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Biomedical subjects

J Arias

Publications and source records attributed to J Arias.

At least 73 records · Page 4Linked to original sources

Regulation of somatostatin gene transcription by cyclic adenosine monophosphate.

Cyclic adenosine monophosphate (cAMP) stimulates transcription of somatostatin and other target genes with burst-attenuation kinetics. The kinetics of protein kinase (PK-A)-dependent cAMP response element binding protein (CREB) phosphorylation closely parallel the changes in transcription of cAMP-responsive genes by run-on assay. Nuclear translocation of PK-A, visualized by microinjection of fluorescently labeled PK-A holoenzyme, appears to represent the rate-limiting step in CREB phosphorylation and transcriptional activation. We and others have recently characterized a CREB-binding protein (CBP), which specifically recognizes sequences within the Ser133 phosphorylated form of CREB. CBP does not regulate the DNA binding, dimerization, or nuclear targeting properties of CREB, but binds selectively to the kinase-inducible 60 amino acid trans-activation domain (KID) of CREB, critical for PK-A-inducible transcription. We developed an antiserum directed against amino acid 634-648 within the CREB-binding domain of CBP. We detected a 265-kd polypeptide by Western blot as predicted from the cDNA, which coincided with the predominant phospho-CREB-binding activity in Hela nuclear extracts by "Far Western" blot assay. An identical phospho-CREB-binding activity was also found in NIH-3T3 cells. This phospho-CREB-binding protein appeared to be specific for Ser133-phosphorylated CREB, because no such band was detected with CREB labeled to the same specific activity at a nonregulatory phosphoacceptor site (Ser156) by casein kinase II (CKII). Following microinjection into nuclei of NIH-3T3 cells, a cAMP response element (CRE)-lacZ reporter was markedly induced by treatment with 8-Br cAMP plus isobutyl methyl xanthine (IBMX). Coinjection of CBP antiserum with the CRE-lacZ plasmid inhibited cAMP-dependent activity in a dose-dependent manner, but control immunoglobulin G (lgG) had no effect on this response. We can now begin reconstituting PK-A-dependent transcription in vitro, using well-characterized proteins such as CREB, TAF 110, and CBP. The assembly of such factors on cAMP-regulated promoters like somatostain may enable responsiveness to a variety of hormonal stimuli that employ cAMP as their second messenger.

3T3 Cells↗

Ebulitins: a new family of type 1 ribosome-inactivating proteins (rRNA N-glycosidases) from leaves of Sambucus ebulus L. that coexist with the type 2 ribosome-inactivating protein ebulin 1.

A new family of single chain (type 1) ribosome-inactivating proteins (RIPs), that we have named ebulitins, have been found in mature leaves of Sambucus ebulus L., a caprifoliaceae plant also known to contain a non-toxic two chain (type 2) RIP named ebulin I in its leaves. Ebulitins are basic proteins of M(r) 32,000, 29,000 and 29,000 for ebulitins alpha, beta and gamma, respectively. The simultaneous presence of different basic type 1 and acidic type 2 RIPs in the same plant and in the same tissue is described here for the first time and opens a new door in research into RIPs.

Amino Acids↗

Long-term experience with nipple-areola tattooing.

Although nipple-areola tattooing is now a well-accepted step in breast reconstruction, little is known about its long-term effectiveness. A retrospective study of our 6-year experience in tattooing 151 patients was thus carried out. Patients were surveyed regarding color match, satisfaction, and complications. Follow-up ranged from 1 to 75 months (mean, 25.2 months). Fifty-seven percent of respondents said their tattoo looked similar to the normal areola. There were five (3%) infections, one rash, and one slough. Ten percent of tattoos needed a touch-up later to correct for excessive fading. Nearly 60% of tattoos were ultimately lighter than the normal. Eighty-four percent of the tattoos were rated as satisfactory, and 86% of the patients said they would repeat the procedure if given the same choice again. Nipple-areola tattooing done with iron oxide and titanium dioxide pigments thus appears to be a reasonably safe and effective procedure in most patients but may require one or more subsequent touch-ups for appropriate color match.

