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Biomedical subjects

Teruo Nishida

Publications and source records attributed to Teruo Nishida.

At least 73 records · Page 4Linked to original sources
PubMed2003

Inhibition by triptolide of IL-1-induced collagen degradation by corneal fibroblasts.

PURPOSE: Extracts of the herb Tripterygium wilfordii hook f, the major component of which is triptolide, have been used in traditional Chinese medicine for the treatment of rheumatoid arthritis. Triptolide also exerts many other biological actions both in vitro and in vivo. The effect of this agent on collagen degradation by cultured corneal fibroblasts was examined. METHODS: Rabbit corneal fibroblasts were cultured in three-dimensional gels of type I collagen and in the absence or presence of interleukin (IL)-1beta or triptolide. The extent of collagen degradation was determined by measurement of the amount of hydroxyproline generated by acid-heat hydrolysis of the culture supernatants. The activities of matrix metalloproteinase (MMP)-1 and plasmin were measured with the specific substrates thiopeptolide and S-2251, respectively. The release of MMPs into the culture supernatant was assessed by immunoblot analysis and gelatin zymography, and the abundance of MMP mRNAs in the cells was determined by reverse transcription and real-time polymerase chain reaction. RESULTS: Triptolide inhibited the IL-1beta-induced degradation of collagen by corneal fibroblasts in a dose- and time-dependent manner. Neither the activity of purified recombinant MMP-1 nor that of plasmin in culture supernatants was affected by triptolide. The IL-1beta-induced expression of MMP-1, -2, -3, and -9 by corneal fibroblasts was inhibited by triptolide at the protein or mRNA level. CONCLUSIONS: Triptolide inhibits collagen degradation by corneal fibroblasts by inducing downregulation of the production of MMPs, without directly affecting the collagenolytic activity of these enzymes.

Animals↗
PubMed2003

Enhancement by neutrophils of collagen degradation by corneal fibroblasts.

Activated corneal fibroblasts and infiltrated leukocytes are thought to contribute to corneal ulceration. The potential roles of neutrophil-fibroblast and cell-matrix interactions in the degradation of stromal collagen associated with corneal ulceration have now been investigated with the use of three-dimensional cultures of rabbit cells in collagen gels. Degradation of collagen fibrils during culture was measured by spectrophotometric determination of released hydroxyproline. Whereas corneal fibroblasts alone degraded collagen fibrils to a small extent, neutrophils did not. However, the addition of neutrophils or neutrophil-conditioned medium (CM) to cultures of corneal fibroblasts resulted in a marked increase in the amount of collagen degraded by the fibroblasts. The effect of CM from neutrophils cultured in collagen gels on collagen degradation by corneal fibroblasts was greater than that of medium conditioned by neutrophils in monolayer culture. Immunoblot as well as reverse transcription and real-time polymerase chain reaction analyses revealed that neutrophil-CM stimulated the synthesis of matrix metalloproteinase (MMP)-1 and MMP-3 by corneal fibroblasts. The stimulatory effect of neutrophils on collagen degradation by corneal fibroblasts was inhibited by the synthetic MMP inhibitor ilomastat and by interleukin-1 (IL-1) receptor antagonist. These results suggest that factors secreted by collagen-stimulated neutrophils augment collagen degradation by corneal fibroblasts through a stimulatory effect on MMP synthesis and that IL-1 released by neutrophils may contribute to this effect.

Animals↗
PubMed2003

[Correlation of the presence of meibomian gland dysfunction with the incidence of superficial punctate keratopathy after penetrating keratoplasty].

PURPOSE: To examine the correlation of the presence of meibomian gland dysfunction(MGD) with the incidence of superficial punctate keratopathy (SPK) after penetrating keratoplasty. SUBJECTS & METHODS: We studied 151 eyes of 141 patients that underwent penetrating keratoplasty. SPK and the presence of MGD were evaluated by slit-lamp examination. Tear function was evaluated by Schirmer test. RESULTS: Among 151 eyes investigated, 78 eyes had neither MGD nor hypolacrimation. The number of eyes with MGD only, with hypolacrimation only, or with both MGD and hypolacrimation was 34, 23, and 16. The presence of SPK after penetrating keratoplasty was correlated with the presence of MGD 1 month or 6 months post-surgery, but no correlation was observed with the presence of hypolacrimation. There was no interaction between the presence of MGD and hypolacrimation and the incidence of SPK. CONCLUSION: This study suggested that the active treatment of MGD is important in the post-surgery management of SPK.

Corneal Diseases↗
PubMed2002

Two brothers with gelatinous drop-like dystrophy at different stages of the disease: role of mutational analysis.

PURPOSE: A report of two Japanese brothers with gelatinous drop-like corneal dystrophy, one with and one without the typical gelatinous drop-like region. DESIGN: Interventional case report and observational case report. METHODS: After penetrating keratoplasty, the corneal button, right eye, of the elder brother, 39 years of age, was stained and examined by microscopy. The M1S1 and BIGH3 genes were examined for mutations using the polymerase chain reaction and direct sequencing. Corneal abnormalities in the younger brother, 37 years of age, were observed. RESULTS: The elder brother had bilateral gelatinous prominences and band-shaped corneal opacities, whereas the younger brother had only bilateral band-shaped opacities. Histologically, corneal deposits beneath the epithelium stained with Congo red. Molecular genetic analysis revealed that M1S1 was homozygously mutated in both brothers (Q118X). CONCLUSION: The Q118X mutation of the M1S1 gene can produce either a gelatinous drop-like region or band-shaped opacities.

Adult↗
PubMed2002

Prevention of ventilatory disturbance while in the face-down position after macular hole surgery.

The aim of the present study was to assess the effects of the face-down position on ventilatory function after macular hole surgery. The transcutaneous carbon dioxide tensions (tcPCO2) were measured in five patients who had undergone intraocular tamponade and in 17 normal subjects. The tcPCO2 measurements were done in patients following vitrectomy in the sitting position and in the prone position with their faces down over the semi-closed spaces of the conventional mats. In normal subjects, minute ventilatory volumes (V.E) were measured simultaneously with tcPCO2 in the sitting position and prone position. The newly introduced face-down mats (new mats) for the prone position were also tested in the normal subjects. In normal subjects, VE in the prone position with the conventional mats was significantly lower than that found in the sitting position (5.06 +/- 1.55 vs 6.06 +/- 1.64 L/min; P < 0.002). The tcPCO2 in the prone position was significantly higher than that in the sitting position (41.7 +/- 2.1 vs 38.0 +/- 1.9 mmHg; P < 0.0001). In post-vitrectomy patients, tcPCO2 in the prone position with the conventional mats was significantly higher than that in the sitting position (41.4 +/- 1.7 vs 38.6 +/- 2.2 mmHg; P < 0.02). The tcPCO2 in the prone position in normal subjects was significantly lower using new mats than that when using conventional mats. The use of conventional mats during a prone position, increased the tcPCO2 values when compared to the tcPCO2 values obtained during the sitting position in patients following vitrectomy. This could be due to either a decrease of the VE caused by limited thoracic movement or rebreathing of the exhaled gas over the semi-closed space, or both. The new mats might be useful in alleviating the increase of tcPCO2 by eliminating the rebreathing of the exhaled gas.

Aged↗
PubMed2002

Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis.

Corneal epithelial lesions distinguish vernal keratoconjunctivitis (VKC) from other ocular allergic diseases. Such lesions result from degradation of the corneal epithelial basement membrane, which comprises mostly type IV collagen and laminin. Matrix metalloproteinase 2 (MMP-2) and MMP-9 catalyze the degradation of these 2 extracellular matrix proteins. The possible role of MMP-2 and MMP-9 in the pathogenesis of corneal lesions associated with VKC was investigated by assaying tear fluid for the presence of these enzymes. Tear fluid was collected from 6 eyes of 6 patients with active VKC, 14 eyes of 14 patients with active allergic conjunctivitis, and 6 eyes of 6 nonallergic healthy volunteers. Gelatin zymography revealed that the tear fluid of healthy volunteers contained inactive proforms of both MMP-2 and MMP-9 but not the active forms of these enzymes. Active forms of MMP-2 or MMP-9 were detected in a minority of patients with allergic conjunctivitis. However, with the exception of one individual for whom active MMP-9 was not detected, tear fluid from all patients with VKC contained both proforms and active forms of MMP-2 and MMP-9. These results implicate MMP-2 and MMP-9 in the pathogenesis of corneal epithelial disorders associated with VKC.

