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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 1,027 records · Page 57Linked to original sources

An important role of tachykinins in ozone-induced airway hyperresponsiveness.

We investigated the role of tachykinins in ozone-induced airway hyperresponsiveness (AHR) in guinea pigs. Airway responsiveness was assessed by determining the provocative concentration (PC200) of a histamine aerosol. Ozone exposure (3.0 ppm for 2 h) caused significant AHR. For vehicle-pretreated animals, the geometric mean pre- and post-ozone PC200 values were 0.87 mg/ml (GSEM 1.33) and 0.11 mg/ml (GSEM 1.17), respectively. Tachykinin depletion by capsaicin (50 mg/kg) prevented this AHR, whereas it did not alter pre-ozone airway responsiveness. The PC200 was 0.36 mg/kg (GSEM 1.64) before ozone and 0.24 mg/kg (GSEM 1.72) after ozone for this group. Ozone also caused a significant increase in neutrophils in bronchoalveolar lavage fluid (BALF) compared with BALF from a normal control group (1.71 +/- 0.69 versus 0.07 +/- 0.02 x 10(5)/ml, respectively). Capsaicin pretreatment attenuated this neutrophil influx (0.23 +/- 0.16 x 10(5)/ml). Morphometric assessment revealed edema of the bronchiolar wall after ozone exposure, which was not observed in the capsaicin group. BAL and morphometry revealed that the degree of ozone-induced epithelial desquamation was similar in both groups. These results suggest that tachykinins may be responsible for ozone-induced AHR, possibly via neurogenic inflammation.

Animals↗

Role of recruited neutrophils in interleukin-8 production in dog trachea after stimulation with Pseudomonas in vivo.

Cell-free supernatant of Pseudomonas aeruginosa (PA) recruits neutrophils into the airways indirectly by inducing the production of chemotactic factors, including interleukin-8 (IL-8). PA products stimulate IL-8 expression selectively in surface airway epithelium, gland ducts, serous cells, and recruited neutrophils. To examine the relative contribution of neutrophils in IL-8 release in the airway lumen, we studied the effect of inhibition of neutrophil recruitment on IL-8 concentration in tracheal fluid after introduction of PA supernatant into the dog trachea in vivo. Tracheal superfusion with PA supernatant caused neutrophil recruitment and increased the IL-8 concentration in the tracheal lumen; NPC 15669 inhibited both effects. To study whether migration of neutrophils into the airway lumen per se induces their expression of IL-8, we compared effects of local introduction of IL-8 and of PA supernatant into the trachea on IL-8 expression in neutrophils recruited into the trachea. PA supernatant, but not exogenous IL-8 alone, induced IL-8 mRNA expression in neutrophils recruited into the trachea. To determine what product(s) of PA stimulate IL-8 expression in neutrophils, we examined neutrophils isolated from peripheral blood. PA supernatant induced IL-8 production in neutrophils, an effect reproduced by PA lipopolysaccharide and inhibited by polymyxin B. These results suggest that neutrophils recruited into the airway lumen play a major role in local IL-8 production in airways in response to bacteria such as PA, depending on the presence of stimuli such as lipopolysaccharide.

Animals↗

Inhibition of mucociliary clearance of the eustachian tube by leukotrienes C4 and D4.

The effect of leukotrienes C4 (LTC4) and D4 (LTD4) and prostaglandin E2 (PGE2) on mucociliary clearance of the eustachian tube was investigated in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated separately with LTC4, LTD4, and PGE2 at concentrations of 10(-8) mol/L and 10(-6) mol/L. Ciliary activity was measured photoelectrically. Leukotriene D4 progressively inhibited ciliary activity, while PGE2 promoted it. Leukotriene C4 also induced ciliary inhibition. One milliliter each of 10(-5) mol/L LTC4, LTD4, and PGE2 was directly injected into the tympanic bullae of chinchillas under anesthesia. The middle ears were examined by otomicroscopy, tympanometry, and auditory brain stem response over time. Clearance of middle ear effusion was delayed by LTC4 and LTD4, as compared with PGE2 and the control. These findings indicate that LTC4 and LTD4 inhibit mucociliary clearance of the eustachian tube.

