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Biomedical subjects

N Mori

Publications and source records attributed to N Mori.

At least 361 records · Page 20Linked to original sources

Transcriptional regulation of the human interleukin-6 gene promoter in human T-cell leukemia virus type I-infected T-cell lines: evidence for the involvement of NF-kappa B.

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of interleukin-6 (IL-6) protein and mRNA. To clarify the mechanisms that lead to the activation of IL-6 gene in HTLV-I-infected cells, we first studied the regulatory regions in the IL-6 gene transcription by transfection of chloramphenicol acetyltransferase (CAT) reporter plasmids containing the IL-6 promoter. When transfected into HTLV-I-infected T-cell lines MT-2 and HUT-102, IL-6 promoter/CAT plasmids were strongly activated without any stimulation. By deletion analysis of 5' upstream region of IL-6 promoter, the DNA region between -73 and -59 bp from the transcription start site of IL-6 gene was important in the expression of IL-6/CAT activities in HTLV-I-infected cells. This region contains nuclear factor (NF)-kappa B binding site. The site-directed mutation of the kappa B motif in IL-6/CAT plasmid resulted in the complete abrogation of IL-6 promoter activity in these cells. Furthermore, when IL-6 promoter/CAT plasmid was introduced into an HTLV-I-uninfected T-cell line, Jurkat, IL-6 promoter activity was silent in the basal level, but strongly increased by the cotransfection with an HTLV-I tax expression plasmid. However, tax expression plasmid showed no transactivation activity, when kappa B site was mutated in IL-6 promoter/CAT plasmid. We found that the IL-6 kappa B site specifically formed a complex with NF-kappa B-containing nuclear extracts from MT-2 and HUT-102 cells. Finally, transfection of HTLV-I tax into Jurkat cells resulted in induction of specific binding of nuclear extracts to the NF-kappa B sequence. These results strongly suggest that HTLV-I tax gene may transactivate IL-6 gene through kappa B site in HTLV-I-positive T-cell lines and activation of NF-kappa B may be crucial in HTLV-I-induced IL-6 gene activation in ATL.

Base Sequence↗

Effects of a novel, selective and potent phosphodiesterase type V inhibitor, E4021, on myocardial ischemia in guinea pigs.

The anti-ischemic effects of a new, selective and potent cyclic 3',5'-guanosine monophosphate-specific phosphodiesterase (phosphodiesterase type V) inhibitor, sodium 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl ]piperidine-4- carboxylate (E4021), in a vasopressin-induced guinea pig anginal model were examined and compared with those of coronary vasodilators with a guanylate cyclase-activating action. An intravenous injection of vasopressin (0.2 IU/kg) into anesthetized guinea pigs produced ST segment elevation on the electrocardiogram (an index of myocardial ischemia) of 0.28 +/- 0.02 mV (n = 10) from the baseline within 30 s. E4021 administered intravenously at doses of 0.03 and 0.1 mg/kg, 5 min before the injection of vasopressin, significantly inhibited the ST segment elevation to 0.15 +/- 0.03 mV (n = 6, P < 0.01) and 0.17 +/- 0.02 mV (n = 6, P < 0.01), respectively. Three guanylate cyclase activators, isosorbide dinitrate (0.1 mg/kg), nicorandil (0.1 mg/kg), and FK409 (0.3 mg/kg), also significantly reduced the ST segment elevation to 0.18 +/- 0.03, 0.11 +/- 0.02 and 0.17 +/- 0.02 mV, respectively. In a second experiment, E4021 was administered intraduodenally 30 min before the injection of vasopressin to examine its oral effectiveness. Intraduodenal E4021, at doses of 1.0 and 3.0 mg/kg, also significantly inhibited the ST segment elevation to 0.16 +/- 0.02 mV (n = 6, P < 0.01) and 0.13 +/- 0.02 mV (n = 6, P < 0.01), respectively. It is concluded that the potent phosphodiesterase type V inhibitor, E4021, administered intravenously or intraduodenally, ameliorated myocardial ischemia similarly to guanylate cyclase activators. Thus, E4021 may be an orally effective drug in the treatment of angina pectoris.

Animals↗

SCG10 mRNA localization in the hippocampus: comparison with other mRNAs encoding neuronal growth-associated proteins (nGAPs).

SCG10 is a nerve growth factor (NGF)-inducible, neuron-specific protein whose expression is tightly correlated with axonal and/or dendritic growth. We have recently shown that the mRNA encoding SCG10 is expressed at significant levels in certain subsets of neurons in the adult rat brain, while its expression is undetectable or negligible in other non-neuronal tissues. Here we show that regional SCG10 mRNA expression in the adult mouse brain is comparable to that in the rat, however, in the hippocampus its expression profile is distinct. In the mouse, SCG10 mRNA is expressed at high levels in pyramidal cells of CA3-CA4 sub-fields of Ammon's horn and at low levels in the CA1-CA2 sub-fields, while it is found rather uniformly throughout the pyramidal cell layer of the rat hippocampus. SCG10 mRNA is not detectable in the dentate gyrus of the mouse hippocampus, although it is expressed in the rat dentate gyrus. Comparison with other mRNAs encoding neuronal growth-associated proteins (nGAPs) such as GAP-43, MAP2, alpha 1-tubulin and stathmin suggests that dentate granule cells express a different repertoire of neuronal growth-associated genes in mouse and rat.

Animals↗

Mouse Mammary Tumor Virus Proviral Integration in the DD/Tbr Mice.

The patterns of mouse mammary tumor virus (MMTV) integration in the DNA of spontaneous-mammary tumors, salivary glands and livers of DD/Tbr mice were examined using MMTV env, int -1c and int-2c probes. The MMTV env probe revealed 1 to 7 new proviral insertions in all mammary tumors. MMTV integration into int-1 was observed in 10 of 18 mammary tumors, whereas that into int-2 was seen in only 2 of 18 tumors. Of the 13 salivary glands examined, only 3 showed new MMTV proviral integrations, but rearrangement in int-1 or int-2 loci by MMTV was not observed. Immuno-collidal gold electron microscopy revealed the presence of MMTV particles both in mammary tumors and in salivary glands, but no tumors were found to be developed in salivary glands. Taken together these results suggest that salivary glands support MMTV replication, but the virions thus produced may not lead to salivary gland tumorigenesis. It is suggested that the salivary gland is the source of horizontally transmitted MMTV in DD/Tbr mice.

Journal Article↗

Effects of a pyranocoumarin compound isolated from a Chinese medicinal plant on ischemic myocardial dysfunction in anesthetized dogs.

A pyranocoumarin compound, 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia), isolated from Bai-Hua Qian-Hu, a Chinese medicine, is known to possess a Ca2+ channel antagonist action. We examined the effect of Pd-Ia on cardiohemodynamics and regional myocardial dysfunction after transient ischemia in anesthetized open-chest dogs. I.v. injections of Pd-Ia (0.1-3.0 mg/kg, n = 7) significantly and dose dependently increased coronary blood flow and decreased mean aortic pressure, maximal rate of rise in left ventricular pressure, rate pressure product and systemic vascular resistance, together with a slight increase in heart rate. Diltiazem (0.03-1.00 mg/kg, n = 6) showed effects on the cardiohemodynamics similar to those of Pd-Ia, except for a marked decrease in heart rate. The effects of Pd-Ia on mean aortic pressure and rate pressure product were approximately 10 times less potent than those of diltiazem. In the second experiment, the effect of a 30-min infusion of Pd-Ia (0.15 mg/kg/min) or vehicle on regional myocardial dysfunction was examined in 16 anesthetized dogs subjected to a 15-min occlusion of the left anterior descending coronary artery followed by a 3-h reperfusion. Infusion of Pd-Ia was started 15 min before coronary occlusion. The vehicle caused a decrease in percent segment shortening throughout the reperfusion period (n = 8). However, Pd-Ia at the dose that produced no significant changes in cardiohemodynamics resulted in a marked improvement in percent segment shortening of the ischemic and reperfused myocardium (n = 8, P < 0.05 vs. control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of effects of bilateral injections of bicuculline and muscimol into the caudate-putamen of amygdaloid-kindled rats.

