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Biomedical subjects

A Maeda

Publications and source records attributed to A Maeda.

468 records · Page 26Linked to original sources
PubMedDate not supplied

Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor.

Cloning and sequence analysis of DNA complementary to porcine cerebral messenger RNA encoding the muscarinic acetylcholine receptor predict the complete amino-acid sequence of this protein. Expression of the complementary DNA produced functional muscarinic receptor in Xenopus oocytes. The muscarinic receptor is homologous with the beta-adrenergic receptor and rhodopsin in both amino-acid sequence and suggested transmembrane topography.

Amino Acid Sequence↗
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Molecular distinction between muscarinic acetylcholine receptor subtypes.

The muscarinic acetylcholine receptor (mAChR) mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels, through the action of guanine nucleotide-binding regulatory proteins. Pharmacologically distinguishable forms of the mAChR occur in different tissues and have provisionally been classified into M1 (I), M2 cardiac (II) and M2 glandular (III) subtypes on the basis of their difference in apparent affinity for antagonists. In an attempt to elucidate the molecular basis of the functional heterogeneity of the mAChR, we have cloned and sequenced DNAs complementary to porcine cerebral and cardiac messenger RNAs encoding mAChRs and have thereby deduced the primary structures of the receptor proteins. We report here that the messenger RNA generated by transcription of the cardiac complementary DNA directs the formation of a functional mAChR in Xenopus oocytes and that this mAChR differs from the mAChR formed by expression of the cerebral cDNA both in acetylcholine (ACh)-induced response and in antagonist binding properties. Our results provide evidence indicating that the mAChR encoded by the cerebral cDNA (designated as mAChR I) and the mAChR encoded by the cardiac cDNA (mAChR II) are of the M1 (I) and the M2 cardiac (II) subtype, respectively.

Acetylcholine↗
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Progression of cellular repopulation and collagen synthesis in fresh-frozen allograft tendons.

The progression of cellular repopulation and collagen synthesis in fresh-frozen rat patellar tendon allografts was investigated by means of indirect immunofluorescence histologic analysis and electron microscopic techniques for 8 weeks after transplantation. In each of 10 procedures, the medial half of the patellar tendon with a tibial bone block was harvested from a Wistar rat and transplanted into a corresponding defect in the medial patellar tendon of a Lewis rat. Actin filaments in the repopulating cells and newly synthesized collagen fibrils in the graft were identified with rhodamine-phalloidin stain and with a polyclonal antibody against type III collagen aminopropeptide. On the first day after transplantation, no specific fluorescence was detected in the graft. One week later, specific labeling for fibrillar-actin (F-actin) and type III collagen aminopropeptide was detected in an area extending from the adjacent granulation tissue into the proximal end of the graft. F-actin and type III collagen aminopropeptide were aligned along the longitudinal axis of the graft and extended from the proximal suture site toward the distal portion. Two weeks after transplantation, fibrillar labeling for F-actin and type III collagen amino-propeptide showed that remodeling had extended to the midportion of the graft. Labeling throughout the entire graft was detected 4 weeks after transplantation. During the entire remodeling process, the repopulated fibroblasts consistently retained their elongated shape and their alignment with the longitudinal axis of the graft. The cells developed well-organized actin bundles at their peripheries, which identified them as having a myofibroblast phenotype. Immunofluorescence detection for type III collagen aminopropeptide also showed consistent alignment parallel to the longitudinal axis of the graft and a fibrillar arrangement. Electron microscopy revealed thinner collagen fibrils in the vicinity of the fibroblasts, which were aligned in the direction of the actin bundles. These results indicate that, during the early remodeling phase, collagen synthesis and deposition in the graft proceeds while the original alignment of the graft matrix is preserved. The close association between the alignment of actin bundles in repopulated "myofibroblastic" cells and that of newly synthesized collagen fibrils along the lines of the graft matrix may represent evidence of force transmission between the actin cytoskeleton and the linking extracellular matrix in vivo.

Journal Article↗
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Delayed latency of peroneal reflex to sudden inversion with ankle taping or bracing.

