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81.
The hematologic disorder paroxysmal nocturnal hemoglobinuria (PNH) occurs following an acquired somatic mutation in the Piga gene within a bone marrow stem cell. The progeny of this mutated cell cannot synthesize glycosylphosphatidylinositol (GPI) anchors, with a resultant deficiency in surface expression of all GPI-linked proteins. The protean clinical manifestations of PNH presumably result from the deficiency of these GPI-linked surface proteins. To explain the observation that neutrophils are affected at a significantly higher percentage than circulating erythrocytes and to analyze the proliferative rates of erythroid production in PNH, we studied 25 patients using flow cytometry. The fluorescent dye thiazole orange was used to detect reticulocytes, and CD59 monoclonal antibody was used to identify GPI-deficient cells. In contrast to the mature circulating erythrocytes, the percentage of abnormal reticulocytes was similar to the percentage of affected neutrophils. However, the vast majority of reticulocytes was completely GPI-deficient, ie, were type III cells, even in patients with only modest numbers of circulating type III erythrocytes. In addition, greater than 5% type II reticulocytes were identified in only 3 patients, although greater than 5% type II mature erythrocytes were identified in 10 of 25 patients. The results show that the erythroid and neutrophil bone marrow precursors have an equivalent proliferative advantage in PNH. The data also have important implications for the origin of type-II erythrocytes in PNH. 相似文献
82.
Stephens RW; Golder JP; Fayle DR; Hume DA; Hapel AJ; Allan W; Fordham CJ; Doe WF 《Blood》1985,66(2):333-337
Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone. 相似文献
83.
Purification and properties of heparin-releasable lipoprotein- associated coagulation inhibitor 总被引:6,自引:0,他引:6
The lipoprotein-associated coagulation inhibitor (LACI) is present in vivo in at least three different pools: sequestered in platelets, associated with plasma lipoproteins, and released into plasma by intravenous heparin, possibly from vascular endothelium. In this study we have purified the heparin-relesable form of LACI from post-heparin plasma and show that it is structurally different from lipoprotein LACI. The purification scheme uses heparin-agarose chromatography, immunoaffinity chromatography, and size-exclusion chromatography and results in a 185,000-fold purification with a 33% yield. Heparin- releasable LACI (HRL), as analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis, under reducing conditions, appears as a major band at 40 Kd and a minor band at 36 Kd. Immunoblot analysis suggests that the 36-Kd band arises from carboxyl-terminus proteolysis that occurs during the purification. HRL has a specific activity similar to that of HepG2 or lipoprotein LACI. HRL and lipoprotein LACI combine with lipoproteins in vitro while purified HepG2 LACI does not. I125-labeled HRL, injected into a rabbit, is cleared more slowly than I125-labeled HepG2 LACI, which may be due to attachment to lipoproteins in vivo. Preliminary evidence suggests that HRL is associated with vascular endothelium, possibly by attachment to glycosaminoglycans. 相似文献
84.
Jardim JR Rico G de la Roza C Obispo E Urueta J Wolff M Miravitlles M;Grupo de Estudio Latinoamericano CAP 《Archivos de bronconeumología》2003,39(9):387-393
Since community-acquired pneumonia (CAP) is a common disease with a high morbidity rate, it is important to obtain information concerning its etiology and susceptibility to antibiotics across different geographic areas. This study presents data obtained in 5 Latin American counties in the course of an international clinical trial that evaluated the efficacy and safety of treatment with either moxifloxacin or amoxicillin administered for 10 days to patients suspected of having CAP caused by a pneumococcal infection. Details are given of the pathogens identified, the patterns of sensitivity to antibiotics observed, and the clinical and microbiological results obtained.A total of 84 patients were studied, of whom 70 (83.3%) were evaluated at the end of the trial to determine the efficacy and safety of the treatment received. Gram-positive bacteria were found in samples from 29 patients (80.5%). The pathogen was Streptococcus pneumoniae in 28 of those cases (77.7%). Gram-negative bacteria were found in 7 patients (19.4%), the most common being Haemophilus influenzae in 3 patients (8.3%). The presence of atypical microorganisms was detected in 18 of the 70 patients (25%), mainly Mycobacterium pneumoniae (n=11), and in 6 cases (8.5%) the infection was mixed. Ten strains of S. pneumoniae (35.7%) were shown to be susceptible to penicillin, 2 (7.1%) were highly resistant, and 16 (57.1%) showed moderate resistance. The clinical success rate at the final visit after treatment was 94.1% for moxifloxacin and 91.7% for amoxicillin. The results of this trial demonstrate a high prevalence of S. pneumoniae with reduced susceptibility to penicillin in patients with CAP in Latin America. It also revealed a high incidence of atypical pathogens and mixed infection in 8.6% of patients. This information should be taken into account when establishing protocols for empirical treatment of CAP in Latin America. 相似文献
85.
The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy 总被引:4,自引:1,他引:4
Grever MR; Siaw MF; Jacob WF; Neidhart JA; Miser JS; Coleman MS; Hutton JJ; Balcerzak SP 《Blood》1981,57(3):406-417
A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2'-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short- lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2'-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration. 相似文献
86.
87.
Maria Auxiliadora Carmo Moreira Maria Alves Barbosa Maria Concei??o de Castro Antonelli Monteiro de Queiroz Kim Ir Sen Santos Teixeira Pedro Paulo Teixeira e Silva Torres Pedro José de Santana Júnior Marcelo Eustáquio Montadon Júnior José Roberto Jardim 《Jornal brasileiro de pneumologia》2013,39(2):155-163
OBJECTIVE:
To identify and characterize alterations seen on HRCT scans in nonsmoking females with COPD due to wood smoke exposure.METHODS:
We evaluated 42 nonsmoking females diagnosed with wood smoke-related COPD and 31 nonsmoking controls with no history of wood smoke exposure or pulmonary disease. The participants completed a questionnaire regarding demographic data, symptoms, and environmental exposure. All of the participants underwent spirometry and HRCT of the chest. The COPD and control groups were adjusted for age (23 patients each).RESULTS:
Most of the patients in the study group were diagnosed with mild to moderate COPD (83.3%). The most common findings on HRCT scans in the COPD group were bronchial wall thickening, bronchiectasis, mosaic perfusion pattern, parenchymal bands, tree-in-bud pattern, and laminar atelectasis (p < 0.001 vs. the control group for all). The alterations were generally mild and not extensive. There was a positive association between bronchial wall thickening and hour-years of wood smoke exposure. Centrilobular emphysema was uncommon, and its occurrence did not differ between the groups (p = 0.232).CONCLUSIONS:
Wood smoke exposure causes predominantly bronchial changes, which can be detected by HRCT, even in patients with mild COPD. 相似文献88.
L B Jardim A Carneiro S Hansel C R Rieder R Giugliani 《Arquivos de neuro-psiquiatria》1991,49(2):211-214
Wilson's disease in an autosomal recessive disorder of copper metabolism where systemic manifestations are secondary to the accumulation of copper in hepatic, nervous and other tissues. In CNS, the structural lesions most commonly found by CT scan are ventricular dilatation, cortical atrophy, basal ganglia hyperdensities, and brainstem and cerebellar atrophy. Degenerative changes of cerebral white matter seen on early anatomo-pathologic studies, but were almost never found on CT scan from recently described patients. We report a case of Wilson's disease with an unusually rapid deterioration where asymmetric low-densities in the subcortical white matter were disclosed by CT scan. 相似文献
89.
90.