Bromodeoxyuridine incorporation and Ki 67 expression in oral hairy leukoplakia

OBJECTIVES: Oral hairy leukoplakia (HL) is an acan-thotic, hyperparakeratotic lesion characterised by the presence of a replicative Epstein-Barr virus (EBV) infection in the superficial and adjoining layers of the epithelium. EBV or its gene products are capable of modifying epithelial differentiation. The aim of this study was to establish whether the presence of EBV was associated with an alteration in cell turnover by assessing bromodeoxyuridine (BrdU) incorporation and Ki 67 expression in lesional tissue and control mucosa.
METHODS: Biopsies of HL together with age, site and sex matched controls ( n = 7 and 8 respectively) were incubated in 200 μM BrdU in vitro , fixed in methacarn and processed to paraffin wax. Following acid hydrolysis, incorporated BrdU and Ki 67 were identified in serial 5 fim sections using a three-stage immunoperoxidase technique and cell density expressed as the number of positive cells per mm basement membrane length.
RESULTS: Overall, there was no difference in the number of BrdU positive cells per mm basement membrane length between control and HL tissue. However, within HL alone, the presence'of focal EBV replication was associated with a significant reduction in the number of basal cells incorporating BrdU compared to adjacent EBV free areas (P < 0.05). There was no significant difference between Ki 67 positive cells in control and HL tissue and no evidence of a reduction of Ki 67 positive cells in areas associated with EBV replication.
CONCLUSIONS: These results suggest that there is no evidence of a generalised alteration of the proliferative capacity of basal cells in HL, although the focal reduction in BrdU incorporation may reflect subtle changes on cell turnover by EBV infection.     

FINE NEEDLE ASPIRATION CYTOLOGY OF LYMPH NODES IN HIV INFECTED PATIENTS

Lymphadenopathy is the commonest presentation in HIV positive individuals. Fine needle aspiration cytology of 196 HIV positive patients was studied during six monthly review. 75% paients in this study who were asymptomatic were detected to have lymphadenopathy during the surveillance. 82% had lymph nodes smaller than 1cm size. Lymphadenopathy at more than one site was observed in 46.8% cases. Commonest opportunistic infection noticed was tuberculosis (TB) in 34.2%. Cyto-morphologically reactive pattern with Add fast bacilli (AFB) positivity was observed in 16.4% of TB cases. In 2.9% cases AFB were detected even in the tissue fluid. Negative images of AFB were observed in the macrophages in 3 cases. TB was detected with equal frequency in both asymptomatic and symptomatic groups. Axillary nodes pose problem due to deeper location. False positives were a case of dermatopathic lymphadenopathy and a case of Kimura''s disease. False negatives include two cases of TB lymphadenitis. Pathogens should be looked for irrespective of cyto-morphology. Biopsy should be done to confirm cases of lymphomas. Fine needle aspiration cytology should be included in the protocol of six monthly review of HIV infected cases.KEY WORDS: AIDS, FNAC, HIV, Lymph node, Tuberculosis     

White matter changes contribute to corpus callosum atrophy in the elderly: the LADIS study

BACKGROUND AND PURPOSE: The corpus callosum (CC) is the most important structure involved in the transmission of interhemispheric information. The aim of this study was to investigate the potential correlation between regional age-related white matter changes (ARWMC) and atrophy of CC in elderly subjects.MATERIALS AND METHODS: In 578 subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the cross-sectional area of the CC was automatically segmented on the normalized midsagittal MR imaging section and subdivided into 5 regions. The ARWMC volumes were measured quantitatively by using a semiautomated technique and segmented into 6 brain regions.RESULTS: Significant correlation between the area of the rostrum and splenium regions of the CC and the ARWMC load in most brain regions was identified. This correlation persisted after correction for global atrophy.CONCLUSION: Increasing loads of ARWMC volume were significantly correlated with atrophy of the CC and its subregions in nondisabled elderly subjects with leukoaraiosis. However, the pattern of correlation between CC subregions and ARWMC was not specifically related to the topographic location of ARWMC. The results suggest that ARWMC may lead to a gradual loss of CC tissue.

