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Biomedical subjects

M Sugimoto

Publications and source records attributed to M Sugimoto.

At least 37 records · Page 2Linked to original sources
PubMed2003

Endoscopic mucosal resection of superficially spreading colonic neoplasms larger than 5 cm in the right colon after injection of dilute sodium hyaluronate: report of two cases.

Submucosal injection is the most important procedure for the safe performance of endoscopic mucosal resection in the large intestine while avoiding the risk of perforation. We used dilute sodium hyaluronate containing Bosmin and achieved safe piecemeal resection of large superficial tumors in the right colon in two patients. Piecemeal snare resection is considered to be acceptable if all the tissue pieces can be collected for histopathological diagnosis.

Colonic Neoplasms↗
PubMed2003

Synaptically activated Cl- accumulation responsible for depolarizing GABAergic responses in mature hippocampal neurons.

It is known that GABA, a major inhibitory transmitter in the CNS, acts as an excitatory (or depolarizing) transmitter transiently after intense GABAA receptor activation in adult brains. The depolarizing effect is considered to be dependent on two GABAA receptor-permeable anions, chloride (Cl-) and bicarbonate (HCO3-). However, little is known about their spatial and temporal profiles during the GABAergic depolarization in postsynaptic neurons. In the present study, we show that the amplitude of synaptically induced depolarizing response was correlated with intracellular Cl- accumulation in the soma of mature hippocampal CA1 pyramidal cells, by using whole cell patch-clamp recording and Cl- imaging technique with a Cl- indicator 6-methoxy-N-ethylquinolinium iodide (MEQ). The synaptically activated Cl- accumulation was mediated dominantly through GABAA receptors. Basket cells, a subclass of fast-spiking interneurons innervating the somatic portion of the pyramidal cells, actually fired at high frequency during the Cl- accumulation accompanying the depolarizing responses. These results suggest synaptically activated GABAA-mediated Cl- accumulation may play a critical role in generation of an excitatory GABAergic response in the mature pyramidal cells receiving intense synaptic inputs. This may be the first demonstration of microscopic visualization of intracellular Cl- accumulation during synaptic activation.

Action Potentials↗
PubMed2002

Diagnosis of Werner syndrome by immunoblot analysis.

Werner syndrome (WS) is caused by mutations in the gene encoding RecQ type DNA helicase (WRN). We report a 53-year-old Japanese male with WS who initially presented with skin ulcers on the feet and the left elbow. The patient had a high-pitched voice, hoarseness, a characteristic bird-like facial appearance with a beak-shaped nose, canities and juvenile cataracts. Immunoblot analysis using a monoclonal antibody directed against the WS gene product DNA helicase revealed that the patient's leucocytes lacked this particular molecule, confirming the diagnosis of WS. This new immunoblot system therefore enables the diagnosis of WS to be made without the need to undertake more complex mutational analysis.

DNA Helicases↗
PubMed2002

Nonrandom X chromosome inactivation in mouse embryos carrying Searle's T(X;16)16H translocation visualized using X-linked LACZ and GFP transgenes.

Only the morphologically normal X chromosome is inactivated in female mice heterozygous for Searle's X-autosome translocation, T(X;16)16H. Here we performed a visual study of the primary and secondary events that culminate in the completely nonrandom inactivation of the X in female embryos having this translocation. The data we have obtained so far indicate that the initial choice of the future inactive X chromosome is biased, with the degree of skewing somewhere between 70:30% and 90:10% in favor of the morphologically normal X chromosome. The majority of genetically unbalanced cells that inactivate a translocated X chromosome are quickly eliminated from the embryo proper by E8.5, although the survival of such cells is sporadically observed thereafter. The initial nonrandom choice demonstrated in this study supports the contention that the T(X;16)16H translocation disrupts one of the loci involved in the randomness of the choice of the future inactive X chromosome. Although the HMG-LACZ transgene in H253 stock mice is an excellent marker of X chromosome inactivation, the present study suggests that it is infrequently de-repressed on the inactive X chromosome.

Animals↗
PubMed2002

KE-758, an active metabolite of the new anti-rheumatic drug KE-298, suppresses production of tumor necrosis factor-alpha and interleukin-1 beta in THP-1, a human monocyte cell line.

