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D Vogel

Publications and source records attributed to D Vogel.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cyclic beta-casomorphin analogues with mixed mu agonist/delta antagonist properties: synthesis, pharmacological characterization, and conformational aspects.

Analogues of the potent and moderately mu-opioid-receptor-selective cyclic beta-casomorphin-5 derivative H-Tyr-c[-D-Orn-Phe-D-Pro-Gly-] (2) were prepared by conventional solution synthesis. Replacement of the Phe3 residue by 2-naphthylalanine (2-Nal) led to a peptide (4) with high affinity for both mu and delta opioid receptors. This compound turned out to be an agonist in the mu-receptor-representative guinea pig ileum (GPI) assay but a moderately potent antagonist against various delta agonists in the delta-receptor-representative mouse vas deferens (MVD) assay. It thus represents the first known cyclic opioid peptide analogue with mixed mu agonist/delta antagonist properties. Interestingly, replacement of 2-Nal3 in compound 4 with 1-naphthylalanine (1-Nal) resulted in an analogue (5) showing high affinity for mu receptors and a full agonist effect in the MVD assay that was mediated by both mu and delta receptors. Substitution of Trp for Phe3 in 2 (compound 8) was well tolerated at both receptors and led to an analogue with agonist activity in both the GPI and MVD assays. Variation of the peptide ring size in 4 was achieved by substitution of D-Orn2 with D-Lys (compound 6) or D-2,4-diaminobutyric acid (compound 7). Analogue 6 was also a mixed mu agonist/delta antagonist with somewhat lower potency than 4, whereas compound 7 displayed mu agonist and partial delta agonist properties. Further reduction of the peptide ring size, as achieved by deletion of the Gly5 residue, produced a compound (9) which was a full agonist in both bioassays. Conformational analysis of analogues 2, 4, and 5 by 1H NMR spectroscopy and molecular mechanics studies suggested that the overall conformation of parent compound 2 and the 2-Nal-containing peptide 4 was similar, while the side-chain orientation of 1-Nal in peptide 5 was different. These results suggest that the delta antagonist properties of analogue 4 may not be due to a difference in its overall conformation as compared to the agonist 2 but may be a direct effect of the 2-naphthyl moiety per se preventing proper alignment of the peptide for receptor activation.

Amino Acid Sequence↗
PubMed1994

Effects of CLIP (corticotropin-like intermediate lobe peptide) and CLIP fragments on paradoxical sleep in rats.

The effects of the POMC-derived peptide CLIP [corticotropin-like intermediate lobe peptide; ACTH(18-39)] and its shorter fragments ACTH(25-39), ACTH(18-24), and ACTH(20-24) on sleep were investigated in rats housed under normal 12-h light/12-h dark conditions (0600 light on). CLIP (10 ng) or equimolar doses of CLIP fragments, respectively, were injected intracerebroventricularly immediately before the 8-h recording period (0800-1600). It was found that paradoxical sleep (PS) was increased by CLIP (+20%) as well as by the N-terminal CLIP fragment ACTH(18-24) (+18%) and by the pentapeptide ACTH(20-24) (+25%), whereas the C-terminal fragment ACTH(25-39) was ineffective. Slow-wave sleep (SWS) was not influenced. These results clearly demonstrate that CLIP and its N-terminal fragments have selective PS-enhancing effects. CLIP and/or CLIP partial sequences are possible candidates for endogenous PS-inducing peptides involved in the physiological regulation of paradoxical sleep.

Adrenocorticotropic Hormone↗
PubMed1994

Ras point mutations occur in acute myeloid leukemia with illegitimate T-cell receptor delta gene rearrangement.

Mutations in the ras proto-oncogenes are the most frequently observed molecular alteration in acute myeloid leukemia (AML). Whether ras mutations occur as late or relatively early events in the multistep process of myeloid transformation, remains an open question. We previously described illegitimate T-cell receptor (TCR)-delta gene rearrangements in a subset of AML. These recombinations were detected in 9 out of 100 de novo AML cases. Southern blot analysis suggested the presence of these recombinations in the vast majority of AML cells and thus could be used as clonal markers. In order to more accurately define the role of ras proto-oncogene mutations in the multistep process of malignant transformation in myeloid leukemias, we performed single strand conformation polymorphism (SSCP) assays, slot blot and direct sequencing analysis on these nine cases with illegitimate TCR delta gene rearrangements. Ras proto-oncogene mutations were found in three of nine cases. Interestingly, SSCP, slot blot and sequencing suggested the presence of the respective mutations in most of the leukemic cells. Thus, ras mutations presumably occurred early in the process of transformation in these three cases.

