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Biomedical subjects

T Usui

Publications and source records attributed to T Usui.

At least 235 records · Page 13Linked to original sources

The double omohyoid muscle in humans: report of one case and review of the literature.

An anomalous muscle was found in the right anterior cervical region of a 68-year-old Japanese man. The muscle was investigated anatomically, with special reference to its supply. Few such reports are available. The anomalous muscle arose from the upper margin of the scapula as an aponeurotic sheet, ran medialocranialward and separated into the superficial and profound fasciculi at the lateral edge of the sternohyoid muscle. The former fasciculus was inserted into the lower border of the hyoid bone without fusing with adjacent muscles, or as an independent fasciculus. Meanwhile, the latter fasciculus incompletely fused with the lateral portion of the sternohyoid muscle. This muscle was supplied from its posterior surface and the upper edge by two slender nerves from the ansa cervicalis (roots of origin: C1, C2 and C3). Based on the nerve supply and a review of the literature, the muscle is discussed in terms of its true nature and its mechanism of formation. As a result of the investigation, this muscle is assumed to be a vestigial structure in humans reduced from the M. episterno-cleido-hyoideus sublimis (Fürbringer), which is observed in lower types of vertebrates (reptilies, etc.).

Aged↗

Molecular cloning and expression of multiple isoforms of human prostaglandin E receptor EP3 subtype generated by alternative messenger RNA splicing: multiple second messenger systems and tissue-specific distributions.

Five distinct cDNA clones encoding four different isoforms of human prostaglandin (PG) E receptor EP3 subtype were isolated from a human kidney cDNA library. Two cDNA clones differed only in their 3'-untranslated regions. The four isoforms, tentatively named EP3-I, EP3-II, EP3-III, and EP3-IV, which were generated by alternative mRNA splicing, had identical amino acid sequences except for their different carboxyl-terminal tails. Transfection experiments revealed that all the four isoforms show high binding affinities to PGE2, PGE1, and M&B28767, an EP3-specific agonist, whereas their downstream signaling pathways are divergent. M&B28767 increased cAMP concentrations in cells expressing EP3-II and EP3-IV, whereas it inhibited forskolin-induced cAMP accumulations in cells expressing all EP3 isoforms. M&B28767 also stimulated phosphoinositide turnover in cells expressing EP3-I and EP3-II. Northern blot analysis revealed that the EP3 gene is expressed in a wide variety of human tissues. The human EP3 mRNA was present most abundantly in the kidney, pancreas, and uterus. A substantial expression was also detected in the heart, liver, skeletal muscle, small intestine, colon, prostate, ovary, and testis. Furthermore, reverse transcription-polymerase chain reaction analysis demonstrated tissue-specific expressions of the five different EP3 mRNA species. The present study suggests the presence of the multiple systems of PGE2/EP3 isoforms and leads to the better understanding of its physiological and pathophysiological implications in humans.

Alternative Splicing↗

[REN plot for a graphic expression method of clinical laboratory data statistics].

Laboratory data have been processed statistically on an assumption that they formed a normal distribution curve by themselves or after their transformation. The data of clinical medicine, however, frequently form distributions different from the normal one and thus they are not exactly represented by simple statistics such as mean and standard deviation. We used non-parametric percentiles(pct) as parameters for an improved expression of data distributions. The parameters used in this method are as follows: mean, 50 pct as median, 25 and 75pct as a concentration indicator, 5 and 95pct as a 90 percent central range, 2.5 and 97.5pct as a 95 percent central range, and minimum and maximum data as a distribution range. These indicators were presented on a new form of box-and-whisker plot. This expression was named as REN plot. Our method was compared to the other statistical expression methods using the data of control surveys of Factor IX activity of normal plasmas and prothrombin time of abnormal standard plasmas as well as APTT of abnormal plasma measured for intra-laboratory quality control. It was found that any form of data distribution, normal or abnormal, was precisely expressed in detail and the gradient of data densities were visually plotted by our method. Also neither the median, central range nor distribution range was influenced by extreme values. It was concluded that REN plot was useful expression for the statistical analysis of clinical laboratory data.

Adult↗

Pharmacokinetics of YM175, a new bisphosphonate, in rats and dogs.

