Biomedical subjects

M Blank

Publications and source records attributed to M Blank.

At least 55 records · Page 3Linked to original sources

PubMed2001

Optimal frequencies for magnetic acceleration of cytochrome oxidase and Na,K-ATPase reactions.

Low frequency magnetic fields increase the activity of the membrane enzymes, Na,K-ATPase and cytochrome oxidase, and the increased activity varies with frequency. Optimal frequencies for increases in the reaction rate constant of cytochrome oxidase and in the rate of splitting of ATP by Na,K-ATPase differ by an order of magnitude, and are in the ranges of the turnover numbers of the respective enzyme reactions. The two frequency dependence curves are similar in that the slope of the low frequency portion is about 10 times greater than the slope of the high frequency portion. The greater slope indicates greater ability to adjust quickly in the low frequency range, which may be significant for optimal biological control of activity.

Animals↗

PubMed2001

Autoantibodies to oxidized low-density lipoprotein in coronary artery disease.

BACKGROUND: The significance of antioxidized low-density lipoprotein (oxLDL) antibodies in atherogenesis is not yet clear, and there are conflicting data regarding anti-oxLDL levels in early hypertension. METHODS: The levels of anti-oxLDL antibodies were studied in coronary artery disease patients with (n = 82) or without (n = 36) hypertension, in association to other risk factors for coronary artery disease. RESULTS: The levels of anti-oxLDL antibodies did not differ significantly between coronary artery disease patients with or without hypertension. (0.132 +/- 0.146 v 0.153 +/- 0.158 optical density at 405 nm, respectively; P = .48). No significant differences in anti-oxLDL antibodies were found between men and women with and without hypertension, between hypertensive patients with normal and abnormal blood pressure measurements, and between medicated and nonmedicated hypertensive patients. The presence of diabetes mellitus, smoking, and hypercholesterolemia, either solely or in combination, did not result in significant differences in antibody levels in the hypertensive or normotensive patients. CONCLUSIONS: Although the levels of oxLDL antibodies might be modified in early hypertension, once advanced coronary artery disease has developed the presence of hypertension does not affect anti-oxLDL levels.

Aged↗

PubMed2001

Correlates of family burden under medicaid managed mental health care.

This study examined predictors of family burden (assistance in daily living, supervision, and subjective concern) for family members of Medicaid recipients with severe mental illness in two regions of Virginia. In the Richmond area, mental health services were provided on a no-risk fee-for-service basis, while in Tidewater these services were provided through a risk-based capitated contract with a managed care organization. No differences in family burden were attributable to the risk-based payment system. Predictors of increased family burden were (a) more reported client symptoms and disruptive behaviors, (b) status as a parent, and (c) living with the client.

Adult↗

PubMed2001

Barriers to help seeking for mental disorders in a rural impoverished population.

This study examined barriers to seeking mental health care reported by individuals in a rural impoverished population, by screening 646 randomly selected adults for depression, anxiety, and alcohol abuse. Respondents who screened positive were randomly assigned to one of three groups: (1) no intervention, (2) an educational intervention alone, or (3) the educational intervention in the presence of a significant other. Those who screened positive for disorders cited barriers to care at significantly higher rates than respondents who screened negative. Respondents who received the educational intervention endorsed several barriers at significantly lower rates in the follow-up telephone call (subsequent to the intervention) than in the original interview (prior to the intervention). Virtually all respondents in a subsample of 142 subjects (99.3%) said they would seek mental health care if they thought mental health services would help them.

Adult↗

PubMed2001

Treatment of MRL/lpr mice, a genetic autoimmune model, with the Ras inhibitor, farnesylthiosalicylate (FTS).

Activation and proliferation of lymphocytes requires the active signal transducer Ras. Activation of lymphocytes, associated with autoimmunity, may therefore be modified by S-farnesylthiosalicylic acid (FTS), a synthetic substance that detaches Ras from the inner cell membrane and induces its rapid degradation. The MRL/lpr mouse is a genetic model of a generalized autoimmune disease sharing many features and organ pathology with systemic lupus erythematosus (SLE) and the primary antiphospholipid syndrome (APS). The objective of the present study was to examine the effect of FTS on laboratory and clinical pathology in the MRL/lpr mouse. Female MRL/lpr (n = 50) and MRL/++ control (n = 35) mice were treated intraperitoneally with either FTS (5 mg/kg/day) or saline between 6 and 18 weeks of age. The mice were weighed, tested for proteinuria and lymphadenopathy, lymphocyte proliferation, antibodies, grip strength and behaviour in an open field. FTS treatment resulted in a 50% decrease in splenocyte proliferation to ConA, LPS and a disease specific antigen, beta(2)-glycoprotein-I, and in a significant decrease in serum antibody levels against cardiolipin and dsDNA. Proteinuria and grip strength were normalized and lymphadenopathy and postmortem lymph node and spleen weights were significantly reduced in FTS treated MRL/lpr mice. These findings indicate that modulation of Ras activation has a significant impact on the MRL/lpr model and may represent a new therapeutic approach for the treatment of systemic autoimmune diseases such as SLE and APS.

Animals↗

PubMed2001

Induction and treatment of the antiphospholipid syndrome--lessons from animal models.

The diagnosis of antiphospholipid syndrome (APS) is based on a combination of clinical and serological criteria. This review summarizes the literature regarding animal models of APS. Animal models of this syndrome help to elucidate pathogenic roles of the characteristic antiphospholipid antibodies in pregnancy morbidity, vascular thrombosis, neurologic disease and atherosclerosis. Furthermore, these models also provide measures to evaluate novel therapies for APS. These include bone-marrow transplantation, intravenous immunoglobulin, anticoagulation, interleukin-3, in addition to other therapies. Experimental induction and treatment of APS largely contributes to our understanding of the disease and to better management of its clinical characteristics.

Adjuvants, Immunologic↗

PubMed2001

Anti-endothelial cell antibodies from patients with thrombotic thrombocytopenic purpura specifically activate small vessel endothelial cells.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon disease of an unknown etiology, characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever and acute thrombotic complications, especially within the cerebral circulation. Although anti-endothelial cell antibodies (AECA) have occasionally been shown to be present in TTP, their role in the pathogenesis of the disease has never been ascertained. In the current study we demonstrated the pathogenic activity of affinity-purified anti-endothelial cell F(ab)2 antibodies (AECA/TTP) from four consecutive patients with active TTP. These AECA/TTP bound to and activated only microvascular endothelial cells (EC) and not large vessel EC. The specificity of AECA/TTP binding to microvascular EC was confirmed by competition assay employing membranes derived from small and large vessels EC. Activation included enhanced IL-6 and von Willebrand factor release from the EC followed by increased expression of adhesion molecules P-selectin, E-selectin and vascular cell adhesion molecule-1 on the EC, as evaluated by ELISA. Increased expression of adhesion molecules was followed by an increase in monocyte adhesion to EC. The level of soluble thrombomodulin (TM) also increased in the culture medium of activated microvascular EC upon exposure to AECA/TTP antibodies and was directly correlated to a decrease in cell-associated TM. Our data suggest that AECA/TTP directed against microvascular EC could play a pathogenic role in the development of endothelial injury in TTP that leads to thrombosis.

Antibody Specificity↗

PubMed2001

The association between anti-thyroid antibodies and pregnancy loss.

The incidence of thyroid autoantibodies in women with recurrent fetal loss, infertility or women who miscarried appears to be increased compared with controls of reproductive age without previous abortions. There are few working hypotheses concerning the asociation between anti-thyroid antibodies and the increased risk for pregnancy loss. The first hypothesis suggests that women with high titers of anti-thyroid antibodies have underlying very mild thyroid "under function". Another theory views the anti-thyroid antibodies as simply secondary markers of a predisposition of autoimmune disease rather than the actual cause of pregnancy loss. An evolutionary explanation suggests that reproductive problems in women with high titers of autoantibodies exist in order to prevent the transmission of autoimmune genes to the next generation. The reason for the association between pregnancy loss and thyroid immunity is still not clear. The working hypotheses above supply multi-factorial explanations, which could act together, may even be in synergy, as the propulsion for the pregnancy loss. Until today the mechanism by which anti Tg are responsible for pregnancy loss is not clear. Induced animal models with high titier of anti Tg could provide direct evidence for the pathogenic role of anti-thyroid antibodies and the mechanism that is responsible for the pregnancy loss in autoimmune thyroiditis. In the current presentation we describe data concerning the association between anti-thyroid antibodies and pregnancy loss, and hypothesis which explains this association.

Abortion, Spontaneous↗

PubMed2001

Coronary artery disease but not coronary calcification is associated with elevated levels of cardiolipin, beta-2-glycoprotein-I, and oxidized LDL antibodies.

