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I Nishimori

Publications and source records attributed to I Nishimori.

At least 19 recordsLinked to original sources
PubMed2005

Serum antibodies to carbonic anhydrase IV in patients with autoimmune pancreatitis.

BACKGROUND AND AIMS: Serum antibodies to carbonic anhydrase (CA) II have been reported in patients with autoimmune pancreatitis (AIP) and Sjogren's syndrome (SjS). However, their significance in the pathogenesis of these diseases is controversial. The aim of this study was to identify serum antibodies to CA isozymes, which are expressed in ductal cells of the pancreas. METHODS: Recombinant proteins of human CAs IV, IX, and XII were obtained using a bacterial expression system, and five CA IV peptides with theoretically high antigenicity were synthesised. Western blotting and enzyme linked immunosorbent assay (ELISA) were used to detect serum antibodies to the CA isozymes. RESULTS: The first screening analysis by western blot showed serum antibodies to CA IV among three CA isozymes in patients with idiopathic chronic pancreatitis, including AIP patients. Further analysis by ELISA showed a significantly increased prevalence of serum antibodies to the truncated CA IV protein and the CA IV synthetic peptide (LGS LTT PTC DEK VVW TVF REP I) in patients with definite AIP (4/15 and 6/20, respectively; p<0.01), probable AIP (6/14 and 3/14; p<0.02), and SjS (9/20 and 8/40; p<0.001) compared with normal controls (0/26). There was no significant difference in the antibody prevalence rates between normal controls and patients with alcoholic chronic pancreatitis (2/15 in each) or pancreatic cancer (2/14 and 1/14, respectively). The presence of serum antibodies to the CA IV peptide showed significant correlations with serum gamma-globulin and IgG levels in AIP patients. CONCLUSIONS: These findings suggest that CA IV may be a target antigen that is commonly expressed in epithelial cells of specific tissues involved in AIP and its related diseases.

Aged↗
PubMed2002

Developmental expression of carbonic anhydrase-related proteins VIII, X, and XI in the human brain.

Three cDNA homologues of carbonic anhydrase with unknown biological functions have been reported: carbonic anhydrase-related proteins (CA-RP) VIII, X, and XI. In the present study, we produced monoclonal antibodies to these CA-RPs and studied their regional and cellular distributions in the human adult and fetal brains by immunohistochemical analysis. In the adult brain, CA-RP VIII was expressed in the neural cell body spreading to most parts of the brain. CA-RP X was expressed in the myelin sheath and its expression was shown in the cytoplasm of cultured tumor cells by immunocytochemical analysis. CA-RP XI was expressed in the neural cell body, neurites, and astrocytes in relatively limited regions of the brain. In the fetal brain, CA-RP VIII and XI were expressed in the neuroprogenitor cells in the subventricular zone as early as the 84th day of gestation and subsequently detected in the neural cells migrating to the cortex. CA-RP X first appeared in the neural cells in the cortex at the 141st day. In the choroid plexus, the epithelial cells gave CA-RP VIII and XI expressions in both adult and fetal brains. From the findings in the present study on the distribution and the developmental expression of CA-RP VIII, X, and XI in the human brain we suggest that these CA-RPs play roles in various biological process of the CNS.

Adult↗
PubMed2001

Quantitative trait locus analysis for chronic pancreatitis and diabetes mellitus in the WBN/Kob rat.

A causative gene mutation is still undefined in approximately half of patients with hereditary pancreatitis, and no genetic factor has been identified in most patients with sporadic chronic pancreatitis. To identify a pancreatitis-associated gene, we performed a quantitative trait locus (QTL) analysis for the traits of chronic pancreatitis and diabetes mellitus in WBN/Kob rats. We identified two highly significant QTLs for chronic pancreatitis and/or hyperinsulinemia on chromosomes 7 and X. These QTLs were located on completely different chromosomal regions from those of causative genes that have been reported for human chronic pancreatitis: PRSS1, CFTR, and SPINK1. For these QTLs, prevalences of the WBN/Kob allele significantly increased in the rats with chronic pancreatitis. These findings indicate that chronic pancreatitis in WBN/Kob rats is controlled by multiple genes, and a genetic analysis in WBN/Kob rats might be useful for gene targeting for human chronic pancreatitis.

Animals↗
PubMed2001

cDNA sequence of human carbonic anhydrase-related protein, CA-RP X: mRNA expressions of CA-RP X and XI in human brain.

