Biomedical subjects

H Sakamoto

Publications and source records attributed to H Sakamoto.

At least 91 records · Page 5Linked to original sources

PubMed2000

Tamoxifen and gonadal steroids inhibit colon cancer growth in association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system.

Estrogen receptor beta (ERbeta) mediated system was tested in three colon cancer cell lines with different sensitivities. These cell lines express ERbeta and androgen receptor (AR) but not the classic estrogen receptor ERalpha. Combinations of ERbeta ligands such as estradiol (E(2)), 17 epiestriol (17E(3)), quercetin (Q) with tamoxifen (TMX) showed marked growth inhibition. The IC(50) were: 2. 0+/-0.3x10(-15), 3.0+/-1.3x10(-10) and 1.2+/-0.5x10(-14) M for DLD-1, DLD-1/5FU and DLD-1/FdUrd, respectively (TMX+E(2) treatment, mean+/-SD, n=3). The IC(50) of TMX+17E(3) were 3.5+/-1.8x10(-8), 2. 6+/-0.9x10(-8) and 1.4+/-1.1x10(-14) M and that of TMX+Q treatment were 3.4+/-2.1x10(-9), 3.6+/-0.2x10(-9) and 2.6+/-1.1x10(-9) M, respectively. This inhibition was significantly different from single agent treatment at the probability level of P<0.002. Thymidylate synthase expression and survivin expression were also markedly inhibited. The inhibition was highest with TMX+Q and lowest with TMX+dehydroepiandrosterone (DHEA). The expression of telomerase was also inhibited by TMX but combination with ERbeta agonists reversed the inhibition. The cellular sensitivity to 5FU was increased: TMX+E(2), TMX+17E(3) and TMX+Q were 1.7+/-0.5x10(-5), 8. 4+/-3.2x10(-8), 8.2+/-2.9x10(-8) and 6.3+/-3.3x10(-8) M for DLD-1 cells and 7.7+/-4.8x10(-5), 9.1+/-4.9x10(-7), 1.5+/-0.3x10(-9) and 5. 7+/-2.2x10(-8) M for DLD-1/5FU. DLD-1/FdUrd cells had IC(50) of 8. 5+/-6.1x10(-5), 1.8+/-0.8x10(-8), 37+/-1.1x10(-9) and 1.6+/-1. lx10(-9) M (mean+/-SD) for the control, TMX+E(2), TMX+17E(3) and TMX+Q. The present data indicate that ERbeta ligands in combination with TMX may have tumor static effects on colon cancer cells.

Antineoplastic Agents, Hormonal↗

PubMed2000

Mitogen-activated protein kinase plays an essential role in the erythropoietin-dependent proliferation of CTLL-2 cells.

Erythropoietin (EPO) and its receptor (EPOR) are required for development of erythrocytes. It has been shown that the ectopic expression of EPOR confers EPO-dependent proliferation on an interleukin 3 (IL3)-dependent cell line, Ba/F3, whereas the IL2-dependent T cell line, CTLL-2 expressing the EPOR (T-ER), fails to proliferate in response to EPO. However, the molecular basis of the EPO unresponsiveness in CTLL-2 has not been clarified. We found that the expression level of JAK2 in T-ER cells was much lower than that in Ba/F3 cells. Therefore, we examined the effects of forced expression of JAK2 in T-ER cells. In T-ER transformants expressing JAK2 (T-JER), EPO induced tyrosine phosphorylation of the EPOR, JAK2, and STAT5, and consequently STAT5-responsive genes including bcl-X and cis1 were normally induced. Furthermore, T-JER cells were resistant to apoptosis until at least 72 h after switching from IL2 to EPO. Although T-JER cells could not continuously proliferate in the presence of EPO, additional expression of JAK2 in T-JER (T-JJER) to a level similar to that in Ba/F3 cells supported long term proliferation in response to EPO. JAK2 was equally co-immunoprecipitated with the EPOR among T-JER, T-JJER, and Ba/F3 cells expressing the EPOR (BF-ER). However, EPO-dependent mitogen-activated protein (MAP) kinase activation was observed in T-JJER and BF-ER cells but not in T-JER cells. EPO-dependent long term proliferation of T-JER cells was conferred by expression of the constitutively activated form of MEK1. Our results suggest that MAP kinase activation is, at least in part, an important component for mitotic signal from the EPOR, and CTLL-2 cells probably lack signaling molecule(s) in JAK2 and the Ras-MAP kinase pathway.

