PubMed Health⌕ Search

Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 19 recordsLinked to original sources
PubMed1996

STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line.

Myeloid leukemia M1 cells can be induced for growth arrest and terminal differentiation into macrophages in response to interleukin 6 (IL-6) or leukemia inhibitory factor (LIF). Recently, a large number of cytokines and growth factors have been shown to activate the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. In the case of IL-6 and LIF, which share a signal transducing receptor gp130, STAT3 is specifically tyrosine-phosphorylated and activated by stimulation with each cytokine in various cell types. To know the role of JAK-STAT pathway in M1 differentiation, we have constructed dominant negative forms of STAT3 and established M1 cell lines that constitutively express them. These M1 cells that overexpressed dominant negative forms showed no induction of differentiation-associated markers including Fc gamma receptors, ferritin light chain, and lysozyme after treatment with IL-6. Expression of either c-myb or c-myc was not downregulated. Furthermore, IL-6- and LIF-mediated growth arrest and apoptosis were completely blocked. Thus these findings demonstrate that STAT3 activation is the critical step in a cascade of events that leads to terminal differentiation of M1 cells.

Acute-Phase Proteins↗
PubMed1996

Essential role of Stat6 in IL-4 signalling.

Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

Animals↗
PubMed1996

Genetic control of in vivo tumor necrosis factor production in mice.

We report on the genetic effect on in vivo production of tumor necrosis factor (TNF)-alpha induced by lipopolysaccharides (LPS) using various congenic mouse strains. B10.A, Bl0.A(3R), B10.AQR, B10.A(5R), and B10.S(7R) produced significantly high TNF-alpha compared with B10.BR, B10.S, C57BL/10, B10.A(2R), B10.A(4R), B10.G, B10.DA(80NS), and B10.RIII(71NS). This suggests that LPS-induced TNF-alpha production is genetically controlled by H-2. Mice with the same alleles on K, A, E, or S loci produced various (high or low) levels of TNF-alpha, thus indicating that regulatory genes are located outside these loci. All strains with H-2Dd produced significantly high levels of TNF-alpha, but strains with other alleles in the H-2D locus produced low levels. Thus, TNF-alpha production appears to be genetically linked to H-2D itself or H-2D linked genes and the allele d is linked to a high responder gene. This was the case with the A background. C3H/HeN (H-2k), however, showed a high TNF-alpha production, suggesting the presence of another controlling gene outside H-2. In addition, high TNF-alpha productivity was transmitted into F1 mice (B10.A X B10.BR) in a dominant fashion. Both LPS-stimulated and unstimulated TNF-alpha mRNA expression in splenic macrophages were enhanced in high responder strains. Thus, we conclude that TNF-alpha production is closely related to genes within or linked to the H-2D locus as well as others outside H-2.

Animals↗
PubMed1996

Plasma adrenomedullin concentrations in essential hypertension.

We designed the present study to assess any changes in plasma concentrations of the novel vasorelaxant peptide adrenomedullin in patients with essential hypertension. Plasma adrenomedullin concentrations were measured in 45 patients with untreated essential hypertension, 15 patients with borderline hypertension, and 30 normotensive control subjects. After 4 weeks of effective calcium channel blocker-based antihypertensive therapy, adrenomedullin concentrations were measured again. The concentrations were higher in hypertensive patients with increased serum creatinine levels or decreased glomerular filtration rates compared with borderline hypertensive patients and normotensive subjects, although values in normotensive and hypertensive individuals overlapped. Plasma adrenomedullin concentrations were positively correlated with serum creatinine levels and inversely correlated with glomerular filtration rates in the hypertensive patients, whereas adrenomedullin values were not correlated with blood pressure level, left ventricular mass index, or left ventricular ejection fraction. Despite blood pressure control with antihypertensive therapy, plasma adrenomedullin concentrations were not changed. Reversed-phase high-performance liquid chromatographic analysis showed that a major component of immunoreactive adrenomedullin in the plasma of normotensive subjects and hypertensive patients is human adrenomedullin-(1-52). These results indicate that plasma adrenomedullin concentrations are elevated in many hypertensive patients with renal dysfunction and its major component is human adrenomedullin-(1-52).

