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Biomedical subjects

C Kaplan

Publications and source records attributed to C Kaplan.

At least 73 records · Page 4Linked to original sources
PubMed1996

Lack of platelet response to collagen associated with autoantibodies against glycoprotein (GP) Ia/IIa and Ib/IX leading to the discovery of SLE.

An increased bleeding time and a prolonged APTT (activated partial thromboplastin time) observed in a 48-year-old woman led to the discovery of SLE confirmed by immunological tests. Platelet function and analysis of membrane glycoproteins revealed an isolated impaired collagen induced platelet aggregation and allowed the detection of autoantibodies directed against GpIa/IIa and GpIb/IX.

Antigens, CD↗
PubMed1996

Genetic susceptibility and anti-human platelet antigen 5b alloimmunization role of HLA class II and TAP genes.

Platelet alloimmunization may result in post-transfusion purpura, and during pregnancy may cause neonatal alloimmune thrombocytopenia (NAIT), with a frequency estimated at 1.3 per 1000 live births. The risk of morbidity is significant: 20% of affected infants have neurologic sequelae and the death rate is about 10%. A better understanding of the immune response to platelet alloantigens would allow for a better definition, and thus better management of pregnant women at high risk. Limited data are available on the immune response against HPA-5b, the second most frequent antigen, after HPA-1a, implicated in NAIT. We studied HLA class II and TAP gene polymorphism in 50 women immunized against HPA-5 system antigens. Our results suggest a strong association of alloimmunization with a cluster of HLA DR molecules sharing a particular polymorphic amino acid sequence at position 69-70 (Glu-Asp encoded by GAA-GAC nucleotide sequence) of the DR beta 1 chain (RR = 2.95, RR = 5.70 when patients were homozygous for this sequence), and a negative association with the DRB1*0301 allele (2.1% vs. 28%; RR = 0.08). Furthermore, increased frequency of a TAP2 dimorphism at position 379 was observed in immunized women against the HPA-5 antigens (RR = 4.7).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

HLA phenotype polymorphism in the Lebanese population.

The HLA-A, -B, -DR and DQ phenotypes have been defined in a panel of 217 Lebanese. These subjects were all unrelated, belonged to different religious communities and originated from the various provinces of Lebanon. All the broad class I specificities tested, except splits A25(10), B54(22) and B56(22), were present in this panel. When HLA-A and -B antigen frequencies were compared with data on the Caucasoids, Negroids and Orientals, several similarities in antigen frequencies could be found between some frequencies observed in the Lebanese and those observed in the Negroids and/or Orientals. There were no frequencies equivalent to those particular to the Caucasoids. In addition, two groups of class I antigens could be distinguished: a first group (A32, B14, B18, B35, B38, B39, B41 and B50) showing higher frequencies, and a second group (A31, B27, B60 and B62) showing lower frequencies than those observed in the Caucasoids, Negroids and Orientals. However, when analysed separately, several mediterranean ethnic groups, notably the Greeks and Italians, have a frequency profile equivalent to that of the Lebanese, with the exception of the B41 specificity, which is particularly high in the Lebanese (14.2%). The data concerning the class II antigens are the most interesting. All the specificities were present in the panel. The HLA-DR5 is the highest frequency of DR antigens in the present panel (58.9%) and nearly all DR5 positive individuals are DR11. The DR11 allele accounts for 33.1% of the total DR gene frequency. The highest DQ antigen frequency is that of DQ3 (76.4%), the majority of which is DQ7 (66.4%). We observed a high DR11-DQ7 haplotype frequency (29.4%) with a significant delta value for linkage disequilibrium. There is no linkage disequilibrium between B41 and DR11. The commonly observed linkage disequilibrium between the DQ5 allele, and the DR1, DR2, DR10 and DR14 alleles are not significant in this Lebanese panel.

Adolescent↗
PubMed1996

Low incidence of specific anti-platelet antibodies detected by the MAIPA assay in the serum of thrombocytopenic MDS patients and lack of correlation between platelet autoantibodies, platelet lifespan and response to danazol therapy.

