Thermodynamic and base-pairing studies of matched and mismatched DNA dodecamer duplexes containing cis-syn, (6-4) and Dewar photoproducts of TT

Cis-syn dimers, (6-4) products and their Dewar valence isomers are the major photoproducts of DNA and have different mutagenic properties and rates of repair. To begin to understand the physical basis for these differences, the thermal stability and base pairing properties of the corresponding photoproducts of the TT site in d(GAGTATTATGAG) were investigated. The (6-4) and Dewar products destabilize the duplex form by approximately 6 kcal/mol of free energy at 37 degreesC relative to the parent, whereas a cis-syn dimer only destabilizes the duplex form by 1.5 kcal/mol. Duplexes with G opposite the 3'-T of the (6-4) and Dewar products are more stable than those with A by approximately 0.4 kcal/mol, whereas the cis-syn dimer prefers A over G by 0.7 kcal/mol. Proton NMR suggests that wobble base pairing takes place between the 3'-T of the cis-syn dimer and an opposed G, whereas there is no evidence of significant H-bonding between these two bases in the (6-4) product. The thermodynamic and H-bonding data for the (6-4) product are consistent with a 4 nt interior loop structure which may facilitate flipping of the photoproduct in and out of the helix.     

The postoperative lumbar spine: evaluation of epidural scar over a 1-year period

BACKGROUND: Results of antituberculous chemotherapy for Mycobacterium avium complex disease remain disappointing. Pulmonary resection during an early stage of the disease, therefore, may be beneficial to patients whose disease is localized and who can tolerate a resectional operation. METHODS: Thirty-three patients with localized M avium complex disease underwent 33 pulmonary resections between 1979 and 1996. There were 17 males and 16 females, with a mean age of 50 years (range, 30 to 69 years). Lobectomy was performed in 26 patients, pleuropneumonectomy in 1, segmentectomy in 5, and wedge resection in 1. RESULTS: There was no operative mortality. After pulmonary resection, 31 (94%) patients attained sputum-negative status. Bronchopleural fistula occurred in one patient who underwent a right upper lobectomy. There were two late deaths. A patient with bronchopleural fistula died of respiratory failure two years postoperatively. Another patient died of an unknown cause 12 years postoperatively. Of the 31 patients with negative sputum status postoperatively, only 2 patients (6%) had relapse at 1 and 9 years after operation. CONCLUSIONS: We recommend that patients with this disease be considered for pulmonary resection as early as possible.     

Somatostatin receptor desensitization in NG108-15 cells. A consequence of receptor sequestration

In NG108-15 cells inhibition of both N-type calcium channel current and adenylyl cyclase by somatostatin (SRIF) was not sustained but rapidly desensitized in the continued presence of the drug. The degree and rate of desensitization were concentration-dependent, and the desensitization was homologous with respect to the delta-opioid receptor. We have been unable to obtain evidence for the involvement of G protein-coupled receptor kinases (GRKs) in this desensitization. SRIF-induced desensitization of N-type calcium channel currents was not reduced in cells stably overexpressing a dominant negative mutant of GRK2 or following intracellular dialysis with GRK2- and GRK3-blocking peptides or with heparin. Inhibitors of protein kinase A, protein kinase C, and protein kinase G were also without effect. In contrast, both the rate and degree of SRIF-induced desensitization were reduced by pretreatment with phenylarsine oxide or concanavalin A, both inhibitors of receptor endocytosis. Furthermore, SRIF-induced desensitization was enhanced by monensin, which prevents receptor recycling back to the plasma membrane. Similarly, SRIF-induced desensitization of adenylyl cyclase inhibition was not reduced in cells stably overexpressing dominant negative mutant GRK2 but was reduced in cells pretreated with the receptor endocytosis inhibitor hyperosmotic sucrose or concanavalin A. These data are consistent with the view that SRIF-induced desensitization in NG108-15 cells results from receptor internalization.     

Low prevalence of human papillomavirus in a geographic region with a high incidence of head and neck cancer

BACKGROUND: The main purpose of this study was to determine the prevalence of human papillomavirus (HPV) infection in patients with head and neck carcinomas from Brazil. MATERIALS AND METHODS: Forty-five patients with head and neck squamous cell carcinoma were included in the study, from 1995 to 1996. Forty-two were male and 3 female, with age ranging from 32 to 82 years (median 61). Five patients (11%) did not have previous history of use of tobacco and 38 (90.5%) were heavy smokers. Tumor sites were pyriform sinus, 10; tongue, 11 (oral, 6; base, 5); larynx, 7; floor of mouth, 3; tonsil, 6; retromolar area, 3; inferior gingiva 2; buccal mucosa, 2; and maxillary sinus in 1 patient. Twenty-five were stage IV, 17 stage III, and 3 stage II. RESULTS: The presence of HPV DNA was detected in 5 of 45 patients (11%), all of them with HPV 16. Two patients had HPV DNA in normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa, and 2 patients were positive for HPV DNA in tumor tissue. Four patients were male and 1 was female; 2 patients were nonsmokers. Three patients had tonsil carcinoma, 1 patient had a tongue carcinoma, and 1 patient had a pyriform sinus cancer. CONCLUSIONS: The role of chemical carcinogens seems to be more important in the genesis of head and neck cancer than is HPV infection. The presence of HPV DNA in 5 of 45 patients stimulates further investigation to determine the role of HPV as a risk factor for head and neck carcinoma.     

