Increased glutamate transporter (GLT-1) immunoreactivity in the rat striatum after repeated intermittent administration of methamphetamine.
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ATP-Binding Cassette Transporters↗
Biomedical subjects
N Nishino
Publications and source records attributed to N Nishino.
Synchronous lymphoma and adenocarcinoma occurring as a collision tumor in the stomach: report of a case.
We report herein the rare case of a 71-year-old man who was initially operated on under the diagnosis of advanced gastric cancer, but was subsequently found to have synchronous lymphoma and early adenocarcinoma of the stomach, confirmed by postoperative pathological examination. The patient had a history of lymphoma of the left tonsil, and histologically the gastric lymphoma was observed to be of the non-Hodgkin's, diffuse, large-cell type. Conversely, the gastric cancer was early well-differentiated tubular adenocarcinoma of type 0-IIa, according to the Japan Gastroenterological Endoscopy Society classification. The two tumors had collided at the fornix. The relationship between these two tumors is analyzed and the most appropriate methods of diagnosis and treatment are discussed.
Adenocarcinoma↗
Endoscopic treatment of gallstone-impacted choledochocele precisely diagnosed by endoscopic ultrasonography.
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Aged↗
Tandem enzymatic resolution yielding L-alpha-aminoalkanedioic acid omega-esters.
The tandem action of serine protease (alpha-chymotrypsin or subtilisin BPN') and Aspergillus genus aminoacylase on racemic N-acetyl-alpha-aminoalkanedioic acid alpha,omega-diester produced L-alpha-aminoalkanedioic acid omega-ester in good yield and high optical purity. L-alpha-Aminosuberic acid omega-ester thus obtained was conveniently introduced into an oxytocin analog, [Asu1,6]oxytocin, by the solid-phase-synthesis and cyclization-cleavage method with oxime resin.
Amidohydrolases↗
Study on the estrous cycle in the Mongolian gerbil (Meriones unguiculatus).
The paucity of information and the unagreed consensus about the estrous cycle of the Mongolian gerbil (Meriones unguiculatus) have rendered such studies rather difficult. The estrous cycle of the Mongolian gerbils in this report were divided into 5 stages: Stage I, proestrus; Stage II, estrus (scattering); Stage III, estrus (gathering); Stage IV, metestrus and Stage V, diestrus. The normal estrous cycle in the Mongolian gerbils was 4-6 days long. In our experimental conditions, 67.9% of virgin females had a 4-6 day cycle, whereas 26.4% had an unsettled cycle and 5.7% assumed pseudopregnancy. The changing pattern of the estrous cycle and copulatory behavior of the Mongolian gerbils after hormone (PMSG: pregnant mare serum gonadotropin, 10 IU; hCG: human chorionic gonadotropin, 10 IU) injection were examined. The change in the estrous stage after hormone injection could be roughly classified into two types. The vaginal smear of virgin females injected with PMSG at Stage I, II or III changed to Stage V the next day and to Stage I or Stage II after 48 hr, but in the case of Stage IV or V, the smear changed to Stage I after 48 hr. The females injected with PMSG at Stage I, II or III copulated at from 13:00 to 23:00, whereas others injected at Stage IV or V scarcely copulated at all between 13:00 and 23:00. Mating of these females with the male midnight was not observed.
Animals↗
Hepatocyte growth factor as a hematopoietic regulator.
Hepatocyte growth factor (HGF) was originally isolated as a mitogen for adult hepatocytes, but this cytokine is now regarded as a multi-functional factor. In the present study, we show that the mouse liver in the middle and/or late stage of the fetal life expresses both HGF and c-met (its receptor) messages. HGF and c-met mRNA are coexpressed not only in the adherent layers of fetal liver long-term cultures (FL-LTCs) and adult bone marrow long-term cultures (BM-LTCs), but also in the stromal cell lines MS-5 and PA-6. Addition of human HGF (2 and 20 ng/mL) to the LTCs enhances (1) nonadherent cell counts (ninefold in FL-LTCs and sixfold in BM-LTCs), (2) nonadherent colony-forming unit-in culture (CFU-C) counts (eightfold in FL-LTCs and fivefold in BM-LTC), and (3) cobblestone colony counts. However, HGF slightly inhibits the proliferation of stromal cells. No direct effect of HGF on freshly isolated BM and/or FL cells is found in the CFU-C assay. However, an approximately 1.5-fold synergistic increase in CFU-C counts is noted when the BM or FL cells are cocultured with HGF in the presence of interleukin-3. These findings strongly suggest that HGF plays a crucial role as a hematopoietic regulator in the proliferation and differentiation of hematopoietic progenitors.
Animals↗
Comparison of the inhibitory effect of the angiogenesis inhibitor, TNP-470, and mitomycin C on the growth and liver metastasis of human colon cancer.
Angiogenesis inhibitors have attracted considerable interest. The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti-neoplastic agent, were investigated using a xenotransplanted human colon cancer, TK-4. Suturing of small pieces of TK-4 tumors to the cecal wall in nude mice (orthotopic transplantation) induced liver metastasis. Mice were randomly divided into 3 groups; a control group given saline solution, a group receiving TNP-470 and a group receiving MMC. TNP-470 was given s.c. on alternate days for 5 weeks from day 10 after cecal transplantation and MMC was administered intraperitoneally (i.p.) once a week from day 10 after cecal transplantation. MMC significantly inhibited cecal tumor growth. In the control group, liver metastases developed in 9 out of 10 mice, including 3 with more than 20 metastatic foci. Liver metastasis also developed in 8 out of 10 mice receiving MMC, 2 of which had many metastases. In contrast, liver metastasis developed in only 2 out of 8 mice in the TNP-470 group and neither of these animals had numerous metastases.
Animals↗
Delayed changes in neural visinin-like calcium-binding protein gene expression caused by acute phencyclidine administration.
Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia, and PCP-treated animals can serve as a model for schizophrenia. The effects of PCP on the gene expression of NVP-1, a novel Ca(2+)-binding protein, were studied in rats. After 24 hours, the NVP-1 mRNA level in the nucleus accumbens showed a significant decrease of 42%. This result suggests that alterations in Ca(2+)-binding protein may be involved in the pathology of PCP-induced psychosis and, presumably, schizophrenia.
Actins↗
Substrate specificity of rabbit liver metalloendopeptidase and its new fluorogenic peptide substrates.
A metalloendopeptidase (MEP) isolated from rabbit liver microsomes with substrate specificity for peptides containing Arg at the P1 and P4 positions has recently proved to be identical to soluble angiotensin-binding protein present in the cytosol. Here we describe the peptide-degrading specificity of MEP, determined using various bioactive peptides and novel fluorogenic substrates for the enzyme. MEP degraded oligopeptides, including bradykinin, alpha-neoendorphin, bovine adrenal medulla dodecapeptide, substance P, bombesin, neurotensin, and alpha-endorphin, but not polypeptides such as reduced lysozyme and histone H4, hence, MEP probably belongs to the family of endo-oligopeptidases. It cleaved most preferentially at the -Phe-Ser- bond of bradykinin (kcat/Km = 2.8 x 10(4) M-1.S-1) but did not cleave high molecular weight and low molecular weight kininogens, the precursors of bradykinin. MEP did not cleave angiotensin I, dynorphin A 1-13, somatostatin, and luteinizing hormone-releasing hormone, some of which are good substrates for metalloendopeptidase-24.15, metalloendopeptidase-24.16, N-arginine dibasic convertase, and yeast endopeptidase-24.15 related peptidase. An active site-directed inhibitor of metalloendopeptidase-24.15, N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate also had no effects on the amidolytic activity of MEP. Based on the cleavage sites of bioactive peptides and processing sites of vitamin K-dependent proproteins, intramolecularly quenched fluorogenic peptide substrates were newly synthesized. Among the thirteen substrates used, the most reactive was 2-aminobenzoyl-Ala-Arg-Val-Arg-Arg-Ala- Asn-Ser-2,4-dinitroanilinoethylamide (kcat/Km = 9.3 x 10(5) M-1.S-1). An angiotensin antagonist, [Sar1, Ala8]-angiotensin II, inhibited hydrolysis of the substrate by MEP in a competitive manner (Kl = 7.6 microM). MEP cleaved oligopeptides even on the carboxyl side of proline residue and these peptides are resistant to hydrolysis by the cytosol-derived proteasome, therefore MEP may participate in the catabolism of oligopeptides in the cytosol, together with other endo-oligopeptidases.
Amino Acid Sequence↗
DNA analysis in hereditary dentatorubral-pallidoluysian atrophy: correlation between CAG repeat length and phenotypic variation and the molecular basis of anticipation.
Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease with variable clinical phenotypes. Progressive ataxia, choreoathetosis, and dementia are the main clinical features of adult-onset cases, whereas the main feature in juvenile-onset DRPLA is progressive myoclonus epilepsy. Earlier onset is apparent in successive generations (anticipation). The molecular abnormality underlying DRPLA is an expanded, unstable CAG trinucleotide repeat on chromosome 12p. We analyzed 71 DNA samples obtained from 12 Japanese DRPLA pedigrees that included 38 affected individuals. Normal alleles had 7 to 23 repeats, DRPLA alleles 53 to 88 repeats. DRPLA alleles also were detected in five asymptomatic family members. Patients with juvenile onset had significantly larger repeats than did those with adult onset, and there was a significant negative correlation between CAG repeat length and age at onset. In 80% of the paternal transmissions, there was an increase of more than five repeats, whereas all the maternal transmissions showed either a decrease or an increase of fewer than five repeats. There was a significant correlation between father-child differences in repeat length and differences in age at onset. The analysis of CAG repeat length is a reliable diagnostic test for DRPLA and is of value for the presymptomatic detection of individuals at risk. The expansion of CAG repeats is important in phenotypic variation and anticipation. In addition, the sex of the transmitting parent has a significant effect on the molecular mechanism of anticipation.
Adolescent↗
[Postoperative abdominal lymph node recurrence of intrathoracic esophageal cancer with a long-term complete response to radiation and split CF therapy (CDDP and 5-FU)--a case report].
We experienced complete remission in a patient with postoperative abdominal lymph node recurrence of intrathoracic esophageal cancer after treatment with radiation (60Co: 30 Gy) and split CF therapy (CDDP: 20 mg/day + 5-FU: 1 g/day for 5 days). Since then, this patient has remained in complete remission for 43 months with intermittent split CF therapy one or two times a year.
Abdomen↗
[An attempt to prevent psychological distress induced by magnetic resonance imaging: effectiveness of psychological interventions].
A magnetic resonance imaging (MRI) examination has reportedly produced psychological distress such as discomfort, anxiety and fear in a certain number of patients. In an attempt to prevent such distress during an MRI, the authors took the following psychological measures: 1) improved psychological support for patients by MRI technicians; 2) providing sufficient information to patients about the imager and the nature of the examination; 3) reassurance of the safety, with the patient free to terminate the examination at any time; 4) environmental modification to induce relaxation, including recorded music, paintings and live plants in the examination room. We then evaluated the effectiveness of these combined psychological support factors for all MRI patients. A questionnaire on psychological distress experienced during an MRI was filled out by 143 patients (mean age, 49.4 years) and 105 patients (mean age, 48.4 years) prior to and after our psychological measures, respectively, after MRI test in Saiseikai Nakatsu hospital, and comparisons made between these two groups (chi 2 test, p < 0.05). The number of patients experiencing psychological distress during an MRI was significantly decreased (50.5%) after the measures were implemented as compared to the number (64.3%) beforehand. In particular, female, 60 or older patients and patients examined for the first time showed significant decreases in experiencing psychological distress after the measures were implemented. The number of patients who reported distress, tended to decrease. Patients who developed certain symptoms, such as palpitation, also tended to decrease. Patients who reported the "long examination time" as a distress factor and those who developed palpitation during the examination significantly decreased. Our results indicate that these combined psychological measures are efficacious in reducing psychological distress during an MRI, mainly by curtailing the patient's subjective sense of examination time. In addition to an MRI examination, our psychological measures should be applied to other medical examinations which tend to generate undue psychological distress.
Adolescent↗
A case of triple early gastric cancer in the remnant stomach.
