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Biomedical subjects

T Muto

Publications and source records attributed to T Muto.

At least 55 records · Page 3Linked to original sources

Immunohistochemical localization of membrane type 1-matrix metalloproteinase (MT1-MMP) in osteoclasts in vivo.

Membrane type 1-matrix metalloproteinase (MT1-MMP) is capable of mediating proteolysis of extracellular matrix. The enzyme has been demonstrated in osteoclasts, in vitro. However, the precise localization in vivo, and therefore the function of the enzyme in osteoclasts, is still unclear. In this study, we immunohistochemically examined the localization of MT1-MMP in rat osteoclasts to clarify the role of MT1-MMP in osteoclastic bone resorption and bone turnover. The localization of MT1-MMP was visualized by the pre-embedding method using anti-MT1-MMP antibody and horseradish peroxidase (HRP) or gold-conjugated antibody. Immunoreactivity of anti-MT1-MMP was found in osteoclasts at the osteoclast-bone interface, but it was not uniform. Ultrastructurally, the immunoreactivity visualized by HRP was found in sealing zone. The plasma membrane at this site showed an irregular border and some invaginations. Immunoreactivity was also found on the surface of certain small vesicles in the cytoplasm. Enhanced silver granules were mainly associated with the sealing membrane. In this study, we demonstrated, for the first time, the localization of MT1-MMP in the sealing zone of osteoclast in vivo. Its distribution suggests that the enzyme modifies the bone surface to facilitate the migration and attachment of osteoclasts as well as scavenging the resorption lacunae.

Animals↗

Risk factors for rupture of abdominal aortic aneurysm based on three-dimensional study.

PURPOSE: Factors influencing the development or rupture of abdominal aortic aneurysms (AAAs) have not yet been confirmed. This study delineated the risk factors for rupture of AAAs as evaluated by means of a combination of three-dimensional (3D) reconstruction and clinical data analysis. METHODS: The study population comprised Japanese patients in whom an atherosclerotic AAA had been diagnosed between January 1980 and December 1997. We obtained 3D-based data by means of computer-aided 3D reconstruction from computed tomography studies of AAAs. The data included the tortuosity of the aneurysm, maximum transverse diameter, length of the aneurysm, aneurysmal volume, aneurysmal surface area, largest aneurysmal cross-sectional area, ratio of transverse aneurysmal diameter to the length of the aneurysm (T/L), and amount of mural thrombus. Clinical data were collected from patient files. All data were assessed by means of multivariate analysis for their predictive value for expansion or rupture of AAA. RESULTS: The most efficient predictor of annual expansion rate of maximum transverse diameter (EX-D) was a combination of largest aneurysmal cross-sectional area, tobacco use, and tortuosity. The most efficient predictor of annual expansion rate of aneurysmal volume (EX-V) was a combination of aneurysmal volume and blood urea nitrogen level. The most efficient predictors of aneurysmal rupture was a combination of EX-D, diastolic blood pressure, and T/L. CONCLUSION: Three-dimensional-based data on aneurysmal morphology, including T/L, largest aneurysmal crosssectional area, and aneurysmal volume, had strong predictive value for expansion and rupture of AAAs.

Aged↗

Short-term effect of beta-adrenoreceptor blocking agents on ocular blood flow.

PURPOSE: In this study the acute effect of the topically-delivered non-selective beta-blockers timolol and carteolol, and the selective beta-blocker betaxolol, were evaluated with respect to ocular blood flow, intraocular pressure (IOP) and vessel resistance in rabbits' eyes. METHODS: In a double masked randomized design, one eye of each subject (n = 9) received two drops of 0.5 % timolol or 2 % cartelol or 0.5 % betaxolol ophthalmic solution and a separate group of nine rabbits received two drops of placebo consisting of physiological saline in both eyes to serve as control. Using hydrogen clearance method, ciliary body blood flow (CiBF), choroidal blood flow (CBF), and retinal blood flow (RBF) were measured. IOP and systemic mean arterial pressure (MAP) of each subject were measured under same condition before and after the administration of respective drugs to calculate the ocular perfusion pressure (OPP) and vessel resistance. RESULTS: In timolol- and carteolol-treated eyes significant reduction was observed in IOP (p < 0.01), CiBF (p < 0.01), CBF (p < 0.01) and RBF (p < 0.01) compared to control eyes. However, in betaxolol-treated eyes a marginal reduction in IOP was observed accompanied by significant increase in CiBF (p < 0.01) and RBF (p < 0.05). The non-selective beta-blocker-treated eyes tended to have increased vessel resistance, whereas, selective beta-blocker-treated eyes tended to have decreased vessel resistance. CONCLUSIONS: Our current results comparing non-selective and selective beta-blockers suggest that the selective beta-blocker betaxolol may be more appropriate for maintenance of retinal blood flow in situations with low perfusion. Currently the mechanism for regulation of IOP is unclear; however, the findings from this study indicate that decreased CiBF may contribute to reduction in IOP.

