A review of inflammatory idiopathic myopathy focusing on polymyositis.

Inflammatory idiopathic myopathies are a group of autoimmune diseases affecting predominantly the proximal skeletal muscles, with raised muscle enzymes, with or without skin involvement and extramuscular organ involvement. Autoantibodies help to characterize patients into different clinical phenotypes. Successful treatment necessitates controlling inflammation early with corticosteroids and invariably requires additional immunosuppressive therapy. This review focuses on the aetiology, pathogenesis, clinical presentation, investigations and management of patients presenting with inflammatory idiopathic myopathies, predominantly focusing on polymyositis and antisynthetase syndrome.

A critical analysis of the tools to evaluate neuropsychiatric lupus.

Neuropsychiatric symptoms occur commonly in patients with systemic lupus erythematosus, but they are not always due to active disease. It is crucial to identify cases that are due to active systemic lupus erythematosus so that appropriate treatment can be instituted. There is no single serological or imaging test that distinguishes active neuropsychiatric systemic lupus erythematosus from neuropsychiatric manifestations caused by other factors such as infection. Most patients with neuropsychiatric systemic lupus erythematosus have generalised features of disease activity. Raised anti-dsDNA and low C3 complement levels are often seen, but are not an invariable guide. The presence of antiphospholipid antibodies is more suggestive of thrombotic than inflammatory causation. A number of other autoantibody tests have been proposed as biomarkers for neuropsychiatric systemic lupus erythematosus, but results in clinical studies have been inconsistent and none has so far entered routine clinical practice. Cerebrospinal fluid features and magnetic resonance imaging appearances are non-specific in neuropsychiatric systemic lupus erythematosus, but are useful in excluding other causes of neuropsychiatric symptoms. Newer magnetic resonance imaging sequences show promise for distinguishing new neuropsychiatric systemic lupus erythematosus activity from previous damage and recent research suggests these may correlate with changes in cognitive function in patients with systemic lupus erythematosus. However, formal cognitive testing is seldom carried out in the acute setting.

Investigating preference-performance relationships in aboveground-belowground life cycles: a laboratory and field study with the vine weevil (Otiorhynchus sulcatus).

The preference-performance hypothesis has principally considered insect herbivores with aboveground lifecycles, although the hypothesis could be equally relevant to insects with life stages occurring both aboveground and belowground. Moreover, most studies have focussed on either laboratory or field experiments, with little attempt to relate the two. In this study, the preference-performance hypothesis was examined in an aboveground-belowground context in the laboratory using the vine weevil (Otiorhynchus sulcatus (F.)) (Coleoptera: Curculionidae) and two cultivars of red raspberry (Rubus idaeus), Glen Rosa and Glen Ample. A two-year field study (2008-2009) was also undertaken to characterise the population dynamics of adult weevils on the two raspberry cultivars. Larval performance (abundance and mass) differed significantly between Glen Rosa and Glen Ample, with Glen Rosa resulting in 26% larger but 56% fewer larvae compared to Glen Ample. Larval abundances were significantly and positively correlated with root nitrogen and magnesium concentrations, but negatively correlated with root iron. However, concentrations of these minerals were not significantly different in the two cultivars. Adult weevils did not preferentially select either of the two cultivars for egg laying (laying 3.08 and 2.80 eggs per day on Glen Ample and Glen Rosa, respectively), suggesting that there was no strong preference-performance relationship between adult vine weevils and their belowground offspring. Field populations of adult vine weevils were significantly higher on Glen Ample than Glen Rosa, which may reflect the higher larval survival on Glen Ample observed in laboratory experiments.

Extreme rainstorms drive exceptional organic carbon export from forested humid-tropical rivers in Puerto Rico.

