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Biomedical subjects

I Tanaka

Publications and source records attributed to I Tanaka.

At least 235 records · Page 13Linked to original sources

Inhibitory effect of E3330, a novel quinone derivative able to suppress tumor necrosis factor-alpha generation, on activation of nuclear factor-kappa B.

(2E)-3-[5-(2,3-Dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid (E3330), is a novel agent with hepatoprotective activity. We report the effect of E3330 on transcriptional activation of tumor necrosis factor (TNF)-alpha gene and on nuclear factor (NF)-kappa B activation. Nuclear run-on experiments showed that E3330 decreases transcriptional activation of TNF-alpha gene induced by lipopolysaccharide (LPS) stimulation in human peripheral monocytes. To investigate the inhibitory mechanisms, we constructed a secreted-type placental alkaline phosphatase (PLAP) reporter gene whose transcription is controlled by a 1.4-kb human TNF-alpha promoter. A stable transformant of the PLAP reporter gene derived from human monocytic cell line showed very little activity on the promoter before stimulation, whereas LPS stimulation led to a dramatic increase in PLAP activity. E3330 inhibited this induced promoter activity in a dose-dependent manner. There are four putative NF-kappa B binding sites (kappa B-1, kappa B-2, kappa B-3, kappa B-4) in human TNF-alpha promoter. By using mutated promoter-PLAP plasmids, we established that these NF-kappa B sites were necessary for induction of TNF-alpha transcription on stimulation with LPS. A gel retardation experiment with synthetic double-stranded oligonucleotides showed that activated NF-kappa B consisting of p50/p65 heterodimer bound to all four putative NF-kappa B DNA probes, suggesting that all four putative NF-kappa B recognition sites play an important role in inducible TNF-alpha expression. E3330 decreased activated NF-kappa B in nuclei, suggesting that E3330 inhibits NF-kappa B activation and/or translocation of the nuclei. Western blotting analysis with anti-I kappa B-alpha antibody indicated that E3330 inhibited degradation of I kappa B-alpha, which is an inhibitory protein of NF-kappa B, in LPS-stimulated monocytes. E3330 may suppress the production of active oxygen species serving as common messengers to activate NF-kappa B.

Alkaline Phosphatase↗

C-type natriuretic peptide in chronic renal failure and its action in humans.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and acts as an endothelium-derived relaxing peptide. To clarify the clinical significance of CNP in renal disorders, we examined the plasma level of CNP in patients with various cardiovascular diseases, including chronic renal failure (CRF) patients who were under hemodialysis therapy. We also investigated biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus injection from the peripheral vein in healthy volunteers and measured systemic hemodynamic variables, plasma levels of CNP, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary excretions of sodium, potassium, chloride and cGMP. The plasma CNP levels in healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml. In CRF patients, the plasma CNP significantly increased up to 3.0 +/- 1.1 fmol/ml. The administration of CNP elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/- 1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP exerted significant diuretic (% increase: +117 +/- 85.0), natriuretic, kalliuretic and chloriuretic actions with the increase of endogenous creatinine clearance. CNP also elicited significant hypotensive actions (delta BPs/delta BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the concomitant increase of heart rate (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from 45.4 +/- 2.3 to 35.4 +/- 4.9 pg/ml 30 minutes after the administration. Taken together, these results suggest a role for CNP in human renal function.

Adult↗

Investigation of normal bacterial flora in the upper respiratory tract.

To study the bacterial flora in the upper respiratory tract we examined bacteria obtained from the larynx, posterior pharyngeal wall, palatine tonsil and nasal cavity to identify the constitutent strains and check for the existence of beta-lactamase in 37 subjects without infectious otolaryngological disease who underwent surgery with general anesthesia. A tendency toward a decrease with aging in aerobes and an increase in anaerobes was observed. The influence of fibronectin was considered to be one of the reasons for this tendency. beta-lactamase production strains showed a tendency to increase in the age group from 20-49 years and decrease in subjects 50 years and older. The number of constitutent strains in the nasal cavity was less than that in the pharynx, which was considered the result of the mucociliary function as a biophylactic function. Comparing the constitutent strain types in the larynx with those in other areas, the posterior pharyngeal wall showed the highest coincident rate of 70%, Notably, the coincident rate was more than 80% among aerobes. This suggests that causative bacteria can be estimated from pharyngeal culture.

Adolescent↗

Transitional concentration of antibacterial agent to the maxillary sinus via a nebuliser.

Surface and tissue transitional concentration of 3% FOM aerosol for treatment of paranasal sinusitis was examined in 18 patients (21 sides) who underwent the Caldwell-Luc operation. In this operation, patients have a bony window on the sinus; we therefore investigated the difference of compliance of the maxillary sinus between when we closed the bony window with subcutaneous tissue and when we did it with a silicone sheet before the FOM nebulization. No significance was found in the mean concentration of FOM either at the maxillary sinus surface or in the tissue with or without the use of the silicone sheet. We also examined the concentration using a jet-type nebulizer and an ultra-sonic type nebulizer. Using the ultrasonic-type nebulizer resulted in a higher transitional concentration at two sites of the maxillary sinus surface than when using the jet-type nebulizer. The results suggest that the ultrasonic-type nebulizer is more effective in the treatment of paranasal sinusitis than the jet-type, and that there was no change of maxillary sinus compliance with or without a bony window.

Anti-Bacterial Agents↗

[Serum concentrations of the pyridoxal and pyridoxal-5'-phosphate in children during sustained-release theophylline therapy].

This study was undertaken to investigate the effect of sustained-release theophylline preparations on circulating vitamin B6 concentrations in children with asthma. Twenty-six children with asthma were treated with sustained-release theophylline preparations. Serum concentrations of theophylline and vitamin B6 [pyridoxal (PL) and pyridoxal-5'-phosphate (PLP)] were evaluated. The results obtained from this study were as follows: 1) The serum PL was significantly correlated with the duration of theophylline administration (r = -0.42). 2) The serum PL and PLP concentrations were significantly correlated with serum theophylline concentrations (r = -0.47, r = -0.59, respectively). 3) Serum PL and PLP concentrations in children treated for more than 5 weeks were significantly lower than those treated for less than 4 weeks (p < 0.01, p < 0.05, respectively). 4) Serum PL and PLP concentrations in children within theophylline therapeutic ranges (5-15 micrograms/ ml) were significantly lower than those with less than 5 micrograms/ml (p < 0.01, p < 0.01, respectively). These findings suggest that long-term theophylline therapy or serum theophylline concentration within the therapeutic ranges (5-15 micrograms/ml) can depress serum vitamin B6 concentration in children with asthma. Theophylline-induced seizure may be caused by decrease in gamma-aminobutyric acid concentration in the brain result from decrease in vitamin B6 concentration, even if the serum theophylline concentration is within the therapeutic ranges.

Asthma↗

[Successful induction of immune tolerance and novel hemostatic effects in a hemophilia A with high-responder inhibitor by regular infusions of factor VIII].

A hemophilia A patient with high responder inhibitor had been treated by (activated) prothrombin complex concentrates (A) PCC and activated factor VII until the occurrence of intracranial bleeding at the age of 6 years. Since the inhibitor titer was decreased less than 1 Bethesda Units/ml, high dose of factor VIII was given followed by the infusions of factor VIII concentrates (100 units/kg) three times a week. In spite of previous episodes of anamnestic responses by factor VIII products before, the inhibitor titer did not increase and disappeared completely 6 months after the FVIII infusion therapy. The specific anti-factor VIII IgG subclasses of the inhibitor were IgG2 and IgG4. The inhibitor recognized both light and heavy chains. He have no bleeding episode for 6 months since the beginning of the prophylactic with factor VIII concentrates.

Blood Coagulation Factors↗

[Two cases of a solitary fibrous tumor with different growth patterns].

We report two cases of a solitary fibrous tumor demonstrating different growth patterns. Case 1: a 46-year-old male presented with a pedunculated solid tumor which was found between the lobes projecting from the lingula lobe. Case 2: a 68-year-old female demonstrated a tumor, measuring 2 cm in size, clearly inside the lung. The tumor was covered with pleura and could be removed bluntly. Histopathologically, spindle shaped fibroblasts were uniformly distributed in abundant, tangled collagen fibers in both cases. Sinusoid-like lumens, lined with one endothelium layer were also found. Immunohistological staining was strongly positive for vimentin and CD34, while it was negative for keratin, cytokeratin and EMA. The diagnosis of a pedunculated solitary fibrous tumor which extruded to outside the lung was made in one case, while in the other case a solitary fibrous tumor proliferating inside the lung was diagnosed. Many investigators have suggested this type of tumor to derive from mesenchymal tissue under mesothelium cells and is thus probably different from diffuse mesothelioma.

Aged↗

Unusual long target duplication by insertion of intracisternal A-particle element in radiation-induced acute myeloid leukemia cells in mouse.

Retrotransmission into the IL-3/GM-CSF gene locus by the retrotransposon intracisternal A-particle (IAP) had been observed in distinct tumor cell lines. We analyzed the locus in genomes from 7 different myeloid leukemia cell strains which were originally generated by whole-body X-irradiation of the inbred C3H/He mice at a dose of 3 Gy and maintained by in vivo passage. In one leukemia cell strain out of 7 such cases, RFLP of an allele of the interleukin-3 gene was found. Sequence analysis after cloning from the genomic library showed that a type I delta 2 IAP element was inserted in the region upstream of the IL-3 gene in the head-to-head orientation. This suggests that the locus in myeloid cells is sensitive for integration of IAP elements. Additionally, an unusual long target duplication of 82 bp, 14-fold larger than normal one, was found at the junction of the element. This suggests the possibility of a radiation-induced integration mechanism which is distinct from normal retrotransmission.

