The role of radiotherapy in the treatment of aggressive fibromatosis

Aggressive fibromatosis is a rare benign soft tissue tumor that is difficult to cure because of its infiltrative nature and high tendency to recur locally. The authors retrospectively analyzed 20 patients with histologically-confirmed fibromatosis. All patients underwent surgery with a wide or marginal margin. Five (25%) cases with histologically-negative margins had recurred. External beam radiotherapy was administered to patients whose margins were positive or who had local recurrence. However, out of concern for safety, radiotherapy was not given to two babies and a reproductive-aged woman. The average dose was 5,020 cGy. During the follow-up (mean 32.6 months), all the patients undergoing radiotherapy showed no evidence of local recurrence. A wide local excision has traditionally been the treatment of choice. However, postoperative radiotherapy could be an effective measure for preventing local recurrence in patients with a histologically-positive surgical margin and recurrence independent of any signs of relapse.     

Production and characterization of monoclonal antibodies against human airway mucins

The objective of this study was to generate and characterize monoclonal antibodies (MAbs) against human airway mucins, and therefore, should serve as a useful tool in studying the regulation of airway mucins in various physiological or pathological situations of human airway. As an antigen, we used a high molecular mass mucin preparation purified from the sputum of normal human subjects. Two monoclonal hybridomas, namely MAbs HM02 and HM03 were obtained and they showed strong immunoreactivity against purified or crude mucin in sputum or bronchial washing of normal human subject. With the high immunoreactivity of these MAbs, mucin contents could be analyzed with more than 100-fold dilution of human airway secretion. The antibodies recognized carbohydrate epitopes because their immunoreactivity was completely abolished by treatment of the mucin with 5 mM periodate. Further characterization of MAbs HM02 and HM03 showed that: (1) they belong to the IgM type; (2) they bind to high molecular mass mucins based on Western blot; (3) they could indirectly immunoprecipitate human airway mucin and as we know, this is the first to demonstrate immunoprecipitation of human airway mucin with anti-human mucin antibodies; and (4) they bind to the goblet cell in airway epithelium as well as some submucosal glands based on immunohistochemistry. Therefore, MAbs HM02 and HM03 should be able to serve as an invaluable tool in studying the regulation of airway mucins in various physiological and pathological situations of human airway.     

Reactive astrocytes express p53 in the spinal cord of transgenic mice expressing a human Cu/Zn SOD mutation

In a previous study, we reported increased NOS expression in the astrocytes in the spinal cord of SOD mutant transgenic mice that are used as ALS animal model. Recently, Messmer and Brune suggested that nitric oxide-induced apoptosis is intimately related with p53-dependent signaling pathway, and de la Monte et al. reported increased p53-immunoreactivity in the spinal cord of ALS patients. In the present study, we performed immunocytochemical studies to investigate the changes of p53-immunoreactivity in the brains of the mutant transgenic mice expressing a human Cu/Zn SOD mutation. Immunocytochemistry showed intensely stained p53-IR glial cells with the appearance of astrocytes in all levels of the spinal cord of the mutant transgenic mice, but no p53-IR glial cells were observed in the spinal cord of the control mice. P53-IR astrocytes were also detected in the brain stem of the mutant transgenic mice. In the medulla, they were observed in the medullary reticular formation, hypoglossal nucleus, vestibular nucleus, dorsal motor nucleus of the vagus and nucleus ambiguus. In the pons, their presences were noted in the pontine reticular formation, and trigeminal and facial nuclei. In the midbrain, astrocytes were detected in the mesencephalic reticular formation, red nucleus and periaqueductal gray matter. In the cerebellum, intensely stained p53-IR astrocytes were detected in the intracerebellar nuclei. In contrast to the mutant transgenic mice, no p53-IR astrocytes were detected in the brain stem and spinal cord of the control mice. Further multidisciplinary investigations involving p53-mediated cellular damage and pathogenesis of ALS are needed to clarify the importance of these results.     

