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191.
Cells of the immune system produce a variety of neuropeptides or peptide hormones, either constitutively or upon induction, and possess specific neuropeptide receptors that display ligand-receptor interactions similar to those described in the central nervous system (CNS). These findings suggest that specific subsets of lymphoid cells can produce and respond to peptides previously thought to be principally neural mediators. Recently, corticotropin releasing factor (CRF) mRNA was detected in the rat thymus and spleen, although the cells that synthesize CRF were not identified. We examined the localization of CRF and its mRNA in the rat spleen, thymus, and mesenteric lymph nodes using immunocytochemistry (ICC) and in situ hybridization (ISH), respectively. Immunoreactive CRF was present in cells in the marginal zone and red pulp of the spleen, in connective tissue septa and the subcapsular region of the thymus, and in the medullary cords and sinuses of the mesenteric lymph nodes. Dual ICC/ISH for CRF and its mRNA, respectively, demonstrated CRF mRNA over CRF-immunoreactive cells, suggesting CRF synthesis. Double-label ICC for CRF and markers for specific immunocyte subsets suggest that CRF+ cells in the spleen and thymus are macrophages. CRF+ cells in primary and secondary lymphoid organs reside in compartments that are innervated by sympathetic nerves, and some cells appears to be contacted by noradrenergic sympathetic nerve fibers, suggesting that CRF release may be influenced by the sympathetic nervous system, as it is in the hypothalamo-pituitary-adrenal axis. The presence of CRF in organs of the immune system suggests that this neuropeptide may modulate immune functions after paracrine release.  相似文献   
192.
von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor VIII binding site/subunit. Prior reports suggest that posttranslational modifications of vWF, including formation of N-terminal intersubunit disulfide bonds and subsequent cleavage of the propeptide, influence availability and/or affinity of factor VIII binding sites. We found that deletion of the vWF propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold lower affinity than multimeric vWF in an equilibrium flow cytometry assay (approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF with the vWF propeptide in trans yielded multimeric vWF that displayed increased affinity for factor VIII. Insertion of an alanine residue at the N-terminus of the mature vWF subunit destroyed binding to factor VIII, indicating that the native mature N-terminus is required for factor VIII binding. The requirement for vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide cleavage site yielding pro-vWF that was defective in factor VIII binding and (2) correlation between efficiency of intracellular propeptide cleavage and factor VIII binding. Furthermore, in a cell-free system, addition of the propeptide-cleaving enzyme PACE/furin enabled factor VIII binding in parallel with propeptide cleavage. Our results indicate that high-affinity factor VIII binding sites are located on N-terminal disulfide-linked vWF subunits from which the propeptide has been cleaved.  相似文献   
193.
The ETV6 (TEL) locus at chromosome band 12p 13 is a major site of translocations in acute leukemia, particularly in childhood acute lymphoblastic leukemia (ALL). In cases with translocations involving ETV6, the normal ETV6 allele is often deleted. In addition, loss of heterozygosity of ETV6 is frequently observed in childhood'ALL. Thus, it has been suggested that ETV6 may have an anti-oncogenic role to play, in addition to its oncogenic role. We have described an unusual case of ALL in which ETV6 is found fused to the ABL gene; ABL is normally activated by fusion to the BCR gene in the 9:22 translocation. We expanded the primary cells from this ETV6/ABL rearranged case of ALL in SCID animals and analyzed them for expression of both ETV6/ABL and the normal ETV6 mRNA. We found that both the rearranged and normal ETV6 mRNAs are expressed in the expanded cell population. Furthermore, sequence analysis of the ETV6 PCR product revealed no point mutations which would influence the amino acid sequence. Thus, deletion of the second ETV6 allele is not necessary for the transformation to leukemia by ETV6/ABL.  相似文献   
194.
195.
An evaluation was done of the state of bulbar microcirculation and aggregability of blood platelets in 47 patients presenting with early manifestations of cerebral circulatory insufficiency. A correlation was established between the revealed disturbances in the microcirculatory bed and augmentation of aggregational activity of thrombocytes. Computation of the integrative guide, microcirculatory-rheologic index, reflecting objectively the degree of intravascular hemocirculatory disorders has been performed. Treatment with calcium antagonist corinfar, antihypoxic agent actovegin was of particular benefit for the patients when administered in combination; more than half of the parameters characterizing microcirculation, rheologic properties of blood, microcirculatory-rheologic index have all returned to normal.  相似文献   
196.
We studied the mutagenic potential of the trematode Opisthorchis felineus in experimentally infected guinea pigs by chromosome analysis. The investigation was conducted on 30 treated (experimentally infected) and 20 normal (uninfected) guinea pigs (Cavia porcellus). A sample of living metacercariae of O. felineus was obtained from the muscle of naturally infected crucian carp captured in the Tom River, and 1 ml suspension containing approximately 50 metacercariae in 0.9% NaCl solution was individually given p.o. to guinea pigs that were used as treated specimens, whereas normal guinea pigs from the same stock were given 1 ml 0.9% NaCl solution per individual to serve as controls. The treated and control animals were killed by CO2 asphyxiation and decapitation at 7, 15, 30, 45, and 120 days after contamination. The smears of bone marrow cells for chromosome analysis were prepared by a standard method. Statistical analysis of the data was done using Student's t-test. We found that experimental infection of guinea pigs with O. felineus induced significantly high frequencies of hypoploid cells and, at the 120th day p.i., led to a considerable incidence of chromatid breaks and polyploidy in bone marrow cells.  相似文献   
197.
Evidence-based medicine is the conscientious, explicit, and judicious use of the best evidence available to make decisions about the care of individual patients. The practice of EBM means integrating individual clinical expertise with the best available external clinical evidence from systematic research. The good practice of EBM begins with a well formulated clinical question, meaning that it should be clear, directly relevant to the problem at hand and answerable by searching in medical literature. This paper begins by presenting the central tasks of clinical work from which clinical questions arise. The components of well formulated clinical questions are then presented. Finally, some of the steps for the correct formulation of questions are discussed.  相似文献   
198.
BACKGROUND: Because cigarette smoking affects the respiratory system earlier than many other systems of the human body, an attempt was made to identify objective and subjective respiratory problems among adolescent smokers. METHODS: Two studies based on a pulmonary function test (PFT), respiratory symptom assessment, and other smoking-related variables were undertaken. Study 1 involved cigarette smokers (N = 18, 22% males, mean age 18.7 years) from a freshman college class who participated in an acute smoking experiment that involved performing a PFT before and after smoking a single cigarette. Study 2 was performed on a combined group of vocational-technical high school students and freshman college students (N = 44, 48% males, mean age 17.8 years) where PFT parameters, respiratory symptoms, and smoking-related health vulnerability were assessed among smokers vs nonsmokers. RESULTS: In Study 1, the average reduction across PFT parameters was 4.4% and the mean estimated lung age increased from 27.15 to 29.84 years. In Study 2, a consistent trend toward reduction of PFT values among smokers vs nonsmokers was observed; the mean forced expiratory volume in 1 sec/forced vital capacity ratio (90.51% vs 94.59%), peak expiratory flow rate (80.32% vs 92.06%), and flow rate of 50% of forced vital capacity (88.39% vs 102.81%) differed significantly. Significant differences in respiratory symptoms were also observed among smokers vs nonsmokers. CONCLUSIONS: The beginning of respiratory health disorders can be identified among adolescent smokers. These findings might provide important clues on how to improve outcomes from health care provider-based adolescent smoking cessation counseling.  相似文献   
199.
The effects of an alternative chelation program in thalassemic patients with severe iron overload are investigated. The schedule of treatment, feasible at home, consists in the administration of deferoxamine intravenously (100 mg/kg/die 8 hours 10 days a month), followed by 50 mg/kg/die subcutaneously in the remaining 20 days of the month. The results in 34 patients who underwent this program over 8 months are reported. After intensive chelation therapy serum ferritin and transaminase levels were significantly lower, and daily urinary iron excretion values were significantly higher when compared to the levels observed before the treatment. After the period of study, echocardiography revealed an ejection fraction (EF) significantly higher in 15 out of 34 cardiopathic patients. In conclusion, the alternative chelation program is effective in reducing iron overload of thalassemic patients, protecting them also against cardiac disease.  相似文献   
200.
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