KE-758, an active metabolite of KE-298, is a novel sulfhydryl antirheumatic drug. We analyzed the effect of KE-758 on tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta production by a human monocytes cell line (THP-1 cells), stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). We compared the effects with other thiol-modifying antirheumatic drugs such as D-penicillamine, bucillamine and auranofin. THP-1 cells were treated with IFN-gamma for 16 h and were then exposed to LPS for an additional 6 h (for TNF-alpha detection) or 24 h (for IL-1 beta detection). The amounts of TNF-alpha and IL-1 beta in culture supernatants were measured using enzyme-linked immunosorbent assay. KE-758 and auranofin but not D-penicillamine and bucillamine significantly suppressed both TNF-alpha and IL-1 beta. Auranofin suppressed IL-1 beta production by reducing cellular viability. Reverse transcriptase-polymerase chain reaction analysis revealed that the suppressive effect of KE-758 is based on the inhibition of messenger ribonucleic acid expression of TNF-alpha and IL-1 beta. KE-758 had no effect on p75 and p55 soluble TNF receptor production in IFN-gamma and LPS-stimulated THP-1 cells. Thus, KE-758 inhibits both TNF-alpha and IL-1 beta production and its antirheumatic profile is apparently distinct from that of D-penicillamine, bucillamine and auranofin.

Antirheumatic Agents↗
PubMed2001

Cerebellar ataxia associated with heteroallelic ceruloplasmin gene mutation.

BACKGROUND: Aceruloplasminemia, an autosomal recessive disorder that affects human iron metabolism, is caused by mutation of the ceruloplasmin gene. Heterozygous individuals with a partial ceruloplasmin deficiency may have normal iron metabolism and no clinical symptoms. METHODS: The authors clinically characterized three Japanese patients from two families who had cerebellar ataxia with hypoceruloplasminemia from the fourth decade of life. Genetic analysis, restriction fragment length polymorphism analysis, and a pathologic study were performed. RESULTS: All three patients presented with cerebellar dysfunction that included relatively nondisabling gait ataxia and dysarthria, as well as hyperreflexia. Brain and abdomen MRI showed cerebellar atrophy and no low-signal intensities in the basal ganglia, thalamus, and liver. Direct mutational analysis excluded SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, SCA-8, SCA-12, and DRPLA. The patients partially lacked serum ceruloplasmin, and the protein concentrations and ferroxidase activities ranged from 36% to 41% of the control values; moreover, they were heterozygous for a nonsense mutation of the ceruloplasmin gene (Trp858ter). Serum iron concentration and transferrin saturation were normal. At autopsy, pathologic and biochemical examinations showed marked loss of Purkinje cells, a large iron deposition in the cerebellum, and small depositions in the basal ganglia, thalamus, and liver. CONCLUSION: Cerebellar ataxia reflects the site of iron deposition. Being heterozygous for mutation of the ceruloplasmin gene may result in cerebellar ataxia.

Aged↗
PubMed2001

A novel spermatogenesis-related factor-1 gene expressed in maturing rat testis.

A rat gene with testis-specific expression coinciding with spermatogenesis was cloned by differential display. This spermatogenesis-related factor-1 (SRF-1) gene was not expressed in other organs. Testicular expression was detected from 5 weeks of age and increased up to 15 weeks; this level of expression was maintained for 63 weeks. The 750-bp cloned gene was coded for an open reading frame of 202 amino acids. According to in situ hybridization at 7 weeks, this gene was expressed mainly in spermatocyte. The gene product may function as a molecular motor in meiosis, as the deduced amino acid sequence showed partial homology with kinesin-related proteins. The action of this gene and its product with respect to division of reproductive cells requires further investigation.

Amino Acid Sequence↗
PubMed2001

Complete genomic sequence of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120.

