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B Diamond

Publications and source records attributed to B Diamond.

At least 55 records · Page 3Linked to original sources
PubMed1998

Osteoarthritis and synovitis as major pathoses of the temporomandibular joint: comparison of clinical diagnosis with arthroscopic morphology.

PURPOSE: The purposes of this investigation were to determine how common osteoarthritis and synovitis are in patients with severe, recalcitrant temporomandibular joint (TMJ) symptoms using clinical diagnostic criteria as well as arthroscopic examination, and to compare the accuracy of the clinical and arthroscopic diagnoses with respect to specificity and sensitivity. PATIENTS AND METHODS: Clinical and arthroscopic diagnoses were established in 126 joints of 84 patients with severe TMJ symptoms recalcitrant to conservative therapy. All joints were classified as having osteoarthritis (OA) or no osteoarthritis (non-OA) and synovitis (syn) or no synovitis (non-syn) using clinical and arthroscopic criteria. Chi-squared analysis was used to determine whether there was a relationship between the clinical and arthroscopic diagnoses. Preoperative clinical diagnoses were compared with arthroscopic morphologic diagnoses to determine the specificity and sensitivity of the clinical diagnostic criteria for synovitis and osteoarthritis. RESULTS: A preoperative clinical diagnosis of OA was established in 59 of 126 joints (47%) compared with an arthroscopic diagnoses of OA in 82 of 126 joints (65%). Chi-squared analysis showed a significant relationship between the clinical and arthroscopic diagnosis of OA. A clinical diagnosis of OA was associated with a high specificity (.977); however, there were 23 of 82 (.293) false-negative findings and a sensitivity of only .707. A preoperative clinical diagnosis of synovitis was established in 114 of 126 joints (90%), compared with an arthroscopic diagnosis of synovitis in 112 of 126 (89%). Chi-squared analysis did not show a significant relationship between the clinical and arthroscopic diagnosis of synovitis. A clinical diagnosis of synovitis was associated with a high sensitivity (.920); however, there were 11 of 14 false-positive findings (.786) associated with a low specificity (.214). CONCLUSIONS: Although there was high specificity for the clinical diagnosis of OA, the sensitivity was very low. (Comparison of clinical and arthroscopic diagnoses showed that osteoarthritis frequently escapes clinical detection. The clinical diagnosis of synovitis showed that low specificity and symptoms may be caused by other pathoses.

Adolescent↗
PubMed1998

Proteoglycans in the synovial fluid of the temporomandibular joint as an indicator of changes in cartilage metabolism during primary and secondary osteoarthritis.

PURPOSE: The specific aim of this investigation was to assess differences between primary and secondary osteoarthritis (OA) of the temporomandibular joint (TMJ) using clinical evaluation and synovial fluid analysis for proteoglycans. MATERIALS AND METHODS: Arthroscopic surgery was performed on 101 TMJs from patients with significant pain or dysfunction and who had failed to respond to treatment. Joints were assessed for primary and secondary osteoarthritis. Synovial fluid aspirates were obtained and analyzed to determine the levels of keratan sulfate (KS) epitope and a novel 3B3(-) epitope by enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty-four patients and 67 joints had OA diagnosed by both clinical examination and arthroscopy. Primary OA was diagnosed in 14 joints (20%), and the remaining 53 joints were regarded as having secondary OA. No differences were detected in the levels of KS in the synovial fluid from the primary and secondary OA joints. Furthermore, the 3B3(-) epitope was not detectable in the synovial fluid aspirates of any TMJ. CONCLUSION: Secondary OA is a common disorder of the TMJ. However, there is no apparent difference in the metabolism of the joints with primary and secondary OA as assessed by proteoglycans in the synovial fluid. The apparent absence of the 3b3(-) epitope, in contrast to its presence in OA of other major synovial joints, suggests that there are some differences between the cartilage metabolism of the TMJ and these other joints during OA.

Adult↗
PubMed1998

FEESST: a new bedside endoscopic test of the motor and sensory components of swallowing.

