A novel base change leading to Hb vanderbilt [β89(F5)Ser→Arg, AGT>AGA]

We describe a high oxygen affinity hemoglobin (Hb) variant (Hb Vanderbilt) as a result of a heterozygous novel base change from T to A at codon 89 (AGT>AGA) leading to an amino acid change from serine to arginine. © 2011 Informa Healthcare USA, Inc.

Diagnosis and management of congenital and idiopathic erythrocytosis

An erythrocytosis occurs when there is an increased red-cell mass. The causes of erythrocytosis are divided into primary, when there is an intrinsic defect in the erythroid cell, and secondary, when the cause is extrinsic to the erythroid cell. An idiopathic erythrocytosis occurs when the increased red-cell mass has no identifiable cause. Primary and secondary defects can be further classified as either congenital or acquired causes. The diagnostic pathway starts with a careful history and examination followed by measurement of the erythropoietin (EPO) levels. This allows a division of those patients with a low EPO level, who can then be investigated for primary causes of erythrocytosis, and those with a normal or high EPO level, where the oxygen-sensing pathway needs to be explored further. Physiological studies in those with congenital defects in the oxygen-sensing pathway show many changes in the downstream metabolism adapting to the defect, which has a bearing on the management of the disorders. Low-dose aspirin and venesection to an achievable target are the main therapeutic options that can be considered in the management of erythrocytosis. Specific guidance on venesection options should be considered with certain causes such as high oxygen-affinity hemoglobins.

A Japanese Family with Congenital Erythrocytosis Caused by Haemoglobin Bethesda

We herein present a case of congenital erythrocytosis caused by haemoglobin (Hb) Bethesda in a Japanese family. A 55-year-old asymptomatic man was referred to our hospital for the investigation of erythrocytosis, which was present in other members of his family. The patient's serum erythropoietin level was normal, and the JAK2 V617F mutation was not detected. His P50 value was mildly decreased, thus we suspected the presence of an Hb variant with a high oxygen affinity. The high-performance liquid chromatography analysis showed an abnormal Hb, and by direct sequencing we identified the Hb Bethesda variant in this patient. For the differential diagnosis, we recommend the estimation of the P50 value as a practical and useful test.

Congenital erythrocytosis

INTRODUCTION: Congenital erythrocytosis is by definition present from birth. Patients frequently present in childhood or as young adults and a family history may be present. The erythrocytosis can be primary where there is a defect in the erythroid compartment of secondary where increased erythropoietin production produced due to the defect leads to an erythrocytosis.

MATERIAL AND METHODS: Primary causes include erythropoietin receptor mutations. Congenital secondary causes include mutations in the genes involved in the oxygen-sensing pathway and haemoglobins with abnormal oxygen affinity. Investigations for the cause include an erythropoietin level, oxygen dissociation curve, haemoglobin electrophoresis and sequencing for known gene variants.

RESULTS: The finding of a known or new molecular variant confirms a diagnosis of congenital erythrocytosis. A congenital erythrocytosis may be an incidental finding but nonspecific symptoms are described. Major thromboembolic events have been noted in some cases. Low-dose aspirin and venesection are therapeutic manoeuvres which should be considered in managing these patients.

CONCLUSIONS: Rare individuals presenting often at a young age may have a congenital erythrocytosis. Molecular investigation may reveal a lesion. However, in the majority, currently no defect is identified.

Affinity of divalent mercury towards nitrogen donor ligands

As with gold, relativistic effects are important in the chemistry of mercury Together with the closed-shell d(10) configuration of Hg2+ they account for the special bonding schemes as preferred linear coordination with highly covalent contributions to chemical bonding or special affinities to nitrogen and sulfur that are so prominent in mercuric chemistry This research report summarizes recent research on coordination compounds with halogen, oxygen and, especially, nitrogen as direct bonding partners of di-valent mercury and their competition with each other. In a rather systematic way N-donor ligands with one, two and more than two nitrogen atoms have been inspected in order to elucidate the influences that lead to the special bonding schemes of Hg-II-N compounds.

The conserved Helix C region in the superfamily of interferon-a/interleukin-10-related cytokines corresponds to a high-affinity binding site for the HSP70 chaperone DnaK.

HSP70 chaperones mediate protein folding by ATP-dependent interaction with short linear peptide segments that are exposed on unfolded proteins. The mode of action of the Escherichia coli homolog DnaK is representative of all HSP70 chaperones, including the endoplasmic reticulum variant BiP/GRP78. DnaK has been shown to be effective in assisting refolding of a wide variety of prokaryotic and eukaryotic proteins, including the -helical homodimeric secretory cytokine interferon- (IFN-). We screened solid-phase peptide libraries from human and mouse IFN- to identify DnaK-binding sites. Conserved DnaK-binding sites were identified in the N-terminal half of helix B and in the C-terminal half of helix C, both of which are located at the IFN- dimer interface. Soluble peptides derived from helices B and C bound DnaK with high affinity in competition assays. No DnaK-binding sites were found in the loops connecting the -helices. The helix C DnaK-binding site appears to be conserved in most members of the superfamily of interleukin (IL)-10-related cytokines that comprises, apart from IL-10 and IFN-, a series of recently discovered small secretory proteins, including IL-19, IL-20, IL-22/IL-TIF, IL-24/MDA-7 (melanoma differentiation-associated gene), IL-26/AK155, and a number of viral IL-10 homologs. These cytokines belong to a relatively small group of homodimeric proteins with highly interdigitated interfaces that exhibit the strongly hydrophobic character of the interior core of a single-chain folded domain. We propose that binding of DnaK to helix C in the superfamily of IL-10-related cytokines may constitute the hallmark of a novel conserved regulatory mechanism in which HSP70-like chaperones assist in the formation of a hydrophobic dimeric "folding" interface.

Measurement of oxygen storage capacity in automotive catalysts

There is considerable disagreement in the literature on available oxygen storage capacity, and on the reaction rates associated with the storage process, for three-way automotive catalysts. This paper seeks to address the issue of oxygen storage capacity in a clear and precise manner. The work described involved a detailed investigation of oxygen storage capacity in typical samples of automotive catalysts. The capacity has also been precisely defined and estimates have been made of the specific capacity based on catalyst dimensions. A purpose-built miniature catalyst test rig has been assembled to allow measurement of the capacity and the experimental procedure has been developed to ensure accurate measurement. The measurements from the first series of experiments have been compared with the theoretical calculations and good agreement is seen. A second series of experiments allowed the effect of temperature on oxygen storage capacity to be investigated. This work shows very clearly the large variation of the capacity with temperature.