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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 163 records · Page 9Linked to original sources

Alpha 1 B- but not alpha 1 A-adrenoceptors mediate inositol phosphate generation.

We used novel highly subtype-selective antagonists to study whether alpha 1A- and/or alpha 1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 microM) and prazosin (100 nM) completely abolished the stimulated inositol phosphate generation. The alpha 1A-selective antagonists 5-methyl-urapidil (100 nM) and (+)- and (-)-niguldipine (10 nM) caused only weak inhibition or none at all although these concentrations occupied alpha 1A-adrenoceptors almost completely. In contrast, pretreatment with the irreversible alpha 1B-selective chloroethylclonidine reduced the noradrenaline-stimulated inositol phosphate generation by 76 +/- 8%. These data demonstrate that alpha 1B-adrenoceptors couple to inositol phosphate generation; the signal transduction system of alpha 1A-adrenoceptors remains unclear.

Adrenergic alpha-Antagonists↗

Does lithium in vitro and ex vivo alter the release of [3H]noradrenaline from brain tissue and the sensitivity of presynaptic autoreceptors?

The effect of lithium on the release of noradrenaline (NA) was investigated in slices of the cerebral cortex and hippocampus from the rat in vitro and ex vivo. In vitro, small concentrations of lithium chloride (1 and 2 mM) failed to alter the electrically stimulated tritiated overflow from slices preincubated with [3H]NA. Larger concentrations of lithium chloride (5 and 10 mM) significantly increased the electrically evoked overflow of [3H]NA by 18-40% as well as the basal 3H efflux. The alpha 2-adrenoceptor agonist clonidine inhibited, whereas the alpha 2-adrenoceptor antagonist rauwolscine facilitated the stimulated overflow of [3H]NA. These effects were attenuated by 10 mM lithium chloride but not by 2 mM. In slices of brain obtained from rats treated for 5 weeks with lithium chloride, the electrically evoked release of [3H]NA, as well as the inhibition of release of [3H]NA, induced by the alpha 2-adrenoceptor agonist clonidine were unaltered. It is concluded that therapeutically relevant concentrations of lithium do not influence the release of NA and that the function of presynaptic alpha 2-autoreceptors is not affected by chronic treatment with lithium. The increase in release of [3H]NA by larger concentrations of lithium may be relevant to its toxic effects.

Animals↗

Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects.

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive; n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups ("drug-free") were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.

Adult↗

Aortoiliac imaging by projective phase sensitive MR angiography: effects of triggering and timing of data acquisition on image quality.

To assess the ability of projective phase sensitive magnetic resonance (MR) angiography to visualize the aortoiliac vascular segment, and to determine the effects of triggering and timing of data acquisition om image quality, we studied 18 healthy volunteers, mean age 33.3 +/- 11 years, by color Doppler imaging and by MR angiography. MR angiography was performed at 1.5 T using a flow-adjustable gradient-echo (FLAG) sequence operated in both ECG-triggered and non-triggered acquisition modes. The images were graded in a blinded fashion by two independent observers. The data were analyzed using Pearson's chi-square analysis. Eighteen triggered time-resolved and 17 non-triggered, time-averaged MR angiograms consisting of 252 and 17 angiographic images, (AI) respectively, were analyzed. In the triggered mode 69 (27.4%) AI and in the non-triggered mode 2 (11.8%) AI were diagnostic. At least one triggered diagnostic AI was obtained in each subject. The image grades were not statistically different between observers (kappa = 0.6686). In the triggered mode diagnostic images were acquired within +/- 90 msec of the peak systolic flow velocity determined by Doppler. The proportion of diagnostic images in the triggered mode was highest (73.3%) within a 30-msec interval before the peak flow. In healthy subjects the aortoiliac segment is reliably visualized by FLAG MR angiography. The optimum results are achieved using the triggered acquisition mode and timing acquisition to the initial 180 msec of the abdominal aortic systolic flow pulse.

Adult↗

[Status-dependent neurochemical parameters in schizophrenic and affective diseases].

