Does tumor necrosis factor-alpha (TNF-α) play a role in post-chemotherapy cerebral dysfunction?

Post-chemotherapy treated cancer patients frequently report cognitive difficulties. The biology of this phenomenon is poorly understood, with uncertainty about possible direct toxic effects on the brain, secondary effects from systemic inflammation, host factors/genetic predisposition to cognitive complaints, or hormonal changes influencing cognitive function. To elucidate possible mechanisms associated with post-treatment cognitive dysfunction among breast cancer survivors, in 2007 we established a prospective, longitudinal, observational cohort study of early stage breast cancer patients, recruited at the end of initial treatments (primary treatment exposure included surgery, ± radiation, ± chemotherapy), and prior to the initiation of adjuvant endocrine therapy. We assessed cognitive complaints, neuropsychological (NP) test performance, markers of inflammation, and brain imaging at baseline, 6 months and 12 months after enrollment. In this analysis of data from the first 93 patients enrolled in the cohort study, we focus on the relationship of circulating levels of proinflammatory cytokines to cerebral functioning and chemotherapy exposure. Among the proinflammatory cytokines tested (IL-1 ra, sTNF-RII, CRP, and IL-6) at baseline, only sTNF-RII was increased among chemotherapy exposed patients, with a significant decline in the year after treatment (p=0.003). Higher baseline sTNF-RII in chemotherapy patients was significantly associated with increased memory complaints. In chemotherapy exposed patients, the longitudinal decline in sTNF-RII was significantly correlated with fewer memory complaints over 12 months (r=-0.34, p=0.04). Higher baseline sTNF-RII was also associated with relatively diminished brain metabolism in the inferior frontal cortex (r=-0.55, p=0.02), as well as relatively increased inferior frontal metabolism after 1 year, in chemotherapy-exposed subjects. These preliminary findings suggest that post-chemotherapy increases in TNF-α may be playing an important role in the manifestations of cognitive complaints in breast cancer survivors.

Changing lives, dynamic plans: Prospective assessment of 12-month changes in pregnancy timing intentions and personal circumstances using data from HER Salt Lake.

OBJECTIVES: To explore the association between changes in personal circumstances and shifts in pregnancy intentions. STUDY DESIGN: New start contraceptive clients, who desired to prevent pregnancy for at least one year enrolled in the survey arm of the HER Salt Lake Contraceptive Initiative (September 2015 -March 2017) and responded to the question "What are your future pregnancy plans?" at enrollment and 12-month follow-up. We estimated multivariable binary logistic fixed-effects regressions to examine the association between changes in personal circumstances and a change from never desiring a pregnancy at enrollment to considering one in the future at 12-month follow-up. RESULTS: The majority of the 2825 participants (2246, 79%) maintained their pregnancy timing intention over the 12-month study period. Multivariable analyses of the 208 participants who changed from never desiring a pregnancy to considering pregnancy in the future at 12-month follow-up indicated that entering cohabitation (aOR 3.14, 95% CI 1.30-7.58), increased household income (aOR 1.06, 95% CI 1.00-1.13), and changes from unemployment to full-time employment (aOR 5.94, 95% CI 1.29-27.36) are associated with increased the odds of desiring a future pregnancy after never wanting one a year prior. CONCLUSIONS: Pregnancy intentions are dynamic over twelve months and covary with partner status, household income, and employment status. Pregnancy intentions are linked to changes in life circumstances. Health care providers need to frequently assess pregnancy intentions and resulting contraceptive or preconception needs.

Distribution and immunochemical characterization of a keratin-like antigen in epithelial tumors using mouse and human monoclonal antibodies.

Using conventional murine hybridoma technology, we have produced a monoclonal antibody (MAb), 89E5, which recognizes two keratin-like polypeptides (Mr 53,000 and 45,000), which are preferentially expressed by epithelial tumors. In addition to detection of tumor cells by immunohistochemistry, MAb 89E5 was able to localize to tumor xenografts in nude mice after iodination of its F(ab')2 fragments. To develop potentially less immunogenic antibodies to antigens defined by MAb 89E5, studies were performed to produce a human counterpart to the mouse MAb. The mouse 89E5 MAb was used to purify the 89E5 polypeptides from tumor cell lines. The partially purified 89E5 antigen was then used to sensitize human splenic lymphocytes in vitro. Immortalization of the sensitized cells by cell fusion resulted in a human IgM MAb, PA1, which showed the same reactivity pattern on a panel of cell lines as did the mouse MAb 89E5. Immunofluorescent studies showed that both 89E5 and PA1 had staining patterns on epithelial cells indicative of antibodies to cytokeratin. Furthermore, PA1 immunoprecipitated two polypeptides (Mr 53,000 and 45,000) which comigrated with the 89E5 polypeptides. Competitive binding assays showed that the PA1 MAb and 89E5 MAb recognized closely associated epitopes. As with the 89E5 MAb, PA1 was reactive with tumor tissues in immunohistochemical studies. These studies indicate that the PA1 MAb is a human counterpart of the mouse 89E5 MAb. Direct comparison of human MAb and mouse MAb against the same antigen could yield valuable information on the efficacy of using human MAb in vivo.

Effects of thalidomide on the local Shwartzman reaction in mice and rabbits.

The Shwartzman reaction is an animal model displaying histopathological vasculitis phenomena. Extravasation and swelling due to increased vascular permeability and cellular infiltration, which are hallmarks of the Shwartzman reaction, were evaluated as leakage of i.v.-injected Evans Blue dye and by histological and immunohistological characteristics in rabbits and mice. (+/-)-Thalidomide, (-)-thalidomide, (+)-thalidomide and dexamethasone inhibited the increase of vascular permeability in the local Shwartzman reaction. Histologically, the intensity of the Shwartzman reaction was reduced. In mice thrombus formation and leukocytoclastic vasculitis was inhibited by (+/-)-thalidomide and (+)-thalidomide. ICAM-1 expression was markedly reduced after (+)-thalidomide injection. Thalidomide and dexamethasone pretreatment reduced Mac-1 expression on perivascular infiltrated granulocytes. The inhibitory effect of thalidomide on vasculitis of the Shwartzman reaction may thus be related to reduction of adhesion molecule expression.

Effects of chronic kombucha ingestion on open-field behaviors, longevity, appetitive behaviors, and organs in c57-bl/6 mice: a pilot study.

Kombucha is a lightly fermented tea beverage popularly consumed as a self-prescribed folk-remedy for numerous ailments. Kombucha is claimed to enhance cognition, aid weight loss, and prolong life. This pilot study reports longevity, general health, and open-field exploratory behavioral outcomes from a 3-y longitudinal study of 64 C57-BL/6 mice (males and females), half of which chronically drank kombucha, and all of which experienced natural mortality. Compared by MANOVA to controls, mice that drank kombucha showed greater vertical exploration (P = 0.001) and a sex-interactive effect in novel object manipulation (P = 0.049). MANOVA of kombucha-drinking mice compared to controls detected differences in appetitive behaviors (food consumption, P < 0.001; beverage consumption, P = 0. 008), and gross body weight (P < 0.001). Appetitive behaviors changed with the addition of voluntary exercise on a running wheel, with differing patterns of change noted for males and females. Both male and female mice who drank kombucha lived longer than controls (P < 0.001), with the greatest variability among the male mice (sex interactive effect, P < 0.001). Comparable effects and mechanisms in humans remain uncertain, as do health safety issues, because serious health problems and fatalities have been reported and attributed to drinking kombucha.

Local skin reactivity after induction of Shwartzman reaction in rabbits.

A local Shwartzman response was elicited in rabbits by an intradermal injection of the Salmonella typhosa endotoxin lipopolysaccharide (LPS) followed 24 hours later by an intravenous challenge injection with zymosan. After the intravenous challenge, necrotizing vasculitis developed in the prepared skin sites which was characterized by microthrombi, accumulation of neutrophil granulocytes, fibrin deposition and extravasation of red blood cells. Evans' blue extravasation into the altered tissue was significantly reduced, and histologically, the intensity of the Shwartzman reaction in the skin was reduced by pretreatment with thalidomide and dexamethasone. The mechanism of reduction of an LPS-induced local Shwartzman reaction by thalidomide is discussed.

