Ultrahigh-vacuum scanning force microscopy: Atomic-scale resolution at monatomic cleavage steps.
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Journal Article↗
Biomedical subjects
E Meyer
Publications and source records attributed to E Meyer.
Different types of structural variation in STRs: HumFES/FPS, HumVWA and HumD21S11.
Alleles of the STR systems HumFES/FPS, HumVWA and HumD21S11 were sequenced and analyzed. Sequence data revealed 3 different systems concerning the complexity of their sequence structure. HumFES/FPS belongs to the STR polymorphism with a simple repeat structure. Only 2 subtypes were found with a base substitution in the 5'-flanking region and no variation in the repeat region. In the STR system HumVWA the sequence structure of the repeat region is more complex, because 2 tetranucleotide units TCTA and TCTG were present. Additionally allele 14 revealed a completely different sequence structure leading to a different electrophoretic mobility. The repeat region of HumD21S11 is compound in structure. The possibility of variation at 3 positions leads to the occurrence of microheterogeneities in fragments of apparent length. In the upper allele range alleles arise with an additional incomplete TA-repeat.
Alleles↗
Levels of prostaglandin E2 and leukotriene B4 in tears of vernal conjunctivitis patients during a therapeutic trial with indomethacin.
A therapeutic trial of 1% indomethacin (Indoptic) eye drops was carried out in 21 children. Looking for possible mediators of inflammation in vernal conjunctivitis, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4 levels in the tears of 9 patients were measured and the effect of the treatment on them examined. A control group of 10 unaffected children was added. Out of 42 eyes in which indomethacin treatment was instilled, only 17 remained in treatment through a 6-week follow-up period. In a few of them a moderate improvement was obtained. The mean level of PGE2 in the patients before treatment was found to be slightly lower than that in the control group, and it dropped even lower during treatment. The average LTB4 level found in patients before treatment was significantly higher than the control group; it decreased somewhat following treatment, but not significantly. This is the first report of elevated LTB4 levels in vernal conjunctivitis, previously not recorded in the literature, it points to the possible role of LTB4 in the pathogenesis of the disease. A constant relationship was observed between low PGE2 levels and high LTB4 content in the patients' tears during highly inflamed states of the eye. We conclude that: (a) indomethacin did not prove to be a highly effective topical treatment for vernal conjunctivitis; (b) PGE2 does not seem to be a dominant mediator of inflammation in this disease; and (c) LTB4, on the other hand, apparently has a role in the mechanism of inflammation of the disease, thus raising hopes for future addition to therapy.
Adolescent↗
Translabyrinthine and transotic surgery for acoustic neuroma.
The results and complications of translabyrinthine and transotic surgery for petrous apex lesions between 1980 and 1992 are presented. An acoustic neuroma was found in 52 patients. In 1988, the translabyrinthine approach was modified into the transotic approach and replaced the former technique. There was no mortality in this series, but two patients had mild brainstem infarcts and there was post-operative bleeding into the cerebellopontine angle in one. Cerebrospinal fluid (CSF) leakage was seen in six patients and meningitis in two. Three suffered deep vein thrombosis in their legs. There was one case each of herniation of the cerebellum and gastric bleeding. Post-operative facial nerve function was good in 88%, moderate in 10% and poor in 2%. In the case of acoustic neuromas the aim was total tumour removal, but if there was a serious risk of damaging the nerve anatomically, near total or subtotal removal was performed. During the study period, there was a gradual decrease in facial nerve morbidity and surgical complications. This was attributed to increasing experience, the modified wider approach and better post-operative care.
Adolescent↗
Distributed processing of pain and vibration by the human brain.
Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (15O-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation in similar regions of SI and SII, regions long thought to be involved in basic somatosensory processing. In contrast, painful stimuli were significantly more effective in activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions.
Adult↗
Pharmacokinetics of acitretin.
Acitretin, the metabolite of etretinate, is eliminated far more rapidly from the human body than is etretinate. It has therefore been suggested that only a short period of contraception would be required following the completion of long-term therapy. However, recent studies have demonstrated the presence of etretinate in the plasma of acitretin-treated patients. In this paper, we review the results of studies at our centre in view of the recently discovered metabolic pathways for acitretin. Re-esterification of acitretin to etretinate, however, results in a loss of the metabolic advantages of acitretin. Because of this new knowledge, the recommended contraception period after acitretin therapy has been lengthened to 2 years.
Acitretin↗
Neural mechanisms underlying melodic perception and memory for pitch.
The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.
Auditory Perception↗
Simultaneous determination of endogenous retinoic acid isomers and retinol in human plasma by isocratic normal-phase HPLC with ultraviolet detection.