Animals↗

[Measurement of airborne fumes in welding factories].

Concentrations and size distributions of airborne welding fumes in work environments were measured. Samples were collected from 20 workplaces in 13 companies. In all workplaces, the stationary samplings including A-sampling and B-sampling and the personal sampling were carried out simultaneously. The fume concentration in the stationary sampling was measured with a digital dust monitor. A low volume air sampler and an Anderson cascade impactor was also used to determine the conversion factor of the values obtained by the digital dust monitor and the size distributions of the fumes. The personal exposure levels were measured with a TR sampler and a personal cascade impactor. The concentrations by the personal sampling (average: 11.3mg/m3) were much higher than those by the A-sampling (average: 0.4mg/m3 and range: 0.15-0.64mg/m3) but lower than those by the B-sampling (average: 46.8mg/m3, range: 0.66-152.8mg/m3). The mass median aerodynamic diameter (MMAD) of the stationary and the personal samplings were 2.41 microns and 0.80 microns, respectively. Fumes were observed under a scanning electron microscope. Most of the fume particles were sphere in shape but smaller fumes were aggregated and formed larger secondary particles.

Dust↗

Flow cytometric analysis of the DNA content of adenocarcinoma of the lung, especially for patients with stage 1 disease with long term follow-up.

BACKGROUND: To assess the prognostic value of DNA ploidy in adenocarcinoma of the lung, the authors performed a flow cytometric study using paraffin embedded archival material from 160 patients (109 [68%] with aneuploid lesions, 51 [32%] with diploid lesions) who underwent surgical resection from 1982 to 1991. METHODS: The proportion of DNA aneuploid tumors increased as the disease stage advanced, from 35 of 63 (55.5%) with Stage 1 disease to 15 of 20 (75.0%) with Stage 2 disease, to 40 of 53 (75.5%) with Stage 3a disease, to 19 of 24 (79.2%) with Stage 3b disease. However, this trend was not statistically significant. Comparison of the survival time of the 160 patients with adenocarcinoma of the lung with a median follow-up of 7.8 years revealed that patients with diploid tumors had significantly longer survival than did those with aneuploid tumors (P < 0.01). RESULTS: Examination by stage showed that patients with Stage 1 disease with diploid tumors had significantly longer survival times than did those with aneuploid tumors (P < 0.05) but that there were no significant differences in clinical outcome in patients with Stage 2, 3a, and 3b diploid tumors. CONCLUSIONS: Analysis of aneuploid versus diploid DNA content in patients with Stage 1 adenocarcinoma of the lung is concluded to be useful in evaluating clinical outcome and prognosis.

Adenocarcinoma↗

Structural organization and chromosomal assignment of the human prostacyclin receptor gene.

Prostacyclin receptor is a member of the prostanoid receptor family in the G protein-coupled receptor superfamily with seven transmembrane domains. We report here the isolation and structural organization of the human prostacyclin receptor gene. Southern blot analysis demonstrated a single copy of the human prostacyclin receptor gene in the human genome. The human prostacyclin receptor gene spanned approximately 7.0 kb and was composed of three exons separated by two introns. The first intron occurred in the 5'-untranslated region, 13 bp upstream to the ATG start codon. The second intron was located at the end of the sixth transmembrane domain, thereby separating it from the downstream coding region and the 3'-untranslated region. By primer extension analysis, the transcription initiation sites were mapped 870-872 bp upstream to the ATG start codon. The 1.2-kb human prostacyclin receptor 5'-flanking region lacked conventional TATA and CCAAT boxes, but it contained several cis-acting regulatory elements including an inverted CCAAT box (Y box) and two copies of SP-1 binding sites. Using human-rodent somatic hybrid cell DNA, the human prostacyclin receptor gene was assigned to human chromosome 19. The present study helps establish the genetic basis for prostacyclin receptor research and provides further insight into the molecular mechanisms underlying the prostanoid receptor family.

Amino Acid Sequence↗

Matrilineal distribution of louse egg-handling techniques during grooming in free-ranging Japanese macaques.

Grooming behavior of which the primary function appears to be the removal of lice on other (Tanaka and Takefushi [1993] Anthropological Science 101:187-193) was studied in Japanese maceques at Jigokudani Monkey Park, Japan, June 1990-July 1993. Several louse egg-handling techniques used during grooming were identified (with differences in efficiency) in a free-ranging group. In the low-ranking maternal lineages, the distribution of these techniques is quite homogeneous, suggesting social transmission with goal emulation (one form of social learning) based on maternal kin. However, there is considerable variation in the high-ranking matriline. The social system of dominance--the tendency of subordinates to groom more often than to be groomed--may result in oblique transmission of more effective techniques from low-ranking monkeys to some offspring of high-ranking females.

Animals↗