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Biomedical subjects

Noriko Makita

Publications and source records attributed to Noriko Makita.

7 recordsLinked to original sources
PubMed2006

Evaluation of the function of human invariant NKT cells from cancer patients using alpha-galactosylceramide-loaded murine dendritic cells.

NKT cells play a role in immunological regulation of certain diseases, and their frequency and/or function may be related to disease prognosis. However, it is often difficult to evaluate NKT cell function in patients with malignancies due to reduced numbers of NKT cells as well as the dysfunction of the APCs used as stimulators. We found that NKT cell function could not be evaluated by conventional ELISPOT assays, confirming the impaired function of APCs in chronic myelogenous leukemia (CML)-chronic phase patients. To overcome this problem, we have established a sensitive assay using murine dendritic cells to evaluate the function of small numbers of human NKT cells independent of autologous APCs. We found that imatinib-treated CML-chronic phase patients showing a complete cytogenetic response had NKT cells capable of producing IFN-gamma, whereas NKT cells from patients who were only partially responsive to imatinib treatment did not produce IFN-gamma. Functional NKT cells found in imatinib-treated, CML-complete cytogenetic response patients may offer the promise of effective immunotherapy with ex vivo-generated alpha-galactosylceramide-pulsed dendritic cells. This new approach should be available for evaluating the functions of NKT cells and APCs in cancer patients.

Animals↗
PubMed2006

An instructive case suggesting cyclical primary hyperparathyroidism.

We report an instructive case of primary hyperparathyroidism in which cyclical secretion of PTH may have caused repeated hypercalcemic crises followed by temporary remission with a spontaneous drop in PTH. A 64-year-old man was admitted to our hospital twice with severe hypercalcemic crisis (corrected calcium (cCa) 15.0 mg/dl and 16.7 mg/dl) accompanied by an increase in intact PTH (220 pg/ml and 470 pg/ml). During both events, the serum PTH values spontaneously dropped followed by remission of the hypercalcemia. The tumor, detected at the left-upper side, showed neither vascularity on ultrasound examination nor washout delay on MIBI scintigraphy, suggesting that two parathyroid adenoma infarctions had occurred. Cervical exploration was undertaken. The histopathological examinations confirmed that the tumor was parathyroid adenoma. Contrary to our expectation, however, it did not reveal necrotic tissue that would indicate recent infarction. The findings in this case may be explained by cyclical secretion of PTH from a parathyroid adenoma. Although cyclical Cushing's syndrome is well known, to our knowledge this is the first documented case suggesting cyclical primary hyperparathyroidism.

Bone Density↗
PubMed2004

Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II.

The angiotensin II type 1 (AT1) receptor has a crucial role in load-induced cardiac hypertrophy. Here we show that the AT1 receptor can be activated by mechanical stress through an angiotensin-II-independent mechanism. Without the involvement of angiotensin II, mechanical stress not only activates extracellular-signal-regulated kinases and increases phosphoinositide production in vitro, but also induces cardiac hypertrophy in vivo. Mechanical stretch induces association of the AT1 receptor with Janus kinase 2, and translocation of G proteins into the cytosol. All of these events are inhibited by the AT1 receptor blocker candesartan. Thus, mechanical stress activates AT1 receptor independently of angiotensin II, and this activation can be inhibited by an inverse agonist of the AT1 receptor.

Angiotensin II↗
PubMed2003

Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in transforming growth factor-beta1 regulation of pancreatic stellate cellular functions.

Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor-beta(1) (TGF-beta(1)) regulates PSC activation and proliferation in an autocrine manner. The intracellular signaling pathways of the regulation were examined in this study. Immunoprecipitation and immunocytochemistry revealed that Smad2, Smad3, and Smad4 were functionally expressed in PSCs. Adenovirus-mediated expression of Smad2, Smad3, or dominant-negative Smad2/3 did not alter TGF-beta(1) mRNA expression level or the amount of autocrine TGF-beta(1) peptide. However, expression of dominant-negative Smad2/3 inhibited PSC activation and enhanced their proliferation. Co-expression of Smad2 with dominant-negative Smad2/3 restored PSC activation inhibited by dominant-negative Smad2/3 expression without changing their proliferation. By contrast, co-expression of Smad3 with dominant-negative Smad2/3 attenuated PSC proliferation enhanced by dominant-negative Smad2/3 expression without altering their activation. Exogenous TGF-beta(1) increased TGFbeta(1) mRNA expression in PSCs. However, PD98059, a specific inhibitor of mitogen-activated protein kinase kinase (MEK1), inhibited ERK activation by TGF-beta(1), and consequently attenuated TGF-beta(1) enhancement of its own mRNA expression in PSCs. We propose that TGF-beta(1) differentially regulates PSC activation, proliferation, and TGF-beta(1) mRNA expression through Smad2-, Smad3-, and ERK-dependent pathways, respectively.

Animals↗
PubMed2003

A novel mitochondrial Ca2+-dependent solute carrier in the liver identified by mRNA differential display.

Pancreatic AR42J cells have the feature of pluripotency of the precursor cells of the gut endoderm. Dexamethasone converts them to exocrine cells or liver cells. Using mRNA differential display techniques, we have identified a novel Ca2+-dependent member of the mitochondrial solute carrier superfamily, which is expressed during the course of differentiation, and have designated it MCSC. The corresponding cDNA comprises an open reading frame of 1407 base pairs encoding a polypeptide of 469 amino acids. The carboxyl-terminal-half of MCSC has high similarity with other mitochondrial carriers, and the amino-terminal-half has three canonical elongation factor-hand motifs and has calcium binding capacity. The deduced amino acid sequence revealed 79.1% homology to the rabbit peroxisomal Ca2+-dependent member of the mitochondrial superfamily, but the subcellular localization of the protein was exclusively mitochondrial, not peroxisomal. Northern blot and Western blot analyses revealed its predominant expression in the liver and the skeletal muscle. In the liver, the expression level of MCSC was higher in the adult stage than in the fetal stage, and MCSC was highly up-regulated in dexamethasone-treated AR42J cells before the expression of albumin. Taken together, MCSC may play an important role in regulating the function of hepatocytes rather than in differentiation in vivo.

Amino Acid Sequence↗