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Kenji Suzuki

Publications and source records attributed to Kenji Suzuki.

At least 19 recordsLinked to original sources
PubMed2026

PUF60 is a Critical Regulator of PKM Splicing During Myogenesis.

Pyruvate kinase M (PKM) catalyzes the conversion of phosphoenolpyruvate to pyruvate in glycolysis and exists as two splice isoforms, PKM1 and PKM2, generated from alternative splicing of mutually exclusive exons 9 or 10, respectively. The expression balance between PKM1 and PKM2 is tightly regulated in a cell-type-specific manner. PKM1 is predominantly expressed in tissues such as skeletal muscle, heart, and brain, whereas PKM2 is prevalent in most other tissues and various cancer cells. Despite its importance, the trans-acting factors promoting exon 9 selection in a tissue-specific context remain largely unknown. Here, using a multi-color splicing reporter system for cell-based cDNA screening, we identified PUF60 as a novel trans-acting factor that promotes PKM1-type splicing. We also demonstrated that PUF60 induction and the resulting splicing switch are essential for myotube formation during C2C12 differentiation. This study establishes PUF60 as a critical regulator of muscle-specific splicing and provides new insights into the fundamental mechanisms governing skeletal muscle differentiation.

Animals↗
PubMed2006

Immunohistochemical detection of GLUT-1 can discriminate between reactive mesothelium and malignant mesothelioma.

The separation of benign reactive mesothelium (RM) from malignant mesothelial proliferation can be a major challenge. A number of markers have been proposed, including epithelial membrane antigen, p53 protein, and P-glycoprotein. To date, however, no immunohistochemical marker that allows unequivocal discrimination of RM from malignant pleural mesothelioma (MPM) has been available. A family of glucose transporter isoforms (GLUT), of which GLUT-1 is a member, facilitate the entry of glucose into cells. GLUT-1 is largely undetectable by immunohistochemistry in normal epithelial tissues and benign tumors, but is expressed in a variety of malignancies. Thus, the expression of GLUT-1 appears to be a potential marker of malignant transformation. Recently, in fact, some studies have shown that GLUT-1 expression is useful for distinguishing benign from malignant lesions. The purpose of the present study was to evaluate the diagnostic utility of GLUT-1 expression for diagnostic differentiation between RM and MPM. Immunohistochemical staining for GLUT-1 was performed in 40 cases of RM, 48 cases of MPM, and 58 cases of lung carcinoma. Immunohistochemical GLUT-1 expression was seen in 40 of 40 (100%) MPMs, and in all cases the expression was demonstrated by linear plasma membrane staining, sometimes with cytoplasmic staining in addition. GLUT-1 expression was also observed in 56 out of 58 (96.5%) lung carcinomas. On the other hand, no RM cases were positive for GLUT-1. GLUT-1 is a sensitive and specific immunohistochemical marker enabling differential diagnosis of RM from MPM, whereas it cannot discriminate MPM from lung carcinoma.

Adenocarcinoma↗
PubMed2006

Chiral 1,1'-binaphthyl-2,2'-diammonium salt catalysts for the enantioselective Diels-Alder reaction with alpha-acyloxyacroleins.

[reaction: see text] A diammonium salt of chiral 1,1'-binaphthyl-2,2'-diamine and trifluoromethanesulfonimide (Tf(2)NH) shows excellent catalytic activity and enantioselectivity for the Diels-Alder reaction of alpha-acyloxyacroleins with cyclic dienes. For example, in the presence of 5 mol % of the ammonium catalyst, the Diels-Alder reaction of alpha-(cyclohexanecarbonyloxy)acrolein with cyclopentadiene proceeded in EtCN at -75 degrees C to give the adducts in 88% yield with 92% exo and 91% ee. This catalyst can be easily prepared in situ by mixing the commercially available chiral diamine and Tf(2)NH.

Journal Article↗
PubMed2006

Frequent EGFR mutations in noninvasive bronchioloalveolar carcinoma.