Adrenomedullin↗
PubMed1996

Interaction of adrenomedullin and platelet-derived growth factor on rat mesangial cell production of endothelin.

Adrenomedullin has recently been isolated from human pheochromocytoma. We designed the present study to examine the effect of adrenomedullin on the production of the vasoconstrictive and growth-promoting peptide endothelin-1 (ET-1) after stimulation with platelet-derived growth factor (PDGF) in cultured rat glomerular mesangial cells. PDGF stimulated ET-1 production in a concentration-dependent manner. Rat adrenomedullin inhibited this stimulated ET-1 production in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Rat adrenomedullin also increased the cellular level of cAMP in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Human adrenomedullin was less effective than rat adrenomedullin with respect to inhibiting ET-1 production and increasing cAMP levels. The addition of 8-bromo-cAMP (10(-3) and 10(-4) mol/L) reduced PDGF-induced ET-1 production. Furthermore, forskolin (10(-4) and 10(-5) mol/L), an activator of adenylate cyclase, reduced PDGF-induced ET-1 production. In contrast, the basal production of ET-1 was not significantly altered by rat and human adrenomedullin. These results indicate that adrenomedullin inhibits PDGF-induced ET-1 production in cultured rat mesangial cells, probably through a cAMP-dependent process.

Adrenomedullin↗
PubMed1996

Cholinergic changes in the hippocampus of stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We investigated age-related changes in the central cholinergic systems in stroke-prone spontaneously hypertensive rats (SHRSP) to examine whether the regional and progressive cholinergic changes occur and are correlated with behavioral changes in the passive avoidance task. METHODS: Tissue levels of choline (Ch) and acetylcholine (ACh) were determined in the cerebral regions, including the hippocampus, of SHRSP (at two ages: 15 to 20 and 30 to 40 weeks) that had been tested in a passive avoidance task and were compared with those of age-matched controls, Wistar-Kyoto rats (WKY). With the use of in vivo microdialysis, high K+-stimulated release of hippocampal ACh, a functional parameter of the cholinergic system, was also determined in 15- to 20-week-old SHRSP. RESULTS: We found that 15- to 20-week-old SHRSP demonstrated a markedly lower level of hippocampal Ch than age-matched WKY. The decrease in the Ch level in 15- to 20-week-old SHRSP was observed in all regions examined; however, in the hippocampus a significant difference from WKY was subsequently observed at the age of 30 to 40 weeks. The hippocampal ACh release was markedly decreased by repetitive stimulation with high K+ in 15- to 20-week-old SHRSP. Behavioral impairment in the passive avoidance task was observed in the two age groups of SHRSP, with significant and positive correlations between the hippocampal ACh levels and the response latency. CONCLUSIONS: A decrease in hippocampal Ch level was observed in both 15- to 20-week-old and 30- to 40-week-old SHRSP, accompanied by performance failure in the passive avoidance task. The abnormal release of hippocampal ACh in response to the repetitive K+ stimulation was also noted in 15- to 20-week-old SHRSP. Thus, cholinergic dysfunction in the hippocampal system may be responsible for behavioral abnormality in the passive avoidance task in SHRSP.

Acetylcholine↗
PubMed1996

Cystic lesions of the maxillomandibular region: MR imaging distinction of odontogenic keratocysts and ameloblastomas from other cysts.

