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Biomedical subjects

M Fujimoto

Publications and source records attributed to M Fujimoto.

At least 145 records · Page 8Linked to original sources
PubMed1999

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents: special references to bacteria isolated between July 1996 and June 1997].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 20 facilities in Japan since July 1982. This paper describes the results obtained during period from July 1996 to June 1997. The number of cases investigated as objectives was 217 for one year. A total of 406 strains were isolated from 177 cases (81.6% of total cases). From primary infections 162 strains were isolated, and from postoperative infections 244 strains were isolated, respectively. From primary infections, anaerobic bacteria were predominant, while from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was the highest. In postoperative infections, the majority of them were Enterococcus faecalis, while in primary infections, many of them were Enterococcus avium. The isolation rate of Staphylococcus spp., especially from postoperative infections, followed that of Enterococcus spp. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli and Enterobacter cloacae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. The isolation rate of aerobic Gram-negative bacillus has decreased with time, while those of anaerobes like B. fragilis group and of aerobic Gram-positive bacteria have gradually increased in both types of infections. We found vancomycin-resistant strains of neither Staphylacoccus aureus nor Enterococcus spp.; however, the MIC of arbekacin for one of strains of S. aureus was 100 micrograms/ml. Both the MIC90's of meropenem and imipenem/cilastatin against P. aeruginosa isolated in this term were 25 micrograms/ml, which were higher than those against the strains isolated in the previous years. Compared with the isolated strains in the year 1995, progress of resistance against carbapenem antibiotics was confirmed.

Anti-Bacterial Agents↗
PubMed1999

Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.

BACKGROUND: Butyrate, a fermentation product of intestinal bacteria, modifies chromatin structure through histone acetylation, thereby altering gene transcription. IL-8 and MCP-1 are chemokines, expressed by intestinal epithelial cells, which attract neutrophils and monocytes, respectively. We hypothesized that butyrate may alter IL-8 and MCP-1 expression by intestinal epithelial cells through histone acetylation. MATERIALS AND METHODS: IL-8 and MCP-1 expression was measured by ELISA and RNA transfer blots. Acetylated histones were separated on acetic acid-urea-triton gels. Butyrate was compared to Trichostatin-A, a specific inhibitor of histone deacetylase and to other short chain fatty acids. RESULTS: Caco-2 cells constitutively secreted MCP-1 but not IL-8. Butyrate reversibly decreased MCP-1 secretion. In contrast, butyrate increased IL-8 production. The effects of butyrate and Trichostatin-A were greater when cells were stimulated with IL-1beta. Butyrate and Trichostatin-A both increased histone acetylation. Trichostatin-A and other short chain fatty acids altered chemokine secretion according to their effect on histone acetylation. CONCLUSIONS: Butyrate reversibly switches chemokine secretion by epithelial cells through histone acetylation. We speculate that butyrate carries information from resident bacteria to epithelial cells. Epithelial cells transduce this signal through histone acetylation, modulating the secretion of chemokines.

Acetylation↗
PubMed1998

Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice.

Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signal pathway is an important component of cytokine signaling. We have previously shown that STAT3 induces a molecule designated as SSI-1, which inhibits STAT3 functions. To clarify the physiological roles of SSI-1 in vivo, we generated, here, mice lacking SSI-1. These SSI-1-/- mice displayed growth retardation and died within 3 weeks after birth. Lymphocytes in the thymus and spleen of the SSI-1-/- mice exhibited accelerated apoptosis with aging, and their number was 20-25% of that in SSI-1+/+ mice at 10 days of age. However, the differentiation of lymphocytes lacking SSI-1 appeared to be normal. Among various pro- and anti-apoptotic molecules examined, an up-regulation of Bax was found in lymphocytes of the spleen and thymus of SSI-1-/- mice. These findings suggest that SSI-1 prevents apoptosis by inhibiting the expression of Bax.

Animals↗
PubMed1998

Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling.

