Biomedical subjects

Masashi Suzuki

Publications and source records attributed to Masashi Suzuki.

At least 37 records · Page 2Linked to original sources

PubMed2005

Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles.

We quantified the mRNA expression of all 22 fibroblast growth factor family members (FGF) and their four receptors (FGFR) in adult mouse full-thickness skin at various stages of the hair growth cycle. We found that in addition to mRNA encoding FGF previously identified in skin (FGF1, 2, 5, 7, 10, 13, and 22), FGF18 mRNA was also strongly expressed. Expression of these FGF varied throughout hair growth cycle: mRNA expression of FGF18 and 13 peaked at telogen; FGF7 and 10 at anagen V; and FGF5 and 22 at anagen VI. In situ hybridization revealed that FGF18 mRNA is mainly expressed in the anagen inner root sheath and telogen bulge of hair follicles. In culture, FGF18 stimulated DNA synthesis in human dermal fibroblasts, dermal papilla cells, epidermal keratinocytes and vascular endothelial cells. When FGF18 was administered subcutaneously to mice in a uniform telogen state, anagen hair growth was observed. Our findings suggest that FGF18 is important for the regulation of hair growth and the maintenance of skin in adult mice.

Animals↗

PubMed2005

Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice.

The highly ordered process of wound healing involves the coordinated regulation of cell proliferation and migration and tissue remodeling, predominantly by polypeptide growth factors. Consequently, the slowing of wound healing that occurs in the aged may be related to changes in the activity of these various regulatory factors. To gain additional insight into these issues, we quantified the absolute copy numbers of mRNAs encoding all the fibroblast growth factors (FGFs), their receptors (FGFRs) and two other growth factors in the dorsal skin of young and aged mice during the healing of full-thickness skin excisional wounds. In young adult mice (8 weeks old), FGF7, FGF10 and FGF22 mRNAs were all strongly expressed in healthy skin, and levels of FGF7 and 10 but not 22 increased 2- to 3.5-fold over differing time courses after wounding. The levels of FGF9, 16, 18 and especially 23 mRNAs were moderate or low in healthy skin but increased 2- to 33-fold after wounding. Among the four FGFRs, expression of only FGFR1 mRNA was augmented during wound healing. Expression of transforming growth factor-beta and hepatocyte growth factor was also high in healthy skin and was upregulated during healing. Notably, in aged mice (35 weeks old), where healing proceeded more slowly than in the young, both the basal and wound-induced mRNA expression of most of these genes was reduced. While these results confirm the established notion that FGFR2 IIIB ligands (FGF7 and FGF10) are important for wound healing, they also suggest that decreased expression of multiple FGF ligands contributes to the slowing of wound healing in aged mice and indicate the potential importance of further study of the involvement of FGF9, 16, 18 and 23 in the wound healing process.

Actins↗

PubMed2005

Stereotactic radiosurgery for recurrent pleomorphic adenoma invading the skull base--case report--.

A 38-year-old man presented with a recurrent pleomorphic adenoma in the parapharyngeal space invading the skull base 19 years after the first operation for a parotid gland tumor. Stereotactic radiotherapy was performed to control the tumor growth using a marginal dose of 8 Gy and maximum dose of 18 Gy with care taken to minimize the dose to nearby structures. The symptoms were reduced within a few months. Magnetic resonance imaging over 5 years showed that the tumor was controlled with no regrowth. Stereotactic radiotherapy is a therapeutic option for the treatment of pleomorphic adenomas.

Adenoma, Pleomorphic↗

PubMed2005

[Serum calcium levels at first renal replacement therapy and patients survival].

In K/DOQI guideline, albumin adjusted serum calcium concentrations between 8.4 to 9.5 mg/dL and serum phosphorus concentrations between 3.5 to 5.5 mg/dL are recommended. But without clinical symptoms relating to hypocalcemia, medication for increasing serum calcium levels is not needed even less than 8.4 mg/dL. To clarify this guideline, we examined the data of 271 patients who started dialysis at Shinrakuen Hospital, their medication before renal replacement therapy and life prognosis. Medication made higher serum calcium concentrations (p< 0.005) at first renal replacement therapy. Concerning serum calcium concentrations, the lower group (<8.4 mg/dL) showed significantly better prognosis than the middle group (8.4 to 9.5 mg/dL) and the higher group (>9.5 mg/dL) (p< 0.05). When serum calcium levels were adjusted for the level of serum albumin, this tendency was stronger (p< 0.0001). We concluded that although serum calcium concentrations might not need control, nutritional states are far more important before starting dialysis.

