Early cyclosporine blood levels impact the incidence of acute rejection and overall mortality in the first year after heart transplantation.
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Cyclosporine↗
Biomedical subjects
F Romero
Publications and source records attributed to F Romero.
Activation of Ca(2+)-activated K+ (maxi-K+) channel by angiotensin II in myocytes of the guinea pig ileum.
We investigated the regulation of the Ca(2+)-activated K+ (maxi-K+) channel by angiotensin II (ANG II) and its synthetic analog, [Lys2]ANG II, in freshly dispersed intestinal myocytes. We identified a maxi-K+ channel population in the inside-out patch configuration on the basis of its conductance (257 +/- 4 pS in symmetrical 150 mM KCl solution), voltage and Ca2+ dependence of channel opening, low Na(+)-to-K+ and Cl(-)-to-K+ permeability ratios, and blockade by external Cs+ and tetraethylammonium chloride. ANG II and [Lys2]ANG II caused an indirect, reversible, Ca(2+)- and dose-dependent activation of maxi-K+ channels in cell-attached experiments when cells were bathed in high-K+ solution. This effect was reversibly blocked by DUP-753, being that it is mediated by the AT1 receptor. Evidences that activation of the maxi-K+ channel by ANG II requires a rise in intracellular Ca2+ concentration ([Ca2+]i) as an intermediate step were the shift of the open probability of the channel-membrane potential relationship to less positive membrane potentials and the sustained increase in [Ca2+]i in fura 2-loaded myocytes. The preservation of the pharmacomechanical coupling of ANG II in these cells provides a good model for the study of transmembrane signaling responses to ANG II and analogs in this tissue.
Angiotensin II↗
Two marine Agrobacterium producers of sesbanimide antibiotics.
Sesbanimides are cytotoxic compounds, originally isolated in 1983 from seeds of the leguminous plants Sesbania drummondii and Sesbania punicea. In this paper we describe the bacterial production of sesbanimides by two "marine Agrobacterium"; strain PH-103 which produces Sesbanimide-A and strain PH-A034C which produces Sesbanimide-C. The isolation and taxonomy of the producing microorganisms, fermentation and isolation of sesbanimides are reported.
Alkaloids↗
[Parry-Romberg syndrome: a form of focal vasculitis].
The Parry-Romberg syndrome (PRS), which was described many years ago, is a process of unknown etiology which evolves with invalidating lesions in one half of the face to which different neurologic, cutaneous or analytical abnormalities may be associated. A clinical, analytical and radiologic study of 5 patients in whom intracranial lesions were shown are herein presented. These findings, together with alterations in the cutaneous biopsies reported in the literature lead to the hypothesis that PRS may be due to a neurovascular alteration of immunologic basis, indicating antiinflammatory or immunosuppressive treatment.
Adolescent↗
A conditionally expressed third partner stabilizes or prevents the formation of a transcriptional activator in a three-hybrid system.
We describe a three-hybrid system that involves three polypeptides that allow or prevent the formation of the transcriptional activator. Beside the two-hybrid fusion proteins, the third partner is under the control of the Met25 promoter, which is positively regulated in medium lacking methionine. We document a situation where such a third partner promotes interaction between two proteins, one fused to a DNA-binding domain and the other fused to an activator domain. This is demonstrated for cdk7-MAT1 interaction stabilized by the presence of cyclin H; these three polypeptides are found either free or associated with the transcription/DNA repair factor TFIIH. We also document the capacity of our system to conditionally inhibit the interaction between two polypeptides that otherwise elicit a positive two-hybrid response. This is demonstrated for Ras-Raf interaction precluded by an excess of Raf. The presence of a methionine-regulated promoter provides an "on" or "off" switch for the formation of the transcriptional activator, thus also providing an excellent control to evaluate the activation or inhibition properties of the third partner.
Artifacts↗
A new member of the amphiphysin family connecting endocytosis and signal transduction pathways.
Src homology 3 (SH3) domains are conserved modules which participate in protein interaction by recognizing proline-rich motifs on target molecules. To identify new SH3-containing proteins, we performed a two-hybrid screen with a proline-rich region of human SOS-1. One of the specific SOS-1 interacting clones that were isolated from a mouse brain cDNA library defines a new protein that was named amphiphysin 2 because of its homology to the previously reported amphiphysin. Amphiphysin 2 is expressed in a number of mouse tissues through multiple RNA transcripts. Here, we report the amino acid sequence of a brain form of amphiphysin 2 (BRAMP2) encoded by a 2. 5-kilobase mRNA. BRAMP2 associates in vitro with elements of the endocytosis machinery such as alpha-adaptin and dynamin. On a biosensor surface, the BRAMP2/dynamin interaction appeared to be direct and partly dependent on a proline-rich sequence of dynamin. Association with dynamin was also observed in PC12 cells after cell stimulation with nerve growth factor, suggesting that amphiphysin 2 may be connected to receptor-dependent signaling pathways. This hypothesis is strengthened by the ability of BRAMP2 to interact with the p21(ras) exchange factor SOS, in vitro, as a possible point of interconnection between the endocytic and signaling pathways.
