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At least 775 records · Page 43Linked to original sources
PubMed1994

Hemoglobin Denver [alpha 2 beta 2(41) (C7) Phe-->Ser]: a low-O2-affinity variant associated with chronic cyanosis and anemia.

OBJECTIVE: To report a previously undescribed low-O2-affinity hemoglobin variant that is associated with chronic cyanosis. DESIGN: Pertinent laboratory and historical data for the index case (from Denver, Colorado) and certain family members were recorded, and the hemoglobin variant was characterized. MATERIAL AND METHODS: Electrophoresis, high-performance liquid chromatography (HPLC), and isoelectric focusing were used to examine blood specimens for the presence of hemoglobin variants, and the O2 affinity of whole blood was determined. The abnormal peptide detected on reverse-phase HPLC of separated globin chains was analyzed for its amino acid composition and sequence. RESULTS: Although no abnormal hemoglobin band separated from hemoglobin A on electrophoresis, HPLC, and isoelectric focusing, a heat test showed hemoglobin instability, and O2 affinity studies disclosed an appreciably right-shifted dissociation curve. On chromatography, the new variant--hemoglobin Denver--was found to be due to a substitution of serine for phenylalanine at position 41 (C7) in the beta chain. In addition to substantial reduction in O2 affinity, hemoglobin Denver is accompanied by moderate reticulocytosis and mild anemia. CONCLUSION: Hemoglobin Denver causes no clinical symptoms other than cyanosis, which is attributable to the low O2 affinity.

Adolescent↗
PubMed1979

The effect of hemoglobin F-Chesapeake (alpha 2 92 Arg. leads to Leu gamma 2) on fetal oxygen affinity and erythropoiesis.

A carrier of hemoglobin Chesapeake, born of a normal mother, had a cord-blood hematocrit of 60%. The oxygen affinity of his blood was increased. Hemoglobin F-Chesapeake (alpha 2 Ches gamma 2), partially purified from the infant's blood, had oxygen affinity greater than that of hemoglobin A, but less than that of the adult form of the abnormal hemoglobin (alpha 2 Ches beta 2). These findings suggest that the conformation of that part of the gamma chain which contacts the site of amino acid substitution in Hb F-Chesapeake is similar to the analogous region of hemoglobin F. They also support the hypothesis that regulation of erythropoiesis in late fetal life is similar to that of the adult, and is under fetal control.

Erythropoiesis↗
PubMed1989

Hemoglobin Villejuif [beta 123(H1) Thr----Ile]: a new variant found in coincidence with polycythemia vera.

A new abnormal hemoglobin, Hb Villejuif [beta 123(H1) Thr----Ile] has been discovered during the exploration of a polycythemia in a 87-year-old patient of French origin. The isoelectric focusing of the lysate revealed the presence of a variant hemoglobin with an isoelectric point very close to that of HbA. The oxygen binding properties of the patient's red blood cells being normal, it was clear that the polycythemia was not a consequence of the presence of this hemoglobin. In fact, the red blood cell morphology and the involvement of the other blood cell lines, demonstrating excessive hemopoiesis, led to the diagnosis of polycythemia vera.

Aged↗
PubMed1967

Hemoglobin Gun Hill: deletion of five amino acid residues and impaired heme-globin binding.

Hemoglobin Gun Hill, a new variant of adult hemoglobin, was found in a Caucasian and one of his three daughters. The abnormal hemoglobin had only half of the expected number of heme groups. Five amino acid residues appeared to be missing from the beta-globin chains. These residues occur in linear sequence in normal beta-chains in a region involved in heme-globin binding. A deletion of five amino acids in the beta-chains of hemoglobin Gun Hill is postulated. The most likely mechanism for the origin of such a hemoglobin variant would appear to be unequal crossing-over during meiosis.

Adult↗
PubMed1975

Hemoglobin Koya Dora: high frequency of a chain termination mutant.

