Search PubMed⌕ Search

Biomedical subjects

S Leikin

Publications and source records attributed to S Leikin.

At least 19 recordsLinked to original sources
PubMed1997

Solvent hydrogen-bond network in protein self-assembly: solvation of collagen triple helices in nonaqueous solvents.

Forces between type I collagen triple helices are studied in solvents of varying hydrogen-bonding ability. The swelling of collagen fibers in reconstituted films is controlled by the concentration of soluble polymers that are excluded from the fibers and that compete osmotically with collagen for available solvent. The interaxial spacing between the triple helices as a function of the polymer concentration is measured by x-ray diffraction. Exponential-like changes in the spacing with increasing osmotic stress, qualitatively similar to the forces previously found in aqueous solution, are also seen in formamide and ethylene glycol. These are solvents that, like water, are capable of forming three-dimensional hydrogen-bond networks. In solvents that either cannot form a network or have a greatly impaired ability to form a hydrogen-bonded network, strikingly different behavior is observed. A hard-wall repulsion is seen with collagen solvated by ethanol, 2-propanol, and N,N-dimethylformamide. The spacing between helices hardly changes with increasing polymer concentration until the stress exceeds some threshold where removal of the solvent becomes energetically favorable. No solvation of collagen is observed in dimethoxyethane. In solvents with an intermediate ability to form hydrogen-bonded networks, methanol, 2-methoxyethanol, or N-methylformamide, the change in spacing with polymer concentration is intermediate between exponential-like and hard-wall. These results provide direct evidence that the exponential repulsion observed between collagen helices at 0-8-A surface separations in water is due to the energetic cost associated with perturbing the hydrogen-bonded network of solvent molecules between the collagen surfaces.

Animals↗
PubMed1996

Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes.

Diacylglycerol, a biological membrane second messenger, is a strong perturber of phospholipid planar bilayers. It converts multibilayers to the reverse hexagonal phase (HII), composed of highly curved monolayers. We have used x-ray diffraction and osmotic stress of the HII phase to measure structural dimensions, spontaneous curvature, and bending moduli of dioleoylphosphatidylethanolamine (DOPE) monolayers doped with increasing amounts of dioleoylglycerol (DOG). The diameter of the HII phase cylinders equilibrated in excess water decreases significantly with increasing DOG content. Remarkably, however, all structural dimensions at any specific water/lipid ratio that is less than full hydration are insensitive to DOG. By plotting structural parameters of the HII phase with changing water content in a newly defined coordinate system, we show that the elastic deformation of the lipid monolayers can be described as bending around a pivotal plane of constant area. This dividing surface includes 30% of the lipid volume independent of the DOG content (polar heads and a small fraction of hydrocarbon chains). As the mole fraction of DOG increases to 0.3, the radius of spontaneous curvature defined for the pivotal surface decreases from 29 A to 19 A, and the bending modulus increases from approximately 11 to 14 (+/-0.5) kT. We derive the conversion factors and estimate the spontaneous curvatures and bending moduli for the neutral surface which, unlike the pivotal plane parameters, are intrinsic properties that apply to other deformations and geometries. The spontaneous curvature of the neutral surface differs from that of the pivotal plane by less than 10%, but the difference in the bending moduli is up to 40%. Our estimate shows that the neutral surface bending modulus is approximately 9kT and practically does not depend on the DOG content.

Diglycerides↗
PubMed1995

Temperature-favoured assembly of collagen is driven by hydrophilic not hydrophobic interactions.

It has become almost axiomatic that protein folding and assembly are dominated by the hydrophobic effect. The contributions from this, and other, hydrophilic interactions can now be better distinguished by direct measurement of forces between proteins. Here we report the measurement of forces between triple helices of type I collagen at different temperatures, pH and solute concentrations. We separate repulsive and attractive components of the net force and analyze the origin of the attraction responsible for the collagen self-assembly. In this case the role of the hydrophobic effect appears to be negligible. Instead, water-mediated hydrogen bonding between polar residues is the most consistent explanation.

Animals↗
PubMed1994

Direct measurement of forces between self-assembled proteins: temperature-dependent exponential forces between collagen triple helices.

We report direct measurements of force vs. separation between self-assembled proteins. These forces are observed between collagen triple helices in native and reconstituted fibers. They are a combination of a short-range repulsion, which varies exponentially over at least five decay lengths, and an inferred, longer-ranged attraction responsible for spontaneous assembly. From 5 degrees C to 35 degrees C the relative contribution of the attraction to the net force increases with temperature. These forces are strikingly similar to the "hydration" forces measured between several other linear macromolecules (DNA, polysaccharides) and between lipid bilayer membranes. The decay length of the repulsive force agrees well with a theoretical estimate based on axial periodicity of the triple helix, suggesting another connection between molecular architecture and protein-protein interaction.

Animals↗
PubMed1994

Temperature-induced complementarity as a mechanism for biomolecular assembly.

Recent advances in the measurement and theory of "hydration" interactions between biomolecules provide a basis on which to formulate mechanisms of biomolecular recognition. In this paper we have developed a mathematical formalism for analyzing specificity encoded in dynamic distributions of surface polar groups, a formalism that incorporates newly recognized properties of directly measured "hydration" forces. As expected, attraction between surfaces requires complementary patterns of surface polar groups. In contrast to usual expectations, thermal motion can create these complementary surface configurations. We have demonstrated that assembly can occur with an increase in conformational entropy of polar residues. Elevated temperature then facilitates recognition rather than hinders it. This mechanism might underlie some temperature-favored assembly reactions common in biological systems that are usually associated with the "hydrophobic effect" only.