Female↗

Selective fixed drug eruption to amoxycillin.

A selective fixed drug eruption to amoxycillin but not other betalactam drugs is reported. Penicillins are the drugs most frequently implicated in immunological adverse reactions. The most important of these are allergic reactions where an IgE-mediated mechanism is well established. Other immunological mechanisms have been described in reactions, such as haemolytic anaemia, serum sickness, drug-induced nephritis, drug fever and contact dermatitis. Fixed drug eruption (FDE) is a type of drug-induced dermatosis, the immunopathogenesis of which remains unknown. FDE is an uncommon reaction to penicillin derivatives, and very few cases have been reported. We present a case of a selective FDE to amoxycillin (AX), with no reaction to other betalactam drugs. Although one similar case has been reported, the reactivity to other penicillin derivatives was not assessed.

Aged↗

Regulation of somatostatin gene transcription by cAMP.

A number of hormones and growth factors stimulate target cells through receptors which are coupled to second messenger pathways. The second messenger cAMP, for example, mediates a wide variety of cellular responses to hormonal signals, including changes in intermediary metabolism, cellular proliferation and cellular motility. In mammalian cells, all of these biological responses are triggered by the activation of the cAMP-dependent protein kinase A, a heterotetramer consisting of paired catalytic and regulatory subunits. Upon hormonal stimulation, cAMP binds tightly to the regulatory subunits, thereby liberating catalytic subunits and promoting the phosphorylation of cellular substrates. In the liver, cAMP functions as a starvation state signal, mediating hormonal cues from the pancreas and adrenal gland to stimulate glucose production. cAMP stimulates glucose production, in part, by regulating transcription of the gene for phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis. Following hormonal stimulation, cAMP induces PEPCK gene expression 10-fold within 20-30 min. This induction appears to be independent of new protein synthesis.

Animals↗

Selective adverse reactions to diflunisal.

BACKGROUND AND OBJECTIVE: Diflunisal is a difluorophenyl derivative of salicylic acid. We report two patients who presented immediate adverse reactions to diflunisal (Dolobid) that consisted of generalized urticaria and chest tightness. METHODS: Diflunisal was conjugated to human serum albumin in order to perform in vivo and in vitro tests (skin prick and intradermal tests, leukocyte histamine release, and RAST). The patients were challenged following a single-blind, placebo-controlled oral procedure with diflunisal and other nonsteroidal antiinflammatory drugs. RESULTS: Skin tests with diflunisal were negative as were leukocyte histamine release tests and RAST in both patients. They tolerated therapeutic doses of aspirin, salsalate, salicylamide, lysine acetylsalicylate, acetaminophen, dipyrone, and propyfenazone. The oral provocation with diflunisal elicited an immediate response at the cumulative dose of 400 mg in both patients. CONCLUSION: These are two exceptional cases of selective adverse reactions to diflunisal with good tolerance to other salicylates and nonsteroidal antiinflammatory drugs. Thus, the inhibition of cyclooxygenase does not seem to be the mechanism involved. The pathogenic mechanism implicated in the reaction remains unclear, both idiosyncratic and immunologic mechanisms could explain our patients' adverse responses.

Aged↗

Hereditary angioedema: an infrequent cause of abdominal pain with ascites.

Patients with hereditary angioedema have episodes of local swelling, usually affecting the face, extremities, upper airway, and gastrointestinal tract. Only infrequently does it cause recurrent abdominal pain (with or without ascites); however, because it has potentially life-threatening complications, an early diagnosis is important. We describe a case of type I hereditary angioedema (a quantitative deficit of C1 inhibitor), the sole initial symptom of which was severe recurrent and self-limited abdominal pain, accompanied by ascites during these episodes. During a 4-yr period of treatment with danazol, the patient was virtually asymptomatic, despite levels of C4 and C1 inhibitor that remained below normal limits, and there have been no major side effects that could be attributed to treatment with androgens.

Abdominal Pain↗

Activation of cAMP and mitogen responsive genes relies on a common nuclear factor.

