Differential expression of galectin-3, beta-catenin, and cyclin D1 in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma of salivary glands

Background: Galectin-3 has been implicated in tumor progression of some malignancies as thyroid, prostate, and salivary gland tumors. Recently, it has been suggested that this protein may be an important mediator of the beta-catenin/Wnt pathway. Moreover, nuclear galectin-3 expression has been implicated in cell proliferation, promoting cyclin D1 activation. Thus, the present study aimed to correlate galectin-3 expression with beta-catenin and cyclin D1 expressions in adenoid cystic carcinoma (ACC) and in polymorphous low-grade adenocarcinoma (PLGA). Methods: Fifteen formalin-fixed paraffin-embedded cases of each tumor were retrieved from the files of the Surgical Oral Pathology Service at the University of Sao Paulo and the proteins were analyzed by immunohistochemistry. Results: Adenoid cystic carcinoma showed galectin-3 immunostaining mainly in the nuclei, while PLGA revealed a positive mostly cytoplasmic reaction to galectin-3 in the largest part of tumor cells. Both tumors showed intense cytoplasmic/nuclear staining for beta-catenin in majority of cases. Cyclin D1 immunoreactivity was not detected in 14/15 PLGA and showed specific nuclear staining in 10/15 cases of ACC in more than 5% of the neoplastic cells. Cyclin D1 expression was correlated with cytoplasmic and nuclear galectin-3 expression in ACC (P < 0.05). Conclusions: These results suggest that in ACC galectin-3 may play a role in cellular proliferation through cyclin D1 activation. In addition, nuclear expression of galectin-3 in ACC may be related to a more aggressive behavior of this lesion. Although beta-catenin seems to play a role in carcinogenesis in both lesions, it seems that it does not bind to galectin-3 for cyclin D1 stimulation.

GABAA receptor β3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population

GABAergic systems have been implicated in the pathogenesis of anxiety, depression and insomnia. These symptoms are part of the core and comorbid psychiatric disturbances in post-traumatic stress disorder (PTSD) In a sample of Caucasian male PTSD patients, dinucleotide repeat polymorphisms of the GABAA receptor beta3 subunit gene were compared to scores on the General Health Questionnaire-28 (GHQ). As the major allele at this gene locus (GABRB3) was GI, the alleles were divided into GI and non-GI groups. On the total score of the GHQ, which comprises the somatic symptoms, anxiety/insomnia, social dysfunction and depression subscales, patients with the GI non-GI genotype had a significantly higher score when compared to either the G1G1 genotype (alpha = 0.01) or the non-GI non-GI genotype (alpha = 0.05). No significant difference was found between the G1G1 and non-Gl non-G1 genotypes. When the GI non-G1 heterozygotes were compared to the combined G1G1 and non-GI non-GI homozygotes, a significantly higher total GHQ score was found in the heterozygotes (P = 0.002). These observations suggest a heterosis effect. Further analysis of GHQ subscale scores showed that heterozygotes compared to the combined homozygotes had higher scores on the somatic symptoms (P = 0.006), anxiety/insomnia (P = 0.003), social dysfunction (P = 0.054) and depression (P = 0.004) subscales. In conclusion, the present study indicates that in a population of PTSD patients, heterozygosity of the GABRB3 major (GI) allele confers higher levels of somatic symptoms, anxiety/insomnia, social dysfunction and depression than found in homozygosity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

2,6,,9-trioxabicyclo[3.3.1]nona-3,7-dienes and 2,4,6,8-tetraoxaadamantanes: Novel chiral spacer units in macrocyclic polyethers