We here introduce an office or bedside method of evaluating both the motor and sensory components of swallowing, called fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST). FEESST combines the established endoscopic evaluation of swallowing with a technique that determines laryngopharyngeal (LP) sensory discrimination thresholds by endoscopically delivering air pulse stimuli to the mucosa innervated by the superior laryngeal nerve. Endoscopic assessment of LP sensory capacity followed by endoscopic visualization of deglutition was prospectively performed 148 times on 133 patients with dysphagia over an 8-month period. The patients had a variety of underlying diagnoses, with stroke and chronic neurologic disease predominating (n = 94). Subsequent to LP sensory testing, a complete dysphagia evaluation was conducted. Various food and liquid consistencies were dyed green, and attention was paid to their management throughout the pharyngeal stage of swallowing. Evidence of latent swallow initiation, pharyngeal pooling and/or residue, laryngeal penetration, laryngeal aspiration, and/or reflux was noted. Recommendations for therapeutic intervention were based on information obtained during the FEESST and often involved the employment of compensatory swallowing strategies, modification of the diet or its presentation, placement on non-oral feeding status, and/or referral to other related specialists. All patients successfully completed the examination. In 111 of the evaluations (75%), severe (>6.0 mm Hg air pulse pressure [APP]) unilateral or bilateral LP sensory deficits were found. With puree consistencies, 31% of evaluations with severe deficits, compared to 5% of evaluations with either normal sensitivity or moderate (4.0 to 6.0 mm Hg APP) LP sensory deficits, displayed aspiration (p < .001, chi2 test). With puree consistencies, 69% of evaluations with severe deficits, compared to 24% with normal or moderate deficits, displayed laryngeal penetration (p < .001, chi2 test). FEESST allows the clinician to obtain a comprehensive bedside assessment of swallowing that is performed as the initial swallowing evaluation for the patient with dysphagia.

Adult↗
PubMed1997

Lupus-specific antibodies reveal an altered pattern of somatic mutation.

The F4 idiotype is a heavy chain determinant expressed almost exclusively on IgG immunoglobulins and is highly associated with specificity for double-stranded DNA. Since high-titered F4 expression is present predominantly in sera of patients with systemic lupus erythematosus (SLE), we thought F4+ IgG antibodies might constitute a useful subset of immunoglobulins in which to investigate lupus-specific alterations in variable (V) region gene expression or in the process of somatic mutation. This molecular analysis of F4+ B cell lines generated from lupus patients demonstrates that despite the strong association of F4 reactivity with specificity for native DNA, there is no apparent VH gene restriction. Furthermore, VH gene segments encoding these antibodies are also used in protective immune responses. An examination of the process of somatic mutation in F4+ antibodies showed no abnormality in frequency of somatic mutation nor in the distribution of mutations in complementarity-determining regions or framework regions. However, there was a decrease in targeting of mutations to putative mutational hot spots. This subtle difference in mutations present in these antibodies may reflect an intrinsic defect in mutational machinery or, more likely, altered state of B cell activation that affects the mutational process and perhaps also negative selection.

Amino Acid Sequence↗
PubMed1997

Light chain usage in anti-double-stranded DNA B cell subsets: role in cell fate determination.

Two major mechanisms for the regulation of autoreactive B cells that arise in the bone marrow are functional silencing (anergy) and deletion. Studies to date suggest that low avidity interactions between B cells and autoantigen lead to B cell silencing, whereas high avidity interactions lead to deletion. Anti-double stranded (ds) DNA antibodies represent a pathogenic autospecificity in Systemic Lupus Erythematosus (SLE). An understanding of their regulation is critical to an understanding of SLE. We now demonstrate in a transgenic model in which mice express the heavy chain of a potentially pathogenic anti-DNA antibody that antibody affinity for dsDNA does not alone determine the fate of anti-dsDNA B cells. B cells making antibodies with similar affinities for dsDNA are regulated differently, depending on light chain usage. A major implication of this observation is that dsDNA may not be the self antigen responsible for cell fate determinations of anti-dsDNA B cells. Light chain usage may determine antigenic cross-reactivity, and cross-reactive antigens may regulate B cells that also bind dsDNA.

Amino Acid Sequence↗
PubMed1997

Peptide inhibition of glomerular deposition of an anti-DNA antibody.

Antibodies to double-stranded DNA are pathognomonic of systemic lupus erythematosus and deposit in the kidneys of lupus patients to cause glomerulonephritis. Recent data suggest that a significant proportion of anti-DNA antibodies may cross-react with renal antigens and be sequestered in the kidney by virtue of this cross-reactivity. If this is true, antigenic competition for pathogenic antibodies might prevent their deposition in kidneys and the ensuing tissue damage. To generate surrogate antigens that could be used for this purpose, we have used peptide display phage libraries to identify peptides that react with R4A, a pathogenic mouse monoclonal anti-DNA antibody that deposits in glomeruli. We have demonstrated that the peptides bind in or near the double-stranded DNA binding site. Furthermore, the peptides are bound preferentially by the R4A antibody as compared with two closely related antibodies derived from it, one of which deposits in renal tubules and one of which displays no renal pathogenicity. Administration of one of these peptides in a soluble form protects mice from renal deposition of the R4A anti-DNA antibody in vivo. This represents a new therapeutic approach in systemic lupus erythematosus that focuses on protecting target organs from antibody mediated injury.

Animals↗
PubMed1997

Studies on the structure, regulation, and pathogenic potential of anti-dsDNA antibodies.

Studies of anti-double-stranded (anti-ds)DNA antibodies have provided insights into how and why these antibodies arise in systemic lupus erythematosus. In this review we discuss the experimental approaches that have been used by our laboratory to study these autoantibodies. Structure/function analyses including site-directed mutagenesis have helped characterize the molecular genetics of anti-dsDNA antibodies, and more recently peptide libraries have been used to define molecular motifs that these antibodies bind. Most of the pathogenic anti-dsDNA antibodies observed in lupus are somatically mutated. We demonstrated in vitro and in vivo that anti-bacterial antibodies can mutate to acquire specificity for dsDNA. Furthermore, using a fusion partner constitutively expressing bcl-2, NSO(bcl-2), we have shown the existence of anergic or preapoptotic B cells making antibodies that cross-react with both bacterial antigen and dsDNA. Whether defects in the regulation of these antibodies might contribute to serum expression of anti-dsDNA antibodies in some individuals remains unknown. A major emphasis of this review is the regulation of anti-dsDNA antibodies in a transgenic mouse model harboring the gene for the heavy chain of a pathogenic anti-dsDNA antibody. Nonautoimmune transgenic mice effectively regulate autoreactive B cells by anergy and deletion, while their autoimmune counterparts do not. The vast majority of anergic B cells expressing high-affinity transgenic anti-dsDNA antibody fail to display allelic exclusion of the heavy chain. We postulate that this may be one mechanism that allows them to escape deletion. Comparative studies on light chain usage in both the autoimmune and the nonautoimmune transgenic mouse strains have demonstrated that within the autoreactive B-cell population, there are subsets that are differentially regulated. Ultimately transgenic animals making pathogenic autoantibodies may provide us with a system for testing novel therapies for autoimmune disease.

Animals↗
PubMed1997

Overexpression of bcl-2 alters usage of mutational hot spots in germinal center B cells.

