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Biomedical subjects

F Milgrom

Publications and source records attributed to F Milgrom.

At least 127 records · Page 7Linked to original sources

Studies on skin-reacting transplantation antibodies.

Evidence is presented that skin-reacting transplantation antibodies (SRTA) can be elicited not only by skin allografts, but also by injection of dispersed allogeneic lymphoid cells. Two mechanisms of action of SRTA, which are not mutually exclusive, are compatible with the experimental results. (1) SRTA may act as homocytotropic antibodies, producing skin reactions by fixing to the skin of the test animal and combining with circulating antigens brought to the test site. (2) SRTA may produce skin reactions by combining directly with "sessile" antigens in the skin. Genetic studies showed that the antigens combining with SRTA are inherited as simple Mendelian traits. Furthermore, it was shown that these antigens are not related to the major rat histocompatibility antigens, Ag-B, nor are they related to any other described rat alloantigen system. Thus, the antigens responsible for SRTA belong to a new antigenic system.

Animals↗

Comparison of various procedures for the detection of antigen-antibody complexes.

The described test of inhibition of AA activity proved to be a procedure of exquisite sensitivity and specificity for detection of immune complexes. This could have been expected since AA is an antibody specifically combining with IgG antibody that suffered molecular transformation in the reaction with its corresponding antigen. Complexes formed at or close to the equivalence zone were most active in inhibiting AA, whereas those at extreme antigen excess did not inhibit it at all. Inhibition of AA was capable of detecting circulating immune complexes as well as immune complexes deposited in the tissues. It was also shown that by using this procedure, identification of the antigen participating in immune complex formation is feasible since excess of the specific antigen converts inhibitory complexes into inactive complexes.

Antibodies, Anti-Idiotypic↗

Characterization of the Hanganutziu-Deicher (serum-sickness) antigen as gangliosides containing n-glycolylneuraminic acid.

Gangliosides that possess the same sugar sequence but differing in the type of sialic acid (N-acetyl- or N-glycolylneuraminic acid) were compared for their reactivity with Hanganutziu-Deicher ('serum sickness') antibodies by double-diffusion gel precipitation tests. Only N-glycolylneuraminic acid containing gangliosides formed precipitation lines with Hanganutziu-Deicher antibodies, thus suggesting that Hanganutziu-Deicher antigens are gangliosides that contain N-glycolylneuraminic acid.

Antibody Specificity↗

Reactions of rabbit antisera to human beta2-microglobulin (beta2-M) with platelets.

Reactions of rabbit antisera to human beta2-M against human platelets and man-mouse hybrid cells were studied by MA tests and cytolysis tests. Evidence is presented that the beta2-M act as species-specific cell surface antigens, some of which are most likely shared by cell surface proteins determined by genes on chromosomes other than the chromosome 15.

Absorption↗

Detection of circulating immune complexes in alcoholic liver disease.

Sera of twenty-five patients with alcoholic liver disease and forty normal control sera were screened for circulating immune complexes by means of the anti-antibody neutralization test and by Raji-cell membrane immunofluorescence assay. IgG-containing immune complexes were detected in thirteen out of twenty-five patients with alcoholic liver diseases and in one out of forty normal individuals; in addition, IgA-containing complexes were demonstrated in seven out of thirteen sera positive for IgG complexes. The presence of immune complexes was restricted to alcoholic hepatitis and active cirrhosis, thus indicating a relationship with disease severity.

Antigen-Antibody Complex↗

Isolation and partial characterization of the heterophile antigen of infectious mononucleosis from bovine erythrocytes.

