Computational model for vocal tract dynamics in a suboscine bird.

In a recent work, active use of the vocal tract has been reported for singing oscines. The reconfiguration of the vocal tract during song serves to match its resonances to the syringeal fundamental frequency, demonstrating a precise coordination of the two main pieces of the avian vocal system for songbirds characterized by tonal songs. In this work we investigated the Great Kiskadee (Pitangus sulfuratus), a suboscine bird whose calls display a rich harmonic content. Using a recently developed mathematical model for the syrinx and a mobile vocal tract, we set up a computational model that provides a plausible reconstruction of the vocal tract movement using a few spectral features taken from the utterances. Moreover, synthetic calls were generated using the articulated vocal tract that accounts for all the acoustical features observed experimentally.

New perspectives on the physics of birdsong.

In this work, we revisit the path that has been travelled during the last few years towards the modelling of the avian vocal organ, the syrinx, using numerical and theoretical techniques from bifurcation theory as analysing tools and present experimental support for the models. This fruitful perspective allowed the retracing of many acoustic features of syllables to intrinsic properties of the syrinx, thereby relocating the bird phonatory organ from the role of a mere vocal instrument of the nervous system to a central source of complex acoustical behaviour.

Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer

Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.

Comparison of blood neoangiogenesis and lymphatic vascularization in colorectal adenomas from patients with and without concomitant colorectal cancer.

Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 microm(2); P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.

Influence of Helicobacter pylori infection on the expression of MLH1 and MGMT in patients with chronic gastritis and gastric cancer.

The aim of the present study was to evaluate the influence of Helicobacter pylori on MLH1 and MGMT mRNA levels in patients with chronic gastritis and gastric cancer. The study included 217 patients, of which 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression levels of MLH1 and MGMT were determined by quantitative real-time PCR and immunohistochemistry. There was an association between infection with cagA, vacA s1m1 strains and gastric cancer development. When the gastric epithelium and associated inflammation were examined for expression of MLH1 and MGMT, an overall increase in expression was observed. On the other hand, these levels decrease significantly among gastric cancer patients. The loss of MLH1 and MGMT expression in gastric cancer patients suggests that it is not an early event in H. pylori-associated gastric carcinogenesis.

Lateralization as a symmetry breaking process in bird song.

The singing by songbirds is a most convincing example in the animal kingdom of functional lateralization of the brain, a feature usually associated with human language. Lateralization is expressed as one or both of the bird's sound sources being active during the vocalization. Normal songs require high coordination between the vocal organ and respiratory activity, which is bilaterally symmetric. Moreover, the physical and neural substrate used to produce the song lack obvious asymmetries. In this work we show that complex spatiotemporal patterns of motor activity controlling airflow through the sound sources can be explained in terms of spontaneous symmetry breaking bifurcations. This analysis also provides a framework from which to study the effects of imperfections in the system's symmetries. A physical model of the avian vocal organ is used to generate synthetic sounds, which allows us to predict acoustical signatures of the song and compare the predictions of the model with experimental data.

Respiratory patterns in oscine birds during normal respiration and song production.

In this work we study the generation of respiratory patterns by oscine birds. We present a model capable of generating realistic respiratory patterns, during normal respiration and song production. The model accounts for the interaction between neural nuclei and air sac dynamics. We performed experiments in vivo in order to test the predictions of the model, measuring air sac pressure during song and normal respiration in canaries (Serinus canaria).

Simple neural substrate predicts complex rhythmic structure in duetting birds.

Horneros (Furnarius Rufus) are South American birds well known for their oven-looking nests and their ability to sing in couples. Previous work has analyzed the rhythmic organization of the duets, unveiling a mathematical structure behind the songs. In this work we analyze in detail an extended database of duets. The rhythms of the songs are compatible with the dynamics presented by a wide class of dynamical systems: forced excitable systems. Compatible with this nonlinear rule, we build a biologically inspired model for how the neural and the anatomical elements may interact to produce the observed rhythmic patterns. This model allows us to synthesize songs presenting the acoustic and rhythmic features observed in real songs. We also make testable predictions in order to support our hypothesis.