Bcl-2 is an anti-apoptotic gene important in B cell development. In order to study how apoptosis regulates somatic hypermutation and selection of B cell clones in the germinal center, we examined the antibody response to phosphorylcholine (PC) in transgenic mice overexpressing bcl-2 in the B cell compartment. The anti-PC antibody response is dominated by the S107V1 variable region heavy chain gene. We, therefore, analyzed S107V1-encoded heavy chains from germinal center cells. The proportion of germinal center sequences that were mutated, and the frequency of mutations did not differ significantly between the two groups of mice. No significant differences were found in the clustering of replacement mutations in the complementarity determining regions (CDRs) and in replacement to silent (R:S) mutation ratios. A significant difference between bcl-2 transgenic mice and controls, however, was found in the targeting of mutations to oligonucleotide motifs presumed to be mutational "hot spots." While non-transgenic mice displayed the expected clustering of mutations in hot spots, mutations from bcl-2 transgenic mice lacked this pattern. This observation suggests that the mechanism for somatic hypermutation includes two distinct functions, a non-specific mutational apparatus and a mechanism to target mutation to hot spots, and that in certain circumstances these functions may be uncoupled.

Amino Acid Sequence↗
PubMed1997

The prisoner.

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Humans↗
PubMed1997

Predictors of reported condom use in central Harlem youth as conceptualized by the health belief model.

PURPOSE: To examine the relationship of reported condom use to specific sociodemographics, psychosocial variables, and perceptions of and motivations for condom use as conceptualized by the Health Belief Model. METHODS: This study performed a cross-sectional survey of 557 adolescents enrolled in a hospital-based pregnancy prevention program in an urban community hospital (Harlem Hospital). Multiple logistic regression analysis examined the combined relationship of the significant psychosocial variables to consistent condom use. RESULTS: Males were less likely than females to report teen-parent conflict and depression and more likely to report support for birth control, participation in community activities, and favorable attitudes toward delaying parenthood. Consistent with the Health Belief Model adjusting for age, the strongest predictors of consistent condom use were partner preference for condoms, perceived benefit of avoidance of pregnancy, male gender, and support for birth control (usually by a parent). CONCLUSIONS: The data on this urban, predominantly African-American sample of adolescents suggest the importance of the influences on specific motivations to use protection--that is, the wish to avoid pregnancy, human immunodeficiency virus/acquired immunodeficiency syndrome, and sexually transmitted diseases, although the mechanisms are still unclear. In addition, gender and the modifying effects of parental and partner support of the use of protection strongly influence the reported use of condoms by adolescents. These factors (in addition to psychosocial factors such as depression) may be important in planning interventions to increase condom use by sexually active teens.

Adolescent↗
PubMed1997

Silent laryngopharyngeal sensory deficits after stroke.

Dysphagia and aspiration are two devastating sequelae of stroke. Recent work has shown that laryngopharyngeal (LP) sensory deficits are associated with aspiration in stroke patients with dysphagia. The phenomenon of silent LP sensory deficits, where the patient exhibits no subjective or objective evidence of dysphagia, yet has an LP sensory deficit, has not been previously described. The aim of this study was to evaluate the sensory capacity of the laryngopharynx in stroke patients who had no subjective or objective complaints of dysphagia. We determined the sensory threshold in the laryngopharynx using air pulse stimulation of the mucosa of the pyriform sinus and aryepiglottic fold. Eighteen stroke patients (mean age 65.6 +/- 11.5 years) and 18 age-matched controls were prospectively evaluated. Normal thresholds were defined as < 4.0 mm Hg air pulse pressure (APP). Deficits were defined as either a moderate impairment in sensory discrimination thresholds (4.0 to 6.0 mm Hg APP) or a severe sensory impairment (> 6.0 mm Hg APP). Stroke patients were followed up for 1 year to determine the incidence of aspiration pneumonia (AP) as verified by chest radiography. In 11 of the stroke patients studied, either unilateral (n = 6) or bilateral (n = 5) severe sensory deficits were identified. The elevations in sensory discrimination thresholds were significantly greater than those in age-matched controls (7.1 +/- 0.6 mm Hg APP versus 2.5 mm Hg APP; p < .01, Wilcoxon score). Among patients with unilateral deficits, sensory thresholds were severely elevated in all cases on the affected side compared with the unaffected side (p < .01, Wilcoxon score). Moreover, the sensory thresholds of the unaffected side were not significantly different from those of age-matched controls. Aspiration pneumonia did not occur in the patients with normal LP sensation or in the patients with unilateral severe LP sensory deficits. However, in the 5 patients with bilateral, severe LP sensory deficits, 2 developed AP, both within 3 months of their LP sensory test. The results of this study showed, for the first time, that stroke patients without subjective or objective clinical evidence of dysphagia could have silent LP sensory deficits. These impairments could contribute to the development of AP following stroke. The findings in this study suggest that LP sensory discrimination threshold testing should not be restricted only to patients with clinical dysphagia.

Aged↗
PubMed1996

The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody.

Anti-double-stranded (ds) DNA antibodies are not only an important diagnostic marker for SLE, but also play an important role in tissue injury. Microbial antigen may be a stimulus for the production of these antibodies. We isolated 99D.7E, an IgG2b monoclonal antibody from a nonautoimmune BALB/c mouse that is cross-reactive with both dsDNA and phosphorylcholine, the dominant hapten on the pneumococcal cell wall. While partially protective against a bacterial challenge, 99D.7E is also pathogenic to the kidney. To identify those molecular motifs that confer on anti-PC antibodies the potential for autoreactivity, we created a panel of 99D.7E mutants with single amino acid substitutions in the heavy chain, and examined the changes in antigen binding and renal deposition. Our results support the hypothesis that charge and affinity for dsDNA are not adequate predictors of the pathogenicity of anti-DNA antibodies. Differential renal damage from anti-dsDNA antibodies may be due to differences in fine specificity, rather than differential affinity for dsDNA. Importantly, high affinity IgG antibodies cross-reactive with bacterial and self antigen exist and can display pathogenic potential, suggesting that defects in peripheral regulation of B cells, activated by foreign antigen but cross-reactive with self antigen, might lead to autoimmune disorders.

Amino Acid Sequence↗
PubMed1996

Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease.

The immune system's ability to distinguish self and nonself is essential for both host defense against foreign agents and protection of self-antigens from autoimmune destruction. Such discrimination is complicated by extensive structural homology shared between foreign and self antigens. One hypothesis to explain the development of an autoimmune response is that some B cells activated by foreign antigen acquire, through somatic mutation, specificity for both the eliciting foreign antigen and self antigen. If such clones arise frequently, there must be a mechanism for their elimination. We have analyzed the extent of autoreactivity arising in a nonautoimmune host during the response to a foreign antigen. To overcome the process of apoptosis in primary B cells that might routinely eliminate autoreactive clones, we generated B-cell hybridomas from spleen cells of immunized mice by using a fusion partner constitutively expressing bcl-2. Multiple lines were obtained that recognize simultaneously the hapten phosphorylcholine and the self antigen double-stranded DNA. This dual specificity was not present early but was detected by day 10 after immunization. Some of these cross-reactive antibodies deposit in kidneys in a pattern similar to what is seen in autoimmune disease. These results demonstrate that autoantibodies arise at a high frequency as part of a response to foreign antigen. It has previously been shown that autoreactivity is regulated by central deletion; these data demonstrate a need for negative selection in peripheral lymphoid organs also, to regulate autoantibodies acquiring their self-specificity by somatic mutation.

Animals↗
PubMed1996

Autoimmunity in heart disease: mechanisms and genetic susceptibility.

Recent studies of heart disease suggest that immunologically mediated processes often accompany cardiac injury and can contribute to pathogenesis. Murine models of myocarditis have provided insight into the mechanisms by which autoimmune responses to cardiac antigens arise and cause tissue pathology. It is now evident that T cells, cytokines and antibodies can all contribute to cardiac injury. Furthermore, murine models have demonstrated that both the propensity to develop autoreactivity following cardiac injury and the vulnerability of the heart to these responses are under genetic control. Continued studies will help to identify susceptibility genes and might aid in the development of strategies to protect individuals at risk from immunologically mediated damage following cardiac injury.

Animals↗