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Biomedical subjects

J M Iglesias

Publications and source records attributed to J M Iglesias.

At least 19 recordsLinked to original sources
PubMed2005

Polyinosinic acid induces TNF and NO production as well as NF-kappaB and AP-1 transcriptional activation in the monocytemacrophage cell line RAW 264.7.

OBJECTIVE: This study evaluates the poly inosinic acid (poly I)-induced activation in the murine monocytemacrophage cell line RAW 264.7, which led to an inflammatory phenotype. MATERIAL: RAW 264.7, and WEHI 164 cell lines were used. RESULTS: The activation process is characterized by the acquisition of a mature macrophage morphology and the production of inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO). The activation by poly I has distinctive features. Thus, poly I induced an increase in nuclear factor kappaB (NF-kappaB) transcriptional activity due to a long-term degradation of inhibitory NF-kappaB (IkappaB) beta while lipopolysaccharide (LPS) induced the degradation of both IkappaBalpha and IkappaBbeta. Poly I also induced an increase in activator protein 1 (AP-1) transcriptional activity, possibly due to the activation of the mitogen activated protein kinases (MAPKs) ERK, Jun N terminal kinase (JNK) and p38. Dextran sulphate (DS) efficiently inhibited the activation induced by poly I including the production of the inflammatory mediators. Dextran sulphate also inhibited AP-1 and NF-kappaB transcriptional activities in poly I-stimulated cells. RAW 264.7 cells express macrophage scavenger receptor 1 (Msr1) type I and Msr1 type II that are differently up-regulated upon treatment with poly I. CONCLUSIONS: The results presented demonstrate that the well-known blocker of scavenger receptors poly I activates macrophages to produce TNF and NO, triggering specific signal transduction pathways.

Animals↗
PubMed2004

Evolutionary perspective on annexin calcium-binding domains.

Molecular systematic analysis of the annexin gene superfamily characterized the evolutionary origin, frequency and range of structural variation in calcium interaction domains that are considered intrinsic for membrane targeting and ion channel function. Approximately 36% of annexin repeat domains in an estimated 100 distinct subfamilies contained amino acid changes consistent with the functional loss of type two calcium-binding sites. At least 11% of annexin domains contained a novel K/H/RGD motif conserved in particular subfamilies and manifest in all phyla, apparently via convergent evolution. The first yeast annexin from Yarrowia lipolytica was classified in the ANXC1 subfamily with fungal and mycetozoan representatives. This clade had intact calcium-binding sites but disruption of the normally well-conserved, mid-repeat 4 region implicated in calcium channel regulation. Conversely, a tandem pair of novel annexins from the amphioxus Branchiostoma floridae resembled annexin A13 in gene structure and conserved the charged amino acids associated with the internal hydrophilic pore, but were devoid of external type 2 calcium-binding sites and incorporated K/RGD motifs instead, like annexin A9. The selective erosion of calcium-binding sites in annexin domains and the occurrence of alternate ligands in the same exposed, interhelical loops are pervasive features of the superfamily. This suggests greater complexity than previously appreciated in the mechanisms controlling annexin membrane interaction and calcium channel operation.

Amino Acid Sequence↗
PubMed2001

Functional analysis of the human annexin A5 gene promoter: a downstream DNA element and an upstream long terminal repeat regulate transcription.

Human annexin A5 is a ubiquitous protein implicated in diverse signal transduction processes associated with cell growth and differentiation, and its gene regulation is an important component of this function. Promoter transcriptional activity was determined for a wide 5' portion of the human annexin A5 gene, from bp -1275 to +79 relative to the most 5' of several discrete transcription start points. Transfection experiments carried out in HeLa cells identified the segment from bp -202 to +79 as the minimal promoter conferring optimal transcriptional activity. Two canonical Sp1 sites in the immediate 5' flanking region of a CpG island were required for significant transcription. Strong repressive activity in the distal promoter region between bp -717 to -1153 was attributed to the presence of an endogenous retroviral long terminal repeat, homologous with long terminal repeat 47B. The downstream sequence from bp position +31 to +79 in untranslated exon 1 was also essential for transcription, as its deletion from any of the plasmid constructs abolished activity in transfection assays. Electrophoretic mobility-shift assays, Southwestern-blot analysis and affinity chromatography were used to identify a protein doublet of relative molecular mass 35 kDa that bound an octanucleotide palindromic sequence in exon 1. The DNA cis-element resembled an E-box, but did not bind higher molecular mass transcription factors, such as upstream stimulatory factor or activator protein 4. The discovery of a downstream element crucial for annexin A5 gene transcription, and its interaction with a potentially novel transcription factor or complex, may provide a clue to understanding the initiation of transcription by TATA-less, multiple start site promoters.

Amino Acid Motifs↗
PubMed2001

Diastereoselective tandem 6-exo carbolithiation intramolecular ring opening in (-)-8-aminomenthol-derived perhydrobenzoxazines. A new synthesis of enantiopure 4-substituted tetrahydro isoquinolines and 2-azabenzonorbornanes.

Aryllithiums prepared by bromine-lithium interchange in chiral 2-(o-bromophenyl)-substituted perhydro-1,3-benzoxazines participate in the intramolecular 6-exo carbolithiation reaction with unactivated double bonds attached to the nitrogen substituent of the heterocycle. When the reaction time is extended or no TMEDA is used, the cyclized lithium intermediates react intramolecularly with the N,O-acetal system leading to 2-azabenzonorbornane derivatives. The reactions are highly stereoselective and constitute a high-yielding synthesis of enantiopure 4-substituted tetrahydroisoquinolines or 7-substituted 2-azabenzonorbornanes.

Journal Article↗
PubMed2001

A novel straightforward synthesis of enantiopure tetrahydroisoquinoline alkaloids.

A novel, direct,and high-yielding stereoselective method for enantiopure 1-substituted tetrahydroisoquinolines (THIQ) is described. The successful approach, which creates the stereocenter during the formation of the THIQ nucleus is based on (i) formation of chiral 2,3-substituted perhydro-1,3-benzoxazines derived from (-)-8-aminomenthol, (ii) diastereoselective intramolecular ring opening of the N,O-acetal moiety by an arylmetal generated from the substituent at the nitrogen atom in the perhydrobenzoxazine ring, and (iii) removal of the chiral auxiliary appendage. The starting perhydrobenzoxazines are easily prepared from (-)-8-aminomenthol and two different aldehydes, and the intramolecular opening is stereospecific, leading to a single stereoisomer. The method allows the preparation of a wide variety of enantiopure 1-substituted THIQ, with different substituents at C-1, by changing the nature of the starting aldehydes.

Indicators and Reagents↗
PubMed1993

Bioavailability and bioequivalence of two formulations of etodolac (tablets and suppositories).

We studied the influence of administration route on the biopharmaceutical behavior of etodolac. The levels obtained in plasma when the same dose of etodolac is administered orally (tablets, dosage form A) and rectally (suppositories, dosage form B) were compared. The study was done in a crossover design with healthy volunteers of both sexes, of average build, and younger than 35 years of age. From the concentration in plasma-time data, the maximum concentration in plasma (Cmax), time to Cmax, and area under the curve up to the last measurable concentration (AUC0t) or infinity (AUC 0 infinity) were calculated and compared by analysis of variance. With the exception of Cmax, no significant differences between treatments were found in the rest of the parameters. Finally, with formulation A (tablets) as a reference, the relative bioavailability was established, on the basis of the ratio (B:A) of AUC0t and AUC 9 infinity, within the range 100 +/- 20%. The results indicate that the two routes of administration are bioequivalent and that the rectal route is an alternative administration route for etodolac.

Adolescent↗
PubMed1993

[Renal carcinoma and solitary pulmonary nodule].

Renal cell carcinoma with solitary metastasis detected at the time of diagnosis has been much discussed and its excision is considered to achieve favorable results. Herein we describe a patient with a solitary pulmonary lesion coexisting with a large renal cell carcinoma. The patient was submitted to radical surgery and the pathological analysis revealed a benign pulmonary tumor with no relationship to the renal cancer.

Aged↗
PubMed1993

[Acute colonic pseudo-obstruction (Ogilvie syndrome) after nephrectomy for renal carcinoma: persistence after decompressive colonoscopy and spontaneous remission].

A 65-year-old male patient presented acute dilatation in the ascendant colon on the third post-operative day following nephrectomy due to renal adenocarcinoma. No changes in colonic diameter were seen after decompressive colonoscopy and, while the patient was asymptomatic, conservative therapy was instituted and the picture was resolved in just a few days. The case is used to review the issue of acute colonic pseudo-obstruction and its relationship to urological operations.

Acute Disease↗
PubMed1991

[A comparison between three questionnaires and laboratory tests for the detection of alcoholism in general practice].

By means of a case/control study, an attempt was made to identify the different questionnaires and biological tests which might be used in the General Practice consulting room for the detection of alcoholic patients. A comparison was made between the CABE, MALT, and Skinner questionnaires, and the MCV, AST, ALT, GGT triglyceride, cholesterol, uric acid, bilirubin and glycemia biological tests. Sensitivity, specificity, predictive value and diagnostic efficiency were studied in a group of 37 confirmed alcoholics and 25 controls making up a population with a high prevalence of alcoholism. Later we analysed the changes which affect the values of the different tests when applied to a population with a low prevalence of alcoholism, in other words, the utility of the tests in general practice was evaluated. The study concludes that the diagnostic performance of the questionnaires together with case history is higher than that of biological tests in general practice, and that the routine application tests in general practice, and that the routine application of the CAGE questionnaire and to a lesser extent of the Skinner questionnaire make it possible to identify those patients suspected of alcoholism and to improve the predictive value of the biological tests applied thereafter. Nevertheless further study is necessary to confirm the diagnostic effectiveness of these questionnaires in the general population of health centre patients.

Adult↗
PubMedDate not supplied

[Cancer of the prostate with rectal invasion].

Rectal invasion in prostate cancer is an uncommon clinical finding to which little attention has been focussed in the literature. However, it can represent important clinical (rectorrhagia, tenesmus and obstruction), diagnostic (confused with rectal cancer) and therapeutic problems. We report two cases of prostatic carcinoma with rectal invasion, one at the time of presentation and the other during the course of the disease, that illustrate the problems associated with this form of neoplastic spread.

Adenocarcinoma↗