Evaluating the special needs of functional neuromuscular stimulation research candidates.

A psychological screening protocol for individuals with paraplegia who, through functional neuromuscular stimulation (FNS), might develop stance and gait control is described. The efficacy of criteria to maximize the appropriate involvement of research candidates is reported. Accurate assessment of special needs for all participants, including persons referred prior to application of the screening protocol, was made based on histories of research involvement. Test and interview data identified two candidates who were inappropriate. Continued monitoring is planned to assess the relationship between FNS utilization, personal and environmental characteristics of participants, and consequences of research involvement. The value of providing social-environmental resources to maximize research outcome is emphasized.

Chronic lead exposure of rats: open-field performance.

Three groups of male hooded rats were chronically exposed to lead in the acetate form prenatally, as well as postnatally via the dam's milk and in the drinking water, at concentrations of 0 ppm, 19 ppm, and 38 ppm for 35 days. No significant differences were found in weight gain, although significant increases in food consumption were noted in animals receiving 19 ppm lead acetate and increased ingestion of lead acetate in animals receiving 19 ppm and 38 ppm. When subjects were tested in an open-field task, no significant differences were found in emotionality, the number of squares traversed, frequency and duration of rearing, or in frequency of grooming. However, subjects receiving 38 ppm lead displayed a significant reduction in duration of grooming when compared to animals receiving either 19 ppm or 0 ppm. The results suggest that prenatal lead exposure, followed by postnatal exposure, may affect some elements of activity, while having little effect on others.

Event-related brain potentials and psychology course mean examination grades.

Since 1965 research into the event-related brain potentials of the human electroencephalogram suggests that these EEG components are closely related to human information-processing activities. In this study were tested 21 normal adult university students (12 women, 9 men, ages 19 to 51 years) from the Alaskan subarctic, using both the auditory and visual event-related potential oddball paradigms. The event-related brain potential recordings were analyzed as explanatory variables of academic performance, as measured by the mean of a series of multiple-choice examinations covering lecture and text material. No high association between these brain electrophysiological measures and students' academic performance was observed. At best, one component explained 27.6% of the variation in mean examination grades.

Behavioral effects following rehabilitation from postnatal exposure to lead acetate.

At 21 days of age three groups of male hooded rats of the Sprague-Dawley strain were exposed to either untreated water or lead acetate at concentrations of 25 or 50 ppm provided ad lib. in the drinking water for 40 days. When tested for spontaneous alternation, the subjects receiving both 50 ppm and 25 ppm lead acetate exhibited significantly reduced rates of alternation below those of untreated control subjects. Immediately subsequent to testing, lead was removed from the diet of the experimental groups and water substituted which was provided ad lib. for the duration of the experiment. This regimen of rehabilitation was continued for 70 days at which time all subjects were tested on the problems of the Hebb-Williams closed-field maze-learning task. No significant differences were found in the time taken to traverse the maze enclosure, the number of squares traversed, or in the total number of error zones entered over the 12 test problems, although significantly increased latencies to leave the start box were noted for subjects previously exposed to lead acetate. These data indicate that some deficits produced by postweaning lead acetate exposure may be reversible and not persist beyond a period of rehabilitation.

Brunswik ratios: a ratio scale for comparative analyses of size constancy data from different experiments.

The literature on visual size constancy implicitly assumes that the perceived size of any dimension of a thing is evidence of how well (a) any other dimension of the thing will be perceived and (b) any visible dimension of any other thing will be perceived under comparable conditions of perception. For tests of these assumptions Brunswik ratios (1956) are described as a common conceptual and numerical basis, a ratio scale, for testing statistically for differences among or the equivalence of two or more sets of data from different experiments on visual size constancy.

Effects of second language study of phonemic discrimination and auditory event-related potentials in adults.

