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Biomedical subjects

A Nagy

Publications and source records attributed to A Nagy.

At least 163 records · Page 9Linked to original sources
PubMed1998

Synthesis and biological evaluation of cytotoxic analogs of somatostatin containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin.

To create cytotoxic hybrid analogs of somatostatin (SST), octapeptides RC-160 (D-Phe-Cys-Tyr-D-Trp- Lys-Val-Cys-Trp-NH2) and RC-121 (D-Phe-Cys-Tyr-D-Trp- Lys-Val-Cys-Thr-NH2) were linked to doxorubicin (DOX) or its superactive derivative, 2-pyrrolino-DOX (AN-201). The conjugation was performed by coupling N-9-fluorenylmethoxycarbonyl (N-Fmoc)-DOX-14-O-hemiglutarate or 2-pyrrolino-DOX-14-O-hemiglutarate to the amino terminus of [Lys(Fmoc)5]RC-160 yielding AN-163 and AN-258, respectively, after deprotection. The respective cytotoxic conjugates of RC-121 (AN-162 and AN-238) were prepared similarly. In vitro tests on human cancer cell lines-MKN-45 gastric cancer, MDA-MB-231 breast cancer, PC-3 prostate cancer, and MIA PaCa-2 pancreatic cancer-demonstrated that the antiproliferative activity of the cytotoxic radicals in these conjugates was virtually retained. In H-345 human small cell lung carcinoma cell line, conjugates of RC-121 preserved the cytotoxic activity of their radicals, but the hybrids with RC-160 showed approximately 10 times lower activity. The ability of the carriers and the hybrids to inhibit the binding of 125I-labeled RC-160 to receptors for SST on rat pituitary membrane preparation was also determined. The cytotoxic conjugates inhibited 50% of the specific binding of the radioligand in the nanomolar concentration range (IC50 < 80 nM). When SST-like activities of AN-238 and its carrier, RC-121, were compared in the rat pituitary superfusion system, both compounds were found to suppress a stimulated growth hormone release at nanomolar concentrations. Preliminary studies in animal models of breast and prostate cancers showed that AN-238 is less toxic than AN-201 and more potent in inhibiting tumor growth. These highly active cytotoxic analogs of SST have been designed as targeted antitumor agents for the treatment of various cancers expressing receptors for SST octapeptides.

Animals↗
PubMed1998

Conditional genome alteration in mice.

The recent ability to inactivate specific genes in mice has significantly accelerated our understanding of molecular, cellular, and even behavioral aspects of normal and disease processes. However, this ability has also demonstrated the extreme complexity of genetic determination in mammals, in particular, that genes in the same family or pathway can be functionally redundant and that a given gene often has multiple roles. Thus, inactivation of a gene often does not indicate its complete spectrum of functions. To circumvent this problem, many new tools and novel applications of classic techniques have been developed to place spatial and temporal restrictions on the genomic alterations. These approaches include chimera and mosaic studies, organ transplantation, complementation assays, dominant negative mutants, conditional gene knockouts, and lineage-specific gene rescue. Not only has this opened up more sophisticated ways to make genomic alterations, but it has provided the opportunity to create animal models for sporadic human genetic diseases.

Animals↗
PubMed1998

Diagnostic accuracy of helical CT for detection of blunt bowel and mesenteric injuries.

OBJECTIVE: To determine the diagnostic accuracy of helical computed tomography (CT) in the detection of blunt bowel and mesenteric injury in a clinical setting. MATERIALS AND METHODS: We evaluated the helical CT and surgical findings in 31 patients with blunt abdominal trauma. Nineteen patients had surgically proven bowel and/or mesenteric injury, and 12 patients had no bowel or mesenteric injury at laparotomy. The CT scans were assessed by three observers in consensus and were graded as showing no injury, minor bowel or mesenteric injury (not requiring urgent surgery), or major bowel or mesenteric injury (requiring immediate surgery). The CT diagnoses were compared with the surgical findings. RESULTS: In the 19 cases of surgically proven bowel injury, CT had an accuracy of 84% (26/31), specificity 84% (16/19), and negative predictive value 89% (16/18) for diagnosis of bowel injury. CT correctly differentiated minor from major bowel injuries in eight of 12 cases (75%). For the 13 cases of mesenteric injury, the accuracy of CT diagnosis was 77% (24/31), specificity 67% (12/18), and negative predictive value 93% (12/13) for diagnosis of mesenteric injury. The CT findings allowed correct differentiation of minor from major mesenteric injuries in seven of 13 cases (54%). CONCLUSION: Helical CT is moderately accurate and has a high negative predictive value in detecting bowel and mesenteric injuries after blunt trauma. Helical CT is not highly accurate in predicting the severity of injury or need for urgent surgery.

Adult↗
PubMed1998

Embryonic stem cells, creating transgenic animals.

