Non-parallel Changes Research Articles

The blackgrass genome reveals patterns of non-parallel evolution of polygenic herbicide resistance.

Globally, weedy plants are a major constraint to sustainable crop production. Much of the success of weeds rests with their ability to rapidly adapt in the face of human-mediated management of agroecosystems. Alopecurus myosuroides (blackgrass) is a widespread and impactful weed affecting agriculture in Europe. Here we report a chromosome-scale genome assembly of blackgrass and use this reference genome to explore the genomic/genetic basis of non-target site herbicide resistance (NTSR). Based on our analysis of F2 seed families derived from two distinct blackgrass populations with the same NTSR phenotype, we demonstrate that the trait is polygenic and evolves from standing genetic variation. We present evidence that selection for NTSR has signatures of both parallel and non-parallel evolution. There are parallel and non-parallel changes at the transcriptional level of several stress- and defence-responsive gene families. At the genomic level, however, the genetic loci underpinning NTSR are different (non-parallel) between seed families. We speculate that variation in the number, regulation and function of stress- and defence-related gene families enable weedy species to rapidly evolve NTSR via exaptation of genes within large multi-functional gene families. These results provide novel insights into the potential for, and nature of plant adaptation in rapidly changing environments.

Parallel and non-parallel changes of the gut microbiota during trophic diversification in repeated young adaptive radiations of sympatric cichlid fish

BackgroundRecent increases in understanding the ecological and evolutionary roles of microbial communities have underscored the importance of their hosts’ biology. Yet, little is known about gut microbiota dynamics during the early stages of ecological diversification and speciation. We sequenced the V4 region of the 16s rRNA gene to study the gut microbiota of Nicaraguan Midas cichlid fish (Amphilophus cf. citrinellus). Specifically, we tested the hypothesis that parallel divergence in trophic ecology in extremely young adaptive radiations from two crater lakes is associated with parallel changes of their gut microbiota.ResultsBacterial communities of fish guts and lake water were highly distinct, indicating that the gut microbiota is shaped by host-specific factors. Among individuals of the same crater lake, differentiation in trophic ecology was weakly associated with gut microbiota differentiation, suggesting that diet, to some extent, affects the gut microbiota. However, differences in trophic ecology were much more pronounced across than within species whereas similar patterns were not observed for taxonomic and functional differences of the gut microbiota. Across the two crater lakes, we could not detect conclusive evidence for parallel changes of the gut microbiota associated with trophic ecology.ConclusionsA lack of clearly differentiated niches during the early stages of ecological diversification might result in non-parallel changes of gut microbial communities, as observed in our study system as well as in other recently diverged fish species.2DLR1RhYgjPSYf_AZYrUvAVideo

Physiological and Ecological Responses of Photosynthetic Processes to Oceanic Properties and Phytoplankton Communities in the Oligotrophic Western Pacific Ocean.

Understanding the dynamics of primary productivity in a rapidly changing marine environment requires mechanistic insight into the photosynthetic processes (light absorption characteristics and electron transport) in response to the variability of environmental conditions and algal species. Here, we examined the photosynthetic performance and related physiological and ecological responses to oceanic properties [temperature, salinity, light, size-fractionated chlorophyll a (Chl a) and nutrients] and phytoplankton communities in the oligotrophic Western Pacific Ocean (WPO). Our results revealed high variability in the maximum (Fv/Fm; 0.08–0.26) and effective (Fq′/Fm′; 0.02–0.22) photochemical efficiency, the efficiency of charge separation (Fq′/Fv′; 0.19–1.06), the photosynthetic electron transfer rates (ETRRCII; 0.02–5.89 mol e– mol RCII–1 s–1) and the maximum of primary production [PPmax; 0.04–8.59 mg C (mg chl a)–1 h–1]. All these photosynthetic characteristics showed a depth-specific dependency based on respective nonlinear regression models. On physiological scales, variability in light absorption parameters Fv/Fm and Fq′/Fm′ notably correlated with light availability and size-fractionated Chl a, while both ETRRCII and PPmax were correlated to temperature, light, and ambient nutrient concentration. Since the presence of nonphotochemical quenching (NPQNSV; 2.33–12.31) and increasing reductant are used for functions other than carbon fixation, we observed nonparallel changes in the ETRRCII and Fv/Fm, Fq′/Fm′, Fq′/Fv′. In addition, we found that the important biotic variables influencing Fv/Fm were diatoms (cells > 2 μm), picosized Prochlorococcus, and eukaryotes, but the PPmax was closely related to large cyanobacteria (cells > 2 μm), dinoflagellates, and picosized Synechococcus. The implication is that, on ecological scales, an interaction among temperature, light, and nutrient availability may be key in driving the dynamics of primary productivity in the WPO, while large cyanobacteria, dinoflagellates, and picosized Synechococcus may have a high contribution to the primary production. Overall, the photosynthetic processes are interactively affected by complex abiotic and biotic variables in marine ecosystems, rather than by a single variable.

