Macrophage Cytostasis and T and B Cell Blastogenic Transformation in Mice Treated with Nystatin

Treatment of normal BALB/c mice with nystatin, an amphoteric polyene, activated macrophages to become tumoricidal for MBL-2 lymphoblastic leukemia target cells while augmenting the in vitro blastogenic response of splenic lymphocytes to B and T cell mitogens. These responses were both shown to be highly dose dependent and occurred 6 days following the intraperitoneal injection of nystatin into normal mice. Macrophages from untreated mice did not show similar activity. The significance of these observations and the potential use of nystatin as a pharmacologic agent is discussed.     

Comparison of radionuclide and contrast ventriculography for detection and quantitation of regions of myocardial ischemia in dogs.

Radionuclide and contrast ventriculography were evaluated for their ability to estimate myocardial ischemia. In 14 closed-chest, sedated dogs, a small and larger region of ischemia were produced by inflating balloon occluders on the left anterior descending coronary artery. The systemic arterial pressure, atrial-paced heart rate, global ejection fraction by radionuclide and contrast ventriculography, regional wall-motion abnormalities (as the percentage of abnormally contracting segments), and regional myocardial blood flow (using the microsphere technique) were measured during an initial control period, two separate ischemic periods, and a final control period. The regional ischemic weights based on myocardial blood flow ranged from 0 to 38.5 g and were grouped as zero, small (range 0 to less than 10 g, mean 3.40 g), and large regions of ischemia (greater than 10 g, mean 24.8 g). Regional wall-motion abnormalities were sensitive qualitative indicators of ischemia. Receiver operating characteristic analysis showed that both ventriculographic methods were highly sensitive, specific, and accurate for detecting regional ischemia. Contrast ventriculography was slightly superior for detecting small regions less than 4 g, but the methods were equal for regions greater than 4 g. The arterial pressure and heart rate were unchanged during ischemia. For small regions of ischemia, the global ejection fraction did not fall using either the contrast or radionuclide technique, but it fell significantly when large regions were produced. There was a quantitative relationship between the percentage of abnormally contracting segments and the grams of myocardial ischemia (for radionuclide ventriculography, r = 0.65, P = 0.003, and for contrast ventriculography, r = 0.75, P less than 0.001), but for many small regions of ischemia, wall-motion changes were greater than anticipated, suggesting hypofunction of the continguous normal tissue. This study demonstrated that both radionuclide and contrast ventriculography were quite sensitive and specific for detecting measured amounts of regional ischemia. The functional changes resulting from ischemia are quantitatively related to the extent of regional ischemia, small areas resulting in regional wall motion abnormalities, and large areas producing both reduced global ejection fraction and wall motion changes.     

Frequency specific effects of stroboscopic rearing in the visual cortex of the rabbit

Rearing animals in stroboscopic illumination deprives those animals of the experience of visual motion. In the rabbit, stroboscopic rearing produces a significant alteration in the response properties of cells in the visual cortex, demonstrating that the rabbit visual system is susceptible to environmental manipulation during early postnatal life. Response properties were determined for single units recorded in the primary visual cortex of 3 groups of rabbits. One group had been reared from birth to 2 months of age at a stroboscopic flash frequency of 8 Hz, a second group was raised at a flash frequency of 4 Hz and a third was reared normally. Compared to normal rabbits, rabbits reared at 8 Hz showed a reduction in the proportion of orientation selective cells which were also direction-selective, and there was an increase in the proportion of cells responsive to stroboscopic flashes. There was no reduction, however, in the overall proportion of orientation-selective cells. This contrasts with the finding for the rabbits raised at a flash frequency of 4 Hz. In addition, cortical cells in the rabbits raised at 8 Hz responded to frequencies of stroboscopic flashes which were significantly higher than the frequencies found for cells in the rabbits raised at 4 Hz. The effects of stroboscopic rearing on the rabbit visual cortex are dependent, therefore, on the flash frequency experienced by the rabbits during development.     

