Marvin A. Lutzner

Xeroderma pigmentosum is a hereditary disease clinically manifested primarily on sun-exposed skin, which develops abnormal pigmentation and malignant tumors. Mental retardation, areflexia, and other neurological abnormalities are seen in some patients. Only one biochemical defect has been found: cells from various tissues repair ultraviolet-induced deoxyribonucleic acid (DNA) damage slowly, compared with normal cells. Cell fusion studies show that genetic complementation can occur between fibroblasts from certain pairs of patients, thus overcoming the DNA-repair defect in each member of the pair and demonstrating the heterogeneity of the genetic lesion. The patients at NIH who have slow DNA repair comprise four distinct complementation groups, indicating that at least four mutations can cause defective DNA repair.

Substantial evidence has accumulated to indicate not only that mycosis fungoides and the Sézary syndrome are closely related malignancies, but to suggest that they are part of a larger spectrum of cutaneous lymphomas. The neoplastic cells of these disorders have membrane features of thymus-derived (T) lymphocytes, a characteristic tissue distribution (skin infiltration, marrow sparing, localization in T-cell regions of lymphoid tissue), and distinctive morphology. For these reasons, we suggest that these lymphoproliferative disorders be grouped together as "cutaneous T-cell lymphomas". The anergy noted in patients of this group with leukemia probably is related to both decreased percentages of normal T cells and presence in the serum of macrophage migration inhibitory activity. Leukapheresis has been particularly effective in the management of selected patients. The homogeneous T-cell populations in the patients with leukemia also provide important opportunities to study many aspects of lymphocyte physiology that are of broad biologic significance.

The Sézary syndrome is a frequently lethal disease characterized by circulating malignant cells of thymus-derived (T)-cell origin. The capacity of circulating malignant lymphocytes from patients with this syndrome to synthesize immunoglobulins and to function as helper or suppressor cells regulating immunoglobulin synthesis by bone marrow-derived (B) lymphocytes was determined. Peripheral blood lymphocytes from normal individuals had geometric mean immunoglobulin synthetic rates of 4,910 ng for IgM, 1,270 ng for IgA, and 1,625 ng for IgG per 2 X 10(6) cells in culture with pokeweed mitogen for 7 days. Purified normal B cells had geometric mean synthetic rates of 198 ng for IgM, 145 ng for IgA, and 102 ng for IgG. Leukemic cells from patients with the Sézary syndrome produced essentially no immunoglobulins. Adding normal T cells to normal B cells restored their immunoglobin producing capacity. Leukemic cells from four of five patients tested had a similar capacity to help immunoglobulin synthesis by purified normal B cells. Additionally, Sézary cells from one patient studied induced a nearly 10-fold increase in IgA synthesis by lymphocytes from a child with ataxia telangiectasia and selective IgA deficiency. Furthermore, these Sézary cells induced more than a 500-fold increase in IgG and IgA synthesis by lymphocytes from a child with Nezelof's syndrome. When Sézary cells were added to normal unfractionated lymphocytes, they did not suppress immunoglobulin biosynthesis. In addition, unlike the situation observed when large numbers of normal T cells were added to purified B cells, there was no depression of immunoglobulin synthesis at very high malignant T-cell to B-cell ratios. These data support the view that Sézary T cells do not express suppressor cell activity. The results presented in this paper suggest that neoplastic lymphocytes from the majority of patients with the Sézary syndrome originate from a subset of T cells programmed exclusively for helper-like interactions with B cells in their production of immunoglobulin molecules.

The Fifth International Congress for Electron Microscopy was convened in Philadelphia on Aug. 29, 1962. This was the 31st anniversary of the construction of the first working electron microscope by M. Knolls and E. Ruska and the 20th anniversary of the founding of the Electron Microscope Society of America. The large number of participants and papers attested to the logarithmic growth of interest in the electron microscope. Over 600 papers were presented on both biological and industrial topics, which have been published in book form. (<i>Electron Microscopy</i>, Volumes I and II, Academic Press). The papers on biology were arranged in sessions with such titles as: biological techniques, virus fine structure, virus reproduction, tumor viruses, experimental pathology, ultrastructure of microorganisms, plant cells, cell surfaces and functions, cytoplasmic organelles, intracellular membrane systems, motility mechanisms, extracellular matrices, nucleic acid and proteins and the nephron. In a report of such a large meeting one