Biomedical subjects

N Tamura

Publications and source records attributed to N Tamura.

At least 73 records · Page 4Linked to original sources

PubMed2000

Development of new drug delivery system for protein drugs using silicone (I).

A novel technique, by which protein drugs effective in small doses can be released over a long period, was developed using silicone and a water-soluble substance. In this study, interferon (IFN) was used as a model of the protein drugs. The IFN-silicone formulation released IFN over long periods of time in vitro and suppressed tumor growth in nude mice for about 100 days after a single administration. This indicates that physiologically active IFN is released over a prolonged period of time from the IFN-silicone formulation in vivo. Silicone formulations are expected to be a practically feasible sustained-release formulation.

Animals↗

PubMed2000

Formation Process of MCM-41 Precursor and Porous Texture of MCM-41.

The formation process of the MCM-41 precursors (silicate/surfactant complex) was investigated on the basis of the pH titration curves of Na(4)SiO(4) in the presence of [C(16)H(33)N(CH(3))(3)]Cl. Measurements of the pH titration curves were carried out using the computer-controlled gravimetric titrator constructed in our laboratory. The white precipitate (MCM-41 precursor) was abruptly formed at pH 11.1 (298 K) and at pH 9.9 (343 K). Formation of the MCM-41 precursor can be explained by coagulation of the rod-like micelle colloids whose surface is covered by the condensed silicate anions of (HSiO(3))(n)(n-). The porous texture of the MCM-41 samples whose precursors were synthesized under different conditions was analyzed on the basis of the adsorption isotherms of nitrogen at 77 K. It has been shown that the MCM-41 sample whose precursor was prepared at pH 9.9 and 343 K shows one sharp peak (r(p) = 1.65 nm) in the pore size distribution curve, but the MCM-41 samples whose precursors were prepared at pH 6.5-5.0 and 343 K give two peaks (r(p) = 1.66 nm and r(p) = 2.12-2.36 nm). The appearance of the second peak (r(p) = 2.12-2.36 nm) has been considered to be in connection with the destruction of the MCM-41 precursor into small fragments in acidic medium. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Cardiac fibrosis in mice lacking brain natriuretic peptide.

Cardiac fibrosis, defined as a proliferation of interstitial fibroblasts and biosynthesis of extracellular matrix components in the ventricles of the heart, is a consequence of remodeling processes initiated by pathologic events associated with a variety of cardiovascular disorders, which leads to abnormal myocardial stiffness and, ultimately, ventricular dysfunction. Brain natriuretic peptide (BNP) is a cardiac hormone produced primarily by ventricular myocytes, and its plasma concentrations are markedly elevated in patients with congestive heart failure and acute myocardial infarction. However, its precise functional significance has been undefined. In this paper, we report the generation of mice with targeted disruption of BNP (Nppb(-/-) mice). We observed multifocal fibrotic lesions in the ventricles from Nppb(-/-) mice. No signs of systemic hypertension and ventricular hypertrophy are noted in Nppb(-/-) mice. In response to ventricular pressure overload, focal fibrotic lesions are increased in size and number in Nppb(-/-) mice, whereas no focal fibrotic changes are found in wild-type littermates (Nppb(+/+) mice). This study establishes BNP as a cardiomyocyte-derived antifibrotic factor in vivo and provides evidence for its role as a local regulator of ventricular remodeling.

Animals↗

PubMed2000

Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary.

