Non-MHC driven exacerbation of experimental thyroiditis in the postpartum period

Many human autoimmune diseases, including those of the thyroid gland, are affected by immune changes during pregnancy and the postpartum period. To investigate this influence, we have developed an animal model of pregnancy thyroiditis by using thyroglobulin (Tg)-induced experimental autoimmune thyroiditis (EAT). We now report a study of the post-partum period in mice with EAT. At 5 weeks postpartum, which was 9 weeks after the completion of a Tg immunization regime, the mean thyroiditis grade was significantly increased in the postpartum group from 0.23 to 0.43 (p<0.05) and the thyroiditis Index, which reflected both the frequency and severity of thyroiditis, was similarly increased compared to controls (29.0 vs 9.0). When Tg immunized CBA/J (H-2k) female mice were mated with BALB/c (H-2d) males, there was a similar increase in the severity of thyroiditis in the postpartum period as seen with CBA/J males suggesting that allogeneic factors were not able to further this postpartum exacerbation. Spleen cell IL-4 secretion was enhanced in the postpartum but only in the presence of thyroiditis indicating enhanced activity of Th2 immune responses. There were no differences in IFN-gamma secretion, titers of anti-Tg, CD8+ & CD4+ T cells and T cell chemokine receptor (CCR5, CCR3) expression between non-pregnant control mice with thyroiditis and postpartum thyroiditis. In summary, we found that the severity of EAT during the postpartum was significantly greater than in non-pregnant control mice and was associated with enhanced Th2 immune responses. The allogenicity of the pregnancy had no influence on these findings. The lack of allogenic impact was in contrast to earlier observations in pregnancy itself where an exacerbation of thyroiditis was male strain-dependent and involved primarily Th1 responses. This indicated that the postpartum exacerbation of autoimmune thyroid disease was not a simple response to fetal antigens but secondary to unique postpartum factors.     

CD1 genotyping of patients with Mycobacterium malmoense pulmonary disease

Mycobacterium malmoense is an opportunistic mycobacterium that occasionally causes disease in non-immunosuppressed individuals. As only a few individuals exposed to these organisms actually develop clinical disease, it is possible there is a genetic component to susceptibility. CD1 molecules are capable of presenting antigens from more virulent mycobacteria to T cells; therefore, we were interested in discovering whether recently described polymorphisms in CD1 molecules modulated susceptibility to M. malmoense pulmonary disease. The CD1 system comprises five genes (CD1A, -B, -C, -D, and -E) located on chromosome 1 (1q22-23). CD1 molecules are structurally and functionally related to major histocompatibility complex (MHC) class I molecules and are expressed on dedicated antigen-presenting cells. The primary function of CD1 molecules is to present lipid and glycolipid antigens to T cells. We have developed an allele-specific polymerase chain reaction-sequence-specific primer (PCR-SSP) method of CD1 genotyping. Using this method, we compared the allele and haplotype frequencies of CD1 in 49 HIV-negative patients with M. malmoense pulmonary disease with those in 342 normal controls. The CD1A and CD1E alleles were nominally identified as CD1A*01, CD1A*02, CD1E*01 and CD1E*02, and the control gene frequencies were found to be 5%, 95%, 67% and 33%, respectively. No significant difference was observed between the patient and control cohorts. Positive linkage disequilibrium values of 0.73 were observed between CD1A*02 and CD1E*01 (P<0.0001; chi2 test), and 0.94 between CD1A*01 and CD1E*02 (P<0.0001; chi2 test). Typing was also performed for two previously described CD1D alleles (CD1D*01 and CD1D*02), although only CD1D*01 was detected.     

Wegener's granulomatosis. Immunomicroscopic and ultrastructural study of four cases

Four cases of Wegener's granulomatosis involving lung are reported in which immunomicroscopy demonstrated that the parenchymal and vascular infiltrates were composed primarily of T cells and monocytes. No IgG, IgA, IgM, or C3 was identified in pulmonary vessels or alveolar septa. Ultrastructural studies failed to demonstrate dense deposits in alveolar septal capillaries or interstitium. These findings indicate that a cellular immune mechanism is active in these forms of pulmonary vasculitis and that immune complex deposition does not play a role.     

Inflammation: the link between insulin resistance, obesity and diabetes

Recent data have revealed that the plasma concentration of inflammatory mediators, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), is increased in the insulin resistant states of obesity and type 2 diabetes, raising questions about the mechanisms underlying inflammation in these two conditions. It is also intriguing that an increase in inflammatory mediators or indices predicts the future development of obesity and diabetes. Two mechanisms might be involved in the pathogenesis of inflammation. Firstly, glucose and macronutrient intake causes oxidative stress and inflammatory changes. Chronic overnutrition (obesity) might thus be a proinflammatory state with oxidative stress. Secondly, the increased concentrations of TNF-alpha and IL-6, associated with obesity and type 2 diabetes, might interfere with insulin action by suppressing insulin signal transduction. This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.     

Alopecia universalis as a single abnormality in an inbred Pakistani kindred

A Pakistani kindred comprising 5 generations contained 9 males and 4 females with alopecia universalis as a single abnormality without any associated defects. The skin biopsy from the scalp showed hair follicles without hair. Analysis of the pedigree is strongly suggestive of autosomal recessive inheritance, and consanguineous loops could account for all affected persons being homozygous for the abnormal allele. © 1993 Wiley-Liss, Inc.     

Identification of a Strong Promoter of Bacteriophage MB78 that Lacks Consensus Sequence Around Minus 35 Region and Interacts with Phage Specific Factor

A strong promoter of bacteriophage MB78 does not have minus 35 consensus sequence although it has a TGn motif immediately upstream of minus 10 sequence as well as the AT rich UP element. It is efficiently recognised by the sigma 70 RNA polymerase, however, a phage-specific factor competes with sigma 70 RNA polymerase for binding to this region, the binding of the factor being stronger than that of the polymerase. Contrary to the reports in the literature the polymerase appears not to bind to the UP element whereas the phage-specific factor does. The latter seems to be involved in the regulation of the promoter activity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis

Summary In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress.Histamine is known as a potent bronchoconstrictor via histamine H₁-receptor stimulation. Administration of H₁-recpetor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H₁-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed.It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.Supported by grant Fe 250/1-1 from the Deutsche Forschungsgemeinschaft (DFG).     

Linkage mapping of a nonspecific form of X-linked mental retardation (MRX53) in a large Pakistani family

Nonspecific X-linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X-linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2-26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081.     

Sunflower seed husk agar: a new medium for the differentiation of Candida dubliniensis from Candida albicans

A sunflower (Helianthus annuus) seed husk agar medium has been developed and evaluated for differentiation of Candida dubliniensis from Candida albicans on the basis of colony morphology and chlamydospore production. All C. dubliniensis isolates (n=40) produced rough colonies with hyphal fringes and abundant chlamydospores whereas 101 of 105 (96.2%) C. albicans isolates produced smooth colonies with no evidence of chlamydospore production. Since this medium is free from oil droplets, chlamydospores can be examined with greater clarity by Dalmau plate technique. This medium provides a simple and cost-effective tool for the presumptive differentiation of C. dubliniensis from C. albicans and is particularly suited for clinical microbiology laboratories where biochemical or molecular methods for the differentiation of these two species are not available.