We prospectively studied the mechanism of thrombocytopenia in 30 patients with myelodysplastic syndrome (MDS), who had a platelet count <or= 70 x 10(9)/l, and marrows blasts <or= 10% by analysis of platelet lifespan, platelet-bound IgG antibodies by platelet radioactive antiglobulin test (PRAT), and circulating and platelet-bound autoantibodies specifically directed against platelet glycoproteins by indirect and direct MAIPA test. PRAT analysis was positive in 21/30 patients (70%), but antiplatelet antibodies were found in only eight by the MAIPA test. Platelet lifespan was shortened in five cases, only one of whom had a positive MAIPA test. Patients were treated by danazol (600 mg/d), and 9/26 evaluable patients (35%) responded, including three of the five patients with shortened platelet lifespan. No correlation between platelet lifespan, results of PRAT and MAIPA tests, and response to danazol was found. In conclusion, specific antiplatelet autoantibodies, reduced platelet lifespan, and efficacy of androgen therapy on platelets were seen in 20%, 17% and 35% of MDS with thrombocytopenia, respectively, but no correlation between these findings was found in this study.

Adolescent↗
PubMed1996

A monoclonal antibody directed against a granule membrane glycoprotein (GMP-140/PADGEM, P-selectin, CD62P) inhibits ristocetin-induced platelet aggregation.

P-selectin (also called CD62, GMP-140, PADGEM, CD62P) is a recently described member of a family of vascular adhesion receptors expressed by activated platelets and endothelial cells that are involved in leucocyte cell adhesion. The aim of this study was to characterize a new monoclonal antibody (LYP7) directed against activated human blood platelets that inhibits ristocetin-induced platelet aggregation. Immunoadsorbent affinity chromatography and immunoprecipitation studies showed that LYP7 (IgG1) bound a surface-labelled glycoprotein (GP) which changed its apparent molecular mass (M(r)) on reduction from 138 kD (situated below GPIIb) to 148 kD (above GPIIb alpha). LYP7 and S12, a monoclonal antibody directed against P-selectin immunoprecipitated the same band. Using ELISA assay, purified P-selectin was shown to bind LYP7 and S12 monoclonal antibodies. Binding sites of 125I-labelled LYP7, which was greatly increased on thrombin-stimulated (2 U/ml) washed platelets (10825 +/- 2886, mean +/- SD) Kd = 1.5 +/- 0.5 nM) compared to resting platelets (2801 +/- 1278, mean +/- SD) (Kd = 1.5 +/- 0.6 nM), was found to be normal on thrombin-stimulated platelets taken from a patient with grey platelet syndrome or a patient with Glanzmann thrombasthenia. LYP7 (IgG1, F(ab')2 or Fab fragments) inhibited ristocetin-induced platelet aggregation of platelets in a dose-dependent fashion without affecting the binding of von Willebrand (vWf) factor. However, agglutination of formaldehyde-fixed platelets induced by ristocetin was not affected by monoclonal antibody LYP7. In addition, the binding of thrombin-activated platelets to neutrophils was inhibited by monoclonal antibody LYP7. These results strongly suggest that P-selectin, by promoting cell-cell contact, may play an active role in platelet-platelet interactions.

Antibodies, Monoclonal↗
PubMed1996

Screening primiparous women and newborns for fetal/neonatal alloimmune thrombocytopenia: a prospective comparison of effectiveness and costs. Immune Thrombocytopenia Working Group.

A prospective study was conducted in three maternity wards to compare the medical outcomes and the costs of two screening strategies for the detection of fetal/neonatal alloimmune thrombocytopenia (FMAIT). A total of 2066 primiparas and 6081 newborns were included. Fifty-two primiparous women with HPA-1b phenotype were found, and 45 were followed during pregnancy. Four women developed antibodies, and two fetuses exhibited FMAIT; therefore, the prevalence of anti-HPA-1a was 2 per 1000, and the prevalence of FMAIT 1 per 1000. Forty-eight thrombocytopenic newborns were found out of a total of 5632 blood samples. Five were HPA-1a children whose mothers were HPA-1b. The cost-effectiveness of screening all primiparous women was $45,000 and of screening all newborns is $18,000-per anti-HPA-1a alloimmunization diagnosed. Costs per fetal death or disability averted were $500,000 for the primiparous strategy and $225,000 for the newborn strategy. In conclusion, screening newborns for neonatal alloimmune thrombocytopenia is more cost-effective than screening primiparous women.

