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Biomedical subjects

M Blank

Publications and source records attributed to M Blank.

At least 73 records · Page 4Linked to original sources
PubMed2000

Comparing provider perceptions of access and utilization management in full-risk and no-risk Medicaid programs for adults with serious mental illness.

This article compares provider perceptions of access to services and utilization management (UM) procedures in two Medicaid programs in the same state: a full-risk capitated managed care (MC) program and a no-risk, fee-for-service (FFS) program. Survey data were obtained from 198 mental health clinicians and administrators. The only difference found between respondents in the FFS and MC sites was that outpatient providers in the MC site reported significantly lower levels of access to high-intensity services than did providers in the FFS site (p < .001). Respondents in the two sites reported similar attitudes toward UM procedures, including a strong preference for internal over external UM procedures. These findings support the conclusion that through diffusion of UM procedures, all care in the Medicaid program for persons with a serious mental illness is managed, regardless of risk arrangement. Implications for mental health services and further research are discussed.

Adult↗
PubMed2000

[Construction and use of a virtual anthropomorphic phantom of the bronchial tree].

MOTIVATION: Usually, phantoms are used to quantify properties of computer algorithms working on spiral CT data. The high complexity of the human bronchial tree, however, complicates the construction of a physical phantom enormously; hence, a virtual phantom must be employed. METHODS: Because the human bronchial tree is fractal, Lindenmayer systems were utilized to generate its structure. Applying the correct diameter and length ratios and branching angles, a virtual anthropomorphic phantom could be generated by a three-dimensional turtle graphic. The simulation of a spiral CT measurement on the virtual phantom delivered synthetic spiral CT data. RESULTS: The computer-controlled growing process supplies exact morphologic and morphometric data. The spiral CT simulation saves the time-consuming and complicated generation of a physical phantom. PERSPECTIVE: The virtual phantom can be completed by the introduction of blood vessels and lung parenchyma partitioned into lobes and segments. The field of application can thus be extended.

Anthropometry↗
PubMed2000

2D and 3D visualisation of head and neck tumours from spiral-CT data.

PURPOSE: This paper intends to demonstrate the possibilities of two- and three-dimensional visualisation methods from spiral-CT data sets in the head and neck region and demonstrates their value based on various studies. MATERIAL AND METHODS: The scanner was a Somatom PLUS 4 (Siemens, Forchheim/Germany). The patients were scanned using a slice thickness of 3 mm and a table feed of 5 mm (pitch 1,6). The images were reconstructed with an increment of 1 mm. Contrast agent (150 ml) was applied intravenously with a flow of 2.5 ml/s and a start delay of 80 s. In one study the start delay was 20 s in order to visualise the carotid arteries (extracranial aneurysm). Volumetric data sets were postprocessed with 'Vitrea' and 'VoxelView' (Vital Images) volume rendering software on a Silicon Graphics O2 workstation (virtual laryngoscopy). Multiplanar reformation and colour-coded 3D-reconstruction were done on a Prominence workstation (Siemens/Forchheim/Germany). RESULTS: In every region of the head and neck MPRs are useful as additional planes (with the exception of the hypopharynx and the larynx), SSDs are always useful if there is extensive bony destruction (skull, spine, skeleton larynx). Colour-coded three-dimensional reformations may be done for extensive tumours and before multi-specialty surgery. Perspective volume rendering is already in use for virtual endoscopy of the paranasal sinuses and the virtual laryngoscopy. In temporal bone evaluation, perspective volume rendering is a new and promising method of the future to assess the inner ear. SUMMARY: Two- and three-dimensional displays are used to visualise pathological findings in their topographic relation to anatomical leading structures. Thus, the radiologist can point out to the clinician the pathological findings by some essential images without having to demonstrate all axial slices.

Aneurysm↗
PubMed2000

Medical volume exploration: gaining insights virtually.

