Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 235 records · Page 13Linked to original sources

PubMed1998

Induction of infarct tolerance by platelet-derived growth factor against reversible focal ischemia.

Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet-derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study. A total of 82 male Sprague-Dawley rats were used. Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 microg in total), 7 days (2 microgram or 4 microgram in total), or 14 days (4 microgram in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF-BB (4 microgram in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF-BB or saline. In the group receiving PDGF-BB (4 microgram in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF-BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF-BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia.

Animals↗

PubMed1998

Requirement for IRF-1 in the microenvironment supporting development of natural killer cells.

Natural killer (NK) cells are critical for both innate and adaptive immunity. The development of NK cells requires interactions between their progenitors and the bone-marrow microenvironment; however, little is known about the molecular nature of such interactions. Mice that do not express the transcription factor interferon-regulatory factor-1 (IRF-1; such mice are IRF-1(-/-) mice) have been shown to exhibit a severe NK-cell deficiency. Here we demonstrate that the lack of IRF-1 affects the radiation-resistant cells that constitute the microenvironment required for NK-cell development, but not the NK-cell progenitors themselves. We also show that IRF-1(-/-) bone-marrow cells can generate functional NK cells when cultured with the cytokine interleukin-15 and that the interleukin-15 gene is transcriptionally regulated by IRF-1. These results reveal, for the first time, a molecular mechanism by which the bone-marrow microenvironment supports NK-cell development.

Animals↗

PubMed1998

Differential expression of rat brain phospholipase C isozymes in development and aging.

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. In the present study we examined developmental and aging changes in three PLC isozymes (beta 1, gamma 1, and delta 1) in the rat brain. Enzyme assays and immunoblot analyses after gel filtration chromatography of brain extracts from embryonic day 19 and postnatal 4- and 48-week rats indicated that gamma-specific activity was highest in fetal brain and decreased with aging, that beta 1-specific activity was high at 4 weeks but essentially undetected in fetal brain, and that delta 1-specific activity was high at both 4 and 48 weeks with faint detection in fetal brain. Our results suggest that the gamma 1 isozyme may be particularly involved in cell division and growth during the histo-genesis of the central nervous system, while beta 1 and delta 1 isozymes may take part in processes of its maturation and maintenance.

Aging↗

PubMed1998

Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer's disease.

Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leukemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) and the caspase family (ICH-1 and CPP32), with apoptosis being prevented by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and control brain. In the membranous fraction, the levels of Bcl-2 alpha, Bcl-xL, Bcl-x beta, Bak and Bad were increased in AD. In the cytosolic fractions, the level of Bcl-x beta was increased, while Bcl-xL, Bax, Bak, and Bad and ICH-1L were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement of cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl-2 and Bcl-x are upregulated in AD brains.

Age Factors↗

PubMed1998

cDNA cloning and characterization of neuron-specific enolase from chicken.

Chicken gamma-enolase cDNA was cloned and its sequence and tissue-specific expression were analyzed. The cDNA, consisting of 2273 bp of nucleotides, was composed of 86 bp of the 5'-noncoding region, 1305 bp of an open reading frame encoding a protein of 434 amino acids and 882 bp of the 3'-noncoding region. The deduced amino acid sequence showed higher homology (more than 90%) to those of mammalian gamma-enolases than to those of chicken alpha- or beta-enolases. Northern blot analysis has revealed that the mRNA for gamma-enolase (2.3 kb) is expressed in the brain and, to much less but significant extents, in the pituitary and adrenal gland of the chicken.

Amino Acid Sequence↗

PubMed1998

Cell cycle regulation of histone H4 gene transcription requires the oncogenic factor IRF-2.

Histone genes display a peak in transcription in early S phase and are ideal models for cell cycle-regulated gene expression. We have previously shown that the transcription factor interferon regulatory factor 2 (IRF-2) can activate histone H4 gene expression. In this report we establish that a mouse histone H4 gene and its human homolog lose stringent cell cycle control in synchronized embryonic fibroblasts in which IRF-2 has been ablated. We also show that there are reduced mRNA levels of this endogenous mouse histone H4 gene in the IRF-2(-/-) cells. Strikingly, the overall mRNA level and cell cycle regulation of histone H4 transcription are restored when IRF-2 is reintroduced to these cells. IRF-2 is a negative regulator of the interferon response and has oncogenic potential, but little is known of the mechanism of these activities. Our results suggest that IRF-2 is an active player in E2F-independent cell cycle-regulated gene expression at the G1/S phase transition. IRF-2 was previously considered a passive antagonist to the tumor suppressor IRF-1 but can now join other oncogenic factors such as c-Myb and E2F1 that are predicted to mediate their transforming capabilities by actively regulating genes necessary for cell cycle progression.

3T3 Cells↗

PubMed1998

Effects of a low-protein diet on prolactin- and growth hormone-producing cells in the rat pituitary gland.

BACKGROUND: It is well known that an unbalanced diet induces various changes in the pituitary gland. However, little attention has been paid to the molecular aspects of this perturbation. We studied the influence of a low-protein diet (LPD) on the prolactin (PRL) and growth hormone (GH) cells in the rat pituitary gland using immunohistochemical staining and in situ hybridization. MATERIALS: Rats aged 20 days were fed a diet containing 27% protein or one with 8% protein (LPD) for 30 days. Pituitary glands were obtained and subjected to either immunohistochemistry or in situ hybridization. Quantitative morphological analysis was then conducted to determine cell number and area as well as the percentage of cells stained by the respective antisera and/or cDNA probe in each experimental group. RESULTS: The average sectional areas of both PRL- and GH-producing cells in the LPD group were smaller in size than those in the controls. The cell numbers per unit area (mm2) of PRL-positive cells and PRL mRNA-positive cells were 3,596.5 and 3,948.6, respectively, in the LPD group, and 3,179.6 and 4,888.5, respectively, in the controls. The numbers per unit area of GH-positive cells and GH mRNA-positive cells in the LPD group were similar (2,252.3 and 2,224.4), as compared to 2,161.3 and 1,684.2, respectively, in the well-fed rats. Whereas PRL-positive cells comprised about 27% of the total number of cells in both animal groups, those given the LPD contained a lower percentage (29%) of PRL mRNA-positive cells as compared to the controls (44%). On the other hand, GH mRNA-positive cells numbered about 15% of the total cell population both animal groups; however, the malnourished rats contained a lower percentage (16%) of GH-positive cells than did their well-fed counterparts (20%). CONCLUSIONS: Taken together, these results indicate that in the rat pituitary gland, administration of an LPD reduced the size of PRL- and GH-positive cells as well as differentially affecting a subpopulation of the PRL mRNA-positive cells and the GH-positive cells.

Animals↗

PubMed1998

Mechanism of selective motor neuronal death after exposure of spinal cord to glutamate: involvement of glutamate-induced nitric oxide in motor neuron toxicity and nonmotor neuron protection.

In this study, we analyzed the mechanism of selective motor neuronal death, a characteristic of amyotrophic lateral sclerosis, using embryonic rat spinal cord culture. When dissociated cultures were exposed to low-level glutamate (Glu) coadministered with the Glu transporter inhibitor L-trans-pyrrolidine-2,4-decarboxylate (PDC) for 24 hours, motor neurons were selectively injured through N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptors. Nitric oxide synthase (NOS) inhibitors attenuated this toxicity, and long-acting nitric oxide (NO) donors damaged motor neurons selectively. Nonmotor neurons survived after exposure to low-dose Glu/PDC, but Glu-induced toxicity was potentiated by coadministration of an NO-dependent guanylyl cyclase inhibitor. In addition, 8-bromo-cyclic GMP, a soluble cyclic GMP analogue, rescued nonmotor neurons, but not motor neurons, exposed to high-dose Glu/PDC. Twenty-four hours' incubation with PDC elevated the number of neuronal NOS-immunoreactive neurons by about twofold compared with controls, and a double-staining study, using the motor neuron marker SMI32, revealed that most of them were nonmotor neurons. These findings suggest that selective motor neuronal death caused by chronic low-level exposure to Glu is mediated by the formation of NO in nonmotor neurons, which inversely protects nonmotor neurons through the guanylyl cyclase-cyclic GMP cascade. Induction of neuronal NOS in nonmotor neurons might enhance both the toxicity of motor neurons and the protection of nonmotor neurons, which could explain the pathology of amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗

PubMed1998

Ocular hypotension induced by intravitreally injected C-type natriuretic peptide.