OBJECTIVES: Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined use of two serum tumor markers, macrophage colony-stimulating factor (M-CSF) and squamous cell carcinoma antigen (SCC), is effective in preoperatively diagnosing squamous cell carcinoma arising in mature cystic teratoma of the ovary, distinguishing it from mature cystic teratoma without malignant transformation. METHODS: Serum levels of M-CSF and SCC were assayed using blood samples collected preoperatively from 31 patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary and 133 patients with mature cystic teratoma of the ovary without malignant transformation. RESULTS: In 22 of the 31 (71.0%) patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary, the serum M-CSF levels exceeded the upper limit of the normal level (1056 U/ml). This positive incidence of the elevated serum M-CSF levels was significantly higher compared with that (13.5%, 18/133) observed in patients with benign cystic teratoma of the ovary (P < 0.0001). Regarding the serum levels of SCC, 13 of 31 (41.9%) patients with malignant tumors showed positive values exceeding the cutoff value of 2.0 ng/ml. Again, this incidence of positive cases was significantly higher compared with that (15.0%, 20/133) observed in patients with benign tumors (P < 0.01). There was no correlation between the serum levels of M-CSF and SCC among patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary. Patients with malignant tumors testing positive for elevated M-CSF did not necessarily test positive for SCC. Patients with positive values for excess M-CSF and/or SCC constituted 87.1% of the total (27/31). Even when patients were restricted to those with stage I tumors, a value as high as 83.3% (15/18) was still obtained for those testing positive for elevated M-CSF and/or SCC. CONCLUSION: Serum M-CSF was proven to be useful as a tumor marker for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. Combined use of serum M-CSF and SCC as a marker seemed to be useful in the selective diagnosis of mature cystic teratoma of the ovary harboring malignant squamous carcinoma, discriminating it from that without malignant carcinoma.

Adolescent↗

PubMed2000

Carinal reconstruction with a Y-shaped collagen-conjugated prosthesis.

BACKGROUND: Carinal reconstruction by direct suturing is associated with a high mortality because high tension at the anastomosis can lead to tracheobronchial fistula. A new tracheal prosthesis was therefore designed for reconstruction of the tracheal bifurcation and applied for experimental carinal replacement in dogs. METHODS: The main frame of the new prosthesis consists of a Y-shaped Marlex mesh tube (C.R. Bard, Inc, Billerica, Mass) reinforced with polypropylene spirals, to which collagen extracted from porcine skin is chemically conjugated to provide biocompatibility and airtightness. This conjugated collagen is composed of amorphous and sponge collagen layers. The tracheobronchial bifurcation was replaced with the prosthesis in 10 beagle dogs. RESULTS: Eight dogs survived the postoperative period, and 2 dogs died within 4 days after the operation. Bronchoscopic examination revealed that the tracheal prosthesis was covered with smooth whitish tissue and that no stenosis or dehiscence was present in the 8 dogs even 6 months after the operation. Slight mesh exposure was recognized in 1 dog. Histologic examination revealed that approximately one half of the luminal surface was covered with ciliated columnar epithelium or nonciliated squamous epithelium. In the remaining lumen, especially in the middle portion of the prosthesis, connective tissue without epithelium was observed. CONCLUSIONS: These long-term results indicate that our bifurcated tracheal prosthesis can be used for reconstruction of the tracheobronchial bifurcation with long-term safety.

Animals↗

PubMed2000

Recurrent ovarian clear cell carcinoma: complete remission after radiation in combination with hyperthermia; a case study and in vitro study.

Since clear cell carcinoma of the ovary does not respond to conventional platinum-based chemotherapy, the prognosis of recurrent tumors is especially poor. In a 51-year old female who underwent surgery for clear cell carcinoma of the ovary, a solitary metastatic carcinoma developed in the pelvic cavity seven months after the initial surgery. The patient underwent a whole pelvic irradiation at a total dose of 65 Gy combined with hyperthermia. Complete remission was achieved 46 months after treatment. A study using gynecologic carcinoma cell lines showed that the mean 50% growth inhibitory dose of radiation was 1.2 +/- 0.4 Gy in several clear cell carcinoma cell lines. The value did not significantly differ from those for serous carcinoma cell lines (2.3 +/- 1.2 Gy) and uterine cervical carcinoma cell lines (1.6 +/- 0.4 Gy). Currently, no anticancer agents are effective for clear cell carcinoma. Radiotherapy combined with hyperthermia may be effective for localized tumors.

Adenocarcinoma, Clear Cell↗

PubMed2000

C-Type natriuretic peptide inhibits proliferation and monocyte chemoattractant protein-1 secretion in cultured human mesangial cells.