The unusual chiral heterocyclic systems, trioxabicyclo[3.3.1]nona-3,7-dienes (bridged bisdioxines), are incorporated as novel spacer molecules into macrocyclic polyether ring systems of various sizes (8, 9 as well as 11-15) by cyclocondensation reaction of the! bisacid chloride 4b or bisesters 6,7 and 10, with several ethylene glycols. The 2:2 macrocycles 12-14 are obtained in approximately 50:50 mixtures of diastereomers. These conclusions are mainly based on HPLC data presented in Table I as well as X-ray analyses of (1R,5R)-8c (space group Pbca, a = 10.163(3) Angstrom, b = 18.999(4) Angstrom, c = 36.187(10) Angstrom, V = 6987(3) Angstrom(3), Z = 8, d(calc) = 1.218 g cm(-3), 6974 reflections, R = 0.0553.), mesolrac-11 (space group P (1) over bar, a = 10.472(5) Angstrom, b = 16.390(5) Angstrom, c = 17.211(5) Angstrom, alpha = 98.69(2)degrees, beta = 93.04(2)degrees, gamma = 98.52(2)degrees, V = 2879.3(18) Angstrom(3), Z = 2, d(calc) = 1.173 g cm(-3), 11,162 reflections, R = 0.0945) and meso-12 (space group P2(1)/c, a = 9.927(2), b = 18.166(3), c = 17.820(3) Angstrom, beta = 96.590(10)degrees, V = 3192.3(10)Angstrom(3), Z = 4, D-c = 1.109 g cm(-3), 3490 reflections, R = 0.0646). The 1:1 macrocycles 8b,c are also formed by intramolecular transesterification of the open-chain bisesters 7b,c and their formation is favored by the use of metal ions as templates. The bridged bisdioxine moieties in 8b and 12 are converted into the corresponding chiral tetra-oxaadamantane spacers to afford macrocycles 16 and 17. Preliminary metal ion complexation studies with selected species (8c, 11-14) were also performed.

Proof of Concept of the Electrochemical Sensing of 3-Iodothyronamine (T1AM) and Thyronamine (T0AM)

Recent studies have shown that, besides the well-recognized T3 and T4 hormones, there are other relevant thyroid hormones circulating in the human body. In particular, this is the case for 3-iodothyronamine (T1AM) and thyronamine (T0AM). One of the reasons for the lack of studies showing their precise importance is the absence of analytical methodologies available. Herein, for the first time, T1AM and T0AM are electrochemically characterized. T0AM was sensed by means of a glassy carbon electrode; furthermore, T1AM was sensed both with a graphitic surface (oxidatively) as well as with mercury (reductively). For both compounds, after oxidation, it was possible to observe the reversible redox reaction concerning the benzoquinone/hydroquinone couple, thus increasing the specificity of the electroanalysis. Therefore, this work provides the basis for an ‘at-point-of-use’ electrochemical strip test for T1AM and T0AM.

Mother's stress, mood and emotional involvement with the infant: 3 months before and 3 months after childbirth

Adverse effects of maternal anxiety and depression are well documented, namely on the foetus/child behaviour and development, but not as much attention has been given to the mother's emotional involvement with the offspring. To study mother's prenatal and postpartum stress, mood and emotional involvement with the infant, the State-Trait Anxiety Inventory, the Edinburgh Postnatal Depression Scale and the Mother-to-Infant Bonding Scale were filled in and cortisol levels were measured, 3 months before and 3 months after childbirth, in a sample of 91 Portuguese women. From pregnancy to the postpartum period, mother's cortisol levels, anxiety and emotional involvement toward the child decrease. No significant change was observed regarding mother's depression. Mother's depression predicted a worse emotional involvement before childbirth, while mother's anxiety predicted a worse emotional involvement with the infant after childbirth. Additionally, pregnant women with a worse emotional involvement with the offspring are at risk of poorer emotional involvement with the infant and higher anxiety and depression at 3 months postpartum. It should be given more attention to mother's poor emotional involvement with the offspring during pregnancy, as it interferes with her emotional involvement with the infant and her psychological adjustment 3 months after childbirth.

A proof that all Seifert 3-manifold groups and all virtual surface groups are conjugacy separable

We prove that the fundamental group of any Seifert 3-manifold is conjugacy separable. That is, conjugates may be distinguished infinite quotients or, equivalently, conjugacy classes are closed in the pro-finite topology.

On the number of K3,3-minor-free and maximal K3,3-minor-free graphs

"Vegeu el resum a l'inici del document del fitxer adjunt."

