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101.
102.
A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids 总被引:2,自引:0,他引:2
Savolainen K Kotti TJ Schmitz W Savolainen TI Sormunen RT Ilves M Vainio SJ Conzelmann E Hiltunen JK 《Human molecular genetics》2004,13(9):955-965
alpha-Methylacyl-CoA racemase (Amacr) deficiency in humans leads to sensory motor neuronal and liver abnormalities. The disorder is recessively inherited and caused by mutations in the AMACR gene, which encodes Amacr, an enzyme presumed to be essential for bile acid synthesis and to participate in the degradation of methyl-branched fatty acids. To generate a model to study the pathophysiology in Amacr deficiency we inactivated the mouse Amacr gene. As per human Amacr deficiency, the Amacr(-/-) mice showed accumulation (44-fold) of C27 bile acid precursors and decreased (over 50%) primary (C24) bile acids in bile, serum and liver, however the Amacr(-/-) mice were clinically symptomless. Real-time quantitative PCR analysis showed that, among other responses, the level of mRNA for peroxisomal multifunctional enzyme type 1 (pMFE-1) was increased 3-fold in Amacr(-/-) mice. This enzyme can be placed, together with CYP3A11 and CYP46A1, to make an Amacr-independent pathway for the generation of C24 bile acids. Exposure of Amacr(-/-) mice to a diet supplemented with phytol, a source for branched-chain fatty acids, triggered the development of a disease state with liver manifestations, redefining the physiological significance of Amacr. Amacr is indispensable for the detoxification of dietary methyl-branched lipids and, although it contributes normally to bile acid synthesis from cholesterol, the putative pMFE-1-mediated cholesterol degradation can provide for generation of bile acids, allowing survival without Amacr. Based upon our mouse model, we propose elimination of phytol from the diet of patients suffering from Amacr deficiency. 相似文献
103.
104.
Professor C. K. Peck G. Barber C. E. Pilsecker R. C. Wark 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1980,41(1):61-74
Summary Visual fields of ten cats which had one or both eyes rotated at 8 days of age were measured by two forms of perimetry and compared to visual fields of two normal cats and of four cats with monocular rotations at 16 days, 3 months or 6 months of age. All animals showed excellent localization of visual stimuli and responded to the actual location of stimuli in space rather than to the retinal locus normally associated with that location. In cats with monocular rotations, the field of the normal eye was always normal, extending from 90 ° ipsilateral to 30 ° contralateral. Cats with rotations of one eye at 3 or 6 months of age had essentially normal fields in the rotated eye as well, while cats with surgery at 8 or 16 days had restricted horizontal fields. They responded only to stimuli in the ipsilateral hemifield; they were blind in the contralateral hemifield. Their superior and inferior visual fields were normal. The field deficits related consistently to visual field coordinates and not to the angle or direction of rotation. In cats with binocular rotations the visual field of at least one eye extended across the midline. Thus, the extent of the field depended upon sensorimotor experiences of the cat both before and after surgery. It is argued that these monocular field deficits have a central origin, not a retinal one.When tested with both eyes open, seven of 14 experimental animals did not respond throughout the visual field seen by each eye alone. The total visual field with both eyes open was less than the sum of the two monocular fields; greatest losses were most pronounced in the extreme periphery of the field ipsilateral to the rotated eye. Since changes in eye position (e.g., convergence during bincocular viewing) were not observed, it is suggested that the binocular losses indicate suppression of the deviated eye which has a central origin.All animals were tested for visual following, visually-triggered extension (placing), and visually-guided reaching. Cats which had been routinely encouraged to use the rotated eye(s) by occlusion of the other eye showed skilful performance within a few weeks after surgery as previously reported by Peck and Crewther (1975), Mitchell et al. (1976) and others. In contrast, two cats reared with both eyes open after unilateral rotation in infancy were profoundly handicapped, as previously reported by Yinon (1975, 1976).This research was supported by Grant NS 14116 from the US Public Health Service 相似文献
105.