Adaptor Protein Complex alpha Subunits↗
Y chromosome markers and Trans-Bering Strait dispersals.
Five polymorphisms involving two paternally inherited loci were surveyed in 38 world populations (n = 1,631) to investigate the origins of Native Americans. One of the six Y chromosome combination haplotypes (1T) was found at relatively high frequencies (17.8-75.0%) in nine Native American populations (n = 206) representing the three major linguistic divisions in the New World. Overall, these data do not support the Greenberg et al. (1986) tripartite model for the early peopling of the Americas. The 1T haplotype was also discovered at a low frequency in Siberian Eskimos (3/22), Chukchi (1/6), and Evens (1/65) but was absent from 17 other Asian populations (n = 987). The perplexing presence of the 1T haplotype in northeastern Siberia may be due to back-migration from the New World to Asia.
Biological Evolution↗
Evaluation of cerebral function after carotid endarterectomy.
Neuroimaging methods have failed to disclose correlation between degree of cerebral atrophy and blood flow in carotid artery stenosis patients. Moreover, intellectual improvement after carotid endarterectomy does not correlate fully with neuroimaging data in such patients. We performed brain electrical activity mapping and psychological testing before and 4 weeks after operation in 28 patients with symptomatic, high-grade, carotid stenosis. Postoperatively, electroencephalographic (EEG) mean frequency and absolute theta power improved significantly (p < 0.01). Mean frequency increased >1 Hz in most areas while power decreased dramatically, mainly because of resolution of high-voltage foci in 8 patients. Differences were conspicuous in both frontal lobes irrespective of the operated side, which suggests changes in perfusion affecting the whole brain. This is a positive effect of endarterectomy. Mini-Mental test and Set Test for verbal fluency had a positive correlation with the qEEG changes. Quantitative EEG as a measure of cerebral function has disclosed discriminative improvement in the early postoperative period. Our results support the thesis of improvement subsequent to endarterectomy.
Adolescent↗
Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activities.
A novel bioactive depsipeptide, thiocoraline, was isolated from the mycelial cake of a marine actinomycete strain L-13-ACM2-092. Based on morphological, cultural, physiological, and chemical characteristics, strain L-13-ACM2-092 was ascribed to the genus Micromonospora. Thiocoraline showed a potent cytotoxic activity against P-388, A-549 and MEL-28 cell lines, and also a strong antimicrobial activity against Gram-positive microorganisms. This compound binds to supercoiled DNA and inhibits RNA synthesis.
Animals↗
[Meta-analysis: trials with melatonin and its effect on the sleep. Letter].
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Blindness↗
Detection of a physical and functional interaction between Csk and Lck which involves the SH2 domain of Csk and is mediated by autophosphorylation of Lck on tyrosine 394.
The COOH-terminal Src kinase (Csk) is responsible for the phosphorylation of the conserved, negative regulatory, carboxyl-terminal tyrosine of most of the Src family protein tyrosine kinases. Up to now, no stable binding of Csk to Src kinases has been detected. We therefore decided to analyze this interaction using two systems which allow detection of transient interaction. We produced and purified recombinant proteins in the glutathione S-transferase prokaryotic expression system. First, using real-time biospecific interaction analysis (BIAcore(TM)), we detected in vitro a specific interaction between Csk and one of its substrates Lck, a lymphocyte-specific member of the Src family. This interaction requires the autophosphorylation of Lck on tyrosine 394 (the phosphorylation of which is correlated with an increase of the kinase activity) and involves a functional Csk SH2 domain. Second, using the yeast two-hybrid system, we confirmed in vivo the physical interaction between Csk and Lck. Furthermore, in vitro we showed that autophosphorylation of Lck on tyrosine 394 enhances the phosphorylation of Lck by Csk on the negative regulatory site, tyrosine 505, suggesting that activated Lck serves preferentially as substrate for Csk. These findings might explain the mechanism(s) by which Csk interacts with most of Src kinases to down-regulate their kinase activity.
Amino Acid Sequence↗
Metastatic tumours of the hand. Report of six additional cases.
Six metastatic tumours of the hand are reported. Five were located in long bones of the hand and one in the soft tissues without bone involvement. The primary tumours arose in the lung, kidney, hard palate, larynx and pharynx. Treatment was palliative and consisted of amputation for distal lesions and local excision and/or radiation for proximal lesions when symptomatic. Short-term prognosis was poor with a median survival of 7 months. In two patients, hand metastases were the first sign of malignant disease.
Aged↗
Structure and function of vav.