Since modern imaging modalities deliver huge amounts of data, which cannot be assessed easily, the visualization techniques are utilized to emphasize the structures of interest. To compare them, the different visualization techniques (maximum intensity projection, multiplanar reformations, shaded surface display and volume rendering) are regressed to a common ground whereby their strengths and weaknesses can be revealed. Additionally, medical image analysis can detect anatomical objects in volumetric data sets and provides their descriptions for further use. Usually, segmentation plays a crucial roll in that process. There are many segmentation methods which can be categorized in boundary-based and content-based ones. The extraction of anatomical objects also allows their quantification. Image analysis and visualization do not squeeze more information out of a data volume, but they provide different ways to look at it. As in real life, this alone may enlarge the insight.

Algorithms↗
PubMed2000

Bromal-derived tetrahydro-beta-carbolines as neurotoxic agents: chemistry, impairment of the dopamine metabolism, and inhibitory effects on mitochondrial respiration.

The mammalian alkaloids tryptoline (1) and eleagnine (2) as well as the highly halogenated (X = F, Cl, Br) tetrahydro-beta-carbolines (THbetaCs) 3-5, structurally similar to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 6), were found to have a common feature of inducing a severe impairment of the nigrostriatal dopamine metabolism and inhibiting complex I of the mitochondrial respiratory chain highly selectively. Within the series of compounds tested, 1-tribromomethyl-1,2,3,4-tetrahydro-beta-carboline ('TaBro', 5), which was prepared in high yields from the biogenic amine tryptamine ('Ta', 7) and the unnatural aldehyde bromal ('Bro', 8) by a Pictet-Spengler cyclization reaction, turned out to be the most potent toxin in vitro and in vivo. As demonstrated by voltammetric measurements on rats, for all the THbetaCs 1-5 investigated, intranigral application of a single dose of 10 microg resulted in a significant reduction of the dopaminergic activity in the striatum, with the strongest effect being observed for TaBro (5). Using rat brain homogenates, again 5 (IC50 = 200 microM) as well as its dehydrohalogenation product 11 (IC50 = 150 microM) exhibited the most pronounced inhibitory potential on mitochondrial respiration. The halogen-free THbetaCs 1 and 2 as well as the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP+), by contrast, showed only a moderate inhibition at concentrations in the millimolar range (e.g. for MPP+: IC50 = 3.5 mM). For an elucidation of the role of hydrophobic portion in the inhibitory action against complex I activity, several N-acyl derivatives (15-21) of 5 were synthesized and tested. An X-ray diffraction study on the 3-dimensional structure of trifluoroacetylated highly halogenated THbetaCs (12-14) revealed the tetrahydropyrido part to adopt a nearly planarized half-chair conformation. Because of the steric demand of the trihalogenmethyl moiety (CF3 < CCl3 < CBr3), the N-substituent is dramatically pushed out of that ring 'plane'.

Animals↗
PubMed2000

Prognosis of persons with type 1 diabetes on intensified insulin therapy in relation to nephropathy.