OBJECTIVE: Differentiating odontogenic keratocysts and ameloblastomas from other cystic lesions in the maxillomandibular region is important because of their high recurrence rates. Conventional radiography, CT, and fine-needle aspiration biopsy are limited for differential diagnosis. The purpose of this study was to review the MR findings in patients with odontogenic keratocysts, ameloblastomas, and other maxillomandibular cysts to determine the value of MR imaging in the differential diagnosis of these lesions. SUBJECTS AND METHODS: MR images were obtained in 38 patients with 43 cystic lesions of the maxillomandibular region. All the lesions (19 odontogenic keratocysts, 11 ameloblastomas, five primordial cysts, five radicular cysts, and three cysts of other types) were pathologically confirmed by surgery or biopsy. Contrast-enhanced MR studies were performed in 34 patients. Images were reviewed to determine various imaging parameters: locularity, solid or cystic pattern, thickness and contrast enhancement of the walls, and homogeneity and signal intensities of the fluids. T2 relaxation times of cystic components were calculated in 31 lesions. RESULTS: MR images of odontogenic keratocysts showed that the cyst were unilocular in 10 lesions and multilocular in nine. In 10 lesions the cysts wall was uniformly thin and had poor contrast enhancement. Seven cysts had thick walls and two had no definite walls. In 17 lesions, the cystic contents showed heterogeneous signal intensity on T1-weighted images, T2-weighted images, or both. Eight cysts had predominantly intermediate or high T1-weighted signal intensity, and six cysts had predominantly intermediate T2-weighted signal intensity. MR findings in ameloblastomas were different from those in odontogenic keratocysts: a mixed solid and cystic pattern (11 lesions), irregularly thick walls (11 lesions), papillary projections (seven lesions), and strong enhancement of solid components (nine lesions). T2 relaxation times of cystic components were significantly shorter in odontogenic keratocysts than in ameloblastomas, with no overlap. All other cysts showed a unilocular, purely cystic pattern, with homogeneous fluids, although the T2 relaxation times of four lesions overlapped those of odontogenic keratocysts. CONCLUSION: From the MR findings of the walls, solid components, and the fluid contents, odontogenic keratocysts could be differentiated from ameloblastomas in all cases, although some other cysts showed MR findings similar to those of odontogenic keratocysts.

Adolescent↗
PubMed1995

Evaluation of contact sensitivity to formaldehyde and tetramethylthiuram monosulfide using a modified lymphocyte transformation test.

To examine the validity of a modified lymphocyte transformation test for evaluating contact hypersensitivity from weak sensitizers, guinea pigs were sensitized with formaldehyde (F) or tetramethylthiuram monosulfide (TMTM) using the maximization test procedure. Lymph node cells from the animals were then cultured with F or TMTM, in the presence or absence of epidermal cells (EC). Transformed lymphocyte counts were evaluated by uptake of 3H-thymidine. Nonsensitized guinea pigs were used as controls. The lymphocytes from sensitized guinea pigs showed stronger blastogenesis when cultured with F or TMTM in the presence of EC than when the sensitizers were not added to the culture and the response depended on the concentration of F or TMTM. Cultures in the absence of EC also showed significant enhancement of blastogenesis by F or TMTM, but the responses were significantly weaker than those in the presence of EC. Lymphocytes from the control animals did not show significantly enhanced blastogenesis in response to F or TMTM, even when EC was added to the cultures. The results suggested that contact sensitivity for weak sensitizers can be evaluated by this modified lymphocyte transformation test, especially when lymph node cells were co-cultured with EC.

Analysis of Variance↗
PubMed1995

Differential expression of transforming growth factor-alpha and epidermal growth factor during postnatal development of rat submandibular gland.

The concentration and the localization of transforming growth factor (TGF)-alpha and epidermal growth factor (EGF) in the submandibular glands (SMGs) of male Wistar rats of different ages (postnatal 0 to 10 weeks of age) were examined. Highest levels of TGF-alpha were seen early, at postnatal day 0; the levels dropped thereafter in an age-dependent manner, while EGF was not detectable before the third postnatal week. Immunoreactive localization of EGF was restricted to the granules of the granular convoluted tubule (GCT) cells in the mature SMGs, whereas TGF-alpha was observed throughout postnatal development over the entire duct system. TGF-alpha was demonstrated in the cytoplasm at early stages when the GCT granules were not observed and was also located on the granules at the late stage, as was the case for EGF, indicating that TGF-alpha is colocated with EGF in the mature SMG. These results demonstrate the differences between the expression of TGF-alpha and that of EGF in the developing rat SMG.

Age Factors↗
PubMed1995

Amino-acid sequence and tissue distribution of guinea-pig leukotriene A4 hydrolase.

The guinea-pig leukotriene A4 hydrolase (LTA4H)-encoding cDNA was isolated from a guinea-pig lung cDNA library by cross-hybridization using a human probe. The deduced amino acid (aa) sequence consists of 611 aa (68 756 Da) and contains all twelve internal peptide and N-terminal sequences determined from the purified enzyme from guinea-pig intestine. The aa identity of the guinea-pig enzyme with its human, mouse and rat counterparts was 92.9, 90.5 and 90.4%, respectively. The previously characterized zinc-binding motif and a putative active site were highly conserved, supporting the aminopeptidase activity described for this enzyme. RNA blot analysis demonstrated ubiquitous expression of the LTA4H mRNA.

Amino Acid Sequence↗
PubMed1995

Increased nitric oxide production in patients with hypotension during hemodialysis.

OBJECTIVE: To determine the involvement of nitric oxide production in hemodialysis-induced hypotension. DESIGN: Examination of nitric oxide synthesis, cyclic guanosine 3'5'-monophosphate (cGMP) levels, and endothelin-1 levels in plasma before and after hemodialysis. SETTING: Veterans Affairs medical center. PATIENTS: 13 patients with end-stage renal failure who were receiving hemodialysis: Six patients had hypotensive episodes during dialysis and 7 did not. INTERVENTION: Patients received heparin at a bolus dose of 2000 U at the initiation of dialysis followed by 1000 U/h during 4-hour hemodialysis sessions. RESULTS: Nitric oxide production markedly increased during hemodialysis-induced hypotensive episodes; this increase was not seen in patients who did not have a hypotensive episode. In both groups, the plasma cGMP and endothelin-1 levels decreased after hemodialysis. According to multiple regression analysis, standard coefficients of nitric oxide production, plasma cGMP levels, and endothelin-1 levels with mean blood pressure after hemodialysis were -0.743, -0.07, and 0.31, respectively. CONCLUSION: Nitric oxide production increased in patients who had a hypotensive episode during hemodialysis but did not increase in those who did not have a hypotensive episode.

Aged↗
PubMed1995

Intracisternal administration of interleukin-1 beta attenuates naloxone-precipitated withdrawal in morphine-dependent mice.

The effect of central administration of interleukin-1 beta on naloxone-precipitated withdrawal in morphine-dependent mice was studied. The degree of physical dependence on morphine was estimated by counting the number of jumps precipitated by naloxone, one of the typical withdrawal signs. Intracisternal (i.c.) administration of interleukin-1 beta (0.01-1 ng/5 microliters per mouse) to morphine-dependent mice 30 min prior to the injection of naloxone (10 mg/kg i.p.) decreased the number of jumps in a dose-dependent manner. The effect of interleukin-1 beta (1 ng) was significantly antagonized when it was co-administered with interleukin-1 receptor antagonist (1 microgram/mouse). These results suggest that centrally administered interleukin-1 beta could attenuate naloxone-precipitated withdrawal in morphine-dependent mice via interleukin-1 receptors in the brain. Co-administration of alpha-melanocyte-stimulating hormone (300 ng/mouse) or alpha-helical corticotropin-releasing factor (CRF)-(9-41), a CRF receptor antagonist (300 ng/mouse), with interleukin-1 beta also antagonized the inhibitory effect of interleukin-1 beta (1 ng). Moreover, i.c. administration of CRF (200 ng/mouse) significantly decreased the number of jumps.

Animals↗
PubMed1995

DAMGO, a mu-opioid receptor selective ligand, distinguishes between mu-and kappa-opioid receptors at a different region from that for the distinction between mu- and delta-opioid receptors.

