Hexachlorobenzene as a possible major contributor to the dioxin activity of human milk

The first evidence that catecholamines might be present in the immune system was provided by capillary electrophoresis combined with electrochemical detection. Here, we present the first structural characterization of the endogenous catecholamines isolated from human peripheral blood mononuclear cells. Dopamine, L-DOPA and norepinephrine were detected and were identified with electrospray ionization mass spectrometry by determination of the protonated molecular species of each catecholamine and their major fragments generated in the electrospray source with a nozzle-skimmer voltage method. This technique, in conjunction with accurate mass measurement, allowed us to identify in an unfractionated sample the content of catecholamines in extracted cells in a quantitative manner, with structure-specific methodology. The data unambiguously confirm our previous tentative findings, and also strengthen the importance of the regulatory function of catecholamines in the immune system and the existence of an autocrine loop, where lymphocytes may down-regulate their own activity.     

Product release is the major contributor to kcat for the hepatitis C virus helicase-catalyzed strand separation of short duplex DNA

Hepatitis C virus (HCV) helicase catalyzes the ATP-dependent strand separation of duplex RNA and DNA containing a 3' single-stranded tail. Equilibrium and velocity sedimentation centrifugation experiments demonstrated that the enzyme was monomeric in the presence of DNA and ATP analogues. Steady-state and pre-steady-state kinetics for helicase activity were monitored by the fluorescence changes associated with strand separation of F21:HF31 that was formed from a 5'-hexachlorofluorescein-tagged 31-mer (HF31) and a complementary 3'-fluorescein-tagged 21-mer (F21). kcat for this reaction was 0.12 s-1. The fluorescence change associated with strand separation of F21:HF31 by excess enzyme and ATP was a biphasic process. The time course of the early phase (duplex unwinding) suggested only a few base pairs ( approximately 2) were disrupted concertedly. The maximal value of the rate constant (keff) describing the late phase of the reaction (strand separation) was 0. 5 s-1, which was 4-fold greater than kcat. Release of HF31 from E. HF31 in the presence of ATP (0.21 s-1) was the major contributor to kcat. At saturating ATP and competitor DNA concentrations, the enzyme unwound 44% of F21:HF31 that was initially bound to the enzyme (low processivity). These results are consistent with a passive mechanism for strand separation of F21:HF31 by HCV helicase.     

Chronic gypsum fertiliser ingestion as a significant contributor to a multifactorial cattle mortality

A number of high-resolution molecular typing systems have been developed in recent years. Their availability raises the new issues of selecting the method (s) best suited for a particular purpose and interpreting and communicating typing results. Most of the currently available methods are comparative only: they allow testing of a sample of isolates for delineation of those closely related from those markedly different in genomic backgrounds. This approach is adequate for outbreak investigation, allowing determination of clonal spread in a microenvironment and identification of the source of infection. Comparative methods with sufficient resolution for most pathogens include restriction fragment-length polymorphism (RFLP), pulsed-field gel electrophoresis (PFGE), and arbitrarily primed and randomly amplified polymorphic DNA-polymerase chain reaction (PCR) analysis. For surveillance systems, monitoring clonal spread and prevalence in populations over extended periods of time requires library typing systems. These must be standardized, must have a high throughput, and must use a uniform nomenclature. Promising or validated methods include serotyping, insertion sequence fingerprinting, ribotyping, PFGE, amplified fragment-length polymorphism (AFLP), infrequent-restriction-site amplification PCR, interrepetitive element PCR typing (rep-PCR) and PCR-RFLP of polymorphic loci. PCR methods generating arrays of size-specific amplicons (AFLP, rep-PCR) can be more reproducibly analyzed by using denaturing polyacrylamide gel or capillary electrophoresis with automated laser detection. Binary probe typing systems appear optimal and should be enhanced further through use of DNA chip technology. In these systems, amplification of polymorphic regions is followed by solid-phase hybridization with a reference panel of sequence-variant specific probes. The resulting binary type results allow determination of reproducible, numeric profiles. However, interpretation and nomenclature of typing results for large-scale surveillance purposes still require a better understanding of population structure and microevolution of most microbial pathogens.     

Compliance in quality of life data: a Norwegian experience

Compliance is of extreme importance in assessing quality of life since lost data never can be retrieved. In order to assess this issue in various studies, a cross-sectional study in cured cancer patients, three prospective trials and a normative study were explored. In the cross-sectional study 82 per cent of the patients completed the questionnaires after one reminder. More females than males answered the questionnaires. The compliance rate varied from 99 per cent to 62 per cent in the prospective studies depending upon time after inclusion. It seems that compliance decreases during follow up, primarily because of disease progression. In one of the prospective studies low compliance rate (approximately 30 per cent) was found in the questionnaire assessing religious issues. In the normative study 68 per cent of the population completed the questionnaire. No gender differences were found, but younger males and elderly women were poor compliers. In conclusion, our data support that most patients complete quality of life questionnaires. It seems that patients with inferior education, reduced physical function and with progressive/terminal disease are low compliers. Introduction of the first quality of life questionnaires to the patients is of great importance. Detailed information about the study should be given and the importance of completing the questionnaires should be underlined.     