This study was designed to investigate the effects of acquisition of a second language on auditory even-related brain potentials and discrimination of foreign language phonemes by 36 women (ages 18 to 47 years), and 25 men (ages 18 to 36 years) and of varying linguistic background, in response to synthetic versions of Japanese phonemes. Subjects were subsequently tested on discrimination between spoken Japanese phonemes. Analysis indicated that the men and women differed in phonological processing and in the way acquisition of the second language affected phonological processing.

Lavender aromatherapy in recovery from exercise.

20 men were randomly assigned to a control or an experimental group. After baseline screening, all subjects performed moderate physical exercise for 2 min., then rested for 10 min., during which the experimental group was exposed to lavender aromatherapy. Recovery measures included diastolic and systolic blood pressure, mean arterial pressure, pulse pressure, and heart rate. As the mean difference in diastolic blood pressure fell just short of statistical significance, further study with larger groups is required.

Learning impairments following postnatal exposure to benzene.

Two groups of male hooded rats of the Sprague-Dawley strain were administered 550 mg/kg of benzene in corn oil or pure corn oil on Days 9, 11, and 13 postpartum. When tested on problems of the Hebb-Williams closed-field maze-learning task, the rats previously exposed to benzene manifest significantly impaired learning ability when compared to control rats in the total number of error zones entered over the 12 test problems. No significant differences were found in food consumption, water consumption, or weight gain. Moreover, none of the overt manifestations characteristic of acute or chronic benzene exposure were observed. Learning deficits were exhibited at levels of exposure previously considered subtoxic.

Apparent size contrasts of retinal images and size constancy as determinants of the moon illusion.

Kaufman and Rock (1962) and Rock and Kaufman (1962) concluded that the moon illusion is a function of and attributable to apparent distance. They also reported a large framing effect as an exception. Analysis of the effect suggests two components which can account for the illusion independently of apparent distance. These are apparent size contrasts of visual images of discriminable features or objects of the earth with the moon's image and size constancy of the features or objects plus the interactions of the two. Apparent distances to horizons are always a consequence of the necessary conditions for the illusion. They are related to the illusion but are not a determinant of it.

Geophysical variables and behavior: LXX. Testing electromagnetic explanations for a possible psychokinetic effect of therapeutic touch on germinating corn seed.

Designs used to test claims for psychic healing of living systems not amenable to suggestion may produce artifact in the results when there is failure to control for other possible explanations. Some experimental methods in psychokinesis may produce electromagnetic field flux which could lead to erroneous conclusions. This study adds electrical and magnetic controls to assess their effect, leading to the conclusion that therapeutically touched corn seeds did not recover from saline injury significantly better than untreated controls.

Effect of exposure to photographs of thin models on self-consciousness in female college students.

The purpose of this study was to assess the immediate influence of brief exposure to images taken from print media on the general self-consciousness and body self-consciousness of 67 college women. After viewing photographs of either thin female models or control photographs, the women completed the Self-consciousness Scale and the Body Self-consciousness Questionnaire. Although alpha was .45, the college women who looked at images of thin female models gave immediate ratings significantly (p < .001) higher on both general Self-consciousness and Body Self-consciousness than those who looked at control images.

Biology of bisexuality: critique and observations.

Differentiation of human sexual orientation, particularly bisexuality, has been little studied. Most studies have lumped bisexuals with homosexuals. Those examining bisexuals separately have uniformly observed that bisexuals are often unlike either heterosexuals or homosexuals. Some authors have overgeneralized the results of animal studies as applying to humans. While animal models can provide useful hypotheses, human sexual orientation is unique. Therefore, conclusions about human sexuality based on animal research are suspect. Human sexual orientation is influenced by biological, cognitive, cultural, and subcultural variable in interaction, leading to multiple types of heterosexuals, bisexuals, and homosexuals. Understanding of human sexual orientation will improve only if these factors are accounted for in research and theory. Several studies seem to indicate that some bisexuals have a predominantly heterosexual or homosexual orientation, but high erotic responsiveness or more "masculine" characteristics, leading to versatility in sexual behavior. Early exposure to masculinizing hormones seems to predispose human females toward bisexuality rather than exclusive homosexuality.