Hepatic dysfunction in Alstr?m disease.

Alstr?m disease is a rare disorder; less than 20 cases have been reported. An 11-year-old girl is described with this condition. She has pigmentary retinopathy, sensory neural deafness, obesity, Type II diabetes mellitus, hyperlipidemia, and acanthosis nigricans. However, in addition she developed hepatic dysfunction, pathologically similar to chronic active hepatitis. This may be a further, previously undescribed systemic manifestation of Alstr?m disease.     

Viability of a capsule- and lipopolysaccharide-deficient mutant of Neisseria meningitidis

Neisseria meningitidis is the only lipopolysaccharide (LPS)-producing gram-negative bacterial species shown to be viable also without LPS. It was thought that the presence of capsular polysaccharide is necessary for this unusual feature. However, we show now that no part of the capsule gene cluster is required for maintaining LPS deficiency in N. meningitidis.     

Skin Cancer Risk Associated with Immunosuppressive Therapy in Organ Transplant Recipients

The aim of this review is to summarise the available literature regarding the epidemiology and proposed mechanisms of skin cancer development in organ transplant recipients who are receiving lifelong treatment with immunosuppressive therapy and to review the different strategies for managing complications in this group of patients. Organ transplantation is complicated by an increased incidence of certain cancers, of which non-Hodgkin's lymphoma, Kaposi's sarcoma and squamous cell carcinoma are the most common. The most important risk factor for these cancers is immunosuppressive therapy. The relative importance of different immunosuppressive therapy regimens in relation to the development of skin cancer is still unclear. Immunosuppression per se may play the most important role, but other mechanisms, which are independent of host immunity and which may be different for the various agents used, may also be of importance for the increased risk of cancer. Apart from immunosuppressive therapy, exposure to sunlight and infection with human papillomaviruses are believed to be the most important risk factors for the development of cutaneous squamous cell carcinoma in organ transplant recipients. Human papillomaviruses, no doubt, benefit considerably from immunosuppression, as is indicated by the large number of warts found in these patients, but many questions remain unanswered about their significance in cutaneous oncogenesis. The E6 protein from a range of cutaneous human papillomavirus types effectively inhibits apoptosis in response to ultraviolet light damage. It is, therefore, conceivable that the development of skin cancer in organ transplant recipients is the result of a complex interplay between exposure to ultraviolet radiation, human papillomavirus infection and genetic predisposition. Measures for protection from the sun are important for reducing the risk of skin cancer in organ transplant recipients. Regular surveillance of patients with skin problems and easy access to a dermatologist for these patients is advised. Changing the immunosuppressive regimen from azathioprine to cyclosporin or vice versa does not seem to relieve the skin problems. Tapering the immunosuppressive therapy to the lowest possible dose may be of some advantage. Oral retinoids, e.g. acitretin, have some effect in reducing the number of keratotic skin lesions and in the prevention of skin cancer in organ transplant recipients. Resurfacing the back of the hand can be a successful treatment for patients with multiple skin cancers on the back of the hand and can be used prophylactically in patients with severely actinically damaged skin.     

Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material

The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH.     

Single nucleotide variation analysis in 65 candidate genes for CNS disorders in a representative sample of the European population

The detailed investigation of variation in functionally important regions of the human genome is expected to promote understanding of genetically complex diseases. We resequenced 65 candidate genes for CNS disorders in an average of 85 European individuals. The minor allele frequency (MAF), an indicator of weak purifying selection, was lowest in radical amino acid alterations, whereas similar MAF was observed for synonymous variants and conservative amino acid alterations. In noncoding sequences, variants located in CpG islands tended to have a lower MAF than those outside CpG islands. The transition/transversion ratio was increased among both synonymous and conservative variants compared with noncoding variants. Conversely, the transition/transversion ratio was lowest among radical amino acid alterations. Furthermore, among nonsynonymous variants, transversions displayed lower MAF than did transitions. This suggests that transversions are associated with functionally important amino acid alterations. By comparing our data with public SNP databases, we found that variants with lower allele frequency are underrepresented in these databases. Therefore, radical variants obtain distinctively lower database coverage. However, those variants appear to be under weak purifying selection and thus could play a role in the etiology of genetically complex diseases.     

The effect of sodium lauryl sulphate and triclosan on hamster cheek pouch mucosa

It has recently been shown that triclosan protects the human skin from the inflammation that may be caused by exposure to sodium lauryl sulphate (SLS). The aim of the present study was to examine whether triclosan can protect the hamster cheek pouch mucosa from the irritation caused by exposure to SLS. After four daily applications of a paste containing SLS, the epithelium of the hamster cheek pouch showed consistently prominent structural changes, especially basal hyperplasia, acanthosis, hypergranulosis, and hyperkeratosis. Identical morphological changes were also observed after applications of a paste containing SLS together with triclosan. In contrast, after applications of a paste containing triclosan alone, the cheek pouch mucosa revealed a histological structure essentially similar to the non-treated control mucosa. From these results, we may conclude that SLS, but not triclosan, irritates the hamster cheek pouch epithelium. Moreover, triclosan does not protect the cheek pouch mucosa against structural changes induced by SLS. It must be taken into account that triclosan does not always offer protection against the side-effects of SLS.     

Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies for inflammatory bowel disease: high prevalence in patients with celiac disease

Both celiac disease and inflammatory bowel disease (IBD) are characterized by chronic diarrhea and the presence of distinct (auto)antibodies. In the present study we wanted to determine the prevalence of serological markers for inflammatory bowel disease, i.e., perinuclear antineutrophil cytoplasmic antibodies (pANCA) and/or anti-Saccharomyces cerevisiae antibodies (ASCA), in 37 patients with biopsy-confirmed celiac disease (Marsh IIIb/c). The majority of the patients was positive for IgA (auto)antibodies typically associated with celiac disease, i.e., antiendomysium antibodies (EMA) (86.5%), antigliadin antibodies (AGA) (73%), and antirecombinant human tissue transglutaminase antibodies (rh-tTGA) (86.5%). Four patients with selective IgA deficiency could be identified by analyzing EMA, AGA, and rh-tTGA for the IgG isotype. The prevalence of pANCA and ASCA, markers that are used for IBD, was unexpectedly high in our cohort of patients with celiac disease: 8 patients were positive for pANCA (IgG) and 16 patients were positive for ASCA (IgG and/or IgA). These results indicate that the presence of pANCA or ASCA in the serum of patients with chronic diarrhea does not exclude celiac disease. A prospective study is required to determine whether pANCA and/or ASCA identify patients at risk for developing secondary autoimmune disease.