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PubMed1994

Identification of a functional cyclic adenosine 3',5'-monophosphate response element in the 5'-flanking region of the gene for transition protein 1 (TP1), a basic chromosomal protein of mammalian spermatids.

Transition protein 1 (TP1) is a small basic chromosomal protein that appears in mammalian spermatids during the period of chromatin condensation. The gene for TP1 from several species contains an apparent cAMP response element (CRE) in the immediate 5'-flanking region. The recent identification of high expression of the novel CRE-activating protein (CREM tau) in advanced testicular germ cells provided a stimulus to ask whether or not the TP1 CRE is functional. To this end we show both by gel retardation and by footprint assays that TP1 CRE forms specific bound complexes with proteins in whole testis nuclear extracts and that these complexes involve CREM as evidenced by recognition by a specific antibody. In addition, the TP1 CRE forms specific bound complexes with bacterially expressed CREM tau. Finally, the TPI CRE conveys protein kinase A-dependent induction to a linked chloramphenicol acetyl transferase gene when transfected into JEG-3 cells. Accordingly, TP1 is a good candidate for a testis-specific gene subject to CREM tau regulation.

Animals↗
PubMed1999

A comprehensive plan for managed care of patients infected with human immunodeficiency virus.

Medicaid is rapidly moving toward managed care throughout the United States and will have a major impact on care programs for those infected with human immunodeficiency virus (HIV). The experience at the Johns Hopkins HIV Care Service is an example of the transition from fee-for-service to managed care. The Maryland Medicaid program, which has required enrollment of all Medicaid recipients since June 1997, uses an adjusted payment rate and separately funds protease inhibitors. Elements that made the transition to a managed care organization possible included the early development of a comprehensive network of services and a database showing that historical Medicaid payments were low compared with the statewide experience. Our Medicaid managed care program promotes unlimited access to specialists, rejects the "gatekeeper" concept for any service, and includes an open formulary. Nevertheless, it is uncertain that the services now provided can be sustained with anticipated reductions in payments that seem inevitable with Medicaid policies here and nationally.

Baltimore↗
PubMed2003

[Electronic structures of organometallic complexes of f elements. Part 54. Electronic Raman and f-f transitions in the low temperature vibrational spectra of Cp3Ce(NCCH3)2].

A comparison of the low temperature Raman spectra of Cp(3)Ce(NCCH(3))(2) (1), Cp(3)La(NCCH(3))(2) (2), Cp(3)La(NCCH(3))(2):Pr(3+) (3), Cp(3)La x NCCH(3) (4), Cp(3)Ce x NCCH(3) (5) and Cp(3)Tb x NCCH(3) (6) shows that the former compound exhibits three additional bands at 320, 2129 and 2154 cm(-1), which we ascribe to electronic Raman transitions. The two latter signals also appear in the low temperature IR spectrum of complex 1, but not in those of compounds 2-6. By performing crystal field (CF) calculations, the terminal states of the observed electronic Raman transitions could be identified. On the basis of both experimental and calculated CF energies as well as calculated wave functions the observed temperature dependence of mu(2)(eff) of complex 1 could be simulated in a satisfactory manner. A comparison of the low temperature Raman spectrum of compound 1 with the low temperature FIR spectrum of complex 2 shows that the selection rules for trigonal-bipyramidal coordination do not hold strictly for the skeletal vibrations. If the additional criterion of allowed vibronic side bands is applied to the transitions Gamma(1)-->Gamma(1, 4, 5, 6) of compound 3, the observed vibrational energies may be partly classified according to their symmetry.

Cerium↗
PubMed2003

A gas microstrip detector for XAS studies in the photon energy region 300-1500 eV.

The ability to perform X-ray absorption spectroscopy (XAS) in the 300-1500 eV energy range allows measurements to be made on transition metal compounds. This paper describes a detector and the technique used to perform fluorescent measurements on such materials. A variety of test sample results are shown to illustrate the low energy and energy-resolving capabilities of the detector (based on gas microstrip technology). Two possible applications are also demonstrated. The first shows how the detector can be used to gather X-ray absorption spectra for the L edges of transition metals and K edges of light elements (C, O and N). The other shows how the magnetic immunity of the detector can be exploited to study the magnetic properties of materials.

Absorptiometry, Photon↗
PubMed1979

Foetal haemopoiesis during the hepatic period. II. Topographic histology.

Serial sections of mouse foetal liver, during the 9th and 16th days of gestation, were studied. The erythropoietic process starts in the central area of the growing hepatic lobes, and subsequently spreads towards the periphery. Each lobe passes successfully through an undifferentiated, proliferating and differentiating period, but does not proliferate and differentiate in a homogeneously synchronized way, since the onset of both histogenesis and erythropoiesis is delayed at the periphery, when compared with the central area. As a consequence, in sections it is possible to find three different zones, namely: marginal, which is the most undifferentiated; intermediate (transitional); and a central area, which is the most mature, since it is the first site where erythropoiesis arises. These zones are distinguishable not only by their cell distribution, but also by the biological behaviour of their elements, specially in the transitional areas between undifferentiated and proliferating zones. The hepatic lobes do not start their organogenesis at the same time; but those of them in which histogenesis is delayed, repeat courses of development similar to those previously organized. The first interstitial erythropoiesis appears in the central area, after the development of an organized network of sinuses, and in close relation to vascular channels. Dynamic images of immature blood cells, between interstitial and vascular spaces, suggesting passage through the endothelium, are often seen. These steps are followed, in a concentric form and spreading towards the periphery, by each hepatic lobe.

Animals↗
PubMed2006

Dissolved oxygen as a physico-chemical supporting element in the Water Framework Directive.

For transitional and coastal waters the Water Framework Directive identifies 5 "General chemical and physiochemical elements supporting the biological elements". The five elements are transparency, thermal conditions, oxygenation conditions, salinity and nutrient conditions. "Supporting" in the context of the directive means that the values of the physicochemical quality elements are such as to support a biological community of a certain ecological status, recognising the fact that biological communities are products of their physical and chemical environment. Physicochemical and hydromophological aspects fundamentally determine the type of water body and habitat, and hence the type specific biological community. The directive does not intended that these supporting elements should be used as surrogates for the biological elements in monitoring. The monitoring and assessment of the physical and physicochemical quality elements will support the interpretation, assessment and classification of the results arising from the monitoring of the biological quality elements. This paper considers the challenges involved in the development of oxygen standards for the directive, their relationship to the biological elements and normative conditions of the directive and to regulatory requirements.

Ecosystem↗
PubMed2003

Transcription enhancer factor 1 binds multiple muscle MEF2 and A/T-rich elements during fast-to-slow skeletal muscle fiber type transitions.

In adult mouse skeletal muscle, beta-myosin heavy chain (betaMyHC) gene expression is primarily restricted to slow type I fibers; however, its expression can be induced in fast type II fibers in response to a sustained increase in load-bearing work (mechanical overload [MOV]). Our previous betaMyHC transgenic and protein-DNA interaction studies have identified an A/T-rich element (betaA/T-rich -269/-258) that is required for slow muscle expression and which potentiates MOV responsiveness of a 293-bp betaMyHC promoter (beta293wt). Despite the GATA/MEF2-like homology of this element, we found binding of two unknown proteins that were antigenically distinct from GATA and MEF2 isoforms. By using the betaA/T-rich element as bait in a yeast one-hybrid screen of an MOV-plantaris cDNA library, we identified nominal transcription enhancer factor 1 (NTEF-1) as the specific betaA/T-rich binding factor. Electrophoretic mobility shift assay analysis confirmed that NTEF-1 represents the enriched binding activity obtained only when the betaA/T-rich element is reacted with MOV-plantaris nuclear extract. Moreover, we show that TEF proteins bind MEF2 elements located in the control region of a select set of muscle genes. In transient-coexpression assays using mouse C2C12 myotubes, TEF proteins transcriptionally activated a 293-bp betaMyHC promoter devoid of any muscle CAT (MCAT) sites, as well as a minimal thymidine kinase promoter-luciferase reporter gene driven by three tandem copies of the desmin MEF2 or palindromic Mt elements or four tandem betaA/T-rich elements. These novel findings suggest that in addition to exerting a regulatory effect by binding MCAT elements, TEF proteins likely contribute to regulation of skeletal, cardiac, and smooth muscle gene networks by binding select A/T-rich and MEF2 elements under basal and hypertrophic conditions.

Animals↗
PubMed2006

Surface-enhanced Raman scattering from transition metals with special surface morphology and nanoparticle shape.

This discussion focuses on our recent approaches at aiming to optimize surface-enhanced Raman scattering (SERS) activity for transition metals (group VIII B elements), by intentionally fabricating desired surface nanostructures or synthesizing nanoparticles. The SERS activity of transition metals critically depends on the surface morphology of electrodes and on size, shape and aggregation form of nanoparticles. A correct surface roughening procedure for transition-metal electrodes is indispensable for fabricating cauliflower-like nanostructures that show a higher SERS activity. Two more methods have been explored to synthesize nanoparticles, i.e., cubic nanoparticles and gold-core palladium-shell nanostructures, respectively. Their SERS activities are considerably higher than those of normal spherical mono-metallic nanoparticles. To explain these observations, a preliminary theoretical calculation, using the three-dimensional finite difference time domain (3D-FDTD) method, was performed to evaluate the local electromagnetic field on transition metal surfaces. The result is in good agreement with the experimental data.

Journal Article↗
PubMed1994

Managed care in Eastern Europe: an opportunity for U.S. firms.

Health care in Eastern Europe is in transition; the former state-run health systems are in shambles. This article describes elements of these systems, discusses transition problems, such as corruption, and suggests areas in which American firms can prosper. Problems with capital development and red tape will need to be overcome. However, the quality of physician training is high, and many doctors are eager to work with American institutions to emulate their standards of care. Their need for training in Western management techniques is quite apparent. The author suggests that managed care organizations can be established rapidly if local partners are included in their development.

Consultants↗
PubMed2005

Biological master games: using biologists' reasoning to guide algorithm development for integrated functional genomics.

We review some powerful new algorithms that build on the intuitive biological interpretation techniques for statistical analysis of functional genomics experiments. Although they were originally designed for transcriptomics, we argue that these algorithms are applicable to any type of -omics study (transcriptomics, proteomics, metabolomics). Rank Products (RP), a strictly non-parametric test statistic to detect differentially regulated elements (genes, proteins, metabolites) in genome-wide screens. RP is particularly powerful for noisy data and low numbers of replicates and makes full use of the availability of a large number of parallel measurements that is typical of modern large-scale experiments. Iterative Group Analysis (iGA), a statistical method that makes the transition from regulated single elements to significant classes of elements, and thus provides an automatic functional annotation of an experiment. Graph-based iGA (GiGA), an extension of iGA that combines experimental data with a broad variety of biological annotations to highlight physiologically relevant regions in a given "evidence graph" (e.g., metabolic networks, signaling pathway diagrams, protein interaction maps). The sequential application of these techniques yields an increasingly abstract interpretation of experimental data that is at the same time quantitative, statistically rigorous, and biologically significant. The results can be used either as helpful tools to guide data visualization and exploration, or as the input for downstream computational applications in a systems biology framework.

Algorithms↗
PubMed1990

Wall structure of arteries and arterioles feeding the spinotrapezius muscle of normotensive and spontaneously hypertensive rats.

Vessel wall structure in feed arteries and their hierarchical ramifications were investigated in a rat skeletal muscle. Emphasis was placed on the transition of wall structure elements from the axillary and thoracodorsal arteries to the feeder arteries and the arcade and transverse arterioles forming the microcirculation of the spinotrapezius muscle. Semi-thin sections, prepared for light microscopy, and ultra-thin sections for electron microscopy were used to compare mature (15-20 week old) normotensive and hypertensive animals. The results demonstrate a gradual transition of the elastica intima and the smooth muscle from the central arteries towards the arterioles, accompanied by an attenuation of the adventitia. The elastica intima in 60-40 microns arcade arterioles is reduced from a continuous sheet in the central arteries to single fibers oriented parallel to the vessel axis. The multiple layers of smooth muscle cells at the level of the feeder arteries are reduced in the majority of arcade arterioles and in transverse arterioles to a single smooth muscle coat. Comparisons of the smooth muscle mass per unit length of vessel at selected sites of normotensive and spontaneously hypertensive rats show evidence for some degree of wall hypertrophy in the axillary artery, but no evidence for wall hypertrophy in arterioles of the microcirculation. There is no evidence of a pressure-mediated structural medial wall hypertrophy along this peripheral vascular pathway.

Animals↗
PubMed1987

Phenol-promoted structural transformation of insulin in solution.

