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Biomedical subjects

S Mori

Publications and source records attributed to S Mori.

At least 163 records · Page 9Linked to original sources

[Human herpes virus and malignancies].

Two type of human herpes viruses, type 4(Epstein Barr virus, EBV) and type 8(HHV8) are known to cause malignancies. Among those, EBV is the very most popular human oncovirus. It can cause malignant lymphomas of various subtypes including Burkitt's lymphoma, opportunistic lymphomas, pyothorax-associated lymphoma, nasal T/NK cell lymphoma, Hodgkin's disease and a part of diffuse large cell lymphomas. HHV8 is a new member of human oncovirus associating with primary effusion lymphoma, a part of solid lymphoma taking diffuse large or anaplastic large cell morphology, and the Castleman's tumor. Introduction of histopathologic methodologies makes the correct diagnosis of those herpes virus-associated tumors an easy routine test.

Herpesvirus 4, Human↗

Bipedal locomotion by the normally quadrupedal Japanese monkey, M. Fuscata: strategies for obstacle clearance and recovery from stumbling.

This study explored how the normally quadrupedal Japanese monkey adjusts to treadmill perturbations, when trained to walk bipedally. The monkey was required to use the left hindlimb to clear an obstacle that was fixed on the left side of a treadmill belt. The monkey either cleared the obstacle (CL: cleared locomotion), or stumbled over it (SL: stumbled locomotion). For CL, it changed its left hind limb's kinematics according to the obstacle's height and position relative to the left foot. In SL, the monkey used a "defensive posture", which included a rapid lowering of the right foot and forelimb movements, to stabilize the perturbed posture and thereby prevent falling. Then, with powerful extensions of its lower limb joints, the monkey raised its center-of-mass to the appropriate level for continuation of normal bipedal walking. The results show that M. Fuscata recruited both anticipatory and reactive neural mechanisms to accommodate to the obstacle.

Animals↗

Expression of erythropoietin in human female reproductive organs.

Erythropoietin (Epo) is known to be a lineage specific cytokine which regulates the number of circulating erythrocytes. Most of it is produced in the kidney. Recently, Epo has been reported to be synthesized in the normal brain, placenta, and capillary endothelium. We also have found that uterine endometrium expresses Epo signals in an estrogen-dependent manner, and that Epo contributes to angiogenesis in the endometrium in mice. To clarify the functional activity of Epo in human reproductive organs, we examined Epo signaling in these organs by Southern analysis of RT-PCR products and studied the distribution of substances relevant to Epo signal transduction by immunohistochemistry and Western blotting. Epo mRNA is expressed in the normal human cervix, endometrium and ovary, but it is not always detected in the specimens. Immunohistochemical analysis revealed Epo-receptor (EpoR) protein in: a) the endothelium of vessels, in glandular and surface epithelial cells, in decidual cells of the endometrium, and b) in follicles at various stages including oocytes, granulosa, theca interna cells and lutein cells of the ovary. Moreover, co-expression of JAK2 and phosphotyrosine, which reflects tyrosine phosphorylation via JAK2, and co-expression of EpoR and STAT5, which is a transcriptional factor relevant to mitogenic activity, were seen at these Epo-responsive sites. Western blotting analysis of these organs confirmed the immunohistochemical results. These findings imply that female reproductive organs can produce Epo, and that signal transduction of Epo contributes to the cyclic changes in the female reproductive organs.

Blotting, Southern↗

[Mid-ventricular obstructive hypertrophic cardiomyopathy associated with an apical aneurysm and sustained ventricular tachycardia: a case report].

A 60-year-old woman presented with mid-ventricular obstructive hypertrophic cardiomyopathy associated with an apical aneurysm and sustained ventricular tachycardia. She was admitted because of drug refractory ventricular tachycardia. She had been treated with several antiarrhythmic agents, including amiodarone, but symptomatic episodes had continued. Echocardiography, magnetic resonance imaging, and left ventriculography showed mid-ventricular obstructive hypertrophic cardiomyopathy with an apical aneurysm. Electrophysiological study easily reproduced sustained pleomorphic ventricular tachycardia, polymorphic ventricular tachycardia, and ventricular fibrillation. The patient underwent implantation of a cardioverter-defibrillator. The relationship between mid-ventricular hypertrophic cardiomyopathy and apical aneurysm is unknown, but mid-ventricular hypertrophic cardiomyopathy is one of the causes of severe ventricular arrhythmias and sudden death.

Cardiomyopathy, Hypertrophic↗

Role of thymidine phosphorylase in Fas-induced apoptosis.

