Transverse resonance island buckets for synchrotron-radiation based electron time-of-flight spectroscopy.

At the Metrology Light Source (MLS), the compact electron storage ring of the Physikalisch-Technische Bundesanstalt (PTB) with a circumference of 48 m, a specific operation mode with two stable closed orbits for stored electrons was realized by transverse resonance island buckets. One of these orbits is closing only after three turns. In combination with single-bunch operation, the new mode was applied for electron time-of-flight spectroscopy with an interval of the synchrotron radiation pulses which is three times the revolution period at the MLS of 160 ns. The achievement is of significant importance for PTB's future programs of angular-resolved electron spectroscopy with synchrotron radiation and similar projects at other compact electron storage rings. The scheme applied here for selecting the photons originating from a particular orbit by optical imaging has been used before in fs slicing applications and may be relevant for the BESSY VSR project of the Helmholtz-Zentrum Berlin.

Exploring three-dimensional orbital imaging with energy-dependent photoemission tomography.

Recently, it has been shown that experimental data from angle-resolved photoemission spectroscopy on oriented molecular films can be utilized to retrieve real-space images of molecular orbitals in two dimensions. Here, we extend this orbital tomography technique by performing photoemission initial state scans as a function of photon energy on the example of the brickwall monolayer of 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA) on Ag(110). The overall dependence of the photocurrent on the photon energy can be well accounted for by assuming a plane wave for the final state. However, the experimental data, both for the highest occupied and the lowest unoccupied molecular orbital of PTCDA, exhibits an additional modulation attributed to final state scattering effects. Nevertheless, as these effects beyond a plane wave final state are comparably small, we are able, with extrapolations beyond the attainable photon energy range, to reconstruct three-dimensional images for both orbitals in agreement with calculations for the adsorbed molecule.

A synchrotron-radiation-based variable angle ellipsometer for the visible to vacuum ultraviolet spectral range.

A rotating analyzer spectroscopic polarimeter and ellipsometer with a wide-range θ-2θ goniometer installed at the Insertion Device Beamline of the Metrology Light Source in Berlin is presented. With a combination of transmission- and reflection-based polarizing elements and the inherent degree of polarization of the undulator radiation, this ellipsometer is able to cover photon energies from about 2 eV up to 40 eV. Additionally, a new compensator design based on a CaF2 Fresnel rhomb is presented. This compensator allows ellipsometric measurements with circular polarization in the vacuum ultraviolet spectral range and thus, for example, the characterization of depolarizing samples. The new instrument was initially used for the characterization of the polarization of the beamline. The technical capabilities of the ellipsometer are demonstrated by a cohesive wide-range measurement of the dielectric function of epitaxially grown ZnO.

Electrophysiological evidence for the presence of receptors for cholecystokinin and bombesin on cultured astrocytes of rat central nervous system.

The action of cholecystokinin (CCK) and bombesin (Bom) was studied on the membrane potential of astrocytes in explant cultures of rat cortex, cerebellum, brain stem and spinal cord. Both peptides (10(-8) and 10(-7) M) caused a hyperpolarization of most astrocytes studied. The hyperpolarization by CCK was markedly reduced or blocked by the CCKB-antagonist L-365,260 whereas addition of the Bom-antagonist [D-Phe12,Leu14]-Bom antagonized the effects of Bom, suggesting a specific action of these peptides. When CCK and Bom were tested on the same cell, both peptides were effective, indicating a colocalization of receptors for CCK and Bom on the glial membrane. Our electrophysiological investigations provide strong evidence for the existence of functional CCK and Bom receptors on astrocytes.

Colocalization of cholinergic, adrenergic and peptidergic receptors on astrocytes.

