Comparative gastrointestinal effects of mycophenolate mofetil capsules and enteric-coated tablets of sodium-mycophenolic acid in beagle dogs.
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Biomedical subjects
Publications and source records attributed to C M Torres.
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Although traumatic seromuscular tears of the colon are often managed conservatively, it is pertinent to detect the tear since it poses a risk for acute or delayed perforation. Unfortunately, clinical findings are inadequate for detecting and monitoring this lesion. Therefore, this complication has not been recognized prior to laporatomy. We have noted that an ahaustral colonic segment following trauma may be a potential marker for seromuscular tear.
A variety of prognostic markers have been related to decreased patient survival in patients with epithelial malignancies. These include expression of the homotypic adhesion molecule E-cadherin (ECAD) and the hyaluronic acid receptor CD44. Expression of ECAD and CD44 was evaluated in Barrett's-associated adenocarcinoma (BAd) from 67 patients. Expression was determined by immunoperoxidase staining and graded semiquantitatively based on the proportion of positively stained cells. These data were then correlated with clinical and pathological parameters, including the presence or absence of chemoradiotherapy (chemrad) and patient survival. There were 56 men and 11 women (mean age, 62 years). Thirty-nine (58%) patients received preoperative chemrad. ECAD expression was detected in all (100%) tumors. The ECAD staining grade did not correlate with other pathological features of the tumors. However, ECAD staining was significantly increased in BAd of patients who received chemrad (P = .003), in comparison with those who did not, and in individual patients when prechemrad biopsies and postchemrad resection specimens were compared (P = .04). In terms of prognosis, increased ECAD expression was associated with shortened patient survival only in BAd patients who had received chemrad (univariate analysis of chemrad patients with stage I and II BAd, P = .02). ECAD expression was not significantly associated with survival in BAd patients who did not receive chemrad. CD44 expression was detected in 88% of cases. CD44 expression did not correlate with any of the pathological features of the tumors or with chemrad status. Increased expression of CD44 was significantly associated with shortened patient survival in chemrad patients only (univariate analysis P = .03, multivariate analysis P = .04), although a strong trend was observed when all patients were analyzed regardless of chemrad status (P = .07). The results of this study indicate that chemrad alters the expression of ECAD in BAd. Thus, the prognostic utility of ECAD expression must be evaluated in the context of chemrad status. CD44 also may be a valuable prognostic marker in BAd.
A series of substituted tetrahydrofurans with an embedded glycerol backbone carrying additional tetrahydrofuranylideneacetate or tetrahydrofuranylacetate motifs were grouped into four distinct templates (I-IV) according to stereochemistry. The compounds were designed to mimic three essential pharmacophores (C(3)-C=O, C(20)-OH and C(13)-C=O) of the phorbol esters according to a new, revised model. The tetrahydrofuran ring was constructed from glycidyl 4-methoxyphenyl ether, and the structures of the isomeric templates were assigned by NMR spectroscopy, including NOE. The binding affinity for protein kinase C (PKC) was assessed in terms of the ability of the ligands to displace bound [(3)H-20]phorbol 12, 13-dibutyrate (PDBU) from a recombinant alpha isozyme of PKC. Geometric Z- and E-isomers (1 and 3, respectively) containing a tetrahydrofuranylideneacetate motif were the most potent ligands with identical K(i) values of 0.35 microM. Molecular modeling studies of the four templates showed that the rms values when fitted to a prototypical phorbol 12,13-diacetate ester correlated inversely with affinities in the following order: I approximately II > III > IV. These compounds represent the first generation of rigid glycerol templates seeking to mimic the binding of the C(13)-C=O of the phorbol esters. The binding affinities of the most potent compounds are in the same range of the diacylglycerols (DAGs) despite the lack of a phorbol ester C(9)-OH pharmacophore surrogate. This finding confirms that mimicking the binding of the C(13)-C=O pharmacophore of phorbol is a useful strategy. However, since the C(9)-OH and C(13)-C=O in the phorbol esters appear to form an intramolecular hydrogen bond that functions as a combined pharmacophore, it is possible the lack of this combined motif in the target templates restricts the compounds from reaching higher binding affinities.
In patients with chronic ulcerative colitis (CUC), polypoid dysplastic lesions (PDLs) are morphologically similar to sporadic adenomas (SAs), but may be biologically distinct from them and are managed differently. p53 mutations have been shown to occur at an earlier phase in the progression of CUC-associated neoplasia when compared with sporadic colon carcinogenesis. In contrast, APC gene mutations are common and occur at an earlier stage in the development of SA. beta catenin is a cell membrane protein that accumulates in the nucleus of colon cancer cells in response to APC gene mutations. This study was performed to test the hypothesis that CUC-associated PDLs have a different molecular profile than do CUC-associated SAs and therefore may be distinguished on this basis. Mucosal biopsy specimens of 38 benign polypoid epithelial neoplasms (17 CUC-associated PDLs and 21 CUC-associated SAs) from 33 patients with CUC and 13 SAs from patients without CUC (controls) were immunohistochemically stained for p53 and beta catenin and graded as follows: 0 = no staining, 1+ = <50% of cells positive, and 2+ = > or =50% of cells positive. The results were correlated with the clinical and histologic features and compared between the two CUC-associated polyp subgroups. Overall, six (16%) polyps were p53-positive, of which five were CUC-associated PDLs (one 1+ and four 2+) and one was a CUC-associated SA (1+) (p = 0.05). Strong (2+) p53 positivity was detected, however, in only CUC-associated PDLs (4 of 5; 80%). Nine of 32 polyps evaluated for beta catenin were positive and included 1 (8%) of 12 CUC-associated PDLs and 8 (40%) of 20 CUC-associated SAs (p = 0.06). Two of the nine beta catenin polyps were strongly positive, and both were CUC-associated SAs. Non-CUC-associated (control) SAs were positive for p53 and beta catenin in 2 (15%) of 13 and 6 (46%) of 13 cases, but none in a strong (2+) fashion. No differences were observed in p53 or beta catenin staining, between CUC-associated and non-CUC-associated SAs. Neither p53 nor beta catenin expression correlated with any clinical or pathologic features, including size and degree of dysplasia of the polyps. CUC-associated PDLs and CUC-associated SAs may have a different molecular genotype. In patients with CUC, the combination of strong p53 expression and absent or weak beta catenin expression is evidence in favor of a CUC-associated PDL in diagnostically difficult lesions. Furthermore, CUC-associated and non-CUC-associated SAs have a similar P53 and beta catenin immunophenotype and thus provide evidence that they are pathogenetically related neoplasms regardless of the presence or absence of colitis.
One of the primary goals of pathologic examination of esophageal squamous cell carcinoma resection specimens is to provide information regarding morphologic features which can help prognosticate and guide management of affected patients. The purpose of this study was to determine the prognostic utility of a variety of histopathologic prognostic factors in patients with esophageal squamous cell carcinoma with and without preoperative chemotherapy and radiotherapy (chemrad). Multiple clinical and histologic features such as peri-tumoral lymphocytic infiltrate, Crohn's-like lymphoid reaction, degree of residual tumor, mitosis per 1000 cells, tumor differentiation, lymphatic/vascular invasion, perineural invasion, desmoplastic reaction, and tumor growth pattern were evaluated in patients with (53) and without (21) preoperative chemrad and correlated with survival (mean follow-up, 25 mo). Data were analyzed for the entire cohort and for each separate treatment group by univariate and multivariate analysis. Patients who received chemrad showed no significant survival benefit (hazard ratio = 2.5, P = .10). In the whole cohort of patients, higher pathologic stage (P = .04), poor tumor differentiation (P = .003), increased mitotic count (P = .005), perineural invasion (P = .01), lymphatic/vascular invasion (P = .002), tumor size (P = .05), and absence of a Crohn's-like lymphoid reaction (P = .05) were significantly associated with poor survival by univariate analysis. In multivariate analysis, poor tumor differentiation (P = .005), high mitotic count (P = .01), and vascular invasion (P = .03) were important prognostic features, independent of pathologic stage, for the entire cohort. In the chemrad group only, tumor size (in patients with macroscopic residual tumor) (P = .05), lymph node metastasis (P = .03), mitotic count (P = .01), and lymphatic/vascular invasion (P = .02) were significant prognostic indicators by univariate analysis. Upon multivariate analysis, only lymphatic/vascular invasion (P = .02) and mitotic rate (P = .01) were independent predictors of survival. In the nonchemrad group, only tumor differentiation was significant by both univariate (P = .008) and multivariate analysis (P = .03). The differences in pathologic prognostic factors between chemrad and nonchemrad treated cases suggests that chemrad has a significant effect on the biologic properties of these tumors.
Methods for the determination of thirteen fungicide and insecticide residues by solid-phase extraction with C18 and graphitized carbon black (GCB) were evaluated. The extraction of the residues was achieved by using matrix solid-phase dispersion (MSPD) and more conventional polar solvent extraction followed by liquid-solid phase partitioning. Determination was carried out by capillary gas chromatography with electron-capture and mass spectrometry detectors. The recoveries were determined by fortifying six different crops (apples, oranges, pears, tomatoes, lettuces and paprikas) with the pesticides studied (bromopropylate, chlorpyrifos methyl, cypermethryn, deltamethryn, fenarimol, fenvalerate, imazalil, lindane, permethryn, phentoate, procymidone, propiconazole and vinclozoline). Although, the data showed that the two extraction methods and both sorbents were able to isolate the pesticide residues from fruit and vegetables, the best results were obtained using MSPD with C18 which gave recoveries ranging from 70 to 105% and practical detection limits between 5.0 and 50.0 micrograms/kg for all the compounds. Ten of these pesticides have been detected in samples taken from Valencia markets, at levels of 0.02-20.50 mg/kg using the described methodology.
