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At least 433 records · Page 24Linked to original sources
PubMed1985

Creatine kinase (CK)-linked IgA in Isaacs' syndrome. An immune complex disease?

Electrophoresis of serum from a patient with Isaacs' syndrome revealed an atypical creatine kinase (CK) isoenzyme pattern which contained an extra band migrating between CK2(MB) and CK3(MM). Immunofixation demonstrated that the extra band was a complex of CK3(MM) and IgA. The presence of this complex seemed to correlate with increased serum CK levels which were associated with the aggravation of symptoms. Immunofluorescence studies on muscle biopsy samples revealed the presence of the complex in the muscle fiber membrane and motor endplate. The existence of CK-linked IgA in an Isaacs' syndrome suggests that an immunological abnormality may play a role in the pathological process of this rare syndrome.

Chemical Phenomena↗
PubMed2006

Sibling cases of Mycobacterium avium complex disease associated with hematological disease.

A 22-year-old man who was admitted to our respiratory division complaining of fever and cough of 1 month's duration had been diagnosed with myelodysplastic syndrome 5 years earlier. On admission, radiological findings showed bilateral diffuse small nodular shadows. Although the results of an acid-fast bacilli examination of blood, sputum, and urine samples were all negative, we initiated antituberculous therapy for suspected miliary tuberculosis because the histological diagnosis from a bone marrow biopsy was epitheloid granuloma. The abnormalities on his chest radiographs improved, but his left cervical lymph nodes became swollen. The histological result of a lymph node biopsy revealed epitheloid granuloma with caseating necrosis. The DNA-DNA hybridization result of a resected lymph node culture indicated Mycobacterium avium. The final diagnosis was disseminated Mycobacterium avium complex (MAC) disease. Both leukocytopenia and thrombocytopenia had been noted in the patient's 19-year-old younger brother, who had been living in the same home 5 years earlier, and for whom a diagnosis of myelodysplastic syndrome was made from bone marrow aspiration on admission. An infiltration shadow with nodular shadows was noted in the right upper lung field on a chest radiograph. A bronchoscopic examination revealed pulmonary MAC disease. As for the route of infection, although we investigated restriction fragment length polymorphism (RFLP), a different pattern was found in the two brothers. We suspect that they were infected by different species of Mycobacterium avium in the same environment rather than by droplet infection from the younger brother to the older brother.

Adult↗
PubMed2004

Microarray reality checks in the context of a complex disease.

A problem in analyzing microarray-based gene expression data is the separation of genes causally involved in a disease from innocent bystander genes, whose expression levels have been secondarily altered by primary changes elsewhere. To investigate this issue systematically in the context of a class of complex human diseases, we have compared microarray-based gene expression data with non-microarray-based clinical and biological data about the schizophrenias to ask whether these two approaches prioritize the same genes. We find that genes whose expression changes are deemed to be of importance from microarrays are rarely those classified as of importance from clinical, in situ, molecular, single-nucleotide polymorphism (SNP) association, knockout and drug perturbation data. This disparity is not limited to the schizophrenias but characterizes other human disease data sets. It also extends to biological validation of microarray data in model organisms, in which genome-wide phenotypic data have been systematically compared with microarray data. In addition, different bioinformatic protocols applied to the same microarray data yield quite different gene sets and thus make clinical decisions less straightforward. We discuss how progress may be improved in the clinical area by the assignment of high-quality phenotypic values to each member of a microarray-assigned gene set.

Computational Biology↗
PubMed2001

Optimized group sequential study designs for tests of genetic linkage and association in complex diseases.

The study of genetic linkage or association in complex traits requires large sample sizes, as the expected effect sizes are small and extremely low significance levels need to be adopted. One possible way to reduce the numbers of phenotypings and genotypings is the use of a sequential study design. Here, average sample sizes are decreased by conducting interim analyses with the possibility to stop the investigation early if the result is significant. We applied optimized group sequential study designs to the analysis of genetic linkage (one-sided mean test) and association (two-sided transmission/disequilibrium test). For designs with two and three stages at overall significance levels of.05 and.0001 and a power of.8, we calculated necessary sample sizes, time points, and critical boundaries for interim and final analyses. Monte Carlo simulation analyses were performed to confirm the validity of the asymptotic approximation. Furthermore, we calculated average sample sizes required under the null and alternative hypotheses in the different study designs. It was shown that the application of a group sequential design led to a maximal increase in sample size of 8% under the null hypothesis, compared with the fixed-sample design. This was contrasted by savings of up to 20% in average sample sizes under the alternative hypothesis, depending on the applied design. These savings affect the amounts of genotyping and phenotyping required for a study and therefore lead to a significant decrease in cost and time.

