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1.
Indian J Public Health ; 64(1): 55-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189684

RESUMO

BACKGROUND: The "Child Health Screening and Early Intervention Services" program aims at early detection and management of the four dimensions prevalent in children-defects at birth, diseases in children, deficiency conditions, and developmental delays, including disabilities. OBJECTIVE: The objective of the study was to assess the morbidity profile of children from birth to 18 years of age screened in the district early intervention center (DEIC). METHODS: A record-based descriptive study was done in the DEIC in Chittoor, Andhra Pradesh. The data were retrieved for 1-year from April 2017 to March 2018 into the excel sheet, and the combined master sheet was prepared for analysis. The analysis was done with SPSS 21.0 Version. RESULTS: A total of 10571 children were screened and referred to the DEIC during the period. Out of them, 5679 (53.7%) were male and 4892 (46.3%) were female. Among all the four types of morbidities screened, majority 4847 (45.9%) were having the childhood diseases, 4177 (39.5%) had developmental delays including disabilities, 1067 (10.1%) had different deficiencies, and 361 (3.4%) had birth defects. Among the adolescent health issues, 119 (1.1%) were screened and sent for the early intervention to the district hospital. CONCLUSIONS: A huge number of children were screened and referred to the DEIC every year for intervention. The health sector has to focus more on the resources like workforce, training of peripheral health workers at regular intervals about the different morbidities screened, that would help in identifying the morbidities at the earliest possible time and receive the intervention at the best center.


Assuntos
Saúde do Adolescente/estatística & dados numéricos , Saúde da Criança/estatística & dados numéricos , Anormalidades Congênitas/epidemiologia , Deficiências do Desenvolvimento/epidemiologia , Intervenção Médica Precoce/estatística & dados numéricos , Hospitais de Distrito/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Deficiências Nutricionais/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Prevalência , Encaminhamento e Consulta/estatística & dados numéricos , Fatores de Risco
2.
Br J Dermatol ; 180(1): 165-171, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30033560

RESUMO

BACKGROUND: The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a reliable outcome measure for cutaneous lupus erythematosus (CLE) in adults used in clinical trials. However, it has not been validated in children, limiting clinical trials for paediatric CLE. OBJECTIVES: This study aimed to validate the CLASI in paediatrics. METHODS: Eleven paediatric patients with CLE, six dermatologists and six rheumatologists participated. The physicians were trained to use the CLASI and Physician's Global Assessment (PGA), and individually rated all patients using both tools. Each physician reassessed two randomly selected patients. Within each physician group, the intraclass correlation coefficient (ICC) was calculated to assess the reliability of each measure. RESULTS: CLASI activity scores demonstrated excellent inter- and intrarater reliability (ICC > 0·90), while the PGA activity scores had good inter-rater reliability (ICC 0·73-0·77) among both specialties. PGA activity scores showed excellent (ICC 0·89) and good intrarater reliability (ICC 0·76) for dermatologists and rheumatologists, respectively. Limitations of this study include the small sample size of patients and potential recall bias during the physician rerating session. CONCLUSIONS: CLASI activity measurement showed excellent inter- and intrarater reliability in paediatric CLE and superiority over the PGA. These results demonstrate that the CLASI is a reliable and valid outcome instrument for paediatric CLE.


Assuntos
Lúpus Eritematoso Cutâneo/diagnóstico , Índice de Gravidade de Doença , Adolescente , Criança , Dermatologistas , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Reumatologistas , Adulto Jovem
3.
Lupus ; 20(9): 952-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21676918

RESUMO

The objective of the study was to compare clinical features, treatment and disease outcome in patients with early versus later onset of childhood-onset systemic lupus erythematosus (cSLE). A retrospective matched cohort study of cSLE patients diagnosed between 1988 and 2008 and followed for a minimum of one year was conducted. Thirty-four pre-pubertal cSLE patients with disease onset prior to their 12th birthday were matched by ethnicity and year of diagnosis to 34 pubertal cSLE patients. The most common criteria at diagnosis in both groups were malar rash, arthritis, hematologic manifestations, and renal disease. After a mean follow-up of more than six years, a similar proportion of patients in the two groups were still prescribed corticosteroids (47% and 41%); patients in the early onset group required a significantly higher daily dose (0.6 mg/kg prednisone-equivalent versus 0.2 mg/kg, p < 0.05). There were no significant differences in organ involvement, disease activity and disease damage between the two groups, and severe complications occurred at similar rates. There were a greater number of admissions to the pediatric intensive care unit (PICU) in the early onset group (18 versus 5, p = 0.01), with time-to-event analysis demonstrating a significantly shorter disease duration from diagnosis to first PICU admission in the early onset group (p < 0.001). While a similar proportion of patients in the early and later onset groups required treatment with cyclophosphamide, patients in the early onset group received treatment earlier in their disease course (mean 13.7 versus 19.9 months, p < 0.001). Early onset cSLE leads to earlier and more frequent PICU admission, earlier use of cyclophosphamide, and higher corticosteroid dose at long-term follow-up.


Assuntos
Idade de Início , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Resultado do Tratamento , Adolescente , Anti-Inflamatórios/uso terapêutico , Criança , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Progressão da Doença , Etnicidade , Feminino , Humanos , Imunossupressores/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Estimativa de Kaplan-Meier , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Nefropatias/fisiopatologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Masculino , Prednisona/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença
4.
J Cell Biol ; 82(1): 1-16, 1979 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-383723

RESUMO

Fibronectin (FN; also called large external transformation-sensitive [LETS] protein or cell-surface protein [CSP]) is a large cell-surface glycoprotein that is frequently observed to be either absent or greatly reduced on the surfaces of malignant cells grown in vitro. Because FN may be a useful molecular marker of cellular malignancy, we have carried out an extensive screening to test the specific association among the degree of expression of FN, anchorage-independent growth, and tumorigenicity in the athymic nude mouse. A variety of diploid cell strains and established cell lines were tested for the expression of surface FN by indirect immunofluorescence using rabbit antisera against human cold insoluble globulin, rodent plasma FN, or chicken cell-surface FN. Concomitantly, the cells were assayed for tumor formation in nude mice and for the ability to form colonies in methylcellulose. Tumorigenic cells often showed very low surface fluorescence, confirming earlier reports. However, many highly tumorigenic fibroblast lines from several species stained strongly with all three antisera. In contrast, the anchorage-independent phenotype was nearly always associated with tumorigenicity in approximately 35 cell lines examined in this study. In another series of experiments, FN-positive but anchorage-independent cells were grown as tumors in nude mice and then reintroduced into culture. In five of the six tumor-derived cell lines, cell-surface FN was not significantly reduced; one such cell line showed very little surface FN. Our data thus indicate that the loss of cell-surface FN is not a necessary step in the process of malignant transformation and that the growth of FN-positive cells as tumors does not require a prior selection in vivo for FN-negative subpopulations.


Assuntos
Glicoproteínas/análise , Proteínas de Membrana/análise , Proteínas de Neoplasias/análise , Neoplasias Experimentais/etiologia , Animais , Adesão Celular , Linhagem Celular , Transformação Celular Neoplásica , Transformação Celular Viral , Imunofluorescência , Humanos , Camundongos , Camundongos Nus
5.
J Clin Invest ; 48(1): 96-104, 1969 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-4303791

