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Biomedical subjects

D G Nathan

Publications and source records attributed to D G Nathan.

At least 199 records · Page 11Linked to original sources
PubMed1976

The acute and transient nature of idiopathic immune hemolytic anemia in childhood.

The records of 22 children with the diagnosis of idiopathic immune hemolytic anemia were reviewed. Fifty per cent of the children had a history of an antecedent infection and 32% had underlying immune deficiency or lymphoproliferative diseases. The majority (77%) of the patients had an acute self-limited disease which was frequently associated with a positive complement or nongamma Coombs test. The anemia was usually severe, and a number of the children had reticulocytopenia at the time of diagnosis. These children responded rapidly to transfusions and corticosteroids and generally remained well on follow-up. Immunosuppressive drugs did not prove useful in two patients refractory to prednisone, but splenectomy was apparently beneficial in three of four patients so treated. Mortality rate was 18%, with most of the deaths related to an underlying disease.

Acute Disease↗
PubMed1976

Detection of genetically determined histocompatibility antigen differences between HL-A identical and MLC nonreactive siblings.

Five patients with aplastic anemia were shown to be sensitized in vivo to the transplantation antigens of HL-A identical and MLC nonreactive sibling bone marrow transplantation donors. The sensitization in four cases were detected by antibody-dependent cell-mediated lysis (AICML) techniques, and in one case by antibody-dependent cell-mediated lysis (ADCML). In two cases the inherited nature of the sensitizing antigen was demonstrated, and in one case the inheritance of the antigen was shown by a family study to be independent of the HL-A and MLC loci. Maximal AICML was demonstrated in two cases at the time of bone marrow graft rejection. Successful transplants after immunosuppression with rabbit anti-thymocyte serum, procarbazine, and cyclophosphamide were performed in two patients, in whom sensitization was detected before transplantation.

Antibody Specificity↗
PubMed1976

Indium chloride scintigraphy: an index of severity in patients with aplastic anaemia.

[111In]Indium chloride scans of the bone marrow were performed in 22 patients with idiopathic aplastic anaemia before therapeutic intervention. In 20 patients there was a marked reduction in the uptake of indium chloride by the marrow, and in two patients the uptake of indium chloride was normal. Nineteen of the 20 patients with reduced marrow uptake of indium chloride, who underwent bone marrow transplantation, died or failed to improve. One of the two patients with normal scans improved and the other has remained stable. Four patients studied both pre and post successful bone marrow transplantation had minimal marrow uptake before transplantation and normal scans after transplantation. Failure of indium-111 choride marrow uptake correlates with poor prognosis in idiopathic aplastic anaemia.

Adult↗
PubMed1976

Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality.

A prospective randomized trial of therapy for severe aplastic anemia was designed to compare early bone marrow transplantation with conventional treatments. All patients with a sibling matched at the major histocompatibility region were transplanted. Transplantation was performed with 17-100 (median 33) days of original diagnosis. Conventional treatments included transfusion support with or without androgens. Twenty-four of 36 patients intered on the transplant arm are alive after 4-20 (median 9) mo with full marrow reconstitution. Only two are limited by chronic graft-versus-host disease. In contrast only 12 of 31 conventionally treated patients are alive. Six of these survivors have improved, five incompletely. The 19 nontransplant deaths have occurred within 1-11 (median 3) mo of diagnosis. Compared to nontransplant regimens, early transplantation more effectively restores normal marrow function and decreases the acute mortality of severe marrow aplasia (p = 0.006). Pending longer follow-up, early marrow transplantation appears to be the most effective available treatment for severe aplastic anemia.

Androgens↗
PubMed1976

Fetal erythropoiesis following bone marrow transplantation.

"Fetal" erythrocytes are present in older children and certain adults with hematologic disorders. To determine if regenerating bone marrow produces such cells, we examined the blood of seven allogeneic bone marrow transplant recipients. Six patients were engrafted with donor cells, while on e patients recovered autologous bone marrow after rejection of a marrow transplant. All seven patients had fetal hemoglobin levels of up to 10% by 100 days after transplant. In three patients, the Ggamma to Agamma ratio in the fetal hemoglobin was "newborn", while in one it was "adult". Gamma chain synthesis in blood and bone marrow never exceeded 20% of total non-alpha globin synthesis. The fetal hemoglobin was heterogeneously distributed in the cells. High titer i antigen also appeared. All fetal characteristics declined by 200 days. Erythropoiesis during bone marrow recovery appears to be associated with an accelerated, albeit partial, recapitulation of ontogeny.