Computational Biology↗
PubMed1980

Systemic immune complex disease following intestinal bypass surgery: bypass disease.

Twenty-one patients with arthritis and dermatitis following intestinal bypass surgery were studied. The arthritis was polyarticular, remittent, and intermittent. Typically, the synovial fluid was inflammatory. The commonest inflammatory skin lesion was a vesiculopustular dermatitis. Nineteen patients and serum immmune complexes using the Raji cell technic. Seventeen patients had serum cryoproteins, primarily consisting of IgG 1, IgG 3, C3, and C4. Three patients had both Escherichia coli antigens and anti-E. coli antibody in their cryoprotein. Five patients had granular and one had linear deposits of immunoglobulin and complement at the dermoepidermal junction. Further evidence that bacterial antigens play a role in tissue injury was provided by detection of granular deposits of E. coli antigen at the dermoepidermal junctions in two patients, and at the glomerular capillary basement membrane in one patient.

Adult↗
PubMed1983

Subacute sclerosing panencephalitis: an immune complex disease?

Vascular osmiophilic deposits of entangled tubular profiles were demonstrated by electronmicroscopy in the cerebral tissue of a patient with subacute sclerosing panencephalitis. Measles viral antigen, IgG, IgM, and C3 were found in the same distribution, indicating that the deposits represent immune complexes. To our knowledge, this is the first demonstration of immune complexes in the vessels of the central nervous system.

Adult↗
PubMed1979

Plasma exchange in immune complex disease.

The effect of plasma exchange on CIC, anti-dsDNA and complement levels and clinical activity was studied in eight patients with SLE, one with idiopathic anaphylactoid purpura and one with mixed cryoglobulinaemia. No association existed between different tests for immune complex detection. Plasma exchange as sole therapy was effective in patients with idiopathic anaphylactoid purpura and mixed cryoglobulinaemia, but not in one SLE patient with CIC. Five SLE patients with CIC treated with corticosteroids showed improvement on plasma exchange but in two patients with and two with CIC plasma exchange was not effective.

Adolescent↗
PubMed2006

"Candidatus Phytoplasma americanum", a phytoplasma associated with a potato purple top wilt disease complex.

Potato purple top wilt (PPT) is a devastating disease that occurs in various regions of North America and Mexico. At least three distinct phytoplasma strains belonging to three different phytoplasma groups (16SrI, 16SrII and 16SrVI) have been associated with this disease. A new disease with symptoms similar to PPT was recently observed in Texas and Nebraska, USA. Two distinct phytoplasma strain clusters were identified. One belongs to the 16SrI phytoplasma group, subgroup A, and the other is a novel phytoplasma that is most closely related to, and shares 96.6 % 16S rRNA gene sequence similarity with, a member of group 16SrXII. Phylogenetic analysis of 16S rRNA gene sequences of the novel PPT-associated phytoplasma strains, previously described 'Candidatus Phytoplasma' organisms and other distinct unnamed phytoplasmas indicated that the novel phytoplasma, termed American potato purple top wilt (APPTW) phytoplasma, represents a distinct lineage and shares a common ancestor with stolbur phytoplasma, "Candidatus Phytoplasma australiense", "Candidatus Phytoplasma japonicum", "Candidatus Phytoplasma fragariae", bindweed yellows phytoplasma (IBS), "Candidatus Phytoplasma caricae" and "Candidatus Phytoplasma graminis". On the basis of unique 16S rRNA gene sequences and biological properties, it is proposed that the APPTW phytoplasma represents "Candidatus Phytoplasma americanum", with APPTW12-NE as the reference strain.

DNA Fingerprinting↗
PubMed1985

Lymphocyte status of lymph node and blood in acquired immunodeficiency syndrome (AIDS) and AIDS-related complex disease.

