Search PubMed⌕ Search

Biomedical subjects

N Kageyama

Publications and source records attributed to N Kageyama.

At least 37 records · Page 2Linked to original sources
PubMed1996

A neurokinin 1-receptor antagonist improves exercise-induced airway narrowing in asthmatic patients.

Recent reports suggest the involvement of vascular phenomena in exercise-induced asthma. Sensory neuropeptides, such as substance P (SP), which causes airway vascular dilatation and plasma leakage, have been demonstrated to play a role in hyperpnea-induced airway narrowing in animal studies. The purpose of this study was to investigate the importance of tachykinins in exercise-induced airway narrowing in patients with asthma using a selective neurokinin 1-receptor (NK1-receptor) antagonist, FK-888. In a double-blind, placebo-controlled, crossover trial, nine subjects with stable asthma were given FK-888 (2.5 mg) or placebo by inhalation 20 min before each exercise at a level previously demonstrated to cause a fall of at least 40% in specific airway conduction (SGaw). Inhalation of FK-888 had no significant effect on baseline SGaw. While the recovery from exercise-induced airway narrowing was significantly faster after treatment with FK-888 the area under the curve for SGaw during the 50 min after exercise was significantly reduced (p<0.05) and the time taken for the SGaw to recover to within 65% of baseline after exercise was also significantly shorter with FK-888 than the placebo (p<0.05). However, treatment with FK-888 did not significantly attenuate the maximal fall in SGaw. These results suggest that NK1-receptor-mediated mechanisms are involved in the recovery phase of exercise-induced airway narrowing. The possible mechanisms of these phenomena are discussed.

Administration, Inhalation↗
PubMed1996

Incubation with IgE increases cholinergic neurotransmission in human airways in vitro.

Airway cholinergic hyperresponsiveness is frequently observed in asthmatic patients. Recent reports suggest the possible involvement of IgE in hyperresponsiveness, although the exact mechanism is still uncertain. In this study, we examined whether incubation with IgE could facilitate the cholinergic function in human airways. Bronchi were obtained from 20 patients undergoing lung resection. Cholinergic contractile responses were induced by electrical field stimulation (EFS) or exogenous acetylcholine (ACh), and they were assessed by isometric tension measurement. EFS-induced ACh release from cholinergic nerves was also measured by high performance liquid chromatography. Incubation with IgE significantly enhanced EFS-induced bronchial contraction and ACh release as compared with the values of the bronchi incubated with heat inactivated IgE (control) (p < 0.05, respectively), but it did not alter the contractile responses induced by exogenous ACh. Pretreatment with the muscarinic M2-receptor agonist pilocarpine reduced the EFS-induced ACh release in the control tissues (p < 0.05), but not in the tissues incubated with IgE. The M2-receptor antagonist methoctramine significantly enhanced the EFS-induced contraction in control bronchi (p < 0.05), but this augmentation was not observed in the tissues incubated with IgE. These results suggest that IgE itself can enhance cholinergic bronchial contraction via facilitation of ACh release from cholinergic nerves and that this augmentation is related to autoreceptor M2 dysfunction at nerve endings.

Acetylcholine↗
PubMed1996

Involvement of endogenous tachykinins in LTD4-induced airway responses.

Leukotriene D4-(LTD4) has been reported to cause tachykinin release from airway sensory nerves. However, the functional significance of endogenously released tachykinins in LTD4-mediated airway responses has not been fully clarified. The aim of this study was to investigate whether LTD4-induced airway responses are due, in part, to tachykinin release in guinea-pigs. Airway plasma exudation and bronchoconstriction were assessed by measuring extravasation of Evans blue dye and by mean pulmonary resistance (RL) in the presence of atropine (1 mg.kg-1 i.v.) and propranolol (1 mg.kg-1 i.v.), respectively. LTD4 (5 micrograms.mL-1 for 1 min) inhalation caused increase in plasma exudation and RL. Capsaicin pretreatment of animals to deplete sensory neuropeptides significantly inhibited LTD4-induced plasma exudation in the main bronchi, but not in the central (cIPA) and peripheral intrapulmonary airways (pIPA). Pretreatment with specific tachykinin neurokinin-1 (NK1)-receptor antagonists, FK 888 (10 mg.kg-1 i.v.) and CP 96345 (4 mg.kg-1 i.v.), also significantly reduced LTD4-induced plasma exudation in the main bronchi, and in the main bronchi and cIPA, respectively. However, these antagonists did not significantly affect the LTD4-induced increase in RL. In contrast, neurokinin-2 (NK2)-receptor antagonist, SR 48968 (0.3 mg.kg-1 i.v.), significantly inhibited the bronchoconstriction after LTD4-inhalation. These results suggest that leukotriene D4-induced bronchoconstriction and plasma exudation in guinea-pigs are, in part, due to tachykinin release from airway sensory nerves.

