Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 55 records · Page 3Linked to original sources

PubMed2001

Partially disordered antiferromagnetic phase in Ca(3)CoRhO(6).

Neutron diffraction experiments are reported on Ca(3)CoRhO(6) which consists of ferromagnetic Ising spin chains on a triangular lattice. It was first confirmed from temperature dependence of the (110) peak intensity that Ca(3)CoRhO(6) realizes a partially disordered antiferromagnetic state, where 2/3 of the ferromagnetic chains order antiferromagnetically with each other and the remaining 1/3 are left incoherent with the other chains. The 1/3 incoherent ferromagnetic Ising chains freeze to maintain a disordered state at lower temperatures. This compound is successfully discussed as a candidate of a nonequilibrium one-dimensional Ising model.

Journal Article↗

PubMed2001

A possible novel isoform of peripheral myelin P0 protein: a target antigen recognized by an autoantibody in a patient with malignant lymphoma and peripheral neuropathy.

We tried to characterize a 35-kD antigen recognized by the serum IgG of a patient with malignant lymphoma and peripheral neuropathy. By Western blotting, the serum IgG reacted with the 35-kD antigen in the human, bovine and mouse peripheral nerve (PN) but not with other neural and non-neural tissues. Immunohistochemical analysis showed immunoreactivity of the IgG in the compact myelin of PN. We constructed a human sciatic nerve cDNA library and screened it using IgG of the patient. Three independent clones were obtained. Sequence alignment indicated that the inserts of these clones were homologous to the P0 cDNA, but that all three corresponded to the 3'-untranslational region of the P0 cDNA. To biochemically analyze the 35-kD antigen, myelin fractions of the human and bovine PN were prepared. The 35-kD antigen was purified from the crude myelin fraction by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. When the immunoreactivities of the 35-kD antigen for the IgG of the patient and a monoclonal anti-P0 antibody were compared with those of P0 protein for these antibodies, the 35-kD antigen reacted with both antibodies, but the P0 protein reacted with only the monoclonal anti-P0 antibody. These results suggest that the 35-kD antigen is an isoform of P0 protein. Although it is unlikely that the autoantibody may be the primary cause of neuropathy, because they were also detected in patients with lymphoma without overt neuropathy, they appear to be a modifying factor in the progression of neuropathy.

Adult↗

PubMed2001

Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5.

Novel low molecular weight spirodiketopiperazine derivatives which potently inhibit R5 human immunodeficiency virus type 1 (HIV-1) infection through their antagonistic effects on CCR5 were identified. One such compound E913 (M(r) 484) specifically blocked the binding of macrophage inflammatory protein-1alpha (MIP-1alpha) to CCR5 (IC(50) 0.002 microm) and MIP-1alpha-elicited cellular Ca(2+) mobilization (IC(50) approximately 0.02 microm). E913 potently inhibited the replication of laboratory and primary R5 HIV-1 strains as well as various multidrug-resistant monocyte/macrophage tropic (R5) HIV-1 at IC(50) values of 0.03 to 0.06 microm. E913 was inactive against T cell tropic (X4) HIV-1; however, when combined with a CXCR4 antagonist AMD-3100, E913 potently and synergistically inhibited the replication of dualtropic HIV-1 and a 50:50 mixture of R5 and X4 HIV-1. Antagonism in anti-HIV-1 activity was not seen when E913 was combined with the reverse transcriptase inhibitor zidovudine or protease inhibitors. E913 proved to compete with the binding of antibodies to CCR5 which recognize the C-terminal half of the second extracellular loop (ECL2B) of CCR5. E913 and its analogs are acid-resistant and orally bioavailable in rodents. These data warrant that spirodiketopiperazine derivatives be further developed as potential therapeutics for HIV-1 infection.

Animals↗

PubMed2001

Expression of HNK1 epitope by the cardiomyocytes of the early embryonic chick: in situ and in vitro studies.