Blood lymphocytes and lymph nodes from three patients with acquired immunodeficiency syndrome (AIDS) and two cases with AIDS-related complex (ARC) were studied during the course of the disease. The lymph node histomorphology could be grossly categorized into three stages: follicle hyperplasia, follicle degeneration and the depleted stage. In the first stage, follicles show large and sometimes irregular-sized germinal centres and narrow B-cell mantles. Dendritic reticulum cells in the germinal centres reveal disruption of their fine dendritic processes; often indentations are visible, filled with small B- and T-lymphocytes of follicle mantle and paracortical origin. These lesions may be the first signs of follicle degeneration, in which only hyalinized remnants of follicle centres are found. The changes in the paracortex are less prominent than those in the follicles. The disturbance in the numerical balance of T-cell subsets of helper-induced and suppressor-cytotoxic phenotypes is less than that found in the blood. In some cases the paracortex reveals a high density of T6-positive elements resembling interdigitating cells, suggestive of continuous antigen exposure. We found follicle hyperplasia in ARC, follicle degeneration in one case of ARC and in full-blown AIDS, while the depleted stage was found in lymph nodes at autopsy of AIDS patients. Lymph node changes do not completely correlate with the changes in the blood lymphocyte pool. Investigations on lymph nodes may be of value in the assessment of the prognosis of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Multipoint affected sibpair linkage methods for localizing susceptibility genes of complex diseases.

Recently, Liang et al. ([2001] Hum. Hered. 51:64-78) proposed a general multipoint linkage method for estimating the chromosomal position of a putative susceptibility locus. Their technique is computationally simple and does not require specification of penetrance or a mode of inheritance. In complex genetic diseases, covariate data may be available which reflect etiologic or locus heterogeneity. We developed approaches to incorporating covariates into the method of Liang et al. ([2001] Hum. Hered. 51:64-78) with particular attention to exploiting age-at-onset information. The results of simulation studies, and a worked data example using a family data set ascertained through probands with schizophrenia, suggest that utilizing covariate information can yield substantial efficiency gains in localizing susceptibility genes.

Age of Onset↗
PubMed2000

Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial. The AIDS Clinical Trials Group 196/Terry Beirn Community Programs for Clinical Research on AIDS 009 Protocol Team.

The efficacy and safety of clarithromycin and rifabutin alone and in combination for prevention of Mycobacterium avium complex (MAC) disease were compared in 1178 patients with AIDS who had < or =100 CD4 T cells/microL in a randomized, double-blind, placebo-controlled trial. MAC disease occurred in 9%, 15%, and 7% of those randomized to clarithromycin or rifabutin alone or in combination, respectively; time-adjusted event rates per 100 patient-years (95% confidence interval [CI]) were 6.3 (4.2-8.3), 10.5 (7.8-13.2), and 4. 7 (2.9-6.5). Risk of MAC disease was reduced by 44% with clarithromycin (risk ratio [RR], 0.56; 95% CI, 0.37-0.84; P=.005) and by 57% with combination therapy (RR, 0.43; 95% CI, 0.27-0.69; P=. 0003), versus rifabutin. Combination therapy was not more effective than clarithromycin (RR, 0.79; 95% CI, 0.48-1.31; P=.36). Of those in whom clarithromycin or combination therapy failed, 29% and 27% of MAC isolates, respectively, were resistant to clarithromycin. There were no survival differences. Clarithromycin and combination therapy were more effective than rifabutin for prevention of MAC disease, but combination therapy was associated with more adverse effects (31%; P<.001).

AIDS-Related Opportunistic Infections↗
PubMed1989

Drug-induced immune-complex disease.

A range of drugs including hydralazine, isoniazid, procainamide and penicillamine cause toxic side effects which resemble systemic lupus erythematosus (SLE). Deficiencies of C1, C4 and C2 are associated with idiopathic SLE, and these defects may compromise the ability of the patient to deal with immune complexes. Immune complexes with protein as antigen, such as has been reported to be diagnostic of procainamide-induced SLE, interact more with the C4A isotype of C4 than the C4B isotype. It is shown that hydralazine, isoniazid and penicillamine inhibit the covalent binding of C4 to a complement-activating surface and that the drugs themselves become covalently bound to C4. For each of these drugs, C4A is inhibited more than C4B, and it is suggested that this is an important contributory factor in the development of the toxic side effects to these drugs involving immune-complex deposition. For procainamide, it is shown that the hydroxylamine metabolite rather than the drug itself inhibits the covalent binding reaction of C4. Hydralazine, isoniazid and procainamide are metabolised by the polymorphic N-acetyltransferase, and slow acetylators are at increased risk of drug-induced lupus. For procainamide, oxidation to the hydroxylamine form is an alternative metabolic route of increased importance in slow acetylators, and it is suggested that investigation of C4 type in susceptible patients could provide a means of identifying those at greatest risk of immunotoxicity.

Humans↗