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J Barnard

Publications and source records attributed to J Barnard.

At least 19 recordsLinked to original sources
PubMed2001

Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS).

Despite reports of familial clustering of sarcoidosis, little empirical evidence exists that disease risk in family members of sarcoidosis cases is greater than that in the general population. To address this question, we estimated sarcoidosis familial relative risk using data on disease occurrence in 10,862 first- and 17,047 second-degree relatives of 706 age, sex, race, and geographically matched cases and controls who participated in the multicenter ACCESS (A Case-Control Etiology Study of Sarcoidosis) study from 1996 to 1999. Familial relative risk estimates were calculated using a logistic regression technique that accounted for the dependence between relatives. Sibs had the highest relative risk (odds ratio [OR] = 5.8; 95% confidence interval [CI] = 2.1-15.9), followed by avuncular relationships (OR = 5.7; 95% CI = 1.6-20.7), grandparents (OR = 5.2; 95% CI = 1.5-18.0), and then parents (OR = 3.8; 95% CI = 1.2-11.3). In a multivariate model fit to the parents and sibs data, the familial relative risk adjusted for age, sex, relative class, and shared environment was 4.7 (95% CI = 2.3-9.7). White cases had a markedly higher familial relative risk compared with African-American cases (18.0 versus 2.8; p = 0.098). In summary, a significant elevated risk of sarcoidosis was observed among first- and second-degree relatives of sarcoidosis cases compared with relatives of matched control subjects.

Adolescent↗
PubMed2001

Sarcoidosis: immunology, rheumatic involvement, and therapeutics.

Sarcoidosis is a systemic granulomatous disorder of unknown cause. It has protean manifestations and can affect any organ, including bones, joints, muscles, and vessels. This article reviews the most recent information on the immunologic and inflammatory pathogenesis of sarcoidosis and its implications for therapy. Sarcoidosis results from an overexuberant T cell-mediated immune response to the unknown antigen. This antigen presentation/T cell antigen recognition event occurs in a microenvironment that is suffused in proinflammatory cytokines and growth factors that promote cell attraction, adhesion, permeability changes, further cytokine production, and release. An amplified cellular immune response ensues, leading to granuloma formation and fibrosis. The article summarizes the new developments in the medical literature related to the rheumatologic manifestations and their detection and management in sarcoidosis patients. Osseous involvement in sarcoidosis is often underdiagnosed because it can be asymptomatic. New imaging techniques improve detection. Management of osteoporosis in sarcoidosis patients requires special attention because these patients often have an underlying disorder in calcium metabolism that results in hypercalcuria and hypercalcemia. Joint manifestations, such as the classic Lofgren syndrome with accompanying erythema nodosum, may be self-limited or may become chronic, presenting an ongoing therapeutic challenge. Sarcoidosis vasculitis can be devastating, affecting virtually any vessel in any organ and causing significant morbidity. Muscle involvement, like the bony involvement, is underdiagnosed. Symptoms of muscle weakness, aches, tenderness, and fatigue should prompt consideration of occult sarcoid myositis, often with accompanying neurogenic atrophy. Sarcoidosis treatment usually starts with a period of observation before pharmacologic intervention. Corticosteroids remain the first-line therapy. Alternatives to corticosteroids are often introduced either because of steroid intolerance or in an attempt to reduce steroid dose and side effects. The advantages and disadvantages of these second line therapies are reviewed. Medical vigilance, with attention to new patient symptoms, is important in the management of sarcoidosis, because of the tendency of this disease to present in so many and diverse patterns.

Bone Diseases↗
PubMed2000

Applying conversation analysis to foster accurate reporting in the diet history interview.

Inaccuracy in reporting dietary intakes is a major problem in managing diet-related disease. There is no single best method of dietary assessment, but the diet history lends itself well to the clinical setting. In many diet histories data are collected orally, so analysis of interviews can provide insights into reporting behaviors. Conversation analysis is a qualitative method that describes the systematic organization of talk between people. Patterns are identified and checked for consistency within and among individual interviews. The aim of this study was to describe consistent ways of reporting diet histories and to identify conversational features of problematic reporting. Diet history interviews from 62 overweight and insulin-resistant adult volunteers (50 women, 12 men) attending an outpatient clinic and 14 healthy volunteers (7 men, 7 women) participating in an energy balance study were audiotaped and transcribed. Conversation analysis identified a remarkably consistent pattern of reporting diet histories and 3 conversational features that indicated problematic reporting: "it depends," denoting variability (least of all at breakfast); "probably," suggesting guesswork (related to portion sizes); and elaborated talk on certain foods, distinguishing sensitive topics (e.g., alcohol, chocolate, butter/margarine, take-out foods) from safe topics. These findings indicate that there are ways in which dietetics practitioners may conduct the diet history interview to foster more accurate reporting.

Adult↗
PubMed2000

Fas activation reduces neutrophil adhesion to endothelial cells.

Polymorphonuclear neutrophils (PMN) express apoptotic markers and lose effector functions including adhesion, chemotaxis, and phagocytosis when cultured overnight. Although the loss of function correlates with apoptosis, it is not clear if functions are lost before an early marker of apoptosis, the display of phosphatidylserine (PS), targets PMN for removal by phagocytic cells. To address this question, freshly isolated PMN were treated with Fas-activating antibodies to induce apoptosis rapidly. Early markers of apoptosis and PMA-stimulated adhesion to endothelial cells were measured. After 1 h of Fas exposure, only 16% PMN had externalized PS. In contrast, Fas activation reduced PMA-stimulated adhesion between 68 and 27% depending on PMA concentration. The loss of adhesion was accompanied by a reduction in beta2 integrin expression and receptor clustering. These results indicate that the Fas-induced loss of adhesion may precede PS externalization and could limit participation in the inflammatory response before PS externalization targets PMN for removal.

Animals↗
PubMed1999

Liver transplantation for glycogen storage disease types I, III, and IV.

UNLABELLED: Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy have dramatically improved the outcome of GSD type I by reducing the incidence of liver adenoma and renal insufficiency. Nine type I and 3 type III patients have received liver transplants because of poor metabolic control, multiple liver adenomas, or progressive liver failure. Metabolic abnormalities were corrected in all GSD type I and type III patients, while catch-up growth was reported only in two patients. Whether liver transplantation results in reversal and/or prevention of renal disease remains unclear. Neutropenia persisted in both GSDIb patients post liver transplantation necessitating continuous granulocyte colony stimulating factor treatment. Thirteen GSD type IV patients were liver transplanted because of progressive liver cirrhosis and failure. All but one patient have not had neuromuscular or cardiac complications during follow-up periods for as long as 13 years. Four have died within a week and 5 years after transplantation. Caution should be taken in selecting GSD type IV candidates for liver transplantation because of the variable phenotype, which may include life-limiting extrahepatic manifestations. It remains to be evaluated, whether a genotype-phenotype correlation exists for GSD type IV, which may aid in the decision making. CONCLUSION: Liver transplantation should be considered for patients with glycogen storage disease who have developed liver malignancy or hepatic failure, and for type IV patients with the classical and progressive hepatic form.

Adolescent↗
PubMed1999

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.

Brain Mapping↗
PubMed1999

Applications of multiple imputation in medical studies: from AIDS to NHANES.

Rubin's multiple imputation is a three-step method for handling complex missing data, or more generally, incomplete-data problems, which arise frequently in medical studies. At the first step, m (> 1) completed-data sets are created by imputing the unobserved data m times using m independent draws from an imputation model, which is constructed to reasonably approximate the true distributional relationship between the unobserved data and the available information, and thus reduce potentially very serious nonresponse bias due to systematic difference between the observed data and the unobserved ones. At the second step, m complete-data analyses are performed by treating each completed-data set as a real complete-data set, and thus standard complete-data procedures and software can be utilized directly. At the third step, the results from the m complete-data analyses are combined in a simple, appropriate way to obtain the so-called repeated-imputation inference, which properly takes into account the uncertainty in the imputed values. This paper reviews three applications of Rubin's method that are directly relevant for medical studies. The first is about estimating the reporting delay in acquired immune deficiency syndrome (AIDS) surveillance systems for the purpose of estimating survival time after AIDS diagnosis. The second focuses on the issue of missing data and noncompliance in randomized experiments, where a school choice experiment is used as an illustration. The third looks at handling nonresponse in United States National Health and Nutrition Examination Surveys (NHANES). The emphasis of our review is on the building of imputation models (i.e. the first step), which is the most fundamental aspect of the method.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Streptococcal histone-like protein: primary structure of hlpA and protein binding to lipoteichoic acid and epithelial cells.

In addition to its role in the nucleoid, the histone-like protein (HlpA) of Streptococcus pyogenes is believed to act as a fortuitous virulence factor in delayed sequelae by binding to heparan sulfate-proteoglycans in the extracellular matrix of target organs and acting as a nidus for in situ immune complex formation. To further characterize this protein, the hlpA genes were cloned from S. pyogenes, S. gordonii, S. mutans, and S. sobrinus, using PCR amplification, and sequenced. The encoded HlpA protein of S. pyogenes has 91 amino acids, a predicted molecular mass of 9,647 Da, an isoelectric point of 9.81, and 90% to 95% sequence identity with HlpA of several oral streptococci. The consensus sequence of streptococcal HlpA has 69% identity with the consensus sequence of the histone-like HB protein of Bacillus species. Oral viridans group streptococci, growing in chemically defined medium at pH 6.8, released HlpA into the milieu during stationary phase as a result of limited cell lysis. HlpA was not released by these bacteria when grown at pH 6.0 or below. S. pyogenes did not release HlpA during growth in vitro; however, analyses of sera from 155 pharyngitis patients revealed a strong correlation (P < 0.0017) between the production of antibodies to HlpA and antibodies to streptolysin O, indicating that the histone-like protein is released by group A streptococci growing in vivo. Extracellular HlpA formed soluble complexes with lipoteichoic acid in vitro and bound readily to heparan sulfate on HEp-2 cell surfaces. These results support a potential role for HlpA in the pathogenesis of streptococcus-induced tissue inflammation.

Amino Acid Sequence↗
PubMed1997

The thiocarboxanilide nonnucleoside UC781 is a tight-binding inhibitor of HIV-1 reverse transcriptase.

The thiocarboxanilide nonnucleoside inhibitor (NNI) UC781 inhibited HIV-1 reverse transcriptase (RT) DNA polymerase activity at a 1:1 molar ratio of inhibitor to enzyme. Inhibition was linear uncompetitive with respect to template/primer (T/P) and mixed noncompetitive with respect to deoxynucleoside triphosphate (dNTP), typical of NNI. When the RT-T/P binary complex was incubated with UC781 and then separated from unbound inhibitor, recovery of enzyme activity was slow, with only about 60% activity recovered after 25 min. The inactivation of the RT-T/P complex was prevented by the presence of a large excess of UC84, another carboxanilide NNI that interacts with this RT mechanistic form. UC781 protected the RT-T/P-dNTP ternary complex from irreversible inactivation by a photoactivatable azido analog of nevirapine, implying that UC781 binds to the NNI pocket of this RT mechanistic form. UC781 did not photoprotect either the free enzyme or the RT-T/P binary complex; however, protein fluorescence quenching studies indicated that UC781 interacted with all RT mechanistic forms, with the order of affinity being RT-T/P-dNTP ternary complex > RT-T/P binary complex > free RT. Reaction progress curve analysis showed that the binding of UC781 to RT is rapid (k(on) approximately 1.7 x 10(6) M(-1) s(-1)), but that dissociation is slow (k(off) approximately 1.6 x 10(-3) s(-1)). UC781 is therefore a rapid tight-binding inhibitor of HIV-1 RT, the first NNI to demonstrate this property.

Anilides↗
PubMed1997

Inhibition of the ribonuclease H and DNA polymerase activities of HIV-1 reverse transcriptase by N-(4-tert-butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone.

HIV-1 reverse transcriptase (RT) is multifunctional, with RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP), and ribonuclease H (RNase H) activities. N-(4-tert-Butylbenzoyl)-2-hydroxy-1-naphthaldehyde hydrazone (BBNH) inhibited both the polymerase and the RNase H activities of HIV-1 RT in vitro. IC50 values for inhibition of RDDP were 0.8-3.4 microM, depending on the template/primer (T/P) used in the assay. The IC50 for DDDP inhibition was about 12 microM, while that for inhibition of RNase H was 3.5 microM. EC50 for inhibition of HIV-1 replication in cord blood mononuclear cells was 1.5 microM. BBNH inhibition of RNase H in vitro was time-dependent, whereas inhibition of RT polymerase activities was immediate. BBNH was a linear mixed-type inhibitor of RT RDDP activity with respect to both T/P and to dNTP, whereas BBNH inhibition of RT RNase H activity was linear competitive. Protection experiments using an azidonevirapine photolabel showed that BBNH binds to the non-nucleoside RT inhibitor (NNRTI) binding pocket. Importantly, the compound inhibited recombinant RT containing mutations associated with high-level resistance to other NNRTI. While BBNH did not inhibit the DNA polymerase activities of other retroviral reverse transcriptases and DNA polymerases, the compound inhibited Escherichia coli RNase HI and the RNase H activity of murine leukemia virus RT. BBNH also inhibited HIV-1 RT RNase H in the presence of high concentrations of other non-nucleoside inhibitors with higher affinities for the NNRTI binding pocket, and of RT in which the NNRTI binding pocket had been irreversibly blocked by the azidonevirapine photolabel. We conclude that BBNH may therefore bind to two sites on HIV-1 RT. One site is the polymerase non-nucleoside inhibitor binding site and the second may be located in the RNase H domain. BBNH is therefore a promising lead compound for the development of multisite inhibitors of HIV-1 RT.

Cell Division↗
PubMed1997

Chemical barriers to human immunodeficiency virus type 1 (HIV-1) infection: retrovirucidal activity of UC781, a thiocarboxanilide nonnucleoside inhibitor of HIV-1 reverse transcriptase.

UC781, a thiocarboxanilide nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), inhibited RT DNA polymerase activity in vitro with marked potency. Significant inhibition was noted at a 1:1 molar ratio of UC871 to RT, characteristic of a tight-binding inhibitor. Infectivity of the HIV-1(IIIB) laboratory strain was eliminated in a concentration-dependent manner following short exposure of isolated virion particles to UC781. Neither nevirapine nor certain other carboxanilide nonnucleoside inhibitors were effective in this manner. Endogenous reverse transcription in UC781-treated virus particles was markedly reduced. Treatment of chronically HIV-1-infected H9 cells with UC781 did not alter virus production, but the infectivity of the virus produced by the cells during drug exposure was markedly reduced. Moreover, the infectivity of nascent virus produced by the UC781-treated H9 cells after removal of exogenous drug was dramatically attenuated. Similarly, pretreatment of peripheral blood lymphocytes isolated from HIV-infected patients abolished the infectivity of virus produced by these cells after removal of exogenous drug, as measured by coculture experiments with uninfected cord blood mononuclear cells, indicating the utility of UC781 against a variety of clinical HIV samples. Importantly, preincubation of uninfected MT2 cells with UC781 rendered these cells refractory to subsequent HIV infection in the absence of extracellular drug, an effect that persisted for several days following removal of exogenous drug. These unique properties of UC781 indicate that this nonnucleoside inhibitor may have considerable promise for use in retrovirucidal formulations to minimize the spread of HIV from infected to noninfected individuals.

Anilides↗