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Biomedical subjects

J Farkas

Publications and source records attributed to J Farkas.

At least 37 records · Page 2Linked to original sources

Acute stroke: improved nonenhanced CT detection--benefits of soft-copy interpretation by using variable window width and center level settings.

PURPOSE: To assess the use of nonstandard, variable window width and level review settings in computed tomography (CT) without contrast material administration in the detection of acute stroke. MATERIALS AND METHODS: Nonenhanced CT was performed in 21 patients with acute (< 6 hours) middle cerebral arterial stroke and nine control patients. Two blinded neuroradiologists rated all scans for presence of parenchymal hypoattenuation. Images were reviewed at a picture archiving and communication system (PACS) workstation, with standard, locally determined center level and window width settings of 20 and 80 HU and with variable soft-copy settings initially centered at a level of 32 HU with a width of 8 HU. Reviewers altered settings to accentuate gray and white matter contrast. RESULTS: With standard viewing parameters, sensitivity and specificity for stroke detection were 57% and 100%. Sensitivity increased to 71% with variable window width and center level settings, without loss of specificity. Receiver operating characteristic analysis revealed a significant improvement in accuracy with nonstandard, soft-copy review settings (P = .03, one-tailed z test). CONCLUSION: In nonehanced CT of the head, detection of ischemic brain parenchyma is facilitated by soft-copy review with variable window width and center level settings to accentuate the contrast between normal and edematous tissue.

Acute Disease↗

Detection of adenovirus hexon sequence in a cat by polymerase chain reaction (short communication).

Adenoviral nucleic acid was detected by polymerase chain reaction (PCR) in pharyngeal and rectal swab samples of a cat seropositive for adenovirus and suffering from transient hepatic failure. The samples were taken at a one-year interval, and both faecal samples as well as the second pharyngeal sample were positive in PCR performed with general adenovirus primers. The size of the amplified products corresponded to that of the positive control. The identity of the amplicons was also confirmed by DNA sequencing. The 301 bp long hexon gene fragment was very similar to but distinguishable from the corresponding hexon sequence of human adenovirus type 2. This result suggests the possibility of persistent carrier status and shedding of adenovirus in cats.

Adenoviridae↗

Investigation of apparent diffusion coefficient and diffusion tensor anisotrophy in acute and chronic multiple sclerosis lesions.

BACKGROUND AND PURPOSE: The various stages of multiple sclerosis (MS) are characterized by de- and remyelination as well as by inflammation. Diffusion MR imaging is sensitive to tissue water motion, which might correspond to these pathologic processes. Our purpose was to demonstrate differences in apparent diffusion coefficient (ADC) and diffusion tensor anisotropy in acute and chronic MS plaques and in normal-appearing brain. METHODS: Twelve MS patients underwent conventional and full-tensor diffusion MR imaging with B = 1221 s/mm2. Derivation of trace ADC and calculation of anisotropic scalars, including eccentricity, relative anisotropy (RA), and fractional anisotropy (FA) was performed on a per-pixel basis. Regions of interest of plaques and normal structures were determined on coregistered maps. MS lesions were classified as acute, subacute, or chronic on the basis of their appearance on conventional images and in relation to clinical findings. RESULTS: Seven patients had acute plaques with a concentric arrangement of alternating high and low signal intensity on diffusion-weighted images. In nine acute lesions, plaque centers had high ADC with reduced anisotropy compared with rim, normal-appearing white matter (NAWM), and chronic lesions. The thin rim of diffusion-weighted hyperintensity surrounding the center showed variable ADC and anisotropic values, which were not statistically different from NAWM. Subacute and chronic MS lesions had intermediate ADC elevations/anisotropic reductions. Calculated FA pixel maps were superior to eccentricity or RA maps; however, quality was limited by signal-to-noise constraints. CONCLUSION: ADC and diffusion anisotropic scalars reflect biophysical changes in the underlying pathology of the demyelinating process.

Adolescent↗

Comparison of the endogenous heptapeptide Met-enkephalin-Arg6-Phe7 binding in amphibian and mammalian brain.

