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Biomedical subjects

T Umemoto

Publications and source records attributed to T Umemoto.

At least 37 records · Page 2Linked to original sources

Autocrine regulation of osteoclast formation and bone resorption by IL-1 alpha and TNF alpha.

Bone resorption is regulated by the cytokines within marrow cells that mediate osteoclast formation and activation. IL-1 and TNF induce bone resorption by stimulating the production of osteoclast-like multinucleated cells and by increasing the bone-resorbing activity of formed osteoclasts. This study was designed to detect IL-1 and TNF in osteoclasts in vitro and to determine whether these cytokines up-regulate osteoclast differentiation and bone resorption. The production of IL-1 alpha, -beta, and TNF alpha, beta in osteoclasts was examined immunohistochemically and by in situ hybridization. In the co-culture of C57BL/6N mouse bone marrow and MC3T3-G2/PA6 cells, a colony of osteoclasts formed, and IL-1 alpha and TNF alpha were detected. However, IL-1 beta and TNF beta were not detected. To investigate the role of IL-1 alpha and TNF alpha from osteoclasts, we enumerated TRAP-positive cells and measured the resorption pit areas in the presence of antibodies against IL-1 alpha and TNF alpha. The addition of antibodies against IL-1 alpha and TNF alpha to the co-culture system decreased the number of TRAP-positive colonies at seven days after incubation (anti-IL-1 alpha, 25.0 +/- 2.3%; anti-TNF alpha, 41.7 +/- 3.7%; anti-IL-1 alpha + anti-TNF alpha, 40.5 +/- 1.3%; and control, 100%), and the ratio of mononuclear to multinuclear cells had changed (anti-IL-1 alpha, 90:10; anti-TNF alpha, 75:25; anti-IL-1 alpha+ anti-TNF alpha, 88:12; and control, 60:40). The total pit areas per dentin slice also decreased with the addition of antibodies (anti-IL-1 alpha, 28,828; anti-TNF alpha, 49,249; anti-IL-1 alpha + anti-TNF alpha, 30,685; and control, 303,139 mm2). These results suggest that local production of IL-1 alpha and TNF alpha by osteoclasts is an important mechanism for regulating the osteoclast differentiation and bone resorptive process.

Acid Phosphatase↗

Serum hepatocyte growth factor in patients with peripheral arterial occlusive disease.

Hepatocyte growth factor (HGF) is a multifunctional protein implicated in tissue regeneration, wound healing, and angiogenesis. We measured serum HGF concentrations in 37 patients with peripheral arterial occlusive disease (PAOD). Among them, 36 patients underwent arteriography. Serum HGF concentrations were also measured in 40 control subjects who remained free of vascular, liver, kidney, or lung disease. Patients with PAOD showed elevated serum HGF concentrations compared with control subjects (0.40+/-0.02 vs. 0.19+/-0.01 ng/mL; P<0.001). Serum HGF concentrations were significantly higher in smokers compared with nonsmokers (0.45+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.003). The serum HGF concentrations in patients with collaterals tended to be higher than those in patients without collaterals (0.43+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.06). Moreover, in patients who underwent bypass surgery or angioplasty, serum HGF concentrations decreased from 0.41+/-0.03 to 0.21+/-0.04 ng/mL after treatment (P<0.001). Serum HGF may be an useful marker for the diagnosis of PAOD. HGF may play an important role in angiogenesis and collateral vessel growth in PAOD.

Adult↗

Imaging of living cultured cells of an epithelial nature by atomic force microscopy.

The present paper describes the applicability of atomic force microscopy (AFM) to the observation of living cultured cells of an epithelial nature (human esophageal squamous cell carcinoma cells, or C7 subclone of KESC2 cells) in a culture medium. For this purpose, we made a fluid chamber system which allows a constant-speed perfusion of fluid at a regulated temperature in the chamber. Using this system, AFM images of living cells were successfully obtained for over one hour at time intervals of 2-4 min during continuous perfusion of the fresh culture medium. A series of these AFM images proved useful for examining the movements of cellular processes in relation to subcellular cytoskeletal elements. Time-lapse movie records produced by sequential AFM images further verify the reality of the cellular dynamics.

Carcinoma, Squamous Cell↗

[Recent progress in biological therapies for cancer].

