Sulfonamide allergy without cross-reactivity to celecoxib.
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Adolescent↗
Biomedical subjects
J Figueroa
Publications and source records attributed to J Figueroa.
Copeptin, derived from isotocin precursor, is a probable prolactin releasing factor in carp.
Control of prolactin (PRL) release is of crucial importance for the multiple functions exerted by PRL in vertebrates. Recently identified hypothalamic PRL-releasing peptides displayed additional neuromodulatory activities and in fish only few could be detected close to lactotrophs. Here we describe the C-terminal peptide processed from the carp isotocin precursor as probable physiologically relevant regulator of PRL release in carp. The amino acid sequence derived from the complete isotocin precursor gene of Cyprinus carpio, predicted a C-terminal peptide uncleaved between the neurophysin (Np) and copeptin (Cp) domain. Accordingly, antibodies against synthetic Np- and Cp-specific oligopeptides both immunodetected a 13kDa protein (cNpCp) in total pituitary proteins and showed abundant immunoreaction in hypothalamic axons in direct contact with lactotrophs in the rostral pars distalis of carp pituitary gland sections. Finally, incubation of cultured carp pituitary explants with purified carp cNpCp resulted in a potent stimulation of PRL release.
Amino Acid Sequence↗
Modular changes of cis-regulatory elements from two functional Pit1 genes in the duplicated genome of Cyprinus carpio.
The pituitary-specific transcription factor Pit1 is involved in its own regulation and in a network of transcriptional regulation of hypothalamo-hypophyseal factors including prolactin (PRL) and growth hormone (GH). In the ectotherm teleost Cyprinus carpio, Pit1 plays an important role in regulation of the adaptive response to seasonal environmental changes. Two Pit1 genes exist in carp, a tetraploid vertebrate and transcripts of both genes were detected by RT-PCR analysis. Powerful comparative analyses of the 5'-flanking regions revealed copy specific changes comprising modular functional units in the naturally evolved promoters. These include the precise replacement of four nucleotides around the transcription start site embedded in completely conserved regions extending upstream of the TATA-box, an additional transcription factor binding site in the 5'-UTR of gene-I and, instead, duplication of a 9 bp element in gene-II. Binding of nuclear factors was assessed by electro mobility shift assays using extracts from rat pituitary cells and carp pituitary. Binding was confirmed at one conserved Pit1, one conserved CREB and one consensus MTF1. Interestingly, two functional Pit1 sites and one putative MTF1 binding site are unique to the Pit1 gene-I. In situ hybridization experiments revealed that the expression of gene-I in winter carp was significantly stronger than that of gene-II. Our data suggest that the specific control elements identified in the proximal regulatory region are physiologically relevant for the function of the duplicated Pit1 genes in carp and highlight modular changes in the architecture of two Pit1 genes that evolved for at least 12 MYA in the same organism.
Animals↗
Cloning of the prepro C-RFa gene and brain localization of the active peptide in Salmo salar.
In all vertebrates, the synthesis and release of prolactin (Prl) from pituitary lactotroph cells is tightly controlled by hypothalamic factors. We have cloned and characterized a hypothalamic cDNA from Atlantic salmon (Salmo salar) encoding C-RFa, a peptide structurally related to mammalian Prl-releasing peptide (PrRP). The deduced preprohormone precursor is composed of 155 amino acid residues presenting a 87.1% similarity to chum salmon C-RFa and a 100% similarity to all fish C-RFa in the bioactive precursor motifs. C-RFa-immunoreactive perikarya and fibres were located in the brain of S. salar, especially in the hypothalamus, olfactory tract, optic tectum and cerebellum. In contrast, immunolabelled fibres were not observed in the pituitary stalk or in the hypophysis. However, interestingly, we detected immunolabelled cells in the rostral pars distalis of the pituitary in the basolateral region in which Prl is synthesized. These results were confirmed by obtaining a strong signal by using reverse transcription/polymerase chain reaction (RT-PCR) on mRNA from both hypothalamus and pituitary. These data show, for the first time, by immunohistochemistry and RT-PCR, that C-RFa is produced in pituitary cells. Finally, based on these results, a possible function for C-RFa as a locally produced PrRP in this teleost is discussed.
