Cytomegalovirus, Macrophages and Breast Cancer.

The human cytomegalovirus (HCMV) is a betaherpesvirus that is highly host specific, infects among others epithelial cells and macrophages, and has been recently mentioned as having oncomodulatory properties. HCMV is detected in the breast tumor tissue where macrophages, especially tumor associated macrophages, are associated with a poor prognosis. In this review, we will discuss the potential implication of HCMV in breast cancer with emphasis on the role played by macrophages.

The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.

Generalized eruptive keratoacanthoma: proposed diagnostic criteria and therapeutic evaluation.

Generalized eruptive keratoacanthoma (GEKA) of Grzybowski is a sporadically occurring, extremely rare variant of keratoacanthoma characterized clinically by severely pruritic, generalized eruption of numerous small follicular papules, often with a central keratotic plug, and histologically by typical features of solitary keratoacanthoma. Despite the continuous addition of new case reports, no definite diagnostic criteria have been established, and an optimum treatment is not yet determined. Herein, we review the different aspects of this rare entity, including pathogenesis, clinical and histopathological features, differential diagnosis, course and prognosis. Different therapeutic approaches and their impact on the course and prognosis of the disease are also evaluated and presented. We propose two sets of diagnostic criteria to define the disease more precisely and to avoid overlapping and confusion with other types of multiple keratoacanthoma. The first set comprises constant clinical and histopathological features that almost always present in every case and the second set includes variable features that were reported in some patients, and to which any emerging finding could be added to avoid missing cases. Although different therapeutic options have been used, either as single agents or in combinations, there is no standard therapy for GEKA and the disease still represents a therapeutic challenge.

Paederus dermatitis in Egypt: a clinicopathological and ultrastructural study.

BACKGROUND: Outbreaks of paederus dermatitis (PD) have been observed in different parts of the world, yet the histopathological and ultrastructural changes and their relationship to pederin toxin have not been described. OBJECTIVE: To describe the clinical presentations of PD in Egypt and to study the effects of pederin toxin on the skin by evaluating the histopathological and ultrastructural changes of some representative cases. METHODS: One hundred and thirteen patients with PD were studied clinically and epidemiologically. Skin biopsies were taken from 40 patients for histopathological examination and from 20 patients for electron microscopic (EM) examination. RESULTS: Clinically, the most common presentation comprised erythematous plaques with micropustules. Blisters exhibited a linear configuration in 40% of the patients and kissing lesions were observed in 13%. Multiple lesions occurred in 78% of the patients and the face was the most commonly involved site (48%). The insect was identified as Paederus alfierii. Histopathological examination revealed features of acute irritant dermatitis in the upper epidermis. Mitotic figures and apoptotic changes such as chromatin condensation and DNA fragmentation were identified in the basal and suprabasal layers. These features were confirmed by EM. CONCLUSIONS: Clinical, histopathological and, for the first time, ultrastructural characteristics of paederus dermatitis are described. The pathological abnormalities of the upper epidermis are caused by the irritant effect of pederin toxin. The presence of apoptosis within the lower epidermis can be related to this toxin, a point that needs further research, hoping for its future implications in the management of hyperproliferative disorders.

Cleaning endodontic files in a washer disinfector.

AIMS: The aim of this study was to compare the cleanliness of endodontic files that had been cleaned in a washer disinfector according to the file holding mechanism within the machine. METHODOLOGY: Selected canals of extracted teeth were filed with new, unused files. One set of files (size 15 to 40) was used for each canal. A total of 192 files were used for cleaning and shaping. The files were divided into three groups. The first group was a control group containing 30 files, which were not cleaned in the washer disinfector. The second and the third groups were the experimental groups with 81 files in each group. These files were cleaned in the washer disinfector using different holding mechanisms (file holder or cleaning basket) for each group. The files were examined for visible debris under a light microscope at x45 magnification. RESULTS: None of the 162 cleaned files were totally free of organic debris. Comparison of the debris scores in the two experimental groups showed that the files in the cleaning basket group were significantly cleaner than those in the file holder group. The files in both test groups were significantly cleaner than those in the control group. CONCLUSIONS: Endodontic files cannot be totally cleaned using a washer disinfector alone. The instrument holding mechanism within the machine has a significant effect on the cleanliness of the files after one intensive cleaning cycle.