We investigated the pharmacokinetics of YM175, a new bisphosphonate, after intravenous and oral administrations in rats and dogs. After intravenous administration at 0.03-0.3 mg/kg, plasma YM175 concentration declined biexponentially with an apparent terminal half-life of 0.37-0.72 hr in rats and 3.30-4.09 hr in dogs. In both species, the area under the plasma concentration vs. time curve increased dose-proportionally, whereas volume of distribution at steady-state and total body clearance changed little among doses, indicating the linear pharmacokinetics of the drug after intravenous administration. After oral administration to rats (3-30 mg/kg) and dogs (0.3-10 mg/kg), maximum concentration and area under the plasma concentration vs. time curve increased more than dose-proportionally at 30 mg/kg in rats and at 3 mg/kg or higher in dogs. Thus, bioavailability increased at higher doses, being 1.0%, 1.2%, and 3.6% at 3, 10, and 30 mg/kg in rats, and being 1.8%, 1.3%, 2.9%, and 11.5% at 0.3, 1, 3, and 10 mg/kg in dogs, respectively. Urinary excretion and bone concentration of radioactivity in rats receiving [14C]YM175 agreed well with those of unchanged drug in both administration routes, and radiochromatograms of rat urine revealed no peaks of metabolites. These findings suggest that YM175 undergoes practically no metabolism and indicate that the increase in bioavailability at higher doses is caused by enhanced drug absorption, and not by any saturation of first-pass metabolism. Finally, concentrations of YM175 in the rib of dogs receiving a 0.3 mg/kg intravenous dose were highest in the epiphyseal costa, followed by the middle costa and cartilage, indicating that the uptake of YM175 into bone is site-dependent. Furthermore, the drug in rib decreased biexponentially with a terminal half-life of 249 days in the epiphyseal costa and 351 days in the middle costa, suggesting that the elimination rate of YM175 from bone is also site-dependent.

Administration, Oral↗

A mapping of histology and cell proliferation in human bladder cancer: an immunohistochemical study.

Transitional cell carcinoma of the urinary bladder is a multifocal disease and the whole bladder mucosa is more or less involved in the neoplastic process. A mapping study of 5 cystectomy specimens was performed, and cell proliferation was evaluated immunohistochemically using anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody. A correlation between the pathological findings and the rates of PCNA-positive cells was observed in both the tumor and the surrounding mucosa in 4 of the 5 cases. The rates of PCNA-positive cells increased in areas with normal mucosa adjacent to those with dysplasia or transitional cell carcinoma, and in areas with normal mucosa or dysplasia adjacent to those with carcinoma in situ or transitional cell carcinoma in 2 cases. These features may indicate that a field change observed in the mapping study of a bladder with cancer is a manifestation of a stepwise progression of the mucosal disease.

Aged↗

Factors related to the outcome of M-VAC in 101 patients with advanced urothelial cancer.

The objective of this study is to identify factors related to the results of intravenous methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for 101 patients with advanced urothelial cancer. The effects of various factors on response and survival were evaluated using univariate and multivariate analyses. The factors included in the analyses were sex, age, performance status (PS), primary site, histological type, grade, T category, N category, M category, prior chemotherapy, prior radiotherapy, and dose of chemotherapeutic drugs. Univariate analysis revealed that M category and prior chemotherapy had a significant correlation with the response, and that factors significantly related to survival were PS, primary site, N category, M category, prior chemotherapy and prior radiotherapy. A multiple logistic regression model showed that N category, M category and prior chemotherapy were related to response. The response rates of patients with N1-4 or M1 or prior chemotherapy were lower than those with N0 or M0 or without prior chemotherapy. A Cox regression model demonstrated that PS and M category independently contributed to survival. Patients with high grade PS or distant metastases showed a lower survival rate than those with low grade PS or localized diseases. M category was the most important factor related to response and survival. These results seem to indicate the low effectiveness of M-VAC for distant metastases, and the inability of this regimen to improve the outcome of patients with advanced urothelial cancer.

Adolescent↗

Cisplatin-based neoadjuvant chemotherapy for invasive bladder cancer.

Between February 1988 and March 1993, 24 patients with locally advanced bladder cancer (stages T2-4N0-3M0) were included in this study. Combination chemotherapy consisting of methotrexate, vinblastine, epirubicin (doxorubicin) and cisplatin (M-VAC) was given to the patients in a neoadjuvant setting. The clinical stage was T2N0M0 in eight patients, T3aN0M0 in three, T3bN0M0 in seven, T4N0M0 in five and T4N3M0 in one. After chemotherapy, total cystectomy was performed in 20 patients and partial cystectomy 4. Of 24 patients, one (4%) showed a pathological complete response, and eight (33%) had a pathological partial response, for an overall response rate of 38% (95% confidence limits 20 to 57%). Nine patients who achieved a pathological response to chemotherapy had a significantly higher survival rate than the nonresponders (p <0.01). In the relationship between the clinical stage and the response to chemotherapy, clinical T2 and T3a diseases were more likely to respond to chemotherapy than clinical T3b and T4 diseases, with a response rate of 64% and 15%, respectively. While a positive relationship between the pathological response and survival was observed, adequate follow-up is needed to assess the ability of neoadjuvant chemotherapy to improve the prognosis of patients with locally advanced bladder cancer.

Adult↗

Cloning and expression of a cDNA for rat prostacyclin receptor.

A cDNA clone for rat prostacyclin receptor was isolated. The cDNA encodes a protein of 416 amino acid residues (M(r) 44,662) with putative seven transmembrane domains, and belongs to the G protein-coupled receptor superfamily. Specific binding of [3H]iloprost was found in membrane of COS-7 cells transfected with the cDNA (Kd = 1.3 nM) and was displaced with unlabeled prostaglandins in the order of iloprost = cicaprost > PGE1 > STA2 = PGE2 = PGD2 > PGF2 alpha. Northern blot analysis demonstrated that rat prostacyclin receptor mRNA is expressed in the lung, spleen, heart, pancreas, thymus, stomach and aorta.

Amino Acid Sequence↗

Oral administration of lipopolysaccharides activates B-1 cells in the peritoneal cavity and lamina propria of the gut and induces autoimmune symptoms in an autoantibody transgenic mouse.

About a half of the antierythrocyte autoantibody transgenic (autoAb Tg) mice, in which almost all B cells are detected in the spleen, lymph nodes, and Peyer's patches, but not in the peritoneal cavity, suffer from autoimmune hemolytic anemia. The occurrence of this disease is strongly linked to production of autoAb by activated peritoneal B-1 cells in the Tg mice. In this study, we have shown that oral administration of lipopolysaccharides (LPS) activated B-1 cells in the lamina propria of the gut as well as the peritoneal cavity in the healthy Tg mice and induced the autoimmune symptoms in all the Tg mice. The activation of peritoneal and lamina propria B-1 cells by enteric LPS is found not only in the anti-RBC autoAb Tg mice and normal mice but also in the aly mice which congenitally lack lymph nodes and Peyer's patches. These results suggest that B-1 cells in the two locations may form a common pool independent of Peyer's patches and lymph nodes, and can be activated by enteric thymus-independent antigens or polyclonal activators such as LPS. The induction of autoimmune hemolytic anemia in the Tg mice by enteric LPS through the activation of B-1 cells in the lamina propria of gut and in the peritoneal cavity suggests that B-1 cells and bacterial infection may play a pathogenic role in the onset of autoimmune diseases.

Administration, Oral↗

Molecular cloning and expression of rat prostaglandin E receptor EP2 subtype.

A cDNA clone encoding the rat prostaglandin (PG) E receptor EP2 subtype was cloned from a rat lung cDNA library. It encodes 488 amino acid residues with putative seven-transmembrane domains. Specific binding of [3H]PGE2 was found in COS-7 cells transfected with the cDNA and was displaced with unlabeled prostaglandins in the order of PGE2 = PGE1 >> iloprost > or = PGF2 alpha > or = PGD2. The binding was also inhibited by misoprostol, an EP2 and EP3 agonist, but not by sulprostone, an EP1 and EP3 agonist. Northern blot analysis demonstrated that the EP2 mRNA is widely expressed in various tissues, the significant expression being observed in the thymus, lung, spleen, heart stomach, and pancreas.

Amino Acid Sequence↗

Sensitive determination of a novel bisphosphonate, YM529, in plasma, urine and bone by high-performance liquid chromatography with fluorescence detection.

A high-performance liquid chromatographic method for the sensitive determination of 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1, 1-bisphosphonic acid monohydrate (YM529) in plasma, urine and bone is described. Plasma obtained in high-dose animal studies is treated by method A, a simple method using 1 ml of plasma, which is based on deproteinization of plasma followed by coprecipitation of the drug with calcium phosphate and dissolution of the precipitate in EDTA. Plasma obtained in low-dose clinical studies is treated by method B, a more sensitive method using 4 ml of plasma, which is based on direct precipitation of the drug prior to the deproteinization in method A. Urine and bone samples are prepared by solid-phase extraction using a Sep-Pak C18 cartridge coupled with method A. The drug is separated with a reversed-phase column using a mobile phase at pH 7, and detected with a fluorescence detector following postcolumn alkalization of the mobile phase to enhance fluorescence intensity. The limit of determination is 0.2 ng/ml for method A and 0.05 ng/ml for method B in plasma, 0.05 ng/ml in urine, and 5 ng/g in bone.

Animals↗

Two lectins from the marine sponge Halichondria okadai. An N-acetyl-sugar-specific lectin (HOL-I) and an N-acetyllactosamine-specific lectin (HOL-II).

