Occurrence Of Haemoglobin Research Articles

Two Familial Cases of Hb Tyne Confirm Instability as Cause of Low Expression

We report a second occurrence of hemoglobin (Hb) Tyne, [β5 (A2) Pro>Ser] HBB:c.16C>T(p.Pro6Ser), which like the first case was associated with normal hematology. We verified the variant was mildly unstable by showing it was greatly enriched in isopropanol precipitates. This minor instability accounts for the slightly decreased expression of the new β chain. The variant was picked up as an interfering component on HbA1c testing using cation exchange high performance liquid chromatography (HPLC). However, this may be an advantage in detecting electrophoretically silent variants. Furthermore, this report also highlights the importance of uneven or sloping baselines on HPLC, which could reflect the presence of a variant hemoglobin even in the presence of normal electrophoresis and full blood count.

Efficacy and safety of biosimilar epoetin alpha in patients with chronic lymphoid neoplasms and chemotherapy-induced anaemia: An observational, retrospective, monocentric analysis.

Epoetin biosimilars are an alternative to originator erythropoietic agents in the treatment of chemotherapy-induced anaemia; however, their effects in patients with lymphoproliferative disorders remain unclear. This analysis examined the response of patients with lymphoproliferative disorders experiencing chemotherapy-induced anaemia to 4- or 8-week treatment with the biosimilar epoetin alpha. Treatment was initiated at first occurrence of haemoglobin (Hb)<10g/dL during chemotherapy and was stopped when Hb was >11g/dL, when chemotherapy was completed, or in case of transfusion dependency. Response to epoetin alpha was defined as an increase in Hb of >1g/dL or as an Hb>11g/dL. Stability was defined as change in Hb of ±1g/dL, and no response was indicated by a decrease in Hb of >1g/dL or acquired transfusion dependence. Overall, 65 patients were enrolled (median age 69years; 47.7%≥70years old). Mean Hb levels at the initiation of epoetin alpha was 9.3±0.5g/dL. Mean Hb levels reached 10.7±1.4 and 10.6±1.5g/dL at weeks 4 and 8, respectively, in patients on first-line chemotherapy and 11.4±1.6 and 9.7±1.3g/dL in those on a second- or higher-line regimen. Overall, 70.8% of patients responded, 26.1% had stable Hb, and 3.1% did not respond. Delays or interruption of any chemotherapy cycle due to anaemia occurred in 18 patients. The biosimilar epoetin alpha was well tolerated and allowed patients with non-Hodgkin lymphoma or chronic lymphoproliferative disorders to continue their course of chemotherapy by effectively increasing and maintaining adequate concentrations of Hb.

Electrospray Mass Spectrometry: An Efficient Method to Detect Silent Hemoglobin Variants Causing Erythrocytosis

Erythrocytosis, which is characterized by high hematocrit (packed cell volume), is a common condition causing complications attributable to hyperviscosity of blood. According to modern nomenclature, patients can be subdivided into one group of “apparent erythrocytosis” and one of “absolute erythrocytosis” (1). The absolute-erythrocytosis group contains both genetic disorders, acquired conditions such as polycythemia, and secondary reactions attributable to chronic hypoxemia or renal disease. The occurrence of hemoglobin (Hb) variants with increased oxygen affinity is a well-known cause of hereditary erythrocytosis, but in recent years interest has also been given to mutations in the erythropoietin receptor gene (2). Theoretically, functional studies of oxygen saturation curves would be the ideal method to screen for Hb variants that cause erythrocytosis, but such methods are not generally available and there are diverging opinions whether P 50 measurements of stored or shipped samples can be used (3)(4). Of the nearly 200 Hb variants with increased oxygen affinity described, fewer than one-half have been found in conjunction with significant erythrocytosis (3). Several of the variants are attributable to amino acid substitutions that do not affect the net charge, i.e., the substitutions are “silent” when investigation is performed by conventional electrophoretic techniques. In contrast, almost all Hb variants in this group can readily be found by mass spectrometry exploiting the change in molecular weight of the variant globin. Using electrospray mass spectrometry (ESMS), we have screened 70 consecutive samples from patients with unexplained erythrocytosis that had showed normal Hb pattern on isoelectric focusing (IEF) (5) and HPLC (6)(7) analysis. The investigation was approved by the Ethics Committee at Huddinge University Hospital. In three cases, we detected β-globin variants. This report illustrates how the information from electrophoretic methods and the knowledge of the wild-type globin gene sequence can facilitate the interpretation of mass spectral …

Hemoglobin Adducts of Benzo[a]Pyrene in Tobacco Smokers : Characterization of Benzo[a]Pyrene Adducts in Maternal and Fetal Blood Samples

The formation of hemoglobin - carcinogen adducts has been detected in carcinogen treated animals and in human populations. Although polynuclear aromatic hydrocarbons are ubiquitous in the human environment and DNA - aromatic hydrocarbon adducts have been detected in human tissue, the occurrence of hemoglobin - polynuclear aromatic hydrocarbon adducts in humans has not been thoroughly described. In this study we examined the effects of reaction condition on the extent of in vitro reaction of human hemoglobin and (+) [3H]benzo[a]pyrene-7,8-diol-9,10-epoxide (anti)(BPDE), a metabolite thought to be largely responsible for the carcinogenic effect of benzo[a]pyrene. The chromatographic properties of the resulting hemoglobin - BPDE adducts were examined by conventional DEAE-cellulose ion exchange liquid chromatography and by reversed phase high performance liquid chromatography. Several adducts were formed which were chromatographically resolved from hemoglobin and from the individual globins. We applied these techniques to the qualitative and quantitative assessment of benzo(a)pyrene hemoglobin adducts in smokers, correlating both maternal and fetal adducts with smoking status.

Occurrence of hemoglobin in the nitrogen-fixing root nodules of Alnus glutinosa

Occurrence of hemoglobin in the nitrogen-fixing root nodules of Alnus glutinosa

Occurrence of hemoglobin in the nitrogen‐fixing root nodules of Alnus glutinosa

A true hemoglobin (Hb) was shown to be present in the root nodules of Alnus glutinosa L. After purification by gel filtration and ion exchange, the Hb formed a stable complex with oxygen. This oxygen complex could then be converted to carboxyhemoglobin by treatment with CO. Optical absorption spectra typical of Hb were observed. The molecular weight was estimated to be 15 100 by gel filtration, and 18 300 by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. The Hb was largely insoluble when the initial homogenization was done in the absence of a detergent. Under these conditions much of the Hb appears to be associated with clusters of Frankia, the nitrogen‐fixing actinomycete that infects plant cells within the nodules. The exact localization of the Hb in vivo is uncertain. The relatively low average concentration of Hb in Alnus nodules suggests that it is either confined to a relatively small fraction of total nodule volume, or has a function other than facilitation of O2 transport.

Reaction of Benzo[a]pyrene-7,8-diol-9,10-epoxide with Human Hemoglobin and the Chromatographic Resolution of the Covalent Adducts

Abstract The formation of hemoglobin - carcinogen adducts has been detected in carcinogen treated animals and in human populations. Although polycyclic aromatic hydrocarbons are ubiquitous in the human environment and DNA - aromatic hydrocarbon adducts have been detected in human tissue, the occurrence of hemoglobin - polycyclic aromatic hydrocarbon adducts in humans has not been thoroughly described. In this study we examined the effects of reaction condition on the extent of in vitro reaction of human hemoglobin and (+) [3H]benzo[a]pyrene-7,8-diol-9,10-epoxide (anti)(BPDE), a metabolite thought to be largely responsible for the carcinogenic effect of benzo[a]pyrene. The chromatographic properties of the resulting hemoglobin - BPDE adducts were examined by conventional DEAE-cellulose ion exchange liquid chromatography and by reversed phase high performance liquid chromatography. Several adducts were formed which were chromatographically resolved from hemoglobin and from the individual globins. Some adduc...

