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The specificity of a "two-site" immunoradiometric assay (IRMA) has been reevaluated by examining its ability to detect heterogeneous adrenocorticotrophin-like immunoreactivity (ACTH-LI) separated by gel column chromatography. Plasma samples from patients with Addison's disease, Nelson's syndrome and ectopic ACTH syndrome and tissue extract of human anterior pituitary were subjected to ACTH-IRMA and the levels of ACTH-LI were compared with those measured by conventional ACTH-radioimmunoassay (RIA). The level of ACTH-LI measured by IRMA was considerably lower than that measured by RIA in the plasma of a case of ectopic ACTH syndrome and the ACTH-LI did not show a dilution curve parallel with that of the standard. Gel exclusion chromatography revealed that the plasma contained a relatively large quantity of "big ACTH" which was found to be poorly detected by the IRMA. In the plasma of Addison's disease or the extract of pituitary gland in which "big ACTH" constituted a small portion, whole ACTH-LI was apparently diluted in parallel with the ACTH standard, although the "big ACTH" also did not show full parallelism with the ACTH standard in the IRMA. These data suggest that "big ACTH" derived not only from an ectopic ACTH-producing tumour but also from a normal human pituitary gland cannot be detected as well as authentic ACTH by the ACTH-IRMA system. Therefore, samples which contain a relatively large proportion of "big ACTH" in the total ACTH-LI should be carefully evaluated by ACTH-IRMA.
After a short "historical" mention of the fundamental stages that produced the protocol and the beginning of the G.I.S.S.I. study, we examine the statistics on the organizing, epidemiological and therapeutic aspects observed during the G.I.S.S.I. study. Even if the collected data are referred only to the 176 CCU participating in the G.I.S.S.I., and the results on mortality and hospitalization time takes into account only the myocardial infarctions randomized for the study, and the criteria used in the analysis (organizational and structural parameters) are considered arbitrary, we underline the evident lack of balance in the geographic distribution of the CCU; this imbalance involves also the instrumental equipment. Furthermore we note a poor, but significative, decrease in the mortality of the Units with a higher hospitalization/year and with a more sophisticated instrumental equipment. Another interesting data, from a clinical and organizational point of view, concerns the high number of patients--10210 out of 20020 (51%)--excluded from the randomization, because hospitalized after 12 hours. This data underlines the big problem of the "pre-coronary" time, which is still to long, actually, in our country. These data must induce to increase the efforts to develop the network of CCU in our Country and to inform the people and the sanitary operators about the usefulness of quicker therapeutic intervention. From an epidemiological investigation, the best results were obtained in the patients hospitalized within the first few hours from the onset of the symptoms.
The prothoracicotropic hormones (PTTHs) are cerebral peptides that control insect postembryonic development by stimulating the prothoracic glands to synthesize ecdysteroids. In Manduca sexta, the tobacco hornworm, two classes of PTTH are distinguished by their M(r), small (ca. 7 kDa) and big PTTH (ca. 25-30 kDa). Little is known about the physical nature of the PTTHs and this study takes a first step towards defining characteristics of the Manduca big PTTH. The neurohormone has a Stokes radius of 2.59 nm and a sedimentation coefficient of 2.76 S. Based on these data, an M(r) of 29,443.7 and an f/fo of 1.27 were calculated. Combined, the physical data reveal Manduca big PTTH is an asymmetrical acidic homodimeric peptide with intra- and intermolecular disulfide bonds.
This study aimed to determine the lag time between increased fluoride (F) intake and F detection in human nails, as well as the influence of nails growth rate and length on this. Ten 20- to 35-year-old volunteers received 1.8 mg F daily, for 30 days. Nail growth rate and length were determined for all fingernails and toenails. Nail samples were collected at the beginning of the study and every 2 weeks (15 collections in all) and F concentrations were determined. The growth rate was statistically higher in fingernails than in toenails. No statistically significant differences were observed between right and left sides. Growth rate was significantly greater for big toenails than for the other toenails, but this pattern was not found for fingernails. The estimated mean lag times for F detection in fingernails and toenails were 101 and 123 days, respectively. An apparent increase in fingernail F concentrations was observed 84 days after the beginning of the study, although this was not statistically different from baseline. For toenails, statistically significant increases in F concentration in relation to baseline were observed 112 and 140 days after increased F ingestion. These increases occurred within the 95% confidence intervals for the calculated mean lag time for fluoride detection in nails. Considering the large amount of sample provided by the big toenails, together with their faster growth rate, as well as the fact that toenails are less prone to environmental contamination, our data suggest that big toenails are more suitable biomarkers of fluoride intake.