Phenolic additives widely used for the preservation of insulin preparations can have a profound effect on the hormone's conformation in solution. m-Cresol, for instance, increases the circular dichroism in the far ultraviolet by 10-20%, corresponding to an increase in helix, and around 255 nm. The CD-spectral changes are strikingly similar to those brought about by halide ions which have been identified to reflect the 2 Zn----4 Zn insulin transition. Its most prominent element is the helix formation at the B-chain N-terminus. In both cases the changes fail to occur with dimeric insulin in the absence of Zn2 and with monomeric des-(B26-B30)-insulin. In the presence of Ni2 which is unable to replace Zn2 in 4 Zn insulin for coordinative reasons, the effect of m-cresol is impeded. m-Cresol thus induces a transition identical with or closely similar to the 2 Zn----4 Zn transformation. 2 Zn insulin crystals, when soaked in m-cresol containing solvents, are destroyed. Crystals grown in the presence of m-cresol, however, are monoclinic and containing symmetrical hexamers of, notably, 4 Zn conformation. Phenol, o- and p-cresol, m-nitrophenol, Nipagin M and benzene were further additives tested, all of them inducing largely the same spectral effects except for benzene. The results presented corroborate the close correspondence of insulin's structure in solution and in the crystal as well as insulin's capacity for structural variation.

Animals↗
PubMed1998

Assessment of cell cycle-related elements p53, p21WAF1/Cip1, cyclin D1 and PCNA in a mixed transitional cell carcinoma and adenocarcinoma of the renal pelvis: a case report.

A case featuring a well differentiated adenocarcinoma mixed with a transitional cell carcinoma (TCC) arising in the renal pelvis of a 63-year-old woman is presented. Daughter tumors, located in the ureter and the uretero-vesical junction, were entirely TCC in character. Immunohistochemical assessment of cell cycle-related proteins revealed overexpression of cyclin D1 but reduced p21WAF1/Cip1 or PCNA expression in the adenocarcinomatous regions. Conversely, expression of p21WAF1/Cip1 and PCNA was high in the TCC components. Immunohistochemical staining for p53 was negative and PCR-SSCP analyses confirmed the absence of any mutation. Therefore, assessments on the altered expression of cell cycle-related elements may contribute to our understanding of tumor biology in adenocarcinomas and TCCs of the renal pelvis and to identifying the similarities and differences between the two different cell types.

Adenocarcinoma↗
PubMed1998

Ventilatory assistance and respiratory muscle activity. 2: Simulation with an adaptive active ("aa" or "a-squared") model lung.

The aim of this study was to develop a lung model which adapted its active simulation of spontaneous breathing to the ventilatory assistance it received--an "aa" or "a-squared" lung model. The active element required was the waveform of negative pressure (pmus), which is equivalent to respiratory muscle activity. This had been determined previously in 12 healthy volunteers and comprised a contraction phase, relaxation phase and expiratory pause. Ventilatory assistance had shortened the contraction and relaxation phases without changing their shape, and lengthened the pause phase to compensate. In this study, the contraction and relaxation phases could be adequately represented by two quadratic equations, in addition to a third to provide a smooth transition. Therefore, the adaptive element required was the prediction of the duration of the contraction phase. The best predictive variables were flow at the end of contraction or peak mouth pressure. Determination of either of these allowed adjustment of the "standard" waveform to the level of assistance produced by an "average" ventilator, in a manner that matched the mean response of 12 healthy conscious subjects.

Airway Resistance↗
PubMed1995

Analysis of sequence-specific binding activity of cis-elements in human thymidine kinase gene promoter during G1/S phase transition.