Administration, Topical↗

Characteristics of health counselling in the workplace via e-mail.

This study was conducted to examine how health counselling via electronic mail (e-mail health counselling) was used in the workplace. The definition of health counselling employed in this study was 'any assistance to an individual seeking to solve any health problem'. A total of 2119 health counsellings conducted at a Japanese company's head office (700 employees) in 1997 and 1998 was used for the analysis, which compared four health counselling methods: e-mail, face-to-face, telephone and ordinary mail. This study distinguished four main characteristics of e-mail health counselling. First, the most and second most frequently used counselling methods were face-to-face and telephone counselling, at 70 and 15%, respectively, with e-mail health counselling ranked third at 13%. e-mail counselling was the second most frequently used method for employees in their 20s and 30s, while it ranked third among those over 40. Only 6% of employees in their 50s used e-mail counselling. Secondly, the proportion of mental health issues treated via e-mail counselling was significantly higher, at 26%, than for other counselling methods, which was at or below 10% for each of the other methods. Thirty-two per cent of all mental health counselling was conducted via e-mail. Thirdly, compared with face-to-face counselling, e-mail counselling dealt with more health issues related to primary prevention than with those related to secondary or tertiary prevention. Fourthly, compared with face-to-face counselling, e-mail counselling dealt more with health issues of third parties. These results suggest that e-mail health counselling may be useful in reaching people other than those targeted by the remaining counselling methods.

Adult↗

[The significance of extracurricular activities in the life of junior high school students].

In this study, the significance of extracurricular activities in the life of junior high school students were examined. Seventh and eighth graders participated in a two-stage questionnaire survey, administered in May and October. Based on developmental stage-environment fit theory (Eccles, Wigfield, & Schiefele, 1998), how well extracurricular activity settings fit needs of the students was analyzed. In support of the theory's hypothesis, results indicated that whether an extracurricular activity satisfied the student's developmental needs affected his/her sense of fulfillment and satisfaction in school life. In addition, the effect of seventh graders' commitment to extracurricular activities on their satisfaction of school life was stronger in October than in May. The findings suggested that for students who felt uneasy in class for whatever reasons, extracurricular activities provided an opportunity for relief.

Adolescent↗

[Future figures of specialties in the surgical field].

A quarter of century has passed since specialties and their governing boards were established in the surgical field. It is now time to reestablish more definitive and rational specialties as we begin the 21st century. The specialty of general surgery should be the first step and require general surgical training of four years or more. The subsequent specialties (subspecialties) would be gastroenterological surgery, cardiovascular surgery, respiratory organ surgery, and pediatric surgery. In addition, the numerous medical associations in Japan could be overseen by a newly created Japan Board of Medical Specialties (proposed name) to manage the various specialties.

Forecasting↗

[To err is human but error can be prevented].

It is believed that behind each reported medical error 29 unreported errors are hidden and in addition 300 irregularities are present. To prevent medical errors, one should learn from those latent errors to reorganize or correct systems and procedures. The Risk Management Committee is in charge of taking measures to prevent errors based on the analyzed data reported by risk managers and/or on incident/accident reports. The incident/accident reports should be made under a blame-free system and the concept should be thoroughly understood by all hospital staff. A lack of mutual communication, lack of a system to prevent medical errors, and lack of seriousness in everyday practice among physicians and nurses were found to be underlying causal factors in medical errors based on the lessons learned in our institution.

Humans↗

[Current status of adjuvant endocrine therapy for hormone responsive breast cancer].