Mutations of the epidermal growth factor receptor gene (EGFR) have been reported to be present in a considerable fraction of lung adenocarcinomas showing dramatic response to EGFR tyrosine kinase inhibitors. To clarify pathogenic significance of the mutations for the development of lung adenocarcinoma, we investigated stage I lung adenocarcinomas for the mutations. First, 107 cases of macrodissected stage I adenocarcinomas were examined for mutations in exons 18-21 of the EGFR gene. EGFR mutations were detected in 36 of the 107 cases (34%). In particular, among the stage I cases, the mutations were detected in 17 of 42 small-sized adenocarcinomas (<or=2 cm in diameter) (40%), including 7 of 11 noninvasive bronchioloalveolar carcinomas (BACs) (64%) and 7 of 25 invasive adenocarcinomas with BAC components (28%). Second, 26 cases of laser capture microdissected small-sized adenocarcinomas, including 9 cases in the first analysis, were examined for the mutations. Reanalysis of microdissected materials in the 9 cases identified the mutations in 2 more adenocarcinomas with BAC components. Moreover, in the analysis of the other 17 microdissected materials, EGFR mutations were detected in 7 of 12 BACs (58%) and in 3 of 5 adenocarcinomas with BAC components (60%). EGFR mutations are present frequently in BACs, and are thus likely to be a critical genetic alteration for the formation of noninvasive lung adenocarcinoma.

Adenocarcinoma↗
PubMed2006

Attenuation of mouse acute colitis by naked hepatocyte growth factor gene transfer into the liver.

BACKGROUND: Hepatocyte growth factor (HGF) has multiple biological effects on a wide variety of cells. It modulates intestinal epithelial proliferation and migration, and critically regulates intestinal wound healing. AIMS: To investigate the therapeutic effect of HGF gene transfer, we introduced the HGF gene into the liver of mice with acute colitis. METHODS: The rat HGF expression plasmid vector, pCAGGS-HGF, was injected via the tail vein into C57BL/6 mice, followed by dosing with dextran sulfate sodium in distilled water. Firstly, the HGF gene was injected once on day 0. Secondly, the HGF gene was injected on day 0 and again on day 2. RESULTS: Injection of the HGF gene ameliorated colitis with inhibition of both loss of body weight and shortening of colon length. It protected the colon from epithelial erosions and cellular infiltration. Expression of mRNAs for IFN-gamma, IL18, and TNF-alpha was reduced in the colon. In contrast, expression of mRNA for IL-10 was increased. The numbers of BrdU-positive intestinal epithelial cells were increased, and the numbers of TUNEL-positive apoptotic cells were decreased. Furthermore, a second injection prolonged the elevation of serum HGF levels, and ameliorated the symptoms better than a single injection. The empty pCAGGS plasmid did not ameliorate acute colitis. CONCLUSIONS: HGF gene transfer attenuated acute colitis by facilitating intestinal wound repair as well as inhibiting inflammation, suggesting a new strategy for treatment of IBD.

Acute Disease↗
PubMed2006

Radiologic classification of small adenocarcinoma of the lung: radiologic-pathologic correlation and its prognostic impact.

BACKGROUND: A new radiologic classification for small adenocarcinoma is necessary for discussions of limited surgical resection for peripheral lung cancer. METHODS: Between 1999 and 2003, 1,697 consecutive patients underwent pulmonary resection for lung cancer. Three hundred forty-nine of these patients with clinical stage IA lung cancer who had lung peripheral adenocarcinoma, 2 cm or less in size, were investigated retrospectively. Radiologic classification was based on the findings of thin-section computed tomographic scan such as the presence of solid and ground-glass opacity (GGO). Type 1 (n = 22), type 2 (n = 26), type 3 (n = 25), and type 4 (n = 43) show a simple GGO, an intermediate homogeneous increase in density, a halo, and a mixed area of GGO and a solid, respectively. Type 5 (n = 54) shows a solid tumor with GGO, and type 6 (n = 179) shows a solid tumor. RESULTS: There was no difference in the maximum tumor dimension among the six groups. All but 1 patient had no lymph node metastases among type 1 to 4 tumors, whereas these were found in 5% and 24% of the patients with type 5 and 6 tumors, respectively. Lymphatic invasions were rarely found in patients with type 1 to 4 tumors (p < 0.001). CONCLUSIONS: Types 1, 2, 3, and 4 are considered to be radiologic early adenocarcinoma of the lung, and their pathologic features were minimally invasive. On the other hand, type 5 and 6 tumors could have lymph node metastases and are considered to be invasive adenocarcinoma. Although limited surgical resection may be enough for type 1 to 4 tumors, anatomic pulmonary resection should be recommended for type 5 or 6 tumor.

Adenocarcinoma↗
PubMed2006

Multiple lung adenocarcinomas showing ground-glass opacities on thoracic computed tomography.

