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T Nishimura

Publications and source records attributed to T Nishimura.

At least 199 records · Page 11Linked to original sources
PubMed1996

The amino-terminally truncated forms of amyloid beta-protein in brain macrophages in the ischemic lesions of Alzheimer's disease patients.

We have investigated the cerebral cortex of Alzheimer's disease in which small infarcts are found on postmortem neuropathological examination. In areas that have been subjected to recent ischemia, immunohistochemical staining for amyloid beta-protein (A beta) is much less intense than in the non-ischemic surround. However, the infiltrating brain macrophages contain granules immunopositive for C-terminal fragments of A beta. The immunohistochemical profile indicates that A beta in these granules lacks epitopes in the N-terminal fragments. These data suggest that appropriately stimulated macrophages can phagocytose A beta deposits and that digestion of the N-terminal region is an early consequence of this phagocytosis.

Aged↗
PubMed1996

First synthesis of cellooctaose by a convergent synthetic method.

The first chemical synthesis of cellooctaose by a convergent synthetic method is described. A challenging glycosylation between cellotetraosyl donor 5 and acceptor 7 proceeded in a one-step reaction using a high-vacuum system for anhydrous glycosylation and minimizing imidate side reactions such as hydrolysis and glycosyl fluoride formation. Pivaloyl, allyl, and benzyl protecting groups of cellooctaose derivative 8 were completely removed with SeO2-AcOH, NaOMe-MeOH, and H2/Pd(OH)2-C, respectively. The acetylation after each deprotection step finally led to cellooctaose hexacosaacetate (20), which is useful for purification and structural identification. Finally, the acetyl derivative 20 was deacetylated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in 20% MeOH-CH2Cl2 to give pure cellooctaose (21). The analogous synthetic route to the present convergent synthetic design of cellooctaose may be a most promising one that enables us to synthesize cellulose with a defined degree of polymerization (dp).

Acetylation↗
PubMed1996

Purinergic cation channels in neurons of rabbit vesical parasympathetic ganglia.

Membrane current was recorded from neurons in rabbit vesical parasympathetic ganglia, utilizing single electrode voltage clamp techniques. ATP (0.1-1 mM) caused an inward current (IATP) associated with an increased conductance at a holding potential of -50 mV. ADP (0.1-1 mM) and 5'-O-3-thiotriphosphate (0.1-0.6 mM) but not AMP (0.3-2 mM) and adenosine (0.1-2 mM) mimicked the actions of ATP. The IATP reversed its polarity at -12.1 +/- 1.4 mV. The amplitude of the IATP was depressed in low sodium solutions and in nominally calcium-free solutions but not in low chloride solutions. Suramin (10-100 microM) and reactive blue 2 (10-100 microM), P2-antagonists, reversibly depressed the IATP. In contrast, hexamethonium (100 microM) did not affect the IATP. These data suggest that ATP activates cation channels through P2X receptor subtypes in parasympathetic neurons.

Animals↗
PubMed1996

Cell adhesion via murine alpha4 human beta1 integrin chimera on transfected K562 cells to endothelial cells.

To evaluate the property of binding activity of alpha4beta1 integrin in cell-cell interaction, we newly established a cell line, alpha4mK562, by transfecting cDNA of murine integrin alpha4 subunit into human erythroleukemic K562 cells. alpha4mK562 transfectant expressed both murine alpha4 and human beta1 subunit, which generated a functional heterodimer. alpha4mK562 cells more efficiently bound to murine endothelial cell lines and recombinant human TNFalpha (rhTNF)-treated human umbilical vein endothelial cells (HUVEC) than the parental K562 cells. These adhesion resulted from the interaction between alpha4beta1 and VCAM-1. Interestingly, treatment with mAb against human beta1 (4B4 clone), which has been known as inhibitory mAb, enhanced binding of alpha4mK562 cells to rhTNF-treated HUVEC but not to murine endothelial cells. This increase in binding induced by 4B4 mAb was completely inhibited by another mAb against human beta1 (mAb13), but only partially by anti-alpha4 mAb (PSsolidus2). The increase in binding induced by 4B4 mAb was also abolished by metabolic inhibitors, indicating that the increased binding is energy dependent. These observations suggest that the binding of 4B4 mAb to the chimeric alpha4beta1 induces an unique outside-in signaling and enhances the specific binding of alpha4mK562 cells to rhTNF-treated HUVEC.

