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Biomedical subjects

M A Lillie

Publications and source records attributed to M A Lillie.

At least 19 recordsLinked to original sources
PubMed2006

Mechanical properties of elastin along the thoracic aorta in the pig.

Understanding the mechanical environment of each component within the arterial wall is fundamental for understanding vascular growth and remodelling and for engineering artificial vascular conduits. We have investigated the mechanical status of arterial elastin by measuring the circumferential mechanical properties of purified elastin as function of position along the descending thoracic aorta of the pig. The tensile circumferential secant modulus, E(sec), measured in uniaxial mechanical tests, increased 30% (P<0.001), from a value of 0.88 MPa in the proximal tissue near the aortic arch to 1.14 MPa in the distal tissue near the diaphragm, indicating the stiffness of the elastin sample increased with position. Breaking stress was 54% higher in the distal tissue compared to the proximal (P<0.001), but the breaking stretch ratio did not change. E(sec) correlated with the ratio of radius to wall thickness measured in the no load state, r(nl)/h(nl), suggesting that the rise in stiffness was linked to ring morphology. The higher stiffness and strength of the distal tissue might be explained by a higher proportion of circumferentially oriented fibres in the distal tissue, which would indicate that the elastin meshwork in the thoracic aorta may become progressively anisotropic with distance from the heart. The ratio r(nl)/(h(nl)E (sec))rose only 7%, which suggests that the in vivo circumferential strain on the elastin may be constant along the pig thoracic aorta. The positional variation in elastin's properties should be taken into account in mechanical studies on purified elastin and in mathematical models of aorta mechanics.

Animals↗
PubMed2006

Tensile residual strains on the elastic lamellae along the porcine thoracic aorta.

AIMS: This study determines the residual strains on the elastic lamellae in the porcine thoracic aorta to understand the distribution of strains amongst the components of the vascular wall. METHODS: Residual strains in aortic rings were released by cutting and purifying the elastin. Strains were calculated from lamellar contour lengths based on lamellar waviness and from mechanical tests. RESULTS: On the release of residual strains, waviness decreased 2-7%, the inner lamellae shortened 2.1 +/- 0.6% and the outer lamellae shortened 7.1 +/- 0.4% (p < 0.001), indicating that all lamellar elastin was under tension in fresh aortic tissue. Lamellar shortening was 3% greater in the distal than in the proximal tissue. Mechanical tests confirmed the morphological results and showed that the residual strains in fresh tissue required both the elastic tissue and the vascular smooth muscle. Tensile residual strains averaging 1.0% remained in the uncut elastin rings. CONCLUSION: When waviness is considered, the residual strains on the individual wall components can differ from the surface residual strains based only on the ring perimeter. The residual strains on the inner elastic lamellae are tensile, not compressive. The strain distribution amongst the individual components is non-uniform and not adequately understood to determine the physiological strains in the aortic wall.

Animals↗
PubMed2002

Effects of lipids on elastin's viscoelastic properties.

Sodium dodecyl sulfate (SDS) was used as a model lipid to identify the molecular basis of possible lipid-induced changes in the viscoelastic behavior of arterial elastin. The chemical composition of the elastin network and the interfibrillar space was calculated from the chemical content of the elastin sample and its swelling behavior. Viscoelastic behavior was measured in aqueous SDS and in SDS plus 1 M sucrose, a deswelling agent. Viscoelastic behavior was also measured in sucrose and potassium thiocyanate solutions to identify the effects of swelling and of changes in network composition exclusive of any direct SDS effects. The hydration of the elastin network decreased at low SDS levels and increased at higher SDS levels. The elastin was stiffer in the dehydrated network and less stiff in the hydrated network. However, once the degree of hydration exceeded that of elastin in pure water, no further decrease in stiffness was obtained despite continued increase in swelling. The stiffness of the network could be accounted for entirely by changes in network hydration. There was no evidence that SDS had any effect on elastin's conformation. We predict that arterial lipids will interact with elastin in a similar way and will have only small effects on elastin's viscoelastic behavior.

Animals↗
PubMed2002

Unusual swelling of elastin.

The swelling behavior of the elastin network has been investigated by comparing the linear expansion of samples of purified elastin with the volume expansion of the network, calculated on the basis of composition. Elastin sample dimensions and sample masses were measured under three conditions in which volume changes: thermal expansion at fixed water contents, deswelling due to dehydration, and swelling to greater than normal levels due to the swelling agent, sodium dodecyl sulfate. Isotropic network swelling usually changes length in proportion to the cube root of network volume, but length was found to be directly proportional to volume, showing a greater increase in length than expected. This unusual swelling behavior is attributed to an unusual elastin structure at the subfiber level, but there is insufficient detail on elastin's molecular organization to identify a mechanism to explain how it occurs. Assuming the network swells homogeneously, we describe two models that correctly predict swelling behavior, but these models imply a significant deviation from the structure generally assumed for an elastomeric polymer network of kinetically free molecular chains. Assuming that the network swells heterogeneously removes part of the difficulty with the models, but the observed direct proportionality between length and network volume remains to be explained.

