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Biomedical subjects

D S Beardsley

Publications and source records attributed to D S Beardsley.

At least 19 recordsLinked to original sources
PubMed2002

Pathophysiology of immune thrombocytopenic purpura.

In 1951, the young hematologist in training, Dr. William Harrington, infused himself with plasma from a patient with immune thrombocytopenic purpura (ITP). He rapidly developed severe, but transient, thrombocytopenia and was at risk for serious hemorrhage. Thus, the humoral autoimmune cause of ITP was established. Since 1953, when Dr. Harrington's in vivo studies ended, in vitro investigations have aimed to determine the molecular and cellular details of immune-mediated platelet destruction.

Animals↗
PubMed1998

Platelet autoantibodies in immune thrombocytopenic purpura.

In summary, the search for a useful clinical laboratory diagnostic assay for the antiplatelet antibodies has been long and difficult. Measurement of platelet associated IgG (PAIgG) has been disappointing as a way to detect autoantibodies. This is primarily due to the fact that platelets normally contain IgG in their alpha granules in an amount that varies with plasma IgG levels and age of the platelets. Furthermore, the amounts of platelet associated IgG is affected by the presence of circulating immune complexes, platelet activation, and drug dependent antibodies. The newer, platelet antigen capture techniques are promising, but further testing will be needed to confirm their value to the clinician. Methods that allow incubation of patient serum or plasma with intact platelets (MAIPA and immunobead) have greater sensitivity than techniques in which the patient antibody is tested against previously isolated platelet glycoproteins. These assays are currently available in a only a limited number of platelet immunology laboratories. Platelet autoantibodies are directed against a number of glycoprotein antigens on the platelet surface. Most studies have shown that anti GPIIb/IIIa antibodies are the most common, although antibodies against GPIb/IX and other targets are frequently detected. Many patients have multiple antiplatelet antibodies circulating simultaneously. The clinical significance of antibodies with different specificity is under investigation. The precise epitopes on GPIIIa that bind antiplatelet autoantibodies have been studied to a limited extent. Some investigators report that the vast majority of platelet antigens are conformation dependent, being destroyed by treatment with EDTA (separation of GPIIb and GPIIIa) or denaturation with detergents. Others report sequence specific peptide antigens. Further investigation promises to better define the targets for platelet autoantibodies; improved clinical management of patients with ITP is the long term goal of these studies.

Anemia, Hemolytic, Autoimmune↗
PubMed1998

Cerebral vasculopathy and neurologic sequelae in infants with cervicofacial hemangioma: report of eight patients.

PURPOSE: To determine the association of cerebral arterial anomalies and progressive cerebral arterial occlusive disease in infants with facial hemangiomas. MATERIALS AND METHODS: The cases of eight infants (seven girls and one boy) with the diagnosis of cervicofacial hemangioma and intracranial arterial anomalies were reviewed retrospectively. Findings from clinical and imaging examinations--including cranial computed tomography, magnetic resonance imaging and angiography, and catheter angiography--were evaluated. Serial imaging findings were studied to document progressive intracranial vascular changes. RESULTS: Five patients had additional associated congenital anomalies. Seven were treated with corticosteroids, interferon alfa-2a, or both. Progressive cerebrovascular occlusive changes were documented in four of the seven patients with serial imaging findings. Four other patients (all treated pharmacologically) had MR imaging documentation of cerebral infarction, and all had consistent, acquired neurologic symptoms. CONCLUSION: Intracranial arterial anomalies can coexist with cervicofacial hemangioma. Aneurysmal and occlusive changes are potentially progressive and can result in cerebral infarction. A causative association between occlusive cerebrovascular disease and pharmacologic treatment has not been excluded.

Abnormalities, Multiple↗
PubMed1996

Local densities orthogonal to beta-sheet amide planes: patterns of packing in globular proteins.

We have investigated the efficiency of packing by calculating intramolecular packing density above and below peptide planes of internal beta-pleated sheet residues in five globular proteins. The orientation of interest was chosen to allow study of regions that are approximately perpendicular to the faces of beta-pleated sheets. In these locations, nonbonded van der Waals packing interactions predominate over hydrogen bonding and solvent interactions. We observed considerable variability in packing densities within these regions, confirming that the interior packing of a protein does not result in uniform occupation of the available space. Patterns of fluctuation in packing density suggest that the regular backbone-to-backbone network of hydrogen bonds is not likely to be interrupted to maximize van der Waals interactions. However, high-density packing tends to occur toward the ends of beta-structure strands where hydrogen bonds are more likely to involve nonpolar side-chain groups or solvent molecules. These features result in internal protein folding with a central low-density core surrounded by a higher-density subsurface shell, consistent with our previous calculations regarding overall protein packing density.