The dynamics of course, i.e., the marked psychopathological fluctuation in acute phases of schizophrenic and other idiopathic psychoses was little considered up to now in investigations referred to correlating clinical and neurochemical findings. Therefore, we selected subgroups of patients, classified as inactive or slight, moderate or severe process-active according to the operational defined actual psychopathological syndrome (Gross et al. 1988, Klosterkötter et al. 1989) at the time of taking of blood samples. We demonstrated in previous studies that the fluctuation and/or sudden development (minutes, hours, up to six days at the latest) of schizophrenic first rank symptoms and certain basic symptoms may reflect also an instability and process-activity of underlying neurochemical changes. In this study we have measured the concentrations of dopamine, noradrenaline, adrenaline, 5-HT, TSH, prolactin, HGH, melatonin, cortisol, T 3, T 4 and 28 amino acids in blood samples (examined 8 times within 24 hours) from 48 schizophrenic patients, divided in 4 subgroups (each 12 cases) with severe, moderate, slight or lacking process-activity, from 20 patients with (inactive or only slight active) depressive phases of affective psychoses and from normal controls. Marked process-active schizophrenics showed significantly higher levels of dopamine, noradrenaline and 5-HT, and significantly lower levels of TSH, compared to healthy controls and process-inactive schizophrenics with pure deficiency syndromes, that reveal a relative hypo-activity of catecholaminergic and presumably also of serotoninergic systems. In the subgroup of depressions were found decreased concentrations of noradrenaline, 5-HT, adrenaline and melatonin when compared to marked process-active schizophrenics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Efficacy of interferons on bowenoid papulosis and other precancerous lesions.

Preliminary results of an open randomized trial of recombinant interferon gamma in patients suffering from bowenoid papulosis are described. Recombinant interferon gamma was given subcutaneously to 12 patients at a daily dose of 4 X 10(6) I.U. by injection. Four patients each were assigned to one of three treatment groups consisting of continuous therapy (group A) with three subcutaneous injections per week for 13 weeks; intermittent block therapy (group B) with four six-week cycles consisting of five injections on days 1, 3, 5, 7, and 9 of each cycle; and intermittent single-dose therapy (group C) with six four-week cycles consisting of only one subcutaneous injection on day one of each cycle. At the twenty-sixth week after onset of therapy, complete responses were seen in three of four patients of treatment group A, whereas in the treatment groups B and C only one patient, respectively, responded partially. These results suggest that in contrast to condylomata acuminata bowenoid papulosis lesions respond better to continuous than to intermittent interferon gamma injections.

Adolescent↗

The effect of reserpine, desipramine and thyroid hormone on alpha 1a- and alpha 1b-adrenoceptor binding sites: evidence for a subtype-specific regulation.

Using radioligand binding techniques we studied whether alpha 1a- and alpha 1b-adrenoceptor recognition sites can be regulated independently by drugs and hormones. In rat cerebral cortex subchronic treatment with reserpine enhanced the number of [3H]-prazosin binding sites and the proportion of alpha 1b binding sites. Desipramine treatment which did not alter Bmax values, increased the proportion of alpha 1a and decreased alpha 1b binding sites. In rat myocardium hypothyroidism decreased alpha 1b-adrenoceptor binding sites. These results suggest that alpha 1-adrenoceptors are regulated in a subtype-selective manner.

Animals↗

Effect of hypo- and hyperthyroidism on binding of [3H]-nitrendipine to myocardial and brain membranes.

The density of calcium channel binding sites as determined by [3H]-nitrendipine binding was found to be decreased in hearts of hyperthyroid rats but hardly altered by hypothyroidism. In contrast, dihydropyridine binding sites in the cerebral cortex were unaffected by dysthyroid states. Myocardial [3H]-nitrendipine binding sites were also decreased after treatment of the animals with isoprenaline but not in spontaneously hypertensive rats. These findings suggest that myocardial hypertrophy is not necessarily accompanied by a loss of calcium channels and that thyroid hormone regulates the density of [3H]-nitrendipine binding sites in a tissue-specific manner.

Animals↗

Timing of data acquisition determines image quality in femoropopliteal phase-sensitive MR angiography.

