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PubMed1996

Identification of the human insulin negative regulatory element as a negative glucocorticoid response element.

Insulin gene transcription in adults is restricted to pancreatic beta cells. Studies with both transgenic mice and islet cell lines have demonstrated that beta cell specific expression is conferred by the 5' flanking region of the insulin gene. Transfection analysis has shown that cell specific expression involved an interaction between both positive and negative promoter cis elements. An upstream region (between -258 and -279) of the human insulin promoter served as a site of negative regulation. Transfection analysis in the pancreatic cell line HIT T-15 M 2.2.2 revealed that a DNA fragment containing this region causes a 45% reduction in promoter activity when linked to the native insulin promoter and a 72% reduction when linked to a heterologous tk promoter. Electrophoretic mobility shift analysis of this negative regulatory region (NRE) reveals a complex pattern of binding, wherein two major and several minor complexes are observed. Competition experiments demonstrated that formation of the fastest mobility complex is completely inhibited with excess cold glucocorticoid responsive element (GRE) consensus oligonucleotide. Purified glucocorticoid receptor binding domain (T7X556) demonstrated binding to the NRE oligonucleotide. Functional studies showed that dexamethasone treatment of HIT T-15 M 2.2.2 cells containing an NRE-tk CAT plasmid decreased CAT gene expression by 48%. Analysis of the NRE revealed 73% homology with the negative GRE consensus sequence. These data show that the human insulin NRE is a negative glucocorticoid response element.

Animals↗

PubMedDate not supplied

Social competence in schizoaffective disorder, bipolar disorder, and negative and non-negative schizophrenia.

Social skill and role functioning were assessed in matched groups of patients with DSM-III-R schizoaffective disorder, bipolar disorder, and schizophrenia. Schizophrenics were categorized as negative syndrome or non-negative on the basis of the SANS. The negative schizophrenics were significantly more impaired on almost every measure of social functioning. The other three groups were not consistently different from one another. The results suggest that when patients are comparable on dimensions such as duration and severity of illness, schizoaffectives do not occupy an intermediate position between schizophrenics without negative syndrome and bipolar patients. Rather, the three groups exhibit similar degrees of social disability. In contrast, negative syndrome schizophrenics were more impaired even when they were similar in chronicity and severity.

Adult↗

PubMed2006

Negatively oriented personality and perceived negative job characteristics as predictors of future psychological and physical symptoms: a meta-analytic structural modelling approach.

OBJECTIVES: There is evidence that perceptions of negative job characteristics (e.g., lack of control) and negatively oriented personality (e.g., negative affect) both predict symptom reporting. However, the relative contribution of these factors is rarely examined. This paper uses meta-analytic structural equation modelling (MA-SEM) to explore their relative contribution. METHODS: A meta-analysis of recent longitudinal studies was conducted. Eight studies covering 10 separate samples met the inclusion criteria (N=2104) and were used in the MA-SEM. Meta-correlations were used to construct structural equations models in which perceived negative job characteristics (PNJC) and negatively oriented personality (NOP) at baseline were used to predict concurrent and future symptom reporting, controlling for symptom reporting at baseline. RESULTS: The results indicated that a model based solely on NOP offered a more parsimonious account for baseline and future symptom reporting than did PNJC. CONCLUSIONS: The evidence indicates interventions should focus on both individuals and organizations, and not just organizational-level interventions.

Affect↗

PubMed2005

The tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for toll-like receptor 2 signaling via negative cross-talk with TRAF6 AND TRAF7.

Toll-like receptor 2 (TLR2) plays an important role in host defense against bacterial pathogens. Activation of TLR2 signaling not only induces the activation of innate immunity and instructs the development of the acquired immunity but also leads to the detrimental inflammatory responses in inflammatory and infectious diseases. To avoid detrimental inflammatory responses, TLR2 signaling must be tightly regulated. In contrast to the relative known positive regulation of TLR2 signaling, its negative regulation, however, is largely unknown. In addition the distal signaling components that link TLR2 to its downstream signaling pathways have yet to be further defined. In the present study we have provided direct evidence for the negative regulation of TLR2 signaling by the tumor suppressor cylindromatosis (CYLD). We showed that activation of TLR2 signaling by TLR2 ligands including peptidoglycan (PGN), MALP-2, and Pam3CSK4 induces activation of IKKs-IkappaBalpha and MKK3/6-p38 pathways not only by TRAF6 but also by TRAF7, a recently identified TRAF family member. The activation of both pathways leads to the transcription of TNF-alpha, IL-1beta, and IL-8 as well as CYLD. CYLD in turn leads to the inhibition of TRAF6 and TRAF7 likely via a deubiquitination-dependent mechanism. The present studies thus unveil a novel autoregulatory feedback mechanism that negatively controls TLR2-IKKs-IkappaBalpha/MKK3/6-p38-NF-kappaB-dependent induction of immune and inflammatory responses via negatively cross-talking with both TRAF6 and TRAF7. These findings provide novel insights into autoregulation and negative regulation of TLR signaling.