We describe a rapid and simple procedure for the simultaneous quantitation of endogenous 13-cis-retinoic acid, all-trans-retinoic acid, and retinol by isocratic normal-phase HPLC with ultraviolet detection, in 0.5 mL of human plasma. A silica adsorption column was eluted with n-hexane:2-propanol:acetic acid (200:0.7:0.135 by vol) at 0.9 mL/min, and the effluent monitored at 350 nm. The arotinoid ethylsulfonic acid Ro 15-1570 was used as the internal standard. High sensitivity, allowing quantitation of physiological concentrations, was achieved, particularly for the retinoic acid isomers. The detection limits were 0.5 microgram/L in plasma for both 13-cis- and trans-retinoic acid, and 10 micrograms/L for retinol. The CVs for between-day determinations of the lowest quality-control concentration (n = 12) were 4.8% for 13-cis-retinoic acid, 3.4% for trans-retinoic acid, and 3.0% for retinol. The mean (+/- SD) concentrations of 13-cis-retinoic acid (1.79 +/- 0.56 microgram/L), trans-retinoic acid (1.35 +/- 0.42 microgram/L), and retinol (533 +/- 58 micrograms/L) measured in plasma from 22 healthy volunteers agreed well with those previously reported.
Adult↗
Dissociation of human mid-dorsolateral from posterior dorsolateral frontal cortex in memory processing.
Work with non-human primates had previously demonstrated that the mid-dorsolateral frontal cortex, which comprises cytoarchitectonic areas 46 and 9, plays a critical role in the performance of non-spatial self-ordered working memory tasks, whereas the immediately adjacent posterior dorsolateral frontal cortex (area 8) is critical for the learning and performance of visual conditional associative tasks. The present study used positron emission tomography with magnetic resonance imaging to demonstrate the existence, within the human brain, of these two functionally distinct subdivisions of the lateral frontal cortex. These findings provide direct evidence that, just as the monkey brain, the human lateral frontal cortex is functionally heterogeneous and that comparable anatomical areas underlie similar functions in the two species.
Adolescent↗
Functional activation of the human frontal cortex during the performance of verbal working memory tasks.
Regional cerebral blood flow was measured with positron emission tomography during the performance of verbal working memory tasks. The same type of verbal response (i.e., reciting numbers) was required in the control and the two experimental tasks. In the control task, the subjects were required to count aloud. In the two experimental tasks, the subjects were required to maintain within working memory the numbers they generated (self-ordered task) or the numbers generated by the experimenter (externally ordered task). Examination of the difference in activation between these conditions revealed strong bilateral activation within the mid-dorsolateral frontal cortex during both experimental tasks. There was, however, no evidence of additional activation within the mid-dorsolateral frontal cortex when monitoring self-generated responses as compared with the monitoring of externally generated responses. These results provide evidence regarding the role of the mid-dorsolateral frontal cortex in mnemonic processing that are in agreement with recent findings from work with non-human primates.
Adult↗
Visual function in hypermetropia. An electroretinographic and psychophysical study.
Dark-adapted retinal function was tested electroretinographically and psychophsysically in patients with severe hypermetropia. These patients were first tested in 1982 and were classified into three electroretinographic categories subnormal, normal and supernormal, according to the amplitudes and the b-wave to a-wave relationships of their dark-adapted electroretinographic responses. These patients were invited for a follow-up examination to examine whether the subnormal electroretinogram represented a stationary or a progressive syndrome, to correlate functional vision to the electroretinographic findings and to determine the changes in refraction and electroretinographic responses that might have occurred during an 8-year period. No significant changes were seen in the amplitudes and b-wave to a-wave relationships of the electroretinographic responses. These observations supported the initial electroretinographic classification of the hypermetropic patients and indicated that the patients belonging to the subnormal group were probably characterized by a stationary defect. The psychophysically determined thresholds at different retinal loci (from 30 degrees nasal to 40 degrees temporal) were within the normal range for all the patients regardless of their electroretinographic characteristics. Thus, the abnormal electroretinographic responses of hypermetropic patients probably did not reflect abnormal retinal function but may be accounted for by changes in the electrical resistances of extraretinal tissues relative to that of the retina itself.
Adolescent↗
Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: a positron emission tomography study.
1. Two experiments were aimed at investigating the functional organization of the human anterior cingulate cortex (ACC) in relation to higher-order motor control. 2. The 15O-labeled H2O bolus method was used to measure relative changes of regional cerebral blood flow (rCBF) in 18 healthy human subjects as they performed oculomotor, manual, or speech tasks. 3. Task-specific rCBF changes were obtained in distinct subregions of the ACC, depending on the output system employed. The oculomotor and the manual task-related foci were found in the rostral and caudal regions of the ACC, respectively, whereas the speech foci were localized within two cingulate subregions, the intermediate dorsal and the rostral ACC. 4. In the manual tasks, two groups of activation foci could be distinguished, one just behind and the other just in front of the vertical plane traversing the anterior commissure. 5. The above pattern of rCBF changes was observed only if there was concomitant activation within the lateral prefrontal cortex (except for the posterior group of foci obtained in the manual tasks). 6. The localization of output-specific rCBF changes within the human ACC is consistent with the known somatotopic organization of the cingulate cortex in the monkey. 7. It is tentatively proposed that the ACC participates in motor control by facilitating the execution of the appropriate responses and/or suppressing the execution of the inappropriate ones. Such a modulatory effect would be of particular importance when behavior has to be modified in new and challenging situations.
Adult↗
Skin, adipose tissue and plasma levels of acitretin with rare occurrence of esterified acitretin during long-term treatment.
