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.     

Investigation of the impact of changes in demand forecasting method on the financial performance of an electricity supply undertaking

Peak demand forecasts obtained from six different univariate forecasting methods, under a range of conditions, were used to drive a capacity acquisition model of a large electrical supply system; and the resulting physical and financial performance of the model was observed for each set of forecasts. The results obtained are discussed in the context of their implications for the choice of load forecasting method used in capacity acquisition planning by a power supply undertaking.     

Biological rhythms as organization and information

The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures.     

Structure of the repeating unit of acid polysaccharide from Alteromonas sp. 4MS17

An acidic polysaccharide from Alteromonas sp. 4MC17 is built up of trisaccharide repeating units containing D-glucose, D-mannose and D-galacturonic acid residues. On the basis of methylation studies, 1H and 13C NMR-spectroscopy data, including two-dimensional homonuclear correlation spectroscopy and nuclear Overhauser effects, the following structure was suggested for the polysaccharide repeating unit: -->4)-beta-D-Glcp-(1-->4)-beta-D-GalpA-(1-->4)-beta-D-Manp-( 1-->.     

Dual flaA1 flaB1 mutant of Serpulina hyodysenteriae expressing periplasmic flagella is severely attenuated in a murine model of swine dysentery

The motility imparted by the periplasmic flagella (PF) of Serpulina hyodysenteriae is thought to play a pivotal role in the enteropathogenicity of this spirochete. The complex PF are composed of multiple class A and class B polypeptides. Isogenic strains containing specifically disrupted flaAl or flaB1 alleles remain capable of expressing PF, although such mutants display aberrant motility in vitro. To further examine the role that these proteins play in the maintenance of periplasmic flagellar structural integrity, motility, and fitness for intestinal colonization, we constructed a novel strain of S. hyodysenteriae which is deficient in both FlaA1 and FlaB1. To facilitate construction of this strain, a chloramphenicol gene cassette, with general application as a selectable marker in prokaryotes, was developed. The cloned flaAl and flaB1 genes were disrupted by replacement of internal fragments with chloramphenicol and kanamycin gene cassettes, respectively. The inactivated flagellar genes were introduced into S. hyodysenteriae, and allelic exchange at the targeted chromosomal flaA1 and flaB1 loci was verified by PCR analysis. Immunoblots or cell lysates with antiserum raised against purified FlaA or FlaB confirmed the absence of the corresponding sheath and core proteins in this dual flagellar mutant. These mutations selectively abolished the expression of the targeted genes without affecting the synthesis of other immunologically related FlaB proteins. The resulting flaA1 flaB1 mutant exhibited altered motility in vitro. Surprisingly, it was capable of assembling periplasmic flagella that were morphologically normal as evidenced by electron microscopy. The virulence of this strain was assessed in a murine model of swine dysentery by determining the incidence of cecal lesions and the persistence of S. hyodysenteriae in the gut. Mice challenged with the wild-type strain or a passage control strain showed a dose-related response to the challenge organism. The dual flagellar mutant was severely attenuated in murine challenge experiments, suggesting that the FlaA1 and FlaB1 proteins are dispensable for flagellar assembly but critical for normal flagellar function and colonization of mucosal surfaces of the gastrointestinal tract. This strain represents the first spirochete engineered to contain specifically defined mutations in more than one genetic locus.     

Inhaled induction and emergence from desflurane anesthesia in the ambulatory surgical patient: the effect of premedication

We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia.     

Quenching of chlorophyll fluorescence by quinones

Obese (Lepr(fa)/Lepr(fa)) Zucker rats have a missense mutation in the leptin receptor gene. One amino acid substitution in the extracellular domain common to all known leptin receptor proteins results from this mutation. Obese Zucker rats are unable to respond behaviorally to leptin which is peripherally administered. However, conflicting reports exist on whether obese Zucker rats can respond to centrally administered leptin. The purpose of this study was to determine whether obese Zucker rats responded behaviorally and metabolically to intracerebroventricularly (i.c.v.) administered leptin and to compare the responses of lean and obese Zucker rats. We found that both lean and obese Zucker rats had similar body weight and food intake responses when administered a single i.c.v. leptin injection in a range of doses (1.25, 2.5, 5, and 10 microg), as well as daily i.c.v. administered leptin for five consecutive days. Both single and daily leptin administration also decreased respiratory quotient (RQ) similarly in lean and obese Zucker rats, indicating mobilization of fat as an energy source for leptin-treated rats. After withdrawal of daily leptin treatment, lean and obese Zucker rats exhibited different recovery responses. It is concluded that obese Zucker rats can respond to exogenous leptin when leptin is delivered into the brain ventricles.     

Elderly men with cancer: social work interventions in prostate cancer

Prostate cancer requires the attention of social workers in health care for three reasons: the growing elderly population which will increase the number diagnosed, the recent introduction of new treatments and the lack of social acceptability for this condition. Interventions for prostate cancer are specific to the stage of the disease. These individual, family and group interventions are a model for social work services to elderly men with other forms of cancer. Social workers have opportunity to research quality of life and decision-making issues to enhance medical practise in prostate cancer.