Approximately 10% of the members of the Koya Dora tribe from Andhra Pradesh (India) carry an alpha chain hemoglobin variant, Hb Koya Dora (Hb KD), usually in amounts of 0.5%-2% of total hemoglobin. In four presumed homozygotes for Hb KD, up to 10% of the abnormal hemoglobin was present. The alpha chain of Hb KD was found to be elongated by at least 16 residues, possibly as a result of a mutation of the normal alpha chain termination codon UAA TO UCA, coding for serine. A pedigree in which two individuals possess Hb KD as well as the alpha chain variant Hb Rampa and normal Hb A proves the existence of two alpha chain loci in this population. Hb DK resembles the previously described Hb Constant Spring [6, 7] in many aspects, probably also in its alpha thalassemia-like expression.

Amino Acids↗
PubMed1990

Theoretical isoelectric points and electric charges of mutated human hemoglobin subunits.

Isoelectric point values have been determined from a theoretical standpoint for alpha, beta, gamma and delta human abnormal subunits bearing elimination or addition of 1-2 different aminoacids with acid-base residues. The charge distribution, in relation to pH values, of the four types of subunits are also reported. These values may be of interest both to predict the electrophoretic behaviour and to characterize human abnormal hemoglobins.

Amino Acid Sequence↗
PubMed2003

Crystallization and preliminary X-ray structural studies of hemoglobin A2 and hemoglobin E, isolated from the blood samples of beta-thalassemic patients.

Hemoglobin A(2) (alpha(2)delta(2)), a minor (2-3%) component of circulating red blood cells, acts as an anti-sickling agent and its elevated concentration in beta-thalassemia is a useful clinical diagnostic. In beta-thalassemia major, where there is a failure of beta-chain production, HbA(2) acts as the predominant oxygen delivery mechanism. Hemoglobin E, is another common abnormal hemoglobin, caused by splice site mutation in exon 1 of beta globin gene, when combines with beta-thalassemia, causes severe microcytic anemia. The purification, crystallization, and preliminary structural studies of HbA(2) and HbE are reported here. HbA(2) and HbE are purified by cation exchange column chromatography in presence of KCN from the blood samples of individuals suffering from beta-thalassemia minor and E beta-thalassemia. X-ray diffraction data of HbA(2) and HbE were collected upto 2.1 and 1.73 A, respectively. HbA(2) crystallized in space group P2(1) with unit cell parameters a=54.33 A, b=83.73 A, c=62.87 A, and beta=99.80 degrees whereas HbE crystallized in space group P2(1)2(1)2(1) with unit cell parameters a=60.89 A, b=95.81 A, and c=99.08 A. Asymmetric unit in each case contains one Hb tetramer in R(2) state.

Chromatography, Gel↗
PubMed1969

Hemoglobin Hiroshima (beta-143 histidine--aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia.

During a survey for hemoglobinopathies in over 9000 residents of Hiroshima Prefecture, Japan, a fast moving hemoglobin was identified in eight members of three generations in a Japanese family. The abnormal hemoglobin, named Hb Hiroshima, constitutes about 50% of the total hemoglobin in hemolysates from the carriers who have a mild erythremia but are otherwise apparently clinically unaffected. All preparations of Hb Hiroshima have increased affinity for oxygen, by either tonometric or oxygen electrode determinations. At pH 7.0, the oxygen pressure, P(50) required to half saturate an unfractionated hemolysate from a carrier was one-half that of Hb A, and the P(50) of a purified sample containing no Hb A was one-fourth that of Hb A. The pH dependence of the oxygen equilibrium (Bohr effect) is below normal, as shown by the absolute value of the Bohr effect factor which is about half that of Hb A, in the pH range between 7.0 and 7.4. The Hill constant, n, for Hb Hiroshima between pH 7.0 and 7.4 is 2-2.4, compared to 2.8-3 for Hb A under the same conditions, indicating reduction of, but not complete abolition of heme-heme interaction. Urea dissociation and canine hybridization tests located the biochemical lesion in the beta chain. Fingerprints (Ingram), carboxypeptidase digestion, and amino acid analysis demonstrated that the substitution was at residue 143 in the beta chain, where histidine was replaced by aspartic acid.In contrast to other recently described high oxygen affinity mutants that show intact Bohr effects, all three of the major characteristics of the reversible combination of hemoglobin with oxygen (oxygen equilibrium, heme-heme interaction, and pH dependence) are affected in Hb Hiroshima. A tentative interpretation of these effects, relating structure to function, is offered in terms of recently developed models of normal hemoglobin.

