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PubMed1977

On the individual pressure tolerance of the glaucomatous eye.

The individual pressure tolerance of any eye can be determined by taking account of the age, the values of the mean arterial pressure APm, the C/D ratio and the degree of deterioration of the visual field. The method developed opens the way to new possibilities in anti-glaucomatous therapy by making it possible to know the value of the maximum pressure (IPT) which can be supported by the eye under treatment. That treatment must succeed in reducing the value Pi to below the value IPT, if it is to be hoped that the evolution of the glaucoma will be stopped.

Blood Pressure↗

PubMed1979

Effect of capping upon the mRNA properties of satellite tobacco necrosis virus ribonucleic acid.

The mRNA guanyltransferase-mRNA methyltransferases of vaccinia virions can be used to introduce a 5'-terminal m7g(5')pp(5')Apm... capping group onto the RNA of satellite tobacco necrosis virus (STNV RNA) to yield intact capped STNV RNA. Studies with an in vitro system from wheat germ and limiting quantities of capped and uncapped STNV RNA show that the rates and extents of formation of initiation complexes of protein synthesis by intact capped and uncapped STNV RNA are identical, suggesting that 5'-terminal cap groups cannot function in the translation of STNV RNA. Also, the cap analogue pm7G equally inhibits the initiation and the translation of limiting quantities of both capped and uncapped STNV RNA. These contrasting observations suggest that the wheat germ system contains a pm7G sensitive protein and that STNV RNA has a tertiary structure that restricts the function of an added 5'-terminal capping group. This theory is supported by observations that fragmented capped STNV RNA is better at forming initiation complexes than is equally fragmented uncapped STNV RNA.

Adenine Nucleotides↗

PubMed2026

Association between smoking, tumor genetics, and outcomes in men with metastatic prostate cancer.

PURPOSE: Smoking has been associated with increased metastatic prostate cancer mortality, but the mechanisms behind this are largely unknown. We hypothesized that smoking increases the risk of genetic alterations associated with aggressive disease and/or the transformation to neuroendocrine prostate cancer (NEPC). PATIENTS AND METHODS: We utilized the Prostate Cancer Precision Medicine Multi-institutional Collaborative Effort (PROMISE) clinical genomic database for this retrospective analysis. We associated patient characteristics and tumor genetic data with smoking exposure at diagnosis (current, former, never and pack years) and with clinical outcomes, including overall survival (OS) from diagnosis or time to developing metastatic disease and NEPC status. RESULTS: We identified 2353 men with prostate cancer and next generation somatic tumor sequencing evaluable for analysis in PROMISE, including 8% current, 39% former, and 52% never smokers. Current smokers were more likely to be younger and to have metastatic (M1 or N1) disease at diagnosis, and less likely to have prior local therapy (all p < 0.001). Current smoking was associated with worse OS from diagnosis (99.9 mo vs 137.6 mo, HR 1.42, 95% CI 1.14-1.77), which remained significant after adjusting for disease characteristics. We found no difference in the percentage of NEPC at initial diagnosis or at any time between current, former, and never smokers (p = 0.8). We found positive associations between smoking status and genetic alterations in SPOP (current: 15%, former 6.7%, never 3.8%; p = 0.018), FGFR1 (current 10%, former 0.4%, never 1.1% p = 0.001), and ARID1A (current 5.1%, former 2.2%, never 0.4%; p = 0.035) in patients with metastatic androgen pathway modulator sensitive prostate cancer (APMS). CONCLUSION: Active smoking is associated with worse overall and prostate cancer specific survival as compared to never/former smoking and was associated with specific tumor genetic alterations but not small cell/NEPC transformation.

Journal Article↗

PubMed1975

Myocardial and plasma levels of adenosine 3':5'-cyclic phosphate. Studies in experimental myocardial ischemia.

Alterations in myocardial and plasma levels of adenosine 3':5'-cyclic phosphate (cyclic AMP) were studied following clamping of the aorta or coronary artery occlusion in 30 dogs. Plasma cyclic APM levels increased markedly after thoracotomy but returned to control levels two hours later. Complete arrest of aortic flow (clamping) induced a significant early increase in the myocardial cyclic AMP levels of all animals studied. No increase was noted following pretreatment with propranolol or sham-occlusion. After localized coronary occlusion, only modest and insignificant changes occurred in plasma cyclic AMP levels in anesthetized animals and also in conscious dogs. The present study suggests that adrenergically mediated changes in tissue cyclic AMP content are an early manifestation of both generalized and local myocardial ischemia, while the plasma cyclic AMP level is a relatively insensitive indicator of small coronary occlusions.

Animals↗

PubMed1977

The differential mobilization of human neutrophil granules. Effects of phorbol myristate acetate and ionophore A23187.

Phorbol myristate acetate (PMA, 2 to 100 ng/ml) and ionophore A23187 (10(-7) to 10(-6) M) cause human neutrophils to release up to 50% of the granule-associated enzyme lysozyme extracellularly without release of beta-glucuronidase or the cytoplasmic enzyme LDH. When azurophil and specific granules are separated from neutrophil lysates by sucrose density centrifugation, it is found that lysozyme release from neutrophils exposed to PMA or to A23187 reflects a selective disappearance of the small, peroxidase-negative (specific) granules from the cells. These studies demonstrate that neutrophils can mobilize the specific and azurophil granules independently. These studies also demonstrate that under certain conditions the specific granules of human neutrophils behave like the storage granules of secretory cells. Finally, these studies show that techniques of separating neutrophil granules according to their sedimentation characteristics successfully divide these granules into populations that are distinct not only by cytochemical and morphologic criteria but also according to their availability for mobilization and extracellular release. (APM J Pathol 87:273-284, 1977).

Anti-Bacterial Agents↗

PubMed1977

Utilization of kerosene by a hydrocarbon-assimilating strain of Fusarium oxisporum.

Fusarium oxysporum IFO 6384 was grown in three different media, one containing glucose and two containing kerosene as carbon source. One of the kerosene media contained also Tween 60. The harvested dry mats were weighed at various stages of growth. Substitution of glucose with kerosene led to a sharp drop in the production of fungal mycelia. Analysis of the mat samples representing maximum yields indicated that the mycelia grown in the kerosene media were richer in free amino acid and poorer in protein as well as in polymeric and low-molecular weight carbohydrates than those grown in the glucose medium. Treatment of the culture filtrates with three volumes of acetone led to the separation of two fractions. In the first, acetone soluble fraction the free sugars and amino acids were determined, whereas the second, acetone precipitable one, was examined for its proteolytic activity. The gelatinase activity of the acetone precipitable material (APM) obtained from the kerosene media was lower than that from the glucose medium. The former activity, in contrast to the latter reached its maximum and minimum values at pHs 4 and 9, respectively.

Cell Division↗