Biomedical subjects

K Noguchi

Publications and source records attributed to K Noguchi.

At least 19 recordsLinked to original sources

PubMed2006

Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons.

Two cold-sensitive transient receptor potential (TRP) channels, TRPA1 and TRPM8, have been identified and considered interesting because of their possible roles in thermosensation, nociception and other functions. Recently, we have reported that the phosphorylation of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase occurred in primary afferent neurons in response to noxious heat stimulation of the peripheral tissue, i.e. activity-dependent activation of extracellular signal-regulated protein kinase and p38 in dorsal root ganglion neurons. In the present study, we investigated the phosphorylation of extracellular signal-regulated protein kinase, p38, and c-Jun N-terminal kinase in the rat dorsal root ganglion by cold stimulation using immunohistochemistry. Cold stimuli (28-4 degrees C) were applied by immersion of the hind paw into a water bath (six times of 10 s stimulation and 10 s interval, total 2 min). Noxious cold stimulation induced phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38, but not phosphorylated-c-Jun N-terminal kinase, in small to medium diameter sensory neurons with a peak at 2 min after stimulation. We found that a cold stimulation at 4 degrees C showed a marked increase in the number of activated neurons. Furthermore, double staining for phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38 showed no colocalization in the dorsal root ganglion neurons. We then performed double-labeling experiments for TRPA1 and TRPM8 mRNA and phosphorylation of mitogen-activated protein kinase. The majority of phosphorylated-extracellular signal-regulated protein kinase-positive neurons also expressed TRPM8 mRNA, whereas phosphorylated-p38 heavily colocalized with TRPA1 mRNA after noxious cold stimulation. Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion.

Animals↗

PubMed2006

Stem cell properties of human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Stem cells have been used for regenerative therapies in various fields. The proportion of cells that possess stem cell properties in human periodontal ligament (PDL) cells is not yet well understood. In this study, we quantitatively characterized human PDL cells to clarify their stem cell properties, including self-renewal, multipotency, and stem cell marker expression. MATERIAL AND METHODS: PDL cells were obtained from extracted premolar or wisdom teeth, following which a proliferation assay for self-renewal, a differentiation assay for multipotency, immunostaining for STRO-1, and fluorescence-activated cell sorter (FACS) analysis for stem cell markers (including CD105, CD166, and STRO-1) were performed. RESULTS: Approximately 30% of 400 PDL cells were found to possess replicative potential and formed single-cell colonies, and 30% of these colonies displayed positive staining for STRO-1, 20% differentiated into adipocytes and 30% differentiated into osteoblasts. FACS analysis revealed that PDL cells, including cell populations, expressed the stem cell markers CD105, CD166, and STRO-1. CONCLUSION: The findings of this study indicated that PDL cells possess crucial stem cell properties, such as self-renewal and multipotency, and express the mesenchymal stem cell markers CD105, CD166, and STRO-1 on their cell surface, although there were some variations. Thus, PDL cells can be used for periodontal regenerative procedures.

Adipogenesis↗

PubMed2006

Saddle embolism after corrective femoral osteotomy: a case report.

We present a case of recurrent saddle embolism 6 days and 9 days following corrective osteotomy of the left femur in a 64-year-old man with a history of atrial fibrillation. Although saddle embolism is a relatively rare event, orthopaedic surgeons should be aware of this condition.

Arterial Occlusive Diseases↗

PubMed2006

Effects of endogenous and exogenous prostaglandin E2 on the proliferation and differentiation of a mouse cementoblast cell line (OCCM-30).