OBJECTIVE: To study the prognosis of persons with type 1 diabetes in relation to the degree of nephropathy at initiation of intensified insulin therapy. DESIGN: Ten years follow-up of a cohort of 3674 patients who had participated in a 5-day group treatment and teaching programme for intensification of insulin therapy between September 1978 and December 1994. SETTING: Ten diabetes centres in Germany. SUBJECTS: A total of 3674 patients (insulin treatment before age 31), age at baseline 27 +/- 10 years, with a diabetes duration of 11 +/- 9 years. Patients were divided into three groups according to baseline renal parameters (group I, normal proteinuria, n = 1829; group II, microproteinuria, n = 1257; group III, at least macroproteinuria, n = 367). MAIN OUTCOME MEASURES: End-stage diabetic complications (blindness, amputations, renal replacement therapy, standardized mortality ratios (SMR) and causes of death. RESULTS: Outcome measures were documented for 97% of patients; 251 (7%) had died. During follow-up, 1% of patients in group I, 4% in group II and 47% in group III had at least one end-stage diabetic complication. SMR for men: nephropathy group I, 2.2 (95% CI = 1.5-3); group II, 3.2 (2.3-4.3); group III, 11.5 (8.8-14.7). SMR for women: group I, 2.5 (1.5-3.8); group II, 3.5 (2.2-5.3); group III, 27 (19.8-35.9). Causes of death for men and women combined: group I (total 58 deaths)--cardiovascular, 21 (36%); hypoglycaemia, 1; ketoacidosis, 3; violent deaths, 17 (29%); others, 16; group II (66 deaths)--cardiovascular, 25 (38%); hypoglycaemia, 2; ketoacidosis, 2; violent deaths, 14 (21%); others, 23; group III (114 deaths)--cardiovascular, 68 (60%); hypoglycaemia, 2; ketoacidosis, 5; infections, 15 (13%); violent deaths, 5 (4%); others, 19. CONCLUSIONS: Patients with microproteinuria have only a slightly worse prognosis than patients with normal proteinuria during the first 10 years after initiation of intensified insulin therapy. Excess mortality amongst patients who started intensified insulin therapy is mainly due to those with manifest clinical nephropathy.

Adult↗
PubMed2000

Ciprofloxacin affects pregnancy loss in CBA/JxDBA/2J mice possibly via elevation of interleukin-3 and granulocyte macrophage-colony stimulating factor production.

PROBLEM: The mechanisms mediating pregnancy loss are far from being understood, but it is believed that modulation of the maternal immune system, that is known to support pregnancy, might serve as a means for the treatment of habitual abortions. Thus, we examined the effect of the anti bacterial agent ciprofloxacin, which was shown to affect maternal immunoreactivity, on pregnancy loss in the resorption-prone CBA/JxDBA/2J mouse combination as well as associated changes in Interleukin (IL)-3 and Granulocyte macrophage-colony stimulating factor (GM-CSF) production. METHOD OF STUDY: CBA/J females mated to DBA/2J males were treated with ciprofloxacin for 5 consecutive days. On day 15 of pregnancy, the number of resorbed embryos was recorded and IL-3 mRNA expression as well as IL-3 and GM-CSF protein production by splenocytes were assayed by northern blotting and ELISA, respectively. RESULTS: Ciprofloxacin treatment resulted in a significant reduction in the resorption rate as compared to the effect of the control antibiotic ceftazidime or PBS only, while not affecting the number of implantation sites/mouse. Also, splenocytes from ciprofloxacin-treated CBA/J mice exhibited an increased level of IL-3 mRNA transcripts as well as an elevation in IL-3 and GM-CSF protein production. CONCLUSIONS: Our data demonstrate the ability of ciprofloxacin to reduce pregnancy loss in the CBA/JxDBA/2J mouse model, possibly via elevation of IL-3 and GM-CSF production.

Abortion, Veterinary↗
PubMed2000

Peptide immunotherapy in autoimmune diseases.

Peptide-mediated immunotherapy has been studied in a number of experimental models of autoimmune diseases and has also been tested in human patients to a certain extent. Copolymer 1 is a synthetic amino acid copolymer that has been demonstrated to suppress experimental autoimmune encephalomyelitis (a model for multiple sclerosis) when administered parenterally. Some study results indicate that mucosal tolerance induced by appropriate recombinant peptide fragments of human AChR is effective in suppressing experimental autoimmune myasthenia gravis and might be considered as a therapeutic modality for patients with MG. A peptide of the heat-shock protein 60 molecule, designated peptide p277, was shown to be a target of T cells in autoimmune diabetes in NOD mice, and intraperitoneal injections of glutamic acid decarboxylase (GAD) peptide 524-543 delayed the onset of diabetes and significantly reduced its incidence. Experimental evidence has revealed that CDR-based peptides may be potential candidates for the therapy of systemic lupus erythematosus. The use of synthetic peptides that focus on neutralization of pathogenic anti-beta 2GPI antibodies represents a possible new therapeutic approach to antiphospholipid syndrome. Studies in both acute and chronic-relapsing experimental autoimmune uveoretinitis have indicated that oral administration of S-Ag, S-Ag-derived peptides, inter-photoreceptor retinoid binding protein or HLA-derived peptides before immunization can protect animals from the disease.

Journal Article↗
PubMed2000

Effects of photodynamic therapy with hypericin in mice bearing highly invasive solid tumors.

The tumoricidal properties of photodynamic therapy (PDT) with hypericin (HY) were evaluated in a highly metastatic adenocarcinoma (DA3Hi) and anaplastic squamous cell carcinoma (SQ2) tumors in vivo. Photosensitization of the tumor site with hypericin (HY-PDT) reduced primary tumor development and significantly prolonged the survival of tumor-bearing (TB) mice. Of these two tumors the squamous cell carcinoma emerged as more sensitive to HY-PDT compared with DA3Hi adenocarcinoma both in vitro and in vivo. HY-PDT caused extensive tumor necrosis that was followed by local, intratumoral, and systemic inflammatory reactions. Analyses of cytokine mRNA profiles reveal increases in mRNA levels of expression confined to inflammation-related cytokines both within the tumor and also systemically (measured in spleens). However, there was no evidence for any HY-PDT-induced antitumoral immune reactions. Our results suggest that PDT with hypericin can be considered as a supplementary treatment in the management of some invasive and metastatic cancers such as squamous carcinoma and similar tumors.

Adenocarcinoma↗
PubMed2000

Immunomodulation of experimental autoimmune diseases via oral tolerance.

The concept of oral tolerance refers to a form of peripheral tolerance in which mature lymphocytes in the peripheral lymphoid tissues are rendered nonfunctional or hyporesponsive by prior oral administration of an antigen. The primary mechanisms mediating oral tolerance include deletion, anergy of antigen-specific T cells and active cellular suppression, the primary determining factor being the dose of fed antigen. Low doses favor active suppression, whereas high doses favor deletion and anergy. Active cellular suppression is mediated by the induction of regulatory T cells in the gut-associated lymphoid tissue, which migrate to the systemic immune system. One of the primary mechanisms of active cellular suppression is via secretion of suppressive cytokines such as TGF-beta, IL-4, and IL-10 following antigen-specific triggering. TGF-beta is produced both by CD4+ and CD8+ GALT-derived T cells and is an important mediator of the active suppression component of oral tolerance. CD4+ cells that primarily produce TGF-beta appear to be a unique T-cell subset and termed Th3 cells. Oral tolerance was successfully studied in a variety of experimental models for autoimmune diseases, among them experimental autoimmune encephalomyelitis, experimental arthritis, experimental anti-phospholipid syndrome, experimental autoimmune uveoretinitis, experimental insulin dependent diabetes mellitus (IDDM), and experimental autoimmune myasthenia gravis. The results obtained in experimental animal models have led to the conduction of several clinical trials of oral tolerance in patients with multiple sclerosis, rheumatoid arthritis, uveitis, and IDDM. Conflicting results were obtained, and although some improvement has been noted in some of the patients, broad ranging clinical improvement has not yet been observed. A more accurate choice of antigens, as well as more precise dosing and timing of antigen-administration might lead to better results in the future.

Animals↗
PubMed2000

Anti-beta 2-glycoprotein I antibodies and anti-endothelial cell antibodies induce tissue factor in endothelial cells.

