Binding and retrograde transport of leukemia inhibitory factor by the sensory nervous system.

Leukemia inhibitory factor (LIF), a peptide growth factor with multiple activities, has recently been shown to support the generation and survival of sensory neurons in cultures of mouse neural crest and dorsal root ganglia (DRG). We have conducted binding experiments with 125I-LIF on cultures of DRG to determine the receptor distribution for LIF on these cells and found that at least 60% of the sensory neurons in the cultures bound 125I-LIF, all of which could be eliminated by the addition of unlabeled LIF. The other cells in the culture, which morphologically appeared to be Schwann cells, did not bind appreciable quantities of 125I-LIF. In order to investigate whether LIF is retrogradely transported to sensory neurons in vivo, 125I-LIF was injected into the footpads and gastrocnemius muscles of newborn and adult mice, following sciatic nerve ligation. Radioactivity accumulated in the distal portion of the sciatic nerve, indicating retrograde transport of LIF. Subsequent experiments on mice with unligated sciatic nerves showed that 125I-LIF is specifically transported into the sensory neurons of the DRG. There was no apparent transport of 125I-LIF into motor neurons in the spinal cord. These experiments demonstrate that LIF can specifically bind to and be transported by sensory neurons and further support the idea that LIF acts as a target-derived neurotrophic factor, analogous to NGF.     

Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome

BACKGROUND: Apical ballooning syndrome (ABS) is a poorly understood clinical entity characterized by acute, transient systolic dysfunction of the left ventricular (LV) apex in the absence of epicardial coronary artery disease and commonly associated with acute emotional stress. We report abnormal regional myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose within 72 hours of presentation with ABS. METHODS: All patients were postmenopausal females, 3 of whom had a major recent life stress event. Coronary angiography revealed no or minimal obstructive epicardial coronary artery disease. All patients exhibited reduced glucose uptake in the mid-LV and apical myocardial segments, which was out of proportion to perfusion abnormalities in half of the cases. CONCLUSION: In all 4 patients, affected regions subsequently recovered regional LV systolic function within 6 weeks.     

Squamous and adenocarcinoma of the uterine cervix: a comparison using routine data

We studied the clinical, demographic and survival characteristics of more than 5,000 women registered with either squamous or adenocarcinoma of the uterine cervix in South Thames Cancer Registry over the period 1968-81. There were similarities with respect to social class, smoking habit, oestrogen/oral contraceptive use and time trends in incidence but differences between the two cancers were found with respect to age distribution, parity, method of detection and survival. Some of the data are of limited value, having been obtained only from case notes, so the results need some caution in their interpretation. However the results are broadly consistent with those of studies performed in other countries on smaller samples. A methodological issue is also raised, viz. the appropriateness of a disease with well-known characteristics as a comparison group. From our results the likely size of various associations can be judged and used in the design of future studies to clarify the epidemiology of cervical adenocarcinoma.     

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.     

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.