Amino Acid Sequence↗
Basiliximab: a comparative study between the use of the recommended two doses versus a single dose in living donor kidney transplantation.
Basiliximab (Simulect) is a high-affinity chimeric and humanized monoclonal antibody, directed against the alpha chain of human interleukin-2 receptor (CD25). The administration of two doses (20 mg intravenously per dose), one given 2 hours before transplantation and the second on day 4 posttransplant, provides suppression of the interleukin-2 receptor for up to 45 days, reducing the rate of acute rejection in kidney transplantation. This study was designed to compare the efficacy of a single dose of Simulect to the recommended two doses. The other objective was the reduction of the costs related to the standard two dose protocol. Fifty-two patients were included: group I (32 patients) received two doses of Simulect; group II (20 patients) received one dose. There were 39 living related donors and 13 living unrelated. All patients were followed for 1 year. Maintenance immunosuppression consisted of tacrolimus or cyclosporine, mycophenolate mofetil, and steroids. The diagnosis of rejection was made clinically. All episodes were treated with intravenous steroids. The incidence of rejection was similar in both groups; there was no graft loss to rejection. There were two deaths in group I, and one death in group II, yielding graft and patient actual survival rates at 1 year of 93% and 95%, respectively. These results suggest that Simulect is equally effective when administered in two doses or in a single dose in kidney transplantation. The reduction of cost by giving a single dose is significant, especially in developing countries without national health insurance.
Adult↗
Seasonal modulation of growth hormone mRNA and protein levels in carp pituitary: evidence for two expressed genes.
Adaptation of eurythermal fish to naturally varying environmental conditions involves modulation of expressions of various factors in the hypothalamo-hypophyseal axis. Here we used three complementary approaches to assess the seasonal variation of growth hormone (GH) protein and mRNA levels in pituitary glands of acclimatized carp fish. First, a polyclonal antibody raised against an oligopeptide derived from the carp GH sequence was used for immunohistochemistry; second, oligonucleotides specific for GH transcripts were used for in situ hybridization. Specific immunodetection of GH coincides with visualization of GH mRNA in the proximal pars distalis, the specific location of somatotroph cells in carp pituitary gland. Finally, competitive RT-PCR analyses confirmed that GH expression exhibits seasonal cyclical reprogramming with higher levels in summer- than in winter-adapted fish. The expression pattern suggests an important role for GH in the molecular mechanisms underlying the acclimatization process. In parallel, amplification of sequences from the fourth intron and adjacent sites from exons IV and V demonstrates the existence of a new GH gene previously undescribed. The detection of transcripts corresponding to each gene suggests that both GH gene copies are active in the duplicated carp genome and that they are similarly affected by seasonal adaptation.
Acclimatization↗
Mustard allergy confirmed by double-blind placebo-controlled food challenges: clinical features and cross-reactivity with mugwort pollen and plant-derived foods.
BACKGROUND: Mustard IgE-mediated allergy is supposed to be a rare cause of food allergy, and its clinical features and cross-reactivities have not been fully elucidated. METHODS: A prospective study was carried out, recruiting mustard allergic patients, and paired control subjects. A clinical questionnaire was administered, and skin-prick tests (SPT) with panels of aeroallergens and foods, serum extraction for in vitro tests and double-blind placebo-controlled food challenges (DBPCFC) were performed. RESULTS: Thirty-eight mainly adult patients, with 10.5% reporting systemic anaphylaxis, were included in the study [age (mean +/- SD): 21.9 +/- 8.6 years]. DBPCFC were performed in 24 patients, being positive in 14 cases (58.3%). Patients with positive outcome showed significantly greater mustard SPT than those with negative outcome (8.2 +/- 3.7 vs 5.3 +/- 2.4 mm, P <0.05), and the receiver-operating characteristic (ROC) curve analysis yielded a cut-off value for mustard commercial SPT of 8 mm, with a specificity of 90% (95% CI, 55.5-98.3), and a sensitivity of 50% (95% CI, 23.1-76.9). A significant association between mustard hypersensitivity and mugwort pollen sensitization was found (97.4% of patients), with partial cross-reactivity demonstrated by UniCAP System inhibition assays. All patients showed sensitization to other members of Brassicaceae family, and cross-reactivity among them was also confirmed. Moreover, significant associations with nut (97.4%), leguminous (94.7%), corn (78.9%), and Rosaceae fruit (89.5%) sensitizations were also shown. Around 40% of these food sensitizations were symptomatic, including food-dependent exercise-induced anaphylaxis in six patients. CONCLUSIONS: Mustard allergy is a not-uncommon disorder that can induce severe reactions. Significant associations with mugwort pollinosis and several plant-derived food allergies are demonstrated, suggesting a new mustard-mugwort allergy syndrome. A relationship between this syndrome and food-dependent exercise-induced anaphylaxis is also reported.
