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Biomedical subjects

A Silva

Publications and source records attributed to A Silva.

At least 19 recordsLinked to original sources
PubMed2000

Involvement of p53 and interleukin 3 in the up-regulation of CD95 (APO-1/Fas) by X-ray irradiation.

Interleukin 3-dependent bone marrow and Ba/F3 cells present constitutive Fas expression. A dose dependent increase in Fas surface expression was induced in these cells by X-ray irradiation. Using primary cell cultures and established cell lines derived from p53-null mice (p53-/-), we demonstrated that the increase in Fas expression upon X-ray irradiation is dependent on the presence of at least one wild-type p53 allele. Fas induction by X-ray irradiation was negatively modulated by IL-3; an earlier Fas induction was observed in the absence of IL-3 or at low IL-3 concentrations. However, IL-3 withdrawal in non-irradiated cells did not induce an increase in Fas expression. X-ray irradiation of Ba/F3 cells induced the expression of functional Fas receptors. Therefore, in IL-3-dependent cells, IL-3 regulates the rate of Fas expression, which is correlated with the degree of apoptosis observed in X-irradiated cells. Finally, we demonstrate that IL-3 controls the degree of Fas expression induced by irradiation through a p53-mediated pathway.

Animals↗
PubMed2000

The role of p53 in death of IL-3-dependent cells in response to cytotoxic drugs.

This report examines the cytotoxicity of chemotherapeutic agents to primary bone marrow-derived IL-3-dependent cells. Such cells derived from p53-null mice were resistant to almost 100-fold higher concentrations of the inhibitors of deoxyribonucleotide synthesis FUdR, methotrexate and hydroxyurea than cells with wild-type p53. In contrast, the cytotoxicity of the DNA damaging agents X-irradiation, cisplatin or bleomycin was p53-independent. The topoisomerase II inhibitor etoposide induced p53-dependent death, which suggests that DNA damage may not be its primary mechanism of cytotoxicity in this cell type. An IL-3-dependent cell line which expresses wild-type p53 was used to demonstrate that the ability of cytotoxic drugs to increase p53 expression level does not control their ability to induce p53-dependent loss of clonigenicity. Finally, comparison with a p53-null IL-3-dependent cell line was used to show that absence of p53 delays the rate of entry into apoptosis following treatment with either DNA damaging agents or inhibitors of deoxyribonucleotide synthesis. This distinguishes short-term effects of p53 on rate of entry into apoptosis from its role in controlling ultimate cell survival. Oncogene (2000) 19, 3556 - 3559

Animals↗
PubMed2000

Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130.

Suppressor of cytokine signaling-3 (SOCS-3) is one member of a family of intracellular inhibitors of signaling pathways initiated by cytokines that use, among others, the common receptor subunit gp130. The SH2 domain of SOCS-3 has been shown to be essential for this inhibitory activity, and we have used a quantitative binding analysis of SOCS-3 to synthetic phosphopeptides to map the potential sites of interaction of SOCS-3 with different components of the gp130 signaling pathway. The only high-affinity ligand found corresponded to the region of gp130 centered around phosphotyrosine-757 (pY757), previously shown to be a docking site for the tyrosine phosphatase SHP-2. By contrast, phosphopeptides corresponding to other regions within gp130, Janus kinase, or signal transducer and activator of transcription proteins bound to SOCS-3 with weak or undetectable affinity. The significance of pY757 in gp130 as a biologically relevant SOCS-3 docking site was investigated by using transfected 293T fibroblasts. Although SOCS-3 inhibited signaling in cells transfected with a chimeric receptor containing the wild-type gp130 intracellular domain, inhibition was considerably impaired for a receptor carrying a Y-->F point mutation at residue 757. Taken together, these data suggest that the mechanism by which SOCS-3 inhibits the gp130 signaling pathway depends on recruitment to the phosphorylated gp130 receptor, and that some of the negative regulatory roles previously attributed to the phosphatase SHP-2 might in fact be caused by the action of SOCS-3.