It is difficult to distinguish multiple primary lung cancers from pulmonary metastasis. We experienced a case of surgically resected lung tumors that showed multiple ground-glass opacities on thoracic computed tomographic scan. There were eight nonsolid and two part-solid ground-glass opacities in the bilateral lungs. Surgical resection was performed because all tumors had a ground-glass opacity appearance on computed tomographic scan, which is compatible with a finding of primary lung adenocarcinoma. The postoperative pathologic diagnoses were two cases of invasive adenocarcinoma, six cases of bronchioloalveolar carcinoma, and eight cases of atypical adenomatous hyperplasia. The patient remains alive without any evidence of recurrence 40 months after surgery. A ground-glass opacity appearance on computed tomographic scan could be interpreted as supportive evidence for multiple primary lung adenocarcinoma rather than pulmonary metastases.

Adenocarcinoma↗
PubMed2006

Image-processing technique for suppressing ribs in chest radiographs by means of massive training artificial neural network (MTANN).

When lung nodules overlap with ribs or clavicles in chest radiographs, it can be difficult for radiologists as well as computer-aided diagnostic (CAD) schemes to detect these nodules. In this paper, we developed an image-processing technique for suppressing the contrast of ribs and clavicles in chest radiographs by means of a multiresolution massive training artificial neural network (MTANN). An MTANN is a highly nonlinear filter that can be trained by use of input chest radiographs and the corresponding "teaching" images. We employed "bone" images obtained by use of a dual-energy subtraction technique as the teaching images. For effective suppression of ribs having various spatial frequencies, we developed a multiresolution MTANN consisting of multiresolution decomposition/composition techniques and three MTANNs for three different-resolution images. After training with input chest radiographs and the corresponding dual-energy bone images, the multiresolution MTANN was able to provide "bone-image-like" images which were similar to the teaching bone images. By subtracting the bone-image-like images from the corresponding chest radiographs, we were able to produce "soft-tissue-image-like" images where ribs and clavicles were substantially suppressed. We used a validation test database consisting of 118 chest radiographs with pulmonary nodules and an independent test database consisting of 136 digitized screen-film chest radiographs with 136 solitary pulmonary nodules collected from 14 medical institutions in this study. When our technique was applied to nontraining chest radiographs, ribs and clavicles in the chest radiographs were suppressed substantially, while the visibility of nodules and lung vessels was maintained. Thus, our image-processing technique for rib suppression by means of a multiresolution MTANN would be potentially useful for radiologists as well as for CAD schemes in detection of lung nodules on chest radiographs.

Algorithms↗
PubMed2006

gammadelta T cells increase with gastric mucosal interleukin (IL)-7, IL-1beta, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis.

BACKGROUND AND AIMS: The purpose of this study was to investigate possible factors that could impact on gammadelta T cell accumulation in the gastric mucosa. METHOD: Subjects were 22 Helicobacter pylori (H. pylori)-free and 75 H. pylori-infected mucosa biopsies classified into grades I approximately III gastritis as per our previous study. The number of gammadelta- and 45 RO-positive T cells were determined by immunostaining. Gastric mucosal anti-H. pylori urease specific antibodies and interleukin (IL)-1beta, IL-2, 4, 7, 10 and IL-12 levels were assayed by enzyme-linked immunosorbent assay (ELISA). CC chemokine receptor 2 (CCR2) expression levels, migration, and cytokine production in gammadelta T cells stimulated by H. pylori urease were also evaluated. RESULTS: The gammadelta T cell count was significantly higher in grade III gastritis which exhibits strong immunoglobulin (Ig)A and IgG responses to H. pylori urease with lymphoid follicles than in other groups. gammadelta T cell count was significantly correlated with IL-1beta and interleukin-7 (IL-7) levels in the gastric mucosa. H. pylori urease immunoreactivity was detected in lamina propria of grade III gastritis, along with many gammadelta T cells. After H. pylori eradication therapy, the gammadelta T cell count in grade III gastritis significantly decreased. H. pylori urease stimulated significant increases in CCR2 expression levels, although to a lesser degree than those induced by IL-7 stimulation in both peripheral and mucosal gammadelta T cells. Interferon (IFN)-gamma and IL-10 production was also stimulated by H. pylori urease in peripheral gammadelta T cells. CONCLUSIONS: Gastric mucosal increases in IL-7 and IL-1beta closely corresponded to the accumulation of gammadelta T cells in gastric mucosa. An association was also seen between gammadelta T cell accumulation and H. pylori urease-specific Ig levels.