Animals↗
PubMed1996

Glucagon-like peptide-1(7-36)amide enhances insulin-stimulated glucose uptake and decreases intracellular cAMP content in isolated rat adipocytes.

We investigated the effect of GLPs on glucose uptake in isolated rat adipocytes. GLP-1(7-36)amide significantly enhanced glucose uptake in the presence of 1 nM insulin. GLP-1(7-36)amide at 15 nM increased glucose uptake maximally by 56.4% as compared with 1 nM insulin alone (P < 0.01). In contrast, with less than 1 nM insulin or without insulin GLP-1(7-36)amide showed no effect on glucose uptake. Full-sequence GLP-1(1-37) at 15 nM in the presence of 1 nM insulin increased glucose uptake by 24.6% as compared with 1 nM insulin alone (P < 0.05). GLP-2 showed no effect on glucose uptake. Further, we examined the effect of GLP-1(7-36)amide on cAMP content in isolated rat adipocytes. Insulin at 1 nM caused a significant decrease of cAMP content. The combination of 15 nM GLP-1(7-36)amide and 1 nM insulin caused a further reduction of cAMP content. These data indicate that GLP-1(7-36)amide possesses augmentative effects on insulin action in isolated rat adipocytes. Furthermore, it is suggested that the stimulatory effect of GLP-1(7-36)amide occurs through the reduction of intracellular cAMP content.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Three different mutations of presenilin 1 gene in early-onset Alzheimer's disease families.

Presenilin-1 (PS-1) gene of three Japanese pedigrees with early-onset familial Alzheimer's disease (FAD) disclosed two novel missense mutations resulting in Val96Phe and Ile213Thr, and one mutation resulting in His163Arg. The mean age at onset in a family with His163Arg mutation was similar to those reported in other families with His163Arg. Our results suggested the existence of a variety of PS-1 mutations, and that early-onset FAD with PS-1 mutations is highly penetrant and is only rarely subject to modulation by genetic or environmental modifying factors.

Age of Onset↗
PubMed1996

Dynamics of bovine glial fibrillary acidic protein phosphorylation.

Recently, the dynamic features of the intermediate filaments (IF) have been revealed. The effect of phosphorylation on the dynamics of bovine glial fibrillary acidic protein (GFAP), the astroglial IF, was studied in vitro with fluorescently labeled GFAP. Soluble GFAP in low ionic strength buffer was rapidly and fully phosphorylated to be used as phosphorylated GFAP. Assembly of GFAP was observed to be inhibited in proportion to the extent of phosphorylation by mixing phosphorylated and non-phosphorylated GFAP at various ratios, and phosphorylated GFAP could not be assembled with non-phosphorylated GFAP into filaments at all. Furthermore, the subunit exchange was suppressed in proportion to the extent of phosphorylation. Phosphorylation affects the dynamic equilibrium of GFAP, and contributes to breaking down GFAP frameworks in mitotic glial cells.

Animals↗
PubMed1996

Potentiation of GABA-induced Cl- current by a series of n-alcohols disappears at a cutoff point of a longer-chain n-alcohol in rat dorsal root ganglion neurons.

We studied the effects of n-alcohols on gamma-aminobutyric acid (GABA)-induced Cl- current of rat dorsal root ganglion neurons in primary culture by a whole-cell, patch-clamp technique. n-Alcohols (C1-C11) at the concentrations inducing anesthesia in whole animals enhanced the current evoked by GABA application to the neurons. Their potencies for current enhancement increased with their carbon chain length, leveled off for higher alcohols and completely disappeared at C12. The potency of the alcohols for current enhancement correlated well with their anesthetic potencies.

