Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already‐described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non‐melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus‐like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.     

High frequency of the TCRBV20S1 null allele in the Sardinian population

Single nucleotide polymorphisms (SNPs) in the T-cell receptor (TCR) gene segments might play a role in shaping the TCR repertoire. Three polymorphisms have been described for the TCRBV20S1 gene segment, one of which is responsible for a nucleotide substitution at position 524, resulting in the introduction of a stop codon. Individuals homozygous for this inactivating polymorphism ("null allele") are unable to express TCRBV20 gene products. Using DNA restriction digestion analysis, we investigated the frequency of this polymorphism in 111 healthy Sardinian subjects. Inhabitants of the Mediterranean island of Sardinia are considered to represent a genetically isolated population. Our analyses revealed an incidence of 19.8% of homozygosity for the null allele, corresponding to an allele frequency of 0.45. Such an incidence, significantly higher than the one detected in 83 non-Sardinian Caucasians (6%), is the most elevated so far reported in the literature. BV20 is a single member subfamily and the null allele produces a gap in the potential TCR repertoire. Therefore, it is possible that an undetermined selective pressure could have played a role in determining the high frequency of this inactivating polymorphism in Sardinians. Alternatively, this finding could be related to a founder effect in this ancient island population.     

Selected pool of peptides from ESAT-6 and CFP-10 proteins for detection of Mycobacterium tuberculosis infection

We have validated a new test for detecting Mycobacterium tuberculosis infection. A pool of synthetic peptides derived from ESAT-6 and CFP-10 proteins was used to detect the number of specific gamma interferon-producing T cells by means of an enzyme-linked immunospot assay. Sixty-eight individuals positive for M. tuberculosis infection, either human immunodeficiency virus-seropositive or -seronegative, were studied. The test results were highly specific (87.5%) and sensitive (93.1%), more so than a classical lymphoproliferative assay (specificity and sensitivity of 77.27%), opening new possibilities for diagnosis and screening of tuberculosis. Moreover, the test allowed us to distinguish individuals infected with M. tuberculosis from those vaccinated with BCG.     

ESR1 and APOE gene polymorphisms, serum lipids, and hormonal replacement therapy

OBJECTIVES: The risks and benefits of hormone replacement therapy (HRT) are, at least in part, mediated by the metabolic individuality of women. Therefore, we investigated the association between polymorphisms at the estrogen receptor 1 gene (ESR1) and at the apolipoprotein E gene (APOE) with lipid and lipoprotein levels in order to verify whether these concentrations are modulated by these gene variants in women with different hormonal status. METHODS: One hundred and eighteen postmenopausal women using oral HRT with estrogen or estrogen plus progestagen (HRT+, mean age=56+/-6.7 years, 39-75 years) and 167 postmenopausal women that were not on HRT (HRT-, mean age=58+/-9.8 years, 38-85 years) participated in the study. The polymorphisms were genotyped by PCR-RFLP methods. RESULTS: No significant effect of ESR1 genotypes or haplotypes and ESR1*HRT interactions were detected on lipid levels in two-way analysis of variance. Postmenopausal women HRT nonusers carriers of the APOE*4 allele had higher T-chol and LDL-C levels than postmenopausal women HRT nonusers carriers of the APOE*3 and APOE*2 allele. T-chol and LDL-C concentrations in postmenopausal users of HRT that were APOE*4 carriers were similar to those in postmenopausal women nonusers of HRT homozygotes for APOE*3 and APOE*2 carriers. A significant APOE*4/HRT interaction was detected on T-chol and LDL-C levels by multiple regression analysis. CONCLUSION: The results from this study suggest that the HRT influence on T-chol and LDL-C levels is modulated by APOE isoforms but not by ESR1 polymorphisms.     

Behavior of the bone-titanium interface after push-in testing: a morphological study

Fourteen titanium dental implants (Tioblast) were implanted singly in the proximal tibia of New Zealand rabbits for 120 days. A bone defect was surgically produced and filled with Bio-Oss around six of these implants. After the animals were sacrificed and their organs harvested, bone segments were fixed and methacrylate embedded after the push-in test had been performed. Microradiography was performed on longitudinal sections of the implants, whereas scanning electron microscope analysis was performed on the remaining embedded half-implants using secondary electrons only. The results showed that the implants were apically and coronally surrounded by bone, whether Bio-Oss was used or not. Fractures were evident through the newly formed bone and between the pre-existing and newly formed bone. Some fracture lines propagated through the bone and stopped at the implant surface without continuing along the bone-titanium interface. Detachment between the implant and the bone occurred at the coronal extremity of the implants and along its cervical region. These results highlight the fact that the bone-titanium interface has a high resistance to loading. It exhibited greater resistance than the newly formed bone and seems to behave in a manner similar to the cement lines of osteons.     

Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation.     

Effectiveness of cervical cancer screening using visual inspection with acetic acid in Peru

Objective

To evaluate the effectiveness of screening using visual inspection with acetic acid (VIA).

Methods

In a low-resource area of Peru in 2005-2008, a randomly selected sample of women who had previously screened negative by VIA and Pap (intervention group), and a group of eligible women previously unscreened by VIA (comparison group) were screened by VIA. The outcome measures were histologically confirmed cervical intraepithelial neoplasia (CIN) 2-3 and invasive cervical cancer.

Results

There were 4252 women in the intervention group and 4392 in the comparison group. Histologically confirmed CIN 2 or worse was diagnosed in 31 (0.7%) and 115 (2.6%) women, and invasive cancer was diagnosed in 4 women (0.09%) and 43 women (1.00%), in the intervention and comparison groups, respectively. The adjusted odds ratio was 4.2 (95% confidence interval [CI], 2.7-6.4) for CIN 2 or worse, and 13.9 (95% CI, 4.9-39.6) for invasive cervical cancer in the comparison group.

Conclusion

A lower prevalence of CIN 2-3 and invasive cervical cancer was seen in women previously screened by VIA, as compared with women not previously screened by VIA, implying that a single VIA screening can lower the population risk for cervical cancer.     

Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate Genes

SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive.