The Histological Basis of Frank’s Sign

Frank’s sign is a diagonal crease of the ear lobe, supposedly related to cardiac pathology, and has strongly been associated with coronary artery atherosclerosis. A total of 45 consecutive adult patients referred for autopsy in a one-and-a-half-year period were extensively studied. Samples from both the ear lobes were obtained for histopathology, as well as cardiac samples from all four cardiac compartments. When compared patients with Frank’s sign and those without it had no statistical difference in age (p = 0.0575). There was however a statistically significant increased cardiac weight (p = 0.0005), left ventricular wall thickness (p = 0.0002), and right ventricular wall thickness (p = 0.0043). Histopathology obtained from the ear lobes revealed myoelastofibrosis in an arterial vessel, located at the base of the crease, diffuse fibrosis, and Wallerian-like degeneration, with eosinophilic inclusions in the peripheral nerves. These changes suggest a time-related progression of the crease-associated changes. Our data suggest a significant correlation between the morphological changes of the myocardium and the presence of the ear lobe creases, with arterial myoelastofibrosis, Wallerian-like degeneration in peripheral nerves and deep tissue fibrosis found in the base of the crease.     

Specific CD8+ response discriminates presumed Epstein-Barr virus-related hepatitis and non-alcoholic fatty liver

During intravenous treatment with terlipressin for recurrent gastrointestinal (GI) bleeding, a 50-year-old male with no history of heart disease developed a newly prolonged QT interval and torsade de pointes. Risk factors present for acquired long QT syndrome were mineral dysbalance and a history of alcohol abuse with hepatic impairment. The patient was brought back to a normal sinus rhythm after a single 300-J counter-shock. Terlipressin was discontinued, and the patient's QTc interval subsequently returned to baseline. During 6 weeks of monitoring, arrhythmia did not recur.     

The age-related changes in the incidence of 'natural' anti-sperm antibodies suggest they are not auto-/isoantibodies

PROBLEM: Establishing the age-dependent patterns of sperm antibody levels among normal humans. METHODS OF STUDY: Sera samples from 498 healthy subjects aged 0-97 years - 246 males and 252 females - were tested by the gelatin agglutination test of Kibrick, tray agglutination test of Friberg, sperm immobilization test of Isojima and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found a significant increase in the level of sperm agglutinins after 40 years, which decreased after 88 years. The antibodies detected by ELISA were the highest among prepubertal subjects and also declined with aging. No age-dependent changes were established for the sperm immobilizins. With few exceptions, there were no significant differences between male and female sera, as well as between sera of newborn and their mothers. CONCLUSIONS: These data are similar to those established for the age-dependent changes of antibodies towards exogenous antigens, suggesting that the 'naturally occurring' antibodies against human spermatozoa are not auto-/isoantibodies.     

Computer-assisted image analysis of amyloid deposits in abdominal fat pad aspiration biopsies

Amyloidosis is a heterogeneous group of diseases with a common outcome: deposition of insoluble protein in the visceral organs and tissues. Primary amyloidosis is a consequence of different plasma cell disorders, and it is the most common form of amyloidosis in the United States with an estimated 2,000 new cases annually. Other forms of amyloidosis include chronic inflammatory processes, familial type of amyloidosis, and localized forms like Alzheimer's disease.The diagnosis of amyloidosis is based on the clinical picture and demonstration of amyloid deposit in tissues with Congo-red stain. In our article, we describe a simple methodology for image analysis of fat pad biopsies for amyloidosis using a commercially available software Adobe Photoshop CS3(c) Extended Edition. The principle is based on calculation of the mean gray value of each blue and green channel and comparison of their ratios. As a negative control, we have used samples from heart, scar tissue, and skin with their representative control. Fibrous tissue often gives a white:blue to blue:green birefringence, which often is confused with the apple: green birefringence of the amyloid stain; however, we were successful in discriminating these colors using the methodology described in this article. We also analyzed 22 patients with at least 2 years follow-up in our institution. The specificity and the sensitivity of the computer-assisted image analysis were calculated to be 75% and 100%, respectively. These results are in agreement with the published papers (references here); however, caution should be exercised before drawing firm conclusions because of the small sample size presented here.     