Three important meetings on adjuvant hormone therapy for breast cancer were held recently: the 5th EBCTCG Meeting, NIH Consensus Meeting, 7th International Conference on Adjuvant Therapy of Primary Breast Cancer. The conclusions of these meetings are: 1. adjuvant hormone therapy should be indicated only for patients with estrogen/progesterone receptor positive cancer, 2. five years of tamoxifen is the standard care at present, 3. ovarian ablation by any means has been proved effective in premenopausal patients and LH-RH agonist should be given at least two years, and 4. aromatase inhibitors should not be used in clinical practice, because several prospective randomized trials are ongoing at present. The patients treated with LH-RH agonist combined with tamoxifen showed better relapse-free survival compared with LH-RH agonist alone in the INT-0101 trial. This was an important trial because combined hormone therapy had not been proven more effective than individual hormone therapy previously. Combined hormone therapy including LH-RH agonist may be considered in premenopausal patients. There is a growing consensus that chemotherapy is effective through the ovarian suppression. In this sense, hormonal therapy should be considered first for hormone responsive patients. On the contrary, standard chemotherapy has shifted from CMF combination to an anthracycline containing regimen. Chemoendocrine therapy may be considered in high risk patients.

Antineoplastic Agents, Hormonal↗

Financial assistance in promoting occupational health services for small-scale enterprises in Japan.

In spite of the diversified views on the governmental financial assistance in promoting occupational health services (OHS) for small-scale enterprises (SSE), the issue has not been much studied. Considering the large differences between countries in the degree of governmental financial assistance, the international comparative research will provide insight into its advantages and disadvantages. In order to conduct such comparative research, the status of each country must first be clarified. This informative piece of study aims at stimulating researchers in other countries to share their experiences and facilitate future comparative studies. This study was conducted to clarify the financial assistance of the Japanese government for SSE. Published reports on financial assistance for SSE were collected and used for the study. The Ministry of Labor initiated the policy of subsidizing OHS for SSE in the early 1960s. Activities to be subsidized through four routes included primary and secondary prevention of occupational injuries and diseases. The amount of subsidy was limited from one-third to two-thirds of costs. There was a fourteen-fold increase in the amount of subsidies for SSE from US$ 7 million in 1986 to US$ 98 million in 1998. The long history of financial assistance for SSE and the increasing amount of subsidies suggest that the Ministry of Labor recognizes the importance of financial assistance in promoting OHS in small scale enterprises.

Financial Support↗

Clustered cancer cells show a distinct adhesion behavior from single cell form under physiological shear conditions.

It remains a question whether hematogeneous metastasis arises from a single cancer cell attached to the local endothelium or from a cluster of cancer cells trapped in the vascular bed in the target organ. Adhesive interaction of the single cell form and the clustered form of cancer cells was examined under flow conditions, using two subclones of mouse colon adenocarcinoma Colon 26. A subclone NL17, but not NL14, formed many clusters composed of tumor cells and platelets just after the addition of platelet rich plasma (PRP). Under the shear of 1.0 dyn/cm3, the clustered form of NL17 tethered on laminin or mouse endothelial cell line in hepatic sinusoids (HSE) more frequently than the single cell form of NL17 and NL14. However, all of the clusters showed only transient attachment and never underwent stable arrest on coated laminin, while the single cell form of NL14 and NL17 underwent immediate arrest under shear conditions. On HSE stimulated with TNF-alpha, a small number of NL17 clusters made stable adhesion, although all the clusters detached if the shear stress was increased above 4.0 dyn/cm2. In contrast, the single form of arrested NL17 as well as NL14 remained adherent even at shear of 8.0 dyn/cm2. Compared with single cell, binding of cancer cell clusters to laminin and HSE showed lower resistance to shear stress, although they had adhesive interactions more frequently in flow condition. Since NL17 cells form significantly more metastases by intravenous injection in vivo, our data suggest that "stable adhesion" observed in our flow assay system is not always a prerequisite for clustered cancer cells to develop into metastatic lesions.

Adenocarcinoma↗

Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).

The activation-induced cytidine deaminase (AID) gene, specifically expressed in germinal center B cells in mice, is a member of the cytidine deaminase family. We herein report mutations in the human counterpart of AID in patients with the autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses.

APOBEC-1 Deaminase↗

Isolation, tissue distribution, and chromosomal localization of the human activation-induced cytidine deaminase (AID) gene.

The gene encoding activation-induced cytidine deaminase (AID), a member of the cytidine deaminase family, was isolated from a murine B cell lymphoma line, CH12F3-2, induced by combined stimulation of TGF-beta, IL-4, and CD40L. We have isolated the human orthologue of mouse AID cDNA, which has an open reading frame of 198 residues containing a conserved cytidine deaminase motif. The amino acid sequence of human AID is 92% identical to that of mouse AID. RT-PCR analysis of 15 human tissues showed that AID mRNA is expressed strongly in lymph nodes and tonsils. The complete human AID gene consisting of five exons was isolated and mapped to chromosome 12p13 by fluorescence in situ hybridization.