After approval of national health insurance for non-specific immunomodulation such as OK-432 (1978) and PSK (1980), lentinan, SPG, bestatin and dried BCG vaccine have been tried. Including cytokines such as IL-2, IL-12, IFN, TNF or monoclonal antibodies, they have been widely used as biological response modifiers (BRM). Progress in BRM therapy may be broken down into the first 10 years as development, the next 10 years as disappointment and the most recent 5 years as dream-like progress owing to molecular biological techniques. An interdisciplinary approach has been taken by the Japanese Research Society for Surgical Cancer Immunology, founded in 1980, and the Japanese Society of BRM founded in 1988. Many investigations have been performed on issues such as the clinical evaluation or criteria for responder cases, host immunocompetency, post-operative adjuvant immuno-chemotherapy, locoregional immunotherapy, cytokine therapy, adoptive immunotherapy, and tumor specific immunotherapy. Attention has also focused on malignant tumor injury, surgical stress, the advantages or disadvantages of splenectomy, and discussions of the current status and future prospects in the next century for new BRM therapy.

Antibodies, Monoclonal↗

[Clinical evaluation of intermittent hepatic arterial infusion therapy with CDDP and 5-FU for liver metastasis of colorectal cancer].

Twenty-seven patients with liver metastasis from colorectal cancer were treated with intermittent intra-arterial infusion chemotherapy for 5 years starting from 1993. Five to ten mg of CDDP, 250 mg of 5-FU and/or 3-6 mg of Leucovorin were administered weekly. In the case of nonresponders, the dose of 5-FU was allowed to increase toward 500 mg. The above schedule was repeated as long as possible. The average number of administrations in 12 out of 27 unresectable patients was 28.7. The response rate was 50% (CR; 4 cases, PR; 2), with 2 NC and 3 PD. Four patients given 500 mg of 5-FU showed some response. The 50% survival period was 466 days, and the 1- and 3-year survival rates were 66.7% and 18.3%, respectively. The average number of administrations in the group of patients who underwent prophylactic treatment and resection of the metastasis was 33.1. During an average observational period 681 days, 7 patients (46.7%) had a recurrence in the liver. The 5-year survival rate was 85.7%. The patients who were treated with 250 mg 5-FU experienced no severe side effects, but one who was given 500 mg 5-FU developed a duodenal ulcer.

Adult↗

[Collagen-binding proteins of human oral spirochetes].

OBJECTIVE: To evaluate pathogenic effect of the collagen-binding proteins(CBP) of human oral spirochetes. METHODS: Immunoblot analysis, immunoelectron microscopy and other experiments had been used. RESULTS: It was showed that: type I, IV and V CBP were detected in heated and unheated preparations from Treponema denticola(Td) ATCC 33520 and Treponema socranskii (Ts) ATCC 35534. Few CBP, however, were detected in heated and unheated preparations from a recently characterized isloate, Treponema medium(Tm) strain G7201. 27,000 type V CBP of Td, 110,000 type I of Ts and 95,000 type IV of Tm were located on the envelopes of the individual cells. The adherence of Td to the collagen-coated surface was significantly greater than that of Tm. CONCLUSION: The CBP on the oral spirochetal cells play an important role in their adherence to collagen-rich connective tissues of the host.

Bacterial Adhesion↗

Overview and initial results of the very long baseline interferometry space observatory programme

High angular resolution images of extragalactic radio sources are being made with the Highly Advanced Laboratory for Communications and Astronomy (HALCA) satellite and ground-based radio telescopes as part of the Very Long Baseline Interferometry (VLBI) Space Observatory Programme (VSOP). VSOP observations at 1.6 and 5 gigahertz of the milli-arc-second-scale structure of radio quasars enable the quasar core size and the corresponding brightness temperature to be determined, and they enable the motions of jet components that are close to the core to be studied. Here, VSOP images of the gamma-ray source 1156+295, the quasar 1548+056, the ultraluminous quasar 0014+813, and the superluminal quasar 0212+735 are presented and discussed.

Journal Article↗

A mutant of Arabidopsis lacking a chloroplastic isoamylase accumulates both starch and phytoglycogen.

In this study, our goal was to evaluate the role of starch debranching enzymes in the determination of the structure of amylopectin. We screened mutant populations of Arabidopsis for plants with alterations in the structure of leaf starch by using iodine staining. The leaves of two mutant lines stained reddish brown, whereas wild-type leaves stained brownish black, indicating that a more highly branched polyglucan than amylopectin was present. The mutants were allelic, and the mutation mapped to position 18.8 on chromosome 1. One mutant line lacked the transcript for a gene with sequence similarity to higher plant debranching enzymes, and both mutants lacked a chloroplastic starch-hydrolyzing enzyme. This enzyme was identified as a debranching enzyme of the isoamylase type. The loss of this isoamylase resulted in a 90% reduction in the accumulation of starch in this mutant line when compared with the wild type and in the accumulation of the highly branched water-soluble polysaccharide phytoglycogen. Both normal starch and phytoglycogen accumulated simultaneously in the same chloroplasts in the mutant lines, suggesting that isoamylase has an indirect rather than a direct role in determining amylopectin structure.