Bicuculline is an antagonist of gamma-aminobutyric acid (GABA) receptors, and muscimol is an agonist of GABA receptors. In this study, the effects of bilateral injections of bicuculline and muscimol into the caudate-putamen (CP) were compared in amygdaloid-kindled rats. Thirty minutes after the injection of bicuculline (1, 10 and 100 pmol per CP) or muscimol (10, 50 and 100 nmol per CP), the kindled amygdala was stimulated at the previously established generalized seizure triggering threshold (GST). Most doses of bicuculline caused no significant alteration either in the seizure stage or in the afterdischarge duration. Only the 100-pmol dose produced a marked reduction in the afterdischarge duration. With 10 nmol of muscimol, there was no significant change in the kindled seizure stage or in the afterdischarge duration. However, 50 and 100 nmol of muscimol markedly suppressed both parameters. These findings suggest that CP efferent pathways are involved in the mechanism that underlies the development of kindled amygdaloid seizures, and support the concept that GABA acts as an anticonvulsant in the brain.

Amygdala↗

Calcification in carcinoma of the stomach: report of a case.

By upper gastrointestinal series, a 57 years-old woman was pointed out to have scattered calcifications along the greater curvature of the stomach. On computerized tomography, the calcifications distributed in the irregularly thickened gastric wall. With a diagnosis of calcified mucinous adenocarcinoma showing Borrmann type III, total gastrectomy with splenectomy was carried out. The characteristics of this lesion were briefly presented with a review of the literature.

Adenocarcinoma, Mucinous↗

[Studies on prostaglandin production relating to the mechanism of dysmenorrhea in endometriosis].

The relationship between prostaglandins (PGs) production and the mechanism of dysmenorrhea in endometriosis is poorly understood. Consequently, we investigated the role of PGs in dysmenorrhea of endometriosis. Slices of normal endometrium, normal myometrium, adenomyosis, leiomyoma, normal ovary and affected ovary were incubated. 6-keto PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha and PGE2 concentrations of the incubation medium were measured by RIA. The results are as follows; 1) PGs production in endometriosis was significantly higher than that of other tissues, especially 6-keto PGF1 alpha, which was a dominant product in adenomyosis. 2) There were significant differences in PGs production between severe dysmenorrhea and non dysmenorrhea, especially tissue of adenomyosis with severe dysmenorrhea which produces large amounts of 6-keto PGF1 alpha. 3) There seems to be interaction between normal endometrium and normal myometrium with regard to 6-keto PGF1 alpha production. We concluded that increased PGI2 in the tissue of endometriosis seems to induce hyperalgesia during menstruation.

6-Ketoprostaglandin F1 alpha↗

Kinetics of intestinal intraepithelial lymphocytes during acute graft-versus-host disease in mice.

We examined the kinetics of intestinal intraepithelial lymphocytes (IEL) and the incidence of apoptosis at villus or crypt sites during the development of non-irradiated acute graft-versus-host disease (GVHD). The first IEL to increase were host-origin on day 3 and the donor-derived IEL appeared first on day 12 after GVHD induction. Unique CD3+CD4+CD8 alpha/alpha+ IEL were significantly increased on day 6 and an appreciable number of IEL bearing T cell receptor V beta capable of recognizing self-superantigen were detected on day 9. The sudden appearance of apoptosis and reduction of mitotic activity occurred on day 12, accompanied by a dramatic decrease of CD3+CD4-CD8 alpha/alpha+ IEL of host origin. CD8 alpha/alpha+ IEL of host origin, which expand and then decrease by apoptosis at the early stage of acute GVHD, may be associated with pathogenesis of the enteropathy occurring during acute GVHD.

Animals↗

The effect of adenosine on cochlear potentials in the guinea pig.

The effect of adenosine on cochlear potentials was examined in the guinea pig. Perilymphatic perfusion with 10(-4) M adenosine produced a significant decrease in the amplitudes of cochlear microphonics, negative summating potential (-SP) and compound action potential (CAP) and significant prolongation of N1 latency with no change in the endocochlear potential. The decreases in the amplitudes of -SP and CAP caused by adenosine were dose-dependent. Perilymphatic perfusion with an inactive analogue, 8-bromoadenosine, produced no changes in the cochlear potentials. The A1-receptor agonist, 2-chloro-adenosine, produced a similar change in cochlear potentials to adenosine, while no changes were produced by the A2-receptor agonist, 5'-(N-ethylcarboxamido)-adenosine. These results suggest that adenosine may have a modulatory function through an A1 receptor in the cochlea.

2-Chloroadenosine↗

Identification of mutation sites of a temperature-sensitive mutant of HCMV DNA polymerase activity.

