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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 883 records · Page 49Linked to original sources

Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation.

We investigated the role of neurogenic inflammation and the subsequent mechanisms in cigarette smoke-induced airway hyperresponsiveness in guinea pigs. Exposure to cigarette smoke was carried out at tidal volume for 3 min. Airway responsiveness to histamine was determined before and after smoke exposure followed by bronchoalveolar lavage (BAL). Plasma extravasation was evaluated by measuring the extravasation of Evans blue dye in the airway. Cigarette smoke produced significant airway hyperresponsiveness and plasma extravasation, with an influx of neutrophils in BAL fluid. FK-224 (10 mg/kg i.v.), a tachykinin antagonist at NK1 and NK2 receptors, significantly inhibited these changes. The thromboxane (Tx) B2 concentration was increased in BAL fluid after smoke exposure and was significantly inhibited by FK-224. OKY-046 (10 mg/kg i.v.), a Tx synthase inhibitor, significantly inhibited airway hyperresponsiveness but had no effect on neutrophil influx or plasma extravasation. The results suggest that neurogenic inflammation and the subsequent generation of Tx in the airway are important in the development of the airway hyperresponsiveness induced by cigarette smoke.

Animals↗

Radiobiological effects of gamma knife radiosurgery on brain tumors studied in autopsy and surgical specimens.

To elucidate the radiobiological effect of Gamma Knife radiosurgery on brain tumors, we performed a histological study on nine cases. In two, the material was obtained at autopsy and in seven following surgery. In the central region of the radiation field, destructive changes occurred both in tumor cells and in vessels. In the peripheral area, destructive and proliferative vascular changes were intermingled with residual tumor tissue. Immunohistochemical staining of surgical specimens showed that the vascular proliferative changes consisted of pericytic proliferation with or without endothelial proliferation. These characteristic changes might suppress tumor growth, at least in the short-term.

Adolescent↗

Gamma thalamotomy for parkinsonian and other kinds of tremor.

On the basis of our experiences with selective ventralis intermedius thalamotomy with microrecording, certain cases of tremor with Parkinson's disease (PD, six cases), intentional tremor (one case) and essential tremor (one case) were treated by Gamma Knife. In all cases, 140-150 Gy were irradiated using 4-mm collimators. Three different strategies were used. (1) Gamma thalamotomy as the primary surgical treatment. (2) As a secondary treatment, irradiation of the symmetric point of the contralateral selective thalamotomy. (3) Extension of the previous thalamotomy. For the first three cases (all PD), a special plug pattern (100 plugs) was used, but was not employed for the later cases. No acute untoward effects were noted, and overall there appeared to be a reduction in tremor. The time course of tremor reduction varied from case to case, from about 5-6 months to 1 year.

Adult↗

Gamma Knife radiosurgery for acoustic schwannoma: effects of low radiation dose and functional prognosis.

The effects of relatively low dose Gamma Knife irradiation on acoustic schwannoma were evaluated in 29 patients followed over 2 years after treatment. The mean dose delivered to the tumor periphery was 12.1 Gy. Lowering of the magnetic resonance signal intensity in the tumor center appeared in 69% and signs of tumor shrinkage appeared in 59% of cases. The cyst in the tumor enlarged in 3 cases, and 2 cases developed hydrocephalus. The percentage of pure-tone hearing preservation was 82% at 3 months, 73% at 6 months, 68% at 12 months. 64% at 18 months and 59% at 24 months in 22 out of 29 cases. Relatively low dose Gamma Knife radiosurgery was effective in suppressing tumor growth, with preservation of hearing.

Adult↗

Cultured epithelial cells release cyclooxygenase-dependent and cyclooxygenase-independent factors that inhibit cholinergic contraction of canine airway smooth muscles.

