Adrenal and gonadal autoimmune diseases.
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Adrenal Gland Diseases↗
Biomedical subjects
B R Smith
Publications and source records attributed to B R Smith.
Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases.
Adrenal autoantibodies characteristic of autoimmune Addison disease are directed towards steroid 21-hydroxylase (21-OH; EC 1.14.99.10). We describe a new assay to measure 21-OH autoantibodies (21-OH Abs), based on immunoprecipitation by the antibodies of 35S-labeled human 21-OH. Using this immunoprecipitation assay (IPA), we detected 21-OH Abs in 42 of 64 (66%) patients with Addison disease and in 14 of 19 (74%) patients with autoimmune polyendocrine syndromes type I and type II. No 21-OH Abs were detected by the IPA in any patients with Addison disease attributable to tuberculosis (n = 9) or adrenoleukodystrophy (n = 9) or in patients with autoimmune thyroid disease (n = 28), systemic lupus erythematosus (n = 10), myasthenia gravis (n = 10), rheumatoid arthritis (n = 10), or insulin-dependent diabetes mellitus (n = 12). None of the 26 sera from healthy normal blood donors was positive for 21-OH Abs by the assay. We found good agreement between 21-OH Abs measured by IPA and by Western blotting (r = 0.83, n = 123, P < 0.001). The inter- and intraassay CVs for IPA were well < 10% at high, medium, and low concentrations of 21-OH Abs. Overall, our studies indicate that the IPA provides a specific, sensitive, and convenient system for measuring 21-OH Abs.
Addison Disease↗
Renal catabolism of recombinant human soluble CD4 after intravenous administration to male Sprague-Dawley rats.
Recombinant soluble CD4 (sT4; mol. wt. 45,000) has been studied extensively in Sprague-Dawley rats, and substantial renal processing has been indicated. In rats and monkeys, renal filtration and precipitation of sT4 in the distal nephron caused tubular cast nephropathy. Intravenous pharmacokinetics in the rat demonstrated that sT4 plasma clearance exceeded the glomerular filtration rate. In an effort to determine quantitatively the extent to which kidney and other tissues were responsible for sT4 catabolism, sT4 was labeled with trace amounts of dilactitol-[125I]tyramine and administered intravenously to Sprague-Dawley rats (1 mg/kg). Dilactitol-tyramine accumulates in lysosomes at the site of protein degradation. It has been used primarily to demonstrate hepatic catabolism of endogenous proteins. Blood samples were drawn for pharmacokinetic analysis, and selected tissues were removed to assess radiolabel distribution. Comparison of pharmacokinetic parameters derived from total plasma radiolabel and functional ELISA were not significantly different. Thus, covalent modification of sT4 with dilactitol-tyramine did not appreciably change the rate of clearance. From 3 to 24 hr after intravenous administration, 81.5 +/- 0.1% of the total administered radioactivity was found in the kidney. Approximately 8-13% of the administered dose was recovered in the liver. Macroscopic autoradiography of the kidney demonstrated accumulation of radiolabel in the cortex. Light microscopic autoradiography of the kidney following intravenous administration of directly radioiodinated sT4 confirmed cortical processing, because radiolabel was located primarily in epithelial cells of P1 and P2 segments of the proximal tubule after low intravenous doses (0.4-4 mg/kg). At 40 mg/kg, distal tubules and cortical collecting ducts were labeled as well. Thus, sT4 was filtered by the glomerulus, reabsorbed in the proximal tubule, and degraded in the lysosomal compartment.
Animals↗
A large necrotic defect secondary to a cutaneous sinus tract of odontogenic origin: a case report.
This article reviews the case of a patient with a periapical dental abscess that drained inferior and posterior to the angle of the jaw and created a large purulent cutaneous defect. Both the diagnosis and treatment issues are discussed.
Adult↗
Magnetic resonance microscopy of mouse embryos.
The increased use of the mouse as a model for various aspects of mammalian biology has caused a renewed interest in developing strategies for examining and comparing normal and abnormal mouse embryonic development and anatomy. In this study, we have explored the use of magnetic resonance microscopy as a tool for these purposes. Techniques for the fixation, embedding, perfusion, and image acquisition of mouse embryos are described. The perfusion of bovine serum albumin-diethylenetriamine pentaacetic anhydride-gadolinium as a contrast agent enhances images of the developing embryonic vasculature during critical stages of organogenesis and allows for comparisons when embryos have been treated with teratogens such as retinoic acid. The acquired three-dimensional data sets are available for archiving, distributing, and postacquisition manipulations such as computer segmentation of anatomical structures.
