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Biomedical subjects

B Luber

Publications and source records attributed to B Luber.

18 recordsLinked to original sources
PubMed2001

Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials.

Testing the therapeutic potential of transcranial magnetic stimulation (TMS) in controlled trials requires a valid sham condition. Sham TMS is typically administered by tilting the coil 45--90 degrees off the scalp, with one or two wings of the coil touching the scalp. Lack of cortical effects has not been verified. We compared sham manipulations in their thresholds for eliciting motor-evoked potentials (MEPs) in human volunteers and in intracerebral measurements of voltage induced in the prefrontal cortex of a rhesus monkey. Three types of sham (one-wing 45 degrees and 90 degrees and two-wing 90 degrees tilt) induced much lower voltage in the brain than active TMS (67--73% reductions). However, the two-wing 45 degrees sham induced values just 24% below active TMS. This sham was about half as potent in inducing MEPs over the motor cortex as active TMS. Some sham TMS conditions produce substantial cortical stimulation, making it critical to carefully select the sham manipulation for clinical trials.

Adult↗
PubMed2000

Different brain networks mediate task performance in normal aging and AD: defining compensation.

OBJECTIVE: To determine whether the pathologic mechanisms of AD alter the brain networks subserving performance of a verbal recognition task. BACKGROUND: Functional imaging studies comparing task-related activation in AD patients and controls generally have not used network analysis and have not controlled for task difficulty. METHODS: H2 15O PET was used to measure regional cerebral blood flow in 14 patients and 11 healthy elders during the performance of a serial verbal recognition task under two conditions: low demand, with study list size (SLS) equal to one; and titrated demand, with SLS adjusted so that each subject recognized words at 75% accuracy. The Scaled Subprofile Model was used to identify networks of regionally covarying activity across these task conditions. RESULTS: In the elders, higher SLS was associated with the recruitment of a network of brain areas involving left anterior cingulate and anterior insula (R2 = 0.94; p < 0.0001). Three patients also expressed this network. In the remaining patients, higher SLS was associated with the recruitment of an alternate network consisting of left posterior temporal cortex, calcarine cortex, posterior cingulate, and the vermis (R2 = 0.81, p < 0.001). Expression of this network was unrelated to SLS in the elders and more intact AD patients. CONCLUSIONS: The patients' use of the alternate network may indicate compensation for processing deficits. The transition from the normal to the alternate network may indicate a point where brain disease has irreversibly altered brain function and thus may have important implications for therapeutic intervention.

Aged↗
PubMed2000

Electrophysiological correlates of the adverse cognitive effects of electroconvulsive therapy.

Resting state, eyes closed, 19-lead EEG recordings were obtained at pre-ECT baseline and just prior to penultimate treatment and during the week following the ECT course in 59 patients with major depression. Patients had been randomized to ECT conditions that varied in electrode placement and stimulus intensity. The EEG data were submitted to power spectral analysis, and global and topographic effects were characterized for the delta and theta frequency bands. Relations between the EEG changes and scores on three cognitive measures were examined. The period of disorientation immediately following RUL ECT was associated with an accentuation of delta power in anterior frontal and temporal regions. Across the electrode placements, increased theta activity in left frontotemporal regions was associated with longer recovery of orientation. Post-ECT decrements in global cognitive status, as assessed by the modified Mini-Mental State exam, were associated with a greater increase in delta relative to theta power, globally across the cortex. The magnitude of retrograde amnesia for autobiographical events correlated with increased theta activity in left frontotemporal regions. The findings suggest that distinct neurophysiological changes subserve the therapeutic and adverse cognitive effects of ECT. Postictal disorientation and post-ECT retrograde amnesia appear to share a common physiological substrate.

Adult↗
PubMed2000

Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. I. Global analyses.

This study examined the effects of electroconvulsive therapy (ECT) treatment conditions, patient individual difference factors, and clinical outcome on global electroencephalogram (EEG) power during and immediately following ECT-induced seizures. Sixty-two patients were randomized to ECT conditions differing in electrode placement (right unilateral versus bilateral) and stimulus dosage (just above seizure threshold versus 2.5 times seizure threshold). At the second and penultimate treatments, global total power (1.5-28.5 Hz) and global power in specific frequency bands were quantified in 19-lead EEG recordings of the generalized seizure and the immediate postictal period. Seizures induced with high dosage, and to lesser extent, with bilateral electrode placement, resulted in greater global power. Patient age, initial seizure threshold, and baseline depression severity were inversely related to global power during seizures. While superior clinical outcome following ECT was associated with greater global power during seizures, this effect was small. The factors associated with more robust seizure expression also resulted in greater postictal bioelectric suppression. Associations with treatment parameters and patient variables were stronger at the second than penultimate treatment. We conclude that manipulations of ECT technique strongly determine the magnitude of seizure expression, but relations with clinical outcome are weak. The findings raise doubt about the clinical utility of algorithms based on analysis of EEG features to guide ECT parameter selection.

Analysis of Variance↗
PubMed2000

Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. II. Topographic analyses.

