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Biomedical subjects

M A Singer

Publications and source records attributed to M A Singer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Health-related quality of life assessment in clinical practice.

Assessment of biochemical responses to therapy is routine in the management of patients with end stage renal disease (ESRD). Assessment of health-related quality of life (HRQOL), however, is less common. Previous research indicates that HRQOL is a meaningful indicator that should be integrated into clinical practice. HRQOL is longitudinally evaluated in in-centre hemodialysis patients using the RAND 36-item Health Survey 1.0. Caregivers incorporate scores from this instrument into their assessment of patient functioning and well-being. HRQOL scores can be utilized to evaluate responses to changes in therapy, and to direct clinical decision-making, adding an important dimension to holistic, quality care for ESRD patients.

Aged↗
PubMed1995

Community participation in health care decision making: is it feasible?

Health care reform strategies proposed by provincial governments include decentralized funding and increased public participation in decision making. These proposals do not give details as to the public participation process, and a number of questions have been raised by the experience of some communities. Which citizens should form the decision-making group? What information do they need? What kinds of decisions should they make? What level of participation should they have? The results of a survey by Abelson and associates (see pages 403 to 412 of this issue) challenge the assumption that "communities" are willing to participate in health-care and social-service decision making. Willingness varied according to the composition of the groups polled, and participants' support for traditional decision makers increased after the complexities of the decision-making process were discussed. However, whereas their study measured willingness to participate at one point in time only, experience gained from Ontario's Better Beginnings, Better Futures project indicates that, given sufficient time, "ordinary" citizens are willing and can acquire the skills needed to decide how resources should be allocated for social services.

Canada↗
PubMed1995

Fiber type composition of morphologic regions in the macaque multitendoned finger muscles.

The extrinsic multitendoned finger muscles seem likely to contain distinct neuromuscular compartments that can act as independent functional subdivisions serving different fingers. Little evidence of such subdivisions is available, however. Regional specialization of histochemical fiber type composition has been described in a number of monotendoned muscles, and in some muscles different neuromuscular compartments have been shown to have different fiber type proportions. Therefore, we examined the fiber type composition of morphologically defined regions in the macaque multitendoned finger muscles. Although some trends were noted, none of the five multitendoned finger muscles showed significant regional differences in fiber type composition. Nor were differences found between muscles of the flexor group or between muscles of the extensor group. Comparing flexors and extensors revealed a slightly but significantly lower proportion of type I fibers in the flexors. We conclude that unlike certain monotendoned wrist muscles (such as FCU), the multitendoned muscles that flex and extend macaque fingers have minimal histochemical specialization.

Animals↗
PubMed1995

Pioneer growth cone migration in register with orthogonal epithelial domains in the grasshopper limb bud.

At the onset of neural development, pioneer growth cones can migrate over epithelia or neuroepithelia along stereotyped routes that establish the pattern of initial neural tracts. These migration routes may reflect the arrangement of distinct epithelial or neuroepithelial domains. In grasshopper limb buds, a pair of afferent pioneer neurons arise in the tibia and their growth cones migrate on a stereotyped path through the limb to the CNS. In the limb buds, circumferentially-oriented epithelial domains expressing semaphorin-I, annulin, or alkaline-phosphatase, and a longitudinal domain, expressing engrailed, have been described. Using multiple-labeling techniques, we describe the relationships of these domains to each other and to the pioneer neuron pathway. Taken together, these domains establish an orthogonal pattern of regionally specific epithelial molecular markers. During much of their migration across the limb epithelium, the pioneer growth cones are in register with the axes of circumferential or longitudinal epithelial domains.

Alkaline Phosphatase↗
PubMed1994

Protein disaggregation mediated by heat-shock protein Hsp104.

The heat-inducible members of the Hsp100 (or Clp) family of proteins share a common function in helping organisms to survive extreme stress, but the basic mechanism through which these proteins function is not understood. Hsp104 protects cells against a variety of stresses, under many physiological conditions, and its function has been evolutionarily conserved, at least from Saccharomyces cerevisiae to Arabidopsis thaliana. Homology with the Escherichia coli ClpA protein suggests that Hsp104 may provide stress tolerance by helping to rid the cell of heat-denatured proteins through proteolysis. But genetic analysis indicates that Hsp104 may function like Hsp70 as a molecular chaperone. Here we investigate the role of Hsp104 in vivo using a temperature-sensitive Vibrio harveyi luciferase-fusion protein as a test substrate. We find that Hsp104 does not protect luciferase from thermal denaturation, nor does it promote proteolysis of luciferase. Rather, Hsp104 functions in a manner not previously described for other heat-shock proteins: it mediates the resolubilization of heat-inactivated luciferase from insoluble aggregates.

HSP70 Heat-Shock Proteins↗
PubMed1994

A new liquid crystalline phase in phosphatidylcholine bilayers as studied by X-ray diffraction.

