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Biomedical subjects

G Arnold

Publications and source records attributed to G Arnold.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cloning and expression of a queen pheromone-binding protein in the honeybee: an olfactory-specific, developmentally regulated protein.

Odorant-binding proteins (OBPs) are small abundant extracellular proteins thought to participate in perireceptor events of odor-pheromone detection by carrying, deactivating, and/or selecting odor stimuli. The honeybee queen pheromone is known to play a crucial role in colony organization, in addition to drone sex attraction. We identified, for the first time in a social insect, a binding protein called antennal-specific protein 1 (ASP1), which binds at least one of the major queen pheromone components. ASP1 was characterized by cDNA cloning, expression in Pichia pastoris, and pheromone binding. In situ hybridization showed that it is specifically expressed in the auxiliary cell layer of the antennal olfactory sensilla. The ASP1 sequence revealed it as a divergent member of the insect OBP family. The recombinant protein presented the exact characteristics of the native protein, as shown by mass spectrometry, and N-terminal sequencing and exclusion-diffusion chromatography showed that recombinant ASP1 is dimeric. ASP1 interacts with queen pheromone major components, opposite to another putative honeybee OBP, called ASP2. ASP1 biosynthetic accumulation, followed by nondenaturing electrophoresis during development, starts at day 1 before emergence, in concomitance with the functional maturation of olfactory neurons. The isobar ASP1b isoform appears simultaneously to ASP1a in workers, but only at approximately 2 weeks after emergence in drones. Comparison of in vivo and heterologous expressions suggests that the difference between ASP1 isoforms might be because of dimerization, which might play a physiological role in relation with mate attraction.

Amino Acid Sequence↗
PubMed1999

[High dosage therapy of Parkinson disease. New dopamine agonist pramipexol allows reduction of L-dopa dose down to zero].

We report a 63-years old patient with Parkinson's disease, who experienced slight fluctuations 10 years after first signs of the disease and two years after initiation of levodopa/carbidopa and biperiden therapy. He was enrolled in a double blind, placebo controlled study with the dopamine agonist pramipexole. This study was extended to an open phase. During this phase we were able to reduce levodopa/carbidopa down to zero, while fluctuations and peak dose dyskinesias ceased. The most important adverse event were hypersomnia and very slight persistent dyskinesias, which were reported tolerable by the patient. Treatment without levodopa/carbidopa could be maintained for 31 months. We conclude that in selected cases patients in Hoehn and Yahrs stages II to III and with mild fluctuations might be treated with pramipexole without levodopa.

Antiparkinson Agents↗
PubMed1999

Relative quantification of signal on T2-weighted images in the basal ganglia: limited value in differential diagnosis of patients with parkinsonism.

A reduction in signal in the basal ganglia on T2-weighted images is said to correlate with a poor response to L-DOPA and may help to identify patients with non-idiopathic parkinsonism. Our aim in this prospective study was to use the contrast-to-noise ratio of the MRI signal on T2-weighted images in various parts of the basal ganglia in 43 patients with de novo parkinsonism. Signal intensity measurements were compared to the response to the dopamine agonist apomorphine and dopamine-D2 receptor binding obtained by 3-iodo-6-methoxybenzamine single-photon emission computed tomography (IBZM-SPECT). A reduced contrast-to-noise ratio in the putamen correlated significantly with a negative response to apomorphine and reduced striatal IBZM binding. No additional signal intensity measurement correlated with response to apomorphine or specific IBZM binding. However, there was a considerable overlap of contrast-to-noise ratios between patients with a positive or negative response to apomorphine or normal and reduced IBZM binding. We suggest that semiquantitative assessment of signal intensity in the putamen shows a significant reduction in patients with probably nonidiopathic parkinsonism compared with patients with probably idiopathic parkinsonism. However, this method does not exclude idiopathic parkinsonism in a given patient.

Adult↗
PubMed1999

Therapy of Migraine Headache in Cancer Patients.

This article reviews how to establish the diagnosis of migraine, the possible differential diagnoses, and the present state of the art of therapy. Emphasis is laid on nonsteroidal antiphlogistic drugs, serotonin receptor agonists (the so called triptans), and antiemetic drugs. The interval therapy consists of beta-blockers, calcium antagonists, antiepileptics, and serotonin receptor antagonists. The pathophysiology is based on the concept of sterile neurogenic inflammation, cortical spreading depression (CSD), and hyperexcitability of the central nervous system (CNS).