Animals↗

PubMed2000

Regulated expression of the BTEB2 transcription factor in vascular smooth muscle cells: analysis of developmental and pathological expression profiles shows implications as a predictive factor for restenosis.

BACKGROUND: We have previously shown BTEB2, a Krüppel-like zinc finger transcription factor, to regulate expression of the SMemb/NMHC-B gene, which has been implicated in phenotypic modulation of smooth muscle cells (SMCs). The present study was done to assess the developmental and pathological expression profiles of BTEB2 and to further evaluate the clinical relevance of BTEB2 expression in human coronary artery disease. METHODS AND RESULTS: Immunohistochemistry showed developmentally regulated expression of BTEB2 with abundant expression in fetal but not in adult aortic SMCs of humans and rabbits. In balloon-injured aortas, predominant expression of BTEB2 was seen in neointimal SMCs. Atherectomy specimens obtained from primary and restenotic lesions showed predominant expression of BTEB2 to stellate SMCs. The incidence of restenosis in primary lesions was significantly higher in lesions containing BTEB2-positive cells than in lesions without (55.6% versus 25.0%, P:=0.01). CONCLUSIONS: The present study shows that BTEB2 expression is developmentally and pathologically regulated. BTEB2 is preferentially expressed in dedifferentiated or activated SMCs. Examination of human coronary artery specimens suggests that primary lesions containing BTEB2-positive cells are associated with higher risk of restenosis than BTEB2-negative lesions. These results suggest that BTEB2 can serve as a molecular marker for phenotypic modulation of vascular SMCs.

Adult↗

PubMed2000

Dendritic cell-like immunoreactivity in the glomerulus of the olfactory bulb and olfactory nerves of mice.

Dendritic cell-like immunoreactivity was examined in the mouse brain. The glomerulus of the olfactory bulb and the olfactory nerves were stained by antibodies against the dendritic cells, NLDC-145 and MIDC-8, while these structures were not stained by antibodies against microglia or macrophages, F4/80, Mac1 or CD45. Immunoelectron microscopy showed that the immunoreaction for NLDC-145 was localized to the sheath and presynaptic terminals of the olfactory nerves. These findings suggest that the sheath and presynaptic terminals of the primary olfactory nerves have some degree of the antigenicity in common with dendritic cells.

Animals↗

PubMed2000

Background levels of atmospheric mercury in Kagoshima City, and influence of mercury emission from Sakurajima Volcano, Southern Kyushu, Japan

Vapor phase mercury concentration was determined daily for 1 year (Jan. 1996-Jan. 1997) in order to present the levels of atmospheric mercury in Kagoshima City and to estimate the influence of mercury emission from Sakurajima Volcano, southern Kyushu, Japan. The atmospheric mercury was collected on a porous gold collector at Kagoshima University and was determined by cold vapor atomic absorption spectrometry; Kagoshima University of Kagoshima City is located approximately 11 km west of Sakurajima Volcano. The mercury concentration obtained was in the range 1.2-52.5 ng m(-3) (mean 10.8 ng m(-3), n = 169). The atmospheric concentration varied from season to season; the concentration was high in summer and lower in winter. A linear relation was obtained by plotting ln[Hg/ng m(-3)] vs. 1/T for the north, south and west winds with correlation coefficients of -0.76, -0.79 and -0.83, respectively, but no such dependency was found for the east wind (r = -0.035). When the wind is blowing from the east, Kagoshima City is on the leeward side of the volcano. The impact of the fumarolic activity of the volcano on ambient air in the city was evident in the disappearance of temperature dependency with the appearance of the east wind. Atmospheric mercury concentration except for the east wind was considered to be background levels of Kagoshima City. As background levels, 8.1 +/- 5.3 ng m(-3), 14.8 +/- 7.9 ng m(-3), 13.9 +/- 11.7 ng m(-3) and 4.4 +/- 1.6 ng m(-3) (mean +/- S.D.) were obtained for spring, summer, autumn and winter, respectively.

Journal Article↗

PubMed2000

Mercury contamination in the Yatsushiro Sea, south-western Japan: spatial variations of mercury in sediment.

Mercury-contaminated effluent was discharged into Minamata Bay from a chemical plant over a 20-year period until 1965 (from 1958 to 1959, effluent was discharged into Minamata River), causing Minamata disease. In an effort to characterize the extent of the contamination in the Yatsushiro Sea, the vertical and horizontal distributions of mercury in sediment were investigated. Sediment was sampled at 62 locations in the southern part of the sea from 4 to 6 March 1996. In the lower layers of the long cores of sediment, the total amount of mercury was at a relatively uniform low concentration. We interpret these low values to represent the background concentration absent of anthropogenic influence. The background value thus estimated for the Yatsushiro Sea was 0.059 +/- 0.013 mg kg(-1) (mean +/- S.D., n = 51). The highest concentration in each sample ranged from 0.086 to 3.46 mg kg(-1) (mean, 0.57 mg kg(-1)). The higher values were obtained at stations near Minamata Bay and the Minamata River (the sources of the pollution). Concentrations decreased with distance from the source. An inspection of the vertical profiles of mercury concentration in cores suggested that the deposited mercury had not been fixed in sediment but had been transported, despite 30 years having past since the last discharge of contaminated effluent. At nine stations, extractable inorganic and organic mercury concentrations were determined differentially. Inorganic mercury is the predominant species in sediment and organic mercury comprising approximately 1% of the total.

Chemical Industry↗

PubMed2000

Detection of spatial localization of Hst-1/Fgf-4 gene expression in brain and testis from adult mice.

HST-1, a member of the fibroblast growth factor (FGF) family (FGF-4), has been shown to be a signaling molecule whose expression is essential for embryonic development. However, HST-1/FGF-4 expression has not been detected or reported in adult tissues so far analysed. To investigate whether there is a possible role of HST-1/FGF-4 in adult stage, we have carried out a highly sensitive RT-PCR analysis of Hst-1/Fgf-4 gene expression in adult mice tissues. Results show Hst-1/Fgf-4 gene expression in the nervous system, intestines, and testis of normal adult mice. In situ hybridization technique was used to localize Hst-1/Fgf-4 gene expression in the cerebellum and testis from 10-week-old mice. Cell type-specific gene expression was detected: Purkinje cells in the cerebellum and Sertoli cells in testis. These findings suggest that the Hst-1/Fgf-4 gene also plays an important role in adult tissues, and may offer insights into the biological significance of HST-1/FGF-4 in cerebellar and testicular functions.

3T3 Cells↗

PubMed2000

Sequential calcium binding to the regulatory domain of calcium vector protein reveals functional asymmetry and a novel mode of structural rearrangement.

Calcium vector protein (CaVP) from amphioxus is a two-domain, calcium-binding protein (18.3 kDa) of the calmodulin superfamily. Only two of the four EF-hand motifs (sites III and IV) have a significant binding affinity for calcium ions. We determined the solution structure of the domain containing these active sites (C-CaVP: W81-S161), in the Ca(2+)-saturated state, using NMR spectroscopy and restrained molecular dynamics. The tertiary structure is similar to other Ca(2+)-binding domains containing a pair of EF-hand motifs. The apo state has spectroscopic and thermodynamic characteristics of a molten globule, with conserved secondary structure but highly fluctuating tertiary organization. Titration of C-CaVP with Ca(2+) revealed a stepwise ion binding, with a stable equilibrium intermediate in which only site III binds a calcium ion. Despite a highly fluctuating structure of the free site IV, the calcium-bound site III has a persistent structure, with similar secondary elements but different interhelix angle and hydrophobic packing relative to the fully calcium-saturated state.

Amino Acid Sequence↗

PubMed2000

Signalling pathways of insulin-like growth factor-I that are augmented by cAMP in FRTL-5 cells.