Inhibitory control as a contributor to conscience in childhood: from toddler to early school age

In this article we report a longitudinal extension of previous findings about the critical role of temperamental inhibitory or effortful control as the contributor to developing conscience in young children. A comprehensive observational battery, highly internally consistent, was developed to measure inhibitory control in 83 children at early school age who had been followed since toddlerhood and had been assessed using similar batteries at toddler and preschool age. We again confirmed the findings of robust longitudinal stability of inhibitory or effortful control, now from toddler to early school age, the increase with age, and gender differences, with girls outperforming boys. We also reaffirmed strong links, both contemporaneous and in the longitudinal sense, between inhibitory control and multiple, diverse measures of children's conscience at early school age, including observations of moral conduct, moral cognition, and moral self. The findings are discussed in view of the increasingly appreciated importance of temperament for critical aspects of socialization.     

Regrowth resistance as a likely significant contributor to treatment failure in drug-sensitive neoplastic diseases

Attempts to improve the effectiveness of therapy for neoplastic diseases have largely focused on increasing the cytotoxic efficacy of therapy. While this approach is logical, there is another approach, based on the concept of regrowth resistance, which offers an alternate means of improving treatment outcome. The term "regrowth resistance" refers to the reduction in treatment efficacy resulting from the regrowth of neoplastic cells between courses of therapy or even between doses of radiation therapy. Regrowth resistance is likely to play a significant role in determining the outcome of treatment in rapidly proliferating neoplasms. A reduction in the rate of tumor regrowth would increase the net effectiveness of cytotoxic therapy and would also inhibit the development of resistance to cytotoxic therapies.     

From replicators to reproducers: the first major transitions leading to life

A classification of replicators is proposed: life depends on replicators that can exist in an indefinitely large number of forms (unlimited heredity), and whose replication is modular rather than processive. The first template replicators would have increased at a rate less than exponential, because of self-inhibition arising from molecular complementarity. The result would be the survival of a varied population of replicators, rather than the victory of one type. This variability was important, because inaccurate copying meant that individual replicators were small (Eigen's paradox). The origin of cooperation between replicators, and the problem of molecular parasites, are discussed. Today, cooperation depends on cellular compartments, and on the linkage of genes on chromosomes, but we argue that at an earlier stage surface metabolism, in which replicators react only with neighbours, was important. The origin of translation and the genetic code is discussed. The essential step is the binding of amino acids to specific oligonucleotides. We suggest that this binding originated, not as a step in protein synthesis, but in the formation of coenzymes in a metabolically complex RNA world. Existing organisms are not replicators (that is, new individuals do not arise by copying), but reproducers that contain replicators. We outline Griesemer's concept of a reproducer, which brings out the essential role of development in evolution.     

Venous disease: from pathophysiology to quality of life

Venous insufficiency is a multifactorial pathology that has an important impact on the quality of life of the patients. The primary factor of venous disease is an abnormal wall distensibility, which seems to be correlated with genetic factors. Facilitating factors include hormonal impregnation and prolonged hydrostatic load, particularly under conditions where the control of the sympathetic nervous system is reduced by an increase in local temperature. The resulting valvular incompetence, combined with the augmented hydrostatic load, leads to varicosis and venous stasis. The ensuing tissue hypoxia and local edema favor inflammation and infection, which ultimately favor the occurrence of ulcers. The available data on the impact of the disease suggest a relation between the physiopathological phenomena and some parameters of health-related quality of life.     

p57KIP2 targeted disruption and Beckwith-Wiedemann syndrome: is the inhibitor just a contributor?

Beckwith-Wiedemann syndrome is a human congenital disorder characterized by a wide variety of growth abnormalities, including developmental defects and predisposition to certain tumors. Genetic evidence has suggested a role for p57KIP2, a member of a family of cell cycle inhibitory genes, in Beckwith-Wiedemann syndrome. Two independent groups have reported the generation and characterization of mice lacking functional p57KIP2. These mice demonstrate a number of abnormal phenotypes which overlap with, although do not completely recapitulate, Beckwith-Wiedemann syndrome. These findings advance the molecular characterization of a human disorder, and provide insight into the interplay between regulation of cell division and development.     

HIV and quality of life: a rehabilitation perspective

Access to families affected by HIV in their own home puts health visitors in a prime position to encourage health promotion strategies for people with HIV infection, and to recognise and make early referral for rehabilitation needs, writes Cherry Lang. Here she describes how physiotherapy and stress management techniques can help tackle symptoms of HIV infection.     

