Allocating effort and anticipating pleasure in schizophrenia: Relationship with real world functioning.

BACKGROUND: Poor motivation to engage in goal-oriented behavior has been recognized as a hallmark feature of schizophrenia spectrum disorders (SZ). Low drive in SZ may be related to anticipating rewards as well as to poor working memory. However, few studies to date have examined beliefs about self-efficacy and satisfaction for future rewards (anticipatory pleasure). Additionally, few studies to date have examined how these deficits may impact SZ patients' real world functioning. METHOD: The present study examined SZ patients' (n=57) anticipatory pleasure, working memory, self-efficacy and real world functioning in relation to their negative symptom severity. RESULTS: Results revealed that SZ patients' negative symptom severity was related to decisions in effort allocation and reward probability, working memory deficits, self-efficacy and anticipatory pleasure for future reward. Effort allocation deficits also predicted patients' daily functioning skills. CONCLUSIONS: SZ patients with high levels of negative symptoms are not merely effort averse, but have more difficulty effectively allocating effort and anticipating pleasure engaging in effortful activities. It may be the case that continuously failing to achieve reinforcement from engagement and participation may lead SZ patients to form certain negative beliefs about their abilities which contributes to amotivation and cognitive deficits. Lastly, our findings provide further support for a link between SZ patients functional daily living skills their effort allocation.

Regulation of oxidative stress by Nrf2 in the pathophysiology of infectious diseases.

The innate immune system, including phagocytic cells, is the first line of defense against pathogens. During infection by microorganisms such as viruses, bacteria, or parasites, phagocytic cells produce an excess of oxidants, a crucial process for the clearance of pathogens. This increase in oxidants creates an imbalance between oxidants and endogenous antioxidants. Left unchecked, this acute or chronic oxidative stress can lead to apoptotic cell-death and oxidative stress-induced diseases including neurodegenerative and cardiovascular disorders, premature aging, secondary infections, and cancer. The activation of nuclear factor E2-related factor 2 (Nrf2) is an efficient antioxidant defensive mechanism used by host cells to counteract oxidative stress. The transcription factor Nrf2 has been identified as the master regulator of several hundred of genes involved in the antioxidant defense response. The review objectives were to collect recent findings on the contribution of oxidative stress to complications of infection, and to highlight the beneficial impact of antioxidants in reducing inflammation and oxidant-related tissue damage. Furthermore, a direct relationship between infection and decline in Nrf2 activity has been demonstrated. Thus, an interesting therapeutic approach in disease prevention and treatment of stress-related diseases may consist in optimizing antibiotic or antiviral therapy with a combination of Nrf2 inducer treatment.

Immunohistochemical study of HLA-G expression in lung transplant recipients.

Human leukocyte antigen-G (HLA-G), a nonclassical HLA class I protein, promotes immune tolerance of solid-organ allografts, yet its role in lung transplantation (LTx) is unknown. We examined the expression of HLA-G in lung allografts through immunohistochemistry by a cross-sectional study of 64 LTx recipients, classified into four groups (stable patients, acute rejection [AR], bronchiolitis obliterans syndrome [BOS] and symptomatic viral shedders). A marked expression of HLA-G in bronchial epithelial cells (BEC) was frequently observed in stable recipients (n = 18/35 [51%]), but not in patients with AR (n = 14) or with BOS (n = 8). HLA-G was also expressed by 4 of 7 symptomatic viral shedders. In addition, HLA-G-positive patients from the stable group (n = 35) experienced lower incidence of resistant AR and/or BOS during long-term follow-up, as compared with their HLA-G-negative counterparts. Finally, in vitro data showed that interferon-gamma, a cytokine present in lung allograft microenvironment, upregulated HLA-G mRNA and protein expression in primary cultured human BEC. We conclude that HLA-G expression in the bronchial epithelium of lung allograft is elevated in some LTx recipients in association with their functional stability, suggesting a potential role of HLA-G as a tolerance marker.

A MDR1 (ABCB1) gene single nucleotide polymorphism predicts outcome of temozolomide treatment in glioblastoma patients.

