Biomedical subjects

T Masaki

Publications and source records attributed to T Masaki.

At least 235 records · Page 13Linked to original sources

PubMed1996

Zonal adult Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease is a congenital disorder which is rare in adulthood. In typical cases the aganglionosis involves mainly the rectum or rectosigmoid colon and the lesion starts from the anal valve. Zonal segmental aganglionosis is a very rare type even in children. PATIENT: A 54 year old women with zonal segmental aganglionosis had an aganglionic segment 18 cm in length located in the rectosigmoid colon with an 8 cm long normal appearing rectum and dilated proximal colon. Resection of the stenotic segment with end to end anastomosis was performed. CONCLUSION: The functional result was excellent five years after the operation.

Colon↗

PubMed1996

Human endothelin converting enzyme gene (ECE1) mapped to chromosomal region 1p36.1.

The chromosomal localization of the human endothelin converting enzyme gene (ECE1) has been identified. Southern blot analysis of human genomic DNA from human x mouse somatic cell hybrids demonstrated that ECE1 maps to chromosome 1. Fluorescence in situ hybridization of a digoxigenin-labeled human ECE1 probe to normal human metaphase chromosomes showed that the gene is located within chromosome band 1p36.1.

Animals↗

PubMed1996

Plasma thrombomodulin: usefulness as a blood access failure marker in hemodialysis patients.

In 144 patients on hemodialysis (76 males and 68 females, median age 55.7 +/- 14.1 years, mean period on dialysis 44.1 +/- 33.3 months), thrombomodulin was determined by enzyme immunoassay prior to initiation of hemodialysis. The results showed that the mean thrombomodulin value of hemodialysis patients was 13.59 +/- 3.63 ng/ml which was significantly higher than the control value (3.20 +/- 0.90 ng/ml). The thrombomodulin values were significantly higher in patients with blood access failure (15.27 +/- 4.45 ng/ml) than in those without (13.11 +/- 3.31 ng/ml), and the rate of blood access failures was also significantly higher in those with thrombomodulin values of 15.0 ng/ml or higher than in those with values < 15.0 ng/ml. It was evident that there is a higher risk of blood access failure in patients with severe systemic vascular endothelial injury, and thrombomodulin is a useful marker of such an injury.

Adult↗

PubMed1996

Endothelin ETA and ETB receptors mediate endothelin-1-induced apamin-sensitive relaxation in the guinea pig ileum.

Endothelin (ET) receptors involved in ET-1-induced responses of the longitudinal muscle of the isolated guinea pig ileum were studied. ET-1 caused concentration-dependent contractions, while ET-3 and selective ETB-receptor agonists, IRL1620 and sarafotoxin 6c (S6c), showed little or no effect. The ET-1-induced contractions were antagonized by BQ-123, an ETA-receptor antagonist, or PD142893, an ETA/ETB-receptor antagonist, indicating that the contraction is mediated by the ETA receptor. In preparations precontracted with carbachol, ET-1 elicited relaxations at lower concentrations and contractions at higher concentrations. ET-3, IRL1620 and S6c caused relaxations. These relaxations were little affected by BQ-123, but greatly antagonized by PD142893. The ET-1-induced relaxations were slightly affected by BQ-788, an ETB-receptor antagonist, but were markedly inhibited by the combination of BQ-788 and BQ-123. In ETB receptor-desensitized preparations, ET-1-induced relaxations were antagonized by BQ-123, whereas ET-3, S6c and IRL1620 showed no response. All these relaxations were abolished by apamin. These results indicate that ETA and ETB receptors mediate relaxation of the ileal smooth muscle through activation of apamin-sensitive K+ channels.

Animals↗

PubMed1996

Endothelin-1-induced mitogenic responses of Chinese hamster ovary cells expressing human endothelinA: the role of a wortmannin-sensitive signaling pathway.

