Collagen Type I, Collagen Type III, and Versican in Vocal Fold Lamina Propria

Objective: To analyze the distributions of collagen type I, collagen type III, and versican in the lamina propria of the human vocal fold. Design: Cross-sectional analysis of cadaveric vocal folds of adult human larynges. Setting: Academic tertiary referral center. Subjects: Larynges harvested at autopsy from 10 adult men and 10 adult women. Main Outcome Measures: Immunohistochemical reactions were performed using antihuman monoclonal antibodies to analyze the expression of collagen type I, collagen type III, and versican. Results: Collagen type I density was lower in the intermediate layer compared with the superficial and deep layers of vocal folds. Collagen type III density was lower in the intermediate layer compared with the deep layer. Versican density was lower in the superficial layer compared with the intermediate and deep layers. Versican density was lower in the lamina propria of women compared with men; this difference was noted in the superficial layer only. There was a positive correlation between collagen type III and versican densities within the lamina propria. Conclusion: Collagen type I, collagen type III, and versican are distributed differently within the lamina propria layers of the adult vocal folds.

Increased Levels of Circulating Endothelial Progenitor Cells in Human T-cell Lymphotropic Virus Type I Carriers

Background and Aims. HTLV-I-transformed T cells secrete biologically active forms of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF). In addition, HTLV-I-transformed cells have a high capacity of adhesion to endothelial cells. Methods. We measured the circulating endothelial progenitor cells (EPCs) and mature endothelial cells (MECs) by flow cytometry in 27 HTLV-I carriers in comparison to 30 healthy, age- and gender-matched subjects. All subjects had HTLV-I positivity confirmed by Western blot and/or polymerase chain reaction (PCR). The numbers of different subpopulations of EPCs and MECSs were evaluated by four-color flow cytometry using a panel of monoclonal antibodies. All reactions were done in duplicate to confirm reproducibility of the results. Results. The median age of all 27 HTLV-I carriers enrolled in this study was 45 years (range: 27-65 years); 11(41%) were male and 16 (59%) were female. The median age of the 30 healthy subjects in the control group was 45.5 years (range: 20-63 years); 11 (36.6%) were male and 19 (63.4%) were female. The number of EPCs was significantly higher in HTLV-I carriers (median 0.8288 cells/mu L, range: 0.0920-3.3176 cells/mu L) as compared to control group (median 0.4905 cells/mu L, range: 0.0000-1.5660 cells/mu L) (p = 0.035). In contrast, the median of the MECs in the HTLV-I carriers was 0.6380 cells/mu L (range: 0.0473-5.7618 cells/mu L) and 0.4950 cells/mu L (range: 0.0000-4.0896 cells/mu L) in the control group, with no statistical difference (p = 0.697). Conclusions. We demonstrated that EPCs, but not MECs, are increased in the peripheral blood of HTLV-I carriers. (C) 2011 IMSS. Published by Elsevier Inc.

Adverse mucocutaneous reactions to chemotherapeutic agents - Part I

The local and systemic treatment of tumors can cause changes in the skin, mucous membranes, hair and nails. Accurate diagnosis and appropriate treatment of side effects require knowledge about the patterns of the most common adverse reactions to drugs the patient may be using. The dermatologist must be familiar with the manifestations of certain soft tissue neoplasms, as well as with the adverse mucocutaneous forms of cancer treatment.

Human apolipoprotein A-I binds amyloid-beta and prevents A beta-induced neurotoxicity

Aggregates of the amyloid-P peptide (A beta) play a central role in the pathogenesis of Alzheimer`s disease (AD). Identification of proteins that physiologically bind A beta and modulate its aggregation and neurotoxicity could lead to the development of novel disease-modifying approaches in AD. By screening a phage display peptide library for high affinity ligands of aggregated A beta(1-42), We isolated a peptide homologous to a highly conserved amino acid sequence present in the N-terminus of apolipoprotein A-I (apoA-I). We show that purified human apoA-I and A beta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by A beta. Significantly, A beta/apoA-I complexes were also detected in cerebrospinal fluid from AD patients. Interestingly, apoA-I and apoA-I-containing reconstituted high density lipoprotein particles protect hippocampal neuronal cultures from A beta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates A beta aggregation and A beta-induced neuronal damage and that the A beta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of A beta toxicity. (C) 2009 Published by Elsevier Ltd.

The frequency of anti-beta(2)-glycoprotein I antibodies is low and these antibodies are associated with pulmonary hypertension in mixed connective tissue disease

The objective of this study is to evaluate the prevalence of antiphospholipid antibodies, mainly anti-beta(2)-glycoprotein I (anti-beta(2)-GPI), and their possible clinical and laboratory relevance in mixed connective tissue disease (MCTD). This study included 39 consecutive patients with MCTD (Kasukawa`s criteria) from January, 2005, to March, 2007, and compared them with 21 age- and sex-matched healthy controls. IgG and IgM anticardiolipin (aCL) and anti-beta(2)-GPI were measured by ELISA. Lupus anticoagulant (LA) was detected by functional coagulation tests. Medium to high titres of aCL and anti-beta(2)-GPI antibodies were found in sera from four (10.2%) MCTD patients. One of these patients was found to be positive for IgM aCL, IgM anti-beta(2)-GPI and LA antibodies simultaneously. Additionally, this patient had a previous history of foetal loss in the second trimester and new-onset pulmonary arterial hypertension (PAH). The other three patients had none of the manifestations of antiphospholipid syndrome (APS) or PAH. The mean value of IgG anti-beta(2)-GPI was higher among those MCTD patients with PAH than in the group without PAH (34.2 +/- 46.8 vs 12.3 +/- 9.1, P = 0.018). None of the controls were positive for antiphospholipid antibodies. High to moderate titres of anti-beta(2)-GPI as well as APS were rare in MCTD, and these antibodies may be correlated with the development of PAH in these patients. Lupus (2009) 18, 618-621.

Suicide behavior and neuropsychological assessment of type I bipolar patients

Background: Neuropsychological deficits are often described in patients with bipolar disorder (BID). Some symptoms and/or associated characteristics of BD can be more closely associated to those cognitive impairments. We aimed to explore cognitive neuropsychological characteristics of type I bipolar patients (BPI) in terms Of lifetime Suicide attempt history. Method: We studied 39 BPI Outpatients compared with 53 healthy controls (HC) matched by age, educational and intellectual level. All Subjects were submitted to a neuropsychological assessment of executive functions, decision-making and declarative episodic memory. Results: When comparing BD1 patients, regardless of suicide attempt history or HC, we observed that bipolar patients performed worse than controls oil measures of memory, attention, executive functions and decision-making, Patients with a history of suicide attempt performed worse than non-attempters on measures of decision-making and there were a significant negative correlation between the number of suicide attempts and decision-making results (block 3 and net score). We also found significant Positive correlation between the number Of Suicide attempts and amount Of errors in Stroop Color Word Test (part 3). Limitations: The sample Studied call be considered small and a potentially confounding variable - medication status - were not controlled. Conclusion: Our results show the presence of neuropsychological deficits in memory, executive functions, attention and decision-making in BPI patients. Suicide attempts BPI scored worse than non-suicide attempt Bill oil measures of decision-making. More suicide attempts were associated with a worse decision-making process. Future research should explore the relationship between the association between this specific cognitive deficits in BPIs, serotonergic function and suicide behavior in bipolar patients as well other diagnostic groups. (C) 2009 Elsevier B.V. All rights reserved.