Dynamics of learning in coupled oscillators tutored with delayed reinforcements.

In this work we analyze the solutions of a simple system of coupled phase oscillators in which the connectivity is learned dynamically. The model is inspired by the process of learning of birdsongs by oscine birds. An oscillator acts as the generator of a basic rhythm and drives slave oscillators which are responsible for different motor actions. The driving signal arrives at each driven oscillator through two different pathways. One of them is a direct pathway. The other one is a reinforcement pathway, through which the signal arrives delayed. The coupling coefficients between the driving oscillator and the slave ones evolve in time following a Hebbian-like rule. We discuss the conditions under which a driven oscillator is capable of learning to lock to the driver. The resulting phase difference and connectivity are a function of the delay of the reinforcement. Around some specific delays, the system is capable of generating dramatic changes in the phase difference between the driver and the driven systems. We discuss the dynamical mechanism responsible for this effect and possible applications of this learning scheme.

Immunoexpression of CD95 in chronic gastritis and gastric mucosa-associated lymphomas

CD95 (Fas/APO-1)-mediated apoptosis plays an important role in immunological regulation and is related to the pathogenesis of autoimmune diseases. Immunoexpression of CD95 has been reported to frequently occur in low grade non-Hodgkin lymphomas, especially of post-germinal center histogenesis, among which those originating in mucosa-associated lymphoid tissue (MALT lymphomas). However, there is no report comparing in situ immunoexpression of this marker in lymphomas and the hyperplastic lymphoid reaction (chronic gastritis) related to Helicobacter pylori infection. The purpose of the present research was to compare the intensity of lymphoid CD95 immunoexpression in 15 cases of H. pylori-related chronic gastritis and 15 gastric MALT lymphomas. CD95 (anti-CD95) was detected by an immunoperoxidase technique in paraffin sections using the catalyzed amplification system. Graduation of reaction intensity (percentage of CD95-positive cells) was semiquantitative, from 1+ to 4+. Nine cases of chronic gastritis were 4+, five 2+ and one 1+. Three lymphomas were 4+, three 3+, four 2+, four 1+, and one was negative. Although 14 of 15 lymphomas were positive for CD95, the intensity of the reaction was significantly weaker compared to that obtained with gastric tissue for patients with gastritis (P = 0.03). The difference in CD95 immunoexpression does not seem to be useful as an isolated criterion in the differential diagnosis between chronic gastritis and MALT lymphomas since there was overlapping of immunostaining patterns. However, it suggests the possibility of a pathogenetic role of this apoptosis-regulating protein in MALT lymphomas.

Immunoexpression of CD95 in chronic gastritis and gastric mucosa-associated lymphomas.

CD95 (Fas/APO-1)-mediated apoptosis plays an important role in immunological regulation and is related to the pathogenesis of autoimmune diseases. Immunoexpression of CD95 has been reported to frequently occur in low grade non-Hodgkin lymphomas, especially of post-germinal center histogenesis, among which those originating in mucosa-associated lymphoid tissue (MALT lymphomas). However, there is no report comparing in situ immunoexpression of this marker in lymphomas and the hyperplastic lymphoid reaction (chronic gastritis) related to Helicobacter pylori infection. The purpose of the present research was to compare the intensity of lymphoid CD95 immunoexpression in 15 cases of H. pylori-related chronic gastritis and 15 gastric MALT lymphomas. CD95 (anti-CD95) was detected by an immunoperoxidase technique in paraffin sections using the catalyzed amplification system. Graduation of reaction intensity (percentage of CD95-positive cells) was semiquantitative, from 1+ to 4+. Nine cases of chronic gastritis were 4+, five 2+ and one 1+. Three lymphomas were 4+, three 3+, four 2+, four 1+, and one was negative. Although 14 of 15 lymphomas were positive for CD95, the intensity of the reaction was significantly weaker compared to that obtained with gastric tissue for patients with gastritis (P = 0.03). The difference in CD95 immunoexpression does not seem to be useful as an isolated criterion in the differential diagnosis between chronic gastritis and MALT lymphomas since there was overlapping of immunostaining patterns. However, it suggests the possibility of a pathogenetic role of this apoptosis-regulating protein in MALT lymphomas.