BACKGROUND: Cementum formation is considered to be a critical event for successful regeneration of periodontal tissues. Cementoblasts share many characteristics with osteoblasts. Prostaglandin E(2) (PGE(2)) is an important local factor in bone metabolism. Although the effects of PGE(2) on osteoblasts are well known, its effects on cementoblasts have not yet been established. We examined the effects of PGE(2) on proliferation and differentiation in a mouse cementoblast cell line, OCCM-30 cells. METHODS: OCCM-30 cells were treated with three concentrations of PGE(2) (10, 100, and 1,000 ng/ml). Cell number, alkaline phosphatase (ALP) activity, and expression for mineralization-related genes were determined. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) expression were also examined by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The addition of PGE(2) at the highest dose used in this study suppressed cell proliferation of OCCM-30 cells. The expression of mineralization-related marker mRNA, such as type 1 collagen, ALP, bone sialoprotein (BSP), and osteocalcin (OCN), was constitutively detected in OCCM-30 cells. PGE(2) dose dependently stimulated ALP activity and BSP-mRNA expression in OCCM-30 cells at day 3. Transcripts for OPG and RANKL and the protein level of OPG in culture media were upregulated with PGE(2) stimulation. CONCLUSION: These results demonstrate that PGE(2) suppressed cementoblast proliferation but stimulated ALP activity and the BSP-mRNA level, suggesting a role of PGE(2) in controlling cementoblast differentiation, and further indicate that PGE(2) modulates RANKL and OPG expression in cementoblasts; the increase of OPG secreted from cementoblasts with PGE(2) stimulation may be essential to protect the root surface from resorption.

Alkaline Phosphatase↗

PubMed2005

The effect of site and type of nerve injury on the expression of brain-derived neurotrophic factor in the dorsal root ganglion and on neuropathic pain behavior.

A number of rat neuropathy models have been developed to simulate human neuropathic pain conditions, such as spontaneous pain, hyperalgesia, and allodynia. In the present study, to determine the relative importance of injury site (proximal or distal to the primary afferent neurons) and injury type (motor or sensory), we examined pain-related behaviors and changes of brain-derived neurotrophic factor expression in the dorsal root ganglion in sham-operated rats, and in the L5 dorsal rhizotomy, L5 ventral rhizotomy, L5 dorsal rhizotomy+ventral rhizotomy, and L5 spinal nerve transection models. L5 ventral rhizotomy and spinal nerve transection produced not only mechanical and heat hypersensitivity, but also an increase in brain-derived neurotrophic factor mRNA/protein in the L5 dorsal root ganglion at 7 days after surgery. In contrast, rats in the L5 dorsal rhizotomy and dorsal rhizotomy+ventral rhizotomy groups did not show both pain behaviors at 7 days after surgery, despite brain-derived neurotrophic factor upregulation in medium- and large-size neurons in the L5 dorsal root ganglion. On the other hand, L5 spinal nerve transection, but not dorsal rhizotomy, dorsal rhizotomy+ventral rhizotomy or ventral rhizotomy, increased the expression of brain-derived neurotrophic factor in the L4 dorsal root ganglion at 7 days after surgery. Taken together, these findings suggest that the upregulation of brain-derived neurotrophic factor expression in the L4 and L5 dorsal root ganglion neurons may be, at least in part, involved in the pathophysiological mechanisms of neuropathic pain and that the selective nerve root injury models may be useful for studying the underlying mechanisms of chronic pain after nerve injury.

Animals↗

PubMed2005

Induction of plasminogen activator inhibitor-1 and -2 in dorsal root ganglion neurons after peripheral nerve injury.

We have previously found that tissue type and urokinase type plasminogen activators (tPA and uPA) are induced in dorsal root ganglia (DRG) neurons after peripheral axotomy and that tPA plays crucial roles in generating neuropathic pain. Here we examined whether the plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) mRNA, endogenous inhibitors of tPA and uPA, are induced in the DRG following sciatic nerve transection. L4 and L5 DRG sections were examined using in situ hybridization histochemistry. The results showed that both PAI-1 and PAI-2 mRNA were up-regulated in DRG neurons within 1 day, and peaked at 1-3 days, after injury. Reduction of these mRNA was observed from 7 days after injury. The precise expression patterns of PAI-1 and PAI-2 mRNA at 3 days after axotomy revealed that PAI-1 mRNA was observed in predominantly small neurons, while much of the PAI-2 mRNA was expressed in large neurons. Double-labeling analysis of these mRNAs with activated transcription factor 3, known as an injury marker, revealed that most PAI-1 and PAI-2 mRNAs was induced in injured neurons. Co-expression of PAI-1, 2 with tPA and uPA in DRG neurons suggests that these inhibitors may act in an autocrine manner to modulate extracellular proteolytic activity after nerve injury.

