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Biomedical subjects

M Nagumo

Publications and source records attributed to M Nagumo.

At least 55 records · Page 3Linked to original sources

Alteration of the curved helical structure located in the upstream region of the beta-lactamase promoter of plasmid pUC19 and its effect on transcription.

The region preceding the beta-lactamase promoter of Escherichia coli plasmid pUC19 has a curved DNA (bent DNA) structure. The center of the curvature was revealed to exist around nucleotide position 2580 of the plasmid, which is just beside RNA polymerase binding region. It was indicated that the identified region is curved even at 60 degrees C. The gross geometry of the curvature was altered by inserting synthetic double-stranded oligonucleotides between positions 2585 and 2586. Effect of the alteration on strength of the promoter was not detected in vitro. However, in vivo analyses showed that the promoter strength is apparently dependent, in part, on the gross geometry of the curvature. Insertions of 4 and 16 bp, both of which altered the gross geometry of the curvature greatly, caused considerable reductions of in vivo level of beta-lactamase mRNA. In vivo, overall three-dimensional structure of the region covering the promoter and the curvature seems to play some significant role in transcription of the gene.

Base Sequence↗

Evaluation of trismus after treatment of mandibular fractures.

This retrospective study examines the effects of treatment modalities and other contributing factors on the duration of trismus following mandibular fractures. Under a strict protocol, 80 cases involving a total of 120 fractures and their treatment modalities were reviewed. An investigation of duration of trismus was carried out in several ways. Although a relationship was established between age, initial interincisal distance, and duration of trismus, no relationship was found with the number or location of fractures, or reduction method. However, after examining the fixation methods separately, it was found that those cases in which Champy plates were used experienced a shorter duration of trismus compared with those using closed reduction with maxillomandibular fixation.

Adolescent↗

Localization of types I, II, and X collagen in the transplanted tumor derived from human osteogenic sarcoma.

We have succeeded in transplanting human osteogenic sarcoma of the mandible into nude mice. As the transplanted tumor shows features of calcified chondrosarcoma, this tumor is thought to be an excellent model for study of the process of dystrophic endochondral calcification. Using this model, we studied relations between the expression of types I, II, and X collagen and chondrogenic differentiation of the transplanted tumor. Collagen distribution during the development and growth of the transplanted tumor was investigated by immunofluorescence with specific antibodies against type I, II or X collagen. Type X collagen was intensely stained in the mineralized region. Almost all tumor cells in this region were hypertrophic. Type II collagen was chiefly distributed in the unmineralized region where tumor cells showed chondrocytic or hypertrophic feature. These results indicate that the type of collagen changes from type II to type X in the hypertrophic region and the type X collagen may be synthesized by hypertrophic tumor cells. Type I collagen was localized in the marginal region of the tumor, though it disappeared in the mineralized region.

Adult↗

Lipid conformational nomenclature: a general method.

We propose a conformational nomenclature for amphiphilic lipid molecules that is general and compatible with the stereospecific numbering scheme, in contrast to earlier methods in which discrepancies with the sn-scheme lead to contradictory assignments of the absolute configuration of the system. The present method can be rationally extended to different classes of lipids, both natural and synthetic. It is simple and provides a convenient framework for conformational studies on widely varying classes of lipids.

Lipids↗

[An adult case of anomalous origin of the left coronary artery from the pulmonary artery].

An adult case of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was presented. A 37-year-old male was admitted for ventricular arrhythmia and chest pain. The catheterization, left ventriculography and coronary arteriography revealed ALCAPA with anterolateral ventricular aneurysm and mild mitral regurgitation. An operation using Takeuchi procedure was performed. The postoperative course was uneventful and the results of the catheterization, left ventriculography and coronary arteriography performed immediately and five years after the operation were excellent except mild supravalvular pulmonary stenosis. Six years later, the patient is asymptomatic and well.

Adult↗

[A median sternotomy approach for symptomatic right subclavian artery in the adult].

A case of 33-year-old woman with aberrant right subclavian artery was reported. She was admitted to the hospital complaining of progressive dysphagia of six months' duration. The esophagogram revealed an oblique tubular defect in the superior thoracic esophagus. Aortograms confirmed the presence of an anomalous right subclavian artery arising as a fourth branch of the aortic arch, passing behind the esophagus in its course to the right arm. Operation was performed on Sept. 4, 1990. Through a median sternotomy, the ascending aorta and the two carotids were dissected free. With gentle forward retraction of the ascending aorta to the left, the origin of the aberrant right subclavian artery could easily be exposed. The right subclavian artery was then divided and its origin from the distal aortic arch oversewn. The vessel was removed from the retroesophageal position and blood flow reestablished to the right arm by an end-to-side anastomosis to the right carotid artery, using a temporary shunt tube. These procedures were accomplished without difficulty. Postoperatively, the patient made an uneventful recovery and was discharged 16 days after the procedure. A postoperative esophagogram confirmed the removal of the esophageal compression. The blood pressure was equal in the two upper extremities. In follow-up study, her symptoms had completely disappeared.

Adult↗

Effects of combinations of transforming growth factor-beta 1 and tumor necrosis factor on induction of differentiation of human myelogenous leukemic cell lines.