Bone Marrow Cells↗
PubMed1975

Expression of the beta-thalassemia gene in the first trimester fetus.

To determine whether beta-thalassemia can be detected in the fetus, blood was obtained from abortuses of normal mothers and of mothers with beta-thalassemia trait. The red cells were incubated with radioactive leucine and the globin chains were analyzed by radiochromatography. Two independent methods were utilized to correct the results for contamination by maternal radioactive beta-chain, and the corrected beta/gamma ratios were compared to a previously established range of normal fetal beta/gamma synthetic ratios obtained by similar measurements in pure fetal cells. In the erythroid cells of three fetuses from mothers with beta-thalassemia trait, the beta/gamma synthetic ratio was normal in two. The third had a beta/gamma ratio of 0.04 at 10 1/2 weeks, a 50% reduction, consistent with fetal beta-thalassemia trait. Two other fetuses, derived from parents both of whom had beta-thalassemia trait, were also studied. One had a beta/gamma ratio of 0.029 at 8 weeks, a 65% reduction, also consistent with beta-thalassemia trait. The cells of the other had a ratio of essentially zero at 11 weeks, highly suggestive of homozygous beta-thalassemia. Although further experience will be needed to distinguish the homozygous and heterozygous states reliably, it now appears that the beta-thalassemia gene is expressed in the first trimester. Therefore these data suggest that the antenatal diagnosis of beta-thalassemia is becoming an attainable goal.

Female↗
PubMed1975

Anemia in adolescence. 2. Hemoglobinopathies and other causes.

Many complex forces are at work during adolescence which can contribute to the occurrence of anemia. Careful consideration of the entire patient should enable a physician to identify the unusual as well as the more common causes of anemia in this age group. Anemia in teenage girls is primarily due to menstrual iron loss. In boys, borderline diets and the demands of rapid growth predominate as causative factors. Hemoglobinopathies (thalassemia, sickle cell disease), G6PD deficiency, infectious mononucleosis, and illicit drug use account for small proportions of cases.

Adolescent↗
PubMed1975

Thalassemia.

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Blood Transfusion↗
PubMed1975

Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Family members from four generations were found to have polycythemia and increased whole blood O2 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two beta-chain peaks, the first of which was eluted at a lower buffer molarity than normal beta chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal beta chain had slower electrophoretic mobility and a greater Rf value. Amino acid analyses of this peptide gave values identical with those of betaTp 14, except that it contained one proline residue and no histidine. Since the one His in betaTp 14 is in position 143, hemoglobin Syracuse in alpha2beta2-143 His leads to Pro. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparative buffers proved very useful in reducing the formation of methemoglobin. Oxygen equilibria of purified hemoglobin Syracuse showed high oxygen affinity (P50 value 12% that of hemoglobin A) and lack of cooperativity between subunits (Hill's n equals 1.1). The alkaline Bohr effect was about half that of hemoglobin A. The proline substitution at betaH21 disrupts the helical configuration and probably prevents the formation of salt bonds that are important in stabilizing the deoxy structure and contribute to the alkaline Bohr effect. Since beta143 His is a binding site for 2,3-diphosphoglycerate (2,3-DPG), it is not suprising that hemoglobin Syracuse had markedly impaired reactivity with 2,3-DPG. Hemoglobin Syracuse auto-oxidized more slowly than hemoglobin A, probably reflecting a slower rate of dissociation of oxygen from fully liganded hemoglobin.

Adult↗
PubMed1975

Selection of patients for bone marrow transplantation in severe aplastic anemia.

Despite androgens and intensive supportive care, satisfactory survival in severe aplastic anemia remains at 20% or less. Histocompatible bone marrow transplantation can restore normal hematopoiesis in approximately 40% of similarly severe individuals. Delay of transplantation for 3 wk after diagnosis allows time for proper evaluation and for many spontaneous recoveries. Further delay increases risks of fatal complications and decreases chances for successful transplantation while the incidence of spontaneous remission declines. When available, early histocompatible bone marrow transplantation may be the treatment of choice for severe aplastic anemia.

Adolescent↗