Biomedical subjects

A Konno

Publications and source records attributed to A Konno.

At least 109 records · Page 6Linked to original sources

PubMed1996

RANTES production in nasal epithelial cells and endothelial cells.

BACKGROUND: It is well documented that the chemokine that is regulated upon activation, normal T expressed and presumably secreted, RANTES, is produced by macrophages, platelets, fibroblasts, and renal tubular epithelial cells. Recently, however, production of RANTES by vascular endothelium and airway epithelial cells was demonstrated in human umbilical vein endothelial cells (HUVECs) and epithelial cell lines. OBJECTIVE: This investigation was aimed at determining whether human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs) produce RANTES when they are stimulated by several cytokines. METHODS: HNECs and HMMECs were isolated from nasal mucosa and subsequent continuous subcultures and were stimulated either by IL-1 beta or by the combination of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). RESULTS: After the combined stimulation by TNF-alpha and IFN-gamma, HNECs and HMMECs dramatically produced RANTES, as previously observed in HUVECs and bronchial epithelial cell line BEAS-2B. IL-1 beta also increased RANTES production to a lesser extent. We also demonstrated that the amount of RANTES induced by TNF-alpha and IFN-gamma was higher in HNECs and HMMECs obtained from patients with nasal allergy than in those from patients without allergy. CONCLUSION: RANTES from HNECs and HMMECs likely plays a critical role in eosinophil infiltration of the nasal mucosa in subjects with nasal allergy.

Adolescent↗

PubMed1996

Inhibitory action of sulfatide, a putative ligand for L-selectin, on B cell proliferation and Ig production.

The interaction of L-selectin and its ligand is widely accepted to mediate leukocyte rolling and adhesion on the endothelial surface. Although L-selectin is ubiqultously expressed on lymphoid cells, its role in execution of lymphocyte functions is unknown. By flow cytometric analysis using mAb specific for sulfatide, a putative ligand for L-selectin, we found that sulfatide was selectively expressed on B cells, but not on T cells. To elucidate the involvement of L-selectin and its ligand in B cell activation, the present study was undertaken to investigate effects of sulfatide on T cell-dependent and -independent Ig production by B cells. In pokeweed mitogen-stimulated cultures, addition of sulfatide resulted in almost complete inhibition of Ig production by B cells in the presence of memory CD4+ T cells, whether L-selectin-positive or -negative. A similar inhibition of Ig production by sulfatide was found when B cells were stimulated with Staphylococcus aureus Cowan I and IL-2. Unlike sulfatide, a desulfated form of sulfatide, galactosylaceramide, did not show any effects on Ig production by B cells. Maximal inhibition of Ig production was observed when sulfatide was added at the early period of culture. Sulfatide suppressed effectively proliferation of B cells, but not of T cells. Sulfatide competed the binding of anti-L-selectin mAb to B cells, suggesting it could interfere B cell activation by blocking L-selectin function. The results suggest a novel role of the L-selectin/its ligand system in the initiation of B cell activation.

Adult↗

PubMed1996

Role of substance P in the vascular response of nasal mucosa in nasal allergy.

The effects of topically administered substance P (SP) on nasal blood flow and nasal airway resistance (NAR) were evaluated in 11 subjects with perennial nasal allergy. The change in NAR induced by SP was compared with those induced by nasal challenge with histamine, leukotriene D4 (LTD4), and antigen. In doses > or = 16 nmol, SP caused a significant increase of nasal blood flow within 5 minutes that lasted for less than 20 minutes. In doses > or = 16 nmol, SP caused a dose-dependent, short-lasting, significant increase in NAR. The magnitude of the increase in NAR was LTD4 > SP > histamine when compared on a molar basis. Our results may suggest that SP released from C fiber terminals is partially involved in an early nasal vascular response after antigen challenge by acting on adjacent vascular smooth muscle to cause a transient vasodilatation of both resistance and capacitance vessels only while sensory stimulation persists in subjects with nasal allergy.

Adolescent↗

PubMed1996

Immunoglobulin as an eosinophil degranulation factor: change in immunoglobulin level in nasal lavage fluid after antigen challenge.

