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1.
Nat Clim Chang ; 8: 825-828, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319714

RESUMO

Global ecosystem function is highly dependent on climate and atmospheric composition, yet ecosystem responses to environmental changes remain uncertain. Cold, high-latitude ecosystems in particular have experienced rapid warming1, with poorly understood consequences2-4. Here, we use a satellite observed proxy for vegetation cover - the fraction of absorbed photosynthetically active radiation5 - to identify a decline in the temperature limitation of vegetation in global ecosystems between 1982 and 2012. We quantify the spatial functional response of maximum annual vegetation cover to temperature and show that the observed temporal decline in temperature limitation is consistent with expectations based on observed recent warming. An ensemble of Earth system models from the Coupled Model Intercomparison Project (CMIP5) mischaracterized the functional response to temperature, leading to a large overestimation of vegetation cover in cold regions. We identify a 16.4% decline in the area of vegetated land that is limited by temperature over the past three decades, and suggest an expected large decline in temperature limitation under future warming scenarios. This rapid observed and expected decline in temperature limitation highlights the need for an improved understanding of other limitations to vegetation growth in cold regions3,4,6, such as soil characteristics, species migration, recruitment, establishment, competition, and community dynamics.

2.
New Phytol ; 184(2): 387-398, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19694965

RESUMO

* We used an inadvertent whole-ecosystem 14C label at a temperate forest in Oak Ridge, Tennessee, USA to develop a model (Radix1.0) of fine-root dynamics. Radix simulates two live-root pools, two dead-root pools, non-normally distributed root mortality turnover times, a stored carbon (C) pool, and seasonal growth and respiration patterns. * We applied Radix to analyze measurements from two root size classes (< 0.5 and 0.5-2.0 mm diameter) and three soil-depth increments (O horizon, 0-15 cm and 30-60 cm). * Predicted live-root turnover times were < 1 yr and approximately 10 yr for short- and long-lived pools, respectively. Dead-root pools had decomposition turnover times of approximately 2 yr and approximately 10 yr. Realistic characterization of C flows through fine roots requires a model with two live fine-root populations, two dead fine-root pools, and root respiration. These are the first fine-root turnover time estimates that take into account respiration, storage, seasonal growth patterns, and non-normal turnover time distributions. * The presence of a root population with decadal turnover times implies a lower amount of belowground net primary production used to grow fine-root tissue than is currently predicted by models with a single annual turnover pool.


Assuntos
Carbono/metabolismo , Respiração Celular , Raízes de Plantas/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimento , Isótopos de Carbono , Ecossistema , Marcação por Isótopo/métodos , Modelos Biológicos , Raízes de Plantas/metabolismo , Estações do Ano , Tennessee , Fatores de Tempo , Árvores/metabolismo
3.
New Phytol ; 172(3): 523-35, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17083682

RESUMO

Characterization of turnover times of fine roots is essential to understanding patterns of carbon allocation in plants and describing forest C cycling. We used the rate of decline in the ratio of 14C to 12C in a mature hardwood forest, enriched by an inadvertent 14C pulse, to investigate fine-root turnover and its relationship with fine-root diameter and soil depth. Biomass and Delta14C values were determined for fine roots collected during three consecutive winters from four sites, by depth, diameter size classes (< 0.5 or 0.5-2 mm), and live-or-dead status. Live-root pools retained significant 14C enrichment over 3 yr, demonstrating a mean turnover time on the order of years. However, elevated Delta14C values in dead-root pools within 18 months of the pulse indicated an additional component of live roots with short turnover times (months). Our results challenge assumptions of a single live fine-root pool with a unimodal and normal age distribution. Live fine roots < 0.5 mm and those near the surface, especially those in the O horizon, had more rapid turnover than 0.5-2 mm roots and deeper roots, respectively.