Animals↗
PubMed2002

The viscoelastic basis for the tensile strength of elastin.

Purified aortic elastin displays failure behaviour characteristic of an amorphous, noncrystalizing elastomer with failure properties showing a strong dependence on viscoelastic behaviour. Tensile breaking stresses and breaking strains measured over a range of temperatures, hydration levels, and strain rates are reducible to single curves by the application of shift factors obtained from dynamic mechanical tests. The breaking stress of rubbery elastin is similar to that found in other elastomers, but glassy elastin is about an order of magnitude less strong than expected. We suggest elastin's ability to be strengthened through viscous dissipation of strain energy and crack tip blunting is limited by its fibrillar structure.

Animals↗
PubMed2001

Evaluation of chronic urticaria in patients with Hashimoto thyroiditis.

The coincidence of Hashimoto thyroiditis (HT) and chronic idiopathic urticaria (CIU) is a commonly observed phenomenon in western New York. Previous literature suggested that there may be a direct relationship between them. We undertook these studies to determine whether humoral or cell-mediated mechanisms might link HT and CIU. Skin biopsies from patients with CIU, with or without HT, were indistinguishable by light microscopy. No immune complex deposition was observed, although only the skin from patients with CIU and HT contained perivascular fibrin deposits. Similarly, immunohistochemical studies evaluating cellular expression of CD3, CD4, CD8, CD20, and CD68 failed to differentiate between CIU with or without HT. Analysis of Vbeta restriction in thyroid tissue of patients with HT and the skin of patients with CIU and HT by in situ polymerase chain reaction failed to reveal any oligoclonal T-lymphocyte subpopulations. In contrast, only patients with CIU and HT had anti-FcepsilonRI antibodies in their sera that could induce degranulation of normal basophils. Some sera from patients with CIU and HT caused degranulation of normal basophils in the absence of anti-FceRI. The factor causing basophil degranulation in these sera was not determined. Patients with CIU and HT failed to improve clinically with thyroid replacement therapy. All CIU patients were equally well managed with symptomatic therapies. In conclusion, HT likely represents a marker of other autoimmunity, rather than being a direct causative agent in CIU. Management of CIU, with or without HT and with or without anti-FceRI antibodies, should be the same. Future studies will have to examine whether cell-mediated responses participate in CIU, especially in association with HT.

Adolescent↗
PubMed1999

The hydrophobicity of vertebrate elastins.

An evolutionary trend towards increasing hydrophobicity of vertebrate arterial elastins suggests that there is an adaptive advantage to higher hydrophobicity. The swelling and dynamic mechanical properties of elastins from several species were measured to test whether hydrophobicity is associated with mechanical performance. Hydrophobicity was quantified according to amino acid composition (HI), and two behaviour-based indices: the Flory-Huggins solvent interaction parameter (chi1), and a swelling index relating tissue volumes at 60 and 1 degrees C. Swelling index values correlated with chi1 and, for most species studied, with HI, suggesting that the different approaches used to quantify hydrophobicity are equally valid. Dynamic mechanical properties were measured both in a closed system, to control the effects of water content, and in an open system, to determine whether the increased swelling of hydrophobic materials at low temperatures offsets the direct stiffening effect of cold. There were no biologically significant differences in mechanical behaviour in either open or closed systems that could be attributed to hydrophobicity. Therefore, although the original function of hydrophobicity in an ancestral elastin may have been to produce molecular mobility, mechanical performance did not drive a subsequent increase in hydrophobicity. Higher hydrophobicities may have arisen to facilitate the manufacture of the elastic fibre.

Alligators and Crocodiles↗
PubMed1998

Mechanical role of elastin-associated microfibrils in pig aortic elastic tissue.

The contribution of microfibrils to the mechanical performance of the meshwork of elastic tissue in mature pig aorta was investigated by comparing the properties of autoclaved tissue containing elastin and microfibrils with autoclaved tissue that had been treated with dithiothreitol (DTT) or hot alkali to remove the microfibrils from the elastin. The uniaxial tensile stress-strain curve of the autoclaved tissue was linear to a strain of 0.6 or 0.7 and increased nonlinearly up to the breaking strain. The nonlinearity at high strains could not be accounted for by nonGaussian behavior and was attributed to the progressive alignment of the elastic fibers with strain. Removal of the microfibrils with DTT or treatment with calcium reduced the modulus at low strains by 12% and 4% respectively and increased the modulus at high strains, suggesting that the microfibrils have the capacity to change the orientation of the elastin fibers, possibly transmitting some of the load from one elastin fiber to another. Our findings suggest two possible roles for the microfibrils in vivo: distributing the load throughout the elastic fibers of the arterial wall and direct load bearing. The modulus and the breaking stress of the rings decreased linearly with the duration of alkali treatment starting immediately. By 45 min the modulus had dropped by 30% and the breaking stress by 50%, even though the amino acid content of the extract gave little evidence of elastin hydrolysis. Alkali treatment should not be used on autoclaved pig aortic tissue to be used for mechanical testing.

