Control of remembered reaching sequences in monkey. I. Activity during movement in motor and premotor cortex.

Motor and premotor cortex firing patterns from 307 single neurons were recorded while monkeys made rapid sequences of three reaching movements to remembered target buttons arrayed in two-dimensional space. A primary goal was to study and compare directionally tuned responses for each of three movement periods during 12 movement sequences that uniformly sampled the directional space in front of the monkey. The majority of neurons showed maximal responses during movements in a preferred direction with smaller increases during movements close to the preferred direction. These responses showed a statistically significant regression fit to a cosine function for 72% of the neurons examined. Comparisons among tuning directions computed separately for the first, second, and third movement periods suggested the near constancy of preferred direction across a rapidly executed series of movements even though these movements began at different starting points in space. Although directionally tuned neurons were only broadly tuned for a specific direction of movement, the neuronal ensemble carried accurate directional information. A population vector computed by summing vector contributions from the entire population of tuned neurons predicted movement direction with a mean accuracy of 20 degrees. This population code made consistent predictions for each of the 36 movements that were studied using a single set of population parameters. Most of the remaining neurons (24%) that were not tuned during movement did show significant changes in activity during other aspects of task performance. Some nontuned neurons had nondirectional increases that were sustained during movement, while others showed identical phasic bursts during the three movement periods. These nontuned neurons may control stabilizations of the shoulder, trunk, and forearm during movement, or forearm movements during button pushing.

Overview of quinapril, a new ACE inhibitor.

Quinapril has been extensively studied for efficacy and safety in patients with hypertension or congestive heart failure (CHF) in the United States and Europe. Thirty-nine clinical pharmacology studies involving 383 patients have been completed. Moreover, 12 controlled, multicenter clinical studies and 3 single-center studies involving 1,793 patients have been conducted in hypertension. Three hemodynamic trials, two of which included both acute and long-term phases, and one placebo-controlled, dose-response study have been conducted in 333 patients with CHF. An additional 519 patients who completed studies on comparative agents were started on quinapril at the initiation of six long-term, open-label trials, which extended for up to 3 years. Twelve of 15 hypertension trials evaluated quinapril as first-line monotherapy in 1,452 patients with hypertension. Comparative agents included placebo in five trials (524 patients), enalapril in three trials (339 patients), captopril in four trials (335 patients), and chlorthalidone in one trial (74 patients). A total of 510 patients received quinapril in addition to a diuretic in double-blind trials: 341 patients with moderate to severe hypertension participated in three trials, and 169 patients with CHF participated in one trial. Quinapril administered once daily (o.d.) was evaluated in four placebo-controlled studies and in two studies of o.d. vs. twice-daily doses. The safety of quinapril has been evaluated in almost 2,700 patients in controlled, double-blind studies or in open-label extensions, for a total of more than 1,600 patient-years of exposure to quinapril. More than one-half of all patients participated in long-term trials: 980 patients were studied for 1 year and 315 patients were studied for 2 years at the time of data analysis. Safety data are available for 451 older patients (aged greater than or equal to 65 years), and comparative safety data from other compounds in the controlled studies are available for 1,058 patients. Quinapril's efficacy is comparable to that of other angiotensin-converting enzyme (ACE) inhibitors, and it has a lower incidence of adverse events or withdrawals due to adverse events than has been associated with captopril or enalapril.

Reproduction in Fischer-344 rats exposed to methyl chloride by inhalation for two generations.

Male and female Fischer-344 rats were exposed to methyl chloride by inhalation (0, 150, 475, or 1500 ppm, 6 hr/day, 5 days/week, 40 males and 80 females per group). The only treatment-related clinical signs were a 10 to 20% body weight gain depression (BWGD) in both males and females exposed to 1500 ppm at all weekly weighings after 2 weeks of exposure and a 5-7% BWGD in 475-ppm exposed animals after Day 57. After 10 weeks the exposure schedule was changed to 6 hr/day, 7 days/week and each male was mated to two exposed females. The mating period was ended after 2 weeks, at which point 10 males/group were necropsied. The only treatment-related lesions found were severe bilateral testicular degeneration (10/10) and granulomas in the epididymis (3/10) in the 1500-ppm males. The remaining 30 males per group were then removed from exposure and mated during a 2-week period with 60 unexposed females. The exposed females were continued on exposure from the start of mating to Postnatal Day 28 (6 hr/day, 7 days/week). The females were not exposed from Gestation Day 18 to Postnatal Day 4, and the pups were never directly exposed prior to weaning. There were no significant differences between groups in the number of exposed or unexposed females that mated, as evidenced by copulation plugs. No litters were born to exposed or unexposed females mated to the 1500-ppm males. There was no significant difference in the number of litters produced by the 150-ppm groups when compared to the control groups. Fewer litters were born in the 475-ppm groups than in the control groups. No differences in litter size, sex ratio, pup viability, or pup growth were found among the 475-ppm, 150-ppm, or control F0 groups. When bred 10 weeks after the cessation of exposures, 5 to 20 1500-ppm F0 males had regained the ability to sire normal litters. The same number of 475-ppm F0 males proved as fertile (15/20) as control F0 males (13/20). After weaning, F1 pups from the 475-, 150-, and 0-ppm groups were exposed to the same concentrations of methyl chloride for 10 weeks and then mated. A trend toward decreased fertility was found in the 475-ppm F1 group.

