RESUMO
BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies-intellectual disability syndrome. One of the complications is keloid formation. Keloids are proliferative fibrous growths resulting from excessive tissue response to skin trauma. OBJECTIVES: To describe the clinical characteristics of keloids in individuals with RSTS reported in the literature and in a cohort of personally evaluated individuals with RSTS. PATIENTS AND METHODS: We performed a literature search for descriptions of RSTS individuals with keloids. All known individuals with RSTS in the Netherlands filled out three dedicated questionnaires. All individuals with (possible) keloids were personally evaluated. A further series of individuals with RSTS from the U.K. was personally evaluated. RESULTS: Reliable data were available for 62 of the 83 Dutch individuals with RSTS and showed 15 individuals with RSTS (24%) to have keloids. The 15 Dutch and 12 U.K. individuals with RSTS with keloids demonstrated that most patients have multiple keloids (n > 1: 82%; n > 5: 30%). Mean age of onset is 11·9 years. The majority of keloids are located on the shoulders and chest. The mean length × width of the largest keloid was 7·1 × 2·8 cm, and the mean thickness was 0·7 cm. All affected individuals complained of itching. Generally, treatment results were disappointing. CONCLUSIONS: Keloids occur in 24% of individuals with RSTS, either spontaneously or after a minor trauma, usually starting in early puberty. Management schedules have disappointing results. RSTS is a Mendelian disorder with a known molecular basis, and offers excellent opportunities to study the pathogenesis of keloids in general and to search for possible treatments.
Assuntos
Queloide/patologia , Síndrome de Rubinstein-Taybi/patologia , Idade de Início , Estudos de Coortes , Feminino , Humanos , Queloide/etiologia , Masculino , Síndrome de Rubinstein-Taybi/etiologia , Inquéritos e Questionários , Adulto JovemRESUMO
To elucidate the intracellular pathways that mediate early B cell development, we directed expression of activated Ras to the B cell lineage in the context of the recombination-activating gene 1 (RAG1)-deficient background (referred to as Ras-RAG). Similar to the effects of an immunoglobulin (Ig) mu heavy chain (HC) transgene, activated Ras caused progression of RAG1-deficient progenitor (pro)-B cells to cells that shared many characteristics with precursor (pre)-B cells, including downregulation of surface CD43 expression plus expression of lambda5, RAG2, and germline kappa locus transcripts. However, these Ras-RAG pre-B cells also upregulated surface markers characteristic of more mature B cell stages and populated peripheral lymphoid tissues, with an overall phenotype reminiscent of B lineage cells generated in a RAG- deficient background as a result of expression of an Ig mu HC together with a Bcl-2 transgene. Taken together, these findings suggest that activated Ras signaling in pro-B cells induces developmental progression by activating both differentiation and survival signals.
Assuntos
Linfócitos B/metabolismo , Ativação Enzimática/genética , Genes RAG-1/genética , Proteínas ras/genética , Animais , Diferenciação Celular/genética , Sobrevivência Celular/genética , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias kappa de Imunoglobulina/genética , Camundongos , Camundongos Knockout , Fenótipo , RNA Mensageiro/genética , Células-Tronco/metabolismo , Transcrição Gênica/genética , Regulação para Cima/genéticaRESUMO
Expression of the membrane-bound version of the human mu chain in transgenic mice results in the allelic exclusion of endogenous mouse Ig heavy chain genes (6). The secreted version of the human Ig transgene has no such effect. F1 hybrid animals that carry transgenes for both secreted and membrane-bound human mu chains produce both forms of the human heavy chain while strongly suppressing endogenous mouse mu expression. The simultaneous expression of the two rearranged transgenes in primary B cells suggests that allelic exclusion operates before the formation of a second functionally rearranged heavy chain gene in vivo.
Assuntos
Genes de Imunoglobulinas , Cadeias mu de Imunoglobulina/genética , Camundongos Transgênicos/genética , Receptores de Antígenos de Linfócitos B/genética , Alelos , Animais , Regulação da Expressão Gênica , Humanos , Camundongos , RNA Mensageiro/genéticaRESUMO
Antibody-producing cells display a special form of regulation whereby each cell produces immunoglobulin from only one of its two sets of antibody genes. This phenomenon, called allelic exclusion, is thought to be mediated by the product of one heavy chain allele restricting the expression of the other. Heavy chains are synthesized in two molecular forms, secreted and membrane bound. In order to determine whether it is specifically the membrane-bound form of the immunoglobulin M (IgM) heavy chain (mu) that mediates this regulation, transgenic mice were created that carry a human mu chain gene altered so that it can only direct the synthesis of the membrane-bound protein. The membrane-bound form of the human mu chain was made by most of the B cells in these animals as measured by assays of messenger RNA and surface immunoglobulins. Further, the many B cells that express the human gene do not express endogenous mouse IgM, and the few B cells that express endogenous mouse mu do not express the transgene. Thus, the membrane-bound form of the mu chain is sufficient to mediate allelic exclusion. In addition, the molecular structures recognized for this purpose are conserved between human and mouse systems.
Assuntos
Alelos , Células Produtoras de Anticorpos/imunologia , Genes , Cadeias mu de Imunoglobulina/genética , Animais , Regulação da Expressão Gênica , Humanos , Imunoglobulina M/genética , Camundongos , Camundongos Endogâmicos , RNA Mensageiro/genética , Transcrição GênicaRESUMO
Wheat (Triticum aestivum L.) embryo germination is inhibited by natural (S)-(+)-abscisic acid (ABA). In this report we have determined critical structural features of the ABA molecule, particularly the methyl and ketone groups of the ABA ring, required for inhibitory activity. To examine the ring residues a series of new optically active ABA analogs have been synthesized in which the 4[prime]-keto, 7[prime]-, 8[prime]-, or 8[prime]- and 9[prime]-carbons have been replaced with hydrogen atoms. Each of the analogs was tested over a range of concentrations as a germination inhibitor. Enantiomers of the analogs altered at the 4[prime]-keto or 8[prime]- and 9[prime]-methyl groups were active, but less so than ABA. Both enantiomers of 7[prime]-demethylABA were inactive as germination inhibitors. The results show that the 7[prime]-methyl group is absolutely required for activity, but that the other residues are less critical for hormone recognition.
RESUMO
The human pathogen Chlamydia trachomatis is an obligate intracellular bacterium, characterized by a developmental cycle that alternates between the infectious, extracellular elementary bodies and intracellular, metabolically active reticulate bodies. The cellular immune effector interferon gamma (IFN-gamma) inhibits chlamydial multiplication in human epithelial cells by induction of the tryptophan degrading enzyme indoleamine 2,3 dioxygenase. IFN-gamma causes persistent C. trachomatis serovar A infections with atypical reticulate bodies that are unable to redifferentiate into elementary bodies and show diminished expression of important immunogens, but not of GroEL. However, the sensitivity to IFN-gamma varies among serovars of C. trachomatis. In our previous study significant IFN-gamma-specific, but tryptophan reversible, induction of proteins in C. trachomatis A and L2 with molecular masses of approximately 30 and 40 kDa was observed on 2D-gels. The 30-kDa protein from C. trachomatis L2 migrated with a significantly lower molecular weight in C. trachomatis A. In this paper we include C. trachomatis B, C and D in our investigations and identify the proteins as alpha- and beta-subunits of the chlamydial tryptophan synthase using matrix-assisted laser desorption/ionization mass spectrometry. DNA sequencing of the trpA genes from C. trachomatis A and C shows that the TrpA in these serovars is a 7.7-kDa truncated version of C. trachomatis D and L2 TrpA. The truncation probably impairs the TrpA activity, thus elucidating a possible molecular mechanism behind variations in the pathogenesis of C. trachomatis serovars.