A number of signalling pathways stimulate transcription of target genes through nuclear factors whose activities are primarily regulated by phosphorylation. Cyclic AMP regulates the expression of numerous genes, for example, through the protein kinase-A (PKA)-mediated phosphorylation of transcription factor CREB at Ser 133. Although phosphorylation may stimulate transcriptional activators by modulating their nuclear transport or DNA-binding affinity, CREB belongs to a class of proteins whose phosphorylation appears specifically to enhance their trans-activation potential. Recent work describing a phospho-CREB binding protein (CBP) which interacts specifically with the CREB trans-activation domain prompted us to examine whether CBP is necessary for cAMP regulated transcription. We report here that microinjection of an anti-CBP antiserum into fibroblasts can inhibit transcription from a cAMP responsive promoter. Surprisingly, CBP also cooperates with upstream activators such as c-Jun, which are involved in mitogen responsive transcription. We propose that CBP is recruited to the promoter through interaction with certain phosphorylated factors, and that CBP may thus play a critical role in the transmission of inductive signals from cell surface receptor to the transcriptional apparatus.

3T3 Cells↗

Recombinant cyclic AMP response element binding protein (CREB) phosphorylated on Ser-133 is transcriptionally active upon its introduction into fibroblast nuclei.

To date, it has not been possible to determine whether the single phosphorylation of the cyclic AMP response element binding factor (CREB) at Ser-133 is sufficient for the transcriptional activation by cAMP-mediated pathways. Previous in vivo studies investigating this point have relied upon transfection of cyclic AMP-dependent kinase (cAPK) or its activation by treatment of cells with cell-permeable cAMP analogs. However, as numerous cellular proteins, including CREB, are substrates for activated cAPK, the possibility remains that cAPK substrates other than CREB are required for the transcriptional activity of CRE-containing promoters. To further address this, we compared the activity of recombinant CREB phosphorylated on Ser-133 in both cell-free transcription assays and in vivo after introduction of the same preparations into fibroblasts by microinjection. The activity of phosphorylated CREB, nonphosphorylated CREB, and a mutant form of CREB, containing Ala substituted for Ser at position 133, was found to be nearly identical in cell-free in vitro transcription assays. In contrast, we found that only the phosphorylated CREB microinjected into fibroblasts resulted in the stimulation of expression of CRE-regulated genes. These results suggest that phosphorylation of CREB on Ser-133 directly stimulates its ability to transactivate gene expression in intact cells.

3T3 Cells↗

[Extrinsic allergic alveolitis caused by Penicillium frequentans. Review and presentation of a case].

We present a case of extrinsic allergic alveolitis due to Penicillium frequentans exposure (suberosis) at a cork factory. Diagnosis was based on clinical history, a restrictive spirometric pattern, evidence of reticular-nodular lung infiltrates on the X-ray, intradermal skin tests with dual reaction and precipitins-positive serum samples in the presence of the P. frequentans fungus. Although the patient refused to submit to a specific bronchial challenge, two natural challenges occurred when he once again happened to handle wet cork after leaving his previous job. The literature referring to this disease is reviewed.

Adult↗

Fixed drug eruption caused by sulfaguanidine.

We report a patient who developed a fixed drug eruption (FDE) due to sulfaguanidine. This drug has not been previously implicated as a cause of FDE. The diagnosis was confirmed by an oral provocation and a biopsy of the lesion. Oral provocations with other sulfonamides, sulfamethoxazole and sulfadiazine, were well tolerated.

Administration, Oral↗

Behaviour of nucleolar organizer regions in the different Wistar rat liver lobes.

The area and number of silver-nucleolar organizer regions (Ag-NORs) in the hepatic lobes were determined in 3 male Wistar rats. There was a statistically significant increase in the percentage of Ag-NORs per nucleus in the right lateral and caudate lobe in relation to the left lateral and middle lobes. The area and number of Ag-NORs are greater in the caudate and right lateral lobes in relation to the left lateral and middle lobes. Since the Ag-NOR is a parameter which indicates hepatocytic protein synthesis, the different activity which corresponds to each lobe of the rat's liver makes it possible to assume that there is a functional heterogeneity which should be considered in the study of the hepatic regeneration according to the type of partial hepatectomy carried out.

Animals↗