Microarray-based characterisation of a Panton–Valentine leukocidin-positive community-acquired strain of methicillin-resistant Staphylococcus aureus

Recent years have witnessed the emergence of novel methicillin-resistant Staphylococcus aureus (MRSA) strains that produce the potent toxin Panton-Valentine leukocidin (PVL). PVL-positive strains can cause complicated skin infections or necrotising pneumonia with high mortality, and these strains have the potential for epidemic spread in the community. In 2004-2005, two case clusters and two isolated cases were observed in eastern Saxony and southern Brandenburg. These were the first known infections with PVL-positive community-acquired MRSA (caMRSA) in this part of Germany. The isolates belonged to agr type III, spa type 44 or spa type 131, and showed a SmaI macrorestriction pattern that corresponded to caMRSA of clonal group ST80. The isolates were susceptible to levofloxacin, macrolides, clindamycin, gentamicin and vancomycin. Most isolates showed resistance to tetracycline and fusidic acid because of the presence of the tetK and far1 genes. A novel plasmid (designated pUB102) harbouring far1, tetK and blaZ was characterised and partially sequenced. Microarray analysis revealed that the caMRSA isolates harboured genes encoding several bi-component toxins (lukF/S-PVL, lukD/E, lukS/F plus hlgA, and another putative leukocidin homologue). Neither tst1 nor genes for enterotoxins A-Y were detected, but the isolates harboured several staphylococcal enterotoxin-like toxin genes (set genes), as well as genes encoding an epidermal cell differentiation inhibitor (edinB) and exfoliative toxin D (etD). Comparative analysis of other isolates from Australia, Germany, Switzerland and the UK showed that these isolates were representative of a widespread clone of caMRSA.     

Deep brain stimulation of the centre median-parafascicular complex in patients with movement disorders

The centre median-parafascicular (CM-Pf) complex of the thalamus is considered to be a possible target for deep brain stimulation (DBS) in patients with movement disorders. In a prospective study on the effect of CM-Pf DBS versus somatosensory thalamic DBS on chronic neuropathic pain, three of 12 patients had additional movement disorders. Bifocal quadripolar electrodes were implanted by computed tomography guided stereotactic surgery under local anaesthesia contralaterally to the side of the pain for test stimulation. Two of the three patients with movement disorders had permanent implantation of CM-Pf electrodes. During test stimulation of the left CM-Pf complex for several days, a 67 year old woman received no benefit with respect to the neuropathic pain, but the choreoathetotic movements of her right foot ceased. As the pain syndrome was not improved, she decided not to have permanent implantation. A 74 year old man with postzoster neuralgia and allodynia enjoyed excellent relief from his pain with chronic CM-Pf DBS. In addition, improvement in the tremor at rest was noted. A 72 year old man had sustained reduction in his stump dyskinesias. Further evaluation of the possible role of the "forgotten" central and medial thalamic nuclei in the treatment of movement disorders may be warranted.     

贴报-P2临床毒理学、药理学和疗效研究

5-Flourouracil（5-FU） is one of well known anti-cancer drugs, but its toxicity in normal lymphocytes remains a major problem in chemotherapy. The eastern traditional drug, Bupleuri radix（BR）, has been used for the treatment of liver diseases and contains series of triterpene saponins.     

Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid beta-oxidation enzymes and peroxisome proliferation in rats treated with dehydroepiandrosterone (DHEA). Evidence of distinct zonal and sex-specific differences

Dehydroepiandrosterone (DHEA) is an intermediate product in the synthesis of male and female sex hormones in the adrenal cortex of man. In livers of rats and mice DHEA increases the levels of cytochrome P450 IVA and peroxisomal beta-oxidation enzymes associated with peroxisome proliferation. Prolonged treatment of rats with DHEA induces liver tumors that are more frequent in females arising mainly in the periportal regions of the liver lobule (Metzger et al., Toxicol. Pathol. 23, 591-605, 1995). Because of paucity of information on hepatic zonation of peroxisomal response to DHEA and controversial reports on gender-specific differences of its effects the present study was undertaken using qualitative immunohistochemical and quantitative immunoelectron microscopical techniques in addition to Western blotting. Rats were treated for 24 weeks with 0.6% DHEA supplied with diet. Immunoblot analysis revealed marked induction of peroxisomal beta- oxidation enzymes, which by quantitative analysis was equally strong in male and female animals, whilst catalase and urate-oxidase were not increased. Cytochrome P450 IVA, in contrast, was induced significantly stronger in male than in female rats. Immunohistochemistry confirmed the induction of cytochrome P450 IVA showing a marked lobular gradient in female animals with strong induction in pericentral and almost no induction in periportal regions of the liver lobule. In male animals cytochrome P450 IVA was expressed more uniformly across the liver lobule. A similar sex specific zone-dependent response was observed for peroxisomes. DHEA induced in females a significant zonal gradient with marked peroxisome proliferation and a strong induction of peroxisomal hydratase/dehydrogenase in pericentral hepatocytes and a much smaller response in periportal regions. Livers of male animals, in contrast, showed a uniform peroxisomal proliferation to DHEA with only slight zonal differences. The striking homologies of the induction patterns of cytochrome P450 IVA and the peroxisome proliferation in both sexes support the notion of a functional relationship. In view of the almost exclusive periportal localization of DHEA-induced tumors in female rats in contrast to the pericentral localization of the peroxisomal proliferation shown by this study, it seems likely that other factors in addition to peroxisome proliferation may contribute to the hepatocarcinogenic effect of DHEA.      