In previous communications [4, 38] we published that [3H]Met-enkephalin-Arg6-Phe7 (MERF) binds to opioid (kappa2 and delta) and sigma2 sites in frog and rat brain membrane preparations, however no binding to kappa1 sites could be established. In the present paper we compare the frog, rat and guinea pig brain membrane fractions with respect to their MERF binding data. No qualitative differences were found between the three species but specific binding of labelled MERF was maximal in frog brain and lowest in guinea pig brain, which corresponds to their kappa2 opioid receptor distribution. The naloxone resistant binding was also present in all investigated species and varied from 25% in frog and guinea pig cerebrum, to 50% in rat cerebrum and cerebellum, but no naloxone inhibition was found in guinea pig cerebellum where no kappa2 opioid receptors have been found. The presence of sigma2-like receptor was demonstrated in each investigated membrane fraction with displacement experiments using (-)N-allyl-normetazocine as competitor of tritiated MERF. It was shown that this site was responsible for 60-80% of [3H]MERF binding. The remaining part of the naloxone resistant labelled MERF binding could be displaced only with endogenous opioid peptides as met-enkephalin, dynorphin and beta-endorphin. The eventual physiological role of multiple MERF receptors is discussed.

Animals↗

Irradiation as a method for decontaminating food. A review.

Despite substantial efforts in avoidance of contamination, an upward trend in the number of outbreaks of foodborne illnesses caused by nonsporeforming pathogenic bacteria are reported in many countries. Good hygienic practices can reduce the level of contamination but the most important pathogens cannot presently be eliminated from most farms nor is it possible to eliminate them by primary processing, particularly from those foods which are sold raw. Several decontamination methods exist but the most versatile treatment among them is the processing with ionizing radiation. Decontamination of food by ionizing radiation is a safe, efficient, environmentally clean and energy efficient process. Irradiation is particularly valuable as an endproduct decontamination procedure. Radiation treatment at doses of 2-7 kGy--depending on condition of irradiation and the food--can effectively eliminate potentially pathogenic nonsporeforming bacteria including both long-time recognized pathogens such as Salmonella and Staphylococcus aureus as well as emerging or "new" pathogens such as Campylobacter, Listeria monocytogenes or Escherichia coli O157:H7 from suspected food products without affecting sensory, nutritional and technical qualities. Candidates of radiation decontamination are mainly poultry and red meat, egg products, and fishery products. It is a unique feature of radiation decontamination that it can also be performed when the food is in a frozen state. With today's demand for high-quality convenience foods, irradiation in combination with other processes holds a promise for enhancing the safety of many minimally processed foods. Radiation decontamination of dry ingredients, herbs and enzyme preparations with doses of 3-10 kGy proved to be a viable alternative to fumigation with microbicidal gases. Radiation treatment at doses of 0.15-0.7 kGy under specific conditions appears to be feasible also for control of many foodborne parasites, thereby making infested foods safe for human consumption. Microorganisms surviving low- and medium-dose radiation treatment are more sensitive to environmental stresses or subsequent food processing treatments than the microflora of unirradiated products. Radiation treatment is an emerging technology in an increasing number of countries and more-and-more clearances on radiation decontaminated foods are issued or expected to be granted in the near future.

Animals↗

Assessment of cerebral perfusion and arterial anatomy in hyperacute stroke with three-dimensional functional CT: early clinical results.

PURPOSE: Our purpose was to determine the clinical feasibility of quantitative three-dimensional functional CT in patients with hyperacute stroke. METHODS: Twenty-two patients who underwent clinically indicated CT angiography were studied: nine patients had no stroke, eight had mature stroke, and five had hyperacute stroke (less than 3 hours since ictus). Maps were obtained of perfused cerebral blood volume (PBV), and CT angiograms were generated by using standard techniques. RESULTS: Normal PBV values (mean +/- SEM) were 4.6 +/- 0.15% in the gray matter, 1.75 +/- 0.09% in the white matter, 2.91 +/- 0.20% in the cerebellum, 3.18 +/- 0.10% in the caudate, 2.84 +/- 0.23% in the putamen, 2.92 +/- 0.29% in the thalamus, and 1.66 +/- 0.03% in the brain stem. For patients with mature stroke, ischemic changes were visible on noncontrast, contrast-enhanced, and PBV scans. In patients with hyperacute stroke, ischemic changes were either absent or subtle before contrast administration, but became apparent on contrast-enhanced scans. Quantitative PBV maps confirmed reduced regional perfusion. CT angiograms in the hyperacute group showed occlusion of vessels in locations appropriate to the PBV deficits seen. CONCLUSION: Quantitative three-dimensional functional CT is feasible for patients with hyperacute stroke. It is performed by using helical CT techniques, and yields measures of cerebrovascular physiological function, which are useful in this patient population.