We observed the effects of supernatants from cultured epithelial cells on the contraction of tracheal smooth muscle evoked by acetylcholine (ACh) or by electrical field stimulation (EFS). Cultured canine tracheal epithelial cells were incubated in Krebs solution with or without indomethacin (10(-5)M) for 30 and 120 min. The amplitude of the tracheal smooth muscle contractions evoked by EFS or exogenously applied ACh were measured before and after the application of each supernatant in the combined presence of both indomethacin (10(-5)M) and propranolol (10(-6)M). The control supernatant incubated without indomethacin markedly suppressed the amplitude of the contraction evoked by EFS, but not by ACh. The supernatant incubated with indomethacin for 30 min did not show any effects on the contractile responses evoked by EFS or ACh. However, the supernatants from the cultured epithelial cells incubated for a longer period (120 min) in the presence of indomethacin significantly suppressed the contraction evoked by EFS, but not by ACh. The prostaglandin E2 (PGE2) concentration was markedly higher in the supernatants incubated without indomethacin (1.39 +/- 0.51 ng/ml, 30 min incubation) than in those with indomethacin (0.02 +/- 0.01 ng/ml, 30 min incubation, and 0.06 +/- 0.01 ng/ml, 120 min incubation). To determine whether PGE2 is responsible for the inhibitory effect of the supernatants, we evaluated the effects of PGE2 on the resting tone, and EFS- or ACh-evoked contraction. 10(-12) to 10(-6) M of PGE2 showed no significant effect on the resting tone. 10(-9) M of PGE2, corresponding to the concentration of the supernatants incubated without indomethacin, and 10(-11) M of PGE2, to that of the supernatants incubated with indomethacin, showed a similar extent of inhibitory effects to the corresponding supernatants on the EFS-evoked contraction, and no effect on the ACh-evoked contraction. These results suggest that cultured airway epithelial cells release at least two factors spontaneously even without stimulation. One of these factors may be prostanoid (PGE2), which acts prejunctionally to inhibit the contractile response. The other factor is distinct from prostanoid and inhibits smooth muscle contraction, presumably by suppressing ACh release from vagus nerve termini.

Acetylcholine↗

Aerosolized human neutrophil elastase induces airway constriction and hyperresponsiveness with protection by intravenous pretreatment with half-length secretory leukoprotease inhibitor.

This study was designed to determine the effects of inhaled human neutrophil elastase (HNE) on airway constriction and airway responsiveness, and to examine the protection by an intravenous recombinant half-length secretory leukoprotease inhibitor, r1/2SLPI in guinea pigs. Aerosol inhalation of HNE (250 microgram/ml, for 3 min) caused a transient but significant airway constriction, in which lung resistance (RL) increased from 194 +/- 18 (mean +/- SEM) to 461 +/- 42 cm H2O/L/s (p < 0.001). Thirty minutes after the end of HNE inhalation, airway responsiveness to intravenous 5-hydroxytryptamine (5-HT) was significantly increased. The provocative dose causing a 200% increase in RL (PD200) was significantly decreased from 10.0 +/- 1.2 to 6.5 +/- 0.8 microgram/kg (p < 0.001). Forty-five minutes after the end of HNE inhalation, total cells in bronchoalveolar lavage fluid (BALF) were significantly increased (p < 0.05). Histologic study of intrapulmonary bronchi demonstrated an acute inflammatory response characterized by damage to the epithelium, airway obstruction by mucus plugs, and recruitment of mononuclear and polymorphonuclear cells to the bronchial epithelium. r1/2SLPI (30 mg/kg) injected 5 min before the initiation of HNE inhalation significantly inhibited the airway constriction (p < 0.05), the airway hyperresponsiveness (p < 0.01), and the increase of cells in BALF (p < 0.05). The present data suggest that HNE plays a role in the induction of airway constriction and airway hyperresponsiveness in various inflammatory lung diseases with pulmonary neutrophil infiltration, such as chronic obstructive pulmonary diseases (COPD) and possibly bronchial asthma. r1/2SLPI may be useful as an antiprotease treatment.

Aerosols↗

Effects of platelet activating factor on mucociliary clearance of the eustachian tube.

The effects of platelet activating factor (PAF) on mucociliary clearance of the eustachian tube were investigated both in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated with PAF at concentrations ranging from 10(-10) to 10(-6) mol/L. Ciliary activity was observed under an inverted microscope and quantified photoelectrically. The PAF dose-dependently inhibited ciliary activity. One milliliter each of 10(-5) mol/LPAF, 10(-5) mol/L prostaglandin E2 (PGE2), 10(-5) mol/LPAF and PGE2, or the control solution (0.1 v/v% methanol-phosphate-buffered saline) was directly injected into the tympanic bullae of anesthetized chinchillas. The middle ear was examined by otomicroscopy, tympanometry, and auditory brain stem response in relation to time. The PAF delayed middle ear clearance, and the PGE2 augmented its delay. These findings suggest that PAF inhibits mucociliary clearance of the eustachian tube from the middle ear, and that PGE2 plays an important role in the augmentation of inflammatory disorders.

Animals↗

Role of thromboxane-A2 and cholinergic mechanisms in bronchoconstriction induced by cigarette smoke in guinea-pigs.

Acute exposure to cigarette smoke provokes bronchoconstriction and increases the concentration of thromboxane (Tx) A2 in bronchoalveolar lavage (BAL) fluid. The purpose of this study was to investigate the role of TxA2 and cholinergic mechanisms in the airway response induced by exposure to cigarette smoke in guinea-pigs. Anaesthetized animals were exposed to 200 puffs of smoke for 10 min. The amount of Evans blue dye extravasated into the bronchial tissue was then measured BAL was performed to determine cell counts and the concentration of TxB2, a stable metabolite of TxA2. The effects of pretreatment with a Tx synthase inhibitor, OKY-046 (10 mg.kg-1), and/or atropine (1 mg.kg-1) were evaluated. Exposure to cigarette smoke caused significant bronchoconstriction (284 +/- 33% of baseline pulmonary resistance (RL)) and plasma extravasation (30.0 +/- 3.8 vs 16.8 +/- 2.6 ng.mg-1 of sham control; main bronchi). OKY-046 or atropine significantly inhibited the bronchoconstriction to a similar extent, without affecting the plasma extravasation. Combined use of these compounds had no additive effect. The cigarette smoke caused significant increase in TxB2 (48 +/- 10 vs 14 +/- 1 pg.mL-1 of sham control) in BAL fluid, which was abolished by OKY-046 but not by atropine. The cellularity in BAL fluid was not different among groups. These results suggest that the bronchoconstriction induced by cigarette smoke is partially mediated by thromboxane A2, which is dependent on a cholinergic pathway.

Animals↗

Determination of total hydroxyproline and proline in human serum and urine by HPLC with fluorescence detection.

A method to measure total hydroxyproline (Hyp) and proline (Pro) in human serum and urine by HPLC was developed. Hyp and Pro in acid hydrolysates of serum and urine were derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)phenysulfonyl chloride after treatment with o-phthaladehyde and cleanup on Bond Elut C18 column. The derivatives of imino acids were separated on a reversed phase column by gradient elution with acetonitrile and phosphate buffer (1 mmol/l, pH 7) and detected by fluorescence measurement at 315 nm (excitation) and 385 nm (emission). Detection limits for both Hyp and Pro were 10 fmol per injection. The within-day and day-to-day relative standard deviations for Hyp and Pro in serum and urine were less than 3.19%. The recoveries of Hyp and Pro added to serum and urine were about 100%. The present method was applied to determine total Hyp and Pro in serum and urine from normal subjects and patients with chronic renal failure.

Adult↗

[Specific inhibitory effect of hybrid liposomes on the growth of hybridoma cells in vitro].

Remarkably high inhibitory effects of the hybrid liposomes composed of L-alpha-dimyristoyl-phosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (C14(EO)n, n = 6-8 and C12(EO)n, n = 8-12)) on the growth of human lymphoma-human B-lymphocyte hybridoma (HF) cells in vitro were obtained. The hybrid liposomes composed of 90 mol% DMPC/10 mol% C14(EO)n (n = 6-8) or C12(EO)n (n = 8-12) were more fluid as compared with 90 mol% DMPC/10 mol% C14(EO)4 or C12(EO)n (n = 4, 23) hybrid liposomes on the basis of fluorescence polarization measurements. These results suggest that the inhibitory effects of the hybrid liposomes on the growth of HF cells should be related to the membrane fluidity. No toxicity to normal rats in vivo was observed in the experiment using 90 mol% DMPC/10 mol% C14(EO)7 or 90 mol% DMPC/10 mol% C12(EO)12 hybrid liposomes.

Animals↗

Inhibitory effect of glycyrrhetinic acid derivatives on capsaicin-induced ear edema in mice.

We examined the effect of glycyrrhetinic acid (Ia) and its derivatives on ear edema induced by topical application of capsaicin in mice. Three dihemiphthalate compounds: di-sodium salt of 18 beta-olean-12-ene-3 beta,30-diol (deoxoglycyrrhetol, IIa) di-O-hemiphthalate (IIb); 18 beta-olean-9(11),12-diene-3 beta, 30-diol di-O-hemiphthalate (IIIa); and olean-11,13(18)-diene-3 beta,30-diol di-O-hemiphthalate (IVa) inhibited capsaicin-induced edema with ED50 values of 52.6, 41.0 and 51.8 mg/kg (p.o.), respectively. However, glycyrrhetinic acid and deoxoglycyrrhetol at a dose of 200 mg/kg (p.o.) had no effect. Compound IIIa (100 mg/kg, p.o.) also inhibited the edema response to capsaicin in mast cell-deficient mice. Furthermore, compounds IIb, IIIa and IVa (25-100 mg/kg, p.o.) prevented ear edema in response to intradermal injection of substance P (SP) and compound 48/80. In addition, these compounds at a high dose of 100 mg/kg (p.o.) produced a significant inhibition of the plasma extravasation in ear skin induced by i.v. administration of SP. The above results suggest that the effect of these compounds on capsaicin-induced ear edema is due at least in part to an inhibition of the increase of vascular permeability induced by vasoactive agents released from mast cells. Moreover, it seems likely that these compounds at a high dose can suppress vasodilatation and plasma extravasation induced by SP involved in capsaicin-induced edema.

Administration, Topical↗

Clinicopathology of chondrosarcoma.

We conducted a clinicopathological analysis of chondrosarcomas in 17 patients treated in our institute. The 5- and 10-year overall survival rates of the patients were 72.3% and 61.9%, respectively. The significant prognostic factors were size and histologic grade of the tumor. Sex, age, location of the primary tumor, or the presence of a preceding exostosis did not affect the treatment results significantly. Chondrosarcomas of histologic grades I and II did not metastasize, while all grade III and dedifferentiated chondrosarcomas metastasized to the lung. The local recurrence rate depended on the surgical margin. Wide excision with an adequate surgical margin is important to achieve local control of the chondrosarcoma.

Adolescent↗

Superoxide dismutase activity in cerebrospinal fluid and its relation to compression of the lumbosacral nerve root.

In the pathophysiology of lumbosacral radiculopathy, inflammation of the nerve root is of critical importance. Additionally, free radicals have been shown to be associated with some inflammatory process. This study was designed to investigate whether free radicals participate in the pathophysiology of nerve root involvement. We measured superoxide dismutase (SOD) activity in cerebrospinal fluid (CSF) of 31 patients with unilateral lumbosacral radiculopathy caused by a herniated disc using electron spin resonance (ESR) spectrometry. Then SOD activity was compared with the type of nerve root compression as seen on preoperative myelography. SOD activity in the normal control group was 7U/ml, while that in the hernia group remarkably decreased. The concentration gradient of SOD activity was different between central herniation and centrolateral herniation. Our findings indicate that free radicals are generated after nerve root compression. Under severe deficiency of SOD activity in CSF, serum SOD penetrates into CSF after further compression. In addition, SOD in CSF may play an important role in protecting against nerve root involvement.