Adult↗
PubMed2006

Inverted ductal papilloma of minor salivary gland: case report with immunohistochemical study and literature review.

Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49-year-old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient's postoperative course was uneventful and there has been no recurrence after 1 year's follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.

Biomarkers, Tumor↗
PubMed2006

Endotoxin adsorption therapy for septic shock using polymyxin B-immobilized fibers (PMX): evaluation by high-sensitivity endotoxin assay and measurement of the cytokine production capacity.

Because of its low sensitivity, the conventional measurement method for endotoxin (ET) is not the most appropriate for monitoring the effect of ET adsorption therapy. Thus, the efficacy of ET adsorption therapy was investigated using a newly developed high-sensitivity ET assay method. The changes in the cytokine production capacity of whole blood were also examined. We treated 24 peritonitis patients who had developed postoperative septic shock with ET adsorption therapy using a column of polymyxin B-immobilized fibers (PMX) and their serum ET levels were measured using the high-sensitivity ET assay based on the kinetic turbidimetric Limulus assay. In addition, the changes in the tumor necrosis factor-(TNF-alpha) production capacity of whole blood following lipopolysaccharide (LPS) stimulation and clinical outcome in the study patients were also examined. The 28-day mortality rate was 12%. PMX-direct hemoperfusion (PMX-DHP) was associated with elevation of the mean arterial pressure and urine output, reduction in the mean dose requirement of vasopressor agents, and recovery from the shock state in all the patients. The PaO2/FIO2 ratio also showed significant improvement. Using the high-sensitivity ET assay, ET was detected in the blood of 20 out of the 24 patients (80%) before the PMX-DHP, and a significant reduction in the ET level was noted after the PMX-DHP. The TNF-alpha production capacity of whole blood, which was found to be lower in the septic shock patients than in healthy subjects, was significantly increased after PMX-DHP. Elimination of ET by PMX-DHP in septic shock patients was confirmed by the high-sensitivity ET assay. PMX-DHP is thus considered to be a useful adjuvant therapeutic technique in the treatment of septic shock. Also, PMX-DHP might alleviate the immunosuppression associated with severe sepsis.

Adsorption↗
PubMed2006

[Bacteria isolated from chronic upper and lower respiratory tract infections and the associated therapeutic strategies--in paranasal sinusitis].

Nasal sinusitis, tonsillitis, and pharyngolaryngitis typify upper respiratory tract infections, while bronchitis and pneumonia typify lower respiratory tract infections. Cases of paranasal sinusitis with severe suppuration are reportedly becoming less frequent, while those of chronic catarrhal paranasal sinusitis and edematous allergic paranasal sinusitis are becoming more so, The primary factor in paranasal sinusitis, a typical infectious disease encountered in otolaryngology, is bacterial infection. The main causative bacteria are Streptococcus pneumoniae, reported in 13.4% of cases, Haemophilus influenzae in 12.8% Moraxella catarrhalis in 5.5%, Staphylococcus aureus in 26.5%, Pseudomonas aeruginosa in 5.2%, and anaerobes. The incidence of strains resistant to antimicrobial agents has grown for S. pneumoniae, H. influenzae, and M. catarrhalis and decreased for S. aureus and P. aeruginosa. Acute exacerbation or severe suppuration in chronic paranasal sinusitis requires the administration of antimicrobial agents, with the same agent administered 2 weeks for maximal effect. First-line agents are AMPC/CVA, SBTPC, CDTR-PI, CFPN-PI, and GFLX for adults, with ASPC, SBPC, ACPC, CTRX, CMZ, FMOX, PAPM/BP, and MEPM injected in severe cases. Attention must be paid to strains that resist cephems and macrolides, such as PISP, PRSP, and BLNAR. In refractory chronic paranasal sinusitis, attention must also be paid to biofilms produced by S. aureus and P. aeruginosa. Suitable antimicrobial agents should be determined for treating of chronic paranasal sinusitis, in addition to the best procedure to ensure early recovery from inflammation, such as puncturing or irrigating the maxillary sinus, injecting a suitable agent, nebulization, and/or surgically widening the middle meatus.

Anti-Infective Agents↗
PubMed2006

Computer-aided diagnostic scheme for the detection of lung nodules on chest radiographs: localized search method based on anatomical classification.