Cytokine-inducible protein SSI-1 [signal transducers and activators of transcription (STAT)-induced STAT inhibitor 1, also referred to as SOCS-1 (suppressor of cytokine signaling 1) or JAB (Janus kinase-binding protein)] negatively regulates cytokine receptor signaling by inhibition of JAK kinases. The SSI family of proteins includes eight members that are structurally characterized by an SH2 domain and a C-terminal conserved region that we have called the SC-motif. In this study, we investigated the roles of these domains in the function of SSI-1. Results of reporter assays demonstrated that the pre-SH2 domain (24 aa in front of the SH2 domain) and the SH2 domain of SSI-1 were required for the suppression by SSI-1 of interleukin 6 signaling. Coexpression studies of COS7 cells revealed that these domains also were required for inhibition of three JAKs (JAK1, JAK2, and TYK2). Furthermore, deletion of the SH2 domain, but not the pre-SH2 domain, resulted in loss of association of SSI-1 with TYK2. Thus, SSI-1 associates with JAK family kinase via its SH2 domain, and the pre-SH2 domain is required for the function of SSI-1. Deletion of the SC-motif markedly reduced expression of SSI-1 protein in M1 cells, and this reduction was reversed by treatment with proteasome inhibitors, suggesting that this motif is required to protect the SSI-1 molecule from proteolytic degradation. Based on these findings, we concluded that three distinct domains of SSI-1 (the pre-SH2 domain, the SH2 domain, and the SC-motif) cooperate in the suppression of interleukin 6 signaling.

Amino Acid Sequence↗
PubMed1998

Cervical lesions related to the systemic progression in rheumatoid arthritis.

STUDY DESIGN: Cross-sectional study of cervical involvement in rheumatoid arthritis. OBJECTIVES: To clarify the correlation between the deterioration of cervical lesions and the systemic progression of rheumatoid arthritis. SUMMARY OF BACKGROUND DATA: The natural course of cervical lesions varies. To date, no systemic parameter has been clarified to predict the progression. METHODS: One hundred seventy-three patients with rheumatoid arthritis participated in this study. The authors studied the progression of cervical lesions and investigated the relation between the types of cervical subluxation at the end of study and the following four variables: the serum level of C-reactive protein, the number of joints with erosion, carpal height ratio, and disease subset (least erosive subset, more erosive subset, and mutilating disease subset). RESULTS: Of the 173 patients, 55 already had cervical subluxation before entering the study. During the follow-up period, 44 patients deteriorated radiographically, and 77 (45%) had cervical involvement, including involvement of upper cervical lesions in 65 patients, upper lesions combined with subaxial subluxation in 10, and subaxial subluxation alone in 2. The upper cervical subluxation progressed in the order of anterior atlantoaxial subluxation, atlantoaxial subluxation combined with vertical subluxation, and vertical subluxation alone. Deterioration of upper cervical lesion and occurrence of subaxial subluxation were closely correlated with an elevation of serum C-reactive protein level, an increase in the number of joints with erosion, and a decrease in the carpal height ratio. The incidence of cervical involvement and the extent of deterioration were different among the disease subsets. CONCLUSIONS: The serum level of C-reactive protein, the number of joints with erosion, and the carpal height ratio correlated closely with the extent of the cervical subluxation. The average C-reactive protein values during the follow-up period correlated with progression of the cervical lesions. The classification of rheumatoid disease subset was useful for predicting the terminal feature of the cervical lesions.

Adolescent↗
PubMed1998

Characterization of electrogenic Na/K pump in rat neostriatal neurons.

The electrogenic Na/K pump current (Ip) was studied in the dissociated neostriatal neurons of the rat by using the nystatin-perforated patch recording mode. The Ip was activated by external K+ in a concentration-dependent manner with an EC50 of 0.7 mM at a holding potential (VH) of -40 mV. Other monovalent cations also caused Ip and the order of potency was Tl+>K+, Rb+>NH4+, Cs+>>>Li+. The Ip decreased with membrane hyperpolarization in an external solution containing 150 mM Na+, while the Ip did not show such voltage dependency without external Na+. Ouabain showed a steady-state inhibition of Ip in a concentration- and temperature-dependent manner at a VH of -40 mV. The IC50 values at 20 and 30 degrees C were 7.1 x 10(-6) and 1.3 x 10(-6) M, respectively. The decay of Ip after adding ouabain well fitted with a single exponential function. At a VH of -40 Mv, the association (k+1) and dissociation (k-1) rate constants estimated from the time constant of the current decay at 20 degrees C were 4.0 x10(2) s-1 M-1 and 6.3 x 10(-3) s-1, respectively. At 30 degrees C, k+1 increased to 2.8 x 10(3) s-1 M-1 while k-1 showed no such change with a value of 1.8 x 10(-3) s-1. A continuous Na+ influx was demonstrated by both the Na+-dependent leakage current and tetrodotoxin-sensitive Na+ current, which resulted in the continuous activation of the Na/K pump. It was thus concluded that the Na/K pump activity was well-maintained in the dissociated rat neostriatal neurons with distinct functional properties and that the activity of the pump was tightly connected with Na+ influxes.

Animals↗
PubMed1998

Loss of material from chromosome arm 1p during malignant progression of meningioma revealed by fluorescent in situ hybridization.