Antithyroid drugs inhibit in vivo HLA-DR expression in thyroid follicular cells in Graves' disease.

Antithyroid drugs have been reported to reduce the expression of HLA-DR in thyrocytes in Graves' disease, but only circumstantial evidence has been provided about their in vivo immunologic effects. This present study was designed to examine the in vivo immunologic effect of antithyroid drugs on thyroid follicular cells. The study was conducted on 25 patients who had Graves' disease in remission or in activity and who were or were not receiving treatment (7 in overt thyrotoxicosis, 6 patients in remission, and 12 patients under medication). HLA-DR expression in thyroid biopsies was verified by immunohistochemistry. The follicular cells of all patients in overt thyrotoxicosis expressed HLA-DR whereas those of patients in remission were negative for HLA-DR. HLA-DR was also not expressed in all patients under medication, but this did not correlate with the clinical evolution after thyroid drug withdrawal. In conclusion, antithyroid drugs inhibit follicular cell HLA-DR expression in Graves' disease, when thyrotoxicosis is controlled. This suggests that additional mechanisms not involving HLA-DR play a role in thyroid autoimmune disease.

Nonlinear aspects of analysis and synthesis of speech time series data.

In this work we study a simple model of voiced sound production. We analyze contributions that the qualitative theory of dynamical systems can make to the analysis and synthesis of human speech.

Autoimmune and non-autoimmune thyroid diseases have different patterns of cellular HLA class II expression.

CONTEXT: Surface HLA-DR antigen is usually only expressed by antigen-presenting cells (APC). In autoimmune thyroid disease, follicle cells function as APC, thus expressing HLA-DR. However, non-autoimmune thyroid diseases may also express surface class II antigens. OBJECTIVE: To evaluate the presence and pattern of HLA class II expression in autoimmune and non-autoimmune thyroid disorders. DESIGN: Retrospective: histopathological and immunohistochemical analysis. LOCATION: Referral center, university hospital. SAMPLE: Ten histologically normal thyroids, 11 Graves' disease, 7 Hashimoto's thyroiditis, 10 atoxic multinodular goiter and 3 toxic adenomas were analyzed by immunohistochemistry, using a monoclonal antibody anti-HLA-DR. MAIN MEASUREMENTS: The presence of these antigens in thyroid follicular cells and their relation to inflammatory infiltrate was evaluated. The pattern of HLA-DR expression in thyroid follicular cells was analyzed: membrane, cytoplasmic or both. RESULTS: Although HLA-DR antigens were sparsely present in one of the 8 normal thyroids, in 6 of the 9 atoxic multinodular goiter and in 2 of the 3 toxic adenomas a net positivity could be seen in large areas. In all 5 Hashimoto's thyroiditis and in 7 of the 10 Graves' disease cases. This expression occurred in follicle cells either in contact with inflammatory cells or not. In non-autoimmune thyroid disease, HLA-DR positivity was essentially cytoplasmic, whereas in Graves' disease and Hashimoto thyroiditis it was mainly in cell membranes. CONCLUSIONS: It is suggested that the HLA class II expression on the surface of follicle cells could be related to auto-antigen presentation to the immune system by these cells, leading to inflammation.

Alteration of the follicular basement membrane in non-obese diabetic mice with spontaneous autoimmune thyroiditis.