Increase in signal intensities on T1-weighted magnetic resonance images in asymptomatic manganese-exposed workers

OBJECTIVES: To clarify the clinical significance of increased signal intensities on T1 weighted magnetic resonance imaging (MRI) we performed a large-scale epidemiological study on asymptomatic manganese (Mn)-exposed workers with its focus on MRI. METHODS: We randomly selected 121 male workers out of a total of 750 workers including Mn-exposed, non-exposed manual, and non-exposed clerical workers in the factories. We studied environmental and biological monitoring, neurological examination, and MRI. RESULTS: The proportion of workers with increased signal intensities among the exposed, the non-exposed manual workers, and the non-exposed clerical workers was 46.1%, 18.8%, and 0%, respectively. Especially, 73.5% of the welders showed increased signal intensities. In no subject, were clinical signs of manganism observed. The pallidal index correlated with blood Mn concentration. CONCLUSION: Increase in signal intensities on the T1-weighted image reflect recent exposure to Mn, but not necessarily manganism. At which increase of signal intensity, the progression of manganism from Mn exposure occurs, remains to be solved.     

c-Fos basal immunoreactivity decreases in rat spinal cord during normal ageing

The pattern of distribution in rat spinal cord and changing pattern during normal ageing of c-Fos expression were investigated by immunohistochemical staining in male Sprague-Dawley rats at the age of 1 week, 5 months and 2 years. c-Fos immunoreactivity was observed diffusely in gray matters in neonatal rats, preferentially located in deep dorsal horn and around central canal. Compared with those of neonatal rats, these cells decreased prominently in adult rats. In aged rats, immunoreactive cells were not seen in any segments. c-Fos immunoreactivity in spinal cord may be related to stress response, functional differentiation, and in part, neuronal death with target dependence. In conclusion, we demonstrated for the first time that c-Fos expression patterns change during normal ageing.     

Distribution of proteoglycans in the human trabecular meshwork: histochemical electron microscopic findings with cuprolinic blue

The distribution of sulfated proteoglycans (PGs) in the normal human trabecular meshwork was studied by histochemical electron microscopy using the cationic dye, cuprolinic blue (CB).. The trabecular meshwork was obtained from human enucleated eyes and incubated for three days. After incubation, they were stained with 0.2% CB at a critical electrolyte concentration and prepared for histochemical electron microscopy. Ultrastructurally, PG-CB complexes were found as small punctate or filamentous structures, and were associated with collagen fibrils in the cores of the trabecular beams and the basal laminae of trabecular endothelial cells. In addition, large filamentous PG-CB complexes were mainly associated with areas of amorphous extracellular matrix between the collagen fiber bundles and in the fine fibrillar material near the basal laminae of endothelial cells of Schlemm's canal. This investigation resulted in an illustration of the ultrastructural distribution of PGs in the human trabecular meshwork. Further studies will be needed to specify the nature of PGs and their role in the aqueous outflow system.     

Cytotoxic constituents from the roots ofAnthriscus sylvestris

Activity-guided fractionation of the roots of Anthriscus sylvestris resulted in the isolation and characterization of five cytotoxic compounds, deoxypodophyllotoxin (1), falcarindiol (2), and angeloyl podophyllotoxin (5) from the hexane soluble fraction and morelensin (3), bursehernin (4) from the chloroform soluble fraction. It is the first report of the occurrence of compound 5 in nature.     

Biomarkers in airway tumors

Despite advances and improvements in diagnosis and treatment of upper aerodigestive tumors including head and neck and lung cancers, the overall survival rate of these patients remains poor. Prevention, early diagnosis, and novel therapy are under active investigation to improve the outcome of the diseases. In particular, chemopreventive strategy is a novel approach to reduce the invasive tumors by reversing the premalignant lesions with certain differentiating agents (i.e., retinoids). To conduct effective chemopreventive trials, there has been a great surge of interest in defining the biomarkers associated with the specific stages of the carcinogenesis and with intermediate end points during the therapy. Carcinogenesis in the upper aerodigestive tract has been explained by two theories, field cancerization and multistep process. The driving forces behind these processes are noted by accumulated genetic abnormalities in the entire epithelium of the airway. These genetic abnormalities include chromosome abnormalities, specific gene alterations (i.e., ras gene family, tumor suppressor genes, growth factors and their receptors), and proliferation and differentiation markers. These biomarkers are herein described in this review article.