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Occupational mental health promotion: a prevention agenda based on education and treatment. The American Psychological Association/National Institute for Occupational Safety and Health, Health Promotion Panel, 1990 Work and Well-Being Conference.

PURPOSE OF THE REVIEW. Psychological disorders are one of the 10 leading work-related diseases and injuries in the United States according to the National Institute for Occupational Safety and Health. This article addresses occupational metal health and preventive stress management in the workplace. The individual and organizational costs are briefly considered with concern for reducing the burden of suffering associated with these problems. SEARCH METHOD. As an American Psychological Association interdisciplinary panel, we searched the psychological, medical, public health, and organizational literature. We selected articles relevant to the problem of psychological disorders in the workplace and to enhancing occupational mental health and preventive stress management. IMPORTANT FINDINGS. The panel proposed a national agenda of education and treatment, combined with a program of evaluation research, for addressing these issues. Target populations are identified, and the need for collaboration among a variety of national constituencies is considered. Advancing occupational mental health and promoting skills in preventive stress management is considered in the context of comprehensive health promotion. MAJOR CONCLUSIONS. The panel concluded that there is a pressing need to: 1) set a 'gold' standard concerning the current state of knowledge in the domains of occupational mental health and stress management; 2) identify Diagnostically Related Groups (DRGs) which are stress-related; 3) establish assessment standards for stress and mental health; 4) set guidelines for reasonable interventions; and 5) establish acceptable post-outcome criteria.

Health Education↗

Characterization of an RNA polymerase activity from HeLa cell mitochondria, which initiates transcription at the heavy strand rRNA promoter and the light strand promoter in human mitochondrial DNA.

An RNA polymerase activity capable of initiating transcription at both the heavy strand rRNA promoter and the light strand promoter of human mitochondrial DNA has been partially purified from HeLa cell mitochondria and characterized in its requirements and products. The ratio of the two transcription initiating activities varied considerably from preparation to preparation. The human mtRNA polymerase partially purified by DEAE-cellulose and heparin-agarose chromatography exhibits a great sensitivity to ionic strength and to Mn2+, characteristics which clearly differentiate this enzyme from bacterial and eukaryotic nuclear RNA polymerases, and in contrast resemble the behavior of the yeast mtRNA polymerase. The human mtRNA polymerase exhibits a requirement for ATP which is 15- to 20-fold higher than that for the other NTPs, a low optimum template DNA concentration, and a marked susceptibility to inhibition by non-mitochondrial DNA.

Adenosine Triphosphate↗

A public health intervention model for work-site health promotion. Impact on exercise and physical fitness in a health promotion plan after 24 months.

We need effective ways of getting adults to exercise if we are to meet the Surgeon General's 1990 health goals for the nation. This study reports a comprehensive effort to evaluate the sustained effect of a public health intervention model to achieve these health goals. Employees at four companies (N = 2,600) were exposed to a health promotion program, while employees at three comparison companies (N = 1,700) were offered an annual health screen. Daily energy expenditure in vigorous activity increased 104% among employees at companies offering the health promotion program, compared with a 33% increase among employees at comparison companies. Changes in exercise habits were corroborated by estimates of maximal oxygen uptake. Exercise and physical fitness improvements were distributed throughout the work force. Meaningful population changes in exercise and physical fitness can be produced at the work site and are of a magnitude that makes it possible to meet the 1990 goals for exercise and physical fitness.

Adolescent↗

[Health promotion. Patterns of traditional health promotion in Korea].

The study attempted to explore the patterns of traditional health promotion activities in Korea. The methods employed in the study were the modified content analysis and the open coding method of grounded theory approach. Three principles of health promotion, conformity with universal law, temperance, and self-regulation were identified in the analysis. The subcategories of the three principles were natural order, harmony, activity and rest, diet, sexual life, convetousness, temperament, and apprehension. These principles stressed the harmony with nature and means of activities in everyday life. The principles also implied the Oriental holism and prevention of disease.

Female↗

OXBOX and REBOX, overlapping promoter elements of the mitochondrial F0F1-ATP synthase beta subunit gene. OXBOX/REBOX in the ATPsyn beta promoter.