BACKGROUND: Mesangial cell proliferation and matrix accumulation are hallmarks of various progressive glomerular diseases. We examined whether C-type natriuretic peptide (CNP) that is known to regulate the proliferation of vascular smooth muscle cells could modulate these pathological processes using human glomerular mesangial cells (GMCs) in culture. METHODS: Proliferation of GMCs cultured with different concentrations of CNP-22 for 48 h was determined by a colorimetric assay using a tetrazolium salt. Monocyte chemoattractant protein-1 (MCP-1) and type IV collagen secretion into the culture media by GMCs in the presence or absence of CNP-22 were evaluated by ELISA. Expression of mRNA for natriuretic peptide receptor B (NPR-B), a specific receptor for CNP, was examined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: CNP-22 (1-10 microM) inhibited serum-induced GMC growth in a dose-dependent manner. The amount of MCP-1 in the culture supernatant was increased approximately 2.4-fold by 5 microg/ml of lipopolysaccharide. This increase was inhibited by CNP-22 at 0.1-1 microM in a dose-dependent fashion. CNP-22 (10 microM) inhibited GMC type IV collagen secretion stimulated by 20 ng/ml of platelet-derived growth factor. Expression of NPR-B mRNA was confirmed in GMCs by RT-PCR. CONCLUSIONS: CNP suppresses GMC proliferation and MCP-1 and type IV collagen secretion by GMCs. It may have a therapeutic potential against human proliferative glomerular diseases, especially those with the involvement of monocytes.

Cell Division↗

PubMed2000

Genetic models reveal that brain natriuretic peptide can signal through different tissue-specific receptor-mediated pathways.

Brain natriuretic peptide (BNP), a hormone produced primarily by the cardiac ventricle, is thought to be involved in a variety of homeostatic processes through its cognate receptor, guanylyl cyclase A (GC-A). We previously created transgenic mice overexpressing BNP under the control of the liver-specific human serum amyloid P component promoter (BNP-transgenic mice) and demonstrated that they exhibit reduced blood pressure and cardiac weight accompanied by an elevation of plasma cGMP concentrations and marked skeletal overgrowth through the activation of endochondral ossification. To address whether BNP exerts its biological effects solely through GC-A, we produced BNP-transgenic mice lacking GC-A (BNP-Tg/GC-A-/- mice) and examined their cardiovascular and skeletal phenotypes. The GC-A-/- mice are hypertensive with cardiac hypertrophyrelative to wild-type littermates, which is not alleviated by overexpression of BNP in BNP-Tg/GC-A-/- mice. The BNP-Tg/GC-A-/- mice, however, continue to exhibit marked longitudinal growth of vertebrae and long bones comparably to BNP-Tg mice. This study provides genetic evidence that BNP reduces blood pressure and cardiac weight through GC-A, whereas it dramatically alters endochondral ossification in the absence of this receptor. Therefore, the BNP-Tg/GC-A-/- mice provide the first experimental model demonstrating that this natriuretic peptide can signal in a tissue-specific manner through a receptor other than GC-A.

Animals↗

PubMed2000

Effect of activin on production and secretion of prolactin and growth hormone in cultured rat GH3 cells.

OBJECTIVE: To evaluate the effect of the growth factor activin A on the secretion of prolactin (PRL) and GH in cultured GH3 cells. METHODS: The concentrations of PRL and GH secreted from GH3 cells cultured in media with and without activin A were measured by RIA, and the expression of PRL mRNA and GH mRNA were analyzed using the Northern blot method. RESULTS: Activin A significantly inhibited PRL release from GH3 cells cultured for 48h in a dose-dependent manner (activin: 0.3-3nM). The inhibitory effects of 3nM activin A were observed in the culture from 12h to 48h (53.2% of control). Activin A (3nM) also significantly inhibited the expression of PRL mRNA at 24h (33.8% of control). In contrast, activin A significantly stimulated GH release from GH3 cells cultured for 48h in a dose-dependent manner (activin: 0.3-3nM). The stimulatory effect of 3nM activin A was observed in the culture for 48h (157.6% of control). Activin A (3nM) also significantly stimulated the expression of GH mRNA at 24h (183.6% of control). In spite of these significant changes in PRL and GH secretion, pit-1 mRNA levels were not significantly changed by activin A. CONCLUSIONS: These findings indicated that activin A modulates PRL and GH secretion through the regulation of PRL and GH gene transcription in GH3 cells, but that these effects are unrelated to pit-1 gene expression.

