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Biomedical subjects

I Varga

Publications and source records attributed to I Varga.

At least 55 records · Page 3Linked to original sources

Semiclassical cross section correlations

We calculate within a semiclassical approximation the autocorrelation function of cross sections. The starting point is the semiclassical expression for the diagonal matrix elements of an operator. For general operators with a smooth classical limit the autocorrelation function of such matrix elements has two contributions with relative weights determined by classical dynamics. We show how the random matrix result can be obtained if the operator approaches a projector onto a single initial state. The expressions are verified in calculations for the kicked rotor.

Journal Article↗

Insect peptides with improved protease-resistance protect mice against bacterial infection.

At a time of the emergence of drug-resistant bacterial strains, the development of antimicrobial compounds with novel mechanisms of action is of considerable interest. Perhaps the most promising among these is a family of antibacterial peptides originally isolated from insects. These were shown to act in a stereospecific manner on an as-yet unidentified target bacterial protein. One of these peptides, drosocin, is inactive in vivo due to the rapid decomposition in mammalian sera. However, another family member, pyrrhocoricin, is significantly more stable, has increased in vitro efficacy against gram-negative bacterial strains, and if administered alone, as we show here, is devoid of in vitro or in vivo toxicity. At low doses, pyrrhocoricin protected mice against Escherichia coli infection, but at a higher dose augmented the infection of compromised animals. Analogs of pyrrhocoricin were, therefore, synthesized to further improve protease resistance and reduce toxicity. A linear derivative containing unnatural amino acids at both termini showed high potency and lack of toxicity in vivo and an expanded cyclic analog displayed broad activity spectrum in vitro. The bioactive conformation of native pyrrhocoricin was determined by nuclear magnetic resonance spectroscopy, and similar to drosocin, reverse turns were identified as pharmacologically important elements at the termini, bridged by an extended peptide domain. Knowledge of the primary and secondary structural requirements for in vivo activity of these peptides allows the design of novel antibacterial drug leads.

Amino Acid Sequence↗

Morphologic, host specificity, and molecular characterization of a Hungarian Cryptosporidium meleagridis isolate.

This study was undertaken in order to characterize Cryptosporidium meleagridis isolated from a turkey in Hungary and to compare the morphologies, host specificities, organ locations, and small-subunit RNA (SSU rRNA) gene sequences of this organism and other Cryptosporidium species. The phenotypic differences between C. meleagridis and Cryptosporidium parvum Hungarian calf isolate (zoonotic genotype) oocysts were small, although they were statistically significant. Oocysts of C. meleagridis were successfully passaged in turkeys and were transmitted from turkeys to immunosuppressed mice and from mice to chickens. The location of C. meleagridis was the small intestine, like the location of C. parvum. A comparison of sequence data for the variable region of the SSU rRNA gene of C. meleagridis isolated from turkeys with other Cryptosporidium sequence data in the GenBank database revealed that the Hungarian C. meleagridis sequence is identical to a C. meleagridis sequence recently described for a North Carolina isolate. Thus, C. meleagridis is a distinct species that occurs worldwide and has a broad host range, like the C. parvum zoonotic strain (also called the calf or bovine strain) and Cryptosporidium felis. Because birds are susceptible to C. meleagridis and to some zoonotic strains of C. parvum, these animals may play an active role in contamination of surface waters not only with Cryptosporidium baileyi but also with C. parvum-like parasites.

Animals↗

Morphologic, host specificity, and genetic characterization of a European Cryptosporidium andersoni isolate.

This study was undertaken in order to characterize a Cryptosporidium muris-like parasite isolated from cattle in Hungary and to compare this strain with other Cryptosporidium species. To date, the large-type oocysts isolated from cattle were considered as C. muris described from several mammals. The size, form, and structure of the oocysts of the Hungarian strain were identical with those described by others from cattle. An apparent difference between the morphometric data of C. muris-like parasites isolated from cattle or other mammals was noted, which is similar in magnitude to the differences between Cryptosporidium meleagridis and Cryptosporidium felis or between Cryptosporidium serpentis and Cryptosporidium baileyi. The cross-transmission experiments confirmed the findings of others, as C. muris-like oocysts isolated from cattle fail to infect other mammals. The sequence of the variable region of small subunit (SSU) rRNA gene of the strain was 100% identical with that of the U.S. Cryptosporidium andersoni and C. andersoni-like isolates from cattle. The difference between the SSU rRNA sequence of bovine strains and C. muris is similar in magnitude to the differences between C. meleagridis and Cryptosporidium parvum anthroponotic genotype or between Cryptosporidium wrairi and C. parvum zoonotic genotype. Our findings confirm that the Cryptosporidium species responsible for abomasal cryptosporidiosis and economic losses in the cattle industry should be considered a distinct species, C. andersoni Lindsay, Upton, Owens, Morgan, Mead, and Blagburn, 2000.