Apoptosis↗

PubMed1990

Negative daily events, positive and negative social ties, and psychological distress among older adults.

This study examined whether positive and negative social ties moderate the effects of negative daily events on psychological distress of 110 community-dwelling elders age 60-89. In accord with the stress-buffering hypothesis, the effect of negative daily events on psychological distress significantly (p less than .05) decreased as positive social ties increased. Contrary to the stress-amplifying hypothesis, negative social ties did not interact with negative daily events to influence psychological distress, but instead, had a significant (p less than .01) additive effect on it.

Aged↗

PubMed2006

Localized gap-edge fields of one-dimensional photonic crystals with an epsilon-negative and a mu-negative defect.

We study the properties of one-dimensional photonic crystals with an epsilon-negative and a mu-negative defect. With suitable parameters, the pair defect is equivalent to a transparent material with zero effective refractive index. This special pair defect has no influence on the spectral gap formed by the interference of propagating waves in positive-refractive-index materials. However, the field distribution is modified noticeably by the decaying wave in the pair defect. Particularly, the gap-edge field can be a highly localized wave instead of the usual standing wave as the size of the pair defect increases. The localized gap-edge field can reduce the switching thresholds for bistability greatly when Kerr-type nonlinear mu-negative material is involved. A nonideal model when the epsilon-negative and mu-negative materials are dispersive and lossy is used to verify the unusual properties.

Journal Article↗

PubMed2005

Systemic analysis and zygosity determination of the RHD gene in a D-negative Chinese Han population reveals a novel D-negative RHD gene.

BACKGROUND AND OBJECTIVES: The aim of this study was to systemically analyse the genetic background of D negativity in a Chinese Han population. MATERIALS AND METHODS: DNA of 74 D-negative samples was analysed by using an RHD multiplex polymerase chain reaction (MPX PCR) for the presence of RHD and by PCR-restriction fragment length polymorphism (PCR-RFLP) for RHD zygosity determination. Sixty-five samples were additionally analysed by using real-time quantitative PCR on RHD exon 7. RHD exon-specific sequencing was performed on discrepant samples. RESULTS: Forty-six samples (62%) showed the absence of RHD-specific exons by RHD MPX PCR and homozygous RHD negativity by PCR-RFLP. Twenty-two samples (30%) showed a 1227G>A mutation, characteristic for the Del phenotype. Five (7%) samples showed all characteristics of the RHD(1-2)-CE(3-9)-D(10) hybrid gene. One sample (1.4%) showed a novel 933C>A nonsense mutation in RHD exon 6, which resulted in a premature stop codon. CONCLUSIONS: The RHD gene deletion, RHD-CE-D hybrid genes and one novel 93C>A mutation were found to be the three mechanisms that cause D negativity in our samples. The 1227G>A Del mutation was found to be the major cause of discrepant results between genotyping and phenotyping strategies, favouring genotyping of D-negative samples.

China↗

PubMed1991

Improved method for detecting poliovirus negative strands used to demonstrate specificity of positive-strand encapsidation and the ratio of positive to negative strands in infected cells.

We have developed a ribonuclease protection method suitable for sensitive detection of an RNA species in the presence of a large excess of its complementary strand, as for the detection of negative strands of positive-strand RNA viruses. By using this method to probe for poliovirus negative strands in virions, we found that positive strands are present in at least 40,000-fold excess over negative strands. Thus, we have confirmed that poliovirus encapsidation is highly specific for positive strands and have demonstrated that the genome-linked protein VPg, which is covalently attached to the 5' ends of both positive and negative strands, cannot be the sole determinant of RNA packaging. We tested the ratios of viral positive strands to negative strands in cells at different times during infection; this value ranged from approximately 40/1 to 70/1, being highest at 4 h and lower at 2 and 6 h postinfection.