The human cytomegalovirus (strain Towne) temperature-sensitive mutant ts 256 exhibits a virus specific DNA polymerase-negative phenotype. The position of the mutation of ts 256 was determined by three step marker-rescue assays to be within a 5.1 kb XbaI-BamHI fragment between map unit 0.33 and 0.35 in a HindIII-D fragment located in a long unique region. Nucleotide sequencing showed that the 5.1 kb fragment contained three open reading frames corresponding to those of the genes for UL52, UL53 and UL54 (DNA polymerase gene), respectively, of strain AD169. The functions of UL52 and UL53 are unknown. Comparison of the DNA sequences of the 5.1 kb fragments of the wild-type and ts 256 mutant revealed two base changes within UL53 and UL54, respectively, which result in amino acid substitutions. The mutation in the UL54 gene was located within a distinct conserved region VI common to alpha-like DNA polymerases, suggesting that this base change would be responsible for DNA negative phenotype.

Amino Acid Sequence↗

Distribution of metastatic lymph nodes in colorectal cancer by the modified clearing method.

PURPOSE: The aim of this study was to clarify the distribution of lymph node metastasis in colorectal cancer. We also examined the relationship between the primary tumor (T) and the regional node (N) categories of the TNM (primary tumor, regional nodes, metastasis) classification. METHOD: Lymph nodes of surgical specimens in 311 consecutive patients with colorectal cancer were studied using the modified clearing method. RESULTS: Lymph node metastasis was seen in 59.2 percent of the total cases. The upward metastasis rate was 30.7 percent. In the longitudinal spread, most of the lymph node metastasis was seen within 10 cm. On the oral side in rectal cancer, there was no metastasis beyond 4 cm. The lateral metastasis rate in rectal cancer was 8.8 percent and in the lower rectum, the rate of cancer within 6 cm from the anal verge or beyond pT3 was much higher. CONCLUSION: In the TNM classification, there was no significant difference between colon and rectal cancer except pT1 with rectal cancer. In the lower rectal cancer within 6 cm from the anal verge or beyond pT3, there is a high risk of lateral metastasis, and lateral lymph node dissection or radiation therapy should be performed.

Anus Neoplasms↗

Value of thallium-201 early reinjection for assessment of myocardial viability.

To assess the efficacy of early reinjection for predicting post intervention improvement in thallium-201 (T1) uptake and regional wall motion, we reinjected a small dose of T1 following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress-redistribution T1 scintigraphy (group II). Conventional stress-redistribution T1 scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion.

Aged↗

Differential localization of SCG10 and p19/stathmin messenger RNAs in adult rat brain indicates distinct roles for these growth-associated proteins.

SCG10 is a developmentally regulated, growth-associated protein (GAP) that was isolated as a neuronal marker of the neural crest. It was recently found that SCG10 shares an amino acid sequence similarity with a phosphoprotein named stathmin or p19 of which phosphorylation is induced by nerve growth factor and vasoactive intestinal peptide in PC12 cells and striatal neurons, respectively. While expression of SCG10 messenger RNA dramatically decreases during postnatal development, significant levels of expression still persist into adulthood. To examine possible roles of SCG10 in the adult brain, we examined the distribution of messenger RNAs encoding SCG10 and p19/stathmin as well as GAP-43 in adult rat brain sections by northern blot, RNase protection and in situ hybridization. SCG10 transcripts are found at high levels in long-distance projecting neurons and neurons with extensive dendritic arbors, while p19/stathmin messenger RNA was weakly distributed over most brain areas. Both messenger RNAs are expressed in neuronal subpopulations but not in glia, although the overall distribution of the transcripts of these two structurally related genes is distinct. The spatial and temporal expression profiles of SCG10 messenger RNA is comparable to that of GAP-43, another neuronal GAP, in the developing nervous system, however the expression of SCG10 messenger RNA in the adult brain is distinct from that of GAP-43, especially in the hippocampus and brain stem, where the dentate granule cells and sensory and motor neurons of brainstem express SCG10 but not GAP-43. These results suggest that SCG10 may have a unique role in the neuronal growth-response of subsets of mature neurons, and that SCG10 plays a stathmin-like function at nerve terminals, to which it may be rapidly transported by means of membrane attachment due to a hydrophobic domain present in SCG10 but not in p19/stathmin. This suggests that SCG10 may play a role in structural plasticity in the adult brain.

Animals↗