Prenatal cocaine but not prenatal malnutrition affects foster mother-pup interactions in rats

The separate and combined effects of prenatal cocaine exposure and malnutrition on mother-pup interactions in rats were assessed daily from postnatal day 2 to day 21. Sprague-Dawley dams were fed a diet of low protein content (6% casein), an isocaloric diet of adequate protein content (25% casein, control), or a laboratory chow diet prior to mating and throughout pregnancy. Within each diet group, rats received either cocaine injections (30 mg/kg IP two times per week prior to mating and then 30 mg/kg SC daily from days 3 to 18 of pregnancy) or saline injections. Litters were fostered on the day of birth to control mothers (i.e., nondrug-exposed dams fed the control or chow diet). Foster mothers fed the 25% casein diet showed increased contact with cocaine-exposed pups compared with nondrug-exposed pups in the second postnatal week but lower levels as the pups approached weaning. Passive nursing was increased in dams caring for prenatally malnourished, cocaine-exposed pups compared with those caring for similar pups with no drug exposure. Chow-fed mothers did not differ in their behavior towards pups with or without prenatal cocaine treatment. Prenatal cocaine and malnutrition independently compromised birth weight and various reflexive milestones but the attainment of physical milestones was affected only by prenatal cocaine. There were no additive effects of the two prenatal insults on any measure of mother-pup interaction or pup development.     

Chromosome 15-linked limb-girdle muscular dystrophy: clinical phenotypes in Reunion Island and French metropolitan communities

Erb's type limb-girdle muscular dystrophy (LGMD) was identified and clinically studied in detail in a small community living in the Reunion Island (RI). It was linked to chromosome 15q and related to mutations in the muscle specific calpain 3 gene. A series of cases were afterwards clinically and genetically identified in the French metropolitan community. The phenotype was identical to the RI type in the great majority of cases, although clinical differences were noticed in a few cases. Six different mutations were identified in the RI families, whereas a series of 39 mutations were detected in the French metropolitan families, all different from those present in the RI patients. Phenotype-genotype correlations were attempted in both communities.     

Synthesis and evaluation of 5-aminosalicyl-glycine as a potential colon-specific prodrug of 5-aminosalicylic acid

OBJECTIVE: To estimate more precisely the risk of fetal loss and congenital abnormalities after maternal parvovirus B19 infection, and to assess the long term outcome for surviving infants. DESIGN: Prospective cohort study of pregnant women with confirmed B19 infection with follow up of the surviving infants. The rate of fetal loss in the study cohort was compared with that in pregnant women with varicella. SETTING: Cases reported by laboratories in England and Wales between 1985-1988 and 1992-1995. SAMPLE: Four hundred and twenty-seven pregnant women with B19 infection and 367 surviving infants of whom 129 were followed up at 7-10 years of age. METHODS: Questionnaires to obstetricians and general practitioners on outcome of pregnancy and health of surviving infants. Maternal infection confirmed by B19-specific IgM assay and/or IgG seroconversion. RESULTS: The excess rate of fetal loss in women with B19 infection was confined to the first 20 weeks of gestation and averaged 9%. Seven cases of fetal hydrops followed maternal infections between 9 and 20 weeks of gestation (observed risk 2.9%, 95% CI 1.2-5.9). No abnormalities attributable to B19 infection were found at birth in surviving infants (observed risk 0%, upper 95% CI 0.86%). No late effects were found at 7-10 years. CONCLUSIONS: Around 1 in 10 women infected before 20 weeks of gestation will suffer a fetal loss due to B19. The risk of an adverse outcome of pregnancy after this stage is remote. Infected women can be reassured that the maximum possible risk of a congenital abnormality due to B19 is under 1% and that long term development will be normal.     

Delimiting ''rural'': implications of an agreed ''rurality'' index for healthcare planning and resource allocation

Apoptosis is known as an active process of cell death forced by radio- and chemotherapy. Therefore, established concepts (terms, therapy schemes) will reflect a picture different from that usually seen, when examined under the apoptotic point of view. Furthermore, the development of new concepts for innovative diagnosis, prognosis and therapy could be accomplished. This is an attempt to reveal actual features of both aspects.