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Biomedical subjects

T Shimakawa

Publications and source records attributed to T Shimakawa.

29 records · Page 2Linked to original sources
PubMed1993

Identification of amino acid residues responsible for the changes of absorption and fluorescence spectra on the binding of subtilisin BPN' and Streptomyces subtilisin inhibitor.

An ultraviolet absorption difference spectrum characteristic of the ionization change of a tyrosyl residue was observed on the binding of subtilisin BPN' with Streptomyces subtilisin inhibitor (SSI) at alkaline pH. This difference spectrum was considered to be induced by a pKa shift (from 9.7 to > or = 11.5) of a tyrosyl residue of subtilisin BPN' in the interaction with carboxyls of SSI [Inouye et al. (1979) J. Biochem. 85, 1115-1126]. In the present paper, the tyrosyl residue in subtilisin BPN' and the carboxyls in SSI were identified by analyzing the difference spectrum using mutants of subtilisin BPN' and SSI: naturally occurring mutants and those prepared by site-directed and cassette mutagenesis. The difference spectrum disappeared on the binding of a mutant subtilisin BPN' of which Tyr104 was replaced by Phe (S-BPN'Y104F) and SSI at pH 9.8. The magnitude of the absorption difference was much smaller when subtilisin BPN' was bound with a mutant SSI of which both Glu67 and Asp68 were replaced by Gly than with the wild-type SSI. These lines of evidence indicated that the difference spectrum was caused by Tyr104 of subtilisin BPN' interacting with Glu67 and Asp68 of SSI. The binding of subtilisin BPN' and SSI is accompanied by an increase of tryptophan fluorescence, which is pH-dependent in the range of pH 7-11 [Uehara et al. (1978) J. Biochem. 84, 1195-1202]. In the present study, this pH-dependence of the fluorescence diminished when SSI bound with S-BPN'Y104F. This suggested that the fluorescence increase was due to Trp106 of subtilisin BPN' and was influenced by the ionization of Tyr104.

Amino Acids↗
PubMed1993

Associations of fish intake and dietary n-3 polyunsaturated fatty acids with a hypocoagulable profile. The Atherosclerosis Risk in Communities (ARIC) Study.

Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors--fibrinogen, factor VII, factor (vWF), protein C, and antithrombin III--in four population-based samples totaling over 15,000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 microgram/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross-sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors.

Animals↗
PubMed1993

Comparison of diets of diabetic and nondiabetic women.

OBJECTIVE: To assess the dietary habits of diabetic women. RESEARCH DESIGN AND METHODS: Participants in the Nurses Health Study, a cohort of 121,700 registered female nurses, were followed since 1976. We compared the usual dietary intakes of women who had been diagnosed with diabetes mellitus by 1980 and age-matched nondiabetic control women; diets of these women were assessed in 1980 and 1984 by a semiquantitative food frequency questionnaire. The study examined 162 IDDM women and 738 NIDDM women. Similar comparisons were made for 429 women who developed NIDDM between 1980 and 1984. RESULTS: Although differences were small, women with IDDM in 1984 and women with NIDDM in 1980 and 1984 consumed less energy from carbohydrates, especially from sucrose, and more energy from protein and fat than did control women. Similar results were also found in 1984 for the 429 women who developed NIDDM between 1980 and 1984. In 1980, energy from nonsucrose carbohydrate was slightly higher in both IDDM and NIDDM women than in the control women. However, in 1984, using a dietary questionnaire designed to assess more complete dietary intake, less consistent results were obtained. Diabetic women tended to avoid desserts and sweets, sugar-containing beverages, and alcoholic beverages but consumed more meat and meat products. Intakes of foods high in complex carbohydrates (e.g., bread, rice, pasta, and potatoes) were similar between diabetic and control women. CONCLUSIONS: The results suggest that these diabetic women did not consume the high-carbohydrate, low-fat diets that the American Diabetes Association has been recommending over the past decade.

Adult↗
PubMed1984

[Roentgenographic and experimental studies of the patella alta].

Patella alta has so far been given attention with reference to the patellofemoral disorder. However, neither its morphological concept has been quite coherent yet nor its clinical significance has been fully understood. In order to clarify these points, the author made a roentgenographic investigation of patella alta and also conducted an experimental study. Defining as patella alta the condition in which the articular surface of the patella is higher than the patellar surface on the femur, the author evaluated the patella position by seizing, from the dynamic viewpoint, the positions of the articular surface of the patella to the patellar surface on the femur by serial roentgenography and their graphic representations. The results obtained revealed that in the patellofemoral osteoarthritis, compared with the normal, there was observed retarded descending of the patella into the femoral intercondylar notch at knee flexion. Moreover, on the rabbit knee whose patellar ligament was lengthened, descending condition of the patella similar to that observed for human patellofemoral osteoarthritis was created, thus leading to an experimental patellofemoral osteoarthritis. The above results suggested an of important role of patella alta in the pathogenesis of patellofemoral osteoarthritis.