Amino Acid Sequence↗
PubMed2000

Growth factor effects on survival and development of calbindin immunopositive cultured septal neurons.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia, senile plaques, fibrillary tangles, and a reduction of cholinergic neurons in areas of the brain, including the septal nucleus. Certain growth factors may promote the long-term survival of this subpopulation of neurons at risk. This study was undertaken to characterize growth factors' long-term effects on survival and development of neurons expressing the calcium-binding protein calbindin. In order to accomplish this, embryonic day 16 rat septal neurons were grown in bilaminar culture with astrocytes and in the absence of serum. These cultures were chronically treated with estrogen (Es), insulin-like growth factors I/II (IGF-I, IGF-II), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF). Insulin-like growth factor II significantly increased the number of neurons immunoreactive for calbindin by 155%, suggesting either an increase in the survival of this subpopulation or an increase in the percentage of cells expressing calbindin. Chronic treatment with NGF, IGF-II, and Es significantly increased the number of primary neuritic processes on calbindin-positive neurons, whereas NGF and Es caused significant increases in the number of secondary processes and in the total lengths of the neuritic processes. Thus, effects of IGF-II, estrogen, and NGF on survival and maintenance of this neuronal subpopulation may be dependent on alterations in neurons which are immunopositive for calbindin.

Animals↗
PubMed2000

Chemokine RANTES in gingival crevicular fluid of adult patients with periodontitis.

BACKGROUND, AIMS: This study presents the first evidence on the presence of the chemokine RANTES in the gingival fluid crevicular (GCF) of patients with periodontitis. RANTES is a chemokine that selectively attracts and activates macrophages and lymphocytes. Leucocytes play a critical rôle in the host response to the subgingival microflora. METHOD: In this study, the presence de RANTES in GCF was determined in samples obtained from adult patients with periodontitis and from control subjects with clinically healthy gingiva. GCF was collected from different probing depths (<3 mm, 4-6 mm, >6 mm) (n = 72); and active (n = 12) and inactive sites (n = 12). An active site was defined as attachment loss >2 mm, as determined by sequential probing and the tolerance method. GFC was collected for 30 s using Periopaper strips, and RANTES was quantified by ELISA. RESULTS: The presence of RANTES was detected exclusively in the group of patients with periodontitis, presenting a total amount of 40.43+/-16 pg and a concentration 67.80+/-41 pg/microl. RANTES concentration was significantly higher in probing depth <3 mm than in probing depth >6 mm (87.24 versus 51.87, p = 0.014). Total amount and concentration in the GCF samples from active sites were higher that in inactive sites (p>0.05). CONCLUSIONS: The finding that RANTES is found only in patients with periodontitis, may represent a general feature of chronic inflammatory in periodontal diseases. Finally, RANTES may be implicated in the biological mechanisms underlying the pathogenesis and progression of periodontal disease.

Adult↗
PubMed2000

The role of alpha-CaMKII autophosphorylation in neocortical experience-dependent plasticity.

Calcium/calmodulin kinase type II (CaMKII) is a major postsynaptic density protein. CaMKII is postulated to act as a 'molecular switch', which, when triggered by a transient rise in calcium influx, becomes active for prolonged periods because of its ability to autophosphorylate. We studied experience-dependent plasticity in the barrel cortex of mice carrying a point mutation of the alpha-CaMKII gene (T286A), which abolishes this enzyme's ability to autophosphorylate. Plasticity was prevented in adult and adolescent mice homozygous for the mutation, but was normal in heterozygotes and wild-type littermates. These results provide evidence that the molecular switch hypothesis is valid for neocortical experience-dependent plasticity.

Age Factors↗
PubMed2000

Management of tracheal agenesis.

Complete tracheal agenesis is a very rare congenital anomaly that is only compatible with life in some cases with associated tracheo-oesophageal or broncho-oesophageal fistula. In most cases, concomitant congenital anomalies of the heart, digestive tract or genitourinary tract are present. It should be suspected in any neonate with a history of hydramnios, absent crying, respiratory distress and difficulty in intubation. The possibility for surgical correction or palliation rests on the extent of atresia present. We present a case of complete tracheal agenesis without tracheo nor broncho-oesophageal fistula (type II by Floyd's classification) - the diagnosis of which was prenatally suspected - and discuss the important features of the airway management of this condition.