Embryonic stem (ES) cells have afforded a means of directly modifying the mouse genome in vitro and then introducing such changes directly into animals. The advent of this technology has made the mouse the mammal of choice for mutagenesis approaches used in the study of embryonic development and disease conditions. This chapter deals with the maintenance and modification of these pluripotent cell lines and describes the routes that can be taken for their efficient introduction to the in vivo environment.

Animals↗
PubMed1998

Effects of a novel, low-molecular weight inhibitor of lipid peroxidation on ischemia-reperfusion injury in isolated rat hearts and in cultured cardiomyocytes.

We investigated the effect of H290/51, a novel, low-molecular-weight inhibitor of lipid peroxidation, on cardiac ischemia-reperfusion injury. Lactate dehydrogenase (LD) release from cultured cardiomyocytes exposed to 1 h hypoxia and 4 h reoxygenation was measured after pretreatment with different concentrations of H290/51. In another series, Langendorff-perfused rat hearts were exposed to 30 min global ischemia and 60 min reperfusion (n=minimum 10 in each group): 1. Control ischemia-reperfusion. 2. Vehicle throughout the experiment. 3. Vehicle during stabilization, and H290/51 (10(-6) mol/l) during reperfusion. 4. H290/51 throughout the experiments. During reoxygenation of isolated cardiomyocytes, H290/51 dose dependently inhibited LD release with an pIC50 value of 7.2+/-0.4 (mean+/-SEM), with 10(-6) mol/l as the lowest efficient concentration. In isolated hearts ischemia-reperfusion induced severe reperfusion arrhythmias, reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and increased LV end-diastolic pressure (LVEDP). LD activity in the effluent increased. H290/51 throughout perfusion (group 4) reduced the occurrence of severe reperfusion arrhythmias (p < .0001), attenuated the decrease of LVDP (p < .008), and CF (p < .006), the increase of LVEDP (p < .008), and the release of LD (p < .002). Tissue contents of thiobarbituric acid-reactive substances did not increase during reperfusion in controls, but was reduced in group 4 (p < .004). H290/51 given only during reperfusion (group 3) tended to improve cardiac function, but significantly so only for increase of CF (p < .01). The lipid peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia-reperfusion.

Animals↗
PubMed1998

Mash2 is expressed in oogenesis and preimplantation development but is not required for blastocyst formation.

The basic helix-loop-helix transcription factor, Mash2, has been shown to be necessary for the development of the spongiotrophoblast of the mature chorioallantoic placenta of the mouse. Here we show that Mash2 is transcribed during oogenesis and expressed throughout preimplantation development, only becoming restricted to the diploid trophoblast around the time of implantation. This expression raised the possibility that Mash2 has earlier functions in the trophoblast lineage that were not detectable in mutant embryos because of the persistence of oogenetically derived protein. This was tested by generating viable Mash2-/- females by tetraploid rescue of the extraembryonic defect. Mutant embryos derived from such females showed no enhanced phenotype over embryos produced from heterozygous females, demonstrating unequivocally that neither maternal nor zygotic Mash2 is required for early trophoblast development. If Mash2 functions in other aspects of trophoblast development, it must act cooperatively with other factors.

Animals↗
PubMed1998

Generating green fluorescent mice by germline transmission of green fluorescent ES cells.

Green fluorescent protein (GFP) and its variants currently represent the only non-invasive markers available for labeling mammalian cells in culture or in a multicellular organism through transgenesis. To date this marker gene has been widely used in the study of many organisms, but as yet has not found large-scale application in mammals due to problems encountered with weak fluorescence and instability of the wild-type protein at higher temperatures. Recently, though, several mutants have been made in the wild-type (wt) GFP so as to improve its thermostability and fluorescence. EGFP (enhanced GFP) is one such wtGFP variant. As a first step in assessing the use of EGFP in ES cell-mediated strategies, we have established a mouse embryonic stem (ES) cell lines expressing EGFP, which can be propagated in culture, reintroduced into mice. or induced to differentiate in vitro, while still maintaining ubiquitous EGFP expression. From the results presented we can suggest that: 1) possible improvements in the efficiency of transgenic regimes requiring the germline transmission of ES cells by aggregation chimeras can be made by the preselection chimeric embryos at the blastocyst stage: (2) the expression of a noninvasive marker, driven by a promoter that is active during early postimplantation development, allows access to embryos during a window of embryonic development that has previously been difficult to investigate (3) the behavior of mutant ES cells can be followed with simple microscopic observation of chimeric embryos or adult animals comprising green fluorescent cells/tissues. and (4) intercrosses of F1 mice and subsequent generations of animals show that progeny can be genotyped by UV light, such that mice homozygous for the transgene can be distinguished from hemizygotes due to their increased fluorescence.

