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Biomedical subjects

B Kupfer

Publications and source records attributed to B Kupfer.

31 records · Page 2Linked to original sources

Placental isoferritin as a physiological downregulator of cellular immunoreactivity during pregnancy.

CM-H-9 monoclonal antibody specific for placental isoferritin (PLF) was used to quantify PLF in the serum and on peripheral blood lymphocytes derived from term delivery women and healthy controls. It was found that the mean level of PLF in maternal sera was 50.4 +/- 50.1 U/ml, whereas in normal adults the mean serum PLF level was very low (4.5 +/- 7.7 U/ml). Furthermore, term mothers exhibited a sub-population of peripheral blood lymphocytes (PBL) which stained positively with CM-H-9 MoAb (mean 11.6 +/- 7.8%). Such lymphocytes were scarce in normal non-pregnant women (mean 0.8 +/- 1.2%). The effect of PLF on lymphocyte transformation in MLC was studied in mixed lymphocyte cultures of maternal-newborn and normal non-related PBL controls. It was found that placental isoferritin was immunosuppressive in comparison to normal adult ferritin. The suppressive effect was significantly higher in maternal-newborn MLC compared to normal adult controls. Furthermore, it was found that PLF which is present in maternal serum has an immunosuppressive activity since, its removal on CM-H-9 MoAb affinity column abrogated this effect. The results of this study suggest that both PLF and PLF binding lymphocytes play a role in the development of immunosuppression during pregnancy. Therefore the lack of one of the factors may result in diminished immunosuppression or in fetal rejection.

Female↗

Preparation and characterization of monoclonal antibodies specific to placenta ferritin.

Ferritins are a group of isomeric proteins which function as the major iron-storage protein of mammalian tissues. Some of the isoferritins have low isoelectric points, and are found in placenta and in malignant tissues and have therefore been termed carcinofetal ferritins. With the use of hybridoma technology, monoclonal antibodies (McAbs) specific to human placenta ferritin(s) were produced in order to characterize the heterogeneity of the molecule and to answer the question whether a specific antigenic determinant is associated with placenta and/or carcinofetal ferritin(s). Two McAbs designated H-9 and G-8 were developed. McAb H-9 bound specifically and exclusively to the ferritin isolated from human placenta, whereas G-8 McAb bound to placenta ferritin and cross-reacted with ferritins isolated from human spleen and liver. No cross-reaction was observed between H-9 and G-8 reactive determinants. It was found further that the two antigenic determinants - the one recognized by G-8 and that recognized by H-9 McAbs - are molecularly associated on placenta ferritin. The results of this study led us to term the G-8 a 'common' ferritin antigenic determinant and H-9 a 'private' embryonic ferritin determinant.

Animals↗

Treatment of patients with transitional cell carcinoma of the urinary bladder with intravesical poly I: poly C effects on natural killer function.

Considerable interest has been focused on the use of interferon (IFN) and IFN-inducers as antineoplastic agents in humans. The current report will focus on the effect of intravesical administration of Poly I: Poly C on NK activity in patients with TCC of the urinary bladder. NK cytotoxicity was measured in 14 patients with primary TCC, 8 patients received Poly I: Poly C and 5 other patients received intravesical thiotepa. Blood samples were obtained prior to and 48 h following each drug treatment. A variation in the initial NK level determined prior to treatment was observed in the different TCC patients: 5 patients treated with Poly I: Poly C and 5 patients treated with thiotepa exhibited low NK activity prior to treatment, whereas the other 3 patients who were treated with Poly I: Poly C had high initial NK levels. Following drug treatment it was shown that a significant elevation in the NK cytotoxicity was only observed in patients treated by intravesical Poly I: Poly C who had low NK activity prior to treatment. No such effect was observed in patients treated with thiotepa or in patients treated with Poly I: Poly C who exhibited a high NK activity prior to treatment.

Adult↗

Ferritin-bearing lymphocytes in the diagnosis of breast cancer.

Four hundred forty-seven women attending a breast clinic because of either suspicious lesions, anxiety about breast cancer, follow-up after the removal of a benign breast lesion, or a family history of breast cancer had a routine test for percentage of ferritin-bearing lymphocytes ( FBL ) in their peripheral blood. Among patients who received surgery following physical examination in the clinic and/or mammography, the test was positive in 40 of the 45 (89%) with Stage I;II carcinoma, 3 of 3 with Stage IV carcinoma, and only in 29 of the 97 (37%) with benign breast disease. The possible reasons for the poorer detection rate in Stage III carcinoma are discussed. The test, however, identified 2 cases of Stage I carcinoma, 1 of breast lymphoma, and 12 with premalignant lesions in those who were found normal on physical examination and mammography. Ferritin-bearing lymphocyte results tended to become negative after surgical removal of the lesion, and became positive on recurrence of the tumor and appearance of metastases. The detection rate was maximized by combining the FBL test with the clinical modes of detection.

Adult↗

Two T lymphocyte subpopulations isolated from human peripheral blood following "in vitro" treatment with adenosine.