Activins↗

PubMed2000

Artificial trachea and long term follow-up in carinal reconstruction in dogs.

We have already reported successful carinal reconstruction of the trachea with an observation period of 1 - 2 years. In this study, we evaluate the long-term safety and efficacy of the reconstruction after 5-years of follow-up. The Y-shaped Marlex mesh tube was reinforced with a polypropylene spiral and coated with atelocollagen made from porcine skin. The prosthesis was 60 mm long with an outer diameter of 18 mm. Replacement of the tracheobronchial bifurcation was preformed through a right thoracotomy in a beagle dog. Bronchoscopical examination and sampling of the tracheal epithelium was performed periodically to check the function of cilia. The implanted prothesis was promptly infiltrated by the surrounding connective tissue and completely incorporated by the host trachea and bronchus. Bronchoscopically, sufficient epithelization was confirmed from the upper to the lower site of anastomosis. After 5 years neither stenosis nor dehiscence was observed. In spite of there being mesh-exposure at the luminal surface, the dog had no clinical symptoms until sacrifice for pathological examination. The bent frequency of the cilia was maintained within the normal range, indicating functional recovery of the regenerating airway. Our tracheal prosthesis is promising for clinical repair of the tracheobronchial bifurcation.

Animals↗

PubMed2000

Expression of renin-angiotensin system and extracellular matrix genes in cardiovascular cells and its regulation through AT1 receptor.

Angiotensinogen (AGT) is a unique substrate of the renin-angiotensin system and fibronectin (FN) is an important component of the extracellular matrix. These play critical roles in the pathophysiological changes including cardiovascular remodeling and hypertrophy in response to hypertension. This study was performed to examine the regulation of AGT and FN gene in cardiac myocytes (CMs) and vascular smooth muscle cells (VSMCs) in response to mechanical stretch. Mechanical stretch significantly increased the AGT mRNA expression in CMs, while these stimuli did not affect FN mRNA levels. On the other hand, mechanical stretch upregulated FN mRNA levels in VSMCs, whereas no increase in AGT mRNA levels was observed in response to stretch stimuli. An angiotensin II type 1 (AT1) receptor antagonist (CV11974) significantly decreased these stretch-mediated increases in mRNA level and promoter activity of the AGT and FN gene, whereas angiotensin II type 2 (AT2) receptor antagonist (PD 123319) did not affect the induction. These results indicate that mechanical stretch activates transcription of the AGT and FN gene mainly via AT1 receptor-pathway in CMs and VSMCs. Furthermore, mechanisms regulating AGT and FN gene seem to be different between CMs and VSMCs.

Angiotensin Receptor Antagonists↗

PubMed2000

Regeneration of the junctional epithelium and connective tissue after transplantation of detergent-processed allo-teeth.

The authors have developed a new artificial dental implant and evaluated it in a dog model in terms of its potential to produce: I) regeneration of junctional epithelium; II) regeneration and attachment of connective tissue. The implants were constructed from allo-teeth. We removed the cell components from the periodontal ligaments of these teeth with a detergent (1% TritonX-100); the remaining acellular periodontal ligament acted as an extracellular matrix upon which regeneration and attachment could proceed. We placed 10 of these implants in the just-extracted sites of three beagle dogs. We observed regeneration of both junctional epithelium and connective tissue at all implant sites after 3 months. The connective tissue was attached in all cases. Use of the acellular periodontal ligament as an extracellular matrix may facilitate regeneration of host periodontal ligament tissue, thus contributing to recovery of host immunological defense and long-term oral function.

Animals↗

PubMed1999

Turnover of the aggregates and cross-linked products of the D1 protein generated by acceptor-side photoinhibition of photosystem II.

It is known that the reaction-center binding protein D1 in photosystem (PS) II is degraded significantly during photoinhibition. The D1 protein also cross-links covalently or aggregates non-covalently with the nearby polypeptides in PS II complexes by illumination. In the present study, we detected the adducts between the D1 protein and the other reaction-center binding protein D2 (D1/D2), the alpha-subunit of cyt b(559) (D1/cyt b(559)), and the antenna chlorophyll-binding protein CP43 (D1/CP43) by SDS/urea-polyacrylamide gel electrophoresis and Western blotting with specific antibodies. The adducts were observed by weak and strong illumination (light intensity: 50-5000 microE m(-2) s(-1)) of PS II membranes, thylakoids and intact chloroplasts from spinach, under aerobic conditions. These results indicate that the cross-linking or aggregation of the D1 protein is a general phenomenon which occurs in vivo as well as in vitro with photodamaged D1 proteins. We found that the formation of the D1/D2, D1/cyt b(559) and D1/CP43 adducts is differently dependent on the light intensity; the D1/D2 heterodimers and D1/cyt b(559) were formed even by illumination with weak light, whereas generation of the D1/CP43 aggregates required strong illumination. We also detected that these D1 adducts were efficiently removed by the addition of stromal components, which may contain proteases, molecular chaperones and the associated proteins. By two-dimensional SDS/urea-polyacrylamide gel electrophoresis, we found that several stromal proteins, including a 15-kDa protein are effective in removing the D1/CP43 aggregates, and that their activity is resistant to SDS.

Chlorophyll↗

PubMed1999

Observational Test of Environmental Effects on the Local Group Dwarf Spheroidal Galaxies.

In this Letter, we examine whether tidal forces exerted by the Galaxy or M31 have an influence on the Local Group dwarf spheroidal galaxies (dSph's) that are their companions. We focus on the surface brightness profiles of the dSph's, especially their core radii, because it is suggested, based on the numerical simulations, that tidal disturbance can make core radii extended. We examine the correlation for the dSph's between the distances from their parent galaxy (the Galaxy or M31) and the compactnesses of their surface brightness profiles by using a parameter C defined newly in this Letter. Consequently, we find no significant correlation. We make some remarks on the origin of this result by considering three possible scenarios-the tidal picture, the dark matter picture, and the heterogeneity of the group of dSphs-each of which has been often discussed as a way of understanding the fundamental properties and formation processes of dSphs.

Journal Article↗

PubMed1999

The effects of the selective ROCK inhibitor, Y27632, on ET-1-induced hypertrophic response in neonatal rat cardiac myocytes--possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy.

A small GTPase, Rho, participates in agonist-induced cytoskeletal organization and gene expression in many cell types including cardiac myocytes. However, little is known about the functions of Rho's downstream targets in cardiac myocytes. We examined the role of ROCK, a downstream target of Rho, in ET-1-induced hypertrophic response. Y27632, a selective ROCK inhibitor, inhibited ET-1-induced increases in natriuretic peptide production, cell size, protein synthesis, and myofibrillar organization. In addition, a dominant-negative mutant of p160ROCK suppressed ET-1-induced transcription of the BNP gene. These findings suggest that the Rho/ROCK pathway is an important component of ET-1-induced hypertrophic signals in cardiac myocytes.

Amides↗

PubMed1999

Isolation and characterization of CA XIV, a novel membrane-bound carbonic anhydrase from mouse kidney.