Model membranes of diacylphosphatidylcholines (CnPC), with saturated linear acyl chains of n > 12 carbons, show a single sharp phase transition (known as the main transition) between the gel phase P beta' and the liquid crystalline phase L alpha with differential scanning calorimetry. However, C12PC (dilauroylphosphatidylcholine) shows, as well as the sharp transition at -2 degrees C, a broad peak at 5 degrees C, originally observed by S. Mabrey and J.M. Sturtevant. The broad peak is not artificial: between the two peaks a new phase Lx was predicted for (C12PC) bilayers on the basis of calorimetry (Finegold, Shaw and Singer, Chem. Phys. Lipids 53 (1990), 177-184). The existence of Lx has now been confirmed by synchrotron X-ray diffraction on samples identical to those of the previous work, of similar preparation and at corresponding scan rates. With temperature, both small-angle (long lamellar) and wide-angle (hydrocarbon chain) spacings show abrupt discontinuities, and separate broader changes, at temperatures corresponding to the calorimetric sharp and broad peaks, respectively. All the X-ray diffraction profiles and spacing results are consistent with the following phase scheme with increasing temperature: gel ripple phase P beta'-->new, less ordered liquid crystalline phase Lx-->most disordered liquid crystalline phase L alpha. The phase Lx possibly exists in other CnPCs, and its examination may provide details of the main transition. Because Lx exists at a higher temperature than the main transition from P beta', it promises to be of biological relevance.

Calorimetry, Differential Scanning↗
PubMed1993

Toxoplasma gondii retinochoroiditis after liver transplantation.

A 48-year-old woman with a previous a liver transplant and a cataract extraction developed a necrotizing retinochoroiditis in her right eye. Vitreous and serum cultures failed to yield a causative organism. As the retinochoroiditis progressed, visual acuity worsened to the point of no light perception, and the eye became blind and painful. An enucleation was performed and histologic examination showed Toxoplasma gondii necrotizing retinochoroiditis. This is the first histologically documented case of T. gondii retinochoroiditis after liver transplantation. The fulminant clinicopathologic appearance of the retinochoroiditis is similar to that previously reported to occur in acquired immune deficiency syndrome (AIDS) and other forms of immunosuppression, unlike the reactivated congenital retinochoroiditis that occurs in immunocompetent patients.

Animals↗
PubMed1993

Measuring and predicting outcomes in ESRD patients.

To test the feasibility of using general health status as a practical dialysis outcome measure, in a longitudinal pilot study, two well-validated instruments were administered to patients from our dialysis unit or clinic. The instruments were administered three times, at eight-week intervals for seven months to 41 hemodialysis (HD) patients. Forty-five transplant (Tx) patients were surveyed once as a validating control. Sociodemographic, imaging and biochemical data were tested as outcome predictors. Unexpected hospitalizations and adverse intercurrent events were used as additional outcome measures. Preliminary analysis shows HD patients scoring low, while Tx patients scored higher (healthier). These preliminary results suggest that assessment of general health status is a valid and practical outcome measure.

Health Status↗
PubMed1992

The permeability and the effect of acyl-chain length for phospholipid bilayers containing cholesterol: theory and experiment.

The model of Cruzeiro-Hansson et al. (Biochim. Biophys. Acta (1989) 979, 166-1176) for lipid-cholesterol bilayers at low cholesterol concentrations is used to predict the thermodynamic properties and the passive ion permeability of lipid bilayers as a function of acyl-chain length and cholesterol concentration. Numerical simulations based on the Monte Carlo method are used to determine the equilibrium state of the system near the main gel-fluid phase transition. The permeability is calculated using an ansatz which relates the passive permeability to the amount of interfaces formed in the bilayer when cholesterol is present. The model predicts at low cholesterol contents an increase in the membrane permeability in the transition region both for increasing cholesterol concentration and for decreasing chain length at a given value of the reduced temperature. This is in contrast to the case of lipid bilayers containing high cholesterol concentrations where the cholesterol strongly suppresses the permeability. Experimental results for the Na+ permeability of C15PC and DPPC (C16PC) bilayers containing cholesterol are presented which confirm the theoretical predictions at low cholesterol concentrations.

Algorithms↗
PubMed1992

Annulin, a protein expressed at limb segment boundaries in the grasshopper embryo, is homologous to protein cross-linking transglutaminases.

Annulin, a protein whose general stage- and position-specific expression pattern in the grasshopper embryo is described in the companion paper, is expressed in epithelial annuli in developing limbs. Here, we show that these annuli comprise narrow circumferential bands of epithelial cells at the boundaries of limb segments. At most boundaries, expression of annulin precedes the first morphological signs of segmentation. The most distal cells in a band underlie the boundary invagination. Bands arise in a stereotyped order and, within a band, expression occurs in an ordered circumferential progression. Annulin has a molecular weight of about 97 kDa and appears to be intracellular and peripherally associated with the inner leaflet of the cell membrane. Using the monoclonal antibody 7H7, two overlapping cDNA clones encoding this protein were isolated from an embryonic Schistocerca cDNA expression library. The nucleotide and deduced amino acid sequences indicate that the annulin protein does not contain either a signal sequence or a transmembrane domain. By sequence comparison, annulin appears to be a transglutaminase, one of a family of enzymes that have protein cross-linking activity. Its expression pattern within the limb and the embryo is associated with areas undergoing morphogenetic rearrangements, movements, or rapid cell division. It may stabilize cells under mechanical stress or participate in some other way in these morphogenetic activities.