A full-length cDNA clone of human carbonic anhydrase-related protein (CA-RP) X was obtained and sequenced. The 2720 bp long cDNA sequence was predicted to encode a 328 amino acid polypeptide. The deduced amino acid sequence showed an overall similarity of 25-57% to other CA isozymes and the highest % similarity to a CA-RP XI. Similar to CA-RP XI, CA-RP X lacked two out of three zinc-liganded histidine residues, suggesting no biological activity of CA. Northern blot analysis demonstrated an approx. 2.8 kb transcript in the human brain and kidney. RNA dot blotting showed significant signals for CA-RP X and XI mRNA expressions in the adult total brain and almost all parts of the central nervous system, but no expression in the fetal brain. These results suggest that CA-RP X and XI play some role in human brain, especially in brain development.

Amino Acid Sequence↗
PubMed2001

Genetic mutations in exons 3 and 4 of the pancreatic secretory trypsin inhibitor in patients with pancreatitis.

PURPOSE: We hypothesized that mutations in the pancreatic secretory trypsin inhibitor (PSTI) gene could promote autodigestion, leading to acute or chronic pancreatitis. Our investigation involved mutation analysis of the PSTI gene in patients with acute or chronic pancreatitis. METHODS: Mutation analysis for the PSTI gene was performed in patients with acute or chronic pancreatitis. Unrelated healthy volunteers and family members of a chronic pancreatitis patient with point mutations in the PSTI gene were also analyzed. RESULTS: Two types of single-point mutation in the PSTI gene were observed in one patient with chronic pancreatitis: 34Asn (AAT)-to-Ser (AGT) (101 A > G N34S: N34S) in exon 3, and 67Arg (CGC)-to-Cys (TGC) (199 C > T R67C: R67C) in exon 4. No mutations with amino-acid substitution were found in other patients or in the volunteer group. In the patient with the PSTI gene mutations, no additional mutations were observed in the cationic trypsinogen gene. The family study revealed that the mother and a maternal uncle were homozygotes for the N34S mutation, while the father and brother were compound heterozygotes for the N34S and R67C mutations. The uncle (N34S/N34S) showed clinical manifestations of pancreatitis, but the other family members did not. CONCLUSIONS: The N34S mutation may cause a predisposition to pancreatitis, with incomplete penetrance. However, with the limited information available, it is not known whether the R67C mutation promotes pancreatitis.

Adolescent↗
PubMed2001

The fine form of Helicobacter pylori on the metaplastic duodenal mucosa is associated with recurrent duodenal ulcers.

BACKGROUND/AIM: It is well known that Helicobacter pylori changes its shapes according to various environmental conditions. The aim of this study was to examine the morphological differences between H. pylori in the duodenum and that in the stomach. METHODS: Duodenal biopsy specimens were obtained from patients with duodenal mucosal lesions, and these specimens were then histopathologically examined. Morphological and genetic properties of cultured H. pylori isolates were analyzed. RESULTS: H. pylori was identified in 16 out of 50 duodenal biopsy specimens. Along with the regular form, we found a fine form of H. pylori in the gastric metaplastic mucosa of ten duodenal specimens that was shorter in length and thinner in diameter than the regular helical form. There were no detectable differences between the ureA-ureB polymorphism of the duodenal fine form and that of gastric regular form in a single patient. As compared with patients without H. pylori in the duodenum, the prevalence of recurrent duodenal ulcers significantly increased in patients with the fine form (p < 0.05), but not in patients with the regular form. CONCLUSION: The fine form of H. pylori in the metaplastic duodenal mucosa could result from its adaptation to the duodenal environment and may be associated with the recurrence of a duodenal ulcer.

Adolescent↗
PubMed2001

Hereditary pancreatitis in Japan: a review of pancreatitis-associated gene mutations.

Pancreatitis-associated gene mutations have been reported in patients with hereditary pancreatitis and idiopathic pancreatitis in the Caucasian population and involve the cationic trypsinogen gene, the pancreatic secretory trypsin inhibitor gene and the cystic fibrosis transmembrane conductance regulator gene. In the Japanese population, mutational screening analyses of these genes have shown several mutations. The present study reviews previous reports from Japan in order to evaluate the racial specificity of pancreatitis-associated gene mutations.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed2000

Idiopathic calcifying pancreatitis in a Japanese pediatric patient.

We recently experienced a rare case of chronic pancreatitis in a 13-year-old Japanese boy. Recently, in hereditary pancreatitis patients, some mutations have been identified in the trypsinogen gene. The purpose of this study was to investigate whether the same mutations could also be found in this patient. Polymerase chain reaction (PCR)-amplified products of his cationic and anionic trypsinogen genes were examined by direct sequence analysis. The gene analysis failed to show any mutation in any exons and their flanking intronic sequences of his trypsinogen genes. These findings indicate that the chronic calcifying pancreatitis in the present patient is "idiopathic", and thus a rare case of juvenile pancreatitis.

Adolescent↗
PubMed2000

Expression of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase isozymes T1 and T2 in human colorectal cancer.

Uridine diphosphate (UDP)-GalNAc: polypeptide N-acetylgalactosaminyltransferase (GalNAc transferase) catalyzes the initial step in mucin type O-glycosylation, and its expression has been assumed to be altered between normal epithelial cells and cancer cells. We studied the alteration of GalNAc transferase expression during the carcinogenesis of human colorectal epithelial cells. We produced polyclonal antibodies against synthetic polypeptides with specific sequence to two GalNAc transferase isozymes, T1 and T2. Surgically resected specimens from 50 patients with colorectal cancer were immunohistochemically stained, and the staining grade (percentage of positively stained cells) was compared between cancer and its normal counterpart in the same specimen. Significant signals for both T1 and T2 expression were seen in the supranuclear region of normal and cancer cells, indicating the subcellular localization of the enzymes in the Golgi apparatus. The prevalence of positive staining for T1 and T2 expression in colorectal cancer was significantly higher than that in normal epithelium (P < 0.05). However, the difference in staining grades between cancer and normal tissues varied in each patient. These results indicate that there is variability in the expression patterns of GalNAc transferase isozymes in normal and cancerous cells colorectal among individuals.

Adenocarcinoma↗
PubMed2000

Elevated serum levels of antibodies to carbonic anhydrase I and II in patients with chronic pancreatitis.

An immune-mediated reaction to pancreatic structures has been postulated for the pathogenesis of chronic pancreatitis (CP). Several reports demonstrate the presence of antibodies to the pancreatic ductal epithelium in some patients suffering from CP. Serum antibodies to carbonic anhydrase I (anti-CA I) and II (anti-CA II) are present in patients affected by idiopathic CP. The aim of this study was to evaluate the presence of anti-CA I and anti-CA II in a series of patients with CP. We studied 78 consecutive CP patients (62 male, 16 female; mean age 48.6 +/- 10.2 years) referred to the Verona University Center for the Study of the Pancreas. As a control group, we studied 26 healthy subjects recruited from among the medical and nursing staff of the center. Serum anti-CA I and anti-CA II levels were quantified by enzyme-linked immunosorbent assay using a standard method with minor modifications. The mean absorbance of antibodies was higher in CP patients than in control subjects (anti-CA I: 0.064 +/- 0.042 vs. 0.047 +/- 0.015, p = 0.051; and anti-CA II: 0.038 +/- 0.02 vs. 0.029 +/- 0.014, p = 0.033). Positive results were arbitrarily defined as absorbance values >0.067 for anti-CA I and 0.047 for anti-CA II. We found anti-CA I and anti-CA II positivity in 21 of 78 (27%) and 20 of 78 (26%) of CP patients, respectively, and in only two of 26 control subjects (7.7%) (p = 0.032 and 0.039). Twenty-two of 26 subjects in the control group (84.6%) and 48 of 78 patients (61.5%) in the CP group tested negative for both antibodies (p = 0.03). None of the control subjects and 12 of 78 (16.6%) of the CP patients tested positive for both anti-CA I and anti-CA II. We observed a significant correlation between anti-CA I and anti-CA II serum levels in control subjects (R = 0.423; p = 0.016) and in CP patients (R = 0.584; p < 0.0001). No correlation was found between serum antibody levels and any of the following variables: length of disease, alcohol consumption, smoking habits, pancreatic surgery, pancreatic calcifications, diabetes, and steatorrhea. Serum levels of anti-CA I and anti-CA II are elevated in some patients suffering from CP.

Adult↗
PubMed2000

A discrepant finding between magnetic resonance imaging and other imaging modalities suggests a microcystic serous cystadenoma of the pancreas.

