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Biomedical subjects

A Inui

Publications and source records attributed to A Inui.

At least 91 records · Page 5Linked to original sources
PubMed1997

Radioimmunodetection with 111In-labeled monoclonal antibody Nd2 in patients with pancreatic cancer.

This report summarizes results from an initial clinical evaluation of radioimmunodetection (RAID) in patients with pancreatic cancer using murine monoclonal antibody Nd2, directed against mucins from pancreatic cancer. Nd2 (2 mg) was labeled with 111In (2 mCi) and injected into 19 patients suspected of having pancreatic cancer. Planar scintigrams were taken 3 days post-infusion. As for final diagnoses after surgery, 14 cases were pancreatic cancer, and one case each was chronic pancreatitis, neurilemmoma, islet cell carcinoma, cholangioma, and apparent absence of suspected recurrent lesion of pancreatic cancer. Of 14 patients with pancreatic cancer, RAID was positive in 10 cases (71.4%). Cases other than pancreatic cancer were all negative, so the specificity was 100%. These results demonstrate that RAID using 111In-Nd2 can be useful in differentiating exocrine pancreatic cancer from benign conditions and other types of carcinomas in the pancreatoduodenal regions.

Adenocarcinoma↗
PubMed1997

Motilin is a biosignal controlling cyclic release of pancreatic polypeptide via the vagus in fasted dogs.

The mechanism of associated fluctuations in plasma motilin and pancreatic polypeptide (PP) concentrations was studied in fasted conscious dogs while gastric motility was monitored. Plasma motilin and PP concentrations were measured by radioimmunoassay. In intact normal dogs, exogenous motilin (0.03-0.3 g/kg) stimulated dose-related release of PP, but PP did not stimulate motilin release. Motilin-induced PP release was completely inhibited by pretreatment with cholinergic blockers and a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and by vagotomy. The cyclic release of PP was abolished after vagotomy and duodenectomy. However, PP release stimulated by exogenous motilin was apparent after duodenectomy but not after vagotomy. In conclusion, motilin appears to stimulate PP release via vagal, cholinergic muscarinic pathways involving 5-HT3 receptors and to act as a biosignal controlling PP release by mediating the interdigestive periodic changes in the duodenum to the center of the autonomic nervous system. This represents a new role for motilin.

Animals↗
PubMed1997

Central cholinergic regulation of pancreatic polypeptide secretion in conscious dogs.

The secretion of pancreatic polypeptide (PP) is regulated by fluctuations in blood glucose concentrations and food intake, in which vagal-cholinergic mechanisms play an important role, especially for the cephalic phase of PP secretion. In this study, we examined whether central cholinergic mechanisms are also important for PP secretion by relaying information in the brain to the vagus nerve and the muscarinic cholinergic receptors in the pancreas. Atropine sulfate (20-200 micrograms) was administered into the lateral cerebral ventricle and its effects on the basal secretion of PP as well as the secretions stimulated by insulin-induced hypoglycemia (Actrapid MC, 0.25 U/kg) and a mixed meal (243 kcal) were studied in seven dogs. Intralateral cerebroventricular (ILV) atropine (100 and 200 micrograms) abolished the fluctuations in basal PP secretion without appearing in the plasma. Pretreatment with 20, 100, and 200 micrograms ILV atropine significantly decreased the PP response to insulin-induced hypoglycemia, with the integrated PP response to 58, 32, and 26% of that of controls respectively. Atropine (100 micrograms ILV) significantly reduced the postprandial PP secretion in both the cephalic and the gastrointestinal phases, whereas increased insulin and glucose levels were unaffected. Centrally administered atropine was able to suppress the basal secretion of PP as well as the secretions stimulated by hypoglycemia and food intake. These findings suggest that (1) the spontaneous release of PP is governed by an oscillating, central cholinergic tone, and (2) the stimulating PP secretion is, at least in part, regulated by the central cholinergic system.

Animals↗
PubMed1997

Mutations in the nonstructural protein 5A gene and response to interferon therapy in young patients with chronic hepatitis C virus 1b infection.

A region associated with sensitivity to interferon (IFN) has been identified previously in the nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) genotype 1b. A study was undertaken to determine whether the presence of mutations in the NS5A2209-2248 sequence could serve as a predictor of response to IFN therapy in children and adolescents with chronic HCV-1b infection. Sixteen children (M/F ratio = 11:5; mean age 11.7 years, range 5 to 19 years) with chronic HCV-1b infection who received IFN-alpha for 6 months (total dose: 8 MU/kg) were enrolled in this study. Twelve of the children (75%) had an underlying malignant disease. Pretreatment NS5A gene sequences were detected by reverse transcription-nested polymerase chain reaction (RT-nested PCR). PCR products were subjected to direct sequencing by the dideoxy chain termination method. The amino acid sequences of NS5A2209-2248 were compared with the published NS5A2209-2248 sequences of HCV-J. The NS5A2209-2248 sequences were detected in 10(63%) of the 16 children. Eight patients had the wild-type sequences, with no amino acid changes; and two patients had the intermediate type, with only one amino acid change. Four (25%) of the 16 patients responded completely to IFN therapy. Three of the four patients had the wild-type sequences, while none of the patients with the mutant type had a complete response. Serum HCV RNA levels in children with the wild type did not differ from those in patients with the mutant type. This study shows that there is no significant correlation between response to IFN and mutations in NS5A2209-2248. The amino acid sequences in NS5A2209-2248 in young patients with chronic HCV-1b infection appear to be conserved.

Adolescent↗
PubMed1996

Polydispersity in sulfation profile of oligosaccharide alditols isolated from the protein-linkage region and the repeating disaccharide region of chondroitin 4-sulfate of bovine nasal septal cartilage.

Proteoglycans of bovine nasal septal cartilage bear predominantly chondroitin 4-sulfate. After exhaustive chondroitinase ABC digestion of a chondromucoprotein preparation rich in proteoglycans and subsequent reductive beta-elimination, five hexasaccharide alditols were isolated from the glycosaminoglycan-protein linkage region. They were analyzed by enzymatic digestion in conjunction with HPLC and by one-dimensional and two-dimensional 1H-NMR spectroscopy. They share the conventional core saccharide structure delta 4.5HexA alpha 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol (where delta 4.5HexA is 4,5-unsaturated hexuronic acid), but have different sulfation profiles. One compound (I) does not contain sulfate. Two of the three monosulfated compounds (II and III) have an O-sulfate group at either C6 or at C4 of the GalNAc residue. The other monosulfated compound (IV) is hitherto unreported and has a O-sulfate at C4 of the Gal residue preceding the GlcA residue, whereas the GalNAc is not sulfated. The disulfated compound (V) has sulfate groups at C4 of both the Gal residue preceding GlcA and the GalNAc residue. The molar ratio of compounds I-V is 38.3:5.9:43.0:1.6:11.2. The structural heterogeneity of these hexasaccharide alditols reflects the polydispersity in the linkage region of the chondroitin sulfate chains. In addition, two trisaccharide and two tetrasaccharide alditols derived from the repeating disaccharide region of the chondroitin sulfate chains were also isolated. Their structures were unambiguously determined by enzymatic analysis and by 1H-NMR spectroscopy as delta 4.5HexA alpha 1-3GalNAc(4-O- or 6-O-sulfate)beta 1-4GlcA-ol and delta 4.5HexA alpha 1-3GalNAc(4-O- or 6-O-sulfate) beta 1-4GlcA beta 1-3GalNAc(4-O-sulfate)-ol, respectively.

Animals↗
PubMed1996

Efficacy of interferon in treating chronic hepatitis C in children with a history of acute leukemia.

Interferon (IFN) is effective in treating adults as well as children with chronic hepatitis C. We investigated the efficacy of IFN therapy in 13 children with underlying acute leukemia who had chronic hepatitis C (age range, 5 to 17 years; mean age, 9.9 years). Natural IFN- alpha was administered at a dose of 0.1 mega unit (MU)/kg (maximum dose, 6.0 MU) daily for 2 weeks and then three times per week for an additional 22 weeks (total dose, 8 MU/kg). IFN treatment was initiated at least 2 years after the completion of treatment for acute leukemia. A complete response was obtained in 5 children (38%). The serum level of anti-hepatitis C virus core antibody was closely related to the response to IFN. IFN therapy was well tolerated by all but 1 of the children, who developed mild transient heart failure 4 months after the initiation of therapy. IFN therapy for children with chronic hepatitis C who had underlying acute leukemia was beneficial. However, further trials are required to confirm the safety and improve the dosage schedule of IFN therapy.

Acute Disease↗
PubMed1996

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion.

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

Adult↗
PubMed1996

Clinical significance of serum CYFRA 21-1 in gastric cancer.

We studied the clinical significance of the soluble cytokeratin 19 fragment detected with monoclonal antibody CYFRA 21-1 in the sera of patients with histologically proven gastric cancer. Sera of 110 patients with gastric cancer were analysed for CYFRA 21-1 levels by a two-step sandwich enzyme immunoassay. There were no significant differences between CYFRA 21-1 levels and the histotype, depth of invasion or vessel invasion. However, CYFRA 21-1 was significantly higher in the presence of peritoneal metastases, liver metastases and extensive nodal involvement. When the positive cut-off value was defined as 5 ng ml-1, the CYFRA 21-1 in the stage IV and recurrent cases was 55.6% and 66.7%, respectively, which was as high as carcinoembryonic antigen (CEA) and greater than carbohydrate antigen 19-9 (CA 19-9). The positivities in stage I/II and III were zero and 5.9%, respectively, and false-positive rate in 76 patients with benign gastrointestinal disorders was 2.6%. There appeared to be no correlation between CYFRA 21-1 and CEA or CA 19-9. The patients with above 5 n ml-1 of CYFRA 21-1 had a significantly poorer prognosis. Multivariate analysis indicated that CYFRA 21-1 was an independent prognostic factor, while CEA and CA 19-9 failed to be of prognostic value. In conclusion, CYFRA 21-1 is a reliable tumour marker for gastic cancer in predicting very advanced cases, recurrence of the disease and overall poor prognosis.

Antibodies, Monoclonal↗
PubMed1996

Effect of nonpeptide motilin agonist EM523 on release of gut and pancreatic hormones in conscious dogs.

BACKGROUND & AIMS: EM523, a nonpeptide motilin agonist, is being developed for clinical use to improve delayed gastric emptying. The aim of this study was to examine the effect of EM523 on endogenous release of gut and pancreatic hormones in conscious dogs. METHODS: Motility of the gastrointestinal tract was monitored using force transducers. Blood concentrations of gut and pancreatic hormones were measured using a specific radioimmunoassay. EM523 (3 micrograms/kg) or normal saline (5 mL) was given during the phase I period of the interdigestive state. RESULTS: A single injection of EM523 always induced phase III-like contractions in the intact gastric antrum and was accompanied by significant (P < 0.01) release of motilin, pancreatic polypeptide, and insulin; glucagon, gastrin, cholecystokinin, and secretin were not released by EM523. The significant release of these hormones was suppressed by pretreatment with atropine and completely eliminated by a 5-hydroxytryptamine 3 receptor antagonist and truncal vagotomy. CONCLUSIONS: The findings suggest that EM523 stimulates the release of pancreatic polypeptide, insulin, and motilin by activating the cholinergic parasympathetic nerve system, finally stimulating the endocrine pancreas through vagally cholinergic muscarinic receptors in the pancreatic islets. The participation of 5-hydroxytryptamine 3 receptors in this system is strongly suggested by the results.

Animals↗
PubMed1996

Serial changes in titers of antibody to hepatitis B surface antigen after immunization of infants born to mothers with hepatitis B e antigen.

To evaluate the long-term protection provided by hepatitis B (HB) vaccine in a high-risk environment, we followed 50 infants born to mothers with hepatitis B e (HBe) antigen. These infants were immunized with a three-dose regimen of plasma-derived HB vaccine and were followed for up to 10 years. Two infants (4%) acquired hepatitis B virus (HBV) infection before 1 year of age. The 48 other infants remained hepatitis B surface (HBs) antigen-negative during the follow-up period. The geometric mean titers of serum antibody to HBs antigen rapidly decreased during the first 4 years but remained at protective levels throughout the follow-up period. These data suggest that protection against significant HBV infection lasts for at least 10 years. We conclude that the long-term protection afforded by plasma-derived HB vaccine is satisfactory and that a routine booster dose before 10 years of age is not necessary.

Female↗
PubMed1996

Radioimmunotherapy for pancreatic carcinoma using (131)I-labeled monoclonal antibody Nd2 in xenografted nude mice.

We investigated the biodistribution, radiolocalization, and radioimmunotherapeutic potential of (131)I-labeled Nd2 in athymic nude mice bearing human pancreatic carcinoma xenografts. (131)I-Nd2 was accumulated at high levels in the tumor, in contrast to blood, liver, spleen, and other normal organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors of mice injected with 7.4 MBq of (131)I-Nd2 were 80% less than those of tumors before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen in histological sections of tumors of 7-week-treated mice. The growth of tumors in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then injected twice with 3.7 MBq of (131)I-Nd2 was suppressed over 7 weeks. Neither leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled Nd2. Thus (131)I-labeled Nd2 may have clinical application in the radioimmunotherapy of pancreatic cancer.

Animals↗