We developed an advanced computer-aided diagnostic (CAD) scheme for the detection of various types of lung nodules on chest radiographs intended for implementation in clinical situations. We used 924 digitized chest images (992 noncalcified nodules) which had a 500 x 500 matrix size with a 1024 gray scale. The images were divided randomly into two sets which were used for training and testing of the computerized scheme. In this scheme, the lung field was first segmented by use of a ribcage detection technique, and then a large search area (448 x 448 matrix size) within the chest image was automatically determined by taking into account the locations of a midline and a top edge of the segmented ribcage. In order to detect lung nodule candidates based on a localized search method, we divided the entire search area into 7 x 7 regions of interest (ROIs: 64 x 64 matrix size). In the next step, each ROI was classified anatomically into apical, peripheral, hilar, and diaphragm/heart regions by use of its image features. Identification of lung nodule candidates and extraction of image features were applied for each localized region (128 x 128 matrix size), each having its central part (64 x 64 matrix size) located at a position corresponding to a ROI that was classified anatomically in the previous step. Initial candidates were identified by use of the nodule-enhanced image obtained with the average radial-gradient filtering technique, in which the filter size was varied adaptively depending on the location and the anatomical classification of the ROI. We extracted 57 image features from the original and nodule-enhanced images based on geometric, gray-level, background structure, and edge-gradient features. In addition, 14 image features were obtained from the corresponding locations in the contralateral subtraction image. A total of 71 image features were employed for three sequential artificial neural networks (ANNs) in order to reduce the number of false-positive candidates. All parameters for ANNs, i.e., the number of iterations, slope of sigmoid functions, learning rate, and threshold values for removing the false positives, were determined automatically by use of a bootstrap technique with training cases. We employed four different combinations of training and test image data sets which was selected randomly from the 924 cases. By use of our localized search method based on anatomical classification, the average sensitivity was increased to 92.5% with 59.3 false positives per image at the level of initial detection for four different sets of test cases, whereas our previous technique achieved an 82.8% of sensitivity with 56.8 false positives per image. The computer performance in the final step obtained from four different data sets indicated that the average sensitivity in detecting lung nodules was 70.1% with 5.0 false positives per image for testing cases and 70.4% sensitivity with 4.2 false positives per image for training cases. The advanced CAD scheme involving the localized search method with anatomical classification provided improved detection of pulmonary nodules on chest radiographs for 924 lung nodule cases.

Databases, Factual↗
PubMed2006

Experimental determination of subjective similarity for pairs of clustered microcalcifications on mammograms: observer study results.

Presentation of images of lesions similar to that of an unknown lesion might be useful to radiologists in distinguishing between benign and malignant clustered microcalcifications on mammograms. Investigators have been developing computerized schemes to select similar images from large databases. However, whether selected images are really similar in appearance is not examined for most of the schemes. In order to retrieve images that are useful to radiologists, the selected images must be similar from radiologists' diagnostic points of view. Therefore, in this study, the data of radiologists' subjective similarity for pairs of clustered microcalcification images were obtained from a number of observers, and the intra- and inter-observer variations and the intergroup correlations were determined to investigate whether reliable similarity ratings by human observers can be determined. Nineteen images of clustered microcalcifications, each of which was paired with six other images, were selected for the observer study. Thus, subjective similarity ratings for 114 pairs of clustered microcalcifications were determined by each observer. Thirteen breast, ten general, and ten nonradiologists participated in the observer study; some of them completed the study multiple times. Although the intraobserver variations for the individual readings and the interobserver variations for pairs of observers were not small, the interobserver agreements were improved by taking the average of readings by the same observers. When the similarity ratings by a number of observers were averaged among the groups of breast, general, and nonradiologists, the mean differences of the ratings between the groups decreased, and good concordance correlations (0.846, 0.817, and 0.785) between the groups were obtained. The result indicates that reliable similarity ratings can be determined by use of this method, and the average similarity ratings by breast radiologists can be considered meaningful and useful for the development and evaluation of a computerized scheme for selection of similar images.

Breast Diseases↗
PubMed2006

Massive-training artificial neural network (MTANN) for reduction of false positives in computer-aided detection of polyps: Suppression of rectal tubes.