Animals↗
PubMed1998

New analogs of human growth hormone-releasing hormone (1-29) with high and prolonged antagonistic activity.

Based on our previous results, in conjunction with various structural considerations, 19 new analogs of the GHRH antagonist [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Abu15,Nle27,Agm29]++ +hGHRH(1-29) (MZ-5-156) were synthesized by the solid-phase method. These compounds were designed to develop further analogs of this class with increased receptor-binding affinity. All analogs had Abu15 and Nle27 modifications and were acylated with phenylacetic acid at the N-terminus. Most of the analogs had D-Arg2 and Phe(pCl)6 substituents and Agm29 or Arg29-NH2 at the C-terminus. Additional single substitutions consisted of the incorporation of D- or L-Tic1, D-Tic2, Tic6 or Phe(pNO2)6 and Arg29-NH2. The Arg29-NH2 analog of MZ-5-156 (KT-48) was further modified by single substitutions using Pal1; D-Tpi2; D- or L-Phe4; Phe(pX)6 X = F, Cl, I; Tyr7; Aib8; Tyr(Me)10 or Phe(pCl)10. Four peptides had multiple substitutions. All the analogs were evaluated for their ability to inhibit GH release induced by hGHRH(1-29)NH2 in vitro and some were also tested in vivo. Peptides [PhAc-Tyr1,D-Arg2,Phe(pI)6,Abu15,Nle27]hGHRH(1-2 9)NH2 (KT-30), [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Aib8,Abu15,Nle27] hGHRH(1-29)NH2 (KT-50) and [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Tyr(Me)10,Abu15,Nle27]h GHRH(1-29)NH2 (KT-40) with Phe(pI)6, Aib8 or Tyr(Me)10 modifications, respectively, showed high and prolonged inhibitory effect in superfused rat pituitary system. Analog KT-50 also exhibited a strong and long-term inhibitory activity in vivo in rats. Most of the new analogs showed high binding affinities to rat pituitary GHRH receptors.

Amino Acid Sequence↗
PubMed1998

Eight-year experience in treatment of hemorrhoidal disease.

During an eight-year period 887 patients with symptoms of hemorrhoids were treated at the Department of Surgery and Outpatient Care of the Vaszary Kolos County Hospital, Esztergom. 178 patients with first degree hemorrhoids received only conservative treatment. Rubber band ligation (RBL) which can be performed on outpatients was applied in 324 patients with first, second and third degree hemorrhoids. Thrombosed external hemorrhoids were treated by excision in 215 patients. Hemorrhoidectomy (H) was mainly carried out in 91 cases for treatment of circular 3rd and 4th degree nodules involving complications. More than 80 per cent of the patients receiving rubber band ligation and hemorrhoidectomy were followed up. 65% of the RBL group and 85% of the H group were symptom free, while 76% of the RBL group and 91% of the H group showed great improvement after the treatment. Personal results, complications, and review of the literature are discussed in detail.

Adult↗
PubMed1997

Growth inhibition of human ovarian cancers by cytotoxic analogues of luteinizing hormone-releasing hormone.

BACKGROUND: Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in nearly 80% of human ovarian cancers. The chemotherapeutic agent doxorubicin can be linked to [D-lysine6]LH-RH to form a cytotoxic analogue (AN-152) that may have greater specificity for tumor cells. This study was conducted to investigate the effects of AN-152 on the growth of LH-RH receptor-positive OV-1063 human epithelial ovarian cancers. METHODS: Nude mice bearing human ovarian tumors, OV-1063 or UCI-107 (LH-RH receptor negative), were injected intraperitoneally with saline (control) or with equimolar doses of AN-152 or doxorubicin; experiments involving mice with OV-1063 tumors also included groups that were administered [D-lysine6]LH-RH either alone or in combination with doxorubicin. Tumor volume, weight, doubling time, and burden (i.e., tumor weight/body weight) as well as tumor apoptotic and mitotic indices were determined. The levels of receptors for LH-RH and epidermal growth factor (EGF) and their messenger RNAs were measured by use of radioreceptor and reverse transcription-polymerase chain reaction assays, respectively. RESULTS: The growth of OV-1063 ovarian tumors in nude mice, as based on reduction in tumor volume, was inhibited significantly (all P<.05, two-sided) 4 weeks after treatment with AN-152, even at the lowest dose tested (413 nmol/20 g weight); the toxic effects of an equivalent dose of doxorubicin caused substantial mortality. High-affinity receptors for LH-RH and EGF were found on cell membranes of OV-1063 cancers; however, after in vivo treatment with AN-152, LH-RH receptor-binding sites were not detectable and EGF receptors were reduced in number. The growth of UCI-107 ovarian cancers was not inhibited by AN-152. CONCLUSIONS: In nude mice bearing LH-RH receptor positive OV-1063 epithelial ovarian cancers, systemic administration of AN-152 is less toxic and inhibits tumor growth better than equimolar doses of doxorubicin.