BACKGROUND: Some patients with glioblastoma multiform do not respond to temozolomide even though they have aberrant promoter methylation of the DNA repair enzyme O(6)-methylguanine methyltransferase (MGMT). This suggests that additional factors hamper temozolomide cytotoxicity. We aimed to confirm first that temozolomide is a target for the multidrug resistance transporter MDR1/ABCB1 and second to investigate whether genetic variants of the MDR1 gene are associated with the survival of glioblastoma patients treated with temozolomide. MATERIALS AND METHODS: Temozolomide-mediated cytotoxicity was determined by the colorimetric methyl-thiazol-tetrazolium assay in MDR-expressing and MDR-nonexpressing cell lines. Genotypes of three single nucleotide polymorphisms (SNPs) of the MDR1 gene (C1236T, G2677T, and C3435T), MDR1 mRNA expression levels, and the MGMT promoter methylation status were analyzed in 112 glioblastoma patients who had been treated either by surgery plus radiotherapy alone or by additional temozolomide chemotherapy. RESULTS: In vitro analysis revealed that temozolomide-mediated cytotoxicity is dependent on MDR1 expression. Multivariate analysis of MDR1 genotypes showed that the C/C variant of the exon12 C1236T SNP is predictive for survival of patients treated with temozolomide. This effect was independent of the MGMT methylation status. Patients with the C/C genotype had a 2-year overall survival of 37% compared with 8% and 10% for patients with C/T and T/T genotypes, respectively (P=0.02). No influence was seen in the group of patients with radiotherapy only. CONCLUSION: The genotype of the MDR1 exon12 C1236T SNP is a novel independent predictive factor for outcome of temozolomide treatment in glioblastoma patients.

Effect of meta-tetra(hydroxyphenyl)chlorin (mTHPC)-mediated photodynamic therapy on sensitive and multidrug-resistant human breast cancer cells.

Meta-tetra(hydroxyphenyl)chlorin (mTHPC) is in clinical trials for the photodynamic therapy (PDT) of localized-stage cancer. The PDT susceptibility of cells expressing multidrug resistance (MDR) phenotype is an attractive possibility to overcome the resistance to cytotoxic drugs observed during cancer chemotherapy. The accumulation, photocytotoxicity and intracellular localization of mTHPC were examined using the doxorubicin selected MCF-7/DXR human breast cancer cells, expressing P-glycoprotein (P-gp), and the wild-type parental cell line, MCF-7. No significant difference in mTHPC accumulation was observed between the two cell lines up to 3 h contact. The photodynamic activity of mTHPC, measured 24 h after irradiation with red laser light (lambda=650 nm), was significantly greater in MCF-7/DXR as compared to MCF-7 cells. A light dose of 2.5 J cm(-2) inducing 50% of cytotoxicity in MCF-7, resulted in 85% cytotoxicity in MCF-7/DXR. The presence of P-gp inhibitors SDZ-PSC-833 and cyclosporin A did not modify the mTHPC-induced cytotoxicity. The difference in intracellular mTHPC distribution pattern between two cell lines may contribute to different photocytotoxicity. Our results indicate that mTHPC mediated PDT could be useful in killing cells expressing MDR phenotype.

Scoring accuracy using the comprehensive system for the Rorschach.

The Comprehensive System (CS; Exner, 1974, 1978) for scoring Rorschach responses is the most widely taught and most widely accepted system in use today. The complexity and labor- intensive nature of the CS makes the issue of scoring accuracy a central concern. Twenty-one graduate psychology students and 12 professionals scored 20 Rorschach responses drawn from normal and clinical protocols. In general. accuracy scores for both students and professionals were below acceptable levels. Accuracy scores were clearly better for the code categories of Location, DQ, Pairs, Popular, and Z than for Determinants, FQ, Content, and Special Scores. Responses from clinical protocols were subject to more error. The results suggest that high levels of scoring errors may exist in the field use of the CS. Training standards may need to be devised to insure scoring competence.