Activating Transcription Factor 3↗

PubMed2005

Protein kinase-A-dependent osteoprotegerin production on interleukin-1 stimulation in human gingival fibroblasts is distinct from periodontal ligament fibroblasts.

Periodontitis, a chronic inflammatory disease, is characterized by increased expression of interleukin (IL)-1 and other inflammatory mediators resulting in extensive osteoclast formation and bone loss. Expression of receptor activator of nuclear factor kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), by osteoblasts is important to regulate osteoclast differentiation. The aim of the present study was to investigate the regulatory effects of IL-1 on RANKL and OPG production by mesenchymal fibroblasts in periodontal tissue. Human gingival fibroblasts (HGF) and periodontal ligament fibroblasts (PDL) were stimulated with IL-1alpha with or without protein synthesis inhibitor cycloheximide (CHX), protein kinase A (PKA) inhibitors, protein kinase C (PKC) inhibitors and prostaglandin E(2) (PGE(2)) inhibitor. In some experiments, the cultured cells were directly stimulated with either PKA or PKC activators. In HGF, IL-1alpha-stimulated OPG mRNA expression was high and could be reduced by CHX. PKA inhibitor completely abrogated IL-1alpha-induced OPG mRNA expression and OPG production. Endogenous PGE(2) further enhanced IL-1alpha-induced OPG production in HGF. In PDL, RANKL mRNA expression was greatly augmented by IL-1alpha. IL-1alpha induced OPG mRNA expression and protein production. PKC inhibitor partially reduced IL-1alpha-induced OPG production and PKC activator enhanced OPG production in PDL. The IL-1alpha-stimulated OPG mRNA expression in HGF was greater than PDL. These results provide new evidence for the possible osteoclastogenesis-inhibitory function of HGF through PKA activity pathway. PDL utilized PKC for OPG production. Thus, we emphasize that HGF and PDL have different characteristics of host defence mechanism against inflammatory process.

Adult↗

PubMed2005

Changes in masseter muscle blood flow during voluntary isometric contraction in humans.

The effect of jaw clenching on local blood flow in the masseter muscle was measured using the hydrogen clearance method in 13 healthy subjects. Sustained isometric masseter-muscle contraction levels of 25 and 50% of maximum voluntary contraction (MVC) were investigated. The blood flow at 25% MVC before contraction, during contraction and after contraction was 12.3 +/- 10.9, 19.2 +/- 12.1 and 78.8 +/- 63.9 mL min(-1) (100 g)(-1) (mean +/- s.d.), respectively. At 50% MVC, it was 14.2 +/- 12.9, 18.6 +/- 10.0 and 80.1 +/- 61.8, respectively. The volume of blood flow was significantly greater after contraction as compared with before contraction at both levels (P < 0.0001) and there was no significant difference between before and during contraction periods (P = 0.17: 25% MVC; P = 0.38: 50% MVC). At 50% MVC blood flow before contraction and the difference in blood flow before and during contraction showed significant negative correlation (r = -0.636, P < 0.02). When the volume of blood flow was low before contraction it tended to increase during contraction and decreased when it was high before contraction. These findings indicate that blood flow in the masseter muscle during sustained isometric contraction is affected by the condition of contraction and may be influenced by the muscle region. It was also indicated that the blood flow during high level contraction was influenced by the volume of blood flow before contraction. Clinically, our findings may help to understand pathological changes which may lead to chronic masticatory muscle pain.

Adult↗

PubMed2005

Down-regulation of interleukin-1alpha-induced matrix metalloproteinase-13 expression via EP1 receptors by prostaglandin E2 in human periodontal ligament cells.

In the present study, we investigated the effect of prostaglandin (PG) E2 on matrix metalloproteinase (MMP)-13 production in human periodontal ligament cells stimulated with interleukin (IL)-1alpha. IL-1alpha enhanced both MMP-13 and PGE2 production. Indomethacin, a nonselective cyclooxygenase inhibitor, and NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly enhanced IL-1alpha-induced MMP-13 production in periodontal ligament cells, although both the agents completely inhibited IL-1alpha-induced PGE2 production. Exogenous PGE2 reduced IL-1alpha-induced MMP-13 mRNA and protein production in a dose-dependent manner. 17-phenyl-omega-trinor PGE2, a selective EP1 receptor agonist, mimicked the inhibitory effect of PGE2 on IL-1alpha-induced MMP-13 mRNA and protein production. On the basis of these data, we suggest that COX-2-dependent PGE2 down-regulates IL-1alpha-elicited MMP-13 production via EP1 receptors in human periodontal ligament cells. PGE2 may be involved in the regulation of destruction of extracellular matrix components in periodontal lesions.