The occurrence of haemoglobin and hydrogenase in nodules of twelve Casuarina-Frankia symbiotic associations

The occurrence of haemoglobin and hydrogenase in nodules of twelve Casuarina-Frankia symbiotic associations

The occurrence of haemoglobin and hydrogenase in nodules of twelve Casuarina‐Frankia symbiotic associations

Seedlings of Casuarina cunninghamiana Miq., C. equisetifolia L. and C. glauca Sieber growing in N‐deficient potting mix were inoculated with Frankia sp. from each of 4 different sources. After ca 4 months, plants were harvested and nodules from the 12 Casuarina‐Frankia combinations evaluated for (1) concentrations of haemoglobin (measured as CO‐reactive haem) and (2) occurrence of hydrogenase. The aim was to determine if these factors were related to nitrogen accumulation and biomass production.There were marked host‐Frankia source interactions with up to 10‐fold differences in plant dry weight and 50‐fold differences in the efficiency of nitrogen fixation (as estimated by N2 accumulated mg−1 nodule dry weight). Differences in plant growth and nitrogen accumulation were apparently related to nodule specific activity, because the 12 associations had similar nodulation characteristics, e.g. time for nodulation to occur.The concentration of haemoglobin in Casuarina nodules ranged from 0 to 27 nmol haem (g FW)−1. There was a strong linear correlation between concentrations of haemoglobin and dry weights of the whole plants (r=0.77, 0.92 and 0.97, P≤0.05) for C. cunninghamiana, C. equisetifolia and C. glauca symbiotic associations, respectively. However, the linear correlation between concentration of haemoglobin and nitrogen content of whole plant was lower (r=0.60, 0.64 and 0.71, P≤0.05) for the three Casuarina symbioses, respectively, and there was only a poor correlation between haemoglobin concentration in nodules and the rate of nitrogen accumulation on nodule weight basis. This indicates that haemoglobin concentration is not the sole physiological determinant of nitrogen fixation in Casuarina.All the Casuarina‐Frankia symbiotic associations studied also showed the presence of a hydrogen uptake enzyme. The activity of the enzyme ranged from 5.1 to 34.1 μmol H2 (g FW)−1 h−1, and hydrogen uptake was not correlated with plant dry weight, nitrogen content or the rate of nitrogen fixation. Hydrogen evolution could not be detected in any of the associations.

Aspects of the Origin and Evolution of Non-Vertebrate Hemoglobins

Hemoglobins, found in members of almost all invertebrate phyla, display an extraordinary diversity of form and function. Although some are intracellular with chains and assemblies similar in size to those of vertebrates, others are giant extracellular proteins with masses as large as 8,000 kilodaltons. Two very different strategies have evolved for the stabilization of these large molecules. The first is the formation of both intra- and interchain disulfide bonds that effectively immobilize segments of the protein, and the second is the evolution by gene duplication of multi-domain chains with from two to eighteen myoglobin-like, heme-containing domains in a single polypeptide that may be as large as ˜260 kilodaltons. The genes for vertebrate globins have a characteristic two-intron, threeexon structure. The gene encoding chain c of the hemoglobin of the earthworm Lumbricus terrestris has precisely the same organization and splice junction positions. This shows that these positions have been conserved for at least 600 million years, the estimated time of divergence of annelids and the ancestor to chordates. The gene encoding a hemoglobin (leghemoglobin) of higher plants shows exactly the same splice junctions as in the globin genes of vertebrates except that the middle exon is split by an additional intron which is believed to have been lost early in animal evolution. The occurrence of hemoglobins in diverse higher plants suggests that they might be present in all plants albeit at very low concentrations and perhaps serving an enzymatic function. Hemoglobin, broadly defined as a heme-containing protein capable of reversible combination with oxygen, also occurs in bacteria and fungi. The discovery of a bacterial hemoglobin that is 26% identical with lupin leghemoglobin indicates a procaryotic origin. The possibility that hemoglobin may have evolved from a cytochrome is suggested by the presence of hemoglobins in the yeast, Candida , and the bacterium, Alcaligenes , that contain both heme and flavin. They must therefore have evolved by the fusion of the genes for two different proteins. However, the possible homology of the heme domains with plant or animal hemoglobins remains to be determined. The lactic dehydrogenase of yeast, cytochrome b2, is also a soluble flavoheme protein with a heme domain that is homologous with mammalian cytochrome b5. Globin may have evolved in part from a member of the cytochrome b5 family, but if so, the event must have occurred so early that only a borderline perhaps random correspondence of amino acid sequences remains

Hemoglobin types in Brazilian populations.

Population surveys performed in different Brazilian ethnic groups, and comprising 23,606 subjects, disclosed, besides the common S and D types, hemoglobins G and Por to Alegre, as well as high F, A'2 and an apparently unstable A2 variant. Additional studies on isolated families revealed the occurrence of hemoglobins I, Niterói, D Punjab, M Boston and J Rovigo. Screening for sickle cells was also performed on 17,412 individuals. Detailed clinical studies on series of sickle cell anemics were also performed. Due to their special interest, the physico-chemical properties of Hb porto Alegre are reviewed in some detail.

Occurrence of hemoglobin D Los Angeles in Brahmins of Andhra Pradesh, South India.

Occurrence of hemoglobin D Los Angeles in Brahmins of Andhra Pradesh, South India.

Blood group phenotypes and the origin of sickle cell hemoglobin in Sicilians.

As an approach to investigating the origin of sickle cell hemoglobin (hemoglobin S) in white persons of Sicilian ancestry, two groups of native Sicilians were tested for blood group evidence of African admixture. Among 100 unrelated Sicilians, the phenotypes cDe(Rho) and Fy(a-b-), and the antigens V(hrv) and Jsa, which are considered to be African genetic markers, were detected in 12 individuals. Among 64 individuals from 21 families with at least one known hemoglobin S carrier, African blood group markers were detected in 7 (11%). These findings indicate that hemoglobin S is only one of multiple African genes present in contemporary Sicilian populations. The occurrence of hemoglobin S in white persons of Sicilian ancestry is considered to be a manifestation of the continuing dissemination of the original African mutation.

Occurrence of hemoglobin G Coushatta in Japan.

An abnormal hemoglobin with a substitution of Ala for Glu at the 22nd residue of the β chain has been found in North American Indians (Hbs G Coushatta and G Saskatoon) (1-3), Koreans (Hb G Taegu) (4-6) and Chinese (Hb G Hsin-Chu) (5,6). Blackwell et al (6) assumed that the Chinese and Korean subjects have the same hemoglobin variant because of gene flow. Surveys in the southwestern parts of Japan have uncovered two apparently unrelated families with this variant. This paper deals with the chemical and functional characterization of the Hb G Coushatta found in Japan.The first family was discovered by agar gel electrophoresis at pH 8.6 (7) in 1971 during a survey of patients in Yamaguchi University Hospital. The patient, a 36-year-old female, had been admitted because of ruptured ectopic pregnancy. She had been healthy with no history of either anemia or jaundice. Routine hematology and blood chemistry twenty months later were normal. Her late father, who was assumed to have transmitted the gene for the var...

The occurrence and distribution of haemoglobin in the entosymbiotic rhabdocoel Paravortex scrobiculariae (Graff) (Platyhelminthes: Turbellaria)

1. 1. The occurrence of haemoglobin in the entosymbiotic turbellarian Paravortex scobiculariae has been demonstrated. 2. 2. The haemoglobin occurs intracellularly in the mesenchyme, around the extrinsic musculature of the pharynx, and in the brain. 3. 3. Haemoglobin could not be detected in Scrobicularia plana, the bivalve molluscan host of P. scrobiculariae, nor in the other British species of Paravortex, P. cardii, which is entosymbiotic in the bivalve Cerastoderma edule. 4. 4. It is suggested that the haemoglobin of P. scrobiculariae is of functional significance when the entosymbiont is feeding at low tide in conditions of reduced oxygen tension.

Occurrence of Haemoglobin H in Leukaemia: a Further Case of Erythroleukaemia

Erythroleukaemia in an elderly Caucasian male was associated with the presence of 15% of haemoglobin H (Hb-H; Hb-beta4) in the haemolysate, identified by electrophoretic analysis, isolation and 'finger-printing'. The peripheral blood picture was dimorphic, with 40% of hypochromic and morphologically abnormal red cells. Inclusion bodies indicative of the presence of Hb-H occurred in 30% of the red cells after supravital staining. The rare occurrence of Hb-H in leukaemic conditions and its distribution in the red cells is discussed in relation to the possible clonal origin of leukaemia and the involvement of red cell precursors.

Hemoglobin switching in sheep and goats: occurrence of hemoglobins A and C in the same red cell.

Sheep and goats switch from the synthesis of hemoglobin A (alpha(2)beta(2)(A)) to hemoglobin C (alpha(2)beta(2)(C)) when made anemic. We have demonstrated the existence of the asymmetrical hybrid hemoglobin, alpha(2)beta(A)beta(C), in the circulating red cells of anemic sheep. These erythroid cells, therefore, synthesized both A and C hemoglobin simultaneously. Thus, the switch appears to be mediated by selective gene expression rather than by a clonal or cellular selective mechanism.

The Occurrence of Hemoglobins E and Esaskatoonin Central Canada

A search for abnormal hemoglobin in central Canada conducted over a 7-year period has resulted in the finding of seven apparently unrelated individuals with a hemoglobin variant with the electrophoretic characteristics of hemoglobin E. By “fingerprinting” technics, five of these were shown to be hemoglobin ESaskatoon ( β 26 Glu→Lys) and two to be hemoglobin ESaskatoon ( β 22 Glu→Lys). Of the former, two instances occurred in Asiatics, and the rest in persons of European origin. Both persons with ESaskatoon were of Scottish origin. Only in one patient was there severe anemia, and this was associated with homozygosity for hemoglobin E. Two instances of hemoglobin E and one of hemoglobin ESaskatoon were found to be unstable on incubation at 50 C. for 60 min.

Occurrence of haemoglobin in Lineus lacteus, L. ruber and L. viridis (Rhynchocoela, Lineïdae)

1. 1. The occurrence of haemoglobin in Lineïdae was demonstrated by spectroscopic and histospectroscopic methods, cytochemicals reactions and staining of the vascular system. 2. 2. The amount of haemoglobin present in one specimen was measured (55 × 10 −3 mg per animal about 100 mg weight). 3. 3. The study of the metabolism of haemoglobin was done by the use of 59Fe.

Another instance of haemoglobin in a flatworm (Phaenocora typhlops Vejdovsky 1880)

Summary(1) The occurrence of haemoglobin in Phaenocora typhlops (Vejdovsky) is reported.(2) Rhabdocoels were examined spectrophotometrically. The distribution of the pigment was studied by a sodium nitroprusside‐benzidine technique, and the distribution of ferric iron with Perl's technique.(3) Characteristic bands of oxyhaemoglobin were observed at 540 and 580 nm. The oxyhaemoglobin was reduced to haemoglobin by the addition of sodium dithionite and an absorption band appeared at about 560 nm.(4) Haematin was found principally around the pharynx, though a little was found in front of the latter and along the length of the gut. Ferric iron was distributed throughout the worm.(5) The occurrence of haemoglobin in P. typhlops and P. unipunctata is compared. It is suggested that less occurs in the former species. Whether or not this is related to the presence of zoochlorellae is considered. Certainly both species burrow actively in mud where reduced oxygen conditions can occur.