BACKGROUND: Atypical and anaplastic meningiomas tend to recur and to invade adjacent brain, bone, and skin. They also can metastasize to extracranial organs such as the lung, liver, or bone, causing death. Recent reports have indicated that allelic deletion of chromosome 1p is associated with malignant progression of meningiomas. METHODS: Cytogenetic analysis of 37 meningiomas was performed using double-target fluorescent in situ hybridization (FISH) and focusing on chromosome arm 1p. The meningioma series included 17 benign meningiomas, 11 atypical meningiomas, and 9 anaplastic meningiomas. FISH was performed with pericentromeric (1q12) and subtelomeric (1p36) DNA probes to cell nuclei prepared from surgically extirpated tumor samples. RESULTS: A high incidence of deletion of at least part of 1p was observed in 60.0% of atypical and 85.7% of anaplastic meningiomas. Furthermore, statistically significant differences were found with respect to these data between benign versus atypical/anaplastic meningiomas. In four cases both primary and recurrent tumors from the same patient also were investigated for allelic status. CONCLUSIONS: The results of the current study support the existence of tumor suppressor gene(s) on 1p associated with malignant progression of meningioma, and suggest that detection of the allelic status of chromosome 1p by FISH may assist physicians in predicting the clinical prognosis of patients affected by this type of brain tumor.

Adult↗
PubMed1998

Characterization of an element positively regulating the transcription of MSSP gene-2 which encodes C-MYC binding proteins.

MSSP gene-2 encodes at least three alternative splicing products, MSSP-1, MSSP-2, and Scr2, which have been implied to function as factors regulating DNA replication, transcription, apoptosis induction, and cell-cycle movement, via the interaction with C-MYC. We have previously shown that the Mup1 sequence from -474 to -440 in the region required for transactivation of the MSSP gene-2 was protected from DNaseI digestion in vitro. Here, we report that the Mup1 sequence carries a positive transcriptional activity, and that the activity was lost by point mutations that inhibited the formation of specific nucleoprotein complexes on the sequence. In Southwestern analyses, two proteins of 38 and 62kDa directly interacted with the Mup1 sequence.

Alternative Splicing↗
PubMed1998

Endothelin ET(B) receptors show different binding profiles in intact cells and cell membrane preparations.

We examined the affinity of endothelin-1, endothelin-3 and four endothelin receptor ligands, BQ788 (cis-2,6-dimethylpiperidinocarbonyl-gamma-methyl-Leu-D-Trp(1-CO 2CH3-D-Nle-ONa), SB-209670 ((+)-(1S,2R,3S)-3-(2-carboxymethoxy-4-methoxyphenyl)-1-(3,4-methylenedio xyphenyl)-5-(prop-1-yloxy)indane-2-carboxylic acid), IRL-1620 (succinyl-[Glu9,Ala11,15]endothelin-1(8-21)), and L-749329 (3',4'-methylenedioxy-1-(2-propyl-4-carboxyphenoxy)-N-(4-isopropyl -phenylsulfonyl)-benzene acetamide), for endothelin ET(B) receptors in human and rat heart cells. The affinities of these ligands showed good correlation between both types of living cells and between their membrane preparations (r = 0.861, P < 0.001), but less significant correlation between each of the living cells and its respective membrane preparation (r = 0.569, 0.02 < P < 0.05). These results suggest that there is no species difference in the affinities of these ligands and that destruction of the intact cell membrane structure may lead to changes in binding properties of the endothelin ET(B) receptor.

Animals↗
PubMed1998

Origin and mechanism of formation of 45,X/47,XX,+21 mosaicism in a fetus.

Chromosome analysis of amniotic fluid cells from a 17-week-old fetus with a nuchal cystic hygroma showed a 45,X/47,XX,+21 karyotype. Analyses of cord blood lymphocytes, skin fibroblasts, amniotic membrane, and chorionic villi demonstrated both cell lines in various proportions. We studied the origin and mechanism of formation of the double mosaic aneuploid using Q-banded chromosomal heteromorphisms, and one RFLP, two VNTRs, one tetranucleotide repeat, 28 CA repeat markers, mapped to every member of chromosomes. The heteromorphic markers examined showed no discordant patterns in parent-to-child transmission or between the two cell lines except for those in chromosomes 21 and X. Fetal DNA was extracted from its established monoclonal fibroblast cell lines with 45,X or 47,XX,+21 karyotypes. Genotyping with the DNA markers showed that each cell line was identical at every locus, except for chromosome 21 or X loci, indicating that the fetus was not a chimera but a mosaic. The 21-trisomic cells had one paternal allele and two maternal heterozygous alleles at the D21S270 locus, and the 45,X (21-disomic) cells had two biparental alleles. Alleles at two X chromosomal loci, DXS991 and DXS8057, were biparental in the 47,XX,+21 cells, whereas only the paternal allele was retained in the 45,X cells. Based on these findings, we concluded that the fetus started as a 47,XX,+21 zygote that had resulted from nondisjunction at the maternal first meiotic division and that one each of the maternally derived chromosomes 21 and X was lost during an early mitotic division, leading to the mosaicism.