Administration, Inhalation↗
PubMed1996

Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs.

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.

Allergens↗
PubMed1995

A staining method for bone canaliculi.

The modified Bodian method with protargol (silver protein) is ordinarily used to detect nerve fibers. With this technique, applied to decalcified rat bone sections, the bone canaliculi were clearly stained black with good contrast to the bone matrix in both lamellar and woven bone. In addition, the connections between the bone canaliculi and other canaliculi, osteoblasts, osteoclasts, and chondrocytes were easily detectable. We found that the bone canaliculi of woven bone were fewer in number and ran more irregularly than those of lamellar bone. We believe that this staining method for bone canaliculi in decalcified bone is superior to previously reported methods and may be useful in studies on bone pathology.

Animals↗
PubMed1995

Chronic allergen exposure enhances cholinergic neurotransmission in sensitized guinea-pigs.

Airway hyperresponsiveness in asthmatic patients may be related to cholinergic hyperresponsiveness. In this study, we examined whether chronic allergen exposure induces cholinergic hyperresponsiveness in ovalbumin (OA) sensitized guinea-pig airways. Three weeks after active sensitization, ovalbumin (0.03%, for 3 min, challenged group) or saline inhalation (control group) was repeated every day for 4 weeks. Cholinergic responses were assessed by isometric tracheal contraction after electrical field stimulation (EFS) or exogenously applied acetylcholine (ACh). The contractions were expressed as a percentage of the maximum response to ACh (10(-3) M) (AChmax). We calculated the effective frequencies producing 25% of AChmax (EF25) from frequency-response curves. EFS-induced contractile responses were significantly enhanced in the challenged group (logEF25 = 0.66 +/- 0.08 (mean +/- SEM)) compared with the control group (logEF25 = 1.12 +/- 0.16). In contrast, exogenous ACh-mediated contractile tracheal responses were almost the same in both groups. We conclude that repeated allergen inhalation causes cholinergic airway hyperresponsiveness, presumably due to the facilitation of cholinergic neurotransmission. This mechanism may be involved in the airway hyperresponsiveness in asthmatic airways.

Acetylcholine↗
PubMed1995

Allergic airway response and potassium channels: histamine release and airway inflammation.

The possible involvement of potassium (K) channels in allergic airway responses was examined in ovalbumin (OA)-sensitized guinea pigs. An ATP-sensitive K channel opener (BRL-38227) inhibited OA inhalation-induced bronchoconstriction and airway plasma leakage. BRL-38227 also had an inhibitory effect on exogenous histamine- and leukotriene-induced responses. In contrast, BRL-38227 did not affect OA-induced histamine release from minced lung tissues. Therefore, the ATP-sensitive K channel opener inhibits allergic bronchoconstriction and plasma leakage as a result of its effect on airway smooth muscle and postcapillary venules. Apamin, a small conductance Ca2+ -activated K channel (PK,Ca) blocker, significantly inhibited both OA-induced tracheal contraction and histamine release from lung tissues, suggesting that this compound reduces allergic airway responses via a mast cell stabilizing effect. We conclude that ATP-sensitive K channel opening and small conductance PK,Ca closure may be beneficial for preventing allergic airway responses.

Adenosine Triphosphate↗
PubMed1994

An immunohistochemical study on pulmonary surfactant of infants diagnosed as sudden infant death syndrome.

Pulmonary tissues from 22 autopsy cases diagnosed as sudden infant death syndrome (SIDS) were examined by immunoperoxidase method using monoclonal antibodies against human pulmonary surfactant apoproteins. In all cases except one, a moderate or large amount of pulmonary surfactant existed in the alveolar spaces. In the cytoplasm of the alveolar type II cells of most cases, a variable number of reaction products were also recognized. This study suggested that SIDS babies suffered lethal hypoxic state, but the staining intensity of pulmonary surfactant did not show a clear difference in sleeping positions.

Humans↗
PubMed1991

Bilateral open laminoplasty using ceramic laminas for cervical myelopathy.

Evaluation was done of 65 patients with cervical myelopathy treated by bilateral open laminoplasty using artificial laminas, between 1984 and 1988, who had been followed for more than 2 years. The mean recovery rate on the Japanese Orthopaedic Association scoring system was 65% in all cases, and 72% in the cases with no other complications. The artificial laminas appeared well adapted to the laminas in computed tomography and dynamic radiographic examinations, and there were no cases of reduction of the enlarged canal. Postoperative restriction of the range of motion of the cervical spine was lessened by the positioning of lateral grooves, more appropriate external fixation, and posterior flexion exercise after operation. This procedure is not technically complicated, it does not involve appreciable blood loss during operation, it prevents grafted free fat from migrating into the spinal canal, and is advantageous for posterolateral bone chip grafting.

