NSAIDS intolerance: clinical and diagnostic aspects.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
J Rodriguez
Publications and source records attributed to J Rodriguez.
Transformation of primary chick embryo fibroblasts by Marek's disease virus.
Marek's disease virus (MDV) is an alphaherpesvirus, which can mediate the malignant transformation of lymphocytes to form lymphomas in chickens. In this study, we demonstrate that MDV can transform primary chick embryo fibroblasts (CEF). The cell line derived from primary CEF infected with the GA strain of MDV was called CEM(MDV). The fibroblast nature of CEM(MDV) was verified by absence of cytokeratin type II. The CEM(MDV) phenotype differed from either primary CEF or MDV-infected CEF. CEM(MDV) were extensively vacuolated, with unusual multilamellar structures in the cytoplasm, The nuclei were considerably larger than those in primary CEF and were uniformly positive for proliferating cell nuclear antigen. The cell line was subcultured for more than 10 generations; however, CEM(MDV) did not support a fully productive MDV infection, because complete nucleocapsids were not detected and infectivity assays showed that cell line produced no infectious virus. PCR analyses demonstrated that this cell line carried both polypeptide 38 (pp38) and Meq DNA, MDV-specific genes associated with transformation. In addition, examination by laser scanning confocal microscopy revealed that CEM(MDV) constitutively produced MDV MEQ protein in nuclei and pp38 as well as glycoprotein B in the cytoplasm and on the plasma membrane. Growth in soft agar assay demonstrated that CEM(MDV) formed colonies, similar to HeLa and human melanoma cells. Retroviral insertion was not detected in DNA from the CEM(MDV) line.
Animals↗
Penaeidins, a new family of antimicrobial peptides isolated from the shrimp Penaeus vannamei (Decapoda).
We report here the isolation of three members of a new family of antimicrobial peptides from the hemolymph of shrimps Penaeus vannamei in which immune response has not been experimentally induced. The three molecules display antimicrobial activity against fungi and bacteria with a predominant activity against Gram-positive bacteria. The complete sequences of these peptides were determined by a combination of enzymatic cleavages, Edman degradation, mass spectrometry, and cDNA cloning using a hemocyte cDNA library. The mature molecules (50 and 62 residues) are characterized by an NH2-terminal domain rich in proline residues and a COOH-terminal domain containing three intramolecular disulfide bridges. One of these molecules is post-translationally modified by a pyroglutamic acid at the first position. Comparison of the data obtained from the cDNA clones and mass spectrometry showed that two of these peptides are probably COOH-terminally amidated by elimination of a glycine residue. These molecules with no evident homology to other hitherto described antimicrobial peptides were named penaeidins.
Amino Acid Sequence↗
Dismantling cell-cell contacts during apoptosis is coupled to a caspase-dependent proteolytic cleavage of beta-catenin.
Cell death by apoptosis is a tightly regulated process that requires coordinated modification in cellular architecture. The caspase protease family has been shown to play a key role in apoptosis. Here we report that specific and ordered changes in the actin cytoskeleton take place during apoptosis. In this context, we have dissected one of the first hallmarks in cell death, represented by the severing of contacts among neighboring cells. More specifically, we provide demonstration for the mechanism that could contribute to the disassembly of cytoskeletal organization at cell-cell adhesion. In fact, beta-catenin, a known regulator of cell-cell adhesion, is proteolytically processed in different cell types after induction of apoptosis. Caspase-3 (cpp32/apopain/yama) cleaves in vitro translated beta-catenin into a form which is similar in size to that observed in cells undergoing apoptosis. beta-Catenin cleavage, during apoptosis in vivo and after caspase-3 treatment in vitro, removes the amino- and carboxy-terminal regions of the protein. The resulting beta-catenin product is unable to bind alpha-catenin that is responsible for actin filament binding and organization. This evidence indicates that connection with actin filaments organized at cell-cell contacts could be dismantled during apoptosis. Our observations suggest that caspases orchestrate the specific and sequential changes in the actin cytoskeleton occurring during cell death via cleavage of different regulators of the microfilament system.