We have reported that pretreatment of rat FRTL-5 thyroid cells with thyrotropin (TSH) markedly potentiates the mitogenic response to insulin-like growth factor-I (IGF-I). The present study was undertaken to determine whether the augmentation by cAMP of IGF-I-dependent tyrosine phosphorylation of known IGF-I receptor substrates plays an important role in the cAMP-dependent potentiation of DNA synthesis induced by IGF-I. Pretreatment with TSH or dibutyryl cAMP did not affect the IGF-I-dependent tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). In contrast, cAMP pretreatment potentiated the tyrosine phosphorylation of IRS-2 induced by IGF-I, but did not affect the amount of IRS-2. We found that the IGF-I-dependent tyrosine phosphorylation of 66 kDa Shc (Src homology collagen) was markedly increased by cAMP pretreatment, and that this change was mainly due to an increase in the levels of 66 kDa Shc protein. Under these conditions, cAMP pretreatment significantly increased binding of Grb2 (growth-factor-receptor-bound protein 2) to Shc in response to IGF-I, and activation of MAP kinase (mitogen-activated protein kinase) induced by IGF-I was also enhanced by cAMP. The presence of PD98059, an inhibitor of MEK (MAP-kinase/Erk kinase), during treatment with IGF-I partially inhibited the cAMP-dependent augmentation of DNA synthesis in response to IGF-I. On the other hand, cAMP pretreatment increased binding of the phosphoinositide 3-kinase (PI 3-kinase) p85 subunit to IRS-2, which was reflected in PI 3-kinase activity. LY294002, a PI 3-kinase inhibitor, strongly depressed IGF-I-dependent DNA synthesis after pretreatment with and without TSH or dibutyryl cAMP. Our results suggest that the interaction between cAMP-dependent and IGF-I-dependent pathways leads to an augmentation of cell proliferation, which is mediated, at least in part, through the MAP kinase and PI 3-kinase signalling pathways. These effects are mediated by changes in tyrosine phosphorylation of IGF-I receptor substrates, including IRS-2 and Shc.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Glyoxalase I is involved in resistance of human leukemia cells to antitumor agent-induced apoptosis.

Abnormality in the machinery of apoptosis is associated with a resistant phenotype of the tumor cell to chemotherapy. To determine the molecular basis of resistance to antitumor agent-induced apoptosis, we performed a complementary DNA (cDNA) subtractive hybridization with messenger RNA (mRNA) from human monocytic leukemia U937 and its variant UK711, which is resistant to apoptosis induced by antitumor agents. We found that glyoxalase I (GLO1), an enzyme that detoxifies methylglyoxal, is selectively overexpressed in the apoptosis-resistant UK711 cells. The GLO1 enzyme activity was significantly elevated in UK711 and UK110 cells, another drug-resistant mutant, as well as in K562/ADM, adriamycin-resistant leukemia cells, compared with their parental cells. When overexpressed in human Jurkat cells, GLO1 inhibited etoposide- and adriamycin-induced caspase activation and apoptosis, indicating the involvement of GLO1 in apoptosis suppression caused by these drugs. Moreover, cotreatment with S-p-bromobenzylglutathione cyclopentyl diester (BBGC), a cell-permeable inhibitor of GLO1, enhanced etoposide-induced apoptosis in resistant UK711 cells but not in parental U937 cells. Taken together, these results indicate that GLO1 is a resistant factor to antitumor agent-induced apoptosis in human leukemia cells and that the GLO1 inhibitor could be a drug resistance-reversing agent.

Antineoplastic Agents↗

PubMed2000

Expression of a subset of the Arabidopsis Cys(2)/His(2)-type zinc-finger protein gene family under water stress.

The genes encoding Cys(2)/His(2)-type zinc-finger proteins constitute a large family in higher plants. To elucidate the functional roles of these types of protein, four different members of the gene family were cloned from Arabidopsis by PCR-aided methods. One was identical to the already reported gene STZ/ZAT10 and three were as yet unidentified genes, then designated AZF1 (Arabidopsis zinc-finger protein 1), AZF2 and AZF3. The AZF- and STZ-encoded proteins contain two canonical Cys(2)/His(2)-type zinc-finger motifs, separated by a long spacer. Three conserved regions, named B-box, L-box, and DNL-box, were also recognized outside the zinc-finger motifs, as in other members of the two-fingered Cys(2)/His(2)-type zinc-finger protein family. These four genes were positioned on the same branch of a phylogenetic tree constructed based on the zinc-finger motif sequences, suggesting their structural and functional relationship. RNA blot analysis showed that all four genes were mainly expressed in roots and at different levels in other organs. Expression of the four genes responded to water stress. High-salt treatment resulted in elevated levels of expression of all of these genes. Low-temperature treatment increased the expression levels of AZF1, AZF3, and STZ, but not AZF2. Only AZF2 expression was strongly induced by ABA treatment, where the time course of the induction was similar to that caused by high salinity. In situ localization showed that AZF2 mRNA accumulated in the elongation zone of the roots under the salt-stress condition. These results suggest that AZF1, AZF2, AZF3, and STZ are all involved in the water-stress response in an ABA-dependent or -independent pathway to regulate downstream genes.

Abscisic Acid↗

PubMed2000

NMR studies on functional structures of the AU-rich element-binding domains of Hu antigen C.

