Biomedical subjects

N Hamano

Publications and source records attributed to N Hamano.

At least 19 recordsLinked to original sources

PubMed2000

Interleukin-13 and tumour necrosis factor-alpha synergistically induce eotaxin production in human nasal fibroblasts.

BACKGROUND: There is increasing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. However, the mechanism involved in the production of eotaxin has yet to be clarified. Most recently, it has been shown that interleukin (IL) -4 induces eotaxin in dermal fibroblasts. A novel cytokine termed IL-13, which binds to the alpha-chain of the IL-4 receptor, shares many biological activities with IL-4. It is known that fibroblasts express the IL-4 receptor and produce collagen type I upon stimulation with IL-4. OBJECTIVE: We investigated whether IL-13, as well as IL-4, are able to induce eotaxin production in human nasal mucosal fibroblasts (HNMFs). Furthermore, we investigated the effect of costimulation of IL-13 and TNFalpha on eotaxin production. METHODS: HNMFs, isolated from inferior nasal mucosa samples, were stimulated by various kind of cytokines for 1-36 h at 37 degrees C in 5% CO2. The change in the expression of eotaxin mRNA was then evaluated by reverse transcriptase-polymerase chain reaction and the Southern blot analysis. The amount of eotaxin in the culture media was measured by ELISA. RESULTS: IL-13 as well as IL-4 dose-dependently induced eotaxin expression in HNMFs. Furthermore, IL-13 and TNFalpha synergistically induced eotaxin expression in HNMFs, while they hardly induced eotaxin expression in endothelial cells, epithelial cells or eosinophils. The synergy was observed when pre-incubation of HNMFs with IL-13 was followed by a stimulation with TNFalpha, or HNMFs were simultaneously stimulated with IL-13 and TNFalpha. CONCLUSION: These results strongly indicate that IL-13, as well as IL-4, may be important in eotaxin-mediated eosinophilic inflammation in nasal mucosa. In addition, in nasal mucosa, fibroblasts are the major cell source for eotaxin.

Adult↗

PubMed2000

Transepithelial migration of activated eosinophils induces a decrease of E-cadherin expression in cultured human nasal epithelial cells.

BACKGROUND: The damage of respiratory epithelium in allergic diseases has a close correlation with the extent of eosinophil infiltration. It seems to be a good possibility that eosinophil infiltration could induce the changes in the expression of the epithelial cell adhesion molecules, which play a key role in the maintenance of structural and functional rigidity of epithelium. OBJECTIVE: We observed the expression of E-cadherin in cultured human nasal epithelial cells (HNECs) to study whether could it be affected by transepithelial migration of inflammatory cells, especially eosinophils. METHODS: In vitro study of the transmigration assay was designed using various types of inflammatory cells and HNEC monolayers. Various assays of each experimental group were done under the stimulation of interleukin-5 (IL-5) and/or platelet activating factor (PAF). Subsequently immunohistochemistry for E-cadherin was performed in the HNECs. The intensity of immunofluorescence of E-cadherin was quantified using confocal laser scanning microscopy (CLSM) system and compared before and after the transmigration. RESULTS: The mean intensity of immunofluorescence for E-cadherin decreased significantly after the transmigration of any types of inflammatory cells. Above all, the migration of eosinophils treated with IL-5 and PAF had an eminent effect on the decrease, whereas the degranulation extracts derived from eosinophils activated by IL-5 and secretory IgA (sIgA) did not affect the intensity. CONCLUSION: This work suggests that transepithelial migration of inflammatory cells can directly induce the decrease in epithelial E-cadherin expression. Furthermore, the most prominent change was induced by transmigration of activated eosinophils, which might be caused by some mechanisms independent of the eosinophil contents. The decrease in E-cadherin expression may trigger the damage of epithelial barrier, which contributes to the pathogenesis of allergic diseases.

Adolescent↗

PubMed2000

Mutation analysis of the PTEN / MMAC1 gene in Japanese patients with Cowden disease.