Collagenases↗

PubMed2005

Er:YAG laser irradiation increases prostaglandin E production via the induction of cyclooxygenase-2 mRNA in human gingival fibroblasts.

BACKGROUND AND OBJECTIVES: It has been reported that both prostaglandin E2 (PGE2) and Er:YAG laser irradiation accelerate wound healing. The stimulatory action of laser seems to occur during the proliferative stage of healing by stimulation of prostaglandin E2 and cyclooxygenase-2 (COX-2), which are crucial early mediators in the natural healing process. We have then investigated the effect of Er:YAG laser irradiation on PGE2 production and COX-2 gene expression in human gingival fibroblast in vitro. MATERIAL AND METHODS: Cultured fibroblasts were exposed to low-power Er:YAG laser irradiation with an energy density of 3.37 J/cm2. The amount of PGE2 production was measured by enzyme-linked immunosorbent assay (ELISA). COX-2 mRNA level, which is a critical enzyme for PGE2 production, was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Er:YAG laser significantly increased PGE2 production by human gingival fibroblasts. COX-2 mRNA, which was hardly detectable in control, increased dramatically after irradiation. COX-2 inhibitor, NS398, completely inhibited the PGE2 synthesis stimulated by Er:YAG laser irradiation. CONCLUSION: Our results showed that Er:YAG laser irradiation appears to exert its stimulative action on gingival fibroblasts proliferation through the production of PGE2 via the expression of COX-2. This should be considered as one of the important regulatory pathways to accelerate wound healing after Er:YAG laser irradiation.

Cell Proliferation↗

PubMed2005

Prostaglandin E2 (PGE2) downregulates interleukin (IL)-1alpha-induced IL-6 production via EP2/EP4 subtypes of PGE2 receptors in human periodontal ligament cells.

OBJECTIVES: Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors, which are divided into four subtypes, EP1, EP2, EP3 and EP4. In the present study, we examined whether PGE2 regulated interleukin (IL)-1alpha-induced IL-6 production in human periodontal ligament (PDL) cells and if so, which subtypes of PGE2 receptors were involved. METHODS: PDL cells were stimulated with vehicle or IL-1alpha in the presence or absence of indomethacin (a cylooxygenase inhibitor), PGE2 or various EP agonists. IL-6 and PGE2 levels were measured by enzyme-linked immunosorbent assay. EP receptor mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Indomethacin significantly enhanced IL-1alpha-induced IL-6 production by PDL cells, although it completely inhibited IL-1alpha-induced PGE2 production. Exogenous PGE2 significantly suppressed IL-1alpha-induced IL-6 production. Butaprost, a selective EP2 agonist, and ONO-AE1-329, a selective EP4 agonist, significantly inhibited IL-1alpha-induced IL-6 production, although 17-phenyl-omega-trinor PGE2, an EP1 agonist, and ONO-AP-324, an EP3 agonist, did not affect it. RT-PCR analysis showed that EP2 and EP4 mRNA was expressed in PDL cells. CONCLUSIONS: We suggest that PGE2 downregulates IL-1alpha-induced IL-6 production via EP2/EP4 receptors in human PDL cells.

Cyclooxygenase Inhibitors↗

PubMed2004

Immuno-localization of COX-1 and COX-2 in the rat molar periodontal tissue after topical application of lipopolysaccharide.