Three positive (PR1-3) and one negative (NR1) transcriptional control domain have been tentatively mapped in the promoter of the human F0F1-ATP synthase beta subunit gene (ATPsyn beta) in the context of expression in myogenic cells. Lipofection of promoter-chloramphenicol acetyltransferase fusion constructs into C2C12 myogenic cells revealed that two of the three positive domains (PR1 and PR2) function in both myoblasts and myotubes, whereas the third positive domain (PR3) and the sole negative domain (NR1) seem to function only in myotubes. PR1 contains a cluster of four CCAAT cis-elements, PR2 is a small 44-base pair region containing an SP1-like motif, and PR3 is a region previously shown to be recognized by both OXBOX- and REBOX-binding factors. By site-directed polymerase chain reaction linker mutations, the activity of the OXBOX/REBOX cis-element in myoblasts is shown to be masked by flanking sequences in PR3. The negative domain, NR1, is located between 300 and 1,000 base pairs upstream from the OXBOX/REBOX elements in a region containing multiple Alu repeats. Mobility gel shift analysis of DNA-protein complexes using competitor DNAs verified the involvement of both OXBOX- and REBOX-binding factors in PR3. Similar experiments show SP1-specific binding at PR2. These data with observations of OXBOX and REBOX-specific binding of an OXBOX/REBOX-like region within the conserved sequence block C of the human mitochondrial DNA D-loop sequence are consistent with the idea that OXBOX- and REBOX DNA-binding factors coordinate the expression of mitochondrial energy genes in highly oxidative tissues by working with well characterized general transcription factors such as SP1 and CCAAT DNA-binding proteins, which exist in the nucleus, and MTF, which exists in the mitochondrion.

Animals↗

Characterization of promoter recognition complexes formed by CRP and CytR for repression and by CRP and RNA polymerase for activation of transcription on the Escherichia coli deoP2 promoter.

The structure of the cAMP-CRP-CytR repression complex and the cAMP CRP-RNA polymerase initiation complex at the deoP2 promoter of E. coli have been probed by DNase I and uranyl footprinting. In the CRP2-CytR complex all protein DNA-phosphate contacts at CRP-1 and CRP-2 are retained, and in addition two new minor groove contacts, ascribed to phosphate-CytR interactions, are observed at -60 between the CRP sites. The contacts are compatible with a model in which the promoter DNA is wrapped around a complex of two CRPs and one CytR. In the RNA polymerase-CRP complex, the CRP-1 phosphate contacts are almost identical to those seen in the repression complex and strong RNA polymerase contacts are seen in the -10 and in the +10 regions. Most noteworthy are minor groove contacts in the -60 region ascribed to RNA polymerase contacts upstream from the CRP. Furthermore, binding of CRP to the CRP-2 target does not seem to interfere with RNA polymerase binding. Thus, a model is suggested in which the DNA is wrapped around a complex of RNA polymerase and one CRP. Finally, the results show that CytR and RNA polymerase are rivals that compete for binding with CRP at deoP2 and that CytR functions as an antiactivator.

Bacterial Proteins↗

Characterization of the human ADP-ribosylation factor 3 promoter. Transcriptional regulation of a TATA-less promoter.

The 5'-flanking region of the human ADP-ribosylation factor 3 gene contains the features of a housekeeping gene. It lacks a TATA or CAAT box, has several GC boxes within a highly GC-rich region, and utilizes multiple transcription initiation sites. The cis-acting elements involved in regulating expression of the gene were identified by transient transfections of IMR-32 neuroblastoma cells. Reporter plasmids were modified to facilitate construction of defined promoter deletions linked to chloramphenicol acetyltransferase or luciferase using ligation-independent cloning. Transfection analyses indicated that sequences within 58 base pairs of the transcription initiation site were necessary for full expression, in particular a sequence containing the 10-base pair palindrome TCTCGCGAGA. Electrophoretic mobility shift assays performed with IMR-32 nuclear extracts demonstrated that a DNA-binding protein, termed TLTF, bound to an oligonucleotide containing this palindrome. Competition experiments showed that mutations within the core of the palindrome abolished in vitro binding and that the same protein bound to a 5'-proximal sequence. Expression of the promoter containing a mutated palindrome was reduced dramatically, consistent with the conclusion that this region functions in vivo to control expression of the ARF3 gene.

ADP-Ribosylation Factors↗

Characterization of the human C6 promoter: requirement of the CCAAT enhancer binding protein binding site for C6 gene promoter activity.