Cowden disease (CD), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with high risk of breast and thyroid cancer. Recently, germline mutations in PTEN / MMAC1, which has nine exons encoding a dual specificity phosphatase with homology to tensin and auxilin, have been identified on chromosome 10q23 in some 40 to 80% of CD patients. Our polymerase chain reaction amplification and sequence analysis of all coding regions identified five different mutations including four novel germline mutations among 5 of 12 unrelated Japanese CD patients. The novel findings included a missense mutation (G --> T) at nucleotide 1004 in exon 8 resulting in an arginine-to-leucine change at codon 335 (R335L), two novel splice-site mutations (209 + 1delGT and 209 + 1delGTAA) in intron 3, and insertion of G at nucleotide 632 in exon 6 (632insG). We also detected a nonsense mutation (C --> T) at nucleotide 697 producing R233X in exon 7, which has been reported previously. From reported phenotypic data concerning CD patients from five different families who had the R233X mutation, it may be suggested that R233X mutation correlates with macrocephaly. Although previous reports have implicated exon 5 as a "hot spot," we found no mutation in exon 5.

Adult↗

PubMed2000

[Cowden disease].

Cowden disease is an autosomal dominant disorder associated with an increased risk of developing benign and malignant tumors in many organ systems including the breast, thyroid, skin, central nervous system and gastrointestinal tract. Recently, germline mutations in PTEN (also known as MMAC1/TEP1) have been identified on chromosome 10q23 in Cowden disease patients. This gene is suggested to be a tumor suppressor gene, because coding-region mutations are observed in several tumor specimens or tumor cell lines. PTEN functions as a dual specificity phosphatase and lipid phosphatase. PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival. Furthermore, PTEN may also inhibit cell migration, spreading, and focal adhesion by interacting with the focal adhesion kinase.

1-Phosphatidylinositol 4-Kinase↗

PubMed1999

Diesel exhaust particulates upregulate histamine receptor mRNA and increase histamine-induced IL-8 and GM-CSF production in nasal epithelial cells and endothelial cells.

BACKGROUND: Histamine is the most important chemical mediator in the pathogenesis of nasal allergy. Diesel exhaust particulates (DEPs) are common air pollutants from diesel engine-powered car exhaust and cause chronic airway diseases. Recently we observed that the nasal reactivity to histamine was enhanced in diesel exhaust-exposed guinea-pigs. It was also revealed that epithelial cells and endothelial cells in the airway produce certain cytokines in response to histamine. OBJECTIVE: We examined the effects of DEP extract on the expression of histamine H1 receptor (H1R) mRNA in human nasal epithelial cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs), and on the production of IL-8 and GM-CSF induced by histamine. METHODS: HNECs and HMMECs were isolated from human nasal mucosa specimens. HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract. The change in the expression of H1R mRNA was then evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and the Southern blot analysis. To investigate the effects of DEP extract on the histamine-induced cytokine production, HNEC and HMMEC monolayers were cultured in the presence or absence of DEP extract for 3-24 h. After three washes with PBS, they were then incubated with 10(-6) mol/L histamine for 24 h. The amounts of IL-8 and GM-CSF in the culture media were measured by enzyme-linked immunoabsorbent assay. RESULTS: DEP extract increased the expression of H1R mRNA in both HNECs and HMMECs. The amount of IL-8 and GM-CSF, induced by histamine, was significantly higher in DEP extract pretreated HNECs and HMMECs than nontreated HNECs and HMMECs. CONCLUSION: These results strongly suggest that DEP accelerates the inflammatory change by not only directly upregulating H1R expression but also increasing histamine-induced IL-8 and GM-CSF production.

Cell Survival↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

Diesel exhaust particulates enhance eosinophil adhesion to nasal epithelial cells and cause degranulation.

Diesel exhaust particulates (DEP) are a common air pollutant from diesel-engine-powered car exhaust and are thought to cause chronic airway diseases. On the other hand, eosinophils are major components of allergic inflammatory disorders such as asthma, nasal allergy and atopic dermatitis. We examined the effects of DEP and DEP extract (extract of polyaromatic hydrocarbons) on eosinophil adhesion, survival rate and degranulation. Eosinophils, human mucosal microvascular endothelial cells (HMMECs) and human nasal epithelial cells (HNECs) were preincubated in the presence or absence of DEP and DEP extract. 35S-labeled eosinophils were allowed to adhere to monolayers of HMMECs and HNECs. After washing, 35S radioactivity was determined and numbers of adherent eosinophils were calculated using each standard curve. The effects of DEP and DEP extract on eosinophil survival rate and degranulation were also determined. Although neither DEP nor DEP extract affected the adhesiveness of HMMECs and HNECs to eosinophils, 5 ng/ml of DEP extract and 50 ng/ml of DEP extract each significancy increased eosinophil adhesiveness to HNECs (134+/-9 and 143+/-8%, respectively; p<0.01 vs. control), but neither effected eosinophil adhesiveness to HMMECs. DEP extract also induced eosinophil degranulation without changing the eosinophil survival rate. Given that eosinophil-derived lipid mediators and toxic proteins play important roles in the development of nasal allergy, the above findings strongly suggest that DEP plays an important role in promoting the nasal hypersensitivity induced by enhanced eosinophil infiltration of epithelium and eosinophil degranulation.

