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Biomedical subjects

A Konno

Publications and source records attributed to A Konno.

At least 73 records · Page 4Linked to original sources

Changes in nasal responsiveness to histamine and to specific antigen after laser surgery.

An initial treatment with several kinds of anti-allergic medicines is useful for reducing nasal allergy symptoms in patients suffering from Japanese cedar pollinosis during the pollen season. Since laser surgery before the pollen season seems to have a preventive effect as well, it would be of interest to know the time course of changes in the nasal reactivity to specific and non-specific stimuli after laser surgery. In this study, we investigated the changes in the nasal reactivities to specific antigen and histamine after CO2 laser surgery. The nasal reactivities to both specific antigen and histamine were enhanced 2 weeks after the laser surgery. On the other hand, they were significantly reduced after 4 weeks. Our data strongly suggest. therefore. that laser surgery must be done more than 4 weeks before the start of the pollen season to avoid temporary enhancement of nasal allergy symptoms.

Adolescent↗

Analysis of long-term results of our combination therapy for squamous cell cancer of the maxillary sinus.

Seventy-four patients between 1971 and 1982 in Period I and 32 patients between 1982 and 1987 in Period II with maxillary sinus squamous cell cancer were treated by combination therapy consisting of preoperative LINAC X-ray irradiation with 5-flourouracil intra-arterial chemotherapy followed by maxillectomy and primary reconstruction. In Period II, 21 patients received preoperative cisplatinum (CPPP) microcapsule chemoembolization and pepleomycin (PEP) i.m. and or postoperative CDDP i.v. with PEP i.m. in addition to the combination therapy administered in Period I depending on systemic conditions, tumor stage and histopathological type. Five and 10-year crude survival rates were 68.9% and 55.4%, respectively, for Period I and 71.9% and 56.3% for Period II, with no significant difference between the two trials. In 21 selected patients in Period II, who had additional chemotherapy with preoperative CDDP chemoembolization and/or postoperative i.v. infusion of CDDP with pepleomycin i.m., 5 and 10-year survival rates were 85.7% and 61.9%, respectively.

Antineoplastic Agents↗

Analysis of factors affecting long-term treatment results of adenoid cystic carcinoma of the nose and paranasal sinuses.

At Akita University Hospital (from 1971 to 1987) and at Chiba University Hospital (from 1983 to 1988), 17 patients with adenoid cystic carcinoma of the nose and paranasal sinuses were treated by en bloc tumor resection followed by primary reconstruction of the maxilla. Pre- and postoperative radiation was combined in 5 and 6 patients, respectively. Ten-year cancer-free survival rates were 59.3% in the 12 patients with maxillary sinus tumors and 50% in the 4 patients with nasal tumors. One patient with a sphenoid sinus tumor died within 5 years. Ten-year cancer-free survival was affected markedly by grade of tumor extension. Among T1N0M0 and T2N0M0 patients (of which there were 1 and 7, respectively), only 1 died of unrelated causes, and 6 patients survived cancer-free for more than 10 years. However, 4 of the 6 T3N0M0 patients died, and the cause of death was distant metastasis in 2, intracranial tumor extension in 1, and unrelated causes in 1. All 3 T4N0M0 patients died, 2 due to intracranial tumor extension and 1 of unrelated causes. The cause of death was distant metastasis in 3, local recurrence in 3, 2 of whom had intracranial tumor extension, and unrelated causes in 2. Prevention of distant metastasis and intracranial tumor extension was considered to be crucial for improving treatment results after en bloc tumor resection. Preoperative radiation was thought to decrease incidence of distant metastasis. In 5 patients who had preoperative radiation. 4 survived cancer-free for more than 10 years, and only 1 patient died of unrelated cause. However. of the 6 patients who had postoperative radiation, 2 died of distant metastasis and another 2 died of intracranial tumor extension. Of the 6 patients who did not have radiation therapy, the causes of death were local recurrence in 1, distant metastasis in 1 and unrelated causes in 1. Preoperative radiation in 5 patients showed histopathologically moderate or marked degeneration and necrosis of tumors in all patients. Although the number of patients in this study is too small to allow statistical analysis of the data, our present modality of treatment for adenoid cystic carcinoma of the nose and paranasal sinuses is routine combination of preoperative full dose radiation, en bloc tumor resection and primary reconstruction, including en bloc resection of the cranial base in selected T4 patients.