Blood Protein Electrophoresis↗
PubMed1977

Hemoglobin Lufkin: beta 29 (B11) Gly replaced by Asp. An unstable hemoglobin variant involving an internal amino acid residue.

Hemoglobin Lufkin was found in a Black-American family. Structural analysis of the abnormal hemoglobin indicates a substitution of aspartic acid for glycine at position 29 in the beta chain. Marked instability of the variant hemoglobin is demonstrated by the rapid formation of inclusion bodies upon exposure of the red cells to redox dyes and by the large percentage of precipitated hemoglobin at 65 degrees C. The oxygen affinity, the Bohr effect, and the degree of cooperativity of Hb Lufkin and Hb A are similar over the physiologic pH range. However, at acid pH the oxygen affinity of the variant is increased. Unlike several other reported variants in the B helix, Hb Lufkin is not associated with methemoglobinemia.

Amino Acids↗
PubMed1993

[A familial case of DRPLA diagnosed by an autopsy associated with hemoglobinopathy (Hb Takamatsu)].

The patient first noticed general muscle stiffness at the age of 36. Two years later, she suffered from a tonic-clonic seizure which brought her to a hospital for the first time. Choreoathetoid movement, ataxia and cognitive deficit were apparent. At the age of 44, tonic-clonic seizures became more frequent and she was admitted to our hospital as being status epilepticus. After the cessation of clinical seizures, she became appllic. Gradual increase of atrophic changes in cerebrum, cerebellum and brain stem were observed by MRI and CT. Hematological study showed that she had abnormal hemoglobin, Hb Takamatsu. Four of her five children were clinically examined; all of them showed abnormal EEG findings; three being mentally retarded and had clinical generalized convulsive seizures; two had hemoglobinopathy (Hb Takamatsu). The patient died from sepsis at the age of 50 and the autopsy was carried out. The brain weighed 930 gram. Histological findings confirmed the diagnosis of dentato-rubro-pallido-luysian atrophy; neuronal loss accompanied by gliosis in dentate nuclei, red nuclei, lateral part of globus pallidus, and subthalamic nuclei. The coincidence of the hereditary traits of two independent diseases, DRPLA and familial hemoglobinopathy (Hb Takamatsu) suggests closeness of their genetic loci.

Atrophy↗
PubMed1967

Hemoglobin Yakina. II. High blood oxygen affinity associated with compensatory erythrocytosis and normal hemodynamics.

Erythrocytosis without clinical illness was noted in a man and his two daughters. Their blood contained approximately 62% hemoglobin A and 38% a new hemoglobin, designated hemoglobin Yakima. The oxygen affinity of whole blood from each subject was greatly increased and heme-heme interactions were impaired. At 37 degrees C and a plasma pH of 7.40, the oxygen pressure required to produce 50% saturation of hemoglobin with oxygen was only 12 mm Hg as compared with a normal of 26 mm Hg. The high oxygen affinity of this blood is attributed to the presence of hemoglobin Yakima; and the increased oxygen affinity was shown to be characteristic of the isolated abnormal hemoglobin. A Bohr effect was present in hemoglobin Yakima. Arterial oxygen pressure, oxygen consumption, and cardiac output at rest were normal. With respect to oxygen delivery to tissues, the increased hemoglobin concentration appears to be the major compensation for the marked displacement of the oxygen-hemoglobin equilibrium curve, although other factors may contribute. The finding of high normal quantities of erythropoietin in the urine is consistent with this degree of erythrocytosis.

Erythropoietin↗
PubMed1992

Hb Kanagawa [alpha 40(C5)Lys----Met]: a new alpha chain variant with an increased oxygen affinity.

An abnormal hemoglobin was suspected in a 70-year-old Japanese male with cerebral infarction and erythremia with high performance liquid chromatography assay of Hb A1c. The hemoglobin variant migrated to the anode more rapidly than Hb A. Structure determination studies, including amino acid analysis of the abnormal peptide and DNA sequencing of a partially cloned alpha-globin gene, demonstrated that it is a new hemoglobin variant which has been named Hb Kanagawa [alpha 40(C5)Lys----Met]. This variant showed an increased oxygen affinity, decreased heme-heme interaction, and a lowered 2,3-diphosphoglycerate effect relative to normal.

Aged↗
PubMed2002

Screening extended families for genetic hemoglobin disorders in Pakistan.

BACKGROUND: We have investigated a strategy for identifying and counseling carriers of recessively inherited disorders in developing countries where consanguineous marriage is common. In such communities, gene variants are trapped within extended families, so that an affected child is a marker of a group at high genetic risk. METHODS: Fifteen large Pakistani families, 10 with a history of a hemoglobin disorder and 5 without any such history (controls), were screened for beta-thalassemia and abnormal hemoglobins. All carriers and married couples consisting of two carriers received counseling, and eight families have been followed for two years. RESULTS: In the control families, no carrier was found among 397 members tested. In the 10 families with an index case, 183 of 591 persons tested (31 percent) were carriers; carriers had a 25 percent risk of being in a marriage at risk for producing an affected child, and 17 of 214 married couples (8 percent) consisted of two carriers. No couple at risk was identified among 350 randomly selected pregnant women and their partners. All carriers reported that they have used the information provided in the testing and counseling process: carriers married to carriers with two or more healthy children have avoided further pregnancy, and most such couples with one or no healthy children have used prenatal diagnosis. Seven of eight new marriages and engagements are known not to be at risk. CONCLUSIONS: Testing of extended families is a feasible way of deploying DNA-based genetic screening in communities in which consanguineous marriage is common.

Anemia, Sickle Cell↗
PubMed1983

A new hemoglobin with high oxygen affinity--hemoglobin bunbury: alpha 2 beta 2 [94 (FG1) Asp replaced by Asn].

Hemoglobin Bunbury was detected in an Italian woman from Bunbury, Western Australia, following detection of an abnormal hemoglobin by electrophoresis. The variant form accounted for 38% of the total hemoglobin and migrated on cellulose acetate electrophoresis between HbS and HbA. Structural analysis demonstrated a new substitution in the beta chain, beta 94 Asp replaced by Asn. Hemoglobin Bunbury is stable to both heat and isopropanol denaturation. This variant shows an increase in oxygen affinity and a reduced Bohr effect. Heterozygosity for Hb Bunbury produces no clinical symptoms or compensatory erythrocytosis.

Adult↗
PubMed1989

Unstable hemoglobins: influence of environment on phenotypic expression of a genetic disorder.

Unstable hemoglobins account for approximately one fifth of the abnormal hemoglobins identified to date. Clinical expression ranges from a continuing and severe hemolytic anemia which may or may not be abated by splenectomy to a compensated hemolytic state with exacerbations of hemolysis after exposure to drugs or during febrile episodes. Other clinical indicators of the disorder include the voiding of urine darkened by the presence of dipyrroles, as well as intermittent episodes of scleral icterus. Recognition and definition of the unstable hemoglobins can be difficult. Approximately one third are spontaneous mutations; many are neutral substitutions, so that routine electrophoretic methods are of limited value; and in some the molecule is so unstable that it is lost during preparative techniques employed for its identification. Most informative are those methods designed to demonstrate the instability of the molecule, including the exposure of red cells or hemolysate to heat, redox dyes, or isopropanol. Each of these tests is easily performed and should be employed in the evaluation of any patient with an unexplained hemolytic disorder, and especially in those patients with drug-or hyperthermic-induced hemolysis. A review of red cell indices of our patients, together with those reported in the literature, indicates the subjects with moderate to severe forms of the unstable hemoglobinopathies have macrocytosis with abnormally low MCHCs. Incubating normal or Hb Zürich red cells in vitro at 37 degrees and 41 degrees C effects similar changes in the red cells, the phenomenon occurring more rapidly in Hb Zürich than in normal cells. The phenotypic expression of the unstable hemoglobinopathies may be influenced by a variety of environmental factors, including smoking, pyrexia, exposure to oxidants, and the presence or absence of splenic function. Especially noteworthy is the effect of smoking on the clinical and laboratory findings in subjects with Hb Zürich. As a result of the 65-fold increase in the affinity of the abnormal beta-globin chain of Hb Zürich for CO, the molecule is stabilized, followed by resistance to oxidative injury, a decreased rate of hemolysis, and a marked increase in oxygen affinity.

Environment↗