William P. Winter

Nitric oxide and cyclic GMP levels in sickle cell patients receiving hydroxyurea

Summary. Recent studies suggest that nitric oxide (NO) may partly be responsible for the beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) patients. NO stimulates cyclic guanosine monophosphate (cGMP) production, which mediates vasodilatation. We investigated the association between NO, cGMP and fetal haemoglobin (HbF) levels after HU administration. Our data showed that chronic HU significantly increased NO, cGMP, and HbF levels in SCD. Recently it was shown that HbF production was stimulated by cGMP‐dependent protein kinase. Our results suggest that NO stimulates cGMP production, which then activates a protein kinase and increases the production of HbF.

Hemoglobin D Ibadan Trait in Combination with δβ Thalassemia

(1979). Hemoglobin D Ibadan Trait in Combination with δβ Thalassemia. Hemoglobin: Vol. 3, No. 1, pp. 77-82.

Genetic mechanisms contributing to the expression of the human hemoglogin loci.

To a greater extent than in any other protein system known, human hemoglobin loci have provided a rich field for the study of the molecular basis of phenotypic variability. At the protein level, over 300 human hemoglobin variants are known. Of these variants, more than 90% involve one of the two main chains, α and β, that comprise the adult form of hemoglobin (α 2 β 2). The balance are variants of the minor components, Hb F (α 2 γ 2) and Hb A2 (α 2δ2). Since variants usually reflect small, discrete abnormalities of primary structure, they have contributed greatly to our understanding of the forces that maintain tertiary and quaternary structure of the hemoglobin molecule and of the role of these structured features in gas transport.

Molecule of the century

Disorders of Hemoglobin: Genetics, Pathophysiology and Clinical ManagementEdited by M.H. Steinberg et al. Cambridge University Press, 2001.UK £180 hbk (1268pages) 0 521 63266 8Hemoglobin: with its ready accessibility, ease of purification, essential physiological function and role in the etiology of important human diseases, hemoglobin is incontestably the most studied and most thoroughly understood protein in the human biochemical armamentarium. Now Steinberg and his co-editors have assembled the most comprehensive compendium ever to be devoted to hemoglobin or any other single protein. In the witty and well-written foreword, Frank Bunn has recognized the impact of hemoglobin studies by nominating hemoglobin as the ‘molecule of the century’. Indeed, at an ever-increasing pace, there have been advancements at every level – biochemical, genetic, developmental, physiological, biological and medical – and a significant portion of that new knowledge is contained in this book. From Perutzs detailed account of hemoglobins structure to the history of its investigation, eloquently set forth by the inimitable Helen Ranney, to the advances in molecular biology, developmental biology, evolution, anthropology and clinical aspects, this volume spans the field. The inclusion of a section describing newer laboratory methods involving transgenic mice is particularly commendable, as this topic is relatively inaccessible to the non-specialist. Similarly, the topics of gene therapy and newer experimental therapies are well chosen for inclusion. The editors are also to be applauded for the outstanding panel of authors they have assembled.But for all the information and insight that the authors and editors have brought together, there are nonetheless a few disappointing downsides to their efforts. The title is slightly misleading, as the emphasis seems to be as much on the molecule itself, its genetics and molecular biology as on its disorders. Detracting from the book is the uneven and in some cases poor quality of the illustrations. The book features a centrally located insert of color plates and, in addition, the chapters themselves contain black and white versions with cross-references to the color plates. However, these black and white versions suffer from the drawback that, in the absence of color, detail is often hard, if not impossible to discern. In several cases, where black and white versions of color figures were used, the captions still explain what features the various colors, now no longer evident, represent. In another, the caption tells us what ‘A’ and ‘B’ in the color plate represent even though only ‘B’ is present. Other illustrations are of questionable quality.It is regrettable that the editors have omitted altogether a comprehensive list of known variants, a feature that has been a centerpiece of earlier volumes tackling this subject. Tables in Chapters 28 and 44 contain only a subset of the known variants associated with the chapters’ topics and suffer the almost inexcusable shortcoming of not providing references to the original publications of the variants listed.Nevertheless, this massive volume contains a prodigious amount of material on almost every aspect of hemoglobin and its disorders and is to be recommended for those who wish to keep abreast of this field, both from the clinical and the molecular perspective.