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Biomedical subjects

Z Szabo

Publications and source records attributed to Z Szabo.

At least 19 recordsLinked to original sources
PubMed2005

Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene.

BACKGROUND: Cutis laxa is an acquired or inherited condition characterized by redundant, pendulous and inelastic skin. Autosomal dominant cutis laxa has been described as a benign disease with minor systemic involvement. OBJECTIVE: To report a family with autosomal dominant cutis laxa and a young girl with sporadic cutis laxa, both with variable expression of an aortic aneurysmal phenotype ranging from mild dilatation to severe aneurysm or aortic rupture. METHODS AND RESULTS: Histological evaluation of aortic aneurysmal specimens indicated classical hallmarks of medial degeneration, paucity of elastic fibres, and an absence of inflammatory or atherosclerotic lesions. Electron microscopy showed extracellular elastin deposits lacking microfibrillar elements. Direct sequencing of genomic amplimers detected defects in exon 30 of the elastin gene in affected individuals, but did not in 121 normal controls. The expression of mutant elastin mRNA forms was demonstrated by reverse transcriptase polymerase chain reaction analysis of cutis laxa fibroblasts. These mRNAs coded for multiple mutant tropoelastins, including C-terminally truncated and extended forms as well as for molecules lacking the constitutive exon 30. CONCLUSIONS: ELN mutations may cause severe aortic disease in patients with cutis laxa. Thus regular cardiac monitoring is necessary in this disease to avert fatal aortic rupture.

Adult↗
PubMed2005

Cloning, sequencing, structural and molecular biological characterization of placental protein 20 (PP20)/human thiamin pyrophosphokinase (hTPK).

Full-length cDNAs of placental protein 20 (PP20) were cloned by screening a human placental cDNA library, which encode a 243 amino acid protein, identical to human thiamin pyrophosphokinase (hTPK) as confirmed by protein sequence analysis. Genomic alignment showed that the PP20/hTPK gene contains 9 exons. It is abundantly expressed in placenta, as numerous EST clones were identified. As thiamine metabolism deficiencies have been seen in placental infarcts previously, these indicate that PP20/hTPK may have a role in placental diseases. Analysis of the 1kb promoter region showed numerous putative transcription factor binding sites, which might be responsible for the ubiquitous PP20/hTPK expression. This may also be in accordance with the presence of the protein in tissues responsible for the regulation of the exquisite balance between cell division, differentiation and survival. TPK activity of the purified and recombinant protein was proved by mass spectrometry with electrospray ionization. By Western blot, PP20/hTPK was found in all human normal and tumorous adult and fetal tissues in nearly equal amounts, but not in sera. By immunohistochemical and immunofluorescent confocal imaging methods, diffuse labelling in the cytoplasm of the syncytiotrophoblasts and weak staining of the trophoblasts were observed, and the amount of PP20/hTPK decreased from the first trimester to the end of gestation. A 3D model of PP20/hTPK was computed (PDB No.: 1OLY) by homology modelling. A high degree of structural homology showed that the thiamin binding site was highly similar to that of the mouse enzyme, but highly different from the bacterial ones. Comparison of the catalytic centre sequences revealed differences, raising the possibility of designing new drugs which specifically inhibit bacterial and fungal enzymes without affecting PP20/hTPK and offering the possibility for safe antimicrobial therapy during pregnancy.

Adult↗
PubMed2004

[Technical note: ulnar "pseudo-pollicisation" in congenital hand differences].

In certain rare cases of thumb aplasia or hypoplasia, pollicisation of the second finger is not recommended or impossible. It happens when the most radial fingers are hypoplastic or abnormal or when an ulnar prehension pattern has already developed. In these cases, if functional, pollicisation of the most ulnar finger in not suitable because of the ugly cosmetic result. In order to combine the functional advantages of the ulnar pollicisation with a satisfactory cosmetic appearance, the authors describe pseudo-ulnar pollicisation by supination osteotomy. This operation combines rotation of the fifth ray with the establishment of a larger web space between the two most ulnar fingers. We have used this technique in five preliminary cases with a minimum follow-up of 18 months.

Esthetics↗
PubMed2004

[The ulnar longitudinal deficiency: proposition of a descriptive classification].