Immunocytochemical detection of herpes viruses in oral smears of HIV-infected patients

Cytologic smears (CS) were taken from the lateral border of the tongue of HIV-seropositive patients (HIV+) (n = 39) and of seronegative controls (HIV-) (n = 19) and examined by immunocytochemistry (APAAP) and in situ hybridization (ISH) (biotinylated DNA probes) for the presence of viral antigens/DNA of EBV and CMV. While none of the HIV controls showed positive results for EBV antigen, 61% (APAAP) resp. 79% (ISH) of oral epithelial cells in the group of HIV+ patients were EBV-positive. While all CS taken from areas with the clinical diagnosis of hairy leukoplakia (HL) were EBV positive (APAAP and/or ISH), the detection of EBV in CS from uninvolved oral mucosa seemed to be associated with the later development of HL. In the group of HIV+ patients the detection rate for CMV was about five times (APAAP) resp. three times (ISH) higher than in HIV- persons. This non-invasive technique seems to be a valuable tool to screen for viral antigens/genomes.     

Parkinsonian action tremor: interference with object manipulation and lacking levodopa response

It has been postulated that Parkinsonian action tremor is distinct from classical resting tremor and that it may contribute to a loss of manual dexterity in Parkinson's disease. We analyzed pinch grip coordination in 20 patients with Parkinson's disease. An object with and without an additional 500 g weight was grasped, lifted and held for a short time with opposed thumb and index finger. Force sensors recorded the force exerted by both fingers. Spectral analysis of the force traces was performed. Transition times between grasping and lifting the object were measured. 18 age matched normal volunteers served as a control group. While holding the object, there were force oscillations in the 3.5-6.5 Hz band indicating (reemerging) classical Parkinsonian tremor in 65% of the patients. This was reduced to 15-20% under levodopa. Oscillations in the 6-15 Hz band were found in 30% (50% with weight) of the patients, remaining unchanged under levodopa, and in 10% (20% with weight) of the normal controls. During lift initiation, 6-15 Hz oscillations were found in all patients and the majority of controls. The band power was positively correlated with the movement transition times in the severely akinetic patients and was significantly higher than in controls. It remained unchanged under levodopa. Our data confirm that Parkinsonian action tremor activated during complex voluntary movements is distinct from classical resting tremor. It does not show a clear levodopa response but affects dextrous movement coordination when associated with clinically severe overall akinesia.     

Quantification of aortic valve calcification with electron beam tomography: a histomorphometric validation study

RATIONALE AND OBJECTIVES: The exact quantification of the amount of calcification in aortic valves may be useful for the identification of risk factors for the progression of aortic valve calcification and to evaluate new therapeutic approaches for aortic valve disease. Electron beam tomography (EBT) allows the in vivo detection of calcifications in coronary vessels and in the aortic valve. The aim of this study was to validate the quantification of aortic valve calcification by EBT with in vivo and in vitro investigations. METHODS: In 15 patients (aortic stenosis in 13, aortic regurgitation in 2 cases), EBT was performed before aortic valve replacement (40 cross sections, 3-mm slice thickness, matrix 512 x 512, field of view 28 cm, ECG trigger at 40% of the cardiac cycle). EBT was repeated on the explanted aortic valve using the same protocol. In both data sets, the amount of aortic valve calcification was determined using a volumetric score. In serial cuts of the explanted valve (distance 1 mm), the calcified volume was determined by an independent investigator using histomorphometric analysis. RESULTS: The mean calcified volume of the aortic valves as quantified by EBT was 1650.0 +/- 1401.0 mm? in vivo (EBT1) and 1544.4 +/- 1266.5 mm? in vitro (EBT2). Histomorphometric analysis showed a mean calcified volume of 1555.7 +/- 1272.5 mm?. The mean difference between EBT1 and EBT2 was 4.2 +/- 14.7%, between EBT1 and histomorphometry 3.6 +/- 12.1%, and between EBT2 and histomorphometry -0.5 +/- 5.9%. CONCLUSION: EBT allows accurate in vivo quantification of aortic valve calcifications.     

Oral manifestations of AIDS-associated non-Hodgkin's lymphomas

While B-cell lymphomas are frequently found in AIDS patients, reports on oral manifestations are rare. Among a group of 465 HIV-infected patients 5 presented with primary oral manifestations of a malignant B-cell lymphoma. The primary site of manifestation was the maxilla in 3 cases and the mandible in 2 cases. Based on the histological and immunohistochemical examination the tumors were differentiated as Burkitt's lymphoma (n = 1), as anaplastic large cell (ALC) lymphoma of the B-cell type (n = 1), as high-grade non-Hodgkin's lymphoma not classifiable according to the Kiel classification (n = 1), as immunoblastic-plasmoblastic lymphoma (n = 1), and as centroblastic lymphoma (n = 1). Serum samples were negative for HTLV-I antibodies in 5/5 cases.     

Venous clots: evaluation with MR imaging

In vitro and in vivo studies were performed to determine the proton relaxation and imaging characteristics of static blood and acute and organized clot in canine jugular veins. In vivo, it was found that two inversion recovery sequences using a short inversion time (100 msec) demonstrated better differentiation of signal intensity of intravascular clot from surrounding soft tissues than did standard T1- and T2-weighted sequences. In vitro, quantitative measurements showed marked reduction of both T1 and T2 relaxation time of acute clot compared with stagnant blood. In addition, the T1 relaxation time, and to a lesser extent the T2 relaxation time, shortened as the clot aged, indicating a potential role for magnetic resonance imaging in determining the age of venous thrombi.