Abnormalities, Multiple↗
PubMed2000

Telereconstruction from computerized tomography images for the distance teaching of medicine.

A system for making remote two- and three-dimensional reconstructions from computerized tomography images has been developed in order to improve medical teleteaching. It allows the automatic two- and three-dimensional remote visualization of the anatomical structure of interest. As a part of this system, software has been developed which allows many visual operations or transformations on a remote three-dimensional model. It permits the remote workstation and the local workstation to visualize every transformation simultaneously. It allows a doctor to interact virtually and remotely with the anatomical structure. The software enables examination of the anatomical model from all angles, even from inside (including planar and three-dimensional presentations).

Education, Distance↗
PubMed2000

Image processing from computerized tomography images: virtual reconstruction for telediagnosis.

We have developed a system for remote three-dimensional reconstruction, which facilitates telediagnosis. The telereconstruction system is based on a computerized tomography (CT) scanner, a workstation connected to the CT scanner, a PC, which can be geographically far away from the workstation, and a computer program that we have developed. The workstation allows CT images to be stored and image processing to be carried out. The PC permits the user to control the workstation in making a three-dimensional reconstruction and allows the remote user to see that reconstruction. From the PC various graphical operations can be performed on the three-dimensional model, such as rotations, translations and cuts through the model. The program therefore allows a remote user to have three-dimensional images and to study them by means of all the options the program provides.

Image Processing, Computer-Assisted↗
PubMed2000

Levels of interleukin-1 beta, -8, and -10 and RANTES in gingival crevicular fluid and cell populations in adult periodontitis patients and the effect of periodontal treatment.

BACKGROUND: Various cytokines have been identified at sites of chronic inflammation such as periodontitis. Cytokines are synthesized in response to bacteria and their products, inducing and maintaining an inflammatory response in the periodontium. The purpose of the present study was to investigate the involvement of interleukin-1 beta (IL-1 beta), IL-8, and IL-10 and RANTES (regulated on activation, normally T cell expressed and secreted) and the cell populations associated with the immune response in destructive periodontitis, as well as the effect of periodontal therapy on cytokine levels in gingival crevicular fluid (GCF). METHODS: Data were obtained from 12 patients with moderate to advanced periodontitis and 6 healthy controls. Patients presenting at least 2 sites with > or =2 mm clinical attachment loss were included in the destructive periodontitis group. After monitoring for 4 months, only 6 patients showed destructive periodontitis and GCF samples and soft tissues biopsies were collected from these patients. GCF samples and biopsies were collected both from active (12 CGF samples and 6 biopsies) and inactive (12 CGF samples and 6 biopsies) sites. The comparison with healthy controls was carried out by collecting GCF samples from 6 healthy volunteers (12 samples) and biopsies during the surgical removal of wisdom teeth. In periodontal patients, clinical data and GCF samples were obtained prior to periodontal treatment (72 samples) and 2 months after periodontal therapy (72 samples). GCF was collected using a paper strip; eluted and enzyme-linked immunoabsorbent assays (ELISA) were performed to determine cytokine levels. The inflammatory infiltrate was analyzed by immunohistochemistry of gingival biopsy samples with monoclonal antibodies against CD3, CD8, CD4, CD11c, and CD19 antigens. RESULTS: Cellular components of the inflammatory infiltrate include B and T lymphocytes and monocyte/macrophages. Active sites contained a higher number of B lymphocytes and macrophages. IL-8 and IL-1 beta and RANTES in GCF were detected in the majority of sites from periodontal patients (100%, 94% and 87%, respectively); IL-10 was found in only 43%. IL-8 was the only cytokine detected in the GCF (75%) of the control group. Moreover, IL-1 beta levels were significantly higher in active sites versus inactive sites (P <0.05). IL-8 and IL-10 and RANTES were increased in active sites; however, differences were not significant (P>0.05). A positive correlation between the IL-8 and RANTES (r = 0.677, P<0.05) was observed in periodontitis patients. Periodontal therapy reduced the total amount of IL-1 beta, IL-8, and IL-10 and RANTES. Data showed a weak correlation between the clinical parameters and the total amount of cytokines in periodontitis. CONCLUSIONS: These data suggest that the amount of crevicular IL-1 beta, IL-8, and IL-10 and RANTES is associated with periodontal status. Removal of the bacterial plaque reduces the antigenic stimuli and consequently could modulate the chemokines present in GCF. We propose that the dynamic interactions between cytokines, their production rates, and their quantity could represent factors controlling the induction, perpetuation, and collapse of the cytokine network present in the periodontal disease.

