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Biomedical subjects

A Inui

Publications and source records attributed to A Inui.

At least 109 records · Page 6Linked to original sources

Response to interferon therapy in children with chronic hepatitis C.

We evaluated the effect of interferon therapy and investigated factors that may influence the outcome in 18 children with chronic hepatitis C. A complete response was obtained in 10 children (56%). The titer for pretreatment serum virus ribonucleic acid (< or = 10(7) copies/ml) was correlated significantly with a complete response to therapy.

Alanine Transaminase↗

Intratumoral injection of an adriamycin immunoconjugate against human pancreatic cancer xenografts.

We have evaluated the effect of an adriamycin conjugate of monoclonal antibody Nd2 (ADM-Nd2) on the growth rate of SW1990 xenografts grown subcutaneously in athymic nude mice. Intravenous or intraperitoneal administration of radiolabeled Nd2 resulted in a maximum tumor accumulation of approximately 45% of the initial dose/g of tumor 3-7 days after administration. However, administration into the tumor produced retention of 1200%ID/g 1 day after, with 50% of this high value remaining even at 7 days after administration. In contrast, intratumoral administration of a non-specific immunoglobulin showed a lower initial retention and rapid loss of label. Both intravenously and intratumorally administered ADM-Nd2 reduced the growth rate of SW1990 xenografts. While a single intravenous administration arrested growth for about two weeks, a single intratumoral injection prevented any increase in tumor size even 45 days after administration. Xenografts treated with ADM-Nd2 showed degenerative changes at the histological level. Neither Nd2 alone nor Adriamycin alone inhibited growth when administered at the same dose as the conjugate.

Animals↗

A new cancer-associated antigen defined by a monoclonal antibody against a synthetic carbohydrate chain.

Carbohydrate antigens can be designed by referring to previously defined carbohydrate structures. We have generated a novel monoclonal antibody (MAb) (F1 alpha-75) against an artificially designed antigen (F1 alpha), using organic-synthetic chemistry methods and hybridoma technology. F1 alpha (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Ser/Thr) belongs to core type 6 of O-linked glycans, which has not been previously reported in human cancers. To produce antibodies against F1 alpha, a glycolipid was synthesized which carries the carbohydrate portion of F1 alpha on a ceramide foundation (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Cer). The MAbs we obtained (F1 alpha-75, F1 alpha-87) specifically recognized F1 alpha and had only a very weak or no cross-reactivity with other glycolipids similar to F1 alpha. We investigated the expression of F1 alpha in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. F1 alpha was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with F1 alpha-75 was 80.0% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. F1 alpha-75 also reacted with the tissues neighboring gastric and pancreatic tumors but not intensely. Among fetal tissues, F1 alpha-75 reacted with the pyloric glands of the stomach, the centro-acinar cells of the pancreas, the convoluted tubules of the kidney and the terminal bronchioles of the lung.

Antibodies, Monoclonal↗

Negative and positive effects of intracerebroventricular scopolamine on memory in mice undergoing passive avoidance and escape tests.

The effects of intracerebroventricular administration of scopolamine on memory and learning in the conscious, freely moving mouse were evaluated using step-down passive avoidance and water maze tests. A new technique was used that allows convenient injection into the cerebral ventricles without disturbing the animal's behavior. No significant changes in locomotor activity were observed after low doses of scopolamine (0.1 and 1.0 microgram). However, 10 micrograms produced an increase in locomotor activity, while 100 micrograms caused an initial decrease followed by an increase in activity. In the passive avoidance test, scopolamine significantly impaired memory acquisition at doses higher than 1.0 microgram, consolidation at a dose of 100 micrograms, and retrieval at doses of 10 and 100 micrograms. In contrast, a dose of 0.1 microgram significantly improved consolidation and retrieval. In the water maze with a bridge, scopolamine either impaired memory acquisition, consolidation, and retrieval, or had no significant effect in the dose range tested. These results suggest that there are differences in the process of memory formation in the passive avoidance and escape tests.

Animals↗

Histologic activity of the liver in children with transfusion-associated chronic hepatitis C.

Adults with chronic hepatitis C develop cirrhosis over a period of 6 to 20 years, but there are few reports of this disorder in children. To determine the histologic activity of chronic hepatitis C in children, we examined 31 biopsy specimens from 25 children (age range 3-16 years) with this disease. All patients were seropositive for antibody to hepatitis C virus by second-generation testing, and for HCV-RNA by the polymerase chain reaction. All cases were transfusion-associated. Patients were divided into two groups according to underlying disease: malignant disease or aplastic anemia (Group A, 17 cases) and non-malignant disease (Group B, eight cases). All patients in Group A, but only one in Group B, had received multiple transfusions. All patients in Group A had received intensive courses of cytotoxic and immunosuppressive agents. The histologic diagnosis was made using the standard criteria and Knodell's histology activity index. Chronic persistent hepatitis was more common in Group B (six patients) than in Group A (three patients). Chronic aggressive hepatitis 2B was found only in Group A (five patients). The mean histology activity index score was higher in Group A than in Group B (8.5 vs. 5.7). Six patients (four in Group A and two in group B) subsequently had a liver biopsy. The pathological diagnosis did not change after the second biopsy in any patient in Group B, while two patients in Group A showed a rapid progression of hepatitis. In each category of the histology activity index, periportal necrosis and intralobular necrosis were more severe in Group A than in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dynorphin binds to neuropeptide Y and peptide YY receptors in human neuroblastoma cell lines.

The modulation of neuropeptide Y (NPY) and peptide YY (PYY) receptors by dynorphin, luteinizing hormone-releasing hormone (LHRH), corticotropin-releasing factor (CRF), and cholecystokinin octapeptide has been studied in human neuroblastoma cell lines SK-N-MC and SMS-MSN, which express Y1 and Y2 receptors for NPY/PYY. Dynorphin A and LHRH inhibited the binding of NPY/PYY to SK-N-MC cell membranes at concentrations ranging from 10(-7) to 10(-5) M, whereas dynorphin A and CRF were effective in SMS-MSN cells. The inhibitory effect of dynorphin A on NPY/PYY binding was observed in the presence of guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analogue, as well as H-7 and H-8, novel inhibitors of protein kinases C and A. However, U-50488, the most potent kappa-selective compound did not mimic the dynorphin action. Dynorphin A showed neither effect on the dissociation of NPY/PYY from their receptors nor inhibition on the basal as well as forskolin-stimulated adenosine 3',5'-cyclic monophosphate response. These results indicate that the interaction of dynorphin A with Y1 and Y2 receptors is not mediated by changes in receptor-G protein interaction, receptor phosphorylation, and allosteric binding to NPY/PYY receptors but that dynorphin A binds to NPY/PYY receptors at high concentrations, probably in an antagonistic manner.

Corticotropin-Releasing Hormone↗

[Hereditary spherocytosis associated with non-Hodgkin's lymphoma in the spleen].

A 60-year-old female was admitted complaining of anemia. We diagnosed her hereditary spherocytosis (HS) from spherocytosis and family history and found a tumor in her enlarged spleen. Splenectomy was performed and swollen paraaortic lymph nodes were found at laparotomy. The tumor in the spleen was diagnosed as Non-Hodgkin's lymphoma (follicular mixed type). After CHOP therapy she entered complete remission. Though the relationship between HS and malignant lymphoma was not clear, splenomegaly due to hemolysis inducing chronic stimulation might have resulted in malignant lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

Effects of pancreatic polypeptide family peptides on feeding and learning behavior in mice.

We studied the effects of intra-third cerebroventricular administration of neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) on the locomotor activity and the feeding and learning behavior of mice. NPY (0.3-10 micrograms), PYY (0.1-10 micrograms) and PP (3.0-10 micrograms) produced significant increases in locomotor activity. A significant decrease was then observed 15 min after administration of 10 micrograms of PYY. NPY, PYY and PP significantly increased food intake at 20 min and this effect continued for 2 to 4 hr at the high doses. The feeding response to PP family peptides were quite similar to that in locomotor activity with respect to dose-response, time course and peptide specificity. Learning behaviors were evaluated at three different stages of memory processing, acquisition, consolidation and retrieval, in a battery of step-down type passive avoidance tests. NPY and PYY had no effect on acquisition, but significantly improved consolidation at a dose of 0.03 and 0.3 microgram, respectively. NPY also improved retrieval at a dose of 0.03 microgram. The ranking order of potency in stimulating feeding and locomotor activity was PYY > NPY > PP, and in improving memory consolidation NPY > PYY >> PP. These observations suggest that NPY and PYY influence different neural substrates in the brain involved in feeding and learning.

Animals↗

Effect of trimebutine maleate on emptying of stomach and gallbladder and release of gut peptide following a solid meal in man.

We investigated the effect of orally administered trimebutine maleate on gastric and gallbladder emptying and on the release of gut peptide, pancreatic polypeptide (PP), and gastrin in humans for 120 min after ingestion of a solid meal. Gastric emptying was measured by a radionuclide technique. Gallbladder emptying was estimated by real-time ultrasonography. The oral administration of 200 mg of trimebutine maleate significantly shortened the lag time in starting gastric emptying (P < 0.05). Considering gallbladder emptying, trimebutine significantly inhibited the fasting emptying induced by neural reflex. Postprandially, there was a tendency toward an accelerated gallbladder emptying in the early phase. Neither the maximal percentage of gallbladder emptying nor the time of peak gallbladder emptying were affected. Trimebutine significantly blunted the post-prandial PP response in the cephalic and gastric phases, reflecting a vagal-cholinergic activity (P < 0.05). The PP response in the intestinal phase was also blunted. Gastrin release was significantly augmented only during the period of fasting after drug administration (P < 0.05). The major effect of trimebutine maleate appears to be a shortening of the lag time at the start of gastric emptying probably via its anticholinergic activity.

Administration, Oral↗