Epidemiological and molecular evidence supports the zoonotic transmission of Glardia among humans and dogs living in the same community

Giardia duodenalis isolates recovered from humans and clogs living in the same locality in a remote tea-growing community of northeast India were characterized at 3 different loci; the SSU-rDNA, elongation factor 1-alpha (ef1-alpha) and triose phosphate isomerase (tpi) gene. Phylogenetic analysis of the SSU-rDNA and ef1-alpha genes provided poor genetic resolution of the isolates within various assemblages, stressing the importance of using multiple loci when inferring genotypes to Giardia. Analysis of the tpi gene provided better genetic resolution and placed canine Giardia isolates within the genetic groupings of human isolates (Assemblages A and B). Further evidence for zoonotic transmission was supported by epidemiological data showing a highly significant association between the prevalence of Giardia in humans and presence of it Giardia-positive dog in the same household (odds ratio 3.01, 95%) CI, 1.11, 8.39, P = 0.0000).

Downregulation of ultraspiracle gene expression delays pupal development in honeybees

Ecdysteroids regulate many aspects of insect physiology after binding to a heterodimer composed of the nuclear hormone receptor proteins ecdysone receptor (EcR) and ultraspiracle (Use). Several lines of evidence have suggested that the latter also plays important roles in mediating the action of juvenile hormone (JH) and, thus, integrates signaling by the two morphogenetic hormones. By using an RNAi approach, we show here that Us p participates in the mechanism that regulates the progression of pupal development in Apis mellifera, as indicated by the observed pupal developmental delay in usp knocked-down bees. Knock-down experiments also suggest that the expression of regulatory genes such as ftz transcription factor 1 (ftz-f1) and juvenile hormone esterase (jhe) depend on Usp. Vitellogenin (vg), the gene coding the main yolk protein in honeybees, does not seem to be under Usp regulation, thus suggesting that the previously observed induction of vg expression by JH during the last stages of pupal development is mediated by yet unknown transcription factor complexes. (C) 2008 Elsevier Ltd. All rights reserved.

The systematics and biology of the south African gall-inducing scale insect, Calycicoccus merwei brain (Hemiptera : Coccoidea : Eriococcidae)

The scale insect genus Calycicoccus Brain has a single described species, C. merwei Brain, which is endemic to southeastern South Africa. Females of C. merwei induce small, mostly conical galls on the foliage of their host tree, Apodytes dimidiata E. Meyer ex Arn. (Icacinaceae), which has a wider, mostly coastal distribution, than that currently known for the scale insect. Calycicoccus has been placed in the family Eriococcidae and may be related to the South American genus Aculeococcus Lepage. No other native eriococcid species have been described so far in South Africa, although the family is diverse in other Gondwanan regions. This paper summarizes the biology of C. merwei, redescribes the adult female, describes the adult male, the second-instar female and the first-instar nymphs for the first time, and reconsiders the phylogenetic relationships of the genus. The adult female is shown to have unusual abdominal segmentation, in that segment I is present both dorsally and ventrally, but a segment is absent ventrally on the middle abdomen. First-instar nymphs are sexually dimorphic; males have a larger and relatively narrower body, larger mouthparts, longer antennae and legs, and more thoracic dorsal setae compared with females. Molecular data from nuclear small-subunit ribosomal DNA (18S) and elongation factor 1 alpha (EF-1a) show C. merwei to have no close relatives among the Eriococcidae sampled to date. Instead, the Calycicoccus lineage is part of a polytomy near the base of the Eriococcidae. Molecular dating of the node suggests that the Calycicoccus lineage diverged from other eriococcids more than 100 Mya. These data support the placement of Calycicoccus as the only genus in the subfamily Calycicoccinae Brain.

