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Biofilms are a diverse and complex collection of microorganisms which are either embedded or attached to a living or nonliving surface. When these biofilms are helpful to the primary organism (i.e., human), then it is considered part of the microbiome. Broad-spectrum antibiotics disrupt the microbiome’s homeostasis, with negative consequences. While antibiotics are ineffective, combination therapies in addition to debridement may be promising at treating biofilms.

After the discoveries of the initial classes of antibiotics in the mid-twentieth century, approximately 40 years passed before a new antibiotic class was discovered. With the rising number of antibiotic-resistant bacteria in the twenty-first century, novel classes of antibiotics and innovative mechanisms of antibiotic delivery have been invented.

We investigated the aberrant promoter methylation status of 12 genes in skin lesions, both malignant (basal cell carcinomas (BCCs), n=68 and squamous cell carcinomas (SCCs), n=35) and non-malignant (tags, n=58) skin lesions and compared the results of lesions from sun exposed (SE) and sun protected (SP) regions. Methylation was studied using a methylation specific PCR (MSP) and methylation of CDH1 was also measured using a semi-quantitative fluorescence based real-time MSP method. The methylation index (MI) was calculated as the methylated fraction of the genes examined. In this report, we found high frequencies of methylation of several known or suspected tumor suppressor genes in tags and skin cancers. Among the 12 genes, for the cadherin genes CDH1 and CDH3 and for two of the laminin 5 encoding genes LAMA3 and LAMC2 methylation frequencies greater than 30% were noted in one or more specimen types. We investigated whether methylation was tumor related. Surprisingly, the differences in the methylation profile of genes among the three specimen types were modest, and the MI, indicators of overall methylation frequencies, was nearly identical. However, significant differences were noted in the frequencies of methylation among the three specimen types for the genes RASSF1A (P=0.002), CDH1 (P=0.007) and one or more of three CAD genes (P=0.02). Methylation was highly significantly related to sun exposure, and sun protected specimens had little or no methylation. As methylation of CDH1 was completely SE specific we analyzed all the skin samples using a semi-quantitative real-time PCR assay for the CDH1 gene. The concordance between standard MSP and real-time MSP for all the samples (n=161) was 75% (P

A subset of individuals with Lynch syndrome (LS) has a variant called Muir-Torre syndrome (MTS) where patients develop multiple sebaceous neoplasms. Absence of gene expression and microsatellite instability (MSI) have been welldocumented in LS neoplasms. It is unclear whether the presence of these abnormalities in isolated sebaceous neoplasms would indicate the likely presence of otherwise unsuspected LS or MTS. 164 specimens of sporadic cutaneous sebaceous neoplasms were obtained. IHC was performed for expression of the DNA mismatch repair (MMR) genes MSH2 and MLH1. A 5-marker mononucleotide repeat microsatellite panel was analyzed to detect MSI, and two or more mutated markers were required for MSI. 164 sebaceous neoplasms were obtained from 162 patients. IHC data was successfully obtained from 162 samples and MSI data was obtained from 138 samples. 50/162 (31 %) had abnormal IHC with loss of staining for either MSH2 (37/162, 23 %), MLH1 (9/162, 5 %) or both (4/162, 2 %). 37 % (52/138) of the tumors had MSI. 82 % (111/136) of those with both IHC and MSI results correlated as expected. 18 % (25/136) showed discordance between IHC and MSI. 69/163 (42 %) had either abnormal IHC or MSI, indicating deficient DNA MMR activity. Given the substantial proportion of DNA MMR deficiency in these sebaceous neoplasms, screening for DNA MMR defects in sebaceous neoplasms would not appear to be an effective way to distinguish patients with LS or MTS from those with sporadic skin lesions and an ordinary risk of cancer.

Background: The effect of smoking on human papillomavirus (HPV) activity and subsequent dysplasia and neoplasia remains controversial Objective: To determine any reported effects of smoking on either HPV activity or HPV-related dysplasia/cancer using retrospective analysis of the literature from 1966 through 1998 via Toxline and PubMed to search for “smoking,” “papillomavirus,” and “cancer.” Conclusion: Several recent large studies demonstrated that smoking was associated with a greater incidence of cervical, vulvar, penile, anal, oral, and head and neck cancer in a dose-dependent fashion, while other studies did not show any correlation between smoking and cervical dysplasia after multivariate adjustment. Recent studies have also indicated that smoking may be more closely related to high-grade lesions of the cervix and vulva. These data provide evidence of an association between HPV, smoking, and cancer. Progression of dysplasia likewise seems to be associated with smoking. Several groups have attempted to discern whether the connection between smoking and cervical cancer is from local immunosuppression and/or from direct carcinogenic effects.

Background. Actin is largely responsible for cell motility and is only sparsely found in normal epithelial cells. An altered expression of actin in some malignancies may facilitate aggressive invasion. Micronodular basal cell carcinoma (BCC) has been shown to require more surgical stages, wider tissue margins, and deeper defects for extirpation during Mohs micrographic surgery relative to nodular BCC. Objective. To provide preliminary data regarding a possible correlation between alpha-smooth muscle actin (α-SMA) expression within the cells or stroma of micronodular BCC and aggressive invasion. In addition, the incidence of α-SMA expression in micronodular, morpheaform, and nodular BCC is evaluated. Methods. Nine micronodular basal cell carcinomas (7 primary, 2 recurrent) were evaluated for neural invasion, depth of tissue invasion, and alpha smooth muscle actin antibodies. The presence of alpha-smooth muscle actin antibodies was assessed using immunoperoxidase staining and compared with 13 morpheaform (13 primary, 0 recurrent) and 12 nodular (12 primary, 0 recurrent). Results. Six of the nine micronodular (67%), eight of the 13 morpheaform (62%), and 0 of the 12 nodular (0%) BCCs stained positive for α-SMA. Of the six micronodular BCCs that stained positive for α-SMA, three invaded the fascia or muscle and three displayed neural invasion. In contrast, of the three micronodular BCCs that stained negative for α-SMA, none invaded the fascia or muscle and only one exhibited neural invasion. Conclusion. Actin was present in 66% of micronodular, 62% of morpheaform, and 0% of nodular BCC. The presence of actin in micronodular BCC may be a marker for aggressive invasion.

The clinical manifestations of the human immune deficiency virus (HIV) were first observed in the late 1970s and HIV was first isolated in the 1980s. After many years of studying this deadly virus, researchers and clinicians agree that early treatment is key to retarding disease progression. Highly active antiretroviral therapy (HAART) has been instrumental in prolonging survival, especially when used early in the disease process. Opportunistic viral infections in HIV-positive patients can create both physical and psychological morbidity and mortality. Cutaneous manifestations of these viral diseases often lead to a diagnosis of HIV or the underlying disease. In this review, we will be focusing on viral diseases in HIV-positive patients, with emphasis on diagnosis and treatment. Human Herpesviruses The human herpesvirus family includes eight viruses: herpes simplex virus (HSV) types 1 and 2, varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesviruses (HHV) 6, 7, and 8. All herpesviruses are enveloped doublestranded DNA viruses that cause either active or latent infection persisting throughout the lifetime of the host.

Mycobacterium kansasii infections of the skin have been described in 31 previously published cases. The median age of these patients is 43 years, and male patients are more frequently affected than female patients. Most patients (72%) with this infection have some alteration of their immune status, but disseminated infection is relatively uncommon (22%). We present the first reported case of cutaneous M. kansasii infection in a patient with previously diagnosed systemic lupus erythematosus. The clinical presentation is similar to that expected in lupus profundus. While the duration of treatment is long (18 months), this case demonstrates that rifampin combined with at least 2 other antibiotics can provide excellent results. Clarithromycin has demonstrated encouraging in vitro results against M. kansasii but has not yet been reported for treatment of cutaneous infections.

The molecular pathology of the common nevocellular nevus (NCN) and its relationship to the genetic model of malignant melanoma (MM) progression has not been fully characterized. We used laser capture microdissection of archival formalin-fixed material to study 34 melanocytic lesions (19 MM and 15 NCN). Twelve of the 15 NCN were acquired, 3 of which were congenital; none had dysplastic features. Ten polymorphic markers on five chromosomal regions (1p36, 6q22-23.3, 8p22-24, 10q23, and 11q23) were selected for loss of heterozygosity (LOH) analysis, based on previous studies demonstrating involvement in MM pathogenesis and progression. Loss of heterozygosity at any allelic locus was observed in 18 of 19 (95%) MM and in 9 of 15 (60%) NCN. Of the three congenital nevi analyzed, none showed LOH at any informative locus. The frequency of allelic loss was highest in the MM at 6q22-23.3 (64%), followed by 10q23 (62%), 8p22-24 (43%), 11q23 (43%), and 1p36 (13%). In the 15 NCN, the most frequent allelic losses were detected at 6q22-23.3 (29%), 1p36 (27%), and 10q23 (25%), with lower frequencies of LOH at 11q23 (10%) and 8p22-24 (7%). LOH at a single polymorphic marker, D6S1038, was detected in 70% of the MM and in 36% of the NCN, suggesting the presence of putative tumor-suppressor genes (TSGs) critical in melanocytic neoplasia at 6q22-23.3. The presence of clonal genetic alterations in acquired NCN justifies their classification as a benign neoplasm. The pattern of LOH in NCN is not random; rather, the relative frequencies of LOH at the chromosomal regions examined are consistent with a multistep model of MM progression that begins with NCN. Molecular analysis of NCN reiterates established epidemiologic and morphologic notions that NCN are precursor lesions for MM. H UM P ATHOL 33:191-197. Copyright 2002, Elsevier Science (USA). All rights reserved.

Human herpesvirus 8 (HHV-8) has been causally linked to Kaposi's sarcoma (KS). There is significant homology between some HHV-8 genes and cellular genes including D-type cyclin (vCYC), G protein coupled receptor (vGCR), macrophage inflammatory proteins (vMIP-I, vMIP-II), bcl-2 (vBCL2), interferon regulatory factor-1 (vIRF1), interleukin-6 (vIL6), and complement-binding protein (vCBP). In this study, we analyzed expression of these viral homologs and HIV-1 Tat by reverse-transcriptase polymerase chain reaction (RT-PCR) coupled with Southern blot hybridization in AIDS-KS (AKS) tissue, classic KS tissue(CKS), and peripheral blood mononuclear cells, and phorbol ester (TPA)-treated and untreated HHV-8 positive lymphoma cells (BCBL1). While vCYC (AKS 6 of 6; CKS 3 of 3), vMIP-I (AKS 5 of 6, CKS 3 of 3), vBCL2 (AKS 6 of 6; CKS 3 of 3), and vIRF1 (AKS 5 of 6, CKS 3 of 3) transcripts were detected in both AKS and CKS, vGCR and HIV-1 Tat were expressed only in AKS samples (vGCR: AKS 3 of 6, CKS 0 of 3; Tat: AKS 4 of 6, CKS 0 of 3). vMIPII, vCBP, and vIL6 expression were not detected in any KS samples. Since vGCR expression is limited to AKS, it is possible that vGCR is activated by HIV-1 Tat. These results suggest that HIV-1 Tat may contribute to AKS pathogenesis through the tumorigenic and angiogenic effects of vGCR.