Nicole Couprie

The effects of high molecular weight- and low molecular weight-heparins on superoxide ion production and degranulation by human polymorphonuclear leukocytes

High molecular weight (HMW) and low molecular weight (LMW) heparins affected superoxide ion production and degranulation by polymorphonuclear leukocytes (PMNL) isolated from either chronic hemodialyzed patients or healthy controls. Low concentrations in HMW-heparin, below 1.76 aXa IU/ml for patients and 1.34 aXa IU/ml for controls, increased O2- production started by phorbol myristate acetate. High concentrations above these values decreased it. Increasing LMW-heparin concentrations constantly decreased O2- production using the same stimulus. Myeloperoxidase (MPO) released by PMNL was found to be significantly HMW- and LMW-heparins dose-dependent. The addition of calcium chloride significantly increased MPO release. Lactoferrin release was not dose-dependent of HMW- or LMW-heparins. However, an increase of the percentage of positive responses for lactoferrin release was observed in the simultaneous presence of HMW-heparin and CaCl2 compared to HMW-heparin alone. Lysozyme release was also not dose-dependent of HMW- or LMW-heparins. An increase of the percentage of positive responses for lysozyme release was observed in the presence of CaCl2 alone compared to HMW-heparin.

Effects of tiaprofenic acid on interleukin 1, phospholipase A2 activity, prostaglandins, neutral protease, and collagenase activity in rheumatoid synovial fluid

IL-1 and prostaglandin (PGE2, PGF2 alpha, TXB2) concentrations, PLA2 activity, neutral protease activity, and collagenase activity specific for types I and II collagen were determined in the SF of patients suffering from RA, before and after treatment with TA. Active and latent forms of protease and collagenases were regularly detected but were unrelated to IL-1, PLA2, and PGE2. TA induced a significant decrease in tested eicosanoids but IL-1, PLA2, and proteases were unchanged.

Two New α Chain Variants: Hb Die [α93(FG5)Val→Ala (α1)] and Hb Beziers [α99(G6)Lys→Asn (α1)]

The first new a chain variant here reported, Hb Die [a93(FG5)Val!Ala (a1)], was found during investigations of an anemia prior to surgery for correcting spina bifida. The patient was a 7-year-old girl, living near the town of Die in Southeast France; her parents were of French Caucasian origin. The hematological findings were as follows: RBC 5.8 10/L, hemoglobin (Hb) 11.9 g/dL, MCV 65.5 fL and MCH 20.5 pg; the serum iron level was 6.6 mmol/L (normal values 9–30 mmol/L). Iron treatment associated with erythropoietin was prescribed. The family refused all transfusion therapy. Unfortunately, no hematological data were available after this treatment and no family studies were possible. The second new a chain variant, Hb Beziers [a99(G6)Lys!Asn (a1)], was found during the determination of Hb A1c by high performance liquid chromatography (HPLC) in a diabetic patient. The new Hb variant was detected in a 72-year-old woman, who was also of French Caucasian origin and lived in the city of Beziers in the south of France. The hematological data were as follows: RBC 4.77 10/L, Hb 13.6 g/dL, MCV 86 fL and MCH 28.5 pg; physical examination was normal, without hepatomegaly or splenomegaly.

Hb AUBAGNE [β64(E8)Gly→Ala]: A NEW UNSTABLE β CHAIN VARIANT FOUND IN A FRENCH FAMILY

Only one hemoglobin (Hb) variant has been reported at the internal position 64(E8)Gly of the b-globin chain: Hb J-Calabria, also known as Hb J-Bari and Hb J-Cosenza (!Asp). We here report a new Hb variant at the same position, namely, Hb Aubagne (!Ala), that was found in a young woman suffering from an anemia. The mutation is close to the distal histidine b63(E7) and leads to moderate instability. Routine Hb analyses were performed by isoelectrofocusing (IEF) and high performance liquid chromatography (HPLC) of Hbs and globin chains. Molecular characterization of the mutation was achieved by polymerase chain reaction (PCR), followed by direct DNA sequencing of the PCR products. PCR amplification of exons 1 and 2 of the b-globin gene was carried out using the following primers: 50-TGTACTGATGGTATGGGGC-30 (primer 1) located 225 nucleotides upstream to the Cap site, and 50-AAACGATCCTGAGACTTCC-30 (primer 2) located in the second intron. PCR amplification of exon 3 was performed using: 50-TATCATGCCTCTTTGCACTC-30 (upstream primer 3)

A new alpha chain hemoglobin variant: Hb Al-Hammadi Riyadh [alpha75(EF4)Asp-->Val (alpha2)].