In the current study, endothelin-1 (ET-1) worked as a mitogen on Chinese hamster ovary cells stably expressing human endothelinA; when applied to serum-deprived cells, ET-1 caused dose-dependent increase in [3H]thymidine incorporation and cell proliferation. No synergism was observed between the effect of ET-1 and that of insulin-like growth factor-1/basic fibroblast growth factor. Both the inhibition of intracellular Ca2+ response by phospholipase C inhibitor U73122 and the down-regulation of protein kinase C (PKC) by pretreatment with phorbol 12-myristate-13-acetate (PMA) partially blocked the ET-1-induced mitogenic responses. Wortmannin, a phosphatidylinositol-3-kinase inhibitor, caused dose-dependent inhibition of the ET-1-induced mitogenic responses in both PMA-treated and -untreated cells. Wortmannin also inhibited ET-1-induced increase in phosphatidylinositol trisphosphate formation and activation of mitogen-activated protein kinase (MAPK), whereas it failed to inhibit PMA-induced activation of MAPK. In accordance with its effect on MAPK activation, wortmannin inhibited ET-1-induced activation of Raf-B, whereas it failed to inhibit the effect of PMA. These results suggested the role of a Ca2+/PKC-independent, wortmannin-sensitive signaling pathway that linked ETA and MAPK cascade in the mitogenic signaling activated by ETA.

Amino Acid Sequence↗

PubMed1996

Multicenter evaluation of a colorimetric microplate antimycobacterial susceptibility test: comparative study with the NCCLS M24-P.

A colorimetric test method using the microplate culture technique for the determination of susceptibility of Mycobacterium tuberculosis against antimycobacterial agents was developed and evaluated by the multicenter study. The test method utilizes an oxidation-reduction dye, 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC), as an indicator of mycobacterial growth. When compared to the presently available test method, some modifications were also included; lower inoculum density (10-fold dilution), inclusion of an inoculum diluted 1:100 as a growth control, and the preparation of inoculum preincubated in Middlebrook 7H9 broth and spectrophotometrically adjusted to McFarland #1 turbidity. The test method evaluated was highly precise and reliable to detect antimycobacterial resistances when the ATCC reference strains were tested. Also, the interpretations of the test result were highly comparable to those determined by the method of NCCLS M24-P, the % agreements ranging from 76.1% (ethambutol) to 91.3% (streptomycin). The test results were also comparable to those determined by Ogawa media; > 90% agreed with susceptible, intermediate, or resistant. The appearance of mycobacterial colonies on the test media was easily read, and the test results were more comparable to those of NCCLS M24-P. With these results, it can be concluded that the colorimetric microplate susceptibility test method described will be more suitable for clinical mycobacteriology laboratories.

Antitubercular Agents↗

PubMed1996

[Therapeutic trials with topical capsaicin cream and iontophoretically applied lidocaine for diabetic painful truncal neuropathy].

We report a 63-year-old man with a history of diabetes mellitus for 23 years. Painful dysesthesia developed in his toes and trunk with weight loss of 2kg in two months, after the therapy for diabetes mellitus. Truncal painful dysesthesia was symmetrically distributed in the bilateral posterior and anterior T8-11 dermatomes, sparing the bilateral lateral tholacic areas. Electromyography showed denervation potentials in bilateral abdominal rectus muscles at the levels of Th8-10. Histopathological study of the biopsied right sural nerve revealed small fiber neuropathy. We suspected the truncal painful dysesthesia of this patient resulted from diabetic small fiber polyneuropathy, which was resistant to ordinary medical treatments such as non-steroidal anti-inflammatory drugs. Capsaicin cream containing 0.075% capsaicin, and lidocaine delivered by iontophoresis were both effective for his painful dysesthesia.

Capsaicin↗

PubMed1996

Major Dermatophagoides mite allergen, Der 1, in soft toys.

BACKGROUND: Allergen avoidance is recommended when treating atopic asthma. OBJECTIVES: Soft toys are often kept in close proximity to children and may serve as a source of exposure. Due to the potential danger from the mite allergen content of these toys, Der 1 from toys was measured. METHODS: We quantified the level of Der 1 (Der p 1 + Der f 1) in both 30 new and 174 old soft toys (weight 216 +/- 2.5 g, height 26.5 +/- 3.4 cm), as well as in washed and in vacuumed soft toys. Dust was collected using an electric vacuum cleaner. Der 1 was measured by monoclonal antibody-based enzyme-linked immunosorbent assay (MoAb-ELISA). RESULTS: In brand new toys Der 1 was 0.1 microgram/g of dust, and in toys used for 1 year, 9.0; 2 year, 22.2; 3 year, 18.9; and more than 4 year, 22.7 micrograms/g of dust. Der 1 in new toys was measured every 4 months for 1 year. Der 1 rapidly increased 10- to 20-fold in the first 4 months, but there was no clear seasonal change. In toys washed using a chemical detergent or cleaned using a vacuum cleaner, there was a stastistically significant (P < 0.001) decrease in Der 1 in the washed group, but not in the vacuumed group. CONCLUSION: These results confirm that mite allergens accumulate rapidly in toys to form a potentially important source of allergens and that washing toys with a chemical detergent is effective in the reduction of allergens.