Adolescent↗
Quality of care in institutionalized deliveries: the paradox of the Dominican Republic.
OBJECTIVES: To better understand the paradox in the Dominican Republic of a relatively high maternal mortality ratio despite nearly universal institutionalized deliveries with trained attendants, a rapid assessment using an adaptation of the strategic assessment method was conducted. METHODS: A multi-disciplinary team reviewed national statistics and hospital records, inventoried facilities, and observed peripartum client-provider interactions at 14 facilities. RESULTS: The major referral hospitals, where more than 40% of births in the country occur, were overcrowded and understaffed, with inexperienced residents overseeing care provided by medical students, interns and nurses. Uncomplicated labor and deliveries were overmedicalized, while complicated ones were not managed appropriately; emergencies were not dealt with in a timely fashion. In the peripheral hospitals physicians were seldom present and clients were either turned away or delivered by unprepared nursing staff. Providers in the busiest facilities suffered from compassion fatigue, and were demoralized and overworked. In all facilities, quality of care was lacking and the delivery and birthing process was dehumanized. CONCLUSIONS: Access and availability of institutional delivery alone is not enough to decrease MMR, it is also the quality of emergency obstetric care that saves lives.
Attitude of Health Personnel↗
Glandular kallikreins in the teleost Cyprinus carpio: tissue distribution, possible involvement in prolactin processing, and effect of 17 beta-estradiol in vivo.
We examined glandular kallikrein (GK), a putative prolactin processing protease, in the teleost Cyprinus carpio. When employing an anti-Centropristis striata GK antibody proteins of 39 kDa in muscle, 52 kDa in gill, 52 kDa in kidney, and two proteins of 46 and 72 kDa in pituitary gland were detected. Immunoreactive kallikreins were recognized in intermuscle cell tissue, epithelial gill cells, apical region of tubular cells, and prolactin producing lactotrophs in pituitary gland, suggesting a osmoregulatory role for this enzyme. We found three prolactin (PRL) variants using anti-tilapia PRL antibodies, in pituitary gland 23 and 16 kDa, and in plasma 23 and 22 kDa forms. Clearly co-localization of GK and PRL in lactotrophs could be demonstrated. In winter-acclimatized male carp, where the pituitary PRL level is low, 17beta-estradiol treatment increased PRL but not GK immunoreactivity. In contrast to GK and PRL co-regulation by estrogen in mammalian pituitary gland, no similar effect on immunoreactive PRL and GK was observed in the ichtyc pituitary. No changes in GK immunostaining occurred in gill or muscle tissue in response to estrogen treatment. These results, taken with the observation of significantly increased GK immunoreactivity in the apical region of kidney tubular cells in estrogen treated male carp, indicate that the regulation of GK expression in pituitary and kidney could be different in fish with respect to mammals.
Acclimatization↗
Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription.
Transforming growth factor-beta (TGF-beta) signaling requires the action of Smad proteins in association with other DNA-binding factors and coactivator and corepressor proteins to modulate target gene transcription. Smad2 and Smad3 both associate with the c-Ski and Sno oncoproteins to repress transcription of Smad target genes via recruitment of a nuclear corepressor complex. Ski-interacting protein (SKIP), a nuclear hormone receptor coactivator, was examined as a possible modulator of transcriptional regulation of the TGF-beta-responsive promoter from the plasminogen activator inhibitor gene-1. SKIP augmented TGF-beta-dependent transactivation in contrast to Ski/Sno-dependent repression of this reporter. SKIP interacted with Smad2 and Smad3 proteins in vivo in yeast and in mammalian cells through a region of SKIP between amino acids 201-333. In vitro, deletion of the Mad homology domain 2 (MH2) domain of Smad3 abrogated SKIP binding, like Ski/Sno, but the MH2 domain of Smad3 alone was not sufficient for protein-protein interaction. Overexpression of SKIP partially overcame Ski/Sno-dependent repression, whereas Ski/Sno overexpression attenuated SKIP augmentation of TGF-beta-dependent transcription. Our results suggest a potential mechanism for transcriptional control of TGF-beta signaling that involves the opposing and competitive actions of SKIP and Smad MH2-interacting factors, such as Ski and/or Sno. Thus, SKIP appears to modulate both TGF-beta and nuclear hormone receptor signaling pathways.
Animals↗
In situ hybridization of somatolactin transcripts in the pituitary glands from acclimatized carp (Cyprinus carpio).
We isolated and cloned a carp somatolactin SL DNA fragment, of which 78% of the nucleotides were identical to the corresponding salmon SL sequence. The results obtained upon Northern blot hybridization of carp pituitary RNA allowed the identification of two transcripts as described for other fish. When the content of SL transcripts in pituitary sections from summer- and winter-acclimatized carp was quantified by in situ hybridization assays, we found no significant differences between the two seasons. In salmonids, plasma SL reaches higher levels in summer than in winter in synchrony with the water temperature cycle; in the eurythermal carp, however, the complex adaptive responses imposed by seasonal environmental changes do not seem to include the regulation of the somatolactin detected with the probe used at the transcriptional level in pituitary glands.
Acclimatization↗
Dyspnea in a woman infected with the human immunodeficiency virus.
Shortness of breath is a common complaint encountered in both the ambulatory and acute care setting. In patients infected with the human immunodeficiency virus, dyspnea often heralds the onset of a potentially life-threatening opportunistic infection. We present a case of a rare cause of dyspnea in the general population and to our knowledge the first such case reported in the setting of human immunodeficiency virus infection in the United States.
Adult↗
Environmental reprogramming of the expression of protein kinase CK2beta subunit in fish.
The dramatic segregation of the nucleolar components in winter-acclimatized carp is the most striking cellular-phenotypical feature observed during the seasonal adaptation of this fish toward the circannual changes in its habitat. Our studies also show that the carp habitat temperature and photoperiod winter conditions provoke a remarkable reduction of both rRNA transcription and the processing of their precursors. To gain knowledge on the mechanisms involved in the regulation of nucleolar activity during the seasonal adaptation process, we studied the behavior of some genes, specifically snoRNA U3 and protein kinase CK2. Consistent with the reduction in the synthesis and processing of pre-rRNA observed during the cold season, the level of CK2beta expression decreases in winter when compared to that attained in summer. Similarly, in winter, liver and kidney cells contain lower levels of CK2beta subunit protein compared to summer. CK2 is associated with or modifies different factors and enzymes involved in the nucleolar activity; therefore, its higher or lower content could be part of the molecular mechanisms underlying the nucleolar seasonal changes that occur during the compensatory acclimatization process.
Animals↗
Environmental acclimatization of the carp modulates the transcription of beta-actin.
A cascade of mechanisms involving changes in gene expression are substantial to shape the adaptive responses that a eurythermal fish requires upon environmental changes in its habitat. We have previously shown that the cyclical reprogramming of rRNA transcription is a remarkable feature in carp under seasonal acclimatization. Using in situ hybridization and competitive RT-PCR we found significant differences in beta-actin transcripts, generally accepted to be coded by a typical housekeeping gene, in tissues from summer- and winter-acclimatized carp. The physiological differential beta-actin transcription herein reported places us on the alert for the reference genes estimated to be constitutive to quantitatively assess gene transcripts.
Actins↗
Seasonal adaptation modulates the expression of the protein kinase CK2 beta subunit gene in the carp.
Carp fish seasonal acclimatization induces a cyclical transcriptional modulation of several genes. Its most dramatic expression results in a concomitant structural rearrangement of the nucleolar components that phenotypically represents profound shifts in the level of ribosomal RNA synthesis. In connection with the recent studies that implicate CK2 in the control of rRNA synthesis in vertebrates, we characterized the cDNA of carp protein kinase CK2beta subunit and assessed its transcriptional behavior in winter- and summer-acclimatized fish. We found a remarkable differential gene expression of CK2beta subunit between summer- and winter-acclimatized carp which correlates with the modulatory pattern observed in rRNA transcription.
Acclimatization↗
The methodology and operation of a pilot randomized control trial of the effectiveness of the Bug Busting method against a single application insecticide product for head louse treatment.
A Department of Health leaflet suggests two treatment methods for head lice: mechanical removal by wet combing; and insecticide lotion/rinses. However, there are no reports in the literature comparing the effectiveness of these two treatment methods and well controlled clinical trials of insecticide treatments are sparse. A pilot randomized control trial of the effectiveness of a specific method of wet combing, 'Bug Busting', against a single application of a proprietary insecticide product is reported. The difficulties of designing a trial are discussed and modifications that would allow a definitive trial to take place are suggested. The pilot study included enzyme analysis of lice for insecticide resistance status assessment.
Animals↗
Clinical applications of non-culture based methods for the diagnosis and management of opportunistic and endemic mycoses.
Nonculture based methods for the detection of infections caused by fungal pathogens are becoming more important tools in the management of infected patients. Detection of fungal antigens and DNA appear to be the most promising in this respect for both opportunistic and endemic mycoses. In this article we present an overview of the most recent developments in nonculture based methods and examine their value in clinical practice.
Antigens, Fungal↗
Pharmacological treatment of Alzheimer disease: from psychotropic drugs and cholinesterase inhibitors to pharmacogenomics.
For the past 20 years the scientific community and the pharmaceutical industry have been searching for treatments to neutralize the devastating effects of Alzheimer disease (AD). During this period important changes in the etiopathogenic concept of AD have occurred and, as a consequence, the pharmacological approach for treating AD has also changed. During the past 2 decades only 3 drugs for AD have been formally approved by the FDA, although in many countries there are several drugs which are currently used as neuroprotecting agents in dementia alone or in combination with cholinesterase inhibitors. The interest of the pharmaceutical industry has also shifted from the cholinergic hypothesis which led to the development of cholinesterase inhibitors to enhance the bioavailability of acetylcholine at the synaptic cleft to a more "molecular approach" based on new data on the pathogenic events underlying neurodegeneration in AD. In our opinion, the pharmacological treatment of AD should rely on a better understanding of AD etiopathogenesis in order to use current drugs that protect the AD brain against deleterious events and/or to develop new drugs specifically designed to inhibit and/or regulate those factors responsible for premature neuronal death in AD. The most relevant pathogenic events in AD can be classified into main categories: primary events (genetic factors, neuronal apoptosis), secondary events (beta-amyloid deposition in senile plaques and brain vessels, neurofibrillary tangles due to hyperphosphorylation of tau proteins, synaptic loss), tertiary events (neurotransmitter deficits, neurotrophic alterations, neuroimmune dysfunction, neuroinflammatory reactions) and quaternary events (excitotoxic reactions, calcium homeostasis miscarriage, free radical formation, primary and/or reactive cerebrovascular dysfunction). All of these pathogenic events are potential targets for treatment in AD. Potential therapeutic strategies for AD treatment include palliative treatment with nonspecific neuroprotecting agents, symptomatic treatment with psychotropic drugs for noncognitive symptoms, cognitive treatment with cognition enhancers, substitutive treatment with cholinergic enhancers to improve memory deficits, multifactorial treatment using several drugs in combination and etiopathogenic treatment designed to regulate molecular factors potentially associated with AD pathogenesis. This review discusses the conventional cholinergic enhancers (cholinesterase inhibitors, muscarinic agonists), noncholinergic strategies that have been developed with other compounds, novel combination drug strategies and future trends in drug development for AD treatment. Stem-cell activation, genetically manipulated cell transplantation, gene therapy and antisense oligonucleotide technology constitute novel approaches for the treatment of gene-related brain damage and neuroregeneration. The identification of an increasing number of genes associated with neuronal dysfunction along the human genome together with the influence of specific allelic associations and polymorphisms indicate that pharmacogenomics will become a preferential procedure for drug development in polygenic complex disorders. Furthermore, genetic screening of the population at risk will help to identify candidates for prevention among first-degree relatives in families with transgenerational dementia.
Journal Article↗