Age Factors↗
Three dimensional magnetic resonance microangiography of rat neurovasculature.
Techniques are described to perform three dimensional (3D) MR microangiography. We have combined the use of a blood pool agent (Gd-DTPA-complexed with bovine serum albumin), three dimensional Fourier encoding, careful animal stabilization, and volume rendering to permit imaging with voxels of 60 x 60 x 60 microns. 3DFT encoding has been performed at 7.1 T with very large arrays (256 x 512 x 512). Interactive volume rendering allows a number of unique display opportunities that effectively exploit these isotropic 3D arrays.
Animals↗
Dermoid cyst in the floor of the mouth. Review of the literature and case reports.
Dermoid cyst, frequently used to describe three closely related histologic cysts, the dermoid, epidermoid, and teratoma, is commonly considered a rare finding in the floor of the mouth. This review, which identifies 195 case reports of dermoid cysts in the floor of the mouth, has unveiled some findings that do not support conclusions expressed in previous articles. Examination of the literature includes muscle influence on clinical presentation and surgical approaches, locations, age distribution, histologic distribution, infection rate, incidence of multiple cysts, fibrous attachments, airway problems, anesthesia administration, surgical difficulties, and diagnostic aids. Brief suggestions in treatment are made in light of the clinical, radiographic, and historic findings. Three clinical cases are also included.
Adolescent↗
Isolation of Actinomyces species and Eikenella corrodens from patients with chronic diffuse sclerosing osteomyelitis.
Cultures from 26 patients with chronic diffuse sclerosing osteomyelitis of the mandible were studied. In most cases there was a mutualistic infection involving any one of the known human Actinomyces species together with Eikenella corrodens. In a few cases, Arachnia species were substituted for Actinomyces and gram-negative anaerobes for E corrodens. The specific culture protocol used to identify these organisms from clinical specimens is described. Taxonomic and experimental evidence that supports an infectious etiology are presented.
Actinomyces↗
The perimeter marking technique for rigid fixation of frontal sinus fractures: procedure and report of cases.
PURPOSE: Fractures of the frontal sinus region frequently need operative intervention in the form of reconstruction and obliteration. This requires removing the anterior table of the frontal sinus to gain access to the floor as well as the entire lateral extent of the sinus. Prior techniques to obtain this access have involved fabrication of preoperative radiographic templates. This article describes a technique of perimeter marking for delineating the precise location of the frontal sinus perimeter without the use of a radiographic template. METHODS: A 7-cm bayonet forceps is used for the perimeter marking. One prong is placed inside the sinus to the maximum peripheral extent and the corresponding prong then reflects its position on the external surface of the outer table. A no. 701 bur in a high-speed drill marks the perimeter adjacent to the bayonet forceps. After sinus marking is complete, the osteotomy is accomplished using either a drill or oscillating saw. RESULTS: Because the exact perimeter of the proposed osteoplastic flap is known prior to the osteotomy, bone plates can be preinserted, removed, and then replaced at the end of the procedure to anatomically reconstruct the frontal contour. Additionally, it is possible to remove a large region of the anterior table during the osteoplasty in one segment. CONCLUSION: This technique creates an unobstructed view of the lateral recesses of the frontal sinus and makes esthetic reconstruction of the frontal bar region possible.
Adult↗
Noninvasive measurement of platelet kinetics in normal and hypertensive pregnancies.