By means of combined immunohistochemical and auto-radiographic techniques we have studied the colocalization of cholinergic, adrenergic and peptidergic binding sites on astrocytes in explant cultures of rat spinal cord, brain stem and cerebellum. Many astrocytes which were immunostained by the monoclonal muscarinic receptor antibody M 35 were also intensely labelled by 3H-noradrenaline, the beta-adrenergic antagonist 3H-dihydroalprenolol and the peptides 125I-angiotensin II, 125I-neuropeptide Y and 3H-bradykinin. Electrophysiological studies demonstrating that muscarine, the adrenergic agonists noradrenaline and isoprenaline as well as angiotensin II, neuropeptide Y and bradykinin affect the membrane potential of the same astrocytes provide further evidence for the coexistence of cholinergic, adrenergic and peptidergic receptors on astrocytes.

Acoustical changes of loudly spoken speech and their effects on speech recognition in hearing-impaired listeners.

The level of speech is usually increased in conversations with unaided hearing-impaired listeners. However, the speaker may talk at conversational levels to aided hearing-impaired persons. In this case, the level of speech is electronically increased by the hearing aid. In the present study, the acoustical changes of loudly spoken speech and their effects on speech recognition were investigated in 20 patients with sensorineural hearing loss. Eight test words of the German Speech Intelligibility Test ('Freiburger Sprachtest') were recorded at original levels of 60 and 75 dB SPL by a male speaker. Both recordings were presented to hearing-impaired subjects at a playback level of 75 dB SPL. Thus, the level of the 60 dB SPL recording was increased electronically by 15 dB. For the 75 dB SPL recording, playback and recording levels were identical. The average whole-word score was 49% for the 60 dB SPL recording and 39% for the 75 dB SPL recording. This difference was statistically significant (0.002 less than P less than 0.005). The results of the speech recognition ability tests could be explained by the acoustical changes of the loudly spoken speech. In the 75 dB SPL recording, the levels of voiceless fricatives, nasals and plosives were significantly lower than in the 60 dB SPL recording. Spectrally, the fundamental frequency was increased and the configuration of the first formant was altered in the 75 dB SPL recording. The significance of the findings for clinical speech audiometry and hearing aid evaluation is discussed.

Transient elevation of urinary catecholamine excretion and cholestatic liver disease in a neonate with hypopituitarism.

Hypothalamic hypopituitarism was diagnosed in a 3-month-old boy presenting with cholestatic liver disease, which resolved 5 weeks after the start of replacement therapy with hydrocortisone and human growth hormone. Clinical and pathohistological features of liver disease associated with neonatal hypopituitarism in this patient are compared to those of patients reviewed from the literature. Urinary excretion of dopa and 3-methoxytyramine but not of other catecholamine metabolites was elevated during cholestatic liver disease. 3-Methoxytyramine excretion normalized when cholestasis resolved. Altered hepatic metabolism of catecholamines due to growth hormone and cortisol deficiency may explain this observation.

Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma.

In 211 patients with neuroblastoma, serum vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were determined and correlated to stage, histological differentiation, ferritin, neuron-specific enolase, lactate dehydrogenase (LDH) and outcome. Elevated serum VMA and/or HVA levels were found 16% less frequently than elevated urine levels. The incidence of the elevated serum levels increased with stage (stages I-III 58%, IV 78%, IVS 100%). Increased VMA/HVA ratios were not associated with a higher grade of tumour differentiation. Serum ferritin and neuron-specific enolase showed no correlation, and LDH a borderline non-random correlation with the serum catecholamine metabolites. Using age-related reference values a quotient of serum VMA/HVA (P = 0.061) < 0.7 indicated a poorer event-free survival (48 +/- 10%) than ratios > or = 0.7 (event-free survival 81 +/- 6%) for children with localised neuroblastoma (P = 0.0004). No correlation with prognosis was detected for patients with stage IV and stage IVS disease. We conclude that serum VMA and HVA determinations may be useful as tumour markers for 71% of neuroblastoma patients, and aid in estimating the prognosis in children with localised disease.

Neuroblastoma screening: arguments from retrospective analysis of three German neuroblastoma trials.

The justification for a neuroblastoma screening program has been discussed controversially. The analysis of 701 patients of the German neuroblastoma trials NB 79, 82, and 85 provides additional information on this subject. The basis of our investigation was the good prognosis of stage I and II patients (92% survival 5-10 years after diagnosis) compared with 66% in stage III and 11% in metastatic disease. The correlation of age and stage (p less than 0.0001), a median progression time of 14.6 months (range 3.4-33.5 mo) from localized to metastatic disease as observed in 18 patients, the high incidence of asymptomatic diseases in stages I (49%) and II (30%) patients and the cost-benefit estimation arguments in favor of a screening program. The key problem for the lab part is the lower incidence of abnormal catecholamine metabolite excretion in stage I and II patients. The origin of 89% of metastatic disease from intraabdominal sites suggests that ultrasonography may be of additional value.

Abnormal 3,4-dihydroxyphenylalanine (dopa) concentrations in plasma and urine of patients with cystic fibrosis.

Plasma and urine concentrations of the free amino acid 3,4-dihydroxyphenylalanine (dopa) were determined in a blind study in 16 children and adolescents with cystic fibrosis (CF), eight heterozygote parents of these children and in 11 healthy subjects who served as controls. To exclude any drug interference with catecholamine metabolism and to evaluate a tentative basic metabolic alteration in cystic fibrosis, the same determinations were done in 11 newly diagnosed infants (age 1-84 months). Free plasma dopa was significantly (P less than 0.01) elevated in CF (27.0 +/- 6.1 nmol l-1 vs. 19.1 +/- 5.0 nmol l-1 in the controls); heterozygotes had the lowest concentration: 11.5 +/- 5.8 nmol l (P less than 0.01 compared with normals). Increased plasma dopa concentrations were measured in the newly diagnosed infants (35.4 +/- 16.9 nmol l-1). Renal dopa clearance was the same in cystic fibrosis (9.26 +/- 5.71 ml min-1 1.73 m-2) and controls (10.87 +/- 2.46 ml min-1 1.73 m-2). A concomitant elevation of metabolic products as dopamine and noradrenaline in plasma and urine was noticed. These data are consistent with a dopa abnormality in this genetic disease.

Dopamine and catecholamines in cystic fibrosis in response to a marathon race.

The excretions of 3,4-dihydroxyphenylalanine (DOPA) metabolites and 5-hydroxyindoleacetic acid (5-HIAA) were followed before, during, and after a marathon race in three patients with cystic fibrosis (CF) and three healthy controls. Moderately increased DOPA excretions in CFs compared with controls before, during, and after the race support the idea that there is an altered metabolism of DOPA in CF. Noradrenaline, adrenaline, homovanillic acid, and vanilmandelic acid were increased in CFs compared with controls mainly during and after the race, which might be a reflection of the heavier working intensity that the CF patients had in comparison with their healthy controls. 5-HIAA, the breakdown product of serotonin, was higher in CFs in comparison with controls before and during the run, but equal thereafter. This reflects an ameliorated serotonin metabolism after the run.

Dopamine-beta-hydroxylase in patients with cystic fibrosis.

The enzymatic activity of plasma dopamine-beta-hydroxylase (DBH) was determined in 92 children/adolescents with cystic fibrosis, in 25 parents (heterozygotes) of these patients and in 68 healthy controls. Statistically significant (P less than 0.01) lower DBH levels were found in cystic fibrosis patients (17.9 +/- 1.4 mumol/min per 1, SEM) compared to the controls (25.5 +/- 2.1 mumol/min per 1). In 37 patients plasma norepinephrine and dopamine levels were compared to the enzymatic activity, no significant correlation between these variables being shown (r = -0.134 for norepinephrine; r = 0.159 for dopamine). However, due to the large variability of DBH within the groups and due to the lack of relationship of this enzymatic activity to plasma catecholamines, it is concluded that these differences may neither account for the observed elevation of plasma dopamine in cystic fibrosis patients (0.94-6.73 nmol/l vs. 0.01-0.986 nmol/l for controls) nor for their putative autonomic dysfunction.

Immunohistochemical localization of neurofilaments and neuron-specific enolase in 29 cases of neuroblastoma.