Biomarkers↗

PubMed2005

[Prediction of atmospheric Japanese cedar pollen counts in Oita University Faculty of Medicine Complex].

BACKGROUND: We investigated the method of predicting atmospheric Japanese cedar pollen counts and the first day of pollen release at Oita University Faculty of Medicine Complex in this study. METHOD: We set up a Durham sampler on the roof (30 m from the ground) of Oita University Faculty of Medicine complex and investigated atmospheric pollen counts day by day from January 1 to April 30 from 1990 through 2004. RESULTS: The total pollen counts per year correlated very well with averaged temperature, averaged relative humidity, and the sunshine duration during the previous July. The sunshine duration yielded the highest correlation coefficient. Multiple regression analysis showed the sunshine duration during the previous July and total pollen count of the previous year to be independent predictors of the current year's total pollen counts. Multiple correlation coefficients was 0.9518 (p<0.001). We considered the Hita area to be the source of the pollen, according to meteorological conditions. Prediction of total pollen counts was more accurate if based on factors within the previous 10 years than on factors within the previous 5 years. There was no correlation between the first day of pollen release and averaged temperature in January. Our data also showed that the first day of pollen release could not be predicted by the cumulative thermal constant method and threshold temperature for the development of male Japanese cedar flowers. Multiple regression analysis showed the minimum temperature from November 1 to the first day of pollen release, the date of minimum temperature, and the averaged temperature for the January to be independent predictors of the number of days from January 1 to the first day of pollen release. CONCLUSION: We concluded that it is important to establish a method of predicting atmospheric Japanese cedar pollen counts that is based on the characteristics of each area.

Cryptomeria↗

PubMed2004

Natural saline-flush is sufficient to maintain patency of immobilized-urokinase double-lumen catheter used to provide temporary blood access for hemodialysis.

BACKGROUND: Thrombotic occlusion is a frequent complication of central venous catheters used to provide temporary blood access on hemodialysis therapy. Heparin-lock is conventionally used to maintain patency of the catheter, but the necessity of heparin-lock has not been determined yet. METHODS: After the immobilized-urokinase double-lumen central venous catheter was inserted into 48 Japanese hemodialysis patients, 22 patients randomized to the heparin group received a 20-ml saline-flush, followed by 2 ml of 1,000 U/ml heparin-lock, and 26 patients randomized to the saline group received only the 20-ml saline-flush once a day for each lumen. RESULTS: Thrombotic occlusion was observed in only 1 out of 22 patients in the heparin group and 1 out of 26 patients in the saline group. No significant difference of the catheter survival was observed between the two groups (p = 0.8599). CONCLUSIONS: Natural saline-flush is sufficient for maintaining the patency of an immobilized-urokinase double-lumen central venous catheter.

Aged↗

PubMed2004

Intranasal immunization with outer membrane protein P6 and cholera toxin induces specific sinus mucosal immunity and enhances sinus clearance of nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHi) is one of the leading pathogens in sinusitis. One of the outer membrane proteins of NTHi, P6, is a common antigen to all strains and is an attractive candidate for a subunit bacterial vaccine. In this study, we characterized normal sinus mucosa (SM) and investigated the potential of intranasal immunization with P6 and cholera toxin (CT) for induction of mucosal protective immunity against NTHi in the maxillary sinuses of rats. Intranasal immunization induced P6-specific sinus mucosal and systemic immunological responses, mainly of the IgA and IgG isotype. The protective effect of intranasal immunization was demonstrated by enhancement of sinus clearance of NTHi. The present study showed that unilateral intranasal immunization has a capacity to induce protective immunity against NTHi in the bilateral maxillary sinuses. Systemic administration of the vaccine did not affect sinus clearance of NTHi. These findings suggest that a nasal vaccine might be useful for preventing sinusitis.

Administration, Intranasal↗

PubMed2004

Altered DNA binding specificity of Arnt by selection of partner bHLH-PAS proteins.