Extreme rainfall events in the humid-tropical Luquillo Mountains, Puerto Rico export the bulk of suspended sediment and particulate organic carbon. Using 25 years of river carbon and suspended sediment data, which targeted hurricanes and other large rainstorms, we estimated biogenic particulate organic carbon yields of 65 ± 16 tC km-2 yr-1 for the Icacos and 17.7 ± 5.1 tC km-2 yr-1 for the Mameyes rivers. These granitic and volcaniclastic catchments function as substantial atmospheric carbon-dioxide sinks, largely through export of river biogenic particulate organic carbon during extreme rainstorms. Compared to other regions, these high biogenic particulate organic carbon yields are accompanied by lower suspended sediment yields. Accordingly, particulate organic carbon export from these catchments is underpredicted by previous yield relationships, which are derived mainly from catchments with easily erodible sedimentary rocks. Therefore, rivers that drain petrogenic-carbon-poor bedrock require separate accounting to estimate their contributions to the geological carbon cycle.

Amazon rain-forest fires.

Charcoal is common in the soils of mature rain forests within 75 kilometers of San Carlos de Rio Negro in the north central Amazon Basin. Carbon-14 dates of soil charcoal from this region indicate that numerous fires have occurred since the mid-Holocene epoch. Charcoal is most common in tierra firme forest Oxisols and Ultisols and less common in caatinga and igapo forest soils. Climatic changes or human activities, or both, have caused rain-forest fires.

A compendium of gene expression in normal human tissues.

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

Hypocalcemia and pregnancy-induced hypertension produced by maternal fasting.

During pregnancy, maternal calcium needs increase as a result of increasing calcium requirements for fetal bone development. These needs have to be completely supplied by the mother via placental transfer. Several studies link low serum ionized calcium concentrations with the development of hypertension and pregnancy-induced hypertension. We hypothesized that maternal hypocalcemia would develop concomitantly with the development of hypertension in sheep that were fasted in late gestation. Sixteen instrumented ewes were used in the present study. After a 2-day baseline period, food was withdrawn from 10 animals in the experimental group (group 2) for 3 days, whereas the remaining six were allowed to eat and drink normally (group 1). Blood pressure, uteroplacental blood flow, and heart rate were monitored daily. Fasted animals were given deionized water (calcium free) to drink, whereas control animals were given tap water containing 32.9 mg/l calcium concentration. Based on the analysis of the ionized calcium concentration response to fasting, group 2 animals were placed in one of two groups: hypocalcemia did not develop in group 2a, whereas in group 2b the ionized calcium concentration decreased 27% (from 1.09 +/- 0.07 to 0.80 +/- 0.06 mM, p = 0.01) by the third day of fasting. Group 2b responded with a 16% elevation in maternal blood pressure (p = 0.01) and a 43% reduction in uteroplacental blood flow. Furthermore, a positive correlation was found between maternal and fetal blood ionized calcium concentrations (r = 0.860).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypocalcemia and pregnancy-induced hypertension produced by low-calcium diet.

Recent studies from our laboratory in fasting pregnant ewes with twin gestation have implicated low serum calcium concentration in the etiology of hypertension in pregnancy. We hypothesized that the reduction in serum calcium concentration produced by feeding of a calcium-deficient diet in twin gestation would lead to a significant increase in maternal arterial blood pressure, vascular resistance, and protein in the urine and decreased uterine blood flow. Twenty-five instrumented ewes were used in the present study. After surgery a calcium-deficient diet and deionized water (calcium ion free) were provided ad libitum to 19 animals. Blood pressure, cardiac output, heart rate, and uterine blood flow were monitored every other day. Six control animals were provided with standard Rumilab diet and tap water (group 1). Animals on a low-calcium diet (group 2) were subdivided according to the blood ionized calcium response to low dietary calcium intake. Non-hypocalcemic animals were assigned to group 2a (n = 10), and hypocalcemic animals (calcium concentration below two standard deviations from the control group) were assigned to group 2b (n = 9). In group 2b calcium concentration decreased from 1.03 +/- 0.04 mmol/L on day 110 of gestation to 0.77 +/- 0.03 mmol/L by day 125 of gestation. Arterial blood pressure increased significantly from 76 +/- 2 to 91 +/- 2 mm Hg, and uterine blood flow decreased from 950 +/- 53 to 579 +/- 48 mL/min. Urinary protein increased from 1.7 +/- 0.3 to 10.5 +/- 1.2 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of continuous infusion of endothelin-1 in pregnant sheep.