Ulnar longitudinal deficiency is an extended malformation sometimes involving the whole upper extremity, even including sometimes the opposite side. The clinical and radiological aspects are variable and none of the existing classifications takes into account all the possible deformities. Multiple decisive factors in the surgical indications are missing such as shoulder stability, elbow position (extension or flexion with or without pterygium), orientation of the hand (internal rotation), wrist inclination and number of digits. Based on a review of our 46 clinical cases as well as the published cases in the literature we have developed a simple way to describe each level.

Humans↗
PubMed2002

Transvaginal extraction of the laparoscopically removed spleen.

Laparoscopic removal of normal and moderately enlarged spleens has become the gold standard operation in recent years because its short operative time, technical safety, and quick patient recovery time. The best method for extraction of the removed spleen, however, has not yet been determined. The authors present a new method for the extraction of the laparoscopically removed spleen. Using a transvaginal approach, the organ is removed through an incision on the posterior vaginal wall and exteriorized in a laparobag. The procedure is similar to a routine vaginal hysterectomy, but is technically much simpler to perform.

Cholecystectomy, Laparoscopic↗
PubMed2001

Changes in sample collection and analytical techniques and effects on retrospective comparability of low-level concentrations of trace elements in ground water.

Ground-water sampling techniques were modified to reduce random low-level contamination during collection of filtered water samples for determination of trace-element concentrations. The modified sampling techniques were first used in New Jersey by the US Geological Survey in 1994 along with inductively coupled plasma-mass spectrometry (ICP-MS) analysis to determine the concentrations of 18 trace elements at the one microgram-per-liter (microg/L) level in the oxic water of the unconfined sand and gravel Kirkwood-Cohansey aquifer system. The revised technique tested included a combination of the following: collection of samples (1) with flow rates of about 2 L per minute, (2) through acid-washed single-use disposable tubing and (3) a single-use disposable 0.45-microm pore size capsule filter, (4) contained within portable glove boxes, (5) in a dedicated clean sampling van, (6) only after turbidity stabilized at values less than 2 nephelometric turbidity units (NTU), when possible. Quality-assurance data, obtained from equipment blanks and split samples, indicated that trace element concentrations, with the exception of iron, chromium, aluminum, and zinc, measured in the samples collected in 1994 were not subject to random contamination at 1 microg/L. Results from samples collected in 1994 were compared to those from samples collected in 1991 from the same 12 PVC-cased observation wells using the available sampling and analytical techniques at that time. Concentrations of copper, lead, manganese and zinc were statistically significantly lower in samples collected in 1994 than in 1991. Sampling techniques used in 1994 likely provided trace-element data that represented concentrations in the aquifer with less bias than data from 1991 when samples were collected without the same degree of attention to sample handling.

Environmental Monitoring↗
PubMed2001

Coordinate regulation of canine glomeruli and adrenal angiotensin receptors by dietary sodium manipulation.

BACKGROUND: This study evaluated the effects of dietary sodium manipulation in dogs on the regulation of canine angiotensin receptors (cAT1 and cAT2) in the kidney and adrenal. METHODS: Isolated glomeruli and membranes from renal medulla and the adrenal gland were used in radioligand binding assays from two groups of dogs: dogs maintained on low-sodium diet for two weeks followed by a high-sodium diet for two weeks (H), and dogs were maintained on the reverse schedule (L). RESULTS: Analysis of the binding data showed that dietary sodium manipulation had no significant effects on cAT1 and cAT2 receptor binding affinities in glomeruli, renal medulla, and adrenal tissues. In contrast, dietary sodium loading induced a marked increase in cAT1 receptor expression in both the glomeruli and adrenal compared with receptor expression in salt-restricted animals [H/L ratio: glomeruli (1.5), renal medulla (1.1), adrenal (1.6)] that inversely correlated with the activity of the plasma renin angiotensin system. Conversely, adrenal cAT2 receptor expression was regulated in an inverse manner in the H and L animal groups [H/L ratio: 0.7]. CONCLUSIONS: This study demonstrates that renal glomerular and adrenal AT1 receptors in the dog are coordinately down-regulated by dietary sodium restriction compared with sodium loading, which is distinctly different from the reciprocal regulation observed for rat AT1 receptors in these tissues. Collectively, these data suggest that postreceptor events in dogs are determinants of the aldosterone response observed during sodium restriction. These findings have important implications for the regulation of the renin-angiotensin system in humans, and suggest that coordinate regulation of AT1 receptors in the adrenal and glomeruli represent a negative feedback mechanism that when functioning normally prevents fluctuations of arterial blood pressure and development of arterial hypertension in response to changes in dietary sodium.