Allergens↗

PubMed1995

Truncation of the receptor carboxyl terminus impairs membrane signaling but not ligand binding of human ETB endothelin receptor.

Human ETB endothelin receptor (hETBR) is a heptahelical G-protein-coupled receptor consisting of 442 amino acids whose carboxyl (C)-intracellular region has four and twelve sites for potential palmitoylation and phosphorylation, respectively. In order to elucidate the functional roles of these modification sites, we constructed a series of C-terminal truncated hETBRs and expressed them in Ltk- cells. All the truncated hETBRs showed ligand-binding profiles similar to those of the wild-type hETBR. The truncated receptors holding Cys-402 retained both normal intracellular calcium ([Ca2+]i) response and its rapid desensitization; however, the deleted receptors lacking Cys-402 failed to induce the [Ca2+]i response. These results showed that Cys-402 of hETBR is necessary for its intracellular calcium signaling and that at least ten of twelve putative phosphorylation sites are irresponsible for the agonist-induced desensitization.

Amino Acid Sequence↗

PubMed1995

Heterogeneity of endothelin ETA receptor-mediated contractions in the rabbit saphenous vein.

The involvement of endothelin ETA receptors in endothelin-1-induced contractions of the rabbit saphenous vein was studied. After desensitization of endothelin ETB receptors by pretreatment with sarafotoxin S6c, endothelin-1 and sarafotoxin S6b and a high concentration of endothelin-3 caused dose-dependent contractions. However, endothelin-1-induced contractions were much less sensitive to an endothelin ETA receptor antagonist, BQ-123 (cyclo (-D-Asp-L-Pro-D-Val-L-Leu-D-Trp-)), than sarafotoxin S6b-induced responses. The pA2 values of BQ-123 for endothelin-1- and sarafotoxin S6b-induced contractions were 5.69 and 7.65, respectively. These results suggest pharmacological heterogeneity of endothelin ETA receptors in the rabbit saphenous vein.

Animals↗

PubMed1995

Capacitative Ca2+ entry in human platelets is resistant to nitric oxide.

Both sodium nitroprusside (SNP) and a phospholipase C inhibitor U73122, when applied to human platelets after the stimulation with thrombin (0.2 U/ml), caused dose-dependent inhibition of Ca2+ influx. The inhibition, however, was not complete for either substance and the U73122-resistant Ca2+ influx was also resistant to SNP. Two lines of evidence suggested that the SNP/U73122-resistant Ca2+ influx was due to the capacitative Ca2+ entry. First, U73122-resistant fraction of Ca2+ influx induced by thapsigargin was also resistant to SNP. Second, both U73122 and SNP failed to inhibit the Ca2+ influx induced by an acid extract from thrombin-stimulated platelets that contained the Ca2+ influx factor activity. We suggest that the capacitative Ca2+ entry in human platelets, once triggered by inositol trisphosphate-induced store-depletion, is not affected by nitric oxide.

Aspirin↗

PubMed1995

Structural basis of G protein specificity of human endothelin receptors. A study with endothelinA/B chimeras.

The endothelin (ET) family of peptides acts via two subtypes of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors termed ETA and ETB. ET-1 stimulated cAMP formation in Chinese hamster ovary (CHO) cells stably expressing human wild-type ETA (CHO/hETA cells) while it inhibited cAMP formation in CHO cells expressing human wild-type ETB (CHO/hETB cells), and pharmacological evidence indicated that the opposite effects were due to the selective coupling of each receptor subtype with G alpha s/G alpha i. To find out a receptor domain(s) that determined the selective coupling, a series of chimeric receptors between hETA and hETB was expressed on CHO cells, and the effect of ET-1 on cAMP formation in each cell line was tested. hETA with the replacement of second and/or third intracellular loop (ICLII and/or -III) to the corresponding region(s) of hETB failed to transmit the stimulatory effect of ET-1. hETB with the replacement of ICLIII to the corresponding region of hETA failed to transmit the inhibitory effect of ET-1. A chimeric receptor with ICLII of hETB and with ICLIII of hETA failed to transmit both effects. In cells expressing chimeric receptors with ICLII of hETA and with ICLIII of hETB, ET-1 inhibited cAMP formation while it stimulated cAMP formation when cells were pretreated with pertussis toxin. These results indicated the roles of ICLII and -III of hETR as a major determinant of the selective coupling of hETA and hETB with G alpha s/G alpha i, respectively. We also demonstrated that each receptor subtype expressed on the same cell could work independently, i.e. for hETA to activate G alpha s and for hETB to activate G alpha i, resulting in dose-dependent dual effects of ET-1 on cAMP formation.

Animals↗

PubMed1995

Processing of proendothelin-1 by human furin convertase.

Endothelin-1 (ET-1) is the most potent vasoactive peptide known to date. The peptide is initially synthesized as an inactive precursor (proET-1) which undergoes proteolysis at specific pairs of basic amino acids to yield bigET-1. Production of ET-1 then proceeds by cleavage of bigET-1 by the endothelin converting enzyme (ECE). Here, we demonstrate that the in vitro cleavage of proET-1 by furin, a mammalian convertase involved in precursor processing, produced bigET-1. Upon further processing, bigET-1 was converted to biologically active ET-1. Furthermore, we demonstrate that the furin inhibitor, decanoyl-Arg-Val-Lys-Arg chloromethylketone, abolished production of ET-1 in endothelial cells.

Amino Acid Chloromethyl Ketones↗

PubMed1995

Cloning and sequencing of a human endothelin converting enzyme in renal adenocarcinoma (ACHN) cells producing endothelin-2.

Endothelin (ET)-2 is a 21 residue vasoactive peptide which is biosynthesized from big ET-2(1-38) by a specific cleavage at Trp21-Val22 with an ET converting enzyme (ECE). To identify an ECE in ACHN (human renal adenocarcinoma) cells which produce ET-2, we have cloned and sequenced a novel cDNA encoding a human ECE in ACHN (hAECE). It encodes a 770 amino acid protein with a zinc-binding motif and a single membrane spanning region. The sequences of nucleic acids and amino acids from Leu45 to Trp770 of hAECE are identical to those from Leu33 to Trp758 of a human ECE in HUVEC (hHECE). The sequences in the amino-terminal moiety are divergent between hAECE and hHECE. Based on the difference of the amino-terminal amino acid sequences, ECEs reported so far, can be classified into two isoforms. These results strongly suggest that an alternative splicing might occur in the 5'-terminal region of the ECE pre-mRNA.

Adenocarcinoma↗

PubMed1995

Polypoid growth and K-ras codon 12 mutation in colorectal cancer.

BACKGROUND: To clarify genetic changes in colorectal tumorigenesis, K-ras codon 12 point mutations were examined in 101 ordinary colorectal carcinomas and 6 that complicated ulcerative colitis (UC) with special attention to growth patterns. METHODS: The depths of invasion of ordinary carcinoma were submucosa (SMCa) in 39 cases, muscularis propria (PMCa) in 33, and far-advanced in 29. Growth patterns of SMCa and PMCa were classified into three types: polypoid-growth type without central depression (Type 1), polypoid-growth type with central depression (Type 2), and nonpolypoid-growth type. DNA samples were extracted from formalin fixed paraffin embedded sections, and K-ras codon 12 mutations were examined by two-step polymerase chain reaction-restriction fragment length polymorphism. RESULTS: K-ras mutation frequency was higher in Type 1 SMCa than in nonpolypoid SMCa, 56% (9/16) versus 6% (1/17), respectively, and in PMCa, 78% (7/9) versus 23% (3/13), respectively. In 6 UC carcinomas, a K-ras mutation was detected in only one polypoid carcinoma and none were detected in five nonpolypoid carcinomas. CONCLUSIONS: These results and the authors' previous study suggest that nonpolypoid carcinomas may be derived from flat adenomas, whose K-ras mutation incidence also was low, and this pathway is different from a genetic model based on the ordinary adenoma-carcinoma sequence through polypoid adenomas.