3T3 Cells↗
Soluble interleukin-2 receptor serum level as a predictor of locoregional control and survival for patients with head and neck carcinoma: results of a multivariate prospective study.
BACKGROUND: The diagnosis and follow-up of head and neck carcinoma patients are based exclusively on clinical staging, which cannot always predict clinical outcome accurately. Because oral squamous cell carcinomas produce interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and express IL-2 receptors, the authors assessed the prognostic value of the serum levels of these markers. METHODS: Serum levels of IL-6, TNF-alpha, soluble IL-2 receptors (s-IL-2-R), and acute phase proteins were measured at the time of diagnosis in a prospective study of 85 patients with primary squamous cell carcinoma of the head and neck. The influence of each clinical and laboratory parameter on locoregional control and survival was analyzed. RESULTS: At presentation, a relationship was observed between advanced tumor (T) classification and high serum levels of CRP (P = 0.0015) and s-IL-2-R (P < 0.05). A high lymph node (N) classification was significantly associated with elevated serum IL-6 (P = 0.01) and CRP levels (P = 0.0002). In the univariate analysis, T classification, N classification, performance status, Prognostic Inflammatory and Nutritional Index, and serum s-IL-2-R level were significantly correlated with both locoregional control and survival. Multivariate analysis showed that the only significant prognostic factors related independently to locoregional control were N classification (P = 0.02) and serum s-IL-2-R level (P = 0.02). In a Cox multivariate analysis, serum s-IL-2-R level was found to be the most predictive factor of survival (P = 0.0001). CONCLUSIONS: This study shows that serum s-IL-2-R level at the time of diagnosis represents a new independent prognostic variable for predicting the risk of locoregional recurrence and survival for patients with head and neck squamous cell carcinoma.
Adult↗
Expression of p53 protein in advanced head and neck squamous cell carcinoma before and after chemotherapy.
BACKGROUND: The expression of p53 protein has been reported to be in the range of 35% to 67% in head and neck squamous cell carcinoma (HNSCC). Mutations of the gene for p53 protein have been associated with rapidly proliferating tumors, and p53 protein expression has been shown to be a significant predictor of worse survival in surgically resected HNSCC. To determine whether p53 protein expression in advanced (stages III and IV) HNSCC has any impact on tumor response to 2 to 3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied prechemotherapy specimens from patients with previously untreated, advanced-stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the p53 status of the tumor changed. DESIGN: The expression of p53 protein was evaluated by immunohistochemical analysis (clone BP53-12-1; Bio-Genex, San Ramon, Calif). SETTING: Tertiary university medical center. INTERVENTION: Two to 3 courses of chemotherapy with paclitaxel and carboplatin. MAIN OUTCOME MEASURES: Pathologic complete remission or residual tumor. RESULTS: The results of p53 immunostaining were positive in 24 (67%) of 36 HNSCC specimens before chemotherapy. After chemotherapy, 8 patients achieved pathologic complete remission. Before chemotherapy, the tumor was p53 negative in 2 patients and positive in 6 patients. CONCLUSIONS: No correlation of p53 protein expression with response to chemotherapy was noted. The expression of p53 protein converted from positive to negative in 5 (42%) of 12 specimens from patients with residual tumor after chemotherapy, with no impact on clinical outcome.
Adolescent↗
Clinically aggressive metastasizing pleomorphic adenoma: report of two cases.
BACKGROUND: It has been suggested that metastasizing pleomorphic adenomas may represent unrecognized malignancy. METHODS: The cytologic and clinical characteristics of two metastasizing pleomorphic adenomas diagnosed by fine-needle sampling are reported. RESULTS: Both showed malignant evolution: the primary tumors arose from the palate and the parotid salivary glands, respectively. Metastases occurred simultaneously with local recurrence in the first patient and after a second local recurrence in the second patient. Both patients were treated by surgery and radiotherapy but died of disseminated disease 8 and 4 years after initial diagnosis. No histologic evidence of malignancy was observed on cytology smears or histology sections in either case. CONCLUSION: Clinically, our cases support the hypothesis that metastasizing pleomorphic adenomas represent unrecognized malignancy, because the biologic course of two tumors led to unequivocally lethal outcome.
Adenoma, Pleomorphic↗
[First comparisons with laser vibrometry measurements and computer simulation of ear ossicle movements].
The dynamic behavior of the ossicular chain is very complex and is frequency-dependent. To date, this has still not been fully investigated or understood. There remains a lack of measurement procedures to pick up the motion of the ossicles and ear drum simultaneously with sufficient resolution. The presented paper reports simultaneous measurements with laser-Doppler vibrometry at two points of the ossicular chain of cadaver specimens. Motions not observed were derived using mechanical simulation models on a computer and then evaluating appropriate mathematical equations. Using a sound stimulus, the displacement velocities of the umbo and stapes footplate were measured, and the corresponding transfer functions were derived by Fourier transform. Results were used for verification of the computer models. In the current investigations these models were refined and allow for the detailed investigation of the dynamic behavior of the ossicular chain, facilitating the optimal design of passive and active middle-ear implants.
Computer Simulation↗
Reproductive toxicology of 3,3',4,4'-tetrachlorobiphenyl in mice.
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Analysis of Variance↗
Parathyroid hormone prevents 1,25 (OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro.
1,25(OH)2D3 has an antiproliferative effect on growth plate chondrocytes when given in high doses, whereas low doses stimulate chondrocyte proliferation. In the present in vitro study we investigated the effects of parathyroid hormone (PTH) when given concomitantly with 1,25(OH)2D3 on cell proliferation and vitamin D receptor (VDR) regulation. Freshly isolated rat tibial chondrocytes were grown in monolayer cultures or in agarose stabilized suspension cultures (10% charcoal-treated FCS). VDR expression was determined by RT-PCR generating a 297 bp fragment and by binding assays (Scatchard analysis) with [3H]-1,25(OH)2D3. Cell proliferation was measured by [3H]-thymidine incorporation, growth curves in monolayer cultures and by colony formation in agarose-stabilized suspension cultures. Optimal concentration of 1,25(OH)2D3 (10(-12) M) and of PTH fragments [bPTH(1-34) or hPTH(28-48), 10(-10)M] showed additive effects on DNA synthesis of and colony formation by growth plate chondrocytes. This may be explained in part by an up-regulation of VDR by PTH: PTH increased both mRNA expression of VDR and binding capacity. 1,25(OH)2D3 (10(-12) M) induced an up-regulation of the VDR within 24 hours followed by a down-regulation after incubation for more than 24 hours. PTH fragments added concomitantly prevented the down-regulation seen with 1,25(OH)2D3. These findings provide evidence that PTH is a growth promoting hormone that also modulates the effects of 1,25(OH)2D3 by regulating the VDR status of 1,25(OH)2D3 target cells.
Animals↗
Synchronous pulmonary cryptococcosis and histoplasmosis.
A chronically immunosuppressed patient receiving oral steroid therapy had a cavitary lesion; both Histoplasma capsulatum and Cryptococcus neoformans were found in samples of respiratory secretions. C neoformans was also found in specimens taken from skin lesions and blood. This is the first reported instance of synchronous infection by these two fungi.
Aged↗
Tumor necrosis factor activity increases in the early response to trauma.
