Give 'til it hurts: trade-offs between immunity and male reproductive effort in the decorated cricket, Gryllodes sigillatus.

Trade-offs between life-history variables can be manifested at either the phenotypic or genetic level, with vastly different evolutionary consequences. Here, we examined whether male decorated crickets (Gryllodes sigillatus) from eight inbred lines and the outbred founder population from which they were derived, trade-off immune effort [lytic activity, phenoloxidase (PO) activity or encapsulation] to produce spermatophylaxes: costly nuptial food gifts essential for successful sperm transfer. Canonical correlation analysis of the outbred population revealed a trade-off between spermatophylax mass and lytic activity. Analysis of our inbred lines, however, revealed that although PO activity, encapsulation, body mass, spermatophylax mass and ampulla (sperm capsule) mass were all highly heritable, lytic activity was not, and there was, therefore, no negative genetic correlation between lytic activity and spermatophylax mass. Thus, males showed a phenotypic but not a genetic trade-off between spermatophylax mass and lytic activity, suggesting that this trade-off is mediated largely by environmental factors.

Inbred decorated crickets exhibit higher measures of macroparasitic immunity than outbred individuals.

Inbreeding is assumed to have negative effects on fitness, including the reduced ability to withstand immune challenges. We examined the immunological consequences of inbreeding in decorated crickets, Gryllodes sigillatus, by comparing lytic activity, phenoloxidase (PO) activity, and encapsulation ability of crickets from eight inbred lines with that of crickets from the outbred founder population. Surprisingly, crickets from inbred lines had a greater encapsulation ability compared with crickets from the outbred population. We suggest that because inbred crickets have reduced reproductive effort, they may, therefore, have the option of devoting more resources to this form of immunity than outbred individuals. We also found that both inbred and outbred females had higher immunity than males in PO activity and implant darkness. This result supports the hypothesis that females should devote more effort to somatic maintenance and immunity than males. PO activity and implant darkness were heritable in both males and females, but lytic activity was only heritable in females. Males and females differed in the heritability of, and genetic correlations among, immune traits, suggesting that differences in selective pressures on males and females may have resulted in a sexual conflict over optimal immune trait values.

Planar imaging versus gated blood-pool SPECT for the assessment of ventricular performance: a multicenter study.

UNLABELLED: Gated blood-pool SPECT (GBPS), inherently 3-dimensional (3D), has the potential to replace planar equilibrium radionuclide angiography (ERNA) for computation of left ventricular ejection fraction (LVEF), analysis of regional wall motion (RWM), and analysis of right heart function. The purpose of this study was to compare GBPS and ERNA for the assessment of ventricular function in a large, multicenter cohort of patients. METHODS: One hundred seventy-eight patients referred in the usual manner for nuclear medicine studies underwent ERNA followed by GBPS. Each clinical site followed a GBPS acquisition protocol that included 180 degrees rotation, a 64 by 64 matrix, and 64 or 32 views using single- or double-head cameras. Transverse GBPS images were reconstructed with a Butterworth filter (cutoff frequency, 0.45-0.55 Nyquist; order, 7), and short-axis images were created. All GBPS studies were processed with a new GBPS program, and LVEF was computed from the isolated left ventricular chamber and compared with standard ERNA LVEF. Reproducibility of GBPS LVEF was evaluated, and right ventricular ejection fraction (RVEF) was computed in a subset of patients (n = 33). Using GBPS, RWM and image quality from 3D surface-shaded and volume-rendered cine displays were evaluated qualitatively in a subset of patients (n = 30). RESULTS: The correlation between GBPS LVEF and planar LVEF was excellent (r = 0.92). Mean LVEF was 62.2% for GBPS and 54.1% for ERNA. The line of linear regression was GBPS LVEF = (1.04 x ERNA LVEF) + 6.1. Bland-Altman plotting revealed an increasing bias in GBPS LVEF with increasing LVEF (Y = 0.13x + 0.61; r = 0.30; mean difference = 8.1% +/- 7.0%). Interoperator reproducibility of GBPS LVEF was good (r = 0.92). RVEF values averaged 59.8%. RWM assessment using 3D cine display was enhanced in 27% of the studies, equivalent in 67%, and inferior in 7%. CONCLUSION: GBPS LVEF was reproducible and correlated well with planar ERNA. GBPS LVEF values were somewhat higher than planar ERNA, likely because of the exclusion of the left atrium.

Quantitative gated blood pool SPECT for the assessment of coronary artery disease at rest.