Ceramics↗
PubMed1991

[Staining of bone canaliculi using decalcified bone tissues].

Recently we were able to stain bone canaliculi using the decalcified bone tissues, according to a modified method of the Bodian staining method, which is commonly used for staining the nerve fibers with silver impregnation of protargol. The bone tissues from normal rabbits, rats, and humans were decalcified with buffered EDTA solution after 10% formalin fixation. The tissues were embedded in paraffin and were sliced at 4 microns then the sections were attached to the gelatin-coated glass slides. These sections were treated first with potassium dichromate followed by 2% protargol solution containing copper. After gold chrolide treatment, they were immersed in oxalic acid. Both the lacunae and canaliculi of osteocytes were stained black in sharp contrast to bone matrix of red purple. Using the present staining method, the bone canaliculi were clearly detectable in fine details without producing apparent artificial damage of soft tissues. The canaliculi showed also markedly complex fine structures. By combining the present staining method with eosin or toluidine blue staining, we were able to recognize even immature osteocytes in enchondral ossification at growth cartilage with fine bone canaliculi. From these results, we conclude that the present method is very useful in histopathological studies of the lacuna-canalicular system of osteocytes in the decalcified bone tissues.

Animals↗
PubMed1990

[Mass-screening for breast cancer using C-mode display ultrasonography].

In order to elevate the detection rate of breast cancer in mass-screening, we examined whether the C-mode display ultrasonography is useful for detection of breast cancer. 1) Diagnostic sensitivity of C-mode ultrasonography was 88.2%, specificity was 66.7% and predictive value was 58.8%, respectively. 2) The detection rate of C0mode ultrasonography was 100% for tumors more than 5.0cm, 87.5% for 2.0-5.0cm, 74.2% for less than 2.0cm. Especially, the diagnostic value of lesser than 1.0cm breast cancer was high, 66.7%. 3) In findings of C-mode ultrasonography, images characteristic of carcinoma can be obtained regarding their unclear margin (70.6%), heterogenous (88.2%) and hypoechoic (70.6%) internal echoes and malignant halo (61.8%). Our present data suggest that C-mode ultrasonography is very useful for the mass screening for breast cancer.

Breast Neoplasms↗
PubMed1989

Liposomes coupled with monoclonal antibodies against glioma-associated antigen for targeting chemotherapy of glioma.

Liposomes have a variety of attributes as a drug delivery system. Targeting of liposomes to specific cells has been investigated by using appropriate cytophilic ligands such as monoclonal antibodies (MAb's). In the present study, liposomes with selective cytotoxicity toward glioma cells were obtained. An MAb which reacts with a glioma-associated antigen, G-22-MAb, was coupled with liposomes by the cross-linking reagent dipalmitoyl L-alpha-phosphatidylethanolamine 3-(2-pyridyldithio)propionate. Interaction of the liposomes with glioma cells was morphologically observed by fluorescence microscopy, and uptake of liposomal contents into glioma cells was analyzed by flow cytometry using carboxyfluorescein as a marker. It was demonstrated that G-22-MAb could be coupled with liposomes without altering its specificity toward glioma cells and that coupling with the MAb led to a significant increase in the uptake of liposomal contents into glioma cells. Liposomes containing an antitumor drug, methotrexate (MTX), were prepared and their cytotoxicity was examined by a colorimetric growth assay. Upon incorporation of MTX into the MAb-coupled liposomes, the cytotoxicity toward glioma cells was increased 100-fold as compared with free MTX. These results indicate that G-22-MAb-coupled liposomes containing MTX have selective cytotoxicity toward glioma cells and could be utilized for targeting the chemotherapy of gliomas.

Antibodies, Monoclonal↗
PubMed1988

Pressure wave with apnoea evaluated by sleep level in patient with ventricular dilation.

Seventeen patients who were suspected of having hydrocephalus, because of ventricular dilation from various causes, were included in this study of the pathophysiologic basis of the appearance of pressure waves (PWs). Pressure waves accompanied by apnoeas originated in arousal responses in the resting state of these patients. Frequent fits of apnoea were included in the entire sleep apnoea syndrome. Most pressure waves characteristically appeared in the state of non-REM sleep. During the appearance of such pressure oscillations, intracranial pressure was elevated transiently. This coincidence in the appearance of pressure oscillations with sleep apnoea was the most characteristic pathophysiologic result from this polygraphic study of the patients.

Adult↗
PubMed1988

Characterization of neuroectodermal antigen by a monoclonal antibody and its application in CSF diagnosis of human glioma.

