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Biomedical subjects

I Goldberg

Publications and source records attributed to I Goldberg.

At least 19 recordsLinked to original sources

Comparison of objective diagnostic tests in glaucoma: Heidelberg retinal tomography and multifocal visual evoked potentials.

PURPOSE: To compare sensitivity and specificity of functional and structural changes in glaucoma using two objective tests: the multifocal visual evoked potential (m-VEP) and Heidelberg retinal tomography II (HRT). PATIENTS AND METHODS: 41 glaucoma patients and 25 normal individuals participated in the study. One eye per individual was included in the study. Individuals were evaluated with Humphrey visual field (HVF) perimetry, m-VEP, and HRT. Moorfield regression analysis findings of HRT were compared with presence of scotoma on m-VEP. Linear regression analysis of quantitative variables, such as HVF mean deviation (MD), m-VEP discriminant score (Accumap Severity Index) and, global HRT parameters was also performed. RESULTS: m-VEP sensitivity and specificity were 93% and 96% respectively. HRT sensitivity and specificity were 79% and 92% respectively. The area under the receiver operating characteristic curve (ROC) for m-VEP was 0.96 and for HRT varied from 0.79 to 0.86 depending on the parameters used. Linear correlation between MD and Accumap Severity Index score was -77%, while that between HRT global parameters, Accumap Severity Index and MD were at best around 50%. Topographic comparison of the presence of scotoma on HVF and m-VEP in different areas of the visual field showed good agreement. Comparison of optic nerve head structural abnormality with corresponding areas of field defects on HVF and m-VEP showed poor to moderate agreement. CONCLUSION: The objective test of optic nerve function (m-VEP) and structure (HRT) can detect glaucomatous damage, with limited correlation. The 2 functional tests, HVF and m-VEP correlate better with each other than with HRT. It remains important to look for both functional and structural changes in order to detect all glaucoma cases.

Aged↗

Topography of the frequency doubling perimetry visual field compared with that of short wavelength and achromatic automated perimetry visual fields.

BACKGROUND: Traquair described the topography of visual field sensitivity as a "hill" or "island" of vision. Achromatic automated perimetry (AAP) demonstrates this shape of the visual field in photopic conditions. Techniques claimed to target the magnocellular pathway (frequency doubling perimetry, FDP) and those using a stimulus targeting the koniocellular pathway (short wavelength (or blue on yellow) automated perimetry, SWAP), might produce one that is different. The authors compared the visual field topography from FDP with those of SWAP and AAP, to investigate whether there were significant differences in their shape. METHOD: A sample of 51 patients with previously confirmed normal perimetry were recruited; either low risk glaucoma suspects or normal controls. AAP, SWAP, and FDP perimetry was performed in random order on the same day. The topography of each field was analysed to determine its average shape and to compare results in the same individuals. RESULTS: The topography of the visual field produced by each perimeter differed significantly. While all three had maximal sensitivity centrally, over the 24 degrees from the centre to the periphery, mean sensitivities decreased by 4.9 decibels (dB) for AAP and 7.3 dB for SWAP, while FDP sensitivities by just 1.8 dB over 20 degrees (the extent of the FDP field). FDP mean sensitivities decreased by approximately 0.3 dB with every 10 year increase in age, compared with 1 dB for AAP and 2 dB for SWAP. CONCLUSION: While the topography of the SWAP (koniocellular) field is steeper than corresponding AAP fields, that of the FDP (magnocellular) visual field was considerably flatter. The difference in this shape may reflect retinotopic or cortical mechanisms, which are specific to the magnocellular pathways.

Adult↗

Libman-Sacks endocarditis associated with antiphospholipid syndrome and infection.

INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated not only with a hypercoagulable state and recurrent fetal loss but with many diverse clinical manifestations including heart involvement, neurological manifestations, as well as skin, kidney and hematologic abnormalities. Cardiac manifestations include coronary by-pass graft and angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease, intracardiac thrombus and complications of cardiovascular surgery. The valvular heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously, we have shown a linear subendothelial deposition of anti-cardiolipin/beta2 glycoprotein I (beta2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta2GPI-related target epitope recognized by the anti-beta2GPI Abs on the valves. MATERIALS AND METHODS: In order to find the beta2GPI-related target epitopes recognized by the anti-beta2GPI antibodies on the valves, we used beta2GPI-related synthetic peptides. The presence of anti-beta2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta2GPI Abs deposited on the patient's valve. The binding was probed by streptavidin-peroxidase and appropriate substrate. The specificity was confirmed by competition assays with control peptide and anti-idiotypic antibody. RESULTS: Among the beta2GPI-related synthetic peptides, two peptides were found in previous studies to mimic common pathogens either bacteriae or viruses, which raised a possible infectious origin for APS. One of these peptides, TLRVYK, is a specific target for anti-beta2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta2GPI anti-idiotypic Abs for binding the anti-beta2GPI Abs on the valve by a competition assay. CONCLUSION: We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin.

Antibodies, Anticardiolipin↗

ErbB2 is a tumor associated antigen and a suitable therapeutic target in Wilms tumor.

PURPOSE: The modern multimodality therapeutic approach to Wilms tumor (WT), combining surgery with radiotherapy and chemotherapy results in high cure rates even for high stage disease. However, the combination of radiotherapy and chemotherapy is associated with severe early and late complications such as neutropenic sepsis, growth retardation and secondary malignancies. Therefore, novel therapeutic strategies, which would decrease the treatment burden, are required. We studied the expression of erbB2 growth factor receptor in WT cells as well as its role as a tumor therapeutic target in an in vivo xenograft model of Wilms tumor. MATERIALS AND METHODS: Paraffin embedded pathological samples from 14 different WT cases as well as xenografts derived thereof were immunostained with anti-erbB2 monoclonal antibody. The immunostaining was graded in comparison to a known positive control (breast cancer) and was scored by the intensity of staining (0 to +3) multiplied by the percentage of cells expressing the antigen. The expression of erbB2 in the human WT xenograft was verified also by fluorescence activated cell sorter analysis. In addition, nude mice bearing established subcutaneous human WT xenografts were treated with either 3 intraperitoneal injections of N29 anti-erbB2 monoclonal antibody or irrelevant antibody. RESULTS: All of the authentic human pathological samples, except 1 anaplastic WT as well the WT xenografts (at different stages), expressed erbB2. Expression was also observed in WT metastasis and in tumors which out grew chemotherapy. Systemic administration of anti-erbB2 monoclonal antibody inhibited and even prevented the growth of WT xenograft in vivo. CONCLUSIONS: ErbB2 is a tumor associated antigen in WT. Being expressed in almost all tumor stages, our in vivo model suggests that erbB2 may serve as a WT therapeutic target. Further work is needed to establish the role of erbB2 in the disease and its potential use in decreasing current treatment burden.

Adolescent↗

Common ancestral origin of pemphigus vulgaris in Jews and Spaniards: a study using microsatellite markers.

Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes. The association of pemphigus with human leukocyte antigen (HLA) is widely accepted. It was described in many ethnic groups and in most countries of the world. Studies showed that the associated HLA haplotype in Jewish pemphigus vulgaris (PV) patients is HLA-B38, DRB1*0402, and DQB1*0302; or HLA-B35, DRB1*0402, and DQB1*0302. Similar associations with class II genes were found in Spanish non-Jewish PV patients. As Jews lived in Spain for hundreds of years and many converted to Christianity, the presence of the same HLA haplotype in the Jewish and Spanish PV suggests that they may share the same founder. Microsatellite markers which span the entire major histocompatibility complex (MHC) locus were used as genetic probes. They were utilized to dissect the MHC region in the search for possible common haplotypes, besides HLA, which may provide an answer to this question. It was found that in both cohorts, in addition to HLA class II genes, there are probably genes in the class I region which are associated with PV. Alleles belonging to the associated markers were used to construct haplotypes and to estimate genetic distances. The distance between the two PV cohorts is relatively short, but the distance between the Jewish patients and the Jewish controls is greater compared to the distance between Spanish patients and Spanish controls. In both PV populations, the same microsatellite haplotypes in addition to a common class II haplotype were found, suggesting that both patient populations originated from the same genetic stock and, therefore, share the same ancestral disease gene.