The purpose of the study is to determine if intravitreal injection of c-type natriuretic peptide (CNP) affects intraocular pressure (IOP), aqueous humor dynamics and guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the aqueous humor of the rabbit eye. Also we investigated whether CNP-like immunoreactivities (CNP-LI) were present in porcine aqueous humor and whether CNP-LI were detected in rabbit and porcine ciliary body. The IOP was measured after intravitreal injection of 2 pmol approximately 20 nmol CNP into rabbit eyes. Aqueous humor dynamics (aqueous humor flow, outflow facility, and uveoscleral outflow) and cGMP concentration in the aqueous humor were determined at approximately 6 hr after CNP injection. The CNP concentration in aqueous was measured by radioimmunoassay in porcine eye, and CNP-LI were detected with a monoclonal antibody in porcine and rabbit eyes. Intravitreally injected CNP caused IOP reduction in a dose-dependent manner (P<0.0001) and the maximum effect was observed at 4 approximately 6 hr. CNP increased total outflow facility by approximately 35%, but did not affect aqueous humor flow or uveoscleral outflow. The cGMP concentration in the aqueous of CNP-treated eyes was about 4- to 14-fold higher than that in the contralateral untreated eyes. CNP concentration in aqueous was about 2-fold higher than that in plasma, and CNP-LI were found in non-pigmented epithelium of the ciliary body of both rabbit and porcine eyes. CNP may play an important role in the regulation of IOP.

Animals↗

PubMed1998

Crystallographic Characterization of the DNA-Binding Domain of Interferon Regulatory Factor-2 Complexed with DNA.

Interferon regulatory factors (IRFs) are transcription factors for interferon-related genes, which manifest both antiviral and tumor-suppressor activities and regulate cell growth in response to DNA damage. For the transcription initiation of the interferon-beta gene, IRFs form a macromolecular assembly bound to the promoter DNA, referred to as an enhancesome, together with several other transcription factors and DNA-binding proteins. The three-dimensional structure of IRF-DNA complex would provide insights into the structure and function of the enhancesome. In this study, we crystallized the DNA-binding domain of interferon regulatory factor-2 complexed with a DNA fragment. The crystals reproducibly grew by the vapor diffusion technique with 2-methyl-pentanediol from solutions containing small detergents, such as n-octyl-beta-d-glucoside. Cryocrystallographic experiments showed that crystals belong to space group P212121 with a = 90.66 Å, b = 101.01 Å, c = 171.58 Å and diffract up to 2.8 Å resolution. The absorption measurements of a solution in which the crystals were dissolved indicate that the DNA-binding domain binds to the DNA as a dimer. The calculated values of the solvent contents suggest that the protein-DNA complexes form a multimer in the crystal. These features may reflect the association of the complexes in the enhancesome. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

Percutaneous autotransplantation of parathyroid tissue into the forearm muscles.

We developed a simple and easy nonsurgical percutaneous method for autografting parathyroid tissue into the forearm muscles. This method was applied to 30 patients suffering from secondary hyperparathyroidism who were then refractory to medical treatment. The operative results were then compared with 16 patients who underwent treatment using Wells' method. The graft "take," judged by a significant intact parathyroid hormone (PTH) ratio (> 1.5) between grafted and nongrafted arm vein blood, was 82% for the percutaneous method group and 75% for the Wells' method group, respectively. The percentage of recurrent hyperparathyroidism necessitating a subtotal removal of the autograft was equal in the two groups. No complications were noted for either method. Wells' method can thus be replaced by this simple and easy nonoperative method.

Adult↗

PubMed1998

Precipitate formed by thiopentone and vecuronium causes pulmonary embolism.

PURPOSE: To examine the effects of a bolus injection of the precipitate formed by thiopentone and vecuronium on the pharmacokinetic behaviour of thiopentone, cardiopulmonary physiology, and lung histology. METHODS: Of 16 female rabbits (2.9 to 3.1 kg), eight were injected with a precipitate formed by a mixture of 5 mg.kg-1 thiopentone and 0.67 mg.kg-1 vecuronium via the external jugular vein. Eight control rabbits were injected with 5 mg.kg-1 thiopentone alone. Plasma thiopentone concentration, systolic arterial pressure and PaO2 were measured for 60 min after injection. Histological changes in the lungs were evaluated at one and 60 min. RESULTS: Maximum blood thiopentone concentration in the precipitate group was lower than in the control group (12.9 +/- 4.5 vs 17.0 +/- 1.6 micrograms.ml, P < 0.05), although the half-life of thiopentone in the precipitate group was longer (32.3 +/- 8.5 vs 21.7 +/- 8.2 min, P < 0.05) and the area under the time concentration curve was similar between the two groups. However, the mean residence time was 28% longer in the precipitate group than in controls (P < 0.05). The PaO2 was lower in the precipitate group than in controls one minute after injection (431 +/- 27 vs 464 +/- 18 mmHg, P < 0.05) but not subsequently. Histologically, crystals (30-150 microns in diameter) obstructed small arteries in the lungs at one minute but not at 60 min after injection. CONCLUSION: Intravenous injection of precipitate causes pulmonary microembolism, with a small transient decrease in PaO2.

