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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 145 records · Page 8Linked to original sources

Origin of Ca2+ necessary for carbachol-induced contraction in longitudinal muscle of the proximal colon of rats.

The origin of Ca2+ necessary for carbachol (CCh)-induced contraction of longitudinal muscle of the proximal colon of rats was studied. CCh induced contraction of the muscle consisting of two phases, phasic and tonic phases, with a concomitant biphasic increase in [Ca2+]i. After removal of Ca2+ from the bathing solution of the colonic segments, CCh-induced contraction was rapidly inhibited; there was almost complete inhibition 1 min after the removal. Nicardipine, a blocker of voltage-dependent calcium channel, also significantly inhibited CCh-induced contraction. On the other hand, treatment of the colonic segments with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, did not significantly affect the contraction except causing a slight decrease in the rate of contraction. These results suggest that Ca> entering through voltage-dependent calcium channels, but not released from SR, is essential for CCh-induced contraction of longitudinal muscle of the proximal colon of rats. This strict dependency of the CCh-induced contraction on extracellular Ca2+ was discussed in relation to the results obtained in the fundus of rats.

Aminobenzoates↗

Light adaptation in motion direction judgments.

We examined the time course of light adaptation in the visual motion system. Subjects judged the direction of a two-frame apparent-motion display, with the two frames separated by a 50-ms interstimulus interval of the same mean luminance. The phase of the first frame was randomly determined on each trial. The grating presented in the second frame was phase shifted either leftward or rightward by pi/2 with respect to the grating in the first frame. At some variable point during the first frame, the mean luminance of the pattern increased or decreased by 1-3 log units. Mean luminance levels varied from scotopic or low mesopic to photopic levels. We found that the perceived direction of motion depended jointly on the luminance level of the first frame grating and the time at which the shift in average luminance occurs. When the average luminance increases from scotopic or mesopic to photopic levels at least 0.5 s before the offset of the first frame, motion in the 3pi/2 direction is perceived. When average luminance decreases to low mesopic or scotopic levels, motion in the pi/2 direction is perceived if the change occurs 1.0 s or more before first frame offset, depending on the size of the luminance step. Thus light adaptation in the visual motion system is essentially complete within 1 s. This suggests a rapid change in the shape (biphasic or monophasic) of the temporal impulse response functions that feed into a first-order motion mechanism.

Adaptation, Ocular↗

Recent progress in T-cadherin (CDH13, H-cadherin) research.

T-cadherin is a unique cadherin cell adhesion molecule that is anchored to the cell surface membrane through a glycosyl phosphatidyl inositol (GPI) moiety. The cytoplasmic domain, which T-cadherin lacks, is believed to be critical for homophilic binding through interaction with submembrane cytoskeletal proteins. Does this mean that T-cadherin is an unimportant molecule? However, the T-cadherin amino acid motif has been well conserved through evolution in vertebrates, suggesting that T-cadherin may have biological significance in higher animals. Consistent with this hypothesis, recent studies have thrown light on the relevance of T-cadherin in the fields of oncology, neurology, respirology and cardiovascular physiology. In this manuscript, we review current advances in T-cadherin research.

Animals↗

Effect of jasplakinolide on the growth, encystation, and actin cytoskeleton of Entamoeba histolytica and Entamoeba invadens.

The effect of jasplakinolide. an actin-polymerizing and filament-stabilizing drug, on the growth, encystation, and actin cytoskeleton of Entamoeba histolytica and Entamoeba invadens was examined. Jasplakinolide inhibited the growth of E. histolytica strain HM-1:IMSS and E. invadens strain IP-1 in a concentration-dependent manner, the latter being more resistant to the drug. The inhibitory effect of jasplakinolide on the growth of E. histolytica trophozoites was reversed by removal of the drug after exposure to 1 microM for 1 day. Encystation of E. invadens as induced in vitro was also inhibited by jasplakinolide. Trophozoites exposed to jasplakinolide in encystation medium for 1 day did not encyst after removal of the drug, whereas those exposed to the drug in growth medium for 7 days did encyst without the drug. The process of cyst maturation was unaffected by jasplakinolide. Large round structures were formed in trophozoites of both amoebae grown with jasplakinolide; these were identified as F-actin aggregates by staining with fluorescent phalloidin. Accumulation in trophozoites of both amoebae of actin aggregates was observed after culture in jasplakinolide. Also, E. invadens cysts formed from trophozoites treated with jasplakinolide contained the actin aggregate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis revealed that the jasplakinolide treatment led to an increase in the proportion of F-actin associated with formation of the aggregate. The results suggest that aggregates are formed from the cortical flow of F-actin filaments, and that these filaments would normally be depolymerized but are artificially stabilized by jasplakinolide binding.