Non-parallel changes in songbird migration timing are not explained by changes in stopover duration.

Shifts in the timing of animal migration are widespread and well-documented; however, the mechanism underlying these changes is largely unknown. In this study, we test the hypothesis that systematic changes in stopover duration—the time that individuals spend resting and refueling at a site—are driving shifts in songbird migration timing. Specifically, we predicted that increases in stopover duration at our study site could generate increases in passage duration—the number of days that a study site is occupied by a particular species—by changing the temporal breadth of observations and vise versa. We analyzed an uninterrupted 46-year bird banding dataset from Massachusetts, USA using quantile regression, which allowed us to detect changes in early-and late-arriving birds, as well as changes in passage duration. We found that median spring migration had advanced by 1.04 days per decade; that these advances had strengthened over the last 13 years; and that early-and late-arriving birds were advancing in parallel, leading to negligible changes in the duration of spring passage at our site (+0.07 days per decade). In contrast, changes in fall migration were less consistent. Across species, we found that median fall migration had delayed by 0.80 days per decade, and that changes were stronger in late-arriving birds, leading to an average increase in passage duration of 0.45 days per decade. Trends in stopover duration, however, were weak and negative and, as a result, could not explain any changes in passage duration. We discuss, and provide some evidence, that changes in population age-structure, cryptic geographic variation, or shifts in resource availability are consistent with increases in fall passage duration. Moreover, we demonstrate the importance of evaluating changes across the entire phenological distribution, rather than just the mean, and stress this as an important consideration for future studies.

Preliminary Experience in Combined Somatic and Cerebral Oximetry Monitoring in Liver Transplantation

The use of cerebral near-infrared spectroscopy (NIRS) has become widespread in cardiac surgery after research demonstrated an association between perioperative cerebral desaturations and postoperative complications. Somatic NIRS desaturation also is associated with an increased risk of postoperative complications and mortality. The objective of this study was to explore the trends of both somatic and cerebral NIRS during liver transplantation. A prospective, single-site, observational case series. Tertiary care center. The study comprised 10 patients undergoing liver transplantation. NIRS sensors were placed on the forehead (cerebral regional oxygen saturation [rSO2]) and on the right arm and right leg (somatic rSO2) to measure tissue perfusion. Desaturation was defined as a 20% decrease of baseline values for 15 seconds. In all patients, parallel changes in both cerebral and somatic rSO2 values were observed during phlebotomy, bleeding, transfusion, portal vein clamping, and the use of vasoactive agents. Induction of anesthesia increased cerebral rSO2 more than it did somatic values. However, ascites removal, abdominal manipulation, and clamping of the inferior vena cava (IVC) were associated with nonparallel changes in cerebral and somatic rSO2. Ascites removal was associated with increased somatic leg rSO2, and IVC clamping and abdominal hypertension were associated with a significant reduction in somatic leg rSO2. Somatic leg desaturation instead of arm or cerebral desaturation was associated with more postoperative complications. The use of combined NIRS monitoring allows for the identification of the source of somatic or cerebral desaturation. Compromised venous flow from the IVC from clamping or abdominal compartment syndrome typically is associated with the appearance of more pronounced leg than arm desaturation.