Thymidine phosphorylase (TP) has chemotactic and angiogenic activity in vitro, and it promotes tumor growth and inhibits apoptosis in vivo. It plays a key role in the invasiveness and metastasis of TP-expressing solid tumors. KB/TP cells transfected with a TP cDNA have been shown to be resistant to hypoxia-induced apoptosis, suggesting that TP has effects on tumor growth and cell death independent of its effects on angiogenesis. However, the mechanisms of cell death inhibition by TP are unknown. In the present study, we demonstrate that caspase-8 is cleaved in control transfectant KB cells early on during Fas-induced apoptosis. Caspase-8 activation leads to the loss of mitochondrial membrane potential, followed by the release of cytochrome c, the activation of caspase-3, and apoptosis. In contrast, Fas-induced caspase-8 cleavage is inhibited in KB/TP cells, which lead to inhibition of the downstream apoptotic cascade and inhibition of apoptosis. These findings indicate that TP plays an important role in intracellular apoptotic signal transduction in the Fas-induced apoptotic pathway. Therefore, inhibition of TP may suppress the progression of TP-overexpressing solid tumors by inducing apoptosis.

Apoptosis↗

Basic study on radon effects and thermal effects on humans in radon therapy.

Because most of the diseases to which radon (222Rn) therapy is applied are related to activated oxygen, in this study the effect of the radioactivity of radon and the thermal effect were compared under a room or a hot spring condition with the same chemical component using as the parameters the activity of superoxide dismutase (SOD), which is an oxidation inhibitor, and lipid peroxide and low density lipoprotein (LDL)-cholesterol, which are closely involved in arteriosclerosis. Results show that the SOD activity was significantly increased, and the lipid peroxide and LDL-cholesterol levels were significantly decreased on days 6 and 7 of study. The results were about 2-fold larger in the radon group than in the thermo group. This suggests that the anti-oxidation function was more enhanced by radon therapy than by thermo therapy, and suggests that radon therapy may help to prevent the causes of life style-related diseases such as arteriosclerosis. These findings are important in understanding the mechanism of diseases in which radon therapy is used as treatment, and most of which are called activated oxygen-related diseases.

Administration, Inhalation↗

Stability in velocity of otolith-ocular reflex with different stimulus frequencies during step-mode linear acceleration.

Velocity changes in the otolith-ocular reflex (OOR) during a step mode of lateral linear acceleration were examined by electrooculography (EOG) in 4 normal subjects. They were oscillated in darkness at a constant stimulus frequency of 0.175 Hz with 4 different G-levels between 0.2-0.4 G and at a constant G-level of 0.3 G with 4 different stimulus frequencies between 0.115-0.215 Hz. The OOR velocity was increased linearly by elevation of the G-level, though the increase varied considerably among subjects. On the other hand, changes in the stimulus frequency had minimal effect on the OOR velocity. The results indicate that the OOR response property is frequency-independent at a low stimulus-frequency range, even when the head was oscillated rectangularly instead of sinusoidally.

Acceleration↗

The immediate early gene 1 product of human cytomegalovirus is sufficient for up-regulation of interleukin-8 gene expression.

We previously observed that human cytomegalovirus (CMV) infection induced a massive production of a chemokine with potent neutrophil chemotactic activity, interleukin-8 (IL-8). Hence, we examined the effect of CMV immediate early (IE) gene products on IL-8 production by the human astrocytoma cell line, U373MG. Transient or stable transfection with a CMV IE1 gene expression vector, but not with a IE2 gene expression vector, significantly augmented IL-8 protein secretion and IL-8 mRNA expression. Luciferase activity was enhanced in U373MG cells when the cells were cotransfected with CMV IE1 and chimeric firefly luciferase reporter genes driven by the transcriptional regulatory region of the human IL-8 gene. Moreover, IE1 gene-mediated enhancement of luciferase activity was abolished by the introduction of mutations into the AP-1 or NF-kappa B factor binding elements in the regulatory region of the IL-8 promoter. Furthermore, electrophoretic mobility shift assays demonstrated that CMV IE1 gene products induced the formation of NF-kappa B or AP-1 complexes. Finally, Western blotting analysis demonstrated that the CMV IE1 gene product increased the amount of NF-kappa B complexes translocated into the nucleus. Collectively, CMV IE1 gene expression may be sufficient to activate AP-1 and NF-kappa B, resulting in IL-8 gene expression.

Base Sequence↗

One-step purification of rabbit histidine rich glycoprotein by dye-ligand affinity chromatography with metal ion requirement.

A simple method for purification of the histidine rich glycoprotein (rHRG) from rabbit sera was developed. The rHRG was purified by one-step affinity chromatography using the triphenylmethane dye "acid fuchsin" as a specific ligand, which gave an overall yield above 80%. Interestingly, the binding of rHRG to the ligand required the divalent transition-metal ions such as Zn2+, Ni2+, and Co2+ at pH 9.5. In the presence of 0.5 mM ZnCl2, the binding was enhanced 15 times compared with that in the absence of ZnCl2. Bound rHRG was efficiently eluted from the affinity absorbent with 100 mM imidazole or histidine. Purified rHRG was homogeneous with an Mr of 94 kDa when analyzed by SDS-PAGE, whereas isoelectric focusing revealed microheterogeniety with pI values ranging from 6.3 to 6.8. Blotting analysis with lectins specific for carbohydrate moieties and treatment with glycosidases demonstrated that rHRG is a highly N-glycosylated protein with diverse carbohydrate structures.