Adult↗
PubMed2000

Inertially compensated force plate: a means for quantifying subject's ground reaction forces in non-inertial conditions.

A system for the measurement of forces in noninertial reference systems, and a possible solution to compensate force plate readings by means of accelerometers were investigated. If the force plate can be considered a rigid body, six linear accelerometers can measure all linear and angular accelerations of the instrument in 3-D space. However, by using nine accelerometers in a proper layout, the force and moment generated by the movement of the plate can be quantified in a way that eliminates the errors due to the time integration of the accelerations. By doing so, no temporal limits are imposed to the compensation. A one degree of freedom numerical model was implemented to evaluate the importance of main error sources in the estimation of inertial forces using accelerometers with different technical characteristics. The inertial compensation of the force plate along one axis was tested, and the performances of a piezoelectric accelerometer and a capacitive accelerometer were compared. With the proposed inertially compensated force plate, accelerations up to 5 g's in amplitude and frequencies from 0 to 100 Hz can be compensated by means of capacitive accelerometers. Such a device can be used for force measurements in moving vehicles, or any situation where the surface on which the instrument is mounted is moving or vibrating.

Acceleration↗
PubMed1999

Endoscopy during laparoscopy. Reduced postprocedural bowel distention with intraluminal CO2 insufflation.

BACKGROUND: Intraluminal endoscopy during laparoscopy can substitute for manual palpation in defining anatomy and pathology, but a potential problem is the persistent bowel distention associated with intraluminal air insufflation. METHODS: To compare the rates of intraluminal absorption, a 30-cm segment of small bowel with an intact vascular supply was insufflated with either air or CO2 during CO2 pneumoperitoneum. Intraluminal pressures and bowel circumferences were monitored after the insufflation was stopped. To study the metabolic and hemodynamic effects of CO2 endoscopy during laparoscopy, the small bowel was insufflated to an intraluminal pressure of 15 mmHg during CO2 pneumoperitoneum. Nitrogen pneumoperitoneum was used to differentiate the effects from intraluminal and peritoneal CO2 insufflation. RESULTS: The intraluminal pressures remained elevated and the bowel distended for the entire 3 h following bowel insufflation with air. Following intraluminal CO2 insufflation, both the intraluminal pressures and the bowel circumferences returned to preinsufflation values within 15 min. Intraluminal CO2 insufflation also led to systemic absorption of CO2 with significant metabolic and hemodynamic changes. These changes were effectively corrected by doubling minute ventilation. CONCLUSIONS: Intraluminal CO2 was absorbed faster than intraluminal air. Although decreased bowel distention is certainly of practical value, endotracheal intubation needs to be done to effectively ventilate the absorbed CO2.

Air↗
PubMed1999

Fibronectin interaction with alpha4beta1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia: correlation with Bcl-2 and Bax.