Two lectins (HOL-I and HOL-II) were isolated from the marine sponge Halichondria okadai by affinity chromatography on a bovine submaxillary mucin (BSM)-Toyopearl and an acid-treated Sepharose 4B columns, respectively. In hemagglutination inhibition assays, GlcNAc, GalNAc, and their methyl glycosides were the most potent inhibitors among the monosaccharides tested against the HOL-I-mediated hemagglutination, suggesting that HOL-I can especially recognize the N-acetyl groups of the sugars. This N-acetyl specificity was supported by 1H NMR analyses; the highest field-shifts of the signal of the N-acetyl group among all the signals in Me beta GlcNAc were observed in 1H NMR spectra of mixtures of HOL-I and the sugar. Among the oligosaccharides tested, GlcNAc beta 1-->4(GlcNAc beta 1-->2)Man alpha 1-O(CH2)2 CH3 was the most potent inhibitor, and the inhibitory potency of the oligosaccharide was 2(4) times greater than those of GlcNAc and GalNAc. On the other hand, N-acetyllactosamine (Gal beta 1-->4GlcNAc) and its analogs were the strongest inhibitors toward HOL-II-induced hemagglutination. The agglutination was completely inert to Gal beta 1-->3GlcNAc, Gal beta 1-->6GlcNAc, Gal beta 1-->3GalNAc, Gal beta 1-->4GalNAc, and Gal beta 1-->6GalNAc. Furthermore, HOL-II exhibited no binding ability to BSM, asialo-BSM, fetuin, asialofetuin, alpha 1-acid glycoprotein, and human transferrin. These results indicate that HOL-II strictly recognizes simple Gal beta 1-->4GlcNAc unit.

Acetylation↗

M-VEC (methotrexate, vinblastine, epirubicin, and cisplatin) with granulocyte colony-stimulating factor for the treatment of urothelial cancer: an effective and safe chemotherapy regimen.

The toxicity of combination chemotherapy is significant, with the most prominent side effect being myelosuppression. To reduce the toxicity, we used a recombinant human granulocyte colony-stimulating factor (rhG-CSF). A total of 52 patients were enrolled in this study. The sites of tumor involvement included the urinary bladder in 24 patients, the renal pelvis in 5, the ureter in 4, lymph nodes in 11, bone in 4, the lung in 1, and miscellaneous sites in 4 patients. The chemotherapy was given in 21-day cycles as follows: 30 mg/m2 methotrexate was given intravenously on day 1, and approximately 24 h later, 3 mg/m2 vinblastine, 30 mg/m2 epirubicin, and 70 mg/m2 cisplatin were given intravenously. The rhG-CSF (2 micrograms/kg per day) was injected subcutaneously on days 3-16 of each cycle. All patients received full doses of the antineoplastic agents on time according to the protocol design. The response rates were 61% for primary sites, 55% for lymph nodes, 0 for bone, and 67% for miscellaneous sites. Of 42 patients evaluated, 5 (12%) achieved a complete response and 20 (48%) achieved a partial response, for an overall response rate of 60%. Of the 42 patients, 27 (64%) are alive, and the median duration of survival is 14 months. The mean nadir white blood count was more than 5,600 cells/mm3. The incidence of mucositis in the total toxic symptoms was low. There was no cardiac toxicity or drug-related death. These results indicate that the present combination chemotherapy with coadministration of rhG-CSF is an effective and safe regimen for the treatment of urothelial cancer.

Adenocarcinoma↗

Enzymic synthesis of the trisaccharide core region of the carbohydrate chain of N-glycoprotein.

Transmannosylation from mannotriose (Man beta 1-4Man beta 1-4Man) to the 4-position at the nonreducing end N-acetylglucosaminyl residue of N,N'-diacetylchitobiose was regioselectively induced through the use of beta-D-mannanase from Aspergillus niger. The enzyme formed the trisaccharide Man beta 1-4GlcNAc beta 1-4GlcNAc (3.7% of the enzyme-catalysed net decrease of N,N'-diacetylchitobiose) from mannotriose as a donor and N,N'-diacetylchitobiose as an acceptor. Mannobiose (Man beta 1-4Man) was also shown to be useful as a donor substrate for the desired trisaccharide synthesis.

Aspergillus niger↗

An autopsy case of pseudosarcoma of the common bile duct.

An autopsy case of pseudosarcoma in the common bile duct is reported. An 82-year-old Japanese male complaining of jaundice was admitted to our hospital; he was examined by abdominal ultrasonography (US), revealing biliary calculus, dilatation of the common bile duct, and choledocholithiasis, considered to be the possible cause of the obstructive jaundice. Endoscopic retrograde biliary drainage (ERBD) and cholangioscopy were performed concurrently, revealing a vaguely whitish tumor near the papilla of Vater. Two months later, the patient died from complications of the liver, infection, and disseminated intravascular coagulation (DIC). An autopsy study revealed tumor cells with extreme pleomorphic changes, growing diffusely, very like sarcoma. Further examination revealed epithelioid arrangements in the metastatic lymph node. Twelve kinds of immunohistochemical examination showed a positive reaction, reflecting the presence of an epithelioid cytoskeleton. Of 28 cases of true and pseudosarcoma of the biliary system reported in the Japanese literature, only 1 case was reported, in 1990, to involve the common bile duct. We therefore report the present case of pseudosarcoma of the common bile duct.

Aged↗