The renin–angiotensin–aldosterone system in pre-eclampsia: the delicate balance between good and bad

Pregnancy demands major changes of the cardiovascular system, and this involves, among others, activation of the RAAS (renin-angiotensin-aldosterone system), allowing an aldosterone-dependent increase in volume. Remarkably, a relative resistance to the pressor response of AngII (angiotensin II) develops simultaneously to prevent the increase in blood pressure that would normally accompany RAAS activation. The increase in volume, the degree of RAAS activation and the diminished pressor response to AngII are less pronounced in pre-eclampsia. However, animal models displaying excessive RAAS activation also result in a pre-eclampsia-like syndrome, and the aldosterone/renin ratio is elevated in pre-eclampsia compared with a normal pregnancy. New insights into the pathogenesis of pre-eclampsia have revealed a major role for VEGF (vascular endothelial growth factor), VEGF-inactivating sFlt-1 (soluble fms-like tyrosine kinase-1) and AT1 (angiotensin II type 1) receptor autoantibodies. The last mentioned activate AT(1) receptors, thereby potentially suppressing circulating renin and aldosterone. VEGF, both directly and indirectly (by increasing capillary density), affects adrenal aldosterone synthesis. The present review summarizes all of the recent findings regarding RAAS regulation in pre-eclampsia compared with normal pregnancy, concluding that factors such as sFlt-1 and AT(1) receptor autoantibodies disturb the delicate balance that normally results in a volume increase and a diminished vasoconstrictor response to AngII in pregnant women. It is possible that there are non-parallel changes in the circulating and renal RAAS in pre-eclampsia, which are potentially reflected by the urinary levels of renin.

Contrasting relationships between species diversity and genetic diversity in natural and disturbed forest tree communities

• This study aimed to reveal species-genetic diversity correlations (SGDCs) and their underlying mechanisms in natural and disturbed forests. • A community survey and molecular analyses were carried out to compare species diversity (SD), the genetic diversity of the dominant tree species Euptelea pleiospermum (GD), the altitudinal patterns of SD and GD, SGDC, genetic differentiation (F(ST) ), community divergence (F(ST) -C), effective population size (N(e) ), and recent migration rate between mountain riparian forests along the Yandu (natural) and Nan (disturbed) rivers. • In natural forests, both SD and GD showed a unimodal altitudinal pattern and GD was positively correlated with SD, whereas a unimodal pattern and positive SGDC were not found in the disturbed forests. SD and F(ST) at the natural sites were higher than those at the disturbed sites. However, there were no significant differences in GD, F(ST) -C, N(e) or recent migration rate between the natural and disturbed sites. • A correlation between the patterns of SD and GD along a geographical gradient (e.g. altitude) is an important driver of positive SGDC. The absence of positive SGDC in the disturbed forests may result from reduced SD but unaffected GD, indicating nonparallel changes in SD and GD. This study furthermore cautions against generalizations about changes in SD and GD following disturbance.

Stochastic Optimization for Portfolios Consisting of Corporate Bonds in an Integrated Market and Credit Risk Framework