The follicular basement membrane (FBM) prevents thyroglobulin from escaping to the peri-follicular space, where it can act as an antigen to induce experimental thyroiditis. Laminin, a component of the FBM, is responsible for directing cell migration and stimulates greater adhesion of activated T lymphocytes. Our purpose was to study the expression of laminin in the thyroid of NOD mice, which have a propensity for autoimmune diseases, including thyroiditis. Thirty NOD mice between 3 and 42 weeks old were studied. Eight had thyroiditis and 22 showed no inflammatory infiltration. An immunohistochemical examination using the streptavidin-biotin-peroxidase technique was conducted on paraffin-embedded tissue sections, with a polyclonal antilaminin antibody. Antigen retrieval was achieved through pepsin digestion and microwave irradiation in citrate buffer. Staining for laminin was restricted to the basement membrane. In thyroids with no infiltration, laminin was shown as a fine, continuous brown line in the basement membrane. In 6 out of the 8 cases of thyroiditis, clearcut interruption and destruction of the FBM was observed, particularly when the follicles were located in lymphocyte infiltrated areas or when there was fibrosis. There were significant alterations in the pattern of the FBM with extensive areas of discontinuity in the distribution of laminin. Such discontinuities could facilitate antigen exposure, especially thyroglobulin, which may contribute to autoimmune thyroiditis in NOD mice.

[Incidence and epidemiology of Barrett's epithelium at the Gastrocentro-UNICAMP]. / Incidência e epidemiologia do epitélio de Barrett no gastrocentro-UNICAMP.

It is very important in the clinical practice to identify the individuals with Barrett's esophagus, because they are at risk to develop adenocarcinoma in the columnar epithelium. The objective of this research is to verify the incidence of this specific kind of epithelium at the "Gastrocentro", at State University of Campinas-UNICAMP, Campinas, SP, Brazil, among the total of 15,976 upper digestive endoscopies, performed from january of 1992 to December of 1995. From the total examinations performed were identified 2,381 patients (14.9%) presenting reflux esophagitis (grades I-IV, Savary-Miller). Among this group of patients, the endoscopist suspected of Barrett's esophagus in 110 cases (4.6%) and biopsed the distal esophagus. However, only in 85 cases (77.3%) the pathologist confirmed the diagnosis of Barrett's epithelium. The patients with Barrett's esophagus were 53 males (62.3%), presenting the mean age of 52.2 years and the following grades of esophagitis: grade I-33 cases (38.8%); grade II-15 cases (17.7%); grade III-15 cases (17.7%), grade IV-12 cases (14.1%) and without esophagitis-10 cases (11.7%). The incidence of Barrett's esophagus among the patients with reflux esophagitis was 3.57%, and among the total of examinations performed at the "Gastrocentro" during the period of four years was 0.53%, totalizing 22,4 cases/100,000 habitants.

[Cytopathological test performed during colonoscopy in the diagnosis of colorectal stenosis]. / Exame citopatológico realizado durante colonoscopia no diagnóstico das estenoses colorretais.

The etiological diagnosis for the colorectal strictures can be very difficult. With the colonoscopy, it was possible to obtain samples with direct vision of the lesion. Consequently, the cytologic efficiency improved, with similar or even better results than histopathology. In the present study (107 patients) it was used the cytopathology performed during colonoscopy. After a specimen was obtained, it was smeared on glass slide, fixed in 95% alcohol, stained by HE, and examined microscopically, with conclusions during the procedure. The results were compared and further correlated to the histopathology of surgical specimen or based on clinical follow-up in those case not submitted to operation. The results showed a striking degree of correlation between both exams. For the cytopathology there were no inconclusive results, false-negative were less frequent than with histopathology, and only one case of false-positive (rectal villus adenoma) was observed. Considering the type, localization and perviousness of the lesion, similar conclusions were drawn, and did not affect the results, except that there were more false-negatives in both exams when the lesions were impervious. The cytopathological and histopathological studies were both highly sensitive and specific for the diagnosis of carcinoma. In conclusion, cytopathology performed during colonoscopy is safe and efficient in the study of colorectal strictures, which contributes to improve the orientation of these patients.