BACKGROUND: Planar gated blood pool imaging (GBPI) has long proven to be useful for the noninvasive assessment of ventricular function. From a practical viewpoint, gated blood pool single photon emission computed tomography (GBPS) acquisition can be accomplished in the same time as a three-view planar series, with the benefit of a tomographic perspective that avoids chamber overlap. METHODS AND RESULTS: Quantitative gated blood pool SPECT was applied to 10 patients who underwent coronary arteriography, contrast ventriculography, and planar gated blood pool imaging. For each patient, the mid-short axis oblique slice was divided into 4 discrete segments using 4 different reference models and 2 forms of segmentation. A center of mass (counts) fixed in the end-diastolic frame and segmentation that bisected the ventricular septum proved to have the highest sensitivity and specificity for determining regional wall motion abnormalities at rest in myocardium supplied by severely diseased coronary arteries (>75 %). GBPS correctly identified 19 of 21 abnormal segments (90%), with good specificity (95%), whereas ventriculography identified 12 (57%) and planar GBPI identified 9 (43%) of the segments supplied by diseased coronaries. CONCLUSION: Quantitative GBPS appears to be a sensitive method for assessing coronary artery disease at rest in myocardium perfused by severely diseased coronary arteries.

Validation of a knowledge-based boundary detection algorithm: a multicenter study.

A completely operator-independent boundary detection algorithm for multigated blood pool (MGBP) studies has been evaluated at four medical centers. The knowledge-based boundary detector (KBBD) algorithm is nondeterministic, utilizing a priori domain knowledge in the form of rule sets for the localization of cardiac chambers and image features, providing a case-by-case method for the identification and boundary definition of the left ventricle (LV). The nondeterministic algorithm employs multiple processing pathways, where KBBD rules have been designed for conventional (CONV) imaging geometries (nominal 45 degrees LAO, nonzoom) as well as for highly zoomed and/or caudally tilted (ZOOM) studies. The resultant ejection fractions (LVEF) from the KBBD program have been compared with the standard LVEF calculations in 253 total cases in four institutions, 157 utilizing CONV geometry and 96 utilizing ZOOM geometries. The criteria for success was a KBBD boundary adequately defined over the LV as judged by an experienced observer, and the correlation of KBBD LVEFs to the standard calculation of LVEFs for the institution. The overall success rate for all institutions combined was 99.2%, with an overall correlation coefficient of r=0.95 (P<0.001). The individual success rates and EF correlations (r), for CONV and ZOOM geometers were: 98%, r=0.93 (CONV) and 100%, r=0.95 (ZOOM). The KBBD algorithm can be adapted to varying clinical situations, employing automatic processing using artificial intelligence, with performance close to that of a human operator.

In utero exposure to cocaine: a review.

Cocaine is now regarded as one of the most dangerous illicit drugs available today. A disturbing trend in the pattern of cocaine use is that groups long considered unlikely to be involved in drug use, including women of childbearing age, pregnant women, the pediatric age group, fetuses, and neonates, are showing an alarming increase in cocaine exposure. Substantial data have been derived from clinical observations, clinical studies, and animal studies indicating that prenatal exposure to cocaine may have detrimental short-term and possibly long-term effects on the mother, the developing fetus, and the neonate. The effects attributed to cocaine may, however, be due to other substances (eg, alcohol) ingested by the drug-using woman, to prematurity, or to the environmental chaos in which the infant must develop. Prospective controlled studies are needed to define further the effects of cocaine as distinct from other negative influences having an impact on the developing fetus, the newborn, or the infant.

The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart.

In order to evaluate the accuracy of blood flow measurement, the single-pass extraction, retention/wash-out and relative net uptake of 99mTc-teboroxime (SQ30217) and 201Tl were evaluated and compared in 20 isolated blood-perfused rabbit hearts at coronary flow rates ranging from 0.49 to 2.85 ml/g wet wt min-1. The average peak extraction of 201Tl (+/- s.d.) (0.67 +/- 0.11) marginally exceeded that of SQ30217 (0.62 +/- 0.12) (p = 0.06). Flow significantly affected the maximum net extraction of 201Tl and the 40-min net extractions of both 201Tl and SQ30217. Unexpectedly, the rate of 201Tl myocardial washout was significantly faster (p less than 0.05) than SQ30217 washout at all flow rates evaluated. Increasing coronary blood flow rate was associated with a more rapid clearance of both tracers from the myocardium (p less than 0.05 for both comparisons). The slope of the linear correlations between relative net SQ30217 uptake versus flow and relative net 201Tl uptake versus flow were found to be similar for up to 10 min after isotope injection. These data were interpreted to indicate that: 1. Thallium-201 might be slightly better extracted than SQ30217. 2. SQ30217 is cleared more slowly from the myocardium. 3. Thallium-201 and SQ30217 appear to be comparable tracers of myocardial perfusion for up to 10 min after injection under the single-pass conditions currently employed. 4. Additional studies are needed to clarify myocardial SQ30217 kinetics.

Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile and thallium-201 extraction, washout, and retention at varying coronary flow rates in rabbit heart.

Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Tc-MIBI) and thallium-201 extraction, washout, and retention were investigated and compared in 20 isolated, isovolumic, retrograde blood-perfused rabbit hearts at flow rates ranging from 0.5 to 3.5 ml/g wet wt min-1 in the absence of tracer recirculation. Mean Tc-MIBI peak instantaneous extraction was lower (0.55 +/- 0.10, p less than 0.001) and more affected by flow rate (p less than 0.05) than 201Tl peak instantaneous extraction (0.83 +/- 0.06). In contrast, the rate of 201Tl washout was significantly faster (p less than 0.05) and initially more dependent on perfusion rate (p less than 0.05) than Tc-MIBI washout. Reflecting its higher peak instantaneous extraction, 201Tl retention was 55-79% higher immediately after isotope injection (p less than 0.001) than Tc-MIBI retention, and relative changes in maximal 201Tl net uptake correlated better (p less than 0.05) with relative flow changes than maximal Tc-MIBI net uptake. However, due to its faster washout rate, the superiority of thallium over Tc-MIBI as a perfusion indicator was lost within 10 minutes of tracer injection under the present single-pass experimental conditions. These data were interpreted to indicate that 1) Tc-MIBI is not as well extracted and has a slower washout rate than 201Tl; 2) varying the coronary flow rate has significant but divergent effects on the extraction, washout, and retention of Tc-MIBI and 201Tl; and 3) the present results support continued evaluation of Tc-MIBI as a possible perfusion indicator.

Response to exercise after withdrawal from chronic alcoholism.

To test for early evidence of alcoholic cardiomyopathy and to assess changes in exercise response after abstinence, 12 asymptomatic alcoholic men (group 1) underwent maximal upright bicycle exercise radionuclide ventriculography two to six days after alcohol withdrawal. Six of these patients (group 1A) had similar testing two to four weeks later. Six control subjects (group 2) had repeated exercise tests without isotope study. Group 1 left ventricular ejection fraction response (LVEF) was normal. LVEF at similar workloads did not differ in group 1A (p = NS). However, unlike group 2 results, the linear regression line relating double product to exercise stage in group 1A was higher at first exercise (p less than 0.05), probably due to the effects of alcohol withdrawal. We conclude that radionuclide left ventriculographic findings in these patients do not support the concept of a preclinical alcoholic cardiomyopathy made apparent by exercise, and exercise very early after alcohol withdrawal is associated with an increased myocardial oxygen demand at any given workload.

Intranasal salmon calcitonin treatment of Paget's disease of bone. Results in nine patients.

To ascertain whether salmon calcitonin, usually given parenterally, could control active Paget's disease when given by nasal insufflation, intranasal salmon calcitonin (INSC) was given to nine men with Paget's disease whose serum alkaline phosphatase (SAP) levels were elevated twofold or more. Treatment with 100, 200, and 400 IU/day for three to nine months was well tolerated. SAP fell 31%-51% in three patients and more than 20% in two others. Three of four men who had previously received salmon calcitonin (SC) by injection had no response of SAP but had a rise in antibodies to SC. INSC is mildly effective and more convenient than parenteral SC, but dose response and efficacy relative to parenteral SC have not been established, thereby raising questions of cost-effectiveness.

Detection of corticosteroid type I binding sites in heart.

Both high affinity (type I) and low affinity (type II) corticosteroid binding sites are detected in cytosolic extracts of atrial and ventricular tissue when [3H]aldosterone is used as the ligand. In the presence of RU-28362, which blocks binding of [3H]hormone to the low affinity type II sites, [3H]aldosterone binds to a single class of high affinity sites. The apparent Kd for binding of the hormone to the type I sites was 1.0 nM in atrial cytosol and 0.75 nM in ventricular cytosol. The concentration of type I sites in atrial (12 fmol/mg protein) and ventricular cytosols (11 fmol/mg protein) is comparable to reported values in renal (17-31 fmol/mg protein) cytosol. Activation of the type I hormone-receptor complexes to the DNA-binding form was examined using chromatography on DEAE-Sephadex anion-exchange resin. The unactivated hormone-receptor complex elutes at a concentration of 400 mM KCl. Following heat treatment (25 degrees C, 30 min) the [3H]aldosterone-receptor complex is transformed to a low salt eluting (200 mM KCl), DNA-binding form. Activation is blocked by inclusion of 10 mM sodium molybdate during heat treatment.

Generation of corticosteroid binder IB from binder II by a sulfhydryl dependent renal cytosolic factor.