Antigens, Human Platelet↗
PubMed1996

Drawbacks of the MAIPA technique in characterising human antiplatelet antibodies.

Monoclonal Antibody-specific Immobilisation of Platelet Antigens (MAIPA) assays have been developed to allow the identification and characterisation of antibodies directed against platelets. A major disadvantage of the MAIPA test is the existence of false negative results. This is due to the competition between human and monoclonal antibodies (MoAb) for epitopes that are either identical or very close. In this report we used the MAIPA technique to test anti-HPA-1a alloantibodies and anti-Naka isoantibodies in conjunction with a panel of murine MoAbs directed against CD41/61 or CD36 respectively. Our data demonstrate that the choice of MoAbs used in MAIPA is very important for accurate diagnosis of clinical conditions and institution of specific therapy. Moreover, the results obtained are in favour of an heterogeneity for the recognition of the alloepitope HPA-1a and of distinguishable epitopes on GPIV.

Antibodies, Monoclonal↗
PubMed1996

Relation of chemical structure to spatial distribution of sensory responses in rat olfactory epithelium.

1. Electroolfactogram (EOG) recordings were made in three configurations from the rat olfactory epithelium. Each configuration compared recordings in the dorsomedial recess of the epithelium with recordings in ventral or lateral parts of the epithelium. Most comparisons were made with simultaneous recordings. The exception was a series in which the dorsal recess and lateral space between the base of two turbinate bones were directly exposed for odor application and recording. The spatial distributions of maximal responses were largely independent of recording configuration. 2. Simultaneous recordings compared dorsomedial and lateral sites in the epithelium during stimulation with a series of 50 odorants. The odorants that evoked larger responses in the lateral sites were usually compounds that lacked oxygen containing functional groups (such as the carbonyl group). This was true for straight chain and cyclic alkanes, for terpine compounds, and for aromatic compounds. The major exception was cineole, a bicyclic compound. All compounds containing ketone groups evoked larger dorsomedial responses. The responses of aldehydes and esters depended upon whether they were attached to aliphatic or aromatic chains. 3. In the three types of preparation, the sites responding best to ketones were in the same expression zone of the epithelium according to published maps for the rat and mouse. The sites responding best to odors without functional groups were in the far lateral or ventral region and corresponded to one of the two most lateral and ventral expression zones. This fact suggests that the receptors in these regions have a preference for particular chemical properties. This level of analysis cannot determine whether all receptors in each zone have a stronger response to certain properties of these odorants or whether each zone contains different proportions of receptors with these properties.

Anesthesia, Inhalation↗
PubMed1996

Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1.

The hereditary ataxias represent a clinically and genetically heterogeneous group of neurodegenerative disorders. Various classification schemes based on clinical criteria are being replaced as molecular characterization of the ataxias proceeds; so far, seven distinct autosomal dominant hereditary ataxias have been genetically mapped in the human genome. We report linkage to chromosome 16q22.1 for one of these genes (SCA4) in a five-generation family with an autosomal dominant, late-onset spinocerebellar ataxia; the gene is tightly linked to the microsatellite marker D16S397 (LOD score = 5.93 at theta = .00). In addition, we present clinical and electrophysiological data regarding the distinct and previously unreported phenotype consisting of ataxia with the invariant presence of a prominent axonal sensory neuropathy.

Axons↗
PubMed1996

[Prenatal management of fetuses with alloimmune thrombocytopenia].

