Discoid lupus erythematosus

Discoid lupus erythematosus is a manifestation of chronic cutaneous lupus erythematosus with a small risk of systemic involvement. In this review article, the role of predisposing factors such as haplotype, hormones, antibodies and sunlight are discussed. The clinical features, including variants and associations, and management options are presented.     

4种支架构建复合式口腔黏膜的组织学特点

目的利用4种不同支架材料构建复合式口腔黏膜,并比较其组织结构特点。方法体外培养人口腔黏膜的成纤维细胞和角质形成细胞,在4种支架材料中加入成纤维细胞,培养7d后,在支架表面加入角质形成细胞,培养4d后,移至气-液界面继续培养7d。苏木精-伊红染色镜下观察构建的复合式口腔黏膜的组织形态学特点。结果 4种支架均可构建形成复层上皮。其中,上皮层与脱细胞真皮基质材料(de-epidermised dermis,DED)结合紧密,形成的人工黏膜有明显的上皮钉突。不同于以往报道,上皮层与Alloderm结合并不十分紧密。以胶原凝胶为基质形成的人工口腔黏膜最厚,有明显分层。以胶原海绵-胶原凝胶为基质形成的复层上皮在部分区域长入至胶原海绵的空隙中。结论以DED和胶原凝胶为支架构建的口腔黏膜更接近于天然结构,而后者脆性较大,限制了其临床应用的可能。     

Prospective evaluation of posttransfusion hepatitis

The incidence of posttransfusion hepatitis (PTH) was determined prospectively at our institution. An active surveillance program of transfused surgical patients was set up; alanine aminotransferase (ALT) levels were determined before transfusion and at monthly intervals for 6 months after transfusion. Patients with confirmed ALT values greater than 2.5 times the upper reference values were referred to the out-patient clinics for diagnosis. Of 4051 surgical patients who underwent transfusion between January 1986 and December 1989, 2459 (60.7%) were enrolled in the surveillance program, and 1018 (25.1%) completed the follow-up; 238 patients received autologous blood only and were used as controls. No PTH was observed in the control patients, and the incidence of the disease in patients receiving homologous blood was 10.97 percent in 1986, 6.58 percent in 1987, 5.55 percent in 1988, and 4.29 percent in 1989; the decreasing trend is significant (p = 0.018).     

A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders

Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population.     

Characterization and Properties of Poly[N‐(2‐cyanoethyl)pyrrole]

PNCPy was prepared by anodic polymerization and its properties in both doped and undoped state were characterized. The doping level of the oxidized material has been found to be larger than that of other conducting polymers; the more relevant electrochemical properties of the doped material were retained after undoping. SEM and AFM data are consistent with a lumpy surface and a multidirectional growing of the polymer chains. Finally, PNCPy has been combined with PEDOT to prepare three‐layer systems with enhanced electroactivity and electrostability. Results suggest that PNCPy is a potential candidate for the fabrication of electric circuit components that are able to block the current flow below a given potential.

     

DFNB74, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 12q14.2-q15

Autosomal recessive nonsyndromic hearing impairment (ARNSHI) segregating in three unrelated, large consanguineous Pakistani families (PKDF528, PKDF859 and PKDF326) is linked to markers on chromosome 12q14.2-q15. This novel locus is designated DFNB74 . Maximum two-point limit of detection (LOD) scores of 5.6, 5.7 and 2.6 were estimated for markers D 12 S 313, D 12 S 83 and D 12 S 75 at θ = 0 for recessive deafness segregating in these three families. Haplotype analyses identified a critical linkage interval of 5.35 cM (5.36 Mb) defined by D 12 S 329 at 74.58 cM and D 12 S 313 at 79.93 cM. DFNB74 is the second ARNSHI locus mapped to chromosome 12, but the physical intervals do not overlap with one another. A locus contributing to the early onset, rapidly progressing hearing loss of A/J mice ( ahl4 , age-related hearing loss 4) was reported to map to chromosome 10 in a region of conserved synteny to DFNB74 , suggesting that ahl4 and DFNB74 may be due to mutations of the same gene in these two species.     

Helminth Infection Can Reduce Insulitis and Type 1 Diabetes through CD25- and IL-10-Independent Mechanisms