The purpose of the present study was to examine the effects of ankle taping and bracing based on the peroneal reflex in the hypermobile and normal ankle joints with and without history of ankle injury. Thirty-six ankle joints of 18 collegiate American football athletes with and without previous history of injury were studied. The angle of talar tilt (TT) was measured by stress radiograph for classifying normal (TT</=5 degrees ) or hypermobile (TT>5 degrees ) ankles. They were tested with taping, bracing, and without any supports as a control. The latency of peroneus longus muscle was measured by a sudden inversion of 25 degrees using surface EMG signals. The results of the present study show no significant three-way Group (hypermobile or normal ankles) by History (previously injured or uninjured ankles) by Condition (control, taping, or bracing) interaction, while Condition main effect was significant (p<0.05). There were significant differences between control (80.8 ms) and taping (83.8 ms, p<0.01), between control and bracing (83.0 ms, p<0.05), but not between taping and bracing (p>0.05). In conclusion, ankle taping and bracing delayed the peroneal reflex latency not only for hypermobile ankles and/or injured ankle joints but also for intact ankle joints.

Adolescent↗
PubMedDate not supplied

Physical performance tests after stroke: reliability and validity.

OBJECTIVE: To evaluate the reliability and validity of the modified physical performance tests for stroke survivors who live in a community. DESIGN: The subjects included 40 stroke survivors and 40 apparently healthy independent elderly persons. The physical performance tests for the stroke survivors comprised two physical capacity evaluation tasks that represented physical abilities necessary to perform the main activities of daily living, e.g., standing-up ability (time needed to stand up from bed rest) and walking ability (time needed to walk 10 m). RESULTS: Regarding the reliability of tests, significant correlations were confirmed between test and retest of physical performance tests with both short and long intervals in individuals after stroke. Regarding the validity of tests, the authors studied the significant correlations between the maximum isometric strength of the quardriceps muscle and the time needed to walk 10 m, centimeters reached while sitting and reaching, and the time needed to stand up from bed rest. CONCLUSIONS: The authors confirmed that there were significant correlations between the instrumental activity of daily living and the time needed to stand up from bed rest, along with the time needed to walk 10 m for the stroke survivors. These physical performance tests are useful guides for evaluating a level of activity of daily living and physical frailty of stroke survivors living in a community.

Activities of Daily Living↗
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An angiotensin-converting enzyme inhibitor protects against doxorubicin-induced impairment of calcium handling in neonatal rat cardiac myocytes.

1. The effects of doxorubicin (DOX) on intracellular calcium transients were examined in neonatal rat cultured cardiac myocytes, as were the cardioprotective effects of an angiotensin-converting enzyme (ACE) inhibitor on DOX-induced impairment of calcium handling. 2. Cultured cardiac myocytes isolated from neonatal Wistar-Kyoto rats were treated with DOX for 24 h. Field-stimulated calcium transients in single myocytes were measured in the presence or in the absence of isoproterenol using fura-2/AM. Calcium transients were also measured after the addition of DOX to myocytes pretreated with M-I (an active metabolite of delapril HCL, an ACE inhibitor. 3. Doxorubicin reduced the amplitude and maximum velocity of increase and decrease of calcium transients, prolonged the time-course of calcium transients and impaired the beta-adrenoceptor responsiveness of calcium transients in a dose-dependent manner. The DOX-induced impairment of calcium transients and beta-adrenoceptor responsiveness was improved by M-I. 4. Doxorubicin impaired both the mobilization and sequestration of intracellular calcium ions in contraction-relaxation cycles and the response of calcium transients to beta-adrenoceptor stimulation. The ACE inhibitor ameliorated DOX-induced impairment of calcium dynamics, suggesting ihat M-I, an active metabolite of delapril, protects against DOX-induced abnormal calcium handling leading to cardiac dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
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Effects of a gastric mucosal protecting agent in rats with liver cirrhosis.

Male Sprague-Dawley rats were fed a 0.1% ethionine-added choline-deficient diet for 8 weeks to induce liver cirrhosis. At the same time 100 mg/kg/day teprenone was administered orally in order to evaluate its effects on the liver and gastric mucosal blood flow. Blood flow increased not only in gastric mucosa but also in liver tissues in the teprenone group. Serum transaminase levels and histopathologic findings of the liver also improved. These findings suggest that teprenone alleviates hepatocellular injuries. This effect may be partly attributable to cytoprotective effects of the catenoid isoprenoid moiety of teprenone on liver cells.

Animals↗
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Articular cartilage lesions in ankles with lateral ligament injury. An arthroscopic study.

