Gertrude Henle

Clinical and laboratory evaluation of cytomegalovirus-induced mononucleosis in previously healthy individuals: Report of 82 cases

The present report describes the clinical and laboratory profile of 82 previously healthy individuals who developed cytomegalovirus (CMV)-induced mononucleosis. Many of these patients posed initial diagnostic problems and were hospitalized with diagnoses such as fever of undetermined origin, active viral hepatitis, acute leukemia, probable systemic lupus erythematosus, autoimmune hemolytic anemia, and severe pancytopenia. These patients underwent a variety of diagnostic biopsies, including liver biopsies (6) and bone marrow aspirations (9). Four patients had exploratory laparotomies, 1 for a ruptured spleen, and another had a splenectomy following an erroneous initial diagnosis of agnogenic myeloid metaplasia. There was no apparent clinical response to a short course of steroid therapy in 3 of 5 cases and acyclovir in another. The vast majority of these patients demonstrated infectious mononucleosis-type reactive blood smears, negative heterophil antibody studies, mildly or moderately elevated aspartate aminotransferase activity, and evidence for subclinical hemolysis on serial specimens. The peak serum bilirubin levels were above 2.0 mg/dl in only 2 of 71 cases tested, both of the latter patients having significant hemolysis (hemoglobin values 8.6-9.3 g/dl). The CMV-IgM test had a high sensitivity for detection of CMV macroglobulins (positive in 81 of 82 cases). In contrast, complement-fixing antibodies to CMV showed diagnostic four-fold titer changes in only 39/82 cases (47.6%). Despite its great sensitivity, the CMV-IgM test is limited by a one-way crossreaction of acute Epstein-Barr virus (EBV)-IM sera and spurious positive reactions in some sera due to the presence of rheumatoid factors. Based on EBV-specific serologic studies, the 82 patients with CMV-IM could be divided into 4 groups: 3 patients without antibodies to EBV; 2) 69 patients with uncomplicated serologic data indicative of long-past EBV infections; (3) 6 patients with unusual antibody profiles, e.g., anti-D responses; and (4) 5 patients, including 1 originally susceptible to EBV, with apparent dual CMV/EBV infections. At the conclusion of our study, final diagnoses and initial hematologic data were correlated in 750 cases in which CMV macroglobulins were searched for. The vast majority of patients with active CMV infections initially demonstrated either markedly or moderately reactive peripheral blood smears. These data support our impression that diagnostic tests for CMV, as well as for EBV, are seldom indicated in symptomatic previously healthy patients whose blood smears during the acute phase (first several weeks) of their illnesses are either nonreactive or minimally reactive.

Immunology of Epstein—Barr Virus

The Epstein-Barr virus (EBV) was initially detected by electron microscopy in a small percentage of cells cultured from Burkitt lymphomas (BL), the most frequent malignancy of African Children (M.A. Epstein et al., 1964). This tumor had become a special target for virologists because epidemiological observations made in endemic regions pointed to participation of an infectious agent either directly or as a cofactor in its development (cf. Burkitt and Wright, 1970). Despite this background, the virus found in the tumor cells was considered by most virologists to be a harmless passenger because it belonged morphologically to the herpes group of viruses and none of its members had as yet been shown to be potentially oncogenic. The fact that it could not be transmitted to any routine cell cultures, chick embryos, or experimental animals suggested that it was not one of the then known three human herpesviruses (herpes simplex, Cytomegalovirus, and varicella virus) and thus provided the first clue that it was a previously unknown agent (M.A. Epstein et al., 1965).

Respiration and glycolysis of human cells grown in tissue culture

Abstract The respiration and glycolysis of nine human cell lines grown in continuous tissue culture have been examined; 5 derived from normal and 4 from malignant tissues. In addition, 2 sublines of one strain were studied which were persistently infected with mumps and Newcastle disease viruses. The general metabolic patterns of respiration, anaerobic glycolysis, and aerobic glycolysis were similar for all the uninfected cell lines. The observed metabolic values appear similar to those reported for slices of malignant tissues. It cannot be concluded on this basis whether all the cells studied are of a “malignant variety” or whether all cells established in continuous tissue culture develop a metabolic behavior similar to that of cancer tissue. Metabolic measurements on the persistently infected lines revealed no significant changes in respiration. However, the cultures carrying Newcastle disease virus exhibited a marked increase in aerobic glycolysis. Although the cell lines fall into two groups on the basis of their viral spectra and morphology, no outstanding differences were noted in the metabolic properties measured.

XX T cells and XY B cells in two patients with severe combined immune deficiency

Immunologic evaluation of two unrelated male infants with clinical and laboratory evidence of severe combined immunodeficiency (SCID) revealed T cells with a mature phenotype in the peripheral circulation of both patients although both had biopsy evidence of thymic alymphoplasia. Both had a normal number of T cells with a cytotoxic/suppressor surface marker (OKT8) but very few T helper cells (OKT4). Lymphocyte stimulation with the mitogens PHA, Con A, and pokeweed or with allogeneic cells resulted in no proliferation. However, addition of T cell growth factor, plus the phorbol ester TPA, to lymphocytes cultured with the T cell mitogen PHA did result in some proliferation of T cells. In both cases these T cells demonstrated an XX female karyotype and were probably of maternal origin. In contrast, proliferating B cells stimulated with Epstein-Barr virus demonstrated a normal XY male karyotype. The possibility that severe combined immune deficiency in these patients was the result of graft-versus-host disease induced by maternal lymphocytes is discussed.

Effect of Gramicidin on Metabolism of Bovine Spermatozoa.

Summary Crude and purified gramicidin after initial stimulation inhibits the oxygen consumption of bovine spermatozoa completely in Ringer phosphate of acid pH and renders the cells immobile. By the use of sufficiently small amounts only stimulation is observed during the period of the experiment. In alkaline phosphate buffer only the increase of oxygen consumption is noted. However, in Ringer bicarbonate medium of the same pH, the respiration again is greatly inhibited; aerobic as well as anaerobic glycolysis are depressed on the average 40% and the motility of the spermatozoa is markedly impaired. Tyrocidine, in the concentrations studied, caused a small reduction in the oxygen uptake and the glycolysis.

Evidence for the propagation of the virus of serum hepatitis in the chick embryo

Evidence has been presented which indicates that the virus of serum hepatitis (SH) has been carried through 15 passages in the amniotic cavity of the chick embryo. 1. Intramuscular injection of amniotic fluid of the 9th and 15th passage into volunteers induced hepatitis without jaundice in 4 out of 6 and 2 out of 5 individuals, respectively, after incubation periods in excess of 60 days. 2. Serum taken from one of the patients in the first group during the acute stage of illness, when given to additional 4 volunteers resulted in 3 cases of hepatitis with, and one without jaundice. Challenge of the volunteers of the 1st group with natural virus (icterogenic serum) 8 months after the primary injection led to a second attack of hepatitis in 2 of the individuals. One of these was the donor of the serum referred to under 2. Possible reasons for the absence of solid immunity after the 1st exposure have been discussed.