Nitric oxide directly activates calcium-activated potassium channels from rat brain reconstituted into planar lipid bilayer

AbstractUsing the planar lipid bilayer technique, we tested whether NO directly activates calcium-activated potassium (Maxi-K) channels isolated from rat brain. We used streptozotocin (STZ) as NO donor, and the NO release was controlled with light. In the presence of 100–800 μM STZ, the Maxi-K channel activity increased up to 3-fold within several tens of seconds after the light was on, and reversed to the control level several minutes after shutting off the light. Similar activation was observed with other NO donors such as S-nitroso-N-acetylpenicillamine and sodium nitroprusside. The degree of activity increase was dependent upon the initial open probability (Pinit). When the Pinit was lower, the activity increase was greater. These results demonstrate that NO can directly affect the Maxi-K channel activity, and suggest that the Maxi-K channel might be one of the physiological targets of NO in brain

Spectra of Chromosomal Aberrations in 325 Leukemia Patients and Implications for the Development of New Molecular Detection Systems

This study investigated the spectrum of chromosomal abnormalities in 325 leukemia patients and developed optimal profiles of leukemic fusion genes for multiplex RT-PCR. We prospectively analyzed blood and bone marrow specimens of patients with acute leukemia. Twenty types of chromosomal abnormalities were detected in 42% from all patients by commercially available multiplex RT-PCR for detecting 28 fusion genes and in 35% by cytogenetic analysis including FISH analysis. The most common cytogenetic aberrations in acute myeloid leukemia patients was PML/PARA, followed by AML1/MGT8 and MLL1, and in acute lymphoid leukemia patients was BCR/ABL, followed by TEL/AML1 and MLL1 gene rearrangement. Among the negative results for multiplex RT-PCR, clinically significant t(3;3)(q21;q26.2), t(8;14)(q24;q32) and i(17)(q10) were detected by conventional cytogenetics. The spectrum and frequency of chromosomal abnormalities in our leukemia patients are differed from previous studies, and may offer optimal profiles of leukemic fusion genes for the development of new molecular detection systems

Association between serum osteoprotegerin level and renal prognosis in nondialysis patients with chronic kidney disease in the Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease (the KNOW-CKD Study)

Background Osteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients. Methods We analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression. Results The median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041–1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results. Conclusion Serum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression

Consonant geminates: Towards a theory of integrity and inalterability

This dissertation investigates the geminate consonant phenomena known as integrity and inalterability with an eye toward providing a general characterization of geminate behavior as well as a deeper understanding of geminates in a principled and systematic way under the Optimality Theoretic framework. The fundamental proposal made in this dissertation is to have the range of surface geminate patterns follow from varying the ranking of key constraints. Depending on the ranking of the key constraints, languages select different output forms from the same input form. Thus, the key constraints not only conspire to produce anti-integrity/anti-inalterability effects, but they also determine what a language does "do" with its input geminates (i.e. integrity/inalterability), giving rise to different resolutions to the geminate puzzle. A chapter is devoted to an indepth discussion of integrity effects in geminates. For this purpose, seven key constraints are proposed: MAX-IO, DEP-IO, ONS, PROSHIER, ALIGN(WD-R, M-R), PLONS, NOBREAKING. By varying the key constraints, we can make several predictions about the possible geminate patterns according to the positions in which they occur. Several patterns are exemplified in this dissertation. We have also provided a discussion of the gaps between what is predicted to exist and what cases are attested. Another chapter is devoted to a more detailed analysis of inalterability effects in geminates. In particular, it is claimed that geminate inalterability matters only when we deal with weakening processes (e.g. spirantization, sonorantization, etc.). It is also proposed that the constraints IDENT-IO(μSF) and NOBREAKING play a pivotal role in explaining typological differences between weakening and assimilation, and other types of inalterability/anti-inalterability concerning geminates. The most interesting part of this dissertation is that we can explain both integrity/inalterability and anti-integrity/anti-inalterability cases uniformly depending on the ranking of the key constraints, without assuming any ad hoc conditions or procedures. Thus, those anti-integrity and anti-inalterability effects are produced as a natural consequence of the interaction of the constraints, just as in the cases of integrity and inalterability. Finally, unlike previous rule-based approaches, our theory allows for a unified account of integrity and inalterability through the interaction of a set of key constraints, making predictions available about both phenomena

Cellular Movements of Calcium and the Activation Process in Mammalian Heart Muscle

154 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1983.The contractile strength of heart muscle is strongly dependent on the rate of beating, and on the pattern of previous contractions over a period of many seconds. The activator calcium ions, which are responsible for the magnitude of contraction triggered by each action potential, are released from two morphologically and functionally different cellular stores. The characteristics of these stores and the cellular movements of activator calcium were studied by means of simultaneous microelectrode and tension recordings, and measurements of extracellular Ca('++) concentration with Ca('++) -selective electrodes. These electrodes were made from one of the neutral ligands developed by Simon and colleagues (ETH 1001), with the electrode tip diameter 2 to 5 micrometers. The time constant of the electrode-recording system was less than 1 second.Changes in calcium activity were measured during steady states at several frequencies and during rest intervals, with the following results. During rest intervals, extracellular Ca('++) concentration changed in two phases: an initial decline for a few seconds was followed by a slow increase through rest intervals up to more than 60 second duration. Thus, it is concluded that most of activator calcium, which leaves the intracellular stores (T-sites) after a few seconds, is transported across the sarcolemma into the extracellular space. Experiments with ryanodine show a larger Ca('++) efflux and indicate that under normal conditions about one third of this released calcium is bound at membrane-sites (M-sites). The Ca('++) transport across the sarcolemma is a Na('+)-dependent process. Vanadate inhibits Ca('++) efflux and potentiates M-site Ca('++) for increased contractile strength at low frequencies. From extracellular calcium measurements during steady-state contractions, it was found that a smaller amount of Ca('++) is exchanged per beat between the cells and extracellular space at 2 contractions per second than at 1 cps. This confirms that the stronger contraction at higher frequency is due to an increase in Ca('++) made available from intracellular stores.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD