in vivo/in vitro technique is ideally suited for the assessment of interventions designed to ameliorate damage following oxidative stress.

Animals↗

The distribution of eosinophil cationic protein positive eosinophils in the nasal mucosa of the nasal allergy patients.

The relationship between the distribution of eosinophils and epithelial damage of the nasal mucosa in nasal allergy was investigated by means of hematoxylin and eosin staining and a technique of immunohistochemistry using the anti-human EG2 mouse monoclonal antibody that reacts with the secreted form of eosinophil cationic protein (ECP). Nasal mucosa tissue of 26 adult nasal allergy patients and of 24 adult non-allergic rhinitis patients was removed surgically. Eosinophilia in the nasal mucosa of the allergy group was greater than that in the non-allergy group. A great number of ECP positive eosinophils accumulating in the nasal mucosa of the allergy group were mostly degranulated at the superficial layer of the lamina propria. Desquamation of the epithelium was observed mainly in the area of eosinophilia with degranulation of the secreted form of ECP in the nasal allergy group.

Adult↗

Seasonal variations of nasal resistance in allergic rhinitis and environmental pollen counts.

We made measurements of nasal airway resistance in a patient with Japanese cedar pollinosis and also measured the environmental pollen counts under different exposure conditions. In the season of high Japanese cedar pollen counts in Japan values of mean nasal airway resistance were significantly increased, remained elevated for 2 months after the season, and eventually decreased. In the season of low pollen counts, the mean values of nasal airway resistance measurements were increased during the season but decreased more rapidly after the season. In a year with no exposure to the environmental allergen because the subject lived out of Japan, the mean nasal airway resistances were relatively increased closely in phase with the Japanese cedar pollen season.

Adult↗

Seasonal variations of nasal resistance in allergic rhinitis and environmental pollen counts. II: Efficacy of preseasonal therapy.

We gave Mao-bushi-saishin-to, a Chinese blended medicine, and azelastine to an adult patient with hay fever due to Japanese cedar pollen and measured nasal resistance and ambient floating pollen counts throughout the time of Japanese cedar pollination in separated years. In the patient Mao-bushi-saishin-to was effective against preseasonal increases in nasal airway resistance but could not control severe episodes of allergic rhinitis caused by high dose exposure to Japanese cedar pollen and also perhaps caused by a priming effect. Azelastine inhibited both pre- and post-seasonal increases in nasal airway resistance but not only on high pollen counts days.

Adult↗

A new crystal form of proteinase A, a non-pepsin-type acid proteinase from Aspergillus niger var. macrosporus.

Proteinase A from Aspergillus niger var. macrosporus is a non-pepsin-type acid proteinase, whose catalytic residues and mechanism remain to be elucidated. A new form of proteinase A crystals more suitable for crystallography than that obtained previously was prepared from an ammonium sulfate solution at pH 3.5 by the hanging-drop vapor diffusion method. The space group of the crystals was P2(1)2(1)2(1), with unit cell dimensions of a = 69.75 +/- 0.06 A, b = 87.55 +/- 0.05 A, and c = 60.83 +/- 0.04 A. On the assumption of two enzyme molecules per asymmetric unit, the calculated volume to unit protein mass ratio (Vm) was 2.08 A3/Da. By assuming the specific volume to be 0.74 cm3/g, the solvent content (Vso1) was estimated to be 41%, i.e., much larger than that of the crystal form obtained previously at pH 2.0 (Vso1 = 26%). Diffraction data were collected up to a resolution higher than 1.6 A, using the Weissenberg camera for macromolecular crystallography with synchrotron radiation.

Ammonium Sulfate↗

[Relationship between lymphocyte subsets of the peripheral blood and noise induced hearing loss].