OBJECTIVE: 1) To determine whether tumor necrosis factor (TNF) up-regulation occurs in the first hours following severe injury. 2) To determine whether the time from injury to blood sampling affects the probability of detecting TNF. METHODS: A prospective, cross-sectional study was performed using a convenience sample of adult major trauma patients ("patients") treated at a university hospital ED (Level-1 trauma center) and 20 healthy volunteers ("controls"). The time interval from injury to specimen collection (delta T), the injury severity scale (ISS) score, patient demographics, and quantitative cytokine [TNF and interleukin (IL-6, IL-8)] levels were measured. In the patients, cytokine levels were analyzed as a function of delta T (using first hourly cutoff points and then the median T as an arbitrary cutoff point) with and without potential confounders (e.g., ISS, age, gender). RESULTS: The mean delta T was 92.8 +/- 49.2 min (range 10-210 min, median 82 min). In the controls, TNF activity was present in 96%, with a mean level of 125 pg/mL. The controls showed no baseline IL-6 activity and only 10% had a measurable baseline IL-8 level. In the patients, TNF was present in 93%, with a mean level of 628 +/- 138 pg/mL. When the patients' specimens were divided at the median to obtain roughly equal-sized groups, more TNF levels were elevated > 2.5 SD above the controls in the early vs late group (51% vs 30%; p = 0.07). The mean levels of TNF and IL-8 also were higher in the early vs late group (756 vs 530 and 287 vs 135, respectively; p < 0.05). CONCLUSIONS: TNF levels are elevated in the immediate 4 hours post-injury. Previous investigators' inability to detect TNF activity increases may be related to delays in sampling. These results are consistent with the theory that increased TNF activity occurs early after major trauma and may initiate subsequent cytokine activity.
Adult↗
Synthesis, affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors and structure-activity relationships of a series of cyproheptadine analogues.
Cyproheptadine is a drug that shows high affinity for type 2 (5-HT2) receptors. We studied a series of compounds obtained by modification of the tricyclic system of Cyp (dibenzocycloheptadiene): 2f (thioxanthene), 2g (xanthene), 2h (dihydrodibenzocycloheptadiene), 2j (diphenyl), 2i (fluorene), and 3b (phenylmethyl). Their activities at the rat cerebral cortex 5-HT2A receptor were (pKi +/- S.E.M.): 8.80 +/- 0.11 (Cyp), 8.60 +/- 0.07 (2f), 8.40 +/- 0.02 (2g), 8.05 +/- 0.03 (2h), 7.87 +/- 0.12 (2j), 6.70 +/- 0.02 (2i) and 6.45 +/- 0.02 (3b); those at the rat stomach fundus 5-HT2B receptor (pA2 +/- S.E.M.) were: 9.14 +/- 0.25 (Cyp), 8.49 +/- 0.07 (2f), 7.58 +/- 0.58 (2g), 7.02 +/- 0.14 (2h), 6.07 +/- 0.20 (2j), and undetectable (2i, 3b): and those at the pig choroidal plexus 5-HT2C receptor (pKi +/- S.E.M.) were: 8.71 +/- 0.08 (Cyp), 8.68 +/- 0.01 (2f), 8.58 +/- 0.20 (2g), 7.95 +/- 0.05 (2h), 7.57 +/- 0.04 (2j), 6.98 +/- 0.04 (2i) and 6.63 +/- 0.20 (3b). The slopes did not differ significantly from unity. The compounds exhibited the same order of activities at every type of receptor, and the most active molecules presented certain steric (butterfly conformation of the tricyclic system) and electrostatic (proton affinity on the top of the central rings) patterns. It is concluded that the activity of cyproheptadine derivatives at 5-HT2 receptors is related to these molecular features, which make feasible a common disposition to interact with all three 5-HT2 subtypes.
Animals↗
[Validation of "myocardial infarction" as cause of death on death certificates in Barquisimeto, Lara state, Venezuela]
Death rates due to Ischemic Heart Disease (IHD) are widely used to assess regional and national cardiovascular health status. However, their validity is questionable, essentially because they are based on death certificates (DCs). The present study was conducted in the Greater Metropolitan Area of Barquisimeto (Lara State, Venezuela), from June 1991 to July 1992. The purpose was to establish the validity of the diagnosis of myocardial infarction in DCs of intrahospital deaths. Efforts were made to locate all clinical charts and any other relevant information. To validate the diagnosis of MI in the DC we used the MONICA project criteria. During the study period a total of 247 eligible DCs were recorded. Sufficient clinical information was located for 136 cases (55%). The results were as follows: definite MI - 62 cases (45.6%); probable MI - 31 cases (22.8%); and non MI - 43 cases (31.6%). These results may indicate an overestimation of MI death rates of about 32% [95% Confidence Interval = 23.8% - 39.4%]. Since these data are from a region with an organized cardiovascular health system, it is expected that the overestimation for the rest of the country may be even higher. Thus, in order to enhance quality and accuracy of DCs, it is necessary to develop a system to improve adherence to existing norms for filling out and processing such forms.