Animals↗

Parathyroid hormone increases the number of tartrate-resistant acid phosphatase-positive cells through prostaglandin E2 synthesis in adherent cell culture of neonatal rat bones.

Tartrate-resistant acid phosphatase (TRAP) is expressed during one of the steps of osteoclast differentiation. The involvement of prostaglandin E2 (PGE2) synthesis in PTH-induced increases in TRAP-positive cell number was studied in an improved slowly adhering cell culture system, prepared by removing preexisting osteoclasts from disaggregated bone cells obtained from 6-day-old rats. The majority of the TRAP-positive cells that appeared were mononuclear. In 1-day culture, PTH (0.025-0.25 nM) and PGE2 (1 microM) increased the number of mono- and multinucleated TRAP-positive cells. Indomethacin (50 microM) inhibited PTH-induced increase, and the inhibition was significantly abolished by the addition of PGE2. SC-19220, a specific antagonist for one class of PGE2 receptor, inhibited the increase induced by PTH and PGE2. PTH significantly stimulated the production of PGE2 in the culture. Peroxides, which are produced as byproducts of PGE2 biosynthesis, were detected in the adherent cells using dichlorofluorescene and increased the number of TRAP-positive cells. Small resorption pits were recognized on the surfaces of bone slices on which slowly adhering cells had been incubated for 3 days with PTH. These findings showed that PTH, through its effects on PGE2 synthesis and the subsequent reactions, induced the step at which TRAP is expressed, possibly during the differentiation of osteoclasts.

Acid Phosphatase↗

Relationship between apparent total body clearance of cyclosporin A and its erythrocyte-to-plasma distribution ratio in renal transplant patients.

To establish an optimal method for determining a cyclosporin A (CyA) regimen based on physiological changes that occur during immunosuppressive therapy, the relationship between apparent CyA body clearance (CL/f) and the CyA erythrocyte-to-plasma distribution ratio (CyA-EP) was examined using clinical time courses obtained during routine monitoring. The CyA-EP, which was calculated by a multiple regression formula using routine data, was increased during renal dysfunction involving the normal recovery phase after transplantation, during nephrotoxicity, during acute tubular necrosis, and during acute renal rejection. CyA total body clearance (CLt), calculated by multiplying CL/f and converted bioavailability, fc (which is equal to 0.009 x LD, where LD represents the CyA level in blood per dose ratio), showed hyperbolic decay with increasing CyA-EP (the mean CLt was defined as follows: CLt = 0.937/CyA-EP), whereas fc showed exponential decay with increasing CyA-EP (the mean fc was defined as follows: fc = 0.593 x exp(-0.155 x CyA-EP)). These findings suggest that total CyA body clearance and its bioavailability were suppressed during the renal dysfunction phase. Hence, the mean CL/f as a function of the CyA-EP was given by the following equation: CL/f = 1.390 x exp(0.204 x CyA-EP)/CyA-EP. Since the CyA-EP reflects a patient's disease state and alterations in the CyA pharmacokinetic profile, these model formulae should provide an adequate method for determining a CyA dosage regimen for several disease states after renal transplantation.

Adult↗

[Synthesis and antiplatelet activity of 2-amino-4,5-diphenylthiazole derivatives].