Water demands in arid and semi-arid areas, coupled with increased human populations and concomitant changes in land use, can greatly alter aquatic ecosystems. A good example of this type of system occurs along the eastern slope of the Colorado Rocky Mountains, U.S.A. Long-term macroinvertebrate metric data from the Big Thompson and Cache la Poudre Rivers, Colorado, were collected at one site above, and three sites in and downstream from urban areas. These data were compared both with regional reference and single reference sites in the respective rivers. Using the surrogate variables of potential urban impact (population and housing units), and the environmental gradient represented primarily by chemical factors, it was determined that there was an effect of urban land use that was reflected in the macroinvertebrate assemblages in both rivers. The most robust results were usually seen when regional reference data were used. However, even using only the upstream reference site in either river indicated some negative impacts from the urban areas. The long-term data, particularly in the Cache la Poudre River, showed that water quality has not been getting worse and there is some evidence of a slight improvement in downstream reaches, even with increased urban development.
Serum insulin-like growth factor II (IGF-II) was characterized by radioimmunoassay and Western immunoblot in 44 patients with non-islet cell tumor hypoglycemia (NICTH). 31 of 44 patients with NICTH had big IGF-II in sera. When the presence of IGF-II in tumors from 20 patients was investigated, IGF-II in tumors was detected in 18 patients and these patients had big IGF-II in sera. In two patients whose tumors did not contain IGF-II, big IGF-II in sera was not detected. In six patients with IGF-II in tumors, hypoglycemia disappeared and the big IGF-II decreased after successful removal of the tumors. These data indicate that the big IGF-II could be related to hypoglycemia, and that the increased serum big IGF-II suggests IGF-II-producing NICTH. Serum IGF-II levels in 31 patients with big IGF-II were greater than those in 13 patients without it (Mean +/- SEM: 723+/-54 vs. 326+/-31 ng/ml), but the elevated IGF-II levels were found in only 13 patients. Serum IGF-I levels were low in all patients with NICTH. In the 13 patients without big IGF-II, serum IGF-II levels were lower than those in the patients with big IGF-II, and serum IGF-I levels were also low. Serum IGF-II/IGF-I ratios in the patients with big IGF-II were elevated and greater than those in the patients without big IGF-II (35.0+/-2.2 vs. 11.5+/-2.4). The present data indicate that IGF-II-producing tumors are not rare in NICTH, and serum big IGF-II and IGF-II/IGF-I ratio are useful for screening patients with IGF-II-producing NICTH.
The newly available techniques for sensitive proteome analysis and the resulting amount of data require a new bioinformatics focus on automatic methods for spectrum reprocessing and peptide/protein validation. Manual validation of results in such studies is not feasible and objective enough for quality relevant interpretation. The necessity for tools enabling an automatic quality control is, therefore, important to produce reliable and comparable data in such big consortia as the Human Proteome Organization Brain Proteome Project. Standards and well-defined processing pipelines are important for these consortia. We show a way for choosing the right database model, through collecting data, processing these with a decoy database and end up with a quality controlled protein list merged from several search engines, including a known false-positive rate.
OBJECTIVES: To explore the extent to which the domains of the Big 5 are risk factors for hypochondriacal concerns (HCs). METHODS: Two longitudinal studies, one using blood donors (over a 16-17-month period) and one using undergraduate students (over a 2.5-month period), were used to collect data on the Big 5 and HCs. RESULTS: Univariate analyses indicated that: (1) emotional stability predicted future levels of HCs once baseline levels of HCs were controlled, and (2) reductions in HCs over time were predicted primarily by increases in conscientiousness and emotional stability scores. Structural modelling of cross-lagged effects indicated that emotional stability was related to future levels of hypochondriacal concerns by contributing to initial levels of HCs. Regression analysis indicated that those who become more conscientious become less health anxious. CONCLUSIONS: Emotional stability and conscientiousness have predictive roles with respect to HCs.
Non-islet cell tumor hypoglycemia (NICTH) is one of major causes of fasting hypoglycemia. In some patients with NICTH, insulin-like growth factor II (IGF-II) produced by and secreted from the tumors is thought to be a hypoglycemic agent. In patients with NICTH, the major form of IGF-II is high molecular weight form of IGF-II, designated as big IGF-II. The generation of big IGF-II in the NICTH syndrome is unclear. It has been reported that in the patients with NICTH big IGF-II lacks normal E-domain O-linked glycosylation, suggesting that the patient's big IGF-II might be generated by abnormal processing of pro-IGF-II. However, we have found that the apparent size of big IGF-II varies in sera from the patients with NICTH, and that there is a possibility that slower migration pattern of IGF-II might be because of a different size of sugar moiety attached to pro-IGF-II. In the present study using the sera from 10 patients with NICTH, we investigated the effect of O-glycosidase digestion on migration of IGF-II and analyzed the results by Western immunoblot. By Western immunoblot analysis the big IGF-II was reduced in size to 9.5 kDa in the enzyme-treated sera of the 10 patients with NICTH. The migration pattern is similar to that observed in sera of normal subjects after O-glycosidase digestion. These data indicate that big IGF-II from patients with NICTH is O-glycosylated, and the sizes of the sugar moiety are larger than those from normal subjects suggesting abnormal glycosylation in NICTH.
