The persistence of sulfadiazine, difloxacin, and their metabolites has been investigated in stored manure. The manure collected from sulfadiazine ((14)C-SDZ) and difloxacin ((14)C-DIF) treated pigs contained N-acetylsulfadiazine (Ac-SDZ), 4-hydroxy-SDZ (4-OH-SDZ), and sarafloxacin (SARA) as the main metabolites, respectively along with their parent compounds. Manures were stored separately at 10 degrees C and 20 degrees C at various moisture levels. About 96-99% of the radioactivity remained in extractable parent compounds and their metabolites after 150d of storage. The formation of non-extractable residue and the rate of mineralization were both negligible in manure containing SDZ and DIF. During storage SDZ concentration increased as a result of the deacetylation of Ac-SDZ, whose concentration decreased proportionally. Hence the environmental effects may be underestimated if the parent compound alone is considered for environmental risk assessment. About 11% and 14% of 4-OH-SDZ were lost after 20 and 40d of storage; thereafter its concentration increased relatively, highlighting hydroxylation of SDZ. DIF degraded very slowly (7% loss after 150d) during the storage of manure; in contrast the concentration of SARA decreased rapidly (72-90% loss after 150d). Dilution of manure and storage at higher temperatures for a reasonable period of time enhanced the rate of reactions of SDZ, DIF and their related metabolites.

Factor VIII (FVIII) inhibitor antibodies are produced against functional epitopes of FVIII in about 30% of severe hemophilia A patients leading to inhibition of its procoagulant activity. The Bethesda assay, the most commonly used method to measure FVIII inhibitors, based on inhibition of coagulant activity of FVIII, is neither able to detect noninhibitory antibodies nor their isotype. In this study we employed an indirect enzyme-linked immunosorbent assay (ELISA) to measure dif ferent isotypes and IgG subclasses of anti-FVIII anti body in the plasma of hemophiliacs (with and without inhibitor) and normal individuals using recombinant FVIII-coated microtiter plates. The results showed a predominance of IgG and IgG4, though IgA was slightly elevated in a few inhibitor-positive patients and IgM was hardly detectable. A highly significant correlation was found between the Bethesda titer and the optical density values of total Ig, IgG and IgG4 anti-FVIII antibodies obtained by ELISA (p<0.0001). These findings suggest a restricted specificity of anti-FVIII response in hemophiliacs towards functional epitopes of the molecule. Furthermore, high specificity and reasonable sensitivity of the ELISA, together with other technical advantages, suggest this method as a suitable supplementary technique for rapid large-scale screening of inhibitor-positive samples, though ELISA-negative samples need to be rechecked by the Bethesda assay to identify patients with a low inhibitor titer.

BACKGROUND

Alexithymia is a disturbance associated with psychosomatic disorders, pain syndromes, and a variety of psychiatric disorders. The Affect School (AS) based on Tomkins Affect Theory is a therapy focusing on innate affects and their physiological expressions, feelings, emotions and scripts. In this pilot study we tried the AS-intervention method in patients with chronic benign pain.

METHODS

The AS-intervention, with 8 weekly group sessions and 10 individual sessions, was offered to 59 patients with chronic non-malignant pain at a pain rehabilitation clinic in Sweden 2004-2005. Pre and post intervention assessments were done with the Hospital Anxiety and Depression scale (HAD), the Toronto Alexithymia Scale-20 (TAS-20), the Visual Analogue Scale for pain assessment (VAS-pain), the European Quality of Life health barometer (EQoL) and the Stress and Crisis Inventory-93 (SCI-93). After the group sessions we used Bergdahl's Questionnaire for assessing changes in interpersonal relations, general well-being and evaluation of AS.

RESULTS

The AS intervention was completed by 54 out of 59 (92%) patients. Significant reductions in total TAS-20 post-test scores (p = 0.0006) as well as TAS-20 DIF and DDF factors (Difficulties Identifying Feelings, and Difficulties Describing Feelings) were seen (p = 0.0001, and p = 0.0008) while the EOT factor (Externally Oriented Thinking) did not change. Improvements of HAD-depression scores (p = 0.04), EQoL (p = 0.02) and self-assessed changes in relations to others (p < 0.001) were also seen. After Bonferroni Correction for Multiple Analyses the TAS-20 test score reduction was still significant as well as Bergdahl's test after group sessions. The HAD, EQoL, SCI-93, and VAS-pain scores were not significantly changed. The AS-intervention was ranked high by the participants.

CONCLUSIONS

This pilot study involving 59 patients with chronic benign pain indicates that the alexithymia DIF and DDF, as well as depression, social relations and quality of life may be improved by the Affect School therapeutic intervention.

BACKGROUND

A highly specific antibody against recombinant human dihydropyrimidine dehydrogenase (DPD) has been developed to immunohistochemically assess DPD expression in tumors. A new oral DPD inhibitory fluoropyrimidine (DIF), S-1, is reportedly effective against gastric scirrhous carcinoma.

METHODS

In this study, the relationship between immunoreactivity to DPD in biopsy specimens and the effects of chemotherapy were investigated in 61 patients treated with first-line fluoropyrimidine-based chemotherapy (S-1:DIF, 5-FU:non-DIF) for gastric scirrhous carcinoma.

RESULTS

The response rate was significantly higher in patients with DPD-positive tumors than in those with DPD-negative tumors in the S-1 group (45.5%, 10.0%: p < 0.05), as compared to the 5-FU group (0%, 5.6%: p = 0.398). According to the median survival time, there was no significant difference between patients with DPD-positive tumors (364 days) and those with DPD-negative tumors (406 days; p = 0.626) in either the S-1 group or the 5-FU group (181 days and 256 days, respectively; p = 0.543).

CONCLUSIONS

This study indicates that S-1 may be effective even in gastric scirrhous carcinoma with a high level of DPD activity.

BACKGROUND

There are diverse causes of cicatricial alopecia characterized by lack of follicular ostia and irreversible loss of hair. While clinical differentiation between the causes may be difficult, particularly with regard to lichen planus (LP), lupus erythematosus (LE) and pseudopelade of Brocq (PB), it has been suggested that both histopathologic examination and direct immunofluorescence studies (DIF) are necessary for an accurate diagnosis.

OBJECTIVE

The aim of this study was to evaluate the diagnostic value of DIF studies in addition to histopathology in patients with cicatricial alopecia as a clinical feature.

METHODS

136 scalp biopsy specimens received for histopathology and DIF during a 5-year period were reviewed.

RESULTS

Definitive diagnosis was achieved by careful evaluation of scalp biopsies. The most prevalent diagnoses in order of frequency were LP (26%), LE (21%) and folliculitis decalvans (20%). PB was diagnosed in 10%. In most cases, the diagnosis could be made on the basis of histopathology and independently of DIF. Characteristic DIF patterns showed high specificity, but low sensitivity for LP, and high specificity and sensitivity for LE. The DIF pattern in PB showed no difference to LP.

CONCLUSIONS

Histopathology permits diagnosis in the majority of cicatricial alopecias. DIF is of value in histopathologically inconclusive cases, particularly when LE is in question.

BACKGROUND

Item response theory (IRT) has been used to examine alcohol use disorder (AUD) symptoms and their psychometric properties but has not been previously applied to AUD symptoms from an American Indian sample.

METHODS

Lifetime DSM-IV AUD symptoms and binge drinking (5+ drinks men/4+ drinks women) at ≥1, ≥4, ≥8, and ≥15 days per month during the period of heaviest lifetime drinking criteria were assessed in 530 American Indian participants. Exploratory factor analysis was used to examine the factor structure of the 10 AUD symptoms and each alcohol consumption criterion. Two-parameter IRT models generated marginal maximum likelihood estimates for discrimination (a) and threshold (b) parameters for 10 DSM-IV AUD symptoms and each consumption criterion. Differential item functioning (DIF) analysis was used to assess AUD symptom severity in groups defined by gender and age at interview.

RESULTS

The AUD symptoms of "Withdrawal" and "Activities Given Up" were the most severe symptoms. "Tolerance" and "Social/Interpersonal Problems" were the least severe. All AUD symptoms fell on the moderate portion of the severity continuum, except "Withdrawal," which fell at the lower end of the severe portion. The consumption criterion of 5+/4+ (male/female) at ≥8 times per month demarcated the portion of the severity continuum where AUD symptoms began to occur at a probability of 50%. DIF analysis showed significant gender and age at interview differences for "Hazardous Use,""Tolerance," and "Activities Given Up," but not for the other AUD symptoms.

CONCLUSIONS

In this American Indian community sample, alcohol abuse and dependence did not represent distinct disorders. Only one AUD symptom was found outside the moderate portion of the underlying AUD severity continuum. Drinking 5+/4+ (male/female) drinks at a frequency of ≥8 times per month during the period of heaviest lifetime drinking was found to function well as both a risk and a diagnostic criterion for lifetime DSM-IV AUD. DSM-IV AUD symptom criteria, as currently assessed, may be limited in their ability to capture the full range of symptom severity of AUDs, at least in this high-risk population.

OBJECTIVE

To investigate possible correlations between cutaneous polyarteritis nodosa (CPN) and antiphospholipid syndrome-associated antibodies.

METHODS

Sixteen patients were referred with CPN features. To investigate the possible role of antiphospholipid antibodies (aPL) in CPN, we measured serum lupus anticoagulant (LAC), IgG and IgM anticardiolipin (aCL) and anti-phosphatidylserine-prothrombin complex (anti-PS/PT) antibodies, and anti-beta(2)-glycoprotein I-dependent cardiolipin (anti-beta(2)GPI/CL) antibodies in the 16 CPN patients, 8 microscopic polyangiitis (MPA) patients, 33 systemic lupus erythematosus (SLE) patients, and 23 healthy controls. LAC was determined according to the Subcommittee on Lupus Anticoagulant/Phospholipid Dependent Antibody guidelines. Anti-PS/PT, aCL, and anti-beta(2)GPI/CL antibodies were measured by enzyme-linked immunosorbent assay.

RESULTS

Anti-PS/PT antibodies and/or LAC were detected in all CPN patients, but not in any controls. Serum IgM anti-PS/PT antibody was found in 13 (81.3%) CPN patients. The mean +/- SD serum anti-PS/PT IgM level (19.9 +/- 12.4 units/ml) in CPN patients was significantly elevated compared with SLE patients (5.7 +/- 5.9 units/ml). IgG anti-PS/PT antibody was detected in 5 (31.3%) CPN patients, but not in any controls. The IgG PS/PT antibody titers were similar in CPN patients (12.3 +/- 12.0 units/ml) and SLE patients (13.8 +/- 14.3 units/ml). Three (18.8%) CPN patients were positive for IgG aCL antibody and 2 (12.5%) for IgM aCL antibody. No MPA patients had aPL. CPN skin manifestations included livedo reticularis (14 [87.5%]). Direct immunofluorescence (DIF) revealed C3 within the affected vessels in 7 (77.8%) of 9 CPN patients.

CONCLUSIONS

Our study demonstrated that presence of anti-PS/PT antibodies and/or LAC could serve as markers in CPN patients. CPN could be dependently associated with the presence of anti-PS/PT antibody. Clinicians need to recognize these titers to permit early accurate diagnosis and treatment. We believe that anti-PS/PT antibodies will become widely recognized as a new factor when diagnosing CPN.

Drosophila immunity and embryogenesis appear to be linked by an evolutionarily ancient signalling pathway, which includes the Rel-domain transcription factors Dif and dorsal, respectively, as well as a common inhibitor, cactus. Previous genetic screens have centered on maternal mutants that disrupt the dorsal pathway. In an effort to identify additional components that influence Rel-domain gene function we have conducted a search for immunodeficiency mutants in Drosophila. One such mutant, which maps near the Black cells (Bc) gene, causes a severe impairment of the normal immune response, including attenuated induction of several immunity genes. Survival assays indicate a positive correlation between the induction of these genes, particularly diptericin, and resistance to bacterial infection. These studies are consistent with the notion that insect anti-microbial peptides work synergistically by binding distinct targets within infecting pathogens. Evidence is also presented that non-specific acquired immunity results from the persistence of bacterial metabolites long after primary infection. We discuss the potential usefulness of this study with regard to the identification of conserved components of Rel signalling pathways.

An in vitro model for the study of pemphigus acantholysis has been developed. The histological changes of pemphigus vulgaris were reproduced in vitro in organ culture by growing normal human skin in the presence of pemphigus vulgaris or pemphigus foliaceus sera. At 24 h a suprabasilar split was noted and at 72 h extensive suprabasilar acantholysis developed. Direct immunofluorescent tests demonstrated that pemphigus antibody became bound to the epidermal intercellular space antigen(s) during the first 6-12 h. As acantholysis increased the presence of tissue-fixed antibody decreased. The fixation of the pemphigus antibody to the skin prior to the development of acantholysis provides strong evidence for the pathogenetic role of this antibody in the production of acantholysis. The data suggest that complement is not required in this model for the production of the acantholytic changes of pemphigus since heating the serum for 30 min at 56 degrees C did not destroy the acantholytic activity and no complement (C3) could be detected by DIF of organ culture explants.

Autophagic or necrotic cell death (ACD and NCD, respectively), studied in the model organism Dictyostelium which offers unique advantages, require triggering by the same differentiation-inducing factor DIF-1. To initiate these two types of cell death, does DIF-1 act through only one or through two distinct recognition structures? Such distinct structures may recognize distinct motifs of DIF-1. To test this albeit indirectly, DIF-1 was modified at one or two of several positions, and the corresponding derivatives were tested for their abilities to induce ACD or NCD. The results strongly indicated that distinct biochemical motifs of DIF-1 were required to trigger ACD or NCD, and that these motifs were separately recognized at the onset of ACD or NCD. In addition, both ACD and NCD were induced more efficiently by DIF-1 than by either its precursors or its immediate catabolite. These results showed an unexpected relation between a differentiation factor, the cellular structures that recognize it, the cell death types it can trigger and the metabolic state of the cell. The latter seems to guide the choice of the signaling pathway to cell death, which in turn imposes the cell death type and the recognition pattern of the differentiation factor.

OBJECTIVE

Upregulation of microRNA 16 (miR-16) contributed to the differentiation of human bone marrow mesenchymal stem cells (hMSCs) toward myogenic phenotypes in a cardiac niche, the present study aimed to determine the role of miR-16 in this process.

METHODS

hMSCs and neonatal rat ventricular myocytes were co-cultured indirectly in two chambers to set up a cardiac microenvironment (niche). miRNA expression profile in cardiac-niche-induced hMSCs was detected by miRNA microarray. Cardiac marker expression and cell cycle analysis were determined in different treatment hMSCs. Quantitative real-time PCR and Western blot were used to identify the expression of mRNA, mature miRNA and protein of interest.

RESULTS

miRNA dysregulation was shown in hMSCs after cardiac niche induction. miR-16 was upregulated in cardiac-niche-induced hMSCs. Overexpression of miR-16 significantly increased G1-phase arrest of the cell cycle in hMSCs and enhanced the expression of cardiac marker genes, including GATA4, NK2-5, MEF2C and TNNI3. Differentiation-inducing factor 3 (DIF-3), a G0/G1 cell cycle arrest compound, was used to induce G1 phase arrest in cardiac-niche-induced hMSCs, and the expression of cardiac marker genes was up-regulated in DIF-3-treated hMSCs. The expression of CCND1, CCND2 and CDK6 was suppressed by miR-16 in hMSCs. CDK6, CCND1 or CCND2 knockdown resulted in G1 phase arrest in hMSCs and upregulation of cardiac marker gene expression in hMSCs in a cardiac niche.

CONCLUSIONS

miR-16 enhances G1 phase arrest in hMSCs, contributing to the differentiation of hMSCs toward myogenic phenotypes when in a cardiac niche. This mechanism provides a novel strategy for pre-modification of hMSCs before hMSC-based transplantation therapy for severe heart diseases.

OBJECTIVE

To examine the cross-sample and temporal stability of the three subscales of the 20-item Toronto Alexithymia Scale (TAS-20) and to study the pattern of associations between the TAS-20 scales, neuroticism, and alexithymia.

METHODS

Two clinical and three nonclinical samples were included in the cross-sectional part of the study. One clinical and one nonclinical sample also participated in the 6-month follow-up study. To test the replicability of the three-factor structure of the TAS-20 across samples, a principal component analysis was conducted, followed by a Procrustes rotation. Linear regression analyses were conducted to examine temporal stability and to determine the specificity of the associations among the TAS-20 scales, neuroticism, and extraversion.

RESULTS

The three-factor structure of the TAS-20 was confirmed across all five samples. With a few exceptions, neuroticism and extraversion attained a higher level of temporal stability than the alexithymia scales. The TAS-subscale measuring difficulty identifying feelings (DIF) was less stable in the clinical than in the nonclinical sample. Neuroticism was most strongly associated with DIF, whereas extraversion was mainly related to externally oriented thinking (EOT). A combination of both neuroticism and extraversion was the best predictor of difficulty describing feelings (DDF).

CONCLUSIONS

Future studies on the psychometric properties and the clinical value of the TAS-20 should pay more attention to its subscales. Especially the EOT facet needs further examination.

BACKGROUND

Calcineurin, the Ca2+/calmodulin-dependent protein phosphatase, plays important roles in various cellular processes in lower and higher eukaryotes. Here we analyze the role of calcineurin in the development of Dictyostelium discoideum by RNAi-mediated manipulation of its expression.

RESULTS

The cnbA gene of Dictyostelium discoideum which encodes the regulatory B subunit (CNB) of calcineurin was silenced by RNAi. We found a variety of silencing levels of CNB in different recombinant cell lines. Reduction of CNB expression in a given cell line was correlated with developmental aberrations. Cell lines with strongly reduced protein levels developed slower than wild type cells and formed short stalks and spore heads with additional tips. Formation of short stalks results from incomplete vacuolization of prestalk cells during terminal differentiation. Expression of the stalk-specific gene ecmB was reduced in mutant cells. Aberrant stalk development is a cell autonomous defect, whereas the breakdown of tip dominance can be prevented by the presence of as low as 10% wild type cells in chimeras.

CONCLUSIONS

Silencing of calcineurin B in Dictyostelium by expression of RNAi reveals an unexpected link between increased intracellular calcium levels, possibly triggered by the morphogen DIF, activation of calcineurin, and the terminal stage of morphogenesis.

BACKGROUND

Significant differences have been reported in the prevalence of depression between Mexicans and Mexican Americans. Whether the differences in prevalence are real or are the results of cultural bias in instrumentation is not known.

OBJECTIVE

To examine the association between acculturation and the responses to the individual depressive symptom item of the Center for Epidemiologic Studies Depression Scale (CES-D).

METHODS

The CES-D was administered to 395 Hispanic women during their 22-24 weeks' pregnancy clinic visit. Acculturation was defined by a subject's language preference of English or Spanish when completing the CES-D. Those who preferred English belong to the acculturated group and those who preferred Spanish are considered nonacculturated. Logistic regression was used to conduct differential item functioning (DIF) analysis for each of the 20 CES-D items to determine whether they operated differently between the acculturated Hispanic group and the nonacculturated Hispanic group.

RESULTS

Reliability of the CES-D total score was .86 and .88 for the nonacculturated and acculturated groups, respectively. None of the items of the Depressed Affect Subscale showed DIF. However, DIF was found in four out of the seven items in the Somatic Activity Subscale and in three out of the four items in the Positive Affect Subscale.

CONCLUSIONS

The results suggest that even within a homogenous Hispanic group of mostly Mexican Americans, responses to the CES-D differ by acculturation. The nonacculturated group are less likely to endorse somatic symptoms but more likely to endorse positive items than the acculturated group. Depression screening in this population needs to account for acculturation differences within the Hispanic group.

Extensive studies in vertebrate cells have assigned a central role to Rel/NF-kappa B and AP-1 family members in the control of apoptosis. We ask here whether parallel pathways might function in Drosophila by determining if Rel/NF-kappa B or AP-1 family members contribute to the steroid-triggered death of larval salivary glands during Drosophila metamorphosis. We show that two of the three Drosophila Rel/NF-kappa B genes are expressed in doomed salivary glands and that one family member, Dif, is induced in a stage-specific manner immediately before the onset of programmed cell death. Similarly, Djun is expressed for many hours before salivary gland cell death while Dfos is induced in a stage-specific manner, immediately before this tissue is destroyed. We show that null mutations in the three Drosophila Rel/NF-kappa B family members, either alone or in combination, have no apparent effect on this death response. In contrast, Dfos is required for the proper timing of larval salivary gland cell death as well as the proper induction of key death genes. This study demonstrates a role for AP-1 in the stage-specific steroid-triggered programmed cell death of larval tissues during Drosophila metamorphosis.

OBJECTIVE

Differentiation-inducing factors (DIFs) are chlorinated alkylphenones found in the cellular slime mold Dictyostelium discoideum. DIF derivatives exhibit antiproliferative activities and promote glucose consumption in mammalian cells in vitro. Here, we assessed the ability of DIFs to regulate the immune system in a mammalian cell-line and investigated their mechanisms of action.

METHODS

We examined the effects of 30 DIF derivatives on concanavalin A-induced interleukin-2 (IL-2) production (CIIP) in Jurkat T-cells. We also examined the effects of these DIF derivatives on the activity of three transcription factors required for CIIP: namely, activator protein-1 (AP-1), nuclear factor of activated T-cells (NFAT), and nuclear factor kappa B (NFκB).

RESULTS

A reporter gene assay suggested that 2 DIF derivatives, termed DIF-1(+1) and DIF-3(3M), significantly promoted CIIP in Jurkat cells, at least in part, by enhancing the activity of AP-1. These 2 DIF derivatives had no significant effect on concanavalin A-induced interferon-γ production.

CONCLUSIONS

The results suggest that DIF derivatives could be developed as novel drugs for the activation of IL-2 production and resultant stimulation of the immune system.

The Drosophila inhibitor-kappaB ortholog Cactus acts as an inhibitor of the Rel-transcription factors Dorsal and Dif. In blastoderm cells and immune competent cells, Cactus inhibits Dorsal and Dif by preventing their nuclear localization. Cactus, Dorsal and Dif are also expressed in somatic muscles, where Cactus and Dorsal, but not Dif, are enriched at the neuromuscular junction. Mutations in dorsal cause neuromuscular defects and mislocalization of Cactus. Here, we investigated whether mutations in cactus affect the neuromuscular system and subcellular localization of Dorsal and Dif. Using locomotion assays, as well as physiological and immunochemical methods, we found that wild type Cactus is necessary for the normal function of the larval neuromuscular system. The phenotype comprises i) altered bouton numbers and impaired neurotransmitter release in the neuromuscular junctions in the abdominal segments, ii) muscular weakness and iii) poor locomotion performance, probably reflecting a general neuromuscular impairment. Interestingly, in cactus mutants the subcellular localization of Dorsal and Dif in muscle is not affected, whereas cactus protein is not detected in the nucleus. This suggests, together with the similarities between the phenotypes induced by cactus and dorsal mutations, that in larval muscles the function of Cactus might be cooperation to the transcriptional activity of Rel proteins more than their cytoplasmic retention. The similarities with inhibitor-kappaB/nuclear factor kappaB interactions and muscle pathology in mammals point to Drosophila as a suitable experimental system to clarify the complex interactions of these proteins in muscle postembryonic development and activity.

BACKGROUND

Large community-based epidemiological surveys have consistently identified high co-morbidity between major depressive episode (MDE) and generalized anxiety disorder (GAD). Some have suggested that this co-morbidity may be artificial and the product of the current diagnostic system. Because of the added direct and indirect costs associated with co-morbidity, it is important to investigate whether methods of diagnostic classification are artificially increasing the level of observed co-morbidity.

METHODS

The item response theory (IRT) log-likelihood ratio procedure was used to test for differential item functioning (DIF) of MDE symptoms between respondents with and without a diagnosis of GAD in the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC).

RESULTS

The presence of GAD significantly increased the chances of reporting any symptom of MDE, with odds ratios ranging from 2.54 to 5.36. However, there was no indication of significant DIF of MDE symptoms in respondents with and without GAD.

CONCLUSIONS

The lack of any significant DIF indicates that cases with GAD do not present with a distinct MDE symptom profile, one that is consistent with the endorsement of symptoms that are conceptually similar in nature between the two disorders, compared to cases without GAD. This does not support the hypothesis that co-morbidity between MDE and GAD is artificially inflated because of the similar symptom criteria required by the current diagnostic system. Instead, MDE and GAD may be thought of as two distinct diagnostic entities that frequently co-occur because of a shared underlying trait.

To clone new replication origin(s) activated under RNase H-defective (rnh-) conditions in Escherichia coli cells, whole chromosomal DNA digested with EcoRI was to with a Kmr DNA fragment and transformed into an rnh- derivative host. From the Kmr transformants, we obtained eight kinds of plasmid-like DNA, each of which contained a specific DNA fragment, termed "Hot", derived from the E. coli genome. Seven of the Hot DNAs (HotA-G) mapped to various sites within a narrow DNA replication termination region (about 280 kb), without any particular selection. Because Hot DNA could not be transformed into a mutant strain in which the corresponding Hot region had been deleted from the chromosome, the Hot DNA, though obtained as covalently closed circular (ccc) DNA, must have arisen by excision from the host chromosome into which it had initially integrated, rather than by autonomous replication of the transformed species. While Hot DNA does not have a weak replication origin it does have a strong recombinational hotspot active in the absence of RNase H. This notion is supported by the finding that Chi activity was present on all Hot DNAs tested and no Hot-positive clone without Chi activity was obtained, with the exception of a DNA clone carrying the dif site.

Catenation links between sister chromatids are formed progressively during DNA replication and are involved in the establishment of sister chromatid cohesion. Topo IV is a bacterial type II topoisomerase involved in the removal of catenation links both behind replication forks and after replication during the final separation of sister chromosomes. We have investigated the global DNA-binding and catalytic activity of Topo IV in E. coli using genomic and molecular biology approaches. ChIP-seq revealed that Topo IV interaction with the E. coli chromosome is controlled by DNA replication. During replication, Topo IV has access to most of the genome but only selects a few hundred specific sites for its activity. Local chromatin and gene expression context influence site selection. Moreover strong DNA-binding and catalytic activities are found at the chromosome dimer resolution site, dif, located opposite the origin of replication. We reveal a physical and functional interaction between Topo IV and the XerCD recombinases acting at the dif site. This interaction is modulated by MatP, a protein involved in the organization of the Ter macrodomain. These results show that Topo IV, XerCD/dif and MatP are part of a network dedicated to the final step of chromosome management during the cell cycle.

