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C Kaplan

Publications and source records attributed to C Kaplan.

At least 127 records · Page 7Linked to original sources
PubMed1991

Recommendations for the evaluation and treatment of neonatal autoimmune and alloimmune thrombocytopenia. The Working Party on Neonatal Immune Thrombocytopenia of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH.

The following recommendations of the Neonatal Hemostasis Subcommittee of the Scientific and Standardization Committee of the ISTH for the management of neonatal immune thrombocytopenia were prepared by the working party on neonatal immune thrombocytopenia. Evaluation, diagnosis, and treatment of the mother and neonate with alloimmune and autoimmune thrombocytopenia are discussed and current recommendations provided. This document is likely to require frequent future revision(s).

Autoimmune Diseases↗
PubMed1991

Osteonectin is an alpha-granule component involved with thrombospondin in platelet aggregation.

We previously showed that thrombospondin, a major alpha-granule glycoprotein of human platelets, forms a specific complex with osteonectin, a phosphoglycoprotein originally described in bone that is also present in human platelets. The storage organelles and the function of osteonectin in platelets are still unknown. In this study, using electron microscopy in combination with immunogold staining, the major storage organelle for platelet-secreted proteins, the alpha-granules. Furthermore, osteonectin was qualitatively and quantitatively assessed by studying normal platelets and the platelets from a patient with gray platelet syndrome. Gray platelet syndrome is a rare congenital bleeding disorder characterized by a selective deficiency in morphologically recognizable platelet alpha-granules and in the alpha-granule secretory proteins. Binding of an iodinated antiosteonectin monoclonal antibody to gray platelet proteins transferred to nitrocellulose from SDS-polyacrylamide gels showed no band corresponding to osteonectin compared to control platelets. Using a polyclonal antiosteonectin antibody-based radioimmunoassay, gray platelets contained 0.2 +/- 0.03 ng osteonectin per 10(6) platelets, which is only 20% of the normal platelet content of osteonectin (0.93 +/- 0.16 ng per 10(6) platelets). Study of the localization of osteonectin to the surface of human platelets demonstrated that a radioiodinated antiosteonectin polyclonal antibody bound specifically to thrombin-stimulated platelets but not to resting platelets. Binding was concentration-dependent, saturable (1710 +/- 453 binding sites per platelet, Kd = 1 microM), and inhibited by an excess of cold antiosteonectin polyclonal antibody. No binding was observed on the surface of thrombin-stimulated gray platelets. To gain further insights into the role of osteonectin released from activated platelets, the effect of an antiosteonectin polyclonal antibody was tested on the aggregation of washed platelets. F(ab')2 fragments from the antiosteonectin polyclonal antibody inhibited in a dose-dependent manner the aggregation of collagen-stimulated, washed human platelets without affecting collagen-induced platelet serotonin release. To characterize the mechanism through which antiosteonectin F(ab')2 fragments inhibit platelet aggregation, the expression of endogenous thrombospondin (TSP) on the surface of thrombin-activated platelets was studied using 125I-labeled anti-TSP monoclonal antibody P10. The endogenous surface expression of TSP to thrombin-stimulated platelets was significantly inhibited in the presence of antiosteonectin F(ab')2 fragments (6286 +/- 2065 molecules of P10 per platelet) compared to 11,230 +/- 766 molecules of P10 per platelet in the presence of nonimmune F(ab')2 fragments.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

X-linked thrombocytopenia and Wiskott-Aldrich syndrome: similar regional assignment but distinct X-inactivation pattern in carriers.

While inherited X-linked (XL) isolated thrombocytopenia is a mild condition, the Wiskott-Aldrich syndrome (WAS) associates severe thrombocytopenia with an immunodeficiency component and has a poor prognosis. Whether these conditions correspond to separate genetic entities or to different mutations of the same gene(s) remains unresolved. The Wiskott-Aldrich syndrome locus has been assigned to Xp 11.2 by means of RFLP studies. The X-inactivation pattern in female carriers has been found to follow a skewed pattern in the hematopoietic cells, thus allowing carrier detection. We studied a family with four members affected by XL thrombocytopenia and report the results of genetic segregation analysis, together with the X-inactivation pattern of hematopoietic cells from an obligate female carrier. Although the affected locus mapped to the same region as that of WAS, lymphocytes presented a skewed pattern of X-inactivation, whereas polymorphonuclear lymphocytes (PMN) did not. These results provide further evidence that the Wiskott-Aldrich syndrome and XL thrombocytopenia are different expressions of mutations within a single locus and that the severity of the disease corresponds to distinct hematopoietic cell selections in obligate carriers.

Adult↗
PubMed1991

HPA-5b (Br(a)) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases.

Maternal alloimmunization against fetal platelets can cause fetal and neonatal thrombocytopenia (NAIT). The HPA-1a (PIA1, Zwa) antigen is by far the most common antigen implicated in NAIT. However, today another antigen often linked with that affection is HPA-5b (Br(a)). This is a report of 39 cases of NAIT involving the HPA-5b antigen. Thrombocytopenia may be of grave consequence. Three infants developed intracerebral haemorrhages (ICH). Of these, one died presumably as a consequence of ICH. Central nervous system (CNS) sequelae in the neonatal period was observed in two children. The potential hazards of death or disabling neurologic sequelae following intracerebral haemorrhage call for rapid and reliable diagnosis and effective therapy. Because there is high risk that subsequent pregnancies might be also affected by NAIT, the mothers of a previously affected child should be managed similarly to the HPA-1b mothers (PIA2, Zwb). The antenatal diagnosis of thrombocytopenia should be made and if necessary the in utero therapy instituted.

Antigens, Human Platelet↗
PubMed1991

Morbidity associated with prenatal disruption of the dividing membrane in twin gestations.

We report eight cases of intrauterine rupture of the dividing membranes in diamniotic twin gestations and the resulting perinatal morbidity and mortality. The poor outcomes associated with these intrauterine amniotic ruptures included fetal and neonatal death secondary to cord entanglement, preterm rupture of the membranes, preterm labor and delivery, and amniotic band syndrome. The overall perinatal mortality rate was 44% (seven of 16), and the mean gestational age at delivery was 29 weeks (range 22-34). Possible etiologies for this intrauterine diamniotic rupture include fetal trauma to the dividing membranes, amniocentesis, infection, and developmental disturbances. A new theory is examined to explain the surviving twin's morbidity associated with intrauterine death of the co-twin. This study suggests that intrauterine rupture of diamniotic twin membranes carries a perinatal mortality consistent with that of true monoamniotic gestations and that, in fact, this entity may be more common than previously thought. Finally, a suspected monoamniotic gestation cannot be ruled out by the historic presence of a dividing membrane on previous ultrasound examination.

Adolescent↗
PubMed1990

Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B.

BACKGROUND AND METHODS: The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated). RESULTS: The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, -7 and +5 percent, respectively), but more substantially among patients treated with lovastatin and colestipol (-46 and +15 percent) or niacin and colestipol (-32 and +43 percent). In the conventional-therapy group, 46 percent of the patients had definite lesion progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11 percent. By comparison, progression (as the only change) was less frequent among patients who received lovastatin and colestipol (21 percent) and those who received niacin and colestipol (25 percent), and regression was more frequent (lovastatin and colestipol, 32 percent; niacin and colestipol, 39 percent; P less than 0.005). Multivariate analysis indicated that a reduction in the level of apolipoprotein B (or LDL cholesterol) and in systolic blood pressure, and an increase in HDL cholesterol correlated independently with regression of coronary lesions. Clinical events (death, myocardial infarction, or revascularization for worsening symptoms) occurred in 10 of 52 patients assigned to conventional therapy, as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol (relative risk of an event during intensive treatment, 0.27; 95 percent confidence interval, 0.10 to 0.77). CONCLUSIONS: In men with coronary artery disease who were at high risk for cardiovascular events, intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions, increased the frequency of regression, and reduced the incidence of cardiovascular events.

Adult↗
PubMed1990

Fetal platelet counts in thrombocytopenic pregnancy.

Fetal platelet counts were assessed by percutaneous umbilical blood sampling in 64 pregnancies (62 women) with maternal thrombocytopenia. In 33 pregnancies associated with chronic immune thrombocytopenia, 11 of the fetuses had platelet counts below 150 x 10(9)/l and 4 were severely thrombocytopenic (less than 50 x 10(9)/l). In 31 pregnancies with symptomless maternal thrombocytopenia as an incidental finding, 4 fetuses were thrombocytopenic, 1 of them severely. Maternal indices, including antiplatelet antibodies, did not correlate with risk of fetal thrombocytopenia; and in those with repeat measurements there was no evidence of benefit from treatment with either corticosteroids (4 cases) or intravenous immunoglobulin (3 cases). Percutaneous umbilical blood sampling, a safe procedure in experienced hands, provides accurate platelet counts in thrombocytopenic pregnancy, as an aid to decisions on mode of delivery and to assessment of treatments.

Blood Specimen Collection↗
PubMed1990

Aequorin-detected calcium changes in stimulated thrombasthenic platelets. Aggregation-dependent calcium movement in response to ADP.

Calcium changes in normal and thrombasthenic platelets were recorded using the PICA-apparatus. Aequorin was loaded in the presence of DMSO, EGTA and PGE1. Platelets of three patients with type I thrombasthenia stimulated with A-23, 187, thrombin, PMA in the presence 1 mM Ca++ and 1 mM Mg++ were able to normally raise their calcium concentrations. The maximal values could be found below the normal range with collagen, ADP and PAF-acether. Calcium mobilization from internal stores in response to thrombin was normal. There were two calcium peaks in normal platelets stimulated with ADP. The second one was suppressed by omitting fibrinogen, stirring, or by adding aspirin, and was absent in thrombasthenic platelets. Thus the GP IIb-IIIa complex is not a prerequisite for calcium fluxes but is involved, when weak agonists such ADP are used, through an aggregation-dependent reinforcement of platelet activation.