RESUMO

Angiotensin infusion evokes marked increases in aldosterone secretion in primary aldosteronism and little change in secondary aldosteronism. The low plasma renin activity of primary aldosteronism and the elevated plasma renin activity of secondary aldosteronism are thought to account for this differential response. The effect of angiotensin on aldosterone and 18-hydroxycorticosterone secretion was studied during adrenal vein catheterization in seven patients with primary aldosteronism (whose plasma renin activity had been elevated following spironolactone therapy), one hypertensive patient with normal plasma renin activity and normal aldosterone secretion, two patients with secondary aldosteronism who had elevated plasma renin activity, and one anephric patient whose plasma renin activity was 0. Adrenal venous aldosterone and 18-hydroxycorticosterone were measured before and after a ten min sub-pressor angiotensin infusion. The cells of the aldosterone-producing adenoma (APA) respond to small increases in plasma angiotensin with large increases in secretion of aldosterone and 18-hydroxycorticosterone. The dose of angiotensin capable of evoking this response from the aldosterone-producing adenoma produces little or no change in the secretion of the steroids from nontumorous glands. The augmentation of aldosterone secretion, induced by angiotensin, in primary aldosteronism is due solely to increased secretion by the adenoma and not by the contralateral zona glomerulosa. The increased sensitivity of the aldosterone-producing adenoma is characteristic of the tumor. This response is independent of fluctuations in endogenous plasma renin activity. This sensitivity is not blunted by high plasma renin activity, nor is it a function of tumor mass for the effect is observed in aldosterone-producing adenomas regardless of size. ACTH injection after angiotensin infusion resulted in a marked increase in aldosterone concentration in the effluent from the nontumorous adrenal, but was not capable of producing further increases in aldosterone concentration in the effluent from the APA. In view of this exquisite sensitivity to infused angiotensin, it may be that the small variations in endogenous plasma renin activity that have been observed in primary aldosteronism may be capable of evoking large changes in aldosterone secretion in patients with aldosterone-producing adenomas.


Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/fisiologia , Aldosterona/metabolismo , Angiotensina II/farmacologia , Hiperaldosteronismo , Glucocorticoides/metabolismo , Humanos , Testes de Função Adreno-Hipofisária , Renina/metabolismo , Espironolactona/uso terapêutico
6.
Structure ; 8(11): 1203-14, 2000 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11080642

RESUMO

BACKGROUND: The traditional picture of charged amino acids in globular proteins is that they are almost exclusively on the outside exposed to the solvent. Buried charges, when they do occur, are assumed to play an essential role in catalysis and ligand binding, or in stabilizing structure as, for instance, helix caps. RESULTS: By analyzing the amount and distribution of buried charged surface and charges in proteins over a broad range of protein sizes, we show that buried charge is much more common than is generally believed. We also show that the amount of buried charge rises with protein size in a manner which differs from other types of surfaces, especially aromatic and polar uncharged surfaces. In large proteins such as hemocyanin, 35% of all charges are greater than 75% buried. Furthermore, at all sizes few charged groups are fully exposed. As an experimental test, we show that replacement of the buried D178 of muconate lactonizing enzyme by N stabilizes the enzyme by 4.2 degrees C without any change in crystallographic structure. In addition, free energy calculations of stability support the experimental results. CONCLUSIONS: Nature may use charge burial to reduce protein stability; not all buried charges are fully stabilized by a prearranged protein environment. Consistent with this view, thermophilic proteins often have less buried charge. Modifying the amount of buried charge at carefully chosen sites may thus provide a general route for changing the thermophilicity or psychrophilicity of proteins.


Assuntos
Conformação Proteica , Proteínas/química , Eletricidade Estática , Substituição de Aminoácidos , Animais , Fenômenos Químicos , Físico-Química , Temperatura Baixa , Bases de Dados Factuais , Glucosiltransferases/química , Hemocianinas/química , Liases Intramoleculares/química , Liases Intramoleculares/genética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Dobramento de Proteína , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Solubilidade
7.
Biochim Biophys Acta ; 592(2): 267-76, 1980 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-6773565

RESUMO

Low temperature (-196C) and room temperature (25C) absorption spectra of a family of allophycocyanin spectral forms isolated from Nostoc sp. phycobilisomes as well as of the phycobilisomes themselves have been analyzed by Gaussian curve-fitting. Allophycocyanin I and B share long wavelength components at 668 and 679 nm, bands that are absent from allophycocyanin II and III. These long wavelength absorption components are apparently responsible for the 20 nm difference between the 680 nm fluorescence emission maximum of allophycocyanin I and B and the 660 nm maximum of II and III. This indicates that allophycocyanin I and B are the final acceptors of excitation energy in the phycobilisome and the excitation energy transfer bridge linking the phycobilisome with the chlorophyll-containing thylakoid membranes. These Gaussian components are also found in resolved spectra of phycobilisomes, are arguing against this family of allophycocyanin molecules being artifactual products of protein purification procedures.


