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J Izdebski

Publications and source records attributed to J Izdebski.

At least 19 recordsLinked to original sources
PubMed2000

Primary structure of fox (Vulpes vulpes) proinsulin based on sequence studies of pancreatic peptides and cDNA.

Insulin and C-peptide were extracted and purified from fox (Vulpes vulpes) pancreas using gel filtration, ion-exchange chromatography and HPLC. Chromatographic data for the insulin, as well as for its oxidized and carboxymethylated chains proved it to be identical to that of polar fox (Alopex lagopus) and dog. The sequence analysis of a peptide which was assumed to be the corresponding C-peptide revealed that it comprises 23 amino acid residues and is identical to the C-peptide fragment isolated from dog pancreas: it differs from polar fox C-peptide by a single substitution (Asp-->Glu). mRNA was isolated from pancreatic tissue and cDNA was obtained by reverse transcription. A polymerase chain reaction was performed using gene-specific primers to obtain a DNA fragment corresponding to part of fox proinsulin. DNA sequencing revealed 100% identity to dog proinsulin at the protein level, although some amino acids were encoded by different codons. The total sequence of proinsulin was deduced from these results.

Amino Acid Sequence↗
PubMed1999

Conformational analysis of a novel cyclic enkephalin analogue using NMR and EDMC calculations.

Conformational space of a novel cyclic enkephalin analogue, cyclo(N(epsilon),N(epsilon')-carbonyl-D-Lys2,Lys5)enkephalin amide, was exhaustively examined. A large number of conformations was selected and clustered into families on the basis of their structure and energy. For representative conformations ROESY spectra were generated and their linear combination was fitted to the spectra measured in water and Me2SO-d6. This procedure yielded an ensemble of most populated conformations of the peptide in the two solvents.

Amides↗
PubMed1998

Postexercise decrease in arterial blood pressure, total peripheral resistance and in circulatory responses to brief hyperoxia in subjects with mild essential hypertension.

The objective of our study was: (1) to compare the influence of moderate exercise on circulatory after-response in mildly hypertensive (n = 8) and normotensive male subjects (n = 9); (2) to examine the circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors at rest and during postexercise period in both groups. Hypertensive men (HTS) with a systolic blood pressure (SBP) 148 +/- 5 mm Hg, diastolic blood pressure (DBP) 92.4 +/- 4 mm Hg; and normotensive men (NTS), with a SBP 126 +/- 3 mm Hg, DBP 75.6 +/- 1.3 mm Hg, were submitted to 20-min of moderate exercise on a cycloergometer (up to the level of 55% of each subject's resting heart rate reserve). Finger arterial BP was recorded continuously with Finapres, impedance reography was used for recording stroke volume, cardiac output and arm blood flow. In HTS a significant decrease in SBP by 14.5 +/- 3.4 mm Hg, DBP by 8.9 +/- 1.9 mm Hg, total peripheral resistance (TPR) by 0.45 +/- 0.05 TPR u. (33.7 +/- 2.7%), and in arm vascular resistance (AVR) by 11.0 +/- 2.7 PRU u. (35.6 +/- 7%), was observed over a 60-min postexercise period. NTS exhibited insignificant changes in SBP, DBP, AVR except a significant decrease in TPR limited only to 20-min postexercise period. Hyperoxia decreased SBP, DBP and TPR in HTS. This effect was significantly attenuated during the postexercise period. Long-lasting antihypertensive effect of a single dynamic exercise in HTS suggests that moderate exercise may be applied as an effective physiological procedure to reduce elevated arterial BP in mild hypertension. We suggest also that the attenuation of the sympathoexcitatory arterial chemoreceptor reflex may contribute to a postexercise decrease in arterial BP and in TPR in mildly hypertensive subjects.

Adult↗
PubMed1996

Effect of chronic administration of a new potent agonist of GH-RH(1-29)NH2 on linear growth and GH responsiveness in rats.

The effects of a repeated or continuous administration of a potent agonistic analog of growth hormone-releasing hormone (GH-RH), [Dat1, Thr8, Orn12,21, Abu15, Nle27, Asp28, Agm29] hGH-RH(1-29)(JI-36), on the linear growth and the GH responses to bolus injections of GH-RH(1-29)NH2 were investigated in male rats about 7 weeks old. Body weight and tail length were monitored. Basal serum GH and IGF-I concentrations and GH responses to GH-RH(1-29)NH2 were measured by RIA. Chronic administration of GH-RH agonist JI-36 by continuous release from osmotic minipumps at the rate of 0.2 microgram/h or twice daily injections of 0.5 and 5 micrograms/rat for 4 weeks significantly speeded up the growth of rats as measured by the tail length. The acceleration of growth was similar in the 3 groups and was associated with stimulation of IGF-I secretion. The GH response to bolus injection of GH-RH(1-29)NH2 was preserved in all groups and no attentuation of the response occurred in rats treated for 4 weeks with agonist JI-36 as compared with the control group. Our results indicate that chronic administration of GH-RH agonist JI-36 significantly increases the growth rate without affecting somatotroph responsiveness in rats. It is therefore likely that this class of GH-RH agonists may be useful clinically.

Animals↗
PubMed1996

Chronic administration of a new potent agonist of growth hormone- releasing hormone induces compensatory linear growth in growth hormone-deficient rats: mechanism of action.

To assess the efficacy of a potent agonist analog of GH-releasing hormone (GH-RH), [Dat1,Gln8,Orn12,21,Abu15,Nle27,Asp28,A gm29]hGH-RH(1-29) (JI-38), we investigated the effects of its chronic administration on growth responses in monosodium glutamate (MSG)-lesioned and normal young rats. Body weight (BW), body length (BL), tibia length (TIL), and tail length (TAL) were monitored. Basal serum GH concentrations, GH responses to bolus injections of GH-RH, pituitary GH and serum IGF-I concentrations were measured by RIA. Pituitary GH-RH receptor concentration and binding affinity was also evaluated after the treatment. Neonatal treatment with MSG resulted, as expected, in blunted growth and a decrease in serum and pituitary GH concentration and serum IGF-I levels. A reduction in GH-RH receptor concentration, associated with increased binding affinity of the GH-RH receptor was also found. Chronic administration of GH-RH agonist JI-38 in doses of 2 micrograms at 12-hour intervals for 2 weeks markedly increased the GH responsiveness to GH-RH and stimulated growth, with MSG-treated animals achieving the growth rate of normal controls. Acceleration of growth was associated with stimulated GH synthesis and IGF-I secretion, although basal serum GH levels did not change. Pituitary GH-RH receptor concentration and binding affinity were not significantly modified by the treatment. Treatment of normal young growing rats with agonist JI-38 did not further increase the normal growth acceleration in these rats, but stimulated the GH synthesis and augmented the GH secretory responsiveness. The treatment of MSG-lesioned rats with GH-RH agonist was generally more effective in female than in male animals, and in some cases masked the sex differences in growth rate. Our findings provide the first evidence that the blunted growth rate of the MSG-lesioned rats is associated with a decreased pituitary GH-RH receptor concentration. Our work demonstrates that administration of GH-RH agonist JI-38 is able to restore the normal growth rate of the GH-deficient rats by stimulating GH synthesis and IGF-I secretion.

Animals↗
PubMed1996

Hemodynamic responses to brief hyperoxia in healthy and in mild hypertensive human subjects in rest and during dynamic exercise.

Hemodynamic consequences of the withdrawal of arterial chemoreceptor drive (ACD) by brief systemic hyperoxia were studied in 16 mild hypertensive subjects (HT) and in 16 healthy subjects (NT) in horizontal position at resting metabolic rate. In another 9 mild HT and match NT measurements were made in resting sitting position and during steady-state mild physical exercise on cycloergometer, (30% of VO2 max.) Tidal volume, minute ventilation, end tidal CO2 and O2 concentration, K+, Na+, pO2, pCO2 values in blood were recorded. Impedance reography was used for recording stroke volume (SV) and arm blood flow (ABF). Cardiac output (CO), ABF and arterial blood pressure (ABF) values were used for calculation of the total peripheral resistance (TPR) and vascular resistance in the arm (AVR). To assess the neurogenic circulatory response to withdrawal of ACD in HT attenuated by opposite peripheral effects of high oxygen, the values of AVR, ABP, TPR and AVR changes during brief hyperoxia in NT, assumed to be of peripheral origin, were subtracted from respective values in HT, assumed to be of mixed neurogenic and peripheral origin. In HT hyperoxia applied in sitting position produced a brief decrease in systolic and diastolic ABP by 5.4 +/- 0.8% and 3.4 +/- 1.1% respectively, of TPR by 12.4 +/- 3% and of AVR by 4.7 +/- 4.6%. Decrease in AVR during hyperoxia was significantly greater in sitting than in horizontal position. In NT hyperoxia produced opposite effects in ABP, TPR and AVR, as compared to those in HT. In HT subjects during steady-state exercise the TPR decreased by 21 +/- 3.7% reaching a value no different from that in NT. We suggest, that in primary hypertension neurogenic sympathoexcitatory ACD is augmented and interacts with the peripheral mechanisms related to tissue oxygen supply.

Adult↗
PubMed1995

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27, Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29); JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38, [Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency 44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.

Amino Acid Sequence↗
PubMed1994

N-cyclohexyl-N'-isopropylcarbodiimide: a hybrid that combines the structural features of DCC and DIC.

N-Cyclohexyl-N'-isopropylcarbodiimide was prepared and used for peptide couplings by various procedures. Reaction between Z-Val and Gly-OEt was used for yield studies and determination of the extent of the side reaction in solution. The value of this reagent for solid peptide synthesis was demonstrated by the synthesis of sequences comprising the 65-74 residues of acyl carrier protein. The efficiency of activation was determined by competition experiments. From all these studies the conclusion can be drawn that N-cyclohexyl-N'-isopropylcarbodiimide is comparable to or even better than the commonly used DCC for mediation of peptide bond formation in solid phase synthesis. By virtue of the solubility of N-cyclohexyl-N'-isopropylurea in dichloromethane, the carbodiimide seems to be a good candidate for practical execution of peptide bond formation by the standard carbodiimide procedure.