Animals↗

Effect of vasoactive intestinal polypeptide (VIP) on growth hormone (GH) and prolactin (PRL) release and cell morphology in human pituitary adenoma cell cultures.

Six GH adenomas and three prolactinomas were investigated by light- and electron-microscopic morphological and immunocytochemical methods and the effect of vasoactive intestinal polypeptide (VIP) on growth hormone (GH) and prolactin (PRL) secretion was tested in vitro. The tumour cells of the acromegalic patients revealed both GH and PRL immunoreactivity while prolactinomas showed only PRL activity. All the adenomas stained immunocytochemically also for VIP. By electron microscopy, the tumours included two densely and two sparsely granulated GH, two mixed GH/PRL, and three sparsely granulated PRL adenomas. The dissociated cells were explanted, and cultured in vitro. The cultures in micro test plates were treated with VIP at different concentrations between 10(-5)-10(-12) M. GH and PRL contents in the culture media were measured by radioimmunoassay. GH release was significantly stimulated by VIP in a dose-dependent manner over the whole concentration range, while VIP was effective on the PRL release only at 10(-6)-10(-7) M concentration. The cells of a mixed adenoma were grown in Petri dishes and used for ultrastructural and immunocytochemical studies. The cytoplasmic structure of the cells treated with VIP corresponded to that of active hormone-secreting cells with large ergastoplasmic fields and Golgi zones containing secretory granules. Massive exocytotic events were encountered mainly in the GH-type cells. GH and PRL double immunocytochemistry showed the predominance of GH cells, many of them containing low amounts of PRL as well. Cells predominantly containing PRL were spread among them, they also might contain GH as well. Some of the cells contained only a single immunoreactive hormone. The intensity of gold labelling of the secretory granules appeared higher in the VIP-treated cells than in the untreated control ones which showed a cytoplasmic structure characteristic of glandular cells with low secretory activity. As all the adenoma cells both contained and reacted to VIP, our results are in agreement with an autocrine or paracrine effect of this peptide. The fine structure of the cells in the cultures treated with VIP supply an additional argument to the assumption that VIP may serve as a growth factor for these cell types.

Acromegaly↗

High level of aspartic acid-bond isomerization during the synthesis of an N-linked tau glycopeptide.

An increased degree of utilization of the potential N-glycosylation site in the fourth repeat unit of the human tau protein may be involved in the inability of tau to bind to the corresponding tubulin sequence(s) and in the subsequent development of the paired helical filaments of Alzheimer's disease. To model these processes, we synthesized the octadecapeptide spanning this region without sugar, and with the addition of an N-acetyl-glucosamine moiety. The carbohydrate-protected, glycosylated asparagine was incorporated as a building block during conventional Fmoc-solid phase peptide synthesis. While the crude non-glycosylated analog was obtained as a single peptide, two peptides with the identical, expected masses, in approximately equal amounts, were detected after the cleavage of the peracetylated glycopeptide. Surprisingly, the two glycopeptides switched positions on the reversed-phase high performance liquid chromatogram after removal of the sugar-protecting acetyl groups. Nuclear magnetic resonance spectroscopy and peptide sequencing identified the more hydrophobic deprotected peak as the target peptide, and the more hydrophilic deprotected peak as a peptide analog in which the aspartic acid-bond just preceding the glycosylated asparagine residue was isomerized resulting in the formation of a beta-peptide. The anomalous chromatographic behavior of the acetylated beta-isomer could be explained on the basis of the generation of an extended hydrophobic surface which is not present in any of the other three glycopeptide variants. Repetition of the syntheses, with altered conditions and reagents, revealed reproducibly high levels of aspartic acid-bond isomerization of the glycopeptide as well as lack of isomerization for the non-glycosylated parent analog. If similar increased aspartic acid-bond isomerization occurs in vivo, a protein modification well known to take place for both the amyloid deposits and the neurofibrillary tangles in Alzheimer's disease, this process may explain the aggregation of glycosylated tau into the paired helical filaments in the affected brains.