BACKGROUND: Autoimmune factors have been shown to play a role in atherosclerosis. The aim of this study is to correlate 5 autoantibodies (anticardiolipin, anti-CL, beta2-glycoprotein-I, beta2GPI, phosphatidylcholine, oxidized low-density lipoprotein, oxLDL, endothelial cell) with the presence of coronary heart disease, angiographic findings, and with coronary artery calcification. METHODS: The levels of the 5 autoantibodies and a control antifibroblast line of 126 coronary heart disease patients and 20 healthy controls were measured. Fifty-one patients underwent coronary angiography, and 98 patients had coronary artery calcium determination using spiral computerized tomography (dual mode). RESULTS: Levels of 3 autoantibodies (anti-CL, beta2GPI, oxLDL) were significantly elevated in coronary heart disease patients compared with controls (p < 0.001, p = 0.001, p < 0.001, respectively). Within the subgroup of patients with significant coronary artery stenosis, anti-CL antibodies were also elevated (p = 0.008). No correlation was found between anti-CL, and anti-beta2GPI autoantibody levels and coronary calcium scores as measured by spiral computerized tomography. However, anti-oxLDL antibodies were raised in patients with no calcification detected by spiral computerized tomography, compared with the patients with any coronary calcification (p = 0.046). CONCLUSION: Anti-CL, beta2GPI and oxLDL antibodies are elevated in coronary heart disease patients regardless of coronary calcification.

Aged↗

PubMed2001

Hyperactivity in a mouse model of the antiphospholipid syndrome.

In the antiphospholipid syndrome (APS), antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI) are associated with recurrent thromboembolic events, spontaneous abortions, thrombocytopenia and central nervous system (CNS) disturbances. Animals immunized with beta2-GPI develop the systemic manifestations of APS but the involvement of the (CNS) in these animals has not been studied. The objective of the present study was to examine mice with induced experimental APS for behavioral changes. Female Balb/C mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone. Four months after immunization the mice were tested in the staircase apparatus and the following two variables were measured: (1) number of rears: and (2) number of stairs climbed by the mice. Immunization with beta2-GPI resulted in elevated levels of circulating anti-negatively charged phospholipids and anti-beta2-GPI antibodies. The APS mice exhibited hyperactive behavior as reflected by more frequent rears (P < 0.023) and higher number of stairs climbed (P < 0.019) by the mice in 3 min. This simple test demonstrated that experimental APS animals are significantly hyperactive and may serve as a marker for CNS involvement in this model.

Animals↗

PubMed2001

AVEMAR (a new benzoquinone-containing natural product) administration interferes with the Th2 response in experimental SLE and promotes amelioration of the disease.

The potential of oral treatment with AVEMAR (AVEMAR), a new benzoquinone-containing fermentation product of wheat germ, on features of experimental systemic lupus erythematosus (SLE) in naive mice, induced by idiotypic manipulation, was studied. We assessed the effect of AVEMAR on the profile of autoantibody production and the response of Th1/Th2 related cytokines as well as the clinical picture of experimental SLE in the SLE-induced mice. When the product was given in the pre-immunization period, down-regulation of autoantibody production (anti-dsDNA, mouse 16/6 Id, and anti-histones) following treatment with AVEMAR was noted (eg anti-dsDNA decreased from 0.898+/-0.097 OD at 405 nm to 0.519+/-0.103 OD following treatment). This effect was sustained for at least 4 weeks after discontinuation of the therapy. Serological manifestations associated with a delay in Th2 response (IL-4 and IL-10) were recorded (eg IL-4 decreased from 91.7+/-8.11 to 59.55+/-7.78 ng/ml in splenocyte condition media). The mice showed normal ESR, WBC and less than 100 mg/dl of protein in the urine in comparison to > 300 mg/dl protein in the SLE non-treated mice. In conclusion, oral intake of AVEMAR can ameliorate the clinical manifestations of experimental SLE, via affecting the Th1/Th2 network inhibiting Th2 response.

Animals↗

PubMed2001

Anti-cancer activities of hypericin in the dark.