Effect of exposure to anti-NGF on sensory neurons of adult rats and guinea pigs

Nerve growth factor (NGF) deprivation was produced in adult rats and guinea pigs by immunization against mouse NGF. Exposure of adult animals to anti-NGF had no effect on sensory ganglion neuronal number or size-frequency histograms. However, the substance P content of sensory ganglia, spinal cord and hind paw skin decreased to as great an extent as was seen in animals exposed to anti-NGF in utero. We conclude that NGF has two separate effects on sensory neurons: adult sensory neurons require NGF for normal function whereas developing neurons require NGF for both survival and transmitter expression.     

Endocrinology of testicular neoplasms

The hypothalamic-pituitary-testicular axis finely regulates levels of circulating sex steroids--especially testosterone and estradiol--and spermatogenesis. Testosterone, directly as an androgen and as a prehormone for estradiol, regulates LH secretion at both hypothalamic and pituitary levels. Leydig cells, principally under the control of LH, produce testosterone. Sertoli cells, under the control of FSH, and sensitive to intratesticular levels of testosterone, produce estradiol. This locally produced estrogen seems to be necessary for maturation of the germ cells. An abnormality in this sensitive control system, leading to elevations in gonadotrophins or steroid levels, may be etiologically important in both germ cell and nongerm cell neoplasia. Testicular cancers are associated frequently with endocrinologic manifestations, which may be more disabling to the patient than the malignant potential of the tumor, especially with childhood Leydig cell tumors. Estrogen dominance with an elevated estrogen/testosterone ratio can be seen in any testicular neoplasm and may result in gynecomastia. It may be due to a decrease in circulating testosterone or to an increase in estrogens. Virilization is seen frequently in Leydig cell tumors of adolescents. Further elucidation of hormonal interrelationships should lead to better understanding of the genesis of testicular neoplasia and to more effective therapy.     

The mode of action of anabolic agents: the effect of testosterone on muscle protein metabolism in the female rat

Testosterone (1 mg/kg body-weight per d) given subcutaneously to female rats increased their growth rate and food conversion efficiency but not their food intake compared with that of the placebo-oil controls. A higher dose of testosterone (10 mg/kg body-weight per d) failed to increase the daily weight gain. The increased growth rate of the testosterone-treated rats appeared to occur in the whole body and not specifically in muscle. There were no significant changes in body composition. The fractional synthetic rate of gastrocnemius muscle protein was higher in the hormone-treated rats than in controls. This contrasts with previous results for the anabolic agent trenbolone acetate and reflects differences in the mode of action of these two different steroids, both with androgenic properties.     

Inpatient-outpatient randomized comparison of Cambridge diet versus milk diet in 17 obese women over 24 weeks

Twenty-two obese women were recruited for a prospective cross-over trial of the effects of either the Cambridge Diet (CD) or 1200 ml milk with iron and vitamin supplements (milk) during a three-week inpatient study, then 20 weeks as outpatients, then a final week as inpatients. Five dropped out, leaving eight who took initially milk and then CD and nine who took CD and then milk. Within each diet group five women had their jaws wired together during the outpatient phase. The four groups (CD/milk, with/without jaw wiring) were initially well matched for age, height, weight and resting metabolic rate (RMR). There was no significant difference (by unpaired t test) between the groups during the initial inpatient phase in rate of weight loss, or N loss/kg weight loss, but patients on CD during days 13-22 had a greater daily N loss than those on milk (2.08 vs 0.28 g N/day, P = 0.02). When the change in weight loss, N loss and N/kg weight loss on changing diet within a patient group was compared by paired t test the patients changing from milk to CD showed no significant change, but patients changing from CD to milk showed a reduced rate of weight loss (0.36-0.23 kg/day; P = 0.012), a reduced N loss (2.02-0.28 g N/day; P = 0.0013) and reduced loss of N/kg (6.26 to 1.02 g N/kg; P = 0.025). During the outpatient phase weight loss was not significantly related to the diet, but patients with jaws wired lost more weight than those without jaw wiring (0.151 vs 0.077 kg/day; P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)