The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex. C6 and most of the complement proteins are mainly synthesized in the liver. However, the human hepatoma-derived cell line Hep-G2, which produces the majority of complement proteins, synthesizes traces of C6. Here, we have isolated and characterized the human C6 promoter. Approximately 1 kb of C6 upstream sequence is shown to be sufficient to achieve tissue-specific expression of a luciferase reporter gene in two hepatic (Hep-G2 and Hep-3B) and two extrahepatic cell lines (fibroblast M1 and HeLa) in a manner similar to endogenous C6. There are wide differences in C6 mRNA expression among the four cell lines, whereas Hep-3B expresses high levels of C6, Hep-G2 and M1 poorly synthesize C6, and HeLa completely lacks C6 expression. Deletional and mutational analysis demonstrates that a C/EBP (CCAAT/enhancer binding protein) site located at -67 is required for C6 expression in Hep-3B cells, but it has little effect in M1 and Hep-G2 cells. Electrophoretic mobility shift assays show that this sequence binds to a C/EBP alpha using Hep-3B nuclear extract, but a negligible activity is detected using a Hep-G2 extract. To further investigate whether C/EBP alpha is the limiting factor for C6 expression, we have transfected a C/EBP alpha expression vector into Hep-G2 and Ml cells. C/EBP alpha expression vector dramatically trans-activates the luciferase reporter gene controlled by the C6 promoter, and it partially restores C6 mRNA expression in Hep-G2 cells.

Animals↗

DNA mismatch repair as an effector for promoting phorbol ester-induced apoptotic DNA damage and cell killing: implications in tumor promotion.

Phorbol ester was known to activate protein kinase C (PKC) and exert numerous cellular effects, including proliferation, apoptosis, and oncogenic transformation. How phorbol ester stimulates both apoptosis and tumor promotion is not clear. Here DNA mismatch repair (MMR)-proficient human colon cancer cells (DLD-1+Ch2; hMSH6+) treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) undergo rapid cell death, which is significantly abolished by staurosporine (PKC inhibitor) or antioxidant, compared with the paired MMR-deficient (DLD-1; hMSH6-) cells. Induction of reactive oxygen species (ROS) by TPA is shown to be one of downstream effectors required, but not sufficient, for cell killing as it is also observed in DLD-1 cells. Strikingly, DLD-1+Ch2 cells selected for resistance to TPA are found to lose the expression of hMSH6. Treatment of TPA-resistant DLD-1+Ch2 cells with 5-aza-2'-deoxycytidine, not only restores hMSH6 expression but also resensitizes TPA-resistant cells to TPA, suggesting that expression of hMSH6 is transcriptionally silenced by cytosine methylation confirmed directly by bisulfite sequencing. Knockdown hMSH6 or hPMS2 with siRNA in DLD-1+Ch2 cells resulted in more resistant to TPA-induced cell killing, further suggesting that MMR proteins involve in TPA or ROS-induced cell killing. Results suggest that deficiency in MMR could promote tumorigenesis by inhibiting apoptotic responses to ROS-mediated DNA damages as ROS are continuously produced as a byproduct of normal metabolism.

Apoptosis↗

Mouse skin chemical carcinogenesis is inhibited by antizyme in promotion-sensitive and promotion-resistant genetic backgrounds.

Elevated polyamine content and increased ornithine decarboxylase (ODC) activity have been associated with neoplastic growth in numerous animal models and human tissues. Antizyme (AZ) is a negative regulator of polyamine metabolism that inhibits ODC activity, stimulates ODC degradation, and suppresses polyamine uptake. Preliminary evidence, obtained from transgenic mice with tissue specific overexpression of AZ indicates that tumor development can be suppressed by AZ. To extend these studies, we have examined the effect of keratin 5 (K5)- or K6-driven AZ transgenes on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical carcinogenesis of the skin, in promotion-resistant C57BL/6 and promotion-sensitive DBA/2 mice. On both genetic backgrounds, K6-AZ mice showed a reduction in tumor multiplicity, with 85% fewer tumors than wild-type controls on the C57BL/6 background and 50% fewer tumors on the DBA/2 background. K5-AZ mice developed 50% fewer tumors than controls on both backgrounds. The percent of mice with tumors and tumor size were also reduced in the K5-AZ and K6-AZ groups. Tumor and TPA-treated skin sections from K6-AZ mice exhibited the strongest AZ expression, with localization mainly in suprabasal keratinocytes. K6-AZ mice also had slightly reduced cell proliferation rates in tumors and TPA-treated skin. The lack of a more pronounced effect on cell proliferation is probably explained by the observation that AZ staining did not colocalize with proliferating cell nuclear antigen (PCNA), a marker for the proliferative compartment. These studies demonstrate a tumor-suppressive effect of AZ in C57BL/6 and DBA/2 mice, and confirm the importance of ODC and polyamines in tumor development.

