Augmenting the immunogenicity of synthetic MUC1 peptide vaccines in mice

Human mucin MUC1 is abundantly expressed in some cancers of epithelia] origin and is largely restricted to the apical surface of secretory cells in normal tissues. It is, therefore, a potential target for cancer immunotherapy. In preparation for clinical trials, vaccines containing synthetic MUC1 peptides of different lengths and sequences mixed with various adjuvants or covalently attached, using different linker methods, to protein carrier keyhole limpet hemocyanin (KLH) were studied in mice. MUC1 peptides (containing 30 amino acids), plus adjuvants QS-21 or Bacillus Calmette-Guerin, were incapable of inducing antibody. However, MUC1 peptides conjugated to KLH (MUCl-KLH), plus QS-21, induced high titer antibody against the immunizing peptides and against MUC1-expressing tumor cells. Although T-cell responses, including delayed-type hypersensitivity, lymphocyte proliferation, and CTL, were not observed in mice immunized with these vaccines, significant protection from MUC1-expressing tumor cell challenge in mice immunized with MUC1-KLH was observed. Based on these studies, a vaccine containing MUC1-KLH conjugate prepared with m-maleimidobenzoyl-N-hydroxysuccinimide ester linker, plus QS-21, has been constructed for testing in clinical trials.     

Compliance, counseling and satisfaction with oral contraceptives: a prospective evaluation

CONTEXT: Oral contraceptive users' risk of accidental pregnancy may be higher than it should be, because of inconsistent pill-taking. However, few reliable data are available on pill users' everyday experiences with their method, especially characteristics that may affect consistency of use. METHODS: Two months after initiating or resuming oral contraceptive use, a nationwide sample of 943 women completed questionnaires examining their compliance with instructions for proper use, the quality of their interactions with their provider, their satisfaction with the method, and the frequency and costs of visits or calls to their providers because of pill-related side effects. Regression analyses were used to determine the factors associated with compliance difficulties and method dissatisfaction. RESULTS: In all, 47% of users missed one or more pills per cycle, and 22% missed two or more. Women who lacked an established pill-taking routine, who did not read and understand all of the informational material accompanying the pill package, or who experienced spotting or heavy bleeding had increased odds of missing two or more pills per cycle. Method satisfaction was most likely among women who were aware of the pill's noncontraceptive benefits, were satisfied with their relationship with their provider, had used the pill in the past and experienced few side effects. Some 22% of users called their provider at least once about pill-related side effects, and 9% made at least one visit for this reason; these women spent $25 and $62, respectively, to treat side effects. CONCLUSIONS: Improving pill use is a shared responsibility of the provider, the patient and, to a lesser degree, pill manufacturers. Awareness of potential difficulties such as inadequate counseling is a key step in helping women use oral contraceptives effectively.     

The influence of precipitation on the work-hardening behavior of the aluminum alloys AA6111 and AA7030

Tensile tests were conducted on the aluminum alloy, AA6111, after various artificial aging treatments in order to examine the influence of precipitation state on yield stress and work-hardening behavior. During artificial aging, significant changes in the work-hardening rate were observed as the precipitation reaction proceeded. A semiempirical model has been developed to interpret these changes in work-hardening rate. This model shows that the significant changes in work-hardening rate can be related to the manner in which flow stress contributions from different obstacles are summed and the transition from shearable to nonshearable precipitates. The present study presents a new approach to determining the shearable/nonshearable transition from a series of tensile tests. Results on the aluminum alloy AA7030 were also found to be consistent with the proposed theoretical framework. Finally, the proposed model allows the overall mechanical response for a variety of aging conditions to be rationalized.     

Body composition development of adolescent white females: the Penn State Young Women''s Health Study

m-Enterococcus agar (m-Ent) has been generally considered the reference medium for faecal streptococci in bathing waters. However, it shows several shortcomings, and therefore it is important to test newly developed media that can guarantee more precise results. In this sense, the recently described oxolinic acid--esculin--azide agar medium (OAA) and m-enterococcus agar (m-Ent) were comparatively evaluated for the detection of faecal streptococci from seawater and fresh water. The OAA medium showed a significantly higher relative recovery percentage and specificity for both types of water than m-Ent. A similar spectrum of species was recorded from both media, Enterococcus faecium being predominant in fresh water and Enterococcus faecalis, in seawater. The superior performance of the OAA medium in both types of bathing waters, added to the fact that it does not require the use of complementary confirmative tests, makes this medium an excellent candidate to be employed for monitoring programmes.     

Thoughts of agoraphobic people during scary tasks.

The authors examined the occurrence of theoretically derived patterns of thinking in 74 agoraphobic participants as they drove alone or tolerated an enclosed place. During the increasingly scary tasks in a behavioral test hierarchy, participants responded to a periodic beep by stating aloud what they were thinking at that moment, yielding more than 1,800 tape-recorded statements. Content analyses revealed that participants were mainly preoccupied with their current anxiety (expressed in 29% of the statements) and with their self-efficacy (15%). Despite participants' mounting feelings of anxiety, fewer than 1% of their statements expressed a thought of danger or an anticipation of future anxiety or panic. The rarity of danger thoughts poses an explanatory challenge for all cognitive theories of phobia and especially for the perceived danger theory of A. T. Beck (1976) and A. T. Beck, G. Emery, and R L. Greenberg (1985). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comments on three recent subliminal psychodynamic activation investigations.

Contends that unwarranted statements about subliminal psychodynamic activation research by the present author (1976, 1983, 1984) were made in the work of J. M. Oliver and R. Burkham (see record 1983-01571-001); K. C. Haspel and R. S. Harris (see record 1983-04952-001); and A. L. Porterfield and S. L. Golding (see record 1986-11992-001). Issues considered include the choice of subliminal stimuli, the present author's statistical analyses, and the necessity of a nonverbal measure of psychopathology in this research. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

241Am removal by DTPA vs. occurrence of skeletal malignancy

PURPOSE: The distribution of hyaluronan (HA) and the cellular response after photokeratitis induced by different ultraviolet (UV) wavelengths in the rabbit cornea was examined to help understand the mechanism of corneal injury and repair after UV damage. HA is a high molecular weight disaccharide polymer capable of binding considerable amounts of water. It is not normally found in the rabbit corneal stroma. The production of HA represents a generalized corneal response to injury. METHODS: Twenty-four albino rabbit corneas were exposed to 270, 290, and 310 nm of UV radiant energy in 8-nm full wavebands in doses producing biomicroscopically significant keratitis (three corneal thresholds for keratitis (Hc): 0.016 J/cm2 for 270 nm, 0.04 J/cm2 for 290 nm, and 0.14 J/cm2 for 310 nm) and in subkeratitis doses (0.7 Hc: 0.004 J/cm2 for 270 nm, 0.008 J/cm2 for 290 nm, and 0.03 J/cm2 for 310 nm). The rabbits exposed to 270 and 290 nm of UV radiation were sacrificed 3 days after exposure. The rabbits exposed to 310 nm of UV radiation were sacrificed 3, 7, and 14 days after exposure, respectively. The corneal tissue specimens were double stained and examined morphologically and histochemically for HA by light microscopy. RESULTS: Evaluation of corneas exposed to 270 and 290 nm of UV radiant energy in both subkeratitis and keratitis doses and those corneas exposed to 310 nm of radiant energy in subkeratitis dose showed neither stromal changes nor production of HA by corneal cells. Corneas exposed to 310 nm of UV radiant energy in keratitis dose at 3 days after exposure showed disappearance of keratocytes in entire thickness of central cornea. Cells bordering this damaged area were staining for HA. By 7 days after exposure almost the whole damaged area, except one fourth of anterior stroma, was repopulated by new keratocytes staining positive for HA. The corneal structures became normal and HA almost completely disappeared 14 days after exposure. CONCLUSIONS: A keratitis dose of 310 nm of UV light irradiation is needed to cause keratocyte damage. A keratitis dose of the shorter wavelengths does not cause keratocyte cell damage at the light microscopic level. The keratocyte production of HA appears to be a sign of cell readiness to repopulate the damaged stroma devoid of keratocytes.     

The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents

Neuronal nicotinic acetylcholine receptors (NAChRs) are pentameric ligand-gated ion channel receptors which exist as different functional subunit combinations which apparently subserve different physiological functions as indicated by molecular biological and pharmacological techniques. It is possible to design and synthesize novel compounds that have greater selective affinities and efficacies than nicotine for different NAChRs, which should translate into different behavioral profiles and therapeutic potentials. Examples of NAChR agonists studied are nicotine, SIB-1508Y, SIB-1553A and epibatidine. These compounds have different degrees of selectivity for human recombinant NAChRs, different neurotransmitter release profiles in vitro and in vivo and differential behavioral profiles. Preclinical studies suggest that SIB-1508Y is a candidate for the treatment of the motor and cognitive deficits of Parkinson's disease, whereas SIB-1553A appears to have potential as a candidate for the treatment of Alzheimer's disease. Epibatidine has a strong analgesic profile, however the ratio between pharmacological activity and undesirable effects is so low that it is difficult to envisage the use of this compound therapeutically. Nicotine has a broad profile of pharmacological activity, for instance demonstrating activity in models for cognition and analgesia. As for epibatidine, the adverse effects of nicotine severely limits its therapeutic use in humans. The discovery of subtype-selective NAChR agonists such as SIB-1508Y and SIB-1553A provides a new class of neuropsychopharmacological agents with better therapeutic ratios than nonspecific agents such as nicotine.     

Modeling the microstructural changes during hot tandem rolling of AA5XXX aluminum alloys: Part III. Overall model development and validation

Part III of this article presents the overall mathematical development for the microstructural and textural evolution during industrial hot tandem rolling of AA5182 and AA5052 alloys and validation of the mathematical model, by comparison to both industrial data and information from the literature. The model consists of a plasticity module to simulate the temperature and deformation in the roll bite and an interstand module to characterize the changing microstructure, texture, and temperature in the strip between the rolling stands. The plasticity module was developed using a commercial finite-element package, DEFORM, a two-dimensional transient Lagrangian model which couples the thermal and deformation phenomena and is able to predict the temperature, strain rate, and strain distribution in the strip at any position in the roll bite. The interstand module incorporates semiempirical equations, developed in this study, which quantify the microstructural (percent recrystallization and recrystallized grain size) and textural changes in the strip between the rolling stands. The interstand model also includes a temperature module to predict the through-thickness temperature distribution in the strip based on one-dimensional heat conduction. Validation of the model against industrial data indicated that it gave reasonable predictions for the temperature, grain size, and volume fraction of some of the deformation texture components after recrystallization was completed. However, the model overestimated the mill loads in the last stands for both the AA5182 and AA5052 alloys and underestimated the amount of cube ({100}〈uvw〉) and S ({123}〈634〉) texture in the recrystallized strip.