Assuntos
Chlamydia trachomatis/enzimologia , Chlamydia trachomatis/patogenicidade , Porinas , Triptofano Sintase/genética , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular , Chlamydia trachomatis/classificação , Chlamydia trachomatis/genética , Eletroforese em Gel Bidimensional , Variação Genética , Células HeLa , Humanos , Interferon gama/farmacologia , Camundongos , Microscopia de Fluorescência , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Triptofano Sintase/química , Triptofano Sintase/metabolismoRESUMO
Serum C-reactive protein and neopterin concentrations were measured in samples taken at an early stage in different types of infection to see whether the combination of markers could contribute to the diagnosis of infection and help distinguish between bacterial and viral infections, tuberculosis, and infections due to "other" pathogens. Both markers were significantly raised in all categories of infection compared with controls, and there were significant differences between the means of both markers when comparing several of the categories of infection. Only C-reactive protein concentrations in bacteraemic patients, however, were both sensitive and specific at distinguishing the type of infection. The additional use of neopterin estimation played only a minor part in increasing the specificity of diagnosis in tuberculosis and in viral infections. On the basis of this study it was not considered worth the time and expense of performing neopterin assays in addition to C-reactive protein estimations to differentiate viral from bacterial infection.
Assuntos
Infecções Bacterianas/diagnóstico , Biopterinas/análogos & derivados , Proteína C-Reativa/análise , Viroses/diagnóstico , Infecções Bacterianas/sangue , Biopterinas/sangue , Humanos , Neopterina , Sepse/sangue , Sepse/diagnóstico , Tuberculose/sangue , Tuberculose/diagnóstico , Viroses/sangueRESUMO
OBJECTIVE: To define better the adult phenotype and natural history of Noonan syndrome. DESIGN: A prospective observational study of a large cohort. RESULTS: Data are presented for 112 individuals with Noonan syndrome (mean age 25.3 (range 12-71) years), who were followed up for a mean of 12.02 years. Mutations in PTPN11 were identified in 35% of probands. Ten subjects died during the study interval; three of these deaths were secondary to heart failure associated with hypertrophic cardiomyopathy. Pulmonary stenosis affected 73 (65%) subjects; 42 (58%) required no intervention, nine underwent balloon pulmonary valvuloplasty (three requiring further intervention) and 22 surgical valvuloplasty (three requiring further intervention). Hypertrophic cardiomyopathy affected 21 (19%) patients, which had remitted in two cases, but one subject required cardiac transplant. No subjects died suddenly or had symptoms suggestive of arrhythmia. The mean final adult height was 167.4 cm in males and 152.7 cm in females. Feeding problems in infancy were identified as a predictor of future outcome. The mean age of speaking in two-word phrases was 26 months for those with no feeding difficulties, compared with 39 months for those with severe problems requiring nasogastric feeding. Attendance at a school for children with special needs for the same groups was 12.5% and 58%, respectively. A statement of special educational need had been issued in 44% overall; however, academic achievement was broadly similar to that of the general population. IMPLICATIONS: Although the morbidity for some patients with Noonan syndrome is low, early predictors of poorer outcome have been identified, which will help ascertain those most in need of intervention.
Assuntos
Síndrome de Noonan/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Adulto , Idoso , Estatura , Causas de Morte , Criança , Escolaridade , Emprego , Feminino , Seguimentos , Crescimento , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/terapia , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Mutação , Síndrome de Noonan/fisiopatologia , Síndrome de Noonan/reabilitação , Fenótipo , Prognóstico , Proteína Tirosina Fosfatase não Receptora Tipo 11 , Proteínas Tirosina Fosfatases/genéticaRESUMO
A general method for synthesis of insect pheromones having alkyl branched carbon skeletons is demonstrated with the preparation of a diastereomeric mixture of 8-methyl-2-decanol, whose propionate is an attractant of someDiabrotica species. The procedure involves reaction of a ketone with lithium acetylide ethylenediamine complex to afford a propargylic alcohol containing the branch of the target molecule. Copper (1) mediated alkylation of the derived propargylic acetate with a primary alkyl halide yields a trisubstituted allene having the desired chain length, and isomerization with an alkali metal amide of either ethylenediamine or 1,3-diaminopropane, affords the alkyl branched terminal acetylene. The triple bond is converted to the methyl ketone and reduced to the methyl carbinol. The reactions proceed in good yield, and can be conveniently carried out on large scale. The method should prove useful for production of pheromone components in cases where diastereomeric mixtures can be employed.
