Anatomy and phylogenetic relationships of a new catfish species from northeastern Argentina with comments on the phylogenetic relationships of the genus Rhamdella Eigenmann and Eigenmann 1888 (Siluriformes, Heptapteridae)

Rhamdella cainguae, a new species of the family Heptapteridae is described from the Arroyo Cuna-Piru, a tributary of the Rio Parana, in the subtropical forest of Misiones, northeastern Argentina. The presence of a large differentiated ovoid area on the supraorbital laterosensory canal along the frontal-sphenotic boundary, delimited by the slender dorsal walls of the bones, and with no foramen for a laterosensory branch, is an autapomorphy for R. cainguae. A detailed description of the skeleton and laterosensory system of R. cainguae is provided. The genus Rhamdella is rediagnosed on the basis of three autapomorphies: a very large opening in the frontal for the exit of the s6 ( epiphyseal) branch of the supraorbital laterosensory canal ( reversed in R. rusbyi), a large optic foramen, and a dark stripe along the lateral surface of the body ( reversed in R. rusbyi). Rhamdella is considered to be the sister group of a large heptapterid clade composed of the Nemuroglanis sub-clade plus the genera Brachyglanis, Gladioglanis, Leptorhamdia, and Myoglanis. Rhamdella is herein restricted to five valid species: R. aymarae, R. cainguae, R. eriarcha, R. longiuscula, and R. rusbyi. A sister group relationship between R. aymarae and R. rusbyi is supported by three synapomorphies. Rhamdella cainguae shares 12 apomorphic features with R. eriarcha and R. longiuscula.

Effects of immunosuppressants on hepatocyte cell mitosis during liver regeneration in growing animal models of partial hepatectomy

Objective. We sought to evaluate the effects of immunosuppressant drugs (corticosteroid, cyclosporine [CsA], and tacrolimus [Tac]) on liver regeneration in growing animals submitted to 70% hepatectomy. Materials and Methods. Newborn and weaning rats were submitted to 70% hepatectomy receiving separately methylprednisolone, CsA, or Tac. All animals were sacrificed 24 hours after the procedure. The remnant liver lobes were subjected to histomorphometric analyses with determination of hepatocyte mitotic index. Results., Administration of immunosuppressants did not change the mitotic index of the regenerating liver in newborn animals. In weaning rats, methylprednisolone reduced the mitotic index (P = .01) and Tac caused a greater increase in this rate (P = .001). CsA had no effect on mitotic index. The number of hepatocyte mitoses in newborn animal livers was greater than that in weaning animal livers (P = .001). Conclusion. In situations in which intense, fast processes of liver regeneration are crucial, the advantages of the use of Tac must be considered, such as in pediatric transplant patients.

The central pathway of primary olfactory axons is abnormal in mice lacking the N-CAM-180 isoform

Although N-CAM has previously been implicated in the growth and fasciculation of axons, the development of axon tracts in transgenic mice with a targeted deletion of the 180-kD isoform of the neural cell adhesion molecule (N-CAM-180) appears grossly normal in comparison to wild-type mice. We examined the organization of the olfactory nerve projection from the olfactory neuroepithelium to glomeruli in the olfactory bulb of postnatal N-CAM-180 null mutant mice. Immunostaining for olfactory marker protein revealed the normal presence of fully mature primary olfactory neurons within the olfactory neuroepithelium of mutant mice. The axons of these neurons form an olfactory nerve, enter the nerve fiber layer of the olfactory bulb, and terminate in olfactory glomeruli as in wild-type control animals. The olfactory bulb is smaller and the nerve fiber layer is relatively thicker in mutants than in wild-type mice. Previous studies have revealed that the plant lectin Dolichos biflorus agglutinin (DBA) clearly stains the perikarya and axons of a subpopulation of primary olfactory neurons. Thus, DBA staining enabled the morphology of the olfactory nerve pathway to be examined at higher resolution in both control and mutant animals. Despite a normal spatial pattern of DBA-stained neurons within the nasal cavity, there was a distorted axonal projection of these neurons onto the surface of the olfactory bulb in N-CAM-180 null mutants. In particular, DBA-stained axons formed fewer and smaller glomeruli in the olfactory bulbs of mutants in comparison to wild-type mice. Many primary olfactory axons failed to exit the nerve fiber layer and contribute to glomerular formation. These results indicate that N-CAM-180 plays an important role in the growth and fasciculation of primary olfactory axons and is essential for normal development of olfactory glomeruli. (C) 1997 John Wiley & Sons, Inc.

