Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Cognitive shifting as a predictor of progress in social understanding in high-functioning adolescents with autism: a prospective study

The pyrolytic behavior of inulin, a (2-->1)-linked fructofuranan, is described. Parallel investigations of the pyrolysis of glucose and of fructose were conducted to supplement the inulin results and to aid comparison with previous results from glucans. Effects of neutral and basic additives are emphasized. As with glucans, the addition of such additives (especially basic) increases the yields of the one-, two-, and three-carbon products (as well as of hexosaccharinolactones), while generally decreasing the yields of anhydro sugar and furan derivatives. The former products include glycolaldehyde, acetol, dihydroxy-acetone, acetic acid, formic acid, and lactic acid. Mechanistic speculations are made regarding the origins of these compounds, as well as of furan derivatives and saccharinic acid lactones. Parallels with alkaline degradation are considered.     

Worldwide experience with the Finetech-Brindley sacral anterior root stimulator

BACKGROUND: Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population. METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed. RESULTS: The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%. CONCLUSIONS: These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality.     

An information-processing perspective on childhood anxiety

In the past decade, cognitive theories of adult anxiety disorders have become increasingly complex, reflecting enhanced understanding of anxiety-related information-processing. This growth has fostered the development and enhancement of numerous assessment and treatment methods. Unfortunately, similar growth has been slower to occur in theories of childhood anxiety. This paper attempts to foster such growth by adopting an information-processing perspective. Doing so expands the extant cognitive perspective on childhood anxiety in four major ways. First, the division of cognitive processing into a sequence of steps provides a framework for organizing predictions regarding cognitive factors in childhood anxiety. Second, consideration of the cognitive operations active during each stage in the sequence facilitates elaboration of the types of cognitive deficits and distortions characteristic of anxious children. Third, it promotes development and application of performance-based assessment methodologies. Finally, an information-processing perspective highlights several targets for clinical intervention that may promote widespread change in an anxiety-supporting cognitive system.     

Expression, exon-intron organization, and chromosome mapping of the human sodium iodide symporter

The active iodide uptake of the thyroid gland in humans is mediated by the human sodium iodide symporter (hNIS). In this report, we show that hNIS expression was detected primarily in thyroid tissue, but also in breast, colon, and ovary tissues. Expression of hNIS is greatly reduced in thyroid tumors compared to normal thyroid tissue. Among tumor tissues, hNIS expression appears to be variable, consistent with the variable response to radioiodide treatment observed for thyroid carcinomas. The coding region of hNIS is interrupted by 14 introns, and the nucleotide sequence of each exon-intron junction is reported. Using this information, an alternatively spliced form of hNIS was identified. Finally, the chromosome location of the hNIS gene was mapped to chromosome 19p.     

Prospective, randomized trial comparing blood and oxygenated crystalloid cardioplegia in reoperative coronary artery bypass grafting

OBJECTIVES: Reoperative coronary artery bypass grafting presents unique challenges for myocardial preservation. The purpose of this study was to compare oxygenated blood cardioplegia with oxygenated crystalloid cardioplegia during reoperative coronary artery bypass grafting using transesophageal echocardiography to assess regional wall motion of the left ventricle before and after cardiopulmonary bypass. METHODS: Sixty-one patients undergoing reoperative coronary artery bypass grafting were prospectively randomized to receive oxygenated blood cardioplegia or oxygenated crystalloid cardioplegia delivered with a combined antegrade-retrograde technique. Transgastric short axis views of the left ventricle were made with transesophageal echocardiography during the operation before cardiopulmonary bypass and immediately after cardiopulmonary bypass. Regional wall motion was graded by a blinded observer, and before cardiopulmonary bypass scores were compared with after cardiopulmonary bypass scores. RESULTS: No significant differences were found in the change in regional wall motion score from before cardiopulmonary bypass to after cardiopulmonary bypass between the blood and crystalloid cardioplegia groups. CONCLUSIONS: This study found blood and crystalloid cardioplegia to be equally efficacious for myocardial preservation during reoperative coronary artery bypass grafting.     

Software reliability estimations for telecommunications products

Reliability of software used in telecommunications networks is a crucial determinant of network performance. Software reliability (SR) estimation is an important element of a network product's reliability management. In particular, SR estimation can guide the product's system testing process and releasability decisions. SR estimation is performed using an appropriate SR estimation model. However, the art of SR estimation is still evolving. There are many available SR estimation models to select from, with different models being appropriate for different applications. Although there is no “ultimate” and “universal” SR model on the horizon (and there may not be one in the foreseeable future), methods have been developed for selecting a trustworthy SR model for each application. The present authors have been analyzing and adapting these methods for applicability to network software. Their results indicate that there already exist methods for SR model selection which are practical to use for telecommunications software. If utilized, these methods can promote significant improvements in SR management. The paper presents the results to date