Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein.

The structural gene for diphtheria toxin, tox, has been modified at its Sph I site by the introduction of an oligonucleotide linker encoding a unique Pst I restriction endonuclease site and a synthetic oligonucleotide encoding alpha-melanocyte-stimulating hormone (alpha-MSH). The resulting fusion gene directs the expression of a diphtheria toxin-related alpha-MSH hybrid protein in which the diphtheria toxin receptor-binding domain has been replaced with alpha-MSH sequences. The chimeric toxin has been partially purified from periplasmic extracts of recombinant Escherichia coli K-12 and has been found to be selectively toxic for alpha-MSH receptor-positive human malignant melanoma NEL-M1 cells in vitro.     

Modulation of vocal and nonvocal behavior in adult squirrel monkeys by selective MAO-A and MAO-B inhibition

The acute effects of monoamine oxidase inhibitors L-deprenyl (0.5-5.0 mg/kg), clorgyline (1.0-10.0 mg/kg), and milacemide (100-400 mg/kg) on the behavior of adult male squirrel monkeys were examined during brief social separations beginning 60 min after subcutaneous drug administration. All three drugs selectively reduced the rate of calling during social separation at doses which did not affect time spent in locomotion, nor the frequency of vigilance-checking. Deprenyl and milacemide, but not clorgyline, produced concurrent decreases in locomotion at the higher doses tested. At threshold doses, clorgyline, but not deprenyl or milacemide, increased call duration and decreased call peak frequency compared to vehicle control values. Plasma levels of MHPG were decreased by an optimal dose of clorgyline but not by deprenyl or milacemide, indicating that substrate specificity was maintained at the drug doses employed. We conclude that different MAO substrates mediate different aspects of vocal and nonvocal behavior in adult male squirrel monkeys.     

Minimizing anisometropia in bilateral pseudophakia.

One hundred twenty patients who had bilateral posterior chamber intraocular lens implantation were analyzed for postoperative anisometropia. All pairs of lenses had the same A constant and similar designs. Several parameters were analyzed to identify patients at higher risk for clinically significant anisometropia upon implantation of the second eye and determine whether the results of the first eye could be used to modify the implant power selected for the second eye to reduce the risk of anisometropia. In most cases, simply using the value of the linear regression prediction for emmetropia in the second eye without modifications minimized anisometropia.     

Hematopoietic growth-promoting effects of natural killer cells in mice in response to in vivo administration of human interleukin-2.

BACKGROUND: Interleukin-2 (IL-2) is currently being evaluated as an anti-neoplastic agent because of its stimulatory effects on the immune system. However, little is known about the effects of systemic IL-2 administration on hematopoietic parameters. PURPOSE: Recombinant human IL-2 (rHuIL-2) was administered to mice to evaluate its in vivo hematopoietic effects. The mechanism underlying the effects of rHuIL-2 administration was also determined. METHODS: Mice were given 5 x 10(4) IU of rHuIL-2 for 5 days, and their hematopoietic progenitor cell status was determined as measured by growth in soft agar. Antiserum to natural killer (NK) cell-specific markers was used to ascertain if NK cells were responsible for the hematopoietic effects of rHuIL-2. NK cells were purified and cultured in vitro with rHuIL-2 and then adoptively transferred into syngeneic mice to determine the effects on hematopoiesis. RESULTS: Treatment of mice with rHuIL-2 resulted in a significant increase in bone marrow and splenic hematopoietic progenitor cell content. Mice with severe combined immune deficiency (SCID), which lack T cells and B cells yet have NK cells, also responded to the myelostimulatory effects of rHuIL-2. However, removal of NK cells from the SCID mice with antiserum to NK cell-specific markers abrogated the myelostimulatory properties of rHuIL-2. Adoptive transfer of NK cells that were propagated in vitro with rHuIL-2 into mice also resulted in an increase in splenic hematopoietic progenitor cells. CONCLUSIONS: rHuIL-2 exerts significant myelostimulatory effects after in vivo administration, and NK cells are responsible for at least some of these effects. IMPLICATIONS: These results suggest that NK cells and rHuIL-2 may be of use clinically to promote hematopoiesis after bone marrow transplantation or in the face of other myelotoxic therapy in the treatment of cancer.     