Amino Acid Sequence↗

Immunogenicity of three oocyst extracts of Cryptosporidium baileyi in experimentally infected chickens.

The immunogenic properties of water-soluble and detergent-extracted components of Cryptosporidium baileyi oocysts were studied. Oocyst cytosol antigen (OCA) containing hydrophilic proteins was obtained by freeze-thaw cycles in liquid nitrogen. This was followed by Triton X-114 extraction of remaining oocyst fragments to dissolve membrane-bound proteins (TRE). The remainder of the pellet was solubilized with sodium dodecyl sulfate and treated with 2-mercaptoethanol to reduce disulfide-linked oocyst wall proteins (BME). The immune recognition of these three extracts was evaluated during the course of experimental cryptosporidiosis in chickens using ELISA, immunoblotting, and the lymphocyte stimulation test (LST). Four groups of chickens were infected at various times with different doses of C. baileyi and one group with the mammalian parasite C. parvum. Analysis of the data revealed that OCA proteins are well recognized by serum antibodies during the infection and to a limited extent by sera from chickens infected with C. parvum. Humoral responses of chicken groups to this antigen did not correlate well with the length of patency in contrast with its cellular recognition in LST. TRE gave lower values than OCA in both ELISA and LST, though it was still specifically recognized by samples from C. baileyi-infected chickens. Antibodies reacted aspecifically with BME, since only samples of birds which were immunocompetent at the time of their infection were able to recognize this extract as antigen. Immunoblotting revealed more specific components in OCA than in TRE or BME.

Animals↗

Investigation of the alveolar macrophages and T lymphocytes in 15 patients with systemic sclerosis.

The cell distribution and function of alveolar macrophages and T lymphocytes were investigated in the bronchoalveolar lavage (BAL) of 15 patients with systemic sclerosis (SSc). In alveolar macrophages, both spontaneous and PMA-stimulated TNF-alpha production were increased in SSc. PMA-induced IL-6 production was also elevated. Spontaneous IL-6 excretion of scleroderma alveolar macrophages was similar to the controls. Yeast and C3b-coated yeast (opsonised yeast) phagocytosis, chemotaxis and Fc receptor activity of alveolar macrophages were normal. The proportion of CD3, CD4 and CD8 T-lymphocyte subsets in the BAL was similar to the control values. The lymphocyte blast transformation index of the non-adherent cells deriving from the BAL fluid was markedly decreased.

Adult↗

Study on the course of Cryptosporidium baileyi infection in chickens treated with interleukin-1 or indomethacin.

The effects exerted by human recombinant interleukin-1 beta (hrIL-1 beta) and the prostaglandin inhibitor indomethacin on the course of Cryptosporidium baileyi infection in chickens were studied. Daily oocyst shedding was monitored by a quantitative method throughout the experiment. Humoral immune response to C. baileyi was assessed by ELISA at 3 weeks of age while the level of cellular immune response to phytohaemagglutinin-P (PHA-P) by a skin test at 23 days of age. Parenteral application of hrIL-1 beta decreased oocyst shedding to 62%, but the infection ran a similar course in treated and control birds. The PHA-P skin test demonstrated increased cellular immune reaction in chickens receiving IL-1 beta, but there was no significant difference in the humoral responses of the two groups as detected by ELISA. On the other hand, indomethacin mixed to the feed lessened oocyst shedding to 13.7% and also shortened its duration. Immunological parameters as reflected by PHA-P skin test and ELISA results indicated enhanced cellular but unaltered humoral immune response. These data suggest that the systemic application of interleukin-1 can induce partial protection against C. baileyi in chickens and that prolonged, abundant oocyst shedding is due to an indomethacin-sensitive immunodepression via the prostaglandin pathway.

Animals↗

Human Dirofilaria repens infection in Hungary: a case in the spermatic cord and a review of the literature.

Orchiectomy was performed in a 37-year-old Hungarian man exhibiting a swelling in his right testicle. Histology revealed a nodule attached to the spermatic cord, consisting of a granulomatous tissue around sections of a nematode. The worm was identified as Dirofilaria repens, an uncommon parasite in Hungary. As the patient had been abroad only in Italy where cases of dirofilariosis in dogs and humans are relatively frequent, it is assumed that the infection might have been acquired in that country 5 years earlier. This is the fifth case, published so far in the world, of such a localization in a human. The human cases of dirofilariosis reported in Hungary are reviewed.

Adult↗

Attempted chemoprophylaxis of cryptosporidiosis in chickens, using diclazuril, toltrazuril, or garlic extract.

Three battery tests were conducted to study the anticryptosporidial efficacy of the 2 commercially available anticoccidial triazinone derivates, diclazuril and toltrazuril, and a garlic extract. At the recommended level, diclazuril reduced the oocyst output of birds by 14.6%. The efficacy of toltrazuril was 52.1% at the recommended level, which could be moderately increased using 5 or 10 times the recommended dose. However, these doses resulted in significant weight gain reduction. The efficacy of garlic extract was 24.4%. It is concluded that none of the drugs can be recommended for chemoprophylaxis or therapy of cryptosporidiosis in chickens.

Animals↗

[Preventive treatment in internal medicine by low-molecular-weight heparin (nadroparine calcium)].

On the basis of literature data the authors discuss the preventive treatment of the low-molecular-weight heparin in various non-surgical disorders. The method was compared with unfractionated heparin in the treatment of 20 high risk patients. The efficacy of the two different heparins was examined on the liver and renal function, blood lipids and the hematologic and hemostaseologic parameters. The thromboembolic and hemorrhagic complications were observed. Significant difference was not found with the comparison of the two preparations. The authors emphasize the simplicity, safety, home treatment possibility of the low-molecular-weight heparin and the regular control of thrombocyte-count only, too.

Fibrinolytic Agents↗

Assessment of maternal immunity to Cryptosporidium baileyi in chickens.

The degree of protection to Cryptosporidium baileyi in the progeny of infected chickens was studied. Hens at the beginning of their laying period were given orally three consecutive, large doses of C. baileyi oocysts at weekly intervals. The infection became patent after 6 days and lasted for another 6 days. Increasing serum IgG, and serum, bile, lachrymal and salivary IgA were demonstrated from their samples. These immunoglobulins were transferred to the eggs, since high levels of maternally derived IgG and lower amount of IgA were present in their yolks. Hatchlings of infected hens were divided into uninfected (UY) and infected (IY) groups, the birds in the latter receiving an oral inoculum of C. baileyi oocysts on the first day of their life. Two other groups, progeny of uninfected hens served as controls (uninfected UC, and infected IC). Maternal IgG was detected in serum samples of UY hatchlings which was eliminated by the third week. The total oocyst shedding of IY chickens was 54.3% lower than that of the controls (IC), however, the prepatent and patent periods did not show significant difference. In spite of the partial protection observed in IY birds, their humoral immune response to C. baileyi was significantly lower when compared to IC. A dot-ELISA was developed to evaluate seroconversion of infected chickens which was 100% in both infected groups. The findings of the present study suggest that infection of hens with C. baileyi results in partial protection of their progeny to this parasite, and factors other than immunoglobulins may also be transferred via the eggs.

Administration, Oral↗

Interaction of chicken anaemia virus and Cryptosporidium baileyi in experimentally infected chickens.

The natural occurrence of concomitant chicken anaemia virus (CAV) and Cryptosporidium baileyi infection was described earlier. In this experiment, 1-day-old chickens were infected with CAV alone (anaemia virus infected, AI) or followed by inoculation with 8 x 10(5) C. baileyi oocysts orally at 1 wk of age (anaemia virus and Cryptosporidium infected, ACI). Another group of chickens received the same dose of C. baileyi oocysts without previous virus infection (Cryptosporidium infected, CI), and two groups of uninfected chickens served as controls. Except one group (uninfected control, UC), all groups -- including the other control group (challenged control, CC) -- were challenged with an oral inoculum of 8 x 10(5) C. baileyi oocysts at the age of 4 wk. Haematological, serological, immunohistochemical and pathological findings confirmed the effect of the virus agent. The individual C. baileyi oocyst shedding did not show significant difference between group CI and ACI, however, after challenge infection the AI chickens shed approximately three times more C. baileyi oocysts than those in group CC. Mortality and the percentage of birds that developed anaemia was significantly higher among ACI than AI chickens, while haematocrit values at 2 wk of age and relative bursal weights at 4 wk of age were moderately lower in the ACI group. The results presented here suggest that concurrent CAV infection increases the reproductive potential of C. baileyi in chickens, and both pathogens have synergistic effect on each other.

Animals↗

p53 protein and its messenger ribonucleic acid in human adrenal tumors.

The role of p53 tumor suppressor gene in the pathomechanism of adrenal tumors was investigated by measuring p53 protein and its messenger ribonucleic acid (mRNA) in 12 normal human adrenals as well as in 56 adrenal tumors (7 aldosterone-producing adenomas, 5 adrenocortical adenomas causing Cushing's syndrome, 19 non-hyperfunctioning adrenocortical adenomas, 5 adrenocortical carcinomas, 12 pheochromocytomas, 3 myelolipomas, 4 ganglioneuromas and 1 hemangioma). The p53 protein concentration was significantly increased in aldosterone-producing adenomas (394+/-36 pg/mg cytosolic protein, mean+/-SE, vs 266+/-18 in normal human adrenals), whereas the concentration of this protein in Cushing's adenomas, non-hyperfunctioning adrenocortical adenomas, pheochromocytomas, and in all but one adrenocortical carcinomas was similar to that measured in normal human adrenal tissues. One adrenocortical carcinoma tissue showed very high p53 protein content (3000 pg/mg cytosolic protein). By contrast, myelolipomas (23+/-20) ganglioneuromas (43+/-15) and a hemangioma (11 pg/mg cytosolic protein) had very low p53 protein content. Northern blot analysis revealed the presence of p53 mRNA in each adrenal tissue examined with highest levels in aldosterone-producing and Cushing's adenomas. It is possible that the differences in p53 protein and/or mRNA contents reflect corresponding differences in the pathogenetic importance of p53 alterations in these types of adrenal tumors.

Adenoma↗

Coexpression of p53 and tissue transglutaminase genes in human normal and pathologic adrenal tissues.

The presence of p53 and tissue transglutaminase (tTG) gene expressions was investigated in human normal and pathologic adrenal tissues with two aims (1) to determine the tissue content of p53 protein, its messenger ribonucleic acid (mRNA) and, especially, tTG mRNA which has not been previously reported and (2) to study possible differences in the coexpression of p53 and tTG in various adrenal disorders. Using Northern blot analysis, p53 and tTG mRNAs were detected in each adrenal tissue examined including 5 normal human adrenals, 6 aldosterone-producing adenomas, 3 Cushing's adenomas, 1 primary nodular adrenocortical hyperplasia causing Cushing's syndrome in an infant, 12 non-hyperfunctioning adrenocortical adenomas, and 4 adrenocortical carcinomas. The results showed a significant positive correlation between these two mRNAs in all adrenal tissues except adrenocortical carcinomas. Compared to normal adrenals, high p53 mRNA levels were observed in aldosterone-producing and Cushing's adenomas and, most markedly, in a tissue from a primary nodular adrenocortical hyperplasia. Also, Cushing's adenomas had significantly higher tTG mRNA contents. Immunohistochemistry for wild-type and mutant p53 protein showed numerous p53 positive cells with a strong nuclear staining in a tissue from a primary nodular adrenocortical hyperplasia, whereas the p53 positive cells were absent, except those with a faint nuclear staining, in all other adrenal tissues. However, all adrenal tissues showed detectable p53 contents by the more sensitive method of luminometric immunoassay (LIA). Using this method, aldosterone-producing adenomas exhibited significantly higher p53 contents than normal adrenal tissues. These observations may support potentially important roles for p53 and tTG in adrenal pathophysiology, especially in mechanisms which influence the evolution and/or progression of aldosterone-producing and Cushing's adenomas and, most probably, hyperplasias.

Adrenal Gland Neoplasms↗

Failure to differentiate Cryptosporidium parvum from C. meleagridis based on PCR amplification of eight DNA sequences.

In order to determine the specificities of PCR-based assays used for detecting Cryptosporidium parvum DNA, eight pairs of previously described PCR primers targeting six distinct regions of the Cryptosporidium genome were evaluated for the detection of C. parvum, the agent of human cryptosporidiosis, and C. muris, C. baileyi, and C. meleagridis, three Cryptosporidium species that infect birds or mammals but are not considered to be human pathogens. The four Cryptosporidium species were divided into two groups: C. parvum and C. meleagridis, which gave the same-sized fragments with all the reactions, and C. muris and C. baileyi, which gave positive results with primer pairs targeting the 18S rRNA gene only. In addition to being genetically similar at each of the eight loci analyzed by DNA amplification, C. parvum and C. meleagridis couldn't be differentiated even after restriction enzyme digestion of the PCR products obtained from three of the target genes. This study indicates that caution should be exercised in the interpretation of data from water sample analysis performed by these methods, since a positive result does not necessarily reflect a contamination by the human pathogen C. parvum.

Animals↗