The antiviral characteristics of monoclonal antibody IAM-41-2F5 (2F5) were determined in cell culture.

Optimization increased both the analytical sensitivity and the clinical specificity of the assay to more effectively discriminate the low-titer antibody response of HPV-infected persons from noninfected individuals. The characteristics of the assay that were optimized included monoclonal antibody (MAb) specificity, scaling up the conjugation of virus-like particles (VLPs) to microspheres, VLP concentration, MAb concentration, sample matrix, sample dilution, incubation time, heat inactivation of sample sera, and detergent effects on assay buffer. The assay was automated by use of a TECAN Genesis Workstation, thus improving assay throughput, reproducibility, and operator safety. Following optimization, the assay was validated using several distinct serum panels from individuals determined to be at low and high risk for HPV infection. The validated assay was then used to determine the clinical serostatus cutoff. This high-throughput assay has proven useful for performing epidemiology studies and evaluating the efficacy of prophylactic HPV vaccines.Cervical cancer is the second most common cancer in women worldwide. Every year, 450,000 women are diagnosed with cervical cancer and 220,000 succumb to this disease (27). Current approaches to cervical cancer control involve lifelong screening using the Papanicolau (Pap) test (13). The goal of screening is to detect precancerous lesions so that they can be removed prior to the development of cancer. Despite widespread Pap testing, there were an estimated 10,520 new cases of cervical cancer and nearly 4,000 cervical cancer-related deaths in the United States in 2004 (1). The national health care burden of current screening systems combined with direct costs of treating precancerous and cancerous lesions is in excess of 3.5 billion U.S. dollars per annum (7).Infection with human papillomavirus (HPV) is the first and obligate step in the development of cervical cancer (3, 4). Infection of the cervical epithelium with HPV results in expression of the E6 and E7 proteins, which have been shown to be potent oncogenes. More than 35 different HPV types are capable of infecting the human genital tract (2, 4, 28). Of these, four types cause the majority of the HPV-related cervical pathology. HPV 16 and 18 together account for 74.6% of all cervical cancers (23), whereas HPV6 and -11 cause a significant fraction of precancerous lesions which rarely develop into cervical cancer but morphologically are indistinguishable from lesions from more dangerous HPV types (37). HVP 6 and 11 are responsible for approximately 90% of all genital wart cases (37).The HPV LI capsid protein, when expressed recombinantly, assembles into empty viral capsids or "virus like particles" (VLPs) (12,15,16,29). Several prophylactic vaccines based on HPV LI VLPs are currently in phases II and III clinical development (14,17,36). The VLPs in the vaccine present the immune system with the conformational, neutralizing epitopes found on the natural virus and prime the immune system to generate antibodies that neutra...

Positron emission tomography (PET) is currently the only technology affording three-dimensional measurement of the brain's energy metabolism which is closely coupled to brain function. Studies of glucose metabolism by PET of (18F)-2-fluoro-2-deoxy-D-glucose are therefore widely applied to show the contribution of various brain structures in the performance of a variety of tasks or their participation in functional deficits associated with various diseases. Although glucose metabolism decreases slightly with age to a regionally different degree, most types of dementia show severe changes in glucose metabolism. Alzheimer's disease (AD) is characterized by metabolic disturbances most prominent in the parietotemporal association cortex and later in the frontal lobe, whereas primary cortical areas, basal ganglia, thalamus, brainstem, and cerebellum are not affected. It is this typical pattern that distinguishes AD from other dementia syndromes. A ratio calculated from the metabolic rates of glucose of "affected" and "nonaffected" brain regions was able to separate patients with AD from age-matched controls and permitted the discrimination of patients with cognitive impairment of other origin in 85%. The discriminative power can be further improved by activation studies. A continuous visual recognition task increased the metabolic rate in normal subjects by 21% and in patients with AD by 6% on average, with significant regional differences. During activation the significant relation between severity of disease and temporoparietal metabolic rate became even stronger. In the assessment of effects of treatment on disturbed metabolism, PET studies demonstrated an equalization of metabolic heterogeneities in patients responding to a muscarinergic cholinagonist, whereas general increases in glucose utilization were observed with piracetam, pyritinol, and phosphatidyl-serine. The therapeutic relevance of such metabolic effects, however, must be proved in controlled clinical trials.