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Biomedical subjects

M Taniguchi

Publications and source records attributed to M Taniguchi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Anti-tumor effect of internal image bearing anti-idiotypic monoclonal antibody in relation to GM3 ganglioside.

Anti-idiotypic antibodies are a new type of useful tools for the possible treatment of cancer patients, since some act as antigen specific immunomodulators. Anti-idiotypic monoclonal antibody (anti-Id MAb) D704 (Ab2) was established which bore the internal image of the determinant defined by MAb M2590 (Ab1) against a sialic acid residue on GM3 ganglioside. In an in vivo syngeneic tumor system, anti-Id MAb D704 was more effective in preventing tumor progression, as compared with anti-GM3 MAb or no treatment. Significant suppression of tumor growth and prolongation of survival by administration of anti-Id MAb D704 in an animal group inoculated with 1 x 10(4)/mouse melanoma cells were seen, but not in a group inoculated with 5 x 10(4) cells/mouse. In an active specific immunotherapy protocol utilizing Ab2, the activity of anti-anti-Id antibodies (Ab3) specific for GM3 (antigen) which has a weak immunogenicity only, was maintained for more than 3 months. Ab2 generated cellular anti-tumor immune responses, including delayed type hypersensitivity (DTH) reaction. Immunohistological analysis indicated a marked infiltration of CD4 and CD8 positive cells into the DTH sites. Our results suggest that internal image bearing anti-Id MAbs have a therapeutic potential against tumors if the number of melanoma cells is relatively low or if hosts are at an early stage of melanoma progression.

Animals↗
PubMed1998

Decreased membrane fluidity and unsaturated fatty acids in Niemann-Pick disease type C fibroblasts.

Niemann-Pick disease type C (NP-C) is an autosomal recessive disorder characterized by the sequestration and trapping of endocytosed cholesterol in lysosomes. The NPC1 gene on chromosome 18 was recently identified but its physiological function remains unknown. We have studied the lipid compositions of cultured human NP-C fibroblasts and mouse SPM-3T3 cell line derived from the C57BL/KsJ NP-C model mouse, which belongs to the same complementation group. Fibroblasts derived from apparently normal age-matched individuals and a subline of SPM-3T3 cells which restores cholesterol metabolism by transfer of human chromosome 18 were used as controls. Levels of free cholesterol in whole cell homogenates increased about 1.5-fold in human NP-C fibroblasts and mouse SPM-3T3 cells, while in the plasma membrane, cholesterol content did not significantly change in NP-C fibroblasts but rather decreased in SPM-3T3 cells. The total phospholipid content did not significantly change; however, among phospholipid head groups, increases in sphingomyelin and decreases in other classes were observed in human NP-C fibroblasts and mouse SPM-3T3 cells. The ratios of saturated fatty acids to unsaturated fatty acids increased in both human and mouse cells. The increase was also confirmed in the plasma membrane fraction of SPM-3T3 cells. Membrane fluidity was examined using a 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescent probe. The DPH anisotropy values were markedly increased in NP-C fibroblasts and in SPM-3T3 cells. The results suggest that a NP-C mutation causes complex alterations in cellular lipid contents and biophysical properties of the membrane.

3T3 Cells↗
PubMed1998

Aberrant muscle activation in patients after resection of non-primary motor areas: demonstration by surface electromyography.

Two patients presented with a tumor involving mainly the supplementary motor area or the premotor cortex. Shortly after tumor resection, each developed transient impairment of voluntary movements. An electromyogram, with the skin electrodes placed over the muscles of the upper arms and forearms, demonstrated aberrant ipsilateral, contralateral or bilateral muscle activation during unilateral motor tasks in both patients. The bilateral activation was more prominent in the patient who had an intact dominant hemisphere. The present study suggests for the first time the importance of non-primary motor areas of the human brain in activating the proper set of muscles on the proper side of the body.

Adult↗
PubMed1998

De novo CD5+ diffuse large B-cell lymphomas express VH genes with somatic mutation.

To clarify the cellular origin of de novo CD5+ diffuse large B-cell lymphoma (CD5+ DLBL), particularly in comparison with other CD5+ B-cell neoplasms such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), we analyzed the nucleotide sequence of the Ig heavy chain variable region (IgVH) genes of de novo CD5+ DLBL cases. All 4 cases examined had extensive somatic mutations in contrast with CLL or MCL. The VH gene sequences of de novo CD5+ DLBL displayed 86.9% to 95.2% homology with the corresponding germlines, whereas those of simultaneously analyzed CLL and MCL displayed 97.6% to 100% homology. The VH family used was VH3 in 1 case, VH4 in 2 cases, and VH5 in 1 case. In 2 of 4 examined cases, the distribution of replacement and silent mutations over the complementarity determining region and framework region in the VH genes was compatible with the pattern resulting from the antigen selection. Clinically, CD5+ DLBL frequently involved a variety of extranodal sites (12/13) and lymph node (11/13). Immunophenotypically, CD5+ DLBL scarcely expressed CD21 and CD23 (3/13 and 2/13, respectively). These findings indicate that de novo CD5+ DLBL cells are derived from a B-1 subset distinct from those of CLL or MCL.

Aged↗
PubMed1998

Efficient production of Cre-mediated site-directed recombinants through the utilization of the puromycin resistance gene, pac: a transient gene-integration marker for ES cells.

Gene targeting in embryonic stem (ES) cells is a powerful tool for generating mice carrying specifically designed mutations in the germline. Puromycin can completely kill ES cells within 24 to 48 h whereas G418 and hygromycin cannot. We have, therefore, proposed that the puromycin N-acetyltransferase ( pac ) gene, may be utilized as a transient gene-integration marker. Using a circular expression vector of cre and pac genes, Cre-mediated mutant cells were effectively enriched by pulse treatment of puromycin without stable integration of their genes. We have thus demonstrated the first application of pac as a transient gene-integration marker for ES cells.

Acetyltransferases↗
PubMed1998

Single photon emission CT images in a case of intraventricular neurocytoma.

Although Tc-99m HMPAO uptakes in various brain tumors have been reported, SPECT images of neurocytoma have not been described. The authors report a patient with intraventricular neurocytoma (IN) who demonstrated significant uptake of Tc-99m HMPAO and Tl-201 Cl before brain biopsy. Residual tumor after biopsy showed significant uptake of I-123 IMP on early SPECT images, but this uptake was decreased on delayed images. The three radionuclides seem to have different uptake mechanisms.

Adult↗
PubMed1998

Gallium-67-citrate scintigraphy of primary renal lymphoma.

We present a case of primary renal lymphoma, which is a rare entity and poses diagnostic challenge. Ultrasound and CT scan demonstrated a nonspecific solid tumor in the left kidney. 67Ga-citrate scintigraphy demonstrated an intense uptake in the tumor, which led to a correct diagnosis, so that we could spare unnecessary laparotomy and possible nephrectomy.

Aged↗
PubMed1998

Primary malignant melanoma of the esophagus associated with adenocarcinoma of the lung.

We herein report an extremely rare case of a 55-year-old Japanese woman with a primary malignant melanoma of the esophagus associated with adenocarcinoma of the lung. The patient was admitted to our hospital with a malignant melanoma of the lower esophagus. The chest X-ray and computed tomography (CT) findings revealed an incidental abnormal shadow in the left lung, which was diagnosed to be adenocarcinoma of the lung by means of a CT-guided needle biopsy. After administering systemic chemotherapy with dacarbazine (DTIC), vincristine sulfate (VCR), and nimustine hydrochloride (ACNU) plus interferon-beta, the esophageal tumor markedly decreased in size. Subsequently, the patient underwent a radical resection of both the malignant melanoma of the esophagus and lung cancer via a left thoracotomy and laparotomy.

Adenocarcinoma↗
PubMed1998

A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumors.

BACKGROUND & AIMS: The c-kit gene encodes a receptor tyrosine kinase (KIT). Recently, we found gain-of-function mutations of the c-kit gene in gastrointestinal stromal tumors (GISTs). All mutations were confined within the 11 amino acids (Lys-550 to Val-560) in the juxtamembrane domain, but one GIST showed a novel deletion-type mutation at codon 579 (Asp) in the juxtamembrane domain. The aim of this study was to clarify whether the mutation is activating. METHODS: Mutant c-kit cDNA was transfected into an interleukin 3 (IL-3)-dependent Ba/F3 murine lymphoid cell line, and the magnitude of autophosphorylation of the mutant KIT was examined with or without stem cell factor (SCF), a ligand of KIT. An in vitro kinase assay was also performed. The biological behavior of the transfectant was estimated by both an in vitro proliferation assay and in vivo transplantation to nude mice. RESULTS: The mutant KIT exhibited constitutive phosphorylation and strong kinase activity without SCF. The transfectant grew autonomously without IL-3 and SCF, and it formed tumors in nude mice. CONCLUSIONS: Deletion at codon 579 (Asp) in the juxtamembrane domain of the c-kit gene is a novel gain-of-function mutation other than the region between Lys-550 and Val-560.