Assuntos
Ficocianina/análise , Pigmentos Biológicos/análise , Cianobactérias , Ficobilissomas , Análise Espectral
8.
J Am Coll Cardiol ; 5(6): 1326-34, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3923077

RESUMO

A hemodynamic-radionuclide study was performed to compare the relations between end-systolic pressure and volume in the left and right ventricles in 10 patients with biventricular failure, and to correlate the end-systolic pressure-volume slope with baseline variables of systolic function. During nitroprusside or nitroglycerin infusion, or a combination of both, linear relations were found between end-systolic pressure and volume for both ventricles. In 9 of 10 patients, the end-systolic pressure-volume slope was greater for the left ventricle (mean +/- SD 1.12 +/- 0.36 mm Hg X m2/ml) than for the right ventricle (0.46 +/- 0.27 mm Hg X m2/ml) (p less than 0.001). In all 10 patients, the volume-axis intercept of the pressure-volume relation was greater for the left ventricle (82 +/- 66 ml/m2) than for the right ventricle (2 +/- 30 ml/m2) (p less than 0.005). Right ventricular pressure-volume slope correlated weakly with baseline right ventricular ejection fraction (r = 0.69, p less than 0.05), strongly with the baseline right ventricular end-systolic pressure-volume ratio (r = 0.89) and inversely with baseline right ventricular end-systolic volume (r = -0.86). In conclusion, 1) in patients with severe biventricular failure, changes in systolic pressure influence end-systolic volume more strongly in the right than in the left ventricle. 2) For the right ventricle, the slope of the end-systolic pressure-volume relation is directly related to rest indexes of systolic function. 3) The greater the end-systolic volume at rest, the greater the predicted improvement in right ventricular emptying for any vasodilator-induced reduction in pulmonary artery end-systolic pressure.


Assuntos
Pressão Sanguínea , Débito Cardíaco , Insuficiência Cardíaca/fisiopatologia , Coração/fisiopatologia , Volume Sistólico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Coração/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Nitroglicerina/farmacologia , Nitroprussiato/farmacologia , Cintilografia , Volume Sistólico/efeitos dos fármacos
9.
J Mol Biol ; 254(5): 918-41, 1995 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-7500361

RESUMO

We report here the refined X-ray crystal structure of muconate lactonizing enzyme (MLE) from Pseudomonas putida PRS2000 at a resolution of 1.85 A with an R-factor of 16.8%. An enzyme from the beta-ketoadipate pathway, MLE catalyses the conversion of cis,cis-muconate to muconolactone. It is a homo-octamer, one monomer consisting of 373 amino acid residues. MLE has two large domains and a C-terminal subdomain: an alpha + beta domain, an alpha beta-barrel domain and a C-terminal meandering subdomain. The alpha beta-barrel domain is highly irregular. Its structure is (beta/alpha)7 beta, with the structural role of the last alpha-helix being replaced by both the C-terminal subdomain and part of the N-terminal domain. The fifth, seventh and eighth barrel strands are unusual because they have left-handed twist about their axes. The strand crossing angles also vary enormously, from +9 degrees to -69 degrees; the first and last strands, which close the barrel, cross at an angle of -69 degrees, making extensive strand-strand hydrogen bonding impossible. The first barrel strand is also unusual because it starts in the N-terminal domain and forms hydrogen bonds to the C-terminal subdomain beta-sheet as well as to its neighbouring strands in the barrel. It thus cements the whole protein together. As in other alpha beta-barrel proteins, the active site of MLE, present in each subunit is at the C-terminal ends of the barrel beta-strands. The active site cleft contains an essential manganese ion, is lined with charged and other polar residues, and contains many of the crystallographic water molecules. The manganese ion is octahedrally co-ordinated to three side-chain carboxylate groups and three water molecules, and is at the centre of a radiating web of ionic and hydrogen-bonding interactions. Additionally, two water molecules are buried in the centre of the barrel and two hydrophilic side-chains (Lys167 and Arg196) make both hydrophobic and hydrophilic packing interactions with much of the barrel interior. The barrel interior is thus also unusual because it is so hydrophilic; the dominating force appears to be the need to solvate the metal ion effectively. This might account for the irregularity of the barrel. The catalytic mechanism has been investigated by docking both substrate and product in the active site with the C-COO- of muconolactone superimposed on the corresponding atoms of cis,cis-muconate. In agreement with earlier kinetic and spectroscopic results, the manganese ion does not interact directly with substrate or product.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Liases Intramoleculares , Isomerases/química , Pseudomonas putida/enzimologia , Cristalização , Cristalografia por Raios X , Conformação Proteica , Dobramento de Proteína , Estrutura Secundária de Proteína
10.
J Mol Biol ; 245(4): 311-4, 1995 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-7837264