Monoclonal antibodies were produced by immunization of the human glioma cell line SK-MG-4. One of the antibodies, designated G-22, reacted with 18 of 20 glioma cell lines, two melanoma cell lines, and three lung cancer cell lines, but not with 39 cell lines derived from sarcoma, carcinoma, or hematopoietic tumors. The antigen was expressed in the brain of human fetuses in early gestation (9 weeks) but not in late gestation (8 months) or in normal adult brain, suggesting that the antibody recognizes neural differentiation antigens expressed by neuroectodermal origin. A high incidence of positive antigens has been observed in gliomas but not in the other neural tumors, such as ependymomas, meningiomas, and neuroblastomas. Thus, the antigen defined by the G-22 monoclonal antibody could be defined as glioma-associated antigen. Pulse-labeling with tritiated leucine and subsequent immunoprecipitation of the solubilized cell membrane revealed that the antigen recognized by this antibody had a molecular weight of 67 kD on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was shown by dot-blot enzyme-linked immunospecific assay (ELISA) that the antigen could be detected in the cerebrospinal fluid (CSF) from patients with gliomas. From analysis of affinity chromatography and SDS-PAGE, the antigen present in the CSF had a molecular weight similar to that of a 1% Nonidet P-40 (NP-40) extract from a glioma cell line. When the antigen in CSF was quantitatively assayed by ELISA, the mean antigen level (expressed as optical density at 450 nm) in the CSF of seven patients was 0.8 +/- 0.28 (mean +/- standard deviation), which was significantly higher than the 0.38 +/- 0.14 level observed in the CSF of 15 patients with nonglioma brain tumors and the 0.23 +/- 0.09 level in the CSF of four patients without brain tumors. These results indicate that the monoclonal antibody G-22 is useful for the diagnosis of glioma.

Antibodies, Monoclonal↗
PubMed1988

Detection of mRNA of prolactin and ACTH in clinically nonfunctioning pituitary adenomas.

Clinically nonfunctioning pituitary adenomas have been thought to synthesize some pituitary hormones as shown by studies involving cell culture, immunocytochemistry, or measurement of hormone levels in tumor homogenates. Nevertheless, they are not associated with hypersecretion of pituitary hormones. To further clarify hormone synthesis in such pituitary adenomas, the presence of messenger ribonucleic acid (mRNA) of prolactin (PRL) growth hormone, and adrenocorticotropic hormone (ACTH) in the cytoplasm of 16 nonfunctioning adenomas was determined by means of a hybridization technique, and compared to the immunocytochemical findings. In three adenomas (19%) PRL mRNA was detected and in one case (6%) ACTH mRNA was detected. The hybridization technique appears to be more sensitive than immunohistochemistry for detection of specific mRNA's in assigning the hormone synthesis potential to clinically nonfunctioning tumors. The results suggest that PRL and ACTH are synthesized in some cases of clinically nonfunctioning pituitary adenomas and that hybridization techniques are useful to investigate hormone synthesis in pituitary adenomas. The ability to demonstrate PRL mRNA in tumor tissues allowed differentiation between hyperprolactinemia caused by synthesis of PRL in the tumor and that due to hypersecretion from the adjacent normal pituitary.

Adenoma↗
PubMed1988

[Changes in monoamine neurotransmitter metabolism in brain ischemia measured by in vivo voltammetry].

A preliminary work with in vivo voltammetry (IVV) in the ischemic brain had been performed by the authors in rats after cardiac arrest, which showed that the IVV system is useful to investigate ischemic brain. In the present report, IVV was applied to ischemic brain by 4-vessel occlusion in rat and changes in dopamine and serotonin metabolism were investigated by measuring peak 2 (3,4-dihydroxyphenylacetic acid, DOPAC) and peak 3 (5-hydroxyindoleacetic acid, 5-HIAA) in the striatum. The change of cerebral blood flow (CBF) were also assessed by a temperature-controlled thermoelectrical method in the striatum of the same model. The heights of peaks 2 and 3 were significantly increased to 600-900% and 200-300% respectively in the striatum during 30 minutes of 4-vessel occlusion. The increase of each peak was maximum at 10 minutes after occlusion. These changes may reflect that release of monoamine neurotransmitters is increased by the ischemia and outward transport of their metabolites are disturbed. On the other hand, after reperfusion by release of carotid occlusion, the heights of peaks 2 and 3 rapidly decreased below the control values, thereafter, peaks 2 and 3 gradually increased to over control values at 180-210 minutes after reperfusion. rCBF in the striatum decreased to almost 0 ml/100 g/min during 4-vessel occlusion ischemia and increased to over control values transiently for 30 minutes after reperfusion, followed by gradual decrease for about 240 minutes. Since monoamine neurotransmitters are known to have various effects on cerebral metabolism and CBF, their disorders may contribute to the change of CBF and the development of postischemic brain damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