Assuntos
Carbono/metabolismo , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/metabolismo , Solo , Árvores/metabolismo , Biomassa , Radioisótopos de Carbono/metabolismo , Ecossistema , Fatores de Tempo
4.
Risk Anal ; 24(1): 73-85, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15028002

RESUMO

Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure scenarios, skin surface loading and unloading rates, and contaminant movement through the epidermis. In this article we (1) develop and test a finite-difference model of contaminant transport through the epidermis; (2) develop archetypal exposure scenarios based on behavioral data to estimate characteristic loading and unloading rates; and (3) quantify 24-hour accumulation below the epidermis by applying a Monte Carlo simulation of these archetypal exposure scenarios. The numerical model, called Transient Transport through the epiDERMis (TTDERM), allows us to account for variable exposure times and time between exposures, temporal and spatial variations in skin and compound properties, and uncertainty in model parameters. Using TTDERM we investigate the use of a macro-activity parameter (cumulative contact time) for predicting daily (24-hour) integrated uptake of pesticides during complex exposure scenarios. For characteristic child behaviors and hand loading and unloading rates, we find that a power law represents the relationship between cumulative contact time and cumulative mass transport through the skin. With almost no loss of reliability, this simple relationship can be used in place of the more complex micro-activity simulations that require activity data on one- to five-minute intervals. The methods developed in this study can be used to guide dermal exposure model refinements and exposure measurement study design.


Assuntos
Poluentes Ambientais/toxicidade , Modelos Biológicos , Pele/efeitos dos fármacos , Criança , Comportamento Infantil , Difusão , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/farmacocinética , Mãos , Humanos , Método de Monte Carlo , Praguicidas/farmacocinética , Praguicidas/toxicidade , Medição de Risco , Pele/metabolismo , Propriedades de Superfície
5.
Environ Sci Technol ; 35(3): 560-7, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11351729

RESUMO

The surface interactions of nicotine and phenanthrene with carpet, painted wallboard, and stainless steel were investigated in a room-sized environmental test chamber. Adsorption kinetics were tested by flash evaporating a known mass of each compound into a sealed 20 m3 chamber containing one or more of the tested sorbents. In each experiment, one or more emissions were performed after the gas-phase concentration had reached an apparent plateau. At the end of each experiment, the chamber was ventilated and resealed to monitor reemission of the compound from the sorbents. Kinetic sorption parameters were determined by fitting a mass-balance model to the experimental results. The sorption capacity of stainless steel was of similar magnitude for nicotine and phenanthrene. Sorption of nicotine on carpet and wallboard was much stronger, with equilibrium partitioning values 2-3 orders of magnitude higher. The sorption capacities of phenanthrene on carpet and wallboard were smaller, approximately 10-20% of the stainless steel values. The rates of uptake are of similar magnitude for all sorbate--sorbent pairs and are consistent with the limit imposed by gas-phase boundary-layer mass transport. The rates of desorption are much faster for phenanthrene than for nicotine. Model simulations predict average nicotine levels in a typical smoking residence that are consistent with published data.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Estimulantes Ganglionares/química , Manufaturas , Nicotina/química , Fenantrenos/química , Adsorção , Estimulantes Ganglionares/análise , Humanos , Cinética , Nicotina/análise , Compostos Orgânicos , Fenantrenos/análise , Fumar , Volatilização
6.
J Interferon Cytokine Res ; 21(12): 1021-30, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11798459

RESUMO

Type 1 diabetes mellitus is a chronic disorder that presumably results from an autoimmune destruction of the insulin-producing pancreatic beta cells. The therapeutic potential of interventions aimed at preventing type 1 diabetes can be assessed in newly diagnosed patients. Because there is a historical experience of a low incidence of spontaneous remission in type 1 diabetes mellitus, interventions preserving beta cell function have been used to identify positive therapeutic outcomes. We treated 10 newly diagnosed type 1 diabetes patients with 30,000 IU ingested interferon-alpha (IFN-alpha) within 1 month of diagnosis and examined the difference between baseline and Sustacal-induced (Mead Johnson Nutritionals, Evansville, IN) C-peptide responses, respectively, at 0, 3, 6, 9, and 12 months. Eight of the ten patients showed preserved beta cell function, with at least a 30% increase in stimulated C-peptide levels at 0, 3, 6, 9, and 12 months after initiation of treatment. There was no discernible chemical or clinical toxicity associated with ingested IFN-alpha. Our results support the potential of ingested IFN-alpha to preserve residual beta cell function in recent onset type 1 diabetes mellitus and the testing of IFN-alpha in a placebo-controlled trial.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ilhotas Pancreáticas/fisiopatologia , Administração Oral , Adolescente , Adulto , Autoanticorpos/sangue , Peptídeo C/análise , Células Cultivadas , Criança , Citocinas/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/fisiopatologia , Humanos , Insulina/uso terapêutico , Interferon-alfa/administração & dosagem , Interferon-alfa/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Cinética , Resultado do Tratamento
7.
Arch Pediatr Adolesc Med ; 154(8): 837-40, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10922283