To examine the involvement of immunologlobulins in eosinophil degranulation, we investigated the change in the amount of immunogobulins in consecutive nasal lavage fluid samples obtained after antigen challenge, as compared with the corresponding eosinophil counts and eosinophil cationic protein (ECP) levels. Eosinophil counts and ECP levels increased both during the early and late phases but more markedly during the late phase. The levels of secretory IgA (sIgA) and IgA were prominently increased at 10 min after challenge, but returned to the respective prechallenge levels by 1 h after challenge. In the late phase they increased again. ECP levels were correlated both with cosinophil counts x sIgA levels and with eosinopil counts x IgA levels. Both sIgA/albumin and IgA/albumin ratios decreased in the early phase, due to the increased permeability of postcapillary vessels, but then increased again in the late phase becoming higher than the respective prechallenge levels. In the late phase, both secretory IgA and IgA seemed to be actively produced and released in nasal mucosa, thus causing eosinophil degranulation.

Adolescent↗

PubMed1996

The effect of anti-VLA-4 monoclonal antibody on eosinophil accumulation and leukotriene production in nasal mucosa.

Eosinophil derived leukotrienes and platelet activating factor are known to cause nasal swelling. Toxic proteins induce nasal hyperreactivity to non-specific stimuli including histamine. Recent studies strongly suggest that very late activation antigen-4 (VLA-4) on the eosinophil surface plays a prominent role in the recruitment of eosinophils from blood vessels and eosinophil locomotion in inflammatory tissues. To test this hypothesis, we examined the effect of a monoclonal antibody (mAb) to VLA-4 on eosinophil accumulation in nasal mucosa after antigen challenge in a guinea pig model. Here we have demonstrated that the mAb depressed the eosinophil accumulation in nasal mucosa. In addition, we have shown that this mAb also inhibited eosinophil activation and leukotriene production. Our results raise a possibility that eosinophils might be activated during the journey from bloodstream to inflammatory tissues by the adhesion to endothelial cells and fibronectin. VLA-4 might act as a signalling as well as an adhesion receptor on eosinophils.

Animals↗

PubMed1996

[The effect of histamine on the adhesion of endothelial cells to eosinophils].

Recent studies have revealed that eosinophils and eosinophil-derived mediators strongly contribute to the onset of nasal swelling and nasal hyperreactivity. The effect of histamine on the adhesion of endothelial cells to 35S-labeled eosinophils and on eosinophil transendothelial migration was investigated. Human microvascular endothelial cells were isolated and cultured from the mucosa of the inferior turbinates of patients with nasal allergy. Histamine caused dose-related enhancement of adhesiveness to eosinophils. Incubation of endothelial cells treated with 10(-5)M and 10(-4)M histamine increased adhesion to eosinophils by a mean of 56.4% (p < 0.05) and 66.0% (p < 0.05), respectively. When eosinophils were incubated with histamine, they did not induce any increase in adhesion to endothelial cells. Preincubation of endothelial cells with anti-ELAM-1 significantly inhibited histamine-induced adhesion, whereas anti-ICAM-1 and anti-VCAM-1 had no inhibitory effect. Histamine did not increase eosinophil transendothelial migration. Histamine is known to be vasoactive, mediating vasodilation and plasma extravasation. In addition, the results of this study raise the possibility that histamine promotes eosinophil adhesion to endothelial cells by increasing ELAM-1 molecules on endothelial cells and promotes nasal inflammatory and allergic reactions.

Adolescent↗

PubMed1996

["Vertigo" the fact analysis of clinical practice by ENT physicians of Chiba Prefecture by "send-out" questionnaires].

Despite the fact that vertigo has been one of the most frequent complaints encountered in daily practice in an ENT outpatient clinic, it is believed to be the most unwelcome subject for ENT physicians. The reasons are diverse; e.g., the understanding of vertigo is still a difficult task for most physicians and requires time-consuming multiple studies. However, answers to those questions, although speculated a posteriori, are yet to be substantiated. Therefore, we have analyzed the data obtained from multiple questionnaires that were addressed to ENT physicians practicing in Chiba Prefecture in November of 1993. However, those who work in publicly run hospitals were excluded from the study. The study included otorhinolaryngologists who were members of the Society of Otorhinolaryngology of Japan. We received filled questionnaire forms from 76 of 155 members (49%). The age ranged from 33 to 82 years (mean 55.8 years, 68 men and 8 women). From these questionnaires, it became apparent that physicians are not necessarily reluctant to see patients with vertigo. Instead, most ENT physicians appeared to be actively paying attention to this symptom and to be making efforts to approach its diagnosis and treatment. Although we are not certain if the data obtained here represent the majority of ENT physicians, the positive attitudes toward the patients with vertigo/dizziness would certainly encourage those of us who are interested in this particular symptom category.

Adult↗

PubMed1996

[Assessment by flow cytometric method of IgE-binding state of basophils in allergic disorders].

Basophils, as well as mast cells, express Fc epsilon RI on the surface. It is known that activation of basophils and mast cells leads to induction of chronic allergic inflammation. In this study, levels of IgE bound to the surface of peripheral blood basophils were measured using a flowcytometry, and their clinical relevance was evaluated. Peripheral whole blood samples were stained with FITC-conjugated anti-IgE. The fluorescence intensity of the FITC-positive cells within mononuclear cell region was determined. Basophil-bound IgE levels increased along with age and reached invariably high levels of adults. The levels of basophil-bound IgE were higher among allergics than normal controls, in early infancy. In addition, many of the infants with repeated wheezing episodes also exhibited high levels of it. These findings suggest that early exposure of predisposed infants to antigens leads to early sensitization of circulating basophils. Basophil-bound IgE levels correlated well with serum IgE concentration, but they remained constant when IgE concentrations exceeded 300 ng/ml, suggesting that IgE-binding capacity of basophils become saturated at this IgE level. In conclusion, it is shown that flowcytometric measurement of basophil-bound IgE provides a useful method of analyzing this rare cell population within the peripheral circulation, and it serves as a critical parameter to evaluate the allergic inflammation in vivo.

Adolescent↗

PubMed1995

Synaptic contact of neuropeptide-and amine-containing axons on parasympathetic preganglionic neurons in the superior salivatory nucleus of the rat.

Parasympathetic preganglionic neurons in the superior salivatory nucleus (SSNNs) projecting to the pterygopalatine ganglion were labeled by retrograde transport of cholera toxin B subunit (CTB) in the rat. Morphological interactions between SSNNs and afferent fibers immunoreactive (IR) for neuropeptide and amine were examined with light and electron microscopes by double-immunostaining techniques. SSNNs were found in the ipsilateral ventrolateral part of the rostral medulla oblongata. Around SSNNs, substance P-, enkephalin-, neuropeptide Y-and somatostatin-IR nerve fibers were very rich and tyrosine hydroxylase (TH)-, serotonin (5-HT)-, vasoactive intestinal polypeptide- and calcitonin gene-related peptide (CGRP)-IR axons showed moderate density. Thyrotropin-releasing hormone-containing axons were scarce in this region. The electron microscopic examinations revealed that CTB-IR structures directly received synaptic input from axon varicosities IR for TH, 5-HT and all neuropeptides except for CGRP. These findings suggest that catecholamine, 5-HT and the neuropeptides directly influence the activity of SSNNs and are concerned with the autonomic regulation of nasal and palatal mucosa, lacrimal glands and cerebral blood vessels of the rat.

Afferent Pathways↗

PubMed1995

Differential protective action of cytokines on radiation-induced apoptosis of peripheral lymphocyte subpopulations.

It is established that soluble factors involved in cell growth can prevent apoptosis of hematolymphoid cell lines in factor-deprived situations. The present study investigates the possible protective effects of various cytokines on radiation-induced apoptosis of apparently quiescent lymphocyte subpopulations. The exposure to gamma-irradiation resulted in appreciable apoptotic changes in all of lymphocyte subpopulations. Natural killer (NK) cells were the most radiosensitive, whereas CD8+ T and B cells showed weaker susceptibility to radiation and CD4+ T cells were relatively radioresistant. The radiation-induced apoptosis in NK cells was significantly inhibited by IL-2. In addition to IL-2, IL-4 and IL-7 rescued both CD4+ and CD8+ T cells from radiation-induced cell death. The viability of B cells was maintained by the presence of IL-4 but not others in culture. Furthermore, we conclude that the protective effect by each cytokine on radiation-induced apoptosis might be partly attributed to enhancement of cellular expression of bcl-2 protein.

Adult↗

PubMed1995

Expression of gamma delta T cell receptor on caprine globule leukocytes.