The heterophile antigen (Paul-Bunnell antigen, PBA) of infectious mononucleosis was isolated by extraction of an aqueous suspension of bovine erythrocyte stromata with chloroform-methanol (2:1). The upper aqueous layer contained gangliosides, PBA, and a high-molecular-weight glycoprotein. PBA and gangliosides were separated from the high-molecular-weight glycoprotein by extraction of lyophilized upper layer with chloroform-methanol solvents. Separation of PBA from gangliosides was carried out by chromatography on DEAE-cellulose with chloroform-methanol solvents. PBA appeared to be a minor glycoprotein component of the erythrocyte membrane and had both hydrophobic and hydrophilic properties. It was soluble in either organic or aqueous solvents. On SDS-polyacrylamide gel electrophoresis, it migrated as a single component that stained for protein with Coomassie blue, for carbohydrate with periodic acid-Schiff reagent, and for lipid with oil red 0; it had an apparent molecular weight of 26,000. It was composed of 62% protein with major amino acids; glutamic acid, proline, glycine, isoleucine, leucine, and threonine (158, 116, 98, 90, 85, and 82 residues per 1,000 residues, respectively). Carbohydrate content was 9.2% with major sugar constituents: sialic acid, galactosamine, and galactose. Serologic activity of PBA was destroyed by pronase but not by trypsin.

Amino Acids↗

Humoral antibody response in rat renal allotransplantation.

Female inbred Fischer (F344) rats were grafted with kidneys from female BN rats. Humoral antibodies in some of the recipients were demonstrated as early as 3 days after transplantation: (1) antibodies bound to the graft were detected by mixed agglutination tests with graft sections and erythrocytes of the donor as indicator cells; (2) lytic and agglutinating antibodies against donor strain erythrocytes were demonstrated in the recipients' sera by hemolysis in agar gel and dextran hemagglutination tests; and (3) similar antibodies secreted by a significant number of cells were detected in the recipients' spleens by plaque assay. The antibody response of the recipients was directed against a single antigen, designated N, which was shown to be present on erythrocytes of 57% of Fischer strain rats and was shared by erythrocytes of all rat strains tested (BN, Lewis, Wistar, ACI, MAXX, and Buffalo). The N antigen did not seem to belong to any known rat histocompatibility antigen system. Segregation of the gene coding for this antigen within the Fischer strain would indicate residual genetic heterogeneity. Evidence was presented that this antigen is present not only on erythrocytes, but also on other cells including splenocytes.

Adrenal Glands↗

Immunochemical studies on a nephritis-associated ubiquitous tissue antigen.

A ubiquitous tissue antigen (UTA), associated with chronic renal diseases was partially purified and characterized. The antigen was extracted by solubilization in 0.5% sodium deoxycholate (DOC) of various organs of human and animal origin. UTA was soluble in ammonium sulfate at 50% concentration and precipitable in 71% ethanol. Considerable purification of UTA was achieved by fractional ammunium sulfate precipitation, zone electrophoresis and gel filtration. Gel filtration on Sephadex G-200 and velocity gradient centrifugation through 10-40% sucrose gradients suggested that the main antigenic component is a macromolecule, although aggregability of DOC-extracted proteins upon removal of the solubilizer prevented more accurate determinations. UTA appeared to be a heat-stable glycoprotein which did not contain lipids detectable by Sudan black B staining. The yield of purest UTA preparations, which did not contain components of homologous serum as tested by double diffusion gel precipitation or immunoelectrophoresis, was 0.1-0.2 mg/100 g of starting tissue. Immunization of rabbits with homologous UTA-containing preparations resulted in anti-UTA antibody formation.

Ammonium Sulfate↗

Studies on adsorption by tumor tissue of erythrocytes sensitized by IgG antibodies.

Cryostat sections of methylcholanthrene-induced murine tumors were previously shown to adsorb erythocytes sensitized by subagglutinating concentrations of antierythocyte antibodies. This type of hemadsorption was seen also with sections of normal murine spleen. It was shown in the present study that immune complexes composed of bovine serum albumin (BSA) and rabbit anti-BSA serum, or human IgG and mouse anti-human IgG serum inhibit adsorption of sensitized erythocytes by tumor and spleen sections. Maximum inhibition was produced by complexes formed at excess of antigen. In contrast inhibition was not seen with complexes formed at equivalence. In addition, heat-aggregated human IgG, but not monomeric human IgG, inhibited hemadsorption by tumor tissue. Anti-BSA, antihuman IgG, BSA or human IgG alone did not produce significant inhibition. These results support the contention that murine tumor cell and lymphocytes have similar Fc receptors on their surface. The implication that the nonspecific attachment of immune complexes to the tumor cells and lymphocytes may alter the immunological response of the host to the tumor is discussed.