This paper aimed to investigate the role played by key psychological factors in the experience of pain in cancer. One hundred and eight consecutive cancer patients were administered validated scales for pain, alexithymia, coping with cancer, and illness behavior. Two groups of patients with (n=45, 42%) and without (n=63, 58%) current pain were compared. Pain was associated to tumor sites and status, poor adjustment to cancer, and higher disease conviction and perception, but not to global alexithymia. However, the component of difficulty identifying feelings (DIF) of the alexithymia construct was significantly higher in pain patients compared to pain-free patients (t=2.88, p<0.01), constituted one of the independent predictors of pain (r=0.37; beta=0.27, p<0.01), and correlated with quality descriptors of pain (r=0.33, p<0.05). The present findings showed for the first time that although alexithymia was not globally related to cancer pain, the DIF component was however associated to pain dimensions, thus suggesting it might be involved in the way patients describe their pain experience, together with maladaptive coping and abnormal illness behavior. Cancer patients experiencing pain should be helped to adopt a more adaptive coping with the disease by identifying more accurately the source of their feelings.

It has been reported that patients with pneumoconiosis occasionally have a diffuse interstitial fibrosis (DIF) that resembles interstitial pneumonia, but little is known about the relation between pneumoconiosis-associated DIF and the risk of lung cancer. In the present study, we evaluated the incidence of DIF by chest CT and its contribution to lung cancer in 563 patients with nonasbestos pneumoconiosis. Fifty-five (10%) of the 563 patients had DIF. Pneumoconiosis with DIF had an exceedingly high concurrence of lung cancers when compared with pneumoconiosis without DIF (29 [53%] of 55 versus 78 [15%] of 508, p < 0.001). Squamous cell carcinomas (SCCs) of the lung from pneumoconiosis with DIF exclusively comprised peripheral-types, as compared with SCCs from pneumoconiosis without DIF (13 [100%] of 13 versus 33 [72%] of 46, p = 0.03). In addition, lung cancers arose frequently from the area of DIF in pneumoconiosis with DIF (20 [74%] of 27). Furthermore, our pathologic examination revealed that dysplasias from pneumoconiosis with DIF were significantly more frequently observed in peripheral bronchioli than were dysplasias from pneumoconiosis without DIF (11 [69%] of 16 versus 20 [30%] of 66, p = 0.01). p53 expression evaluated by immunohistochemistry was frequently observed in dysplasias from pneumoconiosis with DIF, although it was not significantly different compared with that in dysplasias from pneumoconiosis without DIF (5 [50%] of 10 versus 12 [38%] of 32). Taken together, these results may suggest a positive causal relationship between pneumoconiosis and peripheral-type SCCs of the lung, and further indicate a pivotal role of diffuse fibrosis for the excess incidence of lung cancers, especially peripheral-type SCCs, in DIF-type pneumoconiosis.

BACKGROUND

Past research has shown that Filipino cancer patients report lower levels of quality of life (QoL) than other ethnic groups. One possible explanation for this is that Filipinos do not define QoL in the same manner as others, resulting in bias in their assessments. Hence, Filipinos would not necessarily have lower QoL.

METHODS

Item response theory methods were used to assess differential item functioning (DIF) in the quality of life (measured by the EORTC QLQ-C30) of cancer patients across four ethnic groups (Caucasian, Filipino, Hawaiian, and Japanese). The sample consisted of 359 cancer patients.

RESULTS

Results showed the presence of DIF on several items, indicating ethnic differences in the assessment of quality of life. Relative to the Caucasian and Japanese groups, items related to physical functioning, cognitive functioning, social functioning, nausea and vomiting, and financial difficulties exhibited DIF for Filipinos. On these items Filipinos exhibited either higher or lower QoL scores, even though their overall QoL was the same.

CONCLUSIONS

This evidence may explain why Filipinos have previously been found to have lower overall QoL. Although Filipinos score lower on QoL than other groups, this may not reflect lower QoL, but rather differences in how QoL is defined. The presence of DIF did not appear, however, to alter the psychometric properties of the QLQ-C30.