Endometrial stromal neoplasms are immunoreactive with WT-1 antibody.

WT-1 positivity has previously been noted in nonneoplastic endometrial stroma. In this study we examined WT-1 expression in endometrial stromal neoplasms to ascertain whether these tumors are immunoreactive and whether this antibody might be of value in the diagnosis of these lesions. We also stained cases of cellular and highly cellular leiomyomas to investigate whether WT-1 might be of value in distinguishing these from an endometrial stromal neoplasm. We compared WT-1 staining with CD10, desmin, alpha smooth muscle actin, h-caldesmon, and AE1/3, many of these antibodies being commonly used to distinguish between an endometrial stromal and a smooth muscle phenotype. Cases of ESN (n = 5), low grade ESS (n = 14), and cellular or highly cellular leiomyoma (n = 14) were stained with the aforementioned antibodies. Cases were scored on a scale of 0 to 4+, with 4+ cases exhibiting positivity of >50% of cells. Sixteen of 19 endometrial stromal neoplasms were positive with WT-1, most (14 of 16) with 4+ positivity. Staining was nuclear (5 cases), cytoplasmic (5 cases), or combined nuclear and cytoplasmic (6 cases). All endometrial stromal neoplasms exhibited 4+ staining with CD10. Staining for alpha smooth muscle actin was present in most cases (14 of 19) and desmin and h-caldesmon were positive in a smaller number of cases (8 and 2 respectively). There was 4+ positivity with desmin in only 1 case. The 2 cases that were h-caldesmon positive both exhibited 1+ staining (<5% cells positive). Six cases were positive with AE1/3, 1 with 4+ staining. Leiomyomatous neoplasms always exhibited 4+ staining with desmin and alpha smooth muscle actin and in most cases (12 of 14) with h-caldesmon. The other 2 cases exhibited 2+ positivity. Most cases (12 of 14) were positive with WT-1 (7 of 14 with 4+ staining) and CD10 (5 of 14 with 4+ positivity). One case was positive with AE1/3. We conclude that diffuse WT-1 positivity is characteristic of endometrial stromal neoplasms and that this may be of value in diagnosis. However, WT-1 is of limited use in the distinction between an endometrial stromal and a cellular leiomyomatous neoplasm because many of the latter are also positive. This study confirms the value of h-caldesmon in the distinction between an endometrial stromal neoplasm (almost always h-caldesmon negative) and a cellular leiomyomatous neoplasm (h-caldesmon positive). Although CD10 is positive in endometrial stromal neoplasms, the commonly observed immunoreactivity of cellular and highly cellular leiomyomas with this antibody limits its diagnostic usefulness. Desmin is useful as all leiomyomatous neoplasms exhibited diffuse positivity, whereas only a small number of endometrial stromal neoplasms were focally positive and only 1 case exhibited 4+ positivity. Smooth muscle actin is of limited value since most neoplasms studied were positive. The overlapping immunophenotype of endometrial stromal and leiomyomatous neoplasms may reflect the origin of both cell types from a common progenitor within the uterus.     

Effects of periodic weight support in a simulated weightless environment in preventing bone demineralisation.

Anti Orthostatic Hypokinetic posture in rats by tail suspension for 15 days (d) simulates the deconditioning effects of weightlessness on the weight bearing bones. The present study evaluates the effects of daily 4 hour (h) weight support (WS) during simulated weightlessness (S-W) in preventing these changes. Adult male albino rats were divided into three groups as (i) Control (CON, n = 12), (ii) Hind limb unweighing by tail suspension for 15 d (HU, n = 18), (iii) HU with daily 4 h WS (4 HRWS, n = 11). After 15 d tibia from all the animals were removed and subsequently dried, ashed and then calcium content of the bones were determined. HU showed reductions in the water content by 35.8%, organic matrix by 12.2% and calcium content by 33.4% of tibia. 4 h WS during S-W resulted in complete prevention of water loss and organic matrix loss and partial prevention of the loss of calcium content. Calcium content of tibia in 4 HRWS remained 15.2% less as compared to CON. These findings indicate that 4 h WS is partially successful in preventing the demineralisation effects of S-W on weight bearing bone tibia.     

The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.

Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.     

Reversal of startle gating deficits in transgenic mice overexpressing corticotropin-releasing factor by antipsychotic drugs.

Chronically elevated levels of corticotropin-releasing factor (CRF) in transgenic mice overexpressing CRF in the brain (CRF-OE) appear to be associated with alterations commonly associated with major depressive disorder, as well as with sensorimotor gating deficits commonly associated with schizophrenia. In the present study, we tested the hypothesis that antipsychotics may be effective in normalizing prepulse inhibition (PPI) of acoustic startle in CRF-OE mice, which display impaired sensorimotor gating compared to wild-type (WT) mice. The typical antipsychotic haloperidol and atypical antipsychotic risperidone improved PPI in the CRF-OE mice, but were ineffective in WT mice. The atypical antipsychotic clozapine did not influence PPI in CRF-OE mice, but reduced gating in WT mice. This effect of clozapine in the CRF-OE mice may thus be regarded as a relative improvement, consistent with the observed effect of haloperidol and risperidone. As expected, the anxiolytic, nonantipsychotic chlordiazepoxide was devoid of any effect. All four compounds dose-dependently reduced the acoustic startle response irrespective of genotype. These results indicate that antipsychotic drugs are effective in improving startle gating deficits in the CRF-OE mice. Hence, the CRF-OE mouse model may represent an animal model for certain aspects of psychotic depression, and could be a valuable tool for research addressing the impact of chronically elevated levels of CRF on information processing.     

Does systemic inflammation trigger local exercise-induced oxidative stress in COPD?

Inflammatory abnormalities may be involved in the inadequate basal oxidant/antioxidant balance and local exercise-induced oxidative stress in chronic obstructive pulmonary disease (COPD) patients. The time course of oxidative stress and inflammation was investigated in 10 COPD patients and seven healthy subjects before and after local dynamic quadriceps endurance exercise at 40% of maximal strength. Venous samples were collected before, immediately after and up to 48 h after exercise. At rest, levels of an oxidant released by stimulated phagocytes, the superoxide anion, were significantly higher in patients, as were plasma levels of C-reactive protein, tumour necrosis factor-alpha and interleukin-6, inflammatory markers. An inverse relationship was found between baseline C-reactive protein levels and endurance time in patients. Six hours after exercise, superoxide anion release and levels of protein oxidation products, an index of oxidative stress, increased similarly in both groups, whereas thiobarbituric acid reactive substance levels, another index of oxidative stress, increased significantly only in patients. Plasma nonenzymatic antioxidant and inflammatory cytokine levels were unchanged by the exercise protocol. The increased baseline systemic inflammation in chronic obstructive pulmonary disease patients could be related to disturbed oxidant/antioxidant balance, and, together, these may have triggered the exercise-induced oxidative stress. The absence, however, of local exercise-induced systemic inflammation suggests that additional mechanisms explain local exercise-induced oxidative stress.     

Work-related recovery opportunities: testing scale properties and validity in relation to health

Objectives  

Recovery opportunities allow employees to recuperate from work and diminish load effects. The aims of this study are to present a scale for measuring recovery opportunities, study its psychometric properties and its relationship with health.