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Biomedical subjects

A Konno

Publications and source records attributed to A Konno.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

Nitric oxide synthase-immunoreactive nerve fibers in the nasal mucosa of the rat.

An immunohistochemical study was performed to detect the localization of nitric oxide synthase (NOS) in the rat nasal mucosa by light and electron microscopy. NOS-immunoreactive nerve fibers were observed around blood vessels and seromucous glands. They were found in the subepithelial layer and even within the epithelium. But no NOS-immunoreactivity was found in the olfactory neuroepithelium. Electron microscopy showed that NOS-immunoreactive nerve profiles were in close contact with the cytolemma of respiratory epithelial cells and acinar cells of seromucous glands. NOS-immunoreactive axon varicosities were located at a considerable distance from the smooth muscle of arterioles and small veins as well as the endothelial cells of venules and capillaries. We confirmed that NOS-containing nerves innervated the epithelium, blood vessels and seromucous glands of the nasal mucosa. These findings, collectively, suggested the possibility that nitric oxide participated in the sensory function of the epithelium, the secretory activities of the nasal gland, and the regulation of vascular tone and vascular permeability in the nasal mucosa.

Amino Acid Oxidoreductases

Differential expression of bcl-2 and susceptibility to anti-Fas-mediated cell death in peripheral blood lymphocytes, monocytes, and neutrophils.

The recently identified Fas antigen (Ag) is a cell surface molecule that can mediate apoptosis. The cytoplasmic product of proto-oncogene bcl-2 has been shown to prolong the cellular survival by inhibiting apoptosis. To elucidate the physiologic significance of expression of both molecules, we examined the expression of Fas Ag and bcl-2 on blood leukocyte populations and evaluated their sensitivity to the cytolytic action of anti-Fas antibody. Although Fas Ag was expressed on a fraction of lymphocytes, both neutrophils and monocytes expressed Fas Ag constitutively. In contrast, there was marked difference among these leukocytes regarding bcl-2 expression. Lymphocytes expressed bcl-2 intensely, but monocytes showed weaker bcl-2 expression, and neutrophils were essentially absent for bcl-2 expression. Seemingly reflecting this lack of bcl-2-expression, neutrophils more easily underwent apoptotic cell death in vitro as compared with monocytes and lymphocytes. We showed that anti-Fas antibody affectively accelerated apoptotic cell death in neutrophils. However, the apoptosis-inducing effect of anti-Fas antibody was minimal on monocytes, and lymphocytes were resistant to this antibody. These results suggest that anti-Fas-mediated cell death may, in part, be determined by bcl-2 expression status in Fas+ lymphoid and hematopoietic cells.

Adult

Ionizing radiation induces apoptotic cell death in human TcR-gamma/delta+ T and natural killer cells without detectable p53 protein.

The p53 tumor suppressor gene has been shown to be involved in programmed cell death, apoptosis, in murine immature thymocytes after treatment with ionizing radiation. Ionizing radiation also induces apoptosis in peripheral mature lymphocytes. In this work, we investigated the p53 participation in radiation-induced apoptosis in human peripheral blood lymphocytes (PBL) subpopulations. Exposure to gamma-irradiation resulted in an appreciable induction of apoptotic cell death in TcR-alpha/beta+ (CD4+ and CD8+) T cells, TcR-gamma/delta+ T cells, B cells and natural killer (NK) cells, as assessed by DNA fragmentation as well as the morphological characteristics. Importantly, it was found that there was a marked difference among PBL subpopulations as regards the induction of p53 protein by gamma-irradiation. Similar to previous observations for murine thymocytes, p53 induction in TcR-alpha/beta+ T cells and B cells after gamma-irradiation was evident by Western blot analysis. Radiation-induced apoptosis in TcR-alpha/beta+ T cells and B cells was efficiently inhibited by cycloheximide, indicating the requirement of de novo protein synthesis, including p53 protein, for radiation-induced apoptosis in both subpopulations. In marked contrast, no identifiable levels of p53 protein were induced in either TcR-gamma/delta+ T or NK cells after gamma-irradiation. In addition, it was demonstrated that radiation-induced cell death in TcR-gamma/delta+ T and NK cells could be prevented by interleukin-2, but not by cycloheximide. These results imply that radiation-induced lymphocytic apoptosis can be mediated by p53-dependent or -independent mechanisms.

Adult

Biochemical properties of eosinophils and their preferential accumulation mechanism in nasal allergy.