Adolescent↗
PubMedDate not supplied

Alpha-fetoprotein producing Barrett's esophageal adenocarcinoma: a case report.

A 59-year-old man was admitted to our hospital with upper abdominal pain. His serum alpha-fetoprotein (AFP) level was very high, 1500 ng/ml. Upper gastrointestinal endoscopy revealed depressed lesion at 36 cm from the upper incisors, with columnar epithelium lining the esophagus circumferentially to the oral side of the lesion. Histological examination of biopsy specimens revealed a tubular adenocarcinoma as well as the presence of gastric columnar epithelium with intestinal metaplasia. Immunohistochemistry demonstrated AFP in the tumor cells. From these results, a diagnosis of AFP-producing esophageal adenocarcinoma occurring in Barrett's esophagus, a condition which is extremely rare in Japan, was established. Computed tomography (CT) showed multiple metastasis on the liver and wide-ranging lymph node metastasis. Chemotherapy was not effective and the patient died about 2 months after the start of treatment. The AFP-producing esophageal adenocarcinoma presented here had biological characteristics similar to those of AFP-producing gastric cancer.

Adenocarcinoma↗
PubMedDate not supplied

Effect of intratumoral OK-432 administration of thymidine phosphorylase expression in human gastric carcinoma.

It is known that thymidine phosphorylase (dThdPase) is increased in various types of malignant tumors and is induced by cytokines. In this study, we have investigated the effects of OK-432, which induces multiple cytokines, on dTHdPase expression and angiogenesis in human gastric carcinomas. We examined 25 patients who underwent gastrectomy for gastric carcinoma. OK-432 was directly injected in tumors in 16 (OK group) of 25 patients via endoscopy before operation and the other 9 patients were not treated (control group). The dThdPase activity in carcinoma tissues of the OK group was significantly higher than that of the control group (P < 0.05). The amounts of IL-1 alpha, IFN-alpha, and IFN-gamma in carcinomas in the OK group were significantly higher than in the controls (P < 0.05), and these were significantly correlated with the dThdPase activity. Intratumoral OK-432 administration enhances the expression of dThdPase in gastric carcinoma cells by inducing various cytokines.

Antineoplastic Agents↗
PubMedDate not supplied

Study on endoscopic esophageal mucosal resection with ligating device. I--Clinical study.

BACKGROUND/AIMS: EEMRL (endoscopic esophageal mucosal resection with a ligating device) has become increasingly popular. In this article, we review 13 clinical cases of EEMRL. METHODOLOGY: Since 1993, we have performed EEMRL to treat 15 lesions in 13 patients. Twelve squamous cell carcinomas (mucosal cancer in 10 and submucosal cancer in 2) were included among the 15 lesions. RESULTS: EEMRL failed to achieve complete resection of the 2 submucosal lesions (3.0 and 2.8 cm in maximum diameter). However, esophageal lesions could be removed successfully when 2.5 cm or less in maximum diameter. The procedure was not associated with any complication. CONCLUSIONS: Our clinical study showed that this technique may be indicated for esophageal cancer with a maximum diameter < or = 2.5 cm and confined to the mucosa. EEMRL is a technically easy and minimally invasive therapy which could be useful for the treatment of early esophageal cancer.

Aged↗
PubMedDate not supplied

Study on endoscopic esophageal mucosal resection with ligating device. II--Experimental study.

BACKGROUND/AIMS: This study reports on animal experiments regarding the safety of endoscopic esophageal mucosal resection with a ligating device (EEMRL), as well as the amount of mucosa which can be removed by this technique, the depth of resection and the feasibility of piecemeal resection. METHODOLOGY: Three experiments were performed in six mongrel dogs under general anesthesia. RESULTS: When EEMRL was done without submucosal injection of saline, resection reached the muscular layer and caused esophageal perforation. The average dimensions of the mucosal pieces resected using 8-, 10-, and 12-mm devices was 13 x 10 mm, 18 x 15 mm, and 22 x 18 mm, respectively. Resection reached the mid-plane of the submucosa and the depth was almost uniform. After piecemeal resection, there was no macroscopically visible mucosa at the resection site and each mucosal piece was resected along the mid-plane of the submucosa. CONCLUSIONS: The experimental study indicated that submucosal injection of saline is essential to prevent esophageal perforation. It also showed that EEMRL allows resection up to the mid-plane of the submucosa, that the 12-mm device allows en bloc resection of lesions < or = 15 mm in diameter and that EEMRL is suitable for piecemeal resection.

Animals↗