Use of the 2,3-diacyl-trehalose and the purified protein derivative in the serodiagnosis of tuberculosis in AIDS

The effect of the human immunodeficiency virus (HIV) infection on IgG production against purified protein derivative (PPD) and 2,3-diacil-trehalose (SL-IV) was investigated by an enzyme-linked immunosorbent assay (ELISA) test. Comparison between the antigens showed that immunocompetent patients produce preferentially antibodies to SL-IV than to PPD (73.3% versus 63.3%). Combination of these results showed an increase of the sensitivity to 80%, which decreased over the spectrum of immunodepression caused by HIV. In the tuberculous HIV seropositive group the sensitivities of SL-IV and PPD were 36.4% versus 40% and 0% versus 22.2% in the tuberculosis/acquired immunodeficiency syndrome (TB/AIDS) group. Combination of these results gave respectively 54.5% and 20%, showing that serological tests have limited value for diagnosis of tuberculosis in HIV infected patients. High antibody levels were observed in HIV seropositive asymptomatic group, but only two individuals were positive for both antigens. In the follow up, one of them developed tuberculous lymphadenitis, indicating that further work is needed to access the value of serological tests in predicting tuberculosis in HIV infected individuals.

Thy-1 binds to integrin beta(3) on astrocytes and triggers formation of focal contact sites.

BACKGROUND: Thy-1 is an abundant neuronal glycoprotein in mammals. Despite such prevalence, Thy-1 function remains largely obscure in the absence of a defined ligand. Astrocytes, ubiquitous cells of the brain, express a putative Thy-1 ligand that prevents neurite outgrowth. In this paper, a ligand molecule for Thy-1 was identified, and the consequences of Thy-1 binding for astrocyte function were investigated. RESULTS: Thy-1 has been implicated in cell adhesion and, indeed, all known Thy-1 sequences were found to contain an integrin binding, RGD-like sequence. Thy-1 interaction with beta3 integrin on astrocytes was demonstrated in an adhesion assay using a thymoma line (EL-4) expressing high levels of Thy-1. EL-4 cells bound to astrocytes five times more readily than EL-4(-f), control cells lacking Thy-1. Binding was blocked by either anti-Thy-1 or anti-beta3 antibodies, by RGD-related peptides, or by soluble Thy-1-Fc chimeras. However, neither RGE/RLE peptides nor Thy-1(RLE)-Fc fusion protein inhibited the interaction. Immobilized Thy-1-Fc, but not Thy-1(RLE)-Fc fusion protein supported the attachment and spreading of astrocytes in a Mn(2+)-dependent manner. Binding to Thy-1-Fc was inhibited by RGD peptides. Moreover, vitronectin, fibrinogen, denatured collagen (dcollagen), and a kistrin-derived peptide, but not fibronectin, also mediated Mn(2+)-dependent adhesion, suggesting the involvement of beta3 integrin. The addition of Thy-1 to matrix-bound astrocytes induced recruitment of paxillin, vinculin, and focal adhesion kinase (FAK) to focal contacts and increased tyrosine phosphorylation of proteins such as p130(Cas) and FAK. Furthermore, astrocyte binding to immobilized Thy-1-Fc alone was sufficient to promote focal adhesion formation and phosphorylation on tyrosine. CONCLUSIONS: Thy-1 binds to beta3 integrin and triggers tyrosine phosphorylation of focal adhesion proteins in astrocytes, thereby promoting focal adhesion formation, cell attachment, and spreading.

Evidence for the co-circulation of dengue virus type 3 genotypes III and V in the Northern region of Brazil during the 2002-2004 epidemics

The reintroduction of dengue virus type 3 (DENV-3) in Brazil in 2000 and its subsequent spread throughout the country was associated with genotype III viruses, the only DENV-3 genotype isolated in Brazil prior to 2002. We report here the co-circulation of two different DENV-3 genotypes in patients living in the Northern region of Brazil during the 2002-2004 epidemics. Complete genomic sequences of viral RNA were determined from these epidemics, and viruses belonging to genotypes V (Southeast Asia/South Pacific) and III were identified. This recent co-circulation of different DENV-3 genotypes in South America may have implications for pathological and epidemiological dynamics.

Alterations in phosphatidylinositol 3-kinase activity and PTEN phosphatase in the prefrontal cortex of depressed suicide victims.