Journal Article↗
PubMed1999

Protein status of infants with phenylketonuria undergoing nutrition management.

OBJECTIVES: The objectives of this study were to determine if Phenex-1, amino-acid modified medical food with iron maintained normal indices of protein status in infants with phenylketonuria (PKU) and to investigate factors that influence plasma amino acid concentrations. METHODS: A study was conducted for six months in 35 infants with classical PKU diagnosed in the neonatal period. Diet diaries and plasma amino acid concentrations were obtained monthly. Blood for analysis of plasma albumin, blood urea nitrogen (BUN), retinol binding protein (RBP) and transthyretin was obtained at one, three and six months of study. RESULTS: Mean (+/-SEM) total daily intake of medical food and nutrients was 79+/-4 g; 17.3+/-0.6 g protein, 660+/-18 kcal, 255+/-10 mg phenylalanine (Phe), and 1423+/-56 mg tyrosine (Tyr). Mean concentrations of plasma amino acids, except cystine (during entire study), glycine (first month) and Phe were in the normal range. Mean concentrations of plasma Phe were in the treatment range (120 to 360 micromol/L). Plasma concentrations of arginine, methionine, Phe, tryptophan, Tyr, and valine were positively correlated with intakes at various months of study. Concentrations of aspartic and glutamic acids, Phe, and Tyr were positively correlated and 17 amino acids were negatively correlated with the interval between feeding and blood draw. At six months of study, concentration of plasma albumin was 4.1+/-0.1 g/dL, RBP was 3.74+/-0.2 mg/dL, transthyretin was 17.9+/-0.9 mg/dL, and urea nitrogen was 11.9+/-0.5 mg/dL. CONCLUSION: During study, all mean plasma indices of protein status were in normal reference ranges. Phenex-1 supports normal mean plasma amino acid, albumin, RBP, transthyretin, and BUN concentrations when fed in adequate amounts.

Amino Acids↗
PubMed1999

Successful treatment of an invasive aspergillosis of the skull base and paranasal sinuses with liposomal amphotericin B and itraconazole.

Invasive aspergillosis and fulminant aspergillosis are rarities with a high mortality. In the literature there is no patient surviving an extended invasive aspergillosis of the paranasal sinuses and skull base after failure of operative intervention and of postoperative amphotericin B therapy. We report a complete remission of an invasive, partially fulminant aspergillosis. After an incomplete removal of the mycotic mass, we started postoperative drug therapy with amphotericin B. Under this treatment, the mycosis progressed. Additionally, the patient developed severe side effects, so that the treatment was interrupted. At this moment, we started a combined antimycotic drug therapy with liposomal amphotericin B and itraconazole. Within 10 weeks, clinically and radiologically, there was complete remission. The patient died 63 weeks after this treatment, due to a fulminant bacterial pneumonia. Postmortem histologic examination showed no aspergillosis in the skull base, paranasal sinuses, or lung.

Amphotericin B↗
PubMed1998

Cortical spreading depression-associated hyperemia in rats: involvement of serotonin.

We investigated whether the vasoactive neurotransmitter serotonin (5-HT) is involved in cortical spreading depression (CSD)-associated hyperemia in the rat. We focused on the 5-HT2 receptor, which is engaged in 5-HT induced small arteriolar relaxation in cats, as well as on the 5-HT1D/1B receptor, the binding site of the potent antimigraine drug sumatriptan. In male barbiturate anaesthetized Wistar rats (n=25) CSDs were elicited by brain topical application of 1 M KCl, and the DC-potential and regional cerebral blood flow (rCBF, by Laser Doppler flowmetry) were measured over the same hemisphere through dura and thinned bone, respectively. Intravenous application of 8 mg/kg of the 5-HT2A/2C receptor antagonist ritanserin (group I; n=8) significantly reduced the hyperperfusion amplitude during CSD by approximately 44% (p<0.05, from 342+/-124 to 194+/-97%, baseline before CSD=100%), and prolonged its duration by approx. 30%. Vehicle alone (group II; n=4) did not affect CSD hyperperfusion. The highly selective 5-HT1D/1B receptor agonist 311C90 was given in two doses: 100 micrograms/kg i.v. (n=5) had no effect on CSD hyperperfusion, while 800 micrograms/kg (n=5) increased hyperperfusion significantly (p<0.05, from 224+/-86 to 310+/-148%). We conclude that serotonin is, probably via 5-HT2 receptors, involved in the modulation of the regional cerebral blood flow increase during CSD. Novel highly selective receptor antagonists may help to discriminate the differential contribution of various 5-HT receptor subspecies.

