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H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 379 records · Page 21Linked to original sources

Human anti-IgM iso-antibodies: detection of IgM allotypic markers.

IgG class antibodies against human IgM were detected in a human subject up to a titer of 1:1024 against 5 of a group of 23 monoclonal Waldenström macroglobulins. Inhibition studies confirmed at least one antigenic determinant shared by the 5 IgMs. The determinant was present on the mu chain but required tertiary structure for its full expression. Inhibition of the reaction between the antibodies to IgM and erythrocytes coated with 2 of the 5 IgMs was obtained at titers of 1:2 to 1:16 with 51.0% of 300 normal sera (85.2% of sera from 122 Caucasian, 26.1% of sera from 23 Negro, and 27.7% of sera from 155 Japanese individuals). This inhibition was independent of the serum IgM concentration. Family studies indicated that the determinant was inherited according to basic Mendelian laws and appears to be the first allotypic marker on human serum IgM. We have designated it Mm 1.

Antigen-Antibody Reactions↗

Localization of idiotypic antigenic determinants in the Fv region of murine myeloma protein MOPC-315.

Rabbit antisera were prepared against the idiotypic determinants of the mouse IgA myeloma protein-315, its purified heavy and light chains, and the Fv fragment comprising the variable region of both heavy and light chains. Agar diffusion demonstrated a line of identity between protein-315 and its Fv fragment against either homologous antiserum. Protein-315 and Fv fragment were labeled with (125)I and reacted with their anti-idiotypic antisera. Inhibition studies confirmed that the Fv fragment contained all the idiotypic specificities present in the intact protein. Fv was as effective as protein-315 on a weight basis in inhibiting the reaction between anti-idiotypic antiserum and protein-315. Protein-315 has high affinity for the 2,4-dinitrophenyl group, and such ligands can inhibit the reaction between protein-315 and its anti-idiotypic antibodies. Hapten inhibition was also obtained with the Fv fragment and its anti-idiotypic antiserum, implying that Fv contains an intact combining site. In this system with protein-315 the antigenic determinants expressed as idiotypic specificities are entirely within the variable region and are not influenced in their expression by the constant region. We therefore suggest that, in general, idiotypic determinants are antigenic determinants of the Fv protions of immunoglobulins.

Aminobenzoates↗

Erythrocyte catabolism by macrophages in vitro. The effect of hydrocortisone on erythrophagocytosis and on the induction of heme oxygenase.

Phagocytosis of erythrocytes was studied in vitro in an incubation system consisting of rat peritoneal macrophages and antibody-coated (59)Fe-labeled erythrocytes. The system was characterized in terms of the rate and magnitude of erythrophagocytosis, determined by the interiorization of the (59)Fe label. On incubation of 150 x 10(6) macrophages with 75 x 10(6) antibodycoated erythrocytes, erythrophagocytosis began within a few minutes and was essentially completed after 2 h when 50% of the offered red cells had been ingested by the macrophages. Heme oxygenase (HO) activity, which is very low in native macrophages, increased 4- to 10- fold in response to the ingested erythrocytes; this enzyme stimulation occurred with a delay of 3 h in relation to erythrophagocytosis. Actinomycin D or puromycin prevented the increase of HO activity without affecting erythrophagocytosis, which suggests that the enzyme stimulation was due to substrate-mediated enzyme induction. Hydrocortisone (HC) (0.1 mg/ml medium) dissociated erythrophagocytosis from HO induction, leaving the former unimpaired but completely suppressing the latter. The suppressive effect of HC on the enzyme induction was completely prevented by 5 mg glucose and 0.02 U insulin/ml of the medium. In macrophages engaged in erythrophagocytosis. HC also lowered glucose removal from the medium and reduced formation of (14)CO(2) from [1-(14)C]glucose. These results suggest that induction of HO in macrophages by the hemoglobin of ingested erythrocytes requires intact transport or metabolism of glucose. Glucose utilization appears to be impaired by HC, but is restored by additional glucose and insulin. The findings suggest that plasma steroid concentrations in the pharmacological range could reduce bilirubin formation in phagocytic cells in vivo without affecting the sequestration and degradation of erythrocytes. This provides a possible explanation for the observation that in patients with hepatogenous jaundice, steroids often lower the serum bilirubin level.

Animals↗

Thymus-derived rosette-forming cells in various human disease states: cancer, lymphoma, bacterial and viral infections, and other diseases.

Lymphocytes that bind in vitro to sheep erythrocytes in a rosette formation are thymus-derived. A modified technique that does not detect the total number of rosette-forming cells (RFC) was used to study normal subjects and various disease states. Of 100 healthy subjects, 95 had more than 15% RFC (mean 28.4+/-6.5%). We studied 104 patients with solid tumors, who were classified according to clinical status and stage of therapy. Of 19 newly diagnosed patients, 13 had less than 15% RFC. Of 44 untreated patients undergoing relapse, 32 had less than 15% RFC. In both categories, patients with metastases had fewer RFC than patients with localized disease. 11 patients were studied 2 wk after cessation of therapy; four of them showed less than 15% RFC. Only one of 30 patients in remission had less than 15% RFC. In seven patients followed for various periods of time, the numbers of RFC correlated generally with clinical status. 11 patients with chronic lymphatic leukemia had very low percentages of RFC. 21 of 21 patients with symptoms of viral upper respiratory diseases had less than 15% RFC. RFC returned to normal values between 5 days and 7 wk after disappearance of clinical symptoms. 20 patients with bacterial infections had normal numbers of RFC. Of 25 patients with miscellaneous nonimmunologically related diseases, two had low numbers of RFC. It appears that the percentage of RFC may be valuable in evaluating not only immunological defenses but also the status of patients with solid tumors, lymphomas, viral diseases and, perhaps, bacterial infections.

Adolescent↗