Monoclonal antibody HNK1 reacts with a carbohydrate epitope in cell surface glycoproteins and glycolipids. During development, in various species the HNK1 epitopes are expressed in migrating neural crest cells and in the developing conduction cardiomyocytes. The conduction system is generally thought to be developed from cardiomyocytes, but some investigators have hypothesized that it is derived from the neural crest because conduction myocytes express neural antigens, including HNK1. Using immunohistochemistry, we examined the spatiotemporal expression of HNK1 in early chick cardiogenesis (stages 4 to 18) and whether cultured precardiac mesoderm does or does not express HNK1 as well as sarcomeric myosin (MF20). HNK1 was first expressed in the premyocardium at stage 8. At stage 10, HNK1-positive cardiomyocytes were scattered along the straight heart tube. By stage 18, HNK1-positive cardiomyocytes had become restricted to the atrium and sinus venosus. Atrioventricular cushion mesenchyme also expressed an HNK1 epitope. Immunostaining of HNK1 and MF20 in cultured precardiac mesoderm showed that there are at least three types of cells: 1) cardiomyocytes without HNK1 expression, 2) cells possessing both HNK1- and MF20-immunoreactivity, and 3) mesenchymal cells with HNK1. Immunogold electron microscopy showed that cardiomyocytes containing sparsely distributed myofibrils associated with the Z-band react with anti-HNK1 antibody. Our observations showed a direct evidence for the first time that the precardiac mesoderm generates HNK1-positive cardiomyocytes with morphological features similar to those of conduction cardiomyocytes.

Animals↗

PubMed2001

Characterization of monoclonal antibodies against ascorbate peroxidase isoenzymes: purification and epitope-mapping using immunoaffinity column chromatography.

We have developed three monoclonal antibodies against spinach chloroplastic (chl-mAb3 and chl-mAb6) and cytosolic (cyt-mAb1) ascorbate peroxidase (APX) isoenzymes to analyze the cross-reactivity and the structure of the epitopes for each monoclonal antibody. All three antibodies reacted specifically with their respective isoenzymes, but none cross-reacted with the others. Immunoreactive fragments in proteolytic recombinant APX isoenzymes were detected by means of the absorption on the corresponding immunoaffinity column. The cyt-mAb1 reacted with a peptide fragment containing the distal His region obtained by the lysyl endopeptidase digestion. The chl-mAb6 was capable of binding to the fragment, D-I-K-E-K-R, which is consistent with an inherent region of chloroplastic isoenzymes. No fragments reacting to the chl-mAb3 could be found in this study, suggesting that the chl-mAb3 recognizes a conformationally constituted epitope of the chloroplastic APX molecule, which may be destroyed by the enzymatic cleavage. We concluded that the peptides identified as epitopes are characteristic evidence of monoclonal antibodies.

Amino Acid Sequence↗

PubMed2001

Interaction of p130 with, and consequent inhibition of, the catalytic subunit of protein phosphatase 1alpha.

The protein p130 was originally isolated from rat brain as an inositol 1,4,5-trisphosphate-binding protein with a domain organization similar to that of phospholipase C-delta1 but which lacks phospholipase C activity. Yeast two-hybrid screening of a human brain cDNA library for clones that encode proteins that interact with p130 has now led to the identification of the catalytic subunit of protein phosphatase 1alpha (PP1calpha) as a p130-binding protein. The association between p130 and PP1calpha was also confirmed in vitro by an overlay assay, a "pull-down" assay, and surface plasmon resonance analysis. The interaction of p130 with PP1calpha resulted in inhibition of the catalytic activity of the latter in a p130 concentration-dependent manner. Immunoprecipitation and immunoblot analysis of COS-1 cells that stably express p130 and of mouse brain extract with antibodies to p130 and to PP1calpha also detected the presence of a complex of p130 and PP1calpha. The activity of glycogen phosphorylase, which is negatively regulated by dephosphorylation by PP1calpha, was higher in COS-1 cells that stably express p130 than in control COS-1 cells. These results suggest that, in addition to its role in inositol 1,4,5-trisphosphate and Ca(2+) signaling, p130 might also contribute to regulation of protein dephosphorylation through its interaction with PP1calpha.

Catalysis↗

PubMed2001

Antigens of monoclonal antibody NB3C4 are novel markers for oligodendrocytes.

We produced NB3C4, a novel monoclonal antibody specific for oligodendrocytes, using human neuroblastoma IMR-32 cells. NB3C4 specifically recognized oligodendrocytes in the CNS, although it bound to neuroblastoma IMR-32 cells and oligodendrocytes in vitro. Double immunofluorescence staining of rat brain using NB3C4 and anti-GST-pi, anti-glial fibrillary acidic protein (GFAP), or anti-neurofilament 200 (NF) antibody revealed that anti-GST-pi antibody identified an oligodendrocyte marker recognizing NB3C4-positive cells, while both anti-GFAP and anti-NF antibody did not. Western blotting of rat brain homogenates showed that NB3C4 bound three proteins of 22-28 kDa, while the anti-GST-pi recognized a 27 kDa protein. Therefore, antigens recognized by NB3C4 could be novel markers for oligodendrocytes.

