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Biomedical subjects

Z Fuks

Publications and source records attributed to Z Fuks.

At least 253 records · Page 14Linked to original sources

Prostaglandin E2 secretion by subsets of human peripheral blood monocytes.

The present study describes the secretion of prostaglandin E2 (PGE2) by various fractions of human peripheral blood monocytes, differing in their plastic adherence properties. PGE2 was found to be secreted only by phagocytic cells. Complete removal of the phagocytic monocytes, but no repeated adsorptions to a plastic surface, resulted in the abrogation of detectable PGE2 secretion. The monocyte population secreting PGE2 consisted of cells with different affinities to plastic surface. The loosely adherent phagocytic cells secreted more PGE2 than the strongly adherent phagocytic cells. The possible existence of monocyte subsets in human peripheral blood differing in their adherence property and PGE2 secretion is suggested.

Cell Adhesion↗

Binding, internalization, and degradation of insulin in vascular endothelial cells.

The interaction of insulin with the vascular endothelium was studied using bovine aortic endothelial cells in monolayer cultures. Confluent cell cultures exhibited specific binding of 125I-insulin to high- and low-affinity cell surface receptor sites. Binding was reversible, saturable, and accompanied by internalization and degradation of the bound hormone in a temperature- and time-dependent manner. Pre-exposure of the cultures to insulin resulted in a time-dependent reduction in the availability of cell surface receptors (downregulation). It is concluded that the occurrence of reversible insulin binding and of insulin degradation in endothelial cells supports the concept that the vascular endothelium compartment may regulate the level of insulin in the circulation.

Animals↗

Long-term enzyme replacement therapy in beta-glucuronidase--deficient mice by allogeneic bone marrow transplantation.

Enzyme replacement therapy was successfully accomplished in beta-Glu-deficient C3H/HeJ mice after transplantation of BM cells obtained from normal BALB/c donors. Marrow recipients were prepared for transplantation by fractionated TLI. Enzyme activity increased from 20.5 +/- 7.0 nmol/mg of protein per hour to 180 +/- 30.2 in the liver (p less than 0.001) and from 8.2 +/- 2.0 to 17.5 +/- 5.0 nmol/ml/hr in the plasma (p less than 0.05) at 50 days after marrow infusion. Normal enzyme activity was maintained in treated mice for at least 100 days after marrow transplantation, as documented by repeated liver biopsies and examination of plasma samples. The marrow donors and the recipients were fully histoincompatible. Both immunologic rejection of the marrow allograft and GVHD were prevented by the prior conditioning of the recipients with TLI, resulting in bilateral transplantation tolerance of host vs. graft and graft vs. host. The data suggest that allogeneic BM transplantation may provide a possible therapeutic approach for certain enzyme deficiency syndromes.

Animals↗

Comparison of the response to PHA and suppressor macrophage function in different age groups of cancer patients and healthy controls.

The mitogenic response of peripheral blood lymphocytes was examined in 37 healthy individuals and in 44 patients with various malignant neoplasms. Tested individuals were divided into three major age groups (20-40; 40-60; and over 60 years of age). There was a significant decrease in Phytohemagglutinin (PHA) response with age in the normal controls, but no significant change with age was observed in the cancer patients. Comparison between the various age groups of cancer patients and their corresponding normal controls did not reveal a significant difference in mitogenic response of the young and middle age groups. However, the older cancer patients responded significantly better compared with their corresponding older normal controls. The reduced responsiveness of older normal controls was partially explained by a high activity of suppressor macrophages observed in this group. Reduction of the proportion of phagocytic cells improved their response to PHA. On the other hand, the activity of suppressor macrophages in the older cancer patients was much less prominent. These observations emphasize the importance of appropriate age grouping when immune function tests in cancer patients are compared with those performed in normal individuals and suggest the possibility of higher mitogen responsiveness in certain age groups of cancer patients.

Adult↗

Antigen presentation and regulatory functions of human monocytes in the in vitro response of lymphocytes against purified protein derivative of tuberculin (PPD).

Monocyte functions in the primary and secondary proliferative responses of human lymphocytes against purified protein derivative of tuberculin (PPD) have been studied. By applying the antigens either directly to the responding cells or on antigen-treated autologous monocytes, it was possible to distinguish between two different monocyte functions: antigen presentation and regulation. Their helper function in lymphocyte proliferation was found in cell-free supernatants of autologous and allogeneic monocytes and was expressed better in the secondary rather than in the primary responses. The antigen-presenting function of monocytes, however, was found to be more substantial in the primary response of lymphocytes. These results suggest that macrophage dependency of certain immune functions should be considered in regard to the various functions of macrophages, since at least quantitative differences for each of the macrophage functions were found in the primary and secondary proliferative responses.

Adolescent↗

Characterization of human lymphocytes which proliferate "spontaneously" in vitro.

Human peripheral blood lymphocytes proliferate "spontaneously" in vitro following the reduction in the proportion of monocytes in culture. This cell proliferation, which takes place in the absence of any extrinsic antigenic stimulation, was found to reside in a small fraction of a non-T non-B cell population which was also Fc receptor-negative. Concomitant with the in vitro proliferation of the monocyte-depleted cells, an increase in the proportion of E rosette-forming cells was observed. Hence, in addition to the regulation of spontaneous proliferation of lymphocytes, it is suggested that monocytes may also be involved in the regulation of the proportion of T cells or in expression of the E-rosetting marker.

Bromodeoxyuridine↗

The isolation and purification of human peripheral blood monocytes in cell suspension.

A simple method for the isolation of human peripheral blood monocytes in cell suspension is described. The method is based on the adherence and detachment characteristics of monocytes during their in vitro cultivation and does not require any gradient centrifugation or modulating substances. The mean percentage of monocytes recovered from different donors was 81.9% (60-100%) of the original phagocytic cells found in the peripheral blood of the tested donors and the cell suspensions obtained consisted of more than 95% of monocytes. The monocytes isolated in suspensions show high activity in various monocyte functions tested.

Adolescent↗

Immunosuppression and organ transplantation tolerance using total lymphoid irradiation.

Total lymphoid irradiation (TLI) is a method which delivers irradiation daily in fractionated doses (200 rads) to lymphoid organs while shielding bones, lungs, and the majority of the gastrointestinal tract. TLI is lymphocytopenic in mice, rats, dogs, and humans, and both T cells and B cells are eliminated from the circulation. During the recovery phase in mice, B cells appear before Thy 1.2-bearing T cells, and TL-positive T cells are abundant in the spleen and lymph nodes. These T cells exhibit nonspecific suppressive activity on antibody production and cell-mediated immune responses. TLI permits establishment of specific and long-lasting tolerance to alloantigens. Permanent acceptance of allogeneic bone marrow cells without graft-versus-host disease was achieved in rats and dogs across major histocompatibility barriers. Recipients were tolerant to allografts of skin, hearts, and kidney from animals syngeneic to marrow donors or to organs from the marrow donor. This approach may be suitable for pancreas transplantation in diabetes.

Animals↗