Modulation of daunorubicin cellular resistance by combination of P-glycoprotein blockers acting on drug efflux and intracellular drug sequestration in Golgi vesicles.

BACKGROUND: S9788 and PSC833 were developped as P-glycoprotein (Pgp) blockers and found to act additionally on daunorubicin subcellular distribution, involving different putative targets. On this basis, combinations of S9788 and PSC833 were evaluated in Pgp-expressing MCF7(DXR) cells in which we recently demonstrated that daunorubicin was sequestered in Golgi vesicles (Bour-Dill et al.: Cytometry, 39: 16-25, 2000). METHODS: Combinations of S9788 and PSC833 consisted in complementary fractions of iso-effective concentrations (IEC) leading to 90% (IEC90) and median (IEC50) reversion of daunorubicin resistance. Resistance modulation was assessed using cytotoxicity assays, flow cytometry determination of intracellular daunorubicin, and fluorescence microscopy analysis of daunorubicin subcellular distribution. RESULTS: Individually, both S9788 and PSC833 were found to be very potent with IEC90 of 5 and 15 micromol/l, and IEC50 of 0.1 and 0.2 micromol/l, respectively, for S9788 and PSC833. When combined, synergistic cytotoxicity was observed for both IEC90 and IEC50 combinations while intracellular daunorubicin fluorescence was only synergistically increased for IEC90 combinations. For IEC50 combinations, no increase in intracellular fluorescence was observed, and fluorescence microscopy examination of the cells suggested that daunorubicin sequestration in Golgi vesicles could be modulated at concentrations that do not significantly increase daunorubicin cellular concentration. Using immunofluorescence and reverse transcription-polymerase chain reaction analyses, multidrug resistance-associated protein, major vault lung-resistance protein, and anthracycline-resistance associated protein were not found to be implicated. CONCLUSIONS: Synergistic combinations of S9788 and PSC833 might offer alternative ways to decrease the toxicity generated by high-dose Pgp-blockers without altering the efficacy of the resistance modulation.

Resistance to paclitaxel induces time-delayed multinucleation and DNA fragmentation into large fragments in MCF-7 human breast adenocarcinoma cells.

DNA fragmentation was investigated in MCF7 and the MCF7TAX19 paclitaxel-resistant subline exposed to paclitaxel for 24 h. No nucleosome-sized DNA fragmentation was observed by DNA agarose gel electrophoresis in both cell lines. However, DNA fragmentation was detected by flow cytometry sub-G1 peak analysis in both cell lines immediately after paclitaxel exposure. Nuclear abnormalities were observed in both cell lines in the range of 35-40% of the total cell population. This value was reached immediately in MCF7 cells but was time-delayed in MCF7TAX19 cells. Significant morphologic differences were observed between sensitive and resistant cell lines, 24 h after exposure to 50 nmol/l paclitaxel. Although no difference in the sub-G1 cell population was observed between sensitive and resistant cells, a significantly higher rate of multinucleated cell features was observed in resistant cells.

Reversible neuropsychological deficits after mild traumatic brain injury.

OBJECTIVES: To determine the influence of motivation on performance in a divided attention test of patients after mild traumatic brain injury (MBI). METHODS: Comparison of the performance of 12 patients with MBI with 10 patients with severe brain injury (SBI) and 11 healthy controls in a computer supported divided attention task before (T1) and after (T2) verbal motivation. RESULTS: At T1, the MBI group performed the same as the SBI group but significantly worse than the controls in all variables. At T2, the MBI group performed worse than the controls at T2 but the results were equal to the results of the controls at T1 and significantly better than the SBI group at T1 or T2. At T2 the MBI group performed at the level of published norms for the rest. CONCLUSION: Before verbal motivation the MBI group's results in the divided attention task were comparable with those from patients with severe brain injury. They failed to exploit their performance potential when it depended on self motivation but were able to perform at the level of the control group when external motivation was applied.

Determination of intracellular organelles implicated in daunorubicin cytoplasmic sequestration in multidrug-resistant MCF-7 cells using fluorescence microscopy image analysis.

