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Biomedical subjects

S Krieger

Publications and source records attributed to S Krieger.

At least 19 recordsLinked to original sources
PubMed2004

Subcellular localisation of Cdc25A determines cell fate.

Cell division cycle 25A (Cdc25A) was shown to colocalise both with nuclear and cytoplasmic proteins. Recently, we have demonstrated that overexpressed Cdc25A promoted the survival of rat 423 cells through indirect activation of PKB-protein kinase B. Using a Cdc25A:ER fusion protein, which can be shuttled from the cytoplasm into the nucleus, the present investigation evidences that the antiapoptotic effect of Cdc25A was restricted to its cytoplasmic localisation in rat 423 cells. In contrast, nuclear Cdc25A overexpression caused dephosphorylation and nuclear retention of the proapoptotic transcription factor Forkhead in rhabdomyosarcoma-like 1 (FKHRL1) in human N.1 ovarian carcinoma cells. This resulted in the increased constitutive expression of the FKHRL1 targets Fas ligand and Bim, and promoted apoptosis. Thus, the Cdc25A oncogene, which was found to be frequently overexpressed in certain human cancers, can increase or decrease the susceptibility to apoptosis depending on the cell-type-specific subcellular distribution.

Animals↗
PubMed2001

Cognitive subprocesses and schizophrenia. A. Reaction-time decomposition.

OBJECTIVE: The aim of the study is to demonstrate that deficits of information processing in schizophrenic patients can be isolated with reaction-time (RT) decomposition paradigms. METHOD: Three types of visually presented tasks were applied: simple, disjunctive and choice RT-tasks. RT were split into movement latency and time necessary to execute movements. Comparisons of three samples of schizophrenic patients (295.3) with individually matched (age, sex. education and handedness) healthy controls are presented: Sample 1: 10 drug-naive first-onset patients, Sample 2: 10 neuroleptically treated first-onset patients, Sample 3: 10 neuroleptically treated chronically ill patients. RESULTS: Findings indicate that schizophrenia affects primarily subprocesses in which percepts are translated into appropriate actions (response-selection). Neuroleptic treatment improves processing at this stage but is accompanied by slowing of movement execution. CONCLUSION: Response-selection is selectively impaired in first-onset patients. This disturbance, which might be specific for schizophrenia, can be regarded as indication of a disconnection between frontal and posterior areas.

Adult↗
PubMed2001

Cognitive subprocesses and schizophrenia. B. Maze tasks.

OBJECTIVE: In a companion paper we demonstrated that in reaction-time tasks the response selection stage is selectively disturbed in schizophrenia. The aim of the present study is the investigation of subprocesses, which are incorporated into repeatedly activated loops of cognitive processes and need additional information from working memory. METHOD: Maze tasks of varying complexity (with and without bifurcations) were presented to drug-naive and treated first-onset schizophrenic patients. The tasks had to be solved under easy and difficult motor-conditions. Both patient samples were compared with healthy control groups matched by age, sex, education and experience with the experimental setting. RESULTS: In mazes with alternative routes patients exhibited the expected decrease of performance. However, untreated patients improved under difficult motor conditions. This improvement is smaller after neuroleptic treatment. CONCLUSION: Under difficult motor conditions attention is focused on the execution of movements and thus withdrawn from perceiving irrelevant response alternatives, i.e. the effects of disturbed response selection are reduced.

Adult↗
PubMed2001

Reaction-times and bioelectrical brain signals of drug-naive schizophrenic first-onset patients in identification and classification tasks.

OBJECTIVE: The question of the present study is whether disturbances of response-selection in schizophrenic patients are discernible only if overt motor-actions are required, or also if covert cognitive actions are necessary. METHOD: Visual identification (digits) and classification (dot-enumeration) tasks were presented to 18 drug-naive, first-onset schizophrenic patients and healthy controls. It is assumed that enumeration of more than three dots requires additional cognitive processes as buffering and re-focusing of attention. Reaction-times and 21-channel-EEG were measured. For eye-movement artefact-elimination a new non-parametric regression approach was applied. RESULTS: Reaction-times revealed that in the patient group response selection is lengthened in both tasks. Perception of dot numbers is not affected. Bioelectrical data depicted a left-lateralization of posterior P100 and N 100 in the patient group as well as an enhanced fronto-central P200. CONCLUSION: Whereas in reaction-times of patients only a disturbance of response selection is discernible, bioelectrical measurements also point to an altered organization of perceptive processes.

Adult↗
PubMed2000

Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress.

In Kinetoplastida, trypanothione and trypanothione reductase (TRYR) provide an intracellular reducing environment, substituting for the glutathione-glutathione reductase system found in most other organisms. To investigate the physiological role of TRYR in Trypanosoma brucei, we generated cells containing just one trypanothione reductase gene, TRYR, which was under the control of a tetracycline-inducible promoter. This enabled us to regulate TRYR activity in the cells from less than 1% to 400% of wild-type levels by adjusting the concentration of added tetracycline. In normal growth medium (which contains reducing agents), trypanosomes containing less than 10% of wild-type enzyme activity were unable to grow, although the levels of reduced trypanothione and total thiols remained constant. In media lacking reducing agents, hypersensitivity towards hydrogen peroxide (EC50 = 3.5 microM) was observed compared with the wild type (EC50 = 223 microM). The depletion of TRYR had no effect on susceptibility to melarsen oxide. The infectivity and virulence of the parasites in mice was dependent upon tetracycline-regulated TRYR activity: if the trypanosomes were injected into mice in the absence of tetracycline, no infection was detectable; and when tetracycline was withdrawn from previously infected animals, the parasitaemia was suppressed.

Animals↗
PubMed2000

[Success and failure with the Demers catheter in dialysis].

Between January 1995 and January 1999 54 Demers atrial catheters were implanted in 48 uraemic patients. Indications for implantation were: urgent need for haemodialysis with missing vascular access (39), fistula occlusion (7), low shunt flow (3) and problems with a previously implanted catheter (5). We observed 7 catheter infections, 5 catheter occlusions, 1 intraoperative air embolism, 3 haematomas and 1 dacron socket dislocation. The average period of use of an atrial catheter was 170 days, the longest period almost 2 years. The majority of catheters were explanted without any dysfunction. The long time of availability makes Demers atrial catheters an alternative to fistula for multimorbid patients on dialysis with poor long-term survival.

Adult↗
PubMed1999

Mass mailing and staff experience in a total recruitment program for a clinical trial: the SHEP experience. Systolic Hypertension in the Elderly Program. Cooperative Research Group.

The Systolic Hypertension in the Elderly Program (SHEP) staff contacted 447,921 screenees, of whom 11,919 (2.7%) were originally eligible and 4,736 (1.1%) maintained eligibility and were randomized. The total number of participants enrolled at the 16 clinical centers ranged from 133 to 559. The low yield of screenees to randomizations resulted from the study design, not from low levels of agreement to participate, and required the employment of a variety of recruitment strategies in a prudent overall plan. SHEP was one of the first clinical trials to use mass mailing as a primary strategy of recruitment. The study used mailing lists from seven generic sources. More than 3.4 million letters of invitation were mailed; they yielded an overall response rate of 4.3%. Motor vehicle and voter registration lists provided the greatest numbers of names. Mailings to members of health maintenance organizations (HMOs) and registrants of the Health Care Finance Administration (HCFA) provided the greatest response rates. Considerable variability in response rates existed among clinical centers using generically similar mailing lists. Generally, the number of hours spent on recruitment showed a positive, but not statistically significant, association with randomization yields. The recruitment yield was statistically significantly higher in clinics with experienced recruitment coordinators than in clinics with inexperienced ones (p = 0.0008). From these findings we conclude that mass mailing is an important strategy in an overall recruitment program, that the involvement of experienced recruitment staff is important, and that although the total time spent by staff on recruitment may also improve results, it matters less than the staff's level of recruiting experience.

Aged↗
PubMed1999

Cognitive dysfunction in schizophrenia: a new set of tools for the assessment of cognition and drug effects.

Cognitive impairment in schizophrenia must be seen as a disturbance of cortico-sub-cortical connectivity with a neurotransmitter imbalance in a circuitry system, which connects thalamic input with prefrontal processing and supplementary motor cortex and basal ganglia output. The concept of maze-solving behaviour as a continuous cognitive task evoking a conflict between prefrontal cortex and basal ganglia activity is explained and introduced to distinguish between the effects of D2 blocking agents and substances with a predominant 5HT2A receptor affinity, such as clozapine and risperidone. Complex mazes show a cognitive deficit in untreated schizophrenic patients that are impaired by conventional and improved by atypical antipsychotic substances. Processing speed improves most on clozapine, while parallel processing is best supported by the non-sedative atypical substance risperidone. Maze paradigms are presented.

Antipsychotic Agents↗
PubMed1999

Citromicrobium bathyomarinum, a novel aerobic bacterium isolated from deep-sea hydrothermal vent plume waters that contains photosynthetic pigment-protein complexes.

We have taxonomically and phylogenetically characterized a new aerobic bacterial strain (JF-1) that contains photosynthetic pigment-protein complexes and which was recently isolated from black smoker plume waters of the Juan de Fuca Ridge. Strain JF-1 is a gram-negative, yellow-pigmented, motile bacterium that is salt-, pH-, and thermotolerant. These properties are consistent with an oligotrophic adaptation to varied environmental conditions thought to exist around deep-sea hydrothermal vents. The analysis of 16S rDNA sequences revealed that strain JF-1 forms a separate phylogenetic branch between the genus Erythromonas and the Erythromicrobium-Porphyrobacter-Erythrobacter cluster within the alpha subclass of the Proteobacteria. The taxonomic name Citromicrobium bathyomarinum (gen. nov., sp. nov.) is proposed for strain JF-1.

Cell Division↗
PubMed1999

[Vena cava filter--prevention of pulmonary embolism. Report of clinical experiences].

Between 1982 and 1997 inferior vena cava filters were implanted in 182 patients. Indications were recurrent pulmonary embolism, massive embolism and prophylactic use prior to planned high-risk-operations upon patients with thromboembolic complications in shorter history. Kimray-Greenfield, Cardial and Vascor-systems were implanted. Mortality was 0, neither relevant bleedings, nor infections occurred. Vena-cava-filters prevented from re-embolism in 98%. During hospitalisation 3 cases of re-embolism (1.6%) were noticed due to incorrect filter-placement. One patient died (< 1%). Follow-up-examinations were performed in 74 cases 6 to 24 months after implantation. We discovered 8 cases (11%) of filter-migration, 3 cases (4%) of filter-kinking, one case of filter-perforation and one case of filter-shrut-fracture. All these patients remained without clinical sequelae. Cava-thrombosis was found in 2 patients 6 to 24 months after filter-insertion (2.7%). There was no sign of re-embolism in our longterm follow-up. In our opinion the vena cava filter is an effective and safe method to prevent pulmonary re-embolism. Handling is quite easy and filter complications are low. In some elected cases prophylactic use of vena cava filters in high-risk-patients may be indicated.

Adult↗
PubMed1999

The genexpress IMAGE knowledge base of the human muscle transcriptome: a resource of structural, functional, and positional candidate genes for muscle physiology and pathologies.

Sequence, gene mapping, and expression data corresponding to 910 genes transcribed in human skeletal muscle have been integrated to form the muscle module of the Genexpress IMAGE Knowledge Base. Based on cDNA array hybridization, a set of 14 transcripts preferentially or specifically expressed in muscle have been selected and characterized in more detail: Their pattern of expression was confirmed by Northern blot analysis; their structure was further characterized by full-insert cDNA sequencing and cDNA extension; the map location of the corresponding genes was refined by radiation hybrid mapping. Five of the 14 selected genes appear as interesting positional and functional candidate genes to study in relation with muscle physiology and/or specific orphan muscular pathologies. One example is discussed in more detail. The expression profiling data and the associated Genexpress Index2 entries for the 910 genes and the detailed characterization of the 14 selected transcripts are available from a dedicated Web server at. The database has been organized to provide the users with a working space where they can find curated, annotated, integrated data for their genes of interest. Different navigation routes to exploit the resource are discussed.

Base Sequence↗
PubMed1998

Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro.

OBJECTIVE: To investigate the effects of the cartilage-derived morphogenetic proteins (CDMPs) in an in vitro cartilage explant model that mimics the chondrocytic response to matrix depletion, and to demonstrate their presence in articular cartilage. METHODS: Adult bovine articular cartilage and postmortem specimens from adult human donors with and without osteoarthritic (OA) lesions were stained by immunohistochemistry using polyclonal antibodies specific for CDMP-1 and CDMP-2. Extracts of bovine articular cartilage were analyzed by Western blotting for the presence of the CDMPs. Bovine articular cartilage explants were depleted of their matrix by trypsin digestion, followed by a 7-day culture period in a chemically defined serum-free basal medium (BM), with or without recombinant CDMPs 1 and 2. The metabolic activity of chondrocytes was measured by 35S-sulfate incorporation into macromolecules. Newly synthesized proteoglycans (PGs) were analyzed using Sephacryl S-500 HR gel chromatography. The expression levels of the messenger RNA (mRNA) for chondrogenic markers were investigated by Northern analysis. RESULTS: CDMP-1 and CDMP-2 were detected in both bovine and human healthy and OA articular cartilage. Treatment of matrix-depleted cartilage explants with CDMPs 1 and 2 increased equally the incorporation of 35S-sulfate into PGs compared with tissue maintained in BM. Gel chromatography analysis indicated that aggrecan was the predominant PG species. Northern blot analysis showed that the expression of link protein, type II collagen, and aggrecan mRNA transcripts was not modulated by CDMP treatment. CONCLUSION: This study shows the presence of CDMP-1 and CDMP-2 in adult bovine and human articular cartilage. In addition, our in vitro data indicate that CDMPs 1 and 2 stimulate the metabolic activity of articular chondrocytes. Therefore, these signaling molecules may be contributing to the maintenance of the integrity of the joint surface.

Animals↗
PubMed1998

The topography of non-linear cortical dynamics at rest, in mental calculation and moving shape perception.

Differential cortical activation by cognitive processing was studied using dimensional complexity, a measure derived from nonlinear dynamics that indicates the degrees of freedom (complexity) of a dynamic system. We examined the EEG of 32 healthy subjects at rest, during a visually presented calculation task, and during a moving shape perception task. As a nonlinear measure of connectivity, the mutual dimension of selected electrode pairs was used. The first Lyapunov coefficient was also calculated. Data were tested for non-linearity using a surrogate data method and compared to spectral EEG measures (power, coherence). Surrogate data testing confirmed the presence of nonlinear structure in the data. Cognitive activation led to a highly significant rise in dimensional complexity. While both tasks activated central, parietal and temporal areas, mental arithmetic showed frontal activation and an activity maximum at T3, while the moving shape task led to occipital activation and a right parietal activity maximum. Analysis of mutual dimension showed activation of a bilateral temporal-right frontal network in calculation. The Lyapunov coefficient showed clear topographic variation, but was not significantly changed by mental tasks (p<.09). While dimensional complexity was almost unrelated to power values, nonlinear (mutual dimension) and linear (coherence) measures of connectivity shared up to 37% of variance. Data are interpreted in terms of increased cortical complexity as a result of recruitment of asynchronously active, distributed neuronal assemblies in cognition. The topography of nonlinear dynamics are related to neuropsychological and neuroimaging findings on mental calculation and moving shape perception.

Adult↗
PubMed1997

Can negative self-schemes in depressives be altered through sleep deprivation?

This paper addresses the question whether negative cognitive style represents a state or trait variable of depressive patients. For this reason, it studies the influence of sleep deprivation on negative self-schemes of those patients. 10 patients suffering from DSM-III-R major depression were compared with 10 age- and sex-matched controls on a task for rating the self-descriptiveness of positive and negative adjectives as well as a subsequent word recognition task. Three sessions were involved: an initial session (baseline), the second following a night of sleep deprivation, and the third after a successive full night's sleep. During the baseline examination, depressives showed a relatively negative cognitive bias; that is, the same number of positive and negative self-scheme elements. In comparison to controls, they showed significantly more negative and significantly less positive self-scheme elements. The same pattern emerged in a word recognition task for the number of recognized self-scheme elements. These variables indicated no change in the depressive group following sleep deprivation. Depressive subjects' reaction times on self-descriptiveness rating were significantly longer for positive than for negative self-scheme elements at the baseline session. The opposite was true for controls. Here, a sleep deprivation effect was evident. There was no longer a difference in the speed of information processing for positive as compared to negative self-scheme elements. This applied to both depressive and control groups.

Adult↗
PubMed1997

MRI findings in chronic hepatic encephalopathy depend on portosystemic shunt: results of a controlled prospective clinical investigation.

BACKGROUND/AIMS: Deterioration of hepatic encephalopathy is a major concern with the transjugular intrahepatic portosystemic shunt procedure. Symmetric hyperintense globus pallidus on T1-weighted cranial magnetic resonance imaging in patients with liver cirrhosis anticipates hepatocerebral disease. It is hypothesized that hepatic encephalopathy and basal ganglia signal intensity progress in patients with cirrhosis of the liver undergoing transjugular intrahepatic portosystemic shunt. METHODS: Twenty-four patients were randomized to undergo either transjugular intrahepatic portosystemic shunt or elective sclerotherapy. At study entry and 6 months after randomization, neurologic assessment, psychometric tests, standard EEG, and magnetic resonance imaging were performed. The severity of liver failure was graded using Child-Pugh's classification. The signal intensity of the globus pallidus was determined on sagittal T1-weighted magnetic resonance imaging. RESULTS: The T1-weighted signal intensity of the globus pallidus on magnetic resonance imaging significantly increased after transjugular intrahepatic portosystemic shunt placement (p<0.01), but not with elective sclerotherapy. At follow-up, neurological symptoms indicating decline of mental status and motor performance were somewhat more prevalent in transjugular intrahepatic portosystemic shunt patients. Significant deterioration of EEG abnormalities occurred in patients treated with transjugular intrahepatic portosystemic shunt as opposed to elective sclerotherapy (p<0.01). CONCLUSIONS: Transjugular intrahepatic portosystemic shunt procedure increases hyperresonant globus pallidus on magnetic resonance imaging. Neuropsychiatric evaluation shows advancing hepatic encephalopathy, in particular with transjugular intrahepatic portosystemic shunt; however, it does not parallel the augmentation of pallidal signal intensity on magnetic resonance imaging.

Adult↗
PubMed1997

Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study.

Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a "trait" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.

Adult↗
PubMed1997

Recruitment in the Trial of Nonpharmacologic Intervention in the Elderly (TONE).

OBJECTIVE: To compare the effectiveness of different approaches to participant enrollment in a behavior modification trial. DESIGN: Concurrent, prospective evaluation performed in context of recruitment for a randomized, controlled trial. SETTING: Four study centers located in Baltimore, Maryland, Memphis, Tennessee New Brunswick, New Jersey, and Winston-Salem, North Carolina. PARTICIPANTS: Men and women aged 60 to 80 years who were being treated with a prescription medication for control of hypertension. MAIN OUTCOME MEASURES: Visit counts and percent yields were assessed at each stage of the screening and randomization process. Logistic regression was used to contrast the randomization yields for different recruitment strategies and to explore the impact of sociodemographic characteristics and geographic location on recruitment yields. RESULTS: The overall randomization yields from a prescreen contact and a first screening visit to enrollment in the trial were 11% and 31%, respectively. Randomization yields varied significantly by participant age, education, and marital status. CONCLUSIONS: Our results demonstrate the feasibility of recruitment for trials of nonpharmacologic interventions in older people and suggest that mass mailing and mass media advertising campaigns provide an effective means of enrolling in such studies participants with a broad range of personal characteristics.

Advertising↗