Adult↗

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

[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↗

PubMed1993

Intussusception caused by a carcinoma of the cecum during pregnancy: report of a case and review of the literature.

A case of intussusception due to a carcinoma of the cecum during pregnancy is reported. A 27-year-old pregnant female was admitted to Shimodate Municipal Hospital because of abdominal pain, nausea and vomiting. Her abdomen was distended, and a relatively hard mass was palpable in the right hypochondrium. Following a diagnosis of intussusception by ultrasonography, a laparotomy was performed. The lesion causing the intussusception was found to be a carcinoma of the cecum, and thus a right hemicolectomy with lymph node dissection was carried out. Histological examination revealed that the tumor was a well-differentiated adenocarcinoma which had invaded the muscularis propria but was superficial to the subserosa. None of the lymph nodes were cancerous. The incidence of colonic cancer above the peritoneal reflection during pregnancy is very low. Only 24 cases have been previously reported; our patient is only the 25th case, as well as being the first case demonstrating Dukes' A. Due to the intussusception, ultrasonography was effective for diagnosis and the patient was able to undergo a curative operation at an earlier stage than other patients.

Adenocarcinoma↗

PubMed1993

[Two elderly cases of megacolon associated with cerebral infarction and diabetes mellitus].

The authors experienced two elderly patients of megacolon associated with cerebral infarction and diabetes mellitus. The first patient was a 66-year-old female who was admitted to our hospital for rehabilitation with a complaint of knee pain. She had suffered from diabetes mellitus since she was 30 years old and multiple cerebral infarction since age 62. Two months after admission, she had an episode of abdominal distension and obstructive symptoms. The roentgenograms of her abdomen showed diffuse dilatation of the colon. The second patient was a 78-year-old female admitted to our hospital with complaints of abdominal pain, distension of the abdomen and vomiting. Her abdomen was severely distended and plain roentgenograms of the abdomen, X-ray studies of the colon with the aid of contrast medium and CT scan of the abdomen showed striking dilatation of the colon. Megacolon may be congenital or acquired, and in acquired forms the conditions are secondary to organic diseases, smooth muscle atrophy, metabolic and neurological diseases, ulcerative colitis or psychogenic origin (idiopathic). The two patients in this series were suffered from cerebral infarction and diabetes mellitus. The mechanisms of megacolon seen in these two patients are not known, but involvement of the visceral autonomic innervation is presumed. Some elderly patients have chronic constipation, and dilatation of the colon may not be uncommon due to underlying diseases or drugs. Therefore, when examining elderly patients, careful attention should be paid to their bowel movement.

Aged↗

PubMed1983

Organic acids and branched-chain amino acids in body fluids before and after multiple exchange transfusions in maple syrup urine disease.

We successfully treated a critically ill infant with the classical type of maple syrup urine disease by multiple exchange transfusions via a peripheral artery and vein and with positive calorie supplementation in the early stage of therapy. Clinical improvement was definite after the plasma leucine level fell below 1 mmol/l. There was a close linear correlation between plasma concentrations of branched-chain amino acids and their corresponding branched-chain alpha-keto acids and branched-chain alpha-hydroxy acids. alpha-Hydroxy acids were more easily excreted in the urine than alpha-keto acids and amino acids. Our studies on urinary organic acids supported the existence of minor metabolic pathways of branched-chain alpha-keto acids, although they were not thought to be important in eliminating accumulated alpha-keto acids. Urinary excretion of succinic acid and alpha-ketoglutaric acid, which are components of the citric acid cycle, increased transiently during the patient's convalescence. The cerebrospinal fluid/plasma ratios for branched-chain amino acids, alpha-keto acids, and alpha-hydroxy acids were very high before the transfusions and decreased after improvement. The cerebrospinal fluid/plasma ratios for 5-carbon acids, alpha-ketoisovaleric acid and alpha-hydroxyisovaleric acid were much higher than for other branched-chain acids not only in the patient but also in normal controls. Cerebrospinal fluid levels of alpha-ketoisocaproic acid and alpha-hydroxyisovaleric acid were as high as 1 mmol/l in our patient.

Amino Acids, Branched-Chain↗