Amino Acid Sequence↗
PubMed1990

The formation of multilamellar vesicles from saturated phosphatidylcholines and phosphatidylethanolamines: morphology and quasi-elastic light scattering measurements.

The aggregation properties of diacyl phosphatidylcholines (PC) and phosphatidylethanolamines (PE), with linear symmetrical saturated chains, were characterized at temperatures below and above the lipid solid to fluid transition. PEs in the solid state form bundles of closely apposed flat bilayer stacks which at the solid to fluid transition temperature fold into closed multilamellar vesicles. On the other hand, PCs in the solid state form extended multilayer sheets. At the solid to fluid transition, multilamellar vesicles appear to "bud off" from the surface. Quasi-elastic light scattering (QELS) measurements indicated that for the PEs, bundle size is independent of acyl chain length n, but that the sizes of vesicles which form at the solid to fluid transition are positively correlated with n. The results of temperature jump experiments showed that once the transition temperature was reached, vesicle formation was largely complete within 30 s.

Calorimetry, Differential Scanning↗
PubMed1990

Interaction of cholesterol with saturated phospholipids: role of the C(17) side chain.

Cholesterol and 5-androsten-3 beta-ol differ structurally only in the presence of an eight carbon side chain at the C(17) position in the former sterol. Both molecules decrease the main transition enthalpy change (delta H) in a series of phosphatidylcholines and phosphatidylethanolamines, of acyl chain length n, with the reduction being a linear function of sterol concentration (c). The sterol concentrations at which delta H = 0 bear a straight line relationship to n and are equivalent for both cholesterol and 5-androsten-3 beta-ol. In addition, both sterols give identical delta H versus c slopes. These results underscore the importance of acyl chain length in the cholesterol/phospholipid interaction and also indicate that the cholesterol C(17) side group is not an essential requirement for the capacity of the sterol to decrease the enthalpy change of the main transition.

Acylation↗
PubMed1990

Cholesterol interacts with all of the lipid in bilayer membranes. Implications for models.

The interaction of cholesterol with lipid membranes has been studied by differential scanning calorimetry on liposomes, a technique which involves only the natural lipids, with no exogeneous probes. The influence of cholesterol at different molar percent concentrations c on the enthalpy delta H of the main gel to liquid crystal phase transition of saturated phosphatidylcholines of acyl chain length n = 12-20 was well represented by delta H = -9.43 + 1.01n - 0.268c kcal/mol. The linear dependence of delta H simultaneously upon chain length n and upon cholesterol concentration c shows clearly that cholesterol interacts with the deeper part of the lipids, as well as the superficial parts. This observation is not accommodated in any of the current models of cholesterol-lipid interactions.

Calorimetry, Differential Scanning↗
PubMed1990

Composition and thermal properties of membrane lipids in cryptoendolithic lichen microbiota from antarctica.

In Antarctica there exists a cryptoendolithic microbiota which survives extremely low temperatures. Fatty acid analysis of the membrane phospholipids of this microbial community showed a predominance of polyunsaturated fatty acids. Artificial membranes made from the purified community phospholipids remained fluid to below -20 degrees C and had unusual hydration properties.

Journal Article↗
PubMed1987

The ripple phase of phosphatidylcholines: effect of chain length and cholesterol.

Saturated phosphatidylcholine (PC) bilayers display a rippled surface in the temperature region between the pre- and main transitions. Ripple repeat distance was measured from freeze-fracture electron micrographs. All of the lipids examined (C13PC to C16PC; C14C16PC and equimolar C14PC/C16PC) showed a bimodal distribution of ripple repeat distances with the two dominant values being in the ratio of 1:2. Within this series, chain length was a weak determinant of the actual repeat distance. The introduction of increasing concentrations of cholesterol eliminated the bimodal distribution and led to the appearance of a single distribution of increasing repeat distance and decreasing amplitude. Ripples disappeared above a cholesterol concentration of 15 mol%. These observations are discussed within the framework of a model which links the genesis of the ripples (vertical displacement of lipid molecules) to the trans-gauche isomerization known to occur at the pre-transition.

Chemical Phenomena↗
PubMed1987

Interaction of hepatic asialoglycoprotein receptor with dimyristoyl phosphatidylcholine vesicles.

The hepatocyte membrane asialoglycoprotein receptor (ASGP-R) was extracted from rabbit liver, purified, and then incubated with preformed vesicles of dimyristoyl phosphatidylcholine. The association of protein with lipid was dependent on vesicle size and the best results were achieved with small vesicles of about 20 nm diameter. The ligand binding capacity of ASGP-R-vesicle complexes was also measured and found to be approximately sevenfold greater than free receptor in aqueous buffer and twofold greater than receptor solubilized in Triton X-100. Most likely, the reconstitution procedure used in these experiments does not result in transmembrane insertion of the receptor. ASGP-R probably resides on the surface of the vesicle, held there primarily by weak hydrophobic forces.

Animals↗