Hu antigen C (HuC) has three RNA-binding domains (RBDs). The N-terminal two, RBD1 and RBD2, are linked in tandem and bind to the AU-rich elements (AREs) in the 3'-untranslated region of particular mRNAs. The solution structures of HuC RBD1 and RBD2 were determined by NMR methods. The HuC RBD1 and RBD2 structures are quite similar to those of Sxl RBD1 and RBD2, respectively. The individual RBDs of HuC, RBD1 and RBD2 in isolation can interact rather weakly with the minimal ARE motif, AUUUA, while the didomain fragment, RBD1-RBD2, of HuC binds more tightly to a longer ARE RNA, UAUUUAUUUU. Chemical shift perturbations by the longer RNA on HuC RBD1-RBD2 were mapped on and around the two beta-sheets and on the C-terminal region of RBD1. The HuC RBD1-RBD2 residues that exhibited significant chemical shift perturbations coincide with those conserved in Sxl RBD1-RBD2. These data indicate that the RNA-binding characteristics of the HuC and Sxl didomain fragments are similar, even though the target RNAs and the biological functions of the proteins are different.

Adenosine↗

PubMed2000

Glycoprotein Ibalpha-bound thrombin functions as a serine protease to produce macromolecular activators of phagocytosis from platelets.

Production of macromolecular activators of phagocytosis from platelets (MAPPs) was observed when the lysate of fresh platelets was incubated with MAPP precursors and thrombin. An 800-Da MAPP activator (PMA-II) was obtained by Superdex peptide gel filtration of the lysate after thrombin treatment. The necessity of thrombin in MAPP production in fresh platelets was confirmed by the action of anti-thrombin monoclonal antibody or anti-thrombin III and heparin. To specify the thrombin receptor on which the thrombin forming PMA-II binds, the effects of thrombin-receptor-derived peptides and anti-thrombin receptor antibodies on MAPP production by stored platelets which have lost their thrombin content were investigated. DYYPEEDTEGD involved in glycoprotein Ibalpha and anti-glycoprotein Ibalpha antibody prevented stored platelets from producing MAPP. These observations suggest that thrombin bound to glycoprotein Ibalpha functions as a serine protease in MAPP formation.

Amino Acid Sequence↗

PubMed2000

Crystal structure of rat heme oxygenase-1 in complex with heme.

Heme oxygenase catalyzes the oxidative cleavage of protoheme to biliverdin, the first step of heme metabolism utilizing O(2) and NADPH. We determined the crystal structures of rat heme oxygenase-1 (HO-1)-heme and selenomethionyl HO-1-heme complexes. Heme is sandwiched between two helices with the delta-meso edge of the heme being exposed to the surface. Gly143N forms a hydrogen bond to the distal ligand of heme, OH(-). The distance between Gly143N and the ligand is shorter than that in the human HO-1-heme complex. This difference may be related to a pH-dependent change of the distal ligand of heme. Flexibility of the distal helix may control the stability of the coordination of the distal ligand to heme iron. The possible role of Gly143 in the heme oxygenase reaction is discussed.

Animals↗

PubMed2000

Production of macromolecular activators of phagocytosis by lysed platelets.

Macromolecular activators of phagocytosis from platelets (MAPP: 1-MAPP and s-MAPP) are released from activated fresh platelets and enhance leukocyte phagocytosis via the Fcgamma receptors. In this study, production of MAPP was investigated in lysate of freeze-thawed stored platelets (PL). Incubation of PL and thrombin with precursors of MAPP (pre-MAPP: pre-1-MAPP and pre-s-MAPP) produced 1-MAPP and s-MAPP, whereas products released from stored platelets by stimulation with thrombin or collagen did not produce MAPP after incubation with pre-MAPP. The action of thrombin in MAPP formation with PL and pre-MAPP was inhibited by antithrombin III and heparin, and sequential incubation studies indicated that the key site of action of thrombin was on a component of PL. Other serine proteases such as trypsin could be substituted for thrombin in this reaction, whereas the action of thrombin was specific when whole platelets were used instead of PL. Gel filtration of PL before and after treatment with thrombin suggested that a macromolecule in PL (PMA-I) is digested by thrombin and liberates a 700 to 800 Da substance (PMA-II) which converts pre-MAPP to MAPP.

Antithrombin III↗

PubMed2000

Cluster of proliferating cells in rat vomeronasal sensory epithelium.