In a previous study acitretin and its 13-cis-metabolite were monitored in the plasma and epidermis of healthy volunteers. They were given 50 mg of trans-acitretin daily. No drug accumulation was observed in the skin, nor in the plasma. The purpose of the present study was to extend the data from non-psoriatic to psoriatic (n = 11) subjects, treated for at least 1 month with 25 mg acitretin. Plasma, skin biopsies and subcutaneous fat samples were analysed using HPLC. Trough levels of acitretin in skin were below the quantification limit, increasing to 28 +/- 16 ng/g within 5 h after dosing. Fat tissue levels exceeded those of skin, with values of 98 +/- 71 ng/g within 5 h after drug intake. In 2 patients, additional samples were taken 3 days post-therapy. Here, concentrations were below the quantification limit in adipose tissue, confirming that acitretin is not stored in subcutaneous fat. Esterification of acitretin into etretinate was observed in 2 subjects. This observation illustrates the recently described new metabolic pathway for acitretin. On both occasions, the unexpected ethylester metabolite was extensively stored in fat tissue.
Acitretin↗
Functional localization and lateralization of human olfactory cortex.
Anatomical and physiological investigations in monkeys indicate that olfaction is subserved by several cortical regions. But the areas implicated in the human olfactory system have not been definitively identified by functional criteria. Behavioural evidence has suggested that laterally specialized mechanisms for odour processing may exist, but the neuroanatomical substrate remains unknown. We used positron emission tomography to study the cortical representation of human olfactory processing by comparing cerebral blood flow changes evoked during olfactory stimulation with those of a control task. We report here significant cerebral blood flow increases at the junction of the inferior frontal and temporal lobes bilaterally, corresponding to the piriform cortex, and unilaterally, in the right orbitofrontal cortex. The results complement and extend previous data implicating these regions in olfactory processing, and indicate that a functional asymmetry exists in the human brain favouring the right orbitofrontal area in olfaction.
Cerebrovascular Circulation↗
Friction and wear of Langmuir-Blodgett films observed by friction force microscopy.
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Journal Article↗
Purification and characterization of the purE, purK, and purC gene products: identification of a previously unrecognized energy requirement in the purine biosynthetic pathway.
Aminoimidazole riobnucleotide carboxylase, the sixth step in the purine biosynthetic pathway, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to carboxyaminoimidazole ribonucleotide (CAIR). The gene products of the purE and purK genes (PurE and PurK, respectively) thought to be responsible for this activity have been overexpressed and the proteins purified to homogeneity. PurE separates from PurK in the first ammonium sulfate fractionation during the purification. No evidence for association of the two gene products under a variety of conditions using a variety of methods could be obtained. To facilitate the assay for CAIR production, the purC gene product, 5-aminoimidazole-4-N-succinylcarboxamide ribonucleotide (SAICAR) synthetase has also been overexpressed and purified to homogeneity. The activities of PurE, PurK, and PurE.PurK have been investigated. PurE alone is capable of catalyzing the conversion of AIR to CAIR 1 million times faster than the nonenzymatic rate. The Km for HCO3- in the PurE-dependent reaction is 110 mM! PurK possesses an ATPase activity that is dependent on the presence of AIR. No bicarbonate dependence on this reaction could be demonstrated (less than 100 microM), and AIR is not carboxylated during the hydrolysis of ATP. Incubation of a 1:1 mixture of PurE and PurK at low concentrations of bicarbonate (less than 100 microM) revealed that CAIR is produced but requires the stoichiometric conversion of ATP to ADP and Pi. No dependence on the concentration of HCO3- could be demonstrated. A new energy requirement in the purine biosynthetic pathway has been established.
Adenosine Triphosphatases↗
Lateralization of phonetic and pitch discrimination in speech processing.
Cerebral activation was measured with positron emission tomography in ten human volunteers. The primary auditory cortex showed increased activity in response to noise bursts, whereas acoustically matched speech syllables activated secondary auditory cortices bilaterally. Instructions to make judgments about different attributes of the same speech signal resulted in activation of specific lateralized neural systems. Discrimination of phonetic structure led to increased activity in part of Broca's area of the left hemisphere, suggesting a role for articulatory recoding in phonetic perception. Processing changes in pitch produced activation of the right prefrontal cortex, consistent with the importance of right-hemisphere mechanisms in pitch perception.
Acoustic Stimulation↗
Synthesis of aryl D-gluco- and D-galacto-pyranosides and 1-O-acyl-D-gluco- and -D-galacto-pyranoses exploiting the Mitsunobu reaction. Influence of the pKa of the acid on the stereoselectivity of the reaction.
Glycosides (alpha- and beta-D-glucosides and -D-galactosides) derived from three pesticides, 2-tert-butyl-2,4-dinitrophenol,2,6-dibromo-4-cyanophenol, and 5-(2,4-dichlorophenoxy)-2-nitrobenzoic acid, were synthesized from 2,3,4,6-tetra-O-chloroacetyl-D-gluco- and -D-galactopyranose by use of the Mitsunobu reaction. It was shown that selectivity for the beta-D anomer increases with the pKa of the acid component.
Dinitrophenols↗