Biomedical subjects
Publications and source records attributed to R Glaser.
The space-dependent electric potential of erythrocyte membranes is determined on the basis of a mathematical model which takes into account the membrane surface charges of glycophorine A, spectrin and phosphatidyl serine. The calculations are performed by numerical integration of the nonlinear Poisson-Boltzmann-equation.
Temperature dependent sedimentation measurements of individual human erythrocytes showed an anomaly near 20 degrees C in physiological medium at pH 7,4 [2,3]. Results of investigations on the influence of procaine and cholesterol on the sedimentation behaviour are presented. The results suggest a correlation to the thermotropic properties of membrane lipids.
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Four lymphoid cell lines, presumably recent derivatives from non-neoplastic human tonsils, were identified in actuality as established Burkitt lymphoma and lymphoblastoid cell lines (LCL) when tested by chromosome banding and typing for HLA antigens. Additionally, the morphology, growth characteristics, tumorigenicity, expression of Epstein-Barr virus antigens and surface membrane immunoglobulins (SmIg) of the four lymphoid cell lines confirmed the correct identifications. In determining the possibility of cross contamination, the most reliable criteria for the identification of lymphoid cell lines were found to be HLA antigenic profile, karyotype, cellular morphology, and growth characteristics.
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Sera from healthy individuals and patients with infectious mononucleosis, Burkitt lymphoma, nasopharyngeal carcinoma, or other malignancies were examined for their capacity to neutralize Epstein-Barr virus (EBV)-induced DNase activity. Sera were found that neutralized the EBV DNase but not herpes simplex virus type 1 or type 2 DNases, and vice versa. Sera from 46 of the 49 patients with nasopharyngeal carcinoma examined (94%) neutralized > 6 units of EBV DNase per ml of serum. In contrast, only 19% of 47 patients with Burkitt lymphoma, 12% of 183 patient with other malignancies, 4% of 58 patients with infectious mononucleosis, and none of 101 healthy individuals had such levels of neutralizing activity. The neutralizing factor was found in the IgG fraction derived from nasopharyngeal carcinoma sera. There was no correlation between the concentration of these antibodie and the titers of IgG ad IgA antibodies to the EBV capsid antigen, the early antigen complex, or the EBV-associated nuclear antigen.
Nasopharyngeal carcinomas (NPC) from 2 black patients and 1 Caucasian patient were positive for Epstein-Barr virus (EBV) DNA. Of the tumors, 2 were lymphoepitheliomas (undifferentiated NPC) and 1 was a moderately differentiated NPC. All 3 patients had high IgG titers against EBV early antigen and high IgG and IgA titers against virus capsid antigen (VCA). In one patient, the levels of anti-VCA IgA were different than those of anti-VCA IgG over the course of the disease. Our data support the association of EBV and NPC in North America.
With the use of Epstein-Barr virus (EBV), attempts were made to infect epithelial nasopharyngeal explant cell cultures prepared from nonmalignant human and squirrel monkey tissue. Explants were exposed to EBV from both HR-1 and B95-8 cells and examined for EBV-specific antigens by immunofluorescence and electron microscopy. Among the human specimens, no epithelial nasopharyngeal were found that could be infected with EBV. However, similar explants derived from squirrel monkey tissue were infected. The results were consistent with the hypothesis that EBV can infect at least certain explanted epithelial cells of the nasopharynx.
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Aggregation measurements of washed human erythrocytes were carried out in a NaCl-PBS solution under laminar shear conditions. An artificial aggregation was caused by decreased pH and reduced ionic strength, and characterized by the collision efficiency, e.m., the probability of a permanent aggregate formation. It was found that the aggregation increases reducing the ionic strength and decreasing the pH of the medium. Pretreatment with Amphothericin B did not change the aggregation. The results cannot be explained neither by the usual D.L.O.V. theory (force balance between electrostatic repulsion and attraction due to dispersion forces) nor by direct influence of the changed transmembrane potential. It is supposed that this type of aggregation involves reversible changes of the membrane and/or the surface structure.
It is well known that a pH shift of the outside medium from 5 to 9 produces a shape transformation of washed human red blood cells from stomatocytes to echinocytes in isotonic salt solutions. In addition, a stomatocytogenic effect is demonstrated here due to solutions of low ionic strength (below 70 mM). An analysis of the true cell state in these situations, proved by measurements of predicted volume changes, indicates a good correlation between transmembrane potential and cell shape. The fact that amphotericin B acts as echinocytogenic agent in low ionic strength medium at pH 7.4 but not at pH 5.1 underlines this explanation. Therefore, a transmembrane potential positive inside produces stomatocytes, slightly negative inside (below--10 mV), normocytes, and strongly negative, echinocytes. The temperature dependence of this process underlines the rigidity-pattern hypothesis of red blood cell shape (Glaser & Leitmannová, 1975, 1977).
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Epstein-Barr virus and cytomegalovirus have both been associated with Guillain-Barré syndrome after antibody investigations in several patients. In the teenage female patient in this present report, Guillain-Barré syndrome following infectious mononucleosis was associated with sero-conversion against Epstein-Barr virus but not cytomegalovirus. The findings are consistent with the hypothesis that Epstein-Barr virus might be an etiological agent for the Guillain-Barré syndrome and that infection with cytomegalovirus is not a requisite for the syndrome.
The importance and the extent of the inter-actions between herpes viruses and man is beginning to be understood. As more is learned about the natural histories of these viruses, it is becoming apparent that they have in common: Horizontal spread during childhood, often with subclinical infection. Latency in the host for many years, probably for life. Potential for reactivation at a later time. Host immune response maintained for life. Potential for oncogeneiss. A more thorough knowledge of the biochemistry and the biology of these viruses promises to be the foundation of more effective treatment and prevention.
We have used human-mouse somatic cell hybrid to study the association between the EBV genome and the cellular genome. Attempts were made to identify a specific human chromosome(s) with which the EBV genome is associated. Our data suggest that at least in the mouse fibroblast/Burkitt lymphoma hybrid combination studies, the EBV genome is not associated with any specific human chromosome.
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