Acute Disease↗

Met5-enkephalin-Arg6-Phe7, an endogenous neuropeptide, binds to multiple opioid and nonopioid sites in rat brain.

Receptor binding properties of the naturally occurring opioid heptapeptide MERF were studied in rat brain membrane preparations using tritium-labeled derivative of the peptide with 40 Ci/mmol specific radioactivity. Binding assays were performed in the presence of broad-spectrum peptidase inhibitors at 0 degree C. Under these conditions, the equilibrium binding was achieved in 30-40 min, and approximately 90% of the applied radioligand remained unchanged as determined by HPLC analysis. The apparent affinity (Kd value) of [3H]Met-enkephalin-Arg6-Phe7, calculated from saturation binding data, was 10.2 +/- 2.5 nM, and the maximal number (Bmax) of the heptapeptide binding sites was found to be 468 +/- 43 fmol/mg protein. About half the sites represent nonopioid sites because the Bmax was only 255 +/- 30 fmol/mg, when the nonspecific binding was measured with 1 microM naloxone. The rank order potencies of the examined compounds revealed that the opioid component of [3H]Met-enkephalin-Arg6-Phe7 recognition site are probably not mu and certainly not kappa 1 sites, whereas these sites are characterized by a kappa 2-like binding profile. Considering the discrepancies between rat and frog brain found in the affinity of some compounds, including naltrindole and norbinaltorphimine, the presence of a novel, MERF-selective "heptapeptide" binding site in rat brain membranes is also suggested. A number of the heterologous competition curves could be described by a high-affinity stereospecific component and a substantially lower-affinity binding element, which could completely be displaced with several peptide ligands such as Met5-enkephalin, dynorphin(1-13), and unlabeled MERF but not by other compounds such as [D-Ala2-(Me)Phe4-Gly5-ol]enkephalin, morphine, or naloxone. [3H]Met-enkephalin-Arg6-Phe7 binding can also be inhibited by FMRF-amide analogs and sigma receptor ligands, such as (+)N-allyl-normetazocine and haloperidol, although with moderate affinity. It is concluded that the stereospecific high-affinity binding is of opioid in character, whereas the residual sites characterized with their lower affinity are naloxone-insensitive nonopioid sites.

Animals↗

Sutureless anastomosis in the surgery of the gastrointestinal tract.

The idea of the sutureless anastomosis is not a new one, but only the introduction of the VALTRAC-BAR instrument made the wide clinical application possible. The authors have applied this instrument in the case of 32 patients in a two years period. It was used in intestinal procedures in 28, in gastric resection in 4 occasions, respectively. In one case spontaneously recovered stercoral fistula was observed. According to our experiences, the instrument can be used advantageously in preparing anastomoses in the gastrointestinal tract.

Anastomosis, Surgical↗

High-throughput cDNA screening utilizing a low order neural network filter.

A low order neural network-based filter was designed as a rapid screening agent for single-spanning transmembrane regions in an integrated informatics system. A rapid screening algorithm was seen as a compromise between costly structure-specific techniques and simple rules that gave a high false-positive rate for cDNA. The filter was applied to a library of 2123 anonymous cDNA sequences, which resulted in 61 detections. Evaluation of the detections with two other dissimilar computer prediction algorithms yielded strong transmembrane predictions for 15 of the detections, while 8 of the detections resulted in a definitive negative result. Homology searches performed on the sequences with detection reports yielded 13 homologs in the predicted reading frame, four of which are membrane associated.

Animals↗

Proteins lose their nitric oxide stabilizing function after advanced glycosylation.