Animals↗

PubMed1993

Characterization of cytokine LD78 gene promoters: positive and negative transcriptional factors bind to a negative regulatory element common to LD78, interleukin-3, and granulocyte-macrophage colony-stimulating factor gene promoters.

Cytokine LD78 is a human counterpart of the mouse macrophage inflammatory protein 1 alpha/hematopoietic stem cell inhibitor. Promoters of the LD78 alpha and LD78 beta genes showed similar inducible activities in two leukemic cell lines, K562 and Jurkat, but the induction mechanisms differed between the two cell lines. Further characterization of the LD78 alpha promoter indicated that multiple positive and negative regulatory elements are present, some of which are differentially required for induction and repression of the promoter activity in different cells. One of the negative regulatory elements, ICK-1, functioned in both cell lines in the absence and presence of stimulation and was shown to be a recognition site for positive and negative transcriptional factors. This ICK-1 element contained a direct repeat, and similar repeats were also found in the negative regulatory elements of hematopoietic growth factor interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoters. Nuclear extracts from K562 and Jurkat cells formed several protein-DNA complexes with the LD78 alpha ICK-1 element, one of which was also observed with the IL-3 and GM-CSF ICK-1 elements. Results from in vivo and in vitro analyses suggested that the protein forming this complex functions as a negative factor. The binding affinity of this protein, ICK-1A, to the LD78 alpha ICK-1 element was low and was significantly affected by the incubation temperature and the salt concentration in the binding buffer. ICK-1B, another protein bound specifically by the LD78 alpha ICK-1 element, was shown to be a positive factor important for induction of the promoter. These results suggested that ICK-1A plays an important role in balanced expression of LD78, IL-3, and GM-CSF during hematopoietic cell growth and differentiation.

Animals↗

PubMed1998

What makes dreams positive or negative: relations to fundamental dimensions of positive and negative mood.

The present study examined the general emotional content of dreams reported by individuals who typically experience "positive" versus "negative" dreams. Self-reports of the 153 participants indicated that positive versus negative dreamers (ns = 42 and 24, respectively) generally experienced more positive emotions, e.g., joviality, self-assurance, and fewer negative emotions, e.g., fear, sadness. No differences were found in the self-reports of the participants in the experience of surprise, guilt, fatigue, and shyness between the groups, hence, positive and negative dreams do not appear to reflect simply more positive and fewer negative emotions, respectively.

Adolescent↗

PubMed1998

Test of the hopelessness theory of depression: drawing negative inference from negative life events.

The hopelessness theory of depression, i.e., that drawing negative inference from the occurrence of negative life events culminates in depression, was examined. A total of 34 dysphoric and 36 nondepressed undergraduate students participated in a two-stage prospective study lasting three months. The subjects completed the Beck Depression Inventory and Hopelessness Scale at both sessions and the Life Events Experience List at the second session. It is concluded that the inference of negative characteristics about the self from negative life events, coupled with the experience of negative life events contributes to the development of depression through hopelessness. The findings are discussed in relation to the Abramson, et al. hopelessness model of depression.

Adult↗

PubMed1999

CD45 negatively regulates lyn activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells.

Using CD45-deficient clones from the immature B cell line, WEHI-231, we previously demonstrated that CD45 selectively dephosphorylates the Src-family protein tyrosine kinase Lyn and inhibits its kinase activity. To further define the mechanisms of CD45 action on Lyn, we metabolically labeled Lyn from CD45-positive and -negative WEHI-231 cells and analyzed cyanogen bromide fragments by SDS-PAGE analysis. Phosphoamino acid analysis confirmed that Lyn is tyrosine phosphorylated with little serine or threonine phosphorylation. In CD45-negative cells, two bands at 8.2 and 4.1 kDa were phosphorylated in the absence of B cell Ag receptor (BCR) ligation. The 8.2-kDa band corresponded to a fragment containing the positive regulatory site (Tyr397), as assessed by its size and its phosphorylation in an in vitro kinase assay. The 4.1-kDa band was phosphorylated by COOH-terminal Src kinase, suggesting that it contains the COOH-terminal negative regulatory site (Tyr508). CD45 was also shown to dephosphorylate autophosphorylated Lyn in vitro. Thus, CD45 dephosphorylates not only the negative but also the positive regulatory tyrosine residues of Lyn. Furthermore, coimmunoprecipitations using anti-Igalpha Ab demonstrated that Lyn associated with the resting BCR was constitutively phosphorylated and activated in CD45-negative cells. In the parental cells, both regulatory sites were phosphorylated on BCR ligation. Taken collectively, these results suggest that CD45 keeps both BCR-associated and total cytoplasmic pools of Lyn in an inactive state, and a mechanism by which Lyn is activated by relative reduction of CD45 effect may be operative on BCR ligation.

Animals↗

PubMedDate not supplied

The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results.

The high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the prefrontal cortex is a promising method for the treatment of negative symptoms of schizophrenia. Using double-blind sham-controlled parallel design, we evaluated the effect of HF-rTMS over the left dorsolateral prefrontal cortex (DLPFC) on negative symptoms in patients with schizophrenia. Sixteen schizophrenia patients with predominantly negative symptoms on stable antipsychotic medication were treated with 20 Hz rTMS (90% of motor threshold, 2000 stimuli per session) over ten days within 2 weeks with six weeks follow-up. The effect was assessed using PANSS, CGI, MADRS and neuropsychological tests. We failed to find any significant effect of active rTMS. Sham rTMS showed a trend for improvement over time on positive and negative subscales of PANSS and MADRS. Between-group comparisons failed to reveal any significant differences on any rating scales except a positive subscale of PANSS after 8 weeks. Results from our study did not confirm that HF-rTMS over the left DLPCF affects the negative symptoms of schizophrenia and alternative rTMS approaches are discussed.

Adult↗

PubMed1993

Cost-effectiveness of monoclonal antibodies to gram-negative endotoxin in the treatment of gram-negative sepsis in ICU patients.

OBJECTIVE: To evaluate the fiscal impact and the cost-effectiveness of monoclonal antibodies against gram-negative endotoxin (MAbGNE) in the treatment of presumed gram-negative sepsis. DESIGN: A decision analysis model was developed from (1) data from two phase III trials that studied the E5 or HA-1A MAbGNE, and (2) financial data from 1405 septic patients who required intensive care at a large tertiary hospital. SETTING: Intensive care unit (ICU) patients with presumed gram-negative sepsis. PATIENTS: The E5 trial evaluated 468 patients, and the HA-1A study enrolled 543 patients with presumed gram-negative sepsis. INTERVENTIONS: The addition of MAbGNE to standard regimens or standard regimens alone. MAIN OUTCOME MEASURES: Total expected charges and the expected probability of survival were determined for each option. Cost-effectiveness and marginal cost-effectiveness ratios were also derived. Multiple sensitivity and Monte Carlo analyses were performed to test the underlying assumptions. RESULTS: MAbGNE therapy always resulted in higher expected charges; however, these differences were less than its acquisition cost by $870. The cost-effectiveness ratio for MAbGNE, for $2000 and $4000 acquisition costs, was $71,674 and $74,900 per probability of survival, respectively. Sensitivity analysis showed that cost-effectiveness was most affected by diagnostic accuracy, patient selection, and acquisition cost. Monte Carlo analysis showed that MAbGNE was more costly for 71% of simulations, yet the most efficacious option for 79% of simulations. CONCLUSIONS: From the perspective of acute care institutions, MAbGNE is expensive and cannot be justified on a cost-saving basis. However, it may be cost-effective throughout a reasonable range of assumptions.

Antibodies, Monoclonal↗

PubMed1980

Persistently negative tuberculin reactions: their presence among children with culture positive for Mycobacterium tuberculosis (tuberculin-negative tuberculosis).

