Biomedical subjects
Publications and source records attributed to J Howard.
Many vendors and potential users of eligibility verification systems know the obstacles that deter the widespread acceptance and implementation of the technology. On the following pages, executives of firms representing the payor, provider and clearinghouse communities express their perceptions regarding the status and need for online eligibility verification and its cost advantages.
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Kinesin is a motor protein that uses the energy derived from ATP hydrolysis to transport organelles along microtubules. By analyzing the thermal fluctuation of microtubules tethered to glass surfaces by single molecules of kinesin, we have measured the torsional flexibility of the motor protein. The torsional stiffness of kinesin, (117 +/- 19) x 10(-24) N.m.rad-1 (mean +/- SEM), is so low that one kT of energy (approximately 4.1 x 10(-21) J at room temperature) is sufficient to twist a kinesin molecule through more than 360 degrees from its resting orientation. Consistent with this flexibility, motility assays show that one or more kinesin molecules can move a microtubule equally well in any direction. These results explain how a motor on the surface of an organelle can rapidly bind to and capture a microtubule irrespective of the organelle's orientation. Furthermore, the flexibility ensures that several motors can efficiently work together even though they are randomly oriented on the surface of an organelle rather than being in precise arrays like the motors of muscle and cilia.
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Presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules requires MHC-encoded molecules of the adenosine triphosphate binding cassette (ABC) family. Defects in these proteins represent a potential risk, since they are essential links in the machinery of T cell-mediated surveillance which continuously scrutinizes peptide samples of cellular proteins. Nevertheless, transfection of the mouse lymphoma mutant RMA-S with the rat ABC gene mtp2a (homologue to mouse HAM2 and human RING11), commonly termed TAP-2 genes, led to a marked increase in tumor outgrowth potential in vivo. This occurred despite restored antigen presentation and sensitivity to cytotoxic T lymphocytes, and was found to be due to escape from natural killer (NK) cell-mediated rejection. It has previously been proposed that adequate expression of self-MHC class I is one important mechanism to avoid elimination by NK cells. Our data argue that a defect in the machinery responsible for processing and loading of peptides into MHC class I molecules is sufficient to render cells sensitive to elimination by NK cells. The latter thus appear to function as a surveillance of the peptide surveillance machinery.
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Microtubules are long, proteinaceous filaments that perform structural functions in eukaryotic cells by defining cellular shape and serving as tracks for intracellular motor proteins. We report the first accurate measurements of the flexural rigidity of microtubules. By analyzing the thermally driven fluctuations in their shape, we estimated the mean flexural rigidity of taxol-stabilized microtubules to be 2.2 x 10(-23) Nm2 (with 6.4% uncertainty) for seven unlabeled microtubules and 2.1 x 10(-23) Nm2 (with 4.7% uncertainty) for eight rhodamine-labeled microtubules. These values are similar to earlier, less precise estimates of microtubule bending stiffness obtained by modeling flagellar motion. A similar analysis on seven rhodamine-phalloidin-labeled actin filaments gave a flexural rigidity of 7.3 x 10(-26) Nm2 (with 6% uncertainty), consistent with previously reported results. The flexural rigidity of these microtubules corresponds to a persistence length of 5,200 microns showing that a microtubule is rigid over cellular dimensions. By contrast, the persistence length of an actin filament is only approximately 17.7 microns, perhaps explaining why actin filaments within cells are usually cross-linked into bundles. The greater flexural rigidity of a microtubule compared to an actin filament mainly derives from the former's larger cross-section. If tubulin were homogeneous and isotropic, then the microtubule's Young's modulus would be approximately 1.2 GPa, similar to Plexiglas and rigid plastics. Microtubules are expected to be almost inextensible: the compliance of cells is due primarily to filament bending or sliding between filaments rather than the stretching of the filaments themselves.
We tested the hypothesis that kinesin moves parallel to the microtubule's protofilament axis. We polymerized microtubules with protofilaments that ran either parallel to the microtubule's long axis or that ran along shallow helical paths around the cylindrical surface of the microtubule. When gliding across a kinesin-coated surface, the former microtubules did not rotate. The latter microtubules, those with supertwisted protofilaments, did rotate; the pitch and handedness of the rotation accorded with the supertwist measured by electron cryo-microscopy. The results show that kinesin follows a path parallel to the protofilaments with high fidelity. This implies that the distance between consecutive kinesin-binding sites along the microtubule must be an integral multiple of 4.1 nm, the tubulin monomer spacing along the protofilament, or a multiple of 8.2 nm, the dimer spacing.
We have previously demonstrated that cytokeratin levels are coordinately regulated in normal cultured human keratinocytes. In the present study we examine the mechanism of this regulation using human squamous cell carcinoma (SCC) cells. Treatment of SCC-13 cells with 20 or 200 nM trans-retinoic acid results in nearly complete suppression of cytokeratin K5 and K6 expression. This change is accompanied by a simultaneous reduction (> 20-fold) in the level of the mRNAs encoding K5 and K6. Transcriptional analysis indicates that the transcription rate of the K5 and K6 genes drops by approximately four to fivefold in retinoid treated nuclei. Retinol (2000 nM) also promotes this change. In contrast, cytokeratin K19 does not increase in the presence of retinoic acid, thus the normal coordinate regulation of keratin gene expression by retinoids appears to be uncoupled in SCC-13 cells. However, this does not represent a general defect in positive regulation of gene expression by retinoids, since in a transient transfection assay trans-retinoic acid positively regulates a reporter plasmid containing the retinoid response element from the retinoic acid receptor-beta gene. The synthetic retinoids Ro 13-6298 (ethyl ester) and its metabolic derivative Ro 13-7410 (free acid) are both active in modulating the differentiation of normal keratinocytes. In contrast, only Ro 13-7410 is active in SCC-13 cells. As Ro 13-6298 binds poorly to the retinoic acid receptors, this suggests that SCC-13 cells, unlike normal keratinocytes, lack the ability to convert Ro 13-6298 to the active Ro 13-7410.(ABSTRACT TRUNCATED AT 250 WORDS)
Two samples of street youth from the inner city area of Sydney, ranging in age from 13 to 20, with a mean of 17, were surveyed via a lengthy questionnaire. The first survey in 1989/90 (n = 92; 66 males, 26 females) revealed high levels of physical and sexual abuse; violence and negative relationships as major factors in leaving home; safe sexual practice not common (other than for those prostituting); polydrug use widespread and heavier for females; some needle sharing by injecting drug users (IDU). Second survey, 190/91 (n = 100; 70 males, 30 females), confirmed previous picture, but found changes in immunodeficiency virus (HIV) risk behaviours: needle sharing reduced; for those prostituting an increase in safe sexual practices with clients; reduction in regular safe sexual practices with non-paying partners. IDU was significantly linked to prostitution as was needle sharing. Some changes are in an encouraging direction, but more preventive work is needed focusing on safe behaviours with non-paying partners and how to initiate and negotiate these. More qualitative or ethnographic research could better inform such efforts and, indigenous strategies deserve recognition.
OBJECTIVES: Previous attempts at obtaining population estimates of human immunodeficiency virus type 1 (HIV-1) seroprevalence have been beset by problems of cooperation bias. As part of the fourth round of study with an urban African-American community cohort, the following investigation was aimed at assessing HIV-1 prevalence and the relative importance of sex and drug injection as risk factors in infection. METHODS: Personal interviews were conducted in the home with 364 respondents, followed by voluntary blood sample collection from 287 of these individuals. RESULTS: Blood assays showed a point prevalence of 8.4% HIV-1 seropositivity in this community cross section, with a higher female-to-male ratio than appears among acquired immunodeficiency syndrome (AIDS) case reports. Most infected persons were unaware and unsuspecting of their infection. CONCLUSIONS: First, findings underscore the need to focus on risk behaviors rather than on risk groups. Second, the smaller than 2:1 ratio of infected men to women suggests that current AIDS case reports seriously underestimate HIV-1 infection among certain cohorts of African-American women. Finally, widespread ignorance of own infected status and inaccurate risk assessment signal the substantial task for community health educators in reaching inner-city African-American men and women at risk.
This report details procedures to measure annihilation anxiety, a concept derived from Freud's 1926 formulation of traumatic anxiety. A 25-item pencil-and-paper inventory administered to patient and to nonpatient samples is described, along with a brief summary of earlier findings. The delineation of nine interrelated experiential components of annihilation anxiety provides the background for the construction of Rorschach and TAT measures of the concept. Findings comparing the pencil-and-paper inventory and the projective test measures are presented as well as examples of responses judged to reflect annihilation anxiety from Rorschach and TAT protocols.
An analysis of the literature was the basis for a set of predictions regarding the Preschool Embedded Figures Test performance of a small, cross-sectional sample of 37 3- to 5-year-old children. The test scores were modestly reliable. Predicted age-related differences in scores for boys and girls were observed, including an interaction of age with gender; however, other predictions regarding those scores were not supported. Based on a small sample, it was tentatively concluded that the evidence for continued use of the Preschool Embedded Figures Test as a measure of field independence for young children was weak.
Non-inpatient care is assuming greater importance within the Australian health system. The management of the delivery of health services is becoming a responsibility of clinicians. Clinicians, nurses, managers and academics need to come together to advance these issues. This paper outlines the thinking at Monash Medical Centre, a new 747-bed tertiary hospital situated in the south-eastern suburbs of Melbourne.