Adult↗
PubMed2002

Differential regulation of collagen degradation by rabbit keratocytes and polymorphonuclear leukocytes.

PURPOSE: Both activated keratocytes and infiltrated polymorphonuclear leukocytes (PMNs) contribute to corneal ulceration by degrading stromal collagen. The regulation of such collagen degradation by inflammatory cytokines was investigated with rabbit keratocytes and PMNs cultured in three-dimensional collagen gels. METHODS: Rabbit keratocytes or PMNs were cultured for 24 h in three-dimensional gels of type I collagen in the presence of plasminogen and various concentrations of either interleukin (IL)-1alpha, IL-6, IL-8, or tumor necrosis factor-alpha (TNF-alpha). Degradation of collagen during culture was assessed by measurement of released hydroxyproline. RESULTS: IL-1alpha increased the amount of collagen degraded by keratocytes or PMNs in a dose-dependent manner, whereas IL-6 had no effect on collagen degradation by either cell type. IL-8 increased the extent of collagen degradation by PMNs but not that by keratocytes, and TNF-alpha promoted collagen degradation by keratocytes but not that by PMNs. CONCLUSION: Inflammatory cytokines regulate collagen degradation by rabbit keratocytes and PMNs in culture in a differential manner, and therefore may contribute to the roles of these cells in corneal ulceration.

Animals↗
PubMed2002

Role of protein kinase C signaling in collagen degradation by rabbit corneal fibroblasts cultured in three-dimensional collagen gels.

PURPOSE: To understand the mechanism of corneal ulceration by characterizing the intracellular signaling pathways that regulate collagen degradation by corneal fibroblasts cultured in three-dimensional type I collagen gels. Specifically, the potential roles of protein kinase C (PKC) and protein kinase A (PKA) in collagen degradation were investigated. METHODS: Rabbit corneal fibroblasts were cultured in three-dimensional type I collagen gels for 24 hours in the presence of plasminogen and in the absence or presence of activators or inhibitors of PKC or PKA. Degradation of collagen fibrils was then evaluated by measurement of released hydroxyproline, and the production of matrix metalloproteinases (MMPs) was assessed by gelatin zymography and immunoblot analysis. RESULTS: The PKC activator phorbol 12-myristate 13-acetate (PMA) increased the extent of collagen degradation by corneal fibroblasts in a dose-dependent manner, with the maximal effect apparent at a concentration of 0.1 microM. The inactive analog 4alpha-PMA had no effect on collagen degradation. The PKC inhibitor H-7 reduced the extent of collagen degradation by corneal fibroblasts in the absence or presence of PMA. Phorbol 12-myristate 13-acetate also increased the production of proMMP-1, -3, and -9 by corneal fibroblasts, whereas H-7 inhibited this effect. Neither the PKA activators 8-bromo-cAMP, isobutylmethylxanthine, and forskolin nor the PKA inhibitor HA1004 affected collagen degradation by corneal fibroblasts. CONCLUSION: These results demonstrate that PKC plays an important role in collagen degradation by corneal fibroblasts in three-dimensional type I collagen gels, whereas PKA does not appear to participate in this process.

Animals↗
PubMed2002

Inhibition of eotaxin expression in human corneal fibroblasts by interferon-gamma.

BACKGROUND: The chemokine eotaxin is a potent and selective chemoattractant for eosinophils. The production of eotaxin by corneal fibroblasts likely contributes to eosinophil infiltration into the corneal stroma. The regulation of eotaxin synthesis in these cells was investigated by examining the effect of interferon-gamma (IFN-gamma), a T helper cell 1-derived cytokine, on eotaxin expression in cultured human corneal fibroblasts. METHODS: The release of eotaxin from cultured corneal fibroblasts was measured by enzyme-linked immunosorbent assay, and the abundance of eotaxin mRNA in these cells was determined by reverse transcription combined with real-time polymerase chain reaction analysis. RESULTS: IFN-gamma inhibited in a dose-dependent manner the release of eotaxin induced by each of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta in corneal fibroblasts. IFN-gamma also inhibited the increase in the abundance of eotaxin mRNA induced by each of these cytokines. The synergistic increases in eotaxin release and in eotaxin mRNA abundance induced by the combination of TNF-alpha and the T helper cell 2-derived cytokine IL-4 were also both markedly inhibited by the treatment of cells with IFN-gamma. CONCLUSIONS: IFN-gamma inhibited eotaxin expression at both the protein and mRNA levels in cultured human corneal fibroblasts. This effect of IFN-gamma may contribute to the inhibition of eosinophil infiltration into the cornea. Exogenous IFN-gamma thus represents a potential new therapeutic agent for the treatment of corneal disorders associated with inflammatory ocular diseases such as vernal keratoconjunctivitis.

Adolescent↗
PubMed2002

Characterization of the interleukin-4 receptor complex in human corneal fibroblasts.

PURPOSE: To characterize the interleukin (IL)-4 receptor (IL-4R) complex in human corneal fibroblasts. METHODS: The presence of IL-4R subunit mRNAs and proteins in cultured human corneal fibroblasts was examined by reverse transcription-polymerase chain reaction and flow cytometry, respectively. The interaction of 125I-labeled IL-4 with specific cell surface receptors was characterized by saturation binding and Scatchard analysis. The effects of IL-4 on the tyrosine phosphorylation and subcellular localization of signal transducer and activator of transcription 6 (STAT6) were evaluated by immunoblot and indirect immunofluorescence analyses, respectively. The concentration of eotaxin in cell culture supernatant was measured by enzyme-linked immunosorbent assay. RESULTS: Transcripts encoding the IL-4R components IL-4Ralpha, IL-2Rgammac, IL-13Ralpha1, and IL-13Ralpha2 were detected in human corneal fibroblasts; IL-4Ralpha and IL-2Rgammac proteins were also expressed on the cell surface. The maximum number of IL-4 binding sites was 2.3 x 10(4) per cell, and the dissociation constant for the interaction of IL-4 with these sites was 10.1 +/- 0.3 pM. IL-4 induced tyrosine phosphorylation of STAT6 as well as translocation of this protein to the nucleus. Eotaxin release from corneal fibroblasts stimulated by the combination of IL-4 and tumor necrosis factor-alpha was inhibited by pretreatment of the cells with neutralizing antibodies to IL-4R. CONCLUSIONS: Cultured human corneal fibroblasts express high-affinity functional IL-4Rs on the cell surface, suggesting that these cells may contribute to the role of IL-4 as a key mediator of allergic reactions in the cornea.

Adult↗
PubMed2002

Mitogenic and antiapoptotic effects of various growth factors on human corneal fibroblasts.

PURPOSE: To investigate both the effects of various growth factors on the proliferation of human corneal fibroblasts and the abilities of these factors to protect the cells from apoptosis. METHODS: Cultured human corneal fibroblasts were incubated separately with 11 different growth factors whose receptors are expressed by these cells. Cell proliferation was evaluated by measurement of [(3)H]thymidine incorporation. The activation of the protein kinase Akt, which plays an important role in antiapoptotic signaling, was assessed by immunoblot analysis with antibodies specific for a phosphorylated form of the enzyme. Apoptosis was quantitated by the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay. RESULTS: Of the 11 growth factors examined, platelet-derived growth factor, insulin, insulin-like growth factors-1 and -2, and epidermal growth factor, each stimulated the proliferation of corneal fibroblasts, induced the activation of Akt in these cells, and protected them from apoptosis induced by sodium nitroprusside (SNP). Basic fibroblast growth factor, keratinocyte growth factor, nerve growth factor, and hepatocyte growth factor stimulated cell proliferation but did not induce Akt activation or protect the cells from SNP-induced apoptosis. Transforming growth factor-beta1 and -beta2 did not stimulate proliferation and had no effect on Akt activity or on SNP-induced apoptosis. CONCLUSIONS: In terms of their modulatory effects on the proliferation and apoptosis of human corneal fibroblasts, the 11 growth factors examined can be classified into three groups. These growth factors may both contribute to maintenance of the cornea and coordinate the proliferative and apoptotic responses of corneal fibroblasts during corneal wound healing.

Adolescent↗
PubMed2002

Substance P and its metabolites in normal human tears.

