Comparison of production of choriogonadotropin inhibitory protein, prolactin and insulin-like growth factor binding protein-1 by human decidua in vitro

BACKGROUND: Tissue plasminogen activator (tPA) is elevated in cancer patients and is thought to promote tumor angiogenesis by facilitating endothelial cell migration through plasmin-mediated degradation of extracellular matrix. Due to the presence of an epidermal growth factor (EGF)-finger domain in the tPA A-chain and the existence of an endothelial cell (EC) receptor that binds this domain, it was hypothesized that tPA has a direct receptor-mediated effect on EC proliferation, independent of plasmin. METHODS AND RESULTS: Using cultured canine ECs, tPA (7.25 microg/ml, approximately 107 nM) increased proliferation as much as 50 and 170% in the absence and presence of growth factors, respectively. tPA-induced increases in EC proliferation occurred independent of plasmin generation, as the plasmin inhibitor, aprotinin (10 microg/ml) did not inhibit tPA-induced proliferation. However, tPA-induced proliferation was inhibited dose-dependently to a maximum of 78% using a monoclonal antibody against the tPA EGF-finger domain. This antibody, known to inhibit tPA binding to its receptor, did not inhibit tPA-induced plasmin generation. To investigate the role of potential signal transduction pathways, ECs were exposed to lavendustin A, a tyrosine kinase inhibitor, at 33.5 microM (IC50 for basic fibroblast growth factor). Lavendustin A did not inhibit tPA-induced EC proliferation. However, Rp-cAMP, an inhibitor of cAMP-dependent kinases, specifically inhibited tPA-induced EC proliferation in a dose-dependent manner (IC50 = 50.5 microM). Pertussis toxin at maximal concentrations for this system (0.5 ng/ml) did not inhibit tPA-induced EC proliferation. CONCLUSION: These results lend support to the hypothesis that tPA may have a direct receptor-mediated effect on EC proliferation and that this effect occurs independent of plasmin and may be dependent upon protein kinase A activity.     

Perceived race-based discrimination, employment status, and job stress in a national sample of black women: implications for health outcomes

This study examined concordance between self-reported drug use and urinalysis data among 341 applicants for methadone treatment in Sydney, Australia. Rates of under-reporting of use of specific drugs were low (0% to 10%). Irregular drug use, short half-life of some abused drugs, and relatively low sensitivity of the TLC assay procedure led to most detected drugs being found in only one of two urine samples collected. Subjects reported having recently used nearly twice as many drugs as were detected in their urine. Agreement (kappa) between self-report and urinalysis results was in the fair to good range for most drugs. None of the six predictors of misreporting examined were found to be of practical value.     

Electrical pacing of the paralyzed human larynx

This study represents the first attempt to electrically pace the paralyzed human larynx. The goal was to determine if electrical stimulation of the posterior cricoarytenoid muscle could produce functional abduction of the vocal fold in pace with inspiration. An external apparatus was used to sense inspiration and reanimate the unilaterally paralyzed larynx of a thyroplasty patient. Stimuli were delivered through a needle electrode to locate and pace the abductor muscle. The magnitude of electrically induced abduction was comparable to spontaneous movement on the normal side. The abduction was appropriately timed with inspiration: this finding demonstrated that this simple pacing system could effectively modulate stimulation with patient respiration.     

Effects of sex and MK-801 on auditory-processing deficits associated with developmental microgyric lesions in rats

Neonatally induced microgyric lesions produce defects in rapid auditory processing in adult male rats. Given that females across species are less susceptible to the deleterious effects of neural injury and that treatment with neuroprotective agents at the time of injury can reduce neural damage, the authors tested the effects of sex and neuroprotectant exposure on the behavioral consequences of microgyric lesions in rats. Results showed that sham but not microgyric males were able to perform the task at the fastest rate of stimulus presentation. Microgyric females, in contrast, discriminated at all stimulus conditions and did not differ from female shams. Microgyric males treated with MK-801 had reduced cortical damage and performed the discrimination at the fastest condition. Results suggest that females are less susceptible to the behavioral effects of neocortical microgyria and that MK-801 may ameliorate the behavioral consequences of these lesions in male rats.     

Effects of fibinolysis on neurite growth from dorsal root ganglia cultured in two- and three-dimensional fibrin gels

The mechanism of neurite penetration of three-dimensional fibrin matrices was investigated by culturing embryonic chick dorsal root ganglia (DRGs) within fibrin gels, upon fibrin gels, and upon laminin. The length of neurites within three-dimensional matrices of fibrin was decreased in a concentration-dependent manner by agents that inhibited plasmin, e.g. aprotinin, or that inhibited plasminogen activation, e.g., epsilon-aminocaproic acid (EACA), or plasminogen antiserum. In contrast, such agents increased the length of neurites growing out from DRGs cultured upon two-dimensional substrates of fibrin and had no effect on the length of neurites growing out from DRGs cultured upon laminin. Visualization of neurites within three-dimensional fibrin matrices demonstrated that the distance between fibrin strands was much smaller than the diameter of neurites. All these data were consistent with the hypothesis that fibrinolysis localized to the region of the neurite tip is an important mechanism for neurite penetration of a physical barrier of fibrin strands arranged in a three-dimensional matrix.     

Tolerance space and molecular similarity

Molecular similarity methods were used in selecting K nearest neighbors and in estimating mutagenicity of 95 aromatic amines and boiling points of a large set of over 2,900 compounds. Similarity is analyzed in terms of the concept of tolerance space. Specifically, the role of non-transitivity of the tolerance relation in estimating properties using similarity methods is examined.