The amount of data produced by molecular biologists is growing at an exponential rate. Some of the fastest growing sets of data are measurements of gene expression, comparable in quantity only to gene sequences and the vast biological literature. Both gene expression data and sequence data offer hints as to the functions of thousands of newly discovered genes, but neither give complete answers. Therefore, much effort is being focused on integrating these large data sets and combining them with all available functional data to draw inferences about the functions of uncharacterised genes. This review discusses the most pertinent functional data for genome-wide functional inference and describes several methods by which these disparate data types are being integrated.
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A specific radioimmunoassay (RIA) for the carboxyl-terminal fragment (CTF) of big porcine endothelin (pET), an intermediate form of pET, was established to characterize big ET-like and its CTF-like immunoreactivity (LI) secreted from cultured bovine and human endothelial cells (EC). The antibody used crossreacted equally with big pET(1-39) and its CTF(22-39), but not with pET(1-21). Serial dilution curves of the culture media from bovine and human EC were parallel to that of standard CTF. Reverse-phase HPLC coupled with RIAs for big ET and ET of the culture media from bovine and human EC revealed essentially the same elution profiles: two major CTF-LI components, one corresponding to big pET(1-39) and the other to its CTF(22-39), in addition to one major ET-LI component corresponding to pET(1-21). The amounts of CTF-LI were almost equal to that of ET-LI on a molar basis. These data suggest that big ET is processed by a putative ET converting enzyme to yield its CTF and the mature ET(1-21) in EC.
Bolus injections of Big-endothelin-(1-39) (Big-ET; 0.1-3.0 nmol/kg) induced a dose-dependent diuretic and natriuretic response in conscious Sprague-Dawley rats. Endothelin-1-(1-21) (ET-1; 1 nmol/kg) induced an opposite effect with almost complete renal shut down. Renal blood flow did not change with Big-ET but was reduced by half with ET-1. Although the maximal pressor responses of the two peptides were comparable the renal resistance did not change with Big-ET but increased 4-fold with ET-1. These data suggest that Big-ET may have a different mechanism of action than ET-1.
Differential gene expression detection and sample classification using microarray data have received much research interest recently. Owing to the large number of genes p and small number of samples n (p >> n), microarray data analysis poses big challenges for statistical analysis. An obvious problem owing to the 'large p small n' is over-fitting. Just by chance, we are likely to find some non-differentially expressed genes that can classify the samples very well. The idea of shrinkage is to regularize the model parameters to reduce the effects of noise and produce reliable inferences. Shrinkage has been successfully applied in the microarray data analysis. The SAM statistics proposed by Tusher et al. and the 'nearest shrunken centroid' proposed by Tibshirani et al. are ad hoc shrinkage methods. Both methods are simple, intuitive and prove to be useful in empirical studies. Recently Wu proposed the penalized t/F-statistics with shrinkage by formally using the (1) penalized linear regression models for two-class microarray data, showing good performance. In this paper we systematically discussed the use of penalized regression models for analyzing microarray data. We generalize the two-class penalized t/F-statistics proposed by Wu to multi-class microarray data. We formally derive the ad hoc shrunken centroid used by Tibshirani et al. using the (1) penalized regression models. And we show that the penalized linear regression models provide a rigorous and unified statistical framework for sample classification and differential gene expression detection.
A repeater type telemetry system was developed and field tested on a wild elk near laramie, Wyoming, in the summer of 1973. The telemetry system consisted of the following: (a) a heat flow rate sensing implanted transmitter, (b) a repeater type neck collar and (c) a portable receiving station consisting of a receiver, decoding circuitry and analog chart recorder. The transmitter in (a) produced relatively low frequency rf pulses whose repetition rate was directly proportional to heat flow rate through the hide of the animal. In (b), the pulses from the implant are sensed and retransmitted using a relatively high power, high frequency transmitter. A second rf pulse was generated whose pulse spacing was related to animal activity. Details of circuit design and performance are given. Field experience has shown that this method is extremely useful for the monitoring of biological data from secretive big game animals such as elk.
The big brown bat (Eptesicus fuscus) is an aerial-feeding insectivorous species that relies on echolocation to avoid obstacles and to detect flying insects. Spatial perception in the dark using echolocation challenges the vestibular system to function without substantial visual input for orientation. IR thermal video recordings show the complexity of bat flights in the field and suggest a highly dynamic role for the vestibular system in orientation and flight control. To examine this role, we carried out laboratory studies of flight behavior under illuminated and dark conditions in both static and rotating obstacle tests while administering heavy water (D2O) to impair vestibular inputs. Eptesicus carried out complex maneuvers through both fixed arrays of wires and a rotating obstacle array using both vision and echolocation, or when guided by echolocation alone. When treated with D2O in combination with lack of visual cues, bats showed considerable decrements in performance. These data indicate that big brown bats use both vision and echolocation to provide spatial registration for head position information generated by the vestibular system.