OBJECTIVE: Our purpose was to determine platelet kinetics in pregnancy by means of noninvasive reticulated platelet counts and to examine in a pilot study whether increased reticulated platelet values were associated with preeclampsia and pregnancy-induced hypertension. STUDY DESIGN: Nulliparous women had blood samples drawn at enrollment (first prenatal visit) and at 28 and 36 weeks' gestation. The percent of reticulated platelets (an index of marrow platelet release correlating with increased thrombopoiesis), platelet-associated immunoglobulin, and serum antiplatelet antibody were measured and correlated with the clinical course for each patient. RESULTS: In 31 normal pregnancies the percent of reticulated platelets was never significantly higher than the values for normal nonpregnant women (5.8% +/- 2.2%) in spite of a significant decrease in platelet count by 36 weeks. By contrast, the percent of reticulated platelets in four women with preeclampsia rose significantly to 13.9% +/- 11.2% at 28 weeks, before the onset of clinical signs. No women had evidence of immune platelet destruction. CONCLUSION: In normal pregnancy the decline in platelet count is not accompanied by an increase in marrow platelet production, suggesting that the platelet decrease is dilutional without a compensatory thrombopoietic response or alternatively that thrombopoiesis is down-regulated during normal pregnancy. However, platelet production does increase before the onset of symptoms in a small number of women in whom preeclampsia or pregnancy-induced hypertension subsequently develops. These findings may justify a larger prospective study to determine whether noninvasive serial measurement of the percent of reticulated platelets can predict those pregnant women at risk for hypertension and preeclampsia.
Adolescent↗
In vitro characteristics of white cell-reduced single-unit platelet concentrates stored in syringes.
BACKGROUND: Platelet concentrates (PCs) for premature infants may be subjected to filtration, centrifugation, and various storage conditions before transfusion. STUDY DESIGN AND METHODS: As there are few data on the cumulative effect of these procedures on PCs, platelet properties (including biochemical and functional in vitro assays) were evaluated after the processing of single units of PCs through a 1-unit-capacity high-efficiency white cell (WBC)-reduction filter followed by syringe storage at either 22 or 37 degrees C for 6 hours. Two- and 5-day-old PCs, volume-reduced PCs, and prestorage WBC-reduced PCs were evaluated. RESULTS: WBC filtration consistently resulted in a 3 to 4 log10 reduction in WBCs, with less than 15-percent platelet loss. No adverse effects of platelet function or evidence of increased platelet activation as determined by the percentage of P-selectin positivity were noted. A decrease in pH associated with increased lactate production and consumption of glucose was observed following syringe storage under all conditions tested. Such changes were most pronounced, however, with volume-reduced PCs stored at 37 degrees C (pH 6.31 +/- 0.15, lactate 23.0 +/- 3.06 mmol/L). All pH levels at the end of storage were above the minimum Food and Drug Administration requirement (pH 6.0). CONCLUSION: The in vitro data suggest that single units of PCs can undergo WBC filtration followed by syringe storage for up to 6 hours and still maintain acceptable storage characteristics. The practice of maintaining volume-reduced PCs in syringes for 6 hours at 37 degrees C in isolettes during transfusion should, however, be avoided.
Blood Component Removal↗
B-cell precursor bone marrow reconstitution after bone marrow transplantation.
Bone marrow transplantation is characterized by a prolonged period of humoral immunodeficiency in which many patients have abnormal circulating B-cell subsets, and oligoclonal and monoclonal gammapathies. In this study we examine B-cell precursor reconstitution in the post-transplantation marrow. Within 1 month after transplantation there is a marked increase in the percentage of immature B cells (to 80% of marrow lymphocytes), which can persist for more than 1 year. The increase in B-cell precursors is seen in both adults and children and appears to be independent of age. These cells have a normal precursor B-cell surface antigenic phenotype (CD19+, CD10+, CD20 negative to dim) and generally express very little CD34. No monoclonal or oligoclonal immunoglobulin gene rearrangements are detected in these cells, which enables them to be easily distinguishable from common precursor B-cell acute lymphocytic leukemia lymphoblasts.
Adolescent↗
Platelet alpha-granule release in cocaine users.