We investigated the properties of small cells in the vomeronasal sensory epithelium of adult rats. The sensory neurons in the sensory epithelium were stained by antibodies to G(i2alpha) and G(oalpha) in their cell bodies and dendrites, while the small cells, which formed a cluster in the epithelium, were not stained at all. Voltage-activated inward currents were not detected by patch-clamp recordings, but outward currents were induced by the application of voltage step pulses. These results suggest that the small cells are different from the vomeronasal sensory neurons. Bromodeoxyuridine (BrdU) labeling indicated that dividing cells existed in the cluster of small cells.

Animals↗

PubMed2000

The 2-phenylbenzotriazole-type water pollutant PBTA-2 has cytochalasin B-mimetic activity.

The 2-phenylbenzotriazole (PBTA)-type water pollutant, 2-[2-(acetylamino)-4-[N-(2-cyanoethyl)ethylamino]-5-methoxyphenyl]-5- amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), has been recently identified in samples from the Nishitakase River in Kyoto, Japan, and shows potent mutagenic activities in Salmonella typhimurium in the presence of a microsomal metabolizing system (S9 mix). In the present study, we conducted the in vitro micronucleus (MN) test on PBTA-2 in the absence and presence of S9 mix in two Chinese hamster cell lines, CHL and V79-MZ. In the MN test, PBTA-2 was weakly positive in CHL cells and strongly positive in V79-MZ cells. Because the positive results were accompanied by a statistically significant increase in the number of polynuclear (PN) and/or mitotic (M) cells, we examined treated cells in metaphase to see if numerical chromosome aberrations were being induced. We found that PBTA-2 induces polyploidy in both CHL and V79-MZ cells. A detailed analysis of MN preparations showed that in CHL cells, PBTA-2 predominantly induces equal-sized binucleated cells. Rhodamine phalloidin staining revealed that PBTA-2 causes actin filament abnormalities in both cell lines similar to those caused by cytochalasin B. Cytochalasin B induced PN cells predominantly and dose dependently, and almost all the cells were equal-sized and binucleate. The results suggest that PBTA-2 has cytochalasin B-mimetic activity, although agents affecting actin filaments, such as cytochalasins, phallotoxins and chloropeptide, have been derived only from molds so far. This study also suggests that our MN test protocol may be used to identify chemicals that have cytochalasin B-mimetic activity as well as those that induce numerical aberrations.

Actins↗

PubMed2000

Allergen-induced mRNA expression of IL-5, but not of IL-4 and IFN-gamma, in peripheral blood mononuclear cells is a key feature of clinical manifestation of seasonal allergic rhinitis.

OBJECTIVES: To investigate the allergen-induced messenger RNA (mRNA) expression of interleukin (IL) 4, IL-5 and interferon gamma (IFN-gamma) in peripheral blood mononuclear cells from individuals sensitized by Japanese cedar (Cryptomeria japonica) pollens, and to elucidate the clinical role of IL-4, IL-5, and IFN-gamma in the allergen sensitization and clinical manifestation of allergic disorders. DESIGN: This study included 30 patients sensitized to the pollen and 14 nonatopic healthy volunteers. Peripheral blood mononuclear cells (1.0 x 10(6) cells/mL) of each individual were cultured at 37 degrees C for 24 hours in the presence of 10 microg/mL of Cry j 1, a major allergen of the pollens. Total cellular RNA was extracted from the peripheral blood mononuclear cells, and IL-4, IL-5, and IFN-gamma mRNA expression was determined with a reverse transcriptase polymerase chain reaction. RESULTS: From the results of a survey of symptom diary cards and interviews regarding nasal symptoms during the pollen season in 1998, we found that 20 patients (symptomatic group), but not 10 patients (asymptomatic group), had typical symptoms of seasonal allergic rhinitis. Interleukin 4 mRNA was not expressed in the nonatopic subjects but was expressed in 9 asymptomatic patients and in 17 symptomatic patients. Interleukin 5 mRNA was exclusively expressed in the symptomatic patients. Interferon gamma mRNA expression did not differ significantly among the nonatopic subjects, asymptomatic patients, and symptomatic patients. CONCLUSIONS: This study has clearly highlighted an interesting and new concept that IL-4 is implicated in allergen sensitization but not in clinical manifestation, and that IL-5 may not be a feature of atopy in itself but seems to be a hallmark of clinical manifestation of ongoing atopic diseases.

Adolescent↗