Alleles↗

The loss of calretinin expression indicates aganglionosis in Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HD) is a congenital disorder characterised by the absence of ganglion cells in the large bowel, leading to functional obstruction and colonic dilatation proximal to the affected segment. A subclass of nerve cell bodies in both submucosa and myenteric ganglia of the human gastrointestinal tract were found to show immunopositivity for calretinin, a calcium binding protein, which plays an important role in the organisation and functioning of the central nervous system. AIM: To investigate calretinin immunostaining in ganglionic and aganglionic HD colon specimens, and compare it with staining for S100, neurone specific enolase, and c-kit. METHODS: Ten large bowel, full thickness specimens from patients with classic rectosigmoid HD were selected from the pathology repository. In total, 54 paraffin wax blocks-24 from the ganglionic zone, 17 from the aganglionic zone, and 13 from the transitional zone-were processed. RESULTS: Calretinin was not expressed in aganglionic segments of HD and associated nerve fibres, whereas in ganglionic HD segments and in normal colon both ganglion cells and nerve fibres were immunopositive. In addition, c-kit showed an altered distribution in the interstitial cells of Cajal. The transitional zone showed a broad spectrum of histomorphological and immunohistochemical patterns of both calretinin and c-kit expression. CONCLUSION: The absence of calretinin expression may serve as a diagnostic aid in identifying aganglionic segments in HD.

Adult↗

Overexpression of 15-lipoxygenase in the vascular endothelium is associated with increased thymic apoptosis in LDL receptor-deficient mice.

BACKGROUND: 15-Lipoxygenase (15-LO) is a nonheme iron-containing enzyme that catalyzes the peroxidation of fatty acids. Herein, we studied the effect of 15-LO overexpression in the vascular endothelium on thymocyte apoptosis by evaluating thymuses from low-density lipoprotein receptor-deficient (LDL-RD) mice and LDL-RD/15-LO mice. Thymuses were evaluated by immunohistochemistry and by TUNEL whereas in vitro studies were carried out by employing freshly isolated thymocytes from the respective mice and evaluation of apoptosis by propidium iodide and annexin V cytometry. METHODS AND RESULTS: The apoptotic index in LDL-RD/15-LO mice was significantly higher than in the LDL-RD mice. In the thymic medulla the difference was smaller, although still significant. Freshly isolated thymus cells from LDL-RD/15-LO mice exhibited a higher rate of spontaneous cell death than controls. Incubation of thymus cells in the presence of the cell-permeable caspase-3 inhibitor DEVD-CMK resulted in a decrease in the frequency of apoptotic cells in LDL-RD/15-LO thymocytes, whereas no effect was evident in control thymocytes. The antioxidant N-acetylcysteine causes the increase in apoptosis in both groups. CONCLUSION: LDL-RD/15-LO mice exhibit increased thymocyte apoptosis both in vivo and in vitro. These findings may suggest a role for 15-LO in the natural selection of thymocytes.

Acetylcysteine↗

Pemphigus can be induced by topical phenol as well as by foods and drugs that contain phenols or thiols.

Pemphigus is an autoimmune disease that results from the interaction between predisposing genetic factors and exogenous factors, the most common environmental factors being drugs and food. Topical phenol has induced pemphigus in one patient. Drugs and foods that induce pemphigus are divided into three main groups according to their chemical structure: thiols (containing a sulfhydryl group), phenol, nonthiol nonphenol. Thiol and phenol compounds can induce acantholysis in tissue cultures in vitro. The suggested mechanisms for thiol acantholysis include direct biochemical impairment of cell adhesion, protease activation and immunological reaction with the formation of a neoantigen. Possible mechanisms of phenol-induced pemphigus include the induction of IL-1alpha and TNF-alpha release by keratinocytes. These cytokines have been shown to be relevant in the regulation and synthesis of complement and proteases, like plasminogen activator, which has been implicated in the pathogenesis of acantholysis in pemphigus vulgaris. Avoiding exposure of genetically predisposed individuals to these factors is important in treating and preventing this disease.

Journal Article↗

A comparison of perimetric results with the Medmont and Humphrey perimeters.

BACKGROUND: The Humphrey field analyser (HFA), Humphrey-Zeiss frequency doubling perimeter, and the Medmont automated perimeter (MAP) are three commonly used automated perimeters with threshold achromatic methodologies. Visual field loss may be detected earlier with strategies that target cell lines with reduced redundancy or which suffer selective damage. METHOD: To compare these three perimeters, 63 subjects who were glaucoma suspects, ocular hypertensives, glaucoma patients, or normal controls were recruited selectively. All subjects underwent testing using MAP central threshold, MAP flicker perimetry, HFA full threshold, HFA SITA perimetry, HFA short wavelength perimetry (SWAP), and frequency doubling perimetry (FDP). After visual field testing, equivalent tests were compared: MAP central threshold with HFA full threshold and HFA SITA perimetry; Medmont flicker perimetry with HFA SWAP and FDP. RESULTS: On analysis of the MAP central threshold a kappa statistic and an area under the receiver operator curve (AUC) of 0.90 and 0.94, respectively, were found compared with HFA full threshold strategies, and 0.87 and 0.92 respectively, compared with HFA SITA. For MAP flicker a kappa statistic and an AUC of 0.65 and 0.81, respectively, were found compared with HFA SWAP and 0.87 and 0.96, respectively, compared with FDP. A quadrant analysis and comparison of mean defect between tests was also highly significant. CONCLUSION: Medmont and Humphrey perimeters correlated well; both may be used for clinical and research purposes with similar confidence.

Area Under Curve↗

Chromium corroles in four oxidation States.

We have isolated and characterized chromium complexes of 5,10,15-tris(pentafluorophenyl)corrole [(tpfc)H(3)] (1) in four oxidation states: [(tpfc(*))CrO][SbCl(6)] (6); [(tpfc)CrO] (2); [(tpfc)CrO][Cp(2)Co] (4); and [(tpfc)Cr(py)(2)] (3). Complex 6 was prepared both by electrochemical and chemical oxidation of 2; its formulation as a Cr(V)O ligand-radical species is based on UV-visible absorption as well as EPR measurements. Cobaltocene reduction of 2 gave 4; it was identified as a diamagnetic d(2) Cr(IV)O complex from its sharp (1)H NMR spectrum. Reaction of 2 with triphenylphosphine yielded a chromium(III) corrole, [(tpfc)Cr(OPPh(3))(2)] (5). Owing to its air sensitivity, 5 could not be isolated in the absence of excess OPPh(3). The structure of the Cr(III) bis-pyridine complex (3) was determined by X-ray crystallography (Cr-N distances: 1.926-1.952 A, pyrrole; 2.109, 2.129 A, pyridine).

Journal Article↗

Highly selective chlorosulfonation of tris(pentafluorophenyl)corrole as a synthetic tool for the preparation of amphiphilic corroles and metal complexes of planar chirality.

[reaction: see text]. The chlorosulfonation of tris(pentafluorophenyl)corrole proceeds with an extremely high selectivity as to afford one out of 139 possible isomers in very high yield. The bis-chlorosulfonated corrole is an excellent precursor to the planar-chirality (triphenylphosphine)cobalt(III) complex (fully characterized by X-ray crystallography) and to the amphiphilic bis-sulfonic acid derivative, both the first of their kind.

Cobalt↗

Living polymerization and block copolymerization of alpha-olefins by an amine bis(phenolate) titanium catalyst.

An amine bis(phenolate) dibenzyl titanium complex having a methoxy donor on a side arm leads, upon activation with tris(pentafluorophenyl)borane, to unique living properties in alpha-olefin polymerization: exceptionally high molecular weight poly(1-hexene) is obtained in a living fashion at room temperature, living polymerization of 1-hexene is obtained above room temperature, and block copolymerization of 1-hexene and 1-octene at room temperature is described as well.

Journal Article↗

Synthesis and structural characterization of a novel covalently-bound corrole dimer.

The (triphenylphosphine)cobalt(III) complex (2) of 5,10,15-tris(pentafluorophenyl)corrole (1) is shown to be an valuable precursor to complexes that have not been fully characterized previously. In contrast to other cobalt corroles, aromatic amines can be substituted for the triphenylphosphine in 2 to form six-coordinate bis(amine)cobalt(III) complexes. This is demonstrated by spectroscopic methods and by X-ray crystallography of the bis-pyridine complex 4, the first of its kind. While 2 and 4 and even their one-electron oxidized complexes are stable, a spontaneous dimerization of the corrole takes place in the absence of strongly bound ligands. The bis-cobalt complex of the novel corrole dimer 6 was fully characterized by spectroscopic methods and X-ray crystallography.

Cobalt↗

Coordination chemistry of amine bis(phenolate) titanium complexes: tuning complex type and structure by ligand modification.

The coordination chemistry of titanium(IV) complexes of amine bis(phenolate) ligands was investigated by synthesizing various types of complexes and analyzing them specroscopically and structurally. Steric effects of tridentate [ONO]- and tetradentate [ONNO]-type ligands were studied by reacting the ligand precursors with titanium tetra(isopropoxide). [ONNO]-type ligands featuring an amine donor located on a pendant arm led to octahedral bis(isopropoxide) complexes, regardless of the steric bulk around the metal. Several such complexes having varying steric crowding were thus synthesized. On the other hand, steric effects were found to play a major role in determining the complex constitution when [ONO]-type ligands, featuring no side donor, were involved. Relatively sterically undemanding ligands led to octahedral bis(homoleptic) complexes, whereas increased steric bulk resulted in the formation of pentacoordinate bis(isopropoxide) complexes. These pentacoordinate complexes readily lead to bis(heteroleptic) complexes by reaction with nonsterically demanding [ONO]- and [ONNO]-type ligand precursors. In the latter case the sidearm nitrogen remains uncoordinated to the metal. The bis(isopropoxide) complexes of the [ONNO]-type ligands may also lead to bis(heteroleptic) complexes, however, these reactions are much slower.

Journal Article↗

Synthesis and characterization of germanium, tin, phosphorus, iron, and rhodium complexes of tris(pentafluorophenyl)corrole, and the utilization of the iron and rhodium corroles as cyclopropanation catalysts.

The germanium(IV), tin(IV). and phosphorus(v) complexes of tris(pentafluorophenyl)corrole were prepared and investigated by electrochemistry for elucidation of the electrochemical HOMO-LUMO gap of the corrole and the spectroscopic characteristics of the corrole pi radical cation. This information was found to be highly valuable for assigning the oxidation states in the various iron corroles that were prepared. Two iron corroles and the rhodium(I) complex of an N-substituted corrole were fully characterized by X-ray crystallography and all the transition metal corroles were examined as cyclopropanation catalysts. All iron (except the NO-ligated) and rhodium corroles are excellent catalysts for cyclopropanation of styrene, with the latter displaying superior selectivities. An investigation of the effect of the oxidation state of the metal and its ligands leads to the conclusion that for iron corroles the catalytically active form is iron(III), while all accesible oxidation states of rhodium are active.

Journal Article↗