A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC→GTC); α75(EF4)Asp→Val (α2)] corresponding to an A→T transversion on the second exon of the α2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.

Two New δ-Globin Gene Variants: Hb A2-Saint-Etienne [δ14(A11)Leu→Pro (HBD: c.44T>C)] and Hb A2-Marseille [δ22(B4) Ala→Lys (HBD: c.67G>A;68C>A)]

We report two new variants of the δ-globin gene: Hb A2-Saint-Etienne [δ14(A11)Leu→Pro] and Hb A2-Marseille [δ22(B4)Ala→Lys]. The first variant has a low rate of expression, the second results from a double nucleotide mutation on the same codon.

Two new hemoglobin variants: Hb Aix-Les-Bains [β5(A2)Pro→Leu; HBB:c.17 C>T] and Hb Dubai [α122(H5)His→Leu (α2); HBA2:c.368 A>T].

We report two new hemoglobin (Hb) variants; one causing an impairment of the N-terminal glycation of the β-globin chain and the other a hematological phenotype of α-thalassemia (α-thal). The first variant is Hb Aix-les-Bains [β5(A2)Pro→Leu] and the second Hb Dubai [α122(H5)His→Leu (α2)]. These two new Hb variants were detected by chromatographic and electrophoretic methods and characterized by molecular studies. Hb Dubai gives an α-thalassemic phenotype and should be routinely detected for preventing severe Hb H disease in couples at-risk for α-thal.

Two new hemoglobin variants: Hb Brem-sur-Mer [beta9(A6)Ser-->Tyr] and Hb Passy [alpha81(F2)Ser-->Pro (alpha2)].

Two new hemoglobin (Hb) variants: Hb Brem-sur-Mer [codon 9 (TC T→TA T); β9(A6)Ser→Tyr] on the first exon of the β-globin gene and Hb Passy [codon 81 (T CC→C CC); α81(F2)Ser→Pro (α2)] on the second exon of the α2-globin gene, are described. The two variants were characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities: microcytosis and hypochromia were found only in the carrier of Hb Passy. In the absence of an association with an α-thalassemic deletion or mutation, the mutation 81(F2)Pro could induce a possible α-thalassemia (thal).

A Mutation of the β-Globin Gene Initiation Codon, ATG→AAG, Found in a French Caucasian Man

A new mutation of the β-globin gene initiation codon, ATG→AAG (Met→Tyr), is reported in a man originating from the southeast of France. Typical hematological findings of a β-thalassemia (thal) trait were found. We emphasize the importance of characterizing uncommon β-thal mutations for genetic counseling.

Hb GERLAND [α55(E4)Val → Ala (α2)]: A NEW NEUTRAL α CHAIN VARIANT INVOLVING THE α2 GENE

During routine hemoglobin (Hb) investigations for a possible hemoglobinopathy, performed on a 6-year-old boy suffering from mild microcytic anemia, an abnormal Hb was detected by cation exchange high performance liquid chromatography (HPLC) using the VARIANT System with the b-Thalassemia Short Program (Bio-Rad Laboratories, Hercules, CA, USA). The proband’s parents originate from Southeast France. The abnormal variant, accounting for 31% of the total Hb, eluted as a shoulder 0.3 minutes behind Hb A. The abnormal Hb was not detected by isoelectrofocusing (IEF) or by reversed phase HPLC of globin chains (1–4). Family studies showed the presence of the abnormal Hb, in the same amount, in the proband’s sister and in a lower amount in the father, suggesting a possible interaction with an a-thalassemia (thal) gene. Isopropanol instability test, performed on the proband’s hemolysate, was found to be slightly positive at 30 minutes (5). Physical examination revealed no abnormalities. The hematological parameters of all members of this family are presented in Table 1. Serum iron and serum ferritin levels were normal. Molecular characterization of the mutation was achieved by polymerase chain reaction (PCR), followed by direct DNA sequencing of the PCR products HEMOGLOBIN, 25(4), 417–420 (2001)