The potent photodynamic properties of hypericin (HY) elicit a range of light-dependent virucidal and tumoricidal activities. Yet, a relatively low reduction/oxidation potential endows HY with electron accepting and donating properties enabling it to act as both an oxidizing and a reducing agent. HY can thus compete as an electron acceptor from bioenergized reduction/oxidation reactions generating its excitation energy for biological activities from physiological reduction/oxidation reactions in the absence of light. Our studies show that HY can inhibit the growth of highly metastatic murine breast adenocarcinoma and squamous cell carcinoma tumors in culture. Furthermore, we show that HY can interfere with the growth of these tumors in mice reducing tumor size and prolonging animal survival in complete absence of light. While there is no evidence that HY induces apoptosis in these cells in the dark, 3H-thymidine incorporation into DNA was significantly reduced indicating effects that are apparently cytostatic in nature compared to the cytocidal effects of HY with light.

Animals↗

PubMed2000

Coronary calcium and anti-cardiolipin antibody are elevated in patients with typical chest pain.

The aim of this study was to examine whether detection of coronary calcium and the autoimmune response associated with atherosclerosis, either solely or in combination, are different in patients with typical and atypical chest pain. Coronary calcium as detected by spiral computerized tomography and levels of antibodies against cardiolipin (CL), oxidized low-density lipoprotein (ox-LDL), and beta2-glycoprotein-I (beta2-GPI) were studied in patients with typical chest pain (n = 52), atypical chest pain (n = 19), or without chest pain (n = 21). Patients with typical chest pain had higher mean levels of coronary calcium (expressed as natural transformation of total coronary calcium score) compared with patients with atypical chest pain and controls (5.04 vs 3.21 and 2.75, respectively; p < 0.001). The levels of anti-CL were (mean +/- SD of optical density multiplied by 1,000): 262 +/- 140, 170 +/- 82, and 230 +/- 115 for patients with typical chest pain, atypical chest pain, and controls, respectively (p = 0.016). No significant difference was found between groups regarding anti-ox-LDL and anti-beta2-GPI autoantibody levels. In the typical chest pain group, there was a higher prevalence of high total coronary calcium scores (p = 0.03) and high anti-CL levels (p = 0.01) than in the atypical chest pain group. Eighteen of 52 patients with typical chest pain (35%) had both high calcium scores and high antibody levels, whereas none of the 19 patients (0%) who had atypical chest pain had high levels of both (p = 0.003). A combination of both coronary calcium and anti-CL was associated with higher area under the receiver operator characteristic curves than for each separately. High coronary calcium scores or high anti-CL levels are found more often in typical than in atypical chest pain patients, but a combination of high levels of both can better differentiate typical from atypical chest pain patients.

Aged↗

PubMed2000

Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy.

Limb girdle muscular dystrophy is a group of clinically and genetically heterogeneous disorders inherited in an autosomal recessive or dominant mode. Caveolin-3, the muscle-specific member of the caveolin gene family, is implicated in the pathogenesis of autosomal dominant limb girdle muscular dystrophy 1C. Here we report on a 4-year-old girl presenting with myalgia and muscle cramps due to a caveolin-3 deficiency in her dystrophic skeletal muscle as a result of a heterozygous 136G-->A substitution in the caveolin-3 gene. The novel sporadic missense mutation in the caveolin signature sequence of the caveolin-3 gene changes an alanine to a threonine (A46T) and prevents the localization of caveolin-3 to the plasma membrane in a dominant negative fashion. Caveolin-3 has been suggested to interact with the dystrophin-glycoprotein complex, which in striated muscle fibers links the cytoskeleton to the extracellular matrix and with neuronal nitric oxide synthase. Similar to dystrophin-deficient Duchenne muscular dystrophy, a secondary decrease in neuronal nitric oxide synthase and alpha-dystroglycan expression was detected in the caveolin-3-deficient patient. These results implicate an important function of the caveolin signature sequence and common mechanisms in the pathogenesis of dystrophin-glycoprotein complex-associated muscular dystrophies with caveolin-3-deficient limb girdle muscular dystrophy.

Amino Acid Substitution↗

PubMed2000

Cytoprotection by electromagnetic field-induced hsp70: a model for clinical application.

A unique approach to clinical application of cytoprotection is offered by electromagnetic (EM) field induction of stress proteins. EM fields are noninvasive and easily applied, as compared with the current hyperthermia protocols. Fertilized dipteran eggs and cultured rodent cardiomyocytes (H9c2 cells) were used as models to test EM fields for their ability to induce increased hsp70 levels for effective cytoprotection. Eggs preconditioned with an 8 microT 60Hz EM field for 30 min had 114% increase in hsp70 levels, and an average 82% increase in survival, following a lethal temperature of 36.5 degrees C. Thermal preconditioning at 32 degrees C was not nearly as effective in dipteran eggs, inducing only a 44% increase in survival. Preconditioning of cultured murine cardiomyocytes (H9c2 cells) with an 8 microT 60 Hz field induced a 77% average increase in hsp70 levels.

Animals↗

PubMed2000

Pathogenic role of anti-endothelial cell antibodies in systemic vasculitis.

Antiendothelial cell antibodies (AECA), a heterogeneous group of antibodies quite distinct from the ANCA family, have been detected in variety of diseases which share a varying degree of vessel wall damage. This review is mainly focused on Wegener's granulomatosis, Takayasu's arteritis and Kawasaki syndrome, which provide the best examples to evaluate the pathogenic and prognostic value of AECA. There is increasing evidence to show that AECA might be pathogenic in inducing autoimmune vascular disease. It is relevant to note that the presence and titre of AECA has been correlated with disease activity in systemic vasculitis. Experimental in vitro and in vivo models support a potential pathogenic role for AECA in sustaining immune-mediated vessel inflammation. Rather than being cytotoxic to endothelial cells, AECA are able to up-regulate the expression of adhesion molecules (E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and to induce the secretion of cytokine and chemokine which, in turn, cause leukocyte recruitment and adhesion. A recent idiotypic animal model has provided further evidence that AECA can be pathogenic.

Autoantibodies↗

PubMed2000

ERK1/2 phosphorylation, induced by electromagnetic fields, diminishes during neoplastic transformation.

It has been suggested that electromagnetic (EM) fields can act as co-promoters during neoplastic transformation. To examine this possibility, we studied the effects of 0.8-, 8-, 80-, and 300-microT 60-Hz electromagnetic (EM) fields in INITC3H/10T1/2 mouse fibroblast cells. These cells are transformed carcinogenically by methylcholanthrene, but the neoplastic phenotype can be suppressed indefinitely by the presence of retinyl acetate (RAC) in the culture medium. The effects of EM field exposures were examined at three stages: (1) before initiation of transformation (i.e., RAC in the culture media); (2) early in the transformation process (4 days after withdrawal of RAC); and (3) at full of neoplastic transformation (10 days after withdrawal of RAC). EM field exposures induced significant increases in protein levels for hsp70 and c-Fos and in AP-1 binding activity. EM fields induced phosphorylation of MAPK/ERK1/2 before the onset of transformation, but these increases diminished during the transformation process. No phosphorylation in the other major extracellular stress pathway, SAPK/JNK, was detected in cells exposed to EM fields at any time before, during, or after neoplastic transformation. Human cells HL60, MCF7, and HTB124, exposed to EM fields, also showed MAPK/ERK1/2 phosphorylation. Cells treated with the phorbol ester, TPA, served as positive controls for AP-1 activation, c-Fos protein synthesis, and ERK1/2 phosphorylation. There was no indication that EM fields affected the rate of cell transformation or acted as a co-promoter, under the conditions of this study.

Animals↗

PubMed2000

Linseed oil suppresses the anti-beta-2-glycoprotein-I in experimental antiphospholipid syndrome.

The immunomodulatory potential of a diet enriched with n-3 polyunsaturated fatty acids was analysed in naïve mice with experimental antiphospholipid syndrome (APS) induced by active immunization with H-3, a human anti-beta-2-glycoprotein-I (anti-betaGPI) monoclonal antibody (mAb). Fetal loss and other clinical manifestations of APS were prevented in the group of APS mice upon exposure to the enriched n-3 diet compared to the control group. The titers of anti-betaGPI were significantly lower (in O.D. at 405 nm, 1.387+/-0.232 in comparison to non-treated mice 0.637+/-0. 111, P< 0.05). The reduced titer of anti-betaGPI antibodies in the sera of the treated mice was associated with a reduced number of anti-betaGPI forming cells in cultured splenocytes (84+/-14, antibody-forming cells (AFC)/10(5)cells in comparison to 37+/-4 AFC/10(5)cells (P< 0.02).In addition to the suppression of the humoral response in mice with experimental APS fed with linseed oil, we also observed an inhibitory effect on the cellular response. The T-cell response to anti-betaGPI was lower in comparison to mice immunized with H-3 anti-betaGPI mAB, which were kept on a normal diet. These results indicate that polyunsaturated fatty acids may improve clinical and laboratory parameters of APS. The beneficial effects of diets enriched with n-3 should be further examined as a potential mode of therapy for patients with APS.

Animals↗