PURPOSE: To determine amounts and biochemical characteristics of substance P-like immunoreactivity (SPLI) in tears of normal human subjects. METHODS: Forty-three healthy subjects (16 males and 27 females; age range, 17-80 years) participated. Ten microliters of unstimulated tears were collected with a micropipette from one eye of all subjects. Tear samples were partially purified by C-18 cartridges. SPLI concentrations in purified samples were measured by enzyme immunoassay (EIA). For biochemical characterization of SPLI, tear extracts were fractionated by high-performance liquid chromatography (HPLC). Each fraction then was subjected to EIA. To determine the metabolism of substance P in tears, synthetic substance P was incubated in medium containing pooled tears and then analyzed by HPLC with the detector set at a 210-nm wavelength. RESULTS: The SPLI concentration in normal human tears was 306.0 +/- 96.5 pg/mL (mean +/- SD; range, 148-555 pg/mL). SPLI did not significantly vary by age or gender. HPLC analysis indicated that SPLI in tears consisted of five different substances and that substance P was converted to several fragments, including SP(8-11) by enzymes present in tears. CONCLUSIONS: Substance P, a normal component of human tears, presumably is released from the nerve endings in the ocular surface and converted to fragments by degradative enzymes in tears.

Adolescent↗
PubMed2002

Signaling mechanism of TGF-beta1-induced collagen contraction mediated by bovine trabecular meshwork cells.

PURPOSE: To characterize the intracellular signaling mechanism that underlies the contraction of trabecular meshwork (TM) tissue. METHODS: The contraction of collagen mediated by bovine TM cells was evaluated by measuring changes in the diameter of collagen gels in which the cells were embedded. Changes in the organization of the actin cytoskeleton were examined by laser-scanning confocal microscopy of cells stained with fluorescent phalloidin. Cell motility was monitored by time-lapse video microscopy. RESULTS: Transforming growth factor (TGF)-beta1 induced marked TM-cell-mediated contraction of collagen gels in a concentration- and time-dependent manner. Inhibitors of protein kinase C (PKC) blocked this effect of TGF-beta1, whereas an inhibitor of PKA and -G did not. An inhibitor of the small guanosine triphosphatase (GTPase) Rho also inhibited TGF-beta1-induced collagen contraction, whereas an activator of Rho promoted this effect of TGF-beta1. Furthermore, inhibition either of the release of Ca(2+) from internal stores or of the activation of myosin light-chain kinase (MLCK) prevented gel contraction in response to TGF-beta1. The effects of these various agents on TGF-beta1-induced contraction of collagen gels mediated by TM cells were mirrored by their effects on TGF-beta1-induced formation of actin stress fibers, cell spreading (the extension of cellular processes), and cell motility under conditions in which cell contraction was not possible. CONCLUSIONS: TGF-beta1 induces TM-cell-mediated collagen gel contraction through activation of Rho and the Ca(2+)-dependent enzymes PKC and MLCK. These same signaling molecules contribute to TGF-beta1-induced rearrangement of the actin cytoskeleton, cell spreading, and cell motility.

Actins↗
PubMedDate not supplied

Differential regulation of focal adhesion kinase and paxillin phosphorylation by the small GTP-binding protein Rho in human corneal epithelial cells.

PURPOSE: Lysophosphatidic acid (LPA), which activates the small guanosine triphosphate (GTP)-binding protein Rho, was previously shown to promote migration of the rabbit corneal epithelium in culture. The signaling pathway responsible for this effect of LPA was examined in this study with a human corneal epithelial (HCE) cell line. METHODS: The activation of Rho was detected with a pull-down assay. Tyrosine phosphorylation of paxillin and of focal adhesion kinase (FAK) were examined both by immunofluorescence staining and by immunoprecipitation and immunoblot analyses. Expression of integrins alpha5 and beta1 was evaluated by immunoblot analysis. RESULTS: Incubation of cells with LPA (10 micro M) for 2 min resulted in marked activation of Rho, and this effect was blocked by pretreatment with the Rho inhibitor exoenzyme C3 (2 micro g/ml) for 24 h. Tyrosine phosphorylation of both paxillin and FAK was detected in HCE cells under basal conditions by immunofluorescence staining, immunoprecipitation, and immunoblot analyses. LPA induced a concentration- and time-dependent increase in the tyrosine phosphorylation of paxillin, which was maximal at a concentration of 10 micro M and a time of 2 min. Exoenzyme C3 inhibited LPA-induced paxillin phosphorylation. Neither LPA nor exoenzyme C3 affected tyrosine phosphorylation of FAK or expression of integrins alpha5 and beta1. CONCLUSIONS: LPA induces Rho activation and the consequent tyrosine phosphorylation of paxillin in HCE cells, and these effects likely contribute to the promotion of corneal epithelial migration by this agent.