Fetal alloimmune thrombocytopenia is caused by maternal immunization against a fetal platelet alloantigen and transplacental transfer of the antibody into the fetal circulation. Since 10-20% of the fetuses or newborns are threatened by intracranial hemorrhages (ICH) early management is required. Intensive prenatal monitoring should be performed if a maternal HPA-1a antibody is known and a previous infant suffered from thrombocytopenia and/or ICH. Fetal blood sampling (FBS) should be started at 20th to 22nd weeks of gestation to assess fetal phenotype and platelet count. Different concepts to elevate the fetal platelet count have been discussed: corticosteroids, maternal intravenous immunoglobulins (ivIgG), fetal ivIgG and repeated fetal platelet transfusions. In a European survey with data from five centres maternal corticoid treatment and ivIgG infusion were accompanied by increasing fetal platelet counts in only 20 and 24% of the cases, respectively. In fetuses with very low platelet counts only transfusions of compatible platelets in short intervals are able to sustain a safe platelet count. Fetuses with mild thrombocytopenia should be monitored by subsequent FBS since it could be shown that platelet counts tend to decline during gestation. To avoid bleeding complications during and after FBS which was observed in about 5% of the cases every cord vessel puncture should be covered by a platelet transfusion. As no safe and non-invasive therapy exists for fetal alloimmune thrombocytopenia the value of prenatal screening programs in unaffected pregnancies is questionable.

Adrenal Cortex Hormones↗
PubMed1996

Major histocompatibility complex markers and disease heterogeneity in one hundred eight patients with systemic onset juvenile chronic arthritis.

STUDY OBJECTIVES: Long term prognosis of systemic juvenile chronic arthritis range from full recovery to extremely severe crippling polyarthritis. An association between HLA-DR4 and a poor articular outcome has been reported. We studied the frequencies of class I, class II, and class III antigens according to clinical and laboratory test findings, particularly presence of antibodies to type II collagen, in a cohort of 108 patients. METHODS: A number of clinical and laboratory test findings were recorded at the time of the study. Class A, B, C, and DR antigens were assayed using a microcytotoxicity method. Antibodies to type II collagen were evaluated by ELISA. BMDP software was used for the statistical analysis. RESULTS: No significant differences in antigen frequencies were found between patients and controls for any of the loci. There were no significant differences in HLA-DR antigen frequencies between patients with favorable joint outcomes and those with chronic polyarthritis. CONCLUSION: Our findings do not corroborate those of earlier studies in smaller numbers of patients.

Arthritis, Juvenile↗
PubMed1995

The molecular genetic basis of Glanzmann's thrombasthenia in a gypsy population in France: identification of a new mutation on the alpha IIb gene.

Glanzmann's thrombasthenia is a rare inherited bleeding disorder caused by a qualitative or quantitative defect of platelet alpha IIb beta 3. We describe here a new mutation that is the molecular genetic basis of Glanzmann's thrombasthenia in two gypsy families. Our investigation was focused on the alpha IIb gene as a result of biochemical and immunologic analysis of patients' platelets showing undetectable alpha IIb but residual beta 3 levels. The entire alpha IIb cDNA was polymerase chain reaction (PCR) amplified using patients platelet RNA. Sequence analysis showed an 8-bp deletion located at the 3' end of exon 15. This deletion causes a reading-frame shift leading to a premature stop codon and the synthesis of a severely truncated form of alpha IIb. Genomic DNA study showed a G-->A substitution, the Gypsy mutation, at the splice donor site of intron 15. This mutation results in an abnormal splicing occurring at an alternative donor site located 8 bp upstream from the mutation. Based on those results, an allele-specific PCR analysis was developed to allow a rapid identification of the mutation in patients and potential carriers of the gypsy community. This PCR analysis can also be used for genetic counseling and antenatal diagnosis.

Alleles↗
PubMed1995

Detection of antilineage specific leucocyte antibodies by a quantitative immunocytometry method in sera from candidates for renal allografts.

A sensitive and quantitative flow cytometry method for detecting antileucocyte antibodies was developed to study retrospectively samples from candidates using frozen donor cells and frozen recipient sera. This immunofluorescence method was used to compare levels of reactivities of serum antibodies before and after donor specific blood transfusion treatment and after renal transplantation. The results demonstrate that the flow cytometry crossmatch is a sensitive and accurate method which should be used prospectively before precluding transplantation in the presence of a positive B cell standard crossmatch. Antibodies detected by flow cytometry before transplantation could be responsible for an early acute rejection episode. Finally, combination of flow cytometry crossmatch and standard crossmatch assays might thus be useful before precluding transplantation in living related donors.

Adolescent↗