Haematocrits were measured as a function of ultrafiltration in a simulated haemodialysis circuit using bovine blood (plasma conductivity 12 mS cm-1) and hypotonic (8.6 mS cm-1) or hypertonic (16 mS cm-1) dialysates as well as in the absence of dialysate. A comparison was made between measurements by light absorption due to haemoglobin, by impedance in the blood line at 5 kHz using Hanai's model of blood conductivity, by conductivity measurements of blood samples at 1.2 kHz using a conductimeter, by centrifugation of blood samples and by calculations using fluid conservation. The validity of Hanai's model was verified to be satisfactory by direct blood and plasma conductivity measurements. In the absence of ionic transfer the impedance device underestimated the haematocrit by 5 to 7%. This underestimation reached 18% in the case of hypertonic dialysate, but this effect can be minimised if the haematocrit necessary for calibration is measured by centrifugation after 15 min of dialysate circulation when ionic balance is achieved. It was found that the optical method monitors haemoglobin concentration rather than red cell volume changes and is not affected by osmotic red cell swelling in the case of hypotonic dialysate. It can be concluded that the light absorption technique is both more accurate and more convenient to use than impedance. 相似文献
106.
Immunohistochemical Study of Colorectal Tumors for Expression of a Novel Transmembrane Carbonic Anhydrase, MN/CA IX, with Potential Value as a Marker of Cell Proliferation 总被引:6,自引:4,他引:6
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Juha Saarnio Seppo Parkkila Anna-Kaisa Parkkila Kari Haukipuro Silvia Pastorekov Jaromir Pastorek Matti I. Kairaluoma Tuomo J. Karttunen 《The American journal of pathology》1998,153(1):279-285
Carbonic anhydrase isoenzyme IX, MN/CA IX, is a recently discovered member of the carbonic anhydrase (CA) gene family with a suggested function in acid-base balance, intercellular communication, and cell proliferation. Increased expression of MN/CA IX has been observed with certain epithelial tumors. We investigated the expression of MN/CA IX in 69 colorectal neoplasms, consisting of 1 juvenile polyp, 8 hyperplastic polyps, 39 adenomatous lesions, 21 carcinomas, and 7 metastases. Tissue sections were immunostained with a monoclonal antibody specific to MN/CA IX. The proliferative activity of the tumor cells was evaluated by Ki-67 antigen immunoreactivity. The hyperplastic polyps showed a weak or moderate reaction for MN/CA IX only in the cryptal epithelium, as did the normal intestinal mucosa. The adenomas showed immunoreactivity mainly in the superficial part of the mucosa, whereas the distribution in the carcinomas and metastases was more diffuse. Comparative immunostaining of serial sections for Ki-67, a well established marker of cell proliferation, confirmed that MN/CA IX is expressed in areas with high proliferative capacity. Our results show abnormal MN/CA IX expression in colorectal neoplasms, suggesting its involvement in their pathogenesis. The co-occurrence of MN/CA IX and Ki-67 in the same tumor cells indicates its potential for use as a marker of increased proliferation in the colorectal mucosa. 相似文献
107.
Factors related to postmenopausal muscle performance: a cross-sectional population-based study 总被引:2,自引:0,他引:2
Sirola J Rikkonen T Kröger H Honkanen R Tuppurainen M Airaksinen O Saarikoski S 《European journal of applied physiology》2004,93(1-2):102-107
The aim of the present study was to investigate cross-sectionally the association of postmenopausal muscle strength with simple performance tests. A random sample of 1,166 naturally postmenopausal women (born 1932–1941) was selected from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. Grip and quadriceps strength were measured with strain gauge dynamometers and reported in both absolute values (KPa and kg) and per kilogram of body mass (N cm–2 kg–1 and N kg–1). In addition, two performance tests, ability to stand on one foot and ability to squat down to touch the floor were carried out. A five-category self-assessment of overall health (very good, good, moderate, bad, and very bad) was obtained by postal questionnaire. The women that were able to stand on one foot and able to squat down to touch the floor had greater grip and quadriceps strength than their counterparts (P<0.001 and P<0.03 in ANOVA, respectively). In addition, self-assessed health had a strong positive association with muscle strength in the grip and leg extensor muscles in ANOVA (P<0.001 between very good and moderate or poorer state of health) and regression model (P<0.001). Adjustment for age, duration of menopause, body mass, height, physical activity level, use of HRT, and number of diseases and medications did not change any of the main effects. Also, there were no differences in results between absolute measurement values and values reported per kilogram of body mass. According to the present study, a simple performance test may be useful in the prediction of postmenopausal muscle strength. Furthermore, self-assessed state of health is strongly associated with muscle strength in postmenopausal women. 相似文献
108.