A 63-yr-old man, who had undergone distal gastrectomy and gastrojejunostomy (Billroth II method) 32 yr previously for duodenal ulcer, was admitted with suspected gastric remnant cancer. An upper gastrointestinal series and endoscopy revealed a protruding lesion at the stoma of the remnant stomach. Total gastrectomy with resection of the adjacent jejunum was performed. Histological examination demonstrated two well-differentiated adenocarcinomas (a mixed type I and IIc lesion with submucosal invasion and a type IIa lesion with intramucosal invasion) and a type IIc mucocellular carcinoma located in the mucosa. Gastritis cystica polyposa also was observed in the remnant stomach. The combination of three early gastric cancers and gastritis cystica polyposa suggests that the mucosa of the remnant stomach had a high malignant potential. The patient has survived without recurrence for 5 yr since the operation.
Adenocarcinoma↗
Identification of EGF as an angiogenic factor present in conditioned medium from human salivary gland adenocarcinoma cell clones with varying degrees of metastatic potential.
We have previously shown that conditioned medium (CM) from metastasizing human salivary gland adenocarcinoma cell clones contains factor(s) that stimulate the proliferation and migration of bovine aortic endothelial (BAE) cells, and inhibit the production of collagenases by BAE cells (Azuma M. et al. (1993) Cancer Lett., 73, 85-93). To further characterize this, we evaluated the expression level of epidermal growth factor (EGF) secreted by a non-metastasizing cell clone (HSGc) and its metastasizing cell clones, and analysed the effect of EGF on the biologic behaviors of BAE cells. When the secretion of EGF by cell clones was estimated by enzyme-linked immunosorbent assay, metastasizing cell clones released a large amount of EGF as compared with HSGc. However, the number of EGF receptor was detected consistently at a level that was similar in all cell clones. With regard to the effect of EGF on the malignant potential of cell clones such as proteolytic aggressiveness, EGF did not affect the secretion of both collagenases and their inhibitor from cell clones. Alternatively, exogenous EGF stimulated the proliferation and migration of BAE cells, and inhibited the secretion of collagenases from BAE cells. Neutralization with a neutralizing antibody of EGF released into CM abolished the inhibitory effect of CM on the secretion of collagenases from BAE cells. Thus, the CM-contained factor, which is responsible for the induction of biologic behaviors of BAE cells, can be attributed to EGF.
Adenocarcinoma↗
Design, synthesis, and conformation of a model peptide of endothelin with cystine-stabilized alpha-helix motif.
A model 16-peptide of endothelin-1 (MET-1), which has the minimized sequence homology to the corresponding part of endothelin-1 (ET-1), was designed to confirm the cystine-stabilized alpha-helix motif. The model structure consists of an extended structure, a beta-turn part, and an alpha-helix structure that is stabilized by two disulfide bonds. The alpha-helix segment was designed to emphasize the amphiphilic nature. In order to combine the extended structure and the alpha-helix segment, a D-Ala-Pro sequence was selected to fix the beta-turn. The model endothelin 16-peptide amide was synthesized by solid-phase synthesis on a 4-methylbenzhydrylamine resin. Its conformation was examined by CD and two-dimensional (2D) 1H-nmr measurements. MET-1 showed similar CD patterns to ET-1 in both buffer and 50% aqueous trifluoroethanol solution. The 2D nmr experiments in 50% aqueous ethylene glycol revealed that MET-1 closely resembles the conformation of ET-1 with an extended structure, an alpha-helix, and a beta-turn unit in the same position of the sequence. Furthermore, model peptides without disulfide bond(s) could not assume a stable structure in aqueous solution, while they did have similar alpha-helical content in 50% trifluoroethanol with MET-1. When the two disulfide bridges were simultaneously formed, the peptide with the correct disulfide bonds (MET-1) was obtained in threefold excess to the isomer (apamin type, MET-2). These findings obtained by the modeling of ET-1 showed an important role for the stabilization of peptide conformation with disulfide bonds.
Amino Acid Sequence↗
Postoperative changes in plasma tissue-type plasminogen activator and type 1 plasminogen activator inhibitor.
