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J Javid

Publications and source records attributed to J Javid.

At least 19 recordsLinked to original sources
PubMed1985

Determination of the hemoglobin F program in human progenitor-derived erythroid cells.

The absolute adult and fetal hemoglobin (HbF) contents of the erythroid cells derived from the differentiation of normal human and simian erythroid progenitors and of the peripheral blood erythroid burst-forming units (BFU-E) of patients with nondeletion hemoglobinopathies have been measured with a sensitive radioligand immunoassay. The HbF content varied between 0.13 and 2.96 pg/cell, representing between 0.7% and 19.6% of the total hemoglobin with a mean value of 7.0%. The absolute content of HbF was indistinguishable in the well-hemoglobinized progeny of marrow erythroid colony-forming units, marrow or blood BFU-E, or of mixed colony-forming units. The term HbF program refers to this inherent capacity to produce fetal hemoglobin (HbF) in the erythroid cells derived from these progenitors in vitro. The HbF content of marrow erythroblasts as determined by the same radioligand immunoassay was similar to that found in the peripheral blood, suggesting that the switch off of gamma-chain production occurs after the erythroid colony-forming unit stage of maturation. Increasing concentrations of a crude erythropoietin-containing preparation induced higher numbers of erythroid colonies, which were larger in size, but the HbF program was unaffected. In contrast to the hemoglobin accumulation in human progenitor-derived colonies, simian progenitor-derived colonies produced considerably more HbF, and the amount of HbF was strongly influenced by progenitor maturity. Assays of the HbF content of erythroblasts derived from culture of the peripheral blood BFU-E of patients with nondeletion hemoglobinopathies and their parents showed that the HbF program in the progenitors of such patients is highly variable. Some produce only a slight excess of HbF in progenitor-derived erythroblasts, whereas others have extraordinarily high HbF programs. The molecular basis of this variability is presently unknown.

Animals↗
PubMed1985

Immune hemolytic anemia in the aged.

Anemia is a common finding among the elderly. The clinical evaluation and management of anemia in the older patient is substantially similar to management in the general population. There are, nevertheless, notable differences in the prevalence of certain disorders, in the ability of the patient to tolerate the consequences of anemia, and in the safety of particular therapeutic measures. This article describes the different types of immunologically mediated hemolytic anemia and their underlying mechanisms and reviews the clinical features of each type and the current approach to their management.

Aged↗
PubMed1983

Fetal hemoglobin accumulation in vitro. Effect of adherent mononuclear cells.

In clonal cultures of erythroid burst-forming units (BFU-E) obtained from blood, the accumulation of fetal and adult hemoglobins (Hb F and Hb A) was measured by radioligand immunoassay. Inclusion of adherent mononuclear cells in the culture promoted a striking increase in the relative amount of Hb F in each of 44 experiments with 14 donors. In two-thirds of the instances, this was accounted for by a selective increase in the absolute amount of Hb F. The differential effect on Hb F and Hb A accumulation was achieved without altering the maturity of the erythroid cells, their mean hemoglobin content, or the asynchrony of the production of the two hemoglobins. Virtually all bursts produced Hb F, and the population of BFU-E as a whole, rather than a selected subset, appeared to be the target of adherent cell action. When the adherent cells were excluded from the culture input, the base-line value of Hb F was reproducible for each donor over a period of several months, and correlated with the number of in vivo circulating F cells.

Adult↗
PubMed1982

Synthesis of hemoglobin F in adult simian erythroid progenitor-derived colonies.

The simian hematopoietic system is known to respond to anemic stress with the production of erythrocytes containing large amounts of fetal hemoglobin. To determine the regulatory mechanism responsible for hemoglobin F (HbF) production in stress erythropoiesis, adult simian bone marrow cells were cultured in plasma clots in the presence or absence of erythropoietin and burst-promoting activities, and the HbF content of progenitor-derived colonies was determined by radioimmunoligand assay. Three classes of erythroid progenitors were detected: BFU-E, CFU-E, and a very mature cohort of dense highly erythropoietin-responsive cells (HERC). These classes varied in inverse proportion to their maturity with respect to their potential for HbF accumulation in the colonies to which they give rise. Both erythropoietin and burst-promoting activity stimulated HbF production, particularly in colonies derived from immature progenitors. For example, under conditions of high erythropoietin stimulation, BFU-E colonies contained 13.7-37.7% HbF, CFU-E colonies contained 2.8-13.5% HbF, and HERC colonies 0-1% HbF. These results suggest that under nonstress conditions simian erythrocytes are derived almost entirely from HERC progenitors and proerythroblasts in which gamma chain synthesis is suppressed. During stress erythropoiesis, augmented HbF accumulation could be explained by the rapid entrance into the marrow of proerythroblasts directly derived from immature progenitors. Gamma chain production in these proerythroblasts is additionally regulated by the changes in environmental erythropoietin and burst-promoting activities.

Animals↗
PubMed1981

Radio-ligand immunoassay for human hemoglobin variants.