Adrenal Glands↗
PubMed2001

Magnetic resonance image analysis by information theoretic criteria and stochastic site models.

Quantitative analysis of magnetic resonance (MR) images is a powerful tool for image-guided diagnosis, monitoring, and intervention. The major tasks involve tissue quantification and image segmentation where both the pixel and context images are considered. To extract clinically useful information from images that might be lacking in prior knowledge, we introduce an unsupervised tissue characterization algorithm that is both statistically principled and patient specific. The method uses adaptive standard finite normal mixture and inhomogeneous Markov random field models, whose parameters are estimated using expectation-maximization and relaxation labeling algorithms under information theoretic criteria. We demonstrate the successful applications of the approach with synthetic data sets and then with real MR brain images.

Algorithms↗
PubMed2001

In vivo labeling of endothelin receptors with [(11)C]L-753,037: studies in mice and a dog.

UNLABELLED: Endothelin (ET) is a potent mammalian vasoconstrictive peptide and a pressor agent. Its 3 isoforms, ET-1, ET-2, and ET-3, mediate several physiologic actions in several organ systems, binding to 2 major receptor subtypes: ET(A) and ET(B). This study was undertaken to evaluate [(11)C]L-753,037 [(+)-(5S,6R,7R)-2-butyl-7-[2-((2S)-2-carboxy-propyl)-4-methoxyphenyl]-5-(3,4-methylenedioxyphenyl)cyclopenteno [1,2-beta]pyridine-6-carboxylate), a new mixed ET receptor A and B antagonist, as a tracer for in vivo labeling of ET receptors in mice and a dog. METHODS: [(11)C]L-753,037 was synthesized, purified, and formulated from a normethyl precursor, L-843,974, and [(11)C]H(3)I. The tracer was studied for its in vivo kinetics, biodistribution, and ET receptor binding characteristics in mice. In the dog, PET imaging was performed to evaluate binding of [(11)C]L-753,037 to ET receptors in the heart. Specificity of binding was studied in the heart with the selective ET(A) antagonist L-753,164. RESULTS: Kinetic studies in mice showed highest tracer uptake at 5 min after injection in liver (25.0 percentage injected dose per gram [%ID/g]), kidneys (18.7 %ID/g), lungs (15.2 %ID/g), and heart (5.6 %ID/g). Initial high uptake in liver, lungs, and kidneys was followed by rapid washout during the next 10 min and a very slow clearance during the time of observation (2 h after injection). By contrast, the radioactivity in the heart remained constant over 2 h. Administration of both ET(A) (L-753,164) and mixed ET(A)/ET(B) (L-753,137) receptor antagonists resulted in dose-dependent inhibition of [(11)C]L-753,037 binding in mouse heart, lungs, and kidneys but not in the liver. Radioactivity in the brain was very low, indicating that the tracer does not cross the blood-brain barrier. In the dog, a dynamic PET study of the heart showed high tracer accumulation at 55-95 min after injection. Injection of L-753,164 at 30 min before [(11)C]L-753,037 administration led to a significant reduction in tracer binding. [(11)C]methyl triphenyl phosphonium was used as a tracer for reference images of the dog heart muscle. CONCLUSION: The results suggest that [(11)C]L-753,037 binds to ET receptors in vivo and is, therefore, a promising candidate for investigation of these receptors and their occupancy by ET receptor antagonists using PET.

Animals↗
PubMed2000

Toxicodynamics and long-term toxicity of the recreational drug, 3, 4-methylenedioxymethamphetamine (MDMA, 'Ecstasy').

The recreational drug, (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), is a potent serotonin (5-HT) neurotoxin in animals. Whether humans who use MDMA incur 5-HT neural injury is unknown. The present studies utilized positron emission tomography (PET) in conjunction with the 5-HT transporter ligand, [11C]McN-5652 to assess the status of brain 5-HT neurons in human MDMA users. Like nonhuman primates treated with neurotoxic doses of MDMA, humans with a history of MDMA use showed lasting decrements in global brain [11C]McN-5652 binding, with decreases in [11C]McN-5652 binding positively correlated to the extent of previous MDMA use. These results suggest that human MDMA use results in brain 5-HT neurotoxicity.

