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Biomedical subjects

A Nagy

Publications and source records attributed to A Nagy.

At least 19 recordsLinked to original sources
PubMed1992

[Results of extended resection of tumors of the colon and rectum].

The postoperative lethality and 5 year survival of elective extended colon resections in 59 locally advanced colorectal tumour cases has been evaluated. The operation has been extended for one adjacent organ in 47 (Groups I.) and for two or more organs in 12 cases (Groups. II.). The postoperative lethality was 47/1 and 12/2 respectively (P less than 0.01). However the 5 year survival proved to be similar--42% and 40% respectively in both patients group. The 5 year survival of patients group I. and II. was not significantly different comparing to the "simple" elective colorectal resections on the patients in Dukes C stadium operated on in the same period of time. Significantly better 5 year survival has been observed in the patients groups. I. and II. comparing to the outcome of the elective palliative (anus prae and ileo- or colo-colostomies) colorectal operations. The results certify the value of the radical surgical procedures in the locally advanced tumor cases.

Colectomy↗
PubMed1992

Cytotoxic analog of somatostatin containing methotrexate inhibits growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice.

Nude mice bearing xenografts of MIA PaCa-2 human pancreatic cancer cell line were treated for 4 weeks with AN-51, a somatostatin octapeptide analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) containing methotrexate attached to the alpha-amino group of D-Phe in position 1. Control groups of mice received saline, RC-121 or methotrexate. Drugs were given in equimolar doses by daily s.c. injections. After 7 days of treatment with 25 micrograms/day of AN-51, tumor growth was completely inhibited although the treatment had to be suspended because of toxic side effects, especially on the gastrointestinal tract, accompanied by major weight loss of the animals. Mice were allowed to recover for 1 week and treatment was continued with 12.5 micrograms/day AN-51. After 2 weeks of additional therapy, tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased, compared with controls, only in the group treated with AN-51. Methotrexate and RC-121 also inhibited tumor growth, but their effects were not statistically significant. AN-51 retained its hormonal activity and decreased serum growth hormone levels in mice. Binding affinity of AN-51 for somatostatin receptors on MIA PaCa-2 cells was found to be 2.5-times lower than that of parent compound RC-121. This is the first report on inhibition of human pancreatic cancer growth in vivo by somatostatin analogs carrying cytotoxic radicals.

Animals↗
PubMed1992

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and prostate cancers in vivo in animal models.

Amino Acid Sequence↗
PubMed1992

Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic radicals on growth of estrogen-independent MXT mouse mammary carcinoma in vivo.

Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist [D-Lys6]LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (G-HMAQ) and T-121/B (antagonist containing two residues of G-HMAQ) were tested in female BDF1 mice bearing MXT ((3.2)/Ovex) estrogen-independent mammary tumors. All three cytotoxic LH-RH analogs, administered from Alzet Osmotic Minipumps for 3 weeks, produced a significant inhibition of tumor growth. The effects of T-98 and T-121/B were superior to those obtained by treatment with equimolar doses of cytotoxic moiety anthraquinone or the LH-RH carrier alone. We assume that cytotoxic LH-RH analogs have a combined hormonal and cytotoxic activity with a reduced toxicity after administration in vivo. This is the first demonstration of in vivo tumor inhibition by targeted LH-RH analogs bearing cytotoxic radicals.

Amino Acid Sequence↗
PubMed1992

A satellite III sequence shared by human chromosomes 13, 14, and 21 that is contiguous with alpha satellite DNA.

We report the isolation of a clone (pTR9) from a human chromosome 21 lambda phage library, which was found to contain two distinct components: (1) a previously unreported subfamily of human satellite III (pTR9-s3; 1,485 bp) and (2) an alpha satellite sequence (pTR9-alpha; 250 bp) containing 1.5 copies of a 171-bp alphoid unit that shows 88.4% homology to a previously reported alpha satellite consensus sequence. The two components are separated by two direct repeats of 9 bp. Use of the polymerase chain reaction (PCR) to amplify across the junction between pTR9-s3 and pTR9-alpha established that these two sequences are contiguous in total human genomic DNA and in DNA derived from somatic cell hybrids carrying human chromosomes 13, 14, or 21. A related, but considerably more diverged, sequence was also detected on chromosome 15. Southern analysis of somatic cell hybrids at high stringency revealed a common structure of the pTR9-s3 sequence on chromosomes 13, 14, and 21 but not on 15 or 22. This sequence should be useful for the study of the structural organisation of the centromere of these chromosomes and the mechanism of their involvement in Robertsonian translocations.

Base Sequence↗
PubMed1992

[Inclusion cysts. Case report].

Inclusion cysts which are developmental anomalies can be seen either along the midpalatine raphe or on the dental ridges as well as on other areas of the palate in newborns. Based on their localisation and histology these are classified into three types (Epstein's pearls, Bohn's nodules, Dental lamina cysts). These are often taken as natal or neonatal teeth. No treatment is indicated since the lesions will spontaneously disappear few weeks after birth.

Female↗
PubMed1992

Prognostic data of the second follow-up in childhood wheezy bronchitis.

206 non-selected children who had wheezy bronchitis before two years of age were observed in the first follow-up (1985) about 9 years after their clinical wheezy episode. Among them 31 patients (15%) showed bronchial hyperreactivity (B.H.) after acetylcholine challenge and 9 children became asthmatic. In the second follow-up (1988) 28 children who had B.H. and randomly 17 children who did not have B.H. participated. The prognosis of wheezy bronchitis is good, there was no new asthmatic child at this time. The B.H. was found to diminish only in 7 cases. During the last 3 years wheezy episodes developed only in 5 asthmatic patients. The skin prick test (SPT) positivity did not change (26% versus 29%). The familial atopy in the group B.H. is higher (43%) than in the group non B.H. (23%) but the difference is not significant (X2 = 1.72). No significant correlation was found between the familial atopy and SPT positivity. The familial smoking is higher in the group B.H. (78% versus 64%) but no significant influence on the B.H. (X2 = 1.03) could be detected.

Bronchitis↗
PubMed1991

Inefficient muscarinic transduction in cardiomyopathic Syrian hamsters.

Regulation of cyclic AMP (cAMP) production and muscarinic binding were studied in highly washed left ventricular membranes from spontaneously cardiomyopathic Syrian hamsters (TO strain). Basal production of cAMP was decreased relative to that in random-bred (RB) controls, with proportionally similar decreases in stimulated production elicited by 7 beta-deacetyl-7 beta-(gamma-N-methylpiperazino)-butyryl forskolin and by the beta-adrenergic agonist isoproterenol. GTP-stimulated production of cAMP was inhibited fully by the muscarinic agonist carbachol in tissue from controls, but only partially in tissue from TO hamsters. Total muscarinic binding, as revealed by N-[3H]methylscopolamine, was similar in the two strains. Competition between carbachol and the radioligand revealed at least three classes of sites for the agonist, the apparent affinities of which were insensitive to the disease. Upon the addition of guanylyl imidodiphosphate (GMP-PNP, 0.1 mM), there was a disease-dependent redistribution such that the sites appeared to be predominantly of low affinity for the agonist in RB tissue and predominantly of medium affinity in TO tissue. The potency of GMP-PNP in mediating the change in carbachol binding apparently was unaffected by the disease. The loss of muscarinic regulation of cAMP production in TO left ventricular tissue appears to reflect a disease-related change in the coupling of muscarinic receptors to inhibitory GTP-binding proteins.

Adenylyl Cyclases↗
PubMed1979

Effects of zimelidine, a selective 5-HT uptake inhibitor, on serum prolactin levels in man.

The levels of serum prolactin were studied both after an acute intake of zimelidine and during a treatment period of 3--7 weeks. No significant changes in basal serum prolactin levels were seen after single oral doses of zimelidine (100 mg) in healthy volunteers during an investigation period of 12 h. Serum prolactin concentrations remained well within the pretreatment levels also during a continuous treatment of depressive patients with zimelidine up to 150 mg orally b.i.d. It is concluded that clinical doses of the selective 5-HT uptake inhibitor zimelidine does not exert any significant effect on serum prolactin levels.

Adult↗
PubMed1979

Single versus divided daily dosages of clomipramine. Plasma concentration and clinical effect.

Sixteen depressed patients have been treated with a daily dose of 150 mg clomipramine for 20 days. Every patient received the total dose at night for 10 days and three times daily for 10 days according to a double-blind, cross-over design. No differences were noted between the two dose regimens, either regarding the clinical effect or the side effects. The plasma level ratio of parent drug to demethylated metabolite was higher on single than multiple doses.

Adolescent↗
PubMed1979

Epilepsy and brain abscess.

Among 22 children who had recovered from brain abscess, 9 later developed epilepsy. Epilepsy developing as a consequence of brain abscess depends on the length of the catamnestic period and the localization of the abscess. The appearance of epilepsy is more frequent after frontal and temporal abscesses and in cases presenting symptoms in the acute phase of the abscess. Since epilepsy may develop years or even decades after recovery from the brain abscess, it is recommended to keep the patient under control for years.

Adolescent↗
PubMed1979

Ion content of synaptic vesicles.

Proton induced X-ray emission analysis measurements were performed to determine the P, S, K, Ca Fe, Ni, Cu and Zn ion content of presynaptic vesicles prepared from guinea-pig brain cortex. The number of different ions per single vesicle is calculated using the results of the additional protein content determinations. The ion contents of cholinergic and adrenergic vesicles are compared.

Acetylcholine↗