Histochemical characteristics and immunological surface phenotypes of globule leukocytes (GLs) of normal goats were investigated in the intestine. In the small intestine, GLs were concentrated in the base of the villus and around the crypt, whereas in the cecum and colon they were randomly distributed. Their cytoplasmic granules exclusively stained with phosphotungstic acid hematoxylin, and were negative for peroxidase and histamine in contrast to those of subepithelial mast cells. The existence of chondroitin sulfate in some granules of GLs and heparin in most granules of mast cells were revealed by alcian blue staining and digestion with chondroitinase ABC. Isolated intestinal GLs were positive for T cell receptor (TcR) 1-N24 (gamma delta) and CD8 alpha, and negative for WC1-N3 and WC1-N4. Cryostat sections of ileum revealed preferential intraepithelial distribution of both TcR1-N24+ cells and CD8+ cells. WC1-N3+ and WC1-N4+ cells were rarely seen in the epithelium and lamina propria. These results indicate that caprine GLs are a gamma delta T cell subset, which is a different cell population from WC1 positive gamma delta T cells.

Animals↗

PubMed1995

IL-4 upregulates Fc epsilon RI alpha-chain messenger RNA in eosinophils.

By using the reverse transcription polymerase chain reaction and Southern blot hybridization, we demonstrated that Fc epsilon RI alpha-chain (Fc epsilon RI alpha) messenger RNA was expressed in eosinophils purified from the peripheral blood of patients with allergic rhinitis and that this expression was enhanced by IL-4. However, studies in which flow cytometry or immunostaining was used did not reveal the expression of Fc epsilon RI alpha protein on eosinophils from peripheral blood. Neither IL-4 alone nor the combination of IL-4 and other cytokines could induce detectable Fc epsilon RI alpha protein; nevertheless, they do express Fc epsilon RI alpha mRNA. Double-labeling immunostaining on cryostat sections of nasal mucosa clearly demonstrated that some Fc epsilon RI alpha-positive cells were eosinophil cationic protein-positive, which confirms their eosinophilic nature. Not all the eosinophil cationic protein-positive cells express on Fc epsilon RI alpha signal. Considering that Fc epsilon RI alpha mRNA was detectable in four of five samples of eosinophils from those patients with nasal allergy and that only one of five eosinophil samples from normal subjects expressed Fc epsilon RI alpha mRNA, the level of Fc epsilon RI expression may be correlated with the activation of eosinophils. It seems very likely that some other unidentified factors are required for the process from the expression of Fc epsilon RI alpha mRNA to that of Fc epsilon RI as a protein.

Adolescent↗

PubMed1995

The role of thymus in the aging of Th cell subpopulations and age-associated alteration of cytokine production by these cells.

Mouse CD4+ T cells were subdivided into two subpopulations, naive (CD44low CD45RBhigh) and memory (CD44high CD45RBlow) T cells, by flow cytometric analysis. Examination of spleen and peripheral blood of C57BL/6 mice of various ages revealed that there was a reciprocal age-associated change in these two subpopulations, i.e. naive T cells predominant in young mice decreased with age, while memory T cells increased. In order to investigate the role of the thymus in the age change of naive and memory T cells, we employed two experimental systems: radiation bone marrow chimeras constructed between young and old mice, and grafting of young or old thymus into nude mice. Data from these two experiments suggested that the young thymus has a greater ability to provide naive T cells than the old thymus, while the old thymus favors the maintenance of memory T cells rather than naive T cells. In reference to cytokine production by enriched naive and memory T cells, young naive T cells produced mainly IL-2 and young memory T cells mainly IL-4. On the other hand, in old mice, memory T cells produced twice as much IL-2 than naive T cells, although the level was significantly lower than that of young mice. In addition, old naive T cells produced twice as much IL-4 than old memory T cells. These results suggested a distinct age change in the profile of cytokine production and functional heterogeneity of two Th cell subpopulations.

Age Factors↗

PubMed1995

Delineation of producing ability of IgG and IgA subclasses by naive B cells in newborn infants and adult individuals.