RESUMO

An effective method for the determination of the activity of signal peptidase I (SPase I) of Escherichia coli is established using the hybrid protein pro-OmpA-nuclease A as substrate. Pro-OmpA-nuclease A, a hybrid secretory precursor was purified to homogeneity under denaturing conditions. When this protein was refolded, it could be quantitatively processed by purified SPase I. The Km of signal peptidase I was 0.0165 mM. The kcat was 8.73 s-1. The Km is 50 to 100 times lower than that obtained with peptide substrates indicating that SPase I has a significantly greater affinity for the protein substrate. The turnover number, kcat, is two to four orders of magnitude greater as well. Thus, the specificity constant, kcat/Km is six orders of magnitude greater with pro-OmpA-nuclease A than with peptide substrates. This is the first determination of kinetics of SPase I with a protein substrate.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Endopeptidases/metabolismo , Proteínas de Escherichia coli , Proteínas de Membrana , Nuclease do Micrococo/metabolismo , Precursores de Proteínas/metabolismo , Serina Endopeptidases , Sequência de Aminoácidos , Escherichia coli/enzimologia , Hidrólise , Cinética , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional
11.
Protein Sci ; 3(4): 638-49, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8003982

RESUMO

The slow refolding of guanidine-HCl-denatured ribonuclease-A was studied by volume change and by kinetic CD at 222 and 276 nm. Dilatometric measurements revealed that on refolding there is a fast volume change of +232 mL/mol of protein. This is followed by a very slow nonexponential change that takes about 25 min to reach equilibrium. By adding varying amounts of (NH4)2SO4, the slow volume change curve was resolved into 2 concurrent reactions. The faster of the 2 slow events entails a negative volume change of -64 mL/mol of protein and appears to arise from proline isomerization. The slower process, attended by a positive change of +53 mL/mol of protein, has properties consistent with the "XY" reaction of Lin and Brands (1983, Biochemistry 22:563-573). This reaction is so named because the conformational nature of neither its initial (Y) nor its final state (X) is known; the transition is characterized solely by its absorbance and fluorescence kinetics. These are the first direct physical measures attributable to the "XY" process. The early formation of a compact structure in the event responsible for the rapid +232-mL/mol volume change, however, is consistent with the sequential model of folding (Cook KH, Schmid FX, Baldwin RL, 1979, Proc Natl Acad Sci USA 76:6157-6161; Kim PS, Baldwin RL, 1980, Biochemistry 19:6124-6129). The usefulness of volume change measurements as a method of detecting structural rearrangements was confirmed by finding agreement between time constants obtained from parallel volume change and kinetic CD experiments. The measured volume changes arise from both changes in hydration and changes in the packing of atoms in the interior of the protein.


Assuntos
Dicroísmo Circular , Ribonuclease Pancreático/química , Animais , Bovinos , Cinética , Desnaturação Proteica , Dobramento de Proteína
12.
Protein Sci ; 4(7): 1426-9, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7670384

RESUMO

Volume changes among the unfolded (U), native (N), and molten globule (MG) conformations of horse heart ferricytochrome c have been measured. U to N (pH 2 to pH 7) was determined in the absence of added salt to be -136 +/- 5 mL/mol protein. U to MG (pH 2, no added salt to pH 2, 0.5 M KCl) yielded + 100 +/- 6 mL/mol. MG to N was broken into two steps, N to NClx at pH 7 by addition of buffered KCl to buffered protein lacking added salt (NClx = N interacting with an unknown number, X, of chloride ions), and MG to NClx by jumping MG at pH 2 in 0.5 M KCl to pH7 at the same salt concentration. The delta V of N to NClx was -30.9 +/- 1.4 mL/mol protein, whereas MG to NClx entailed a delta V of -235 +/- 6 mL/mol. Within experimental error, the results add up to zero for a complete thermodynamic cycle. We believe this to be the first volumetric cycle to have been measured for the conformational transitions of a protein. The results are discussed in terms of hydration contributions from deprotonation of the protein, other hydration effects, and the formation and/or enlargement of packing defects in the protein's tertiary structure during the steps of folding.


