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PubMed1999

Analysis of proopiomelanocortin gene transcription mechanisms in bronchial tumour cells.

The ectopic ACTH syndrome results from the transcription of the proopiomelanocortin (POMC) gene in non pituitary tumors. To determine its mechanisms, we examined in the human bronchial carcinoma cell line DMS-79 transacting factors binding to the human POMC gene promoter. Three binding sites were identified in the proximal promoter and proteins were studied by gel-shift assays. One of them is a binding site for Nur77/Nurr1 proteins in corticotroph cells but is bound in DMS-79 cells by factor(s) distinct from these proteins. The remaining two binding sites bound yet unidentified proteins and were both functionally active in DMS-79 cells. We also showed that DMS-79 cells lacked a factor required for tissue-restricted POMC gene expression in corticotroph cells. Altogether, our results indicate that POMC gene expression in DMS-79 cells is achieved without several of the corticotroph factors and provide a preliminary characterization of some factors involved in this process. They also reveal that DMS-79 cells are deficient in proteins involved in the regulation by cAMP and glucocorticoids.

ACTH Syndrome, Ectopic↗
PubMed1993

A 168 bp derivative of Suppressor-mutator/Enhancer is responsible for the maize o2-23 mutation.

From a directed transposon tagging of the maize Opaque-2 gene (O2), we have isolated a stable mutant o2 allele, o2-23. Cloning and molecular analysis of the allele revealed a 168 nucleotide insertion in the third exon of o2. The sequence of this small insertion indicated identity with the 5' and 3' ends of the 8.3 kb Suppressor-mutator/Enhancer (Spm/En) transposable element. This represents the smallest deletion derivative of Spm (dSpm) thus far characterized in maize. Genetic crosses of plants homozygous for o2-23 with plants homozygous for both an o2 null allele (o2-R) and an autonomous Spm produce stable opaque seed having no apparent sectors of vitreous endosperm. DNA fragments of the size expected if the dSpm were to excise were not detectable by Southern analysis, suggesting that this element is unable to transpose. Northern analysis detected an o2-23 mRNA that was much more abundant in o2-23 seeds lacking Spm than in o2-23 seeds containing Spm, consistent with the idea that Spm transacting functions can suppress the accumulation of the o2-23 transcript.

Alleles↗
PubMed2004

Martin Lister (1639-1712) and fools' gold.

Seventeenth-century physician Martin Lister is best known for his work in natural history and participation in the early Royal Society. However, little attention has been focused upon Lister's work in chemistry, the most salient examples being his analysis of pyrites or "fools' gold" near mineral springs in the De Fonbibus medicatis Angliae Exercitatio of 1684 (Exercises on the healing springs of England), his contributions to the Philosophical Transactions in the 1670s and 1680s, and his unpublished manuscript " A Method for the History of Iron, Imperfect." He defined pyrites more specifically as " ironstone marcasites" which were "nothing else but a body of iron disguised under a vitriolic varnish"; "vitriol" referred to iron (II) sulfate which occurred as a weathering product of pyrites. This paper demonstrates that an understanding of Lister's work on pyrites and vitriol is best attained by placing him in the intellectual context of the seventeenth-century chemical debate about minerallogenesis. Lister believed that the volatile exhalations of pyrites and its vitriol in the air were important in the transformation of matter, and he subscribed to the sixteenth-and seventeenth-century theory of witterung (weathering) or ore exhalations as an explanation for the formation of minerals. Despite his allegiance to the theories of witterung, I will illustrate that Lister made use of his interests in natural history to go one step beyond them, postulating that the sulfurous exhalations from pyrites were responsible for the heating of hot springs, as well as meteorological and geological effects.

Chemistry↗
PubMed1984

Technology policy and planning in the Third World pharmaceutical sector: the Cuban and Caribbean community approaches.

There has been growing international concern over many aspects of the use and flow of medicines in developing countries. This article briefly reviews factors which have contributed to problems in this area including marketing and promotional practices of the pharmaceutical companies, rising drug import costs, and the unsuitability or poor quality of available drugs. This analysis is primarily concerned with policies that have emerged from efforts to alleviate such problems, to increase control over multinational drug companies, and to bring about changes in the technology transaction processes and in the pharmaceutical sector. It focuses on two cases: the regional cooperation scheme of the Caribbean countries (CARICOM) and the national-level policy of Cuba. It is shown that the CARICOM strategy has significant limitations, primarily due to its voluntary nature and lack of enforcement mechanisms for member countries. On the other hand, the Cuban approach has brought about positive effects and progressive changes, made through political commitment to achieve social benefits, and in conjunction with integrated broad reforms of the entire health system within a socialist framework. Thus, the problems and promises of such strategies are viewed in a context which emphasizes the prevailing forces of the global political economy. The lessons from this study, applicable to other developing countries, not only reveal important measures for the pharmaceutical sector, but also stress the ultimate need for strong commitment to enforce policies at the national level and for major structural changes, in order to adequately meet the health and medical needs of the people.