Amides↗
PubMed1996

Reticulated platelet values in normal and thrombocytopenic neonates.

OBJECTIVES: Reticulated platelets (RPs) are newly synthesized platelets with increased ribonucleic acid content. The percentage of RPs is elevated in adults with thrombocytopenia as a result of increased platelet destruction. The objectives of this study were to determine normal RP values in neonates at birth and to determine whether neonates with thrombocytopenia as a result of increased platelet destruction have an increased percentage of RPs. STUDY DESIGN: The RP percentages were measured at birth in 89 neonates without thrombocytopenia in three gestational age groups (<30,30 to 36, and >36 weeks), six neonates with immune thrombocytopenia, and one neonate with thrombocytopenia as a result of decreased platelet production. RESULTS: The RP percentages in neonates without thrombocytopenia >36 weeks and 30 to 36 weeks of gestation were 4.0% +/- 2.4% (mean +/- SD) and 4.6% +/- 1.7%, respectively, similar to values reported in healthy adults. Neonates younger than 30 weeks of gestation had significantly higher RP percentages (8.8% +/- 5.1%) than older neonates (p </= 0.0001). Term neonates with immune thrombocytopenia had significantly higher RP percentages (38.3% +/- 23.1%) than term neonates without thrombocytopenia (p = 0.0001), with no overlap in RP values. A lower RP percentage (1.5%) and significantly lower absolute RP count were measured in the one neonate with decreased platelet production. CONCLUSIONS: These preliminary data establish normal RP percentages in term and preterm neonates at birth and demonstrate elevated RP percentages in neonates with immune platelet destruction. The RP values may be helpful in evaluating the causes of neonatal thrombocytopenia.

Blood Platelet Disorders↗
PubMed1996

Nonoperative management of a splenic tear in a Jehovah's Witness with hemophilia.

Splenic laceration, the most common visceral lesion following blunt abdominal trauma, can be treated in a nonoperative fashion in only a select group of stable patients with minimal injury. We report a unique case of life-threatening splenic trauma in a Jehovah's Witness with hemophilia that was successfully managed without surgery.

Adolescent↗
PubMed1996

Varicella-associated thrombocytopenia: autoantibodies against platelet surface glycoprotein V.

Varicella zoster infection in children can be complicated by acute idiopathic thrombocytopenic purpura (ITP). To determine the etiologic mechanism of this thrombocytopenia, we studied three children with clinically diagnosed varicella infection. Immunoblot analysis of these patients' anti-platelet antibodies identified a unique band at 85 kD. Characterization of this protein revealed that it was platelet surface glycoprotein V (GPV) because it was not affected by a disulfide bond reduction but was cleaved by thrombin. Bernard-Soulier syndrome (BSS) platelets deficient in GPIb-IX and GPV did not react with the sera from our varicella-infected study patients. There was no apparent cross-reactivity between anti-varicella antibody and patients' anti-GPV Ig. We report here the first cases of GPV as the target antigen in autoimmune thrombocytopenia.

Adolescent↗
PubMed1996

The frequency of homozygous deletion of a developmentally regulated Vh gene (Humhv3005) is increased in patients with chronic idiopathic thrombocytopenic purpura.

Little is known of the genetic factors that may contribute to the development of chronic idiopathic thrombocytopenic purpura (cITP). We have previously shown that a developmentally regulated Vh gene (Humhv3005) is absent in 10/41 (24%) of patients with systemic lupus erythematosus while it is absent in only 7/88 (8%) of normal controls. This finding suggests that a homozygous deletion of an Ig variable (V) gene may alter the immune system and thus predispose the host to an autoimmune disorder. We have analyzed the same gene in 44 patients with cITP and found that Humhv3005 and like genes were absent in a higher percentage of patients (14 of 44, 31.8%) than they were absent in either normals (7/88, 8%, p = 0.002) or thrombocytopenic patients without cITP (6/53, 11.3%, p = 0.042); the hv3005 deletion frequency in the latter group did not differ from that in normals (P = 0.74). These data suggest that deletions of Humhv3005 and/or highly homologous Vh genes may predispose individuals to the development of cITP, and may contribute toward production of pathogenic antiplatelet antibodies.

