Enhanced coagulation activation in preeclampsia: the role of APC resistance,microparticles and other plasma constituents

In the Second Northwick Park Heart Study, the activation peptides of factor IX (FIXpep) and factor X (FXpep) were measured in 1261 middle-aged men by double-antibody radioimmunoassay. During follow-up 147 men who had a first coronary heart disease (CHD) event were found to have had an increased FIXpep (p = 0.003) and a reduced FXpep (p = 0.05) at baseline compared with those remaining CHD-free (controls). Plasma FIXpep and FXpep were positively associated, but the rate of rise in FIXpep with increasing FXpep was higher in cases than controls (p for interaction = 0.01). In a sample of 87 controls, FIXpep was positively and independently related to the concentrations of a polymorphonuclear-specific fibrinogen degradation product (p = 0.036) and FXpep (p = 0.004), but in larger samples no statistically significant associations were found either with C-reactive protein or with fibrinogen concentration. The findings suggested that the increased FIXpep in men at high CHD-risk may have been partly due to the generation of factor IX inactivation peptides by inflammatory proteolysis and their recognition together with true FIXpep in the radioimmunoassay. Direct evidence for this hypothesis requires development of assays for human elastase-specific factor IX inactivation peptides.     

Expression and distribution of id helix-loop-helix proteins in human astrocytic tumors

The Id family of helix-loop-helix proteins is involved in a variety of processes, such as development, proliferation, and angiogenesis. In this study, we investigated the expression pattern of Id1, Id2, and Id3 in surgical specimens of human glial tumors. Western blot analysis demonstrated that all three Id proteins were expressed in astrocytic tumors. Expression levels in high-grade tumors were higher than in low-grade tumors. Immunohistochemical analysis confirmed that many of the tumor astrocytes exhibited strong Id1-3 IR. In contrast, in adult human normal brain, Id expression was low both in resting astrocytes and in endothelial cells. In tumor cells, Id proteins displayed cytoplasmic as well as nuclear localization. Id1-3 IR scores in tumor cells were positively correlated with proliferation indices. Moreover, Id1-3 IR was detected in endothelial cells of the astrocytic tumor blood vessels. The vascular Id1-3 expression correlated positively with tumor vascularity and grade. These results support the role of the Id gene family in the enhanced proliferative potential of tumor astrocytes. The evidence also supports the involvement of the Id gene family in tumor angiogenesis, a process that critically influences the malignant behavior of glial tumors.     

Selective enhancement of spatial learning under chronic psychosocial stress

The hippocampus has long been proved to be implicated in several learning and memory processes. Being integrated into the limbic-hypothalamus-pituitary-adrenal axis, the hippocampus also plays an active role in the regulation of the stress response. Long lasting elevated levels of glucocorticoids resulting from a prolonged stress exposure affect hippocampal functions and structure, inducing learning and memory alterations and suppressing cell proliferation in the adult dentate gyrus. Here, adult male tree shrews (Tupaia belangeri) exposed to chronic psychosocial stress were tested repeatedly on a holeboard apparatus using two different learning tasks devised to evaluate hippocampal-dependent and hippocampal-independent cognitive function. We show that chronic stress enhanced learning in animals performing the hippocampal-dependent task, whereas no stress-induced effect was found in the hippocampal-independent task. Additionally, after five weeks of stress, cell proliferation was reduced in the hippocampal dentate gyrus. These results indicate that specific memory processes not only may remain intact, but indeed are facilitated by chronic stress, despite elevated cortisol levels and suppressed hippocampal cell proliferation.     

Decreased redox state in red blood cells from patients with sarcoidosis

BACKGROUND AND AIM OF THE WORK: The glutathione system has a key role in the defence against oxidative stress. To function properly, this system needs NADPH to maintain glutathione (GSH) in its reduced form. We hypothesized that the clinical problems associated with sarcoidosis might be related to a decreased anti-oxidant defence and we therefore measured the activity of the NADPH-generating enzyme glucose-6-phosphate dehydrogenase (G6PD), the GSH-regenerating enzyme glutathione reductase (GR) and indirectly the level of NADPH in red blood cells from patients with sarcoidosis. METHODS: In a population of sarcoidosis (n = 88) patients, G6PD, GR and GR activity after incubation with chromate (GR-Cr) were measured in erythrocytes. A decreased concentration of NADPH was revealed by an increased GR-Cr (> 0.6 IU/g Hb). To exclude a mutation in the G6PD gene, sequencing was performed in cases with an abnormal GR-Cr. Sarcoidosis pulmonary disease severity was evaluated by means of laboratory data, radiographic staging, HRCT scoring, pulmonary function and exercise capacity testing. RESULTS: Fourteen (29.2%) females and one (2.5%) male demonstrated an increased GR-Cr test, indicative of a decreased NADPH level. Patients with an abnormal test result demonstrated also significantly increased ACE and GR values (p < 0.05). Only one female case (of 6 tested) appeared to have a mutation in the G6PD gene. CONCLUSION: In a considerable percentage of female patients with sarcoidosis, a decreased level of NADPH in the erythrocytes was found.     

Eradication of glioblastoma,and breast and colon carcinoma xenografts by Hsp70 depletion

Heat shock protein 70 (Hsp70) is an antiapoptotic chaperone protein highly expressed in human tumors. Here we demonstrate that locoregional application of adenovirus expressing antisense Hsp70 cDNA (Ad.asHsp70) eradicates orthotopic xenografts of glioblastoma and breast carcinoma, as well as s.c. xenografts of colon carcinoma in immunodeficient mice. Ad.asHsp70-treated tumors showed massive apoptosis-like cell death and recruitment of macrophages. Human monocyte-derived macrophages effectively removed the corpses of Ad.asHsp70-treated tumor cells in vitro. Interestingly, both tumor cell death and phagocytosis were caspase-independent. Thus, Hsp70 appears as a promising target for the treatment of cancers resistant to classic caspase-mediated apoptosis.     

The impact of a self-help pamphlet on reducing risk drinking among 30- to 49-year-old men in Helsinki, Finland

This study evaluates the impact of a self-help pamphlet designed to support self-control of drinking. It was conducted in Helsinki, Finland, in 2001 and 2002 and focused on men between 30 and 49 years of age. The respondents were randomly selected in an intervention and a control area and compared with each other before and after the intervention using independent samples (N = 4418) The results support previous findings showing that interventions like this serve as a supplement to other prevention and early treatment measures. Although the results were encouraging, there is a need for more in-depth studies in the field.     

Timing and choice of intervention in necrotising pancreatitis

Three patients, men aged 49, 62 and 33 years, were admitted with acute abdominal symptoms due to necrotising pancreatitis. They underwent multiple interventions during a hospital stay of several months, but ultimately recovered completely. In case of infected (peri-)pancreatic necrosis, intervention is required. Good clinical judgement in the differentiation between the septic inflammatory-response syndrome, sepsis and infected necrosis as the cause of the clinical condition is important. Because of the different intervention strategies, treatment by a team comprising a radiologist, gastroenterologist, intensive care specialist and gastrointestinal surgeon is required. Randomised studies on intervention in infected pancreatic necrosis are lacking. In 2002, to improve the treatment of patients with acute (necrotising) pancreatitis via a combination of research, consultation and centralisation, the Dutch Acute Pancreatitis Study Group was formed.     

Carotid stenosis degree in CT angiography: assessment based on luminal area versus luminal diameter measurements

The aim of this study was to investigate CT angiography (CTA) luminal area measurements in the assessment of carotid artery stenosis compared with the current clinically used criteria based on lumen diameter measurements. Seventy-two vessels in 36 patients were evaluated by CTA and digital subtraction angiography (DSA). Two observers measured area and diameter stenosis degrees using automated 3D CTA analysis software. The ratio of the largest/smallest luminal diameter at the level of maximal stenosis (L/S ratio) was used to describe lumen morphology. Diagnostic agreement between CTA and DSA was calculated. For the assessment of area stenosis, interobserver and intraobserver correlation coefficients were 0.898 and 0.906 (p<0.001). The correlation coefficient between the diameter stenosis and area stenosis was lower in stenoses with extremely noncircular lumen (L/S ratio 1.5) (r=0.797, p<0.001) compared with stenoses with circular lumen (LS ratio <1.2) (r=0.978, p<0.001). Only satisfactory agreement ( 0.54-0.77, p<0.001) was obtained between area stenosis on CTA and diameter stenosis on DSA. Assessment of stenosis degree with area measurements on 3D CTA proved to be reproducible. Area stenosis provides a less-severe estimate of the degree of carotid stenosis but might theoretically express the real hemodynamic significance of the lesion better than diameter stenosis, especially in stenoses with noncircular lumen.     

Impairment of lung function in asbestos-exposed workers in relation to high-resolution computed tomography

OBJECTIVES: The aim of the study was to determine the causes of impairment of ventilatory function and diffusing capacity in smoking asbestos-exposed workers (N=590) showing radiological pleural thickenings or pulmonary fibrosis. METHODS: High-resolution computed tomography (HRCT) and spirometry were performed, and diffusing capacity was measured. The workers were divided into five groups based on the HRCT scoring: pleural disease (N=190), pulmonary fibrosis (N=68), emphysema (N=148), combined fibrosis and emphysema (N=74), and marked adhesions (N=110). The graded lung function impairment was compared between the groups. RESULTS: Moderate impairment of forced expiratory volume in 1 second [odds ratio (OR) 2.72, 95% confidence interval (95% CI) 1.31-5.57] and forced vital capacity (OR 2.81, 95% CI 1.05-6.89) was associated with the persons with combined fibrosis and emphysema. Marked impairment of diffusing capacity was associated with the combined fibrosis and emphysema (OR 4.94, 95% CI 2.48-9.77) but not with pleural disease (OR 0.21, 95% CI 0.09-0.45) or pulmonary fibrosis (OR 0.36, 95% CI 0.08-1.05). For the persons with combined fibrosis and emphysema, the mean fibrosis score did not differ between normal, slightly reduced, or markedly reduced diffusing capacity, but the emphysema score was significantly higher for the patients with marked impairment than for those with normal diffusing capacity (P < 0.01). CONCLUSIONS: Different profiles of asbestos- and smoking-induced pulmonary or pleural disease were found. The results indicate that the most important factor determining the degree of functional impairment in smoking asbestos-exposed workers is the presence of pulmonary emphysema.     

Regeneration of human auditory nerve. In vitro/in video demonstration of neural progenitor cells in adult human and guinea pig spiral ganglion

Time lapse video recordings of cultured adult human and guinea pig spiral ganglion (hSG and gpSG) show that mitogen responsive progenitor/stem cells develop in the form of spheres that proliferate and differentiate into mature neurons and glia cells. Neurospheres, cultured with EGF and bFGF showed expression of nestin and incorporation of 5'-Bromo-2-deoxyuridine (BrdU). Newly formed BrdU labelled cells were positive for beta-tubulin, and also for GFAP demonstrating that neuronal cells were derived from a dividing population of progenitor cells. Dissociated spheres cultured either with glia cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), induced differentiation of the progenitor cells. Video microscopy showed that neurons develop from subcultured spheres maintained for up to four weeks. Neurons showed fasciculation and migration with a speed of 10-30 microm/h, and some cells had up to 6 mm long neurites coexpressing TrkB and TrkC receptors. Precise dissection suggests that the neurons formed are cochlea-specific. The results suggest that the mammalian auditory nerve has the capability for self-renewal and replacement. Transplantation of progenitor cells together with established means to induce neural differentiation and fiber growth may facilitate strategies for better repair and treatment of auditory neuronal damage.