BACKGROUND: Serous cystadenoma of the pancreas is generally considered as having no malignant potential. Thus, of clinical importance is a differential diagnosis of this neoplasm from other solid tumors that are often malignant. RESULTS: We report a case of microcystic serous cystadenoma of the pancreas. Abdominal ultrasonography, computed tomography, and endoscopic ultrasonography showed a solid mass in the body of the pancreas with a diameter of 15 mm, but magnetic resonance imaging revealed it as a unilocular cystic lesion. Histological examinations on the surgically resected tissue specimen showed a honeycombed tumor with innumerable tiny cysts appearing grossly as a solid mass. The discrepant finding between magnetic resonance imaging and other imaging modalities observed in this case is suggestive of and might be specific to microcystic serous cystadenoma of the pancreas. CONCLUSIONS: Magnetic resonance imaging is a mandatory modality to identify pancreatic serous cystadenoma that contains no visible cystic compartments on computed tomography and ultrasonography.

Cystadenoma, Serous↗
PubMed1999

Human carbonic anhydrase XIV (CA14): cDNA cloning, mRNA expression, and mapping to chromosome 1.

A full-length cDNA clone of a human carbonic anhydrase XIV (HGMW-approved gene symbol CA14) was obtained and sequenced. The cDNA sequence was 1757 bp long and was predicted to encode a 337-amino-acid polypeptide with a molecular mass of 37.6 kDa. The deduced amino acid sequence of CA XIV showed an overall similarity of 29-46% to other active CA isozymes. The highest percentage similarity was with a transmembrane CA isoform, CA XII. As observed for CA XII, CA XIV has hydrophobic segments at both termini of the deduced protein for a putative signal sequence and a transmembrane domain. CA XIV showed low activity and was sensitive to acetazolamide, but not to sulfonamide. Northern blot analysis demonstrated an approximately 1.7-kb transcript in the adult human heart, brain, liver, and skeletal muscle. RNA dot-blot analysis for CA XIV mRNA expression showed a strong signal in all parts of the human brain and a weaker signal in the colon, small intestine, urinary bladder, and kidney. RT-PCR analysis showed an intense signal in the liver and spinal cord and a faint signal in the kidney. No CA XIV mRNA was seen in the salivary gland and pancreas. In contrast, CA XII mRNA was expressed in the kidney, salivary gland, and pancreas, but not in the liver or spinal cord. The CA XIV gene was localized to human chromosome 1q21. These findings indicate genetically distinct but closely related isoforms of human transmembrane CAs, CA XII and CA XIV, which have different patterns of tissue-specific expression.

Amino Acid Sequence↗
PubMed1999

Human mitochondrial carbonic anhydrase VB. cDNA cloning, mRNA expression, subcellular localization, and mapping to chromosome x.

A cDNA clone for a novel carbonic anhydrase (CA) isozyme was isolated from human pancreas and salivary glands. The cDNA sequence of 1182 base pairs encoded a 317-amino acid protein with a predicted mass of 36.4 kDa. The highest similarity of this cDNA and the deduced amino acid sequence is to human CA V (mitochondrial CA), hereafter referred to as CA VA. Recombinant protein expressed in COS-7 cells transfected with this cDNA clone was enriched in a mitochondrial fraction. Confocal fluorescence microscopy showed cytoplasmic granular signals in COS-7 cells expressing a fusion protein of the novel CA and green fluorescent protein. Several lines of evidence suggest that the cDNA clone presented herein encodes a novel human mitochondrial CA isozyme, designated CA VB. CA VB has a hydrophobic N-terminal mitochondrial signal sequence (33 amino acid residues). Western blot analysis showed a 36-kDa protein precursor and a 32-kDa mature protein for CA VB. Similar to CA VA, CA VB is a "low activity" enzyme with a sensitivity to acetazolamide. The CA VB gene is located on Xp22.1. Northern blot analysis in normal human tissues demonstrated expression of a 1.3-kilobase transcript in heart and skeletal muscle, and reverse transcription-polymerase chain reaction analysis showed expression of CA VB in pancreas, kidney, salivary glands, and spinal cord but not in liver. CA VA mRNA expression was observed only in liver. These findings indicate these are two genetically distinct isoforms of human CA V, designated CA VA and CA VB, which have different patterns of tissue-specific distribution, suggest different physiological roles for the two mitochondrial isozymes.

Amino Acid Sequence↗
PubMed1999

Carbonic anhydrase in human pancreas: hypotheses for the pathophysiological roles of CA isozymes.