Animals↗
PubMed2000

Suturing and knotting techniques for thoracoscopic cardiac surgery.

The preceding description of E-CABG may seem excessively detailed, even redundant, for trained cardiac surgeons; however, the authors' extensive experience with training surgeons on endoscopic techniques suggests that, despite a high level of proficiency and dexterity that a surgeon may possess in open surgery, becoming equally proficient and dexterous in the endoscopic environment is not simple. Participating in an in-depth, systematic endoscopic microvascular surgery training program in a laboratory setting is essential before applying the previously described E-CABG techniques in humans. The E-CABG procedure is one of the most challenging endoscopic techniques. Successful completion of this procedure requires that the surgeon be motivated to succeed and willing to invest the time and effort necessary to develop the new skills. Also critical is the avoidance of the temptation to use devices and systems that promise to obviate the need to bother with learning these difficult endoscopic skills. Long term results of the minimally invasive approach remain to be defined. However, some early studies of port-access procedures are encouraging. To date, a prospective randomized clinical trial comparing conventional LAD bypass to E-CABG has not been conducted. Although most investigators believe that long term patency of the IMA to the LAD using either technique should be the same, this is as yet unproven. Nonetheless, the adaption of endoscopic skills by the cardiac surgeon will further advance the evolution of this specialty.

Coronary Artery Bypass↗
PubMed2000

Membrane-permeabilizing activities of cyclic lipodepsipeptides, syringopeptin 22A and syringomycin E from Pseudomonas syringae pv. syringae in human red blood cells and in bilayer lipid membranes.

The pore-forming activities of cyclic lipodepsipeptides (CLPs), syringopeptin 22A (SP22A) and syringomycin E (SRE) were compared on the human red blood cell (RBC) membrane and on bilayer lipid membranes (BLMs). SP22A above a concentration of 4 x 10(5) molecules/cell significantly increased the RBC membrane permeability for 86Rb. With electric current measurements on BLM, it was proved that like SRE, the SP22A formed two types of ion channels in the membrane, small and large, the latter having six times larger conductance and longer dwell time. Both CLPs formed clusters consisting of six small channels, and the channel-forming activity of SP22A is about one order of magnitude higher than that of SRE. A Hill coefficient of 2-3 estimated from the concentration dependence of these CLPs-induced lysis gave a proof of the pore oligomerization on RBCs. Transport kinetic data also confirmed that SP22A pores were oligomers of at least three monomers. While SRE pores were inactivated in time, no pore inactivation was observed with SP22A. The 86Rb efflux through SP22A-treated RBCs approached the tracer equilibrium distribution with a constant rate; a constant integral current was measured on the BLM for as long as 2.5 h as well. The partition coefficient (Kp = 2 x 10(4) l/mol) between the RBC membrane and the extracellular space was estimated for SRE to be at least six times higher than that for SP22A. This finding suggested that the higher ion permeability of the SP22A-treated cells compared to that of SRE was the result of the higher pore-forming activity of SP22A.

Cell Membrane Permeability↗
PubMed2000

Column-switching HPLC for the analysis of plasma in PET imaging studies.

A column-switch high performance liquid chromatography method for the analysis of 4 mL of plasma is described with six examples of chromatography of [(11)C]-labeled positron-emission tomography imaging agents. Complete extraction of all but the most polar metabolites by the reverse phase capture column is achieved by disruption of plasma protein binding by 8 M urea.

Chromatography, High Pressure Liquid↗
PubMed2000

Novel treatment of conformational flexibility using interval analysis

A revolutionary new flexible conformational search technique is presented together with its application to geometrical docking. The algorithm is guaranteed to find all (even an infinite number of) solutions in a continuous manner. Examples are given using 2-(4'-amidinophenyl)pyruvate (APPA) docked to trypsin. Other potential applications are briefly discussed.

Journal Article↗
PubMed1999

Altered bladder function in transgenic mice expressing rat elastin.

