PubMed Health⌕ Search

Biomedical subjects

C Kessler

Publications and source records attributed to C Kessler.

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

Subcortical correlates of differential classical conditioning of aversive emotional reactions in social phobia.

BACKGROUND: Conditioning processes have been proposed to play a role in the development of anxiety disorders. As yet, the neurobiologic correlates of emotional learning have not been fully understood in these patients. Accordingly, brain activity was studied in subcortical and cortical regions involved in the processing of negative affect during differential aversive classical conditioning. METHODS: Twelve patients with social phobia and 12 healthy control subjects were presented with paired conditioned (CS; neutral facial expressions) and unconditioned stimuli (US; negative odor vs unmanipulated air). Functional magnetic resonance imaging (fMRI) was utilized to examine regional cerebral activity during habituation, acquisition,a nd extinction trials. Activity was measured with echo-planar-imaging (EPI), and signal intensity in individually defined anatomic regions were analyzed. RESULTS: Subjective ratings of emotional valence to the CS indicated that behavioral conditioning occurred in both groups. The presentation of CS associated with negative odor led to signal decreases in the amygdala and hippocampus of normal subjects, whereas an opposite increased activation in both regions was observed in patients. Regional differences were not found during habituation and extinction. CONCLUSIONS: Results suggest that conditioned aversive stimuli are processed in subcortical regions, with phobic patients differing from control subjects.

Adult↗
PubMed1999

Enhancement of BOLD-contrast sensitivity by single-shot multi-echo functional MR imaging.

Improved data acquisition and processing strategies for blood oxygenation level-dependent (BOLD)-contrast functional magnetic resonance imaging (fMRI), which enhance the functional contrast-to-noise ratio (CNR) by sampling multiple echo times in a single shot, are described. The dependence of the CNR on T2*, the image encoding time, and the number of sampled echo times are investigated for exponential fitting, echo summation, weighted echo summation, and averaging of correlation maps obtained at different echo times. The method is validated in vivo using visual stimulation and turbo proton echoplanar spectroscopic imaging (turbo-PEPSI), a new single-shot multi-slice MR spectroscopic imaging technique, which acquires up to 12 consecutive echoplanar images with echo times ranging from 12 to 213 msec. Quantitative T2*-mapping significantly increases the measured extent of activation and the mean correlation coefficient compared with conventional echoplanar imaging. The sensitivity gain with echo summation, which is computationally efficient provides similar sensitivity as fitting. For all data processing methods sensitivity is optimum when echo times up to 3.2 T2* are sampled. This methodology has implications for comparing functional sensitivity at different magnetic field strengths and between brain regions with different magnetic field inhomogeneities.

Adult↗
PubMed1999

Anomalous expression of microtubule-associated protein 1B in the hippocampus and cortex of aged rats treated with pentylenetetrazole.

The aim of the present study was to assess the age-dependent response of microtubule-associated protein 1B, a plasticity-associated protein deriving from a late gene, following administration of an epileptogenic stimulus. The effect of a single administration of the convulsant pentylenetetrazole on microtubule-associated protein 1B expression in the hippocampal formation and cortex of three-, 18- and 28-month-old rats was assessed using northern blot analysis, in situ hybridization and immunohistochemistry. In three-month-old rats, we detected initial increases in microtubule-associated protein 1B messenger RNA at 15 h following pentylenetetrazole administration in the granule cells of the dentate gyrus, in the CA3 region of the hippocampus and in layers II/III of the entorhinal cortex, and these reached a maximum at 44 h. However, in the hippocampus and cortex of 18-month-old rats, the peak occurred at 15 h, and in the brains of 28-month-old rats a blunted peak was reached at 3 h. Pentylenetetrazole treatment in young rats resulted in a robust induction of microtubule-associated protein 1B immunoreactivity in the granule cells of the dentate gyrus and in layers II/III of the entorhinal cortex, but also produced a large decrease in the retrosplenial cortex. However, following pentylenetetrazole treatment in older rats, the granule cells of the dentate gyrus were nearly devoid of microtubule-associated protein 1B immunoreactivity, whereas the retrosplenial cortex showed no changes at all, and the entorhinal cortex had an expression pattern similar to that of young rats. Aberrant immunolabeling of microtubule-associated protein 1B occurred in cortical layer VI of the aged rats where, unlike in young rats, there was heavy staining of neuronal somata. These results suggest that the regulation of the plasticity-associated protein microtubule-associated protein 1B is altered in the ageing rat brain, with the peak of expression shifted to earlier times in 18-month-old rats and blunted, variable increases at even earlier times in 28-month-old rats.

