Allelic loss on chromosome-13 can preceed histological-changes in head and neck-cancer

Seventy paired tumor and blood samples from patients with upper aerodigestive tract squamous cell carcinoma (UADT SCC) were tested for allelic loss on chromosome 13. Increased loss of heterozygosity (LOH) was observed at 11 of 13 different highly polymorphic microsatellite 'CA' dinucleotide repeat-containing loci. Increasing percent LOH correlated with lymph node metastasis (N Stage) (p=0.016). LOH was also detected in 10 of 16 (63%) informative samples of histologically normal mucosa adjacent to the tumors. These findings demonstrate that allelic loss on chromosome 13 is a frequent event in UADT SCC. Furthermore, these genetic alterations can be detected prior to histological changes in normal mucosa adjacent to these tumors.     

Characterization of adult human prostatic epithelial-cells immortalized by polybrene-induced DNA transfection with a plasmid containing an origin-defective sv40-genome

Normal adult human prostatic epithelial cells were infected with an adenovirus 12-SV40 virus or transfected by polybrene-induced gene transfer with a plasmid (pRSV-T) containing the SV40 early region genes or with a plasmid (pRNS-1) containing an origin-defective SV40 genome and a plasmid carrying the neomycin resistance gene. Colonies of morphologically altered cells were isolated, cultured in a serum-free medium and characterized. These cells had extended lifespan in culture compared to normal adult human prostatic epithelial cells. Both Ad12-SV40-infected and pRSV-T-transfected cultures eventually underwent senescence. pRNS-1-transfected cells (pRNS-1-1), however, have now been grown for more than 50 passages. These cells contain the SV40 genome, express SV40 T-antigen, and are not tumorigenic in nude mice. They express cytokeratins 5 and 8, like the parent cells, and are pseudodiploid. Analysis of growth regulatory processes revealed that the growth of pRNS-1-1 cells was stimulated similarly to that of normal prostatic epithelial cells by epidermal growth factor, insulin-like growth factor, and pituitary extract. The response of pRNS-1 cells to a growth-inhibitory factor, retinoic acid, was also similar to that of normal cells. However, pRNS-1-1 cells were less responsive than normal cells to growth inhibition by transforming growth factor-beta, and had lost altogether the ability of normal cells to be inhibited by tumor necrosis factor-alpha and 1,25 (OH)2 vitamin D3. Therefore transformation appeared to alter growth-inhibitory but not growth - stimulatory mechanisms. These cells should be useful in elucidating the multistep mechanism of carcinogenesis of the prostate.     

Defective RNA molecules associated with citrus tristeza virus

Preparations of single-stranded (ss) RNA extracted from particles of the Israeli VT strain of citrus tristeza virus (CTV-VT), and ss- and double-stranded (ds) RNA preparations extracted from infected Alemow (Citrus macrophylla) plants, contained a population of molecules with features that suggest that they are defective RNAs. The prototype of 2424 nt was cloned and sequenced and was found to be composed of two genomic regions corresponding to the 5' (1151 nt) and the 3' (1259 nt) termini of the genomic CTV-RNA, with two perfect direct repeats of eight nucleotides of unknown origin at the junction site. Northern hybridization analysis demonstrated that this 2.4-kb defective RNA is an abundant species among the other CTV-specific ss- and ds-RNAs in infected plants. The 2.4-kb RNA was found encapsidated by the CTV coat protein indicating that the CTV origin of assembly is located close to the 5' or 3' terminus. This is the first defective RNA to be reported for a member of the closterovirus group.     

Association of apolipoprotein ɛ4 allele and neuropathologic findings in patients with dementia

Apolipoprotein E (APOE) is a lipoprotein expressed in liver and brain as one of three isoforms (APOE 2, APOE 3 and APOE 4). Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease. We extended these observations by determining the frequency of APOE alleles in patients with pathologically confirmed Alzheimer's Disease (AD), Parkinson's disease (PD), diffuse Lewy Body disease (DLBD), AD with concomitant PD pathology, demented PD patients without or with concomitant AD pathology and in schizophrenics with a progressive dementia (SCHIZ+DEM). The APOE genotype was determined by restriction digestion of polymerase chain reaction-amplified DNA isolated from frozen brain samples. The frequency of the APOE 4 allele was highest among sporadic AD and DLBD patients (0.30 and 0.38, respectively) and lowest in the SCHIZ+DEM and non-demented PD patients (0.06 and 0.1, respectively). Thus, the APOE 4 allele is over-represented selectively in patients with dementias associated with plaques and tangles and/or cortical Lewy bodies, but not in demented schizophrenics or non-demented PD patients.     

Basic neuroscience

Poster Session 1

Basic neuroscience     

Evaluation of the Heart To Heart Project: lessons from a community-based chronic disease prevention project

PURPOSE. To present an evaluation of a 5-year, community-based, chronic disease prevention project managed by a state health department to determine whether the department could replicate similar previous projects that had received more funding and other resources. DESIGN. The evaluation used a matched comparison design and a review of archive and interview data. SETTING. Florence, South Carolina (population: 56,240). SUBJECTS. A random sample of 1642 persons in Florence (and 1551 in the comparison) who responded to a risk factor questionnaire and underwent a physical assessment; 70.7% of baseline subjects participated in the postintervention. Forty key persons were interviewed concerning project effectiveness. INTERVENTIONS BY PROJECT. Walk-a-thons, a speakers' bureau, media messages, restaurant food labeling, and cooking seminars. More than 31,000 participants were involved in 585 activities. MEASURES. Questionnaires focused on hypertension, obesity, high cholesterol, smoking, and exercise. Physical assessments determined lipid, lipoprotein, apolipoprotein, and blood pressure levels. Analysis of covariance was used for baseline and postintervention comparisons. Content analysis was used on archive and interview data. RESULTS. The project had a slightly favorable intervention effect on cholesterol and smoking, but failed to have an effect on other risk factors for cardiovascular disease. The project influenced community awareness, enlisted influential community members, and fostered linkages among local health services. CONCLUSIONS. Health departments can be instrumental in community risk reduction programming; however, they may not replicate projects having greater resources.     

Unilateral modified Harada-lto procedure for excyclotorsion secondary to unilateral superior oblique palsy

Background: The Fells modification of the Harada-lto procedure is usually performed bilaterally for the correction of excyclotorsion secondary to acquired bilateral superior oblique paresis. Excyclotorsion is not usually a major complaint in true unilateral superior oblique paresis. Occasional cases, however, may find this symptom bothersome and it may interfere with fusion. The purpose of the present study is to determine the effect of the unilateral modified Harada-lto procedure on the correction of symptomatic excyclotorsion in unilateral superior oblique paresis. Method: A retrospective case-note review of patients with unilateral superior oblique paresis undergoing unilateral modified Harada-lto procedures during the five-year period 1988-1993 was performed. Results: Six patients fulfilled the inclusion criteria. Superior oblique paresis was congenital in one case, secondary to trauma in two cases and idiopathic acquired in three cases. There were four males and two females aged from 25 to 63 years and all but one had previous surgery. The mean pre-operative excyclotorsion was approximately 10 degrees (range 8-14 degrees). Mean post-operative excyclotorsion was 3 degrees (range 2 degrees incyclotorsion -10 degrees excyclotorsion). Conclusion: The unilateral modified Harada-lto procedure is an effective surgical treatment of excyclotorsion resulting from superior oblique paresis and may improve sensory and motor fusion.