Biochemical examination and two-color flow cytometric analysis of lymphocyte subsets of the peripheral blood were carried out in 107 healthy males working in high noise environments. The level of hearing disorder was compared with these results. By audiometry at six frequency levels, 51 of the 107 healthy males showed hearing loss. Their mean value of hearing ability was 30 dB and/or above. Among the peripheral lymphocyte subsets, helper T cells of CD4+CD45R- were significantly increased and the CD4/CD8 ratio tended to be elevated. CD20 that indicate B cells were reduced. These results suggested a relationship between susceptibility to acoustic trauma and cell-mediated immunity.

Adult↗

[Serum concentration of type IV collagen in urological cancer--comparison with serum concentration of laminin].

In recent years, it has become clear that various extracellular substrates play an important role in the process of invasion and metastasis of malignant tumors. In a previous study, we reported that the serum concentration of laminin in renal cell carcinoma and prostate cancer is elevated, and furthermore, is remarkably high in patients with metastasis. However, in bladder cancer, this level is elevated only in those with metastasis, indicating that the serum concentration of laminin is useful as a marker for metastasis or clinical progression of the malignant tumor. In the present study, we measured the serum concentration of type IV collagen 7S-domain, which, as laminin constructs the basement membrane, and compared the result with the serum concentration of laminin, to evaluate the clinical significance of the findings. The serum concentration of type IV collagen 7S-domain was not elevated significantly in any tumor type, although the serum concentration of laminin was elevated in patients with renal cell carcinoma, prostate cancer and bladder cancer with metastasis. There were no significant differences in the serum concentration of type IV collagen 7S-domain in any group with metastasis.

Carcinoma, Renal Cell↗

[Influence of S-1108 on intestinal bacterial flora].

The effect of S-1108, a new oral cephem antibiotic, on intestinal bacterial flora was studied in tetra-contaminated mice and pediatric patients. S-1108 in a fine granular form was administered at a dose of 15 mg/kg once a day for 5 consecutive days to mice infected with Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. The viable fecal bacterial cell count of each of these 4 species of bacteria was slightly reduced in 5 days after the start of the drug administration. Five boys (weighing 12.0 to 42.0 kg) with bacterial infections were entered into this pediatric study. Their ages ranged from 2 years 4 months to 9 years 3 months. S-1108 (fine granules) was administered at a dose of 2.3 to 6.0 mg/kg, 3 times a day for 5 to 11 days. Cell counts of primary aerobes, anaerobes and total anaerobic cells decreased markedly in three patients, but in the remaining two patients the total number of aerobic and anaerobic cells did not change appreciably. Glucose-nonfermentating Gram-negative rods did not become predominant during the period of S-1108 administration. Candida became predominant in the three patients in whom the other bacteria had markedly decreased. Counts of predominant aerobic and anaerobic bacteria decreased markedly during the regimen in 3 out of 5 cases. S-1006 was detected in stools of the 3 cases at concentrations ranging from 235 to 516 micrograms/g during the administration of S-1108. Intestinal bacteria that produce beta-lactamase were not present in the feces of any of the patients. Based on these results, S-1108 (fine granules) appears to have relatively little effect on intestinal bacterial flora similarly to other new oral cephems. Because of individual differences, however, the drug may be excreted in the feces at high concentrations, and this would result in changes in intestinal bacterial flora. Therefore, attention must be given to fecal drug concentrations.

Administration, Oral↗

[Criteria for clinical evaluation of antibiotics in pediatrics. The purpose and process for establishing the criteria].

This paper describes the purpose and process for establishing "Criteria for Clinical Evaluation of Antibiotics in the Pediatric Field", which was reported in the Japanese Journal of Antibiotics Vol. 46, May, 1993. The Criteria Committee was organized in November 1991. Four meetings were held to establish the draft criteria. The criteria were applied to the evaluation of oral cephem S-1108 and parenteral cephem SCE-2787. When the criteria were compared with the conventional criteria, the results indicated that no difference was obtained in the efficacy rate as a whole, the sum of "Good" and "Excellent" cases, but there was a difference in the cases judged to be "Excellent". Partial alteration was made to the draft criteria and the Committee produced the final version of the criteria. However, the criteria are far from complete, so it will be subjected to further revision it accordance with future advance in chemotherapy.