Mantoux tests were performed on 200 children with culture-proven Mycobacterium tuberculosis infections. A group of 28 patients initially had negative reactions to 5 TU PPD-S. Of these, 17 had had extensive or overwhelming tuberculous disease at the time of admission, seven of whom reacted to 250 TU PPD; after a course of chemotherapy, all the survivors had positive reactions to 5 TU PPD-S. The 11 with less severe disease had negative reactions to 5 TU PPD-S and 250 TU PPD, as well as to PPD-A/B/G; in only two could a ready explanation be found for the negative reactor state. In general, a small number of children without life-threatening forms of tuberculosis may have persistently negative tuberculin reactions without any apparent cause. In such cases, other criteria for diagnosis must be relied on, such as lymphocyte transformation, culture, and biopsy.

Adolescent↗

PubMed1988

Multilineage cell involvement in Ph1-negative, bcr-negative chronic myeloid leukemia.

We report a case of Ph1-negative, bcr-negative CML-BC, in which the primary leukemic cells displayed T-related antigens (CD7, CD4) in addition to HLA-DR and CD25 determinants. No B-lymphoid, myeloid and megakaryoblastic surface antigens were detected. In spite of this phenotype, DNA analysis revealed a germ-line configuration of the T-cell receptor beta chain gene region. Moreover, in-vitro culture studies demonstrated a proliferative response of the blast cell population to natural and recombinant myeloid-related factors, while no proliferative signal was observed in the presence of IL-2. The myeloid lineage was further demonstrated by the expression of myeloid-associated antigens on cultured blast cells, which still retained the CD7 antigen. Finally, cytogenetic analysis revealed a monosomy 7 which is usually associated with a stem cell leukemia. These results support the hypothesis that Ph1-negative, bcr-negative CML is characterized by the involvement of a multipotent stem cell capable of multilineage expression and indicate that differentiative and proliferative assays provide a further tool towards a more precise recognition of hematological disorders of uncertain origin.

Aged↗

PubMed1994

Evaluation of RapID onE system for identification of 379 strains in the family Enterobacteriaceae and oxidase-negative, gram-negative nonfermenters.

The ability of the RapID onE system (Innovative Diagnostic Systems, Inc., Norcross, Ga.) to identify 364 strains in the family Enterobacteriaceae and 15 oxidase-negative, gram-negative, nonfermentative rods was evaluated. Kits were inoculated with no. 2 McFarland standard suspensions, and reactions were interpreted after 4 h of incubation at 35 degrees C. Overall, the method correctly identified (to the species level or to the genus level for salmonellas and non-Shigella sonnei Shigella species) 363 strains (95.8%) without additional tests. For four strains (1.0%), additional tests were required to delineate the correct identification from a range of two or more possibilities; these included one Serratia liquefaciens (Serratia marcescens or Serratia liquefaciens), one Serratia rubidaea (Serratia rubidaea or Serratia odorifera), one Salmonella typhi (Leminorella richardii or Salmonella sp.) and one Yersinia enterocolitica (Yersinia frederiksenii, Yersinia intermedia, or Yersinia enterocolitica). Twelve strains (3.2%) were misidentified or yielded codes with no identification; these comprised one Citrobacter amalonaticus (no identification), three Enterobacter hormaechei (not in the RapID onE database; two Enterobacter amnigenus, one Enterobacter sp.), one Serratia liquefaciens (Enterobacter cloacae), one Serratia rubidaea (no identification), four Serratia fonticola (not in RapID onE database; two Enterobacter aerogenes, one Serratia marcescens, one not identified), one Proteus mirabilis (Proteus penneri), and one Proteus vulgaris (Providencia rustigianii). If the seven strains not included in the database had been excluded, correct identification rates would have risen to 97.6% without additional tests and 98.7% with additional tests, with misidentification rates dropping to 1.3%. The RapID onE system is easy to set up and the results are easy to read, and the system provides an accurate, nonautomated commercially available method for the same-day identification of members of the family Enterobacteriaceae and oxidase-negative, gram-negative nonfermenters.

Bacteriological Techniques↗

PubMed1994

The contingent negative variation in positive and negative types of schizophrenia.

The authors analyzed the contingent negative variations of 20 medicated patients with schizophrenia diagnosed according to DSM-III-R and 20 age- and sex-matched normal comparison subjects. For the patients with schizophrenia, there were significant correlations between contingent negative variation amplitude and two items on the Scale for the Assessment of Negative Symptoms (affective flattening and avolition-apathy) and the total score on this scale. These findings have implications regarding the underlying pathology of negative and positive symptoms of schizophrenia.

Adult↗