Epigallocatechin-3-gallate induces apoptosis and cell cycle arrest in HTLV-1-positive and -negative leukemia cells.

The objective of this study is to evaluate the efficacy of epigallocatechin gallate against ATL cells. The anti-proliferative and pro-apoptotic effects of EGCG were evaluated in HTLV-1-positive and -negative cells. EGCG exhibited a marked decrease in proliferation of ATL cells at 96 h of treatment. The results indicated that TGF-alpha was down-regulated whereas levels of TGF-beta2 increased. Cell cycle distribution analysis revealed an increase in cells in the pre-G(1) phase which was confirmed by ELISA. The results on proteins showed an up-regulation of p53, Bax and p21 protein levels while the levels of Bcl-2alpha were down-regulated.

Mechanistic aspects of apoptosis induction by l-lysine in both HTLV-1-positive and -negative cell lines.

The retrovirus human T-cell lymphotrophic virus type-1 (HTLV-1) causes adult T-cell leukemia (ATL), which remains with no cure. This study evaluates the effects of l-lysine on proliferation and induction of apoptosis using non-cytotoxic concentrations of the test compound against HTLV-1 positive and negative malignant cell lines. The anti-proliferative effect of lysine was established and confirmed by studying the effects of the test compound on the expression of TGF mRNA expression by RT-PCR. To investigate the effect of l-lysine on the induction of apoptosis, DNA flow cytometry analyses was done and the results verified by cell death ELISA. The results indicated that a significant increase in the preG(1) phase and a decrease in the S phase of the cell cycle in all of the ATL cells tested. l-Lysine up-regulated p53, p21, and Bax protein levels and a down-regulation of Bcl-2alpha in all the cell lines tested. l-Lysine was found to exert its effect through the NF-kappaB pathway by inhibiting the p65 subunit specifically. Also l-lysine caused a decrease in the levels MMP-2 and MMP-9 as well as their enzymatic activity.

Apoptosis induction by Epican Forte in HTLV-1 positive and negative malignant T-cells.

The effects of a novel nutrient formulation Epican Forte (EF) were evaluated on proliferation and induction of apoptosis using non-cytotoxic concentrations against HTLV-1 positive (HuT-102 & C91-PL) and negative (CEM & Jurkat) cells. EF showed anti-proliferative effect as determined by MTT assay and TGF mRNA protein expression using RT-PCR. EF resulted in the down-regulation of TGF-alpha and an up-regulation in TGF-beta2. EF caused a significant increase in apoptotic cells in the preG1 phase. These results were confirmed using Cell Death ELISA and Annexin V-FITC. Induction of apoptosis was caused by an up-regulation of p53, p21 and Bax protein levels and a down-regulation of Bcl-2alpha protein expression level.

Different low doses of broad-band UVA in the treatment of morphea and systemic sclerosis.

BACKGROUND: Numerous treatment modalities, some with potentially hazardous side effects, are currently used for morphea (M) and systemic sclerosis (SS) with limited success. Low-dose ultraviolet A (UVA) phototherapy (20 J/cm(2)) was found to be highly effective for sclerotic patches, even in patients with advanced and rapidly evolving lesions. OBJECTIVE: To determine the effectiveness of different low doses of UVA in treating patients with M and SS. METHODS: Sixty-three patients complaining of M and 15 patients complaining of SS received 20 sessions of UVA (320-400 nm) each. Patients were divided randomly into three groups that received 5, 10 and 20 J/cm(2), with cumulative UVA doses of 100, 200, and 400 J/cm(2), respectively. The efficacy of therapy was judged clinically (by sequential inspection and palpation) and histopathologically by morphometry in M cases. RESULTS: Obvious clinical improvement, with no comparable differences between various low UVA doses, was noted in patients with M and SS, accompanied by histopathological changes towards normalization of collagen. CONCLUSIONS: After 20 sessions, it appears that lower doses of UVA (5, 10 J/cm(2)) are as beneficial as the relatively higher dose (20 J/cm(2)) in the treatment of M and SS.