Chemical Phenomena↗
PubMed1994

Bending, hydration and interstitial energies quantitatively account for the hexagonal-lamellar-hexagonal reentrant phase transition in dioleoylphosphatidylethanolamine.

We have accounted for the unusual structural change wherein dioleoylphosphatidylethanolamine undergoes a hexagonal-lamellar-hexagonal transition sequence as the water content is reduced systematically. We describe the role played by the energies of bending, hydration, voids in hexagonal interstices, and van der Waals interaction in this transition sequence. We have used the X-ray diffraction and osmotic stress experiments on the two phases to derive the structural parameters and all of the force constants defining the energetics of the hexagonal and lamellar phases. We have calculated the chemical potentials of lipid and water in both phases and derived the phase diagram of the lipid with no free, adjustable parameters. The calculated temperature/osmotic stress and temperature/composition diagrams quantitatively agree with experiment. The reentrant transition appears to be driven by a delicate balance between the hydration energy in the lamellar phase and bending energy in the hexagonal phase, whereas the energy of voids in hexagonal interstices defines its energy scale and temperature range. Van der Waals attraction between the bilayers in the lamellar phase does not appear to be important in this transition.

Mathematics↗
PubMed1993

The role of adolescents in decisions concerning their cancer therapy.

Because adolescents are codified as incompetents, their health care decision-making authority often is encroached upon. When a teenager develops a serious disease such as cancer, others are even more likely to appropriate decision-making authority than under normal circumstances. Adolescents can contribute to decisions concerning their treatment provided certain guidelines are used. These guidelines stem from bioethical concerns and our understanding of the development in cognitive ability related to decision-making. This article summarizes considerations relating to each of these two areas. Because the clinical stage of the malignancy also affects bioethical concerns, the adolescent's role in decision-making at the time of initial diagnosis and recurrence are discussed.

Adolescent↗
PubMed1993

Hydration forces.

Explore the source record for details and available documents.

Aluminum Silicates↗
PubMed1991

Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure.

Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the "lymphoma syndrome" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL.

Adolescent↗
PubMed1989

When parents demand treatment.

In striving to provide quality medical care to the child and in serving as an educator and counselor to the family, the pediatrician can pursue several different decision making paths. The chosen path will depend on the pediatrician's medical knowledge and skill, but will also be influenced significantly by views of moral responsibility in medicine and attention to the emotional and social factors in the physician-patient encounter.

Ethics, Medical↗
PubMed1987

Children's Hospital ethics committees. A first estimate.

Special committees are being formed in hospitals to help deal with ethical problems presented by seriously ill infants and children. The functions of these multidisciplinary groups are to recommend policy and educate staff members about ethical matters and provide ethical consultation to parties involved in the care of these patients. This article provides a historical background of the formation of these committees and describes the development, constitution, and practices of the recently formed ethics committee of the Children's Hospital National Medical Center, Washington, DC. Ethical decision-making for the sick incompetent child requires determining his or her best interest. The committee's problems related to this determination and other questions are discussed to inform those working in pediatric health care and to help guide them in their future efforts in ethical decision making for minors.

Child↗
PubMed1985

Significance of X granules in histiocytosis X: an ultrastructural study.

Histiocytosis X is characterized by the presence of cytoplasmic rod structures called Langerhans' cell granules or X granules (XG). It has been speculated that histiocytosis X is a Langerhans' cell disorder. This ultrastructural study was performed to quantitate the number of XG containing histiocytes in the histiocytosis X lesions. Twenty-four specimens from 22 patients with histiocytosis X were studied: 4 from skin, 5 from lymph node, 11 from bone, 2 from lung, 1 from gingiva, and 1 from cheek. The majority of the histiocytes in histiocytosis X lesions do not contain X granules. The majority of the histiocytes in histiocytosis X lesions do not contain X granules. The percentage of histiocytes with XG in a lesion has no relation to the age of the patient or the organ from which it was obtained, except for skin, where they were quite numerous. The relative percent-age of histiocytes with granules does not correlate significantly with the prognosis of these patients.

Adolescent↗
PubMed1984

Results in children with local and regional neuroblastoma managed with and without vincristine, cyclophosphamide, and imidazolecarboxamide. A report from the Children's Cancer Study Group.

Members of children's cancer study group designed Study CCG 351 to determine whether three drug chemotherapy improved the survival experience of children with localized neuroblastoma. Patients in stages I-III were treated with surgical removal of the primary tumor and those in stages II and III received radiation therapy to the tumor bed and chemotherapy. Treatment included cyclophosphamide, imidazolecarboxamide, and vincristine given in 5-day pulses each month for 12 courses. The results were compared to those from a previous study, CCG 011, for localized neuroblastoma, in which children were randomized between a treatment regimen that included cyclophosphamide and one with no chemotherapy. There were 133 evaluable patients, subdivided as follows: stages I-26, stages II-74, and stages III-33. The 3-year life-table survival rates by stage of 96, 89 and 50% were not significantly different from the patients in CCG 011 similarly staged who received either no chemotherapy or oral CPM. These data suggest that multiagent chemotherapy, as prescribed, did not improve the outlook for children with locally advanced but nonmetastatic neuroblastoma. The staging criteria employed showed a modest difference in outcome between patients in stages I and II, but a significant poorer survival for stage III as compared to either stage I or II.

Aminoimidazole Carboxamide↗