Angiocidin promotes pro-inflammatory cytokine production and antigen presentation in multiple sclerosis

Angiocidin was originally identified as a potent inhibitor of angiogenesis and tumor growth in vivo. In addition to its involvement in the regulation of carcinogenesis, recent studies indicate that angiocidin may also play a significant role in immune system modulation. This report describes the expression and potential function of angiocidin in multiple sclerosis (MS), a severe demyelinating, inflammatory and autoimmune disease of the central nervous system (CNS). We demonstrated that angiocidin and interleukin-7 (IL-7) are over-expressed in brain lesions of MS patients. Angiocidin-treated monocytes, peripheral blood T cells and primary astrocytes secreted various cytokines and chemokines including, IL-6, IL-7, GM-CSF, and MCP-1. Addition of recombinant angiocidin to cell cultures was able to promote differentiation of monocytes into a macrophage-like cell, induce MHC class I and class II gene expression and activate CD4(+) and CD8(+) T lymphocytes. Consistent with these findings, angiocidin induced mononuclear phagocyte migration and adhesion as well as increased the IL-2 response by antigen-specific T cells to myelin basic protein peptide presented to them by autologous mononuclear phagocytes. Furthermore, we examined STAT3 expression in angiocidin stimulated mononuclear phagocytes, T cells, and primary astrocytes. We found that angiocidin markedly stimulates STAT3 expression in these cell populations. Angiocidin, therefore appears to play a previously unappreciated and potentially important role in the regulation of immune response during the clinical course of MS.     

Novel lymphocyte-independent mechanisms to initiate inflammatory arthritis via bone marrow-derived cells of Ali18 mutant mice

Objective. In a large-scale ENU (N-ethyl-N-nitrosourea) mousemutagenesis programme, we previously have identified and characterizeda novel mutation Ali18 that causes inflammatory arthritis likelesions in peripheral joints. In this study, we analysed theimmune system of Ali18 mice to understand mechanisms underlyingthe spontaneous inflammation. Methods. Humoral and cellular components of the immune systemwere phenotyped by ELISA and flow cytometry. The contributionof the immune system for phenotype expression was analysed indisease transfer experiments. The involvement of the adaptiveimmune system was investigated in Ali18;Rag1 double mutantsand the influence of environmental factors was analysed in Ali18mice reared under germ-free conditions. Results. Bone marrow cells from Ali18 mice were able to transferthe disease phenotype to naïve wild-type recipients suggestingthat cellular components of the reconstituted immune systemwere sufficient to induce arthritis. Ali18 mice revealed abnormalleucocyte populations including lymphocytes and granulocytes,as well as increased plasma IL-5 and IgE levels. Ali18;Rag1double homozygous mutants, which lack mature lymphocytes, stilldeveloped arthritis, suggesting that the phenotype is independentof the adaptive immune system. In addition, the arthritis phenotypeappeared to be independent from environmental conditions asdemonstrated in mice reared under germ-free conditions. Conclusions. The Ali18 mutation induces inflammatory arthritisthrough bone marrow-derived cells. However, non-pro-inflammatorycytokine cascades and mature lymphocyte independent-mechanismsare crucial for initiation and progression of the phenotype.Ali18 mice may thus represent a model to study mechanisms involvedin seronegative arthritis induced by cells of the innate immunesystem. KEY WORDS: Psoriatic arthritis, Animal model, Inflammatory arthritis, ENU, Mouse mutant Submitted 19 June 2007; revised version accepted 6 December 2007.     

Antichlamydial and antisperm antibodies in patients with chlamydial infections

PROBLEM: Establishing the correlation between antichlamydial antibodies (AchAbs) and antisperm antibodies (ASA) in patients with chlamydial infections. METHOD OF STUDY: ASA were studied in sera from patients (142 with genital, 57 with ocular chlamydial infections) and control group (n = 100) by gelatin and tray agglutination test (TAT), sperm immobilization test (SIT) and ELISA. AchAbs were revealed by ELISA. RESULTS: A significantly higher (P < 0.05) ASA incidence was noted in patients with genital infections as compared with controls and patients with ophthalmologic infection (P < 0.0001), but not between patients with ophthalmologic infection and controls (P > 0.05). A significant correlation was established between AchAbs and ASA for TAT (r = 0.8214, P = 0.0341), SIT (r = 0.797, P = 0.032) and ELISA (r = 0.8519, P = 0.0313) in patients with genital infections only. CONCLUSIONS: The genital Chlamydia infection may play a role in the induction of ASA. This is probably a result of the inflammatory process, but not of cross-reactivity between sperm and Chlamydia trachomatis antigens.