Actin Cytoskeleton↗
PubMed1996

Elastin dehydration through the liquid and the vapor phase: a comparison of osmotic stress models.

The swelling and viscoelastic behaviors of samples of purified arterial elastin were investigated to develop a model for studying the viscoelastic behavior of elastin. Two osmotic stress models were used: the vapor phase model (VPM), in which the stress on the elastin sample was applied through the vapor phase by equilibrating the sample over a saline solution, and the liquid phase model (LPM), in which the stress was applied through the liquid phase by equilibrating the sample in aqueous solutions of large molecular weight polymers. The elastin in the VPM showed a highly varied viscoelastic response, and was slightly stiffer and had a slightly higher damping coefficient than the elastin in the LPM at equivalent nominal relative humidities. We believe the difference in behavior of the elastin in the two models was due to geometric distortions of the elastin that occur during dehydration in the VPM. In the LPM, the spaces between the elastin fibrils are filled with water, and in the VPM these spaces collapse when the water is removed. Removal of only the interfibrillar water deswelled the tissue and increased its stiffness and damping coefficient. Viscoelastic spectra obtained at different levels of osmotic stress in the LPM were reducible to one master curve, indicating that the dominant effect of dehydration is a nonspecific reduction of molecular mobility. We conclude that the LPM is a better model than the VPM for studying the effects of dehydration on the mechanical behavior of elastin.

Animals↗
PubMed1996

Swelling and viscoelastic properties of osmotically stressed elastin.

The swelling and viscoelastic properties of purified elastin were studied in aqueous solutions of superswelling agents or osmotic deswelling agents to develop models to study the behavior of elastin at frequencies not easily accessible by direct measurement. Increasing the concentration of any of the deswelling solutes (glucose, sucrose, sodium chloride, ammonium sulphate, dextran, and polyethylene glycol) increased the tensile storage and loss moduli. The viscoelastic behavior was independent of solute when compared on the basis of swelling behavior. The data collected at various solute concentrations at 37 degrees C could be reduced to one master curve, and the master curves for elastin in each of the deswelling solutes were themselves superposable. The ability to reduce the data indicates that dehydration can be used to model elastin's viscoelastic behavior at high frequencies or over short times. The viscoelastic behavior of elastin in the superswelling agents [potassium thiocyanate (KSCN), dimethyl sulfoxide (DMSO), and ethylene glycol (EG)] depended on the solute and was independent of swelling behavior. In KSCN the behavior of elastin seemed to be a continuation of the pattern established by the deswelling agents in that an increase in swelling was accompanied by a decrease in both moduli, and the viscoelastic spectra were reducible to one master curve. In high concentrations of DMSO and EG the spectra were not reducible. KSCN appears a suitable superswelling solute to model elastin's viscoelastic behavior at low frequencies or over long times.

Animals↗
PubMed1994

The effects of heating on the mechanical properties of arterial elastin.

Autoclaving is a standard way of purifying arterial elastin for mechanical testing, but recent evidence suggests that heating native elastin might affect its mechanical behavior. We therefore examined the quasi-static tensile properties of pig arterial tissue to see if the mechanical properties of native elastin are altered by autoclaving. From an analysis of the shapes of the stress-extension ratio curves of tissues before and after 8 h of autoclaving, we determined that the mechanical characteristics of elastin dominated the behavior of unautoclaved arterial tissue at wall stresses around 25+/-5 kPa. Autoclaving did not change the tangential modulus of the tissue at this wall stress (+/-4% 95% CI), indicating that elastin can be heated during purification without affecting its mechanical behavior. Autoclaved tissue was tested daily to determine the effects of prolonged heating of autoclaved elastin. Between tests the elastin was incubated at either 80 degrees C (experimental group) or 37 degrees C (control group). After 6 days the average modulus of the control group was unchanged from the initial value, while the average modulus of the experimental group was 7%+/-2% (95% CI) lower. At shorter times the modulus of the experimental group was not significantly reduced. The slight decrease in modulus suggests a slow chemical degradation may occur with prolonged heating, but its time course and magnitude are such that it would not affect standard mechanical tests.