Up-regulation of prostaglandin E2 (PGE2) production in the periodontal tissue is considered to be important for periodontal tissue destruction. The purpose of the study was to demonstrate the dynamic changes of immuno-localization of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in rat periodontal tissue after topical application of lipopolysaccharide (LPS: 5 mg/ml in physiological saline) from Escherichia coli into the rat molar gingival sulcus. In the normal periodontal tissue, small numbers of junctional epithelium (JE) cells and numerous osteocytes embedded in alveolar bone constitutively expressed COX-1. The COX-1 expression was not effected by LPS application. JE cells, especially in the coronal portion of JE also expressed COX-2. LPS application induced the JE cells with consequent transient expression of COX-2 with a peak at day 1. These findings suggest that JE cells may play a critical role in first defense line against LPS challenge and PGE2 from JE cells may be responsible for the initiation of periodontal inflammation. In the deep periodontal tissue, cementoblasts and osteoblasts showed constitutive expression of COX-2, which may be induced by continuous cyclic tension force due to occlusal pressure. LPS application caused a transient up-regulation of COX-2 expression in periodontal ligament fibroblasts, cementoblasts and osteoblasts. It is suggested that the inducible production of PGE2 via COX-2 by these cells may be associated with connective tissue destruction and alveolar bone resorption.

Administration, Topical↗

PubMed2004

Activation of extracellular signal-regulated protein kinase in the dorsal root ganglion following inflammation near the nerve cell body.

Inflammation of the primary afferent proximal to the dorsal root ganglion (DRG) and the DRG itself is known to produce radicular pain. Here, we examined pain-related behaviors and the activation of extracellular signal-regulated protein kinase (ERK) in the DRG after inflammation near the DRG somata. Inflammation of the L4/5 nerve roots and DRG induced by complete Freund's adjuvant (CFA) produced mechanical allodynia on the ipsilateral hindpaw and induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase (trk) A-expressing small- and medium-size neurons. This CFA-induced increase in ERK phosphorylation was mediated through trk receptors, because intrathecal treatment with the tyrosine kinase inhibitor, K252a, reduced the activation of ERK. On the other hand, an increase in brain-derived neurotrophic factor (BDNF) mRNA/protein in the DRG concomitant with the ERK activation was also observed. Furthermore, we found that nerve growth factor (NGF) injection directly into the L4/5 nerve roots and DRG produced mechanical allodynia, and an increase in the phosphorylation of ERK and BDNF expression in the DRG, but the mitogen-activated protein kinase (MAPK) kinase1/2 inhibitor, U0126, inhibited the effects induced by NGF. Therefore, we suggest that after inflammation near the cell body, NGF synthesized within the nerve root and DRG induces BDNF expression through trkA receptors and intracellular ERK-MAPK. The activation of MAPK in the primary afferents may be involved in the pathophysiological mechanisms of inflammation-induced radiculopathy and MAPK pathways in the primary afferents may be potential targets for pharmacological intervention for neuropathic pain produced by inflammation near the DRG somata.

Animals↗

PubMed2004

Identification of the novel canine CYP1A2 1117 C > T SNP causing protein deletion.

The pharmacokinetics of YM-64227 (4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]-pyrimidine-2-(1H)-one), a novel and selective phosphodiesterase type 4 inhibitor, was characterized in beagle dogs. Based on the plasma parent drug to major hydroxylated metabolite ratio, 21 dogs were phenotyped as 16 extensive metabolizers (EM) and five poor metabolizers (PM). Nucleotide sequences of CYPs 1A2, 2B11, 2C21, 2D15, 2E1 and 3A12 were investigated in the EM and PM dogs. A CYP1A2 1117 C>T single nucleotide polymorphism was found, which resulted in an amino acid change from an Arg codon to a stop codon at position 373. All dogs phenotyped as PM were T/T homozygous, whereas EMs were C/C homozygous and C/T heterozygous. In Western blotting of liver microsomes, CYP1A protein expression was detected in the C/C and C/T types, but not in the T/T type. Of 65 dogs genotyped using genome DNA, the frequencies of the C and T alleles were 0.61 and 0.39, respectively, suggesting approximately 15% of the dogs would not express the CYP1A2 protein. The findings provide a coherent explanation for the inter-individual variability in the pharmacokinetics of CYP1A2 substrate drugs in dogs.

Alleles↗

PubMed2004

Mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus: report of a case.

