The Pattern of Stem Cell Repopulation in Heavily Irradiated Mice Receiving Transplants of Fetal Liver

Pluripotential cells derived from fetal liver had a lower plating efficiencythan adult marrow cells, but estimates of the generation time derived fromthe growth curve are significantly shorter and may account for the earliererythroid population.

Submitted on June 18, 1969 Accepted on August 12, 1969     

Growth and Differentiation of Transplanted W/Wv Marrow

This paper reports new data on the effect of the action of the mutant genesW and W^v on murine hemopoiesis. Our studies demonstrate that the presenceof these mutant genes produces: (1) a macrocytic anemia with neithergranulocytopenia nor thrombocytopenia; (2) a severe defect in the earlystages of hemopoietic repopulation manifested by (a) an apparent block inthe differentiation of immature cells into erythroid precursors, and (b) a greatly reduced rate of proliferation of differentiated hemopoietic elements.

These data demonstrate the existence of genetic influence on repopulationand differentiation of transplanted marrow and suggest that severe anemia mayresult not only from defects in the late stages of erythroid development butalso from abnormalities in the early stages of erythroid maturation andhemopoietic repopulation.

Submitted on February 15, 1967 Accepted on May 5, 1967     

Pretreatment hematocrit as an independent prognostic variable in Hodgkin's disease

Pretreatment hematocrit in 117 advanced-stage Hodgkin's disease patients treated with a combined modality therapy program was evaluated as an independent prognostic variable with regard to survival and relapse-free survival. Age greater than 40 years, and multiple extranodal sites of involvement were found to be statistically significant independent negative prognostic factors with regard to survival. Pretreatment hematocrit, however, was not an independent negative prognostic variable.     

Activation of human platelets by immune complexes prepared with cationized human IgG

The present study shows that the ability of soluble immune complexes (IC), prepared with human IgG and rabbit IgG antibodies against human IgG, to trigger platelet activation was markedly higher for IC prepared with cationized human IgG (catIC) compared with those prepared with untreated human IgG (cIC). CatIC induced platelet aggregation and adenosine triphosphate release in washed platelets (WP), gel-filtered platelets (GFP), or platelet-rich plasma (PRP) at physiologic concentrations of platelets (3 x 10(8)/mL) and at low concentrations of catIC (1 to 30 micrograms/mL). On the contrary, under similar experimental conditions, cIC did not induce aggregation in PRP, WP, or GFP. Low aggregation responses were only observed using high concentrations of both WP (9 x 10(8)/mL) and cIC (500 micrograms/mL). Interestingly, catIC were also able to induce platelet activation under nonaggregating conditions, as evidenced by P-selectin expression. Cationized human IgG alone did not induce platelet aggregation in PRP but triggered either WP or GFP aggregation. However, the concentration needed to induce these responses, was about eightfold higher than those required for catIC. The responses induced either by catIC or cationized human IgG were completely inhibited by treatment with heparin, dextran sulphate, EDTA, prostaglandin E1, or IV3, a monoclonal antibody against the receptor II for the Fc portion of IgG (Fc gamma RII). The data presented in this study suggest that IgG charge constitutes a critical property that conditions the ability of IC to trigger platelet activation.     

RENAL TRANSPLANTATION IN PATIENTS WITH DIABETES MELLITUS

Experience with renal transplantation in eight patients with overt diabetes mellitus suggests that renal transplantation from living related donors is not contraindicated as treatment for end-stage nephropathy.     

Intestinal Mucosal Mechanisms Controlling Iron Absorption

Radioautographic studies provide evidence to support a concept of themechanism whereby the small intestine controls absorption of iron. Threedifferent states of the body’s iron stores have been considered in this regard:iron excess, iron deficiency and normal iron repletion. As the columnarepithelial cells of the duodenal villi are formed they incorporate a portion ofintrinsic iron from the body’s iron store, the amount depending upon thebody’s requirement for new iron. It is predicated that with iron excess theiron-receptor mechanism in these cells is saturated with intrinsic iron; thisthen prevents the cell from accepting dietary iron. In the normal state ofiron repletion the receptor mechanism remains partly unsaturated, allowingsmall amounts of dietary iron to enter the cell. Part of this proceeds into thebody to satisfy any metabolic requirement for iron. Part is retained in themucosal epithelial cells to complete the saturation of the iron-receptormechanism. This bound iron is subsequently lost when the epithelial cellsare sloughed at the end of their life cycle. In iron deficiency it is postulatedthat the receptor system is inactive or diminished so that entry of dietary ironinto the body is relatively uninhibited.

Submitted on February 12, 1963 Accepted on April 3, 1963     

Diagnostic Specificity of Sucrose Hemolysis Test for Paroxysmal Nocturnal Hemoglobinuria

The diagnostic specificity of the various modifications of the sucrose hemolysis test for PNH was examined in detail. In whole blood screening tests thegreatest specificity was achieved using citrated or oxalated blood and roomtemperature incubation (23°). Defibrinated whole blood should not be usedsince "false positive" hemolysis may occur in blood disorders other than PNH.Mechanisms were suggested for this phenomenon. The validity of the confirmatory sucrose hemolysis test employing normal serum was further reported.Because of the clear, colorless character of serum-sucrose mixtures, an insignificant degree of hemolysis (i.e., less than 5%) is more readily visible thanin other PNH hemolytic tests employing undiluted serum. Definitive instructions and criteria for interpretation were given for both the whole bloodscreening test and the confirmatory sucrose hemolysis test.

Submitted on June 18, 1969 Accepted on December 8, 1969     

Diffuse large cell lymphoma in a patient with hairy cell leukemia: immunoglobulin gene analysis reveals separate clonal origins

A 75-year-old man with hairy cell leukemia (HCL) was found to have an immunoblastic lymphoma of the small bowel. Immunologic and genotypic characterization of these neoplasms revealed both the HCL and the immunoblastic lymphoma to be of the B cell lineage. The HCL expressed the HCL-associated antigens detected by the monoclonal antibodies HC-1 and HC-2, whereas the immunoblastic lymphoma failed to react with these antibodies. In addition, surface immunoglobulin light chains could not be accurately determined for the hairy cells, whereas the immunoblastic lymphoma was shown to express only kappa immunoglobulin light chains. These immunophenotype differences were compatible with either the clonal evolution of the HCL into the immunoblastic lymphoma or a separate clonal origin for these two neoplasms. An analysis of tumor DNA by Southern blot hybridization revealed different heavy-chain and kappa light-chain gene rearrangements in these two malignancies. Thus the occurrence of the large cell lymphoma most likely represents the emergence of a second clonally unrelated B cell malignancy.