High credit spreads in 2009 have attracted a lot of interest from investors seeking higher yields outside of government bonds. Investment grade corporate bonds have indeed been a popular investment in 2009. The corporate bond market today is one of the largest and most liquid of the financial markets. Corporate bonds markets can be appealing as they are generally considered safer than stocks and they often provide higher yields and more liquidity than government bonds markets. After the World Financial Crisis central banks set interest rates at their historically low level affecting positively bonds’ prices. The question for a corporate bond portfolio manager is which decisions to take in order to hedge portfolio against volatility of interest rates. Additionally managers have to analyse the factors that affect bonds’ prices volatility and is due to credit risk. For this reasons managers have to implement a risk management framework in order to identify the factor that affect whole portfolio value and finally optimize its value. In an integrated market and risk perspective the future value of a corporate bond portfolio is decomposed into the risk that a bond issued by a firm downgraded by rating agencies and possible drives to default, the correlation between credit events, the risk that changes occur on the average spread of exposures with the same final rating as the firm and the effect of interest rate uncertainty.In chapter 1 we introducing the main types of bonds, analyzing how to valuate non-callable bonds and calculating their yielding and we present factors that affect bond process and price volatility when interest rates changes a bit in a parallel way.In chapter 2 we make an introduction to risk management by referring the risks that affect corporate bond prices. Then we explain the term structure of interest rates and how we can immunize a portfolio of bonds when interest rates changes in a parallel way. Then we introduce a multi-factor model for corporate bonds and present a portfolio immunization model based on factors to protect portfolio value against non-parallel changes of interest rates, introducing the appearance of shape risk.In chapter 3 we added an introduction of credit risk referring the main sources of credit risk in a portfolio of corporate bonds. Then we model credit risk based on a reduced-form approach which defines the default as the instantaneous likelihood of default, called the hazard rate. In chapter 4 we present an integrated market and credit risk framework using scenario generation in order later to optimize a corporate bond portfolio using stochastic programming models. Scenario generation is a tool to model the uncertainty. We develop a model for stochastic interest rates and credit spreads based on the Hull-White algorithm. Interest rates and credit spreads stochasticity based on extended Vasicek model and we produce scenarios of interest rates and credit spreads using trinomial lattice structures which capture the correlation between interest rates and default intensities. Finally we model the correlation between default and migration.In chapter 5 we present the necessity for Conditional Value-at-Risk as a coherent risk measure for corporate bond portfolios. The right risk measure is of paramount importance when we optimize corporate bond portfolios because of tail effects (heavy tails) in the distribution of returns that could result in significant losses and destroy portfolio efficiency. Then we present a linear program for minimizing portfolio risk using CVaR.In chapter 6 we implement portfolio optimization models using stochastic programming in a dynamic aspect. Initially we present an anticipative model where we only take into account stochasticity in future prices without taking recourse actions. Then we present a multistage recourse model where we can take recourse decisions at the preceding time periods based on information we take at discrete time in the future. We assume that there are transaction costs when we buy or sell bonds in order to make models more sophisticated. Finally we analyze one by one the equations of multistage recourse model.

Assessing Interest Rate Risk Beyond Duration – Shift, Twist, Butterfly

High fiscal deficits, a sharp rise in the issuance of sovereign debt from major developed economies, rising inflation expectations, and possible changes in central bank rates could cause the yield curves from around the world to change significantly. In the US, the yield curve has already experienced significant steepening in the past twelve months. This environment poses challenges for Fixed Income professionals who need to address possible non-parallel changes to the term structure. This paper illustrates the capabilities of Shift-Twist-Butterfly (STB) factor models to help address these challenges. We provide a longer-term perspective on term structure changes in the Euro zone, US and Japan. Using four portfolio case studies, we show that the use of risk measures such as duration, convexity or key rate durations have some limitations and may not be very efficient. Therefore we show how these limitations can be efficiently overcome by the complementary use of advanced fixed income risk models based on STB interest rate risk factors.

