Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasminogen activating system plays a key role in the cascade of tumour-associated proteolysis leading to extracellular matrix degradation and stromal invasion. Changes in the expression of this system, consisting of urokinase- and tissue-type plasminogen activators (uPA and tPA, respectively), plasminogen activator inhibitors (PAI-1, PAI-2) and uPA receptor, have been associated with tumour aggressiveness in a variety of solid malignant tumours. This paper describes a study of squamous intraepithelial lesions (SILs, n=36), squamous cell carcinomas (SCCs, n=42), and normal mucosa (n=5) of the uterine cervix by in situ hybridization with (35)S-labelled RNA probes. uPA transcripts were absent from normal mucosa and non-invasive lesions, but present in atypical epithelial cells of all microinvasive carcinomas ( n=19) and in some of the more advanced invasive carcinomas (n=11). PAI-1 transcripts were found in stromal cells of most tissue samples with, however, significantly increased levels in invasive SCC compared with SIL, microinvasive SCC, and normal mucosa. uPA-positive invasive carcinomas often displayed additional PAI-1 expression by tumour cells. At variance with uPA, tPA transcripts were found in atypical epithelial cells of low- and high-grade SILs. In the majority of SCCs tested (27/29 cases), the HPV 16 E6/E7 oncogene and uPA transcription were correlated. uPA and PAI-1 expression indicates invasive growth when expressed by atypical epithelial cells of squamous cervical lesions. Moreover, the presence of uPA transcripts is indicative of early invasive growth. uPA and tPA seem to have different functions in the development of invasive properties in uterine cervical squamous epithelium.
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PMID:Urokinase gene expression indicates early invasive growth in squamous cell lesions of the uterine cervix. 1054 82

Exposure to high altitude induces pulmonary hypertension that may lead to life-threatening conditions. In a randomized, double-blind, placebo-controlled study, the effects of oral sildenafil on altitude-induced pulmonary hypertension and gas exchange in normal subjects were examined. Twelve subjects (sildenafil [SIL] n = 6; placebo [PLA] n = 6) were exposed for 6 days at 4,350 m. Treatment (3 x 40 mg/day) was started 6 to 8 hours after arrival from sea level to high altitude and maintained for 6 days. Systolic pulmonary artery pressure (echocardiography) increased at high altitude before treatment (+29% versus sea level, p < 0.01), then normalized in SIL (-6% versus sea level, NS) and remained elevated in PLA (+21% versus sea level, p < 0.05). Pulmonary acceleration time decreased by 27% in PLA versus 6% in SIL (p < 0.01). Cardiac output and systemic blood pressures increased at high altitude then decreased similarly in both groups. Pa(O(2)) was higher and alveolar-arterial difference in O(2) lower in SIL than in PLA at rest and exercise (p < 0.05). The altitude-induced decrease in maximal O(2) consumption was smaller in SIL than in PLA (p < 0.05). Sildenafil protects against the development of altitude-induced pulmonary hypertension and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.
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PMID:Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. 1551 32

Self-assembly of poly(styrene)-block-poly(isoprene)-block-poly(lactide)-block-poly(styrene) (PS-PI-PLA-PS' or SILS') tetrablock terpolymers, where the volume fractions of the first three blocks are nearly equivalent, was studied both experimentally and using the self-consistent field theory (SCFT). SCFT indicates that addition of the terminal PS' chain to a low-molecular-mass, hexagonally packed cylinders forming, SIL precursor can produce a disordered state due to preferential mixing of the polystyrene end-blocks with the PI and PLA midblocks in the SILS' tetrablock, alleviating the unfavorable contact between the highly incompatible PI and PLA segments. In contrast, SCFT predicts that higher-molar-mass triblock precursors will maintain an ordered morphology upon addition of the terminal PS' block due to stronger overall segregation strengths. These predictions were tested using three sets of SILS' polymers that were synthesized based on three precursor SIL triblock polymers differing in total molar mass (14, 30, and 47 kg mol-1) and varying the length of the terminal PS' chain. In the lowest-molar-mass set of tetrablock polymers, the shift from order to disorder was observed in the materials at ambient temperature as the molar mass of the terminal PS' block was increased, consistent with SCFT calculations. Disorder with longer S' chain lengths was not found in the two higher-molar-mass polymer sets; the medium-molar-mass set showed both microphase separation and long-range order based on transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS), while the largest of these block polymers microphase separated but showed limited long-range order. The combination of the experimental and theoretical results presented in this work provides insights into the self-assembly of ABCA'-type polymers and highlights potential complications that arise from frustration in accessing well-ordered materials.
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PMID:Order and Disorder in ABCA' Tetrablock Terpolymers. 3313 93