Animals↗

Direct and cooperative mechanisms of lymphocyte triggering in liquid and solid cultures.

The role of cell interactions in lymphocyte stimulation was analyzed by studying the kinetics of lymphocyte proliferation at different cell concentrations, and also by a lymphocyte microculture technique in solid medium. An absolute requirement for cell interactions was found in lymphocyte responses to concanavalin A, pokeweed mitogen, sodium periodate, purified protein derivative from Mycobacterium tuberculosis, and zinc chloride. No requirement for cell interactions was found in lymphocyte responses to calcium ionophore A23187. The existence of lymphocyte subpopulations with different requirements for cell interactions was observed in lymphocyte responses to phytohemagglutinin P, phytohemagglutinin HA 17, tetradecanoyl-phorbolacetate, antiserum to MOLT-4 lymphoblasts, antiserum to B411-4 lymphoblasts, antiserum to human embryo lung fibroblasts, and antiserum to HeLa cells infected with Herpes simplex virus. Lymphocyte responses to phytohemagglutinin P were potentiated by incorporation into the solid cultures of red blood cells of their membrane preparations suggesting that membrane-membrane interactions, either directly, or through soluble mediators are likely to be the basis of cell cooperation in this system. In solid cultures, phytohemagglutinin P, phytohemagglutinin P plus red blood cells, phytohemagglutinin HA 17, tetradecanoyl-phorbol-acetate and antiserum to MOLT-4 lymphoblasts were found to stimulate mainly thymus-dependent lymphocytes, whereas antiserum to Hela cells infected with Herpes simplex virus stimulated mainly non-thymus-dependent lymphocytes. Antiserum to B411-4 lymphoblasts stimulated both thymus-dependent and non-thymus dependent lymphocytes.

B-Lymphocytes↗

Paul-Bunnell antigen in lymphoma and leukemia spleens.

Lymphoid cells obtained from spleens of patients with lymphomas or leukemias were studied for the presence of heterophile (Paul-Bunnell (P-B)) antigen. A mixed agglutination (MA) test was established utilizing monolayers of cells attached to poly-L-lysine-coated wells of plastic U plates. After incubation of the monolayers with infectious mononeucleosis (IM) sera, indicator cells, sheep, or trypsinized bovine erythrocytes were added. The results were assessed according to sedimentation patterns of the indicator cells on the monolayers. Positive MA reactions were shown to be due to specific binding of P-B antibodies to the corresponding antigens on the spleen cells. Positive results were obtained with 15 of 37 spleens from patients with Hodgkin's disease, 5 of 8 lymphoma spleens, 4 of 15 chronic myelocytic leukemia spleens and 2 of 4 chronic lymphocytic leukemia spleens. Only 2 of 25 spleens from patients with various other diseases and 1 of 26 apparently normal thymus specimens gave positive results. This study confirmed demonstration of P-B antigen in lymphoma and leukemia by means of absorption experiments, which was reported previously.

Agglutination Tests↗

Fetal and neonatal fatality in rat hybrids from mothers stimulated with parental skin.

A breeding experiment was conducted in which MAXX female rats were mated with BN male rats. These two strains of inbred rats are identical for AgB antigens and differ only in antigens governed by minor histocompatibility loci. MAXX females, which were exposed before pregnancies to four BN skin grafts, delivered 117 offspring of which 28 (23.9%) were stillborn and 10 (8.5%) dead within 24 hr of birth. In contrast, of 126 offspring in control groups, only one was stillborn and one dead within 24 hr. In BN-grafted MAXX females, placentas were partially necrotic with marked polymorphonuclear reaction, which could account for stillbirths or the newborn deaths shortly after birth. The stillborn fetuses had grossly noticeable wrinkled skin. Histologically, the architecture of the epidermis was disturbed. The dermis was edematous and contained occasional mononuclear cells.

Animals↗