Anti-beta 2-glycoprotein I antibodies bind to endothelial cells through beta 2-GPI. The antibodies are present in patients with systemic lupus erythematosus and antiphospholipid syndrome and are associated with the pathogenesis of the disease. Anti-endothelial cell antibodies that react with constitutive antigens on ECs are present in patients with vasculiditis and other diseases. Both types of antibodies can activate ECs. Frequent findings in APLS and vasculitis are fibrin deposits and thromboembolic phenomena. These indicate that the coagulation system is activated. However, the mechanism of activation is not clear. ECs generate tissue factor upon stimulation with various substances. In the present study we report that monoclonal anti-beta 2-GPI antibodies and AECAs, derived from a patient with primary APLS and a patient with Takayasu's arteritis, respectively, induce a potent tissue factor in ECs. The production of TF activity, TF antigen and TF mRNA is dose and time dependent. The TF activity was induced also by F(ab)2 but not by Fc fragments and was abolished completely by pre-incubation with ant-TF antibodies. The TF that is induced in ECs by AECAs with and without beta 2-GPI specificity may activate the coagulation and thereby play a major role in the pathogenesis of fibrin deposition and thrombus formation in diseases that are associated with the presence of these antibodies.

Antibodies↗
PubMed1999

Electromagnetic fields may act directly on DNA.

A wide variety of environmental stimuli induce the expression of stress response genes, including high temperatures, hypoxia, heavy metal ions, and amino acid analogs. Stress genes are also induced by low frequency magnetic fields. The cellular response to magnetic fields is activated by unusually weak stimuli, and involves pathways only partially associated with heat shock stress. Since magnetic fields interact with moving charges, as we have shown in enzymes, it is possible that magnetic fields stimulate the stress response by interacting directly with moving electrons in DNA. In this paper, we review several lines of evidence that support this hypothesis.

Animals↗
PubMed1999

A magnetic field-responsive domain in the human HSP70 promoter.

HSP70 gene expression is induced by a wide range of environmental stimuli, including 60-Hz electromagnetic fields. In an earlier report we showed that the induction of HSP70 gene expression by magnetic fields is effected at the level of transcription and is mediated through c-myc protein binding at two nCTCTn sequences at -230 and -160. in the human HSP70 promoter. We report on the identification of a third c-myc binding site (between -158 and -162) that is an important regulator of magnetic field-induced HSP70 expression. We also show that the heat shock element (HSE), lying between -180 and -203, is required for induction of HSP70 gene expression by magnetic fields. The HSE centered at -100 alone is insufficient.

Binding Sites↗
PubMed1999

Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides.

Antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, repeated thromboembolic phenomena, and thrombocytopenia. The syndrome is believed to be caused by antiphospholipid beta-2-glycoprotein-I (beta2GPI)-dependent Abs or anti-beta2GPI Abs by themselves. Using a hexapeptide phage display library, we identified three hexapeptides that react specifically with the anti-beta2GPI mAbs ILA-1, ILA-3, and H-3, which cause endothelial cell activation and induce experimental APS. To enhance the binding of the peptides to the corresponding mAbs, the peptides were lengthened to correspond with the site of the beta2GPI epitope being recognized by these mAbs. As a result, the following three peptides were prepared: A, NTLKTPRVGGC, which binds to ILA-1 mAb; B, KDKATFGCHDGC, which binds to ILA-3 mAb; and C, CATLRVYKGG, which binds to H-3 mAb. Peptides A, B, and C specifically inhibit both in vitro and in vivo the biological functions of the corresponding anti-beta2GPI mAbs. Exposure of endothelial cells to anti-beta2GPI mAbs and their corresponding peptides led to the inhibition of endothelial cell activation, as shown by decreased expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1) and monocyte adhesion. In vivo infusion of each of the anti-beta2GPI mAbs into BALB/c mice, followed by administration of the corresponding specific peptides, prevented the peptide-treated mice from developing experimental APS. The use of synthetic peptides that focus on neutralization of pathogenic anti-beta2GPI Abs represents a possible new therapeutic approach to APS.

Animals↗
PubMed1999

Overproduction of the Opi1 repressor inhibits transcriptional activation of structural genes required for phospholipid biosynthesis in the yeast Saccharomyces cerevisiae.