Amylopectin↗

Involvement of human CRM1 (exportin 1) in the export and multimerization of the Rex protein of human T-cell leukemia virus type 1.

We investigated the role of human CRM1 (hCRM1) (exportin 1) in the function of Rex protein encoded by human T-cell leukemia virus type 1. hCRM1 promoted the export of Rex protein from the nucleus to the cytoplasm. A Rex protein with a mutation in the activation domain, RexM90, lost both the ability to bind to hCRM1 and the ability to multimerize. The overexpression of hCRM1 complemented the functional defects of RexM64, which contains a mutation in the multimerization domain of Rex. A dominant-negative mutant of Rex which sequesters cofactors of Rex abrogated multimerization as well as the activity of the wild-type Rex protein. These two functions were simultaneously restored by the overexpression of hCRM1. Taken together, these results suggest that hCRM1 plays important roles in the multimerization and export of Rex protein.

Biological Transport↗

Spontaneous remission of hypertrophic lymphocytic gastritis associated with hypoproteinemia.

A 54-year-old woman came to our office because of pretibial edema. She had no gastrointestinal symptoms. Laboratory tests revealed severe hypoproteinemia. Upper gastrointestinal endoscopy demonstrated enlarged gastric folds and multiple aphthoid nodules on the body and the fornix of the stomach. The biopsy specimen revealed a large number of CD8 positive intraepithelial T-lymphocytes infiltrating the gastric mucosa. Both serum total protein and the gastric lesions improved eight months after her first visit without any therapy for peptic ulcer or eradication of Helicobacter pylori. The data suggest that spontaneous remission may occur in lymphocytic gastritis without any gastrointestinal symptoms.

Biopsy↗

Local health care system utilizing the LPG (liquid propane gas) network.

JAC's LPG monitoring network system is mainly provided in mountain villages. However, by using this system, it will be possible to start a Digital Network Program for the Elderly while maintaining superior economic feasibility and public benefit using existing information infrastructures. This project also has the capabilities for the creation of a fire/disaster monitoring system, as well as a health care system by using conventional LPG monitoring systems. Telemedicine is an option for the future, as well, by connecting medical equipment and a tele-conferencing system.

Aged↗

[Clinical evaluation of intermittent hepatic arterial infusion therapy for metastatic liver tumor of gastric and colorectal cancer].

Eleven patients with liver metastasis from gastric cancer were treated by intermittent arterial infusion using OK-432 and recombinant IL-2 in combination with anticancer drugs. The direct effects for liver metastasis were PR 3 (response rate 30%), MR 2, NC 3, PD 1 and NE 1. Papillary adenocarcinoma showed a highly effective rate. The mean survival period was 326 days and the 50% survival period was 318 days. Out of 4 patients who underwent surgical resection for metastatic liver tumor, one showed recurrence, and the other is now healthy without any sign of recurrence for 8 years after the operation. In 7 patients with liver metastasis from colorectal cancer, intermittent arterial infusion therapy using Leucovorin, CDDP and 5-FU was performed. The direct effects were CR 2, PR 1, MR 1, PD 2, NE 1; the mean survival period was 478 days, and the 50% survival period 556 days. Out of 8 patients who underwent liver resection for metastasis, all patients remained alive for 687 mean survival days without liver recurrence. No severe side effects were noted in either therapy.

Adenocarcinoma, Papillary↗

Construction of a plasmid vector for transformation of Porphyromonas gingivalis.

A host-vector system for transformation of Porphyromonas gingivalis was constructed using a set (1) strains that can incorporate plasmid DNA by electroporation regardless of its source and (2) stable vector plasmids with a selectable marker. First, restriction-negative mutants were isolated, because P. gingivalis possesses restriction modification systems by which DNA introduced by transformation even from heterologous strains of the same species is excluded. For screening of the mutants, plasmid pE5-2 was employed since it could be transconjugated (mobilized) to P. gingivalis from Escherichia coli and is able to replicate in this species, albeit not stably. pE5-2 DNA prepared from E coli was introduced by electroporation into chemically mutagenized P. gingivalis cells. By this method, three putative restriction-negative clones were selected. These strains exhibited a capacity for electroporation with plasmid DNAs both from E. coli and from various P. gingivalis strains at a similar efficiency. Using one of the derivatives thus obtained, YH522, we then screened for plasmids that could replicate stably in P. gingivalis. Since no plasmids were found from P. gingivalis, cryptic plasmids from other species of black-pigmented oral anaerobic rods were examined for their ability to transform P. gingivalis. A series of plasmids constructed by ligation with pBR322 for replication in E. coli and the EcoRI-B fragment from pBF4 containing erythromycin resistance were prepared from E. coli and were used for electroporation of P. gingivalis. Among these, a recombinant plasmid containing the replicon of pYHBA1 from Porphyromonas asaccharolytica, designated pYH400, was found to be incorporated into the restriction-negative P. gingivalis strain and replicated stably. This set of recipient strains and stable plasmids with a selectable marker constitutes the first practical host-vector system for this species.

