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Biomedical subjects

I Nishimori

Publications and source records attributed to I Nishimori.

At least 37 records · Page 2Linked to original sources
PubMed1999

Serum antibodies to Mycobacterium paratuberculosis in patients with Crohn's disease.

Mycobacterium paratuberculosis has been suggested as a causative organism of Crohn's disease. Despite a long-term debate to prove this possibility, the role of this bacteria in the pathogenesis of Crohn's disease is still a subject of controversy. In the present study, serum antibodies (IgG, IgA, and IgM) to the protoplasmic antigen of M. paratuberculosis were quantified in patients with Crohn's disease and in control subjects by using an enzyme-linked immunosorbent assay whose specificity was increased by preabsorbing the sera with cell extracts of Mycobacterium phlei. As compared to normal controls (1/20; 0.062+/-0.022), a significant difference was seen in the antibody-positive prevalence rate and mean values of the serum IgG titer in patients with Crohn's disease (5/13; 0.102+/-0.039) (P < 0.05), but not in patients with ulcerative colitis (2/20; 0.065+/-0.035) and tuberculosis (0/4; 0.053+/-0.008). No significant differences were seen in the antibody-positive prevalence rate and mean values of the serum IgA and IgM titers among the four study groups. These results indicate the unique immune response to M. paratuberculosis in patients with Crohn's disease, suggesting that this organism may play some role in the pathogenesis of Crohn's disease.

Adolescent↗
PubMed1999

Autoimmune pancreatitis, pancreatic mass, and lower gastrointestinal bleed.

Autoimmune pancreatitis (AIMP) is a recently described clinical entity causing chronic pancreatitis. It often presents with diffuse enlargement of the pancreas and/or a focal mass at the head of the pancreas causing common bile duct obstruction and jaundice. In most instances, AIMP is mistaken for pancreatic cancer. A number of laboratory abnormalities such as positive antinuclear antibody, hypergammaglobulinemia, and antibody to carbonic anhydrase are often present in these patients. Currently, pancreatic biopsy demonstrating characteristic histopathologic changes is essential to establish the diagnosis. We report the first case of AIMP presenting as a pancreatic tail mass and lower gastrointestinal bleed.

Adult↗
PubMed1999

Identification of carbonic anhydrase IV and VI mRNA expression in human pancreas and salivary glands.

Cytoplasmic carbonic anhydrase (CA) II is involved in acid-base balance in a wide variety of tissues. Extracellular CAs, membrane-bound CA IV and excretory CA VI, play a cooperative role with CA II in regulating the luminal pH in kidney and salivary glands, respectively. To extend the evidence into pancreas, we studied messenger RNA (mRNA) expressions of CA IV and CA VI in human pancreas. mRNA expressions of CA II, IV, and VI were studied in human pancreas, kidney, liver, and salivary glands by three different detection methods: reverse transcription-polymerase chain reaction (RT-PCR), RT-PCR-Southern blot, and Northern blot analyses. CA IV mRNA expression was consistently detected in all four tissues except for liver; only RT-PCR-Southern blot successfully identified its expression in liver. In contrast, RT-PCR and RT-PCR-Southern blot identified CA VI mRNA in salivary glands and pancreas, but Northern blot failed to detect its expression in pancreas. There was no detectable signal of CA VI expression in kidney and liver by all detection methods. CA II mRNA expression was consistently detected in all tissues studied. These results indicate that pancreas and salivary glands contain both of CA IV and VI and suggest that the extracellular CA isozymes may form a mutually complementary system with CA II to regulate the luminal pH of the pancreatic duct system.

Blotting, Northern↗
PubMed1999

Cholecystokinin A and B receptor mRNA expression in human pancreas.

Little information is available on the expression of cholecystokinin (CCK) receptors in the human pancreas, especially in the developing pancreas. We evaluated expression patterns for the CCK receptors in human pancreas at three different ages: fetus, infant, and adult. Expressions of CCK-A and CCK-B receptor messenger RNA (mRNA) were studied in human midtrimester fetus (14-15 weeks' gestation), infant (50 days old), and adult pancreas by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Expression levels of mRNA for both receptors also were evaluated by Northern blot analysis of adult pancreas. Northern blot analysis showed a strong signal for CCK-B receptor mRNA in adult pancreas, but no detectable signal for CCK-A receptor mRNA. However, RT-PCR/Southern blotting showed the presence of CCK-A receptor mRNA in adult pancreas. This was confirmed by sequencing of the complementary DNA (cDNA). RT-PCR/Southern blot analysis also showed CCK-A and CCK-B receptor mRNA expression in fetal and infant pancreas. These results show that the both CCK receptor types are expressed in human pancreas at stages of early gestation, but there is predominant expression of CCK-B receptor in adult pancreas.