Changes in stomatal conductance and net photosynthesis during phenological development in spring wheat: implications for gas exchange modelling

Gas exchange was measured from 1 month before the onset of anthesis until the end of grain filling in field-grown spring wheat, Triticum aestivum L., cv. Vinjett, in southern Sweden. Two g ( s ) models were parameterised using these data: one Jarvis-type multiplicative g ( s ) model (J-model), and one combined stomatal-photosynthesis model (L-model). In addition, the multiplicative g ( s ) model parameterisation for wheat used within the European Monitoring and Evaluation Programme (EMEP-model) was tested and evaluated. The J-model performed well (R (2)=0.77), with no systematic pattern of the residuals plotted against the driving variables. The L-model explained a larger proportion of the variation in g ( s ) data when observations of A (n) were used as input data (R (2)=0.71) compared to when A (n) was modelled (R (2)=0.53). In both cases there was a systematic model failure, with g (s) being over- and underestimated before and after anthesis, respectively. This pattern was caused by the non-parallel changes in g ( s ) and A (n) during plant phenological development, with A (n) both peaking and starting to decline earlier as compared to g ( s ). The EMEP-model accounted for 41% of the variation in g ( s ) data, with g ( s ) being underestimated after anthesis. We conclude that, under the climatic conditions prevailing in southern Scandinavia, the performance of the combined stomatal-photosynthesis approach is hampered by the non-parallel changes in g ( s ) and A (n), and that the phenology function of the EMEP-model, having a sharp local maximum at anthesis, should be replaced by a function with a broad non-limiting period after anthesis.

Methionine-enkephalin Modulated Regulation of Oxidant/Antioxidant Status in Liver of CBA Mice

Reactive oxygen species (ROS) are formed by all aerobic organisms, and are involved in the numerous physiological and pathophysiological processes. Opioid peptides belong to a class of bioactive compounds of great interest because of their opiate-like activity. We determined the influence of methionine-enkephalin (MENK) on age-associated oxidant/antioxidant status in liver of CBA mice. Lipid peroxidation (LPO), total superoxide dismutase (tSOD), catalase (CAT), and glutathione peroxidase (Gpx) activities of 1, 4, 10 and 18 months old male and female control and MENK treated (10 mg/kg bw) CBA mice were determined. MENK showed gender-related effect on both oxidant/antioxidant parameters. It stimulated LPO in males, but suppressed in females. CAT and Gpx activities were lowered upon MENK exposure in males, but in females the activities were modulated by MENK. The relative mRNA levels for the antioxidant enzymes CuZnSOD, MnSOD, CAT and Gpx-1 were determined by reverse transcriptase polymerase chain reaction (RT-PCR) in groups where differences in activities between control and treated samples were observed. Changes of mRNA level in MENK treated groups showed that transcriptional regulation is both gender- and age-related. Comparison of enzyme activities and mRNA levels in control and MENK treated groups showed that, in some cases parallel changes occurred, while in other cases nonparallel changes were found. These results suggest that transcriptional changes are in accordance with enzyme activities in some cases, while in other cases posttranscriptional regulation of antioxidant enzymes may exist.

Managing Yield-Curve Risk with Combination Hedges

The method presented here to evaluate and regulate the risk exposure of default-free bonds generalizes the traditional duration concept by taking nonparallel changes in the term structure of interest rates into account. The article shows how to immunize a default-free bond by hedging with two standard hedging instruments (a combination hedge) and how to replicate a diversified bond portfolio by using a few standard hedging instruments. This standard hedging instrument representation can provide comprehensive information about the risk structure of the portfolio, and trading the standard hedging instruments can help fine-tune a position.

Exercise modulates antioxidant enzyme gene expression in rat myocardium and liver.

Our previous studies have shown that exercise caused changes in the tissue activities of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase in spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. To determine whether the changes observed were due to changes in mRNA levels of the enzymes, levels of tissue mRNA were determined by quantitative RNase protection assay. Comparisons of tissue enzyme activities and mRNA levels in sedentary and exercised animals showed that, in some cases (e.g., glutathione peroxidase in SH and WKY myocardium), parallel changes in enzyme activity and mRNA levels occurred, whereas in other cases (e.g., catalase in SH and WKY liver), nonparallel changes were found. Exercise of hypertensive rats altered antioxidant enzyme mRNA levels to those seen in normotensive animals in some, but not all, cases. The results suggest that transcriptional control over changes in exercise-related antioxidant enzyme activities is operative in some cases, although in other cases posttranscriptional regulatory mechanisms may exist.