To clarify the changes which occur postoperatively in intravascular fibrinolysis, plasma levels of tissue-type plasminogen activator (t-PA) antigen, the total plasminogen activator inhibitor type-1 (PAI-1) antigen, and the t-PA-PAI-1 complexes were assayed in this study. Blood samples were taken the morning before surgery, then at 0, 12, 24, 36, 60, 108, and 156 h postoperatively in ten patients who underwent radical surgery for thoracic esophageal cancer. The plasma levels of the t-PA and total PAI-1 antigens, and the t-PA-PAI-1 complexes were then measured by enzyme immunoassay. The plasma t-PA and total PAI-1 levels increased significantly in the immediate postoperative period, the percent increase of the latter being much greater than that of the former. Moreover, the calculated free t-PA antigen level was decreased throughout the postoperative period, suggesting postoperative hypofibrinolysis. The platelet count and neutrophil elastase level were significantly correlated with the free t-PA antigen level at r = 0.630, P < 0.001, and r = -0.447, P < 0.01, respectively. The results of this study indicated that post-operative hypofibrinolysis caused by the increased synthesis of PAI-1 may enhance postoperative hypercoagulability, and this may lead to the development of organ damage. Thus, the concentration of the PAI-1 antigen may be a potentially important index for the prediction of postoperative illness.
Aged↗
Cytotoxicity of simvastatin to pancreatic adenocarcinoma cells containing mutant ras gene.
Simvastatin (SV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits the synthesis of mevalonic acid. The dose-dependent (0.1-100 micrograms/ml) cytotoxicity of SV towards human (MIAPaCa-2, Panc-1, HPC-1, HPC-3, HPC-4, PK-1, PK-9) and hamster (T2) pancreatic carcinoma cell lines was determined by MTT assay. At up to 20 micrograms/ml of SV, the effect was reversible and was restored by 60 micrograms/ml mevalonic acid. Point mutation of Ki-ras at codon 12 in each cell line was detected by means of the modified polymerase chain reaction. The concentration of SV necessary to achieve 50% cytotoxicity was about 10 micrograms/ml, and at this concentration of SV, DNA synthesis assayed in terms of [3H]thymidine uptake, isoprenylation of p21ras examined by Western blotting and cell progression from G1 to S phase of the cell cycle analyzed by flow cytometry were all inhibited. Isoprenylation inhibitors of p21ras, such as SV, are expected to be useful for the treatment of pancreatic cancer.
Adenocarcinoma↗
Suppression of polymorphonuclear leucocyte chemotaxis by Pseudomonas aeruginosa elastase in vitro: a study of the mechanisms and the correlation with ring abscess in pseudomonal keratitis.
Bacteria, or the culture supernatants of an elastase non-producing strain of Pseudomonas aeruginosa, elicited a chemotactic response from polymorphonuclear leucocytes (PMN) in vitro. The chemoattractive capacity was diminished under the presence of Boc-Phe-Leu-Phe-Leu-Phe, a receptor antagonist of N-formyl-Met-Leu-Phe (fMLP) which is a bacterial chemotactic peptide to PMN. This indicated that the chemoattractant derived from Pseudomonas aeruginosa was a fMLP-like molecule(s). In contrast, culture supernatants of an elastase producing strain of Pseudomonas aeruginosa produced negligible chemotactic response from PMN. Indeed, an inhibitory effect of the culture supernatants or of purified Pseudomonas aeruginosa elastase (PAE) on PMN chemotaxis was observed when fMLP was used as a chemoattractant. Another fMLP-induced function of PMN, respiratory burst activation, was also diminished by pretreatment of PMN with PAE. PAE hydrolysed fMLP at the Met-Leu bond and diminished the chemoattractant capacity. In addition, a receptor analysis with fML-3H-P demonstrated a decrease in numbers of fMLP receptors on PMN without changing the dissociation constant values after the treatment of the cells with PAE. In the primary structure of the fMLP receptor previously reported, a preferential amino acid sequence for cleavage by PAE was identified in what was believed to be an extracellular portion of the receptor molecule. These results suggested that PAE could diminish PMN infiltration in response to Pseudomonas aeruginosa in vivo by cleavage of the fMLP-like pseudomonal chemotactic ligand and the receptors on PMN.
Abscess↗