Effects of transforming growth factor-beta 1 (TGF-beta 1), either alone or in combination with TNF, on the induction of differentiation of human myelogenous leukemic cell lines were examined. TGF-beta 1 alone induced differentiation of a human monocytic leukemia U-937 line into the cells with macrophage characteristics. When combined with TNF, TGF-beta 1 synergistically or additively induced differentiation associated properties. A human myeloblastic leukemia cell line, ML-1, differently responded to TGF-beta 1 in induction of differentiation. FcR activity and phagocytic activity induced by TNF were suppressed by TGF-beta 1. However, nitroblue tetrazolium reducing activity was synergistically induced by combinations of TGF-beta 1 and TNF. Scatchard analysis of TNF receptors indicated that the number of binding sites and dissociation constant of TNF for its receptors on U-937 or ML-1 cells were not changed by treatment with TGF-beta 1. Although IFN-gamma, IL-6, granulocyte CSF, and granulocyte-macrophage CSF-induced nitroblue tetrazolium reducing activity of U-937 cells, only IFN-gamma, and TNF induced it synergistically in combination with TGF-beta 1. Synergism between TGF-beta 1 and TNF was also observed in inhibition of growth of U-937 and ML-1 cells. Although TGF-beta 1 induction of differentiation of other monocytoid leukemic THP-1 cells was similar to that of U-937 cells, TGF-beta 1 only slightly induced differentiation of promyelocytic leukemic HL-60 cells, either alone or in combination with TNF. Our observations indicate that TGF-beta 1 strongly modulates differentiation and proliferation of human myelogenous leukemia cells, macrophage precursors.

Cell Differentiation↗

Identification of fetomodulin, a surface marker protein of fetal development, as thrombomodulin by gene cloning and functional assays.

Fetomodulin (FM) was previously shown to be a surface marker protein of parietal endoderm by in vitro differentiation of F9 embryonal carcinoma cells and by immunohistochemistry of in vivo embryos. BALB/3T3 and sarcoma S180 cells of the mouse were also shown to possess a protein which was indistinguishable from FM by immunological and structural criteria. We now show by protein and DNA sequencing and by functional assays that FM is identical to thrombomodulin, an anticoagulant endothelial thrombin receptor. Partial amino acid sequences of FM from S180 cells suggested homology between FM and thrombomodulin. An FM cDNA fragment was obtained by screening an expression library, which was constructed with restricted BALB/3T3 cDNA, with polyclonal anti-FM antibody. Several longer cDNA clones were than isolated using this fragment as a probe. They elucidated a 3369-bp partial sequence which encompassed 93% of the coding sequence. The remaining structure was determined from a genomic DNA clone. The deduced FM structure proved to be identical to that of thrombomodulin of mouse lung. Affinity-purified FM of BALB/3T3 and differentiated F9 cells was as active as thrombomodulin of the lung in binding thrombin and also as an anticoagulant. Structural and functional identity of the two proteins was thus confirmed. During embryonic development, FM immunoreactivity is localized not only in vasculatures but also at sites of cell-to-cell contact, including lung bud and neural epithelium, which were not expected a priori to possess this endothelial surface protein. FM may be a multifunctional protein with unique roles in embryonic development.

Amino Acid Sequence↗

Induction of differentiation of human monoblastic and myeloblastic leukemia cell lines by TNF muteins.

The differentiation inducing activity of five recombinant human tumor necrosis factor (rHuTNF) muteins, prepared by protein engineering techniques, was compared by measuring the ability to reduce nitroblue tetrazolium dye of human myelogenous leukemia cells. TNF(C-Phe), in which the C-terminal leucine of TNF molecule was replaced by phenylalanine, was 20-times as potent in induction of differentiation of U-937 cells as the parent TNF(N-Met), in which methionine was added to N-terminal sequence of TNF. The differentiation inducing activity of TNF muteins was not always proportional to their binding activity to the receptors nor to their cytotoxicity on U-937 cells.

Amino Acid Sequence↗

Suppression of TNF-stimulated proliferation of diploid fibroblasts and TNF-induced cytotoxicity against transformed fibroblasts by TGF-beta.

Human transforming growth factor-beta (TGF-beta) dose-dependently inhibited proliferation of WI-38 cells, normal human diploid fibroblasts, stimulated by tumor necrosis factor (TNF). Inhibition occurred at 1 ng/ml concentration of TGF-beta. Also, TGF-beta dose-dependently suppressed cytotoxicity of TNF against L-929 cells, murine transformed fibroblasts. The concentration of TNF required for 50% cytolysis of L-929 cells was changed from 30 ng/ml to 350 ng/ml by 10 ng/ml TGF-beta. This suppression was abolished when L-929 cells were treated with actinomycin D or cycloheximide, suggesting that TGF-beta might inhibit the action of TNF via de novo protein synthesis. This response was not due to down regulation of TNF receptors nor to alteration of the affinity of TNF for its receptor.

Animals↗

Study on the function of the bent DNA within adenovirus type 2 EIA enhancer: analysis using an in vitro transcription system.

The role of the bent DNA within human adenovirus type 2 (Ad2) enhancer in transcriptional activation of E1A gene has been investigated. The bent region of the enhancer was substituted by a straight DNA fragment or by a bent DNA fragment of 194 bp from origin region of phage lambda replication. Employing an in vitro transcription system using HeLa cell extract, effects of mutant enhancers on E1A gene transcription were analyzed. The results obtained showed that the amount of transcripts is affected by changes in local conformation in and around the enhancer.

Adenovirus Early Proteins↗