The proto-oncogene vav is expressed solely in cells of hematopoietic origin regardless of their differentiation lineage. However, recently an homologue of vav, which is widely expressed (vav2) has been identified. Vav is a complicated and interesting molecule that contains a number of structural features found in proteins involved in cell signaling. Vav has a leucine-rich region, a leucine-zipper, a calponin homology domain, an acidic domain, a Dbl-homology domain, a pleckstrin homology domain, a cysteine-rich domain, two Src homology 3 domains, with a proline-rich region in the amino-SH3 domain, and finally an Src homology 2 domain. These domains have been implicated in protein protein interactions and strongly suggest that vav is involved in signaling events. vav is also rapidly and transiently tyrosine phosphorylated through the activation of multiple receptors on hematopoietic cells. Furthermore, vav is tyrosine phosphorylated upon the activation of several cytokines and growths factors. Recently, the generation of nice vav-/- showed that vav has an essential role in proliferation/activation of T and B cells. The purpose of this review is to summarize the current knowledge on vav and to evaluate the roles of vav in cellular functions.
Amino Acid Sequence↗
p95vav associates with the nuclear protein Ku-70.
The proto-oncogene vav is expressed solely in hematopoietic cells and plays an important role in cell signaling, although little is known about the proteins involved in these pathways. To gain further information, the Src homology 2 (SH2) and 3 (SH3) domains of Vav were used to screen a lymphoid cell cDNA library by the yeast two-hybrid system. Among the positive clones, we detected a nuclear protein, Ku-70, which is the DNA-binding element of the DNA-dependent protein kinase. In Jurkat and UT7 cells, Vav is partially localized in the nuclei, as judged from immunofluorescence and confocal microscopy studies. By using glutathione S-transferase fusion proteins derived from Ku-70 and coimmunoprecipitation experiments with lysates prepared from human thymocytes and Jurkat and UT7 cells, we show that Vav associates with Ku-70. The interaction of Vav with Ku-70 requires only the 150-residue carboxy-terminal portion of Ku-70, which binds to the 25 carboxy-terminal residues of the carboxy SH3 domain of Vav. A proline-to-leucine mutation in the carboxy SH3 of Vav that blocks interaction with proline-rich sequences does not modify the binding of Ku-70, which lacks this motif. Therefore, the interaction of Vav with Ku-70 may be a novel form of protein-protein interaction. The potential role of Vav/Ku-70 complexes is discussed.
Base Sequence↗
beta haplotypes of three Mexican Mestizo families with Spanish (delta beta)o-thalassemia.
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Codon↗
The proline-rich region of Vav binds to Grb2 and Grb3-3.
Vav has structural features found in signaling proteins and is expressed only in hematopoietic cells. The recent development of mice Vav -/- has confirmed a major role of Vav in early blood cell development. We previously showed that Vav constitutively interacts with glutathione-S-transferase-Grb2. Coimmunoprecipitation experiments supported the idea of a complex formed by Vav-Grb2 in vivo. This complex is of potential interest in signaling of hematopoietic cells. In this work we localize the domains of Vav and Grb2 involved in this interaction. By the use of an in vivo genetic approach (the double hybrid system) and through in vitro experiments (glutathione-S-transferase fusion proteins) we furnish evidence that the interaction between Vav and Grb2 involves the C-SH3 domain of Grb2 and the proline-rich region located in the N-SH3 of Vav. Furthermore this was confirmed by the use of both Vav and Sos derived proline-rich peptides which blocked the binding. In addition we show that Vav also interacts with Grb3-3, a naturally occurring Grb2 isoform wich lacks functional SH2 domain.
Adaptor Proteins, Signal Transducing↗
Bridging Ral GTPase to Rho pathways. RLIP76, a Ral effector with CDC42/Rac GTPase-activating protein activity.
Ra1A and Ra1B are GTPases of unknown function and are activated by proteins, Ra1GDS, that interact with the active form of another GTPase, Ras. To elucidate Ral function, we have searched for proteins interacting with an activated form of Ra1A using the two-hybrid method and a Jurkat cell library. We have identified a partial cDNA encoding a protein, RLIP1, which binds to activated Ra1A and this binding requires an intact effector domain of Ra1A. Biochemical data with purified Ra1A confirm the genetic results. This protein also bears a region of homology with GTPase-activating protein (GAP) domains that are involved in the regulation of GTPases of the Rho family and, indeed, RLIP1 displays a GAP activity acting upon Rac1 and CDC42, but not RhoA. This GAP region is not required for RLIP1 binding to Ra1. The whole cDNA was cloned, and it encodes a 76-kDa polypeptide, RLIP76, which also binds RalA. The Rho pathway is involved in membrane and cytoskeleton modifications after mitogenic stimulation and acts in parallel to and synergistically with the Ras pathway. We propose that these pathways are linked through a cascade composed of Ras --> Ra1GDS --> Ra1 --> RLIP76 --> CDC42/Rac1/Rho, allowing modulation of the Rho pathway by the Ras pathway.
ATP-Binding Cassette Transporters↗