Mango starch degradation. I. A microscopic view of the granule during ripening

The starch content of unripe mango Keitt is around 7% (FW), and it is converted to soluble sugars during the ripening of the detached fruit. Despite the importance of starch-to-soluble sugar metabolism for mango quality, little literature is found on this subject and none concerning the physical aspects of starch degradation. This manuscript presents some changes in the physical aspects of the starch granule during ripening, as analyzed by light microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). According to the analysis, unripe Keitt-mango-starch being spherical in shape and measuring around 15,mu m, has A-type X-ray diffraction pattern with a degree of crystallinity around 21% with slight changes after 8 days of ripening. AFM images of the surface of the granules showed ultra microstructures, which are in agreement with a blocklet-based organization of the granules. The AFM-contrast image of growing layers covering the granule showed fibril-like structures, having 20 nm in diameter, transversally connecting the layer to the granule. The appearance of the partially degraded granules and the pattern of degradation were similar to those observed as a result of amylase activity, suggesting a hydrolytic pathway for the degradation of starch from mango cultivar Keitt. These results provide clues to a better understanding of starch degradation in fruits.

Angiotensin II Binding to Angiotensin I-Converting Enzyme Triggers Calcium Signaling

Angiotensin (Ang) I-converting enzyme (ACE) is involved in the control of blood pressure by catalyzing the conversion of Ang I into the vasoconstrictor Ang II and degrading the vasodilator peptide bradykinin. Human ACE also functions as a signal transduction molecule, and the binding of ACE substrates or its inhibitors initiates a series of events. In this study, we examined whether Ang II could bind to ACE generating calcium signaling. Chinese hamster ovary cells transfected with an ACE expression vector reveal that Ang II is able to bind with high affinity to ACE in the absence of the Ang II type 1 and type 2 receptors and to activate intracellular signaling pathways, such as inositol 1,4,5-trisphosphate and calcium. These effects could be blocked by the ACE inhibitor, lisinopril. Calcium mobilization was specific for Ang II, because other ACE substrates or products, namely Ang 1-7, bradykinin, bradykinin 1-5, and N-acetyl-seryl-aspartyl-lysyl-proline, did not trigger this signaling pathway. Moreover, in Tm5, a mouse melanoma cell line endogenously expressing ACE but not Ang II type 1 or type 2 receptors, Ang II increased intracellular calcium and reactive oxygen species. In conclusion, we describe for the first time that Ang II can interact with ACE and evoke calcium and other signaling molecules in cells expressing only ACE. These findings uncover a new mechanism of Ang II action and have implications for the understanding of the renin-Ang system. (Hypertension. 2011;57:965-972.) . Online Data Supplement

Synthesis, spectroscopic characterization, DFT studies and biological assays of a novel gold(I) complex with 2-mercaptothiazoline

A new gold(I) complex with 2-mercaptothiazoline (MTZ) with the coordination formula [AuCN(C(3)H(5)NS(2))] was synthesized and characterized by chemical and spectroscopic measurements, OFT studies and biological assays. Infrared (IR) and (1)H, (13)C and (15)N nuclear magnetic resonance (NMR) spectroscopic measurements indicate coordination of the ligand to gold(I) through the nitrogen atom. Studies based on OFT confirmed nitrogen coordination to gold(I) as a minimum of the potential energy surface with calculations of the hessians showing no imaginary frequencies. Thermal decomposition starts at temperatures near 160 degrees C, leading to the formation of Au as the final residue at 1000 degrees C. The gold(I) complex with 2-mercaptothiazoline (Au-MTZ) is soluble in dimethyl sulfoxide (DMSO), and is insoluble in water, methanol, ethanol, acetonitrile and hexane. The antibacterial activities of the Au-MTZ complex were evaluated by an antibiogram assay using the disc diffusion method. The compound showed an effective antibacterial activity against Staphylococcus aureus (Gram-positive) and Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacterial cells. Biological analysis for evaluation of the cytotoxic effect of the Au-MTZ complex was performed using HeLa cells derived from human cervical adenocarcinoma. The complex presented a potent cytotoxic activity, inducing 85% of cell death at a concentration of 2.0 mu mol L(-1). (C) 2011 Elsevier Ltd. All rights reserved.