Phase II Trial of Infusional Fluorouracil, Irinotecan, and Bevacizumab for Metastatic Colorectal Cancer: Efficacy and Circulating Angiogenic Biomarkers Associated With Therapeutic Resistance

Purpose We investigated the efficacy of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in a phase II trial in patients previously untreated for metastatic colorectal cancer (mCRC), and changes during treatment in plasma cytokines and angiogenic factors (CAFs) as potential markers of treatment response and therapeutic resistance. Patients and Methods We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m(2)), bolus FU (400 mg/m(2)), and leucovorin (400 mg/m(2)) followed by a 46-hour infusion of FU (2,400 mg/m(2)). Levels of 37 CAFs were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, during treatment, and at the time of progressive disease (PD). Results Forty-three patients were enrolled. Median progression-free survival (PFS), the primary end point of the study, was 12.8 months. Median overall survival was 31.3 months, with a response rate of 65%. Elevated interleukin-8 at baseline was associated with a shorter PFS (11 v 15.1 months, P = .03). Before the radiographic development of PD, several CAFs associated with angiogenesis and myeloid recruitment increased compared to baseline, including basic fibroblast growth factor (P = .046), hepatocyte growth factor (P = .046), placental growth factor (P < .001), stromal-derived factor-1 (P = .04), and macrophage chemoattractant protein-3 (P < .001). Conclusion Efficacy and tolerability of FOLFIRI + B appeared favorable to historical controls in this single arm study. Before radiographic progression, there was a shift in balance of CAFs, with a rise in alternate pro-angiogenic cytokines and myeloid recruitment factors in subsets of patients that may represent mechanisms of resistance.

Protein profile of the luteal phase endometrium by tissue microarray assessment

To investigate the luteal phase endometrial expression of leukemia inhibitor factor (LIF), insulin-like growth factor 1 (IGF-1), progesterone receptor (PR), claudin 4 (CLDN4), vascular-endothelial growth factor receptor 3 (VEGFR-3), bone morphogenetic protein 4 (BMP-4) and citokeratin 7 (CK-7), we obtained luteal phase endometrial samples from 52 women. Samples were dated and integrated using a tissue microarray (TMA). Samples were immunostained for LIF, IGF-1, PR, CLDN4, VEGFR-3, BMP-4 and CK-7. Frequencies of positive expressions at the early, mid and late luteal phases were compared by two proportions test. Concomitant expression of these proteins was assessed with Chi-square or Fischer`s test. The frequency of LIF was positively correlated to the frequency of IGF-1 (r = 0.99; p < 0.05) and PR (r = 0.99; p < 0.05), and the correlation between IGF-1 and PR tended to be significant (r = 0.98; p < 0.1). The expression of PR was associated with the absence of CLDN4 (p < 0.001). Thus, expression of LIF, IGF-1 and PR are correlated during the luteal phase, and immunohistochemistry for these proteins might be used to assist in the assessment of endometrial maturation. In addition, the expression of CLDN4 and PR was not concomitant, warranting further investigation on the relationship of their endometrial expression.

Management of acromegaly in Latin America: expert panel recommendations

Although there are international guidelines orienting physicians on how to manage patients with acromegaly, such guidelines should be adapted for use in distinct regions of the world. A panel of neuroendocrinologists convened in Mexico City in August of 2007 to discuss specific considerations in Latin America. Of major discussion was the laboratory evaluation of acromegaly, which requires the use of appropriate tests and the adoption of local institutional standards. As a general rule to ensure diagnosis, the patient`s GH level during an oral glucose tolerance test and IGF-1 level should be evaluated. Furthermore, to guide treatment decisions, both GH and IGF-1 assessments are required. The treatment of patients with acromegaly in Latin America is influenced by local issues of cost, availability and expertise of pituitary neurosurgeons, which should dictate therapeutic choices. Such treatment has undergone profound changes because of the introduction of effective medical interventions that may be used after surgical debulking or as first-line medical therapy in selected cases. Surgical resection remains the mainstay of therapy for small pituitary adenomas (microadenomas), potentially resectable macroadenomas and invasive adenomas causing visual defects. Radiotherapy may be indicated in selected cases when no disease control is achieved despite optimal surgical debulking and medical therapy, when there is no access to somatostatin analogues, or when local issues of cost preclude other therapies. Since not all the diagnostic tools and treatment options are available in all Latin American countries, physicians need to adapt their clinical management decisions to the available local resources and therapeutic options.

Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis

Purpose of review The aim of this review is to summarize current evidence about the impact of obstructive sleep apnea (OSA) and intermittent hypoxia on dyslipidemia and provide future perspectives in this area. Recent findings Intermittent hypoxia, a hallmark of OSA, induces hyperlipidemia in lean mice. Hyperlipidemia of intermittent hypoxia occurs, at least in part, due to activation of the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) and an important downstream enzyme of triglyceride and phospholipid biosynthesis, stearoyl-CoA desaturase-1. Furthermore, intermittent hypoxia may regulate SREBP-1 and stearoyl-CoA desaturase-1 via the transcription factor hypoxia-inducible factor 1. In contrast, key genes involved in cholesterol biosynthesis, SREBP-2 and 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase, are unaffected by intermittent hypoxia. In humans, there is no definitive evidence regarding the effect of OSA on dyslipidemia. Several cross-sectional studies suggest that OSA is independently associated with increased levels of total cholesterol, low-density lipoprotein and triglycerides, whereas others report no such relationship. Some nonrandomized and randomized studies show that OSA treatment with continuous positive airway pressure may have a beneficial effect on lipid profile. Summary There is increasing evidence that intermittent hypoxia is independently associated with dyslipidemia. However, the role of OSA in causality of dyslipidemia remains to be established.

Analysis of Craniofacial and Extremity Growth in Patients with Growth Hormone Deficiency during Growth Hormone Therapy

Background/Aims: There are many controversies regarding side effects on craniofacial and extremity growth due to growth hormone ( GH) treatment. Our aim was to estimate GH action on craniofacial development and extremity growth in GH-deficient patients. Methods: Twenty patients with GH deficiency with a chronological age ranging from 4.6 to 24.3 years (bone age from 1.5 to 13 years) were divided in 2 groups: group 1 (n = 6), naive to GH treatment, and group 2 (n = 14), ongoing GH treatment for 2-11 years. GH doses (0.1 -0.15 U/kg/day) were adjusted to maintain insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels within the normal range. Anthropometric measurements, cephalometric analyses and facial photographs to verify profile and harmony were performed annually for at least 3 years. Results: Two patients with a disharmonious profile due to mandibular growth attained harmony, and none of them developed facial disharmony. Increased hand or foot size (>P97) was observed in 2 female patients and in 4 patients (1 female), respectively, both not correlated with GH treatment duration and increased levels of insulin-like growth factor 1. Conclusions: GH treatment with standard doses in GH-deficient patients can improve the facial profile in retrognathic patients and does not lead to facial disharmony although extremity growth, mainly involving the feet, can occur. Copyright (C) 2009 S. Karger AG, Basel

CXCL12 rs1801157 polymorphism and expression in peripheral blood from breast cancer patients

The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3`A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p = 0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome. (C) 2011 Elsevier Ltd. All rights reserved.

CXCL12 rs1801157 Polymorphism in Patients with Breast Cancer, Hodgkin`s Lymphoma, and Non-Hodgkin`s Lymphoma

Chemokines and their receptors regulate the trafficking of immune cells during their development, inflammation, and tissue repair. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/ stromal cell-derived factor-1 (SDF1)-3`A) in CXCL12/SDF1 gene was assessed in breast cancer, Hodgkin`s lymphoma (HL), and non-Hodgkin`s lymphoma (NHL), since the chemokine CXCL12, previously known as SDF1, and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis, and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using a restriction enzyme Hpall cleavage. No significant difference was observed in genotype distribution between breast cancer patients (GG: 57.3%; GA: 39.8%; AA: 2.9%) and healthy female controls (GG: 62.9%; GA: 33%; AA: 4.1%) nor between HL patients (GG: 61.1%; GA:27.8%; AA: 11.1%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%), whereas a significant difference was observed in genotype distribution between NHL patients (GG: 51.4%; GA: 47.1%; AA: 1.5%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%). Further studies will be necessary to elucidate the cancer chemokine network. However, this study suggests that CXCL12 rs1801157 polymorphism may have important implications in the pathogenesis of NHL. J. Clin. Lab. Anal. 23:387-393, 2009. (C) 2009 Wiley-Liss, Inc.

Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells

Development of hypoxic areas occurs during infectious and inflammatory processes and dendritic cells (DCs) are involved in both innate and adaptive immunity in diseased tissues. Our group previously reported that macrophages exposed to hypoxia were infected with the intracellular parasite Leishmania amazonensis, but showed reduced susceptibility to the parasite. This study shows that although hypoxia did not alter human DC viability, it significantly altered phenotypic and functional characteristics. The expression of CD1a, CD80, and CD86 was significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49 and HLA-DR expression remained unaltered in DCs cultured in hypoxia or normoxia. DC secretion of IL-12p70, the bioactive interleukin-12 (IL-12), a cytokine produced in response to inflammatory mediators, was enhanced under hypoxia. In addition, phagocytic activity (Leishmania uptake) was not impaired under hypoxia, although this microenviroment induced infected DCs to reduce parasite survival, consequently controlling the infection rate. All these data support the notion that a hypoxic microenvironment promotes selective pressure on DCs to assume a phenotype characterized by pro-inflammatory and microbial activities in injured or inflamed tissues and contribute to the innate immune response.

The role of tumor hypoxia in MUC1-positive breast carcinomas

Mucin 1 (MUC1) is a glycoprotein that is expressed on apical cell membranes in a variety of normal tissues. MUC1 is involved in cell signaling, inhibition of cell-cell and cell matrix adhesion, apoptosis, proliferation, and transcription. Hypoxia is an important factor that promotes cancer metastasis and stimulates angiogenesis and tumor progression. Hypoxia inducible factor 1 (HIF-1 alpha) and carbonic anhydrase IX (CAIX) are two molecules that are involved in this process. The role of hypoxia in MUC1+ invasive ductal breast carcinomas is not well established. In this study, the expression of MUC1 was correlated with the hypoxia-associated markers HIF-1 alpha and CAIX, as well as several immunohistochemical markers and clinicopathologic features of prognostic significance in 243 invasive ductal carcinomas. MUC1 was overexpressed in 37.0% of patients and correlated with the expression of estrogen receptor (p = 0.0001), progesterone receptor (p = 0.0001), HIF-1 alpha (p = 0.006), VEGF (p = 0.024), and p53 (p = 0.025). In breast cancer, MUC1 expression has been associated with increased degradation of inhibitor of NF-kappa B (I kappa B alpha), driving NF-kappa B to the nucleus and blocking apoptosis and promoting cell survival. We analyzed NF-kappa B expression in MUC1+ breast carcinoma and found a very significant relationship between these proteins (p = 0.0001). Our findings indicate that MUC1 may play a role in the regulation of hormone receptors by increasing the inactivation of p53 and targeting NF-kappa B to the nucleus. Our data also support the notion that activation of HIF-1 alpha in MUC1+ breast carcinomas may modulate VEGF expression, allowing a metabolic adaptation to hypoxia.

A study of adrenocortical tumors in children and adolescents by a comparative genomic hybridization technique

Adrenocortical tumors (ACT) are rare neoplasms of the adrenal glands accounting for 0.2% of all pediatric cancers. However, the incidence of ACT in South Brazilian children is 10 to 15 times greater than the worldwide incidence. Comparative genomic hybridization studies have revealed the presence of a high degree of chromosomal instability in ACT. We evaluated 16 ACT, 8 of them carcinomas and 8 adenomas. The presence of changes in DNA copy numbers was determined by comparative genomic hybridization, and the findings were validated by real-time polymerase chain reaction on the basis of IGF-II gene expression. The adenomas showed a mean of 19.7 imbalances per case, with the most frequent gain and loss being 4p15.1-p15.3 and 20p11.2-p13.2, respectively. The carcinomas presented with a mean of 35.5 imbalances per case, with the more frequent gain being 2q14.1-q24.3 and the more frequent losses being 3q21-q26.2, 20q12-qter, and 22q11.2-q13.3. The most frequent imbalances in both adenomas and carcinomas were gains of 1p21-p31.2, 2p12-p21 and loss of 20p11.2-p12. The expression of IGF-II mRNA (11p15.5) was higher in samples that presented with a gain of this region. It has been established that great genomic instability exists in pediatric ACT.