Animals↗
PubMed1997

[Mycoplasma pneumoniae epidemic as zoonosis].

At a secondary school in Budapest, in the first class, 30 students became sick with fever and upper respiratory catarrhal symptoms between September 19 and October 31, 1995. Two children were hospitalized with a diagnosis of pneumonia, in case of the two children treated at the Szent László Hospital, suspect of Mycoplasma infection raised which was also confirmed by cold agglutination test. During the epizootiological examination on the spot they found a terrarium in the classroom where the students raised a Syrian gold hamster family. Mycoplasmas were isolated from the lung samples of the hamsters during the pathological examination which proved to be Mycoplasma pneumoniae. Owing to the close etiologic relationships between epidemiological anamnesis, characteristics of the epidemic, as well as findings of patients and pathological or histological findings in the hamsters together with the results of bacteriological examinations, the epidemic should be considered as a zoonosis.

Animals↗
PubMed1997

[Study of the Leiden mutation (factor VQ 506), the most frequent cause of thrombophilia, in 116 thrombosis patients].

The incidence of Leiden mutation was examined by PCR method in 116 thrombophilic patients in random fashion. Mean age at the first thrombotic episode was 30.97 years. 90 patients had positive family history for thrombosis, 67 had more than one thrombotic episodes. APC resistance with laboratory test was found in 51 cases (44%). F V Leiden mutation was proven in 44 patients (38%). 10 being homozygous and 34 heterozygous out of them.

Adolescent↗
PubMed1997

Mash2 acts cell autonomously in mouse spongiotrophoblast development.

The Mash2 gene, which encodes a basic helix-loop-helix transcription factor, is one of the mammalian homologues of the Drosophila achaete-scute genes. It is strongly expressed in diploid trophoblast cells of the postimplantation mouse embryo. Targeted mutagenesis of Mash2 revealed that loss of function results in embryonic lethality at midgestation, due to placental failure associated with a lack of spongiotrophoblast and reduced labyrinthine trophoblast layers. For the further study of Mash2 function in development of the trophoblast cell lineage, we have performed chimeric analysis combining Mash2 mutant and wild-type embryos. We have addressed the question of whether the phenotype of the Mash2 mutant embryo, which affects all of the three trophoblast cell layers, is caused by a cell autonomous or non-autonomous defect and whether Mash2 is required in both spongiotrophoblast and labyrinthine trophoblast development. Our results showed no contribution of Mash2 mutant cells to the spongiotrophoblast layer in chimeric placentae at 10.5 and 12.5 days postcoitum, suggesting that the product of the Mash2 gene is required cell autonomously during the development of the spongiotrophoblast. However, it seems that Mash2 is not required for development of labyrinthine trophoblast or giant cells, since high contributions of Mash2 mutant cells were observed in those trophoblast cell layers in the chimeric placentae analyzed. We can therefore conclude that the primary and cell-autonomous function of Mash2 appears to be an involvement in the development of diploid trophoblast cells in the ectoplacental cone to form the spongiotrophoblast cell layer of the mature chorioallantoic placenta.

Animals↗
PubMed1997

[Successful surgical management of spontaneous multiple free ileum perforation caused by regional enteritis (Crohn disease)].

Spontaneous free perforation of the small intestine is a rare early (first) complication of the Crohn's disease. Case reports have not exceeded the hundred. The authors report the case history of a 40 years old male patient who was successfully operated on double, multiple free perforation of ileum as first sign of the Crohn's disease. First the suture of the perforated small bowel and second the resection of reperforated ileum was carried out. The base on the macroscopic and microscopic appearance of the resected bowel, the diagnosis was supposed by pathologists too. Presented paper based on the very rare clinical finding.

Adult↗
PubMed1997

Radiation-induced chromosomal rearrangement as an aid to analysis of the genetic constitution of Phaffia rhodozyma.

Electrophoretic karyotypes of 80 auxotrophic and morphological mutants obtained from two Phaffia rhodozyma strains (ATCC 24203 and ATCC 24229) by gamma-radiation were investigated. Contour-clamped homogeneous gel electrophoresis separation of the chromosomal size DNAs revealed 29 new chromosomal patterns after mutagen treatment. No correlation was found between a given type of chromosomal aberration and any phenotypic character. However, analysis of the chromosomal rearrangements proved to be useful for a more exact determination of chromosome number and genome size. The total genome size of ATCC 24229 was found to be 19.3 Mb, with nine chromosomes, while analysis of the mutant derivatives of ATCC 24203 suggested the presence of 11 chromosomes, with an estimated total genome size of 22.2 Mb. The advantages of the analysis of mutant electrophoretic karyotypes for genome characterization are discussed.

Chromosomes, Fungal↗