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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 433 records · Page 24Linked to original sources

Expression of H-2b alloantigens in a variant of a Moloney virus-induced YAC (H-2a) lymphoma.

Splenocytes of A(H-2a), BALB/c(H-2d) and C57BL/6(H-2b) mice that were sensitized against several allogeneic normal lymphocytes and lymphoma cells in mixed lymphocyte cultures (MLC) and mixed lymphocyte-tumor cell cultures (MLTC) exhibited the expected cell-mediated cytotoxic responses against normal and tumor cells carrying the relevant alloantigens. In contrast, strong cytotoxic reactivity cross-reactive with C57BL/6 target cells was observed when a variant of YAC lymphoma (YAC-b) of strain A mice were employed either as sensitizers or as targets. Furthermore, this 'unpredicted' cross-reactivity was also obtained with syngeneic responder splenocytes sensitized to YAC-b cells. The possibility that the nonspecific cytotoxicity was caused by activation of natural killer (NK) cells in the culture was excluded by the finding that the cytotoxic capability of sensitized effector cells was greatly diminished by treatment with anti-Thy 1.2 serum and complement. Serologic analysis with anti-H-2 alloantisera revealed that the YAC-b tumor line, but not the parental YAC lymphoma, carried H-2b alloantigens. It is concluded that the 'unpredicted' cytotoxic responses here observed is a result of conventional antigen recognition and of specific sensitization to alien H-2b components expressed on the YAC-b subline.

Animals↗

Effects of parathyroidectomy and hemigastrectomy on exocrine pancreatic secretion on dogs.

The effects of parathyroidectomy on secretory functions of the pancreas were studied in a group of dogs with previous hemigastrectomy. Free flow of pancreatic juice was obtained by direct cannulation of the main pancreatic duct. A gastric fistula prevented the entry of gastric acid into the duodenum. Parathyroidectomy caused a significant decrease in the secretin-induced volume and bicarbonate secretion. Pentagastrin administration produced a slight increase in volume and bicarbonate secretion which remained below preparathyroidectomy levels. These results were not dependent on calcium blood levels and did not change after calcium administration to the hypocalcemic-parathyroidectomy dog. It is suggested that parathyroid hormone effect on pancreatic secretion is not mediated via gastrin but due at least in part to direct action on the parenchyma.

Animals↗

Hydrodynamic and rejection properties of a coil dialyzer.

Compliance of coil dialyzers follows a linear dependence on pressure when measured in saline; compliance measurements with non-wetting fluids are inappropriate and underestimate the blood compartment expansion experienced with pressure. The arithmetic mean of inlet and outlet pressures can be used to predict ultrafiltration rate independent of venous outlet pressure, and blood compartment volume varies both with inlet pressure and blood flow. The rejection of carbohydrate marker solutes increases from about 10% for 1,200 Daltons to 100% for 12,000 Dalton species.

Compliance↗

Tumor biopsy cells participating in systems in which cytotoxicity of lymphocytes is generated. Autologous and allogeneic studies.

Freshly separated tumor cells from sarcomas and carcinomas were used in various roles in lymphocyte-target cell interaction assays. They were poorer allogeneic stimulators than lymphocytes. They were however good allotargets for the cytotoxicity generated in mixed lymphocyte cultures. They were also killed as third party targets by lymphocytes activated in MLC. In a proportion of experiments, lymphocytes activated in MLC killed autologous tumor cells. Autotumor killer effect was generated in the majority of mixed cultures containing lymphocytes and tumor biopsy cells from the same individual. Generation of cytotoxicity against K562 was a good measure of lymphocyte activation and could be used as a sensitive indicator for the occurrence of the recognition step in the mixed cultures. We propose that for the search of lymphocytes with specific receptors, activation is a more reliable parameter than specific cytotoxicity since the latter function is also influenced by the sensitivity of the target. The results confirmed that patients with carcinomas and sarcomas possess autotumor-reactive lymphocytes. These can be activated for cytotoxicity by in vitro confrontation with the tumor cells and occasionally through stimulation which is unrelated to the tumor cells.

Adolescent↗

EBV infection of mitogen-stimulated human B lymphocytes.

B lymphocytes from human blood were treated with the mitogen Protein A (Staph, aureus), which induces DNA synthesis in, as well as differeniation of, the B lymphocytes. The cells were subsequently exposed to Epstein-Barr virus (EBV). EBV-infected and mitogen-stimulated cells were detected simultaneously, by using a combination of immunofluorescence (for EBNA) and autoradiography (for DNA-synthesis). In the initial phase (1-2 days) after addition of the mitogen, stimulated cells were as susceptible to infection as resting cells. Thereafter, their susceptibility decreased. This suggests that, although initiation of DNA-synthesis does not seem to limit sensitivity to the viral infection, differentiation of the B cells might do so. The intensity and pattern of EBNA-staining in prestimulated cells different from that of the controls.

Autoradiography↗

Reduced humoral and cellular cytotoxic sensitivity in histocompatibility variants of the YAC (Moloney) lymphoma.