BACKGROUND: Cocaine use has been associated with arterial occlusion resulting from platelet-rich thrombi and with an accelerated, often atypical atherosclerotic lesion that could be ascribed to platelet activation and platelet alpha-granule release. METHODS AND RESULTS: Using a flow cytometric method to quantitate the percent of circulating activated platelets in whole blood (those that express the alpha-granule membrane protein P-selectin), we found that 5 of 25 samples from 12 long-term cocaine users had a baseline level of circulating activated platelets > 3 SD (range, 19% to 60%) above the mean (4.4 +/- 3.7%, mean +/- 1 SD) for 85 nonusers (sample n = 130). This subset resulted in a significantly higher mean baseline level of circulating activated platelets (11.8 +/- 14.4%) for all cocaine users (P = .01). By contrast, cocaine and its metabolites, at concentrations documented as obtainable during in vivo cocaine use (10(-7) to 10(-5) mol/L), had no effect on in vitro platelet activation or aggregation, either directly or in concert with platelet agonists. However, in experiments in which cocaine users received blinded infusions of placebo or cocaine, the mean percent of circulating activated platelets rose significantly (P < .05) after infusion of either placebo (peak 77 +/- 31%) or cocaine (peak 65 +/- 28%), the latter at doses resulting in peak plasma cocaine levels averaging < 10(-6) mol/L. CONCLUSIONS: Long-term cocaine use in some subjects is intermittently associated with high basal levels of circulating platelets that have undergone alpha-granule release. The inability of cocaine and its metabolites at concentrations of 10(-7) to 10(-5) mol/L to cause platelet P-selectin expression in vitro in this study, coupled with the acute increase in circulating activated platelets observed in vivo after either cocaine or placebo infusion, suggests that in vivo platelet alpha-granule release associated with cocaine use may occur through indirect rather than direct effects of the drug.
Blood Platelets↗
Naturally occurring mutations in human steroid 21-hydroxylase influence adrenal autoantibody binding.
Human 21-hydroxylase (21-OH) genes containing various mutations, truncations, and deletions were expressed in yeast, and autoantibody binding was studied by Western blotting using patient sera and rabbit antibodies to 21-OH. 21-OH autoantibodies in 13 Addisonian sera showed a marked reduction in their ability to recognize 21-OH mutated at Pro453-->Ser (mean +/- SD, 31 +/- 9% of binding to wild type), whereas the effect on rabbit antibody binding was small (88 +/- 11% of binding to wild type; n = 7). Mutation at Arg339-->His had a less pronounced effect on autoantibody binding (85 +/- 11% of binding to wild type; n = 13) and caused a small enhancement of rabbit antibody binding (124 +/- 16% of binding to wild type; n = 7). These studies indicate that Pro453 has a key role in forming an autoantigenic epitope on 21-OH. It is important to note, however, that the Pro453 mutation caused only partial loss of autoantibody binding, i.e. all Addisonian sera studied still reacted with the mutated protein. This may indicate that each serum sample contains at least two different populations of 21-OH autoantibodies, only one of which recognizes a site dependent on Pro453. A series of more extensive modifications of the 21-OH sequence, including truncations (amino acids 460-494, 448-494, and 418-494) and deletions (amino acids 165-379, 142-240, and 142-280) indicated that most of the sequence of amino acids from 241-494 is important for autoantibody binding. The involvement of such an extensive region of the molecule suggests that the binding sites are generated by three-dimensional folding, with Pro453 having a critical role in forming at least one major autoantigenic epitope.
Adrenal Glands↗
Autoimmune Addison's disease--evidence for a role of steroid 21-hydroxylase autoantibodies in adrenal insufficiency.
Autoantibodies to steroid 21-hydroxylase (21-OH) are characteristic of adult onset Addison's disease and we have investigated the effects of these autoantibodies on recombinant human 21-OH enzyme activity. Antibody preparations from 11/11 Addison sera inhibited the ability of 21-OH to convert progesterone to deoxycorticosterone with 8 IgGs showing almost complete inhibition, 2 partial inhibition and 1 weak inhibition. Control IgGs from patients with autoimmune thyroid disease and normal blood donors had little or no effect on 21-OH activity. Our results suggest that 21-OH autoantibodies have the potential to contribute to adrenal failure in Addison's disease by inhibiting the 21-OH enzyme.
Addison Disease↗
Appropriacy judgements and pragmatic performance.
This paper examines judgements of inappropriacy made by groups of independent raters from different professional backgrounds when presented with data from two boys with semantic, pragmatic and syntactic difficulties, who are interacting with adults, and when presented with data in a transcript or video format. The purpose is to explore the nature of such judgements with the view to highlighting the centrality and the complex nature of inappropriacy judgements in the clinical management of pragmatic impairment. The current study suggests that consensus of view as to what is or is not appropriate in interactions involving child clients may not exist in the general population. It further suggests that professional experience with children may direct one's attention primarily to the child client. Video presentation of information also appeared to direct attention to the child interactant. Given that audiovisual presentation of data is able to reproduce the non-linguistic 'oddness' of a child (e.g. averted gaze, slumped posture, monotonous voice), a situation seems to be created in which the linguistic content is perceived as equally 'odd' or inappropriate. This study has implications for assessment, diagnosis and treatment of pragmatic difficulties in children.