The nucleotide sequence of the entire genome of a filamentous cyanobacterium, Anabaena sp. strain PCC 7120, was determined. The genome of Anabaena consisted of a single chromosome (6,413,771 bp) and six plasmids, designated pCC7120alpha (408,101 bp), pCC7120beta (186,614 bp), pCC7120gamma (101,965 bp), pCC7120delta (55,414 bp), pCC7120epsilon (40,340 bp), and pCC7120zeta (5,584 bp). The chromosome bears 5368 potential protein-encoding genes, four sets of rRNA genes, 48 tRNA genes representing 42 tRNA species, and 4 genes for small structural RNAs. The predicted products of 45% of the potential protein-encoding genes showed sequence similarity to known and predicted proteins of known function, and 27% to translated products of hypothetical genes. The remaining 28% lacked significant similarity to genes for known and predicted proteins in the public DNA databases. More than 60 genes involved in various processes of heterocyst formation and nitrogen fixation were assigned to the chromosome based on their similarity to the reported genes. One hundred and ninety-five genes coding for components of two-component signal transduction systems, nearly 2.5 times as many as those in Synechocystis sp. PCC 6803, were identified on the chromosome. Only 37% of the Anabaena genes showed significant sequence similarity to those of Synechocystis, indicating a high degree of divergence of the gene information between the two cyanobacterial strains.

Anabaena↗
PubMed2001

Total synthesis of agosterol A: an MDR-modulator from a marine sponge.

The first total synthesis of agosterol A, a modulator of multidrug resistance (MDR) mediated by P-gp and MRP1, and isolated from a marine sponge, was achieved from ergosterol by utilizing a regioselective epoxy-cleavage reaction and regioselective dehydroxylation as the key reactions.

Animals↗
PubMed2001

Traumatic T9 burst fracture in an 8-month-old infant: incomplete neurologic deficit and its recovery.

STUDY DESIGN: Case report of a rare burst fracture of the ninth thoracic vertebra in an 8-month-old male infant. OBJECTIVES: To describe a rare traumatic lesion in an infant. SUMMARY OF BACKGROUND DATA: There are two reported cases of fracture-dislocation in an infant in the literature, both of which were managed surgically. However, this is the first reported clinical case of burst fracture in an infant. METHODS: The patient was treated conservatively and observed for 40 months. His spine was examined by using roentgenography and magnetic resonance imaging. His neurologic condition was evaluated by clinical examination and somatosensory-evoked potential (SEP). RESULTS: The infant became ambulant with no need for support 2 years after injury. At that time, the burst vertebra was remodeling gradually and showed no spinal deformity. CONCLUSION: Fracture-dislocation of the spine with neurologic deficit requires surgical management. However, burst fracture can be managed conservatively, provided the neurologic condition improves.

Accidents, Traffic↗
PubMed2001

Inhibitory effect of theophylline on recombinant GABA(A) receptor.

Convulsions due to systemic toxicity are a major and frequently fatal side effect of theophylline. The cause of theophylline-induced convulsions is not clear, but antagonism of the inhibitory nervous system may be implicated, so we examined the effects of theophylline on GABA-induced currents using recombinant GABA(A) receptor (GABA(A)-R). Theophylline dose-dependently inhibited GABA-induced currents: the IC50 value was 1841+/-63 microM and Hill coefficient 1.09+/-0.03. The inhibitory action of theophylline on GABA-induced currents was competitive and voltage dependent. The inhibition of GABA-induced currents by theophylline may be a primary mechanism underlying theophylline-induced convulsions.

Animals↗
PubMed2001

Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.

The p16INK4a cyclin-dependent kinase inhibitor is implicated in replicative senescence, the state of permanent growth arrest provoked by cumulative cell divisions or as a response to constitutive Ras-Raf-MEK signalling in somatic cells. Some contribution to senescence presumably underlies the importance of p16INK4a as a tumour suppressor but the mechanisms regulating its expression in these different contexts remain unknown. Here we demonstrate a role for the Ets1 and Ets2 transcription factors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their patterns of expression during the lifespan of human diploid fibroblasts. The induction of p16INK4a by Ets2, which is abundant in young human diploid fibroblasts, is potentiated by signalling through the Ras-Raf-MEK kinase cascade and inhibited by a direct interaction with the helix-loop-helix protein Id1 (ref. 11). In senescent cells, where the Ets2 levels and MEK signalling decline, the marked increase in p16INK4a expression is consistent with the reciprocal reduction of Id1 and accumulation of Ets1.

Animals↗
PubMed2001

Screening and characterization of trehalose-oleate hydrolyzing lipase.

