Specificity of cytotoxic effector cells directed against trinitrobenzene sulfonate-modified syngeneic cells. Failure to recognize cell surface- bound trinitrophenyl dextran

Mouse splenic lymphocytes and lymphoid tumor cells were modified with the trinitrophenyl (TNP) group either by treatment with trinitrobenzene sulfonate (TNBS) (which covalently modifies cell surface proteins) or with TNP stearoyl dextran (TSD) (which binds to the cell by noncovalent forces). These cell preparations were compared for their ability to: (a) sensitive syngeneic splenic lymphocytes leading to the generation of cytotoxic effector cells; (b) serve as lysable targets in a 4-h(51)Cr- release assay for effector cells generated in (a); and (c) act as blocking cells in the lysis of TNBS-medified targets lysed by TNP self effector cells generated in (a). In none of these three experimental systems did TSD-medified syngeneic spleen or H-2-matched tumor cells act either as a sensitizing immunogen or as a target antigen, despite the demonstration that quantitatively equivalent mounts of TNP were exposed on the cell surface in the TNBS- and TSD-modified cells. In contrast, TNBS-modified spleen cells sensitized syngeneic lymphocytes to generate effectors against TNBS-modified syageneic targets. Furthermore, TNBS- modified, H-2-matched cells served as specific lysable targets and as inhibiting cells for such effectors. These results indicate that the manner in which TNP is associated with the cell surface is important in the immunogenicity and antigenicity of hapten-modified syngeneic stimulating cells in generating H-2-associated cell-mediated lympholysis (CML) reactions. These findings raise the possibility that a covalent or at least a stable linkage with cell surface proteins (possibly H-2- controlled products) is important for immunological function. Furthermore, these observations do not favor the dual receptor model for H-2-restricted syngeneic CML if it is assumed in such a model that one receptor is specific for the TNP moiety and the second for unmodified self major histocompatibility products.     

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.     

贵池日本血吸虫对江苏沿海地区钉螺感染性的初步研究

目的　了解异地血吸虫品系对江苏省沿海残存钉螺的感染性。方法　用安徽省贵池现场感染性钉螺逸出的尾蚴感染家兔所取得的毛蚴 ,以毛蚴与钉螺 2 0∶ 1感染现场采集的钉螺 ,比较钉螺感染率和尾蚴逸出前期。结果　贵池血吸虫对如东、东台和贵池 3地钉螺感染率分别为 4 .35 %、16 .0 0 %和 4 0 .5 8% ,尾蚴平均逸出前期分别为 (72 .6 9± 8.73) d、(6 8.35± 5 .78) d和 (71.5 0± 9.0 7)d,贵池血吸虫对当地钉螺感染率显著高于对江苏沿海钉螺的感染率 (x1 2 =2 4 .5 8,x2 2 =14 .35 ,P <0 .0 1) ,尾蚴逸出前期差异无显著性 (t1 =0 .0 2 35 ,t2 =0 .1732 ,P>0 .1)。结论　江苏沿海地区钉螺在室内能被贵池血吸虫实验感染 ,长江流域血吸虫的输入 ,有可能导致血吸虫病的再流行     

Evaluation of a new enzyme-linked immunosorbent assay test for rotavirus antigen in faeces

A new commercial test for the diagnosis of rotavirus gastroenteritis was assessed. With some modifications it compared favourably with electron microscopy and immunofluorescence.     

Intranasal exposure to Stachybotrys chartarum enhances airway inflammation in allergic mice

RATIONALE: Exposure to building dampness, often associated with growth of microbes such as Stachybotrys chartarum, has been linked to respiratory symptoms. We have shown previously in a murine model that exposure to S. chartarum can induce lung inflammation characterized by infiltration of neutrophils and lymphocytes; this process is regulated by proinflammatory cytokines and leucocyte-attracting chemokines. OBJECTIVES: Because an atopic predisposition may influence the response to microbes, we examined the effects of S. chartarum on allergic mice in an experimental model. BALB/c mice were sensitized to ovalbumin by intraperitoneal injections and exposed for 3 wk to spores of S. chartarum. MEASUREMENTS AND MAIN RESULTS: Numbers of eosinophils and neutrophils were drastically increased in bronchoalveolar fluid from these mice as compared with the ovalbumin-sensitized/challenged mice or those exposed to S. chartarum without ovalbumin sensitization. Histologic sections showed severe granulomatous inflammatory cell infiltrates in all compartments of the lung, including peribronchial, perivascular, and alveolar spaces. The mRNA levels of proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha and the chemokine CCL3/MIP-1alpha were also markedly increased in the lungs. Despite the enhancement of the pulmonary inflammatory reaction, exposure to S. chartarum spores significantly down-regulated airway hyperresponsiveness and showed a tendency to decrease levels of Th2 cytokines in the lung. CONCLUSION: Exposure to S. chartarum modulates the inflammatory reaction and airway hyperresponsiveness, depending on the allergic status of the exposed mice.     

Familial hemiplegic migraine: a clinical comparison of families linked and unlinked to chromosome 19

We compared the clinical characteristics of 50 patients from three unrelated families with familial hemiplegic migraine (FHM) linked to chromosome 19, with those of 20 patients from two families with FHM not linked to chromosome 19. We found no significant differences for age at onset, frequency and duration of attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In the linked families, significantly more patients reported unconsciousness during attacks (39%, vs 15%; p<0.05) and provocation of attacks by mild head trauma (70% vs 40%; p< 0.05). In one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Interestingly, so far an association with cerebellar ataxia was only described in chromosome 19-linked families. FHM linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features.     

Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden

The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility. Received: 13 August 2001 / Accepted: 11 February 2002     

The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation

Despite matching for serologically defined HLA-A, B, DR antigens, acute graft-versus-host disease (GVHD) is a major complication contributing to increased morbidity and mortality in patients who undergo marrow transplantation from unrelated donors. The extent to which unrecognized mismatching for alleles that encode DR1-DR18 contribute to the increased risk of acute GVHD and overall survival is unknown. We analyzed 364 patients and their HLA-A, B, DR serologically matched donors to determine whether molecular typing of DRB1 alleles can allow more accurate donor/recipient matching and thereby improve clinical outcome after marrow transplantation. DRB1 alleles were typed by sequence-specific oligonucleotide probe hybridization methods. Selected alleles were confirmed by DNA sequencing. Of the 364 pairs, 305 were matched and 59 were mismatched for DRB1. The probability of moderate to severe acute GVHD was .48 for the matched and .70 for the mismatched patients. Compared with mismatched patients, the estimated relative risk (RR) of GVHD for matched patients was .58 (95% confidence interval [CI], .40 to .85). DRB1 matching decreased the risk of transplant- related mortality (RR, .66; 95% CI, .44 to .97) and was associated with decreased overall mortality (RR, .71; 95% CI, .51 to 1.0). Therefore, matching DRB1 alleles of the donor and recipient decreases the risk of acute GVHD and improves survival after unrelated marrow transplantation. These results indicate that prospective matching of patients and donors for DRB1 alleles is warranted.