Expression of constitutively activated human c-Kit in myb transformed early myeloid cells leads to factor independence, histiocytic differentiation, and tumorigenicity

The cDNAs encoding wild type (WT) human receptor tyrosine kinase c-Kit and a constitutively activated mutant, V816Kit, were introduced into granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent early murine hemopoietic cells, which had been transformed with activated Myb, WTKit cells were able to grow in the presence of the human ligand for Kit, stem cell factor (SCF), but displayed reduced growth and clonogenic potential in either SCF or GM-CSF compared with the parental cells in GM-CSF. In contrast, V816Kit cells grew without factor at a higher rate than the parental cells in GM-CSF and displayed increased clonogenicity. Dissection of the growth characteristics in liquid culture showed that in the presence of appropriate factors, the different populations had similar proliferation rates, but that V816Kit profoundly increased cell survival compared with WTKit or parental cells, This suggests that the signals transduced by WTKit activated with SCF, and by V816Kit, were not identical. Also, WTKit and V816Kit-expressing cells both varied from the early myeloid progenitor phenotype of the parental cells and gave rise to a small number of large to giant adherent cells that expressed macrophage (alpha-naphthyl acetate) esterase and neutrophil (naphtol-AS-D-chloroacetate) esterase, were highly phagocytic and phenotypically resembled histiocytes. Thus, WTKit activated by SCF and V816Kit were able to induce differentiation in a proportion of Myb-transformed myeloid cells. The factor independent V816Kit cells, unlike the parental and WTKit expressing cells, were shown to produce tumors of highly mitotic, invasive cells at various stages of differentiation in syngeneic mice. These results imply that constitutively activated Kit can promote the development of differentiated myeloid tumors and that its oncogenic effects are not restricted to lineages (mast cell and B-cell acute lymphoblastic leukemia), which have been reported previously. Furthermore, the mixed populations of cells in culture and in the tumors phenotypically resembled the leukemic cells from patients with monocytic leukemia with histiocytic differentiation (acute myeloid leukemia-M5c), a newly proposed subtype of myeloid leukemia. (C) 1997 by The American Society of Hematology.

A new large-caliber trocar for percutaneous endoscopic gastrostomy by the introducer technique in head and neck cancer patients

Background and study aims In many patients, percutaneous endoscopic gastrostomy (PEG) can be limited by digestive tract stenosis. PEG placement using an introducer is the safest alternative for this group of patients, but the available devices are difficult to implement and require smaller-caliber tubes. The aim of this study was to evaluate the modification of an introducer technique device for PEG placement with regard to the following: procedure feasibility, possibility of using a 20-Fr balloon gastrostomy tube, tube-related function and problems, complications, procedure safety, and mortality. Patients and methods Between March 2007 and February 2008, 30 consecutive patients with head and neck malignancies underwent introducer PEG placement with the modified device and gastropexy. Each patient was evaluated for 60 days after the procedure for the success of the procedure, infection, pain, complications, mortality, and problems with the procedure. Results The procedure was successful in all cases with no perioperative complications. No signs of stomal infection were observed using the combined infection score. The majority of patients experienced mild-to-moderate pain both in the immediate postoperative period and at 72 hours. One major early complication (3.3%) and two minor complications (6.7%) were observed. No procedure-related deaths occurred during the first 60 days after the procedure. Conclusion The device modification for PEG using the introducer technique is feasible, safe, and efficient in outpatients with obstructive head and neck cancer. In this series, it allowed the use of a larger-caliber tube with low complication rates and no procedure-related mortality.

Executive dysfunction correlates with impaired functional status in older adults with varying degrees of cognitive impairment

Background: Previous studies have reported an association between executive dysfunction and the ability to perform activities of daily living (ADL)s among older adults. This study aims to examine the association between executive functions and functional status in a cross-section of older adults with varying degrees of cognitive impairment. Methods: 89 individuals (mean age 73.8 years) were recruited at a memory clinic in Sao Paulo, Brazil. Subjects underwent evaluation, and were allocated into three diagnostic groups according to cognitive status: normal controls (NC, n = 32), mild cognitive impairment (MCI, n = 3 1) and mild Alzheimer`s disease (AD, n=26). Executive functions were assessed with the 25-item Executive Interview (EXIT25), and functional status was measured with the Direct Assessment of Functional Status test (DAFS-R). Results: Significantly different total DAFS-R scores were observed across the three diagnostic groups. Patients with AD performed significantly worse in EXIT25 compared with subjects without dementia, and no significant differences were detected between NC and MCI patients. We found a robust negative correlation between the DAFS-R and the EXIT25 scores (r=-0.872, p < 0.001). Linear regression analyses suggested a significant influence of the EXIT-25 and the CAMCOG on the DAFS-R scores. Conclusion: Executive dysfunction and decline in general measures of cognitive functioning are associated with a lower ability to undertake instrumental ADLs. MCI patients showed worse functional status than NC subjects. MCI patients may show subtle changes in functional status that may only be captured by objective measures of ADLs.