Antineoplastic Agents↗

Metastasis of renal cell cancer to the ethmoid sinus.

The origin of metastatic tumors in the nasal or paranasal sinuses is often renal cancer, and metastasis to the nasal or paranasal sinuses sometimes takes a long time after nephrectomy. The present paper deals with one patient with metastasis of renal cancer to the ethmoid sinus 2 years after nephrectomy. Even though many metastatic tumors originating from renal cancer develop in multiples, most metastatic tumors in the nasal or paranasal sinuses are single and treated surgically. However, even if multiple tumors are found in the nasal and paranasal region and other organs, surgery will be effective in preventing epistaxis and subsequent anemia. Also, when removing a tumor it will be effective to identify the feeding arteries of the tumor, perform embolization therapy, and clip the necessary arteries.

Blood Loss, Surgical↗

Late phase response in nasal mucosa closely correlated with immediate phase reaction and hyperreactivity to histamine.

It has been suggested that the onset of the late phase response (LPR) and hyperreactivity to non-specific stimuli occurs in the lower airway. However, its relationship in the nose has not yet been studied. This study was designed to examine the mechanism of LPR and the relationship between LPR and hyperreactivity. A total of 25 Japanese cedar pollinosis patients participated in this study. On the first visit, the frequency of sneezes, weight of nasal discharge, and the nasal airway resistance (NAR) were time-dependently measured without antigen challenge. The histamine reactivity was observed after 12 h. The same protocol was used during the second to fourth visits. The frequency of sneezes, weight of nasal discharge, and NAR were measured continuously for 12 h after antigen challenge, and nasal reactivity to histamine was observed. The percent change of NAR during immediate phase response (IR) and during LPR showed a significant correlation. The frequency of sneezes and weight of nasal discharge induced by histamine were both significantly higher in the positive than in the negative LPR group. These results suggest that the chemical mediators and inflammatory cells inducing nasal swelling during IR cause, directly or indirectly, nasal swelling during LPR, and induce hyperreactivity to histamine.

Acute-Phase Reaction↗

The potential role of interleukin-13 in eosinophilic inflammation in nasal mucosa.

BACKGROUND: Recent studies have revealed that interleukin (IL)-13, as well as IL-4, causes de novo surface expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of the umbilical vein and accelerates selective eosinophil migration. However, its role in allergic rhinitis remains to be clarified. Of particular interest is whether IL-13 upregulates VCAM-1 expression in human mucosal microvascular endothelial cells (HMMECs), to which eosinophils adhere in nasal mucosa. METHODS: To understand the potential role of IL-13 in eosinophilic inflammation in nasal mucosa, we examined the effects of IL-13 on the adhesiveness between HMMECs and eosinophils. RESULTS: IL-13 increased VCAM-1 expression in HMMECs, the adhesiveness of endothelial cells to eosinophils, and the transendothelial migration. On the other hand, IL-13 decreased the adhesiveness of eosinophils to HMMECs, and, as a result, accelerated eosinophil infiltration. Those effects are more potent than was those of IL-4. In addition, we also report that the amount of IL-13 in nasal mucosa was higher than that of IL-4. CONCLUSIONS: These results strongly indicate that IL-13, as well as IL-4, may be important in eosinophilic inflammation in the nasal mucosa.

Adolescent↗

Yolk sac tumor with a unique uniform hepatoid pattern histology.

BACKGROUND: Yolk sac tumors (YST) exhibit several different histological subtypes and the mechanisms of cellular differentiation and prognosis of each subtype remain unknown. RESULTS: We report two infants with sacrococcygeal YST; one represented a typical histological subtype and the other showed a hepatoid subtype with uniform histology. The isoform of alpha-fetoprotein (AFP) in the patient with the hepatoid pattern was examined by lectin-affinity immunoelectrophoresis and represented as a YST, but not hepatocellular, subtype. The patient with typical YST responded well to VAB-6 combination chemotherapy. However, this regimen was only partially effective to the patient with the pure hepatoid histological subtype, and an etoposide with ifosfamide and cisplatin (VIP) regimen as a salvage chemotherapy combined with complete tumor resection was useful to achieve complete remission (CR). Both of the patients have been in CR for more than four years.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of histamine receptors in nasal epithelial cells and endothelial cells--the effects of sex hormones.

BACKGROUND: Hyperreactivity of the nasal mucosa is a characteristic of nasal allergy. During pregnancy, aggravation of nasal allergic symptoms is occasionally observed in subjects with nasal allergy. METHODS: Using the reverse transcription-polymerase chain reaction and Southern blot hybridization method, we investigated histamine H1 receptor mRNA (H1R mRNA) expressions in specimens of nasal epithelial layer obtained by scraping, as well as cultured human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs). We compared the expressions on the specimens from patients with nasal allergy with those with nonallergic rhinitis or those from normal volunteers. In addition, we investigated the effects of female hormones on the H1R mRNA expressions in HNECs and HMMECs. RESULTS: H1R mRNA was detected in scraped specimens of nasal epithelial layer, as well as in HNECs and HMMECs. The mRNA expressions in nasal mucosal scraped specimens of epithelial layers and HNECs were more marked in patients with nasal allergy than in the other two groups. In addition, the present study demonstrates that the female hormones beta-estradiol and progesterone significantly increase the expressions of H1R mRNA on HNECs and HMMECs. CONCLUSION: The increase of the expressions of H1R mRNA may explain, in part, the nasal hyperreactivity to histamine observed in patients with nasal allergy. It has also been suggested that sex hormones are related to the preponderance of females in the incidence of allergic rhinitis after puberty, and that they are related, at least partially, to the aggravation of the nasal hyperreactivity symptoms during pregnancy through the enhanced expression of H1R mRNA on HNECs and HMMECs.

Adolescent↗

Immunohistochemical study of E-cadherin and ZO-1 in allergic nasal epithelium of the guinea pig.

Nasal epithelial damage during allergic inflammation was studied by observing the distribution of cell adhesion molecule E-cadherin and tight junction (zonula occludens) cell-cell contact associated protein ZO-1. The guinea pig model of nasal allergy, sensitized with intraperitoneally administered ovalbumin (OA) and subsequently challenged with OA intranasally, was used. In control epithelium, E-cadherin immunoreactivity was detected continuously along neighboring epithelial cell borders. ZO-1 spot-like immunoreactivity was detected in the apicolateral portion of epithelial cells corresponding to the tight junction (TJ) position, but no changes in immunoreactivity were found between control and challenged epithelia. In the challenged epithelium of sensitized animals, marked infiltration of eosinophils and structural changes, such as widening of the intercellular spaces and detachment of adjacent epithelial cells, were observed concurrently. In addition, spots negative for E-cadherin immunoreactivity were noted in the epithelium, associated with the extracellular deposition of eosinophil granule proteins. Immunoelectron microscopy revealed a decrease or disappearance of E-cadherin immunoreactivity, which took place not only in regions where intercellular spaces were wide and adjacent epithelial cells were detached, but also at the point of contact between infiltrating eosinophils and epithelial cells. Approximately 87% of eosinophils observed in the challenged epithelium were associated with such loss of E-cadherin immunoreactivity. These results suggest that the intimate epithelial cell contact mediated by E-cadherin is loosened as a consequence of eosinophil infiltration, which may trigger the initial step of subsequent epithelial destruction in allergic states.

Animals↗

Comparison of static mechanical properties of the passive pharynx between normal children and children with sleep-disordered breathing.

Collapsibility of the active pharynx, where active contraction of the upper airway muscles is evident, was previously reported to be higher in children with obstructive sleep apnea (OSA) than in those with primary snoring during sleep. Contribution of neuromuscular and anatomic factors to the increased collapsibility, however, was not estimated. We therefore evaluated collapsibility of the passive pharynx, in which upper airway muscle activities were eliminated. Our aim in the present study was to test the hypothesis that children with sleep-disordered breathing (SDB) have a structurally narrowed and a more collapsible pharynx compared with normal children. The static pressure/area relationship of the passive pharynx was endoscopically quantified in 14 children with SDB and in 13 normal children under general anesthesia with complete paralysis. The majority of children with SDB primarily closed their airways at levels of enlarged adenoids and tonsils with positive closing pressure (Pclose) (3.5+/-4.3 cm H2O), whereas half of the normal children closed their airways at the soft palate edges and the other half at the tongue bases with subatmospheric Pclose (-7.4+/-4.9 cm H2O). Cross-sectional area of the narrowest segment was significantly smaller in SDB children than in normal children. Interestingly, collapsibility of the retropalatal and retroglossal segments significantly increased in SDB children, compared with the normal subjects. We conclude that anatomic factors play a significant role in the pathogenesis of pediatric OSA and that predisposing structural abnormalities of the entire pharynx are likely to contribute to manifestation of OSA in addition to enlarged adenoids and tonsils.

Adenoids↗

Immunohistochemical diagnosis of a Merkel cell tumor in a dog.

We examined the clinical and immunohistochemical features of a Merkel (neuroendocrine) cell tumor on the skin between the eyes of a 12-year-old male Yorkshire Terrier dog. The tumor was characterized by locally expansive dermal nodules composed of solid nests or clusters of epithelioid cells surrounded by fine fibrous stroma. Basal cell epithelioma, Merkel cell tumor, and extramedullary plasmacytoma were also considered as diagnoses. Because the cytoplasm of the tumor cells stained positively for cytokeratin and chromogranin A but not for immunoglobulins, the tumor was diagnosed as a Merkel cell tumor. An electron-microscopic study of a tissue specimen revealed electron-dense granules approximately 200 nm in diameter. These granules were irregularly dispersed throughout the cytoplasm of the tumor cells, which would be expected in neuroendocrine cells. Twelve months after resection, a 0.8-cm-diameter tumor recurred at the original site. However, further follow-up of 22 months revealed no evidence of additional tumor growth, invasion, or metastasis, so we concluded that this tumor was benign.

Animals↗

Decrease in gamma-actin expression, disruption of actin microfilaments and alterations in cell adhesion systems associated with acquisition of metastatic capacity in human salivary gland adenocarcinoma cell clones.

In order to clarify how cytoskeletons and adhesion systems change through acquisition of metastatic capacity in a cancer cell, we examined the expressions of beta- and gamma-actin, the morphology of actin microfilaments and focal contacts, and also the expression of vinculin in a salivary gland adenocarcinoma cell clone cl-1, which acquired metastatic capacity, in comparison with its original clone HSGc lacking metastatic ability. Two-dimensional gel electrophoresis of Triton-insoluble fractions and combined Western blot analysis by immunostaining with anti actin-isoform antibodies showed that the expression of gamma-actin was somewhat lower than that of beta-actin in HSGc, and cl-1 expressed a comparable amount of beta-actin to HSGc, whereas gamma-actin expression by cl-1 was far less than that by HSGc. Northern blot analysis demonstrated that there was little difference in the level of beta-actin mRNA between HSGc and cl-1, while the level of gamma-actin was markedly decreased in cl-1 as compared with HSGc. In terms of morphology, cl-1 cells showed disruption of actin microfilaments and a decrease in the size and number of focal contacts on the cell surface. Furthermore, cl-1 showed decreased expression of vinculin, which became obscured even at the end of actin microfilaments. These results demonstrated that a decrease in gamma-actin, disruption of actin microfilaments, and suppression of focal contacts as well as vinculin take place in the transformation from a non-metastatic condition to a metastatic one in the human salivary gland adenocarcinoma cell clones. Thus, it was strongly suggested that these changes contribute to a decrease in cell adhesiveness and an increase in cell motility, which is probably a major cause for acquisition of metastatic potential.