Aging↗
PubMed1999

Upregulation of MAP1B and MAP2 in the rat brain after middle cerebral artery occlusion: effect of age.

Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. This is especially important when studying restorative processes that are age dependent. To explore the potential of older animals to initiate regenerative processes after cerebral ischemia, the authors studied the expression of the juvenile-specific cytoskeletal protein, microtubule-associated protein (MAP) 1B, and the adult-specific protein, MAP2, in male Sprague-Dawley rats at 3 months and 20 months of age. The levels of MAP1B and MAP2 transcripts and the corresponding proteins declined with increasing age in the hippocampus. In the cortex, the levels of the transcripts did not change significantly with age, but the morphologic features of immunostained fibers were clearly affected by age; that is, cortical MAP1B fibers became thicker, and MAP2 fibers, more diffuse, in aged rats. Focal cerebral ischemia, produced by reversible occlusion of the right middle cerebral artery, resulted in a large decrease in the expression of both MAP1B and MAP2 in the infarct core at the messenger ribonucleic acid and protein levels. However, at 1 week after the stroke, there was vigorous expression of MAP1B and its messenger ribonucleic acid, as well as MAP2 protein, in the border zone adjacent to the infarct of 3-month-old and 20 month-old male Sprague-Dawley rats. The upregulation of these key cytologic elements generally was diminished in aged rats compared with young animals, although the morphologic features of fibers in the infarct border zone were similar in both age groups. These results suggest that the regenerative potential of the aged rat brain appears to be competent, although attenuated, at least with respect to MAP1B and MAP2 expression up to 20 months of age.

Aging↗
PubMed1999

Influence of valproate monotherapy on platelet activation and hematologic values.

PURPOSE: Valproate (VPA) has been linked to coagulation disturbances, with both impaired and exaggerated clotting, which has been attributed to an effect of VPA on platelets or hemostatic proteins. Additional thrombocytic function testing may help to identify patients at risk of increased bleeding caused by platelet dysfunction. METHODS: We evaluated the influence of VPA on hematologic routine values and platelet activation by using immunostaining and flow cytometry in 30 patients receiving long-term VPA therapy and in 30 controls. RESULTS: The fraction of activated platelets was similar in both groups; however, the general extent of platelet activation was significantly lower in the patient group, with considerable interindividual variability. In addition, patients had a significantly lower platelet count, prolonged thrombin time, and higher mean corpuscular hemoglobin. CONCLUSIONS: Our data confirm the previously reported hematologic changes caused by VPA and additionally suggest that VPA impairs procoagulatory thrombocytic function, which is reflected by reduced platelet activation and increased thrombin time. Possible mechanisms of VPA-platelet interaction are discussed.

Adult↗
PubMed1999

Circulating platelets show increased activation in patients with acute cerebral ischemia.

Platelet activation plays a central role in acute arterial stenosis as has been shown in coronary heart disease. Likewise it can be assumed to be of importance in the evolution of acute cerebral ischemia (ACI), particularly in patients with large vessel disease. Flow cytometric detection of platelet adhesion molecules as a marker of platelet activation in a group of patients with ACI and different etiologies has not been evaluated. In 72 patients with ACI and 72 controls, the exposure of activation-dependent adhesion molecules was determined using flow cytometry after immunostaining with monoclonal antibodies against CD 62, CD 63 and thrombospondin. The extent of platelet activation differed as a function of the etiology of ACI: platelets from patients with atherosclerosis of brain-supplying arteries expressed significantly more activation markers than did controls, whereas patients with cardioembolic stroke did not. By analyzing platelet adhesion molecules it is possible to describe platelet activation profiles in patients with acute cerebral ischemia. This diagnostic procedure will be useful for monitoring individualized anti-platelet therapy and may enable distinguishing different subgroups of stroke patients.

Acute Disease↗
PubMed1998

Differential amygdala activation in schizophrenia during sadness.

Several studies have reported impaired emotion processing in schizophrenic patients. However, the corresponding functional cerebral correlates of such impairment have not been fully understood, leaving the neurobiological basis of their affective symptoms unknown. Functional magnetic resonance imaging (fMRI) was utilized to examine brain activity in subcortical and cortical regions of 13 medicated male schizophrenic patients and 13 matched healthy controls during happy and sad mood induction. Results show brain activity in the amygdala of normal controls during negative affect, which is in line with previous neuroimaging findings. Unlike controls, schizophrenic patients have not demonstrated amygdala activation during sadness despite matched ratings to normal controls indicating a similar negative affect. Recognizing that structural abnormalities exist in the amygdala of schizophrenic patients, our results provide new evidence of functional abnormalities in the limbic system.

Adult↗
PubMed1998

Altered expression of microtubule-associated protein 1B in cerebral cortical structures of pentylenetetrazole-treated rats.

Using Northern blot, immunoblotting, immunocytochemistry, and in situ hybridization, we show that a single administration of the convulsant pentylenetetrazole leads to robust, long-term changes in microtubule-associated protein 1B and its mRNA, in the adult rat brain. The first increases in MAP1B mRNA were detected at 15 hr following pentylenetetrazole administration in the temporal (Te2) and perirhinal cortex followed by increases in microtubule-associated protein 1B immunoreactivity at 72 hr postseizure. In contrast, the levels of microtubule-associated protein 1B mRNA and protein in layers I-II of the retrosplenial and parietal cortex (Par2) declined visibly by 24 hr and 72 h, respectively, post-seizure. The changes included loss of staining in layers I-II and development of structures resembling "strings-of-beads" along the fibers of projection neurons of layer V. The levels of microtubule-associated protein 1B mRNA in the entorhinal cortex peaked at later times (72 h), especially in layers II-III, and returned to control levels by 10 days. Whereas the levels of microtubule-associated protein 1B immunoreactivity in the retrosplenial and parietal cortex recovered by 5-10 days, it persisted at high levels through day 35 in layer V of the temporal cortex (Te2), layers II-III of the perirhinal cortex and layers I-II of the lateral entorhinal cortex. These results indicate that seizure activity leads to long-term upregulation of genes coding for structural elements that are characteristic of the immature brain such as microtubule-associated protein 1B.

Animals↗
PubMed1998

Transcranial duplex sonography of middle cerebral artery stenosis: a comparison of colour-coding techniques--frequency- or power-based Doppler and contrast enhancement.

The main limitation of transcranial colour-coded duplex sonography (TCCD) is the inadequate acoustic window, which prevents transtemporal identification of the basal cerebral arteries in up to 30% of cases, especially in the elderly. TCCD with different colour-coding techniques, including frequency-based colour-flow (CFD) or power (PD) Doppler sonography, used alone or in combination with contrast media, were used in 23 patients with middle cerebral artery (MCA) stenosis. In 10 patients a contrast medium (400 mg/ml SHU 508 A) was administered because of inadequate colour-coded visualisation with TCCD. The data were compared with angiographic methods. Digital subtraction angiography (DSA) revealed 2 low-grade, 11 middle-grade and 10 high-grade stenoses in the M1 segment. With TCCD, we found a 7.7% higher blood flow velocity (systolic peak velocity) than with transcranial duplex sonography without colour-coding because of visual angle correction and a 20% higher systolic peak velocity using contrast enhancement. CFD did not differ from PD in identification of low- and middle-grade MCA stenoses, but PD alone revealed two more cases of high-grade stenosis than CFD. The contrast medium increased diagnostic confidence in 8 of 10 cases. Only 2 of 23 MCA stenoses (9%) could not be shown using TCCD.

Adult↗
PubMed1998

Prevalence of factor V Leiden mutation in young adults with cerebral ischaemia: a case-control study on 225 patients.