Hyperoxic effects on alveolar sodium resorption and lung Na-K-ATPase.

Active Na+ transport by the alveolar epithelium keeps alveoli relatively dry. Hyperoxia increases epithelial permeability, resulting in pulmonary edema. We sought to determine whether active Na+ resorption from the air spaces and Na-K-ATPase activity increased in rats exposed to > 95% O2 for 60 h. The permeability x surface area products for unidirectional resorption of alveolar [14C]sucrose (PSsucrose) and 22Na+ (PSNa+) were measured in isolated, perfused rat lungs immediately after hyperoxia and after 3 and 7 days of recovery in room air. At 60 h of hyperoxia, the mean PSsucrose and PSNa+ increased from 6.71 +/- 0.8 x 10(-5) to 12.6 +/- 1.6 x 10(-5) cm3/s (P = 0.029) and from 23.6 +/- 1.1 x 10(-5) to 31.0 +/- 1.6 x 10(-5) cm3/s (P < 0.008), respectively. However, the values in individual rats ranged widely from no change to nearly a fourfold increase. Subgroup analysis revealed that benzamil- or amiloride-sensitive (transcellular) PSNa+ was significantly reduced in the exposed lungs with normal PSsucrose but was maintained in the lungs with high PSsucrose. By day 3 of recovery, mean Na+ and sucrose fluxes returned to values similar to control. Na-K-ATPase membrane hydrolytic maximal velocity (Vmax) activity fell significantly immediately after hyperoxic exposure but recovered to normal values by day 3 of recovery. The Na-K-ATPase beta 1-subunit antigenic signal did not significantly change, whereas the alpha 1-subunit levels increased during recovery. In summary, there was a heterogeneous response of different rats to acute hyperoxia. Hyperoxia led to complex, nonparallel changes in Na+ pump antigenic protein, hydrolytic activity, and unidirectional active Na+ resorption. Active Na+ transport was differentially affected, depending on degree of injury, but permeability and transport normalized by day 3 of recovery.

Bile induced acute oedematous pancreatitis in rats: non-parallel changes in pancreatic morphology and amylase release in vitro.

Pancreatic morphology and amylase release from isolated pancreatic acini in response to caerulein was studied in the course of an experimental bile induced acute pancreatitis without acinar necrosis. The inflammation was induced by retrograde microinfusion of 25 microliters bile into the rat bile pancreatic duct. A dissociation between functional and structural findings was seen. One hour after the bile injury, there was a transient change in acinar cell function. The response to stimulation by caerulein was reduced by 50%, whereas the sensitivity to caerulein was normal. There was oedema and an initial leucocyte infiltration of the gland. Six hours, one day, three days, and seven days after the bile injury, there was an acute interstitial oedematous pancreatitis with a modest polymorphonuclear leucocyte infiltration of the interstitium and widespread acinar vacuolisation. Morphological changes were most pronounced at the third postoperative day. Acinar amylase release, however, was normal both in terms of sensitivity and responsiveness to stimulation. These results show that bile injury may result in an initial disturbance of acinar cell function. Normal acinar amylase release prevailing in the course of the inflammation suggests that disturbance of the acinar amylase secretory response is not a primary stimulant of the inflammation before the development of acinar necrosis.

Age-related changes in brainstem auditory neurotransmitters: Measures of GABA and acetylcholine function