Adult↗
Neutrophil but not monocyte activation inhibits P-selectin-mediated platelet adhesion.
Selectins are Ca(2+)-dependent glycoprotein receptors that mediate the adhesion of activated platelets or endothelial cells to unstimulated leukocytes. Using purified cell fractions, we examined activated neutrophil adhesion to P-selectin-expressing platelets and found that phorbol 12-myristate 13-acetate (PMA), platelet activating factor C16 (PAF), and n-formyl-met-leu-phe (fMLP) pretreatment of neutrophils inhibited activated platelet adhesion. Furthermore, PMA and PAF were capable of dissociating established resting neutrophil-activated platelet conjugates. Since L-selectin is downregulated after leukocyte activation and has been postulated as a ligand for P-selectin, we preincubated resting neutrophils with Dreg-2 and Dreg-56, blocking monoclonal antibodies (MoAb) to L-selectin; these MoAb failed to inhibit activated platelet adhesion. To more closely approximate in vivo conditions of leukocyte and platelet activation, we also employed a whole blood (WB) model of leukocyte-platelet adhesion. We found that simultaneous activation of both platelets and leukocytes by PMA caused an immediate rise in the % of P-selectin-positive platelets accompanied by a rapid increase in monocyte-platelet and neutrophil-platelet conjugates; however, the % of neutrophil-platelet conjugates subsequently declined over 30-60 min to baseline levels while monocyte-platelet adhesion remained elevated over 90 min. By contrast, selective platelet activation in WB by thrombin resulted in an increase in platelet P-selectin expression accompanied by a sustained (90 min) elevation in both monocyte- and neutrophil-platelet conjugates. This increase in leukocyte-platelet conjugates after thrombin was not inhibited by preincubation of WB with Dreg-2 or Dreg-56. We conclude that neutrophil activation decreases the expression of the ligand for platelet P-selectin within 30-60 min resulting in inhibition of neutrophil-platelet adhesion and dissociation of existing neutrophil-platelet conjugates.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Adhesion Molecules↗
Platelet-leukocyte activation and modulation of adhesion receptors in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass.
Cardiopulmonary bypass has been shown in adults to activate platelets and leukocytes, lead to the formation of circulating platelet-leukocyte conjugates, and alter adhesive receptors on both cell types. Pediatric patients with congenital heart disease undergoing cardiopulmonary bypass, however, have not been extensively studied and may represent a group at particular clinical risk for bleeding and pulmonary dysfunction. We studied 13 patients with congenital heart disease undergoing operations necessitating bypass, 7 with cyanotic and 6 with noncyanotic congenital heart disease. We determined that (1) the surface density of platelet glycoprotein Ib was significantly lower at baseline and throughout bypass in patients with cyanotic heart disease than in noncyanotic patients; (2) platelet glycoprotein Ib in both cyanotic and noncyanotic congenital heart disease decreased significantly during bypass, with a nadir of 75% of baseline values; (3) platelets were activated to a high degree, comparable with that seen in adults; (4) mean circulating monocyte-platelet conjugates rose significantly during bypass, increasing from 36% to 66% by the end of bypass, whereas neutrophil-platelet conjugates and lymphocyte-platelet conjugates declined; and (5) both monocytes and neutrophils were activated by cardiopulmonary bypass, as assessed by increased surface expression of CD11b and, in the case of monocytes, CD11b expression continued to increase even after termination of bypass. Patients with cyanotic and noncyanotic heart disease did not differ with respect to platelet or leukocyte activation or the formation of platelet-leukocyte conjugates. We conclude that in children with congenital heart disease cardiopulmonary bypass causes loss of platelet adhesion receptors, activation of platelets, formation of platelet-leukocyte conjugates, and leukocyte activation. Cyanotic and noncyanotic patients are qualitatively similarly affected; however, cyanotic patients demonstrate a baseline deficit in the platelet adhesion receptor glycoprotein Ib. These cellular changes may contribute to both the hemostatic and inflammatory complications associated with cardiopulmonary bypass.
Blood Platelets↗