Animals↗

Attenuation of expression of gamma-glutamylcysteine synthetase by ribozyme transfection enhance insulin secretion by pancreatic beta cell line, MIN6.

Low levels of intracellular antioxidant enzyme activities as well as glutathione (GSH) concentrations have been described in pancreatic beta cells. We examined the effects of intracellular GSH depletion on insulin secretion and the role of intracellular GSH in signal transduction in beta cell line, MIN6 cells. Anti-gamma-glutamylcysteine synthetase (gamma-GCS) heavy subunit ribozyme was stably transfected to MIN6 cells to reduce intracellular GSH concentration. In the presence of 10 mM glucose, ribozyme-transfected cells (RTC) increased insulin secretion from 0.58 microg/10(6) cells/h in control cells (CC) to 1.48 microg/10(6) cells/h. This was associated with increased intracellular Ca(2+) concentration in RTC, detected by fluo-3 staining. Our results demonstrated that intracellular GSH concentration might influence insulin secretion by MIN6 cells, and suggest that enhanced insulin secretion by beta cells conditioned by chronic depletion of GSH is mediated by increased intracellular Ca(2+) concentration.

Adenosine Triphosphate↗

Wherefore Art Thou Copper? Structures and Reaction Mechanisms of Organocuprate Clusters in Organic Chemistry.

Organocopper reagents provide the most general synthetic tools in organic chemistry for nucleophilic delivery of hard carbanions to electrophilic carbon centers. A number of structural and mechanistic studies have been reported and have led to a wide variety of mechanistic proposals, some of which might even be contradictory to others. With the recent advent of physical and theoretical methodologies, the accumulated knowledge on organocopper chemistry is being put together into a few major mechanistic principles. This review will summarize first the general structural features of organocopper compounds and the previous mechanistic arguments, and then describe the most recent mechanistic pictures obtained through high-level quantum mechanical calculations for three typical organocuprate reactions, carbocupration, conjugate addition, and S(N)2 alkylation. The unified view on the nucleophilic reactivities of metal organocuprate clusters thus obtained has indicated that organocuprate chemistry represents an intricate example of molecular recognition and supramolecular chemistry, which chemists have long exploited without knowing it. Reasoning about the uniqueness of the copper atom among neighboring metal elements in the periodic table will be presented.

Journal Article↗

Lactation defect in mice lacking the helix-loop-helix inhibitor Id2.

Id proteins are thought to be negative regulators of cell differentiation and positive regulators of cell proliferation. Mammary glands of Id2(-/-) female mice reveal severely impaired lobulo-alveolar development during pregnancy. Id2(-/-) mammary epithelia show no precocious maturation, but instead exhibit intrinsic defects in both cell proliferation and cell survival, implying that the role of Id2 in pregnant mammary epithelia is mainly stimulation of cell proliferation and support of cell viability. Expression studies of genes required for mammary gland development suggest Id2 to be a downstream or parallel factor of these genes. A decrease in the DNA binding activity of Stat5 was also observed in Id2(-/-) mammary glands at 7 days post-coitus. Our results indicate an indispensable role of Id2 in pregnant mammary glands.

Animals↗

Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype.

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P <.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.

Adolescent↗

Pretransplant tumor antigen-specific immunization of allogeneic bone marrow transplant donors enhances graft-versus-tumor activity without exacerbation of graft-versus-host disease.

Allogeneic bone marrow transplantation (BMT) causes a beneficial graft-versus-tumor (GVT) immune response that is often associated with graft-versus-host disease (GVHD). There is substantial interest in developing therapeutic strategies that augment GVT without GVHD. We have demonstrated recently that immunization of BMT donors with cellular tumor vaccines leads to curative GVT but induces unacceptable GVHD because of the presence of recipient minor histocompatibility antigens (mHAgs) in whole-cell tumor vaccines. This study tested the hypothesis that immunization of BMT donors against a defined tumor-specific antigen with a vaccine not containing recipient mHAgs would help to separate the two responses by enhancing GVT activity without exacerbating GVHD, even when cellular vaccines were used after BMT. Recipient strain C57BL/6 fibrosarcoma cells engineered to express the well-characterized model tumor antigen, influenza nucleoprotein (NP), were used in these studies. C3H.SW donors were immunized against NP prior to BMT, and cytolytic T cells were transferred along with bone marrow into irradiated H-2-matched, mHAg-mismatched C57BL/6 recipients with established micrometastatic 205-NP tumors. Donor immunization led to a significant increase in GVT activity, as measured by reduction in tumor growth and enhanced survival. However, deaths in recipients of tumor antigen-specific immune BMT ultimately occurred because of the growth of antigen-loss variants; such tumor growth did not occur in animals receiving BMT from donors treated with whole-cell vaccines. Donor immunization did not lead to an exacerbation of GVHD, even when BMT recipients received additional immunization after BMT with a 205-NP "whole" tumor cell vaccine (which was shown to induce fatal GVHD when used for donor immunization). In conclusion, immunization of allogeneic BMT donors against a tumor-specific antigen significantly enhances GVT activity without an associated exacerbation of GVHD.

Animals↗