The Ah receptor (AhR) and HLF are transcription factors involved in xenobiotic metabolism and hypoxic response, respectively. AhR and HLF heterodimerize with Arnt as the common partner, and bind to asymmetric E-boxes termed XRE and HRE, respectively. In order to investigate nucleotide preference of the heterodimers, reporter plasmids with oligonucleotides for XREs or HREs with systematic mutations were constructed and their activity was determined. Comparison of the activity revealed that DNA length and nucleotide preference recognized by Arnt subunit in the two heterodimers were largely different between XRE and HRE. We expressed AhR-Arnt and HLF-Arnt in Escherichia coli and used them for DNA binding. The dissociation constant of HLF-Arnt-HRE was 10.4 +/- 1.6 nM. Competition activity of mutated XREs or HREs with wild type was consistent with their transcription activity. Bending of XRE and HRE induced by binding of the relevant heterodimers was observed with stronger bending of XRE than of HRE. By deletional and mutational analyses, an alanine and three arginine (Ala 8, Arg 9, Arg 11 and Arg 12) residues in the basic sequence of HLF were found to be indispensable for the transcriptional activity.

Amino Acid Sequence↗

PubMed2004

Enantioselective total synthesis of FR900482.

The development of two approaches for the enantioselective total synthesis of FR900482 is described. A precursor for the formation of the benzazocine ring was assembled effectively by a modification of the Sonogashira coupling of an aryl triflate with a chiral acetylene unit derived from tartaric acid and the subsequent novel ketone formation via conjugate addition of pyrrolidine to the o-nitrophenylacetylene derivative. The first-generation approach to the key pentacyclic intermediate of our racemic total synthesis utilizes an intramolecular Mitsunobu reaction of an omega-hydroxynitrobenzenesulfonamide to form the benzazocine ring and a stepwise sequence to construct the hydroxymethyl group at the C(7) position. The key intermediate could be synthesized in optically pure form via formation of the characteristic hydroxylamine hemiacetal and a stereoselective epoxide formation. In the second-generation approach, the N-hydroxybenzazocine ring could be constructed directly from an omega-formylnitrobenzene derivative by intramolecular reductive hydroxylamination. The crucial stereoselective hydroxymethylation and the formation of the hydroxylamine hemiacetal could be performed efficiently by a one-pot sequence. After leading to the pentacyclic key intermediate, the total synthesis of (+)-FR900482 was accomplished by a modification of our protocol established in the racemic total synthesis. Stereochemical issues involved in the hydroxymethylation at the C(7) position and formation of the hydroxylamine hemiacetal are also discussed in detail.

Antineoplastic Agents↗

PubMed2004

Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization.

Pretreatment with a combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) has been reported to attenuate left ventricular (LV) remodeling after acute myocardial infarction (MI). We here examined whether the cytokine treatment started after MI has also beneficial effects. Anterior MI was created in the recipient mice whose bone marrow had been replaced with that of transgenic mice expressing enhanced green fluorescent protein (GFP). We categorized mice into five groups according to the following treatment: 1) saline; 2) administration of G-CSF and SCF from 5 days before MI through 3 days after; 3) administration of G-CSF and SCF for 5 days after MI; 4) administration of G-CSF alone for 5 days after MI; 5) administration of SCF alone for 5 days after MI. All the three treatment groups with G-CSF showed less LV remodeling and improved cardiac function and survival rate after MI. The number of capillaries, which express GFP, was increased and the number of apoptotic cells was decreased in the border area of all the treatment groups with G-CSF. Even if the cytokine treatment is started after MI, it could prevent LV remodeling and dysfunction after MI--at least in part--through an increase in neovascularization and a decrease in apoptosis in the border area.

Animals↗

PubMed2004

The archaeal feast/famine regulatory protein: potential roles of its assembly forms for regulating transcription.

The classification feast/famine regulatory proteins (FFRPs) encompasses archaeal DNA-binding proteins with Escherichia coli transcription factors, the leucine-responsive regulatory protein and the asparagine synthase C gene product. In this paper, we describe two forms of the archaeal FFRP FL11 (pot0434017), both assembled from dimers. When crystallized, a helical cylinder is formed with six dimers per turn. In contrast, in solution, disks are formed, most likely consisting of four dimers each; an observation by cryoelectron microscopy. Whereas each dimer binds a 13-bp sequence, different forms will discriminate between promoters, based on the numbers of repeating 13-bp sequences, and types of linkers inserted between them, which are either of 7-8 or approximately 18 bp. The amino acid sequences of these FFRPs are designed to form the same type of 3D structures, and the transition between their assembly forms is regulated by interaction with small molecules. These considerations lead us to propose a possible mechanism for regulating a number of genes by varying assembly forms and by combining different FFRPs into these assemblies, responding to environmental changes.