Animals↗

Bacteriophage lambda-E. coli K12 vector-host system for gene cloning and expression under lactose promoter control. II. DNA fragment insertion at the vicinity of the lac UV5 promoter.

Bacteriophage vectors derived from lambda plac5 have been constructed. Their genomes have one EcoRI restriction site which is located at the very beginning of the lac Z gene. The major part of this gene was deleted by an in vivo intramolecular recombination. These vectors allow the fusion of a gene or an operon with the beginning of the lac Z gene, placing them under the control of the lac promoter, which carries the UV5 mutation. Some of these vectors (lambda Y) also include the lac Y gene and it too is under the control of the lac promoter. The lambda YEQS, which carries the Qam73 and Sam7 mutations, as safety mutations, has been certified as a B2 (EK2) vector by the French control commission "recombinaison génétique in vitro".

Coliphages↗

Induction of Epstein-Barr virus early antigens by tumor promoters of the diterpene ester type in Raji cells and specific (receptor) binding as compared to irritant and promoting activities.

Sixteen new diterpene esters (DTE) of the tigliane, ingenane, daphnane, and 1 alpha-alkyldaphnane types were investigated in two in vitro assays: as inhibitors of specific binding of 3H-labeled 12-O-tetradecanoylphorbol 13-acetate (TPA) to protein kinase C in a receptor preparation from mouse brain, and as inducers of Epstein-Barr virus (EBV) early antigens in Raji cells. Inhibition of binding of [3H]TPA to the receptor preparation by tigliane and ingenane DTE correlates with irritant activity in vivo, while some daphnane and 1 alpha-alkyldaphnane DTE inhibit binding of [3H]TPA in a less pronounced manner but still are very irritant. Tumor-promoting activity does not correlate consistently with the receptor-binding data. To test the hypothesis that early antigen induction in Raji cells by DTE is coupled to functional DTE receptors (protein kinase C), the latter were searched on these Raji cells by a 'cold acetone-filter assay' and shown to be present. The dependence of the early antigen induction rate on the concentration of the DTE tested was demonstrated. At a given concentration of DTE, differences in the induction rate between various DTE are seen. However, a clear quantitative correlation either between early antigen induction and receptor binding data in vitro, or early-antigen-inducing activity in vitro versus irritancy and tumor-promoting activity in vivo was not observed.

Animals↗

Stimulation of cell proliferation by tumor-promoting phorbol esters and inhibition by some inhibitors of tumor promotion in suspension cultures of a human lymphoblastoid cell line.

A human lymphoblastoid cell line, SCC-1, was established from the bone marrow of a patient with acute nonlymphocytic leukemia. 12-O-Tetradecanoylphorbol-13-acetate (TPA) enhanced cell proliferation of SCC-1 cells in suspension culture. A positive correlation was found between the tumor-promoting activities of several plant diterpenes and their enhancing effects on the growth of SCC-1 cells. Various compounds that inhibit tumor promotion were tested for their capacity to inhibit cell proliferation at a physiological concentration. These compounds were not cytotoxic but cytostatic even at high concentration.

B-Lymphocytes↗

The polyomavirus early promoter: role of proximal promoter elements in the formation of 5' termini in vivo.

Analysis of polyomaviruses with altered early promoter sequences indicates that in vivo (1) the polyomavirus early ATA motif and nearby upstream sequences dictate homogeneity of 5' termini, in contrast to what has been observed in vitro, where the cap site was reported to affect homogeneity of 5' termini (P. Jat, V. Novak, A. Cowie, C. Tyndall, and R. Kamen, 1982, Mol. Cell. Biol. 2, 737-751). (2) Substitution of the polyomavirus ATA motif by the adenovirus 2 major later promoter suppresses minor early 5' termini between the origin and the early cap sites, indicating that these termini are not the result of DNA replication.

Base Sequence↗

Construction of plasmid cloning vehicles that promote gene expression from the bacteriophage lambda pL promoter.