Alleles↗
PubMed1998

Binding characterization of [3H]S-0139, an antagonist of the endothelin ET(A) receptor subtype.

S-0139 (27-O-3-[2-(3-carboxy-acryloylamino)-5-hydroxyphenyl]-acryloylo xy myricerone, sodium salt) is a highly specific nonpeptide endothelin ET(A) receptor antagonist. The binding of [3H]S-0139 was compared to that of [125I]endothelin-1 to characterize the binding of the antagonist in porcine aortic smooth muscle membranes. Scatchard analysis revealed a single class of [3H]S-0139 binding sites with a Kd value of 0.61 +/- 0.10 nM and a Bmax of 0.72 +/- 0.16 pmol/mg protein. These sites were saturable and reversible. [125I]Endothelin-1 also showed binding with high affinity (Kd = 0.12 +/- 0.02 nM) to a homogeneous population of binding sites, whose Bmax (0.71 +/- 0.20 pmol/mg protein) was almost the same as that for [3H]S-0139. In both cases, the binding could be displaced by known endothelin receptor ligands and their IC50 values in each case showed a very close correlation (r = 0.986). The potency of seven endothelin receptor antagonists to displace [3H]S-0139 binding also correlated highly to the potency for inhibiting the endothelin-1-induced increase in cytosolic Ca2+ concentration (r = 0.949). Myriceric acid A showed a more potent functional activity than expected from its binding affinity, but this seemed to result from the different assay conditions, such as incubation time. Together, the results suggest that S-0139 labels only endothelin ET(A) receptor binding sites in porcine aortic smooth muscle.

Animals↗
PubMed1998

Isolation and characterization of a novel bioactive peptide, Carassius RFamide (C-RFa), from the brain of the Japanese crucian carp.

A novel bioactive peptide with the C-terminal RFamide was isolated from the brain of the Japanese crucian carp, Carassius auratus langsdorfii, by using the intestine of the fish as the bioassay system. The primary structure of the peptide was determined to be SPEIDPFWYVGRGVRPIGRFamide and it was designated Carassius RFamide (C-RFa). The sequence of C-RFa was found to be significantly homologous to the molluscan neuropeptide termed Achatina cardioexcitatory peptide 1 (ACEP-1). Both peptides have RPXGRFamide structure in their C-terminal moieties. C-RFa was found to have an excitatory effect on visceral muscle tissues of fish, newt, quail, and rat. In the stomach of the fish, Zacco temminckii, IGRFamide (C-RFa 17-20) was shown to be the minimal structure required for the excitatory effect and PIGRFamide (C-RFa 16-20) to be almost equipotent with the parent peptide C-RFa.

Amino Acid Sequence↗
PubMed1998

Evidence of intra- and extracellular modifications of monoclonal IgG polypeptide chains generating charge heterogeneity.

The heavy and light chains of IgG monoclonal antibodies (mAbs) can be shown to be heterogeneous, with respect to isoelectric points, when analyzed by two-dimensional electrophoresis (2-DE). The molecular basis for this charge heterogeneity has not been clearly defined but it has been suggested that it could be due, in part, to differences in glycosylation. To investigate this possibility we have compared the 2-DE pattern of glycosylated and aglycosylated forms of the mouse IgG1 mAb (1B7-11), produced in vitro in the presence and absence of tunicamycin. Charge heterogeneity was shown not to be a consequence of glycosylation status. Intracellular and secreted IgG mAbs were also analyzed to investigate the time course of change in charge properties of the heavy and light chains. The charge heterogeneity was found to be generated intracellularly, and alterations in charge properties could be induced during incubation under physiological conditions. Semilogarithmic plots of the density of the principal heavy and light chain spots against incubation time showed linear relationships, suggesting that the charge shifts result from a first-order reaction. The semilogarithmic plot for the light chain correlated well with the time after IgG synthesis. These results suggest that the charge heterogeneity of an IgG mAb is due to intra- and extracellular modifications of the polypeptide chains which reflect "aging" of antibody molecules.