This study was designed to determine if there are age-related alterations in the bio-synthetic enzyme glutamic acid decarboxylase (GAD), the degradative enzyme GABA-transaminase (GABA-T), and the uptake system for GABA in the central nucleus of the inferior colliculus (CIC), the cochlear nucleus (CN), and/or nuclei of the lateral lemniscus (NLL) of Fischer-344 rats. For purposes of comparison, the cholinergic neuronal system was studied in parallel in young adult (3–7 months), mature (15–17 months) and aged (24–26 months) rats. In young adults GAD activity was highest in the CIC (219 nmol/mg protein/h; N = 5), intermediate in NLL (82 nmol/mg protein/h), and lowest in CN (34 nmol/mg protein/h). Choline acetyltransferase (ChAT) activity was highest in NLL and CN, and approximately 35–40% lower in CIC. A more uniform pattern was observed with GABA-T activity. Reductions in GAD activity were seen in the CIC of mature (-31%) and aged (-30%) rats that were not graded with age when compared to young adult, P < 0.05 ( N = 5). This effect was regionally selective, since the CN did not show any loss of GAD or ChAT activity. The neurotransmitter selectivity of this deficit in CIC is supported by the non-parallel changes in ChAT activity (-22%, aged vs. mature, P < 0.05) that occurred after the changes in GAD activity. In contrast to the loss of GABAergic biosynthetic capacity in aged CIC, high affinity uptake processes (K d and V max) for 14C-GABA and 3H- d-aspartate were not significantly altered ( P > 0.05). Similar to the CIC, the NLL showed remarkable age-related deficits, but these deficits were more substantial for the cholinergic system (ChAT activity: -56% aged vs. young adult. P < 0.05; GAD activity: -35% aged vs. mature). None of the areas examined showed a significant loss of GABA-T activity with aging. These data suggest: 1) Age-related loss of GABA-mediated inhibition in the CIC of Fischer-344 rats is not attributable to changes in uptake or degradation of GABA, but may be related loss of biosynthetic capacity (i.e. activity or quantity) of the GAD present; 2) processing centers of the central auditory pathway (i.e. CIC and NLL), but not necessarily primary (i.e. CN) integrativc nuclei, demonstrate selective, age-related neurochemical deficits; and 3) age-related neurochemical changes in central auditory structures may contribute substantially to the abnormal perception of signals in noise and loss of speech discrimination observed in neural presbycusis.

Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy.

We studied the GH-insulin-like growth factor-I (IGF-I) axis serially over 24-36 months in six patients with medulloblastoma who underwent surgical removal of the tumor followed by craniospinal irradiation therapy for 6 weeks and then chemotherapy for 42 weeks. Eighteen and 24 months after beginning irradiation there was a decline in the peak GH secretory response to acute stimulation with arginine/insulin hypoglycemia. Six months after irradiation and during chemotherapy there was a transient decline in IGF-I, IGF binding protein-3 (IGFBP-3), and GH-BP values (respective mean values of 56.1 +/- 9.0 ng/mL, 1.1 +/- 0.2 microgram/mL, and 7.6 +/- 3.3% of radioactivity as compared to time 0 values: 13%%o/- 15 ng/mL, 2.2 +/- 0.2 micrograms/mL, and 20.0 +/- 4.0%, P < 0.001), although provoked GH secretion was normal at this time. The IGF-I, IGFBP-3, and GH-BP returned to pretreatment ranges by 12-36 months after initiation of the study. There was also a decline in body mass index and serum protein values at 6 months, suggesting suboptimal nutrition during this period. Six months after irradiation in ligand and immunoblot analysis there was a decline in IGFBP-3 and an abnormal electrophoretic mobility of IGFBP-2 that were both normalized at 36 months. In one patient we observed a high level of IGFBP-3 proteolysis at this time. This study demonstrates that before the decrease of GH secretion in patients receiving cranial irradiation there is a transient phase of GH insensitivity that may be characteristic of the acute therapeutic phase including the chemotherapy. This partial insensitivity may explain the early growth retardation observed in these patients.

Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

Nonparallel changes of growth hormone (GH) and insulin-like growth factor-I, insulin-like growth factor binding protein-3, and GH-binding protein, after craniospinal irradiation and chemotherapy

Duodenal juice total protein and pancreatic enzyme synthesis, turnover, and secretion in patients after acute pancreatitis.