Twenty-nine neuroblastomas have been examined with the use of rabbit antibodies specific for each of the three neurofilament polypeptides, with a monoclonal antibody specific for the NF-L polypeptide, and with a rabbit antibody specific for neuron-specific enolase. When frozen material was used, all neuroblastomas were positive with the neurofilaments antibodies. When alcohol-fixed paraffin-embedded material was used, neurofilament staining was weaker and the fixation procedure appeared to destroy the epitopes recognized by the NF-L antibodies preferentially. Although all neuroblastomas were positive for neurone-specific enolase, so were two rhabdomyosarcomas, suggesting that NSE is not an appropriate marker to distinguish the different small blue cell tumors of children.

Production and characterization of monoclonal antibodies against human neuroblastoma.

MAb were derived from mice immunized with cells of the human neuroblastoma line IMR-32. Five hybridomas were selected according to their selective binding to human cell lines, tumors and normal tissues. One of them, CE7, reacted with all sympatho-adrenomedullary cells (neuroblastoma, ganglioneuroblastoma, ganglioneuroma, pheochromocytoma, adrenal medulla, sympathetic ganglion cells). Weak cross-reactivities were observed with melanocytes and with some human melanoma and glioma cell lines. The antigen recognized by CE7 was markedly expressed on neuroblastoma tumors of all histological grades, independently of the adrenergic or cholinergic nature of these cells. MAb derived from clones AD2, BC1, BC4 and CB10 bound variably to some, but not to all, neuroblastoma cells. By using these MAb, 3 phenotypes of neuroblastoma lines could be distinguished. The binding profiles of these types, however, showed no correlation with origin of the cell lines or stage of the disease.

Plasma and urinary catecholamines in patients with cystic fibrosis.

In 43 patients with cystic fibrosis (age 8-23 yr, 26 boys and 17 girls) attending a summer camp in a mountain rehabilitation center and in 25 parents (heterozygotes) plasma epinephrine, norepinephrine, dopamine and plasma activity of dopamine-beta-hydroxylase were determined as well as the 24-h excretion of the free urinary amines (epinephrine, norepinephrine, dopamine), their O-methylated products (metanephrine, normetanephrine, 3-methoxytyramine) and the urinary phenolic acids (vanilmandelic and homovanillic). Also the metabolic breakdown product of serotonin in urine, the 5-hydroxyindoleacetic acid, was determined. Significantly elevated plasma dopamine (0.03-0.45 nmol/liter for controls versus 1.70-2.21 nmol/liter for cystic fibrosis) and slightly higher plasma norepinephrine levels were found in patients with cystic fibrosis. An increased 5-hydroxyindoleacetic acid excretion was noticed in adolescent patients which correlated with the disease state and the extent of lung involvement. No abnormalities of plasma amine levels were seen in the parents of the patients. Despite controversial results, CF patients seem to have an alteration in catecholamine metabolism which is reflected in higher plasma dopamine levels.

Different effects of selective and nonselective beta adrenoceptor blockade on urinary catecholamine and creatinine excretion in stress.

We tested the hypothesis that (1) beta 1-selective and nonselective beta adrenoceptor blockades have a different influence on stress-induced catecholamine overshoot, and (2) beta 1-selective blockade shifts the epinephrine/norepinephrine ratio in favor of norepinephrine. Seven violinists were investigated; each performed four times in public after ingesting different beta blockers. A significantly greater urinary norepinephrine/creatinine excretion was found with selective beta blockade than with nonselective. In addition during selective beta blockade creatinine excretion decreased significantly in comparison with nonselective blockade. This might be due to a higher concentration of circulating norepinephrine, stimulating alpha receptors in the renal vasculature.

The role of surgery, radio- and chemotherapy in the treatment of neuroblastoma and ganglioneuroblastoma.

Personal experiences with biochemical assessments of the urinary catecholamine metabolite excretion in 460 patients with neuroblastoma and 55 patients with ganglioneuroblastoma, as well as prognostic factors and selected data characterizing the role of surgery, radio- and chemotherapy in the treatment of neuroblastoma are reviewed. Recommendations regarding optimal combinations of the 3 treatment modalities are made, taking into account age and stage.