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Biomedical subjects

R F Rieder

Publications and source records attributed to R F Rieder.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effects of thalassemia and microcytosis on the hematologic and vasoocclusive severity of sickle cell anemia.

The characteristic clinical heterogeneity of sickle cell anemia (HbSS) may be, in part, a result of its interactions with alpha-thalassemia. Although alpha-thalassemia clearly affects some hematologic features of HbSS, its role in modulating the vasoocclusive severity of disease is not clear. To further explore this relationship, we examined the incidence of painful episodes, acute chest syndrome, aseptic bone necrosis, and leg ulcers in 3 patient groups with sickle cell disease: (1) 2,147 patients over age 2 yr, stratified according to mean corpuscular volume (MCV); (2) 183 patients selected on the basis of microcytosis and elevated HbA2, on whom globin biosynthesis studies were done; and (3) 125 patients who had alpha-globin genotype assigned by restriction endonuclease gene mapping. When patients were stratified by MCV, there was a reciprocal relationship between HbA2 levels and MCV, reflecting the presence of patients with beta o and alpha-thalassemia in the low MCV groups. The erythrocyte indices and HbA2 levels in patients classified as HbSS-alpha-thalassemia, by either globin synthesis studies or gene mapping, were very similar to those previously reported by others. Neither microcytosis, beta o, or alpha-thalassemia appeared to provide any clear protection from the vasoocclusive complication evaluated, and the prevalence of aseptic necrosis was increased in patients with microcytosis over age 20 yr and in groups with alpha-thalassemia. The effects of a reduced MCV and mean corpuscular hemoglobin concentration (MCHC), of possible benefit by themselves, when accompanied by a reduction in hemolysis and rise in hemoglobin concentration, as in HbSS-alpha-thalassemia, may cause sufficient rise in blood viscosity in critical vascular beds to impair blood flow and negate any amelioration of vasoocclusive complications in HbSS.

Adolescent↗
PubMed1983

The effects of alpha-thalassaemia in HbSC disease.

In HbSC disease, as in sickle cell anaemia, there is a spectrum of clinical severity. A reduced mean corpuscular volume and haemoglobin concentration, traits typical of thalassaemia, might retard sickling. We therefore ascertained the prevalence of alpha-thalassaemia in 53 adults with HbSC disease and related alpha-globin gene deletion to the haematologic and clinical findings. Alpha-globin genotype was identified by restriction endonuclease gene mapping. Indirect ophthalmoscopy and fluorescein angiography were used to document the presence of proliferative retinopathy. Bone necrosis and infarction were determined roentgenographically or by radionuclide scanning. Either heterozygous or homozygous alpha-thalassaemia-2 was present in 26% of patients. There was no relationship between alpha-globin genotype and haematocrit, pain crises, bone lesions, proliferation retinopathy or clinical severity score.

Adolescent↗
PubMed1983

Alpha-thalassemia in Ashkenazi Jews.

Members of a Jewish family of Polish origin were found to have hypochromic, microcytic erythrocytes. By restriction endonuclease analysis of DNA, the propositus, a brother, and an aunt were found to have a single alpha-globin gene on each chromosome 16. Five family members have one chromosome bearing two alpha-genes (5' and 3') with a single alpha-gene on the homologous chromosome. Gene mapping indicated that the chromosome bearing a single alpha-gene arose via an unequal crossover between misaligned 5' and 3' alpha-genes and was introduced into the family from three separate sources. In addition, a Jewish man of Hungarian origin was found to have alpha-thalassemia trait with single alpha-genes on both chromosomes 16 and a survey of 25 Jewish subjects yielded one man of German origin with an alpha-gene deletion. Alpha-thalassemia should be considered in the differential diagnosis of disease in Jewish persons with microcytic, hypochromic erythrocytes.

Adult↗
PubMed1982

Interaction of chromosomes bearing 1, 2 or 3 alpha-globin genes in an American black family with alpha-thalassemia.

Utilizing restriction endonuclease mapping and molecular hybridization we have determined the number and arrangement of the alpha-globin genes in members of an American Black family in which alpha-thalassemia is present. In addition to chromosomes bearing 0, 1 or 2 alpha-genes, an unusual chromosome bearing 3 alpha-globin genes was detected in 3 family members. In 2 family members the 3 alpha-globin gene chromosome was present opposite a chromosome containing a single alpha-globin gene; these cases represent the first reports of the alpha alpha alpha/-alpha genotype. The presence of the stigmata of "mild" alpha-thalassemia trait in one of these subjects indicates that the 3 alpha-gene chromosome probably does not direct the synthesis of significantly more alpha-globin chains than does the 2 alpha-gene chromosome.

Chromosomes, Human, 16-18↗
PubMed1981

Rapid destruction of newly synthesized excess beta-globin chains in HbH disease.

A subject with HbG Philadelphia-HbH disease exhibited an unusually high alpha/beta synthesis ratio; when peripheral blood was tested in vitro on several occasions, ratios of 0.63 - 0.89 were obtained after incubations of 30-120 min. HbH amounted to 5%-8% of the circulating hemoglobin. Rapid destruction of excess newly synthesized beta-globin was demonstrated in kinetic and pulse-chase experiments. After 2 min of incubation, the alpha/beta synthesis ratio was 0.48; this figure rose to 0.89 by 30 min. The zero time alpha/beta ratio was estimated to be 0.35. The degradation of beta-chains was calculated to proceed at approximately one-half the rate of beta-globin synthesis; this result was confirmed by the loss of 50% of the specific activity in beta-chains during 9 min of a chase experiment following a 10-min radioactive pulse. The results suggest that efficient proteolysis may be responsible, in some blacks, for the low levels of excess beta-globin chains in HbH disease as well as for the mildness of the clinical disorder.

Adult↗
PubMed1980

Proportion of hemoglobin G Philadelphia (alpha 268 Asn leads to Lys beta 2) in heterozygotes is determined by alpha-globin gene deletions.

In humans the alpha-globin genes are duplicated and closely linked. Whereas individuals heterozygous for most alpha-chain mutations possess approximately 25% abnormal hemoglobin, heterozygotes for the alpha-chain variant Hb G Philadelphia synthesize either 33% or 50% Hb G. Both variable gene dosage and interaction with alpha-thalassemia have been proposed to explain this observation. To differentiate between these models, we have performed restriction endonuclease mapping and hematological studies on individuals with Hb G from four families. In every case the alpha G locus was carried on an EcoRI or EcoRI + BamHI fragment approximately 4 kilobases shorter than that bearing the two linked alpha A loci of hematologically normal individuals. Bgl II digestion revealed that the alpha G gene is the only alpha locus on the affected chromosome. Erythrocyte indices and alpha/beta synthesis ratios indicated that the alpha G chromosome confers alpha-thalassemia. In addition to the alpha G gene, subjects who synthesized 33% Hb G possessed two alpha A genes on the homologous chromosome and exhibited the mild form of alpha-thalassemia trait ("silent carrier"). Subjects who synthesized 50% Hb G possessed a single alpha A gene trans to the alpha G locus and displayed the more pronounced form of alpha-thalassemia trait. One subject, who synthesized 100% alpha G chains and had Hb G-Hb H disease, was found to have a single nonfunctional alpha gene trans to the alpha G gene. Thus the proportion of Hb G synthesized by heterozygotes is determined by interaction with alpha-globin gene deletions cis and trans to the alpha G locus.

Base Sequence↗
PubMed1980

The varied arrangement of the alpha globin genes in alpha thalassemia and Hb H disease in American blacks.

Both Eco RI and Eco RI x Bam HI restriction endonuclease digests of DNA from black Americans with alpha thalassemia yielded an alpha-specific fragment 4 kb shorter than in normals. In Hb H disease, only the shorter fragment was noted, while in "silent carriers" (alpha-thal 2 trait), both the normal and shorter fragments were detected. One subject with single gene deletions on both homologous chromosomes (alpha-thal 1 phe. A non-deletional form of alpha thalassemia also was discovered.

Black or African American↗
PubMed1979

Alpha thalassaemia in American blacks: a study of a family with five cases of haemoglobin H disease.

Five cases of HbH disease were discovered in a large family of American Blacks. Anaemia was mild with PCV ranging from 0.275 to 0.405. The amount of HbH was 2--6%. Studies of haemoglobin synthesis in peripheral blood reticulocytes demonstrated marked deficits in alpha globin production with an average alpha/beta ratio of 0.31 (range 0.22--0.36). Eighteen additional family members had evidence of thalassaemia trait and were provisionally classified as either alpha-thal-1 (average MCV 65.2 fl; range 59--70) or alpha-thal-2 (average MCV 79.6 fl; range 74--88). A subject with altha-thal-1 trait had an alpha/beta ratio of 0.56; the average for five cases of alpha-thal-2 was 0.73. One other family member was thought to be homozygous for alpha-thal-2 trait and exhibited an MCV of 65 fl with an alpha/beta ratio of 0.5. These data reconfirm that in Blacks with alpha thalassaemia the proportion of HbH is lower and the severity of anaemia is less than in certain other racial groups, e.g. Southeast Asians. However, the degree of hypochromia and microcytosis and the imbalance in alpha and beta globin synthesis appear to be similar in Blacks and other races. These results suggest that the milder clinical course of HbH disease in Blacks is not a result of greater alpha globin production in that population of thalassaemics.

Adult↗
PubMed1979

In vitro culture of erythroid colonies from human fetal liver and umbilical cord blood.