To study the effects of timing of data acquisition on quality of femoropopliteal magnetic resonance (MR) angiograms, the authors studied 16 healthy men, mean age 34.3 +/- 6 years, by color Doppler imaging and by phase-sensitive (PS) MR angiography. PS MR imaging was performed at 1.5T using a flow adjustable gradient (FLAG) pulse sequence. The images were graded in a blinded fashion by two independent observers. Of 16 MR angiograms consisting of 141 angiographic images (AI), 45 (31.9%) were diagnostic. At least 1 diagnostic AI was obtained in each subject, and 38 (84.4%) of the diagnostic images were acquired within the first 120 milli-seconds (ms) of the systolic flow pulse. The highest yield of diagnostic images (90.9%) was obtained in the interval of thirty to sixty ms before the peak flow velocity. In healthy man diagnostic PS MR angiography requires triggering to the femoropopliteal systolic flow pulse. The highest yield of diagnostic images is acquired during the flow pulse acceleration.

Adult↗

Urapidil analogues are potent ligands of the 5-HT1A receptor.

Urapidil and three derivatives with hypotensive properties (5-acetyl-, 5-formyl-, 5-methylurapidil) bind selectively to 5-HT receptors of the 5-HT1A subtype and to alpha 1-adrenoceptors labeled by [3H]8-OH-DPAT and [3H]prazosin, respectively. Binding to these receptors is likely to contribute to their hypotensive action. 5-Methylurapidil, the most potent of these drugs, was used in its 3H-labeled form as a radioligand. After blockade of alpha 1-adrenoceptors by prazosin, [3H]5-methylurapidil binds with nanomolar affinity to a binding site that is similar to the (5-HT1A) site labeled by [3H]8-OH-DPAT. No binding to other 5-HT1 and 5-HT2 receptors was observed. 5-HT uptake inhibitors did not inhibit [3H]5-methylurapidil binding. [3H]5-methylurapidil binding is sensitive to GTP and is modulated by divalent cations. Our results show that urapidil derivatives bind to the 5-HT1A recognition site and that [3H]5-methylurapidil is a valuable tool for the investigation of this receptor subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Multicenter evaluation of triamcinolone acetonide nasal aerosol in the treatment of adult patients with seasonal allergic rhinitis.

Triamcinolone acetonide aerosol inhalation therapy is effective for the prophylactic treatment of asthma. Recently, the delivery system for this preparation has been modified for use in allergic rhinitis. A total of 180 adult patients with symptomatic seasonal allergic rhinitis participated in this double-blind, placebo-controlled, multicenter trial. Patients received either placebo or approximately 25 mg per actuation of triamcinolone acetonide aerosol per nostril, qid, for 4 weeks. Each patient kept a daily diary rating rhinitis symptoms. Both the patient and the physician also gave global evaluations of drug efficacy. Of 168 evaluable patients, significant reductions were seen at week 1, week 2, and in the overall study evaluation of ratings for intensity (P less than .001) and duration (P less than .05) of various rhinitis symptoms such as nasal stuffiness, discharge, and sneezing in the group given triamcinolone acetonide. Superiority to placebo group was evident as early as day 1 and maintained throughout the study. Both patients and physicians rated triamcinolone acetonide as significantly more effective than placebo for the duration of the study (P less than .001). There was a marked reduction in nasal smear eosinophils in the triamcinolone acetonide group. There was no difference between groups in safety evaluations including no evidence of suppression of the adrenal axis and no evidence of fungal infection. This study demonstrates that triamcinolone acetonide in a dose of 25 micrograms per nostril, qid, is effective, well tolerated, and safe in reducing symptoms in adult patients with seasonal allergic rhinitis.

Administration, Intranasal↗

Demonstration of alpha 1A- and alpha 1B-adrenoceptor binding sites in human brain tissue.

Radioligand binding studies suggest that alpha 1-adrenoceptor recognition sites are heterogeneous. Several adrenergic agents discriminate between two adrenoceptor binding sites designated alpha 1A and alpha 1B. In the present study we demonstrate for the first time that these two subtypes exist in the human brain. 5-Methyl-urapidil and (+)-niguldipine, which have previously been shown to be alpha 1A-selective, inhibited [3H]prazosin binding to cortical membranes in a biphasic manner. The irreversible alpha 1B-ligand, chloroethylclonidine, preferentially eliminated the binding sites with low affinity for (+)-niguldipine. In contrast, BE 2254 and unlabelled prazosin displaced the radioligand in a monophasic manner. The IC50 values for prazosin were not affected by pretreatment of the membranes with chloroethylclonidine. Our data on human brain membranes are in excellent agreement with recent findings in rat tissues and suggest that the alpha 1-adrenoceptor subtypes in human brain are similar to those in rat tissues.