Cell Line↗
PubMedDate not supplied

Eyelid fusion and epithelial differentiation at the ocular surface during mouse embryonic development.

PURPOSE: To investigate epithelial differentiation at the ocular surface of the developing mouse eye by examining temporal and spatial changes in the expression of specific keratins. METHODS: Ocular tissues, including the entire eyeball, conjunctiva, and eyelid, of mouse embryos at embryonic day (E) 12.5 to E18.5 as well as of adult mice were examined by hematoxylin-eosin staining and by immunohistochemistry with antibodies to keratins K4, K10, K12, and K14. RESULTS: Hematoxylin-eosin staining revealed that eyelid fusion occurred at E17.5. Keratin immunohistochemistry demonstrated that: (1) K4 was expressed before K12, which in turn was expressed before K10; (2) expression of K4, K12, and K14 was spatially heterogeneous in the epithelia of the eyelid invaginations before eyelid fusion, but thereafter was continuous and homogeneous in the entire conjunctival epithelium, corneal epithelium, and basal cell layer of the surface epithelia, respectively; and (3) K10 immunoreactivity was not detected before eyelid fusion but was apparent in the epidermis of the eyelid thereafter. CONCLUSIONS: Eyelid fusion is a critical period for differentiation of the ocular surface ectoderm into the epithelia of the conjunctiva, cornea, and eyelid skin. The conjunctival epithelium differentiates before the corneal epithelium, which in turn differentiates before the eyelid epidermis.

Animals↗
PubMedDate not supplied

Additional reduction in intraocular pressure achieved with latanoprost in normal-tension glaucoma patients previously treated with unoprostone.

PURPOSE: To determine whether treatment with latanoprost eye drops is able to further reduce intraocular pressure (IOP) in normal-tension glaucoma (NTG) patients whose IOP has been well controlled with unoprostone. PATIENTS AND METHODS: A total of 34 eyes (34 individuals) with NTG that had been treated with 0.12% unoprostone eye drops twice daily for >or=3 months were switched to treatment once daily with eye drops containing 0.005% latanoprost. IOP was measured before and 1, 2, and 3 months after the switch to latanoprost. RESULTS: The mean IOP of all eyes was decreased significantly by 1.8, 2.9, and 2.3 mmHg at 1, 2, and 3 months after the switch from unoprostone to latanoprost treatment. The IOP of patients with an initial IOP of 12 mmHg was reduced by 11.0 or 19.9%, respectively, after 3 months on latanoprost. The IOP of 30 (88.2%) of the 34 eyes was further reduced by the switch from unoprostone to latanoprost. CONCLUSIONS: Latanoprost reduced the IOP of NTG patients who had already been treated with unoprostone, even though both drugs are prostaglandin-related. Switching to latanoprost might thus achieve a maximal decrease in IOP and thereby better prevent damage to the optic nerve and loss of visual field in NTG patients.

Aged↗
PubMedDate not supplied

An analysis of BIGH3 mutations in patients with corneal dystrophies in the Kyushu district of Japan.

PURPOSE: To assess the involvement of BIGH3 in corneal dystrophies (CD) with an autosomal dominant trait, in patients referred to a hospital in the Kyushu district of Japan. METHODS: Forty-five CD patients from 44 families were studied. Genomic DNA was extracted from peripheral blood, and exons 4 and 12 of the BIGH3 gene were amplified by polymerase chain reaction followed by direct sequencing. RESULTS: In exon 4, an R124H mutation associated with Avellino corneal dystrophy (ACD) was found in 39/44 families (86.4%) and an R124C mutation associated with lattice corneal dystrophy type 1 (LCD1) was detected in 2/44 families (4.5%). In exon 12, an R555W mutation associated with granular corneal dystrophy (GCD) was detected in 4/44 families (9.1%). CONCLUSIONS: Codons R124 and R555 of the BIGH3 gene represent mutational hotspots in the genomes of Japanese patients with autosomal-dominant CD.

Adolescent↗