Apparent unilateral visual neglect in MPTP-hemiparkinsonian monkeys is due to delayed initiation of motion.

Monkeys made hemiparkinsonian by infusion of a solution of MPTP into one carotid artery appeared to ignore food presented from the contralateral side. Initial observations suggested neglect of visual stimuli presented as fruit treats by automated delivery system in the half-field contralateral to MPTP treatment. Further studies in which fruit treats were left in the 'neglected' visual field indicated that this apparent neglect, unlike neglect attending cortical lesions, was rather a marked delay in initiating movements (unilateral hypokinesia). These observations may explain apparent subcortical neglect and are consistent with the known role of nigrostriatal dopaminergic neurones in movement regulation. This is a useful animal model in which difficulties in initiation of movement (hypokinesia). a cardinal symptom of Parkinson's disease, can be studied separately from other deficits in motor performance.

Design of flow chamber with electronic cell volume capability and light detection optics for multilaser flow cytometry.

A multibeam optical detection system has been developed with a high optical efficiency, achieved through a reduction in the number of optical interfaces employed in the system. This reduction is made possible by a combination of employing simple lenses, gluing the objective lens directly upon the face of the flow cuvette and the extraction of only one fluorescence signal from each laser beam. A modified flow chamber is also described that includes fluidic resistance elements for the elimination of most of the electric shielding normally associated with electronic cell volume measurements.

The biology of tumor growth in the non-Hodgkin's lymphomas. A dual parameter flow cytometry study of 220 cases.

Dual parameter flow cytometry studies (cell DNA content and electronic cell volume) were performed in 220 cases of non-Hodgkin's lymphoma. All cases were characterized as B or T cell malignancies, based on immunologic surface marker characteristics. Aneuploidy by flow cytometry was more common among the B cell lymphomas than among the T cell lymphomas, and was most common among the large B cell lymphomas and B cell lymphomas of intermediate size. Ploidy index distributions showed a prominent hyperdiploid peak, as well as tumor cell populations with near-tetraploid DNA contents. In serial studies, a decrease in ploidy index was observed in association with clinical and histologic transformation in one case. The highest S fractions were observed among the large and intermediate B cell lymphomas and among the aggressive T cell lymphomas. In clinical samples consisting of mixtures of diploid and aneuploid populations, the data on the aneuploid components could often be separated from other components of the mixture in multiparameter studies on the basis of the larger electronic cell volumes of the aneuploid cells. In each case, the aneuploid large cell component almost invariably had a higher S fraction than the residual component(s) of the mixture. Overall, the data are consistent with a model of clonal selection and clonal evolution in the lymphomas in which early cytogenetic abnormalities that involve little or no change in total cell DNA content are followed by cell tetraploidization that is associated with cytogenetic instability and chromosome loss over the course of time.

Effects of vincristine on cell survival, cell cycle progression, and mitotic accumulation in asynchronously growing Sarcoma 180 cells.

The effects of vincristine (VCR) on cell survival, cell cycle progression, DNA synthesis, and metaphase accumulation were studied in relation to drug concentration and drug exposure duration in Sarcoma 180 cells in vitro. VCR was found to affect cells in interphase, producing a transient G2 block at all drug concentrations and drug exposure durations studied. VCR did not affect DNA synthesis directly. Increases in the metaphase index were delayed and always peaked at approximately 8 hr after drug removal, regardless of the duration of drug exposure. Increases in the metaphase index of sufficient magnitude to be commensurate with VCR lethality were observed only with prolonged drug exposure. VCR produced both nuclear fragmentation and polyploidy. The proportion of cells undergoing polyploidy increased progressively with increasing drug exposure duration. Interference with cytokinesis during prolonged VCR exposure may represent a lethal effect of VCR that is separate from its short-term effects. This could serve as the basis for the clinical study of the antitumor effects of prolonged VCR infusions.

Schedule dependence of vincristine lethality in Sarcoma 180 cells following partial synchronization with hydroxyurea.

The effects of exposure to 0.1, 0.5, or 2 microM vincristine for 4 hr were studied in Sarcoma 180 cells at various times after synchronization with 5 mM hydroxyurea for 1 hr. Maximum sensitivity to the lethal effects of vincristine was observed at 10 to 14 hr after hydroxyurea exposure at the higher vincristine concentrations, compared to a period of a maximum sensitivity to a second dose of hydroxyurea at 8 to 12 hr. Serial flow cytometry studies indicated that the apparent decrease in sensitivity to vincristine at 14 to 18 hr was due to the division of cells in the leading segment of the synchronized wave and their entry into the relatively resistant G1 phase prior to vincristine exposure. Synchronized cells that had not divided at the time of vincristine exposure were blocked transiently in G2. Serial metaphase index studies suggested that the G2 cells closest to the end of the cell cycle at the time of vincristine exposure were likely to exhibit the greatest degree of mitotic disorganization when they overcame the G2 block and entered metaphase. The present studies suggest that sensitivity to vincristine increases progressively as cells approach mitosis. The molecular mechanisms underlying this phenomenon are considered in relation to the increase in cell tubulin content during the course of cell cycle progression.

A practical graphical method for estimating the fraction of cells in S in DNA histograms from clinical tumor samples containing aneuploid cell populations.

A graphical method for the analysis of unperturbed DNA histograms is presented in which the area of the normalized histogram subtended by the fraction of cells in S is represented by a trapezoid whose dimensions are dependent on features common to all such histograms. The technique takes measurement variability into account. This method was applied to a variety of synthetic DNA histograms. Overall, calculated values for the fraction of cells in S correlated well with actual values. This method was applied to 36 diploid cases of non-Hodgkin lymphoma; results correlated well with those obtained by a computer-based method. The results of the graphical-method were also highly reproducible between different observers. The graphical method can be used in the presence of aneuploid cell populations. Techniques for calculating S fractions in the presence of aneuploidy in clinical samples are described. These techniques were applied to synthetic histograms of mixed diploid and aneuploid populations. Calculated values correlated well with actual values.

Automated radioautographic grain counting. Correction for grain overlap.

An algorithm is described for the calculation of radioautographic cell grain count from measurements of total cell nuclear area and total grain area. This algorithm provides a statistical correction for grain overlap that is based on the solution to the occupancy problem in probability theory. This method permits the use of automated grain counting over a wide range of grain counts per cell, and extends the useful dynamic range of radioautographic grain counting to well over 200 grains/cell.

Multicompartment analysis of cell proliferation and cell migration in the Sezary syndrome.

Serial radioautographic data obtained in two patients with Sezary syndrome following intravenous tritiated thymidine administration were analysed using multicompartment kinetic models. In both patients, the grain count halving time in the cutaneous Sezary cell compartment was too long to account for the grain count halving rate observed in the peripheral blood. This implies that some proliferating cell compartment other than the skin is primarily responsible for producing the Sezary cells that circulate in the peripheral blood. In both patients, the cell compartment that served as the source of circulating Sezary cells consisted of 5-6 X 10(11) cells (500-600 g of tumor) with an average cell cycle time of 3-4 days. By comparison, the cutaneous Sezary cell compartment was estimated to contain 2.2-4.6 X 10(12) cells (2.2-4.6 kg of tumour) with an average cell cycle time of 7-70 days. While this study does not permit direct anatomic localization of the primary site of Sezary cell production, the properties of this compartment that can be deduced from the available data suggest the lymph nodes as likely candidates. Thus, the Sezary syndrome may well be a true lymph node malignancy with prominent cutaneous manifestations.

Immunological and physiological responses to whole-body hyperthermia.

Current information on the effect of systemic hyperthermia on the host-tumor immunologic response was reviewed. Changes in physiology caused by whole-body heat are described in a review of current studies at the National Cancer Institute and others, with particular regard to cardiovascular, endocrine, and nervous system changes with heat. The importance of these heat-affected alterations of physiology and immunology on chemotherapy and radiotherapy administration is discussed.

The pupil dark response in normal volunteers.

A new semi-automatic videopupillometer with a two-channel video integrator uses prismatic displacement of pupil images for binocular recording with a single infrared-sensitive video camera. The video integrator graphically records pupil area or diameter during testing and can reanalyze and plot information from videotape recordings of pupil responses. This new pupillometer was used to evaluate the pupil dark response in 178 eyes of 89 normal human volunteers (ages 18-75 years). The time course of pupil dilation was similar in volunteers of all ages, even though the average pupil area became progressively smaller with increasing age.

Erythrocyte osmotic fragility in patients receiving hyperthermia with and without chemotherapy.

The osmotic fragility of erythrocytes was studied in 24 patients receiving whole-body hyperthermia, with and without concomitant chemotherapy, for 2-4 hours as an adjuvant to chemotherapy for advanced metastatic disease. No alteration in osmotic fragility of erythrocytes was observed with whole-body hyperthermia.

Hemodynamic and plasma catecholamine responses to hyperthermic cancer therapy in humans.

Cancer patients, treated with hyperthermia (to 41.5 degrees C) under thiopental and fentanyl anesthesia, had smaller increases in heart rate and cardiac index and lesser decreases in mean arterial pressure than those reported in normal volunteers. At basal body temperature anesthesia did not alter catecholamine levels. Increasing body temperature to 39.5 degrees C and 41.5 degrees C resulted in parallel increases in heart rate and cardiac index that were directly related to the increases in plasma norepinephrine levels. At basal temperature cutaneous venous plasma norepinephrine levels exceeded those of arterial; mixed-venous plasma levels were intermediate. At 39.5 degrees C and 41.5 degrees C there were sequential increases in plasma norepinephrine. The increases in mixed-venous and arterial norepinephrine were significantly greater than in cutaneous venous blood. The differential increases in norepinephrine levels in cutaneous venous, mixed-venous, and arterial blood indicate that during hyperthermia sympathetic nerve activity in skin is decreased while that in other areas is increased, suggesting that alterations in sympathetic activity modulate the hemodynamic changes that attend hyperthermia in man.

[K+]o clearance in cortex: a new analytical model.

1. It has been suggested that passive diffusion is the principal mechanism of the clearance of locally elevated extracellular potassium, K+o, in the cerebral cortex. This concept was based on the assumption that elevated K+ could be modeled as a point source. In the present study, the functional role of passive diffusion was reevaluated in the anesthetized cat cortex following local electrical stimulation. 2. The initial spatial distribution of extracellular potassium activity, [K+]o, elevated by monopolar stimulation, could be modeled by a two-dimensional Gaussian function at and below the 500-micron cortical depth. Azimuthal symmetry around the stimulating electrode was assumed and cylindrical spatial coordinates were used. 3. The observed clearance of transiently elevated [K+]o as a function of space and time was much more rapid than that predicted by an analytical model consisting of the homogeneous diffusion equation whose initial condition was the Gaussian spatial distribution of [K+]o at the onset of the clearance process. 4. It is concluded that passive diffusion does not significantly contribute to the rapid clearance of locally elevated extracellular potassium in the cortex. Active uptake of potassium by cortical cells should be more seriously considered as being primarily responsible for the potassium clearance.

An alternative approach to dose reduction in dental radiography.

A responsible approach to dose reduction in dental radiography requires that relative exposure be related to the specific diagnostic task performed. All but the most demanding tasks can be performed when suitable film is used in conjunction with high-speed screens. Placing the source of radiation inside the mouth permits radiographic information to be recorded on an improved Polaroid cassette that has a relatively high quantum efficiency. As a result, the radiation dose can be significantly reduced in a versatile system which provides for instantaneous processing and interpretation from prints rather than negatives.