A rare case of mucinous adenocarcinoma with neuroendocrine differentiation of the mandibular ramus is presented. The patient, an 80-year-old man, was referred to our hospital with chief complaint of swelling and pain in the left buccal mucosa. CT and MRI examination showed an osteolytic tumor mass occupying the upper region of the left mandibular ramus. Macroscopically, the excised tumor was a relatively well-defined, solid mass with diffuse bone resorption, measuring 3 cm x 3.2 cm x 3 cm. Microscopical examination showed that the tumor forming glandular structures with abundant mucous production and high cellular atypia. Immunohistochemical studies demonstrated the positive reactivities for pan-keratin, cytokeratin 7, vimentin,alpha-amylase, alpha-smooth muscle actin, neuron-specific enolase, glial fibrillary acid protein, calcitonin, and somatostatin in tumor cells. These findings suggested that the tumor was originated from heterotopic or misplaced salivary gland in the mandible.

Actins↗

PubMed2004

Prostaglandin E2 regulates interleukin-1beta-induced matrix metalloproteinase-3 production in human gingival fibroblasts.

Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors (EP1, EP2, EP3, and EP4). In the present study, we investigated whether PGE2 regulated interleukin (IL)-1beta-induced matrix metalloproteinase (MMP)-3 production in human gingival fibroblasts (HGF) derived from periodontally healthy subjects and diseased patients. In HGF from healthy gingiva, PGE2 down-regulated IL-1beta-induced MMP-3 production, whereas in HGF from periodontitis patients, PGE2 enhanced it. Butaprost (an EP2 agonist) and ONO-AE1-329 (an EP4 agonist) suppressed IL-1beta-induced MMP-3 production, and 17-phenyl-omega-trinor PGE2 (an EP1 agonist) mimicked the PGE(2) effect in HGF from healthy and periodontally diseased tissues, respectively. Analysis of these data suggests that, in HGF from healthy tissue, IL-1beta-induced MMP-3 production is down-regulated by PGE2 via EP2 and EP4 receptors, whereas in cells from periodontally diseased tissue, IL-1beta-induced MMP-3 production is up-regulated via EP1 receptors. Different regulation of IL-1beta-induced MMP-3 production by PGE2 between healthy and periodontally diseased tissues may be involved in the pathogenesis of periodontal disease.

Adult↗

PubMed2003

Serial diffusion-weighted imaging in a patient with MELAS and presumed cytotoxic oedema.

A patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was studied with serial diffusion-weighted MRI (DWI) after stroke-like episodes and the apparent diffusion coefficient (ADC) was measured in an infarct-like lesion. In the acute and subacute stages, the affected area gave high signal on DWI and its ADC was much lower than that in a normal control region. In the chronic stage, the ADC became higher than that in normal brain. We therefore suggest that the stroke-like episodes did not cause vasogenic oedema but were related to energy failure and cytotoxic oedema.

Brain Edema↗

PubMed2003

The effects of lansoprazole on erosive reflux oesophagitis are influenced by CYP2C19 polymorphism.

BACKGROUND: The acid suppressive effect of lansoprazole is influenced by the P450 2C19 (CYP2C19) polymorphism. AIM: To investigate whether the CYP2C19 genotype is related to the healing of erosive reflux oesophagitis during treatment with lansoprazole. METHODS: Eighty-eight Japanese patients with erosive reflux oesophagitis were treated with a daily oral dose of 30 mg lansoprazole for 8 weeks. The CYP2C19 genotype, Helicobacter pylori infection status and serum pepsinogen I/II ratio were assessed before treatment. At 4 and 8 weeks, the healing of erosive reflux oesophagitis was evaluated endoscopically. RESULTS: The healing rates were 57.1%, 69.2% and 72.7% at 4 weeks and 77.4%, 95.0% and 100% at 8 weeks in homozygous extensive metabolizers, heterozygous extensive metabolizers and poor metabolizers, respectively. At 8 weeks, the healing rate of erosive reflux oesophagitis was significantly lower in homozygous extensive metabolizers than in the other two groups (P < 0.05). The H. pylori status and serum pepsinogen I/II ratio had less influence than CYP2C19 polymorphism on the healing rate of erosive reflux oesophagitis. CONCLUSIONS: The therapeutic effect of lansoprazole on erosive reflux oesophagitis is influenced by the CYP2C19 genotype status. Therefore, a test of CYP2C19 genotype may be useful for the medical treatment of reflux oesophagitis with lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