In vivo generated nitric oxide, NO, circulates in plasma mainly as an S-nitroso adduct of serum albumin. Compared to free NO, this NO-adduct is relatively long-lived. It exerts EDRF-like effects of vasodilation and platelet inhibition. Free NO is directly inactivated ('quenched') by advanced glycosylation end products (AGEs), glucose-derived protein moieties that form nonenzymatically and accumulate primarily on long-lived tissue proteins. They have been implicated in many of the long-term complications of diabetes mellitus. We found that the antiproliferative effects of thiol-stabilized NO (SNO-BSA) on Con A-stimulated lymphocytes from peripheral blood were even stronger than those of the NO-generating drug SNAP. The antimitogenic activity of SNO-BSA, however, was not significantly enhanced by the low molecular weight NO-carrier glutathione. NO liberated from SNO-BSA in molar excess was almost completely quenched by AGE-BSA. NO-dependent activating effects such as enhanced rate of glucose uptake or generation of cGMP in resting peripheral mononuclear cells (PBMC) and the antiproliferative activity of the NO-carrier BSA on Con A-stimulated cells were thereby abolished. In contrast, advanced glycosylation impaired the ability of BSA to function as NO-carrier, as evidenced by the lack of antiproliferative activity of NO-AGE-BSA and its inability to activate glucose transport or cGMP generation.

Blood Proteins↗

Growth of untreated and radiation-damaged Listeria as affected by environmental factors.

The growth of untreated Listeria monocytogenes 4ab No. 10 and that of the surviving fraction of its population treated with 0.8 kGy gamma rays was investigated in a microtitreplate system at incubation temperatures between 3 degrees C and 35 degrees C in Tryptic Phosphate Broth (TPB) or Brain Heart Infusion Broth (BHIB) media containing NaCl between 0.25 to 16.75% (w/v), and acidified with citrate-phosphate buffers to pH values between 4.63 and 7.06. The initial viable count was 3 x 10(3)/ml. Time periods to visible growth were recorded. Radiation survivors showed increased salt- and pH-sensitivities and increased minimum temperature for growth in TPB-based media. Adverse effects of sub-optimal environmental factors (reduced water activity, pH and temperature) and radiation injury were much less pronounced in BHIB-based media. Polynomial equations describing the combined effects of hydrogen ion and salt concentrations on the detectable growth at 30 degrees C were constructed for quantitative assessment of interactions. The results demonstrate that combining environmental stresses with low-dose irradiation can control growth of L. monocytogenes.

Culture Media↗

Transfected lymphocyte extracts of patients with urological tumours: complement temperature-sensitive adenovirus mutants in vitro.

Patients with renal or bladder cancers exhibit a unique association with adenovirus (Ad) infections. About 60% of them contain antibodies to Ad early antigens. Both in their tumour cells and peripheral blood lymphocytes (PBL) they have detectable early Ad antigens known to be involved in malignant cell transformation. Transfection of tumour cell extracts resulted in complementing temperature-sensitive (ts) Ad mutants at nonpermissive temperatures (39 degrees C) indicating that some cells of the tumour mass possess active functions for Ad. Only 4 to 18% of control subjects were positive in these tests. Here we studied whether lymphocytes might be involved in tumourigenesis by Ad. PBL extracts of patients were transfected into HEp-2 culture cells, which were subsequently superinfected with Ad-5 ts18 and ts19 mutants at 39 degrees C. Titration of virus yields indicated complementation in 76% of patients with renal and bladder cancers in contrast to 20% of control individuals. Complementing ability of lymphocytes which had been prestimulated with phytohaemagglutinin (PHA) approached that of tumour extracts. It means that both specimens contain advanced functions in contrast to resting lymphocytes. Lymphocytes are nonpermissive for latently carried Ad infections. Expression, possible transfer of early Ad gene products via frequent contacts with tissue cells can result in removal of tumour suppressor gene products from complexes regulating cell cycle negatively. Further interaction with hormone-sensitive protooncogenes explains tissue, age and gender specificity of urological malignancies. These phenomena suggest an important cofactorial role for Ad in kidney and bladder tumours.

Adenoviruses, Human↗

Characterization of [3H]Met-enkephalin-Arg6-Phe7 binding to opioid receptors in frog brain membrane preparations.