Plasma concentration of endothelin-1, a potent vasoconstrictor produced by the vascular endothelium, has been observed to be significantly increased in a number of pathophysiological states, including preeclampsia. In the present study we have evaluated the effects of elevated plasma endothelin-1 in pregnant sheep by continuous exogenous endothelin-1 administration. Nine pregnant ewes (110+/-5 days' gestation) were instrumented for measurements of maternal mean arterial pressure, renal blood flow, and uterine blood flow. After recovery, endothelin-1 was infused intravenously for 4 hours at a dose that was adjusted to raise mean arterial pressure by approximately 20 mm Hg by the end of the first hour (range 5 to 20 ng/kg per minute). Mean arterial pressure, renal blood flow, uterine blood flow, urinary protein excretion, hematocrit, and plasma endothelin-1 concentration were measured hourly, and renal and uterine vascular resistances were calculated. Endothelin-1 produced significant increases (% change from baseline at t=4 hours) in mean arterial pressure (45+/-8%), renal vascular resistance (353+/-66 %), and uterine vascular resistance (59+/-21%). Endothelin-1 also increased microvascular permeability both systemically and within the kidney, as suggested by marked increases in hematocrit (0.27+/-0.01 to 0.32+/-0.01) and urinary protein concentration (0.95+/-0.1 to 7.9+/-3.2 mg/mL per mg creatinine). There was a highly significant correlation (P<.0001) between plasma endothelin-1 and mean arterial pressure, renal vascular resistance, uterine vascular resistance, hematocrit, and urinary protein content in all sheep studied. In addition, plasma endothelin-1 corresponded well with the time course of the changes in cardiovascular parameters and urinary protein excretion observed. These results provide evidence to suggest that elevation of circulating endothelin-1 in pregnant sheep can produce cardiovascular and hemodynamic changes that in many ways resemble the human disease preeclampsia. This supports the hypothesis that endothelial cell damage and/or dysfunction that is associated with increased production of endothelin-1 could directly contribute to the progression of preeclampsia.

Correcting for signal saturation errors in the analysis of microarray data.

A variety of technical errors have arisen in data analysis when using cDNA or oligonucleotide microarrays. One of the most insidious problems is the saturation of the hybridization signal of high-abundant transcripts. This problem arises from the truncation of the laser fluorescence signal. When the hybridization signal on the microarray is very strong, this truncation can result in serious consequences that may not be readily apparent to the user. As an illustration of this problem, two subclasses of normal human tissue samples (six liver and six lung samples) were analyzed with GeneChip probe arrays to evaluate the patterns of expression for approximately 7000 human genes. Five of these data sets were found to suffer from signal truncation. This caused several tissues to be incorrectly classified using hierarchical clustering. To rectify this problem so that the gene expression data could be properly compared and clustered, we developed a "filtering" procedure that identifies a subset of genes least affected by the signal saturation. This filtering procedure can be obtained at www.hugeindex.org.

Pregnancy causes a decrease in the number and affinity of myometrial angiotensin II receptors.

The pressor response to exogenously infused angiotensin II is decreased in normal human and ovine pregnancy when compared to the nonpregnant state. This study was designed to determine the mechanism for decrease in target organ sensitivity by examining pregnancy-induced changes in the affinity and number of angiotensin II receptors in myometrium from pregnant and nonpregnant sheep. Tissues were obtained from four ovariectomized sheep given 50 micrograms estradiol-17 beta on days 3 and 5 postsurgery and from four pregnant sheep (mean gestational age 136 days). Binding of 125I-angiotensin II was determined in particulate fractions of myometrium prepared by differential centrifugation. The 125I-angiotensin II binding to myometrial preparations was specific, saturable, and linear with protein concentration. In the nonpregnant group, binding capacity for angiotensin II in myometrium was 502 +/- 76 fmol/mg protein, whereas in the pregnant group it was 184 +/- 65 fmol/mg protein (P less than .01). Receptor affinity also was less (Kd 1.72 +/- 0.39 nM) during pregnancy compared with the nonpregnant sheep uterus (3.9 +/- 0.80 nM; P less than .01). These data support the hypothesis that the decrease in target organ sensitivity to exogenously administered angiotensin II during pregnancy in human and ovine species may be secondary to a decrease in the total number and affinity of specific angiotensin II receptors.