Carbodiimides↗
PubMed1994

Reinvestigation of the reactions of carbodiimides with alkoxycarbonylamino acid symmetrical anhydrides. Isolation of two N-acylureas.

Alkoxycarbonylamino acid symmetrical anhydrides were allowed to react with N,N'-diisopropylcarbodiimide. The determination of the decrease in carbodiimide concentration indicated that the reaction was slow and proceeded indirectly. It is presumed that symmetrical anhydride in the presence of basic carbodiimide is converted into oxazolone and alkoxycarbonylamino acid. The latter reacts with carbodiimide to give O-acylisourea which, in turn, rearranges to N-acylurea. A second minor product was found to be N-(N1,N2-bisalkoxycarbonyldipeptidyl)urea. The main pathway leading to the formation of this product starts with rearrangement of the symmetrical anhydride to N1,N2-bisalkoxycarbonyldipeptide acid. These experiments suggest that the reaction between anhydride and carbodiimide is not the source of N-acylurea in peptide synthesis.

Acylation↗
PubMed1989

Synthesis and biological evaluation of human preproenkephalin (100-111) and its analogs.

The dodecapeptide sequence, Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly-Phe-Met (BI), which is totally conserved in the primary structures of human, bovine, rat and toad preproenkephalins, has been synthesized by the solid-phase method. Coupling reactions were achieved by using symmetrical anhydrides of tert.-butyloxycarbonylamino acids performed with N-tert.-butyl,N'-methylcarbodiimide. 6-Arg and 7-Lys analogs have also been obtained. The peptides show opiate activity in both GPI and MVD assay, and possess antinociceptive properties as estimated by the hot-plate test in mice when applied intracisternally.

Amino Acids↗
PubMed1989

Primary structure of fox pituitary growth hormone.

Tryptic digests of fox growth hormone (fGH) were separated by reverse phase high performance liquid chromatography (HPLC) and by paper electrophoresis. From the amino acid composition of these tryptic peptides and from their alignment with the expected tryptic peptides from bovine growth hormone (bGH), the primary structure of fGH is proposed. There are only 17 amino acid residues which are different in these two growth hormone molecules.

Amino Acid Sequence↗
PubMed1988

Isolation and characterization of growth hormone from blue fox pituitary glands.

Growth hormone has been purified to homogeneity from blue fox pituitary glands. It has 191 amino acids with two disulfide bridges and a single tryptophan residue. The somatotropin activity is only 8% when compared with the bovine hormone in the receptor-binding assay. From radioimmunoassay data using baboon antisera to porcine or bovine growth hormone, the fox hormone has 14-17% immunoreactivity of bovine or porcine hormone.

Amino Acid Sequence↗
PubMed1988

The influence of aminophylline on human neutrophils--possible protection of lung from proteolytic injury.

Protease-antiprotease imbalance in the lung is considered to be a likely pathogenetic mechanism in the development of lung injury--particularly emphysema. Aminophylline is often used in bronchitis, bronchial asthma and emphysema. To assess, whether aminophylline indeed affects this mechanism we evaluated in vitro its influence at therapeutical concentrations (12 and 20 micrograms/ml) on phagocytosis, release of total protein and lysosomal enzymes after phagocytosis, spontaneous migration and chemotaxis of human neutrophils to zymosan-activated serum. There were no significant differences in phagocytosis, release of leukoprotease and acid phosphatase between neutrophils with and without aminophylline at both concentrations. However, the release of total protein was different (p less than 0.02, 12 micrograms/ml) and lower (p less than 0.02, 20 micrograms/ml) than the control. The mean decrease in protein release was 13.5 +/- 6% of the control and aminophylline inhibited the release of the protein with molecular weight below 35.000 daltons. Significant migration inhibition was found in 22% cases (12 micrograms/ml, n = 9) and in 53% (20 micrograms cm-3, n = 13). Neutrophil chemotaxis was different (p less than 0.02, 12 micrograms/ml) and lower (p less than 0.05, 20 micrograms/ml) than the control. The obtained results suggest that high doses, of aminophylline may diminish inflammatory recruitment of neutrophils--a rich source of elastase to the lung, and thus diminish proteolytic pulmonary injury.

Acid Phosphatase↗
PubMed1987

Isolation and amino acid sequence of insulins and C-peptides of European bison (Bison bonasus) and fox (Alopex lagopus).

Insulins and C-peptides were extracted and purified from bison and fox pancreatic glands. The insulins were reduced and pyridylethylated, and the derived A- and B-chains separated by HPLC. Amino acid sequence determinations of the pyridylethylated A- and B-chains proved bisontine insulin to be identical to bovine insulin and fox insulin to be identical to dog and porcine insulin. Bisontine C-peptide proved to be identical to bovine C-peptide. The isolated fox C-peptide comprises 23 amino acid residues and probably represents a major tryptic fragment of a larger C-peptide. The fox C-peptide fragment is identical to the dog C-peptide (9-31) except for residue 3 (residue 11 in the dog C-peptide), which is aspartic acid as compared with glutamic acid in the dog C-peptide.

Amino Acid Sequence↗