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PubMed2001

Formation of binary alloy cluster ions from group-14 elements and cobalt and comparison with solid-state alloys.

By using laser ablation on mixtures of transition metal cobalt and group-14 elements, binary alloy cluster anions were produced while no binary alloy cluster cations were detected, and the homocluster cations of group-14 elements appeared at very low abundance. The differences between clustering abilities of germanium, tin and lead with cobalt are described, and the chemical bonds in the binary alloy cluster anions appear to indicate a transition from covalent to metal bonds. The cluster anion [CoPb10](-) appears in very high abundance (magic number), and an endohedral structure is proposed for this cluster. The cluster anion [CoPb12](-), also representing a magic number, probably has an icosahedral structure. Compared with solid-state Co/Ge binary alloys, the compositions of most binary alloy cluster anions are germanium-rich, in which the covalent bonds are predominant.

Journal Article↗

PubMed2003

The cyclin E/Cdk2 substrate p220(NPAT) is required for S-phase entry, histone gene expression, and Cajal body maintenance in human somatic cells.

Cyclin E/Cdk2, a central regulator of the G1/S transition, coordinates multiple cell cycle events, including DNA replication, centrosome duplication, and activation of the E2F transcriptional program. Recent studies suggest a role for cyclin E/Cdk2 in activation of histone transcription during S phase via the Cajal body-associated protein p220NPAT, and in addition, p220 can promote S-phase entry independently of histone transcriptional activation when overexpressed. Here we have examined the requirement for p220 in histone transcription, cell cycle progression, and Cajal body function through analysis of human somatic HCT116 cells engineered to contain a conditional p220 allele. p220 is required for proliferation of HCT116 cells, as assessed after expression of Cre recombinase in p220(flox/-) cells. This defect was due to an inability of these cells to transit from G0/G1 into S phase, and cell cycle arrest occurred in the presence of elevated Cdk2 kinase activity. Expression of human papillomavirus E7, but not E6, eliminated cell cycle arrest in response to p220 depletion. Optimal expression of all four core histone genes required p220, as did optimal transcription of a histone H4 promoter-luciferase construct. Basal histone H4 expression in G0/G1, although p220 dependent, occurs in the absence of detectable phosphorylation of p220 on Cdk2 sites. Cells lacking p220 displayed defects in the localization of the Cajal body component p80coilin as cells progressed from G0 to S phase in response to mitogenic signals. These finding indicate that p220 is an essential downstream component of the cyclin E/Cdk2 signaling pathway and functions to coordinate multiple elements of the G1/S transition.

CDC2-CDC28 Kinases↗

PubMed2000

Structures and phase transitions of the A7PSe6 (A = Ag, Cu) argyrodite-type ionic conductors. II. Beta- and gamma-Cu7PSe6

The crystal structures of two of the three polymorphic forms of the Cu7PSe6 argyrodite compound are determined by means of single-crystal X-ray diffraction. In the high-temperature form, at 353 K, i.e. 33 K above the first phase transition, gamma-Cu7PSe6 crystallizes in cubic symmetry, space group F43m. The full-matrix least-squares refinement of the structure leads to the residual factors R = 0.0201 and wR = 0.0245 for 31 parameters and 300 observed independent reflections. In the intermediate form, at room temperature, beta-Cu7PSe6 crystallizes again in cubic symmetry, but with space group P2(1)3. Taking into account a merohedric twinning, the refinement of the beta-Cu7PSe6 structure leads to the residual factors R = 0.0297 and wR = 0.0317 for 70 parameters and 874 observed, independent reflections. The combination of a Gram-Charlier development of the Debye-Waller factor and a split model for copper cations reveals the possible diffusion paths of the d10 species in the gamma-Cu7PSe6 ionic conducting phase. The partial ordering of the Cu+ d10 element at the phase transition is found in concordance with the highest probability density sites of the high-temperature phase diffusion paths. A comparison between the two Cu7PSe6 and Ag7PSe6 analogues is carried out, stressing the different mobility of Cu+ and Ag+ and their relative stability in low-coordination chalcogenide environments.

Journal Article↗

PubMedDate not supplied

[Stimulation modalities in the study of visual evoked potentials].

An evoked potentials (EPs) is an electrical manifestation of the brain's reception of and response to an external stimulus. The classification of visual evoked potentials (VEPs) depend primarily on stimulus characteristics. The visual content of a stimulus can be divided into two types: patterned and diffuse. VEPs to patterned stimuli are due mainly to the density of light and dark contrast borders; VEPs to diffuse light flashes are due to change in luminance only. Transitions between light and dark pattern elements have sharp borders in checkerboard patterns and in bar gratings. Those transitions can be represented by a spatial square wave. In sine wave gratings the change of luminance between light and dark stripes is gradual. The visual angle describes the size of the image of one light or dark element. The spatial frequency equals the number of repetitions of one light plus one dark element.

Brain↗

PubMed2000

Serial transplants of DMBA-induced mammary tumors in fischer rats as model system for human breast cancer: V. Myoepithelial-mesenchymal conversion during passaging as possible cause for modulation of pineal-tumor interaction.

An elevation of melatonin secretion parallel to an enhanced production of macrophage-derived biopterin was observed in female F344 Fischer rats bearing passage 2 serial transplants derived from a malignant mammary tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA). As opposed to that both parameters were depressed at passage 12. These results indicate the presence of divergent immunoneuroendocrine interactions during different phases of tumor growth. Since these biochemical events must have their common origin in changes taking place within these tumor transplants the current histopathological study was initiated. The primary tumor used for serial transplantation was a moderately differentiated adenocarcinoma of the mammary gland showing cytokeratin-positive epithelial components located in the inner epithelial tubule layer. In addition, bland-looking round or elongated actin-positive myoepithelial cells were detected which apart from epithelial cells are known to constitute the main cellular components of the mammary ductal system which resemble smooth muscle cells both morphologically and functionally. The tumor of passage 1 showed glandular tubules, lined by an inner epithelial layer, and many nests of clear, bland-looking actin-positive myoepithelial cells lying around tubules as well as in the stroma between actin-negative epithelial elements. The tumor of passage 2 used for transplantation consisted of a chaotic mixture of epithelial carcinomatous cells, forming a few irregular small tubules or solid nests, and, predominantly, of elongated plump or spindle-shaped, "myoid" atypical myoepithelial cells with a strong actin-positive reaction and some of these cells showed a focal vimentin expression. The tumor was characterized as a carcinosarcoma. At passage 12 epithelial cells were not identified. The tumor displayed features of a pleomorphic sarcoma consisting mainly of giant cells with bizarre nuclei being cytokeratin- and desmin-negative, weakly vimentin-positive but strongly actin-positive. These results indicate that DMBA-induced mammary tumor cells in female F344 Fischer rats undergo dramatic morphological changes during serial transplantation characterized by a total loss of malignant epithelial (carcinomatous) cells and the emergence and subsequent predominance of malignant (sarcomatous) mesenchymal cells. It appears that these sarcomatous cells develop out of myoepithelial cells since atypical myoepithelial cells with a strong actin-positive reaction showed a focal vimentin expression at passage 2 indicating myofibroblastic differentiation as part of mesenchymal transition. The loss of epithelial cell elements as well as a parallel transition of myoepithelial to mesenchymal cell elements during passaging could lead to a lack of immunological recognition of these tumor transplants and to depression of melatonin. Possible mechanisms involved in these phenomena as well as the relevance of these findings for a better understanding of the role of melatonin in human mammary cancer are discussed.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

Farnesyltransferase as a target for anticancer drug design.

The currently understood function for Ras in signal transduction is in mediating the transmission of signals from external growth factors to the cell nucleus. Mutated forms of this GTP-binding protein are found in 30% of human cancers with particularly high prevalence in colon and pancreatic carcinomas. These mutations destroy the GTPase activity of Ras and cause the protein to be locked in its active, GTP bound form. As a result, the signaling pathways are activated, leading to uncontrolled tumor growth. Ras function in signaling requires its association with the plasma membrane. This is achieved by posttranslational farnesylation of a cysteine residue present as part of the CA1A2X carboxyl terminal tetrapeptide of all Ras proteins. The enzyme that recognizes and farnesylates the CA1A2X sequence, Ras farnesyltransferase (FTase), has become an important target for the design of inhibitors that might be interesting as antitumor agents. Several approaches have been taken in the search for in vivo active inhibitors of farnesyltransferase. These include the identification of natural products such as the chaetomellic and zaragozic acids that mimic farnesylpyrophosphate, bisubstrate transition state analogs combining elements of the farnesyl and tetrapeptide substrates and peptidomimetics that reproduce features of the carboxyl terminal tetrapeptide CA1A2X sequence. This last group of compounds has been most successful in showing highly potent inhibition of FTase and selective blocking of Ras processing in a range of Ras transformed tumor cell lines at concentrations as low as 10 nM. Certain peptidomimetics will also block tumor growth in various mouse models, with apparently few toxic side effects. These results suggest that farnesyltransferase inhibitors hold considerable promise as anticancer drugs in the clinic.

Alkyl and Aryl Transferases↗

PubMed1977

Ultrastructure of gonadoblastoma and disgerminoma (seminoma) in a patient with XY gonadal dysgenesis.

The gross and fine morphology of gonadoblastoma and disgerminoma in a young phenotypic female with male karyotype and gonadal dysgenesis is described. Both the rudimentary gonads contain gonadoblastomas on the left side in association with a disgerminoma. In the light microscope the gonadoblastomas show peculiar hyaline masses, surrounded by Sertoli-like cells. In some areas a direct continuation between hyaline masses and basement membranes of round nests or large anomalous seminiferous tubules is obvious. At the ultrastructural level the hyaline masses consist of densely packed, largely concentric membranes closely similar to basement membranes or basal laminae of seminiferous tubules. These observations and the finding of transitional zones with gonadoblastoma elements in enlarged tubular structures suggest that gonadoblastomas originate inside tubules of dysgenetic testes. The peculiar hyaline masses with their concentric membranes might reflect hyperplasia and death of the Sertoli cells, each new generation of cells producing a basement membrane outside the preceding one.

Adolescent↗

PubMed1992

Cerebral granular cell tumors: report of a case and a note on their nature and expected behavior.

A case of cerebral granular cell tumor (GCT) is reported. Histologically, the growth was composed of benign astrocytes, granular cells and transitional forms between both elements. Glial fibrillary acidic protein was detected in the glial component and, to a lesser extent, in the granular cells. Alpha-1-antichymotrypsin was demonstrated in the latter component only. Ultrastructural study also supported the evidence that neoplastic astrocytes became granular cells. The survey of the literature and our own results suggest that GCTs in this particular location, even when histologically benign, seem to have a worse prognosis than the low-grade supratentorial astrocytomas.

Astrocytes↗

PubMed1999

[Skull and mandible. On Joseph Beuys' "ancient sled." Medical art history observation].

Few people are aware that Joseph Beuys (1921-1986), one of the most important artists at the end of the twentieth century, studied various aspects of the human skull. Beuys used teeth (especially molars), antlers, and horns as organically differentiated formations of solid substances of the viscerocranium, associating them in a very visual way with the "streaming circulation" principle. In addition, in his early drawings, in particular, Beuys replaced the lower jaw with a sledge. The artist has thus created interesting and strange constructions concerned with the structure of the jaw and the craniovertebral transition. Certain characteristic structural elements of sledges show a remarkable formal analogy to the ramus of mandible. The base of the body of mandible becomes a sliding surface, the iron runners of the sledge. Replacing the lower jaw with a sledge raises questions concerning movement and the effect of energy on the skull and on the earth. The artist's understanding of anatomy goes for beyond than that of normal medicine. It is formed by his thinking, his energy plan, and by his own theory of metamorphosis. With his skull and Urschlitten motif, Beuys makes us aware of the transitory layers of consciousness between life and death. "Head" and "sledge" are early forms of sculptural thinking in the work of Joseph Beuys.

Germany↗

PubMed2006

[The role of health care reporting for the planning of long-term care at the community level].

A key element in the demographic transition process is the increase in the number of very old people (80+) leading to a rising need for long-term care. For the municipalities the efficient organisation of the local support for senior citizens is an important task for legal, political and financial reasons. The local planning process must be based on systematic reporting about long-term care in the community. This report must contain fundamental facts about the demographic situation, the health care system, including the quality of care in nursing homes, by ambulatory services and families as well as the resulting costs in the local welfare budget. Comparing the problem to the methods in local health promotion it is favourable to establish an office to manage the planning process and a committee for matters of care. Committee members should be all relevant stakeholders of the local health, the care and the social sector. The first priority is to achieve the participation of patients, their relatives and the local politicians to agree on targets and measures in the planning process. Key targets are the prevention of risks for long-term care, to secure the quality of care and the preference for ambulatory services, optimisation of local cooperation and minimising the costs for the community. The whole process should be guided by these targets for the provision of care.

Community Health Planning↗

PubMed2003

X-ray absorption spectroscopy to analyze nuclear geometry and electronic structure of biological metal centers--potential and questions examined with special focus on the tetra-nuclear manganese complex of oxygenic photosynthesis.

X-ray absorption spectroscopy (XAS) has become a prominent tool for the element-specific analysis of transition metals at the catalytic center of metalloenzymes. In the present study the information content of X-ray spectra with respect to the nuclear geometry and, in particular, to the electronic structure of the protein-bound metal ions is explored using the manganese complex of photosystem II (PSIII) as a model system. The EXAFS range carries direct information on the number and distances of ligands as well as on the chemical type of the ligand donor function. For first-sphere ligands and second-sphere metals (in multinuclear complexes), the determination of precise distances is mostly straightforward, whereas the determination of coordination numbers clearly requires more effort. The EXAFS section starts with an exemplifying discussion of a PSII spectrum data set with focus on the coordination number problem. Subsequently, the method of linear dichroism EXAFS spectroscopy is introduced and it is shown how the EXAFS data leads to an atomic resolution model for the tetra-manganese complex of PSII. In the XANES section the following aspects are considered: (1) Alternative approaches are evaluated for determination of the metal-oxidation state by comparison with a series of model compounds. (2) The interpretation of XANES spectra in terms of molecular orbitals (MOs) is approached by comparative multiple-scattering calculations and MO calculations. (3) The underlying reasons for the oxidation-state dependence of the XANES spectra are explored. Furthermore, the potential of modern XANES theory is demonstrated by presenting first simulations of the dichroism in the XANES spectra of the PSII manganese complex.

Absorptiometry, Photon↗

PubMed1998

How powerful is the dwell-time analysis of multichannel records?

Exact algorithms for the kinetic analysis of multichannel patch-clamp records require hours to days for a single record. Thus, it may be reasonable to use a fast but less accurate method for the analysis of all data sets and to use the results for a reanalysis of some selected records with more sophisticated approaches. For the first run, the tools of single-channel analysis were used for the evaluation of the single-channel rate constants from multichannel dwell-time histograms. This could be achieved by presenting an ensemble of single channels by a "macrochannel" comprising all possible states of the ensemble of channels. Equations for the calculations of the elements of the macrochannel transition matrix and for the steady-state concentrations for individual states are given. Simulations of multichannel records with 1 to 8 channels with two closed and one open states and with 2 channels with two open and two closed states were done in order to investigate under which conditions the one-dimensional dwell-time analysis itself already provides reliable results. Distributions of the evaluated single-channel rate constants show that a bias of the estimations of the single-channel rate constants of 10 to 20% has to be accepted. The comparison of simulations with signal-to-noise ratios of SNR = 1 or SNR = 25 demonstrates that the major problem is not the convergence of the fitting routine, but failures of the level detector algorithm which creates the dwell-times distributions from noisy time series. The macrochannel presentation allows the incorporation of constraints like channel interaction. The evaluation of simulated 4-channel records in which the rate-constant of opening increased by 20% per already open channel could reveal the interaction factor.

Algorithms↗

PubMed2006

[Requirements of a regional medical service for drug addicted patients].

Modern services for persons with disorders resulting from psychoactive drug abuse must conform to the complexity of their needs. Low threshold access, standards for the prescription of opiates, out-patient, in-patient and day-hospital detoxification, rehabilitation and abstinence oriented strategies are fundamental prerequisites. The quality of services for drug dependent patients is defined by the percentage finding access to the service, the percentage of those continuing in the service, the easy and rapid transition between the different elements of the service, the degree of abstinence, decriminalization, physical comorbidity and mortality. Finally the cost of treated and untreated drug dependence should be considered.

Austria↗

PubMed1989

Chemical dependence treatment review guidelines.

During the last decade, there has been an explosive increase in the development of chemical dependence (CD) inpatient/freestanding units (Yahr: J Stud Alcohol 49:233-239, 1988) to the point that fully one third of all mental health admissions reviewed involve chemical dependence (L. Goldstein, personal communication; APA, Office of Quality Assurance, unpublished data). This dramatic increase has raised serious concerns among clinicians about the quality and appropriateness of treatment programs and among third-party payors about the cost of care. Five major categories should be considered when reviewing CD cases: (1) patient characteristics, including age, gender, severity of illness, course, past treatments, and impact of an intervention; (2) level of care, including outpatient, day treatment, freestanding units, hospital, and detoxification units; (3) match of services appropriate to patient's needs; (4) treatment program, including level of staff involvement, program elements, and planning for patient transition; and (5) peer review, including reviewing with a peer, being a patient advocate, and being a consultant. If these elements in these five categories are considered, a competent review is accomplished.

Health Services Needs and Demand↗

PubMed2005

Crosstalk between primase subunits can act to regulate primer synthesis in trans.

The coordination of primase function within the replisome is an essential but poorly understood feature of lagging strand synthesis. By using crystallography and small-angle X-ray scattering (SAXS), we show that functional elements of bacterial primase transition between two dominant conformations: an extended form that uncouples a regulatory domain from its associated RNA polymerase core and a compact state that sequesters the regulatory region from the site of primer synthesis. FRET studies and priming assays reveal that the regulatory domain of one primase subunit productively associates with nucleic acid that is bound to the polymerase domain of a second protomer in trans. This intersubunit interaction allows primase to select initiation sites on template DNA and implicates the regulatory domain as a "molecular brake" that restricts primer length. Our data suggest that the replisome may cooperatively use multiple primases and this conformational switch to control initiation frequency, processivity, and ultimately, Okazaki fragment synthesis.

Bacteriophage T7↗

PubMed1985

Malignant mixed mesodermal tumor of bladder occurring after radiotherapy for cervical cancer: report of a case.

A rare case of radiation-induced malignant mixed mesodermal tumor of the bladder is reported. A 78-year-old woman complained of hematuria, which originated from a polypoid tumor in the bladder 15 years after radiotherapy for squamous cell carcinoma of the uterine cervix. The bladder tumor recurred 9 months after resection and partial cystectomy then was performed. Histological findings revealed malignant mixed mesodermal tumor composed of carcinomatous and sarcomatous elements. The former element consisted mainly of transitional cell carcinoma with occasional foci of squamous metaplasia and glandular differentiation, while the latter consisted of spindle cell sarcoma showing partly cartilaginous and osseous differentiation. The histogenesis of malignant mixed mesodermal tumor of the bladder also is discussed.

Aged↗

PubMed1990

Corrosion behavior of Pd-Cu and Pd-Co alloys in synthetic saliva.

Pd-based alloys are major alternatives to gold-based alloys for PFM applications. In electrolytes simulating oral fluids, these alloys exhibit electrode behavior similar to passivity of active metals, i.e., a potential region of almost constant current density up to a critical potential, above which the current increases. The objective of this study was to correlate the electrode behavior with the results of solution analyses and changes in the surface composition of the alloys. Binary alloys Pd-15 wt% Cu and Pd-19 wt% Co, as well as the pure components, were examined. Corrosion potentials vs. time, potentiodynamic anodic polarization curves, polarization resistances vs. time, and potentiostatic anodic charges were measured with synthetic saliva used as the electrolyte. The concentrations of Pd, Cu, and Co in the solution after various exposures were determined by atomic absorption. The surfaces of the alloys were examined by x-ray photoelectron spectroscopy before and after the exposures. The results show that selective dissolution of the less-noble components occurred on the surfaces of both alloys for all the exposures, leaving the surfaces highly enriched in Pd. This enrichment contributed to the potential changes and the passive-type behavior. Copper dissolved more than cobalt at longer exposures and higher potentials, in spite of its higher nobility. Dissolution of cobalt seemed to be limited by the formation of a surface film, which may be related to the transition character of this element.

Cobalt↗

PubMed2002

Neural pathways underlying vocal control.

Vocalization is a complex behaviour pattern, consisting of essentially three components: laryngeal activity, respiratory movements and supralaryngeal (articulatory) activity. The motoneurones controlling this behaviour are located in various nuclei in the pons (trigeminal motor nucleus), medulla (facial nucleus, nucl. ambiguus, hypoglossal nucleus) and ventral horn of the spinal cord (cervical, thoracic and lumbar region). Coordination of the different motoneurone pools is carried out by an extensive network comprising the ventrolateral parabrachial area, lateral pontine reticular formation, anterolateral and caudal medullary reticular formation, and the nucl. retroambiguus. This network has a direct access to the phonatory motoneurone pools and receives proprioceptive input from laryngeal, pulmonary and oral mechanoreceptors via the solitary tract nucleus and principal as well as spinal trigeminal nuclei. The motor-coordinating network needs a facilitatory input from the periaqueductal grey of the midbrain and laterally bordering tegmentum in order to be able to produce vocalizations. Voluntary control of vocalization, in contrast to completely innate vocal reactions, such as pain shrieking, needs the intactness of the forebrain. Voluntary control over the initiation and suppression of vocal utterances is carried out by the mediofrontal cortex (including anterior cingulate gyrus and supplementary as well as pre-supplementary motor area). Voluntary control over the acoustic structure of vocalizations is carried out by the motor cortex via pyramidal/corticobulbar as well as extrapyramidal pathways. The most important extrapyramidal pathway seems to be the connection motor cortex-putamen-substantia nigra-parvocellular reticular formation-phonatory motoneurones. The motor cortex depends upon a number of inputs for fulfilling its task. It needs a cerebellar input via the ventrolateral thalamus for allowing a smooth transition between consecutive vocal elements. It needs a proprioceptive input from the phonatory organs via nucl. ventralis posterior medialis thalami, somatosensory cortex and inferior parietal cortex. It needs an input from the ventral premotor and prefrontal cortex, including Broca's area, for motor planning of longer purposeful utterances. And it needs an input from the supplementary and pre-supplementary motor area which give rise to the motor commands executed by the motor cortex.

Animals↗