To investigate intraarticular lesions producing persistent postoperative pain, we arthroscopically examined 31 ankles in 31 patients (15 women and 16 men) with lateral ligament injury. The patients ranged in age from 15 to 33 years, with a mean of 20 years. Nine patients were freshly injured, and 22 patients had chronic injuries. All of the patients underwent arthroscopic examination immediately before the ligament operation. Chondral lesions were found in 89% of the freshly injured ankles and 95% of the ankles with chronic injuries. Most of these lesions were in the medial half of the ankle joint, especially in the anteromedial edge of the tibial plafond. After followup for 1 year postoperatively, persistent pain was noted in 4 patients who had chondral lesions of greater than one-half the thickness of the articular cartilage. Pain and tenderness were localized at the anteromedial joint line, corresponding to the location of the chondral lesions. Chondral lesions of greater than one-half the thickness of the articular cartilage were found in 8 ankles in the chronic injury group, but there were none in the fresh injury group. Thus, in lateral ligament injuries of the ankle, the longer the time elapsed from the initial injury, the more severe the associated chondral lesions became. These chondral lesions appear to cause persistent pain.

Acute Disease↗
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Anterior cruciate ligament reconstruction with multistranded autogenous semitendinosus tendon.

We evaluated 41 knees 24 to 48 months after anterior cruciate ligament reconstruction was performed using multiple autogenous semitendinosus tendons. The ipsilateral free semitendinosus tendon was tripled or quadrupled to make a graft 7 to 10 mm in diameter and more than 60 mm long. When the diameter of the graft was less than 7 mm, an ipsilateral doubled gracilis tendon was also used (in seven cases). Twenty-three patients (56%) returned to their preinjury activity levels. According to the patients' subjective assessment, 34 (83%) graded themselves as normal or nearly normal. No patient reported giving way of the knee or limitation of knee motion. The average anterior laxity difference between the involved knee and contralateral uninjured knee was 1.5 mm at 200 N. Twenty-nine patients (71%) demonstrated an anterior laxity difference of 3 mm or less when the involved knee was compared with the contralateral uninjured knee. Quadriceps muscle strength was 90% compared with the contralateral healthy limb, and hamstring muscle strength was equivalent to the contralateral limb. In our study, tripled or quadrupled semitendinosus free tendons were excellent anterior cruciate ligament grafts for restoring knee stability, recovering thigh muscle power, and preserving knee motion.

Adolescent↗
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Health care financing and delivery in developing countries.

Developing countries account for 84 percent of world population and 93 percent of the worldwide burden of disease; however, they account for only 18 percent of global income and 11 percent of global health spending. Limited resources and administrative capacity coupled with strong underlying needs for services pose serious challenges to governments in the developing world. This paper analyzes health spending, health outcomes, and health delivery system characteristics for the six developing regions of the world as well as for low-, medium-, and high-income country groupings.

Cost of Illness↗
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Epstein-Barr virus-infected B-chronic lymphocyte leukemia cells express the virally encoded nuclear proteins but they do not enter the cell cycle.

OBJECTIVES: To understand the mechanism for the refractoriness of B-chronic lymphocyte leukemia (B-CLL) cells for EBV-induced immortalization. STUDY DESIGN/METHODS: Cells from four B-CLL patients were infected with Epstein-Barr virus (EBV). Noninfected and infected aliquots were exposed to CD40L. Five days later, the cultures were analyzed for cell survival, activation, DNA synthesis, and expression of EBV-encoded and of cellular regulatory proteins retinoblastoma (Rb), p53, recombinant sequence binding protein (RBP)Jk, and PU.1. The proteins were detected by immunoblotting and by immunofluorescence. RESULTS: A proportion of the cells were activated and expressed Epstein-Barr nuclear antigens (EBNAs) and elevated Rb level but not latent membrane protein (LMP)-1 and p53. They did not enter the cell cycle. Exposure to CD40L induced DNA synthesis but it did not modify the expression of the EBNAs. CONCLUSIONS: The virus could activate CLL cells, but the full course of the early events that leads to immortalization--as seen in normal B cells--did not proceed beyond a certain point. Compared to B lymphocytes, the critical point is between activation and initiation of the cell cycle.

B-Lymphocytes↗
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Epstein-barr virus can infect B-chronic lymphocytic leukemia cells but it does not orchestrate the cell cycle regulatory proteins.

OBJECTIVES: To understand the mechanism for the refractoriness of B-chronic lymphocytic leukemia (B-CLL) cells for Epstein-Barr virus (EBV)-induced immortalization. STUDY DESIGN/METHODS: Cultures were initiated with EBV-infected tonsillar B and B-CLL cells. Expression of EBNA-2 and some of the key players regulating G1/S phase transition such as c-myc expression, phosphorylation of Rb protein, expression of G1 cyclins, and the cyclin-dependent kinase inhibitor p27 were followed. RESULTS: In line with earlier studies, EBV infection induced c-myc expression, pRb phosphorylation, D2 and D3 expression, and disappearance of p27 in normal B cells. In contrast, EBV-infected B-CLL cells remained resting and they did not express c-myc; cyclin D2, ppRb and cyclin D3 were seen only in occasional cells. Importantly, p27 expression was maintained. CONCLUSIONS: In B-CLL cells, the expression of the EBV-encoded nuclear proteins EBNAs is not followed by entrance to the cell cycle. Thus, the difference in the interaction of EBV-normal B cells and EBV-B-CLL cells is already apparent early after infection.