Adult↗

Capillary architecture in the skeletal muscles in the rat hind limb.

We observed differences in the capillary architecture of the skeletal muscles that have different fiber metabolism. The soleus, the vastus intermedius and the tibialis anterior muscles of adult Wistar rats were prepared using two different techniques. Samples for adenosine triphosphatase (ATPase) staining were prepared following Dubovitz's method, and the distributions of fiber type, Types 1, 2A and 2B, were analyzed. Then, corrosion casts of capillary architecture of these muscles prepared following Murakami's method were observed with a scanning electron microscope (SEM) and compared with the fiber distribution. The fiber type composition of the soleus muscle showed Type 1 (slow-twitch) dominance and that of the vastus intermedius and the tibialis anterior muscle showed Type 2 (fast-twitch) dominance. The capillaries of the soleus muscle were tortuous, and this was thought to be advantageous for blood supply. In contrast, the capillaries of the vastus intermedius and tibialis anterior muscles had a relatively parallel pattern. Additionally, two different patterns of capillary architecture that appeared to correspond to certain metabolic characteristic of different muscle fiber types were preserved with corrosion casting. In conclusion, comparative studies on capillary architecture of the skeletal muscles are useful for analyses of its function.

Adenosine Triphosphatases↗

Femoral neck fracture following avascular necrosis of the femoral head.

Four cases of femoral neck fracture following avascular necrosis of the femoral head were studied histologically. All four patients were women who had received steroid therapy, three of them for systemic lupus erythematosus and the other for idiopathic thrombocytopenic purpura. Two types of fracture were found according to the site and the mechanism of fracture. One was at the junction between the necrotic bone and the repairing bone, and it can thus be regarded as a stress fracture. The other type of fracture commenced at the superior portion of the junction between the femoral head and neck, which was weak due to the repair reaction. The fracture line extended to the inferior cortex of the femoral neck, as often occurs in the elderly. In one patient, the femoral neck fracture was the first sign of avascular necrosis of the femoral head.

Adrenal Cortex Hormones↗

Muscle fiber changes of the vastus medialis in rheumatoid patients.

To study the pathology of muscle atrophy in rheumatoid arthritis (RA), we examined the vastus medialis in rheumatoid patients histologically. The relationship of the findings to their ambulatory ability and long-term steroid therapy was investigated. The muscles of the RA patients were also compared with those of patients with osteoarthritis (OA). Specimens of the vastus medialis were collected from 29 knees of 23 patients with RA and 16 knees of 13 patients with OA during total knee arthroplasty. Muscle fibers were classified according to their type, and the ratio between the area of single type I and type II fibers as well as the ratio between the total area of these fibers was calculated. The total area of type II fibers in the RA group was significantly greater than in the OA group (P < 0.05). In the RA group, the mean proportion of the type II fibers relative to the total muscle fiber area tended to increase with the decline of ambulatory ability, while there was no such increase in the OA group. The proportion of type II fibers was increased significantly in RA patients on long-term steroid therapy when compared to those without therapy. In the ratio of the area of a single fiber, there was no clear relationship to ambulatory ability and long-term steroid therapy. It is considered that muscle atrophy in RA is not solely disuse atrophy, but also has a close relationship to steroid therapy and the pathology of the disease itself.

Aged↗

Spinal schwannomas: a review of 42 cases.

In this study, 42 cases of spinal schwannomas are reviewed. We analyzed the therapeutic results of patients with spinal schwannomas in order to investigate the factors which affect the clinical outcomes. Early diagnosis and treatment could help procure a good result for the patient. The delay in diagnosis and the subsequent duration of symptoms was significantly longer in cases of lumbar lesions compared to cervical and thoracic lesions. Tumor recurrence was rare, but in some cases where complete resection was not possible, close follow-up of the patients postoperatively with MRI was indicated.

Adolescent↗