Immunoendocrinology of the Thymus in Chagas Disease

During immune response to infectious agents, the host develops an inflammatory response which could fail to eliminate the pathogen or may become dysregulated. In this case, the ongoing response acquires a new status and turns out to be detrimental. The same elements taking part in the establishment and regulation of the inflammatory response (cytokines, chemokines, regulatory T cells and counteracting compounds like glucocorticoids) may also mediate harmful effects. Thymic disturbances seen during Trypanosoma cruzi (T. cruzi) infection fit well with this conceptual framework. After infection, this organ suffers a severe atrophy due to apoptosis-induced thymocyte exhaustion, mainly affecting the immature double-positive (DP) CD4+CD8+ population. Thymus cellularity depletion, which occurs in the absence of main immunological mediators involved in anti-T. cruzi defense, seems to be linked to a systemic cytokine/hormonal imbalance, involving a dysregulated increase in Tumor Necrosis Factor alpha (TNF-alpha) and corticosterone hormone levels. Additionally, we have found an anomalous exit of potentially autoimmune DP cells to the periphery, in parallel to a shrinkage in the compartment of natural regulatory T cells. In this context, our data clearly point to the view that the thymus is a target organ of T. cruzi infection. Preserved thymus may be essential for the development of an effective immune response against T. cruzi, but this organ is severely affected by a dysregulated circuit of proinflammatory cytokines and glucocorticoids. Also, the alterations observed in the DP population might have potential implications for the autoimmune component of human Chagas disease. Copyright (C) 2011 S. Karger AG, Basel

In pursuit of prognostic factors in children with pilocytic astrocytomas

This study described a 23-year experience in the treatment of children with pilocytic astrocytomas (piloA) with the aim of identifying putative clinical, histopathological, and/or immunohistochemical features that could be related to the outcome of these patients. Clinical data of 31 patients under 18 years of age with piloA were obtained from 1984 to 2006. The mean age at the time of surgery was 7.8 +/- 4.2 years (1 to 17 years), and the mean follow-up was 5.7 +/- 5.4 years (1 to 20 years). The most common site of tumor formation was the cerebellum (17), followed by brainstem (4), optic chiasmatic hypothalamic region (4), cerebral hemisphere (3), cervical spinal cord (2), and optic nerve (1). Gross total resection (GTR) was achieved in 23 (74.1%), mainly in those with tumors located in the cerebellum and cerebral hemispheres (P = 0.02). The global mortality rate was 6.4%. Nine patients were reoperated. Rosenthal fibers, eosinophilic granular bodies, microvascular proliferation, and lymphocytic infiltration were observed in most cases. The mean Ki-67LI was 4.4 +/- 4.5%. In all cases, Gal-3 expression in tumor cells was observed with variable staining pattern. Aside from GTR, no other clinical, histopathological, or immunohistochemical features were found to be related to the prognosis. We postulate that strict follow-up is recommended if piloA is associated with high mitotic activity/Ki67-LI, or if GTR cannot be achieved at surgery. Tumor recurrence or progression of the residual lesion should be strictly observed. In some aspects, childhood piloA remains an enigmatic tumor.

Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa

Cytogenetic studies of choroid plexus tumors, particularly for atypical choroid plexus papillomas, have been rarely described. In the present report, the cytogenetic investigation of an atypical choroid plexus papilloma occurring at the posterior fossa of a 16-year-old male is described. Comparative genome hybridization analysis demonstrated gains of genetic material from almost all chromosomes. Chromosome losses involved 19p, regional losses at chromosome X and loss of chromosome Y. The presence of polyploid cells was confirmed by fluorescence in situ hybridization analysis with probes directed to centromeric regions. Furthermore, the microscopic analysis of cultures showed nuclear buds, nucleoplasmic bridges, and micronuclei in 23% of tumor cells suggesting the presence of complex chromosomal abnormalities. Previous cytogenetic studies on choroid plexus papillomas showed either normal, hypodiploid or hyperdiploid karyotypes. To the best of our knowledge, this is the first report of polyploidy in choroid plexus papilloma of intermediate malignancy grade. Although the mechanisms beneath such genome duplication remain to be elucidated, the observed abnormal nuclear shapes indicate constant restructuring of the tumor`s genome and deserves further investigation.

Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency

The Myc oncogene regulates the expression of several components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, RNA polymerase III and ribosomal DNA(1,2). Whether and how increasing the cellular protein synthesis capacity affects the multistep process leading to cancer remains to be addressed. Here we use ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in E mu-Myc/+ transgenic mice to normal levels, and show that the oncogenic potential of Myc in this context is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc- overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a new mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective messenger RNAs. We show that an aberrant increase in cap- dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site ( IRES)- dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic- specific expression of the endogenous IRES- dependent form of Cdk11 ( also known as Cdc21 and PITSLRE)(3-5), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in E mu-Myc/+ mice. When accurate translational control is re- established in E mu-Myc/+ mice, genome instability is suppressed. Our findings demonstrate how perturbations in translational control provide a highly specific outcome for gene expression, genome stability and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post- genomic level.

Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution

Aim To evaluate gastrointestinal motility during 5-fluorouracil (5-FU)-induced intestinal mucositis. Materials and methods Wistar rats received 5-FU (150 mg kg(-1), i.p.) or saline. After the 1st, 3rd, 5th, 15th and 30th day, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage, apoptotic and mitotic indexes, MPO activity and GSH concentration. In order to study gastrointestinal motility, on the 3rd or 15th day after 5-FU treatment, gastric emptying in vivo was measured by scintilographic method, and stomach or duodenal smooth muscle contractions induced by CCh were evaluated in vitro. Results On the third day of treatment, 5-FU induced a significant villi shortening, an increase in crypt depth and intestinal MPO activity and a decrease in villus/crypt ratio and GSH concentration. On the first day after 5-FU there was an increase in the apoptosis index and a decrease in the mitosis index in all intestinal segments. After the 15th day of 5-FU treatment, a complete reversion of all these parameters was observed. There was a delay in gastric emptying in vivo and a significant increase in gastric fundus and duodenum smooth muscle contraction, after both the 3rd and 15th day. Conclusions 5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.

BUBR1 expression in benign oral lesions and squamous cell carcinomas: Correlation with human papillomavirus

Oral squamous Cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, all important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also it significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence oil BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC. but not in benign oral lesions.

Identification of genes differentially expressed in a strain of the mold Aspergillus nidulans carrying a loss-of-function mutation in the palA gene

To identify genes differentially expressed in a strain of the mold Aspergillus nidulans carrying a loss-of-function mutation in palA, a gene in the pH-responsive signal transduction pathway, suppression subtractive hybridization was performed between RNA isolated from the biA1 and biA1 palA1 strains grown under limiting inorganic phosphate at pH 5.0. We have identified several genes upregulated in the biA1 palA1 mutant strain that play important roles in mitotic fidelity, stress responses, enzyme secretion, signal transduction mechanisms, development, genome stability, phosphate sensing, and transcriptional regulation among others. The upregulation of eight of these transcripts was also validated by Northern blot. Moreover, we show that a loss of function mutation in the palA gene drastically reduced the neutral sugar content of the acid phosphatase PacA secreted by the fungus A. nidulans grown at pH 5.0 compared with a control strain.

Regeneration of the Corneal Epithelium after Debridement of its Central Region: An Autoradiographic Study on Rabbits

Purpose: To investigate the proliferative behavior of the corneal and limbal epithelia after debridement on the central region of the rabbit cornea. Methods: After scraping a circular epithelial area, 5 mm in diameter, in the center of the cornea, (3)H-thymidine ((3)H-TdR) was injected intravitreally, and the rabbits killed from 1 to 49 days afterward. The cornea, together with the adjacent conjunctiva, was processed for autoradiography. Results: The regenerating epithelium at the center of the cornea exhibited high frequencies of labeled nuclei when compared to controls. The mitotic indexes for the limbus were comparable in experimental and control eyes. The unique basal stratum of the limbal epithelium exhibited quick proliferation and vertical migration in all eyes. Cells that remained labeled for four weeks or more were observed throughout the corneal epithelium, including its basal stratum, and this did not depend on epithelial damage. Conclusion: Corneal epithelium wounds are healed by sliding and proliferation of cells surrounding the epithelial gap without any evidence for the participation of the limbal epithelium. Daughter cells labeled with (3)H-TdR were visualized in all layers of the corneal epithelium up to 7 weeks after the DNA precursor injection. However, at this long interval, the only labeled cells in the limbus were in the suprabasal layers.

Cytotoxic and genotoxic effects of two medicinal species of Verbenaceae

Lantana camara L. and Lippia alba (Mill.) N. E. Br. are two important species of Verbenaceae family and are commonly used in folk medicine in many countries of Central and Southern America. The aim of this study was to investigate, for the first time, the cytotoxic and genotoxic effects of aqueous extracts from leaves of both species on Lactuca sativa (lettuce) root tip meristem cells using a cytogenetic approach. Seeds of lettuce were separately treated during 72h with different concentrations of L. camara and L. alba aqueous extracts (5, 10, 20 and 30g/L). The percentage of germination, root development and cellular behavior were analyzed and the results showed that the highest concentration of aqueous extracts reduced the mitotic index, the seeds germination and the root development of lettuce. The extracts also induced chromosome aberrations and cellular death in roots cells of L. sativa. The cytogenotoxicity of L. camara and L. alba extracts was comparatively described.