Cerebral ischaemia in young adults is a well-recognised disease, and approximately half of the cases remain aetiologically unclear despite extensive investigations. Thrombophilias are known to cause a subset of ischaemic strokes in this population. The factor V Leiden (FVL) mutation, causing resistance to activated protein C, has recently been recognised as the most important genetic thrombophilia in the Western population. Carriers of this gene mutation have a sevenfold increased risk of phlebothrombosis. We undertook this study to evaluate whether the FVL mutation constitutes a risk factor for juvenile cerebral ischaemias. A total of 225 patients aged < or = 45 years at onset of cerebral ischaemia and 200 age-matched healthy controls were investigated. The overall frequency of heterozygosity for the FVL mutation did not differ significantly between patients (8.4%) and controls [6.0%; odds ratio (OR) 1.4, 95% confidence interval (CI) 0.7-3.1]. In the subgroup of patients with cryptogenic cerebral ischaemia (n = 94), however, a significantly higher frequency of this gene defect (15.9%) was found compared with the controls (OR 3.0, CI 1.3-6.6). Further trends towards higher frequencies of the FVL mutation were found in patients with patent foramen ovale (OR 1.9), individual (OR 2.1) or family history of previous thrombembolisms (OR 2.0), and in those aged 25 years at onset of disease (OR 1.9, all not significant). In conclusion, the FVL mutation is not a risk factor for cerebral ischaemia of the young. However, our results suggest that this gene mutation plays an aetiological role in the subgroup of patients suffering from 'cryptogenic' ischaemic events.

Adolescent↗
PubMed1998

Adaptation and psychometric properties of the German version of the Dissociative Experience Scale.

We introduce the 'Fragebogen zu Dissoziativen Symptomen' (FDS), a German adaptation of the Dissociative Experience Scale (DES) which was developed to screen for dissociation within an ICD-10 framework. In addition to the original 28 DES items, the FDS contains 16 items covering dissociative phenomena included in the ICD-10, particularly pseudoneurological conversion symptoms. The psychometric properties of the FDS were studied in 927 clinical and nonclinical subjects from different diagnostic groups and compared to results of American studies. The scale had good test-retest reliability of .88, high internal consistency (split-half = .90, Cronbach's alpha = .94) and good construct validity. These results indicate that the FDS may be a valuable screen for dissociative psychopathology in German-speaking countries.

Adult↗
PubMed1998

Apolipoprotein E4 promotes incipient Alzheimer pathology in the elderly.

To evaluate the influence of the apolipoprotein E (ApoE) epsilon4 allele on the age at which Alzheimer-like lesions appear in the brain, we analyzed the degree of cerebral beta-amyloidosis and neurofibrillary tangle formation in the hippocampal formation and adjacent cortical areas 28, 27, and 36 of persons who had died between the ages of 50 and 93 years and who had shown no signs of clinical dementia. The occurrence of the three common polymorphisms of the ApoE gene in this sample of 147 routine autopsy cases from eastern Germany was comparable to previously reported values in European and North American populations: ApoEepsilon2/2, 0.7%; ApoEepsilon2/3, 14.3%; ApoEepsilon2/4, 4.1%; ApoEepsilon3/3, 56.5%; ApoEepsilon3/4, 22.4%; and ApoEepsilon4/4, 2.0%. Nondemented persons carrying the ApoEepsilon4 allele were significantly more likely to have senile plaques, diffuse amyloid deposits, cerebrovascular amyloid, and neurofibrillary tangles than were those lacking E4. Comparing the two largest ApoE subgroups, ApoEepsilon3/3 and ApoEepsilon3/4, the relative increase in the occurrence of beta-amyloid in the epsilon3/4 group was evident by the mid-60s, with the relative increase in neurofibrillary tangles in this group emerging slightly earlier. The ApoEepsilon2 allele appears to delay the appearance of the lesions somewhat. We conclude that ApoEepsilon4 promotes the early appearance of beta-amyloid and neurofibrillary tangles in the elderly and that the increased frequency of these lesions is related to the higher risk of Alzheimer disease in persons bearing the ApoEepsilon4 allele.

Aged↗
PubMed1998

Transcranial power mode Doppler duplex sonography of intracranial aneurysms.