Adenosine Diphosphate↗
PubMed1990

C4 null alleles in childhood onset systemic lupus erythematosus. Is there any relationship with renal disease?

C4 genotyping was performed in 38 unrelated patients with systemic lupus erythematosus (SLE) aged 2-16 years at onset. Null alleles were found in 68% of patients. Ten patients had one null allele at the C4A locus and 11 others had one null allele at the C4B locus. One patient was homozygous for C4A*Q0, 2 homozygous for C4B*Q0 and 1 heterozygous C4A*Q0/B*Q0. The last patient was C4A*Q0B*Q0/B*Q0. Three patients, being heterozygous C2 deficient, had thus a combined C2 and C4 deficiency. A significant increase in C4 null alleles in SLE patients has been reported by different authors who have suggested that the C4 null alleles confer susceptibility to SLE. However, when considering only the 20 patients of French descent, no differences in gene frequencies were found between this group and the French population. Disease patterns were compared in patients with or without null C4. Renal involvement was more frequent in the C4A*Q0 or C4A*Q0/C4A*Q0 patients than in the patients without null C4 (9/11 vs 3/12). These data suggest that differences between these results and those of others might be due to clinical heterogeneity of the disease, as exemplified by the frequency of renal involvement in the different groups. In susceptible individuals the absence of one C4A gene product may predispose the patient to renal involvement.

Adolescent↗
PubMed1990

New families of adhesion molecules play a vital role in platelet functions.

Adhesion molecules play a crucial part in cell-matrix and in cell-cell interactions. These interactions, which are essential to the body's defense processes, involve adhesion molecules belonging to different families: integrins, immunoglobulins and selectins. Integrins are expressed by a large number of tissues, whereas other adhesion molecule families are restricted to a small number of cell types. A recent symposium dealt with the recruitment of circulating platelets at specific sites, their adhesion to extracellular matrix components and their activation by agonists leading to aggregation or attachment to other cells. These events, supporting hemostasis and thrombosis, involve integrins, selectins and other adhesion molecules. This report focuses on newly reported integrins (GPIa, GPIc, GPIIa), selectins (GMP-140) and GPIIIb, previously known as 'minor' surface oriented platelet glycoproteins. Major membrane glycoproteins such as GPIIb-IIIa (an integrin) and GPIb, which also play a vital role in platelet functions, have been extensively reviewed elsewhere.

Blood Platelets↗
PubMed1990

DR-restricted T-cell reactivities associated with the Dw19 specificity can be directed against the products of either locus DRB3 (DRw52c) or locus DRB1.

HLA-Dw 19 antigen presenting cells express two different DR beta chains encoded respectively by DRB1 and DRB3 genes. In the present study we determined which of these two DR beta chains is recognized by DR-restricted T-cell clones. First we selected influenza-specific, DR-restricted T-cell clones of which restriction is strictly associated with the Dw19 specificity. Then we characterized by oligonucleotide typing one antigen presenting cell (HC12M) which exhibits a new haplotype associating a DRB1 gene highly related or identical to that from Dw 18 haplotypes with a DRB3 gene highly related or identical to that from Dw19 haplotypes. Finally, by testing the reactivity of the selected T-cell clones against Dw18, Dw19, and HC12M antigen presenting cells, we show that these DR-restricted "Dw19-specific" effectors can recognize either the DRB1-encoded chain present only on Dw19 antigen presenting cell or the DRB3-encoded chain shared by Dw19 and HC12M antigen presenting cells. Interestingly, our results show that DRB1 chains from Dw19 and Dw18 which differ by a single amino acid substitution at position 86 may be distinguished by T cells, implicating that this residue plays a role in T-cell recognition of HLA-DR-antigen complex. The implication of our results with regard to the new nomenclature of HLA specificities defined by T-cell clones will be discussed.

Antigen-Presenting Cells↗
PubMed1990

HLA-DRw52a is involved in alloimmunization against PL-A1 antigen.

The alloimmunization against the platelet PL-A1 antigen is strongly associated with a HLA class II structure in mothers of thrombocytopenic neonates. Most of the immunized women have first been shown to possess the DR3 specificity and subsequently the DRw52 allele. The 18 immunized mothers studied here by restriction fragment length polymorphism analysis had the DRw52a specificity at the DRB3 locus whatever their HLA-DRB1 gene product. This finding strongly suggests that the DRB3 chain is directly involved in the presentation of the PL-A1 antigen to the specific T cell. In addition, the similarities between DR3 and DRw52 structures due to a hypothetical gene conversion event should be considered in order to understand the high frequency of DR3 among the DRw52a-responding women. Alternatively, the high frequency of DR3 among the DRw52-responding mothers might be due to the high responder status associated with the former specificity.

Antigens, Human Platelet↗