It is controversial whether acute pancreatitis has longterm effects on pancreatic function. Pancreatic enzyme synthesis, turnover, and secretion were measured in 10 patients in clinical remission who had had one or more (one to six) attacks of acute alcoholic pancreatitis. The studies were done between two and 29 months after the most recent attack. A control group included five patients with no evidence of pancreatic disease. A four hour primed/continuous intravenous infusion of [14C]L-leucine tracer was given with secretin (2 U/kg/h) and cholecystokinin (0.5 U/kg/h) and secreted duodenal juice aspirated. Amylase and trypsin were extracted from duodenal juice by affinity chromatography, permitting measurement of the rate of isotope incorporation into total protein, amylase, and trypsin. The results showed non-parallel changes in enzyme synthesis and turnover with decreases in total enzyme protein and amylase synthesis and turnover but preservation of trypsin synthesis and turnover. The low turnover rates may be ascribed to continuing pancreatic cell malfunction after recovery from acute alcoholic pancreatitis and suggest that the decreased amylase secretion rates are partly a consequence of impaired amylase synthesis and not simply because of loss of pancreatic tissue.

Nonparallel changes in global left ventricular chamber volume and muscle mass during the first year after transmural myocardial infarction in humans

Objectives. This study was designed to serially assess time-dependent changes in both chamber volume and myocardial muscle mass after infarction in humans.Background. Dilation of the left ventricular chamber has been previously described after transmural myocardial infarction.Methods. Global left ventricular chamber volumes and muscle mass were quantified by using cine computed tomographic scanning in 18 patients at hospital discharge and 6 weeks, 6 months and 1 year after an initial transmural myocardial infarction (12 anterior and 6 inferior). No patient had heart failure during the initial hospital stay or on any subsequent follow-up visit.Results. The patients with anterior myocardial infarction (estimated infarct extent 27 ± 2% of left ventricle) demonstrated a progressive increase in left ventricular end-diastolic volume from 148 ± 9 ml (mean ± SEM) at hospital discharge to 180 ± 9 ml at 1 year after infarction (p < 0.001). However, global left ventricular muscle mass decreased significantly during the 1st 6 weeks after infarction but returned by 1 year to nearly the value determined at hospital discharge (177 ± 13 vs. 165 ± 10 g, p = NS). The changes in global muscle mass did not parallel the steady and progressive increases in chamber end-diastolic volume. The end-diastolic chamber volume to muscle mass ratio, an index of global left ventricular wall tension, increased steadily after hospital discharge but remained level by 1 year after infarction. The time course of changes in global end-systolic chamber volume was roughly proportional to the concomitant changes in end-diastolic volume. During this same time period, left ventricular stroke volume remained constant or improved from that determined at baseline. Global left ventricular end-diastolic and end-systolic volumes remained relatively static daring the 1st year in the patient subgroup with inferior wall myocardial infarction (estimated infarct extent 10 ± 1% of left ventricle), but global muscle (myocardial) mass initially decreased and then increased in a pattern similar, although of smaller magnitude, to that observed in patients with anterior wall myocardial infarction.Conclusions. Overall, left ventricular end-diastolic and eadsystolic chamber volumes increase progressively from hospital discharge to 1 year after an initial transmural myocardial infarction in patients with a moderately large anterior wall infarction hut remain stable in patients with a small inferior wall infarction. Concurrently, total left ventricular muscle mass decreases significantly during the initial 6 weeks after infarction (presumed largely secondary to changes in the necrotic segments) but then returns to the hospital discharge baseline values by 1 year. These data are consistent with the late development of, at most, limited ventricular hypertrophy in the noninfarcted myocardium that occurs well after the early and progressive left ventricular chamber dilation observed in patients with a moderate to large myocardial infarction. These data, in particular as applied to patients with anterior infarction, suggest that ventricular wall tension is significantly elevated at least during the 1st year after an initial transmural myocardial infarction. These observations nay explain the potential utility of agents aimed at reducing afterload or ventricular wall tension during the early convalescent phase after myocardial infarction.