Amino Acid Sequence↗
PubMed1998

Invasion depth diagnosis of depressed type early colorectal cancers by combined use of videoendoscopy and chromoendoscopy.

BACKGROUND: Depressed type early colorectal cancers are found less frequently than other polypoid cancers although they have a higher submucosal invasion rate. Recently videocolonoscopy and chromoendoscopy have become available and precise descriptions of these lesions are now routine. Because endoscopic mucosal resection is designated for intramucosal and focally extended submucosal (m-sm1) cancers, an evaluation of the characteristic findings indicating invasion depth with these modalities is important. METHODS: Between January 1991 and March 1996, 64 depressed type early colorectal cancers were detected and treated. When a faint abnormality of the mucosa was suspected by routine videocolonoscopy, 0.1% of indigo carmine solution was sprayed on the mucosal surface (chromoendoscopy). Colonoscopic findings of m-sm1 cancers and moderately and massively extended submucosal (sm2-3) cancers were retrospectively reviewed and compared with confirmed histologic findings. RESULTS: Characteristic colonoscopic findings needed for surgical operation were as follows: (1) expansion appearance, (2) deep depression surface, (3) irregular bottom of depression surface, and (4) folds converging toward the tumor. By using these findings, the invasion depth of depressed type early colorectal cancers could be correctly determined in 58 of 64 lesions (91%). CONCLUSIONS: Characteristic colonoscopic findings obtained by a combination of videocolonoscopy and chromoendoscopy are useful for determination of the invasion depth of depressed type colorectal cancers, an essential factor in choosing a treatment modality.

Colon↗
PubMed1998

Mammalian Polycomb group genes are categorized as a new type of early response gene induced by B-cell receptor cross-linking.

Polycomb group (PcG) genes were initially described in Drosophila melanogaster as regulators of the homeobox gene. Four mammalian homologues, mel-18, bmi-1, M33 and rae-28, are analyzed in this study. They not only regulate mammalian homeotic genes by analogy with their Drosophila counterparts, but also have some influence on the growth and differentiation of B lymphocytes. Here we report that these four mammalian PcG genes are rapidly induced after antigen-receptor cross-linking in B cells. Thus we would like to propose that mammalian PcG genes can be categorized as a new type of immediate early gene.

Animals↗
PubMed1998

Cellular expression of inducible nitric oxide synthase following rat cortical incision and its suppression by hydroxyl radical scavenger, 1,2-bis(nicotinamido)propane.

Cellular expression of an inducible isoform of nitric oxide synthase (iNOS) was studied immunohistochemically 1,3 and 7 days following rat cortical incision. The induction of iNOS was demonstrated almost exclusively in the macrophages accumulated within the incision cavity on day 3. They were significantly reduced in number by the treatment with 1,2-bis(nicotinamido)propane (P < 0.01), suggesting the involvement of hydroxyl radicals in the macrophage activation after cortical injury.

Animals↗
PubMed1998

Accumulation of cholesterol and GM2 ganglioside in cells cultured in the presence of progesterone: an implication for the basic defect in Niemann-Pick disease type C.

Cultured fibroblasts from patients with Niemann-Pick disease type C (NP-C) are characterized by lysosomal accumulation of unesterified cholesterol and a defect in intracellular trafficking of cholesterol. We have found the accumulation of GM2 ganglioside in NP-C fibroblasts [Yano T, Taniguchi M, Akaboshi S, Vanier MT, Tai T, Sakuraba H, et al. Proc Japan Acad 1996;72B:214-219]. In this communication we show that several inhibitors known to inhibit intracellular cholesterol transport, progesterone, imipramine and KN-62, elicit accumulation of not only unesterified cholesterol but also GM2 ganglioside. This finding suggests that intracellular transport of cholesterol may be coupled with that of GM2 ganglioside. The accumulation of free cholesterol and GM2 ganglioside may be a clue for understanding the basic defect of NP-C. Recently NPC1 gene is found by the positional cloning. The mechanism of accumulating of GM2 ganglioside should be further investigated by studying of the functions of NPC1 gene.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Increased levels of GM2 ganglioside in fibroblasts from a patient with juvenile Niemann-Pick disease type C.

A 15-year-old boy was suffering from splenomegaly and a 10-year history of a neurologic disorder that included mental retardation, vertical supranuclear gaze palsy, dysarthria, ataxia, and dystonia. Bone marrow aspirates revealed foamy cells with storage materials which were positive with filipin staining. Cultured skin fibroblasts derived from the patient showed moderate loss of sphingomyelinase activity and the impairment of cholesterol esterification. The characteristic clinical presentations and typical histochemical findings of this patient met the diagnostic criteria of Niemann-Pick disease type C (NPC). In the fibroblasts from the patient, there was an accumulation of GM2 ganglioside around their cytoplasms. Increased levels of glycolipids. including GM2 ganglioside are reported in the cerebral cortex of NPC, but not in the fibroblasts. The fibroblasts derived from NPC may reflect the abnormal metabolism of glycolipids in the central nervous system of NPC.

Adolescent↗
PubMed1998

mel-18 negatively regulates cell cycle progression upon B cell antigen receptor stimulation through a cascade leading to c-myc/cdc25.

mel-18 is a mammalian Polycomb group gene encoding a transcriptional repressor with tumor suppressive activity. Overexpression of mel-18 in mice results in cell cycle arrest of B cells upon B cell receptor stimulation with downregulation of c-myc. This phenotype is rescued in mel-18/c-myc double-transgenic mice, suggesting that c-myc locates downstream of mel-18. In mel-18 transgenic mice, the downregulation of cyclins D2 and E; CDK4, -6, and -7; and CDC25A causes the impairment in the activities of cyclin-dependent kinases, resulting in hypophosphorylation of the retinoblastoma protein. In contrast, the upregulation of c-Myc, CDC25, and CDC2/CDK2 kinase activities results in the augmentation of B cell proliferation in mel-18-deficient mice. We therefore propose that mel-18 negatively regulates the cell cycle through a c-myc/cdc25 cascade.

Animals↗
PubMed1998

Norepinephrine-augmenting lipolytic effectors from Astilbe thunbergii rhizomes.

An EtOAc-soluble fraction from a 80% Me2CO extract of the rhizomes of Astilbe thunbergii enhanced norepinephrine-induced lipolysis in rat fat cells, while an EtOAc-insoluble fraction had no effect. The active substances isolated from the EtOAc-soluble fraction of the rhizomes were identified as eucryphin (1), bergenin (2), and astilbin (3), which enhanced norepinephrine-induced lipolysis at concentrations of 10-1000 microgram/mL, while they themselves did not cause lipolysis. Furthermore, these compounds slightly stimulated adrenocorticotrophic hormone-induced lipolysis and inhibited insulin-induced lipogenesis from glucose.

Adipocytes↗
PubMed1998

A response-regulator homologue possibly involved in nitrogen signal transduction mediated by cytokinin in maize.

A cDNA clone, pZmCip1, encoding a maize (Zea mays) cytokinin-inducible protein 1 was isolated utilizing the differential display technique, and studied using the expression of ZmCip1 in nitrogen-starved maize plants. The cloned cDNA contained an open reading frame consisting of 157 amino acids with a predicted molecular mass of 16.7 kDa, which possesses similarity with the response-regulators of bacterial two-component signalling systems. In detached leaves, accumulation of ZmCip1 transcript by t-zeatin was dose-dependent in a range of 10(-9) M to 10(-7) M, and occurred within 30 min after treatment. The effect of t-zeatin was replaceable by isopentenyl-adenosine or isopentenyl-adenosine-5'-monophosphate. Pretreatment of detached leaves with cycloheximide did not inhibit the accumulation of the transcript. In whole plants, ZmCip1 transcript was transiently accumulated exclusively in leaves by supply of nitrate or ammonium ions to the roots, whereas the transcript was not accumulated in detached leaves by supply of the nitrogen nutrients. Both the cytokinin- and nitrate-responsive accumulations of ZmCip1 transcript were accompanied by an increase in the immunotitratable protein. Isopentenyladenosine and/or its phosphorylated form(s) accumulated in roots 2 h after supply of nitrate to plants. These results, taken together, suggest that ZmCip1 is a primary response gene to cytokinins, and that it involves, at least in part, the nitrogen-signal transduction mediated by cytokinin in maize.

Amino Acid Sequence↗