Animals↗

PubMed2001

Pretreatment with topical all-trans-retinoic acid is beneficial for wound healing in genetically diabetic mice.

OBJECTIVE: Topical pretreatment with aIl-trans-retinoic acid (atRA) is known to improve healing of cutaneous wounds. We tested the effect of atRA on wound healing of genetically diabetic db/db mice. It is known that cutaneous wounds of db/db mice show delayed wound healing due to impaired wound contraction, delayed granulation tissue formation and underexpression of keratinocyte growth factor (KGF). METHODS: 0.1% atRA in 100 mg aqueous gel was applied to the back skin of db/db mice as well as to their normal heterozygous littermates, db/+ mice, for five consecutive days, and 2 days after completion of the atRA treatment, two round excisional wounds were created down the panniculus carnosus with a 6-mm punch biopsy on the back skin of each mouse. RESULTS: After 5 days treatment with 0.1% atRA, significant hypertrophy of the epidermis and dermis, neovascularization, and inflammatory cell invasion were seen in the skin of the db/db mice, but these effects were seen only weakly in db/+ mice. Wounds in atRA-treated db/db mice closed more rapidly than those in vehicle-treated db/db mice. KGF mRNA expression, which is usually significantly lower in db/db mice than in normal mice, in wounds of atRA-treated db/db mice on day 1 of treatment was as strong as in db/+ mice. CONCLUSION: Pretreatment with atRA reversed the impaired wound healing in db/db mice.

Administration, Topical↗

PubMed2001

Chemically charging the pore constriction opens the mechanosensitive channel MscL.

MscL is a bacterial mechanosensitive channel that protects the cell from osmotic downshock. We have previously shown that substitution of a residue that resides within the channel pore constriction, MscL's Gly-22, with all other 19 amino acids affects channel gating according to the hydrophobicity of the substitution (). Here, we first make a mild substitution, G22C, and then attach methanethiosulfonate (MTS) reagents to the cysteine under patch clamp. Binding MTS reagents that are positively charged ([2-(trimethylammonium)ethyl] methanethiosulfonate and 2-aminoethyl methanethiosulfonate) or negatively charged (sodium (2-sulfonatoethyl)methanethiosulfonate) causes MscL to gate spontaneously, even when no tension is applied. In contrast, the polar 2-hydroxyethyl methanethiosulfonate halves the threshold, and the hydrophobic methyl methanethiolsulfonate increases the threshold. These observations indicate that residue 22 is in a hydrophobic environment before gating and in a hydrophilic environment during opening to a substate, a finding consistent with our previous study. In addition, we have found that cysteine 22 is accessible to reagents from the cytoplasmic side only when the channel is opened whereas it is accessible from the periplasmic side even in the closed state. These results support the view that exposure of hydrophobic surfaces to a hydrophilic environment during channel opening serves as the barrier to gating.

Biophysical Phenomena↗

PubMed2001

Eosinophils in the cerebrospinal fluid of mice infected with Angiostrongylus cantonensis are resistant to apoptosis.

Interleukin-5 (IL-5) transgenic mice were used to assess the immunological features of CSF eosinophils from mice infected with Angiostrongylus cantonensis. CSF eosinophils were hypodense by day 14 post infection (p.i.). CSF eosinophils survived longer in vitro than peritoneal eosinophils collected from cadmium sulphate (CdSO(4)) -treated normal IL-5 transgenic mice. Apoptosis was measured by Annexin V binding and the presence of a distinct laddering pattern of DNA fragmentation on agarose electrophoresis. Regardless of the presence or absence of Actinomycin D, CSF eosinophils collected from IL-5 transgenic mice from days 15-36 p.i. exhibited less apoptosis than peritoneal eosinophils collected from uninfected IL-5 transgenic mice. CSF eosinophils collected from A. cantonensis infected C57BL/6 mice at days 15-34 p.i. showed elongation of survival time and less apoptosis during in vitro cultivation. Reduced apoptosis was noted only in CSF eosinophils, but not in peritoneal eosinophils recovered from the same infected IL-5 transgenic mice. CPP32/Caspase 3 activity of cultured peritoneal eosinophils from both infected and uninfected IL-5 transgenic mice was higher than that of cultured CSF eosinophils. Stimulation with A23187 readily induced apoptosis of peritoneal eosinophils, but not CSF eosinophils or peritoneal eosinophils cultured with mouse recombinant IL-5. The latter cells were morphologically identical to hypodense eosinophils. RT-PCR analysis indicated that bcl-2 and bcl-x(L) mRNA expression was higher in CSF eosinophils compared with peritoneal eosinophils and this expression in the latter cells was upregulated after culture with mouse recombinant IL-5. These results suggest that CSF eosinophils, shifting to hypodense status through an accumulation from peripheral blood, are resistant to apoptosis. These changes may explain the long-lasting, helminthotoxic and neurotoxic actions of CSF eosinophils in A. cantonensis infection.