Adult↗
PubMed1999

Mutations in exons 2 and 3 of the cationic trypsinogen gene in Japanese families with hereditary pancreatitis.

BACKGROUND/AIMS: Single-point mutations in the cationic trypsinogen gene have been reported in hereditary pancreatitis kindreds in the white population. The aim of the present study was to investigate whether similar gene mutations are present in Japanese hereditary pancreatitis kindreds. METHODS: All five exons of the cationic trypsinogen gene were amplified by polymerase chain reaction and sequenced in six Japanese families with hereditary pancreatitis. RESULTS: Two types of single-point mutation in the cationic trypsinogen gene, which were identical with those reported in white families with hereditary pancreatitis, were observed in separate Japanese families with hereditary pancreatitis: 21Asn (AAC) to Ile (ATC) (N21I) in exon 2 and 117Arg (CGC) to His (CAC) (R117H) in exon 3. Pancreatitis occurred at more advanced ages in patients with the N21I mutation than in those with the R117H mutation. Besides normal polymorphisms in exons 4 and 5, no mutation was found in patients in the remaining four families with hereditary pancreatitis, 21 patients with sporadic chronic pancreatitis, or five normal subjects. CONCLUSIONS: These results show heterogeneity, but no racial specificity, in the cationic trypsinogen gene mutations in hereditary pancreatitis kindreds. A distinctive clinical feature for each of the mutation types is suggested: adult onset for the N21I mutation and childhood onset for the R117H mutation.

Adolescent↗
PubMed1997

Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines.

The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma.

Actins↗
PubMed1997

Increased sensitivity of gastric cancer cells to natural killer and lymphokine-activated killer cells by antisense suppression of N-acetylgalactosaminyltransferase.

UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases (GalNAc transferases) catalyze the initial reaction in O-linked (mucin type) oligosaccharide biosynthesis. To attempt to inhibit the synthesis of O-glycan, we transfected antisense cDNA of GalNAc transferase type 1 (GalNAc-T1) into a human gastric cancer cell line, JRST. A decreased expression of GalNAc-T1 at the level of both mRNA and protein was observed in the resultant transfectants. They demonstrated a significantly increased sensitivity to NK and lymphokine-activated killer cells in vitro compared with parental cells and mock transfectants. Although there was no significant difference in in vitro cell proliferation among parental cells, mock transfectants, or antisense transfectants, the in vivo growth rate of antisense transfectants using SCID mice was clearly lower than that of parental cells and mock transfectants. Furthermore, the treatment of mice with anti-asialo-G(M1) Ab abolished this growth-inhibitory effect of antisense transfection. From these results, we conclude that antisense suppression of GalNAc-T1 could increase the sensitivity of tumor cells to NK and lymphokine-activated killer cells, suggesting that this strategy may be of use as a new immunogene therapy.

Animals↗
PubMed1997

Endosonography-guided endoscopic resection of duodenal carcinoid tumor.

Endoscopic resection techniques using snare polypectomy with or without submucosal saline injection have also been applied to resect smaller duodenal carcinoid tumors. We report on two patients where endoluminal ultrasound using a small diameter probe was used to visualize the adherence of the carcinoids to the underlying wall layers and the separating effect of subtumoril saline injection. One patient, in whom a clear separation between the tumor and the underlying tissue after saline injection was visualized, underwent successful endoscopic resection. In the other patient no clear separation could be achieved after saline injection and the patient underwent surgical removal of his tumor; both tumors were 1 cm or less in their maximal diameter.

Aged↗
PubMed1996

Serum antibodies to carbonic anhydrase I and II in patients with idiopathic chronic pancreatitis and Sjögren's syndrome.