Alcohols↗
PubMed1996

The splenic marginal zone is absent in alymphoplastic aly mutant mice.

aly is a unique spontaneous autosomal recessive mutation in mice that causes a deficiency in the systemic lymph nodes (LN) and Peyer's patches (PP). aly also induces abnormal histological findings in the spleen and a deficiency in humoral and cell-mediated immune functions, although lymphocytes of the aly/aly mouse show virtually normal immune responses in vitro. We studied the structure of the spleen of aly mice in detail by immunohistochemistry and electron microscopy. We found that the spleen of the aly/aly mouse was deficient in the expression of specific antigens for marginal metallophils (MM), marginal zone macrophages (MZM) and fibroblastic reticular cells (FRC), which are components of the marginal zone (MZ) of the spleen. Morphological analysis indicated that the aly/aly spleen is deficient in the structure of MZ, which may, in part, account for the severe immunodeficiency in the aly/aly mouse. We then performed reciprocal bone marrow transplantation experiments (BMT) between normal and aly mice and found a clear correlation between the formation of LN and the development of the splenic MZ in these mice; i.e. successful development of LN was invariably associated with the appearance of the MZ structure, whereas the failure of LN development was always associated with the absence of the development of MZ. These BMT results suggest that a common factor may regulate the generation of both LN and MZ of the spleen.

Animals↗
PubMed1996

Regulation of NK activity by the administration of bromocriptine in haloperidol-treated mice.

Haloperidol (HPD) is a dopamine receptor blocker and a major causative agent of neuroleptic malignant syndrome. To investigate the influence of HPD on immune responsiveness, the natural killer (NK) cell activity of mice was examined after intraperitoneal administration of HPD for 5 days. NK cell activity was markedly decreased without a depletion of NK cells. Bromocriptine (BROMO), which is used for the treatment of neuroleptic malignant syndrome, also decreased NK cell activity. The suppressive effect on NK cell activity was inhibited by injecting both HPD and BROMO simultaneously. Serum levels of prolactin (PRL) decreased after BROMO injection, although serum PRL level was not decreased after the combined administration of HPD and BROMO agents. The reduction of NK cell activity caused by BROMO and by HPD was prevented by the co-injection of PRL and by a beta-adrenergic blocker, respectively. These results indicate that HPD decreases NK cell activity in a PRL-independent manner and that BROMO decreases it via PRL reduction. It seems that the PRL-independent suppressive effect of HPD on NK cells, which is neutralized by BROMO, is mediated by splenic sympathetic function via the beta-adrenergic receptor system. Therefore, BROMO helps to alleviate the depressed NK cell activity caused by HPD therapy.

Adrenergic beta-Antagonists↗
PubMed1996

Synchronous lymphoma and adenocarcinoma occurring as a collision tumor in the stomach: report of a case.

We report herein the rare case of a 71-year-old man who was initially operated on under the diagnosis of advanced gastric cancer, but was subsequently found to have synchronous lymphoma and early adenocarcinoma of the stomach, confirmed by postoperative pathological examination. The patient had a history of lymphoma of the left tonsil, and histologically the gastric lymphoma was observed to be of the non-Hodgkin's, diffuse, large-cell type. Conversely, the gastric cancer was early well-differentiated tubular adenocarcinoma of type 0-IIa, according to the Japan Gastroenterological Endoscopy Society classification. The two tumors had collided at the fornix. The relationship between these two tumors is analyzed and the most appropriate methods of diagnosis and treatment are discussed.

Adenocarcinoma↗
PubMed1996

Blink reflex in meningomyelocele, with special reference to its usefulness in the evaluation of brainstem dysfunction.

The electrically elicited blink reflex (BR) was studied in 30 patients with meningomyelocele (MMC), including 21 with Chiari type II malformation. The relationship between the BR and brainstem auditory evoked potentials (BAEPs) is discussed with regard to its usefulness in the evaluation of MMC's brainstem dysfunction. The following results were obtained: (1) The R2 component was abnormal in 90% of these patients. The BR disclosed subclinical lesions in the medulla oblongata which were not detected by BAEPs alone. (2) In all patients in whom the BAEPs suggested the presence of stretched cochlear nerves, the BR indicated the existence of some dysfunction of the medulla oblongata. (3) No close relationship was found between the dysfunction detected by the BR and the degree of hindbrain anomaly on the neuroimaging. (4) Combining results from assessment of the measurement of the BR and BAEPs permits evaluation of the function of the fifth, seventh, and eighth cranial nerves, as well as the brainstem including the medulla oblongata, which is more comprehensive than evaluation by neuroimaging alone.