Actins↗

Spontaneous rupture of the amyloid spleen in a case of usual interstitial pneumonia.

We describe a rare case of secondary amyloidosis associated with usual interstitial pneumonia (UIP), who died from spontaneous rupture of the amyloid spleen. A 68-year-old man was admitted to evaluate to his interstital lung disease. Chest radiography showed reticular shadow in bilateral lower lung fields. Two years later, he suddenly felt severe abdominal pain. In spite of maximum therapy, he died from hypovolemic shock. Postmortem examination revealed massive intraabdominal hemorrhage. The diagnosis of lung disease was UIP and amyloid A type deposits were observed in various organs including the ruptured spleen.

Aged↗

Functional defect of B lymphocytes in a patient with selective IgM deficiency associated with systemic lupus erythematosus.

Selective IgM deficiency (SIgMD) is a rare primary immunodeficiency disease, which is found in some patients with autoimmune diseases. The pathogenesis of SIgMD and the relationship of these diseases have remained unclear. The absence of secreted IgM was recently reported to accelerate the development of autoimmune diseases in lupus-prone lymphoproliferative (Ipr) mice. The reduction of secreted IgM production may relate with the progression of autoimmune diseases in human. We present a case of SIgMD associated with systemic lupus erythematosus (SLE), and examined the function and the IgM heavy chain gene of patient's lymphocytes. The number and the surface IgM expression of the patient's B cells were normal. In vitro stimulation of peripheral mononuclear cells by recombinant IL-2 and a B cell activator, Staphylococcus aureus Cowan strain I, could not overcome the reduction of IgM production, although the secreted form of IgM mRNA was detected. Sequence analysis of the IgM heavy chain gene and the IgM mRNA revealed no mutation or deletion. These findings suggested that SIgMD in this case was involved in the abnormality during B cell maturation. Further analysis is required to reveal the pathogenesis of SIgMD associated with SLE.

Antibody Formation↗

Insufficient effect of p27(KIP1) to inhibit cyclin D1 in human esophageal cancer in vitro.

The cell cycle is controlled by protein complexes composed of cyclins and cyclin-dependent kinases. p27KIP1 (p27) is one of the Kip/Cip family cyclin-dependent kinase inhibitory proteins which negatively regulate cell cycle progression, and have been proposed as candidate tumor suppressor genes. To examine the role of p27 in the development of human esophageal squamous cell carcinoma (ESCC), we performed Western blot and immunoprecipitation analyses of the levels of expression of p27 protein in a series of ESCC cell lines. This protein was expressed at various levels in these cell lines during exponential growth. p27 level was significantly associated with that of cyclin D1, but not of cyclin E. Further cell cycle synchronization studies demonstrated that p27 was free or bound with affinity to cyclin E-CDK2 more than to cyclin D1-CDK4 or cyclin D1-CDK6. It is known that overexpression of cyclin D1 rather than cyclin E is involved in the pathogenesis of ESCC. Our findings indicated that high expression of p27 throughout the G1 to S phase may inhibit more likely cyclin E, than cyclin D1, which promotes tumor growth of esophageal squamous cell carcinoma.

Cell Cycle Proteins↗

Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2. II. Structure determination and synthesis.

The structures of tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2, were determined by analysis of various NMR experiments. The 1H and 13C NMR of tyropeptins were complicated due to the presence of an aldehyde group. Therefore, tyropeptins were converted to their alcohols by sodium borohydride. These alcohol derivatives gave assignable NMR spectra. The stereochemistry of tyropeptins were determined by analysis of acid hydrolysis products from tyropeptins, and further confirmed by the total synthesis. The structures of tyropeptins A and B were found to be isovaleryl-L-tyrosyl-L-valyl-DL-tyrosinal and n-butyryl-L-tyrosyl-L-leucyl-DL-tyrosinal, respectively.

Cysteine Endopeptidases↗

Tripropeptins, novel antimicrobial agents produced by Lysobacter sp. I. Taxonomy, isolation and biological activities.

Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp. The differences among these components are in the lengths of the alkyl side chain. Tripropeptins are active against Gram-positive bacteria including MRSA in vitro. Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.

Anti-Bacterial Agents↗

Synthesis and biological evaluation of cytogenin derivatives.

To enhance the stability in vivo, new derivatives of cytogenin were synthesized, and their biological activity and stability in mice were estimated. 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid (NM-3) was found to be the most stable among them. It modified collagen-induced arthritis in mice. It also showed potent anti-angiogenic activity in a mouse dorsal air sac assay.