Neonatal B cells with the naive (sIgD+) phenotype are able to generate IgG- and IgA-producing cells as well as IgM production in the presence of memory CD4+ T cells expressing L-selectin (CD62L) in pokeweed mitogen-stimulated cultures. We used this system to examine comparatively the ability of naive B cells to produce IgG and IgA subclasses in newborn infants and adult individuals. Naive B cells were enriched from both donors on the basis of sIgD positivity, and memory (CD45RO+) CD4+ T cells with CD62L expression were isolated from adults. We here demonstrate some differences in profiles of IgG and IgA subclass production between neonatal and adult naive B cells. In neonatal B cells, IgG1 and IgG3 were predominantly produced, but IgG2 and IgG4 production was virtually absent. Similar to neonatal B cells, adult naive B cells produced mainly IgG1 and IgG3, although memory (sIgD-) B cells from adults secreted all of the IgG subclasses. It should be noted that low but detectable levels of IgG2 and IgG4 were found in adults' naive B cell cultures. Although IgA produced by neonatal B cells was exclusively IgA1, IgA2-secreting cells were identifiable in adult naive B cells. The results suggest that further class switch of naive B cells to IgG2, IgG4 and IgA2 in addition to IgG1 and IgG3 may be controlled by their own age-dependent maturation process.

Adult↗

PubMed1995

Advancement of the mandible improves velopharyngeal airway patency.

The velopharynx is the most common site of obstruction in patients with obstructive sleep apnea (OSA). Advancement of the mandible effectively reverses the pharyngeal obstruction. Accordingly, we hypothesized that mandibular advancement increases cross-sectional area of several segments of the upper airway, including the velopharynx and the oropharynx. We examined the pressure-area properties of the pharyngeal airway in 13 patients with OSA. Under general anesthesia and total muscle paralysis, the pharynx was visualized with an endoscope connected to a video-recording system. During an experimentally induced apnea, we manipulated the nasal pressure from 20 cmH2O to the point of total closure at the velopharynx. The procedure was repeated after maximal forward displacement of the mandible. Measurements of the cross-sectional area at different levels of nasal pressure allowed construction of a static pressure-area relationship of the "passive pharynx," where active neuromuscular factors are suppressed. In 12 of 13 patients with OSA, advancement of the mandible stabilized the airway by reducing the closing pressure and increasing the area at any airway pressure. Thus the maneuver shifted the static pressure-area curve of the velopharynx and the oropharynx upward in these patients. We conclude that anterior movement of the mandible widens the retropalatal airway as well as that at the base of the tongue in the passive pharynx of OSA patients.

Adult↗

PubMed1995

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis.

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Adolescent↗

PubMed1995

Differential diagnosis of pulsatile neck masses by Doppler color flow imaging.

A pulsatile neck mass (PNM) requires careful judgment in its evaluation, and it is difficult and inaccurate to diagnose a PNM only by physical examination, even though a thrill or bruit is present. Doppler colorflow imaging (DCI) was performed as an initial evaluation in nine patients with PNMs. Intravenous digital subtraction angiography, intra-arterial angiography, X-ray computed tomography, and magnetic resonance imaging were performed in selected cases. The DCI revealed seven vascular masses (three tortuosities of the common carotid artery, two tortuosities of the brachiocephalic artery, one pseudoaneurysm, and one traumatic arteriovenous fistula) and two nonvascular masses (one neurofibroma and one metastatic lymph node). The clinical diagnoses of all the vascular masses were defined by DCI. In nonvascular masses, fine-needle aspiration biopsy could be performed relatively safely and accurately by monitoring the feeding artery or the common carotid artery by DCI. This method was quite useful for the initial evaluation in the differential diagnosis of PNMs.

Adult↗

PubMed1995

Role of capsaicin-sensitive trigeminal nerves in development of hyperreactive nasal symptoms in guinea pig model of nasal allergy.

The effect of capsaicin pretreatment on frequency of sneezing, decrease of nasal patency, and increase of vascular dye leakage induced by antigen or histamine challenge on the guinea pig nasal mucosa was investigated. The animals were sensitized intraperitoneally with ovalbumin. Capsaicin pretreatment significantly inhibited sneezing induced by nasal challenge with histamine and antigen, indicating that capsaicin-sensitive sensory nerves constitute an afferent pathway of the sneezing reflex in nasal allergy. Although capsaicin pretreatment tended to inhibit the decrease of nasal patency and the increase of vascular dye leakage of the nasal mucosa induced by antigen challenge, this tendency was not statistically significant. The present study indicated that the participation of a local reflex via capsaicin-sensitive trigeminal nerves in nasal vascular responses observed after antigen challenge in the guinea pig model of nasal allergy is rather small compared to the large direct vascular effects of chemical mediators released from basophilic cells in the nasal mucosa.

Airway Resistance↗