Expression of thymidine kinase (TK) gene in normal human diploid, cells is both cell cycle and age dependent and appears to be transcriptionally regulated. Several studies have indicated that the G1/S control sequence may reside within the region of about 130 bp upstream of the transcription initiation site. We have previously shown that a trans-acting factor, CBP/tk (CCAAT binding protein for TK gene), binds to either one of the two inverted CCAAT boxes in a cell cycle- and age-dependent manner (Pang and Chen, 1993, J. Biol. Chem., 268:2909-2916). An upstream 25 bp fragment (-109/-84), containing both Yi-like and E2F-like binding sites, has recently been proposed to be essential for the G1/S regulation of human TK gene. To assess the contribution of various cis-elements in human TK promoter to the G1/S regulation, we have examined the binding activity of these cis-elements in the nuclear extracts derived from human IMR-90 cells at low passage number. Our results indicated that no binding activity could be detected using either the 25 bp fragment (-109/-94) or the authentic Yi sequence. However, Yi binding activity was observed in SV-40 transformed IMR-90 cells. In contrast, the 28 bp fragment (-91/-64) that contains the distal inverted CCAAT box exhibited a strong binding in serum-stimulated young IMR-90 cells. The binding of CBP/tk to the 28 bp fragment was abolished by a single base mutation in the CCAAT box. The CBP/tk binding of the 28 bp fragment could not be displaced by either the 25 bp fragment or the authentic Yi element. A deletion of the 5'-flanking region of the 28 bp fragment up to 5 bases also abolished the binding activity. The CBP/tk binding in IMR-90 cells was supershifted by antiserum against NF-Ya, but not by antiserum made against p107, pRb, cyclin A, p33cdk2, or p34cdc2. Taken together, our results suggest that the G1/S regulatory cis-element in human TK promoter may be confined only to CBP/tk binding sites.

Base Sequence↗
PubMed1983

Hemoglobin tertiary structural change on ligand binding. Its role in the co-operative mechanism.

Analysis of the tertiary structural alterations in hemoglobin induced by ligand binding demonstrates that an allosteric core composed of the heme, histidine F8, the FG corner and part of the F-helix plays an essential role in co-operativity. This conclusion is based on structural and spectroscopic data and theoretical studies of hemoglobin chains. The methodology employed in the calculations is presented with details of the empirical energy function. Energy minimized structures of the unliganded hemoglobin chains, which serve as reference systems for the analysis, are described. To determine the structural changes induced by ligand binding, the effects of Fe--N bond shortening and of heme translation and tilting perturbations are examined. Energy minimization in the presence of the perturbations serves to provide information concerning the globin structural modifications produced by them. The validity of the results is supported by comparisons with the X-ray data of Anderson, Pulsinelli, Baldwin and Chothia on tertiary changes in the hemoglobin subunits. Internal to the allosteric core, there appear to be two stable positions for its elements: one of these corresponds to the liganded and the other to the unliganded species. The unliganded geometry fits without strain into the deoxy tetramer, while the liganded one fits without strain into the oxy tetramer. On ligation of a subunit in the deoxy tetramer, the structural changes within the allosteric core are in the direction of those found in going from the unliganded deoxy to the liganded oxy system, although they are reduced by the presence of constraints due to the other subunits in the deoxy tetramer. In addition, the quaternary constraints in the deoxy tetramer prevent the large overall displacement of the allosteric core that occurs in the transition to the liganded oxy tetramer. The coupling between the changes internal to the allosteric core, produced on ligation and the overall displacement of the core that accompanies the quaternary transition, is an essential element of the co-operative mechanism. As shown in previous work (Gelin & Karplus, 1977), the proximal histidine serves as the link between the position of the heme and the F-helix; the asymmetric orientation of the histidine in the deoxy structure, coupled with contributions from other heme-protein interactions, appears to initiate the tertiary structural changes induced by ligand binding. The reduced oxygen affinity of hemoglobin results not from tension on the heme in the unliganded structure (there is none) but instead from strain in the liganded subunit of the tetramer within the deoxy quaternary structure.(ABSTRACT TRUNCATED AT 400 WORDS)

Allosteric Site↗
PubMed1976

Polypoid spindle-cell carcinoma (pleomorphic carcinoma). Report of a case occurring on tongue and review of the literature.

A case of spindle-cell carcinoma (pleomorphic carcinoma), a rare polypoid tumor of the tongue, is reported. The characteristic clinical, gross, and microscopic features of this peculiar lesion and its common sites of location are presented. Origin and pathogenesis of the sarcoma-like elements of the lesion are discussed and the literature on the subject is reviewed. Sites of apparent transition between the spindle cell elements of the tumor and the overlying epithelium were observed in light microscopic sections, and the electron micrographs of the spindle-cell portion of the lesion demonstrated the presence of tonofilaments and desmosomes in many tumor cells. These findings support the concept that this group of lesions are pleomorphic variants of squamous-cell carcinoma with predominantly spindle-cell pattern. Current evidence in the literature also suggests that metaplastic transformation of the tumor cells into mesenchymal elements may take place in some of these lesions, and that "metaplastic carcinoma" may probably be a more proper designation for them.

Aged↗