Actin Cytoskeleton↗

Effect of female hormones on the production of IL-4 and IL-13 from peripheral blood mononuclear cells.

In this study we compared the concentrations of IL-4, IL-13, and IFN-gamma, which were produced by human peripheral blood mononuclear cells (PBMC) in the presence or absence of preincubation with beta-estradiol or progesterone both after a specific antigen challenge and without a specific antigen challenge. The concentrations of IL-4 and IL-13 from PBMC which had been preincubated with progesterone or gamma-estradiol for 18-24 h were significantly greater than those of IL-4 and IL-13 from PBMC which had been preincubated with PBS, the control. On the other hand, the concentration of IFN-gamma from PBMC was unchanged. We were able to confirm that the female hormones beta-estradiol and progesterone, at levels similar to those occurring during pregnancy, have the ability to induce production of IL-4 and IL-13 in human mononuclear cells. These results suggest that female hormones may aggravate nasal allergy symptoms during pregnancy by increasing IgE synthesis and inducing selective eosinophil infiltration.

Cells, Cultured↗

The effects of eotaxin on the surface adhesion molecules of endothelial cells and on eosinophil adhesion to microvascular endothelial cells.

Eosinophil recruitment occurs in tissues as the result of allergic diseases. Human eotaxin is thought to be specific to eosinophils. In this study, we examined the effects of human eotaxin on the expression of adhesion molecules on nasal microvascular endothelial cells and on eosinophil adhesion to endothelial cells. Eotaxin upregulated the expression of ICAM-1 and VCAM-1 on human nasal mucosal microvascular endothelial cells (HMMEC), but not human umbilical vein endothelial cells (HUVEC). The eotaxin-induced eosinophil adhesion to HMMEC was increased at 10 ng/ml and significantly increased at the concentration of 100 ng/ml. On HUVEC, however, eotaxin did not induce increases of eosinophil adhesion. Anti-ICAM-1 and anti-VCAM-1 mAbs significantly decreased eotaxin-induced eosinophil adhesion. These results suggest that eotaxin regulates eosinophil accumulation to the nasal mucosa through its effect on the adhesion molecules on microvascular endothelial cells.

Adult↗

Immobilization stress increases hepatic IL-6 expression in mice.

When mice were subjected to restriction of movement in a small cylinder (immobilization stress), the serum interleukin (IL)-6 level rose in 1 h, following increased expression of IL-6 mRNA in both the liver and the spleen. The IL-6 mRNA induction was much greater in the liver than in the spleen when compared on a whole-organ basis. Intraperitoneal injection of bacterial lipopolysaccharide (LPS) also increased IL-6 mRNA expression in these organs, but more preferentially in the spleen. Immunohistochemical examinations of liver tissue using an antibody against murine IL-6 revealed that immobilization stress induced IL-6 mainly in hepatic parenchymal cells, whereas LPS injection did so only in sinusoidal mononuclear cells. These results indicate that immobilization stress induces IL-6 production in the liver, especially in hepatic parenchymal cells, probably by a different mechanism from that for IL-6 induction by LPS.

Animals↗

Immunohistochemical studies on glutamatergic, GABAergic and glycinergic axon varicosities presynaptic to parasympathetic preganglionic neurons in the superior salivatory nucleus of the rat.

After the superior salivatory nucleus (SSN) neurons were labeled by administration of cholera toxin B subunit (CTB) or wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) to the pterygopalatine ganglion, morphological interactions between SSN neurons and fibers afferent to SSN neurons were examined by light and electron microscopy with double-immunostaining techniques. Antibodies to either the neurotransmitters or its receptor were used to label glutamatergic, GABAergic and glycinergic synapses on these neurons. By light microscopy, SSN neurons were identified in the ipsilateral ventrolateral part of the rostral medulla oblongata, and rich distributions of glutamate- and GABA-immunoreactive (ir) axon varicosities were observed around SSN neurons. Electron microscopy revealed that dendrites of SSN neurons received asymmetric synapses from glutamate-ir axon varicosities. Somata as well as dendrites received symmetric synapses from GABA-ir varicosities, or showed immunoreactivity for glycine receptors. Quantitative analysis by electron microscopy showed that glutamate-ir axon varicosities comprised 45.3% of total axon profiles in the SSN region, while GABA-ir varicosities were 20.8% and varicosities presynaptic to glycine receptors were 19.9%. These findings suggest that glutamatergic, GABAergic and glycinergic inputs, originated from a variety of nuclei, directly affect the activity of SSN neurons, and play a role in the regulation of the pterygopalatine ganglion of the rat.

Animals↗

Eosinophil adhesion regulates RANTES production in nasal epithelial cells.

Among the many known chemotactic factors for eosinophils, the proinflammatory chemokine RANTES is particularly important, because it is potently and selectively chemotactic for eosinophils. Throughout the process of the migration of eosinophils from the blood vessels into the nasal cavity, eosinophil functions are assumed to be regulated by surface adhesion molecules. Conversely, the messages conferred by the eosinophils to the endothelial and epithelial cells are also of great interest. In the present study, we showed that eosinophil adhesion to human nasal epithelial cells (HNECs) inhibits RANTES production in HNECs. Eosinophils were isolated from peripheral blood obtained from patients with allergic rhinitis. Human mucosal microvascular endothelial cells and HNECs were isolated from human nasal mucosa specimens. After stimulation of the HNECs in the presence of eosinophils, the secretion of RANTES, induced by a combination of TNF-alpha and IFN-gamma, appeared to have decreased. The amount of the decrease was a function of the number of involved eosinophils. On the other hand, the presence of eosinophils did not affect RANTES production by the endothelial cells. After pretreatment of the eosinophils with anti-CD18 mAb or coculture with HNECs in Transwell culture inserts, these cells did not inhibit the TNF-alpha- and IFN-gamma-induced RANTES production. These results were virtually identical with those observed on RANTES mRNA expression. The adhesion of eosinophils to HNECs plays a key role in the inhibition of RANTES production. Our data indicate that a certain established system causes the signal transfer from eosinophils to HNECs to inhibit RANTES production, thus decreasing the eosinophil infiltration.

Adult↗

Involvement of reactive oxygen intermediates in spontaneous and CD95 (Fas/APO-1)-mediated apoptosis of neutrophils.

Apoptosis is well known to be mediated by oxidative stress. To evaluate the functional role of reactive oxygen intermediates (ROI) produced by neutrophils, we compared the rates of apoptosis in neutrophils isolated from normal donors and from patients with chronic granulomatous disease (CGD), a hereditary defect in ROI production. Spontaneous cell death in CGD neutrophils in vitro was significantly inhibited relative to normal neutrophils. The acceleration of apoptosis induced by anti-Fas monoclonal antibody (MoAb) in CGD neutrophils was much slower than that seen in normal neutrophils. These findings suggest that the apoptosis of neutrophils may be mediated by endogenous oxidative products. This suggestion was confirmed by observation that apoptosis of normal neutrophils was markedly inhibited by reduction of intracellular levels of hydrogen peroxide (H2O2). The inhibition of apoptosis in normal neutrophils by adding catalase occurred regardless of the presence of anti-Fas MoAb. H2O2 increased both spontaneous apoptosis and Fas-mediated apoptosis of the CGD neutrophils in proportion to that seen in normal neutrophils. Although several factors that mediate the apoptosis of neutrophils remain to be determined, these results suggest that ROI are major mediators of the apoptosis in neutrophils and may be involved in Fas-mediated signal transduction pathway.

Apoptosis↗