A series of 4,5-diphenylthiazoles containing morpholinoalkyl amino groups at the 2 position was synthesized and their anti-platelet activities were evaluated. The inhibitory effects of the compounds in which phenyl groups at the 4 position were substituted by methoxy groups were more potent than those of aspirin and ibuprofen on the collagen-induced rabbit platelet aggregation. These compounds were also shown to have potent efficacies on the arachidonic acid-induced platelet aggregation. On the other hand, these compounds did not affect the ADP-induced platelet aggregation similarly to non-steroidal anti-inflammatory agents. Moreover, their efficacies on the inhibition of prostaglandin synthesis were more potent than that of ibuprofen. Therefore, we thought that 2-(morpholinoalkyl)amino-4,5-diphenylthiazoles, in spite of their basic properties, inhibited the platelet aggregation based on cyclooxygenase.

Adenosine Diphosphate↗

Participation of serotonin in capsaicin-induced mouse ear edema.

We investigated the involvement of serotonin (5-HT) in mouse ear edema induced by topical application of capsaicin (250 micrograms/ear). Application of capsaicin to the ear caused degranulation of mast cells in skin connective tissue. Capsaicin-induced ear edema was significantly inhibited by preadministration of 5-HT2 receptor antagonists such as ketanserin (2 mg/kg, i.v.) and LY 53857 (1 mg/kg, i.v.), but not 5-HT1-, 5-HT3- and 5-HT4-receptor antagonists. Intradermal injection of alpha-methyl 5-HT (5-HT2-receptor agonist) and 5-HT into ear skin produced edema formation more potently than 8-OH-DPAT (5-HT1A agonist) and 2-methyl 5-HT (5-HT3 agonist). 5-HT2 antagonists markedly suppressed the edema response to 5-HT and its receptor agonists, whereas any antagonist for 5-HT1, 5-HT3 and 5-HT4-receptors had no effect. Furthermore, 5-HT2-receptor antagonists partly prevented ear edema in response to substance P (SP), a putative mediator or capsaicin-induced edema, and compound 48/80, a releaser of vasoactive amines form mast cells. These results suggest that 5-HT released from mast cells is partly involved in the development of capsaicin-induced mouse ear edema via 5-HT2 receptors in the ear skin.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Cloning, nucleotide sequence, and expression of tef-1, the gene encoding translation elongation factor 1 alpha (EF-1 alpha) of Neurospora crassa.

The tef-1 gene encoding translation elongation factor 1 alpha was cloned from the ascomycete fungus Neurospora crassa. The sequences of genomic DNA and cDNA clones showed that the tef-1 gene contained one ORF of 1380 bp length that is interrupted by three short introns. The deduced polypeptide contained 460 amino acid residues, and the sequence had a high similarity with those of EF-1 alpha polypeptides from other species. The level of tef-1 mRNA was low in conidia but high in growing cells. When mycelia were transferred to poor nutrient media, the level of tef-1 gene mRNA decreased remarkably. The pattern of tef-1 expression was similar to the expression of genes for ribosomal proteins. The tef-1 gene was mapped between arg-3 and leu-4 loci on linkage group I by restriction fragment length polymorphism mapping. Southern blot analysis showed that Neurospora genomic DNA contained only one copy of the tef-1 gene in a genome.

Amino Acid Sequence↗

Molecular cloning of a cDNA for proctase B from Aspergillus niger var. macrosporus and sequence comparison with other aspergillopepsins I.

A cDNA for proctase B from Aspergillus niger var. macrosporus was isolated and sequenced. The deduced amino acid sequence (394 residues) of the preproform of the enzyme was highly homologous (98% identify) with those of aspergillopepsins I from A. awamori and A. saitoi, and moderately homologous (68% identity) with that of A. oryzae. Most of the sequence differences were found in the carboxyl-terminal domain.

Amino Acid Sequence↗

Strongly anionic sites in peripheral axons of the rat sciatic nerve: light and electron microscopic detection using cationic colloidal iron.