The structural basis of opioid receptors (OPRs) for the subtype-selective binding of DAMGO, a mu-opioid receptor selective ligand, was investigated using chimeric mu/kappa-OPRs. Replacement of the region from the middle of the fifth transmembrane domain to the C-terminal of mu-OPR with the corresponding region of mu-OPR remarkably decreased the binding affinity to DAMGO, while the reciprocal chimera revealed the high affinity to DAMGO. These results indicate that DAMGO distinguishes between mu- and mu-OPRs at the region around the third extracellular loop, different from the case of the distinction between mu-and delta-OPRs in which the region around the first extracellular loop is important. Furthermore, displacement studies revealed that the region around the third extracellular loop is involved in the discrimination between mu- and kappa-OPRs not only by peptidic mu- selective ligands but also by non-peptidic ligands, such as morphine and naloxone.

Amino Acid Sequence↗
PubMed1995

Expression of insulin receptor-related receptor mRNA in the rat brain is highly restricted to forebrain cholinergic neurons.

Insulin receptor-related receptor (IRR) is a member of the insulin receptor family. However, its endogenous ligand and the physiological roles of IRR are unknown. To elucidate the physiological roles of IRR in the brain, we examined the expression of its mRNA in the rat brain by in situ hybridization. In contrast to the widespread expression of insulin receptor and insulin-like growth factor-1 receptor mRNAs in the brain, the expression of IRR mRNA was highly restricted to the forebrain cholinergic neurons. All the forebrain cholinergic neurons expressed IRR mRNA. The present findings indicate that IRR has a selective role in the brain for forebrain cholinergic function.

Animals↗
PubMed1995

Gz coupling to the rat kappa-opioid receptor.

We have expressed the cloned rat kappa-opioid receptor in human embryonic kidney 293 cells and studied the ability of kappa-selective ligands to inhibit adenylyl cyclase. In transfected 293 cells, activation of the kappa-opioid receptor by U50,488 and the dynorphins resulted in the inhibition of cAMP accumulation. The inhibitory response was sensitive to pertussis toxin and highly selective for kappa-agonists; neither mu- nor delta-opioids were able to activate the kappa-opioid receptor. Upon co-transfection with the alpha subunit of Gz, inhibition of cAMP accumulation by kappa-agonist became refractory to pertussis toxin, indicating that the kappa-opioid receptor can couple to both G(i) and Gz proteins.

Adenylate Cyclase Toxin↗
PubMed1995

Analysis of an initial step of T cell adhesion to endothelial monolayers under flow conditions.

We analyzed an initial step of T cell adhesion to endothelial cells under flow conditions. An initial step in T cell-endothelial cell interactions was characterized either by a rolling phase, or by an immediate arrest without rolling. Anti-E- and P-selectin Abs inhibited T cell rolling on endothelial cells under flow conditions. The rolling velocity of T cells on endothelial cells increased after treatment of endothelial cells with anti-E- or P-selectin Abs. Also, rolling of T cells was observed on E-selectin-transfected CHO cells but not on ICAM-1-transfected CHO cells. Thus, rolling of T cells under flow condition was dependent on E-selectin as well as P-selectin expressed on endothelial cells. In contrast, neither anti-E- nor P-selectin Abs inhibited the immediate arrest of T cells on endothelial cells significantly and anti-ICAM-1 Abs also failed to inhibit the immediate arrest of T cells. Therefore, other adhesion molecules may play an important role in the immediate arrest of T cells under flow conditions. The number of CD45RA- T cells rolling on E-selectin-transfected CHO cells was much higher than that of CD45RA+ T cells.

Animals↗
PubMed1995

Immunocytochemical localization of mu-opioid receptor in the rat caudate-putamen.

A guinea pig antibody against a C-terminal peptide of rat mu-opioid receptor (MOR) was produced to examine the distribution of MOR in the rat caudate-putamen (CP). The anti-peptide antibody recognized a protein of M(r) 69,000 in Triton X-100 extract of rat brain and in the membrane fraction of MOR-expressing culture cells. Intense MOR-like immunoreactivity (LI) was observed in island-like areas of the CP. Some MOR-LI was located on the cell bodies and dendrites of CP neurons. Double immunofluorescence study revealed that the intensely MOR-immunoreactive areas showed weak calbindin-LI, surrounded by intensely calbindin-positive regions. The results indicate that MOR-LI is enriched in the 'patches' of the neostriatal mosaic compartmentation.

Animals↗