Animals↗
PubMed1998

123I-IBZM binding compared with long-term clinical follow up in patients with de novo parkinsonism.

We performed a prospective clinical follow up (mean follow up, 36 months; range, 24-56 months) of 65 patients with de novo parkinsonism in whom imaging of dopamine D2 receptors was performed before the initiation of dopaminomimetic therapy by means of 123I-iodobenzamide-single-photon-emission computed tomography (IBZM-SPECT). The results of IBZM-SPECT were compared with the long-term response to dopaminomimetic drugs, the development of motor fluctuations, and the development of clinical signs incompatible with Parkinson's disease (PD). A total of 55 patients had normal and 10 patients had reduced IBZM binding; 45 patients showed a good response to levodopa (L-dopa), 11 showed an equivocal response, and nine did not respond; 31 patients developed a fluctuating response to dopaminomimetic drugs and seven patients developed clinical signs indicative of multiple-system atrophy (n = 5), progressive supranuclear palsy (n = 1), or corticobasal ganglionic degeneration (n = 1). Chi-squared analysis showed a significant correlation of the results of IBZM-SPECT with the long-term response to dopaminomimetic therapy (p < 0.0001) and the development of motor fluctuations (p < 0.001) or clinical signs incompatible with PD (p < 0.0001). We conclude that IBZM-SPECT can help to differentiate between patients who will show a good response to L-dopa and will develop motor fluctuations (most likely patients with PD) and those patients who will not respond to L-dopa and might develop clinical signs compatible with another hypokinetic disorder of the basal ganglia.

Adult↗
PubMed1998

[Valproic acid in prophylactic treatment of migraine].

In 1988, the first report on valproate in migraine prophylaxis was published. Since 1992, 359 patients have been investigated in five double blind studies. Valproic acid was effective in all studies compared to placebo; one study confirmed an effect similar to propranolol. There are no analyses of efficacy in comparison to plasma levels. Adverse events seem to occur somewhat more frequently than in propranolol, but are well known in epilepsy therapy. In the international literature and according to the recommendations of the German Headache Society, valproic acid is a well-established second-choice drug in migraine prophylaxis.

Clinical Trials as Topic↗
PubMed1998

Temporary vitreous gas tamponade by perfluoromethylcyclopentane.

Using perfluoromethylcyclopentane (FMCP; US patent no. 5,441,989, granted 1995) we have developed a new vitreous gas tamponade in a rabbit model that allows complete filling of the vitreous cavity without vitrectomy and without a significant increase in intraocular pressure. In humans this procedure would allow the blockage of inferior and posterior retinal holes without special positioning of the patient. Perfluoromethylcyclopentane (FMCP), a liquid perfluorocarbon with a boiling point slightly above body temperature, is injected in minute volumes into the vitreous cavity, where it vaporizes, thereby filling a gas volume approximately 500 times its liquid volume. FMCP was injected into the midvitreous in six rabbits (six eyes). After 2-3 days a complete gas tamponade was achieved in three eyes. Two eyes showed 75-90% filling, and one eye was filled only 50% with gas. Intraocular pressure was highest in the completely filled eyes, ranging from 26.6 to 38.8 mmHg. In all eyes the maximum expansion of the gas bubble lasted 2 weeks. One eye developed a retinal detachment. All eyes showed transient subcapsular cataracts. The results of this study showed that intravitreal injection of FMCP, a new perfluorocarbon liquid, results in a complete gas tamponade of the vitreous cavity which lasts 2 weeks without severe intraocular pressure rise and without vitrectomy. This procedure will be especially useful for eyes that have retinal detachment from inferior or posterior retinal holes. Injection of a conventional gas such as SF6 or C3F8 usually does not block retinal holes in inferior or posterior locations without tedious positioning and risk of (transient) glaucoma. Since the mechanism of transition of FMCP from liquid to gas in the vitreous is poorly understood, we are currently studying FMCP vaporization in an in vitro eye model.

Animals↗
PubMed1998

Pharmacologic heart rate reduction: effect of a novel, specific bradycardic agent on the heart.

Because heart rate (HR) is a major determinant of myocardial oxygen consumption (MVO2) a decrease in HR could prevent ischemia or reduce its consequences. We examined the effects of a novel bradycardic agent of the benzazepinone type, DK-AH 269 (DK), on ventricular function and perfusion in 12 isolated, blood-perfused rabbit hearts. HR was significantly reduced by 1mumol/L DK (160 +/- 28 vs. 124 +/- 23 min-1); diastole lengthened from 235 +/- 69 to 334 +/- 85 ms. Aortic flow tended to fall after DK (50.0 +/- 29.6 vs. 35.6 +/- 21.5 ml/min), but stroke volume remained unchanged (0.29 +/- 0.16 vs. 0.28 +/- 0.17 ml) following DK. Peak left-ventricular pressure (LVPmax) (106 +/- 29 vs. 92 +/- 35 mmHg) and dp/dtmax (1482 +/- 582 vs. 1247 +/- 644 mmHg/s) were decreased. dp/dtmin, as a measure of early relaxation, was also decreased (-1361 +/- 362 vs, -1125 +/- 488 mmHg/s), whereas the end-diastolic pressure (LVPed) was increased (20 +/- 12 vs. 25 +/- 17 mmHg). Coronary blood flow (CBF) per beat was not affected by DK: 0.07 +/- 0.02 vs. 0.07 +/- 0.02 ml. However, the coronary resistance increased with DK from 0.76 +/- 0.29 to 1.13 +/- 0.66 mmHg/(ml/min/100 g). The MVO2 was decreased (6.8 +/- 3.4 vs. 5.9 +/- 2.8 ml/min/100 g). The relation between subendocardial and subepicardial flow (colored microspheres) was unchanged after DK (1.12 +/- 0.22 vs. 1.13 +/- 0.16). Using electrical pacing to restore the control HR, dp/dtmax, LVPed, and MVO2 were nearly restored to predrug levels. In contrast, stroke volume, LVPmax, dp/dtmin and CBF per beat were less than control. In summary: DK effectively reduces heart rate and increases diastole. In parallel with the moderately reduced contractile function, MVO2 is reduced whereas CBF per beat is preserved. These results suggest that this novel bradycardic agent could be useful in treating unwanted tachycardia in the experimental setting, postoperative tachycardia in patients with heart disease or be useful even in treating coronary heart disease.

Animals↗
PubMed1998

Separation, characterization and sexual heterogeneity of multiple putative odorant-binding proteins in the honeybee Apis mellifera L. (Hymenoptera: Apidea).

According to precise molar mass determined by mass spectrometry and N-terminal sequence, some 25 odorant-binding-like proteins were characterized from the antennae and legs of worker and drone honeybees. Antennal specific proteins, composed of six different molecules, were classified into three subclasses according to N-terminal sequence homology. The major sexual difference was shown to lie in the relative abundance of these antennal specific proteins and in the occurrence of a drone-specific isoform. At least 19 other related proteins were found to occur in antennae and legs, forming another class showing homology with insect OBP. Genotype comparison of two honeybee races revealed a variability limited to this second class. Provided that these odorant-binding-like proteins are indeed able to bind odorants or pheromones, the question of whether their peculiar multiplicity contributes to the remarkable capacity of the honeybee to discriminate among a wide range of odor molecules is raised.

Amino Acid Sequence↗
PubMed1998

Basal metabolism does not account for high O2 consumption in stunned myocardium.

Myocardial O2 consumption (MVo2) in stunned myocardium is relatively high compared with the reduced ventricular function. The mechanism of this "oxygen paradox" could occur at different levels: basal metabolism, excitation-contraction coupling, and energy production. In one previously reported series on 12 isolated, blood-perfused rabbit hearts, left ventricular systolic and diastolic function in stunned myocardium were significantly decreased compared with control, whereas total MVo2 was not. The MVo2 for the unloaded contraction was overproportionately high for the decreased function in stunned myocardium, and contractile efficiency was clearly deteriorated. To assess whether the basal metabolism specifically is elevated in stunned myocardium, a second series (n = 14) with a similar protocol was performed in this study. Basal MVo2 after KCl arrest (0.5 +/- 0.3 ml.min-1.100 g-1) was significantly lower than that measured after KCl arrest (1.2 +/- 0.5 ml.min-1.100 g-1) in an additional series on nonischemic hearts (n = 8). Our conclusion is that basal MVo2 in stunned myocardium is not elevated. Thus this O2-consuming portion of total MVo2 is not responsible for the inefficiency in stunned myocardium. Instead, a "metabolic stunning" occurs at the level of both excitation-contraction coupling and force development by the contractile apparatus.

Animals↗
PubMed1998

Perivascular nerves contribute to cortical spreading depression-associated hyperemia in rats.

We investigated the contribution of perivascular nerves and neurotransmitters to cortical spreading depression (CSD)-associated hyperperfusion in the rat. Chronic transection of the nasociliary nerve (NCN, 2 wk before) decreased ipsilateral CSD-associated hyperperfusion by 23 +/- 13% (mean +/- SD; n = 5, P < 0.05), whereas acute transection of the NCN or sham surgery had no effect (n = 8). When the NCN and parasympathetic nerve fibers (PSN) were both chronically transected, CSD hyperperfusion was attenuated by 55 +/- 19% (n = 5, P < 0.05). Cerebrovascular reactivity to hypercapnia was not significantly affected. Brain topical superfusion of the muscarinic receptor antagonist atropine (10(-4) M) caused a reduction of CSD hyperperfusion by 41 +/- 13% (n = 5, P < 0.05). The competitive blockade of calcitonin gene-related peptide (CGRP) receptors by CGRP-(8-37) (5 x 10(-7) M) afforded a decrease by 49 +/- 19% (n = 5, P < 0.05), without affecting CO2 reactivity (n = 4). The combined application of both CGRP-(8-37) and atropine further attenuated CSD hyperperfusion (by 69 +/- 17%, n = 5, P < 0.05). After chronic NCN and PSN transection brain topical superfusion of CGRP-(8-37) (5 x 10(-7) M) reduced CSD hyperperfusion slightly by 9.5 +/- 5% (n = 3). Atropine (10(-4) M) afforded a decrease by 17 +/- 6% (n = 3). These reductions were not statistically significant. We conclude that CSD-associated hyperperfusion is mediated in part by a depolarization of trigeminal sensory and parasympathetic nerve fibers, resulting in a release of vasoactive trigeminal and parasympathetic neurotransmitters.

Animals↗
PubMed1998

[Psychosomatic aspects of idiopathic spasmodic torticollis. Results of a multicenter study].

Idiopathic spasmodic torticollis (IST) is one of the most frequent dystonic movement disorders. Its classification as a focal dystonia, as well as its treatment with botulinum toxin resulted in groups of patients being regularly seen by neurologic specialists. In a multicentre study, we investigated psychosocial changes, coping and psychopathology, and their interrelations with signs, symptoms and course. 256 patients were included in the study (59.3% women, 40.7% men). The mean age was 49.1 years. Rotating torticollis occurred more often than latero-retrocollis and antero-retrocollis. A family history of IST was seen in 3.1% of the total sample. 34% of the patients had additional dystonic symptoms. Most frequently, these affected the upper extremities (13%), less often the legs. 19.1% of the patients had experienced a period of complete remission. The General Symptom Index of the SCL 90-R in 27% of the patients ranged above the double standard deviation of the normal controls, indicating a clinically significant psychopathology.

Adaptation, Psychological↗
PubMed1997

Functional methionine synthase deficiency due to cblG disorder: a report of two patients and a review.

Functional methionine synthase deficiency due to abnormal methylcobalamin metabolism causes megaloblastic anemia, moderate to severe developmental delay, lethargy, and anorexia in association with homocystinuria. Patients with this disorder of cobalamin metabolism can be classified into two separate groups, cblE or cblG, primarily on the basis of complementation analysis with cultured skin fibroblasts. We describe two unrelated boys, ages 3 and 5 years, with the cblG defect in methylcobalamin synthesis. Both children presented with severe developmental delay, lethargy, anorexia, and megaloblastic anemia. The diagnosis of homocystinuria was delayed in each case due to difficulties with detection of small amounts of homocystine in physiologic samples. The clinical course of cblG disease is favorably altered by treatment with intramuscular hydroxycobalamin. Megaloblastosis in the presence of adequate supplies of cobalamin and folate in the blood must alert the clinician to the possibility of functional methionine synthase deficiency and should prompt a careful search for associated biochemical hallmarks, including homocystinuria/emia.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