A new method for evaluation of intracellular inhibition of multiplication or killing by mononuclear phagocytes

A new method for evaluation of the capacity of mononuclear phagocytes to inhibit intracellular microorganisms is described. The system provides a means for assessing this effect of macrophages without concern for multiplication of extracellular organisms, effect of antibiotics, and the potential observer bias which may result from visual evaluation. It involves measurement of amount of [6-3H]UdR incorporated by Toxoplasma gondii. Differences between uptake of [6-3H]UdR by infected and uninfected macrophages can be augmented by cytosine arabinoside as this agent inhibits macrophage DNA synthesis but does not substantially alter DNA synthesis by the test organism, T. gondii.     

Effect of excess thymidine on the growth of human melanoma cells transplanted in thymus deficient nude mice

The effect of thymidine (TdR) on the growth of a human melanoma transplanted in nude mice has been studied. It was found that the injection of 1 g/kg/h of TdR for at least 72 h is sufficient to suppress the growth of the melanoma cells. This inhibition lasts for the duration of the treatment, and causes no apparent toxicity to the host. Nude mice treated for 6--9 days with TdR survived 158 days after melanoma transplant versus 126 days for the controls.     

Studies on the role of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects

These experiments were performed to determine the importance of cephalic-vagal stimulation in the acid secretory response to eating in normal human subjects. Cephalic stimulation was induced by a modified sham feeding (MSF) technique, during which subjects chewed and expectorated appetizing food. The response to MSF was compared with that to gastric distention with 600 ml NaCl, glucose, or food. In addition, we measured the extent to which cephalic stimulation augments acid secretion that has been stimulated simultaneously by these other mechanisms. Our conclusions are as follows: (a) cephalic stimulation accounts for approximately one-third of the acid secreted when all mechanisms act simultaneously (food-distention plus MSF); (b) within the limits imposed by the maximal secretory capacity, the response to MSF is approximately the same, regardless of whether acid secretion is otherwise unstimulated or is stimulated simultaneously by gastric distention with NaCl, glucose, or food; and (c) gastric distention prolongs the response to cephalic stimulation.     

Cyclic changes in platelet dynamics and the pathogenesis and prophylaxis of migraine

Continuous linear gradients improve electrophoretic separations in polyacrylamide. They are obtained by overlayering equal volumes of two monomer solutions with different acrylamide concentrations, namely 180-260 and 23-50 g/l, in the usual gel tubes. The tubes are tilted 3-10 degrees to the horizontal, and rotated around their longitudinal axis until the parts of both solutions in contact are mixed homogeneously. Subsequent polymerization takes place in the vertical position. The more concentrated lower solution contains 4-nitrophenol, so that the final polymer concentration at any point of the gel can be measured densitometrically. The construction and handling of the rotation device are simple and yield highly reproducible results. This versatile method was evaluated for the separation of proteins, lipoproteins, and enzymes in human serum and yields 27-30 protein fractions by additional use of a pH-gradient.     

Nephrotoxicity of cephaloridine in newborn rabbits: role of the renal anionic transport system

The nephrotoxicity of cephaloridine, cefazolin and mercuric chloride was studied in rabbits of various ages. Cephaloridine produced dose-related elevations in serum urea nitrogen, creatinine and renal tubular necrosis in adult and 30-day-old rabbits, only slight changes at 15 days of age and no effect in 5-day-old rabbits. Cefazolin also produced dose-related nephrotoxicity in adult rabbits but no effect in 15-day-old rabbits. Mercuric chloride administration resulted in similar nephrotoxicity in 5-, 15- and 30-day-old rabbits and adults. The development of susceptibility to cephaloridine nephrotoxicity paralleled the maturation of the renal anionic transport system as determined by the accumulation of p-aminohippurate by renal cortical slices in vitro. Substrate stimulation of the anionic transport system by p-aminohippurate or penicillin increased the nephrotoxicity of cephaloridine in between rabbits. The authors concluded that the lack of cephaloridine nephrotoxicity in newborn rabbits is due to the incomplete development of the renal anionic transport system.     

Autoantibodies to the insulin receptor. Effect on the insulin-receptor interaction in IM-9 lymphocytes

The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.     

A comparison of transesophageal and transthoracic echocardiographic assessment of left ventricular function in pediatric patients with congenital heart disease

OBJECTIVE: To determine the quantitative utility of transesophageal echocardiographic assessments of left ventricular function in pediatric patients with congenital heart disease by evaluating the variability between observers and between echocardiographic windows. DESIGN: Retrospective, blinded analysis. SETTING: University-associated pediatric hospital. PARTICIPANTS: Transthoracic and transesophageal echocardiographic images of 25 pediatric patients with congenital heart disease were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: End-diastolic area, end-systolic area, and fractional area change were measured from short-axis images of the left ventricle at the midpapillary level by two separate investigators. These measurements were compared by the method of Bland and Altman and Sheiner and Beal. Significant differences in measurements of end-diastolic and end-systolic area by different observers were noted, but they were systematic. A similar situation was noted for the comparison of transthoracic and transesophageal measurements of end-diastolic and end-systolic area. In the comparison of fractional area change between observers or windows, bias and absolute prediction error were lower, with 95% confidence limits of bias or absolute prediction error of 10% or less. CONCLUSIONS: The potential error in the measurement of fractional area change in 10% under optimal conditions. This would suggest that the assessment of ventricular function in the operating room or intensive care unit, under less than optimal conditions, should be viewed as a qualitative, rather quantitative, measurement. There may be significant interobserver and interwindow variability.