Animals↗
PubMed1989

Interferon and interferon inhibitor levels in patients infected with varicella-zoster virus, acquired immunodeficiency syndrome, acquired immunodeficiency syndrome-related complex, or Kaposi's sarcoma, and in normal individuals.

PURPOSE: Previous studies had reported that normal individuals do not have measurable levels of interferons in their circulation, whereas high levels have been found in patients in the early stages of AIDS (acquired immunodeficiency syndrome) and in those with AIDS-related complex (ARC). This study was undertaken to compare levels of interferon and interferon inhibitors in plasma samples from patients with AIDS, ARC, Kaposi's sarcoma, or varicella-zoster virus infection, and from control subjects. PATIENTS AND METHODS: A total of 206 persons were tested for the presence of interferon and interferon inhibitors in their plasma: 76 with ARC or AIDS, with or without Kaposi's sarcoma or lymphoma; 32 with varicella-zoster infection; 12 with AIDS-unrelated Kaposi's sarcoma; and 86 normal control subjects at high or low risk of AIDS with or without positive antibody levels to human immunodeficiency virus-1. Total interferon activity was measured by bioassay and the subtypes were not separated. RESULTS: Of 86 normal control subjects, 85 had no significant levels of interferon or interferon inhibitor. One disease-free homosexual exhibited measurable interferon levels. Patients acutely infected with varicella-zoster virus showed no measurable interferon or inhibitor levels except if they were in a high-risk group for AIDS. Seventy-six patients with ARC or AIDS exhibited measurable circulating interferon levels. Only patients with AIDS had interferon inhibitors in their circulation. Of 12 patients with Kaposi's sarcoma unrelated to AIDS, none had measurable interferon inhibitor levels, but some exhibited measurable interferon levels. CONCLUSION: It is suggested that levels of interferon inhibitor should be considered when interferon is used therapeutically in viral or neoplastic diseases.

AIDS-Related Complex↗
PubMed1987

Elevation of serum IgG levels and normalization of T4/T8 ratio after hepatitis in a patient with common variable hypogammaglobulinemia.

Acute hepatitis infection developed in a 47-year-old male patient with common variable hypogammaglobulinemia as a consequence of plasma transfusion therapy. Coincident with increases in serum transaminase activities indicative of acute hepatitis, serum IgG levels continued to rise to 506 mg/dl. When plasma replacement therapy was stopped, a transient decline in IgG level (to 371 mg/dl) was produced, followed by a sharp increase in IgG to 607 mg/dl. During this period, the patient's T4/T8 ratio, which had been inverted (0.89), exhibited significant normalization to 1.57. Nevertheless, the patient failed to produce specific antibody after immunization with a number of defined antigens. The mechanism whereby this presumed non-A, non-B hepatitis augmented endogenous IgG production in this patient remains unknown but may be related to diminished suppressor T cell activity. The patient's inability to produce specific antibody during this period suggests an underlying defect in one or more lymphocyte subsets involved in either helper T cell activity and/or immunologic memory.

Agammaglobulinemia↗
PubMed1986

Interferon inactivator(s) in patients with AIDS and AIDS-unrelated Kaposi's sarcoma.

Interferon inhibitory activity was found in the plasma of 11 of 14 patients with the acquired immune deficiency syndrome (AIDS). This was not seen in 75 normal persons, including six whose specimens were randomly and blindly interspersed among the patient samples. Plasma from a single patient with the AIDS prodrome (AIDS-related complex), who later demonstrated AIDS, did not contain interferon inhibitors but did contain high levels of interferon. Three patients with AIDS-unrelated Kaposi's sarcoma had neither significant levels of interferon nor interferon inhibitory activity. The existence of interferon inhibitory activity in the plasma has to be taken into account when interferon preparations are administered therapeutically.

AIDS-Related Complex↗
PubMed1984

Interferon and interferon inactivators in patients with acquired immune deficiency syndrome and Kaposi's sarcoma. A preliminary report.

The interferon system has been implicated in the diagnosis and potential treatment of acquired immune deficiency syndrome (AIDS). In our study of AIDS patients we have identified the presence of circulating serum interferon inactivator(s). These interferon inactivators were not detected in AIDS prodrome patients or in patients with classical Kaposi's sarcoma. The evidence suggests that interferon inactivators may play a role in the clinical manifestation of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Desensitization to experimental asthma with 48/80.

The mast cell disintegrating histamine releaser, compound 48/80, given daily for 5 days by aerosol to guinea pigs produced relative resistance to 48/80 induced asthma, but not to histamine induced asthma. After 3 days of rest, sensitivity to the respiratory effects of 48/80 returned to baseline level. It was thought that the effects observed were due to depletion of pulmonary mast cells or their asthma mediators and regeneration after a period of rest.

Aerosols↗