A review concerning the determination of pesticide residues in fruit and vegetables is presented. The basic principles and recent developments in the extraction and quantitation of pesticides are discussed. Consideration is given to solid phase and supercritical extraction techniques, automation and robotic systems, and immunoassay procedures.
A multiresidue extraction method based on matrix solid-phase dispersion (MSPD) is optimized for the extraction and gas chromatographic screening of eighteen insecticides (aldrin, carbophenothion, captafol, chlorpyriphos, chlorfenvinphos, diazinon, dicofol, alpha-endosulfan, beta-endosulfan, ethion, fenitrothion, folpet, methidathion, malathion, methyl-azinphos, methyl-parathion, phosmet, and tetradifon) from oranges. After optimization of different parameters, such as type of solid phase used and the amount of solid phase or eluent, recoveries ranged from 67 to 102% with relative standard deviations ranging from 2 to 10%. The limits of detection, calculated as 3 times the baseline noise ranged from 2 to 171 micrograms/kg. These limits of detection were about 10 times lower than the maximum residue levels established by the European Community. Compared with classical methods, the described procedure is simple, less labour intensive and does not require preparation and maintenance of equipment. Troublesome emulsions, such as those frequently observed in liquid-liquid partitioning did not occur.
Root nodules were harvested from chamber-grown soybean (Glycine max L. Merrill cv Woodworth) plants throughout development. Apparent nitrogenase activity (acetylene reduction) peaked before seeds began to develop, but a significant amount of activity remained as the seeds matured. Nodule senescence was defined as the period in which residual nitrogenase activity was lost. During this time, soluble protein and leghemoglobin levels in the host cell cytosol decreased, and proteolytic activity against azocasein increased. Degradative changes were not detected in bacteroids during nodule senescence. Total soluble bacteroid protein per gram of nodule remained constant, and an increase in proteolytic activity in bacteroid extracts was not observed. These results are consistent with the view that soybean nodule bacteroids are capable of redifferentiation into free-living bacteria upon deterioration of the legume-rhizobia symbiosis.
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BACKGROUND: Trisomy 21 in humans and trisomy 16 in mice (a model of Down syndrome) are associated with increases in rates of depolarization and repolarization and decreases in duration of action potential of neurons, due to overexpressing protein subunits of Na(+) and K(+) channels in a gene dose-dependent manner. These chromosomes also have genes for voltage-gated Na(+) and K(+) channels expressed by myocardial cells. Thus, it would be expected that heart cells would have alterations in their action potentials similar to those found in neurons in both aneuploidies. METHODS: Myocardial cells from normal and trisomy 16 mouse fetuses were compared in relation to their electrical membrane properties using intracellular microelectrodes. RESULTS: At 13 and 17 days of gestation, trisomic cells, as compared with control cells, had higher amplitude and rates of depolarization and repolarization, with lower duration of plateau of action potential at 25, 50, and 75% of repolarization. This suggests that Ca(2)+ influx is reduced in trisomic cells, which could impair Ca(2)+-dependent fetal myocardial functions (i.e., contractility or matrix secretion). CONCLUSIONS: Myocardial cells of Ts-16 mice showed electrophysiologic alterations qualitatively similar to those observed in trisomic neurons, in agreement with the gene dose-dependent hypothesis (see Introduction).
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Approximately 200 citrus samples from markets of the Valencian Community (Spain) were analyzed to establish their residue levels in 12 organophosphorus pesticide residues during the 1994-1995 campaign. The organophosphorus pesticides carbophenothion, chlorpyriphos, chlorfenvinphos, diazinon, ethion, fenitrothion, malathion, methidation, methylparathion, phosmet, quinalphos, and tetradifon were simultaneously extracted by matrix solid-phase dispersion and determined by gas chromatography-mass spectrometry using selected ion monitoring mode. A total of 32.25% contained pesticide residues and 6.9% exceeded the European Union Maximum Residue Levels (MRLs). The pesticides found in the samples with residues above MRLs were carbophenothion, ethion, methidathion, and methyl parathion. Lower level residues of these and the other pesticides studied (except diazinon) were frequently found. The estimated daily intake of the 12 organophosphorus pesticide residues during the studied period was 4.87 x 10(-4) mg/kg body weight/day. This value is lower than the provisional tolerances dairy intakes proposed by the Food and Agriculture Organization and the World Health Organization.