The corpus callosum (CC) is the most important commissural tract in the brain containing myelinated axons transversing the subcortical white matter. The CC serves to unite the 2 hemispheres anatomically and functionally, and CC atrophy may be associated with cognitive and motor deficits.^1–5 A gradual decline in the area and width of the CC has been reported after the fourth decade of life.⁶There is a considerable interindividual variability in the area and shape of the CC in the healthy elderly. Both positive and negative results have been obtained regarding the correlation of CC cross-sectional areas to factors such as sex and handedness,^7–15 number of lacunes and the presence of infarcts in the cerebral hemispheres,^16,17 and/or brain size.¹⁸The mechanism for CC atrophy is poorly understood, but CC atrophy may reflect pathologic changes in subcortical white matter, as reported in patients with multiple sclerosis¹⁹ and vascular dementia.²⁰ In healthy elderly subjects, CC atrophy may result from axonal disruption due to white matter damage.The association between age-related white matter changes (ARWMC) and CC atrophy was previously examined in 5 studies of the elderly with leukoaraiosis,²¹ infarcts and cardiovascular risk factors,¹⁶ Alzheimer disease (AD),^21–23 and healthy elderly controls.^16,21–23 Each of these studies was based on relatively small sample sizes, and taken together, they have not provided a common conclusion concerning the potential influence of ARWMC on the size of the CC. For example, in 3 studies analyzing MR imaging from patients with AD, 1 study (N = 15) found significant correlation between ARWMC and CC atrophy, whereas 2 studies (N = 21 and N = 29) did not find any significant correlation.^22,23 In healthy elderly controls, 3 ^21,22 of 4 studies (n ≤ 29)^16,21–23 found a significant correlation between ARWMC and CC atrophy. The same association was found in a population with cardiovascular risk factors (n = 14) and infarcts (n = 30).¹⁶ However, in the population of elderly subjects with leukoaraiosis (N = 62), Yamauchi et al (2000)²⁴ did not find any significant correlation between ARWMC and CC atrophy.The contradictory conclusions could be due to the use of different methods for segmentation and subdivision of the CC or to different rating techniques for assessment of ARWMC and CC. Small populations and the use of subjective rating scales may obscure potential correlations.The aim of this study was to investigate the correlation between regional ARWMC and atrophy of CC subregions in a large population of nondisabled elderly subjects with leukoaraiosis.     

The association of bacterial adhesion with dental caries.

Saliva adhesion of bacteria is a key event in oral biofilm formation. Here, we used partial least-squares (PLS) analysis to correlate adhesion of cariogenic (Streptococcus mutans Ingbritt) and commensal (Actinomyces naeslundii LY7) model bacteria, and their agglutinin and acidic proline-rich protein ligands, respectively, with high and low caries experiences in 38 children reflecting today's skewed caries distribution. Adhesion of S. mutans was among the factors correlating strongest with high caries experience when PLS modeled together with traditional factors (e.g., sugar intake, lactobacilli counts). Saliva phenotypes with high agglutinin levels and Db-s (an acidic PRP variant) coincided with both high caries experience and S. mutans adhesion. A. naeslundii adhesion correlated with low caries experience. Non-Db phenotypes (i.e., acidic PRP-1 and PRP-2 variants) coincided with both low caries experience and S. mutans, but high A. naeslundii, adhesion. Thus, bacterial adhesion may modulate susceptibility and resistance to dental caries.     

Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics

Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS). However, those studies utilized small numbers of ALS and control subjects. Additional studies using larger subject cohorts are required to verify these candidate biomarkers. Cerebrospinal fluid (CSF) samples from 100 patients with ALS, 100 disease control, and 41 healthy control subjects were examined by mass spectrometry. Sixty‐one mass spectral peaks exhibited altered levels between ALS and controls. Mass peaks for cystatin C and transthyretin were reduced in ALS, whereas mass peaks for posttranslational modified transthyretin and C‐reactive protein (CRP) were increased. CRP levels were 5.84 ± 1.01 ng/ml for controls and 11.24 ± 1.52 ng/ml for ALS subjects, as determined by enzyme‐linked immunoassay. This study verified prior mass spectrometry results for cystatin C and transthyretin in ALS. CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb‐onset disease. Our biomarker panel predicted ALS with an overall accuracy of 82%. Muscle Nerve 42: 104–111, 2010     

Granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 greatly enhance the interaction of human eosinophils with opsonized particles by changing the affinity of complement receptor type 3

Eosinophil functions can be modulated by several cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin- 3 (IL-3), and IL-5. We have investigated the modulatory role of these cytokines on the interaction of human eosinophils with opsonized particles (serum-treated zymosan [STZ]). Addition of STZ to eosinophils isolated from the peripheral blood of normal human donors resulted in an interaction of the STZ particles with only 15% to 25% of the cells. Treatment of the eosinophils with GM-CSF, IL-3, or IL-5 strongly enhanced both the rate of particle binding and the percentage of eosinophils binding STZ. The effect of the cytokines is most likely mediated by a change in affinity of the complement receptor type 3 (CR3) on the eosinophils for the complement fragment iC3b on the STZ particles. This is indicated by the observation that (1) the effect of the cytokines on STZ binding was prevented by a monoclonal antibody against the iC3b-binding site on CR3 and (2) the enhanced binding was already apparent before upregulation of CR3 on the cell surface was observed. In a previous study, similar results were obtained with platelet-activating factor (PAF)-primed eosinophils. Because we found that the cytokines strongly enhanced the STZ-induced PAF synthesis, we investigated the role of both released PAF and cell-associated PAF in the priming phenomenon by the cytokines. Cytokine priming appeared to be largely independent of the synthesis of PAF.     

Two UV-induced episodes of myelitis in a patient with systemic lupus erythematosus.

Two flares of acute myelitis were observed in a 31-year-old woman with previously known mild SLE. The two myelitic episodes both occurred within 1 week after intense sun exposure, and for this reason photobiological induction of the manifestation is considered likely. The diagnostic utility of MRI in the acute situation and the possible influence of sex-steroids on SLE manifestations are also illustrated by this case.