Colony formation by erythroid precursors from human fetal liver, umbilical cord blood and adult peripheral blood has been studied in a plasma clot culture system. Fetal liver (FL) was obtained at post-mortem examination from 13-22 week abortuses. After mincing in Hanks' solution, cells in suspension were harvested by Ficoll-Hypaque centrifugation. Mononuclear cells were obtained by centrifugation of umbilical cord blood (CB) and normal adult peripheral blood (PB). All three types of preparations were incubated up to 14 d in 0.1 ml plasma clot cultures containing 0-4 u/ml erythropoietin (Epo) and 10(6) cells/ml. No colonies formed in the absence of Epo. Normal adult PB produced late-appearing colonies; there were no colonies at day 7 and up to 100 colonies/0.1 ml at day 14. CB produced early and late colonies with up to 200 colonies/0.1 ml at day 7 and 125 at day 14. Cells from FL produced many early colonies; over 1500 colonies/0.1 ml were sent at day 7 and there was a subsequent decline in colony count with longer incubation. In cultures of both CB and FL, colonies composed of either mature or immature cells were noted during both early and late stages of incubation suggesting that these cell sources contain a heterogeneous population of erythroid colony progenitors. Measurement of differential beta and gamma globin chain synthesis by erythroid colonies grown from fetal liver and umbilical cord blood gave results similar to those obtained by direct pulse-labelling of the original source of the cultured cells.

Cell Count↗
PubMed1978

Aplastic anemia with fetallike erythropoiesis following androgen therapy.

A 43/4-yr-old black girl with acquired aplastic anemia had an increase in total hemoglobin (Hb) from 4.5 to 16.8 g/dl and fetal hemoglobin (HbF) from 0.8 g/dl (18.8%) to 9.6 g/dl (60.2%) following combined androgen-adrenal steroid therapy. Discontinuation of the drugs was followed by a decline in both HbF and total Hb. Reinstitution of the combined steroids prompted a second rise in total and fetal hemoglobin. During these responses the subject's erythrocytes exhibited an increased i antigen score and a low level of red cell carbonic anhydrase. The glycine:alanine ratio at position 136 of the gamma chains of HbF was of the fetal type (proportion of chains with glycine residues, 0.74). Hemoglobin A2 was low (0.4%). The synthesis of alpha and non-alpha chains was balanced. These results indicate that the stimulation of red cell proliferation in this subject, in response to androgen therapy, resulted in the production of cells with several characteristics of "fetal" erythrocytes.

Anemia, Aplastic↗
PubMed1976

The interaction of alpha-thalassaemia and haemoglobin G Philadelphia.

An American Negro woman was found to have HbH disease in association with HbG Philadelphia (alpha68-asn leads to lys). Starch gel electrophoresis failed to reveal the presence of any HbA or HbA2 and studies of globin chain synthesis indicated absence of alphaA production. The alphaG/beta synthesis ratio was 0.63. The woman's son and her two half-sibs had alpha-thalassaemia trait with no HbH and alpha/beta synthesis ratios of 0.84, 0.84 and 0.76. The data indicate that there is no functioning alphaA gene linked to the alphaG gene. The absence of alphaA synthesis by the propositus also indicates that the alpha-thalssaemia gene trans to the alphaG gene completely suppresses alpha chain production, the first evidence for such a gene in Negroes.

Adult↗
PubMed1976

Globin chain synthesis in HbD (Punjab)-beta-thalassemia.

A 23-yr-old man of Greek-Italian ancestry with mild anemia was found to be heterozygous for HbD (Punjab) beta121 glu leads to gin and beta-thalassemia. HbA was not detected upon electrophoresis of the subject's hemolysate, and no synthesis of betaA globin was demonstrated after incubation of peripheral blood or bone marrow with 3H-leucine. The thalassemia gene was thus of the betao variety. The betaD/alpha synthesis ratios were almost equally unbalanced in the blood and bone marrow: 0.53 and 0.61, respectively. The mother of the propositus had beta-thalassemia trait. In peripheral blood the betaA/alpha synthesis ratio was 0.38. The mutant betaD gene thus appeared potentially capable of directing the synthesis of globin chains as efficiently as a normal betaA gene. The mildness of the HbD-betao-thalassemia syndrome appeared to be due to the maintenance of a relatively high total beta/alpha synthesis ratio in the presence of a physiologically neutral structural mutation.

Adult↗
PubMed1976

Translation of human globin mRNA: globin synthesis in cells containing Hb Leiden.

Most structurally abnormal hemoglobins are present in smaller amounts than HbA in the erythrocytes of heterozygous subjects. In the presence of a hemoglobinopathy, alpha and beta globin synthesis remains balanced with equal production of the two types of chains. In reticulocytes of subjects with Hb Leiden (beta 6 or 7 glu leads to 0) there is greater production of alpha than beta globin in vitro (beta/alpha = 0.67), and slightly more beta A is synthesized than beta Leiden (beta A/beta Leiden = 1.28). Differences in specific mRNA content, rates of initiation of chain synthesis, or rates of chain elongation could be responsible for such differential polypeptide synthesis. In the present study, the ribosomal assembly of beta A, beta Leiden, and alpha globin chains was examined in peripheral blood. The translation times of the three chains did not differ significantly (average times: beta A = 65.4 sec, beta Leiden = 70.8 sec, alpha = 53.5 sec). These results indicated that an altered rate of translation was not the source of the anomalous globin synthesis observed in vitro in cells containing Hb Leiden. The experiments suggested that the observed imbalance in alpha/beta production was due to either differential rates of initiation of globin chain synthesis or quantitative differences in the amounts of the specific mRNAs present in the cells.

Cell-Free System↗