BACKGROUND: Recent studies have reported alterations in protein kinase B (PKB)/Akt and in its downstream target, glycogen synthase kinase 3β, in depression and suicide. The aim of the present study was to investigate possible impairment of the upstream regulators, namely phosphatidylinositol 3-kinase (PI3K) and PTEN. METHODS: The ventral prefrontal cortex (Brodmann's area 11) of 24 suicide victims and 24 drug-free nonsuicide subjects was used. The antemortem diagnoses of major depression disorder were obtained from the institutional records or psychological autopsy, and toxicological analyses were performed. Protein levels of PI3K and PTEN were assayed using the immunoblot method, and the kinase activity of PI3K and Akt was determined by phosphorylation of specific substrates. RESULTS: A decrease was observed in the enzymatic activity of PI3K [ANOVA: F(3, 44) = 9.20; p < 0.001] and Akt1 [ANOVA: F(3, 44) = 13.59; p < 0.001], without any change in protein levels, in both depressed suicide victims and depressed nonsuicide subjects (p < 0.01 and p < 0.002, respectively). PTEN protein levels were increased in the same groups [ANOVA: F(3, 44) = 10.5; p < 0.001]. No change was observed in nondepressed suicide victims. CONCLUSION: This study concludes that attenuation of kinase activity of PKB/Akt in depressed suicide victims may be due to the combined dysregulation of PTEN and PI3K resulting in insufficient phosphorylation of lipid second messengers. The effect is associated with major depression rather than with suicide per se. Given the cellular deficits reported in major depression, the study of enzymes involved in cell survival and neuroplasticity is particularly relevant to neurotrophic factor dysregulation in depression.

Comparison of the metabolic and endocrine effects of 3,5,3'-triiodothyroacetic acid and thyroxine.

To test the hypothesis that 3,5,3'-triiodothyroacetic acid (Triac) is more active as a TSH suppressor than on peripheral parameters of thyroid hormone action, the following parameters were studied: basal metabolic rate, sleeping energy expenditure (SEE), sex hormone-binding globulin, and cholesterol. In a double blind trial, 14 subjects received during 3 weeks (phase 1) 180 micrograms T4 or 1700 micrograms Triac daily, divided into 3 doses, to suppress thyroidal secretion. The dosage was doubled for the next 3 weeks (phase 2). Under T4 treatment, TSH reached 0.11 mU/L during phase 1 and less than 0.03 mU/L during phase 2. With Triac, a marked TSH inhibition occurred after 1 week (0.17 mU/L), followed by an escape during the following 2 weeks (0.63 mU/L). During phase 2, an almost complete TSH suppression was obtained (0.03 mU/L). Both Triac doses suppressed endogenous thyroid hormone secretion, as evidenced by T4 and rT3 levels. Both substances induced a 2-fold stimulation of sex hormone-binding globulin during phase 2. Serum cholesterol decreased similarly, without affecting the high/low density lipoprotein ratio. T4 increased SEE by 4.1% and 8.5% during phases 1 and 2. Triac failed to induce the expected peripheral metabolic responses of the thyroid hormones, as demonstrated by an unchanged SEE and basal metabolic rate. These results clearly show a preferential action of Triac on TSH suppression.

Right coronary artery flow velocity and volume assessment with spiral K-space sampled breathhold velocity-encoded MRI at 3 tesla: accuracy and reproducibility.

PURPOSE: To evaluate accuracy and reproducibility of flow velocity and volume measurements in a phantom and in human coronary arteries using breathhold velocity-encoded (VE) MRI with spiral k-space sampling at 3 Tesla. MATERIALS AND METHODS: Flow velocity assessment was performed using VE MRI with spiral k-space sampling. Accuracy of VE MRI was tested in vitro at five constant flow rates. Reproducibility was investigated in 19 healthy subjects (mean age 25.4 +/- 1.2 years, 11 men) by repeated acquisition in the right coronary artery (RCA). RESULTS: MRI-measured flow rates correlated strongly with volumetric collection (Pearson correlation r = 0.99; P < 0.01). Due to limited sample resolution, VE MRI overestimated the flow rate by 47% on average when nonconstricted region-of-interest segmentation was used. Using constricted region-of-interest segmentation with lumen size equal to ground-truth luminal size, less than 13% error in flow rate was found. In vivo RCA flow velocity assessment was successful in 82% of the applied studies. High interscan, intra- and inter-observer agreement was found for almost all indices describing coronary flow velocity. Reproducibility for repeated acquisitions varied by less than 16% for peak velocity values and by less than 24% for flow volumes. CONCLUSION: 3T breathhold VE MRI with spiral k-space sampling enables accurate and reproducible assessment of RCA flow velocity.