BACKGROUND & AIMS: Patients with idiopathic chronic pancreatitis and Sjögren's syndrome show immune responses against a 60-kilodalton protein isolated from human pancreas extracts. Monoclonal antibody SP3-1, raised against the 60-kilodalton protein, reacts with ductal cells in several exocrine organs and cross-reacts with human carbonic anhydrase II. The present study evaluated serum from patients with these diseases for antibodies to human carbonic anhydrase I and II. METHODS: An enzyme-linked immunosorbent assay was used to quantify serum antibody against carbonic anhydrase I and II. RESULTS: Serum antibodies against carbonic anhydrase I and II were detected in 7 and 11 of 33 patients with idiopathic chronic pancreatitis, respectively, and in 8 and 13 of 21 patients with Sjögren's syndrome, respectively. The positive prevalence rates of patients with antibodies of carbonic anhydrase II were significantly different among patients with idiopathic chronic pancreatitis and Sjögren's syndrome compared with normal patients (1 of 21). There were no significant differences in the prevalence rates of patients with alcoholic chronic pancreatitis (3 of 20), gallstone-related chronic pancreatitis (0 of 7), and primary biliary cirrhosis (1 of 11). CONCLUSIONS: The results suggest that carbonic anhydrase II is one candidate target antigen recognized during the autoimmune pathophysiology observed in idiopathic chronic pancreatitis and Sjögren's syndrome.

Antibody Specificity↗
PubMed1995

Induction of experimental autoimmune sialoadenitis by immunization of PL/J mice with carbonic anhydrase II.

Experimental autoimmune sialoadenitis was induced in PL/J (H-2u) mice by intradermal immunization with human carbonic anhydrase II (CAII) and adjuvant containing monophosphoryl lipid A and trehalose diorynomycolate. Mice immunized with CAII showed a significant increase in the number and size of foci with lymphocytic infiltration in the salivary gland compared with mice immunized with adjuvant alone and untreated mice. In mice immunized with CAII, lymphocytic foci were observed around intercalated and intralobular ducts in the salivary glands, resulting in atrophy and replacement of acinar units. The epithelial cells of salivary ducts adjacent to the lymphocytic foci showed both degenerative and regenerative changes. Similar lymphocytic infiltrations were observed in the pancreas and kidney of a few mice immunized with CAII. Among several mouse strains with different H-2 haplotypes (p, q, r, s, and u), strains bearing H-2s and H-2u were susceptible to CAII-induced sialoadenitis. These results indicate that sialoadenitis induced by the immunization of CAII in mice may serve as a disease model of Sjögren's syndrome and that CAII or its derived peptides in association with the MHC may be one Ag recognized by an autoimmune response in this syndrome.

Animals↗
PubMed1995

Pancreatic involvement in patients with Sjögren's syndrome and primary biliary cirrhosis.

Serum pancreatic enzyme activities, exocrine pancreatic function, and pancreatic ductal morphology were evaluated in patients with one or both of Sjögren's syndrome and primary biliary cirrhosis. Ten of 20 patients with Sjögren's syndrome (50%), 6 of 17 patients with primary biliary cirrhosis (35%), and 4 of 11 patients with both diseases (36%) had an elevated level of at least one pancreatic enzyme, including elastase-1, lipase, and trypsin. Diminished excretion of N-benzoyl-L-tyrosyl-para-aminobenzoic acid was observed in 3 of 17 patients with Sjögren's syndrome (18%), 4 of 16 with primary biliary cirrhosis (25%), and none of 7 with both diseases. Endoscopic retrograde pancreatograms demonstrated an abnormal pancreatic ductal configuration in 3 of 11 patients with Sjögren's syndrome (27%), 2 of 9 with primary biliary cirrhosis (22%), and 3 of 4 with both diseases (75%). Only minimal changes in branches of the pancreatic duct were observed in the pancreatogram. Finally, 9-30% of patients with Sjögren's syndrome and/or primary biliary cirrhosis had a mild and intermittent abdominal pain. These findings support the concept of a disease complex, "autoimmune exocrinopathy," in patients with Sjögren's syndrome, primary biliary cirrhosis, and chronic pancreatitis.

4-Aminobenzoic Acid↗
PubMed1994

N-acetylgalactosamine glycosylation of MUC1 tandem repeat peptides by pancreatic tumor cell extracts.