Assuntos
Grupo dos Citocromos c/química , Animais , Fenômenos Químicos , Físico-Química , Cavalos , Concentração de Íons de Hidrogênio , Miocárdio/química , Cloreto de Potássio/farmacologia , Conformação Proteica , Dobramento de Proteína , Termodinâmica
13.
Protein Sci ; 4(10): 2168-78, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8535254

RESUMO

The Saccharomyces cerevisiae adhesion protein alpha-agglutinin is expressed by cells of alpha mating type. On the basis of sequence similarities, alpha-agglutinin has been proposed to contain variable-type immunoglobulin-like (IgV) domains. The low level of sequence similarity to IgV domains of known structure made homology modeling using standard sequence-based alignment algorithms impossible. We have therefore developed a secondary structure-based method that allowed homology modeling of alpha-aggulutinin domain III, the domain most similar to IgV domains. The model was assessed and where necessary refined to accommodate information obtained by biochemical and molecular genetic approaches, including the positions of a disulfide bond, glycosylation sites, and proteolytic sites. The model successfully predicted surface exposure of glycosylation and proteolytic sites, as well as identifying residues essential for binding activity. One side of the domain was predicted to be covered by carbohydrate residues. Surface accessibility and volume packing analyses showed that the regions of the model that have greatest sequence dissimilarity from the IgV consensus sequence are poorly structured in the biophysical sense. Nonetheless, the utility of the model suggests that these alignment and testing techniques should be of general use for building and testing of models of proteins that share limited sequence similarity with known structures.


Assuntos
Região Variável de Imunoglobulina/química , Peptídeos/química , Conformação Proteica , Estrutura Secundária de Proteína , Saccharomyces cerevisiae/fisiologia , Aglutininas/química , Sequência de Aminoácidos , Sequência Consenso , Fator de Acasalamento , Modelos Moleculares , Dados de Sequência Molecular , Biossíntese Peptídica , Homologia de Sequência de Aminoácidos
14.
Protein Sci ; 10(6): 1113-23, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11369849

RESUMO

The yeast cell adhesion protein alpha-agglutinin is expressed on the surface of a free-living organism and is subjected to a variety of environmental conditions. Circular dichroism (CD) spectroscopy shows that the binding region of alpha-agglutinin has a beta-sheet-rich structure, with only approximately 2% alpha-helix under native conditions (15-40 degrees C at pH 5.5). This region is predicted to fold into three immunoglobulin-like domains, and models are consistent with the CD spectra as well as with peptide mapping and site-specific mutagenesis. However, secondary structure prediction algorithms show that segments comprising approximately 17% of the residues have high alpha-helical and low beta-sheet potential. Two model peptides of such segments had helical tendencies, and one of these peptides showed pH-dependent conformational switching. Similarly, CD spectroscopy of the binding region of alpha-agglutinin showed reversible conversion from beta-rich to mixed alpha/beta structure at elevated temperatures or when the pH was changed. The reversibility of these changes implied that there is a small energy difference between the all-beta and the alpha/beta states. Similar changes followed cleavage of peptide or disulfide bonds. Together, these observations imply that short sequences of high helical propensity are constrained to a beta-rich state by covalent and local charge interactions under native conditions, but form helices under non-native conditions.