Amino Acid Sequence↗

PubMed2004

Role of Na+-Ca2+ exchanger in myocardial ischemia/reperfusion injury: evaluation using a heterozygous Na+-Ca2+ exchanger knockout mouse model.

We used Na(+)-Ca(2+) exchanger (NCX) knockout mice to evaluate the effects of NCX in cardiac function and the infarct size after ischemia/reperfusion injury. The contractile function in NCX KO mice hearts was significantly better than that in wild type (WT) mice hearts after ischemia/reperfusion and the infarct size was significantly small in NCX KO mice hearts compared with that in WT mice hearts. NCX is critically involved in the development of ischemia/reperfusion-induced myocardial injury and therefore the inhibition of NCX function may contribute to cardioprotection against ischemia/reperfusion injury.

Animals↗

PubMed2004

Origins of protein stability revealed by comparing crystal structures of TATA binding proteins.

The crystal structure of TATA binding protein (TBP) from a mesothermophilic archaeon, Sulfolobus acidocaldarius, has been determined at a resolution of 2.0 A with an R factor of 20.9%. By comparing this structure with the structures of TBPs from a hyperthermophilic archaeon and mesophilic eukaryotes, as well as by comparing amino acid sequences of TBPs from archaea, covering a wide range of optimum growth temperatures, two significant determinants of the stability of TBP have been identified: increasing the interior hydrophobicity by interaction between three residues, Val, Leu, and Ile, with further differentiation of the surface, and increasing its hydrophilicity and raising the cost of unfolding. These findings suggest directions along which the stability of TBP can be engineered.

Amino Acid Sequence↗

PubMed2004

Mutations in components of the Wnt signaling pathway in adenoid cystic carcinoma.

The Wnt signaling pathway is essential for normal development and organogenesis. However, inappropriate activation of Wnt signaling, which results in the nuclear translocation of beta-catenin, is associated with the development of various types of neoplasm. In this study, we investigated possible mutations in the genes for components of this pathway, namely, CTNNB1 (the gene for beta-catenin), AXIN1, and APC, in adenoid cystic carcinoma, by PCR, analysis of single-strand conformational polymorphism, and sequencing. Among a total of 20 cases of adenoid cystic carcinoma, seven cases (35%) were associated with mutations in one or more of these three components. A mutation in CTNNB1 was detected in one case. Five cases, including the case with a mutation in CTNNB1, were associated with missense mutations in AXIN1. An aberration in the mutation cluster region of APC was detected in two cases. Mutations trended to be detected more frequently in adenoid cystic carcinoma with solid growth pattern than that with tubular and cribriform growth pattern. In the cases in which we detected mutations, it is possible that the presence of the abnormal products of the mutated genes resulted in the inappropriate activation of the Wnt signaling pathway to tumorigenesis and the growth of adenoid cystic carcinoma.

Adenomatous Polyposis Coli Protein↗

PubMed2004

Cytokine expression in experimental chronic otitis media with effusion in mice.

OBJECTIVES: Although otitis media with effusion (OME) is still a common disease in children and adults, the pathogenesis is not yet fully understood. We studied the effects of intratympanic injection with endotoxin purified from nontypeable Haemophilus influenzae on the characteristics of middle ear effusion (MEE). METHODS: Murine model of OME was developed by eustachian tube (ET) blockage followed by intratympanic inoculation with endotoxin (endotoxin group) or saline (control group). The mice were decapitated and histological changes and the production of inflammatory cytokines in MEEs were examined 3 days, 2 weeks, and 2 months after injection. RESULTS: All mice showed OME until 2 months after ET blockage. Most MEEs in the control group were serous, and mucoid or pultaceous MEEs were found only in the endotoxin group. Subepithelial space of middle ear mucosa was severely thickened with the infiltration of a large number of mononuclear cells in the endotoxin group. The levels of tumor necrosis factor-alpha (TNF-alpha) in MEEs were significantly higher in the endotoxin group than in the control group at all time points. Further, in situ hybridization showed that TNF-alpha messenger RNA was expressed not only by leukocytes and macrophages in MEEs but mononuclear cells present in the subepithelial space of middle ear mucosa. CONCLUSIONS: These results indicate that ET blockage is essential for the induction of serous MEE and additional administration of endotoxin is associated with the production of mucoid MEE accompanied by histological changes with inflammatory cell infiltration and cytokine production in the tympanic cavity.

Animals↗

PubMed2004

Bulge- and basal layer-specific expression of fibroblast growth factor-13 (FHF-2) in mouse skin.

A variety of polypeptide growth factors are involved in the dynamic maintenance of the skin and hair. Here, we demonstrate the presence of high levels of fibroblast growth factor (FGF)-13 in the bulge region of hair follicles. Using real-time PCR, we found that expression of FGF-13 mRNA is comparable to, or higher than, that of other FGF known to regulate hair growth and wound healing. To gain additional insight into the function of FGF-13, we evaluated its distribution using in situ hybridization and immunohistochemical staining. Unlike other FGF, the distribution of FGF-13 mRNA and protein in adult mice was mainly restricted to cells in the bulge region of hair follicles, although lower levels were detected with less frequency in keratinocytes in the basal layer of the epidermis. FGF-13 protein was detectable in the bulge region throughout the hair growth cycle, but its distribution was especially wide during telogen and early anagen. During hair follicle morphogenesis in newborn mice, FGF-13 protein was first detected in the bulge region and basal layer keratinocytes 3 d after birth. These findings suggest that FGF-13 may play a role in regulating the function of cells in the bulge region and basal layer of the epidermis.

Age Factors↗

PubMed2004

Loss of function of 3-hydroxy-3-methylglutaryl coenzyme A reductase 1 (HMG1) in Arabidopsis leads to dwarfing, early senescence and male sterility, and reduced sterol levels.

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) catalyzes the first committed step in the cytosolic isoprenoid biosynthesis pathway in higher plants. To understand the contribution of HMGR to plant development, we isolated T-DNA insertion mutants for HMG1 and HMG2. The hmg1 and hmg2 mutants were both more sensitive than the wild type (WT) to lovastatin, an inhibitor of HMGR. The hmg2 mutant showed no visible phenotype under normal growth conditions. In contrast, the hmg1 mutant exhibited dwarfing, early senescence, and sterility. Expression of senescence-associated genes 12 (SAG12), a marker gene for senescence, was induced in the hmg1 mutant at an earlier stage than in the WT. Levels of trans-cytokinins--hormones known to inhibit senescence--were not lower in hmg1. The mutant did not have the typical appearance of brassinosteroid (BR)-deficient mutants, except for a dwarf phenotype, because of the suppression of cell elongation. The expression of several genes involved in cell elongation was suppressed in hmg1. WT plants treated exogenously with inhibitors of sterol biosynthesis had similar gene expression and sterility characteristics as the hmg1 mutants. Pleiotropic phenotypes were rescued by feeding with squalene, the precursor of sterols and triterpenoids. The sterol levels in hmg1 mutants were lower than in the WT. These findings suggest that HMG1 plays a critical role in triterpene biosynthesis, and that sterols and/or triterpenoids contribute to cell elongation, senescence, and fertility.

Arabidopsis↗

PubMed2004

Arresting dialysis-related amyloidosis: a prospective multicenter controlled trial of direct hemoperfusion with a beta2-microglobulin adsorption column.

We investigated the clinical efficacy of direct hemoperfusion with a beta2-microglobulin (beta2-m) adsorption column for the treatment of patients with dialysis-related amyloidosis. A 2-year prospective controlled study was performed to compare the effects of passaging blood through a (beta2-m) adsorption column (Lixelle) before it is passaged through the dialysis polysulfone membrane on the severity of amyloidosis in these individuals. Patients (n = 22) whose blood went through the Lixelle column prior to dialysis had a higher beta2-m removal rate compared to an equal number of controls, and they showed earlier improvement in their symptoms which included impaired daily activities, joint stiffness, and pain. The appearance of additional bone cysts was prevented in pre-adsorbed patients but not in the controls. Thus, the Lixelle column is useful in preventing the progression of dialysis-related amyloidosis and in ameliorating or arresting the progression of the symptoms of this disorder.

Activities of Daily Living↗