Synthetic peptides corresponding to the human mucin MUC1 tandem repeat domain (20 residues) were glycosylated in vitro by using UDP-N-[3H]acetyl-D-galactosamine (GalNAc) and lysates of pancreatic tumor cell lines. Results obtained with peptides of different lengths (from one to five repeats) suggest that increasing the number of tandem repeats has neither a positive nor a negative effect on the density of glycosylation along the MUC1 tandem repeat protein backbone. Purified glycopeptides were sequenced on a gas-phase sequencer, and glycosylated positions were determined by measuring the incorporated radioactivity in fractions collected following each round of Edman degradation. The results showed that two of three threonine residues on the MUC1 tandem repeat peptides were glycosylated by pancreatic tumor cell lysates at the following positons: GVTSAPDTRPAPGSTAPPAH (underlined T indicates position of GalNAc attachment). None of the serine residues were glycosylated. Determination of the mass of the glycopeptides by mass spectrometry confirmed that a maximum of two molecules of GalNAc were covalently linked to each 20-residue repeat unit in the peptides. The data presented here show that acceptor substrate specificity of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase detected in lysates of pancreatic and breast tumor cell lines is identical and is limited to some but not all threonines in the MUC1 tandem repeat peptide sequence. The influence of primary amino acid sequence on acceptor substrate activity was evaluated by using several peptides that contain single or double amino acid substitutions (relative to the native human MUC1 sequence). These included substitutions in the residues that were glycosylated and substitutions of the surrounding primary amino acid sequence. The results of these studies suggest that primary amino acid sequence, length, and relative position of the residue to be glycosylated dramatically affect the ability of peptides to serve as acceptor substrates for the UDP-GalNAc:polypeptide N-acetylgalatosaminyltransferase.

Acetylgalactosamine↗
PubMed1994

Influence of acceptor substrate primary amino acid sequence on the activity of human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase. Studies with the MUC1 tandem repeat.

Synthetic peptides (30 and 20 residues long) corresponding to the native MUC1 tandem repeat sequence (20 residues long) were glycosylated in vitro using UDP-[3H]GalNAc and lysates from the human breast tumor cell line MCF7. Purified glycopeptides were sequenced on a gas-phase sequenator, and glycosylated positions were determined by measuring the incorporated radioactivity in fractions collected following each round of Edman degradation. The results showed that 2 of 3 threonines on the MUC1 tandem repeat peptides were glycosylated at the following positions: GVTSAPDTRPAPGSTAPPAH (underlined Thr residues indicate positions of GalNAc attachment); no glycosylation of serine residues was detected. Determination of the mass of the glycopeptides by mass spectrometry showed that a maximum of two molecules of GalNAc were covalently linked to each 20-residue repeat unit in the peptides. The influence of substrate primary amino acid sequence in determining the substrate specificity of UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl-transferase activity was evaluated using as acceptor substrates a series of overlapping 9-residue peptides that represent a moving set through the tandem repeat of the MUC1 mucin. In addition, the influence of primary amino acid sequence on acceptor substrate activity was evaluated using several peptides that contained single or double amino acid substitutions (relative to the native human MUC1 sequence). These included substitutions in the residues that were glycosylated and substitutions in the surrounding primary amino acid sequence. This study demonstrates that primary amino acid sequence, length, and relative position of the residue to be glycosylated dramatically affect the ability of peptides to serve as acceptor substrates for UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase.

Amino Acid Sequence↗
PubMed1994

Identification of autoantibodies to a pancreatic antigen in patients with idiopathic chronic pancreatitis and Sjögren's syndrome.

A serum autoantibody to a pancreatic antigen was identified in patients with idiopathic chronic pancreatitis and Sjögren's syndrome by radioimmunoassay and Western immunoblotting. Antigen from porcine and human pancreas extracts was partially purified using a monoclonal antibody, SP3-1, which recognizes the antigen in duct cells of various exocrine organs. Solid phase radioimmunoassay of the pancreatic antigen showed a positive result in 6 of 20 patients with idiopathic chronic pancreatitis (30%), 3 of 11 patients with Sjögren's syndrome (27%), and 1 of 15 patients with alcoholic chronic pancreatitis (7%). Among seven patients with stone-related chronic pancreatitis, six patients with autoimmune thyroiditis, and 14 normal controls, none showed evidence of autoantibodies to the pancreatic antigen. Western immunoblotting showed that serum antibody commonly reacted with a 60-kD molecule of either porcine or human pancreatic antigen, with which SP3-1 also reacted. These results show the existence of the autoantibodies to pancreas, especially to an antigen expressed in ductal cells of exocrine glands, in idiopathic chronic pancreatitis and Sjögren's syndrome, and suggest the possibility of an autoimmune mechanism in the pathogenesis of idiopathic chronic pancreatitis.