B cell chronic lymphocytic leukemia (B-CLL) consists of the accumulation of malignant cells that apparently escape normal apoptotic regulation. We have studied the role of alpha4beta1 integrin/fibronectin interaction in preventing apoptosis of these cells in vitro. B cells from 16 patients showed constant expression of alpha4beta1 and little or no alpha5beta1. B-CLL cells cultured on fibronectin or two previously described fibronectin recombinant fragments (H89 and H0) which contain the ligands for alpha4beta1, consistently showed higher viability than control cells cultured on poly-lysine. The H89 fragment, containing the high affinity ligand CS-1, was the most efficient substrate with mean cell viability values of 72, 60 and 35% at days 2, 5 and 8 of culture, respectively. For control cells these values were 40, 27 and 15%, respectively. Parallel cell cycle analysis confirmed these results. The anti-apoptotic effect required direct contact with immobilized substrata since it was not observed when using B-CLL conditioned media alone or when clustering alpha4beta1 with specific mAbs in suspension. Quantitation of the apoptosis regulatory proteins Bcl-2 and Bax revealed that cells cultured on the H89 fragment showed high/moderate levels of Bcl-2 (with some interpatient variation) and low levels of Bax resulting in an elevated Bcl-2/Bax ratio. These results indicate that adhesion of B-CLL cells to fibronectin upregulate the Bcl-2/Bax ratio and this may contribute to the anti-apoptotic effect induced via alpha4beta1 integrin.

Adult↗
PubMed1999

Blue rubber bleb naevus: case report and literature review.

Blue rubber bleb naevus syndrome is a rare cutaneous-digestive angiomatosis, described first by William Bean in 1958. Today, there are more than 200 cases published. The dangers of this syndrome include angiomata in the brain, kidneys or lungs (due to vasculature obliteration by in situ thrombosis). Patients are scanned with technetium-labelled red blood cells in order to identify the affected organs. Multiple techniques are used to treat the lesions by gastrointestinal endoscopy.

Aged↗
PubMed1999

Preliminary assessment of the safety and immunogenicity of a new CTXPhi-negative, hemagglutinin/protease-defective El Tor strain as a cholera vaccine candidate.

Vibrio cholerae 638 (El Tor, Ogawa), a new CTXPhi-negative hemagglutinin/protease-defective strain that is a cholera vaccine candidate, was examined for safety and immunogenicity in healthy adult volunteers. In a double-blind placebo-controlled study, no significant adverse reactions were observed in volunteers ingesting strain 638. Four volunteers of 42 who ingested strain 638 and 1 of 14 who received placebo experienced loose stools. The strain strongly colonized the human small bowel, as evidenced by its isolation from the stools of 37 of 42 volunteers. V. cholerae 638, at doses ranging from 4 x 10(7) to 2 x 10(9) vibrios, elicited significant serum vibriocidal antibody and anti-Ogawa immunoglobulin A antibody secreting cell responses.

Adult↗
PubMed1999

Helicobacter pylori infection in indigenous families of Central America: serostatus and oral and fingernail carriage.

Helicobacter pylori infection remains one of the most common in humans, but the route of transmission of the bacterium is still uncertain. This study was designed to elucidate possible sources of infection in an isolated, rural population in Guatemala. A total of 242 subjects in family units participated in the study. A medical history, including a history of dyspepsia, was taken by a physician and immunoglobulin G antibodies to H. pylori were detected with the QuickVue (Quidel, San Diego, Calif.) onsite serology test. Overall, 58% of subjects were seropositive, with a positive relationship between mother and child (P = 0.02) and a positive correlation between the serostatuses of siblings (intraclass correlation coefficient = 0.63). There was no association between serostatus and gastric symptoms. Oral H. pylori was detected from periodontal pockets of various depths and the dorsum of the tongue by nested PCR. Eighty-seven percent of subjects had at least one oral site positive for H. pylori, with the majority of subjects having multiple positive sites. There was no association between periodontal pocket depth and the detection of H. pylori. Nested PCR was also used to detect H. pylori from beneath the nail of the index finger of each subject's dominant hand. Overall, 58% of subjects had a positive fingernail result, with a significant positive relationship between fingernail and tongue positivity (P = 0.002). In conclusion, the results of this study suggest that oral carriage of H. pylori may play a role in the transmission of infection and that the hand may be instrumental in transmission.

Adolescent↗