The application of different color-coding techniques in transcranial color-coded duplex sonography (TCCD) was assessed for detection and measurement of the size of intracranial aneurysms. Thirty-two consecutively examined patients with 36 angiographically verified cerebral aneurysms underwent TCCD with color Doppler flow imaging (CDFI), power Doppler imaging (PDI), and both methods with contrast enhancement. The diameters of the aneurysms were measured in comparable planes by means of angiography and TCCD-PD with and without 400 mg/ml of the monosaccharide microparticle contrast agent Levovist. TCCD with CFD enabled detection of 27 of 36 aneurysms (75%), and PD depicted 29 aneurysms (80%). After administration of Levovist, an additional two aneurysms were detected with CFD and three with PD color coding. Measurements of aneurysm size obtained by means of PD with contrast enhancement corresponded more highly with angiographic findings than did measurements obtained with PD alone. Use of alternative color-coding techniques with the addition of contrast agents increases the number of intracranial nonthrombosed aneurysms detectable with TCCD.

Adolescent↗
PubMed1998

beta-Amyloid precursor protein and ss-amyloid peptide immunoreactivity in the rat brain after middle cerebral artery occlusion: effect of age.

BACKGROUND AND PURPOSE: Previous studies have shown that the ss-amyloid precursor protein (ssAPP) is upregulated after cerebral ischemia and that the ss-amyloid (Ass) fragment may be toxic to brain cells. Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. To test the hypothesis that the upregulation and/or persistence of amyloidogenic proteins is exacerbated in aged rats after cerebral ischemic stroke, we studied the expression of ssAPP and its proteolytic product Ass in the brains of young and old rats 7 days after temporary cerebral ischemia. METHODS: Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. After 1 week, brains were removed and immunostaining was performed for ssAPP, Ass, and ED1 for macrophages and glial fibrillary acidic protein (GFAP). RESULTS: Histological staining revealed that the degree of necrotic cavitation in the infarct core was relatively less in aged rats than in young rats, suggesting a slower pace of degenerative change and/or tissue removal in older animals. ssAPP immunoreactivity was robustly increased, primarily in macrophage-like, ED1-positive cells in the infarct core and in the penumbra of both young and aged animals. Ass immunoreactivity was evident in GFAP-positive astrocytic somata and processes, and also in clusters of small spherical structures in the penumbra. These Ass-immunoreactive minispheres were more numerous in aged rats than in young rats. CONCLUSIONS: The presence of ssAPP and Ass immunoreactivity in the infarct core and penumbra indicates that cerebral ischemia promotes conditions that are favorable to the focal accumulation of ssAPP and its proteolytic fragments, especially in the aged brain.

Aging↗
PubMed1998

Phosphoinositol glycan derived mediators and insulin resistance. Prospects for diagnosis and therapy.

While much work remains, the evidence has become strong that IPG generation following insulin action is a significant signaling mechanism. A considerable body of data has established IPG release by insulin and other growth factors from cell membranes, cells and in human blood and muscle biopsies in vivo. Two separate IPG species containing D-chiro-inositol and myo-inositol have been separated by ion exchange. These IPGs have separate actions in vitro and are both active as insulin surrogates in vivo. A deficiency of the chiro-inositol system has been demonstrated in urine and tissues in humans and directly related to insulin resistance. Accordingly, D-chiro-inositol was administered to STZ diabetic rats and rhesus monkeys and shown to decrease hyperglycemia and enhance glucose disposal. Two trials in humans with impaired glucose tolerance and women with PCOS have now also proven successful. Thus, the pathophysiology in the chiro-inositol system related to insulin resistance and its reversal by chiro-inositol administration, in addition to the basic work, argues strongly for the physiological significance of this novel signaling system in the control of glucose metabolism.

Animals↗
PubMed1998

Tuberculosis control in refugee populations: a challenge to both relief agencies and national programs.

Today's worldwide tuberculosis epidemic and the movement of a growing number of refugees overlap geographically and have made tuberculosis control in refugee populations an issue of increasing importance. However, in developing countries, where both of these problems are concentrated, tuberculosis control in refugee populations remains a largely unmet need. Experience shows that despite difficult field conditions, tuberculosis control programs can be managed successfully in this setting. The range of outcome results reported for treatment completion and defaulting is, however, wide. Analyzing possible determinants for observed variation in treatment outcome results, this paper outlines prerequisites for establishing a tuberculosis control program in a refugee setting. An attempt is made to formulate a general strategy for the main policies which, if applied consistently, will reduce morbidity, mortality and transmission of tuberculosis among refugee populations living in camps. Criteria for the evaluation and monitoring of such a program are discussed.

Communicable Disease Control↗