Immunofluorescent localization of human pituitary luteinizing hormone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32182/1/0000238.pd

Understanding the dynamics of cellular responsiveness to modifications of metabolic substrates in perifusion

A novel microperifusion system with capabilities for continuous, real-time, potentiometric monitoring of extracellular hydrogen ion concentration has been used to define the response of HeLa cells to abrupt changes in extracellular energy sources or introduction of an inhibitor of glycolysis. Glycolytic inhibition, induced by removal of glucose or introduction of iodoacetate, each led to a rapid, continuous decrease in acid release. The response to iodoacetate took longer than removal of glucose, perhaps due to the time required for binding and activation. Once inhibition began, however, the rate of change was greater than following glucose removal. Conversely, recovery time following iodoacetate inhibition was much slower than with glucose removal. Unlike the response to short-term glucose depletion, a second pulse of iodoacetate resulted in a faster response followed by an even longer recovery time. The response to switching between glucose and glutamine began almost without evident delay. The response patterns revealed that HeLa cells prefer glutamine to glucose, but, in the presence of both energy sources, some glucose continues to be used. In summary, these results indicate that continuous, real-time monitoring of the kinetics of hydrogen-ion release can be used to gain new insights into the dynamics of cellular response to perturbations of extracellular energy sources. © 1994 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49889/1/1041600103_ftp.pd

Competition for the in vitro binding of radioiodinated human follicle-stimulating hormone in reptilian, avian, and mammalian gonads by nonmammalian gonadotropins

Radioiodinated human FSH (125I-hFSH) was used to study the specificity of the gonadotropin binding sites of various reptilian, avian, and mammalian gonadal tissues by examining competitive interactions with several nonmammalian gonadotropins. All preparations of nonmammalian gonadotropins showed some activity in these radioligand assays, but wide variations in activities were evident depending on the source of the tissue and source of the hormone. Several cases of marked species specificity in binding were apparent: Nonmammalian hormones were relatively inactive with porcine granulosa cells; frog and snake hormones were relatively inactive in turtle tissues; and frog hormones were essentially inactive in avian tissues. FSH-LH specificity of binding determined with hormones of nonmammalian origin differed significantly from that previously described with the aid of mammalian gonadotropins. In particular, when tested with some tissues, three preparations of LH, from the turkey, sea turtle, and frog, were in some cases more active in competing for 125I-hFSH binding than preparations of FSH from the same species; this activity could not be readily accounted for by FSH contamination. These comparative data demonstrate the existence of considerable overlap in the binding characteristics of some species of FSH and LH; the observed differences probably reflect evolutionary changes in both gonadotropin binding sites and in the structure of the gonadotropins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21644/1/0000028.pd

Hapten-radioimmunoassay: A general procedure for the estimation of steroidal and other haptenic substances

Hapten-radioimmunoassay may be used for sensitive and specific quantitation of low molecular weight substances which can be made immunogenic by conjugation to a protein, This method, which involves radioiodination of the protein-portion of the conjugate, has been used for quantitation of non-conjugated estrogenic steroids.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32963/1/0000346.pd

Computer program sequence for analysis and summary of radioimmunoassay data

A sequence of three programs is described for efficient design and analysis of radio-immunoassays. The first program designs the assay; the second program analyzes all available data according to the organizational base provided by the first program; and the third program summarizes the results of several assays in either tabular or graphical form. The analysis program uses a logit response-log dose transformation to obtain a linear inhibition curve for all preparations assayed at multiple levels. The curves are subjected to a weithted, least squares, regression analysis. All curves are tested for linearity and parallelism with the curve chosen as standard, and a weighted mean potency estimate with error limits is computed for all preparations run at single or multiple dose levels with any degree of replication.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34088/1/0000369.pd

Broad-Scale Patterns of Late Jurassic Dinosaur Paleoecology

There have been numerous studies on dinosaur biogeographic distribution patterns. However, these distribution data have not yet been applied to ecological questions. Ecological studies of dinosaurs have tended to focus on reconstructing individual taxa, usually through comparisons to modern analogs. Fewer studies have sought to determine if the ecological structure of fossil assemblages is preserved and, if so, how dinosaur communities varied. Climate is a major component driving differences between communities. If the ecological structure of a fossil locality is preserved, we expect that dinosaur assemblages from similar environments will share a similar ecological structure.This study applies Ecological Structure Analysis (ESA) to a dataset of 100+ dinosaur taxa arranged into twelve composite fossil assemblages from around the world. Each assemblage was assigned a climate zone (biome) based on its location. Dinosaur taxa were placed into ecomorphological categories. The proportion of each category creates an ecological profile for the assemblage, which were compared using cluster and principal components analyses. Assemblages grouped according to biome, with most coming from arid or semi-arid/seasonal climates. Differences between assemblages are tied to the proportion of large high-browsing vs. small ground-foraging herbivores, which separates arid from semi-arid and moister environments, respectively. However, the effects of historical, taphonomic, and other environmental factors are still evident.This study is the first to show that the general ecological structure of Late Jurassic dinosaur assemblages is preserved at large scales and can be assessed quantitatively. Despite a broad similarity of climatic conditions, a degree of ecological variation is observed between assemblages, from arid to moist. Taxonomic differences between Asia and the other regions demonstrate at least one case of ecosystem convergence. The proportion of different ecomorphs, which reflects the prevailing climatic and environmental conditions present during fossil deposition, may therefore be used to differentiate Late Jurassic dinosaur fossil assemblages. This method is broadly applicable to different taxa and times, allowing one to address questions of evolutionary, biogeographic, and climatic importance

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation