Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 1,081 records · Page 60Linked to original sources

PubMed1992

Low toxic derivatives of istamycin B: synthesis and preliminary evaluation.

3-O-Demethylistamycin B derived from istamycin B was one of the most potent aminoglycoside antibiotics against various bacteria. 3-O-Demethylistamycin B, however, showed considerable acute toxicity in mice. The authors attempted to prepare the derivatives of istamycin B having high potency and low toxicity. The selective N-acylation or N-amidination at the C-2 position of istamycin B could not improve the acute toxicity. The replacement of the amino group at the C-2 position of istamycin B by a hydroxyl group markedly decreased the acute toxicity. Among 2'-deamino-2'-hydroxyistamycins, 4-N-(beta-alanyl)-2'-deamino-3-O-demethyl-2'-hydroxyistamycin B0 (9d) showed good antibacterial activity against Gram-positive and Gram-negative bacteria and a low acute toxicity in mice.

Aminoglycosides↗

PubMed1992

New hydroxybenanomicins produced by Actinomadura.

A soil microorganism, Actinomadura sp. MH193-16F4, produces an antifungal antibiotic benanomicin A and several related compounds. Among them, benanomicin A is the best candidate as a chemotherapeutic agent in terms of antifungal activity, toxicity and water-solubility. Three novel hydroxyl congeners, 3'-hydroxybenanomicin A, 7-hydroxybenanomicin A and 7-hydroxybenanomicinone have been isolated from the culture broth of the MH193-16F4 strain or its mutant. Interestingly, 3'-hydroxy-benanomicin A was as effective as benanomicin A, but the 7-hydroxy congeners were inactive. The inactive congeners differ from benanomicin A and 3'-hydroxyenanomicin A in their conformational structures at C-5 and C-6.

Anthracyclines↗

PubMed1992

Therapeutic activity of deoxyspergualin in comparison with cyclosporin A, and its combined use with cyclosporin A and prednisolone in highly allogeneic skin transplantation in the rat.

The present paper demonstrates the efficacy of a novel immunosuppressive agent, deoxyspergualin (DSG), in rat skin transplantation despite major histocompatible antigen differences, both by itself and in combination with cyclosporin A (CyA) and prednisolone (PD). DSG significantly prolonged the median survival time (MST) of WKAH skin on F344 rats, when given at daily doses of 1.5-12 mg/kg i.p. for 10 days starting from day one after grafting. A significant increase of the MST has been observed also in the rats orally receiving CyA at daily doses of 12.5-50 mg/kg according to the same dosing protocol. DSG was as effective as CyA in prolonging the MST. In contrast, when treatment started 4 days after grafting (at the time of the rejection crisis), DSG (6 mg/kg) was able to reverse the rejection, whereas CyA (50 mg/kg) was not. When DSG (1.5 mg/kg) and CyA (6.25 or 12.5 mg/kg) were given together from day one after grafting, the combined therapy was superior to each monotherapy. Similarly, when DSG (1.5 mg/kg) and PD (10 mg/kg) were given simultaneously from the rejection crisis, the combined therapy was demonstrated to have stronger activity than any of the monotherapies. Moreover, the skin-allografted rats could be switched successfully either from CyA to DSG treatment or from DSG to CyA treatment.

Animals↗

PubMed1992

[Clinical application of extracorporeal shock wave lithotripter (Dornier MFL-5000) for upper urinary tract stones].

The results of clinical application of an extracorporeal shock wave lithotripter (MFL-5000, Dornier, Germany) were presented. The treatments were performed from August 1989 to November 1989 at the University of Tokyo. A total of 40 sessions were carried out on 32 patients with 51 upper urinary tract stones. On the X-ray films obtained three months after the last sessions, 10 patients (34.5%) were free from stone fragments and 4 (13.8%) had stone fragments equal or less than 4 mm. After treatment no serious adverse effect was observed. Macroscopic hematuria was observed in almost all patients, pyrexia in 7 (21.9%), and flank pain in 6 (18.8%). On the laboratory data after treatments, there were slight and transient changes which were milder than those of the first generation lithotripter. It is concluded that MFL-5000 is useful and safe in the management of patients with upper urinary tract stones.

Adult↗

PubMed1992

[Successful repair of tetralogy of Fallot combined with aortic valve replacement in a 65-year-old woman].

Survival to seventh decade with tetralogy of Fallot is uncommon. Herein we report a successful repair of tetralogy of Fallot combined with aortic valve replacement for concomitant aortic valve regurgitation in a 65-year-old woman. She had been in severe congestive heart failure and respiratory failure, and also showed liver and renal dysfunction preoperatively. Postoperative course has been good but ventricular arrhythmia of Lown grade II persisted.

Aged↗

PubMed1992

[Atypical leukemia accompanied by vitamin B12 deficiency].

A 76 year old female with atypical leukemia complicated by vitamin B12 deficiency demonstrated marked fluctuation in blast percentage and hemopoiesis over 8 month period. She underwent surgical removal of pancreas head cancer 5.5 years ago. In January 1989 severe pancytopenia and mild increase of bone marrow blast were found. Blood transfusions and inadvertent administration of Vitamin B12 resulted in alleviation of pancytopenia and decrease in blast percentage. Several months later her bone marrow blast exceeded 30%, when serum B12 concentration was below 90 pg/ml. B12 injection and blood transfusion resulted in significant improvement in her hematological condition, but shortly thereafter she died of fulminant hepatitis. Her bone marrow cells showed a polyclonal constitution, as assessed by the RFLP-methylation technique using the PGK gene as a probe. The coexistence of leukemic- and normal clones under Vitamin B12 deficiency conditions and the differing behavior of such clones to B12 supplementation may explain the unusual clinical course observed in this patient.

Aged↗

PubMed1992

[Studies on clinical remission of rheumatoid arthritis].

Clinical remission was observed in 19 out of 276 patients with rheumatoid arthritis. Remission rate was higher in male patients. In order to determine the clinical characteristics of remission cases, comparative study was performed. Although the time between initiation of treatment and clinical remission varied from case to case, the remission was related to early diagnosis and use of immunomodulating drug. No exacerbation was observed in our 19 patients with remission for the periods of 17 observation months. However, serial X-ray examination of hands disclosed that the erosive changes developed even after clinical remission.

Adjuvants, Immunologic↗

PubMed1991

Hair pigmentation in transgenic mice.

A mouse tyrosinase minigene, mg-Tyrs-J, in which genomic 5' noncoding flanking sequence was fused to a mouse tyrosinase cDNA, was introduced into fertilized eggs of BALB/c albino mice. Six transformed mice that exhibited brown agouti hair with some variations in the intensity of pigmentation were obtained. By crossing the founder mice with BALB/c albino mice, transgenic lines and sublines were established. Each subline expressed a characteristic phenotype with their respective band patterns in Southern blot analysis. This indicates that the character is expressed by transgenes integrated at a single location of the chromosomes. The difference in phenotypes among sublines is probably due to the position effect of the chromatin where the transgene is integrated, although a possibility that modification in the nucleotide sequence of the transgene is responsible for the difference cannot be excluded at present.

Animals↗

PubMed1991

Enhanced expression of human tyrosine hydroxylase in the lower brainstem of transgenic mice.

We have previously reported the distribution of human tyrosine hydroxylase (TH) transgene expression in dopaminergic neurons (ventral tegmental area and substantia nigra), adrenal gland, and non-catecholaminergic neurons in the forebrain of transgenic (Tg) mice. In this paper, we analysed the transgene expression in catecholaminergic (CAergic) neurons in the lower brainstem of Tg mice, by in situ hybridization and immunocytochemistry at the light and electron microscopic levels. High-level hybridization signals of the human TH mRNA were observed in the locus ceruleus and nucleus tractus solitarii of the Tg brain. Intense TH immunoreactivity was expressed specifically in the Tg brainstem, as was observed in non-Tg mice. These results reveal that the human TH transgene contains the regulatory elements responsible for the expression in three kinds of CAergic (dopaminergic, noradrenergic and adrenergic) neurons of the mouse brain.

Animals↗

PubMed1991

Expression of human pancreatic polypeptide in heterologous cell lines.

Pancreatic polypeptide (PP) is initially synthesized as a larger precursor that requires post-translational processing to produce the biologically active hexatriacontapeptide. These steps include tryptic cleavage at paired basic residues, their subsequent removal by a carboxypeptidase B-like enzyme, and formation of a carboxyl-terminal amide moiety via the action of peptidyl-glycyl alpha-amidating monooxygenase. To examine these reactions further, we utilized the pZIPneo(SVX) retroviral vector to express a cDNA clone encoding human PP in several cell lines including a fibroblast line (psi-2), two endocrine cell lines known to produce amidated peptides (AtT-20 and PC12), and two lines that do not ordinarily produce amidated peptides (RIN5-f and GH3). Transfected psi-2 cells produced an unprocessed precursor of PP that appeared to be secreted constitutively with little remaining in intracellular stores. No post-translational processing of the PP precursor was evident in these cells. By contrast, all 4 endocrine-derived cell lines, regardless of the nature of their endogenous products, were capable of expressing fully processed and carboxyl-terminally amidated PP. Moreover, these lines had the ability to store the processed products. Our results support the notion that post-translational processing of peptide hormone precursors requires storage in secretory granules that contain the appropriate processing enzymes. Furthermore, enzymes such as peptidyl-glycyl alpha-amidating monooxygenase that are required for processing peptides may be a common feature of endocrine-derived cells regardless of the requirement for their activity to process endogenous products.

Amino Acid Sequence↗

PubMed1991

Dexamethasone and phorbol ester, but not cytokines, increase the production of plasminogen activator inhibitor type-2 in the PL-21 human promyelocytic leukemia cell line.

PL-21 is a promyelocytic leukemia cell line that produces plasminogen activator inhibitor 2 (PAI-2). Differentiation-linked expression of PAI-2 was investigated by adding cell-differentiation promoting agents [such as phorbol myristate acetate (PMA), retinoic acid (RA), dexamethasone (Dex), and recombinant cytokines, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), granulocyte-colony stimulating factor (G-CSF), and interleukin-6 (IL-6)] into the culture medium of PL-21 cells. PAI-1 and PAI-2 antigens were measured by an enzyme-linked immunoassay. The PAI-1 antigen, however, became detectable only after stimulation. The presence of PAI-2 antigen was further verified by immunoblotting using a monoclonal antibody against PAI-2 purified from a PL-21 culture medium. PAI activity both in the culture medium and in the cell lysate increased approximately 70-fold after exposure to PMA. Both PAI-1 and PAI-2 antigens increased, but the amount of the latter in the culture medium and in the cell lysate was approximately 10 times and 2,500 times, as much, respectively, as that of the former. Dex also increased the intracellular PAI activity approximately 6-fold, parallel with PAI-2 antigen. PAI-1 antigen increased only slightly in the culture medium but not in the cell lysate after Dex-stimulation. As with the case of PMA, TNF-alpha and IL-6 induced PL-21 cells to macrophage-like cells, but did not affect the PAI activity. Thus, the increase of the PAI-2 production by PMA may not necessarily depend on differentiation into macrophages. Other cytokines examined did not increase the PAI activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines↗

PubMed1991

The possibility of diagnosing small pancreatic cancer (less than 4.0 cm) by measuring various serum tumor markers. A retrospective study.

Comparative studies measuring various tumor markers such as SPan-1, CA 19-9, carcinoembryonic antigen (CEA), DUPAN-2, and elastase I were done in 74 patients with small pancreatic cancer including 23 cases of T1 pancreatic cancer (tumor size less than 2.0 cm) and 51 cases of T2 pancreatic cancer (tumor size between 2.1 to 4.0 cm), retrospectively. Although the mean value of these tumor markers in T1 and T2 pancreatic cancer were higher than those of the control cutoff levels, their sensitivities were different. In T1 pancreatic cancer, 13 of 23 cases (56.5%) of SPan-1 and 14 of 23 cases of (60.7%) of CA 19-9 had levels above normal. Although the numbers of patients were small, sensitivities of CEA, DUPAN-2, and elastase I were 30.8%, 22.2%, and 28.6%, respectively. In T2 pancreatic cancer, 41 of 51 cases (80.4%) of SPan-1 and 40 of 51 cases (78.4%) of CA 19-9 showed higher levels than normal, but only 46.9% of CEA, 40.0% of DUPAN-2, and 52.6% of elastase I were positive. The overall sensitivities in small pancreatic cancer (less than 4.0 cm) were 73% for SPan-1 and CA 19-9 but were less for CEA, DUPAN-2, and elastase I. These results indicate that even small pancreatic cancers release detectable pancreatic cancer-associated antigens in serum in more than 70% of cases, especially SPan-1 and CA 19-9. The measurement of these two tumor markers makes it possible to detect small pancreatic cancers after using imaging diagnostic procedures.

Adult↗

PubMed1991

Change of intracellular calcium of neural cells induced by extracellular ATP.

Exposure of various neural cells to ATP increased intracellular Ca2+ and the production of inositol trisphosphate. The Ca2+ responses were also observed in the absence of extracellular Ca2+, suggesting that a part of Ca2+ mobilization took place from cytosolic storage. Since adenosine had no effect on intracellular Ca2+ increment, ATP appears to act through a P2-purinergic receptor. Islet-activating protein or pertussis toxin pretreatment hardly influenced the increase in intracellular Ca2+ and inositol trisphosphate production induced by ATP, suggesting that IAP-sensitive GTP-binding proteins do not play a practical role in this reaction.

Adenosine↗

PubMed1991

Expression in brain sensory neurons of the transgene in transgenic mice carrying human tyrosine hydroxylase gene.

We have recently reported the production of transgenic (Tg) mice carrying the human tyrosine hydroxylase (TH) gene, and have described tissue-specific expression of the transgene in catecholaminergic (CAergic) neurons and adrenal glands. This paper describes the transgene expression in non-catecholaminergic (nCAergic) neurons in the brain of Tg mice by immunocytochemistry and in situ hybridization. In adult Tg mice, human TH was atypically expressed in the olfactory (typically, the anterior olfactory nucleus and pyriform cortex) and visual (typically, n. suprachiasmaticus and n. parabigeminalis) systems, in addition to typical CAergic neuron-rich nuclei in the brain. These results suggest the possibility that TH plays some novel roles in sensory systems.

Animals↗

PubMed1991

Monoclonal antibody SN10 which shows a highly selective reactivity with human B leukemia-lymphoma and is effectively internalized into cells.

The monoclonal antibody termed SN10 (IgG1-k) which was generated and characterized in the present study shows a highly selective reactivity with fresh (uncultured) human leukemia-lymphoma cells. The antigen defined by SN10 is a cell surface glycoprotein composed of a single polypeptide chain of Mr 36,000 and designated as gp36. The primary reactivity of SN10 is against mature B-lineage leukemia-lymphoma cells. For instance, SN10 reacted with all of the 17 B non-Hodgkin's lymphoma specimens, all of the 15 B chronic lymphocytic leukemia specimens, both of the 2 B prolymphocytic leukemia specimens, all of the 3 B hairy cell leukemia specimens, and 2 of the 3 B acute lymphoblastic leukemia specimens tested. Of normal peripheral blood cells, only a marginal reactivity of SN10 was detected with a minor subpopulation (less than 1-4% among different specimens) of isolated B-cells from healthy donors. No significant reactivity of SN10 was detected against any other isolated normal peripheral blood cells which include T-cells, granulocytes, monocytes, erythrocytes, and platelets. Furthermore, no significant reactivity of SN10 was detected against normal bone marrow specimens. In immunohistological studies using frozen tissue sections, SN10 reacted well with malignant lymphomas and showed varying patterns of reaction with hyperplastic reactive lymph nodes. Various normal human tissues tested were unreactive with SN10. In general, glycoprotein 36 was more abundantly expressed on fresh (uncultured) leukemia-lymphoma cells than on cultured leukemia-lymphoma cell lines. No significant amount of circulating SN10 antigen was detected in the plasma of leukemia-lymphoma patients or normal healthy donors. Scatchard plot analysis of direct binding of radiolabeled SN10 to a fresh (uncultured) B non-Hodgkin's lymphoma cell specimen, a fresh B chronic lymphocytic leukemia cell specimen, and DND-39 (an American Burkitt's lymphoma cell line) showed equilibrium constants of 5.2, 5.8, and 6.8 x 10(8) liters/mol, respectively. Thus, SN10 shows a high binding avidity to each of the 3 B leukemia-lymphoma cell specimens tested. Ricin A chain conjugate of SN10 killed leukemia-lymphoma cells effectively, whereas the same conjugate showed no cytotoxicity against control cells. Thus, SN10 bound to target antigen on the cell surface was effectively internalized into the cell. The present results suggest the potential of SN10 for therapy as well as for diagnosis of various forms of leukemia-lymphoma, particularly mature B-lineage leukemia-lymphoma.

Antibodies, Monoclonal↗

PubMed1991

Nonisotopic receptor-binding assay for benzodiazepine receptors utilizing a fluorophore labeled ligand.

A nonisotopic receptor-binding assay method provides a new approach for the study of receptor-ligand interactions and a possible receptor assay for benzodiazepine drugs. The proposed method is based upon the use of fluorescence-labeled drugs and a chromatographic system which accepts samples without deproteinization. The effectiveness of the technique is illustrated in a study of benzodiazepine receptor-drug-binding interactions.

Affinity Labels↗

PubMed1991

Expression and post-translational processing of gastrin in heterologous endocrine cells.

The biosynthesis of gastrin involves a complex series of post-translational processing reactions that result in the formation of a biologically active secretory product. To study the mechanisms for two specific reactions in gastrin processing, namely dibasic cleavage and amidation, we infected AtT-20, GH3, and Rin5-f cells with the retroviral expression vector, pZip-NeoSV(X), containing human gastrin cDNA. We detected gastrin and its glycine extended post-translational processing intermediates (G-gly) in the media and cell extracts of successfully infected cells. Characterization of the molecular forms of gastrin in these cell lines revealed that GH3 and Rin5-f processed gastrin in a manner similar to antral G-cells but the cleavage of the Lys74-Lys75 bond that converts G34 to G17 appeared to be suppressed in AtT-20 cells. Even after conversion of this site to Arg74-Arg75 via site-directed mutagenesis, the At-20 cells synthesized G34 predominantly. All of the infected cells amidated gastrin but the gastrin/G-gly ratio, a reflection of amidation within the cells, was enhanced in GH3 and Rin5-f cells but diminished in AtT-20 cells upon treatment with dexamethasone (10(-4) M) for 3 days. The dibasic cleavage of gastrin was uneffected by dexamethasone. Our data suggest that the activities of post-translational processing reactions responsible for the synthesis of biologically active gastrin exhibit considerable tissue and substrate specificity.

Animals↗

PubMed1991

Clinical usefulness of chemosensitivity testing using the MTT assay.

The results of in vitro chemosensitivity testing using the MTT assay of tumor cells from 140 patients were analyzed with reference to the clinical antitumor effects of the chemotherapy. One hundred and twenty-four (88.6%) of 140 specimens were successfully tested by the method of Mosmann (J Immunol Methods 65:55-63, 1983) with some modifications. When the results of the assay were compared with the clinical effects of chemotherapy in 22 patients with remaining measurable tumor lesions, the overall prediction rate was 86.4% (19/22). Among 31 patients with stage III-V gastric and colorectal carcinomas without remaining measurable tumor lesions, the survival rate of nine patients treated with drugs shown to be effective in the assay was significantly (P less than 0.05) better than that of 22 patients treated with drugs shown to be ineffective.

Adult↗