Two multiple-copy, ColE1-type, plasmid cloning vehicles, pHUB2 and pHUB4, have been constructed that carry four different single restriction sites down-stream from the phage lambda promoter pL. The promoting activity of pL is switched off at low temperature in the presence of a cIts gene that specifies a temperature-sensitive repressor but could be activated by heat induction. cIts was located either on the host chromosome, or on a second plasmid pRK248 that is compatible with the cloning vehicle, or on the vehicle itself. Three different restriction fragments, each carrying the gene trpA of Salmonella typhimurium or Shigella dysenteriae, have been inserted into the EcoRI, BamHI and SalI sites, respectively, of these plasmids and pL dependent expression of the inserted gene in Escherichia coli was determined by measuring the enzymatic activity of the trpA gene product. Heat induction resulted in a level of expression of trpA corresponding to 1 to 6.6% of the total soluble cell protein as trpA protein. The level of trpA protein production depended on the particular insert and the plasmid used.

Bacterial Proteins↗

Expression of a cloned Saccharomyces cerevisiae gene (URA1) is controlled by a bacterial promoter in E. coli and by a yeast promoter in S. cerevisiae.

The expression of a cloned yeast URA1 gene in Escherichia coli and in Saccharomyces cerevisiae was studied. In E. coli, only one orientation of the cloned yeast DNA segment inserted into the bacterial vector (pBR322) allows URA1 expression. Moreover, the permissive orientation changes with the cloning site. The absence of URA1 expression in E. coli can be corrected by the spontaneous integration into the cloned yeast DNA of a 0.9-kb bacterial DNA. Several copies of such a bacterial IS element have been detected in the host E. coli genome. The results strongly suggest that, in E. coli, transcription of the yeast URA1 needs a prokaryotic promoter for its initiation. In S. cerevisiae, the expression of non-chromosomally cloned URA1 does not depend on the orientation of the cloned fragment. Furthermore, it remains under the control of a nuclear regulatory gene (pprX-1) which constitutively enhances the expression of URA1 as well as URA3 at the transcriptional level. Therefore, in S. cerevisiae, transcription of non-chromosomally cloned URA1 involves a physiological yeast promoter cloned along with the structural part of the gene.

Cloning, Molecular↗

Structure and transcription promoter activity of mouse flap endonuclease 1 gene: alternative splicing and bidirectional promoter.

Flap endonuclease 1 (FEN1) is a structure-specific nuclease involved in DNA replication and repair. The mouse Fen1 gene, which has two exons, is located immediately adjacent to the gene corresponding to full-length cDNA of Riken 1810006K21 (1810006K21Rik) in a head-to-head orientation. Transcription initiation sites of each gene are 274 bp apart in the mouse genome. The spacer sequence between the bidirectional genes contains a CpG island, but lacks the typical TATA box. In the present study, transcription of the mFen1 gene was started from two initiation sites, and the first noncoding exon was spliced to the second exon using two different splicing donor sites, producing 3 kinds of mFen1 transcripts. A 594-bp fragment between the mFen1 and 1810006K21Rik genes, which contains two conserved sequence blocks (CSB) between mouse and human sequence, functions as a bidirectional promoter. The multiple cis-elements, including an Ets-binding site and E-box in the CSB, are involved in activation or repression of transcription in both directions. Interestingly, the E-box activates mFen1 transcription and simultaneously represses promoter activity in the opposite direction. Mutation of either splicing donor site of the mFen1 gene produced limiting alternative splicing products, but did not affect luciferase activity. In contrast, the splicing-defective mutation produced by disruption of the acceptor site completely lacked luciferase activity, indicating that the splicing has a significant effect on production of luciferase protein by shortening the 5'-untranslated region of the mRNA.

5' Untranslated Regions↗

The role of trivalent dimethylated arsenic in dimethylarsinic acid-promoted skin and lung tumorigenesis in mice: tumor-promoting action through the induction of oxidative stress.

We investigated the relationship between lung- and skin-tumor promotion and oxidative stress caused by administration of dimethylarsinic acid (DMA(V)) in mice. The incidence of lung tumors induced by lung tumor initiator (4NQO) and DMA(V) were, as well as 8-oxo-2'-deoxyguanosine (8-oxodG), suppressed by cotreatment with (-)epigallocatechin gallate (EGCG). When mice were topically treated with trivalent dimethylated arsenic (DMA(III)), a further reductive metabolite of DMA(V), not only an increase in skin tumors but also an elevation of 8-oxodG in epidermis were observed. These results suggest that tumor promotion due to DMA(V) administration is mediated by DMA(III) through the induction of oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