It has long been debated whether binder IB represents a unique form of the glucocorticoid receptor or is derived from the larger molecular weight form, binder II, by limited proteolysis. Transformed glucocorticoid receptors in kidney, liver and mixed kidney/liver cytosols were examined using anion exchange and gel filtration chromatography. The transformed receptor in liver cytosols chromatographs as binder II on DEAE-Sephadex A-50 anion exchange columns and has a Stokes radius of approx 6.0 nm. The transformed receptor in kidney cytosols chromatographs as binder IB on DEAE-Sephadex A-50 anion exchange columns and has a Stokes radius of 3.0-4.0 nm (3.2 nm on agarose; 3.0-4.0 nm on Sephadex G-100). Using cytosols prepared from mixed homogenates (2 g kidney plus 8 g liver tissue), our experiments show that binder II is converted to a lower molecular weight form (Rs = 3.2 nm on agarose; Rx = 3.9 nm on Sephadex G-100) that is identical to binder IB in its elution position from DEAE-Sephadex anion exchange resin. Identical results are obtained using kidney/liver/cytosols mixed in vitro in which only the hepatic receptor, binder II, is labelled with [3H]TA. These results support the hypothesis that the renal receptor, binder IB, is a proteolytic fragment of binder II and does not represent a polymorphic form of the glucocorticoid receptor. The renal converting activity is dependent on free-SH for full activity but is insensitive to the protease inhibitors leupeptin, antipain, and PMSF. The conversion of hepatic binder II to binder IB in in vitro mixing experiments can be prevented if kidney cytosol is gel filtered on Sephadex G-25 and the eluted macromolecular fraction is adjusted to 10 mM EGTA (or EDTA) prior to mixing with the [3H]TA labelled hepatic cytosol.

Steroid receptor activation: the glucocorticoid receptor as a model system.

The glucocorticoid receptor has been used as a model for steroid receptor activation. Because of recent evidence for the essentially nuclear location of the unoccupied receptors of 1,25-dihydroxycholecalciferol and 17 beta-estradiol, the significance of the activation mechanism converting unactivated receptor complexes to DNA-binding forms is unclear for some receptors. Up to now the weight of evidence favors a cytoplasmic location of the unactivated glucocorticoid receptor. In this article we describe studies on the nature of the activation mechanism and of regulatory factors.

Reversibility of intrapulmonary arteriovenous shunts in liver cirrhosis documented by serial radionuclide perfusion lung scans.

Using serial perfusion lung scans, we have documented the opening up and closure of right-to-left intrapulmonary arteriovenous shunts over a period of several weeks in a patient with chronic alcoholic liver disease. The presence of the shunts correlates well with the severity of hypoxemia and the presence of nodular mottling on chest radiographs. The time course of these changes with clinical status suggests lability and the functional nature of these shunts.

Reverse ventilation--perfusion mismatch.

Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a "reversed" ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients.

Glucocorticoid stimulation of sodium absorption in colon epithelia is mediated by corticosteroid IB receptor.

Studies with RU26988, a synthetic glucocorticoid which does not bind to aldosterone receptors, suggest glucocorticoid-induced colonic cation transport is affected through glucocorticoid-specific receptors. RU26988 produced a 700% increase in sodium absorption and doubled transmural potential difference in proximal and distal colon of adrenalectomized rats. Scatchard analysis suggested a single class of receptors with a KD of approximately 10(-9) M. Competition of unlabeled steroids for [3H]triamcinolone acetonide-binding sites paralleled the steroids' biologic potency as glucocorticoids. Heat treatment (25 degrees C, 30 min) markedly enhanced binding of the glucocorticoid-receptor complexes to DNA-cellulose. The activated receptor from both proximal and distal colon was eluted in the prewash from DEAE-Sephadex A-50 anion exchange columns both in the presence and absence of protease inhibitors and has an estimated molecular weight (Stokes radius) of 33,000-37,000 (25-26 A). These results identify the colonic receptor as glucocorticoid binder IB, a receptor previously identified as the major binder only in kidney cortex. The finding of an apparently unique receptor in the two tissues where glucocorticoids stimulate cation transport suggests that the phenotypic response mediated by glucocorticoids in different tissues might be determined by the structure of the receptor and that glucocorticoid binder IB is the glucocorticoid cation transport receptor.

Identification of a macromolecular inhibitor of glucocorticoid-receptor complex activation in rat liver cytosol.

We have identified an endogenous regulator of the glucocorticoid receptor following fractionation of dialyzed rat liver cytosol on DEAE-cellulose. The macromolecular regulator, purified approximately 20-fold as judged by Lowry-reactive material, inhibits activation of glucocorticoid-receptor complexes when assayed by DNA-cellulose binding and by chromatography on DEAE-cellulose minicolumns. In addition the active DEAE-cellulose fraction stabilizes the unoccupied glucocorticoid receptor against heat inactivation. Evidence is presented that the observed inhibition of activation by the active DEAE-cellulose fraction is not due to concentration of cytosolic proteases or RNA. The inhibitory molecule in the active fraction is not stable to heating at 90 degrees C (15 min) and is partially inactivated at 45 degrees C (15-60 min).