Monoterpene glucosides from Origanum syriacum.

From the aerial parts of Origanum syriacum, three new monoterpene glucosides thymoquinol 2,5-O-beta-diglucopyranoside (3), carvacrol 2-O-beta-glucopyranosyl-(1-->2)-beta-glucopyranoside (4) and p-menth-1-ene-3,4-diol 4-O-beta-glucopyranoside (5) together with two known monoterpene glucosides thymoquinol 2-O-beta-glucopyranoside (1), thymoquinol 5-O-beta-glucopyranoside (2) have been isolated. The structures of the isolated compounds were verified by means of MS and NMR spectral analyses.

Cardiac glycosides from Cryptostegia grandiflora.

From the leaves of Cryptostegia grandiflora, four new cardiac glycosides oleandrigenin 3-O-beta-glucopyranosyl-(1-->4)-beta-cymaropyranosyl-(1-->4)-beta-digitoxopyranoside, cryptostigmin I, oleandrigenin 3-O-beta-glucopyranosyl-(1-->4)-alpha-rhamnopyranoside, cryptostigmin II, 16-propionylgitoxigenin 3-O-beta-glucopyranosyl-(1-->4)-alpha-rhamnopyranoside, cryptostigmin III and oleandrigenin 3-O-beta-glucopyranosyl-(1-->6)-beta-glucopyranosyl-(1-->4)-beta-cymaropyranosyl-(1-->4)-beta-digitoxopyranoside, cryptostigmin IV have been isolated together with two known cardenolides subalpinosid and 16-O-acetyl-digitalinum verum. The structures of the isolated compounds were verified by means of MS and NMR spectral analyses.

Recognized globe perforation during strabismus surgery: incidence, risk factors, and sequelae.

BACKGROUND: Inadvertent perforation of the globe is a well-recognized complication of extraocular muscle surgery. We evaluated the incidence, risk factors, and sequelae of this complication at our institution. METHODS: Medical records of patients who underwent extraocular muscle surgery at King Khaled Eye Specialist Hospital, Saudi Arabia, between September 1983 and April 1997, were reviewed for the occurrence of globe perforation. We documented preoperative visual acuity and refraction, surgical procedure, how the perforation occurred, and immediate management, as well as the sequelae of the perforation, its management, and final outcome. RESULTS: Recognized perforations occurred in 15 of 4886 procedures, for an overall incidence rate of 3/1000. Perforations were 3 times more common in myopic eyes (>-6.00 D, P =.05) and 2 times more common in eyes with previous extraocular muscle surgery. Perforations occurred during muscle reattachment (5 cases), placement of traction sutures at the limbus (4 cases with transient hyphema), muscle disinsertion (3 cases), and placement of sutures at the muscle insertion before disinsertion (3 cases). One patient had a large scleral laceration with uveal prolapse, necessitating scleral patch graft at the time of surgery, and later had retinal detachment surgery with loss of 2 lines of visual acuity. Endophthalmitis, cataract, glaucoma, and phthisis bulbi were not encountered in our review. CONCLUSION: The current incidence of globe perforation is low and only rarely associated with serious sequelae.

Hepatotoxicity of flunitrazepam and alcohol in vitro.