Parasitic helminth infection has been shown to modulate pathological inflammatory responses in allergy and autoimmune disease. The aim of this study was to examine the effects of infection with a helminth parasite, Heligmosomoides polygyrus, on type 1 diabetes (T1D) in nonobese diabetic (NOD) mice and to elucidate the mechanisms involved in this protection. H. polygyrus inoculation at 5 weeks of age protected NOD mice from T1D until 40 weeks of age and also inhibited the more aggressive cyclophosphamide-induced T1D. Moreover, H. polygyrus inoculation as late as 12 weeks of age reduced the onset of T1D in NOD mice. Following H. polygyrus inoculation of NOD mice, pancreatic insulitis was markedly inhibited. Interleukin-4 (IL-4), IL-10, and IL-13 expression and the frequency of CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells were elevated in mesenteric and pancreatic lymph nodes. Depletion of CD4⁺ CD25⁺ T cells in vivo did not abrogate H. polygyrus-induced T1D protection, nor did anti-IL-10 receptor blocking antibody. These findings suggest that infection with H. polygyrus significantly inhibits T1D in NOD mice through CD25- and IL-10-independent mechanisms and also reduces the severity of T1D when administered late after the onset of insulitis.Helminth parasites infect about 1.5 billion people worldwide, especially in developing countries, and cause chronic infection that leads to malnutrition, anemia, impaired growth, and significant mortality. Intestinal nematode parasites can produce strong polarized Th2-type responses in mice. This immune response is characterized by eosinophilia, mucosal mast cell hyperplasia, elevated immunoglobulin E (IgE) secretion, and increased production of Th2 cytokines, such as interleukin-4 (IL-4) and IL-13. Recent studies have suggested that helminth infection can regulate infectious, allergic, or autoimmune inflammatory diseases. Helminth infection enhances susceptibility to certain infectious diseases, like tuberculosis (11, 35) and viral hepatitis (10, 17). Conversely, helminth infection is protective in murine models of asthma (19), multiple sclerosis (40), and inflammatory bowel disease (42).Type 1 diabetes (T1D) is a life-threatening disease that affects approximately 1 out of 400 children in westernized societies (18). Over the past 3 decades, the rate of T1D has increased by approximately 4% per year in both Europe and the United States (8, 12, 39). This increase in disease incidence may result in part from a dysregulated immune system due to lack of exposure to certain environmental pathogens, such as helminth parasites (5, 7, 32). Studies with nonobese diabetic (NOD) mice showed that inoculation with Trichinella spiralis, Heligmosomoides polygyrus, or Schistosoma mansoni markedly reduced the rate of T1D and suppressed lymphoid infiltration in the islets (9, 37). T1D was also prevented in NOD mice by injection of whole eggs or soluble antigens from the schistosome egg antigen or the schistosome worm antigen, but only if treatment was started at 4 weeks of age (49). Moreover, the addition of oral insulin B chain to schistosome egg antigen-treated mice augmented the induction of regulatory T cells (Tregs) that secreted IL-4, IL-10, and transforming growth factor beta (TGF-β) (27).We were interested in further examining potential mechanisms contributing to the control of T1D during infection with the intestinal nematode parasite H. polygyrus. This strictly enteric parasite triggers a potent Th2-type response without eliciting an associated Th1-type response (4). We found that H. polygyrus infection exerted significant protection against T1D in NOD mice when administered at 5 and 7 weeks of age and even when given as late as 12 weeks of age (30% protection). This was associated with reduced lymphoid infiltration in the islets and an increased frequency of CD25⁺ Tregs with augmented Th2-type responses, including induction of alternatively activated macrophages (AAMΦs) and IL-10 mRNA in pancreatic lymph nodes (PLN). When H. polygyrus-inoculated NOD mice were treated with cyclophosphamide (Cyp), an agent known to accelerate T1D, T1D prevention was sustained. Similarly, when H. polygyrus-inoculated NOD mice were treated with anti-CD25 monoclonal antibody (MAb) in vivo, we observed no change in insulitis between this group and those receiving a control monoclonal Ig. Furthermore, in Cyp-treated NOD mice, administration of an anti-IL-10 receptor (IL-10R) blocking MAb did not abrogate H. polygyrus-induced protection from T1D. These findings suggest that H. polygyrus inoculation suppressed T1D even after the development of insulitis and that suppression of T1D in H. polygyrus-treated NOD mice is accomplished through CD25- and IL-10-independent mechanisms.     

IgM antibody response to antigens prepared from vegetative and coccoid forms of Helicobacter pylori

This report describes the utility of antigens prepared from different coccoid and spiral forms of Helicobacter pylori in a serological method. The presence of IgM antibody to H. pylori was determined in 22 human sera on antigens prepared from 24 strains of H. pylori. Antigens prepared from spiral form of certain strains of H. pylori detected IgM in all confirmed positive sera. Antigens obtained from the coccoid cells of the same strains could not completely detect IgM in the same sera. Testing sera on boosted antigens of the coccoid cells showed reduction in the number of false negative, indicating that the coccoid cells do not have one or more antigenic fractions essential for accurate detection of antibody. Our data suggest that H. pylori may lose CagA during the coccoid conversion process and regain it in the spiral form. In conclusion, we suggest that the antigen used for the detection of antibodies to H. pylori in serological methods should contain a broad spectrum of antigenic fractions and should be prepared from certain strains and culturable cells of H. pylori.