Carbonic anhydrase (CA) is involved in various physiological processes such as acid-base balance and transport of carbon dioxide and ions. In this study, we have succeeded in the isolation of a novel CA from the mouse kidney by use of the signal sequence trap method. It is a 337-amino acid polypeptide with a calculated molecular mass of 37.5 kDa, consisting of a putative amino-terminal signal sequence, a CA domain, a transmembrane domain, and a short hydrophilic carboxyl terminus, which we designated CA XIV. The CA domain of CA XIV is highly homologous with those of known CAs, especially extracellular CAs including CA XII, IX, VI, and IV. The expression study of an epitope-tagged protein has suggested that CA XIV is located on the plasma membrane. When expressed in COS-7 cells, CA XIV exhibits CA activity that is predominantly associated with the membrane fraction. By Northern blot analysis, the gene expression of CA XIV is most abundant in the kidney and heart, followed by the skeletal muscle, brain, lung, and liver. In situ hybridization has revealed that, in the kidney, the gene is expressed intensely in the proximal convoluted tubule, which is the major segment for bicarbonate reabsorption and also in the outer border of the inner stripe of the outer medulla. In conclusion, we have cloned a functional cDNA encoding a novel membrane-bound CA. This study will bring new insights into our understanding of carbon dioxide metabolism and acid-base balance.

Amino Acid Sequence↗

PubMed1999

Optimal distances for squirrels to transport and hoard walnuts.

Walnuts, Juglans airanthifolia, are an important food item for Japanese squirrels, Sciurus lis, which hoard them for later use. We set up feeders in small walnut patches in secondary forest, mounted radiotransmitters on nuts, placed them on the feeders and tracked them when they were cached. Of 720 nuts placed on the feeders over a 3-year period, 32.6% were eaten immediately and 50.6% were scatter-hoarded 0-168 m from the feeders. With increasing distance to the cache site, the squirrels took longer to return to the feeders (range 0.35-35 min). However, the further away a cache was, the less likely it was to be stolen by conspecifics or other nut-eating animals: nuts we hoarded ourselves disappeared more quickly from near the source trees. Squirrels took nuts further away later in the season when caches were lost at a higher rate. Using a simple model maximizing the rate of energy gain per unit time taken to search for and hoard the nuts at different distances from the source, we discuss whether squirrels alter the transport distance of hoarding nuts according to cache survival rate and/or nut availability. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed1999

C-Type natriuretic peptide/guanylate cyclase B system in rat osteogenic ROB-C26 cells and its down-regulation by dexamethazone.

There is recent evidence that natriuretic peptides are important regulators of bone and cartilage, although they were originally identified as the cardiac hormones causing natriuresis and hypotension. Three members of natriuretic peptide family are known: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biologically active receptors for these peptides are particulate guanylate cyclases; the two known types are GC-A and GC-B. ANP and BNP have high affinities for GC-A, and CNP is the preferred ligand for GC-B. In this paper we report the results of our study of the expression and possible role(s) of natriuretic peptides in the ROB-C26 cell, which is an osteogenic cell line with multiple potentials for differentiating into myoblast, osteoblast, and adipocyte. ROB-C26 cells produced cGMP in response to natriuretic peptides at both their basal state and after enhanced differentiation into osteoblast which was induced by bone morphogenetic protein [(BMP)-2]. CNP was far more potent than ANP in cGMP production. In contrast, enhanced differentiation into adipocyte by dexamethasone resulted in the marked decrease in their responsiveness to natriuretic peptides. Although the messages for GC-A and GC-B were demonstrated by Northern blot analysis at both the basal stage and after BMP treatment, they were down-regulated after dexamethasone treatment. The presence of CNP was shown by RT-PCR and immunohistochemistry in ROB-C26 cells. C3H10T1/2, which is another and more primitive mesenchymal cell line, also produced cGMP in response to CNP, and less potently to ANP. Culturing ROB-C26 cells with CNP or 8-bromo cGMP decreased [(3)H]thymidine uptake and slightly increased the message for alkaline phosphatase, which is a marker for osteoblast differentiation. These results suggest that the CNP/GC-B system is preferentially expressed in the cells of osteogenic lineage and their expression is down-regulated with differentiation into adipocyte lineage. The CNP/GC-B system is likely to be an autocrine/paracrine regulator of osteoblast growth and differentiation.

Alkaline Phosphatase↗