Cloning, Molecular↗

The lipid A moiety of Porphyromonas gingivalis lipopolysaccharide specifically mediates the activation of C3H/HeJ mice.

The lipid A preparation isolated from Porphyromonas gingivalis was found to induce splenocyte mitogenicity and TNF-alpha release from peritoneal macrophages in LPS-unresponsive C3H/HeJ mice to the same extent as in LPS-responsive mice. In order to clarify whether the activation of C3H/HeJ mice was specifically caused by the lipid A and not by contaminating protein, two strategies were employed. The lipid A fraction from P. gingivalis was subjected to either hydrochloric acid or alkaline treatment to eliminate either glycosylated phosphate or O-acylated fatty acids from the lipid A structure, and the biologic activities of the derivatives were compared in both LPS-responsive and unresponsive C3H/HeJ mice. De-1-O-phosphorylated P. gingivalis lipid A showed partial loss, and de-O-acylated lipid A complete loss of splenocyte mitogenic and TNF-alpha-inductive activities from peritoneal macrophages in both LPS-responsive and unresponsive mice. The relative activities of the intact and treated lipid A compounds in splenocyte mitogenicity and TNF-alpha-inductive activity in macrophages were similar to the relative activities of these preparations in Limulus gelation activities. The LPS-specific antagonist, succinylated lipid A precursor, inhibited P. gingivalis lipid A-mediated splenocyte mitogenicity and TNF-alpha induction in macrophages in a similar manner in LPS-responsive and unresponsive mice. These results strongly suggest that the activation of LPS-unresponsive C3H/HeJ mice by P. gingivalis lipid A was specifically mediated by the lipid A portion and not by contaminating protein. The characteristic action of P. gingivalis lipid A on LPS-unresponsive C3H/HeJ mice was thought to reflect the unique chemical properties of this compound.

Amino Acids↗

Clinical study of the relationship between cytological behavior and postoperative prognosis in colorectal cancer cases with special reference to nuclear DNA content and nucleolar organizer regions.

BACKGROUND: We studied the usefulness of nuclear DNA patterns and argyrophylic nucleolar organizer regions (AgNORs) for evaluating the malignant potential of colorectal cancers, which is increasingly being regarded as important in predicting patients' prognosis and for their appropriate postoperative management. METHODS: We measured these two factors in curatively resected specimens of 91 colorectal cancer cases, which were followed up for 1,549 +/- 788 days postoperatively. Ploidy pattern was either diploid or aneuploid, and AgNORs score was either low (LS) or high (HS). Thus, we classified our cases into Group I (diploid, LS). Group II (aneuploid, LS), Group III (diploid, HS), and Group IV (aneuploid, HS). Postoperative survival curves in the cases belonging to these groups were analyzed. RESULTS: Survival rates in Groups I and II were significantly higher than those in Group IV. Correlation between subgroups and clinicopathological factors such as average age, histologic type, depth of invasion, and histologic stage were observed. Incidence of lymph node metastasis at the time of operation and that of postoperative recurrence were higher in group IV than that in groups I and II. CONCLUSIONS: Measurement of DNA ploidy patterns and AgNORs score were found to be useful in evaluating malignant potential of colorectal cancers.

Adult↗

A case of liver metastasis from colon cancer masquerading as focal sparing in a fatty liver.

Focal sparing in diffusely fatty liver is a well recognized entity. However, it occasionally creates some problems in the diagnosis of hepatic mass lesions. We recently experienced a case of liver metastasis from colon cancer which appeared as a wedge-shaped hyperdense area on non-enhanced CT (computed tomography). Other imaging techniques also demonstrated a wedge-shaped area which was difficult to distinguish from mere focal sparing in the fatty liver. CT arteriography and dynamic magnetic resonance images were useful for diagnosing this metastatic tumor. CT during arterial portography showed a wedge-shaped ischemic area in the anterior segment caused by intrahepatic portal vein blockade. The histological findings eventually revealed that the tumor, an adenocarcinoma, was surrounded by fibrotic tissue that mimicked focal sparing. We present the radiological features of this case and discuss how to arrive at a correct diagnosis.

Adenocarcinoma↗