A quantitative method is described for the individual assay of human hemoglobin variants occurring singly or in mixture. The hemoglobin to be assayed is bound to specific antibody; the immune complex is attached to protein A-containing S. aureus and removed from the mixture. The hemoglobin thus isolated is quantified by its ability to bind radiolabeled haptoglobin. The technique is accurate and distinguishes among the 4 hemoglobins tested, namely Hb A, S, C and F. It has the advantage over conventional radioimmunoassay that a single probe, radiolabeled haptoglobin, is needed for the specific assay of any hemoglobin.

Genetic Variation↗
PubMed1978

Immunologic characterization and quantification of haemoglobin A1c.

Sheep antiserum developed against the human glycohaemoglobin, Hb A1c, distinguishes this fraction from the major component Hb A0. Partial cross reactivity is observed with Hb A1a and Hb A1b, as well as with analogous glycohaemoglobins from mouse and dog haemolysates. The reactivity of the haemoglobins with this specific antiserum is abolished by the reduction of the keto group of the sugar ligand. The immunological specificity displayed provides the basis of a quantitative assay for Hb A1c, suitable for studies of clinical and experimental diabetes.

Animals↗
PubMed1977

Ulcers of the leg in thalassemia.

Four patients had thalassemia and leg ulcers. In three patients the hematologic diagnosis of thalassemia had not been previously made; the presenting symptom was the leg ulcer. The diagnosis of thalassemia should be considered in patients who have unexplained chronic leg ulcers; the incidence of this complication of thalassemia may be higher than previously reported.

Adult↗
PubMed1976

The immunologic identification of abnormal hemoglobins.

Guinea pig antisera against human hemoglobin contain antibodies to multiple antigenic determinants. Hemoglobin variants having single amino acid substitutions affecting these determinants are recognized as antigenically deficient in a radioimmunoassay system. The multivalent antisera may be made more selective by appropriate absorption with hemoglobin variants. Three such antisera containing antibodies specific, respectively, for the beta-chain of Hb A, Hb S, and Hb C are described. They can differentiate among the hemoglobins of individuals who possess these variants alone or in any paired combination. Their discriminating ability is not hindered by the presence of 1,000-fold concentrations of Hb F and may therefore be extended to the early prenatal diagnosis of sickling disorders. The antisera described also detect several other variants of Hb A. The approximate location of the substitution in variants so detected can be determined by a complementation test. This is based on the finding that two antigenically deficient hemoglobins will complement each other in mixture provided their amino acid substitutions involve different determinants.

Fetal Blood↗
PubMed1975

The modification of hemoglobin-antihemoglobin reaction by haptoglobin.

In radioimmunoassay and double diffusion experiments, the reaction between hemoglobin (Hb) and antihemoglobin antibody is markedly affected by the presence of haptoglobin (Hp). Binding with haptoglobin exposes "neoantigenic" determinants in hemoglobin, probably as a result of conformational changes exposing previously inaccessible structures. Some of these are shared by both Hb A and Hb F an may be located on alpha-chains. The exposure of these determinants requires the binding of hemoglobin by haptoglobins of the phenotype Hp 2-2 or Hp 2-1. The phenotype Hp 1-1 and guinea pig haptoglobin have no discernible effect in this context. It thus appears that the conformational change induced in hemoglobin by the "polymeric" forms of haptoglobin differ from those, if any, caused by the "monomeric" forms such as Hp 1-1. Most antisera raised against free hemoglobin contain some antibodies specific for these hidden determinants which may have become exposed during the processing of the immunizing antigen. These findings have significant implication in the interpretation of radioimmunoassay data.

Animals↗
PubMed1968

Immunogenetics of human haptoglobins. I. The antigenic structure of normal Hp phenotypes.

The various antigenic determinants of serum haptoglobins (Hp) may be studied semiquantitatively in a radioimmunoassay system. Using three antisera of overlapping specificities, we constructed an antigenic model of the various Hp phenotypes comprising four distinct determinants. This adds a new determinant, situated near the hemoglobin binding site, to the three determinants reported in the literature. The assay system is sensitive to 0.2 mug or less of serum Hp. Furthermore, it can detect determinants that are not recognized by double diffusion studies.

Animals↗
PubMed1968

Immunogenetics of human haptoglobins. II. Hp Bellevue, a cross-reacting mutant.

Using a radioimmunoassay method in conjunction with double diffusion studies, we characterized the antigenic determinants of the three Hp Bellevue phenotypes. An antigenic model based on these data indicates that each phenotype comprises a heterogeneous group of proteins with properties depending on their content of normal (hpbeta) and of mutant (hpbeta-Bellevue) chains of haptoglobin. The loss of the hemoglobin binding capacity and of a specific Hb-sensitive antigenic determinant is a consequence of the structural alteration in hpbeta-Bellevue and is expressed to various extents by the populations of proteins containing this chain. It is suggested that those molecules with a preponderance of mutant beta-chains are without significant hemoglobin binding capacity and are degraded more slowly in vivo than the ones capable of hemoglobin binding.

Animals↗