Cytogenetic analysis of lymphocytes from rats following formaldehyde inhalation.

Male and female Fischer-344 rats were exposed to target concentrations of 0.5, 6, or 15 ppm formaldehyde by inhalation for 6 h/day for 5 days. Blood was removed by cardiac puncture within 1 h following termination of exposures and cultured in the presence of 5-bromodeoxyuridine (BrdU) (4 microM) for analyses of sister-chromatid exchange (SCE) and chromosome breakage. Formaldehyde did not cause a statistically significant increase in either SCE frequency or in the number of metaphases displaying chromosome aberrations.

Studies of immune function and host resistance in B6C3F1 mice exposed to formaldehyde.

A series of immune function and host resistance parameters were examined in female B6C3F1 mice following a 21-day (6 hr/day) inhalation exposure to 15 ppm of formaldehyde (HCHO). Immune parameters examined included delayed hypersensitivity to keyhole limpet hemocyanin, antibody plaque-forming cell response to sheep erythrocytes (T-lymphocyte-dependent antigen) and TNP-Ficoll (T-lymphocyte-independent antigen), lymphoid organ weights and histopathology, routine hematology, bone marrow cellularity and CFU progenitor cell enumeration, lymphocyte subpopulation quantitation by cell surface markers, mitogen-induced lymphocyte blastogenesis, macrophage function parameters, and host resistance to challenge with the bacterium Listeria monocytogenes and transplantable tumor cells. Lymphoid organ weight, bone marrow cellularity, and hematology parameters were unchanged in HCHO exposed mice. Similarly, the percentage of T and B lymphocytes and their proliferative responses to mitogens were not significantly altered. Antibody (IgM) plaque-forming cell response following antigen challenge was unchanged. Macrophage function was normal although some evidence of enhanced H2O2 production associated with elevated bactericidal activity was observed in resident macrophages. Resistance to challenge with the bacteria Listeria monocytogenes was significantly enhanced, while resistance to tumor challenge remained unchanged. No evidence of immunosuppression following short-term exposure to HCHO was observed.

Analysis of cytogenetic damage in rat lymphocytes following in vivo exposure to nitrobenzene.

Male F-344 rats were exposed to target concentrations of 0, 5, 16, or 50 ppm nitrobenzene for 6 h/day, 5 days a week, for 21 days during a 29-day period. Isolated spleen (ISLs) and peripheral blood lymphocytes (PBLs) were cultured in the presence of 2 microM 5-bromodeoxyuridine and scored for sister-chromatid exchange (SCE) and PBLs were also scored for chromosome aberrations. No significant increase in SCE frequency or chromosome aberrations was found in the PBLs, and no significant increase in SCEs was observed in the ISLs at any of the concentrations. Thus, cytogenetic analysis of ISLs and PBLs provide no evidence of a genotoxic potential for nitrobenzene.

The structure and reliability of health belief indices.

A wealth of research using the Health Belief Model provides empirical evidence of the model's utility in predicting health, illness, and sick role behaviors. Until recently, however, little attention has been paid to the important issues of the validity and reliability of measures used to assess various health belief dimensions. Using factor analysis, our study demonstrates that moderately reliable indices covering a wide spectrum of distinct health beliefs can be constructed and then replicated across independent samples. The factor analysis approach revealed that condition-specific measures of perception of susceptibility and severity and situation-specific measures of perceived barriers are empirically distinct from general measures of these beliefs. We therefore recommend caution in mixing general and specific questionnaire items within the same index when measuring these beliefs. A factor representing perceptions of health threat emerged, but its composition require further clarification. The degree of similarity between the factor structures in the two independent samples provides support for the existence of independent health belief dimensions.