The bone marrow stromal environment is a major factor in myeloma cell resistance to dexamethasone

The expression of several markers of epithelial cell proliferation was analyzed to establish baseline data for future chemoprevention studies of oral premalignant lesions. Punch biopsies (n = 60) from three different sites of oral mucosa (bucca, lateral tongue, and the floor of the mouth) were obtained from 20 normal donors of both sexes. After formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect the proliferation markers Mib-1, cyclin D1, and centromere-associated protein CENP-F. Analysis of sections stained for the three markers showed similar patterns, i.e., a low labeling index (LI) in the basal layer and a high LI in the parabasal layer at all three intraoral sites. No proliferative activity was seen above the parabasal layer (superficial layer). All sites showed similar Mib-1 LI values for the proliferative markers. The tongue epithelium exhibited higher parabasal LIs of cyclin D1 and CENP-F than did the other two sites. No significant differences were detected between smokers and nonsmokers. The data from normal mucosa were compared with those from low (n = 30)- and high (n = 17)-grade dysplastic leukoplakias. The Mib-1 LI showed a very significant change, with a 9-fold increase in the basal layer LI in dysplastic leukoplakias. Cyclin D1 and CENP-F showed similar trends with increments of up to 7-fold in the basal layer of high-grade dysplasia. Although the proliferative activity of the parabasal layer was similar in normal and leukoplakic epithelia, the superficial layer showed a significant increment in proliferative activity mainly in high-grade leukoplakia. These studies suggest that proliferation markers in the basal and superficial cells of premalignant lesions may serve as surrogate end point biomarkers for chemoprevention trials.     

Similarity of post-interview trait rating intercorrelations as a contributor to interrater agreement in a structured employment interview.

Examined the influence of degree of interview structure, use of scaled-expectation rating scales, and similarity of postinterview trait rating intercorrelations on interrater agreement in employment interviews. 9 nursing interviewers sat as a selection board and interviewed and independently rated 54 senior nursing students. The interviews were highly structured, and ratings were recorded on scaled-expectation scales for general staff nursing positions. Although all interviewers shared essentially the same structure among their postinterview trait ratings, interrater agreement was no better than in previous studies. This finding shows the power of halo in the interview setting (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of quality of life in oncology

Studies of quality of life are more and more becoming an integral part of cancer care in situations when treatment of cancer patients is burdened with significant toxicity, and results of survival of these patients are unsatisfactory. Modern concept of health-related quality of life measurement means consensus about its two basic features: multidimensionality of concept, and essentially subjective experience in a treated person. As a minimum, domains of physical, psychological and social are assessed, and the patient is considered to be the primary source of information. The most widely used instruments for quality of life assessment are questionnaires, especially developed for cancer patients, with supplemental items for particular diagnosis. These instruments must satisfy the basic psychometric properties-validity and reliability. Quality of life studies are focused mostly on phase III trials, where differences between treatment arms for tumour response and survival are expected to be small. Another approach is developed in parallel which, based upon quality of life measurement, initiates decisions for the treatment of a set of patients up to health policy level. In these "cost-utility" studies, efficacy and cost of the treatment, and improvement of patients' quality of life are independently estimated, and then integrated in medical decision making.     

Assessment of quality of life in a multicultural cancer patient population.

Quality of life (QOL) is increasingly assessed in cancer patients. In this article, the authors examined the psychometric performance of a commonly used QOL questionnaire, the Quality of Life Questionnaire--Cancer 30 (QLQ-C30; N. K. Aaronson et al., 1993), in multiethnic cancer patients. Content validation studies in patients and clinicians identified possible new items. Multiple-group confirmatory factor analysis supported equivalent structure across ethnic groups (Caucasians and Asian/Pacific Islanders [APIs]). A higher order QOL factor appeared to directly affect functioning scales and symptom count. Exploratory factor analysis examined effects of new items. Ten factors were extracted, 6 consistent with the original instrument and 4 reflecting potentially new aspects of QOL: Positive Social Support, Coping, Existential Well-Being, and Sexuality/Intimacy. The QLQ-C30 appears appropriate for use in API cancer patients. Further work needs to ensure that it includes all important domains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A research approach to improving our quality of life.

Presents a progress report on developing and applying a research approach to improve the quality of life. Steps in the plan include (a) the empirical definition of the quality of life of adults, (b) surveys of 3 age groups (30-, 50-, and 70-yr-olds) showing their ratings of importance and assessments of needs met for the 15 factors defining quality of life, (c) a study of the specific factors tending to make 85% of American adults report their quality of life as good or better, (d) illustrations showing the advantages of using in-depth studies of individuals to identify the determiners of quality of life, and (e) development of a simulation model to evaluate proposals for improving the quality of life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)