von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Brain circuitry underlying pain in response to imagined movement in people with spinal cord injury

Pain following injury to the nervous system is characterized by changes in sensory processing including pain. Although there are many studies describing pain evoked by peripheral stimulation, we have recently reported that pain can be evoked in subjects with complete spinal cord injury (SCI) during a motor imagery task. In this study, we have used functional magnetic resonance imaging to explore brain sites underlying the expression of this phenomenon. In 9 out of 11 subjects with complete thoracic SCI and below-level neuropathic pain, imagined foot movements either evoked pain in a previously non-painful region or evoked a significant increase in pain within the region of on-going pain (3.2 ± 0.7–5.2 ± 0.8). In both controls (n = 19) and SCI subjects, movement imagery evoked signal increases in the supplementary motor area and cerebellar cortex. In SCI subjects, movement imagery also evoked increases in the left primary motor cortex (MI) and the right superior cerebellar cortex. In addition, in the SCI subjects, the magnitude of activation in the perigenual anterior cingulate cortex and right dorsolateral prefrontal cortex was significantly correlated with absolute increases in pain intensity. These regions expanded to include right and left anterior insula, supplementary motor area and right premotor cortex when percentage change in pain intensity was examined. This study demonstrates that in SCI subjects with neuropathic pain, a cognitive task is able to activate brain circuits involved in pain processing independently of peripheral inputs.     

Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.     

Placental transfer of hexachlorophene (HCP) in the marmoset monkey (Callithrix jacchus)

Autoradiography was used to study the distribution of 2,2'-14C-methylene-bis-(3,4,6-trichlorophenol) (HCP) in pregnant marmoset monkeys in early (day 30-50) and late (around day 120) gestation and in a newborn (11 days old) pup. Radioactivity was present in the conceptus at all stages of gestation, although the foetal concentration was lower than the maternal. In the embryo an accumulation was observed in the neural tube and in the embryonic membranes. In the late foetus and newborn monkey the highest concentration of radioactivity was found in the liver and the intestinal contents. The brain of the adult and newborn animals showed low concentration. A partial blood-brain barrier was present in the late foetus but, in relation to other tissues, the foetal brain concentration was higher than that of the mother.     

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.      

Uptake of lead by Pomphorhynchus laevis cystacanths in Gammarus pulex and immature worms in chub (Leuciscus cephalus)

The uptake of lead by cystacanths of the acanthocephalan Pomphorhynchus laevis in naturally infected amphipods, Gammarus pulex, and by immature parasites in experimentally infected fish, Leuciscus cephalus, was examined following 3-week experimental exposures (0.01 and 0.1 mg l⁻¹ Pb²⁺). Both G. pulex and the cystacanths of P. laevis accumulated lead but concentrations in the parasites were lower than in the host tissues at the low lead dose and significantly lower at the high dose. P. laevis from chub exposed to 0.01 mg l⁻¹ lead contained significantly more of the metal than the tissues of their host. Interestingly, there was an increase in the mean lead levels in the parasites from the control chubs which was concurrent with a decrease in host tissue concentrations. The results of this experimental study therefore confirm previous suggestions that heavy metals are predominantly accumulated by acanthocephalans inside the fish definitive host and not by␣cystacanths in the haemocoel of the amphipod intermediate host. The microhabitat of the parasite is therefore of primary importance rather than its developmental stage. Furthermore, metal concentrations in adult acanthocephalans will respond rapidly to changes in environmental exposure of their hosts. Received: 15 November 1997 / Accepted: 11 February 1998     

Endovascular aspiration of a symptomatic free-floating common carotid artery thrombus

Free-floating thrombi of the common carotid artery (CCA) are a very rare cause of ischemic stroke. To date, only a few reports have been described in the academic literature. Revascularization is indicated due to the risk of thromboembolic disease and hemodynamic-related stroke syndromes. Medical treatment typically includes anticoagulation and, in some circumstances, open surgical thrombectomy is an additional option. Although rarely described in the literature, endovascular thrombectomy is a viable treatment alternative in these patients.     

Indications for breast imaging in women under age 35 years

To determine appropriate indications for breast imaging in young women, the authors correlated patient histories with mammographic and/or sonographic findings and biopsy or follow-up results for 625 patients aged 13-34 years. The only important indications were a palpable mass and suspicion of an abscess. Of the 335 studies performed for evaluation of a palpable mass, 184 (55%) were normal, 28 (8%) were compatible with benign disease, and 123 (37%) were suggestive of malignancy. Biopsies were performed in 73 patients; the findings were benign in 67 cases, and carcinoma was found in six. Imaging studies were considered helpful in four of the 15 cases of suspected abscess, in that the studies established the presence and extent of an abscess. Studies in 275 women were performed for a variety of other indications. The findings were normal in 239 (87%) studies, benign in 21 (8%), and suggestive of malignancy in 15 (5%); there were no known carcinomas in any of the patients. Women with the "low-yield" indications identified in this study should be followed up clinically rather than referred for imaging studies.