Anionic sites in the rat sciatic nerve were studied by light and electron microscopy using a fine-granular cationic colloidal iron staining method (Murakami et al., 1986). The axon, as well as the endoneurium, the epineurium and the basement membrane of Schwann cells, were all confirmed to react strongly to the cationic colloidal iron even at a pH value of 1.0-2.0. Prior hyaluronidase digestion decreased the colloidal strain of the epineurium; chondroitinase ABC weakened that of the endoneurium and the basement membrane of Schwann cells. However, as axons retained stainability with cationic colloidal iron even after combined digestion with hyaluronidase, chondroitinase ABC, heparitinase and keratanase, the authors consider sulfated glycoconjugates and not those substances which are digestible with such common enzymes. The acid groups ionized at pH 1.0 are most likely sulfate groups. Methylation deprived the axon of the reactivity to cationic colloidal iron staining, and even subsequent saponification could not recover this reactivity to its full extent. In the axon, electron microscopy revealed a deposition of colloidal iron on the external surfaces of microtubules and neurofilaments in the axoplasm and of very fine filaments connecting them. This highly negatively charged intra-axonal network could also serve toward a supportive function in maintaining the spatial distribution of microtubules either mechanically or through electrostatic repulsion or, possibly, serve as an intra-axona cation exchange reservoir.

Animals↗

Rotationplasty for patients with osteosarcoma around the knee joint.

The results of rotationplasty for patients with osteosarcoma around the knee joint are presented. After an average observation period of 13.3 months, there has been no local recurrence or metastasis. The ankle joints (the new knee joints) of the patients were able to support their body weight with an average range of motion of 75 degrees. All patients could walk well without crutches and without risk of the giving way phenomenon. The average rate of the functional evaluation according to the re-modified system by Enneking was 84.5% (range, 80.0-86.7%). No patient had psychological trouble in accepting the shortened and rotated extremity. The results show that rotationplasty is a useful reconstructive method for the treatment of osteosarcoma around the knee joint.

Adolescent↗

Localization of the glycosaminoglycans in the synovial tissues from osteoarthritic knees.

Localization of the glycosaminoglycans (GAG) was examined in the synovial membranes of patients with osteoarthritis under light microscopy using a fine cationic colloidal iron staining method combined with enzymatic digestion. Our staining method was very useful for demonstrating the difference in the localization of GAG in regions of the inflammatory site in the osteoarthritic synovial membrane. Hyaluronic acid was mainly located in connective tissues in the surface intercellular and perivascular spaces, chondroitin sulfate A/C in the highly fibrous part of and connective tissue around blood vessels, dermatan sulfate (chondroitin sulfate B) in the subsurface interstitium and vascular endothelial cells and heparan sulfate in part of vascular endothelial cells. No keratan sulfate was detected. GAG is reported to have an important role in cell movement, adherence and aggregation in the inflammatory sites. These findings should be useful for understanding the role of GAG in physiological and pathologic processes of secondary synovitis.

Adult↗

Relationship between retention of the posterior cruciate ligament and postoperative flexion in total knee arthroplasty.

This study was conducted to retrospectively analyzed the outcome of 192 total knee arthroplasties in 132 patients with rheumatoid arthritis (118 women, 14 men). The Okayama Mark II prosthesis, which requires the posterior cruciate ligament (PCL) to be resected, was used in 83 knees (group I), the Mark II prosthesis, which allows the PCL to be retained, was used in 68 knees (group II), and the new Okayama PCL-R prosthesis, which also allows the PCL to be retained, was used in 41 (group III). According to the Japanese Orthopaedic Association knee scoring system, the clinical outcome of groups I, II and III at 1 year after the operation were 64.9, 71.2 and 72.3 points, respectively, and the average flexion angles in each group at 1 year were 78.4, 92.6 and 101.3 degrees. Postoperative flexion in groups III was significantly greater than in groups I and II. These results suggest that postoperative flexion is greater when the posterior cruciate ligament is retained.

Arthritis, Rheumatoid↗

Finite element analysis of pathogenesis of osteoarthritis in the first carpometacarpal joint.

Stress distribution in the first carpometacarpal joint was analyzed in 49 cadaveric hands using the finite element method to clarify the pathogenesis of osteoarthritis in the joint. The results of the finite element method analysis were compared with those of the contact pressure distribution in the first carpometacarpal joint of cadaveric specimens using pressure-sensitive film, and with the simple roentgenographical and microradiographical manifestations of spur formation, and with histological findings of osteoarthritis to verify the accuracy of the models of computer simulation models. The comparison of these results showed that osteoarthritic changes of the first carpometacarpal joint were found in areas where stress was concentrated during movement of the joint. The saddle shape of this joint is essentially well-designed for the dispersion of normal stress, however minimal displacement due to instability could easily induce osteoarthritis. Furthermore the shallow trapezial configuration may contribute to the high incidence of osteoarthritis changes. The finite element method helped clarify the relationship between stress patterns and osteoarthritis response.

Computer Simulation↗

Questioning the usefulness of the non-parametric analysis of quantitative data by transformation into ranked data in toxicity studies.

The so-called "decision tree" for computed programs for data analyses of toxicity studies indicates that, when a set of quantitative data is heterogeneity in variance among groups, then data should be transformed into ranked data to test the significant difference among mean values. However: 1. Hypothetical sets of data indicate that the minimum sample size needed to detect a significant difference among mean values by multiple-comparison test of ranked data is too large when compared with the practical number of animals (e.g. 4 dogs or 10 rats per sex per group) used in toxicity studies. 2. The homogeneity test of variances among groups may provide itself important information on the toxicity of test compound, as well as the test for significant differences among mean values indicates. 3. On the assumption that variances in data for most test items in toxicity studies are homogeneous as far as the test items are not greatly affected by the treatment with test compounds, it seems practical to test the significant difference among mean values by parametric procedures even if the data are heterogeneous in their variances among groups.

Animals↗

Gamma knife radiosurgery for acoustic schwannoma: early effects and preservation of hearing.

The effects of relatively low dose gamma knife irradiation on acoustic schwannoma were evaluated. The signal intensity change and tumor shrinkage on magnetic resonance (MR) images, change in hearing, and complications in 28 patients (mean age 47.0 +/- 13.6 yrs) were studied. Three patients had bilateral tumors. Six were already deaf when treated. The maximum tumor diameter was 35 mm. The mean dose delivered to the tumor was 12.1 +/- 1.6 Gy at the periphery, and 25.2 +/- 4.3 Gy at the center. The mean follow-up time was 16 months and the longest 24 months. Lowering of the MR signal intensity in the tumor center appeared after 3 months at earliest but generally after 6 months. Signs of tumor shrinkage appeared within 12 months on average. Cyst in the tumor enlarged rapidly after treatment in two patients. The percentage of hearing preservation was 85% (17/20) at 3 months, 80% (16/20) at 6 months, 72% (13/18) at 9 months, 75% (12/16) at 12 months, 67% (8/12) at 15 months, 60% (6/10) at 18 months, and 50% (2/4) at 24 months. Subtle changes in hearing were detected by speech tone audiometry. Temporary facial numbness and weakness was seen in one patient each. No patient had lower cranial nerve paresis. Relatively low dose gamma knife radiosurgery is effective in suppressing growth of acoustic schwannoma with preservation of hearing.

Adult↗

A mouse model of a sudden death induced by noise exposure is useful to investigate human responses to physical stress.

Stress has become an increasingly important occupational health matter in Japan. We found that noise exposure, 6 kHz wave and its higher harmonics at the sound pressure level of 112 dB, induced typical audiogenic seizures in the MRL/l mouse strain. The seizures are often fatal. Wild running preludes to seizures. Inhibition of wild running by restricting animal's activities successfully prevented the seizures, suggesting that an excessive physical load is a necessary step. The present finding indicates that MRL/l mice may be a useful model for human sudden deaths after excessive work loads.

Acoustic Stimulation↗