The elasticity of tissues subjected to repeated deformation is provided by the presence of elastic fibers in the extracellular matrix (ECM). The most abundant component of elastic fibers is elastin, whose soluble precursor is tropoelastin. To establish the role elastin plays in the bladder, this study describes the biosynthetic, histologic, and physiologic consequences of expression of an isoform of rat tropoelastin in transgenic mouse bladder. The polymerase chain reaction (PCR) was used to determine expression of a rat tropoelastin minigene in transgenic mice. Histochemical methods were used to demonstrate changes in elastic fibers in frozen sections of bladder. Cystometric analysis was carried out in transgenic and non-transgenic mice, prior to and after 3 weeks of partial outlet obstruction. The PCR assay demonstrated that bladder tissue of transgenic mice expressed rat tropoelastin mRNA, whereas non-transgenes did not. Increased deposition of elastic fibers was demonstrated with the Verhoeff-van Gieson stain. Bladders of transgenic animals were more compliant than bladders of their non-transgenic littermates. Partial outlet obstruction resulted in increased bladder volume and more compliant bladders in non-transgenic mice. In contrast, the bladder volume and compliance in transgenes was almost unchanged by obstruction. This study demonstrates that normal elastic fiber assembly is prerequisite for the compliant properties of the bladder wall. Moreover, the response of the bladder to obstruction is critically influenced by elastin synthesis.

Animals↗
PubMed1999

Effect of tracer metabolism on PET measurement of [11C]pyrilamine binding to histamine H1 receptors.

The present study was carried out to investigate the time course of [11C]pyrilamine metabolism and the degree of entry of metabolites into the brain. PET studies were performed in seven healthy volunteers and arterial plasma concentrations of [11C]pyrilamine and its labeled metabolites were determined. After intravenous injection, [11C]pyrilamine metabolized gradually in the human body, with less than 10% of plasma activity being original radioligand at 60 min. Tracer metabolism markedly affected the input function and the calculated impulse response function of the brain. Rat experiments demonstrated that although metabolites of [11C]pyrilamine might enter the brain, they were not retained for prolonged periods of time. At 30-90 min after injection of [11C]pyrilamine, less than 1% of the radioactivity in the brain was originating from metabolites of [11C]pyrilamine. Based on the rat data, the contribution of 11C-labeled metabolites to total [11C]pyrilamine radioactivity in the human brain was estimated and found to be negligible. These results suggest that the metabolites of [11C]pyrilamine do not accumulate within the cerebral extravascular space and that there is minimal metabolism of [11C]pyrilamine by brain tissue itself. Therefore, [11C]pyrilamine metabolites can be neglected in kinetic analysis, using either a compartmental or a noncompartmental model, of the [11C]pyrilamine binding to histamine H1 receptors.

Adult↗
PubMed1999

The value of a baseline bone scan in patients with newly diagnosed prostate cancer.

PURPOSE: This study evaluated the role of bone scans in managing newly diagnosed, untreated prostate cancer. METHODS: Two hundred seventy consecutive staging bone scans in patients (mean age, 69 years) with newly diagnosed prostate cancer who had serum prostate-specific antigen (PSA) determinations and biopsies between January 1995 and October 1997 were evaluated retrospectively. RESULTS: The bone scans were positive for metastatic bone disease in 24 patients and negative in 246. Serum PSA levels, the number of positive biopsy cores, the extent of tumor in the prostate gland, and Gleason scores were all significantly correlated with scintigraphic bone metastases (P < 0.0001 for each). Of the 177 patients with PSA levels less than 10 ng/ml, three had bone metastases. Bone metastases were found in 2 of 34 patients with PSA levels of 10.1 to 20 ng/ml, in 3 of 29 patients with PSA values of 20.1 to 50 ng/ml, and in 16 of 30 patients with PSA levels greater than 50.1 ng/ml. Only one patient had a bone metastasis when the prostate cancer involved fewer than 2 biopsy cores (1 of 135) or when disease was confined to one lobe (1 of 131), but the incidence increased significantly when the malignancy involved three or more biopsy cores (20 of 114) or disease was present in both prostate lobes (20 of 118). Four of 160 patients with Gleason scores less than 6 had bone metastases, whereas 20 of 110 patients with Gleason scores greater than 7 had bone metastases. CONCLUSIONS: The likelihood of bone metastases is low in patients with newly diagnosed, untreated prostate cancer when the initial PSA level was less than 10 ng/ml, the number of positive biopsy cores was less than 2, tumor was confined to one lobe, or the Gleason score was less than 6. However, none of these criteria can be used to exclude metastatic bone disease. A baseline bone scan is an important staging procedure and should be obtained to provide maximum data for clinical management of the disease.

Aged↗