Uncertain role of cAMP in platelet function.
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Animals↗
Biomedical subjects
M J Droller
Publications and source records attributed to M J Droller.
Thrombin-induced increase in intracellular cyclic 3',5'-adenosine monophosphate in human platelets.
The present data disagree with earlier suggestions that thrombin's effect on platelets is to cause a decrease in intracellular cyclic 3',5'-adenosine monophosphate. Washed human platelets or platelet-rich plasma were incubated at 37 degrees C with human thrombin. After centrifugation, the supernates were assayed for nucleotides and calcium released. The platelet pellets, and in some experiments the supernates as well, were assayed by radioimmunoassay for intracellular cyclic AMP. In the washed platelet system, increasing doses of thrombin to 0.5 U/cc induced increasing release of nucleotides and calcium. This was accompanied by an average twofold increase in intracellular cyclic AMP levels. Prostaglandin E(1), which inhibited 30-50% of release, induced a four- to fivefold increase in cyclic AMP levels that was additive to the cyclic AMP-stimulatory effect of thrombin. Theophylline, which inhibited only 20-40% of nucleotide release, was synergistic with thrombin in the intracellular accumulation of cyclic AMP. The time-course of cyclic AMP accumulation in response to thrombin was slower than thrombin-induced nucleotide release. Similar findings were made in the platelet-rich plasma system where thrombin stimulation of nucleotide release also resulted in a marked accumulation of intracellular cyclic AMP. Thrombin did not appear to stimulate the release of intracellular cyclic AMP. The mechanism underlying these observations was not apparent. The thrombin had no measurable inhibitory effect on platelet phosphodiesterase activity in either intact washed cells or the platelet homogenate supernates. Furthermore, thrombin inhibited, rather than stimulated, platelet adenyl cyclase activity in both intact washed cells and washed platelet particulate fractions. Of note, however, was the finding that thrombin did not completely inhibit the adenyl cyclase activity of prostaglandin-stimulated cells. Further work is needed to clarify the significance of this observation.Nonetheless, the accumulation of intracellular cyclic AMP in response to thrombin observed in the present study suggests that the antagonistic actions of various agents on the platelet release reaction, thought to underlie platelet function, may depend upon a mechanism more intricate than a straightforward mediation through directly opposite effects on platelet cyclic AMP.
Adenylyl Cyclase Inhibitors↗
An electron microscope study of yolk formation during oogenesis in Lebistes reticulatus guppyi.
The present investigation describes the fine structural changes that occur during proteid yolk formation in the developing oocytes of the guppy (Lebistes reticulatus), an ovoviviparous teleost. These changes suggest the operation of a number of different intra- and extraoocyte processes that may account for the synthesis and deposition of the proteid yolk. Early in oogenesis, the egg's Golgi systems proliferate and begin to disclose an electron-opaque content. Numerous 70-mmicro diameter vesicles apparently pinch off from the Golgi systems, transport this material through the egg, and probably then fuse to form a crenate, membrane-limited yolk droplet. At the same time, the rough-surfaced endoplasmic reticulum accumulates a flocculent substance that differs in appearance from the Golgi content. Smooth vesicles, presumably derived from the ER, then coalesce to form a second type of intraoocyte yolk droplet. These dissimilar, separately derived droplets subsequently fuse, thus combining the materials that constitute the intraoocyte contribution to the proteid yolk. Somewhat later in development, the egg appears to ingest extracellular material via 75-mmicro diameter bristle-coated micropinocytotic pits and vesicles. These structures apparently fuse to form tubules which then coalesce into large yolk droplets. At a later stage, bristle-coated micropinocytotic vesicles of 100 mmicro diameter presumably take up a material that is then probably immediately deposited into a second type of proteid yolk droplet. It is postulated that these two different micropinocytotic structures are specifically involved with the selective uptake of dissimilar extracellular proteid materials.
Animals↗
Role of immunotherapy in the treatment of bladder and renal cell carcinoma.
Much remains to be learned about the immune response in human neoplasia both in a phenomenological sense and in its therapeutic possibilities. Recruitment of immune response mechanisms in the defense against cancer development and in the cure of advanced disease, though theoretically sound, remains to be proven in demonstration of both its phenomenological and clinical efficacy. The most important steps in this regard will require an analysis of those mechanisms that may truly be active in human cancer. Their enhancement and effective delivery to various tumor sites, then reliable monitoring, and proof of their efficacy will be necessary to accomplish before any conclusive statement can be made as to the usefulness of immunotherapy in the treatment of genitourinary neoplasia and of human cancer in general.
Antigens, Neoplasm↗
Biology of metastasis: clinical implications.
Bladder tumor has a spectrum of neoplastic activity. Some behave in a benign fashion, and others are highly aggressive and lead rapidly to metastatic disease and death. The processes of metastasis can be described as a sequence of interrelated steps. The processes involve 1) tumor cell adhesion to basement membranes, 2) the degradation of basement membranes, and 3) the migration of tumor cells through the destroyed stroma into blood and lymphatic vessels. Each of these processes involves the expression of molecular factors unique to tumor cells. With better understanding of the molecular basis of these factors, novel prognostic and potential therapeutic agents can be generated and applied to the clinical arena.
BCG Vaccine↗
Bladder cancer: state-of-the-art care.
The challenge in bladder cancer is to control superficial disease and prevent its recurrence or progression. Patients with invasive disease need to be identified earlier, when disease may be less advanced and more amenable to cure. An important area for further investigation is the biology of the various forms of bladder cancer and the various pathways of development they may follow.
Biomarkers, Tumor↗