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Biomedical subjects

K Frick

Publications and source records attributed to K Frick.

At least 19 recordsLinked to original sources

Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10.

We have used the yeast two-hybrid system to study the interaction between the IGF-I receptor and two putative substrates, IRS-1 and Shc. In addition, we have identified Grb10 as a protein that binds to the insulin-like growth factor I (IGF-I) receptor. This two-hybrid system (the interaction trap) utilizes a hybrid protein containing the LexA DNA-binding domain fused to the intracellular portion of the IGF-I receptor (LexA-IGFIR beta) and hybrids containing an activation domain fused to either IRS-1 (Ad-IRS-1), Shc (Ad-Shc), or a cDNA library. A positive interaction of LexA-IGFIR beta with the activation domain hybrid results in activation of reporter genes, LacZ and LEU2, in the yeast. Western blotting of extracts from transformed yeast demonstrated that the LexA-IGFIR beta fusion protein was expressed and phosphorylated on tyrosine residues. Coexpression of LexA-IGFIR beta with Ad-IRS-1 resulted in strong activation of both reporter genes; activation did not occur with a kinase-negative receptor mutant. IRS-1 residues 160-516 were sufficient for this strong interaction. Coexpression of LexA-IGFIR beta with Ad-Shc also resulted in strong activation of both LacZ and LEU2 reporter genes. This interaction was also dependent upon a tyrosine kinase-active receptor and required tyrosine 950 in the juxtamembrane region of the receptor. An N-terminal fragment of Shc (amino acids 1-232) interacted almost as strongly as full-length Shc whereas the Shc SH2 domain only activated the more sensitive LEU2 reporter. Full-length Shc was phosphorylated on tyrosine when coexpressed with IGFIR beta but not when coexpressed with the kinase-negative receptor mutant. To identify additional proteins that interact with the IGFIRs, a human fetal brain cDNA library was screened using the interaction trap system. This analysis identified partial cDNAs for Grb10. Coexpression of LexA-IGFIR beta with Ad-Grb10 resulted in strong activation of both LacZ and LEU2 reporter genes; this interaction was dependent upon a tyrosine kinase-active receptor but did not require tyrosine 950.

Adaptor Proteins, Signal Transducing

Bivariate global frequency analysis versus chaos theory. A comparison for sleep EEG data.

Various quantitative descriptors for EEG data will be compared taking sleep as an example. In this contribution, Hjorth's mobility and complexity measures will be used to classify sleep stages. The results will be compared with those of a dimensionality analysis. Several authors have shown that the correlation exponent can describe the complexity of sleep EEG data and is able--with the exception of REM sleep--to distinguish significantly between sleep stages. The discriminative power of a bivariate global frequency analysis appears to be superior to that of the correlation exponent. Furthermore a very high statistical correlation between the estimator of fractal dimension and Hjorth's mobility was obtained.

Adult

Differences in semantic information processing in schizophrenics.

Well-established findings in schizophrenics suggest that they have difficulties in interpreting contextual information. We used electrophysiological means to investigate this hypothesis. The N 400 paradigm was used in 29 acute schizophrenic patients and 28 controls. The main findings were a changed topographical distribution of amplitude in the schizophrenic group; that is, a reduced amplitude at the frontal sites and a pronunciation at the occipital sites. We did not find latency differences. When remitted patients (n = 17) were reinvestigated, a negative correlation of the amplitude to the total amount of neuroleptics used was found. These results are discussed in relation to structural and functional findings supporting the hypofrontality hypothesis in schizophrenia.

Acute Disease

["Neuroadaptation" in long-term cannabis abuse. A clinical and electroencephalographic case study].

This report is about electroencephalographic changes in a twenty-eight year old patient with longterm heavy cannabis use. He was admitted to our hospital after he had developed a depressive-apathetic syndrome. Two days after the last cannabis-intake, the patient had recovered from initial psychopathology and his EEG was completely inconspicuous at this day. Some days later however the patient's behavior became increasingly impulsive and unstable, while his EEG showed a marked disturbed regulation of vigilance. In the following weeks his impulsiveness became less and his EEG returned to normal. We suggest that these alterations may reflect a discontinuation of the initial neuroadaption of the central nervous system to the drug.

Adult

Lithium effect on smooth pursuit eye movements of healthy volunteers.

Smooth pursuit eye movement (SPEM) dysfunctions in major affective disorder patients have been reported to be associated with lithium treatment. We report that SPEM of 13 healthy volunteers, either taking lithium (n = 7) or placebo (n = 6), were not significantly impaired by lithium. This could point to a pathophysiologic difference between affective disorder patients and a normal population.

Adult

[Saccadic reaction times and visuospatial disorders of attention in schizophrenic patients with negative symptoms].

Schizophrenics display various oculomotor disturbances. In this study we investigated saccadic reaction times in 47 unmedicated schizophrenics (ICD-9) as well as 28 age and sex matched normal controls. Using a cluster analysis according to the BPRS we determined two subgroups each with high and low negative symptoms; we expected poorer results from patients with negative symptoms on account of existing attentional deficits. The eye movements were recorded with electrooculography. Stimuli were presented at random with amplitudes of 5 degrees at a minimum and 20 degrees maximally; the distances between the angles were kept as short as possible, and we chose a fast stimulus rate (800, 1.000 and 1.200 ms). Only the group of schizophrenics with pronounced negative symptoms showed significantly delayed saccadic reaction times, whereas other schizophrenic patients did not differ from the controls. An unfavorable course of the illness also was associated with delayed reaction times. The saccadic reaction times were delayed in both the right and left visual field to the same degree. The poorer performance of the schizophrenics with pronounced negative symptoms are being discussed in relation to attentional deficits regarding visuospatial functions.

Adolescent

PDGF induces c-myc mRNA expression in MG-63 human osteosarcoma cells but does not stimulate cell replication.

The platelet-derived growth factor (PDGF) modulated growth response of the MG-63 human osteosarcoma cell line, which neither expresses c-sis mRNA nor secretes a PDGF analogue, was characterized. Scatchard analysis demonstrated that the MG-63 cells have 23,000 receptors per cell with a Kd of 5 X 10(-11) M. The receptor became phosphorylated, in a PDGF concentration-dependent manner, when 32P-orthophosphate-labeled cells were treated with PDGF for 3 h at 4 degrees C. The phosphorylated receptor was identified by autoradiography and gel electrophoresis after isolation of the 32P-labeled receptor using a solid-phase monoclonal antibody directed against phosphotyrosine. Binding of the receptor to the antibody was inhibited by 5 mM phenyl phosphate, further suggesting that PDGF stimulated tyrosine-specific receptor autophosphorylation. In addition, treatment of MG-63 cells with PDGF for 3 h at 37 degrees C induced a 7.5-fold increase in c-myc mRNA accumulation as analyzed on Northern gels. However, MG-63 cells grew equally well in either serum-(which contains PDGF) or plasma-(which does not) supplemented medium. Furthermore, PDGF did not stimulate DNA synthesis in growth arrested MG-63 cells, nor did it potentiate DNA synthesis modulated by somatomedin C. Thus MG-63 cells are a naturally occurring cell variant in which PDGF stimulates c-myc expression but does not modulate mitogenesis.

Animals

Visuomotor performance of schizophrenic patients and normal controls in a picture viewing task.

The eye movements of 20 partially remitted schizophrenic outpatients (ICD-9) under neuroleptic maintenance medication and those of 20 normal controls were recorded using corneal reflection pupil-center measurement. The visuomotor performance during a 1-min picture viewing task was studied on the basis of several eye movement parameters. Clinical evaluation comprised self-ratings (Frankfort Complaint Questionnaire) and observer ratings (BPRS, CGI, GAS), as well as recording of current daily neuroleptic dosage (mg CPZ). The main results are that schizophrenics differ from normals in their correlational pattern of fixation- and movement-related parameters, reflecting two opposite viewing styles in schizophrenics: staring and extensive scanning. Both styles are differently related to clinical symptomatology. There was no strongly marked relationship with neuroleptic dosage.

Adult

Interindividual variability of lithium-induced EEG changes in healthy volunteers.

A placebo-controlled, double-blind study on the effects of lithium on the electroencephalogram (EEG) was performed in 20 healthy volunteers. A reanalysis of the data which previously had been evaluated by factor analysis and other techniques is presented. The aim of this reanalysis is a quantitative reconstruction of visually defined vigilance stages. In 8 of the 10 healthy subjects who received lithium, a "stabilization" of vigilance on a slightly lowered level (i.e., increased continuity of alpha activity and a tendency in the direction of increased alpha anteriorization) could be demonstrated after a 2-week medication period (mean lithium plasma level: 0.65 mmol/l), indicating that in these subjects lithium counteracts the physiological decline of vigilance to be expected under resting conditions. The interpretation of this finding as a reduction of physiological variability, or as a "dynamic restriction," corresponds to findings in other areas of lithium research which can be interpreted in an analogous manner. In two subjects, however, a small decline of vigilance was observed. These two subjects showed an especially pronounced alpha rhythm in their predrug EEG compared with the other volunteers. The authors discuss whether the delineation of different EEG reaction types contributes to the responder problem in lithium research.

Adult

Eye movement research with schizophrenic patients and normal controls using corneal reflection-pupil center measurement.