Amino Acid Sequence↗

Functional analysis of the C-terminal region of recombinant human thrombopoietin. C-terminal region of thrombopoietin is a "shuttle" peptide to help secretion.

Thrombopoietin (TPO) is a cytokine that primarily stimulates megakaryocytopoiesis and thrombopoiesis. TPO has a unique C-terminal tail peptide of about 160 amino acids that consists mostly of hydrophilic residues and contains six N-linked sugar chains. In order to investigate the biological function of the C-terminal domain, two series of mutations were performed. One is systematic truncation from the C terminus. Another is elimination of N-glycosylation sites in the C-terminal domain by Asn to Gln mutations. After the mutant proteins were expressed by mammalian cells, it was found that the elimination of the N-linked sugar sites did not affect the biological activity, whereas truncation of the C-terminal domain resulted in elevation of in vitro activity up to 4-fold. The C-terminal peptide itself was found to inhibit the in vitro activity. Moreover, both the C-terminal truncation and the elimination of the N-glycosylation sites decreased the secretion level progressively down to (1)/(10) that of wild type, and the amount of the mutant left in the cell increased. The N-glycosylation in the C-terminal region was found to be important for secretion of TPO. Among six N-glycosylation sites in the C-terminal region, two locations, Asn-213 and Asn-234, were found to be critical for secretion, and two other locations, Asn-319 and Asn-327, did not affect the secretion.

Animals↗

Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20.

Most mitochondrial proteins are synthesized in the cytosol as precursor proteins with a cleavable N-terminal presequence and are imported into mitochondria. We report here the NMR structure of a general import receptor, rat Tom20, in a complex with a presequence peptide derived from rat aldehyde dehydrogenase. The cytosolic domain of Tom20 forms an all alpha-helical structure with a groove to accommodate the presequence peptide. The bound presequence forms an amphiphilic helical structure with hydrophobic leucines aligned on one side to interact with a hydrophobic patch in the Tom20 groove. Although the positive charges of the presequence are essential for import ability, presequence binding to Tom20 is mediated mainly by hydrophobic rather than ionic interactions.

Aldehyde Dehydrogenase↗

Expression of platelet-derived endothelial cell growth factor correlates with good prognosis in patients with colorectal carcinoma.

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that has potent chemotactic activity for endothelial cells. Although it is expressed in the majority of colorectal tumors, and some reports suggest that its high expression is related to poor prognosis, to the authors' knowledge there is yet no consensus regarding whether PD-ECGF expression is a prognostic factor. To investigate the prognostic value of PD-ECGF and its role in tumor angiogenesis, an immunohistochemical study of PD-ECGF expression and tumor vasculature was performed and their relation with the clinicopathologic factors in patients with advanced colorectal carcinoma was evaluated. METHODS: Formalin fixed, paraffin embedded specimens from 86 colorectal carcinoma patients (40 cases in the muscularis propria and 46 cases in the subserosa) were immunostained for PD-ECGF and CD31 as a marker for vascular endothelial cells and expression of PD-ECGF was evaluated using an image analysis system. Patients were divided into high expression and low expression groups based on PD-ECGF expression, and were divided into high vascular grade and low vascular grade groups based on the microvessel density. Correlations between PD-ECGF expression and vascular grade and between PD-ECGF expression,vascular grade, and the clinicopathologic features of the patients were evaluated statistically. RESULTS: PD-ECGF expression was observed predominantly in the tumor stroma and not in tumor cells. The cells that stained strongly for PD-ECGF were confirmed to be macrophages infiltrating the interstitial tissue of the tumor. High PD-ECGF expression was found in 56 cases (65.1%) and low expression was detected in 30 cases (34.9%). Thirty-one of 86 tumors (36.0%) showed high vascular grade and 55 (64.0%) showed low vascular grade. No correlation between PD-ECGF expression and vascular grade was found, but there was an inverse correlation between PD-ECGF expression and the rate of incidence of lymph node and hematogenous metastasis. These correlations were statistically significant. Vascular grade was not found to correlate with the clinicopathologic features. CONCLUSIONS: Patients with high PD-ECGF expression had a lower rate of incidence of lymphatic and hematogenous metastasis, with a consequently better prognosis than patients with low PD-ECGF expression. PD-ECGF expression did not correlate with vascular grade, suggesting that PD-ECGF plays little role in tumor angiogenesis of colorectal carcinoma. Based on these data, the authors conclude that macrophages infiltrating the tumor stroma produce PD-ECGF and play important roles in the immune reaction against the tumor rather than in tumor angiogenesis.

Adult↗