Lucio phenomenon mimicking antiphospholipid syndrome: The occurrence of antiphospholipid antibodies in a leprosy patient

Lucio phenomenon is an atypical reaction of leprosy, characterized by vasculitic lesions that can mimic antiphospholipid syndrome (APS) clinically. Distinguishing the two can be difficult as antiphospholipid autoantibodies may be present in patients with leprosy. We report on a 32‐year‐old female patient presenting with a sudden onset of fever, hemorrhagic bullae, and skin necrosis on her lower legs. She was treated for APS due to the presence of antiphospholipid antibodies but had an inadequate response. A skin biopsy revealed thrombotic vasculopathy and necrotizing vasculitis associated with aggregation of foam cells in the perivascular area and subcutis, with acid‐fast bacilli in the histiocytes and blood vessel walls. Direct immunofluorescence showed IgM, C3, and fibrinogen deposition in the superficial and deep dermal blood vessels. The pathology confirmed the diagnosis of Lucio phenomenon, and appropriate therapy was given. It is essential to evaluate the patient comprehensively, including clinical, serological, and pathological aspects, to obtain the correct diagnosis.     

Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.     

Histamine‐2 Receptor Antagonists and Semen Quality

Histamine‐2 receptor antagonists are a class of drugs used to treat the acid‐related gastrointestinal diseases such as ulcer and gastro‐oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine‐2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine‐2 receptor‐independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine‐2 receptor antagonists.     

Cancer risks associated with 10 inorganic dusts: results from a case-control study in Montreal

A multicancer site, multifactor case-control study was undertaken to generate hypotheses about possible occupational carcinogens. Probing interviews were carried out with eligible cases, comprising all incident cases of 20 types of cancer who were male, aged 35-70 years, and a resident in Montreal. The interview was designed to obtain detailed lifetime job histories and information on potential confounders. Each job history was reviewed by a team of chemists and industrial hygienists who translated it into a history of occupational exposures. These occupational exposures were then analyzed as potential risk factors in relation to the sites of cancer included; 3,726 cases were interviewed. For each site of cancer analyzed, controls were selected from among the other sites in the study. This report concerns the associations between the 12 main types of cancer in our series and 10 inorganic dusts that are found mainly in construction and metal industries. All site-exposure combinations were investigated. After intensive control for confounding, nonadenocarcinoma (NAC) of the lung was associated with long duration-high level exposure to silica (odds ratio [OR] = 1.4), excavation dust (OR = 1.9), concrete dust (OR = 2.5), abrasives dust (OR = 1.4), and alumina (OR = 1.5). It was difficult to disentangle the relative effects of those substances, and confounding among them was a distinct possibility. Although residual confounding by some uncontrolled factors may explain the elevated ORs, the results were compatible with the hypothesis of a nonspecific relation between NAC of the lung and respirable inorganic dusts as a class. Other associations that remained suggestive after in-depth analysis were silica and stomach cancer (OR = 1.2) and concrete dust and lymphoma (OR = 2.9).     

Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains

Hereditary nephrotic syndrome is a heterogeneous disease, characterizedby heavy proteinuria and renal failure. Mutations of NPHS1 orNPHS2, the genes encoding for nephrin and podocin, lead to earlyonset of heavy proteinuria, and rapid progression to end-stagerenal disease, suggesting that both proteins are essential forthe integrity of the glomerular filter. Podocin is a stomatinprotein family member with a predicted hairpin-like structurelocalizing to the insertion site of the slit diaphragm of podocytes,the visceral glomerular epithelial cells of the kidney. Herewe investigate the pathomechanisms of different disease-causingpodocin mutations. We show that wild-type podocin is targetedto the plasma membrane, and forms homo-oligomers involving thecarboxy and amino terminal cytoplasmic domains. The associationof podocin with specialized lipid raft microdomains of the plasmamembrane was a prerequisite for recruitment of nephrin intorafts. In contrast, disease-causing mutations of podocin (R138Qand R138X) failed to recruit nephrin into rafts either becausethese mutants were retained in the endoplasmic reticulum (R138Q),or because they failed to associate with rafts (R138X) despitetheir presence in the plasma membrane. None of the mutants didaugment nephrin signaling, suggesting that lipid raft targetingfacilitates nephrin signaling. Our findings demonstrate thatthe failure of mutant podocin to recruit nephrin into lipidrafts may be essential for the pathogenesis of NPHS2. ^* To whom correspondence should be addressed. Tel: +49 7612703559;Fax: +49 7612706362; Email: benzing{at}med1.ukl.uni-freiburg.de      

The congo red stain revisited

The Congo red stain has undergone several modifications since it was first used by Bennhold in 1922 in order to increase the specificity for staining amyloid. Most of the laboratories in the United States use the method of Puchtler which uses alkaline Congo red solution. Some of the variables associated with the procedure were investigated by us. Our results showed the following: (1) amyloid showed green birefringence at all levels between 4 to 12 mu thick sections with better visualization of small deposits with increased thickness. Best results were obtained with 8 mu thick sections; (2) omission of the pretreatment with alkaline alcoholic solution of sodium chloride (NaCl) did not affect the sensitivity of the method; (3) the use of polar mounting media had no effect on amyloid and collagen birefringence; (4) 50 percent saturation of the Congo red staining solution with NaCl caused strong staining of collagen, elastic fibers and eosinophilic granules. In addition, collagen showed green birefringence and dichroism and its differentiation from amyloid became difficult; and (5) using the staining solution fully saturated with NaCl, no positive staining was seen with tissues other than amyloid. Collagen and elastic fibers showed red fluorescence which was of less intensity than amyloid. It is our conclusion that the method of Puchtler for detecting amyloid gives better results if the staining solution is fully saturated with NaCl. The pretreatment step may be deleted without compromising the quality of staining. Improved staining of amyloid enhances the specificity of green birefringence, dichroism, and red fluorescence.     

Parathyroid hormone related protein in hypercalcaemia of Hodgkin''s disease.

The role of parathyroid hormone related protein (PTHRP) as a humoral mediator of hypercalcaemia was investigated in a patient with lymphocyte depleted Hodgkin's disease during an episode of hypercalcaemia, using an immunohistochemical staining technique for PTHRP on the tumour tissue and an immunoradiometric (IRMA) assay for PTHRP1-86 on the patient's plasma. The plasma PTHRP was less than 0.23 pmol/l in the range found in normocalcaemic controls, and the immunohistochemical staining was not positive for protein. PTHRP did not have a role in the pathogenesis of hypercalcaemia in this patient.     

Cytokeratin 5/6 in normal human breast: lack of evidence for a stem cell phenotype

In recent studies, B?cker and colleagues described a population of cells in paraffin wax sections of normal human breast that express cytokeratins (CK) 5/6 without expression of CK8/18 or smooth muscle actin (SMA). They proposed that these represent stem cells that give rise to differentiated luminal and myoepithelial cells. The data have been used to generate a model for breast cancer progression and classification with associated implications for management of pre-invasive disease. In this study, the expression of CK5/6, CK8/18, and SMA was investigated using multiple immunofluorescence on matched pairs of paraffin wax-embedded and frozen breast specimens. The staining patterns reported previously in antigen-retrieved paraffin wax-embedded sections were confirmed but no CK5/6-only cells were found in frozen sections of normal breast. There were cells with low levels of CK8/18 expression in frozen sections that may correspond to the CK8/18 'negative' cells seen in paraffin wax sections. This study brings into question the previously described profile of breast 'stem cells' based on CK5/6 staining and hence the breast cancer progression model and classification based on this phenotype.     

Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast

AIMS: To analyse the expression of proteins involved in DNA double strand break detection and repair in the luminal and myoepithelial compartments of benign breast lesions and malignant breast tumours with myoepithelial differentiation. METHODS: Expression of the ataxia telangiectasia (ATM) and p53 proteins was immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours of the breast. Fifteen benign breast lesions with prominent myoepithelial compartment were also evaluated for these proteins, in addition to those in the MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with those seen in eight independent non-cancer (normal breast) samples and in the surrounding normal tissues of the benign and malignant tumours examined. RESULTS: ATM expression was higher in the myoepithelial compartment of three of 15 benign breast lesions and lower in the luminal compartment of eight of these lesions compared with that found in the corresponding normal tissue compartments. Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was consistently negative in benign lesions and was overexpressed in eight of 18 malignant tumours. In benign breast lesions, expression of the MRN complex was significantly more reduced in myoepithelial cells (up to 73%) than in luminal cells (up to 40%) (p=0.0005). CONCLUSIONS: Malignant myoepithelial tumours rarely overexpress ATM but are frequently positive for p53. In benign breast lesions, expression of the MRN complex was more frequently reduced in the myoepithelial than in the luminal epithelial compartment, suggesting different DNA repair capabilities in these two cell types.