Commerce↗
PubMed2000

Medical smart cards: health care access in your pocket.

The wallet-sized medical smart card, embedded with a programmable computer chip, stores and transmits a cardholder's clinical, insurance coverage and biographical information. When fully deployed, smart cards will conduct many functions at the point of care, from claims submission to medical records updates in real time. Ultimately, the smart card will make the individual patient record and all clinical and economic transactions within that patient log as portable, accessible and secure as an ATM account.

Costs and Cost Analysis↗
PubMedDate not supplied

Analyzing lease/purchase options.

The authors' previous article, "Equipment Acquisition Using Various Forms of Leasing," covers information necessary for selecting among the different kinds of leases. This article explains how to reach a proper financial analysis, preferably using two phases. Using a representative example, the article guides the reader through the first phase and introduces the elements needing review in the second phase. Key elements include pretax aftertax and cash flow analyses. Different organizations use different yardsticks to measure the financials of a transaction, but in general, cash is king. Therefore, the most widely used comparison is the purchase versus lease IRR (internal rate of return) produced by measuring the cash flow of the purchase case compared to the cash flow of the lease case.

Capital Expenditures↗
PubMed2006

Mapping transactional sex on the Northern Corridor highway in Kenya.

Even in generalized HIV/AIDS epidemics, vulnerable populations such as sex workers and truckers require special attention in programming. Combining a number of elicitation methods, centred on Geographical Information Systems (GIS) mapping, the Kenyan section of the Northern Corridor highway was studied to characterize the 'hot spots' where transactional sex is concentrated and to provide estimates of numbers of truckers and sex workers and the volumes of transactional sex taking place on the highway. An average of 2400 trucks park overnight at the 39 hot spots identified. These spots have an estimated sex worker population of 5600 women. Analysis of 403 sex worker diaries shows an average of 13.6 different clients and 54.2 sex acts in a month. Condom use is 69% in liaisons with regular clients and 90% with casual clients. The use of GIS is demonstrated at regional and local scales. The 'bridge population' of clients of sex workers, containing a wide rage of occupations, supports the concept of programming for 'vulnerable places' as well as vulnerable groups.

Female↗
PubMed1983

The rules and frames of the psychoanalytic situation.

Classical psychoanalytic theory and technique are still coherent, flexible, viable, and developing. But there is a need to develop an interactional theory which would be compatible with intrapsychic theory. One approach, utilizing a relativistic view of social realities, is "frame analysis," the study of the rules (which operate primarily outside of awareness) delimiting and governing specific social interactions. Applied to the analytic situation, it is a useful way to analyze the transactions. A clinical vignette is presented for purposes of illustration.

Adult↗
PubMed2001

A Modified General Regression Neural Network (MGRNN) with new, efficient training algorithms as a robust 'black box'-tool for data analysis.

A Modified General Regression Neural Network (MGRNN) is presented as an easy-to-use 'black box'-tool to feed in available data and obtain a reasonable regression surface. The MGRNN is based on the General Regression Neural Network by D. Specht [Specht, D. (1991). A General Regression Neural Network. IEEE Transactions on Neural Networks, 2(6), 568-576], therefore, the network's architecture and weights are determined. The kernel width of each training sample is trained by two supervised training algorithms. These fast and reliable algorithms require four user-definable parameters, but are robust against changes of the parameters. Its generalization ability was tested with different benchmarks: intertwined spirals, Mackey-Glass time series and PROBEN1. The MGRNN provides two additional features: (1) it is trainable with arbitrary data as long as a suitable metric exists. Particularly, it is unnecessary to force the data structure to vectors of equal length; (2) it is able to compute the gradient of the regression surface as long as the gradient of the metric is definable and defined. The MGRNN solves common practical problems of common feed-forward networks.

Algorithms↗
PubMed1994

Novel cis-acting elements in the human platelet-derived growth factor B-chain core promoter that mediate gene expression in cultured vascular endothelial cells.

Platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant constitutively expressed by a variety of normal and transformed cells. Transient transfection and deletion analysis of the human c-sis proto-oncogene in cultured vascular endothelial cells revealed a minimal core promoter region extending 82 base pairs upstream from the TATA box. Two novel and functional cis-acting elements were identified within the core that share considerable sequence homology with consensus binding elements for transacting factors of the ETS class and those involved in AP-1 complexes. Deletion or mutation of either the ETS-like site or the AP-1-like site resulted in significant attenuation in the ability of the core to drive transcription. Electrophoretic mobility shift assays revealed that proteins from bovine aortic and human umbilical vein endothelial nuclear extracts bound to these elements in a specific manner and that both sites were essential for protein binding. Ferguson analysis predicted a combined molecular mass of 153 kDa for these proteins. In addition, transient transfection, gel shift, and DNase I footprint analysis were used to identify a functional Sp1 binding site downstream of these elements in the core promoter. By localizing the functional cis-acting elements in the PDGF-B promoter, it may be possible to elucidate the normal transcriptional control of the gene, as well as the mechanisms that activate it in pathologic settings.

Animals↗
PubMed1998

Children's and adolescents' perception of their asthma bronchiale.

The present study examines the perception of asthma bronchiale in a large sample of 382 children and adolescents (mean age = 12.5 years) across three different treatment settings (outpatient, short-term rehabilitation, residential treatment) by using a revised child version of the 'Asthma Problem Behavior Checklist.' A PCA reveals two factors (eigenvalues: 26.3; 4.2; 0.9 ..) with a complementary structure: 'appraisal of asthma-related distress' (explained variance: 48.5%) and 'appraisal of resources in coping with asthma-related distress' (explained variance: 20.9%). Implications for clinical psychological assessment of young patients with asthma and the congruence with the LAZARUS transactional conceptualization of stress and coping are discussed.

Adaptation, Psychological↗
PubMed2000

An empirical application of transaction-costs theory to organizational design characteristics.

The environmental uncertainty component of transaction-costs theory was used to predict the organizational structural characteristics of size (number of employees) and horizontal differentiation (number of vice presidents) using financial and management information from the COMPACT DISCLOSURE data base (which contains the most recent annual and periodic reports for more than 12,000 public companies). Organizations were categorized as low- or high-uncertainty industries according to Dess and Beard's (1984) Dynamism Scale, and net sales volume was controlled. As predicted, high-uncertainty companies had significantly higher horizontal differentiation than low-uncertainty firms, a finding that supports the transaction-costs expectation that organizations may require more departments or personnel to cope with increasing uncertainty. Surprisingly, low-uncertainty firms were found to have significantly more employees than high-uncertainty organizations, which is the opposite of what transaction-costs theory predicts. Possible explanations for this unexpected finding and further potential limitations are discussed.

Cost-Benefit Analysis↗
PubMed2005

RGG-boxes of the EWS oncoprotein repress a range of transcriptional activation domains.

The Ewings Sarcoma Oncoprotein (EWS) interacts with several components of the mammalian transcriptional and pre-mRNA splicing machinery and is also found in the cytoplasm and even on the cell surface. The apparently diverse cellular functions of EWS are, however, not well characterized. EWS harbours a potent N-terminal transcriptional activation domain (the EAD) that is revealed in the context of oncogenic EWS-fusion proteins (EFPs) and a C-terminal RNA-binding domain (RBD) that recruits pre-mRNA splicing factors and may couple transcription and splicing. In contrast to EFPs, the presumed transcriptional role of normal EWS remains enigmatic. Here, we report that multiple RGG-boxes within the RBD are necessary and sufficient for cis-repression of the EAD and that RGG-boxes can also repress in-trans, within dimeric partners. Lys can functionally substitute for Arg, indicating that the basic nature of the Arg side chain is the critical determinant of RGG-box-mediated repression. In addition to the EAD, RGG-boxes can repress a broad range of activation domains (including those of VP16, E1a and CREB), but repression can be alleviated by the simultaneous presence of more than one activation domain. We therefore propose that a key function of RGG boxes within native EWS is to restrict promiscuous activation by the EAD while still allowing EWS to enter functional transcription complexes and participate in other transactions involving pre-mRNAs.

Amino Acid Motifs↗
PubMed2004

Differential expression and splicing isoform analysis of human Tcf-4 transcription factor in brain tumors.