Angiostrongylus cantonensis↗

PubMed2001

Microwave thermotherapy for benign prostatic hyperplasia with the Dornier Urowave: response durability and variables potentially predicting response.

OBJECTIVES: To evaluate the clinical efficacy and durability of transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia. The clinical variables useful in predicting outcome were identified. METHODS: From October 1996 to March 2000, 58 patients with symptomatic benign prostatic hyperplasia were treated with TUMT using the Urowave device. Treatment outcome was evaluated by the International Prostate Symptom Score (IPSS), quality-of-life assessment score, and urodynamic investigation. The patients were divided into those having a good and poor response on the basis of the degree of IPSS decrease at 3 months. RESULTS: The mean IPSS significantly decreased from 19.2 at baseline to 13.3 at 3 months (P <0.0001). The mean quality-of-life score changed from 4.6 at baseline to 2.9 at 3 months (P <0.0001). No statistically significant differences in peak flow rate, postvoid residual volume, Schäfer's obstruction scale, or detrusor pressure at peak flow were noted before or after TUMT. The pretreatment IPSS of the good response group was significantly higher than that of the poor response group (P=0.017). A more significant difference was obtained for the obstructive score (P = 0.002), and no difference was observed in the irritative score (P = 0.631). The Schäfer grading scale score of the good response group was significantly smaller than that of the poor response group (P = 0.047). CONCLUSIONS: TUMT with the Urowave was effective in eliminating symptoms associated with benign prostatic hyperplasia, but did not markedly improve the objective voiding parameters. Patients with urodynamically less obstructive symptoms but subjectively more obstructive symptoms are therefore probably good candidates for TUMT.

Aged↗

PubMed2001

Strong inhibition of crystal-cell attachment by pediatric urinary macromolecules: a close relationship with high urinary citrate secretion.

OBJECTIVES: To investigate other reasons for the low incidence of pediatric urolithiasis, we evaluated the difference in the crystal-cell adhesion inhibitory activity of urinary macromolecules (UMMs) between children and adults. We also evaluated whether citrates influence the above inhibitory activity, because citrates are important in pediatric urine. METHODS: Urine samples were collected from children and healthy male adults during a 24-hour period, and urinary components with a molecular weight of 3 kDa or greater were extracted as UMMs to compare their inhibitory activity during the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells between children and adults. Subsequently, various concentrations of citrates were added to adult UMMs to evaluate the changes in the crystal-cell adhesion inhibitory activity of UMMs. RESULTS: Pediatric UMMs more strongly inhibited the adhesion of calcium oxalate monohydrate crystals to cultured Madin-Darby canine kidney cells at a concentration of 0.1 mg/mL compared with adult UMMs. In addition, pediatric UMMs contained higher proportions of fibronectin and glycosaminoglycans, both of which exhibit crystal-cell adhesion inhibitory activity. When citrates were added to adult UMMs, the crystal-cell adhesion inhibitory activity of UMMs was increased in a dose-dependent manner. However, citrates alone did not result in any differences in the inhibitory activity at any of the three different concentrations. CONCLUSIONS: We speculate that the incidence of pediatric urolithiasis is low because pediatric UMMs more potently inhibit the adhesion of calcium oxalate crystals to renal tubular cells or because the higher proportion of citrates in pediatric urine enhances the crystal-cell adhesion inhibitory activity of UMMs in a dose-dependent manner.

Adult↗

PubMed2001

A novel monoclonal antibody K1 recognises early neurones in the rat cortex.

The aim of this study was to produce monoclonal antibodies specific for neurones that are generated earliest in the rat neocortex. One of the established clones, K1, showed a strong immunoreactivity in the marginal zone at the 19th day of gestation (E19). The immunoreactivity of K1 initially appeared in the primordial plexiform layer at E15, in the subplate at E16, and in the marginal zone by E17. It became undetectable in the first postnatal week. The immunoreactivity was not detected in the neocortex of adults or elderly. Western blotting analysis revealed reactive bands at positions corresponding to proteins of 290 and 280 kDa for the neocortical membrane fractions prepared from E16 to E21 embryos. In these stages, smears of bands were also found at positions corresponding to higher molecular weights. A single band of protein of 280 kDa was detected for the soluble fractions prepared from the embryos at E19 and E21. These reactivities were susceptible to protease, but not to enzymatic or chemical destruction of carbohydrate residues. Electron microscopic analysis showed that the K1 immunoreactivity was detected primarily on the cellular membranes of neurites. In the marginal zone at E19, the K1 immunoreactivity was localised where neurites make contact with other neurites or somata. A portion of these contact points had typical features of synapses. In the cortical plate of the same stage, arrays of tiny K1-immunoreactive puncta were observed on a subset of radial processes. These results suggest that monoclonal antibody K1 is a marker recognising neurites of subplate neurones that extend radially and make neuronal contacts in the marginal zone.

Animals↗

PubMed2001

Prevalence of positive anticardiolipin antibody in benign infantile convulsion.

We report six anticardiolipin antibody (aCL)-positive cases among 18 children with epilepsy showing various seizure types in our initial study. These six cases revealed normal coagulation tests. As three of these six cases involved benign infantile convulsion (BIC), we further investigated the high frequency of positive aCL-Immunoglobulin (Ig) G in BIC in our subsequent study of nine cases that included three cases from the previous study and an additional six BIC cases followed and/or diagnosed by co-author (T.K.). As a result, eight of nine BIC cases were positive for aCL-IgG and the values of aCL-IgG decreased over long-term observation in three of these cases. The frequency of positivity for aCL-IgG in BIC was obviously higher than that of controls. Based on these results, we suggest that some immunological responses may be responsible for the pathogenesis of BIC.

Adolescent↗

PubMed2001

Effects of all-trans retinoic acid on melanogenesis in pigmented skin equivalents and monolayer culture of melanocytes.

The effects of all-trans retinoic acid (RA) on melanogenesis and the mechanism of its action in topical treatment have not been elucidated. The purpose of this study was to determine the effects of RA on melanogenesis in the pigmented skin equivalent as well as in monolayer culture of melanocytes, and to determine whether RA, hydroquinone (HQ), and hydrocortisone (HC) show synergistic depigmenting effects in combined treatments of each other. The suppressing effect of RA on melanogenesis was not observed in pigmented skin equivalents and monolayer culture of murine and human melanocytes, although HQ showed strong inhibition of melanogenesis. The synergistic effects between RA, HQ, and HC were not particularly seen. The results suggested that RA neither has direct inhibitory effects on melanogenesis of melanocytes, nor influences the cell-cell interactions between melanocytes, keratinocytes and fibroblasts, such as paracrine actions with regard to melanin production. The role of RA in bleaching treatments appears to be in other specific actions, such as promotion of keratinocytes proliferation and acceleration of epidermal turnover.

Animals↗

PubMed2001

Cutaneous mast cells are altered in normal healthy volunteers sitting in front of ordinary TVs/PCs--results from open-field provocation experiments.