Adult↗
PubMed1993

Detection of p53 mutations using nonradioactive SSCP analysis: p53 is not frequently mutated in myelodysplastic syndromes (MDS).

p53 is one of the most frequently mutated genes in human cancers. Since p53 has been implicated in lymphatic and some myeloid leukemias, such as the blastic phase of chronic myelogenous leukemia, we sought to address the role of p53 gene mutations within exons 4-9 in myelodysplastic syndromes (MDS), a myeloid preleukemic condition. In order to avoid the potential hazard of using radioactive single-strand conformation analysis (SSCP), we used a nonradioactive SSCP method based on the silver stain of small minigels. In cell lines with known point mutations of the p53 gene, aberrant migrating bands were found. Serial dilutions indicated a sensitivity comparable to radioactive methods. Furthermore, a common polymorphism within the 4th exon of the p53 gene was easily detected. However, of 17 primary samples from patients with MDS, none harbored a p53 gene mutation. We conclude that this nonradioactive method can easily be used to screen for p53-gene mutations, and that p53-gene mutations do not play a major role in the pathogenesis of MDS.

Alleles↗
PubMed1991

The use of transdermal scopolamine to control drooling. A case report.

Drooling is a serious social handicap experienced by some neurologically impaired patients. No one method has been identified to control drooling for all patients, however, anticholinergic drugs recently have been utilized. In the case study described, transdermal scopolamine patches were found to be effective for controlling drooling in a traumatic brain-injured patient for whom more conservative methods failed. From a baseline saliva flow rate, saliva flow decreased an average of 30% with one-patch and 59% with two-patch dosing. No significant side effects were observed with treatment, and the decrease in drooling was maintained for a 4-month period. Although transdermal scopolamine may represent one acceptable facet of long-term treatment, it must be stressed that efficacy is variable across patient populations and that treatment approaches must be individualized.

Administration, Cutaneous↗
PubMed1989

Children's responses to different forms of expression of anger between adults.

Anger is not a homogeneous stimulus, but can vary on a variety of dimensions and domains. This study examined children's responses to anger as a function of: (a) the mode of expression of anger (nonverbal, verbal, verbal-physical), and (b) whether or not anger between others was resolved. Children were presented with videotaped segments of angry and friendly interactions and asked questions concerning their responses. All angry interactions, including non-verbal anger, were perceived as negative events and elicited negative emotions. Unresolved anger was perceived as a far more negative event than resolved anger and induced greater feelings of anger and distress in children. Verbal-physical anger was perceived as the most negative form of expression of anger. Boys reported more angry feelings in response to anger than girls. Distress responding was greater in children from homes in which there was interparent physical aggression and in children with behavior problems. Finally, the utility of this methodology is supported by relatively high test-retest reliability and limited evidence of context effects.

Adaptation, Psychological↗
PubMed1984

Cellular immunosenescence in F344 rats: decreased natural killer (NK) cell activity involves changes in regulatory interactions between NK cells, interferon, prostaglandin and macrophages.

