Louis Lowenstein

A factor stimulating DNA synthesis derived from the medium of leukocyte cultures.

BAIN et al.1,2 have shown that when human peripheral blood leucocytes from two individuals are mixed and cultured, large immature cells appear and the incorporation of tritiated thymidine into DNA is stimulated. It has been suggested that variations in this response may reflect differences in the number of histocompatibility antigens shared by the donors of the cells1–3. It has also been shown that transplantation antigens can be detected in the medium from tissue cultures of rabbit4 and dog5 spleen cells. We, therefore, decided to determine whether factors released into the medium from cultured peripheral blood leucocytes might stimulate tritiated thymidine uptake (radioactive content) in cultures of leucocytes from another individual.

Genetic Studies on the Mixed Leukocyte Reaction

When leukocytes from pairs of unrelated human subjects are mixed and cultured for several days, blast-like cells appear that are capable of DNA synthesis and mitosis. This reaction can be estimated quantitatively by measuring the uptake of tritiated thymidine in the cultures. In experiments with 15 sibling pairs, the leukocytes of most individuals reacted less strongly with those of their siblings than with those of an unrelated subject.

Blood volume and hematologic studies in pregnancy and the puerperium.

Abstract This investigation was initiated in an effort to clarify the conflicting results which exist regarding the hemodilution in pregnancy, to attempt to correlate the hematologic picture with this hydremia, both ante partum and post partum, and to establish normal hematologic values for pregnancy, a deviation from which might permit the diagnosis of an early pathologic anemia. The literature varies with regard to the normal hematologic findings in pregnancy.

Drug-induced Hemolytic Anemia

Excerpt Hemolytic Anemia may result from the administration of oxidant drugs, including primaquine, sulfonamides, nitrofurantoin, acetylsalicylic acid, and acetophenetidine (1-4). Recent publicatio...

Correlation of blood loss with blood volume and other hematological studies before, during and after childbirth.

P OSTPARTUM hemorrhage is today a major cause of maternal morbidity and mortality.l, 2 Previous hematologic and blood volume studies of the normal pregnancy and puerperium at the Royal Victoria Hospital showed that the loss of circulating blood due to childbirth greatly exceeded the obstetrician’s estimate. The present study was initiated to explain this discrepancy and to determine in greater detail the blood loss in normal delivery. Many observers have measured blood loss during the third stage of labor, using receptacles to collect. blood escaping from the vagina and perineum. Table I demonstrates the wide variations found in fifteen reported series.3-1” The average blood loss ranged from 150 to 600 ml. At the Royal Victoria Hospital the blood loss in normal delivery is commonly estimated at 200 ml. 01’ less by the attending obstetrician. Tysoe and llowensteinll followed the serial blood volume changes of a group of women during pregnancy and for two months post partum at the Royal Victoria Hospital and were impressed with the marked diminution of total red cell volume after delivery (Fig. 4). In recent years the T-1824 dye-hematocrit, carbon monoxide, red cell differential agglutination, and radioactive tracer methods of blood volume determination have been applied to the measurement of blood loss resulting from surgical operations, traumat,ic injuries, battle casualties, and gastrointestinal hemorrl~age.l”-‘” A number of authors have used one or more of these methods in measuring blood volumes in pregnancy and the puerperium. Table II is a composite table computed from their data.“, =, z.i, ~3 z7 Although the number of cases reported in each series was small, their close agreement seems significant,. The average apparent blood loss by these methods ranged from 810 to 1,250 ml. These findings suggested that maternal blood loss from the active circulation occurring after delivery is greater than is commonly believed and led to the following studies.

An immunologic basis for acquired resistance to oral administration of hog intrinsic factor and vitamin B12 in pernicious anemia.

In pernicious anemia, vitamin B12 deficiency develops owing to the failure of gastric intrinsicfactor secretion. Patients with this disease absorb vitamin B12 from the gastrointestinal tract when it is fed together with an extract of hog pyloric mucosa. Some patients have relapsed during the course of oral therapy with this mixture (1-3). These subjects absorb vitamin B1.2 administered with normal human gastric juice but do not absorb it when it is administered with hog preparations possessing intrinsic-factor activity (3). These patients have become refractory to the hog preparations. It has been reported that sera obtained from most of these refractory patients (4), and from a minority of nonrefractory patients and normal subjects (5, 6), possess intrinsic factor-neutralizing properties. Such observations have directed attention to a possible immunologic mechanism for the refractory state. This study was undertaken to determine whether the refractory state might be due to antibodies against the hog intrinsic-factor preparation, which could be detected in vitro.

Correlation of red cell loss at delivery with changes in red cell mass

In sixteen pregnant women decrease in red cell mass at delivery was compared with external loss of red cell using Cr51-tagging of red cells and a large well-type scintillation detector. There was good agreement between the two sets of measurements. It was shown that previous discrepancies were largely due to use of the venous hematocrit employed in the indirect method of calculation of red cell mass. The significantly greater loss of red cells at delivery in primiparas than in multipara is attributed to the practice of episiotomies in the former group.

Hormonal Control of Erythropoiesis during Pregnancy in the Mouse

Summary. Increased plasma erythropoietic activity was observed during pregnancy in the mouse, first appearing on the 5th day. Reticulocytosis, increase of red‐cell volume, decrease of plasma iron and increase of the total iron binding capacity appeared on the 10th day. The major increase of red‐cell volume and plasma volume occurred during late pregnancy as the reticulocytes and plasma iron progressively decreased. Suppression of endogenous erythropoietin production in pregnant mice by hyperoxia did not completely abolish either plasma erythropoietic activity or the rise of the red‐cell volume observed in unexposed pregnant mice. Placental lactogen was found to have some erythropoietic activity and increased the plasma volume. Ovarian hormones were erythropoietically ineffective and, in fact, oestrogen appeared to inhibit the activity of placental lactogen.

Inhibition of the Stem-Cell Action of Erythropoietin by Estradiol.

Summary Injection of estradiol into poly-cythemic mice stimulated to produce endogenous erythropoietin inhibited the incorporation of Fe59 into their erythrocytes when it was injected during the stage of stem-cell differentiation, but not during the latter stages of erythroid cell development. In doses up to 20 times that of daily endogenous estrogen production, secretion of erythropoietin was not inhibited and utilization of erythropoietin by the bone marrow appeared to be blocked.

Irradiated and Preserved Leukocytes in Mixed Leukocyte Cultures.

Summary and conclusions When leukocytes received 1,5-00 r or more in vitro, they were rendered incapable of DNA synthesis and mitosis in mixed leukocyte cultures, but did not lose their ability to stimulate the blastogenesis of allogeneic intact leukocytes. The sum of the “one-way” (Ax + B) and (A -f- Bx) reactions was approximately equal to the “two-way” (A + B) reaction. Therefore, irradiated leukocytes can be used for unidirectional quantitation of the mixed leukocyte reaction. When leukocytes were irradiated with less than 6,000 r and cultured with PHA, some transformation to blasts occurred. Leukocytes stored at —70°C for 2 weeks retained their capacity for blast transformation when cultured in the presence of X-irradiated allogeneic cells. Frozen storage of irradiated leukocytes reduced their blas-togenic effect variably up to 30% of that of fresh controls.