One of the limitations of the current computer-aided detection (CAD) of polyps in CT colonography (CTC) is a relatively large number of false-positive (FP) detections. Rectal tubes (RTs) are one of the typical sources of FPs because a portion of a RT, especially a portion of a bulbous tip, often exhibits a cap-like shape that closely mimics the appearance of a small polyp. Radiologists can easily recognize and dismiss RT-induced FPs; thus, they may lose their confidence in CAD as an effective tool if the CAD scheme generates such "obvious" FPs due to RTs consistently. In addition, RT-induced FPs may distract radiologists from less common true positives in the rectum. Therefore, removal RT-induced FPs as well as other types of FPs is desirable while maintaining a high sensitivity in the detection of polyps. We developed a three-dimensional (3D) massive-training artificial neural network (MTANN) for distinction between polyps and RTs in 3D CTC volumetric data. The 3D MTANN is a supervised volume-processing technique which is trained with input CTC volumes and the corresponding "teaching" volumes. The teaching volume for a polyp contains a 3D Gaussian distribution, and that for a RT contains zeros for enhancement of polyps and suppression of RTs, respectively. For distinction between polyps and nonpolyps including RTs, a 3D scoring method based on a 3D Gaussian weighting function is applied to the output of the trained 3D MTANN. Our database consisted of CTC examinations of 73 patients, scanned in both supine and prone positions (146 CTC data sets in total), with optical colonoscopy as a reference standard for the presence of polyps. Fifteen patients had 28 polyps, 15 of which were 5-9 mm and 13 were 10-25 mm in size. These CTC cases were subjected to our previously reported CAD scheme that included centerline-based segmentation of the colon, shape-based detection of polyps, and reduction of FPs by use of a Bayesian neural network based on geometric and texture features. Application of this CAD scheme yielded 96.4% (27/28) by-polyp sensitivity with 3.1 (224/73) FPs per patient, among which 20 FPs were caused by RTs. To eliminate the FPs due to RTs and possibly other normal structures, we trained a 3D MTANN with ten representative polyps and ten RTs, and applied the trained 3D MTANN to the above CAD true- and false-positive detections. In the output volumes of the 3D MTANN, polyps were represented by distributions of bright voxels, whereas RTs and other normal structures partly similar to RTs appeared as darker voxels, indicating the ability of the 3D MTANN to suppress RTs as well as other normal structures effectively. Application of the 3D MTANN to the CAD detections showed that the 3D MTANN eliminated all RT-induced 20 FPs, as well as 53 FPs due to other causes, without removal of any true positives. Overall, the 3D MTANN was able to reduce the FP rate of the CAD scheme from 3.1 to 2.1 FPs per patient (33% reduction), while the original by-polyp sensitivity of 96.4% was maintained.

Algorithms↗
PubMed2006

Role of IP-10/CXCL10 in the progression of pancreatitis-like injury in mice after murine retroviral infection.

Exocrinopathy and pancreatitis-like injury were developed in C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus, which is known to induce murine acquired immunodeficiency syndrome (MAIDS). The role of chemokines, especially CXCL10/interferon (IFN)-gamma-inducible protein 10 (IP-10), a chemokine to attract CXCR3+ T helper 1-type CD4+ T cells, has not been investigated thoroughly in the pathogenesis of pancreatitis. B6 mice were inoculated intraperitoneally with LP-BM5 and then injected every week with either an antibody against IP-10 or a control antibody. Eight weeks after infection, we analyzed the effect of IP-10 neutralization. Anti-IP-10 antibody treatment did not change the generalized lymphadenopathy and hepatosplenomegaly of mice with MAIDS. The treatment significantly reduced the number of IP-10- and CXCR3-positive cells in the mesenteric lymph nodes (mLNs) but not the phenotypes and gross numbers of cells. In contrast, IP-10 neutralization reduced the number of mononuclear cells infiltrating into the pancreas. Anti-IP-10 antibody treatment did not change the numbers of IFN-gamma+ and IL10+ cells in the mLN but significantly reduced their numbers, especially IFN-gamma+ and IL-10+ CD4+ T cells and IFN-gamma+ Mac-1+ cells, in the pancreas. IP-10 neutralization ameliorated the pancreatic lesions of mice with MAIDS probably by blocking the cellular infiltration of CD4+ T cells and IFN-gamma+ Mac-1+ cells into the pancreas at least at 8 wk after infection, suggesting that IP-10 and these cells might play a key role in the development of chronic autoimmune pancreatitis.

Animals↗