Increased mechanical fragility and intravascular lysis of erythrocytes in cats fed a propylene glycol-containing diet

The mechanism responsible for the decreased red blood cell (RBC) lifespan associated with feeding propylene glycol (PG)-containing diets was investigated to understand better how Heinz body-contained RBC are destroyed. Three cats were fed a diet containing 12% PG for 14 days and three other cats served as control. The experimental group developed reticulocytosis and increased Heinz body numbers. Red blood cell membrane immunoglobulih G (IgG) concentration and phagocytosis of RBC by peritoneal macrophages were lower in the PG group compared to the control group suggesting that neither IgG nor non-IgG-mediated phagocytosis was responsible for the RBC destruction. Osmotic fragility, rate of RBC proteolysis and mild mechanical fragility test results were not statistically different from controls. However, when RBC from cats fed PG were exposed to severe mechanical stress, their fragility were increased 2.2–2.8 times. Additionally, haptoglobin concentrations were decreased in the PG group. These data suggest that intravascular lysis may be involved in the pathogenesis of PG-induced RBC destruction.     

Ethnicity, pressor reactivity, and children's blood pressure. Five years of observations.

During the 5 years of this investigation, resting blood pressure and pressor reactivity were measured in 292 white children and 46 black children in 1987, 1988, 1989, and 1991. In 1987, all children were in the third grade; in 1991, the children were in the seventh grade. Reactivity was assessed with a standardized psychological stressor, a television video game. Children displayed significant stability of absolute blood pressure and heart rate reactivity between grades 3 and 7. At all examinations, black children demonstrated blood pressure reactivity that was significantly greater in magnitude (both absolute level and change from resting measurements) than that of white children. Black children exhibited significantly greater heart rate reactivity only when defined as change from the resting measurements; absolute levels of heart rate reactivity were comparable for blacks and whites. For black children, blood pressure reactivity in 1987 was the strongest predictor of resting blood pressure (both systolic and diastolic) in 1991. Among white children, resting blood pressure was the strongest predictor of future resting blood pressure. Further research is needed to determine if ethnic differences in children's pressor reactivity are associated with ethnic differences in the prevalence of hypertension.     

Lack of age-related differences in temporal lobe volume of very healthy adults.

PURPOSETo evaluate age-related differences in temporal and supratemporal brain regions in carefully selected, very healthy men 19 to 92 years of age.METHODSMR quantification of brain regions used image segmentation into cerebrospinal fluid and brain matter based on nonlinear modeling of pixel intensity distributions.RESULTSThere was a significant age-related decrease (approximately 1% per decade) of posterior frontal lobe volume, but not of temporal lobe volume. The mean volume of the right temporal lobe was significantly greater than the left, and this relation did not change with age.CONCLUSIONIn very healthy aging, the volume of the temporal lobes remains constant over the age range of human life.     

Space time clustering of births in SIDS: do perinatal infections play a role?

The aetiology of sudden infant death syndrome (SIDS) remains uncertain; many causal pathways have been proposed. In this paper we have examined firstly the variation in the risk of SIDS with age, month of death and month of birth; and secondly the space time clustering of SIDS deaths, and, separately, space time clustering of their births. Data were obtained from the Office of Populations, Censuses and Surveys on all certified SIDS deaths in the period; children were assigned grid references for the address of birth and of death. Data on number of births were abstracted from published material. A log-linear modelling technique was used to investigate the separate effects of age, month of death and month of birth on the risk of SIDS. The Knox method was used to investigate space time clustering of deaths and of births of children who died of SIDS. Separate, statistically significant effects were found for age, month of death and month of birth. There was minor space time clustering of SIDS births and deaths at large time and space intervals, and a marked space time clustering of births in short space time intervals in the first quarter of the year. The finding of an effect of month of birth on the risk of SIDS, and of space time clustering of births suggest that a perinatal hazard--possibly of infectious origin--may play a role in the aetiology of SIDS.