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Biomedical subjects

T Parker

Publications and source records attributed to T Parker.

At least 19 recordsLinked to original sources
PubMed2001

Lactic acid-stabilised albumin for microsphere formulation and biomedical coatings.

Microspheres of ovalbumin (OVA) ranging from 1 to 15 microm were prepared by emulsifying an aqueous solution of albumin in soya oil at room temperature then raising the temperature to 45 degrees C for 30 min, prior to harvesting of the microspheres. Production of OVA nanospheres with size less than 500 nm was achieved by desolvation from aqueous albumin solutions using acetone. In both cases, lactic acid was added to the starting albumin solution to stabilise the resulting particles. Utilisation of an endogenous substance avoids the use of chemical crosslinking agents such as glutaraldehyde and associated toxicological concerns. Protein coating of knitted Dacron vascular grafts was performed by impregnation of the textile structure with lactic acid-stabilised ovalbumin nanospheres thereby providing a surface potentially resistant to blood platelet adhesion but conducive to endothelialisation. Protein release testing carried out in PBS at 37 degrees C revealed that approximately 60% of the original albumin coating was retained by the Dacron graft material after 4 days and remained at this level for upto 4 weeks. Apart from the formulation of albumin microspheres for drug delivery, diagnostic applications and coating of biomedical textiles, the process of albumin stabilisation using lactic acid may be usefully applied to improve protein immobilisation on a wide range of biomaterial surfaces.

Blood Vessel Prosthesis↗
PubMed2000

Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies.

In the human inflammatory myopathies (polymyositis and dermatomyositis), the early, widespread appearance of MHC class I on the surface of muscle cells and the occurrence of certain myositis-specific autoantibodies are striking features. We have used a controllable muscle-specific promoter system to up-regulate MHC class I in the skeletal muscles of young mice. These mice develop clinical, biochemical, histological, and immunological features very similar to human myositis. The disease is inflammatory, limited to skeletal muscles, self-sustaining, more severe in females, and often accompanied by autoantibodies, including, in some mice, autoantibodies to histidyl-tRNA synthetase, the most common specificity found in the spontaneous human disease, anti-Jo-1. This model suggests that an autoimmune disease may unfold in a highly specific pattern as the consequence of an apparently nonspecific event-the sustained up-regulation of MHC class I in a tissue-and that the specificity of the autoantibodies derives not from the specificity of the stimulus, but from the context, location, and probably the duration of the stimulus. This model further suggests that the presumed order of events as an autoimmune disease develops needs to be reconsidered.

Animals↗
PubMed2000

The inhibition of apoptosis in myositis and in normal muscle cells.

The mechanism of injury and death of muscle cells in the inflammatory myopathies (dermatomyositis, polymyositis, and inclusion body myositis) remains obscure. We and others have not detected apoptosis in the muscle biopsies from patients with myositis despite clear evidence of cell damage and loss. We provide evidence in this study that Fas ligand (FasL) as well as Fas is present on muscle cells and inflammatory cells in myositis biopsies: Fas is present on most muscle cells and lymphocytes, and FasL is present on degenerating muscle cells and many infiltrating mononuclear cells. The expression of both Fas and FasL in the inflamed tissue makes the absence of apoptosis more striking. To address the mechanisms of this resistance to classical apoptosis in muscle cells, we have investigated the expression of the antiapoptotic molecule FLICE (Fas-associated death domain-like IL-1-converting enzyme)-inhibitory protein (FLIP) in muscle biopsies of myositis patients and in cultured human skeletal muscle cells. Using laser capture microscopy, we have shown that FLIP is expressed in the muscle fibers and on infiltrating lymphocytes of myositis biopsies. Furthermore, we have shown that FLIP, but not Bcl-2, is expressed in cultured human skeletal muscle cells stimulated with proinflammatory cytokines, and inhibition of FLIP with antisense oligonucleotides promotes significant cleavage of poly(ADP-ribose) polymerase autoantigen, a sensitive indicator of apoptosis. These studies strongly suggest that the resistance of muscle to Fas-mediated apoptosis is due to the expression of FLIP in muscle cells in the inflammatory environment in myositis.

Apoptosis↗
PubMed2000

Effects of noradrenaline depletion in the brain on response on novelty in isolation-reared rats.

RATIONALE: Social isolation from weaning in the rat produces a variety of neurochemical and behavioural effects in the adult that in part parallel changes seen in human schizophrenia. OBJECTIVES: The study investigated the effects of central noradrenaline (NA) depletion by the selective neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), on the behaviour of isolation-reared rats. METHODS: Male Lister hooded rats were reared singly or in groups after weaning. During week 2, the rats were tested in photocell activity cages and were then injected with DSP-4 (25 mg/kg, IP). During week 4, rats were tested in the open field under the following conditions: open field alone, with two novel stimuli (T1), and with a familiar and a novel object (T2), and in the activity cages. RESULTS: DSP-4 significantly reduced cortical and hippocampal NA levels with no effect on the hypothalamus. Isolation-reared rats exhibited locomotor hyperactivity and reduced habituation to the testing arena, although their exploration of the novel objects in T1 was not significantly different from group-reared rats. DSP-4 treatment in group-reared rats increased inner zone activity in the open field but did not significantly affect the exploration of novel objects. DSP-4 treatment in isolates reduced exploration of objects at T2 while increasing exploration of the general environment. CONCLUSIONS: Isolation rearing influences the behavioural effects of central NA depletion. The results suggest isolation-induced changes in the central noradrenergic system in the isolated rat, supporting the view that early environmental factors can have long-term effects on central noradrenergic function as well as other neurotransmitter systems.

Animals↗
PubMed2000

Effect of soy protein foods on low-density lipoprotein oxidation and ex vivo sex hormone receptor activity--a controlled crossover trial.

Plant-derived estrogen analogs (phytoestrogens) may confer significant health advantages including cholesterol reduction, antioxidant activity, and possibly a reduced cancer risk. However, the concern has also been raised that phytoestrogens may be endocrine disrupters and major health hazards. We therefore assessed the effects of soy foods as a rich source of isoflavonoid phytoestrogens on LDL oxidation and sex hormone receptor activity. Thirty-one hyperlipidemic subjects underwent two 1-month low-fat metabolic diets in a randomized crossover study. The major differences between the test and control diets were an increase in soy protein foods (33 g/d soy protein) providing 86 mg isoflavones/2,000 kcal/d and a doubling of the soluble fiber intake. Fasting blood samples were obtained at the start and at weeks 2 and 4, with 24-hour urine collections at the end of each phase. Soy foods increased urinary isoflavone excretion on the test diet versus the control (3.8+/-0.7 v 0.0+/-0.0 mg/d, P < .001). The test diet decreased both oxidized LDL measured as conjugated dienes in the LDL fraction (56+/-3 v 63+/-3 micromol/L, P < .001) and the ratio of conjugated dienes to LDL cholesterol (15.0+/-1.0 v 15.7+/-0.9, P = .032), even in subjects already using vitamin E supplements (400 to 800 mg/d). No significant difference was detected in ex vivo sex hormone activity between urine samples from the test and control periods. In conclusion, consumption of high-isoflavone foods was associated with reduced levels of circulating oxidized LDL even in subjects taking vitamin E, with no evidence of increased urinary estrogenic activity. Soy consumption may reduce cardiovascular disease risk without increasing the risk for hormone-dependent cancers.

Adult↗
PubMed2000

The effect on serum lipids and oxidized low-density lipoprotein of supplementing self-selected low-fat diets with soluble-fiber, soy, and vegetable protein foods.

An increased intake of soluble fiber and soy protein may improve the blood lipid profile. To assess any additional benefit on serum lipids of providing soy protein and soluble-fiber foods to hyperlipidemic subjects already consuming low-fat, low-cholesterol therapeutic diets, 20 hyperlipidemic men and postmenopausal women completed 8-week test and control dietary treatments in a randomized crossover design as part of an ad libitum National Cholesterol Education Program (NCEP) step 2 therapeutic diet (<7% saturated fat and <200 mg/d cholesterol). During the test phase, foods high in soy, other vegetable proteins, and soluble fiber were provided. During the control phase, low-fat dairy and low-soluble-fiber foods were provided. Fasting blood lipid and apolipoprotein levels were measured at 4 and 8 weeks of each phase. On the test diet, 12 +/- 2 g/d soy protein was selected from the foods chosen. Direct comparison of test and control treatments indicated an elevated high-density lipoprotein (HDL) cholesterol concentration on the test diet (6.4% +/- 2.4%, P = .013) and a significantly reduced total to HDL cholesterol ratio (-5.9% +/- 2.3%, P = .020). The proportion of conjugated dienes in the low-density lipoprotein (LDL) cholesterol fraction was significantly reduced (8.5% +/- 3.3%, P = .020) as a marker of oxidized LDL. A combination of acceptable amounts of soy, vegetable protein, and soluble-fiber foods as part of a conventional low-fat, low-cholesterol therapeutic diet is effective in further reducing serum lipid risk factors for cardiovascular disease.

Adult↗
PubMed2000

A beta vasoactivity: an inflammatory reaction.

Mounting evidence from in vitro and in vivo studies in transgenic mice overproducing beta-amyloid peptides (A beta) suggests that A beta can induce vasoconstriction and decrease cerebral blood flow. In this report, we describe the vasoactive properties of A beta, in particular the enhancement of endothelin-1-induced vasoconstriction and A beta's induction of a long-lasting vasoconstrictive event. Furthermore, we show that low doses (as low as 50 nM) of freshly solubilized A beta similar to those observed in the plasma of patients suffering from Alzheimer's disease are vasoactive. By using various inhibitors and activators of the phospholipase A2 (PLA2)/arachidonic acid (AA) cascade, we demonstrate that A beta vasoactivity is dependent on activation of this intracellular signaling pathway, resulting in stimulation of downstream cyclooxygenase-2 and 5-lipoxygenase, which mediate production of proinflammatory eicosanoids. Taken together, our data show that A beta directly activates an intracellular proinflammatory pathway, which is responsible for its vasoactive properties.

Alzheimer Disease↗
PubMed2000

Effect of protein denaturation on void fraction in foam separation column.

Foam fractionation is a cost-effective process that uses air to extract protein from a liquid (in this case "crude" dilute egg-albumin solution). This article deals with how the void fraction (fraction of air in the aerated solution) of foam is affected by heat denaturation of the protein. A 2-mm glass tube was used to sample the foam-liquid interface fluid in a 35-mm-diameter column in order to detect small changes in void fraction and foam production, which are not easily detected directly from the bulk foam. The main control variable in this study was the protein solution preheating time. As the preheating time increased, the initial void fraction in the column decreased. The initial void fraction of the undenatured solution ranged from about 0.73 to 0.80, and the void fraction for significant preheating times of 5 min ranged from approx 0.68 to 0.72. Furthermore, the period of foam production increased from 5 to 7 min for undenatured proteins in solution to as long 15 min for 5-min preheated solutions. Side-port sampling through a small capillary tube has the potential to be used as a rapid and inexpensive way to determine the level of protein denaturation by directly determining the void fraction and then estimating the effect of denaturation from a protein denaturation calibration curve of the void fraction.

Biotechnology↗
PubMed2000

Do quality report cards play a role in HMOs' contracting practices? Evidence from New York State.

OBJECTIVE: To answer two related questions: (1) Do managed care organizations (MCOs) in New York State (NYS) consider quality when they choose cardiac surgeons? (2) Do they use information about risk-adjusted mortality rates (RAMR) provided in the New York State Cardiac Surgery Reports? DATA SOURCES: (1) Telephone interviews with and contracting data from the majority of MCOs licensed in NYS; (2) RAMR, quality outlier designation, and procedure volume for all cardiac surgeons, as reported in the Cardiac Surgery Reports. STUDY DESIGN: Interview data were analyzed in conjunction with patterns revealed by contracting data. Null hypotheses that MCOs' contracting choices were random with respect to the information published in the Cardiac Surgery Reports were tested. PRINCIPAL FINDINGS: Sixty percent of MCOs ranked the quality of surgeons as most important in their contracting considerations. Although 64 percent of MCOs indicated some knowledge of the NYS Cardiac Surgery Reports, only 20 percent indicated that the reports were a major factor in their contracting decision. Analyses of actual contracting patterns show that in aggregate, the hypothesis of random choice could be rejected with respect to high-quality outlier status and high procedure volume but not for RAMR or poor-quality outlier status. The panel composition of the majority of MCOs (80.2 percent) was within two standard deviations of the expected mean under the null hypothesis. CONCLUSIONS: Despite a professed preference for high-quality surgeons, the use of publicly available quality reports by MCOs is currently low, and contracting practices for the majority of MCOs do not indicate a systematic selection either for or against surgeons based on their reported mortality scores. This study suggests that policy initiatives to increase the effective use of report cards should be encouraged.

Cardiac Surgical Procedures↗
PubMed1999

Activation of microglial cells by the CD40 pathway: relevance to multiple sclerosis.

It is well known that microglial cells perform a key role in mediating inflammatory processes, which are associated with neurodegenerative diseases such as multiple sclerosis (MS). In this study, we report that CD40 expression on microglia is greatly enhanced by a low dose (10 U/ml) of IFN-gamma. We also find that ligation of microglial CD40 by CD40L triggers a significant production of TNF-alpha. Activation of microglia by ligation of CD40 in the presence of IFN-gamma results in cultured cortical neuronal injury, which is markedly attenuated by blockade of the CD40 pathway or neutralization of TNF-alpha. Finally, we find significant levels of IFN-gamma and TNF-alpha in the medium of co-cultured activated CD4+ T cells and microglial cells, showing that microglia can supply the CD40 receptor to activated CD4+ T cells and suggesting that this cellular interaction is a key event in MS pathophysiology.

Animals↗
PubMed1999

Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet.

Dietary treatment of hyperlipidemia focuses on reducing saturated fat and dietary cholesterol. Other aspects of diet are not emphasized at present, despite growing evidence that a number of plant components decrease serum cholesterol. We therefore determined whether a combination of two plant components, vegetable protein and soluble fiber, further reduce serum lipids when incorporated into the currently advocated low-saturated-fat diet. Thirty-one hyperlipidemic men and women ate two 1-month low-fat (<7% of total energy from saturated fat), low-cholesterol (<80 mg cholesterol/d) metabolic diets in a randomized crossover study. The major differences between test and control diets were an increased amount of vegetable protein (93% v 23% of total protein), of which 33 g/d was soy, and a doubling of soluble fiber. Fasting blood samples were obtained at the start and end of each phase. On the last 3 days of each phase, fecal collections were obtained. Compared with the low-fat control diet, the test diet decreased total cholesterol (6.2% +/- 1.2%, P < .001), low-density lipoprotein (LDL) cholesterol (6.7% +/- 1.7%, P < .001), apolipoprotein B (8.2% +/- 1.2%, P < .001), and the ratios of LDL to high-density lipoprotein (HDL) cholesterol (6.3% +/- 2.0%, P = .004) and apolipoprotein B to A-I (5.4% +/- 1.5%, P = .001). A combination of vegetable protein and soluble fiber significantly improved the lipid-lowering effect of a low-saturated-fat diet. The results support expanding the current dietary advice to include increased vegetable protein and soluble fiber intake so that the gap in effectiveness between a good diet and drug therapy is reduced.

Aged↗
PubMed1999

Effect of wheat bran on serum lipids: influence of particle size and wheat protein.

OBJECTIVE: Wheat fiber appears to protect from cardiovascular disease despite its lack of consistent effect on serum lipids. We therefore wished to determine whether reported inconsistencies in the effect of wheat bran resulted from differences in particle size or its high gluten content. METHODS: Two studies were conducted. In one-month metabolic diets, 24 hyperlipidemic subjects consumed breads providing an additional 19 g/d dietary fiber as medium or ultra-fine wheat bran and extra protein (10% of energy as wheat gluten). In two-week ad libitum diets, 24 predominantly normolipidemic subjects consumed breakfast cereals providing an additional 19 g/d of dietary fiber as coarse or a mixture of ultra-fine and coarse wheat bran with no change in gluten intake. Both studies followed a randomized crossover design with control periods when subjects ate low-fiber breads and cereals respectively with no added gluten. Fasting blood lipids were measured on day zero and at the end of each phase. RESULTS: Wheat bran had no effect on total, LDL or HDL cholesterol irrespective of particle size or level of gluten in the diet. However, consumption of increased gluten in the metabolic study was associated with a 13+/-4% reduction in serum triglycerides (p = 0.005) which was not seen in the normal-gluten ad libitum study. CONCLUSIONS: The protective effect of wheat fiber in cardiovascular disease cannot be explained by an effect of wheat bran in reducing serum cholesterol although in hyperlipidemic subjects displacement of carbohydrate by gluten on the high-fiber phases was associated with lower serum triglycerides.

Adult↗
PubMed1998

Alzheimer's beta-amyloid vasoactivity: identification of a novel beta-amyloid conformational intermediate.

The beta-amyloid (A beta) peptide has previously been shown to enhance phenylephrine or endothelin-1 induced constriction of aortic rings in vitro. The characteristics of A beta vasoactivity (dose, fragment length, timing) suggest that the mechanism is distinct from A beta cytotoxicity. To identify which properties of A beta determine its biological activity on vessels, we investigated a number of A beta analogues and fragments, individually and in combination, including those that are known to be associated with Alzheimer's disease (A beta(1-42)) and hereditary cerebral hemorrhage with amyloidosis--Dutch type (A beta(22Q)(1-40)). The vasoactivity appears to be related to the conformation adopted by the peptide in solution. The beta-pleated sheet rich A beta(1-42) and A beta(22Q)(1-40) were each less vasoactive than the mainly random coil wild type A beta(1-40). However, the most vasoactive A beta peptides were combinations which contain mixtures of random coil and beta-sheet structure. The finding that peptides containing low or high levels of beta-pleated conformation are less vasoactive than those containing intermediate amounts of this structural motif allows us to propose the existence of a transitional form between random coil and beta-pleated that is the vasoactive species of A beta. This is the first time that A beta conformational intermediates have been identified and a biological activity associated with them.

Amyloid beta-Peptides↗
PubMed1997

PRIME-MD: its utility in detecting mental disorders in American Indians.

OBJECTIVE: To examine the utility of using PRIME-MD (Primary Care Evaluation of Mental Disorders) for diagnosing mental disorders in American Indians. METHOD: One hundred randomly selected, adult, American-Indian patients who receive health care services at an urban Indian Health Service primary care clinic were evaluated for mental disorder by three primary care physicians using the PRIME-MD diagnostic assessment procedure. The main outcome measures were PRIME-MD diagnoses, diagnoses by an independent mental health professional, and treatment/referral decisions. RESULTS: Eighteen percent of the patients had a threshold (met full DSM-IV criteria ) PRIME-MD diagnosis, and an additional 17 percent had a subthreshold PRIME-MD diagnosis. The most frequently occurring PRIME-MD diagnoses were: probable alcohol abuse/dependence, major depressive disorder, and generalized anxiety disorder. Over 60 percent of the patients with a PRIME-MD diagnosis who were known "somewhat" or "fairly well" to their physician had not been recognized as having that psychiatric disorder prior to the PRIME-MD assessment. Therapy and/or referral was initiated for nineteen of the twenty-seven patients with a PRIME-MD diagnosis who were not previously receiving treatment. The primary care physicians were able to complete the PRIME-MD evaluations within an average of 7.8 minutes. There was a fair agreement between the PRIME-MD diagnoses and the diagnoses of the mental health professional (kappa = 0.56; overall accuracy rate = 79%). CONCLUSIONS: The present study represents the first formal examination of the use of PRIME-MD with American Indians. The results are encouraging. Further studies using PRIME-MD with other urban groups and reservation populations are recommended.

Adolescent↗