The eye movements of 20 partially remitted outpatient schizophrenics (ICD 9), for the most part receiving neuroleptic maintenance medication, and 20 normal controls were recorded using corneal reflection-pupil center measurement. Performance was investigated on the basis of widely varied measurement parameters during a fixation task and a visual search task (list of letters). Psychopathological data were additionally recorded for the group of patients by means of self and observer ratings, current social adjustment, and neuroleptic dosage. The schizophrenic patients showed the tendency to perform more poorly than the normal controls in the eye movement parameters recorded, and there was marked variation in performance within the group of schizophrenic patients. In particular, various abnormalities in fixation performance were connected differentially with individual psychopathological syndromes and neuroleptic dosage. Connections between fixation performance and search performance were found only within the group of patients. They are interpreted as an indicator of disturbed interhemispheric coordination in schizophrenics. Based upon specific pupillary findings one concludes that the processing load imposed on the attentional system by the search task is different for various schizophrenic subgroups.

Adult

A new quantitative approach to the assessment of stages of vigilance as defined by spatiotemporal EEG patterning.

Electroencephalographically oriented research on vigilance needs valid measures for assessing the level of vigilance between wakefulness and sleep. When studying different psychologically, psychopathologically, and pharmacologically induced states, special attention has to be paid to minor alterations of the level of vigilance which are reflected, essentially, in topographical changes of alpha-activity (Stage A). Since vigilance is a dynamic process, brief fluctuations in the range of a few seconds must also be recorded. In our opinion existing methods of quantification do not fully meet these demands. We have, therefore, developed a relatively simple procedure which can be characterized as an attempt quantitatively to reconstruct visually, i.e., spatiotemporally defined patterns of vigilance. The usefulness of this method, which also has certain limitations, has been demonstrated in psychopharmacological studies.

Alpha Rhythm

The lateralization of occipital alpha-power under resting conditions in the EEG of healthy volunteers. A state- and a trait-variable.

Using a structural analysis of lateralization of occipital alpha-power in 20 healthy volunteers under resting conditions, a clear vigilance-dependence could be shown for the great majority. In contrast the state of four subjects showed almost no dependence on vigilance. Additional findings according to which these two subgroups also differ in a characteristic manner with regard to various other aspects, especially occipital alpha-quantity and vigilance dynamics, point to a maturational dimension.

Adult

Asymmetry of occipital alpha-rhythm under resting conditions: a neurophysiological measure of "hemisphericity".

Using the resting EEGs of 20 healthy subjects in semirecumbent position with eyes closed and left undisturbed, we studied the question whether and, if so, to what extent, lateralization of occipital alpha-rhythm depends on level of vigilance. As a simple indicator of vigilance, the relative alpha-power for each 2-sec. epoch of 02-CZ (occipital right) was calculated. Lateralization was defined as the ratio of absolute alpha-powers in 01-CZ and 02-CZ (occipital left and right). This was also calculated epoch by epoch. The results of individual analysis of data from each subject allowed categorization into 3 types. This typological differentiation obtained quantitatively could be supported by visual pattern analysis. The findings are discussed in relation to the state- vs trait-problem which constantly confronts us when we interpret experimentally obtained functional asymmetries of hemispheres.

Adult

Interrelation between changes in the EEG and psychopathology under pharmacotherapy for endogenous depression. A contribution to the predictor question.

With the predictor problem in mind, we studied in-patients with endogenous depression whether relationships exist among the EEG, the therapeutic response, and the severity of psychopathology. We found that clinically defined responders and non-responders differ in respect of their average power spectra calculated for the two occipital regions. In addition, it was shown that there is a statistically significant correlation between the EEG before treatment and the severity of AMP-documented psychopathology after a 4-week treatment period. This correlation was stronger for the left occipital region than for the right.

Amitriptyline

[Quantitative microbiologic studies of the sulcus fluid in patients with immunodeficiencies].

Quantitative microbiologic examinations of fluid taken from gingival sulci were carried out with patients suffering from chronic lymphatic leukemia (CLL), i.e. with disturbed immune response, and with healthy subjects. The pathogen count in each case was correlated with the gingival index, the plaque index, the amount of fluid in the gingival sulcus, and the pocket depth. Patients with chronic lymphatic leukemia with gingiva clinically free of inflammation showed one to 20 times more bacterial flora in fluid from the gingival sulcus than fluid from healthy control subjects. The quantitative values tend to equalize only if imflammation is severe. If the pathogen count is considered a function of the amount of plaque or pocket depth, markedly more microorganisms/mm3 of sulcus fluid were found with CLL patients than in the control group. It therefore may be concluded that immunologic reactions contribute decisively to the causation and maintenance of gingivitis with all of its consequences and that these reactions play an important role in the destruction of pathogens found in the region of the gingival pocket.

Aged