Adrenergic alpha-Antagonists↗

Effects of nicorandil on coronary circulation and myocardial ischemia.

The effect of the new antianginal drug, nicorandil, was studied in several models of myocardial ischemia in anesthetized dogs. In animals subjected to an acute or chronic coronary artery occlusion, nicorandil produced increases in collateral perfusion when changes in aortic pressure were minimized. In a model of irreversible ischemia, nicorandil produced a marked (50%) decrease in myocardial infarct size. In several models of reversible ischemia-reperfusion injury, the "stunned myocardium," nicorandil was shown to enhance the recovery of systolic segment shortening after a brief period (15 to 30 minutes) of coronary occlusion. Other vasodilators such as nitroglycerin or nifedipine were not as efficacious as nicorandil. In a model of multiple (n = 3) coronary occlusion (5 minutes) with intermittent (30 minutes) reperfusion, nicorandil improved the recovery of systolic segment shortening during reperfusion and prevented the loss of adenosine triphosphate and tissue edema that occurred in untreated hearts. The beneficial effects of nicorandil on functional and metabolic recovery after recurrent ischemia was shown to be partially the result of an energy-sparing effect of nicorandil to reduce free fatty acid use during the ischemic period. Cyclooxygenase blockade with indomethacin did not block the beneficial effects of nicorandil in the stunned myocardium. These results suggest that nicorandil does not promote an increase of prostacyclin. Finally, nicorandil was found to inhibit superoxide anion production by human neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine plus cytochalasin B. These results suggest that part of the beneficial actions of nicorandil may occur during reperfusion and may be the result of a reduction in oxygen free radical production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of warm and cold ischemia on mitochondrial functions in brain, liver and kidney.

The purpose of this work was to study the effects of warm (37 degrees C) and cold (4 degrees C) ischemia on different mitochondrial functions in rat brain, liver and kidney. After 10 to 60 minutes of ischemia at 37 degrees C the energy coupled respiration as well as the ADP-induced malate-aspartate shuttle activity in brain and liver mitochondria or the rate of mitochondrial ATP synthesis in kidney were significantly decreased. However, the respiratory rates and the shuttle activity in the absence of ADP remained unchanged. These data suggest that ischemia primarily affects electron transport in the respiratory chain rather than the hydrogen shuttle and the energy coupling system. When the temperature during the indicated ischemic periods was decreased to 4 degrees C, in brain and liver no significant alterations of these mitochondrial functions were found in comparison with the non-ischemic controls. When rat kidneys were stored for 36 hours at 4 degrees C according to Collins mimicking transplantation conditions, the mitochondrial respiration and ATP synthesis were only slightly decreased. It therefore appears that hypothermia can prevent effectively mitochondrial dysfunction due to ischemia.

Adenosine Triphosphate↗

Cellular localization of induced human interferon-beta mRNA by non-radioactive in situ hybridization.

Induced interferon-beta (IFN-beta) mRNA was localized in human FS-4 fibroblasts by in situ hybridization using biotinylated probes. The hybridization sites were detected by incubation with a nick-translated genomic DNA probe (1.8 kb) via streptavidin-colloidal gold followed by silver contrast enhancement. The positive signals were observed by reflection-contrast light microscopy. IFN-beta mRNA was transiently induced by poly r(I): r(C) in fibroblasts 2-4 h after induction. Induction in the presence of cycloheximide and actinomycin D (superinduction conditions) exhibited an enhanced level of IFN-beta mRNA with a maximum at 4-8 h. The kinetics of the IFN-beta mRNA expression in the cytoplasm as revealed by in situ hybridization proved to be compatible with the results of Northern blotting experiments of total cellular RNA.

Cells, Cultured↗