Bacterial Infections↗

[Effect of nitroprusside on gap junctions of single tracheal smooth muscle cells excised from rats].

To investigate the effect of nitroprusside on gap junctions of tracheal smooth muscle cells, we ionophoretically injected sodium nitroprusside into single tracheal smooth muscle cells excised from rats. The input resistance of the tracheal smooth muscle cells increased after the injection of nitroprusside. This results suggests that nitroprusside blocks gap junctions of tracheal smooth muscle cells.

Animals↗

[Laboratory and clinical studies on S-1108 in the pediatric field].

Laboratory and Clinical Studies on S-1108, a new oral cephem antibiotic, were carried out to evaluate its usefulness at a dose between 2 and 4 mg/kg a day for 7 to 14 days in the pediatric field. 1) Pharmacokinetic studies S-1108 at a dose of 2 mg/kg was administered to evaluate the pharmacokinetic parameters in 1 subject. Cmax, T1/2 and AUC were 0.69 hour, 1.42 hours and 2.15 micrograms.hr/ml, respectively. 2) Antimicrobial activities MICs against various clinically isolated organisms (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Branhamella catarrhalis, Escherichia coli and Haemophilus influenzae) were determined. The MIC values of S-1006 were similar to those of cefteram, the MICs against S. pyogenes, and H. influenzae were < or = 0.025 and 0.10 microgram/ml, respectively. 3) Clinical studies S-1108 was administered to patients with various pediatrics infections in 34 cases (upper respiratory tract infections: 12 cases, lower respiratory tract infections: 5 cases, urinary tract infections: 9 cases, skin and soft tissue infection: 6 cases, otitis media: 2 cases). Clinical efficacy rate was evaluated according to "Standard of clinical evaluation in pediatrics field". The responses were all good or excellent. 4) Side reactions There were no serious adverse reactions in any cases. The above results suggest that S-1108 is potent effective and safe agent in the pediatric field at a dose between 2-4 mg/kg (t.i.d.) a day.

Bacteria↗

[A clinical study on cefditoren pivoxil in pediatrics].

Clinical evaluations of cefditoren pivoxil (CDTR-PI, ME 1207) in granules were carried out. The obtained results are summarized as follows. 1. Thirty-nine patients with pediatric infections were treated with CDTR-PI. Clinical responses of 36 assessable cases were excellent in 25, good in 9 and fair in 2. The overall efficacy rate was 94%. 2. Bacteriologically, 30 of the 31 identified bacteria presumed to be pathogens were eradicated and the eradication rate was 97%. 3. Side effects observed were diarrhea in 3 of 39 patients. The incidence was 7.7%. Abnormal laboratory test results were not observed. The results suggested that CDTR-PI might be a very useful and safe drug for the treatment of pediatric infections.

Bacterial Infections↗

Decreased adenylate energy charge and superoxide anion release in polymorphonuclear leukocytes in septic patients after hepatectomy.

To clarify the process of multiple organ failure after hepatectomy, the adenylate energy charge (EC) and superoxide anion (O2-) release of polymorphonuclear leukocytes (PMN) were measured 19 times on 11 septic patients after curative hepatic resection in relation to arterial ketone body ratio (AKBR), which reflects hepatic mitochondrial redox potential. PMN EC was measured by labeling the adenine nucleotide pool of PMN with radioactive adenine. The data of the septic patients (n = 19) was divided into two groups according to the hepatic energy status: AKBR above 0.7 (septic state A; n = 8) and AKBR below 0.7 for at least 3 successive days (septic state B; n = 11). Thirteen nonseptic patients undergoing hepatic resection were applied to the control group, and all of them showed AKBRs higher than 0.7. The PMN EC of septic patients was significantly lower than that of nonseptic patients [0.80 +/- 0.01 (SEM) vs. 0.88 +/- 0.02, P < 0.01]. In septic patients, moreover, the PMN EC of septic state A was significantly higher than septic state B (0.85 +/- 0.01 vs. 0.77 +/- 0.03, P < 0.05). Superoxide anion release of septic patients was significantly lower than that of nonseptic patients (19.0 +/- 2.1 nmol/5 x 10(5) cells/15 min vs. 29.3 +/- 1.7 nmol/5 x 10(5) cells/15 min, P < 0.01). Superoxide anion release of septic state A was significantly greater than that of septic state B (26.0 +/- 2.8 nmol/5 x 10(5) cells/15 min vs. 15.0 +/- 1.9 nmol/5 x 10(5) cells/15 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Linear correlation between acetoacetate/beta-hydroxybutyrate in arterial blood and oxidized flavoprotein/reduced pyridine nucleotide in freeze-trapped human liver tissue.