A tritiated heptapeptide, [3H]Tyr-Gly-Gly-Phe-Met-Arg-Phe ([3H]Met-enkephalin-Arg6-Phe7), with high specific radioactivity has been synthesized in order to characterize its opioid binding activity to frog brain membrane fractions. The apparent KD value of the radioligand calculated from homologous displacement experiments was 3.4 nM, and the maximal number of specific binding sites was 630 fmol/mg of protein. The KD determined from equilibrium saturation binding studies was found to be 3.6 nM. However, the Hill coefficient was far below unity (nH = 0.43), which suggests the presence of a second, lower affinity binding site. The presence of this binding component is strengthened by the displacement experiments performed with levorphanol and some other ligands. It is assumed that the lower affinity site has no opiate character. The rank order of potency of the applied ligands in competing reversibly with [3H]Met-enkephalin-Arg6-Phe7 binding reflects a kappa 2- and/or delta-subtype specificity of the heptapeptide. Binding to a kappa 1 and/or mu site of opioid receptors is excluded, but the existence of a novel endogenous opiate receptor subtype for Met-enkephalin-Arg6-Phe7 in frogs cannot be ruled out. The [3H]-Met-enkephalin-Arg6-Phe7 binding was inhibited by both sodium ions and GppNHp, which suggests the opioid agonist character of the heptapeptide.

Analgesics↗

The effect of prostaglandins on the replication of adenovirus wild types and temperature-sensitive mutants.

Replication and transformation by adenoviruses involve their interaction with several cellular regulatory mechanisms. Alterations in the phosphorylation of both cellular and viral polypeptides by secondary messenger cAMP and cGMP dependent protein kinases (PK) determining outcome of viral effects may be influenced by external physiological stimuli, among them by prostaglandins (PG). HEp-2 cells infected with representative serotypes of human adenovirus (Ad) groups and two temperature sensitive (ts) mutants were treated prior to and late postinfection at permissive (32 degrees C) and restrictive (39 degrees C) temperatures by different PGs. PGF2 alpha augmented replication of both oncogenic Ad-12 and latent Ad-1, Ad-5 serotypes as well as Ad-5 mutants at 32 degrees C and that of mutant ts18 (defective in pVI phosphorylation) but not that of ts19 (defective in pX phosphorylation) at 39 degrees C. PGE2 was shown to be inhibitory, but the replication of nononcogenic Ad-8 was not affected by PGs. PGI2 slightly enhanced all types, while indomethacin, inhibitor of endogenous PG synthesis with double unsaturated bonds moderately inhibited replication of all serotypes, except that of Ad-12. It is concluded that augmenting effects by PGF2 alpha during viral entry, cytoplasmic transport and late phase, but not in the early phase of adenovirus replication cycle, are due to enhancement of the non-specific cellular mechanisms, which support mitosis in the uninfected cells. Their activities are controlled by the late viral replication machinery, which process had been programmed in the early interaction of viral and cellular regulatory factors.

Adenoviruses, Human↗

Endotoxins and prednisolone alter replication of type 5 adenovirus and its temperature sensitive mutants.

Latency, replication or transformation by adenoviruses require cooperation between their gene products and cellular factors, which are controlled by external stimuli. Clinical observations suggest that bacterial endotoxin (LPS) and steroid hormones have direct effects on the viral permissivity and activation. Therefore, HEp-2 cultures were infected with low multiplicity of wild type (WT) human adenovirus 5 (Ad-5) and its temperature-sensitive mutants ts18 and ts19 damaged in the phosphorylation of structural polypeptides VI and X at 39 degrees C, respectively. Cultures were treated at permissive (32 degrees C) and nonpermissive (39 degrees C) temperatures with native and radio-detoxified (RD) LPS, alpha-tocopherol and prednisolone alone or in combination. Titration of virus yields showed dose-dependent activation and enhanced replication of latent WT and ts mutants by both LPS preparations. alpha-Tocopherol diminished these processes. LPS was likewise unable to augment virus producing capacity of cells. Prednisolone, although activating no latent virus, resulted in augmenting Ad-5 production at 32 degrees C. No compounds activated mutants at 39 degrees C except synergistic effect of LPS and prednisolone resulted in limited but significant replication of mutant ts19. Deliberation of lysosomal enzymes, enhanced cGMP and tumour necrosis factor alpha (TNF-alpha) productions by LPS as well as interaction of Ad early gene expression with prednisolone-utilized cellular transcription factors including AP-1 (c-jun, c-fos) are implicated in these processes. Excluding the role in activation of Ad proteinase processing viral structural polypeptides draws attention to the importance of cellular factors in virus replication.

Adenoviruses, Human↗