RESUMO
Chlamydia trachomatis is an obligate intracellular bacterium causing human ocular and genital disease. The lymphokine interferon gamma (IFN-gamma) is an important immune effector exerting antimicrobial effects towards several intracellular parasites, the chlamydia included. IFN-gamma has been reported to inhibit the chlamydial replication in vitro in part by depleting intracellular levels of tryptophan in a dose-dependent manner. In addition, down-regulation of important immunogens has been described. These findings are extended in this paper, in which we are combining pulse labeling with [35S]methionine and two-dimensional gel electrophoresis with immobilized pH gradients in order to investigate changes in the protein expression of C. trachomatis serovar A and L2 caused by treatment with IFN-gamma. In contrast to what was observed in C. trachomatis L2, our results showed that, in C. trachomatis A, down-regulations of the chlamydia major outer membrane protein and of several other proteins were detectable upon IFN-gamma treatment. In addition, we report the up-regulations of C. trachomatis A and L2 proteins with molecular masses of approximately 30 kDa and 40 kDa which may be part of an, as yet, uncharacterized chlamydial response to IFN-gamma treatment.
Assuntos
Antígenos de Bactérias , Proteínas de Bactérias/biossíntese , Chlamydia trachomatis/efeitos dos fármacos , Eletroforese em Gel Bidimensional , Interferon gama/farmacologia , Anticorpos Monoclonais , Proteínas da Membrana Bacteriana Externa , Chlamydia trachomatis/metabolismo , Regulação para Baixo , Técnica Indireta de Fluorescência para Anticorpo , Células HeLa , Humanos , Proteínas de Membrana , Microscopia de Fluorescência , SorotipagemRESUMO
The HeLa cell line, a human adenocarcinoma, is used in many research fields, since it can be infected with a wide range of viruses and intracellular bacteria. Therefore, the mapping of HeLa cell proteins is useful for the investigation of parasite host cell interactions. Because of the recent improvements of two-dimensional gel electrophoresis with immobilized pH gradients (IPG) compared to isoelectric focusing with carrier ampholytes, a highly reproducible method for examining global changes in HeLa cell protein expression due to different stimuli is now available. Therefore, we have initiated the mapping of [35S]methionine/cysteine-labeled HeLa cell proteins with the 2-D PAGE (IPG)-system, using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and N-terminal sequencing for protein identification. To date 21 proteins have been identified and mapped. In order to make these and future data accessible for interlaboratory comparison, we constructed a 2-D PAGE database on the World Wide Web.
Assuntos
Resinas Acrílicas , Bases de Dados Factuais , Eletroforese em Gel Bidimensional/métodos , Mapeamento de Peptídeos/métodos , Proteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Células HeLa , Interações Hospedeiro-Parasita , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Proteínas/isolamento & purificação , SoftwareRESUMO
Interferon gamma (IFN-gamma) is a potent immunomodulatory lymphokine, secreted by activated T-lymphocytes and NK-cells during the cellular immune response. Actions of IFN-gamma are mediated through binding to the IFN-gamma-receptor, present on most cells, and the subsequent activation of a great magnitude of IFN-gamma responsive genes has been reported previously. Our goal is to identify and map IFN-gamma-regulated HeLa cell proteins to the two-dimensional polyacrylamide gel electrophoresis with the immobilized pH gradient (IPG) two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) system. A semiconfluent layer of HeLa cells was grown on tissue culture plates, and changes in protein expression due to 100 U/mL IFN-gamma were investigated at different periods after treatment, using pulse labeling with [35S]methionine/cysteine in combination with 2-D PAGE (IPG). The identity of eight protein spots was elucidated by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS), and several variants of the IFN-gamma-inducible tryptophanyl-tRNA synthetase (hWRS) were detected by immunoblotting.