Animals↗
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Effect of interferon therapy in a patient with chronic active hepatitis type C associated with interstitial pneumonia and rheumatoid arthritis: a case report.

Interferon (IFN) is widely used to treat patients with chronic hepatitis types B and C but has been found to occasionally aggravate rheumatoid arthritis (RA) or cause interstitial pneumonia. We administered 6 MIU/d IFN-beta by intravenous injection for 6 weeks to a 55-year-old man with chronic active hepatitis type C associated with RA and interstitial pneumonia. Transaminase levels rapidly returned to normal after treatment and hepatitis C virus-RNA (nested RT-PCR method) was negative on completion of treatment. No significant adverse reactions or aggravation of RA or interstitial pneumonia occurred. These findings suggest that use of IFN-beta in the treatment of patients with chronic hepatitis type C associated with RA and/or interstitial pneumonia presents no problem if appropriate precautions are taken.

Anti-Inflammatory Agents, Non-Steroidal↗
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Role of eicosapentaenoic acid in lipid metabolism in the liver, with special reference to experimental fatty liver.

Choline-deficient feed was given to three groups (n = 7 in each) of male Sprague-Dawley rats for 4 weeks to induce the development of fatty liver. In addition, two of the groups received eicosapentaenoic acid (EPA), 1000 mg/kg/d, administered orally either for all 4 weeks or for only the last 2 weeks of the study, respectively. The third group received the choline-deficient diet but no EPA. The untreated control group (n = 7) received only normal feed. The efficacy of EPA in preventing fatty liver was assessed based on the evaluation of pathologic and biochemical parameters and hepatic blood flow. EPA markedly improved fatty liver, probably due to both direct effects (inhibition of the synthesis of triglyceride in the liver) and indirect effects (increased hepatic blood flow). Decreased blood flow due to sinusoidal block is responsible for the progression of fatty liver. EPA has been shown to decrease thromboxane A2 production and blood viscosity and to enhance red cell deformability. These effects are thought to have contributed to the increases in hepatic blood flow.

Animals↗
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Inhibitory effect of ursodeoxycholic acid on the progression of chronic hepatic disorders with special reference to increases in blood flow.

Ursodeoxycholic acid (UDCA), which is commonly used as a cholesterol-gallstone-dissolving agent, is now expected to be effective not only for primary biliary cirrhosis but for chronic active hepatitis as well. In this study, we administered 0.1% ethionine-added, choline-deficient diet for 8 weeks to male Sprague-Dawley rats to prepare an animal model of chronic hepatic disorders. At the same time, UDCA (50 mg/kg/day) was administered orally to these animals, and its effects on the liver, including effects on hepatic blood flow determined with a laser Doppler blood flow meter, were evaluated. Hepatic blood flow increased significantly in the UDCA group compared with the untreated groups. Transaminase levels decreased significantly in the UDCA group compared with the untreated group. Histologic differences were noted between the UDCA and untreated groups in histopathologic examinations of the liver, with liver cirrhosis or early liver cirrhosis being present in the untreated group, compared with only chronic active hepatitis in the UDCA group. These findings suggest that UDCA is able to prevent or inhibit the progression of chronic hepatic disorders, an effect that may be due in part to increases in hepatic blood flow.

Alanine Transaminase↗
PubMedDate not supplied

Experimental use of pravastatin in patients with primary biliary cirrhosis associated with hypercholesterolemia.

Primary biliary cirrhosis (PBC) is a refractory liver disease for which no medical treatment has been established. The investigators administered 20 mg/day of pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, to 2 PBC patients with hypercholesterolemia (1010 and 306 mg/dl) for 3 years and 10 months in order to decrease the blood concentration of bile acids and prevent adverse effects on the hepatocellular membrane. The drug markedly decreased not only cholesterol levels but also total bile acid levels, producing particularly pronounced decreases in cholic acid and chenodeoxycholic acid. Histologically, progression was inhibited in one patient, whereas improvement was seen in the other. Bile duct enzymes and other biochemical parameters showed improvement in both cases. General pruritus and blepharal and palmar xanthoma also improved. These findings suggest that pravastatin may be useful in the treatment of PBC associated with hypercholesterolemia.

Biopsy↗