Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1

Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.     

Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.     

Regional activation of L-type voltage-sensitive calcium channels in experimental thiamine deficiency

At present (putative) human carcinogens are identified via epidemiological studies and testing using the chronic 2-yr rodent bioassay. Both methods have severe limitations in that they are slow, insensitive, expensive, and are also hampered by many uncertainties. The development of methods to modify specific genes in the mammalian genome has provided promising new tools for use in identifying carcinogens and characterizing their (qualitative) risk. Several transgenic mouse lines are currently under study to test their possible use in short-term carcinogenicity testing. One such candidate alternative transgenic model is the XPA knock-out mouse. These mice have an almost complete deficiency in DNA nucleotide excision repair (NER). Nevertheless, XPA-deficient mice are viable and have a background of a low incidence of spontaneous development of cancers. Approximately 15% of the mice develop hepatocellular adenomas (only after 1.5 yr). After treatment with ultraviolet-B radiation or 7,12-dimethylbenz(a)anthracene, the XPA-deficient mice developed squamous cell carcinomas and papillomas, respectively, on their skin. Oral treatment of XPA-deficient mice with benzo[a]pyrene (B[a]P), 2-acetylaminofluorene (2-AAF), and 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) resulted in lymphomas (B[a]P), liver and bladder tumors (2-AAF), and intestinal adenomas plus lymphomas (PhIP). These results look encouraging, but it should be noted that the compounds and agents tested thus far have all been substrate for nucleotide excision repair. Animal studies with different genotoxic or nongenotoxic compounds, as organized for instance within the framework of the International Life Sciences Institute/Health and Environmental Sciences Institute program, are needed to further evaluate the suitability of the XPA model for short-term carcinogenicity testing.     

Social support and depression among older adults living alone: the importance of friends within and outside of a retirement community

Using socioemotional selectivity theory as a framework, the study described in this article examined the extent to which social support from friends both within and outside of a retirement community was associated with depression. Although levels of social support from friends within the retirement community were quantitatively high, they failed to have a significant effect on depression. In contrast, social support from friends living elsewhere consistently predicted low levels of depression. Practice implications include the importance of maintaining friendship ties with people living elsewhere and of strengthening friendship ties within the retirement community.     

Possible involvement of plasmids in degradation of malathion and chlorpyriphos by Micrococcus sp

Culture is the basic method in bacteriology. It allowed the discovery of Helicobacter pylori. Problems in the culture of this fragile, slow-growing bacterium concern transport and processing in the laboratory, but they can be solved. Culture has a 100% specificity. When performed properly, it has a sensitivity in the range of the other best diagnostic methods for Helicobacter pylori. It allows strain typing and, most importantly, susceptibility testing to antibiotics, because an increased rate of acquired resistance of Helicobacter pylori is currently observed. Culture must be performed in clinical trials, at least when antibiotics, to which Helicobacter pylori may be resistant, are used. In clinical practice, culture and susceptibility testing can generally be restricted to treatment failures. However, it is important to monitor Helicobacter pylori susceptibility to antibiotics at a national or regional level in order to give recommendations for primary treatment.     

Delayed endodontic and orthodontic treatment of cross-bite occurring after luxation injury in permanent incisor teeth

A case is presented in which combined endodontic and orthodontic therapy was performed in traumatically injured teeth 12 months after an accident. Calcium hydroxide treatment was used to halt any possible resorption during orthodontic treatment. The teeth were repositioned in a desirable manner without any complication by orthodontic treatment. Root canal obturation was accomplished after the completion of active orthodontic treatment. Recall examination 12 months after completion of root canal treatment showed clinical and radiographic evidence of healing.