Assuntos
Cisteína Endopeptidases , Eletroforese em Gel Bidimensional/métodos , Interferon gama/imunologia , Mapeamento de Peptídeos/métodos , Proteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Sequência de Aminoácidos , Anexina A1/análise , Cisteína , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Interferon gama/farmacologia , Queratinas/análise , Metionina , Dados de Sequência Molecular , Proteínas/imunologia , Proteínas/isolamento & purificação , Radioisótopos de Enxofre , Triptofano-tRNA Ligase/análise , Regulação para CimaRESUMO
Membrane-bound immunoglobulin (mIg) is the antigen receptor on B lymphocytes mediating early events in antigen presentation and signal transduction. Wild-type human mIgM constructs transfected into the murine B-cell lymphoma A20 are expressed as transmembrane proteins with antigen presentation and signaling functions comparable to the endogenous mIgG2A; the transfected wild-type mIgM is internalized rapidly after anti-Ig cross-linking. Transfected constructs lacking the normal three-amino acid cytoplasmic tail are expressed exclusively as phosphatidylinositol-linked proteins, lack both antigen presentation and signal transduction functions, and are internalized slowly following anti-Ig binding. The molecular mass of the cytoplasmic tail-deleted phosphatidylinositol-linked Ig molecule is consistent with cleavage of the transmembrane residues during processing. Cytoplasmic domains may therefore regulate the mode of expression of membrane proteins and thereby influence their functional capabilities.
Assuntos
Imunoglobulina M/fisiologia , Proteínas de Membrana/fisiologia , Fosfatidilinositóis/metabolismo , Receptores de Antígenos de Linfócitos B/fisiologia , Animais , Antígenos/metabolismo , Clonagem Molecular , Endocitose , Humanos , Técnicas In Vitro , Camundongos , Proteínas Recombinantes , Transdução de Sinais , Relação Estrutura-AtividadeRESUMO
During B cell development, rearrangement and expression of Ig heavy chain (HC) genes promote development and expansion of pre-B cells accompanied by the onset of Ig light chain (LC) variable region gene assembly. To elucidate the signaling pathways that control these events, we have tested the ability of activated Ras expression to promote B cell differentiation to the stage of LC gene rearrangement in the absence of Ig HC gene expression. For this purpose, we introduced an activated Ras expression construct into JH-deleted embryonic stem cells that lack the ability to assemble HC variable region genes and assayed differentiation potential by recombination activating gene (RAG) 2-deficient blastocyst complementation. We found that activated Ras expression induces the progression of B lineage cells beyond the developmental checkpoint ordinarily controlled by mu HC. Such Ras/JH-deleted B cells accumulate in the periphery but continue to express markers associated with precursor B cells including RAG gene products. These peripheral Ras/JH-deleted B cell populations show extensive Ig LC gene rearrangement but maintain an extent of kappa LC gene rearrangement and a preference for kappa over lambda LC gene rearrangement similar to that of wild-type B cells. We discuss these findings in the context of potential mechanisms that may regulate Ig LC gene rearrangement.
Assuntos
Linfócitos B/imunologia , Proteínas de Ligação a DNA/metabolismo , Rearranjo Gênico de Cadeia Leve de Linfócito B , Genes de Imunoglobulinas , Cadeias Pesadas de Imunoglobulinas/genética , Proteínas ras/metabolismo , Animais , Linfócitos B/citologia , Sequência de Bases , Blastocisto/citologia , Blastocisto/imunologia , Diferenciação Celular , Proteínas de Ligação a DNA/genética , Embrião de Mamíferos , Cadeias Leves de Imunoglobulina/genética , Região Variável de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/genética , Rim/imunologia , Camundongos , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Baço/imunologia , Células-Tronco/imunologia , Transfecção , Proteínas ras/genéticaRESUMO
The membrane-bound form of immunoglobulin serves as an antigen-specific receptor for B cells mediating signal transduction and antigen presentation. We have developed an assay that reconstitutes both these physiologic responses with respect to the antigen phosphorylcholine. By introducing specific mutations in the human Ig mu chain gene, we have shown that certain transmembrane residues and the short cytoplasmic domain are crucial for these two activities. Moreover, elimination of a single transmembrane hydroxyl group severely inhibits antigen presentation without affecting signal transduction, suggesting that these two functions are mediated by different protein interactions.