Assuntos
Peptídeos/química , Algoritmos , Sequência de Aminoácidos , Adesão Celular , Dicroísmo Circular , Dissulfetos , Meio Ambiente , Concentração de Íons de Hidrogênio , Imunoglobulinas/química , Fator de Acasalamento , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mapeamento de Peptídeos , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/química , Espectrofotometria Infravermelho , Temperatura , Raios Ultravioleta
15.
Am J Med ; 60(4): 523-30, 1976 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1274986

RESUMO

To determine the clinical usefulness of 67 gallium (Ga) scanning in the evaluation of patients with lymphomas, we reviewed 142 total body Ga scans performed on 44 patients with Hodgkin's disease and 53 patients with non-Hodgkin's lymphoma. Fifty-two per cent (123 of 236) of known disease sites were detected on scan. The false-positive rate was less than 5 per cent. The accuracy of detecting lymphoma varied in individual anatomic areas from 33 per cent in the axilla to 73 per cent in the thorax. In eight patients with bone involvement, all bone lesions were detected on scan. The size of the lesion appeared to influence accuracy, since tumors greater than 3 cm in diameter were more often positive.


Assuntos
Radioisótopos de Gálio , Linfoma/diagnóstico , Cintilografia , Adolescente , Adulto , Idoso , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Linfografia , Linfoma/diagnóstico por imagem , Linfoma/patologia , Masculino
16.
Pediatrics ; 98(5): 890-7, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8909482

RESUMO

OBJECTIVES: National data now exist on incidence, prevalence, and cost of injury. However, the personal impact of injury on work and family finances has not been thoroughly studied. We examine the extent and nature of work and financial problems after pediatric trauma and identify predictors. Clinicians are alerted so they can better counsel parents about potential postinjury work and financial difficulties. METHODS: Staff collected comprehensive data on the acute care and short-term rehabilitation of 182 Massachusetts children with injuries. Consenting parents were surveyed and their children were given a battery of medical, functional, and psychosocial tests. Information on work and financial impact at 1 and 6 months postinjury was available from 120 parents. RESULTS: Given these children's generally mild injuries, the impact on work and family finances was remarkable. For many families work and financial problems were short-lived; however, for others serious problems remained at 6 months postdischarge. Families whose children were severely injured were at highest risk for work and financial problems. Middle-class parents and parents on public assistance or in our other insurance category reported more work and financial problems than those in health maintenance organizations. Long acute hospital stay and four or more impairments at discharge were also strong predictors. CONCLUSION: Childhood injury can lead to serious work and financial problems for families. Given the central role of the family in pediatric rehabilitation, clinicians and policymakers involved in acute trauma care and rehabilitation should pay greater attention to the financial repercussions of injury.


Assuntos
Família , Trabalho , Ferimentos e Lesões/economia , Criança , Feminino , Humanos , Renda , Escala de Gravidade do Ferimento , Tempo de Internação , Masculino , Massachusetts , Classe Social , Inquéritos e Questionários , Ferimentos e Lesões/reabilitação , Ferimentos e Lesões/terapia
17.
J Nucl Med ; 17(7): 639-46, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-178842

RESUMO

The gross and subcellular localizations of 99mTc-labeled pyrophosphate and tetracycline in myocardial infarcts were studied in a rabbit model. Experiments utilizing double-nuclide labeling were carried out using a useful mapping technique. Concentration of the various chelates decreases in an expected manner from the center of the infarcted area toward its periphery, but it is higher near the epicardial surface than toward the endocardium. Technetium-99m-pyrophosphate is concentrated in the same infarcted areas as 45Ca ion or 32P-pyrophosphate, but to a much greater degree. The uptake is dependent on both the degree of necrosis and residual blood flow. Gel filtration experiments with rabbit serum indicate that 99mTc-tagged pyrophosphate, tetracycline, and diphosphonate are mainly protein-bound, whereas 32P-pyrophosphate is not. Subcellular localization studies show that 99mTc-tetracycline and 99mTc-pyrophosphate are bound primarily to soluble protein, and only a small fraction is associated with nuclei, mitochondria, and microsomes. The uptake of technetium chelates in myocardial infarcts may be due to the formation of polynuclear complexes with denatured macromolecules rather than to the deposition of calcium in mitochrondria.