Adenoma↗

PubMed1995

Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors.

The coupling of two endothelin receptor subtypes (ET(A) and ETB) to several types of guanine-nucleotide-binding regulatory protein (G protein) was examined. Two subtypes of receptor cDNAs were transfected alone or together with four different G protein alpha subunit cDNAs in COS-7 cells. In ET(A) receptor-transfected cells, endothelin-1 (ET-1) activated phosphatidylinositol-specific phospholipase C as measured by the production of phosphatidylinositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. ETB-receptor-transfected cells also produced Ins(1,4,5)P3 on stimulation by ET-1. The ET-1-induced production of Ins(1,4,5)P3 was markedly higher in G alpha q-cotransfected or G alpha 11-cotransfected cells than in cells transfected with each receptor alone. ET-1 also stimulated production of cAMP in ET(A) or ETB receptor-transfected cells. The production of cAMP was synergistically amplified by G alpha s co-transfection with each receptor. In contrast, when G alpha i2 was co-transfected with the ET(A) or ETB receptor, ET-1 displayed an inhibitory action on forskolin-stimulated cAMP accumulation. Pertussis-toxin treatment of the G alpha i2-transfected cells resulted in abolition of the endothelin-induced inhibition of cAMP accumulation. These observations indicate that both ET(A) and ETB receptors are able to couple to Gq, G11, Gs and Gi2, and suggest that endothelin receptors stimulate multiple effectors via several types of G protein simultaneously. The overall effects induced by endothelin may differ in cell types depending on the level of expression of each G-protein subtype in the cell.

Animals↗

PubMed1995

A peroperative comparison of Western and Oriental colonic anatomy and mesenteric attachments.

It has been suggested that the Oriental colon is easier to colonoscope than its Western counterpart. The aim of this study was to investigate possible differences in colonic anatomy between Western and Oriental patients that might explain this observation. Measurements of colonic length and mesenteric attachments were taken according to a set protocol from 115 Western (Caucasian) and 114 Oriental patients at laparotomy. Sigmoid adhesions were found more frequently in Western (17%) compared to Oriental (8%) patients, P = 0.047. A descending mesocolon of > or = 10 cm occurred in 10 (8%) Western patients but only 1 (0.9%) Oriental patient, P = 0.01. The splenic flexure was more frequently mobile in Western patients (20%) compared to Oriental (9%) patients, P = 0.016. In 29% - of Western patients the mid-transverse colon reached the symphysis pubis, or lower when pulled downwards in contrast to 10% of Oriental patients, P < 0.001. There was no significant difference in total colonic length comparing Western (median = 114 cm, range 68-159 cm) to Oriental (median = 111 cm, range 78-161 cm) patients. Western patients have a higher incidence of sigmoid colon adhesions and increased colonic mobility when compared to Orientals. These findings support the observation that colonoscopy is a more difficult procedure in Western patients.

Adult↗

PubMed1995

Covalently-bound human C4b dimers consisting of C4B isotype show higher hemolytic activity than those of C4A in the C3-bypass complement pathway.

The ability to form a covalent dimer of human C4b was investigated with purified isotypes C4A and C4B, and antibody-sensitized liposomes supplemented with C1. In this system, no C4A or C4B formed a complex with the antibody or C1. Whereas both C4A and C4B isotypes formed dimers to a similar extent, C4B formed an ester-linked dimer and C4A an amide-linked dimer. Both of these dimers served as a subunit for the C3-bypass pathway C5 convertase, since liposomes bearing Ab, C1 and a dimer of C4A or C4B, allowed the formation of C5 convertase by the addition of C2. The degree of complement-mediated liposome lysis however, was observed to be 2-3 times higher in the C4B-bearing particles than in those bearing C4A. These results indicate that the second C4b-binding site on the first C4b is different between C4A and C4B, and that in the C3-bypass pathway, C4B has a higher degree of hemolytic activity than C4A, as in the conventional classical complement pathway.

Biopolymers↗