Flunitrazepam (FNZ) is a benzodiazepine derivative more potent than diazepam. FNZ abuse in the US has emerged in the last few years and has a growing popularity among young people and drug abusing populations. Ethanol (EtOH) consumption with FNZ enhances euphoria and onset of action. It is postulated that FNZ and EtOH cause liver cell injury. In this study, hepatocytes are employed to study the hepatotoxicity of FNZ, EtOH and their combination (FNZ-EtOH). Hepatocytes (2x10(6) cells/ml) isolated from male Sprague-Dawley rats were exposed to saline, FNZ, EtOH or FNZ-EtOH in combination. The uptake of 0.4% trypan blue and the leakage of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes into the incubation media were used to assess cell membrane damage of hepatocytes. Where metabolism of FNZ is nearly complete through several hepatic pathways, animal pretreatment with Phenobarbital was used to study the effect of microsomal enzyme induction on cellular injury. FNZ (0.16mm), EtOH (32.56mm) or their combination caused a significant (P<0.05) decrease in cell viability. Compared with control, FNZ and FNZ-EtOH in combination caused significant AST leakage over the 2-hour incubation period. EtOH alone caused significant AST leakage after 2 hours of incubation. The leakage of ALT enzyme was significant for FNZ, EtOH and FNZ-EtOH over the 2-hour incubation period. While FNZ alone did not produce any significant enzymatic leakage in the Phenobarbital pretreated groups, the leakage of ALT and AST were significant for FNZ-EtOH in combination as early as 30 minutes of incubation. A significant depletion (P<0.05) of glutathione (GSH) was observed for EtOH and FNZ-EtOH in combination treated samples. This investigation suggests that FNZ and EtOH cause hepatotoxicity, and their combinations have an additive effect in increasing liver toxicity. Induction of microsomal enzymes revealed that FNZ is more hepatotoxic than the metabolites. And FNZ alone has no effect on GSH content.

[Systemic lupus erythematous and myasthenia gravis: case report]. / Lupus eritematoso sistêmico associado a miastenia gravis. Relato de caso.

We report the case of a 24-year-old white woman admitted with a four year diagnosis of systemic lupus erythematosus and the recent onset of myasthenia gravis discussing the main differential diagnosis of weakness and fatigue in this patient. A review of literature approaching the association of myasthenia gravis and systemic lupus erythematosus is also done with emphasis on the clinical characteristics of these patients and the role of thymoma and thymectomy in the development of systemic lupus erythematosus in myasthenic patients.

Specificity of IS6110-based amplification assays for Mycobacterium tuberculosis complex.

The specificity of IS6110 for the Mycobacterium tuberculosis complex has recently been questioned. We observed no cross-reaction with 27 nontuberculous mycobacteria using strand displacement- and PCR-based amplification of the nucleotide 970 to 1026 and 762 to 865 regions of IS6110. These data support use of selected regions of IS6110 as M. tuberculosis complex-specific targets.

Staphylococcal vertebral osteomyelitis: case report.

A 65-year old male Saudi patient presented with rapidly progressive quadriparesis. Lower cervical myelopathy was associated with radiological features of bone destruction, inflammatory disease of the spine and a paravertebral mass. Although tuberculosis and brucellosis are more commonly responsible for this clinical picture in our practice, Staphylococcus aureus was isolated from tissue recovered at surgery. He has been followed up for 12 months and has made an almost complete recovery after surgical decompression of spinal cord and a 2-month course of intravenous flucloxacillin. This case underscores the need for tissue diagnosis in patients presenting with inflammatory paravertebral swellings even in areas endemic for tuberculosis and brucellosis.

Horner's syndrome secondary to angiogram negative, subadventitial carotid artery dissection.

A 59-year-old man presented with the acute onset of paresthesias and pain in the left neck, face, and forehead. On subsequent investigation he was found to have a subadventitial type of carotid artery dissection, producing an ipsilateral Horner's syndrome with normal carotid angiography. MRI imaging of the neck structures, using fat saturation technique, showed the subadventitial dissection, sparing the vessel lumen. MRI offers a non-invasive method of diagnosis and follow-up for carotid artery dissection.