Anesthetics, Intravenous↗

PubMed1998

Effects of three peptidase inhibitors, amastatin, captopril and phosphoramidon, on the hydrolysis of [Met5]-enkephalin-Arg6-Phe7 and other opioid peptides.

The contents of [Met5]-enkephalin-Arg6-Phe7 (met-enk-RF) and its six hydrolysis products: Y, YG, YGG, YGGF, YGGFM, and YGGFMR were estimated after incubating met-enk-RF with either a guinea-pig ileal or striatal membrane fraction for various times at 37 degrees C. After 45 min incubation with either ileal or striatal membranes, met-enk-RF was completely hydrolyzed, yielding Y as the major product. Incubation with either membrane preparation for 60 min in the presence of the aminopeptidase inhibitor amastatin hydrolyzed 90 or 92% of met-enk-RF, respectively, with YGG being the major product. If the dipeptidyl carboxypeptidase I inhibitor captopril is also included in the incubation, met-enk-RF hydrolysis decreases by about half for both membranes, with YGG remaining the major product. Inclusion of three peptidase inhibitors, amastatin, captopril, and phosphoramidon (inhibition of endopeptidase-24.11) further reduced met-enk-hydrolysis, with 87% or more remaining intact. This shows that met-enk-RF was mainly hydrolyzed by three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I and phosphoramidon-sensitive endopeptidase-24.11, in both ileal and striatal membranes. Additionally, estimations of [Leu5]-enkephalin (leu-enk), alpha- and beta-neoendorphins (alpha- and beta-neoends), and dynorphin B (dyn B) contents after incubating the individual peptides with striatal membrane for 60 min in the presence of the three peptidase inhibitors showed that 98, 32, 5, and 23%, respectively, remained intact. Our previous studies together with the data obtained here show that one group of endogenous opioid peptides: met-enk, leu-enk, met-enk-RF, met-enk-RGL, and dyn A-(1-8) are largely or almost exclusively hydrolyzed by the three enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I, and phosphoramidon-sensitive endopeptidase-24.11, and indicate that an unidentified fourth enzyme(s) is involved in the hydrolysis of another group of peptides: alpha-neoend, beta-neoend, and dyn B.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Nicotine administration decreases the number of binding sites and mRNA of M1 and M2 muscarinic receptors in specific brain regions of rat neonates.

Nicotine has been shown to delay the developmental increase of muscarinic receptors in brain of rat neonates. In this study, we have examined the muscarinic receptor binding sites and corresponding messenger RNA in rat neonates, whose mothers received nicotine in the drinking water, using competition binding study and northern blot analysis. On postnatal 14th day, nicotine treatment led to a 61% reduction in the proportion of high-affinity sites for pirenzepine (M1-subtype) to total [3H]quinuclidinyl benzilate binding sites in cerebral cortex in rat neonate. Nicotine treatment also decreased that for 11-2[[2-[(diethylamino)methyl]-1-piperidinyl]-5,11-dihydro-6H-pyrido [2,3-b] [1,4] benzodiazepin-6-one (AF-DX 116) (M2-subtype) by 77% in cerebellum on postnatal 14th day. The levels of m1 and m2 muscarinic receptor messenger RNAs in the same brain regions were also decreased in the same day after nicotine treatment. On postnatal 35th day, no difference was observed in binding sites or in messenger RNA levels of the brain regions tested (cerebral cortex, midbrain, hippocampus, cerebellum and brainstem). Our results show that nicotine reduces muscarinic receptor subtypes in developing rat brain, in part, through suppression of the messenger RNA expression, but that the effects are different among brain regions and subtypes.