Animals↗
PubMed1998

Analysis of heat shock-induced monophosphorylation of stathmin in human T lymphoblastic cell line JURKAT by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis (2-DE) was used to study alterations in intracellular proteins of the human T lymphoblastic cell line JURKAT by heat shock at 45 degrees C for 30 min. The 2-DE patterns indicated an increase in the amount of a spot of molecular weight (M(r)) 18,500 and isoelectric point (pI) 5.6, which was a monophosphorylated form of stathmin. Stathmin is a major substrate for a proline-rich peptide-specific serine protein kinase, a mitogen-activated protein kinase, however, the enzyme was not activated by the heat shock. Further examinations of the effects of cAMP, phorbol myristate acetate, cyclosporin A, and staurosporine on phosphorylation suggest that cyclin-dependent kinases might be responsible for the heat shock-induced monophosphorylation of stathmin.

Amino Acid Sequence↗
PubMed1998

CD19 regulates B lymphocyte responses to transmembrane signals.

CD19 is a component of a cell surface receptor complex that regulates B lymphocyte responses to transmembrane signals including those generated through the B cell antigen receptor. Studies in mice which lack or overexpress CD19 show that changes in CD19 expression levels have significant effects on B cell development and function. Recent studies suggest that CD19 establishes a Src-family kinase activation loop that amplifies tyrosine phosphorylation of numerous downstream effector molecules including potentially positive and negative regulatory elements. These observations provide an understanding of how CD19 governs the molecular ordering and intensity of signals transduced through multiple B cell receptors.

Animals↗
PubMed1998

Serum concentrations of carboxyterminal propeptide of type 1 procollogen and tissue inhibitor of metalloproteinase 1 in patients with dermatomyositis.

Serum levels of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type I procollagen (PINP) have been used as indices of collagen synthesis in patients with various fibrotic diseases during the active stages. One of the suggested contributory factors to the development of tissue fibrosis is a decrease in collagenase activity, which may be related to levels of serum tissue inhibitors of metalloproteinases-1 (TIMP-1). In this study, the serum levels of PICP and PINP in 20 patients with dermatomyositis and 29 control subjects and of TIMP-1 in 29 patients with dermatomyositis and 29 control subjects were measured using an enzyme-linked immunosorbent assay (ELISA) or a radioimmunoassay (RIA). We found that the mean PICP level in patients with dermatomyositis was significantly higher than that in normal controls (mean +/- SD 326+/-76 ng/ml vs 135+/-88 ng/ml; P < 0.001). In 60% of dermatomyositis patients, the serum PICP level was elevated (more than 311 ng/ml, i.e. 2 x SD above the mean control value). Elevated serum PICP levels were correlated with the incidence of elevated serum creatine kinase levels in patients with dermatomyositis. The serum concentration of PINP was not elevated in comparison with that of the normal control subjects (mean +/- SD 36+/-30 ng/ml vs 63+/-34 ng/ ml). The mean TIMP-1 level in the patients with dermatomyositis was also significantly higher than in the normal control subjects (mean +/- SD 438+/-328 ng/ml vs 163+/-63 ng/ml; P < 0.001). In 59% of dermatomyositis patients, the mean serum TIMP-1 level was elevated (more than 289 ng/ml, i.e. 2 x SD above the mean control value). Serum PICP and TIMP-1 levels might be useful for detecting disease activity or severity in dermatomyositis.

Adolescent↗
PubMed1998

The gene for mesomelic dysplasia Kantaputra type is mapped to chromosome 2q24-q32.

Mesomelic dysplasia Kantaputra type (MDK) (MIM *156232) is a new autosomal dominant skeletal dysplasia characterized by dwarfism, shortening of the forearms/lower-legs, carpal/tarsal synostosis, and dorsolateral foot deviation. We studied a Thai family in which 15 members in 3 generations were affected with MDK. With reference to the breakpoints of a balanced translocation [t(2;8)(q31;p21)] in patients from a previously reported Italian family with a skeletal dysplasia that appears similar to MDK, a linkage analysis was performed in the Thai family using 50 CA-repeat markers mapped to nearby regions (2q22-q34 and 8p24-p21) of the translocation breakpoints. The results clearly ruled out a linkage of MDK to marker loci at the 8p24-p21 region, whereas all nine affected members available for the study shared a haplotype at four loci (D2S2284, D2S326, D2S2188, and D2S2314) spanning about 22.7 cM in the 2q24-q32 region. The computer-assisted two-point linkage analysis revealed maximum logarithm of odds (lod) scores of 4.82, 4.21, 4.82, and 4.21 (theta = 0) at these loci, respectively. These data indicated that the MDK locus is in the vicinity of D2S2284 and D2S2188 loci that are most likely mapped to 2q24-q32.

Chromosome Mapping↗