Bousquet J Yssel H Demoly P 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2000,13(1):61-75
AbstractAllergen-specific immunotherapy is widely used to treat allergic diseases, andcurrent research is now focusing on the development of therapeutic vaccines actingon the IgE immune response following allergen challenge. The IgE immuneresponse is dependent on genetic and environmental factors; production of IgEresults from complex interactions among B cells, T cells, mast cells, basophils,surface and adhesion molecules and various cytokines. New vaccination methods under investigation involve allergen-specific ornonspecific methodology. Allergen-specific methods currently being developedinclude allergoids, passive saturation of effector cells, plasmid DNA immunisationand antigen-antibody complexes. The mechanisms of immunotherapy usingallergen-specific methods differ with the allergens and the route of immunisationused (parenteral, intranasal, sublingual, oral or bronchial). Many vaccines beingdeveloped at present comprise synthetic, recombinant or highly purified subunitantigens, which although they have increased safety may also be less immunogenic.It is hoped that the addition of adjuvants will overcome this drawback. Methods ofincreasing the dose of allergen while reducing the possibility of an anaphylacticreaction include the use of non-anaphylactic isoforms of the allergens, alteration ofthe tertiary structure of the allergens and construction of minimal allergen-derived Tcell peptides. Nonspecific approaches include humanised anti-IgE antibodies,moderation of the T(H)2 cytokine network and antisenseoligodeoxynucleotide therapy. 相似文献
109.
Buchs A Slovik Y Rapoport M Rosenfeld C Khanokh B Nitzan M 《Medical & biological engineering & computing》2005,43(2):252-257
Photoplethysmography (PPG) records the cardiac-induced changes in tissue blood volume by light-transmission measurements.
The baseline and amplitude of the PPG signal show very low-frequency (VLF) spontaneous fluctuations, which are mediated by
the sympathetic nervous system, and high correlation between right and left extremities of healthy subjects. As sympathetic
neuropathy is one of the diabetic complications, the right-left correlation of the PPG fluctuations was examined in diabetic
patients. The PPG signal was simultaneously measured in the two index fingers and the two second toes of 35 diabetic patients
and 33 non-diabetic subjects. For each PPG pulse, the baseline and amplitude were determined, and the right-left correlation
coefficients of the VLF fluctuations in the baseline and amplitude were derived. The VLF fluctuations in the baseline showed
high right-left correlation, both for fingers (0.93±0.05) and toes (0.93±0.06), for the non-diabetic subjects, and significantly
lower correlation (0.78±0.22 and 0.84±0.17, respectively) for the diabetic patients. Similar results were obtained for the
amplitude VLF fluctuations. The right-left correlation coefficients for diabetic patients decreased with the disease duration
for the toe baseline and toe amplitude fluctuations and correlated with heart rate response to deep breathing for the finger
baseline and toe amplitude fluctuations. The right-left correlation coefficients of the PPG fluctuations provide a simple
and convenient means for assessing the adequacy of the sympathetic nervous system function. 相似文献
110.
Kunnas TA Lehtimäki T Karhunen PJ Laaksonen R Janatuinen T Vesalainen R Nuutila P Knuuti J Nikkari ST 《Journal of molecular medicine (Berlin, Germany)》2004,82(12):821-825
Most of the effects of estrogens are mediated by estrogen receptors. Vascular endothelial cells and smooth muscle cells express estrogen receptor (ESR1) in both genders. A long genotype group of a common thymine-adenine (TA) dinucleotide repeat polymorphism in the regulatory region of this gene has previously been related to coronary artery disease. The present study examined whether coronary blood flow is affected by this genotype. A total of 49 healthy men were genotyped by PCR and divided into three groups according to median number of the ESR1 promoter TA repeat (=19), i.e., in the short allele genotype group both alleles were of fewer than 19 repeats whereas in the long allele group both alleles were 19 repeats or more. The intermediate group comprised men who had one short and one long allele. Myocardial blood flow was measured by positron emission tomography using [15O]water, performed at rest and during adenosine stimulation. Men with long alleles had lower adenosine-stimulated coronary flow than those with short alleles and those with one short and one long allelle. Our results suggest that adenosine-stimulated myocardial perfusion is lower in subjects with ESR1 long alleles than the other TA repeat genotypes. 相似文献