Assuntos
Difosfatos , Infarto do Miocárdio/diagnóstico , Cintilografia , Tecnécio , Tetraciclina , Animais , Coelhos
18.
J Nucl Med ; 17(9): 786-7, 1976 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-956892

RESUMO

Immediately after brain scanning with 99mTc-glucoheptonate, the kidneys were imaged in 200 prospectively studied cases. Abnormalities were found in 22 cases (11%); they included renal metastases, renal cysts, and kidney displacement or obstruction by masses. In five instances, significant previously unknown abnormalities were found. The renal contours were usually better seen than on intravenous urograms or bone scans. Most kidney studies could be completed in less than 2 min, making renal imaging worthwhile as a low-cost high-yield routine addition to brain scanning.


Assuntos
Encefalopatias/diagnóstico , Nefropatias/diagnóstico , Cintilografia , Açúcares Ácidos , Tecnécio , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade
19.
Am J Cardiol ; 54(1): 132-6, 1984 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-6430055

RESUMO

The right ventricular (RV) end-systolic pressure-volume relation during vasodilator administration was studied in 10 patients with pulmonary arterial (PA) hypertension, most of whom had biventricular failure. RV end-systolic volumes were estimated from equilibrium radionuclide RV counts and forward cardiac output. Simultaneous radionuclide and hemodynamic values were measured at rest and during nitroglycerin and nitroprusside infusion. Vasodilator administration resulted in decreases in PA mean and systolic pressures in all 10 patients, with an average decrease in end-systolic pressure (p less than 0.001) from 48 +/- 11 to 38 +/- 9 and 35 +/- 10 mm Hg during nitroglycerin and nitroprusside administration, respectively. In each patient, a direct linear relation was observed between the vasodilator-induced decrease in PA end-systolic pressure and in RV end-systolic volume. Average RV end-systolic volume decreased (p less than 0.001), from 130 +/- 69 ml/m2 at baseline to 108 +/- 62 and 102 +/- 55 ml/m2 during nitroglycerin and nitroprusside infusion, respectively. The slope of the RV end-systolic pressure-volume relation was directly related to RV ejection fraction. Thus, the vasodilator-induced decrease in PA systolic pressure is accompanied by a linear decrease in RV end-systolic volume, with a slope which is dependent on RV systolic function. This linear relation is analogous to the left ventricular end-systolic pressure-volume relation.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Ferricianetos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Ventrículos do Coração/fisiopatologia , Hipertensão Pulmonar/tratamento farmacológico , Nitroglicerina/uso terapêutico , Nitroprussiato/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Adulto , Idoso , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Cintilografia
20.
Semin Nucl Med ; 5(4): 325-38, 1975 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-174226

RESUMO

Ultrasonic examination of the pancreas is rendered difficult by the echogenic characteristics of the organ, by its depth, by the overlying gas, and by bony structures and anatomic variations. The reintroduction of gray-scale imaging promises to simplify the technique and expand its usefulness. The 75Se-/-selenomethionine scan is a reliable test when performed after effective pancreatic stimulation with a scintillation camera that permits the angulation required to separate pancreas from liver. Gallium-67-citrate may be important for both mapping inflammatory processes and imaging some tumors. Retrograde pancreatography has developed into a rather reliable and sensitive method of visualizing pancreatic duct abnormalities. Angiography remains the most reliable technique for finding small lesions, while computerized axial tomography appears a promising modality in the near future. In acute pancreatitis, gallium scanning may find a place alongside plain films, GI series, and echography. Chronic pancreatitis appears best studied by pancreatography, possibly with selenomethionine scanning as a function study and echography to find associated mass lesions. Pseudocysts are most easily located by ultrasound examination. Screening for pancreatic carcinoma is done most effectively with selenomethionine scanning when the index of suspicion is low and with pancreatography or arteriography when it is high. Echography is useful for localization for aspiration biopsy and for sequential evaluation of therapeutic response. Islet-cell tumors are best found by angiographic studies.


Assuntos
Pancreatopatias/diagnóstico , Cintilografia , Ultrassonografia , Doença Aguda , Adenoma de Células das Ilhotas Pancreáticas/diagnóstico , Adulto , Feminino , Radioisótopos de Gálio , Hormônios Ectópicos/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Pancreatite/diagnóstico , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Selenometionina , Vasopressinas/metabolismo , Síndrome de Zollinger-Ellison/diagnóstico
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