Among more than ten isozymes of the carbonic anhydrase (CA) family, only cytoplasmic CA II and membrane-bound CA IX have been reported to be expressed in human pancreas. To study the mRNA expression of CA isozymes in human pancreas, reverse transcriptase-polymerase chain reaction (RT-PCR)-Southern blot analysis and cDNA sequencing following RT-PCR were employed. CA II, IV, VI, IX, and XII were clearly identified in polyA+ RNA from normal human pancreas by RT-PCR-Southern blotting. Results with cultured pancreatic tumor cell, lines suggest that CA II, IV, IX, and XII are expressed in the ductal cells, and CA VI is expressed in the acinar cells. We propose a hypothesis for the pathophysiological function of CA isozymes in human pancreas; (1) the intraluminal CA isozymes (CA IV, VI, and possibly XII) form a mutually complementary system with cytoplasmic CA II to regulate the luminal pH of the pancreatic duct system and work as a self-defense mechanism against pancreatitis; (2) CA II and other CA isozymes play a pathological role in the autoimmune process of idiopathic chronic pancreatitis.

Animals↗
PubMed1999

cDNA sequence, mRNA expression, and chromosomal localization of human carbonic anhydrase-related protein, CA-RP XI.

A full-length cDNA clone of a human carbonic anhydrase-related protein, CA-RP XI encoded by CA11, was obtained and sequenced. The cDNA sequence was 1475 bp long and predicted to encode a 328-amino acid polypeptide with a molecular mass of 36200 Da. The deduced amino acid sequence of CA-RP XI showed an overall similarity of 42-53% to the active site residues of other active CA isozymes; however, it lacked three zinc-binding histidine residues, raising questions regarding its CA catalytic activity. Northern blot analysis demonstrated strong expression of an approx. 1.5 kb transcript in the human brain, particularly in the cerebellum, cerebral cortex, and putamen. A single copy of the CA11 gene was localized to the human chromosome 19q13.2-3. These results suggest that CA-RP XI plays a general role in the human central nervous system.

Amino Acid Sequence↗
PubMed1999

High levels of ezrin expressed by human pancreatic adenocarcinoma cell lines with high metastatic potential.

Ezrin is a membrane cytoskeleton crosslinker protein that is a member of the ERM (ezrin/radixin/moesin) family. Ezrin binds adhesion molecules such as CD43, CD44, ICAM-1, and ICAM-2, which are implicated in cell migration and metastasis. Ezrin is expressed by many tumor cell lines; however, little is known about the function of ezrin in tumorigenesis and metastasis. Here, we investigated expression of ezrin in pancreatic adenocarcinoma cell lines of different metastatic potential. Among 16 pancreatic adenocarcinoma cell lines, several cell lines showed strong expression of ezrin. Two cell lines with high metastatic potential, S2-CP9 and S2-VP10, showed very high levels of ezrin mRNA and protein, whereas other sublines showed lower levels. There was no relationship between the expression levels of ezrin and the differentiation grades of the cell lines. These results suggest that there is a relationship between high expression of ezrin and metastatic potential of pancreatic carcinomas.

Adenocarcinoma↗
PubMed1999

The ability of anti-carbonic anhydrase II antibody to distinguish autoimmune cholangitis from primary biliary cirrhosis in Japanese patients.

Serum antibody against carbonic anhydrase (CA) II has been described as a serological marker for distinguishing autoimmune cholangitis (AIC) from primary biliary cirrhosis (PBC). To validate this finding in a Japanese population, we evaluated sera from patients with PBC and AIC for antibody to human CA II. An enzyme-linked immunosorbent assay was employed to quantify serum antibody against CA II in patients with PBC (n = 40), AIC (n = 23), autoimmune hepatitis (n = 10), and extrahepatic obstructive jaundice (n = 10). Compared with the finding of a 4% prevalence of anti-CAII antibody in healthy subjects (n = 24), a significantly higher prevalence of anti-CA II antibody was detected in patients with PBC (35%) and AIC (30%) (P < 0.05), but not in patients with autoimmune hepatitis and patients with obstructive jaundice. No significant difference was observed between PBC and AIC patients. These results showed that AIC and PBC would be indistinguishable by anti-CA II antibody testing in Japanese patients. However, the finding of serum anti-CA II antibody in patients with PBC and AIC supports the disease concept of autoimmune exocrinopathy.

Autoantibodies↗