Animals↗
PubMed1994

Immune complex specific for the pancreatic duct antigen in patients with idiopathic chronic pancreatitis and Sjögren syndrome.

Circulating immune complexes (ICs) containing the pancreatic antigen against SP3-1 monoclonal antibody were measured in patients with idiopathic chronic pancreatitis (ICP) and Sjögren syndrome (SjS) by Raji cell and solid-phase radioimmuno-assays (RIA). The mean serum levels of ICs measured by solid-phase RIA were significantly higher in patients with ICP (n = 23) and SjS (n = 21) than control (n = 15, p < 0.05, p < 0.02, respectively). ICs were positive in 10 patients with ICP (43%) and 12 SjS patients (57%). Raji cell assay also revealed a significantly higher serum ICs levels in patients with ICP (n = 17) and SjS (n = 12) compared with those of control (n = 7, p < 0.025, p < 0.005, respectively). Seven patients with ICP (41%) and 8 SjS patients (67%) had positive ICs. This was in contrast to the normal level of ICs in patients with alcoholic chronic pancreatitis, primary biliary cirrhosis, and chronic thyroiditis. Our analysis demonstrated a significant and positive relationship between RIA and Raji cell assay (r = 0.70, p < 0.05). Our results suggest that ICs specific for SP3-1 may play a role in the pathophysiology of ICP and SjS.

Alcoholism↗
PubMed1994

Incidence of female breast cancer among atomic bomb survivors, 1950-1985.

An incidence survey among atomic bomb survivors identified 807 breast cancer cases, and 20 second breast cancers. As in earlier surveys of the Life Span Study population, a strongly linear radiation dose response was found, with the highest dose-specific excess relative risk (ERR) among survivors under 20 years old at the time of the bombings. Sixty-eight of the cases were under 10 years old at exposure, strengthening earlier reports of a marked excess risk associated with exposure during infancy and childhood. A much lower, but marginally significant, dose response was seen among women exposed at 40 years and older. It was not possible, however, to discriminate statistically between age at exposure and age at observation for risk as the more important determinant of ERR per unit dose. A 13-fold ERR at 1 Sv was found for breast cancer occurring before age 35, compared to a 2-fold excess after age 35, among survivors exposed before age 20. This a posteriori finding, based on 27 exposed, known-dose, early-onset cases, suggests the possible existence of a susceptible genetic subgroup. Further studies, involving family histories of cancer and investigations at the molecular level, are suggested to determine whether such a subgroup exists.

Adult↗
PubMed1993

Specific cellular immune responses to pancreatic antigen in chronic pancreatitis and Sjögren's syndrome.

The specific cellular immune response to the partially purified pancreatic antigen was studied by the peripheral blood lymphocyte proliferation assay in patients with chronic pancreatitis, Sjögren's syndrome, and primary biliary cirrhosis. A significant positive result (stimulation index > 2.0) was observed in 7 of 21 patients with idiopathic chronic pancreatitis (33%; P < 0.05), 6 of 7 patients with Sjögren's syndrome-associated chronic pancreatitis (86%; P < 0.0005), and 6 of 11 patients with Sjögren's syndrome (55%; P < 0.01), compared to normal controls whose stimulation index was 0.94 +/- 0.28 (mean +/- SD; n = 14; range, 0.56-1.60). On the other hand, patients with alcoholic chronic pancreatitis (17%; n = 12), stone-related chronic pancreatitis (0%; n = 7), primary biliary cirrhosis-associated chronic pancreatitis (33%; n = 3), primary biliary cirrhosis (0%; n = 4), systemic lupus erythematosus (17%; n = 6), and autoimmune thyroiditis (0%; n = 6) showed no significant difference from normal controls. Furthermore, in patients with idiopathic chronic pancreatitis who had positive results, a lymphocyte proliferative response to the pancreatic antigen was observed in T cells, especially in the CD4+ T cell subpopulation. These results suggest that the pancreatic antigen plays a role in the pathogenesis of a part of idiopathic chronic pancreatitis and Sjögren's syndrome in association with T cell responses and, also, suggest that autoimmunity may be a possible etiological factor in chronic pancreatitis.

Animals↗