Adolescent↗
PubMed1996

Somatosensory evoked potentials to median nerve stimulation in meningomyelocele: what is occurring in the hindbrain and its connections during growth?

Twenty patients with meningomyelocele (MMC) and shunted hydrocephalus, ranging in age from 3 to 23 years old, underwent serial recording of short-latency somatosensory evoked potentials (SEPs) to median nerve stimulation, on the basis of which to assess the evolution of dysfunction in the brainstem and its connections (cervical spinal cord, cervical nerve roots, lower cranial nerves). Eighteen patients had Chiari type II malformations, none of which was symptomatic. In all 20 patients, serial SEP recordings were obtained repeatedly after periods ranging from 2 to 7 years. The results were as follows: (1) the ratio of EP-N13 interpeak latencies (IPLs) to body height (BH) tended to lengthen gradually after starting in the normal range with growth. (2) In contrast, the ratio N13-N20 IPLs/BH decreased continuously to the normal range with growth, after initial prolongation. These findings and our earlier studies of brainstem auditory evoked potentials suggest that compression and traction result in strangulation of the cervical spinal cord and kinked medulla as well as stretching of the cervical nerve roots and lower cranial nerves. However, primary intrinsic functional disorders of the brainstem appeared to improve gradually during growth. The natural history of Chiari type II malformations involves these opposing dynamic phenomena in the hindbrain and its connections.

Adolescent↗
PubMed1996

Kinetics of radioiodinated species in subcellular fractions from rat hearts following administration of iodine-123-labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP).

It is recognized that iodine-123-labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP) slowly washes out of the myocardium. The mechanism for the washout was investigated in normal rat hearts by analyses of the subcellular distribution and lipid classes based on the BMIPP metabolism. Rat hearts were excised at 1-120 min after intravenous injection of 123I-BMIPP. After counting the radioactivity, the hearts were digested with Nagarse and homogenized, and then fractionated into the cytosolic, mitochondrial, microsomal and crude nuclear fractions by centrifugations. The radioactivity of each fraction was counted, and the lipid classes were analysed by radio-thin-layer chromatographic and high-performance liquid chromatographic methods. The heart uptake of 123I-BMIPP was maximal at 5 min (6.81%+/-0.36% ID/g), and 41% of the radioactivity disappeared within 120 min. The myocardial radioactivity was immediately distributed into the cytosolic, mitochondrial, microsomal and crude nuclear fractions. The distribution (%) of each fraction was almost identical from 5 min through 120 min. The cytosolic fraction was always the major site of radioactivity deposition (60%), and the time-activity curve of the cytosolic fraction paralleled that of the whole heart throughout the 120-min study period. In the cytosolic fraction, most of the radioactivity was incorporated into the triglyceride class, and the rest was present in the free fatty acid, phospholipid (phosphatidylcholine) and diglyceride classes. In the mitochondrial fraction, the radioactivity was mostly incorporated into the phospholipid class (phosphatidylethanolamine), followed by free fatty acids. The final metabolite of 123I-BMIPP, 123I-p-iodophenylacetic acid (123I-PIPA), initially appeared in the mitochondrial fraction as early as 1 min, and subsequently in the cytosolic fraction at 5 min. Another intermediary metabolite, 123I-p-iodophenyldodecanoic acid (123I-PIPC12), was found only in the mitochondrial fraction after 5 min. In conclusion, the slow washout kinetics of 123I-BMIPP from the myocardium mainly reflects the turnover rate of the triglyceride pool in the cytosol. The BMIPP metabolism, i.e. initial alpha-oxidation followed by subsequent cycles of beta-oxidation, was confirmed in vivo. The participation of the mitochondria in the metabolism was also proven.

Animals↗