BACKGROUND: Considerable controversy has surrounded the question of possible biological responses to electromagnetic fields (EMFs) generated from visual display terminals (VDTs), such as personal computers (PCs) and ordinary television sets (TVs). The cellular and molecular mechanisms for such potential harmful health hazards have not yet been understood, although clues from the literature include mast cells and histamine. The aim of this study was therefore to investigate possible biological mast cell responses to TV/PC screens. METHODS: Using the indirect immunofluorescence technique, we studied the presence of histamine-containing mast cells in the dermis of healthy volunteers. Cutaneous biopsies taken before and after exposure to ordinary TV/PC screens for 2 or 4 h were investigated in 13 healthy subjects. RESULTS: Our present in vivo study indicates that normal cutaneous mast cells could be altered by exposure from ordinary TV/PC screens. To our great surprise, we found the number of mast cells in the papillary and reticular dermis to increase, to varying degrees, in 5 out the 13 subjects after such an exposure. A migration of mast cells towards the uppermost dermis appeared as the most important event. Thus, the normally upper "empty zone" of the dermis disappeared, and instead, a higher density of mast cells were found in this zone. These cells also seemed to have a tendency to increase in number towards the epidermal-dermal junctional zone and some of them lost their granular content and the cytoplasm shrunk (=degranulation). These findings could only be seen in the exposed skin. Two of the 13 cases instead showed a decrease in mast cell number, but the shift in mast cells towards the upper dermis was still visible. Twenty-four h after the provocation, the cellular number and location were normalized in all subjects. CONCLUSIONS: By definition, normal healthy volunteers are assumed not to react to a TV/PC screen provocation. To our great surprise, this proved not to be true. The present results might lay a foundation to understand the underlying cause of so-called "screen dermatitis" with special reference to mast cells. However, blind or double-blind experiments using patients ought to be further investigated in order to find out the exact cause for the observed changes. Such causes include the effects of surrounding airborne chemicals, stress factors, etc.

Adult↗

PubMed2001

Successful immunogene therapy using colon cancer cells (colon 26) transfected with plasmid vector containing mature interleukin-18 cDNA and the Igkappa leader sequence.

IL-18 is a novel cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. In the present study, we constructed plasmid vectors encoding the murine mature IL-18 cDNA linked with the Igkappa leader sequence and the pro-IL-18 cDNA to estimate the efficacy of the mature IL- 18 vector and to evaluate IL-18--producing tumor cells as a tumor vaccine. Colon 26 cells were transfected with the abovementioned vectors or with vector alone (mock). Reverse transcription-polymerase chain reaction analysis showed increased expression of murine IL-18 cDNA in both mature IL-18 and pro-IL-18 transfectants in comparison to that in mock transfected cells. The ability of the culture supernatants of mature IL-18 transfectants to induce IFN-gamma secretion was extremely high (40-140 pg/10(6) cells) in comparison to that of pro-IL-18 transfectants (4-18 pg/10(6) cells). When injected into syngeneic BALB/c mice, the growth of mature IL-18 transfectants, but not pro-IL-18 transfectants, was significantly less than that in mock transfected cells ( P< .01, by ANOVA and analysis of covariance). In addition, injection of colon 26 or Meth-A cells into mice immunized with a mature IL-18 transfectant revealed acquired immunity. Depletion of natural killer cells did not affect the growth of transfectants. However, the growth inhibitory effects were partially abrogated following treatment with anti-CD4+ and anti-CD8+ antibodies. These data suggest that the rejection of mature IL-18/colon 26 cells was mediated through T-cell activation. Gene therapy using mature IL-18 transfectants containing a plasmid vector and the Igkappa leader sequence may be a useful tumor vaccine.

Adenoviridae↗

PubMed2001

Type 2-biased expression of cytokine genes in lung granulomatous lesions induced by Nippostrongylus brasiliensis infection.

Infections with helminthic parasites occasionally induce pulmonary diseases with possible involvement of immunological mechanisms. In rats infected with the nematode Nippostrongylus brasiliensis, pulmonary granulomatous lesions develop and persist after the larvae have migrated through the lungs. To determine the pathogenesis of this lesion, we examined cytokine gene expression in the lungs using RT-PCR and in situ hybridization. Two weeks after infection, when fully developed lesions appeared, levels of IL-3 and of type2 cytokines IL-4, IL-5, IL-6 and IL-13 gene expression were markedly enhanced in whole lung homogenates. Those of IL-2 and IFN-gamma were also slightly increased 2 weeks postinfection. IL-12 mRNA level did not change after 2 weeks but was slightly increased after 4 weeks. Levels of IL-10 and proinflammatory cytokine TNF gene expression did not show significant changes, although a slight increase was observed in IL-1beta message after 2 weeks. In situ hybridization studies showed that lung granulomatous lesions were composed mainly of lymphoid cells expressing IL-3, IL-4 and IL-13 mRNA, but not IFN-gamma mRNA. IL-5 mRNA-expressing cells were fewer in number than these cells. RMCP II immunohistochemistry revealed that mast cells increased in number in the lung granulomas. From these results, it was concluded that the nematode infection-associated lung granuloma was a type 2 lesion.

Animals↗