A comparison of two methods of measuring liver mitochondrial redox state demonstrated that a linear correlation exists between acetoacetate/beta-hydroxybutyrate ratio in arterial blood (arterial ketone body ratio; AKBR) and oxidized flavoprotein/reduced pyridine nucleotide in human liver tissue (FP/PN) as measured by tissue fluorescence spectroscopy, such that [FP/PN] = 0.64 + 0.49 x [AKBR] (r = 0.84, P less than 0.001). This result supports the validity of AKBR as a method of measuring the hepatic mitochondrial redox state of pyridine nucleotide using arterial blood.

3-Hydroxybutyric Acid↗

Crystallization and preliminary X-ray investigation of proteinase A, a non-pepsin-type acid proteinase from Aspergillus niger var. macrosporus.

Proteinase A from Aspergillus niger var. macrosporus is a non-pepsin-type acid proteinase distinctly different in various properties from the family of pepsin-type aspartic proteinases, and so far it remains unknown which residues participate in the catalysis of the enzyme and how the mechanism operates. The acid proteinase A was crystallized from an ammonium sulfate solution by the hanging-drop vapor diffusion method. The space group of the crystals was P2(1)2(1)2(1) with unit cell dimensions of a = 54.7 A, b = 70.4 A and c = 38.0 A. On the assumption that there is one enzyme molecule in the asymmetric unit, the calculated ratio of volume to unit protein mass (Vm) was 1.64 A3 per dalton. Diffraction data were collected up to a resolution higher than 1.5 A, using the Weissenberg camera for macromolecular crystallography with synchrotron radiation. The crystal of proteinase A is, therefore, suitable for the structural analysis with a high resolution.

Aspartic Acid Endopeptidases↗

ADF (adult T cell leukemia-derived factor)/human thioredoxin and viral infection: possible new therapeutic approach.

ADF (adult T-cell leukemia-derived factor), originally defined as an inducer of interleukin 2 receptor/alpha (IL-2R/alpha), is a homologue of thioredoxin. ADF is constitutively produced by human lymphoid cell lines transformed by human T-lymphotropic virus type I (HTLV-I) or Epstein-Barr virus (EBV). ADF augments the proliferation of HTLV-I and EBV transformed cells as an autocrine growth factor. These data are indicative of the possible involvement of ADF in virus-related transformation of cells and their autocrine growth. On the other hand, thioredoxin contains a redox active disulfide and has a reducing activity in the presence of thioredoxin reductase and NADPH. To clarify the role of ADF/thioredoxin system in the viral transformation, we tested the effect of 13-cis-retinoic acid (RA), which is a competitive inhibitor of thioredoxin reductase, on the growth of ADF high producing cells. The expression of IL-2R/alpha on HTLV-I (+) cells was suppressed by RA. RA dose-dependently reduced the cell number and viability of ADF high producing lymphoid cells. Moreover, it had a suppressive effect on the proliferation of ADF high producing cells. It is suggested that RA has an inhibitory effect on the activation and the growth of cells producing ADF and that inhibition of the ADF/thioredoxin system may be a new therapeutic approach for retrovirus-related disorders.

Amino Acid Sequence↗