BACKGROUND: Anthracycline resistance is known to be mediated by P-glycoprotein (P-gp) or multidrug-resistance related protein (MRP) as well as intracellular sequestration of drugs. METHODS: The resistance phenotype of doxorubicin-selected MCF-7(DXR) human breast adenocarcinoma cell line was characterized by cellular and nuclear daunorubicin efflux, P-gp and MRP expression and apoptosis induction. Daunorubicin sequestration was investigated through organelle markers (lysosomes, endoplasmic reticulum and Golgi apparatus) and daunorubicin co-localization by dual-color image analysis fluorescence microscopy using high numerical aperture objective lenses to achieve the smallest field depth and the best lateral resolution. Signal to noise and specificity ratios were optimized for daunorubicin and organelle fluorescent probes labeling. RESULTS: An original image analysis procedure was developed to investigate daunorubicin and organelles co-localization. The reliability of the image analysis was controlled through chromatic shift and intensity linearity measurement using calibrated microbeads. The main contribution (65%) of Golgi vesicles in daunorubicin sequestration was demonstrated. Although no rational relationship could be established between daunorubicin sequestration and apoptosis induction, no apoptosis was observed in MCF-7(DXR) cells. CONCLUSIONS: In addition to P-glycoprotein mediated drug efflux and without MRP overexpression, MCF-7(DXR) daunorubicin resistance phenotype involves drug sequestration within intracellular vesicles identified as Golgi vesicles and resistance to apoptosis induction.

Mitochondrial transcript processing and restoration of male fertility in T-cytoplasm maize.

Cytoplasmic male sterility (CMS) systems have been useful in the production of hybrid seed in a number of crops. The Texas or T-cytoplasmic male-sterile (cms-T) system was used extensively in the 1960s to eliminate the need for hand detasseling in hybrid maize production. As a consequence of the 1970 epidemic of southern corn leaf blight, cms-T is no longer widely used commercially. However, it has been developed as a model system to study the genetic and molecular mechanisms underlying male sterility and fertility restoration. Male sterility in T-cytoplasm maize results from the action of a T-cytoplasm-specific mitochondrial gene, T-urf13. Full (or partial) fertility restoration of T-cytoplasm maize is mediated by the Rf2 nuclear restorer in combination with one of three other restorers: Rf1, Rf8, or Rf*. Rf2 encodes a protein highly similar to mitochondrial aldehyde dehydrogenases; Rf1, Rf8, and Rf* each mediate discrete T-urf13 mitochondrial transcript processing events. To test the functionality of Rf1, Rf8, or Rf*, a T-cytoplasm transformation system is under development. AFLP bulk-segregant analysis has been used to identify DNA markers closely linked to the Rf8 locus. These tools will provide a foundation for determining mechanisms of nuclear-directed mitochondrial RNA processing and fertility restoration.

Glaucoma: what the ophthalmic nurse should know.

Glaucoma is both an international and a national public health issue. Worldwide, glaucoma is one of the leading causes of blindness. More than 2 million persons in the United States have glaucoma, yet only half of them are aware that they have the disease. The diagnosis of glaucoma requires an extensive ocular examination. Glaucoma consists of a group of ocular diseases that result in optic disk cupping and visual field loss. Although glaucoma is a blinding disease, in most cases, blindness may be prevented through early detection and treatment. Glaucoma management is determined by the type of glaucoma a person has.

Glaucoma: what the nurse practitioner should know.

Glaucoma is both an international and a national public-health issue. Worldwide, glaucoma is one of the leading causes of blindness. Although more than two million people in the United States have glaucoma, yet only half of them are aware that they have the disease. The diagnosis of glaucoma requires an extensive ocular examination. Glaucoma consists of a group of ocular diseases that result in optic disk cupping and visual field loss. Although glaucoma is a blinding disease, in most cases, blindness may be prevented through early detection and treatment. Glaucoma management is determined by the type of glaucoma one has.

Rf8 and Rf* mediate unique T-urf13-transcript accumulation, revealing a conserved motif associated with RNA processing and restoration of pollen fertility in T-cytoplasm maize.

Rf8 is a newly described nuclear gene that can substitute for Rf1 to partially restore pollen fertility to male-sterile, T-cytoplasm maize. Families segregating for Rf8 were used to investigate the mechanism of this fertility restoration and to compare it to the restoration conditioned by Rf1. Although Rf8 is unlinked to the rf1 locus, it also alters T-urf13 mitochondrial transcript accumulation and reduces the accumulation of the URF13 protein. Like the 1.6- and 0.6-kilobase (kb) T-urf13 transcripts that accumulate in T-cytoplasm plants carrying Rf1, 1.42- and 0.42-kb transcripts accumulate in plants that are partially restored by Rf8. A survey of T-cytoplasm maize lines, inbreds, and F1 hybrids by mitochondrial RNA gel blot analyses revealed that Rf8 is rare in maize germplasm. These surveys revealed the presence of another rare, weak restorer factor, Rf*, which is uniquely associated with the accumulation of 1.4- and 0.4-kb T-urf13 transcripts. Primer extension analyses position the 5' termini of the 1.42/0.42-kb and 1.4/0.4-kb transcripts at +137 and +159 nucleotides, respectively, 3' of the AUG initiation codon of the T-urf13 reading frame. The conserved motif, 5'-CNACNNU-3', overlaps the 5' termini of the Rf1-, Rf8-, and Rf*-associated transcripts and the 380 nucleotide, Rf3-associated orf107 transcript from cytoplasmic male sterility sorghum. These results demonstrate that multiple unlinked, nuclear genes can have similar but distinct effects on the expression of the unique T-urf13 mitochondrial coding sequence to restore pollen fertility to T-cytoplasm maize.

Mutator-induced mutations of the rf1 nuclear fertility restorer of T-cytoplasm maize alter the accumulation of T-urf13 mitochondrial transcripts.

Dominant alleles of the rf1 and rf2 nuclear-encoded fertility restorer genes are necessary for restoration of pollen fertility in T-cytoplasm maize. To further characterize fertility restoration mediated by the Rf1 allele, 123,500 gametes derived from plants carrying the Mutator transposable element family were screened for rf1-mutant alleles (rf1-m) Four heritable rf1-m alleles were recovered from these populations. Three rf1-m alleles were derived from the progenitor allele Rf1-IA153 and one was derived from Rf1-Ky21. Cosegregation analysis revealed 5.5- and 2.4-kb Mu1-hybridizing EcoRI restriction fragments in all of the male-sterile and none of the male-fertile plants in families segregating for rf1-m3207 and rf1-m3310, respectively. Mitochondrial RNA gel blot analyses indicated that all four rf1-m alleles in male-sterile plants cosegregated with the altered steady-state accumulation of 1.6- and 0.6-kb T-urf13 transcripts, demonstrating that these transcripts are Rf1 dependent. Plants carrying a leaky mutant, rf1-m7323, revealed variable levels of Rf1-associated, T-urf13 transcripts and the degree of pollen fertility. The ability to obtain rf1-m derivatives from Rf1 indicates that Rf1 alleles produce a functional gene product necessary for the accumulation of specific T-urf13 transcripts in T-cytoplasm maize.

Heat Inactivation of the Alkaline Phosphatase in Human Milk and Colostrum 1.

Time-temperature relationships were developed for heat inactivation of alkaline phosphatase in pooled human milk and colostrum. Heat inactivation of the enzyme in human milk proceeds at the same rate as in cows' milk. The heat sensitivity of the enzyme is slightly greater in human colostrum than in human milk.

The changing image of Catholic women.

The characteristics of Roman Catholic women in today's society were investigated. Subjects were 154 Catholic women, both religious and lay, who participated on a volunteer basis. The Catholic lay women (111) were divided into two groups: those who attended a Catholic elementary school (63) and those who attended a non-Catholic elementary school (48). Catholic women religious were found to be more dominant and independent minded than in previous research. All of the women studied were found to be more aggressive and more critical of authority than in previous studies. Likewise, Catholic women no longer see themselves in the role of nurturers.