Major histocompatibility complex (MHC) class II but not MHC class I molecules are required for efficient control of Strongyloides venezuelensis infection in mice

P>Strongyloides stercoralis is an intestinal nematode capable of chronic, persistent infection and hyperinfection of the host; this can lead to dissemination, mainly in immunosuppressive states, in which the infection can become severe and result in the death of the host. In this study, we investigated the immune response against Strongyloides venezuelensis infection in major histocompatibility complex (MHC) class I or class II deficient mice. We found that MHC II(-/-) animals were more susceptible to S. venezuelensis infection as a result of the presence of an elevated number of eggs in the faeces and a delay in the elimination of adult worms compared with wild-type (WT) and MHC I(-/-) mice. Histopathological analysis revealed that MHC II(-/-) mice had a mild inflammatory infiltration in the small intestine with a reduction in tissue eosinophilia. These mice also presented a significantly lower frequency of eosinophils and mononuclear cells in the blood, together with reduced T helper type 2 (Th2) cytokines in small intestine homogenates and sera compared with WT and MHC I(-/-) animals. Additionally, levels of parasite-specific immunoglobulin M (IgM), IgA, IgE, total IgG and IgG1 were also significantly reduced in the sera of MHC II(-/-) infected mice, while a non-significant increase in the level of IgG2a was found in comparison to WT or MHC I(-/-) infected mice. Together, these data demonstrate that expression of MHC class II but not class I molecules is required to induce a predominantly Th2 response and to achieve efficient control of S. venezuelensis infection in mice.

Immunolocalization and pathological alterations following Strongyloides venezuelensis infection in the lungs and the intestine of MHC class I or II deficient mice

The present study, investigated the mechanisms involved in the immune responses of Major Histocompatibility Complex class I or class II knockout mice, following Strongyloides venezuelensis infection. Wild-type C57BL/6 (WT), MHC II(-/-) and MHC I(-/-) mice were individually inoculated with 3000 larvae (U) of S. venezuelensis and sacrificed on days 1, 3, 5, 8, 13 and 21 post-infection (p.i.). Samples of blood, lungs and small intestines were collected. The tissue samples were stained with hematoxylineosin for the pathological analysis. The presence of the parasite was demonstrated by immunoperoxidase analysis. MHC II(-/-) mice presented a significantly higher number of adult worms recovered from the small intestine on day 5 p.i. and presented elevated numbers of eggs in the feces. The infection by S. venezuelensis was completely eliminated 13 days after infection in WT as well as in MHC I(-/-) mice. In MHC II(-/-) mice, eggs and adult worms were still found on day 21 p.i., however, there was a significant reduction in their numbers. In the lung, the parasite was observed in MHC I(-/-) on day 1 p.i. and in MHC II(-/-) mice on days 1 and 5 p.i. In the small intestine of WT mice, a larger number of parasites were observed on day 8 p.i. and their absence was observed after day 13 p.i. Through immunohistochemistry analysis, the parasite was detected in the duodenum of WT on days 5 and 8 p.i., and in knockout mice on days 5, 8 and 13 p.i.; as well as in posterior portions of the small intestine in MHC I(-/-) and MHC II(-/-) on day 13 p.i., a finding which was not observed in WT mice. We concluded that immunohistochemistry analysis contributed to a more adequate understanding of the parasite localization in immunodeficient hosts and that the findings aid in the interpretation of immunopathogenesis in Strongyloides infection. (C) 2008 Elsevier B.V. All rights reserved.

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa. (C) 2011 Elsevier Ltd. All rights reserved.

Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study

Background Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with retapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta. Methods Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m(2) cyclophosphamide and 10 mu g per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation. Findings Between January 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8-11) and patients were discharged from hospital on mean day 11 (range day 8-13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24-48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0.0001), neurological rating scale score (p=0.0001), paced auditory serial addition test (p=0.014), 25-foot walk (p<0.0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0.0001). Interpretation Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.

Val/Leu(247) Polymorphism of beta 2-glycoprotein I in Brazilian Patients with Antiphospholipid Syndrome-A Genetic Risk Factor?

A genetic polymorphism of the beta 2-glycoprotein I (beta 2-GPI) is recognized by antiphospholipid antibodies (aPL) and may even play a role in the development of antiphospholipid syndrome (APS). The objectives of this study were to determine a Val/Leu SNP at position 247 of the beta 2-GPI gene in Brazilian patients with APS and to compare these data with clinical and laboratory manifestations. Polymorphism assignment was performed by PCR followed by Rsa I restriction endonuclease. The titration of anti-beta 2-GPI antibodies was detected by ELISA. The results showed significantly higher frequencies of the V-encoding allele and the homozygous VV genotype in patients with APS than in control subjects (OR = 1.781, P = 0.0068; and OR = 6.413, P < 0.0001, respectively). The frequency of this genotype was also significantly higher in patients with arterial and venous thrombosis than in the control group (52% and 44%, respectively, versus 13%). Anti-beta 2-GPI-positive patients had significantly higher frequencies of the VV genotype than the controls subjects (OR = 8.179, P < 0.0001). These results suggest that the V-encoding allele and the homozygous VV genotype at position 247 of the beta 2-GPI gene may play a role in the generation of anomalous beta 2-GPI, with consequent auto-antibody production, and in phenotype expression of arterial and venous thrombosis in APS patients.

Sustained Ventricular Tachycardia Is Associated with Regional Myocardial Sympathetic Denervation Assessed with (123)I-Metaiodobenzylguanidine in Chronic Chagas Cardiomyopathy

Cardiac sympathetic denervation and ventricular arrhythmia are frequently observed in chronic Chagas cardiomyopathy (CCC). This study quantitatively evaluated the association between cardiac sympathetic denervation and sustained ventricular tachycardia (SVT) in patients with CCC. Methods: We prospectively investigated patients with CCC and left ventricular ejection fraction (LVEF) greater than 35% with SVT (SVT group: n = 5 15; mean age +/- SD, 61 +/- 8 y; LVEF, 51% +/- 8%) and patients without SVT (non-SVT group: n = 11; mean age +/- SD, 55 +/- 10 y; LVEF, 57% +/- 10%). Patients underwent myocardial scintigraphy with (123)I-metaiodobenzylguanidine ((123)I-MIBG) for the evaluation of sympathetic innervation and resting perfusion with (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) for the evaluation of myocardial viability. A visual semiquantitative score was attributed for regional uptake of each radiotracer using a 17-segment left ventricular segmentation model (0, normal; 4, absence of uptake). A mismatch defect was defined as occurring in segments with a 99mTc-MIBI uptake score of 0 or 1 and a (123)I-MIBG score of 2 or more. Results: Compared with the non-SVT group, the SVT group had a similar (99m)Tc-MIBI summed score (6.9 +/- 7.5 vs. 4.4 +/- 5.2, respectively, P = 0.69) but a higher (123)I-MIBG summed score (10.9 +/- 7.8 vs. 22.4 +/- 9.5, respectively, P = 0.007) and a higher number of mismatch defects per patient (2.0 +/- 2.2 vs. 7.1 +/- 2.0, respectively, P < 0.0001). The presence of more than 3 mismatch defects was strongly associated with the presence of SVT (93% sensitivity, 82% specificity; P = 0.0002). Conclusion: In CCC, the amount of sympathetically denervated viable myocardium is associated with the occurrence of SVT. Myocardial sympathetic denervation may participate in triggering malignant ventricular arrhythmia in CCC patients with relatively well-preserved ventricular function.