Chronic Disease↗
PubMed1995

Characterization of autoantibodies against the platelet glycoprotein antigens IIb/IIIa in childhood idiopathic thrombocytopenia purpura.

The majority of children with idiopathic thrombocytopenia (ITP) have an acute self-limiting course and no diagnostic test has been identified which will predict the course of thrombocytopenia and detect those with the chronic autoimmune form. The detection of autoantibodies directed against the platelet glycoprotein complex IIB/IIIa, may identify patients with chronic ITP. Serum anti-GP IIb/IIIa antibodies were assessed by the indirect MAIPA assay in 54 children with immune thrompocytopenia at initial presentation along with an additional 7 children previously diagnosed with chronic ITP, to determine if there was a difference in antibody positivity between acute and chronic ITP patients, and whether the identification of antibodies could be used as a predictive test at diagnosis. There was no significant difference in the percentage of antibodies detected in children classified with acute ITP (27/40-68%) compared to children with chronic ITP (13/21-62%, P > 0.05). Patients with acute ITP had significantly lower mean platelet counts at diagnosis compared to the chronic ITP group (16,225/mm3 vs 32,250/mm3, P < 0.05), though there was no significant difference in the bleeding manifestations between the acute and chronic ITP groups. Serum anti-GP IIb/IIIa antibodies are detected in a high percentage of children with ITP and autoantibodies appear to be involved in the pathogenesis of both acute and chronic ITP. The detection of anti-GP IIb/IIIa antibodies at diagnosis, however, does not appear to be a useful prognostic test in childhood ITP.

Adolescent↗
PubMed1991

Hemostasis in the perinatal period: approach to the diagnosis of coagulation disorders.

A wide range of hemostatic disorders may complicate the clinical course of the mother or fetus during pregnancy and the perinatal period. Given the potentially life-threatening implications of hemorrhage or thrombosis, it is important to evaluate these clinical emergencies with an organized approach to the diagnosis of the pertinent derangement and its etiology in order to institute corrective action promptly. Therapeutic interventions are outside the scope of this presentation; however, it is evident that an efficient and precise diagnosis is the first step toward effective, corrective action. The three elements of the hemostatic system that have been presented, blood vessels, platelets, and plasma proteins, provide a logical framework for initiating the hemostatic evaluation and interpreting screening hemostasis tests. Optimum patient management is rewarding, since many of the disorders discussed in this article are of brief duration, improving after the peripuerium. In contrast, the manifestations of hemorrhage may lead to life-long complications.

Blood Coagulation Disorders↗
PubMed1990

Immune thrombocytopenia in the perinatal period.

In recent years, considerable progress has been made in understanding the pathogenic mechanisms involved in the allo- and autoimmune thrombocytopenias. A number of new platelet-associated alloantigens have been described and platelet autoantigens continue to be studied in more detail. Specific assays for antibodies directed against the major antigenic platelet glycoproteins are now available. Important recent clinical investigations have led to modification of the management of immune thrombocytopenia in the perinatal period, resulting in a reduced risk of hemorrhagic complications for both mother and infant. Future investigations are likely to further improve the outcome of these pregnancies.

Autoimmune Diseases↗
PubMed1989

Platelet autoantigens: identification and characterization using immunoblotting.

Antiplatelet autoantibodies are important in the etiology of idiopathic (or immune) thrombocytopenic purpura (ITP). Studies using immunoblotting techniques have been helpful in identifying the antigenic target proteins for the antibodies. Antibodies against the glycoprotein (GP) IIIa portion of the GPIIb/IIIa complex were the first to be demonstrated by this approach. Similar GPIIIa autoantigens have also been found to be the most frequent targets of ITP antibodies. Not all anti-GPIIIa antibodies are directed against the same epitope on GPIIIa. A subset of anti-GPIIIa antibodies found in patients with an acquired qualitative platelet dysfunction actually interfere with fibrinogen binding to normal platelets. Antibodies directed against targets on GPV have been found in patients with acute ITP of childhood. In patients with ITP associated with lupus erythematosus, antibodies which bind to intracellular proteins of apparent molecular weights of 66 and 108 kDa have been detected. Thus, ITP antibodies can have a variety of target antigens. Study of larger series of patients will determine whether identification of platelet autoantigens correlates with clinical course of ITP.

Autoantigens↗