Assuntos
Formação de Anticorpos , Antígenos/imunologia , Cadeias mu de Imunoglobulina/genética , Receptores de Antígenos de Linfócitos B/genética , Transdução de Sinais , Sequência de Aminoácidos , Animais , Linfócitos B/imunologia , Sequência de Bases , Cálcio/metabolismo , Linhagem Celular , Membrana Celular/imunologia , Citoplasma/imunologia , Humanos , Cinética , Camundongos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Sondas de Oligonucleotídeos , Homologia de Sequência do Ácido Nucleico , TransfecçãoRESUMO
Transgenic mice carrying an immunoglobulin enhancer-driven c-myc oncogene develop rapid-onset pre-B cell lymphomas. The incidence of these malignancies is greatly reduced when an additional transgene encoding the membrane-bound form (but not the secreted form) of human Ig mu is bred into the susceptible strain. This suppressive effect correlates with a subtle alteration in B-cell development induced by the immunoglobulin transgene.
Assuntos
Genes de Imunoglobulinas , Linfoma/genética , Proteínas Proto-Oncogênicas/genética , Proto-Oncogenes , Vírus da Leucemia Murina de Abelson , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Medula Óssea/patologia , Transformação Celular Neoplásica , Transformação Celular Viral , Elementos Facilitadores Genéticos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Cadeias mu de Imunoglobulina/genética , Linfoma/imunologia , Linfoma/patologia , Camundongos , Camundongos Transgênicos , Fenótipo , Proteínas Proto-Oncogênicas c-myc , RNA Mensageiro/metabolismoRESUMO
Structural analogues of the phytohormone (+)-abscisic acid (ABA) have been synthesized and tested as inhibitors of the catabolic enzyme (+)-ABA 8'-hydroxylase. Assays employed microsomes from suspension-cultured corn cells. Four of the analogues [(+)-8'-acetylene-ABA, (+)-9'-propargyl-ABA, (-)-9'-propargyl-ABA, and (+)-9'-allyl-ABA] proved to be suicide substrates of ABA 8'-hydroxylase. For each suicide substrate, inactivation required NADPH, increased with time, and was blocked by addition of the natural substrate, (+)-ABA. The most effective suicide substrate was (+)-9'-propargyl-ABA (K(I) = 0.27 microM). Several analogues were competitive inhibitors of ABA 8'-hydroxylase, of which the most effective was (+)-8'-propargyl-ABA (K(i) = 1.1 microM). Enzymes in the microsomal extracts also hydroxylated (-)-ABA at the 7'-position at a low rate. This activity was not inhibited by the suicide substrates, showing that the 7'-hydroxylation of (-)-ABA was catalyzed by a different enzyme from that which catalyzed 8'-hydroxylation of (+)-ABA. Based on the results described, a simple model for the positioning of substrates in the active site of ABA 8'-hydroxylase is proposed. In a representative physiological assay, inhibition of Arabidopsis thaliana seed germination, (+)-9'-propargyl-ABA and (+)-8'-acetylene-ABA exhibited substantially stronger hormonal activity than (+)-ABA itself.
Assuntos
Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/química , Oxigenases de Função Mista/antagonistas & inibidores , Ácido Abscísico/agonistas , Ácido Abscísico/análogos & derivados , Ácido Abscísico/química , Ácido Abscísico/metabolismo , Ligação Competitiva , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Germinação , Hidroxilação , Cinética , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Reguladores de Crescimento de Plantas/síntese química , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas , Sementes/enzimologia , Sementes/fisiologia , Especificidade por SubstratoRESUMO
BACKGROUND: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. METHODS: We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. RESULTS: A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. CONCLUSIONS: Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.