Recent information intensely suggests that eosinophils are pivotal proinflammatory cells in a variety of allergic inflammatory diseases including bronchial asthma, nasal allergy, hypereosinophilic syndrome, and various cutaneous diseases. Eosinophils, via their release of basic proteins and lipid mediators, are strongly implicated in the onset of allergic symptoms of the nose. They play an important role particularly in nasal swelling and hyperreactivity. Despite the current multitude of research investigating eosinophils in vitro, the mechanism that mediates and controls the accumulation of eosinophils in vivo is incompletely understood. In this article the following issues will be addressed: (1) How do eosinophils migrate into the nasal mucosa? (2) What factors contribute to preferential eosinophil accumulation and their degranulation in nasal mucosa? (3) How can we inhibit the eosinophil accumulation and activation?

Animals

Mode of action of a topical steroid on immediate phase reaction after antigen challenge and nonspecific nasal hyperreactivity in nasal allergy.

This study compared the effects of 2-week administration of a topical steroid (fluticasone propionate [FP] 100 micrograms twice daily) with placebo in 28 patients with perennial nasal allergy who were allergic to house dust and mites in a double-blind randomized study. The number of inflammatory cells and decidual epithelial cells and concentrations of tryptase and eosinophil cationic protein in nasal lavages, and reactivity of the nasal mucosa to histamine and to antigen were investigated. The topical steroid, FP, significantly inhibited all of these assessments. The degree of improvement of nasal reactivity to histamine significantly correlated with the degree of decrease in eosinophil cationic protein levels.

Administration, Topical

Mechanism of eosinophil infiltration in the patient with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (Kimura's disease). Mechanism of eosinophil chemotaxis mediated by candida antigen and IL-5.

Kimura's disease is a chronic granulomatous disease of unknown etiology. Although eosinophilia is one of the characteristic features in this disease, little is known about the mechanism of eosinophilia. In the present study it was demonstrated that interleukin-5 (IL-5) was produced and released from the site of a granuloma and lymph nodes after stimulation with candida antigen. It was also shown that peripheral blood eosinophils from patients with Kimura's disease contained a large proportion of hypodense eosinophils and that their viability was prolonged. These results strongly suggest that locally produced IL-5 induced by candida antigen contributes to the eosinophilia in this disease.

Adult

Hemodynamic changes in the head and neck after ligation of the unilateral carotid arteries: a study using color Doppler imaging.

For evaluation of the hemodynamics of the collateral circulation to the ligated external carotid artery (ECA) region, we measured the blood flow direction and volume in branches of the ECA in patients with unilateral carotid artery ligation before and during digital suppression of the common carotid artery (CCA) on the ligated and nonligated sides with color Doppler imaging and angiography. The main collateral pathway to the ligated ECA region was the ipsilateral occipital artery through Richter's anastomosis from the vertebral artery in the case of unilateral ECA ligation, and was the contralateral carotid artery in the case of unilateral CCA, ECA, and internal carotid artery resection. The superior and inferior labial arteries were important as the collateral pathway from the contralateral ECA.

Blood Flow Velocity

Effect of psychic stimulation on plasma catecholamine concentrations and nasal patency in patients with nasal allergy.

To compare the degree of sympathoadrenal and nasal vascular response to psychic stimulation between patients with nasal allergy and normal controls, we measured the changes in plasma norepinephrine and epinephrine concentrations and nasal patency elicited by cannulation into the forearm vein and mental arithmetic in 28 patients with nasal allergy and age- and sex-matched normal controls. Ten of the 28 allergy patients had markedly swollen, pale, edematous nasal mucosa and served as a subgroup of nasal allergy patients. Plasma catecholamine levels increased significantly, with a synchronous increase of nasal patency, during stimulation. Among the three groups, no statistical differences were observed in plasma catecholamine levels either at rest or during stimulation. There was no significant difference in extent of increase of nasal patency induced by stimulation in the total group of subjects with nasal allergy compared with normal controls. However, it was significantly smaller in a subgroup of nasal allergy patients having markedly pale, edematous swelling of the nasal mucosa.

Adult

Perforin-like immunoreactivity in feline globule leukocytes and their distribution.

Distributional and immunohistochemical characteristics of the feline globule leukocyte (GL) were investigated by light microscopy. The GL, which contained eosinophilic large granules in the cytoplasm, was frequently found in the epithelia of the intestine and gall bladder, and less frequently found in those of the gastric pit, intrahepatic bile duct, and interlobular secretory duct of the pancreas. No GL was seen in the respiratory and urogenital organs. The GLs composed a homogeneous cell population including no mast cells according to the following histochemical stainings; phosphotungstic acid hematoxylin, alcian blue and peroxidase. The feline GL showed perforin-like immunoreactivity to anti-human perforin monoclonal antibody, but did not show histamine-immunoreactivity to anti-histamine polyclonal antibody. The results suggest that the feline GL is a lineage of large granular lymphocytes. The epitheliotropism and characteristics as granular lymphocytes of the feline GLs were similar to those of the intestinal gamma delta T cells of the mouse.

Animals