Incubation of human peripheral blood lymphocytes (PBL) with adenosine resulted in a decrease in the level of E-rosette forming cells (ERFC). Isolated ERFC rerosetted with sheep erythrocytes in the presence of adenosine yielded two T lymphocyte subpopulations: a major one, rosetting or "E(R)" and a minor one, non-rosetting or "E(S)" T cells. Characterization of the two isolated subpopulations revealed that both E(R) and E(S) cells were positive for human T lymphocyte antigen. However, in contrast to E(R) cells, E(S) cells had low rosetting capacity, high spontaneous thymidine incorporation and low PHA proliferative response.

Adenine↗

De novo synthesis of purine nucleotides and metabolic availability of phosphoribosylpyrophosphate in leukemic leukocytes.

Among normal peripheral blood leukocytes, lymphocytes were found to contain most of the de novo purine synthesizing capacity. The rate of purine synthesis de novo was accelerated in leukocytes from patients with acute and chronic myelocytic leukemias, chronic monocytic leukemia, myelofibrosis and plasma cell leukemia, but was normal in most patients with chronic lymphocytic leukemia. The rate of de novo purine synthesis exhibited positive correlation with the percentage of immature cells in the leukocyte population. The metabolic availability of phosphoribosylpyrophosphate (PRPP) exhibited positive correlation with the state of de novo purine synthesis. These finding suggest that the accelerated rate of de novo purine synthesis and the increased metabolic availability of PRPP are characteristic properties of the immature leukemic granulocyte.

Humans↗

Immunodiagnostic test for the early detection of carcinoma of the breast.

A cytotoxic assay for the identification of circulating lymphocytes bearing surface ferritin was performed on 100 patients with malignant disease of the breast and in 50 healthy women. Forty-five patients were found to have a subpopulation of ferritin bearing lymphocytes, and all of them proved to have Stages I and II carcinoma of the breast. No such lymphocytes were identified in normal women, and in the remaining 55 patients, 33 had benign disease of the breast, 20 had Stage III carcinoma of the breast and two had Stages I and II carc-noma of the breast. It appears that this immunodiagnostic test may provide an additional tool for the early detection of carcinoma of the breast and may have a prognostic implication.

Breast Neoplasms↗

De novo synthesis of purine nucleotides in human peripheral blood leukocytes. Excessive activity of the pathway in hypoxanthine-guanine phosphoribosyltransferase deficiency.

Human peripheral blood leukocytes were studied for the presence and the regulatory properties of the pathway of de novo synthesis of purine nucleotides. The cells were found to incorporate the labeled precursors formate and glycine into purines. The rate of [14C]-formate incorporation was decreased by several compounds known to inhibit purine synthesis by affecting the activity by glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase, the first committed enzyme in the pathway, either through decreasing the availability of PRPP, a substrate for this enzyme, or through exerting inhibition on this enzyme. PRPP availability in the leukocyte was found to be limiting for purine synthesis. Increased PRPP availability resulting from activation of PRPP synthetase by increasing inorganic phosphate (Pi) concentration caused acceleration of purine synthesis. On the other hand, no clear-cut evidence was obtained for the availability of ribose-5-phosphate in the leukocyte being rate limiting at physiological extracellular Pi concentration for PRPP generation, and thus for purine synthesis. However, the addition of methylene blue, which accelerates the oxidative pentose shunt that produces ribose-5-phosphate, resulted in acceleration of PRPP generation and of purine synthesis only when PRPP synthetase was largely activated at high Pi concentration. These results may be taken to suggest that ribose-5-phosphate availability is indeed not limiting for PRPP generation under physiological conditions. Purine synthesis de novo was accelerated more than 13-fold in the leukocytes of two gouty patients affected with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase, but was normal in the leukocytes of an obligate heterozygote for this enzyme abnormality. The results domonstrate in peripheral human leukocytes the presence of the complete pathway of de novo synthesis of purine nucleotides and the manifestation in these cells of the biochemical consequences of hypoxanthine-guanine phosphoribosyltransferase deficiency, i.e., increased availability of PRPP and acceleration of purine synthesis de novo. The results indicate the usefulness of leukocytes as a model tissue for the study of purine metabolism in man.

Amidophosphoribosyltransferase↗

Suppressor cel activity of ferritin-bearing lymphocytes in patients with breast cancer.

In patients with early stages (I, II) of breast cancer we identified a subset of circulating lymphocytes that carry ferritin on their surface. No such lymphocytes were identified in normal women nor in women with benign breast disease. These cells did not form spontaneous rosettes with sheep red blood cells. Further studies revealed that in vitro treatment of the patients' lymphocytes with levamisole resulted n the removal of the surface ferritin and in an increase in the reactivity of the lymphocytes in mixed lymphocyte culture (MLC). Separation of the ferritin-positive lymphocytes from the E-rosetting T cells resulted in an increased reactivity of the patients' T cells in MLC. Readdition of the fraction containing the ferritin-positive cells to a mixed lymphocyte culture resulted in a decrease in the proliferative response of the patients' T lymphocytes. It is suggested that the ferritin-positive lymphocytes in breast cancer patients represent an active suppressor cell subset.

Breast Neoplasms↗