RESUMO

BACKGROUND: The Third National Health and Nutrition Examination Survey, 1988-1994(NHANES III) revealed that 11.5% of adolescents were obese. The NHANES III sample size for Mexican Americans was small. OBJECTIVE: To determine the prevalence of adolescent obesity in a South Texas population that is preponderantly low-income Mexican Americans. DESIGN: Cross-sectional prevalence study. SETTING: All secondary school campuses of one rural independent school district with a low-income Mexican American population. SUBJECTS: Four thousand three hundred seventy-five students, aged between 12 and 17 years, enrolled in 4 secondary school campuses of 1 Rio Grande Valley, South Texas, independent school district for academic year 1998-1999. MAIN OUTCOME MEASURES: Body mass index (BMI) was calculated for all 4375 students using weights and heights measured by school nurses on enrollment. Each student's BMI was then plotted on a sex-specific chart and the percentile range for age was determined. Those within the 85th to the 95th percentile were classified as at risk for obesity and those above the 95th percentile were classified as obese. RESULTS: Of 2149 adolscent girls and 2226 adolescent boys, 18% were at risk for obesity and 22. 1% were obese. A total of 40.1% had a BMI at the 85th percentile or higher for age and sex. The prevalence of obesity also continues to rise even after puberty more markedly in adolescent girls than adolescent boys. Furthermore, the mean BMI progressively increases with age and is generally at the 85th percentile or higher. CONCLUSIONS: Our data revealed a much higher prevalence rate of obesity in this adolescent Mexican American population than the rate obtained in NHANES III. It is even higher than the rate specific for Mexican American adolescents in NHANES III. The NHANES III significantly underestimates the prevalence of adolescent obesity in preponderantly impoverished Mexican American adolescents. This consequently leads to underestimation of the public health risks as well as the present and future cost of health care associated with obesity in this population. Arch Pediatr Adolesc Med. 2000;154:837-840


Assuntos
Americanos Mexicanos , Obesidade/etnologia , Adolescente , Estatura , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pobreza , Prevalência , Texas/epidemiologia
8.
Arch Pediatr Adolesc Med ; 153(12): 1272-8, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10591305

RESUMO

OBJECTIVE: To compare the incidence of diagnosis and morbidity in newborns who were screened with newborns who were not screened for congenital adrenal hyperplasia (CAH). DESIGN: A retrospective cohort study. SETTING: Arkansas, Oklahoma, and Texas. PATIENTS: An unscreened population in Arkansas and Oklahoma (n = 400118) was compared with a screened population in Texas (n = 1613378) during a 5-year period. Simultaneous data were collected on the incidence of diagnosis and associated morbidity in patients with CAH. MAIN OUTCOME MEASURES: Diagnosis of CAH, age (in days) at diagnosis, and frequency and length of initial hospitalization. RESULTS: The incidence of diagnosis of classic CAH per 100000 newborns in the unscreened cohort (5.75) and in the screened cohort (6.26) was similar (relative risk, 0.92; 95% confidence interval, 0.58-1.44). The unscreened group had 0.73 fewer male newborns with salt-wasting CAH diagnosed per 100000 newborns (relative risk, 0.73; 95% confidence interval, 0.35-1.56). The median age at diagnosis was 26 days for male newborns with salt-wasting CAH in the unscreened cohort vs 12 days in the screened cohort (z = 2.49; P = .01). Male newborns with simple-virilizing CAH and newborns with nonclassic CAH were detected only in the screened cohort. CONCLUSIONS: There was not a statistically significant (P = .73) increase in the diagnosis of salt-wasting CAH in the screened cohort. Male newborns benefited as a result of significantly (P = .01) earlier diagnosis, reduced morbidity, and shorter lengths of hospitalization. Large collaborative studies or meta-analyses are needed to determine the life-saving benefits of screening.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Triagem Neonatal , 17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/epidemiologia , Arkansas/epidemiologia , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Oklahoma/epidemiologia , Distribuição de Poisson , Estudos Retrospectivos , Estatísticas não Paramétricas , Texas/epidemiologia
9.
Postgrad Med ; 105(2): 111-3, 117-8, 124-6, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10026707

RESUMO

Planning ahead for a trip is always wise, but it is especially important for patients with diabetes. A pretravel office visit gives physicians the opportunity to review diabetes management with patients and to provide helpful information and precautions for safe travel. The authors provide practical recommendations and resources to help diabetic patients travel safely and avoid emergencies on the road.


Assuntos
Diabetes Mellitus , Viagem , Complicações do Diabetes , Diabetes Mellitus/terapia , Armazenamento de Medicamentos , Humanos , Insulina/administração & dosagem , Visita a Consultório Médico , Educação de Pacientes como Assunto
10.
J Pediatr Endocrinol Metab ; 12(3): 449-53, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10821225

RESUMO

Moyamoya disease is a rare cerebral vascular disease that results in narrowing of the vessels of the circle of Willis and the formation of a network of collateral vessels at the base of the brain for compensatory perfusion. Moyamoya disease has the highest incidence during the first decade of life, and children present most frequently with transient ischemic attacks. We present two cases of Moyamoya disease in children with associated hypothalamic-pituitary dysfunction. Both children presented to the endocrinologist for decreased growth velocity. One child had hypothyroidism and both had growth hormone deficiency. A review of the literature reveals a few isolated case reports of hypothalamic-pituitary dysfunction occurring with Moyamoya disease and with other states of cerebral vascular insufficiency. We suggest that children with compromise of cerebral vascular perfusion be monitored closely for clinical signs and symptoms of hypothalamic-pituitary dysfunction.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Doença de Moyamoya/complicações , Doença de Moyamoya/fisiopatologia , Doenças da Hipófise/etiologia , Doenças da Hipófise/fisiopatologia , Artérias Carótidas/patologia , Artérias Carótidas/fisiopatologia , Feminino , Hormônio do Crescimento Humano/deficiência , Humanos , Sistema Hipotálamo-Hipofisário/patologia , Lactente , Imageamento por Ressonância Magnética , Masculino , Doença de Moyamoya/patologia , Doenças da Hipófise/patologia
11.
Public Health Rep ; 113(2): 170-8, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9719819

RESUMO

OBJECTIVE: Texas mandates a two-test newborn screening program for congenital adrenal hyperplasia (CAH): one test at birth and a second test at approximately one to two weeks after birth. The authors compared the dollar cost of detecting infants with CAH clinically and through the screening program. METHODS: The authors estimated the costs of screening newborns in 1994 for CAH, including resources used by the Texas Department of Health and the broader cost to society. RESULTS: Fifteen infants with classic CAH were diagnosed in Texas in 1994 among 325,521 infants born (1:21,701 cumulative incidence). Seven infants were detected clinically and the others were detected through screening, six on the first screen and two on the second screen. The first screen identified all previously undetected infants with severe salt-wasting CAH. The cumulative cost to diagnose the seven infants detected clinically was $79,187. The incremental costs for the screening program were $115,169 per additional infant diagnosed through the first screen and $242,865 per additional infant diagnosed through the second screen. CONCLUSIONS: If the goal is early diagnosis of infants with the severe salt-wasting form of CAH, a single screen is effective. If the goal is to detect infants with the simple virilizing form of the disorder who may benefit from early treatment, the second screen is necessary, but it is not as cost-effective as the first screen.


Assuntos
Hiperplasia Suprarrenal Congênita/prevenção & controle , Triagem Neonatal/economia , Hiperplasia Suprarrenal Congênita/diagnóstico , Fatores Etários , Peso ao Nascer , Custos e Análise de Custo , Humanos , Recém-Nascido , Triagem Neonatal/métodos , Texas
12.
J Am Geriatr Soc ; 45(12): 1446-53, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9400553

RESUMO

OBJECTIVE: To compare current coronary heart disease (CHD) risk factor values in older athletes with mid-life measures and to examine the associations between changes in CHD risk factors with aging, physical training, and physical fitness. DESIGN: Prospective study with three longitudinal evaluation points: initial (T1), 10-year (T2), and 20-year (T3). Subjects were selected because of their elite status in Masters track competition. SETTING: University and medical center laboratories. PARTICIPANTS: Participants were 60 to 92 years of age and included 21 of the initial 27 subjects. At T3, subjects were divided into three groups, based on physical activity levels: high intensity (H), remained elite in national and international competition (n = 9); moderate intensity (M) continued frequent rigorous endurance training but rarely competed (n = 10); and low intensity (L) greatly reduced their training volume and intensity (n = 2). MEASUREMENTS: Smoking history; family history of coronary or cerebrovascular disease; resting blood pressure; resting electrocardiogram (ECG); serum total cholesterol, plasma glucose; body weight, % body fat, body mass index, waist:hip ratio; training pace and mileage; maximal oxygen consumption VO2 max). MAIN RESULTS: Several risk factors (smoking, diabetes, obesity) were never present, and the prevalence of other risk factors (family history of cardiovascular disease, abnormal resting ECG) remained low through T3 (< or = 14% of subjects). Mean systolic and diastolic blood pressure remained low without medication, but diastolic blood pressure measurements had the greatest redistribution between evaluation periods of any risk factor (r = .16, P = .479, T1 to T2). Mean total cholesterol was lower at T2 (-13%, P = .005) and T3 (-14%, P = .019) compared with T1. Change in VO2 max was correlated with changes in body weight (r = -.44, P = .048) and % fat (r = -.52, P = .015) from T1 to T2, whereas age was correlated to changes in systolic blood pressure (r = -.61, P = .003) and total cholesterol (r = -.49, P = .023) from T2 to T3. CONCLUSIONS: The prevalence of CHD risk factors remained low, and mean risk factor values remained low and generally stable in older athletes who had maintained habitual exercise training.


Assuntos
Doença das Coronárias/etiologia , Aptidão Física , Esportes , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Complicações do Diabetes , Exercício Físico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos
13.
J Clin Endocrinol Metab ; 80(12): 3739-43, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8530627

RESUMO

The international community of diabetologists is rapidly becoming involved in intervention trials aimed at preventing insulin-dependent diabetes in high risk relatives. Whereas age and relationship to a proband with insulin-dependent diabetes mellitus interacting with detected islet cell autoantibodies (ICA) are risk factors, their independent contribution to that risk remains unclear. In a prospective study of 6851 nondiabetic relatives of 2742 probands conducted between 1979-1993, we found age, but not relationship, to be a dramatic risk variable in ICA-positive persons as estimated by the Cox regression model. The 5-yr risk of insulin-dependent diabetes mellitus was 66% for those found to have ICA detectable before age 10 yr, falling progressively to less than 16% for ICA-positive relatives over age 40 yr. In ICA-negative relatives, age and relationship are independent prognostic variables.


Assuntos
Envelhecimento/fisiologia , Diabetes Mellitus Tipo 1/genética , Família , Adolescente , Adulto , Anticorpos/análise , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Ilhotas Pancreáticas/imunologia , Masculino , Prognóstico , Estudos Prospectivos , Análise de Regressão , Fatores de Risco
14.
Health Phys ; 68(5): 689-98, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7730066

RESUMO

Two new radon mitigation techniques are introduced and their evaluation in a field study complemented by numerical model predictions is described. Based on numerical predictions, installation of a sub gravel membrane at the study site resulted in a factor of 2 reduction in indoor radon concentrations. Experimental data indicated that installation of "short-circuit" pipes extending between the subslab gravel and outdoors caused an additional factor of 2 decrease in the radon concentration. Consequently, the combination of these two passive radon mitigation features, called the membrane and short-circuit (MASC) technique, was associated with a factor of 4 reduction in indoor radon concentration. The energy-efficient active radon mitigation method, called efficient active subslab pressurization (EASP), required only 20% of the fan energy of conventional active subslab depressurization and reduced the indoor radon concentration by approximately a factor of 15, including the numerically-predicted impact of the sub-gravel membrane.


Assuntos
Poluição do Ar em Ambientes Fechados/prevenção & controle , Contaminação Radioativa do Ar/prevenção & controle , Radônio/isolamento & purificação , Fenômenos Biofísicos , Biofísica , Difusão , Habitação , Humanos , Métodos , Modelos Teóricos , Pressão , Pesquisa , Tecnologia Radiológica/instrumentação
16.
Hum Immunol ; 38(4): 243-50, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8138419

RESUMO

In view of the potential functional importance of quantitative expression of HLA antigens, a series of studies were conducted to determine the relative quantities of specific HLA-A and -B antigens expressed in MNLs and platelets of HLA-phenotyped family members and unrelated individuals. An mAb that reacts with a well-defined monomorphic epitope in the alpha 3 domain of the heavy chains of HLA molecules was developed and used to quantify each HLA-A or -B antigen on western blots of IEF gels. The results of these studies demonstrated that the relative quantities of HLA-A and -B antigens in platelets and MNLs of an individual did not change over time. Further studies showed that the relative quantities of HLA-A and -B antigens for haplotypes shared among first-degree relatives were always the same and followed Mendelian inheritance. In contrast, the relative quantities of HLA-A and -B antigens for a haplotype shared by unrelated individuals varied significantly. All these findings support the hypothesis that the quantitative expression of HLA antigens is genetically predetermined and may play important roles in determining disease susceptibility and severity.


Assuntos
Plaquetas/imunologia , Antígenos HLA/sangue , Antígenos HLA/genética , Leucócitos Mononucleares/imunologia , Anticorpos Monoclonais , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Humanos , Immunoblotting , Focalização Isoelétrica , Testes de Precipitina
17.
J Clin Endocrinol Metab ; 77(3): 743-9, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8370696

RESUMO

Using time-dependent methods, the temporal relationships between the detection of insulin and islet cell autoantibodies and the onset of insulin dependent diabetes (IDDM) were analyzed in a prospective study of 4694 nondiabetic relatives of 1929 patients with IDDM who had been followed for a median of 4 yr. Insulin autoantibodies were detected in 1.5% of relatives at their initial test whereas an additional 1.0% subsequently became positive for these antibodies during follow-up. Islet cell autoantibodies were detected in 2.6% of the relatives at the time of their first test and an additional 0.9% were observed to develop them during the follow-up period. The risk of developing IDDM was significantly higher (P = 0.0001) among those who were found to have one of these antibodies, but was highest among those under the age of 20 yr at inception of this study who tested positive for both. Among older relatives, the detection of insulin autoantibodies among those who were islet cell antibody positive did not convey an additional risk of IDDM. In a subset of relatives, the presence of either antibody was associated with a higher frequency (P < 0.001) of diabetes associated human leukocyte antigen-DR 3/4 heterozygotes. Islet cell autoantibodies were highly associated with elevated fasting and 60-min glucose concentrations (P = 0.0001) as well as decreased early phase (1 and 3 min) insulin response to an iv glucose tolerance test (P = 0.0001). Insulin antibodies were significantly associated with decreased early phase insulin response to iv glucose (P = 0.0003). These data confirm independent risks associated with each antibody and suggest that their temporal relationship may be an important reflection of the pathogenic process underlying IDDM observations which facilitate its predictability.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Anticorpos Anti-Insulina/sangue , Adolescente , Adulto , Glicemia/metabolismo , Criança , Diabetes Mellitus Tipo 1/genética , Jejum , Teste de Tolerância a Glucose , Antígenos HLA-DR/análise , Humanos , Fenótipo , Estudos Prospectivos , Fatores de Risco
18.
J Autoimmun ; 6(1): 107-19, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8457282

RESUMO

We previously reported a significant increase in percentages of peripheral blood gamma delta+ T cells in islet cell antibody (ICA) positive relatives of patients with insulin-dependent diabetes (IDD). In the present study, we further characterized this T cell abnormality in a larger group of ICA+ subjects and report that (1) Percentages of gamma delta+ T lymphocytes were significantly increased only in subjects with high ICA titers (> or = 20 JDF units) (P = 0.005) and resulted from an increase in absolute numbers of gamma delta+ T lymphocytes. (2) In these subjects, the increase in gamma delta+ T lymphocytes was associated with an increase in the V gamma 9 V delta 2 subpopulation (r = 0.99). (3) In these same subjects, high percentages of gamma delta+ T lymphocytes were associated with normal beta cell function while low percentages were associated with diminished insulin response. Using 65 microU/ml as the threshold of abnormal intravenous glucose tolerance test (IVGTT) response, percentages of gamma delta+ T lymphocytes could significantly predict IVGTT status in these subjects (P < 0.01). A longitudinal follow-up further suggested that the development of an abnormal IVGTT response and progression to diabetes was associated with a decrease in percentages of gamma delta+ T lymphocytes while patients whose gamma delta+ T cell percentages remained high retained normal beta cell function. Our data therefore suggest that gamma delta+ T lymphocytes and more specifically V gamma 9 V delta 2 T cells are implicated in the autoimmune process leading to diabetes and may have a regulatory role. The monitoring of their percentages in the blood of patients at risk for diabetes may be useful as an additional predictor of diabetes development.


Assuntos
Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Teste de Tolerância a Glucose , Humanos , Imunidade Celular , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/fisiopatologia , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/patologia , Fatores de Tempo
19.
Diabetes Care ; 15(10): 1313-6, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1425095

RESUMO

OBJECTIVE: To review current practice in centers that use the IVGTT for prediction of IDDM. To establish consensus protocol for performance of the test. RESEARCH DESIGN AND METHODS: Postal questionnaires were delivered to 12 centers. RESULTS: Eleven centers used a glucose dose of 0.5 g/kg and 1 used 0.3 g/kg; the dosage in adults was limited to a maximum of 25-50 g in some centers but others applied no upper limit. The glucose concentration of the infusate varied between 20 and 66%. Eight centers injected glucose manually, two used a syringe pump, and two used gravity infusion. The period of infusion ranged from 30 +/- 10 s to 4 +/- 2 min, and time zero was taken as the start (1 center), middle (1 center), or end (10 centers) of the infusion. The potential range in timing of the +1-min sample varied between 1 and 7 min from the start of the infusion. Quality-assurance standards for the insulin assays used were not always appropriate for the fasting and low stimulated range of insulin levels. CONCLUSIONS: The first-phase insulin response to the IVGTT is widely measured as an index of risk of progression to IDDM. We established that methodology varies widely. Because of this, a new standard protocol for use in prediction of IDDM was agreed by an ICARUS working group and is described herein.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Teste de Tolerância a Glucose/normas , Adulto , Glucose/administração & dosagem , Humanos , Infusões Intravenosas , Controle de Qualidade , Inquéritos e Questionários
20.
Am J Epidemiol ; 136(5): 503-12, 1992 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-1442714

RESUMO

The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules.


Assuntos
Anticorpos/sangue , Doenças Autoimunes/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Marcadores Genéticos/genética , Antígenos HLA-DQ/imunologia , Ilhotas Pancreáticas/imunologia , Adolescente , Adulto , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Feminino , Testes Genéticos/normas , Teste de Histocompatibilidade/normas , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Análise Multivariada , Pennsylvania/epidemiologia , Valor Preditivo dos Testes , Sistema de Registros , Fatores de Risco
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