Transcription of structural genes required for phospholipid biosynthesis in the yeast Saccharomyces cerevisiae is repressed by high concentrations of inositol and choline. The ICRE (inositol/choline-responsive element), which is necessary and sufficient for regulation by phospholipid precursors, functions as a binding site for the heterodimeric Ino2/Ino4 activator. ICRE-dependent transcription becomes constitutive in the absence of the Opi1 repressor. Opi1 contains a leucine zipper motif and two glutamine-rich stretches. In this work we describe a molecular analysis of OPI1 function and expression. Opi1 mutant variants altered at the leucine zipper and a glutamine-rich region, respectively, were no longer functional repressors. In contrast, an Opi1 deletion variant lacking the N-terminal 106 amino acids still mediated negative regulation. Although the leucine zipper suggests that Opi1 may act as a DNA-binding protein, our data do not support a direct interaction with the ICRE. Despite its function as an antagonist of INO2 and INO4, expression of OPI1 is stimulated by an upstream ICRE. Overexpression of OPI1 under control of the GAL1 promoter severely inhibited activation of ICRE-dependent genes, leading to inositol-requiring cells. Growth inhibition of GAL1-OPI1 was observed with INO2 and INO4 alleles activated by either the natural promoter or a heterologous control region. Although induction of GAL1-OPI1 strongly repressed ICRE-dependent gene expression, the concentration of the Ino2/Ino4 activator remained unchanged. This finding suggests that differential expression of phospholipid biosynthetic genes may occur even in the presence of a constant amount of the specific activator.

Basic Helix-Loop-Helix Proteins↗
PubMed1999

Monoclonal anti-endothelial cell antibodies from a patient with Takayasu arteritis activate endothelial cells from large vessels.

OBJECTIVE: To create monoclonal anti-endothelial cell antibodies (mAECA) from a patient with Takayasu arteritis to evaluate their ability to activate human umbilical vein endothelial cells (HUVEC), and to characterize the mechanism of EC activation. METHODS: A panel of mAECA was generated from peripheral blood lymphocytes of a patient with Takayasu arteritis, using Epstein-Barr virus transformation. Activity against macrovascular EC (HUVEC) and microvascular EC (human bone marrow EC immortalized by SV40) antigens was detected by enzyme-linked immunosorbent assay. Inhibition studies were used to select the monoclonal antibodies (mAECA) which share the same EC epitope binding specificity as the total IgG-AECA from the Takayasu arteritis patient. The binding of the mAECA to human aortic EC was studied by immunohistochemistry. The secretion levels of interleukin-6 (IL-6) and von Willebrand factor (vWF) were determined, to serve as markers for EC activation. The activated EC were examined for the adherence of a monocytic cell line (U937), as well as for expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin. In addition, nuclear extracts of the mAECA-treated EC were analyzed for the induction of translocation of nuclear factor kappaB (NF-kappaB), using a specific NF-kappaB oligoprobe in an electrophoretic mobility shift assay. RESULTS: Six mAECA were selected, the mixture of which produced 100% inhibition of binding of the original IgG (from the patient with Takayasu arteritis) to HUVEC. All mAECA possessed high activity against macrovascular EC, but none had significant antimicrovascular EC activity. The mAECA, but not normal human IgG, had anti-human aortic EC activity. Four of the 6 mAECA activated EC, manifested by increased IL-6 and vWF secretion. The 4 mAECA induced EC expression of adhesion molecules and increased adhesion of U937 monocytic cells to EC. In addition, these mAECA stimulated the nuclear translocation of the NF-kappaB transcription factor. CONCLUSION: Our findings suggest that AECA may directly stimulate EC in Takayasu arteritis through elevation of adhesion molecule expression associated with NF-kappaB activation and adhesion of monocytes, and may therefore play a pathogenic role in the development of the vasculopathy in Takayasu arteritis.

Adult↗