Previously we have reported that two sublines of the YAC lymphoma selected for reduced expression of H-2a and Moloney-virus determined cell-surface (MCSA) antigens are, in contrast to YAC, allotransplantable in H-2-incompatible recipients, and resistant to rejection by preimmunized semisyngeneic hosts. A third YAC variant with reduced MCSA but unchanged H-2-antigen expression, was not allotransplantable and showed only a slight decrease in its immunosensitivity in preimmunized semisyngeneic hosts in vivo. This suggested that H-2-antigen expression may be more important than MCSA expression for recognition and rejection by semisyngeneic mice. We have not tested the sublines expressing low H-2a for their in vitro sensitivity to humoral and cell-mediated lysis. - The variants were more resistant than YAC to complement lysis by anti-H-2a , anit-MCSA, anti-Thy 1.2 and antispecies sera. Absorption tests with antispecies serum indicated that the decreased cytolytic sensitivity of the variants was not related to the concentration of the relevant antigens, which was similar to that of the original YAC tumor. As expected from the low amount of H-2a the variants showed a decreased sensitivity to the killing effect of allogeneic cytotoxic T lymphocytes (CTL). They were also lysed to a lesser extent than YAC by semisyngeneic CTL, probably directed against virally determined antigens. However, they were also less sensitive to lysis by natural killer (NK) cells, although NK lysis is probably unrelated to MHC expression. In conclusion, our selection for reduced H-2-expression appears to have resulted in the isolation of variants with a generally increased resistance to various humoral and cell-mediated lytic functions.

Animals↗

Further observations on sleep abnormalities in Kleine-Levin syndrome: abnormal breathing pattern during sleep.

In two adolescent and two adult patients with Kleine-Levin syndrome, polygraphic sleep recording performed during somnolent and non-somnolent periods revealed various forms of abnormal breathing patterns during sleep. These included periodic breathing and hypopnoeic episodes associated with brief arousals and, in one adult patient, a full blown sleep apnoea syndrome. It is suggested that abnormal breathing in sleep in this syndrome may result from central hypoexcitability.

Adolescent↗

Use of cryopreserved lymphocytes for the indirect leukocyte migration inhibition assay.

Production of leukocyte migration inhibitory factor (LIF) by fresh and cryopreserved lymphocytes from the same donors was detected by indirect leukocyte migration inhibition (LMI) assay. The same results were obtained when fresh and frozen lymphocytes were tested in parallel. This indicates that cryopreservation does not impair the ability of lymphocytes to produce LIF.

Freezing↗

T-cell response to B-cells and Epstein-Barr virus antigens in infectious mononucleosis.

After Epstein-Barr virus (EBV) infection in vivo, B-cells with latent virus infection persist indefinitely through life. These cells grow in vitro on explanation and can be established as immortal B-cell lines. To reconcile the unlimited growth potential in vitro with the maintenance of a low proportion of B-cells infected by EBV in vivo, a strict in vivo control mechanism has to be postulated. Certain aspects of this control are apparent when the primary infection is followed by infectious mononucleosis. This is characterized by lymphocytosis and the presence of activated T-cells. The T-cell proliferation is probably the manifestation of the immune response against EBV antigens. However, the reaction of T-cells upon encounter of B-blasts is also likely to contribute to the events. At present, it is difficult to detect an EBV-specific component in the action of the T-cells in the acute phase of mononucleosis exerted on B-cells. However, for the clinical course of the disease the activation of T-cells is important. The activated T-cells may control and also eliminate the B-cells infected by EBV. In addition to the immunity which develops during the disease, th immunoregulatory mechanism is likely to have a role in the inhibition of B-cell proliferation.

Antigens, Viral↗

Activated T cells in the synovial fluid of arthritic patients. II. In vitro activation of the autologous blood lymphocytes.

Lymphocytes isolated from the synovial fluid of arthritic patients were shown to express characteristics of immunoactivated T cells, such as the formation of stable E rosettes and natural attachment to normal and malignant cells. During 5 days incubation in autologous serum, the synovial T cells reverted to resting state. If, however, the synovial serum was present in the culture, the activated state was maintained. The blood lymphocytes of these patients did not have the markers of activation. When blood lymphocytes were mixed in vitro with the autologous synovial T cells, a proportion of them acquired the capacity to form stable E rosettes and to express natural attachment. Synovial polymorphonuclear cells or synovial serum were without effect on the blood lymphocytes. This phenomenon may represent an in vivo mechanism for the perpetuation of the cellular immune reactivity in the joint cavity.

Arthritis, Rheumatoid↗

Middle molecule definition in terms of membrane permeability.

The term "Middle Molecules" originated as an operational definition for metabolites whose removal rate in the dialyzers of the 1970s was limited principally by the devices then used. Improvements in both the device designs and membrane performance require that we reexamine the definition. This discussion presents the relationship between membrane properties and operating conditions so that a general prediction can be made for metabolite clearance using either dialysis or hemofiltration. The current theories of solute/solvent coupling during membrane transport require that the designer and user consider not only the intrinsic membrane properties, but also the ultrafiltration velocity applied during therapy. This is particularly important in the use of hemofiltration, but may also be significant when high ultrafiltration rate dialyzers are employed. To provide a working definition of middle molecules, we reference the transport of solutes of increasing hydrodynamic radius to the transport of urea. Data for a series of membranes used in current and experimental devices will be presented.

Glomerular Filtration Rate↗