Various soil samples were collected to screen the presence of microorganisms which have ability to degrade TOE. One strain (AKU-883) with good TOE degrading activity was isolated and identified as Burkholderia cepacia and the extracellular enzyme was purified to homogeneity. The purification was achieved by ultrafiltration, Super Q anion-exchange chromatography and Superdex 200HR gel-filtration in the presence of Triton X. The enzyme was purified to 85-fold, and specific activity of 4.910 kU mg protein(-1). The peak preparation on gel filtration showed a single band of 34 kDa on SDS-PAGE and native PAGE which indicate the monomeric nature of the enzyme. The pI of the enzyme was 6.3. The enzyme showed the maximum activity at pH 9 and 65 degrees C, and was stable in the range of pH 5--10 and up to 60 degrees C. Almost all the activity (92%) was kept after incubation for more than 1 week at 50 degrees C (pH 7.3). High activities remained even in water-miscible solvents such as ethanol, dimethyl formamide, diisopropyl ether, and dioxane. The N-terminal 16 amino acid residues were determined as A-N-G-Y-A-A-T-R-Y-P-I-I-L-V-G-G, which showed a consensus sequence for lipases from Burkholderia species. Thus the enzyme was concluded to be a kind of lipase.

Amino Acid Sequence↗
PubMed2001

Clonal chromosomal aberrations accompanied by strong telomerase activity in immortalization of human B-lymphoblastoid cell lines transformed by Epstein-Barr virus.

Human B-lymphoblastoid cell lines transformed by Epstein-Barr (EBV-LCLs) are considered to be immortalized, although most of them show a normal diploid karyotype. Recently, we and others have shown that only part of EBV-LCLs is immortalized by developing strong telomerase activity that stabilizes the telomeres. In this study, we investigated the change in karyotypes during immortalization. All the eight immortalized cell lines developed clonal chromosomal aberrations accompanied by the development of strong telomerase activity. Interestingly, abnormal chromosomes were not shared among the immortalized cell lines. These results strongly suggest that chromosomal rearrangements and induction of strong telomerase activity are two events that take place in parallel in the process of immortalization of EBV-LCLs, and indicate that EBV-LCLs are clearly divided into two distinct groups, pre-immortal cell lines mostly with a normal diploid karyotype and post-immortal cell lines with a clonally abnormal karyotype.

B-Lymphocytes↗
PubMed2001

Participation of the beta-hydroxyketone part for potent cytotoxicity of callystatin A, a spongean polyketide.

The participation of the beta-hydroxyketone part of callystatin A in the potent cytotoxicity was analyzed through the analogue-syntheses and the assessment of their biological potencies. The ketonic carbonyl, the 19-hydroxyl, and the three asymmetric methyl groups located in the beta-hydroxyketone part of callystatin A were revealed to contribute to the cytotoxic potency, respectively. Moreover, the alpha,beta-unsaturated delta-lactone portion was shown to serve as a conclusive functional group for the cytotoxic activity.

Animals↗
PubMed2001

Comparative analyses of the pigment-aggregating and -dispersing actions of MCH on fish chromatophores.

In melanophores of the peppered catfish and the Nile tilapia, melanin-concentrating hormone (MCH) at low doses (<1 microM) induced pigment aggregation, and the aggregated state was maintained in the presence of MCH. However, at higher MCH concentrations (such as 1 and 10 microM), pigment aggregation was immediately followed by some re-dispersion, even in the continued presence of MCH, which led to an apparent decrease in aggregation. This pigment-dispersing activity at higher concentrations of MCH required extracellular Ca(2+) ions. By contrast, medaka melanophores responded to MCH only by pigment aggregation, even at the highest concentration employed (10 microM). Since it is known that medaka melanophores possess specific receptors for alpha-melanophore-stimulating hormone (alpha-MSH), the possibility that interaction between MSH receptors and MCH at high doses in the presence of Ca(2+) might cause pigment dispersion is ruled out. Cyclic MCH analogs, MCH (1-14) and MCH (5-17), failed to induce pigment dispersion, whereas they induced aggregation of melanin granules. These results suggest that another type of MCH receptor that mediates pigment dispersion is present in catfish and tilapia melanophores, and that intact MCH may be the only molecule that can bind to these receptors. Determinations of cAMP content in melanophores, which were isolated from the skin of three fish species and treated with 10 nM or 10 microM MCH, indicate that MCH receptors mediating aggregation may be coupled with Gi protein, whereas MCH receptors that mediate dispersion may be linked to Gs. The response of erythrophores, xanthophores and leucophores to MCH at various concentrations was also examined, and the results suggest that the distribution patterns of the two types of MCH receptors may differ among fish species and among types of chromatophore in the same fish.

Animals↗