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101.
Martínez Ara J Picazo ML Torre A Pascual D Díaz Rodríguez C Riñón C 《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2000,20(4):383-386
Sclerodema renal crisis is the usual form of presentation of renal disease in systemic sclerosis. We report a woman who at age 63 was given a diagnosis of scleroderma with Raynaud's phenomenon and cutaneous, oesophageal and lung involvement but no evidence of renal disease and no treatment with D-penicillamine. Two years later she developed progressive renal failure, nephrotic range proteinuria, haematuria and the presence of serum MPO-ANCA; she was normotensive. Renal biopsy revealed extracapillary and necrotizing glomerulonephritis and skin biopsy showed leucocytoclastic vasculitis. This clinical picture was compatible with necrotizing vasculitis of the microscopic polyarterits type. After treatment with pulse steroids followed by oral steroids and monthly intravenous cyclophosphamide her renal function stabilised and the serum MPO-ANCA disappeared. 相似文献
102.
Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation 总被引:2,自引:0,他引:2
Gerritsen EJ; Van Tol MJ; Van 't Veer MB; Wels JM; Khouw IM; Touw CR; Jol-Van Der Zijde CM; Hermans J; Rumke HC; Radl J 《Blood》1994,84(12):4374-4382
After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell-dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell- depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B- cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers. 相似文献
103.
Andrea Cippitelli Jinhua Wu Kelly A Gaiolini Daniela Mercatelli Jennifer Schoch Michelle Gorman Alejandra Ramirez Roberto Ciccocioppo Taline V Khroyan Dennis Yasuda Nurulain T Zaveri Conrado Pascual Xinmin Xie Lawrence Toll 《British journal of pharmacology》2015,172(7):1834-1845
Background and Purpose
The α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT-1001 has been recently described as a high-affinity and selective α3β4 nAChR antagonist that blocks nicotine self-administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine-suppressive effects of AT-1001.Experimental Approach
Effects of AT-1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline.Key Results
AT-1001 and its analogue AT-1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT-1001 and varenicline also had very different in vivo properties. Firstly, AT-1001 did not exhibit reinforcing properties per se while varenicline was self-administered. Secondly, systemic treatment with AT-1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT-1001 selectively blocked nicotine self-administration without altering alcohol lever pressing as assessed in an operant co-administration paradigm.Conclusions and Implications
These findings describe a more complex AT-1001 in vitro profile than previously appreciated and provide further support for the potential of AT-1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications. 相似文献104.
Rosas J Ramos-Casals M Ena J García-Carrasco M Verdu J Cervera R Font J Caballero O Ingelmo M Pascual E 《Rheumatology (Oxford, England)》2002,41(6):670-675
OBJECTIVES: To examine salivary function in patients with primary Sj?gren's syndrome (SS) by assessing unstimulated and stimulated flows using 5 mg of pilocarpine in a 5% solution, in order to define their clinical usefulness in the evaluation of xerostomia in patients with primary SS as well as to identify those factors related to the increase in salivary flow after pilocarpine stimulation. METHODS: We investigated the clinical and immunological characteristics of 60 consecutive patients with primary SS. All patients fulfilled four or more of the preliminary diagnostic European criteria for SS. We measured unstimulated (basal) salivary flow (BSF) in all patients. In patients with BSF =1.5 ml, stimulated salivary flows (SSF) were also measured after stimulation with an ophthalmic 5% pilocarpine solution (0.1 ml=5 mg, administered sublingually). SSF was also measured after oral administration of 50 mg anetholetrithione (ANTT) in the same patients. These stimulated salivary flows were measured 1, 2 and 3 h after the stimulus. RESULTS: Of the 60 patients, 55 were women and five men, with a mean age at the SS onset of 61 yr (range 18-82 yr). The mean BSF for SS patients was 1.40+/-0.17 ml. Fifty (83%) patients showed a BSF less than 1.5 ml. The stimulated salivary flow after 1 h was 3.23 ml in the pilocarpine group and 0.57 in the ANTT group (P<0.001); after 2 h it was 1.32 ml in the pilocarpine group and 0.52 in the ANTT group (P=0.02) and after 3 h it was 0.80 ml in the pilocarpine group and 0.41 in the ANTT group (P=0.046). No clinical or immunological differences were found between SS patients with BSF more or less than 1.5 ml, although patients with a BSF less than 1.5 ml showed a parotid scintigraphy class III or IV more frequently (42 vs 0%, P=0.01). SS patients with a pilocarpine SSF less than 1.5 ml had a longer duration of SS (73.3 vs 31.3 months, P=0.03) and a higher prevalence of positive anti-Ro/SS-A (70 vs 36%, P=0.038), anti-La/SS-B (65 vs 32%, P=0.038), parotid scintigraphy class III-IV (79 vs 9%, P<0.001) and positive salivary gland biopsy (90 vs 43%, P<0.001). CONCLUSION: The study of xerostomia using basal and pilocarpine SSF is simple to perform, acceptable to patients and needs no special equipment. We describe a significant increase in SSF using a solution of 5% pilocarpine in comparison with salivary flow obtained after stimulation with ANTT. Twenty-two of the 46 patients with low BSF had stimulated flows over 1.5 ml. These 'responder' patients showed a shorter duration of sicca symptoms, a lower frequency of positive immunological markers and milder grades of scintigraphic patterns and lymphocytic infiltrates in salivary gland biopsies. This subset of patients probably maintain a residual capacity of their salivary glands, as opposed to the 'non-responder' patients, who had a longer duration of sicca syndrome evolution with more severe involvement of the salivary glands. 相似文献
105.
Hyperimmune γ-globulins have proven efficacious in the prevention and treatment of viral infections, including those caused by hepatitis A and B viruses, cytomegalovirus, parvovirus. Interest in the prevention and/or treatment of infections caused by human immunodeficiency virus (HIV) has led to clinical trials with anti-HIV immune plasma and purified immune globulin prepared from donors who are actively infected with HIV. The handling and fractionation of this or other infectious plasma requires the construction and operation of virus containment facilities designed to protect fractionation employees and the immediate environment. This requirement would be reduced substantially by applying virucidal procedures prior to or during plasma pooling. We have shown that heating plasma at 56°C for 1 h followed by treatment with 1% tri(n-butyl) phophate (TNBP) and 1% Triton X-100 for 4 h at 30°C resulted in the inactivation of ≥ 1012.1 tissue culture infectious doses (TCID50) of HIV. With this treatment, the recovery of IgG was 87±3%. Fractionation of treated plasma by cold ethanol precipitation proceeded normally, and overall recovery, purity, and potency against selected viral markers were unaffected. The additional treatment of plasma with 15 g/l Aerosil for 4 h at 45 °C removed 104.5 TCID50 of HIV but resulted in substantial IgG losses both prior to and following fractionation. We conclude that potentially infectious plasma can be treated at 56°C for 1 h and by TNBP/Triton X-100 at 30°C for 4 h prior to fractionation. These steps appear sufficient to assure safety and to permit routine fractionation of plasma. Aerosil treatment, under the condition evaluated, was less satisfactory, although lower concentrations or temperatures than those evaluated may prove advantageous. 相似文献
106.
Age-related physiologic changes together with high prevalence of chronic illness and the use of multiple medications predispose older adults to syncope. The causes of many of these patients' syncope are unexplained and most remained symptomatic. A thoughtful diagnostic strategy is essential to pinpoint the cause in each patient. The initial assessment includes a comprehensive medical history, preferably with an eye witness account, and a thorough physical examination. The decision for further diagnostic tests often depends on whether there is evidence of underlying structural heart disease. In the absence of heart disease, tilt table testing and the related autonomic function testing are usually most productive. Various cardiac studies will be more appropriate for those with suspected structural heart disease. A cause of syncope can only be concluded if there is a sufficiently strong correlation between syncopal symptoms and the detected abnormalities on investigations. A strategic evaluation of syncope of the elderly subjects should allow a correct diagnosis and appropriate management. 相似文献
107.
Pascual J 《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2001,21(6):524-5; discussion 526-7
108.
Takeuchi S; Bartram CR; Miller CW; Reiter A; Seriu T; Zimmerann M; Schrappe M; Mori N; Slater J; Miyoshi I; Koeffler HP 《Blood》1996,87(8):3368-3374
Cytogenetic analysis of acute lymphoblastic leukemia (ALL) of childhood identified nonrandom chromosomal abnormalities of the short arm of chromosome 12. The alterations include deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. To refine further the chromosomal localization of this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 100 primary ALL samples using 22 polymorphic markers and identified two distinct smallest common deleted regions on chromosome 12p13. One region is flanked by D12S77 and D12S98 and has a size of 4 cM. Twenty-six percent of informative patients showed LOH in this region. This region may contain the TEL gene. The other region is flanked by D12S269 and D12S308 including the KIP1 gene. Forty-four percent of informative patients showed LOH in this second region. Mutational analysis of KIP1 using polymerase chain reaction-single- strand conformation polymorphism analysis and Southern blot analysis showed no homozygous deletions and point mutations suggesting that the altered gene in this second region is not the KIP1. Clinical data showed that LOH of 12p was demonstrated more frequently in precursor-B ALLs (32 of 80; 40%) than in T-ALLs (1 of 20; 5%) (P = .0027). Furthermore, patients with 12p LOH were younger (P = .013), with a lower DNA index (P = .046), but they had the same survival rates at 3 years. In summary, these data suggest that two different tumor suppressor genes are on chromosome arm 12p, which act separately in the development of childhood precursor-B ALLs. One of the tumor suppressor genes is in the region the KIP1 gene, but our data suggest this gene is not abnormal. The other target is in the region of the TEL gene; and this candidate deserves further study. 相似文献
109.
Plasma concentration of asymmetric dimethylarginine,an endogenous inhibitor of nitric oxide synthase,is elevated in hyperthyroid patients 总被引:3,自引:0,他引:3
Hermenegildo C Medina P Peiró M Segarra G Vila JM Ortega J Lluch S 《The Journal of clinical endocrinology and metabolism》2002,87(12):5636-5640
Cardiovascular manifestations are frequent findings in patients with thyroid hormone disorders. Nitric oxide (NO) plays a key role in vascular, endothelial-mediated relaxation. NO is synthesized from L-arginine by NO synthase, an enzyme inhibited by endogenous compounds, mainly asymmetric dimethylarginine [asymmetric N(G),N(G)-dimethyl-L-arginine (ADMA)]. The aim of our work was to investigate whether plasma L-arginine and dimethylarginine concentrations and NO production are altered in hypo- and hyperthyroid patients, compared with control subjects. L-arginine, ADMA and symmetric dimethylarginine were analyzed by HPLC. NO was measured as plasma nitrite plus nitrate (NO(x)) concentration by a colorimetric method based on Griess reagent. L-arginine, ADMA, and symmetric dimethylarginine plasma levels in the hypothyroid group were similar to those of the control group; whereas in hyperthyroidism, these values were significantly increased. However, the L-arginine/ADMA ratio was decreased in hyperthyroid patients, resulting in diminished NO(x) production. When all subjects were analyzed together, free T(4) levels were directly correlated with ADMA and inversely correlated with NO(x). 相似文献
110.