Animals↗

Isolation and structural determination of phepropeptins A, B, C, and D, new proteasome inhibitors, produced by Streptomyces sp.

We have isolated four related compounds named phepropeptins A, B, C, and D, as inhibitors of proteasome proposed to regulate many cellular functions. From an NMR analysis, the phepropeptins appeared as cyclic hexapeptides, differing in the two residues of the constituent amino acids from one another, with four conserved amino acid moieties. Based on an amino acid analysis, we synthesized two possible cyclic peptides to phepropeptin B that differ in the configurations. A comparison of the properties between the natural and synthesized compounds revealed that the structure of phepropeptin B was cyclo(-L-Leu-D-Phe-L-Pro-L-Phe-D-Leu-L-Val-). The phepropeptins showed inhibition to the proteasomal chymotrypsin-like activity but not to alpha-chymotrypsin.

Amino Acids↗

Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp. MK993-dF2. I. Taxonomy, isolation, physico-chemical properties and biological activities.

Tyropeptins A and B, new proteasome inhibitors, were isolated from the culture broth of Kitasatospora sp. MK993-dF2. They were purified using ethyl acetate extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and HPLC. Tyropeptin A inhibited the chymotrypsin-like (ChT-L) and trypsin-like (T-L) activities of 20S proteasome with IC50 values of 0.1 microg/ml and 1.5 microg/ml respectively, but did not inhibit the peptidylglutamyl-peptide hydrolyzing (PGPH) activity of 20S proteasome at a concentration of 100 microg/ml. The inhibitory activities of tyropeptin A were about two times as strong as that of tyropeptin B. Taxonomy of the producing strain is also described.

Animals↗

Improvement of lacrimal function by topical application of CyA in murine models of Sjögren's syndrome.

PURPOSE: The object of this study was to evaluate improvement of lacrimal gland (LG) function after topical cyclosporin A (CyA). METHODS: Topical CyA (0.01% and 0.1%) was applied to two mouse models of Sjögren's syndrome, the NFS/sld after thymectomy and the nonobese diabetic (NOD) mouse, and the functional integrity of the lacrimal gland was evaluated by measuring basal and stimulated tear secretion and its histologic integrity by examining it for apoptosis and lymphocyte invasion. RESULTS: After treatment with CyA at 0.1% in the NFS/sld mice, tear function increased, and there was a decrease in lymphocyte infiltration of the LG and a decrease in apoptotic figures among the acinar cells. In the NOD mice, tear function also improved, but there was no associated decrease in lymphocyte infiltration. However, the expression of Fas ligand (FasL) in NOD mice by infiltrating lymphocytes was suppressed with 0. 1% CyA eye drops. CONCLUSIONS: CyA appears to improve tear secretion in mouse models of Sjögren's syndrome by preventing lymphocyte-induced apoptosis of acinar cells. In one model this was achieved by preventing lymphocyte infiltration and in the other by reducing expression of FasL expression on infiltrating lymphocytes.

Administration, Topical↗

Genetic analysis of hMLH1 in transitional cell carcinoma of the urinary tract: promoter methylation or mutation.

PURPOSE: Loss of DNA mismatch repair due to diminished expression or mutation of hMLH1 is associated with genomic instability followed by cancer. We performed genetic analyses of hMLH1 to determine whether hMLH1 alterations have a role in urothelial tumorigenesis. MATERIALS AND METHODS: We examined genomic DNA from 118 sporadic transitional cell carcinomas, including 83 bladder and 35 renal pelvis or ureter cases, for aberrant promoter methylation and mutation in the hMLH1 gene. Immunohistochemical reactivity to hMLH1 protein and genome instability in these transitional cell carcinomas were also studied. RESULTS: Two of the 118 cases (1.7%) had microsatellite instability and hMLH1 promoter methylation with loss of or reduced hMLH1 protein expression. A single transitional cell carcinoma (0.8%) without microsatellite instability had an hMLH1 missense mutation with a C-to-T transition, resulting in the substitution Arg217 --> Cys. Immunostaining with antihMLH1 antibody was found in this transitional cell carcinoma. CONCLUSIONS: To our knowledge these findings provide the first in vivo evidence for the type and frequency of possible involvement of promoter methylation and mutation of hMLH1 in sporadic urothelial transitional cell carcinoma. They also suggest that hMLH1 alterations may not account for many cases of sporadic transitional cell carcinoma tumorigenesis.

Adaptor Proteins, Signal Transducing↗