Journal Article↗
[Laryngeal cancer and conservative treatment. Place of combined radiotherapy chemotherapy and modified fractionation radiotherapy].
For patients with early stages of laryngeal carcinomas, the local therapeutic modalities of surgery and/or radiation are the accepted standards of treatment. Recently, combined chemotherapy-radiotherapy and new fractionation schedules have received much attention as an alternative to surgery in patients with resectable locally advanced cancer of the larynx to preserve the larynx function. This article is intended to update the reader on the most recent articles written about the treatment of laryngeal carcinomas. The different points are: the results of conventional radiotherapy, the importance of parameters of radiotherapy (dose, fractionation, overall treatment time), new fractionation schedules, combined chemo-radiotherapy, randomized trial results.
Antineoplastic Combined Chemotherapy Protocols↗
Initiation of the tissue factor pathway of coagulation in the presence of heparin: control by antithrombin III and tissue factor pathway inhibitor.
Activation of factor X by both the unactivated tissue factor:factor VII complex (TF:VII) and the activated tissue factor:factor VIIa complex (TF:VIIa) has been studied in the presence of tissue factor pathway inhibitor (TFPI), antithrombin III (ATIII), and heparin. At near-plasma concentrations of TFPI, ATIII, and factor X, factor X activation that occurs in response to TF:VII is essentially abolished in the presence of heparin (0.5 micromol/L). This effect requires both inhibitors, acting on different targets: (1) ATIII, which in the presence of heparin blocks the activation of TF:VII, and (2) TFPI, which inhibits the TF:VIIa that is generated. In the absence of ATIII, TFPI alone with heparin reduces but does not abolish factor X activation. Conversely, in the absence of TFPI, ATIII + heparin reduces but does not abolish TF:VIIa generation and allows continuing activation of factor X. These results indicated that when the unactivated TF:VII complex is the initiating stimulus, heparin-dependent reduction in the rate and extent of factor X activation requires both ATIII and TFPI. In contrast, if TF:VIIa is used to initiate activation, only TFPI is involved in its regulation.
Amino Acid Chloromethyl Ketones↗
Observation of the Cabibbo-suppressed charmed baryon decay Lambda c+-->p phi.
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Journal Article↗
Mechanisms involved in the relaxant effect of estrogens on rat aorta strips.
The effects of estrogens 17beta-estradiol (17beta-E2), 17alpha-estradiol (17alpha-E2) and diethylstilbestrol (DES) on CaCl2 (3mM)-induced contractions on rat aorta strips have been assayed. Both 17alpha-E2 and DES, but not the 17beta-E2 relaxed and inhibited the contraction induced by CaCl2. The antiestrogen tamoxifen (0.1, 1 and 3 microM) antagonizes, in a concentration-dependent way, the relaxant effect of 17alpha-E2 but the relaxation induced by DES is only significantly antagonized with 3 microM of tamoxifen. Cycloheximide (0.1 and 0.3 mM) does not modify the 17alpha-E2 or DES effects. However, the inhibitors of cAMP-dependent protein kinase TPCK (1 microM) and Rp-cAMPS (10 microM) inhibit the relaxation induced by 17alpha-E2 and DES. The elimination of endothelium by rubbing, significantly inhibits the effect of DES but does not modify the effect of 17alpha-E2. Our results suggest that estrogen-induced relaxation is a non-genomic effect possibly or presumably produced by activation of estrogenic receptors and mediated by cAMP. The DES-effect is partially endothelium-dependent but the effect of 17alpha-E2 is independent of endothelium.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