The maternal and fetal physiologic effects of nicotine.

The effects of nicotine are seen in every trimester of pregnancy, from increased spontaneous abortions in the first trimester, to increased premature delivery rates and decreased birth weights in the final trimester. The birth weight of a baby is dependent on two factors: the gestational age of the fetus at the time of delivery and the rate of fetal growth. Nicotine has been shown to affect both of these factors. Carbon monoxide, also found in tobacco, forms carboxyhemoglobin, which inhibits the release of oxygen into fetal tissues. Nicotine readily gains access to the fetal compartment via the placenta, with fetal concentrations generally 15% higher than maternal levels. The primary metabolite of nicotine, cotinine, has a half-life of 15 to 20 hours and serum concentrations that are 10-fold higher than nicotine; thus, cotinine provides a better index of nicotine exposure because of its longer half-life. Nicotine concentrates in fetal blood, amniotic fluid, and breastmilk. The fetus and neonate may also have environmental tobacco exposure that may be significant. In animal models and humans, nicotine increases maternal blood pressure and heart rate, with a concomitant reduction in uterine blood flow. An increase in fetal heart rate is also seen, which is thought to be caused by catecholamine release. The impact of nicotine on the respiratory and central nervous system is also reviewed. In conclusion, the physiological effect of tobacco on fetal growth seems to be a culmination of both the vasoconstrictive effects of nicotine on the uterine and potentially the umbilical artery and the effects on oxygenation by carboxyhemoglobin.

Connectedness and autonomy support in parent-child relationships: links to children's socioemotional orientation and peer relationships.

Connectedness and autonomy support in the parent-child relationship are constructs that emerge from object relations and attachment theories but that overlap with other commonly studied qualities of parent-child relationships to provide a unifying focus for research in this domain. In this study, these constructs were examined in relation to children's relational competence, including socioemotional orientation, friendship, and peer acceptance. Semistructured conversations between mothers and their 5-year-olds (N = 192) were videotaped at home and rated for (a) connectedness between the members of the dyad and (b) the parent' s support for the child's autonomy. Results showed that connectedness was correlated with children's socioemotional orientations, number of mutual friendships, and peer acceptance and that the relation between parent-child connectedness and children's peer relationships was mediated by children's prosocial-empathic orientation. Implications of these findings for theories that link parent-child relationships to the development of relational competence in children are discussed.

Systemic and uterine vascular response to serotonin in third trimester pregnant ewes.

Released from aggregating platelets, serotonin (5HT) among other vasoactive components is considered to play an important role in preeclampsia, one of the most common medical complications of pregnancy. This study was designed to evaluate the simultaneous uterine and systemic vascular effects of systemically administered serotonin in pregnant sheep and compare them to the well known effects of angiotensin II and norepinephrine. Nine instrumented pregnant ewes received intravenous (inferior vena cava) infusions of increasing doses of serotonin, norepinephrine and angiotensin II in random order. Cardiac output, arterial blood pressure, heart rate, and uterine blood flow were recorded. Systemic administration of serotonin at doses of 2, 4, and 8 micrograms/kg body weight/min caused a slight increase in mean arterial blood pressure (1, 4 and 11%), a large decrease in uterine blood flow (10, 37, and 71%) but did not change cardiac output. Serotonin led to an increase in uterine vascular resistance with only small changes in systemic vascular resistance (UVR 17, 107, and 363% vs. SVR 3, 10 and 11%). In contrast, angiotensin II increased both systemic and uterine vascular resistance (SVR 16, 37, 56, and 95% and UVR 5, 16, 28 and 99%). Norepinephrine also raised both systemic and uterine vascular resistance, though to a different extent (SVR 5, 17, 37, and 118% vs. UVR 5, 46, 84 and 304%). Systemic infusions of serotonin in third trimester pregnant ewes resulted in uterine vasoconstriction. In contrast to the marked effect on the uterine vasculature, the systemic cardiovascular responses were small, thus demonstrating a nearly selective effect of serotonin on the uterine vasculature at the doses administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen-induced increases in coronary blood flow are antagonized by inhibitors of nitric oxide synthesis.

OBJECTIVE: Estrogen receptors have been found in coronary arterial endothelial and vascular smooth muscle cells. Therefore the present study was designed to determine if estradiol-17 beta can increase coronary blood flow and if so whether the changes are mediated by nitric oxide. STUDY DESIGN: Five oophorectomized non-pregnant sheep were chronically instrumented to measure blood pressure, heart rate, cardiac output, left circumflex coronary blood flow and central venous pressure. Animals received estradiol-17 beta (1.0 micrograms/kg) and cardiovascular responses were followed for 135 min. RESULTS: Estradiol-17 beta (1.0 micrograms/kg) increased left circumflex (coronary) blood flow 28 +/- 3%, cardiac output 15 +/- 1% and heart rate by 13 +/- 3%. Coronary vascular resistance decreased 23 +/- 5%, systemic vascular resistance decreased by 12 +/- 2% while blood pressure did not change significantly. Administration of the nitric oxide synthetase inhibitor L-nitroarginine methylester (L-NAME), had no effect on basal coronary blood flow but completely reversed estradiol-17 beta induced increases in coronary blood flow. CONCLUSION: These results demonstrate that estrogen increases coronary blood flow in the non-pregnant sheep and that L-NAME, an inhibitor of nitric oxide, is able to reverse the estrogen induced flow changes.

Uterine blood flow--a determinant of fetal growth.

An adequate increase of uterine blood flow throughout gestation is essential for uterine, placental and fetal growth. Maternal cardiovascular adaptation has to provide the uterine perfusion that is necessary to meet the requirements of the developing and growing fetus by providing transport of nutrients and oxygen to the placenta and the fetus. Thus, uterine blood flow is inextricably linked to fetal growth and survival. Reductions of uterine blood flow can occur under acute or chronic conditions or in a combination of both. Chronic reductions of uterine blood flow can be observed in pregnancy-induced hypertension (PIH), diabetes mellitus in pregnancy and intrauterine growth restriction (IUGR). Chronic restrictions in uterine blood flow will elicit a placental and fetal response in the form of growth adaptation to the reduced supply of oxygen and nutrients to the conceptus. If compensatory growth restriction reaches its limits intrauterine fetal distress can ensue. Among the great number of experimental models of intrauterine growth restriction, those involving a generalized reduction in the uteroplacental blood supply are of significance to questions relating to human pregnancy. Despite physiological differences, particularly with regard to maternal metabolism and placentation, the occlusion model in the pregnant sheep is suitable for investigating questions about fetal and placental growth.

Viability of stored equine embryos.

Equine embryos were recovered nonsurgically 6.5 d after ovulation (Exp. 1) and those greater than 200 microns were stored in one of three media: 1) Ham's F10 + 10% fetal calf serum (FCS) under 5% CO2, 5% O2 and 90% N2 at 24 C (Ham's F10); 2) Minimal Essential Medium with Hank's balanced salts + 10% FCS in air (MEM) at 24 C or 3) MEM at 5 C n = 10/treatment). Embryos less than or equal to 200 micron (n = 10) were bisected microsurgically; one-half of each embryo was stored in Ham's F10 and the other half in either Dulbecco's phosphate-buffered saline + 10% FCS in air at 24 C (DPBS), or MEM in air at 24 C. At 0, 12 and 24 h, embryos were: 1) measured; 2) assigned a developmental score of 1 to 4 (1 = tight morula, 4 = expanding blastocyst) and 3) assigned a quality score of 1 to 5 (1 = excellent, 5 = degenerate). Whole embryos stored in MEM at 5 C or 24 C did not (P greater than .05) advance in development by 24 h, whereas those stored in Ham's F10 at 24 C were more (P less than .05) advanced (i.e., higher developmental score) by 24 h. From 0 to 24 h, 1 of 10, 6 of 10 and 7 of 10 whole embryos developed when stored in MEM 5 C, MEM 24 C and Ham's F10 24 C, respectively. Embryo quality was better at 24 h (P less than .05) for embryos stored in Ham's F10 at 24 C compared with MEM at 5 C.(ABSTRACT TRUNCATED AT 250 WORDS)