Psoralen photochemotherapy

Psoralens and sunlight have been used by the Egyptians and Indians for hundreds of years for treating vitiligo. The combination of oral psoralens and artificial ultraviolet A (PUVA) therapy was approved for managing severe psoriasis by the Food and Drug Administration in 1982. Since then, PUVA therapy has been an effective modality for treating many cutaneous conditions (psoriasis, atopic dermatitis, vitiligo, and mycosis fungoides). However, proper knowledge and administration of PUVA therapy are vital to treatment success and reducing side effects.     

A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.     

Rethinking infant knowledge: toward an adaptive process account of successes and failures in object permanence tasks

Infants seem sensitive to hidden objects in habituation tasks at 3.5 months but fail to retrieve hidden objects until 8 months. The authors first consider principle-based accounts of these successes and failures, in which early successes imply knowledge of principles and failures are attributed to ancillary deficits. One account is that infants younger than 8 months have the object permanence principle but lack means-ends abilities. To test this, 7-month-olds were trained on means-ends behaviors and were tested on retrieval of visible and occluded toys. Means-ends demands were the same, yet infants made more toy-guided retrievals in the visible case. The authors offer an adaptive process account in which knowledge is graded and embedded in specific behavioral processes. Simulation models that learn gradually to represent occluded objects show how this approach can account for success and failure in object permanence tasks without assuming principles and ancillary deficits.     

Moving up the corporate ladder: A longitudinal study of the leadership motive pattern and managerial success in women and men.

Using TAT data collected prior to entering management positions, sex differences in motive patterns related to leadership were examined in a 12-yr longitudinal study of 211 men and 180 women (aged 21–43 yrs at initial assessment) who entered a large utility corporation between 1977 and 1982. Ss were followed up in 1990 and recorded as to how far they had advanced in management level. While the results showed no sex differences in motivational predictors of attained management level, the content analysis revealed 2 distinct styles of power-related themes that distinguished the successful men from the successful women. The successful male managers were more likely to use reactive power themes while the successful female managers were more likely to use resourceful power themes. Differences between the sexes in the power themes were less pronounced among the managers who had remained in lower levels of management. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification.     

Effect of exercise on the plasma nonesterified fatty acid composition of dogs and goats: Species with different aerobic capacities and diets

The goals of this study were to determine: (i) whether mammals mobilize particular nonesterified fatty acids (NEFA) preferentially during locomotion, (ii) if differences in aerobic capacity or diet can affect the pattern of NEFA mobilization and (iii) which individual NEFA are most representative of total NEFA concentration changes, to use them as tracers for turnover studies. Individual NEFA were measured in trained dogs and goats (VO₂max dog/VO₂max goat=2.2; where VO₂max=max-imal oxygen consumption) during treadmill exercise at 40 and 60% VO₂max. Important interspecies differences in individual NEFA concentrations could be attributed to differences in aerobic capacity. The more aerobic species (dog) had much higher plasma NEFA concentrations for all but one NEFA (18∶0), when compared with the low-aerobic species (goat). In addition, exercise caused a large increase in concentration of individual NEFA in the dogs, with the largest increases seen in 18∶1 (150% above resting values) and 16∶0 (60% increase), but it had no effect in goats. Therefore, the aerobic species has a much higher ability for mobilizing and transporting NEFA in plasma than its low-aerobic counterpart. Two NEFA accounted for more than half total plasma NEFA in both species, 18∶1 (about 35% total NEFA) and 16∶0 (20%). Calculation of variability in percent composition reveals that oleate and palmitate also closely reflect changes in total NEFA and are therefore the most appropriate tracers forin vivo kinetic studies in exercising mammals. Differences in diet and digestion physiology explained some differences in the plasma NEFA composition of the two species; this was reflected in the percent contributions of individual fatty acids to total NEFA: in dogs 18∶1>16∶0>18∶2>18∶0, while in goats 18∶1>16∶0>18∶0>18∶2. Also, only goats had 18∶3 (6% total NEFA), a fatty acid of plant origin, while only dogs had 16∶1 (7% total NEFA). Overall, however, the plasma NEFA composition of goats did not exactly reflect that of their diet due to preabsorptive modification of unsaturated fatty acids, while in dogs there was a good correlation between dietary and plasma NEFA.