Tcf family transcription factors are the downstream effectors of the Wnt signal transduction pathway that regulates developmental and oncogenetic processes among species. The alternative splicing of consecutive exons in the 3' part of the Tcf-4 gene and an error-prone A9 repeat in exon 17 have recently been examined in several tumors. To further understand the roles played by differential expression and splicing isoforms of human Tcf-4 in brain tumorigenesis, the expression of the 3' part of the Tcf-4 gene (exons 10-17) was analyzed by RT-PCR, nested RT-PCR and DNA sequencing. The results showed that at least 13 of the Tcf-4 alternative splicing isoforms were found and most of them were overexpressed in various brain tumors. L3 isoform was particularly dominant in metastasis. Several novel splicing isoforms were identified. One that contains different combinations of exon 16 (10-11-12-16-17, S5) was found in normal brain and pituitary adenoma but not in astrocytoma, meningioma or metastasis, whereas the other that contains part of intron 16, designated exon-16', was found in metastasis. Overall 23% of sequencing analysis in brain tumors exhibited frameshift mutations in an A9 repeat region of exon 17. These mutants exhibited 2-base or 1-base deletion (A7, A8) and 1-base insertion (A10). Nonetheless, in vitro functional assay showed that these mutants did not affect the transactivity of Tcf-4 comparing to wild-type Tcf-4. Collectively, our data suggest that a large number of alternative splicing isoforms may together with variable mutations of A9 repeat region maintain balanced pools of Tcf-4 isoforms during brain tumorigenesis.

Adenoma↗
PubMed1985

Narcotics control in anesthesia training.

Recent studies document that substance abuse is a significant problem among anesthesia personnel. We have developed a system to better control the accountability of narcotics and other potentially addictive drugs. The system consists of a three-phase approach: (1) an individual anesthesia cart/narcotics box; (2) computer analysis of drug usage; and (3) an anesthesia drug audit. A standard stock issue of drugs is maintained by each resident. Drugs are issued daily to those residents administering anesthesia. Each drug transaction is recorded by the resident according to the patient's name, hospital number, type and length of the surgical procedure, type and amount of drug used, and the amount of each drug discarded. A weekly computer-generated report shows individual usage trends for each drug and a summary of "high" users for that period. The computer does not "flag" an individual as a drug abuser, but monitors trends in controlled substance usage. Those residents having a significant alteration in their drug usage pattern that is not explained legitimately are comprehensively audited.

Anesthesia Department, Hospital↗
PubMed2000

Expression of the human poliovirus receptor/CD155 gene during development of the central nervous system: implications for the pathogenesis of poliomyelitis.

The gene for the human poliovirus receptor (hPVR/CD155) is the founding member of a new family of genes encoding proteins belonging to the immunoglobulin superfamily. To determine whether CD155 is expressed during mammalian development, we have made use of the previously characterized promoter of the CD155 gene and generated mice transgenic for a CD155 promoter-driven beta-galactosidase reporter gene. Expression of the reporter gene in transgenic embryos was observed during midgestation in anterior midline structures of the developing central nervous system and in the neuroretina. During that period, reporter gene expression appeared within the notochord and floor plate along the entire spinal cord reaching into the caudal diencephalon. In addition, transgene expression was observed in axonal projections emanating from retinal ganglion cells forming the optic nerve to reach the future region of the optic chiasm. Analysis of expression of CD155 during human embryonic development confirmed the distribution of reporter gene expression specified by CD155 promoter activity. The anatomical distribution of CD155 promoter activity during embryogenesis matches that of transacting factors previously identified to regulate transcription of the CD155 gene. Expression of CD155 within embryonic structures giving rise to spinal cord anterior horn motor neurons may explain the restrictive host cell tropism of poliovirus for this cellular compartment of the CNS.

Animals↗
PubMed1983

How environments and persons combine to influence problem drinking. Current research issues.

In this chapter, a brief review of existing empirical research on environmental correlates of problem drinking is presented. The review shows that environmental factors do relate to the prevalence of drinking problems and also to the way drinking problems are expressed. In the major section of the chapter, however, it is shown that our present knowledge of how environmental and personal factors combine to influence problem drinking is quite limited, perhaps because almost all of the existing empirical research has attempted to account for problem drinking by means of individual variables alone, environmental variables alone, or in terms of linear combinations of individual and environmental variables. It is shown that alternative approaches offer more promise for understanding how individual and environmental factors combine to influence problem drinking; these approaches are aimed at accounting for problem drinking in terms of the mutual interdependence between persons and their environments. Within two hypothetical sets of data, a number of conceptual and methodological issues, problems, and features of these kinds of interactional or transactional approaches are then illustrated. It is shown that although such approaches offer a promise of greater understanding, they also present a set of interrelated problems which run the gamut from measurement, statistical analysis, experimental design, and sampling issues to paradigm issues lying close to the realm of the philosophy of science.

Adolescent↗