Detection of Epstein-Barr virus in lymphoid tissues of patients with infectious mononucleosis by in situ hybridization.

Although the immunological response during infectious mononucleosis (IMN) has been studied in detail, little is known about the spread of Epstein-Barr virus (EBV) in lymphoid organs or the topographical distribution of the infected cells. In this study, EBV was detected in 11 lymph nodes, 4 tonsils, and 1 spleen of 16 patients with IMN. The predominant cell type positive for the EBV genome was identified as small lymphocytes localized chiefly within typical T areas, preferentially in perifollicular and interfollicular regions of the lymph node. A few endothelia of epithelioid venules were also found to be positive. Furthermore, a small number of sinus lining cells of lymph nodes exhibited labelling. Altogether, only a small number of cells, not exceeding 1 per cent of all cells, were infected with EBV. Our results show that only a small number of lymphocytes carry the EBV and that besides B lymphocytes, other cell constituents of lymphatic tissues are infected by EBV during IMN.

High-dose chemotherapy and autologous bone marrow transplantation in relapsing angioimmunoblastic lymphadenopathy with dysproteinemia (AILD).

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) or lymphogranulomatosis X is a lymphoproliferative disorder with a histological picture resembling that of reactive lesions but with frequent cytogenetic and molecular abnormalities characteristic of malignant T cell lymphoma. Clinically, the disease runs a fatal course in the majority of patients although occasional spontaneous remissions have been observed. Median survival approaches only 1 year even with the most effective treatment protocols implemented so far. Fewer than 20% of patients survive 5 years after diagnosis and cure seems exceedingly rare. High-dose chemotherapy (HDCT) followed by autologous bone marrow transplantation (ABMT) represents a promising new treatment modality for patients with advanced lymphoma conceivably including AILD. We report the first patient with relapsed AILD successfully treated by HDCT and ABMT. This 21-year-old male is alive and free of disease 27 months after ABMT with a Karnofsky score of 100%.

Remission of juvenile chronic myeloid leukemia following graft failure of an unrelated marrow transplant and autologous recovery of marrow function promoted by GM-CSF and IL-3.

The unusual course of a boy with juvenile chronic myeloid leukaemia is presented. After bone marrow transplantation (BMT) from an unrelated donor followed by graft failure and subsequent stimulation by rhu GM-CFC and II-3, this patient experienced complete recovery of autologous haematopoiesis. At 17 months post-BMT the patient was off any therapy with completely normal blood counts and no signs of disease.

Long term culture of nasal epithelial cells.

Cystic fibrosis (CF) basic research has been hampered by the lack of a suitable animal model and is therefore dependent on the availability of human tissue. To date, the basic defect remains unknown, however, over the last decade convincing data have been produced that link the defect to altered epithelial electrolyte transport. Moreover, recent results of DNA analysis could confirm that the putative CF gene product is indeed expressed in epithelial tissues. Unfortunately, epithelial cells are difficult to maintain in culture, especially transport-active epithelia tend to be short-lived. We have devised a simple method for the subculturing of nasal epithelium which has been shown to exhibit altered electrolyte transport in CF patients. Nasal epithelial cells were isolated from nasal polyps obtained at surgery by protease digestion. Subsequently, cells were plated in culture medium and irradiated mouse fibroblasts were added as a feeder layer after 48 h. After 5-15 d, epithelial cells could be subcultured without loosing their growth potential, and were continuously maintained in culture for up to 4 months. The cells were frozen in liquid nitrogen following standard methods. Growth could be reinstituted after thawing the epithelium. Subcultured and thawed cells were clearly characterized as of epithelial origin and distinguished from mesodermal cells by their reaction with antibodies against keratin, vimentin, and desmin.

Successful stimulation of autologous bone marrow recovery by GM-CSF and IL-3 after an unrelated donor BMT for juvenile CML complicated by graft failure.

We report the case of a boy with juvenile chronic myeloid leukemia (jCML), who after initial treatment with interferon alpha-2 (IFN) and hydroxyurea underwent bone marrow transplantation (BMT) from a matched unrelated donor complicated by graft failure. Subsequent stimulation of hematopoiesis by GM-CSF and IL-3 promoted autologous recovery. In contrast to the course of disease pre-BMT, the boy is now off any therapy remaining in complete remission more than 500 days after BMT.

The influence of the protease inhibitor aprotinin on tumor invasion of three cell lines in vitro.

The production of protease by malignant cells has been held responsible for invasion. The effect of aprotinin, a broad-spectrum protease inhibitor, on malignant invasion was examined histologically in organotypical cocultures of precultured embryonic chick heart fragments with two human melanoma cell lines and one virus-transformed fetal mouse carcass cell line. In the presence of 400 KIU/ml aprotinin, invasion was still permissive, while in the comparison with 0.1 microgram/ml vincristine, a microtubule and directional motility inhibitor and a well-documented anti-invasive agent, invasion was completely stopped. Aprotinin remained stable in the culture medium so that the presence of invasion cannot be explained by low drug concentration. It is concluded that aprotinin-sensitive proteases are not implicated in invasion in vitro in the cell types investigated, and that this in vitro technique deserves further interest for the study of protease inhibitors in the mechanism of invasion.

Metabolism and proliferation of L929 mouse fibroblasts cultured in the presence of sodium fluoride.

L 929 mouse fibroblasts were cultured as monolayers with different amounts of sodium fluoride, corresponding to those used therapeutically. Proliferation of the cells was inhibited in the logarithmic phase of cell growth. There was no change in the protein concentration in the cells, but the concentration of hydroxyproline containing substances in the cells increased while that of hexuronic acid containing substances decreased. The changes in proliferation and in the concentrations of hydroxyproline containing substances and hexuronic acid containing substances were statistically significant. Although the findings cannot be explained in detail it can be concluded that at therapeutic concentrations sodium fluoride has a definite action in contact with the fibroblast, the typical connective tissue cell. This dose dependant action corroborates clinical experience.