Adaptive modification of saccadic eye movements.

Experiments are reported in which the target for a saccadic eye movement was displaced during the saccade. Subjects adapted to the displacement by altering the amplitudes of subsequent saccades to compensate for it. Analysis of kinematic details of the saccade trajectories revealed that the adaptation did not arise from a simple remapping of perceived target locations. Instead, the adaptation appeared to be accomplished by a change in the gain of the saccadic system. The gain change arose primarily from a change in the magnitude of the force pulse for the saccade, not a change in the duration of the pulse. These results have implications for the mechanisms that underlie saccades in normal situations. In particular, people can separately adjust the magnitudes and durations of the force pulses used to produce saccades.

Diagnostic and prognostic significance of Sézary cells in peripheral blood smears from patients with cutaneous T cell lymphoma.

Blood smears stained with Wright-Giemsa were obtained from 124 patients with pathologically confirmed cutaneous T cell lymphoma (CTCL), 70 patients with various other cutaneous disorders, and ten healthy adult volunteers. These were examined in a blinded fashion for atypical lymphocytes with cerebriform nuclei (CLs), which were characterized further according to cell diameter. CLs, comprising up to 15% of lymphocytes in smears, were observed in 20% of the patients with benign dermatitis. CLs, comprising up to 89% of lymphocytes in smears, were found in 22%, 30%, 50%, and 96% of patients with patch, plaque, tumor, and erythrodermic CTCL, respectively. Large-diameter CLs (15 to 20 micron) were observed only in smears from patients with CTCL. Total CL counts above 15 per 100 lymphocytes and/or the presence of large CLs occurred in 33 of 49 (67%) patients with erythrodermic disease and in only two patients with other skin manifestations. Blood smears obtained at the time of cytogenetic studies indicated that a total CL count above 15% was the smear criterion that correlated best with the demonstration of a chromosomally abnormal malignant clone in the blood. The presence of large CLs per se, although also predictive of a malignant clone, was less useful. Multivariate survival analysis showed that the duration of disease before the blood smear and the proportion of large CLs within the total CL population were the covariates that correlated most significantly with survival. We speculate that the reduced survival of patients with increased proportions of large CLs in smears reflects the presence of polyploid malignant lymphocytes in the blood.

Characterization of Epstein-Barr virus-carrying cell lines established from chronic lymphocytic leukemia.

Attempts were made to establish lymphoid cell lines from the cultured peripheral blood lymphocytes of six patients with chronic lymphocytic leukemia. In only one case was cell growth obtained following the addition of exogenous transforming Epstein-Barr virus, and those cell cultures proved not to have acquired the ability to proliferate permanently. In the same case, cell lines were established spontaneously from the peripheral blood without addition of Epstein-Barr virus. The cells which grew spontaneously were large, were occasionally weakly surface adherent, and grew in suspension as loose clumps or as single cells. They were negative for surface immunoglobulins and spontaneous rosette formation with sheep erythrocytes and positive for intracytoplasmic immunoglobulins (Fc and C3 receptors). At an early passage, the spontaneous lines had an aneuploid karyotype with some triploid and some tetraploid cells. Structural chromosomal aberrations include a 14q+. Electron microscopy of the chronic lymphocytic leukemia lines revealed relatively smooth surfaces with numerous mitochondria, widespread vacuolization, and numerous unusual "myelin" figures. Five to 10% of the cells were phagocytic as detected by internalization of latex particles; however, they were Epstein-Barr nuclear antigen positive. The nature of these cells and their possible relationship to the etiology of chronic lymphocytic leukemia are discussed.

Biophysical characterization of normal T-lymphocytes and Sézary cells.

Blood lymphocytes from 18 patients with cutaneous T-cell lymphoma (Sézary syndrome and mycosis fungoides) were characterized using multiparameter laser flow microfluorimetry (FMF) and automated image analysis (AIA) and the results correlated with routine blood smears, cytogenetic studies and observations made on PHA-stimulated normal T-lymphocytes in vitro. Specimens from all 9 patients with Sézary syndrome and 5 of 9 patients with mycosis fungoides contained one or more discrete subpopulations of neoplastic (Sézary) lymphocytes that were detected by FMF. Studies with AIA demonstrated that neoplastic T-lymphocytes are distinguished from normal quiescent (G0) lymphocytes not only by alterations in DNA content (aneuploidy) but also by chromatin structuring (increased chromatin dispersion), which may be a more sensitive index of neoplastic transformation than ploidy levels. In several patients, small and large Sézary cells were present with DNA-chromatin properties quite similar to normal cycling G1 and G2 lymphocytes respectively, but their presence was not explained by an increase in proliferative activity in the blood. These findings indicate that Sézary syndrome consists of a heterogeneous group of related disorders differing in terms of the Sézary cell population. The response to treatment and prognosis may differ accordingly.