Animals↗

PubMed1998

Alpha1-adrenoceptor subtypes and two receptor systems in vascular tissues.

The subtypes of alpha1-adrenoceptor are coexpressed in many tissues. We examined the relationship between coexpressed alpha1-adrenoceptor subtypes and their functions in blood vessels. Rat and rabbit aortas coexpressed three subtypes (alpha1A, alpha1B, alpha1D) and four subtypes (alpha1A, alpha1B, alpha1D, alpha1L), respectively. In rat aorta however, noradrenaline-induced contraction was mediated predominantly through the alpha1D subtype, and oxymetazoline produced alpha1B-mediated contraction. In rabbit aorta, concentration-response curves for noradrenaline were composed of two components (alpha1B and alpha1L-mediated), while oxymetazoline produced alpha1L-mediated contraction. Therefore, the inhibitory actions of some antagonists varied markedly among tissues and agonists. These results demonstrate diversity of the two receptor systems and suggest that the heterogeneity of physiological responses reflects the differences in functional subtypes among tissues and in their sensitivities to agonists and antagonists.

Adrenergic alpha-Agonists↗

PubMed1998

Induction of inducible nitric oxide synthase and heme oxygenase-1 in rat glial cells.

Recent observations suggest a possible interaction between the nitric oxide (NO)/NO synthases and carbon monoxide (CO)/heme oxygenases systems. We examined the effects of lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and NO donor such as S-nitroso-N-acetylpenicillamine (SNAP) on induction of inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) in mixed glial cells and in rat hippocampus. In in vitro glial cells, treatment with LPS induced the expression of 130-kDa iNOS after 6 h, and NO2- accumulation and enhancement of the protein level of 33-kDa HO-1 after 12 h. In addition, treatment with SNAP induced HO-1 expression after 6 h. Although a NOS inhibitor, such as N(G)-nitro-L-arginine (NNA), did not change LPS-induced iNOS expression, the inhibitor suppressed both NO2- accumulation and the enhancement of HO-1. Immunocytochemistry showed that LPS-treatment induced iNOS-immunoreactivity predominantly in microglia, while this treatment induced HO-1-immunoreactivity in both microglia and astrocytes. These results suggest that endogenous NO production by iNOS in microglia causes autocrine- and paracrine-induction of HO-1 protein in microglia and astrocytes in rat brain.

Animals↗

PubMed1998

Growth arrest associated with 12-o-tetradecanoylphorbol-13-acetate-induced hematopoietic differentiation with a defective retinoblastoma tumor suppressor-mediated pathway.

The retinoblastoma tumor suppressor (Rb) gene product plays an essential role in cell-cycle regulation. However, its role in terminal differentiation of hematopoietic cells is speculative. Here we show a model of 12-o-tetradecanoylphorbol-13-acetate (TPA)-induced hematopoietic differentiation and growth arrest with a defective Rb-mediated pathway. TPA treatment arrested the cell cycle of a human hematopoietic cell line, MEG-01s, at the G1-S boundary and induced expression of p21/SDI1/WAF1/CIP1 and p27/KIP1. Both of these proteins were present in cyclin E-associated complexes, the histone H1 and Rb kinase activities of which were then inactivated. However, MEG-01s cells lacked the intact Rb protein and the Rb-mediated pathway was defective. This model raises a question about the role for Rb in terminal differentiation of hematopoietic cells.

Blotting, Northern↗

PubMed1998

Effect of adrenomedullin on ion transport and muscle contraction in rat distal colon.

We have investigated the effects of adrenomedullin (AM) on mucosal ion transport using the Ussing method and smooth muscle contraction using the Magnus method in rat. Our results indicate that AM increases Isc (short-circuit current) for Cl- secretion (100 nM:170.0 +/- 41.2%, 1 microM:193.8 +/- 45.5%, 100% Isc:28.2 +/- 3.1 microA/cm2) with an initial small decrease of Isc, inhibiting Na+ absorption. Tetrodotoxin (TTX) inhibits the Isc response elicited by AM (86%). In addition, AM relaxes potassium-induced contraction (10 nM:11.1 +/- 8.51%, 100 nM:33.4 +/- 12.7%, 100% contraction: 1.8 +/- 0.22 g), and TTX inhibits the response elicited by AM (90%). We conclude that AM modulates water and ion transport as well as bowel movement, mainly through the colonic nervous system.

Adrenomedullin↗