Natural killer (NK) activity of F344 rat spleen cells remained constant between 1 and 18 months of age under specific pathogen-free (SPF) conditions. Between 18 and 24 months of age, however, there was a dramatic decline in activity which remained at a low baseline throughout the normal lifespan. Removal of adherent cells on G-10 Sephadex columns revealed age-related changes in adherent cell regulation of NK activity. Young (4-6 week) NK activity was consistently decreased by adherent cell removal while old (24-30 month) NK activity was slightly but reproducibly increased. Moreover, splenic macrophages from old rats purified by adherence to microexudate-coated surfaces were highly suppressive to young nonadherent NK activity. A role for endogenous prostaglandin (PG) in suppressed old rat NK activity was suggested by the effectiveness of anti-PGE2 in vivo to boost old NK activity. Although old rat NK activity was boosted to a relatively greater extent by interferon (IFN) in vitro than was young NK activity, IFN-boosted NK activity of old rats was much more sensitive to PGE2 inhibition than was IFN-boosted young rat NK activity. IFN treatment in vitro or poly(I:C) treatment in vivo induced protection against PGE2 inhibition of NK activity in young rats, while no resistance to PGE2 inhibition was induced in old rat NK cells by similar treatments. In vivo, the same protocol of IFN administration which boosted young rat NK activity further suppressed old rat activity. These results support the hypothesis that immunosuppression related to aging, which supersedes the boosting effect of IFN, involves the combined effects of suppressor macrophages (via PGE2) and intrinsic changes in effector (NK) cells which render them more sensitive to PGE2 inhibition.

Aging↗
PubMed1982

Hormonal and metabolic parameters following insulin-induced hypoglycemia.

The present study was conducted in 12 healthy volunteers to determine the effect of porcine insulin (0.15 U/kg i.v.) on a number of different metabolic and hormonal parameters measured simultaneously. The nadir of blood glucose (19.0 +/- 2.7 ng/100 ml) is detected 30 min following insulin application, paralleled by suppressed levels of FFA and beta-hydroxybutyrate. The lowest level of potassium (3.39 +/- 0.09 mval/l) is observed 45 min following insulin application. The hormones of counterregulation show an uniform pattern of response. Peak levels of norepinephrine (228.9 +/- 36.0 ng/l) and epinephrine (720.6 +/- 125.6 ng/l) are observed at 30 and 45 min, those of cAMP (33.4 +/- 2.5 pmol/ml), glucagon (0.209 +/- 0.024 ng/ml), ACTH (166.0 +/- 40.1 ng/ml), and prolactin (28.1 +/- 7.8 ng/ml) at 45 min and finally those of cortisol (26.1 +/- 3.3 micrograms/100 ml) and growth hormone (21.6 +/- 3.1 ng/ml) at 60 min following insulin injection. As the blood glucose level is already rising after 30 min it is concluded that the catecholamines and glucagon play a major part in the restitution of normal blood glucose levels. At the end of the test, blood glucose and hormone levels have almost normalized, but FFA and beta-hydroxybutyrate levels are doubled and almost triplicated as compared to the starting point levels.

3-Hydroxybutyric Acid↗
PubMed1981

Analysis of bicarbonate binding to crocodilian hemoglobin.

Crocodilian hemoglobin has a high intrinsic oxygen affinity but does not react with those organic phosphate esters that normally control the oxygen affinity of blood in higher vertebrates. Instead, its oxygen affinity is greatly lowered by CO2. The present study was undertaken to determine the nature of the CO2 binding to the hemoglobin of a crocodilian species, the Caiman, both qualitatively and quantitatively. The following parameters were measured: (a) carbamino compounds of deoxy- and oxyhemoglobin, (b) the effect of CO2 (at constant pH) on the oxygen affinity of Caiman hemoglobin, (c) total CO2 concentration of hemoglobin solutions at different pH and pCO2 values, and (d) the effect of CO2 on CD spectra of Caiman aquomethemoglobin. An analysis of the results of these measurements revealed that CO2 binding in the form of carbamate was not oxygen-linked and cannot, therefore, mediate the CO2 effect on the oxygen affinity. It was found, however, that 2 mol of bicarbonate can be bound/hemoglobin tetramer and that the association constant of the bicarbonate anion greatly depends upon the state of ligation. At pH 7.02 and 25 degrees C, a numerical value of 2.0 X 10(3) M-1 was obtained for deoxyhemoglobin, while for oxyhemoglobin no significant bicarbonate binding could be observed. At more alkaline pH (pH greater than or equal to 7.5), the association constant for deoxyhemoglobin decreases. Circular dichroism of Caiman aquomethemoglobin decreased considerably in the 287-nm region upon addition of CO2 at constant pH, an effect very similar to the one caused by inositol hexaphosphate in human aquomethemoglobin.

Alligators and Crocodiles↗