This study tested three alternative theories of the mechanisms of therapeutic action of electroconvulsive therapy (ECT). The theories differed in predictions about the global and topographic effects of effective and ineffective forms of ECT on electroencephalogram (EEG) seizure expression. At the second treatment, 19-lead EEG recordings were obtained in 57 depressed patients randomized to conditions that differed in ECT electrode placement and stimulus dosage. Power in the delta frequency band was quantified during the seizure and analyzed with traditional multivariate methods and the Scaled Subprofile Model. Electrical dosage of the ECT stimulus had a powerful effect on ictal global delta power and, more so, than electrode placement. Greater ictal global delta power was associated with superior therapeutic outcome, but the magnitude of this effect was small. Effective forms of ECT resulted in a topography where delta power was accentuated in prefrontal EEG sites. High dosage right unilateral ECT also resulted in stronger asymmetry in prefrontal regions than the ineffective, low dosage right unilateral ECT. Greater bilateral generalization of seizure expression does not appear to be a prerequisite for therapeutic effects. Instead, more intense seizure expression in prefrontal regions may be critical for efficacy.

Analysis of Variance↗
PubMed2000

Tumor-derived mutated E-cadherin influences beta-catenin localization and increases susceptibility to actin cytoskeletal changes induced by pervanadate.

E-cadherin participates in homophilic cell-to-cell adhesion and is localized to intercellular junctions of the adherens type. In the present study, we investigated the localization of adherens junction components in cells expressing mutant E-cadherin derivatives which had been previously cloned from diffuse-type gastric carcinoma. The mutations are in frame deletions of exons 8 or 9 and a point mutation in exon 8 and affect the extracellular domain of E-cadherin. Our findings indicate that E-cadherin mutated in exon 8 causes beta-catenin staining at lateral cell-to-cell contact sites and, in addition, abnormally located beta-catenin in the perinuclear region. Moreover, the various mutant E-cadherin derivatives increased the steady-state levels of alpha- and beta-catenin and were found in association with these catenins even after induction of tyrosine phosphorylation by pervanadate. Sustained pervanadate treatment led, however, to rounding-up of cells and induction of filopodia, changes which were first detectable in cells expressing E-cadherin mutated in exon 8. The deterioration of the cell contact was not accompanied with disassembly of the E-cadherin-catenin complex. Based on these observations, we propose a model whereby in the presence of mutant E-cadherin tyrosine phoshorylation of components of the cell adhesion complex triggers loss of cell-to-cell contact and actin cytoskeletal changes which are not caused by the disruption of the E-cadherin-catenin complex per se, but instead might be due to phosphorylation of other signaling molecules or activation of proteins involved in the regulation of the actin cytoskeleton.

Actin Cytoskeleton↗
PubMed1999

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility.

A major function of the cell-to-cell adhesion molecule E-cadherin is the maintenance of cell adhesion and tissue integrity. E-cadherin deficiency in tumours leads to changes in cell morphology and motility, so that E-cadherin is considered to be a suppressor of invasion. In this study we investigated the functional consequences of three tumour-associated gene mutations that affect the extracellular portion of E-cadherin: in-frame deletions of exons 8 or 9 and a point mutation in exon 8, as they were found in human gastric carcinomas. Human MDA-MB-435S breast carcinoma cells and mouse L fibroblasts were stably transfected with the wild-type and mutant cDNAs, and the resulting changes in localization of E-cadherin, cell morphology, strength of calcium-dependent aggregation as well as cell motility and actin cytoskeleton organization were studied. We found that cells transfected with wild-type E-cadherin showed an epitheloid morphology, while all cell lines expressing mutant E-cadherin exhibited more irregular cell shapes. Cells expressing E-cadherin mutated in exon 8 showed the most scattered appearance, whereas cells with deletion of exon 9 had an intermediate state. Mutant E-cadherins were localized to the lateral regions of cell-to-cell contact sites. Additionally, both exon 8-mutated E-cadherins showed apical and perinuclear localization, and actin filaments were drastically reduced. MDA-MB-435S cells with initial calcium-dependent cell aggregation exhibited decreased aggregation and, remarkably, increased cell motility, when mutant E-cadherin was expressed. Therefore, we conclude that these E-cadherin mutations may not simply affect cell adhesion but may act in a trans-dominant-active manner, i.e. lead to increased cell motility. Our study suggests that E-cadherin mutations affecting exons 8 or 9 are the cause of multiple morphological and functional disorders and could induce the scattered morphology and the invasive behaviour of diffuse type-gastric carcinomas.

Actins↗
PubMed1999

The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines.

The role of hepatitis B virus HBx protein in the carcinogenesis associated with chronic viral infection remains ill-defined. Indeed, pleiotropic effects have been ascribed to HBx: in addition to its well-documented ability to indirectly stimulate transcription, the protein has been reported to affect cell growth, signal transduction, DNA repair and apoptosis. In this work, we generated Chang (CCL-13)-derived cell lines constitutively expressing wild type or mutant HBx, as a model of HBx-host cell interaction closer to the chronic infection setting, than the classically used transient expression systems. We document the potentiation by HBx of the apoptotic cell death pathway in the recipient cells. This effect is unlikely to rely on p53 activity since the protein is functionally inactivated in CCL-13. In addition, antioxidants and cyclosporin A failed to reduce the apoptotic response back to the normal level, suggesting that production of reactive oxygen species and calcineurin activation are not directly involved in the proapoptotic effect of HBx. In contrast, our data show that transactivation and stimulation of apoptosis are tightly linked HBx activities. Finally, expression of transactivation-active protein did not result in detectable change in the pattern of MAP kinases phosphorylation nor did it affect the ability of the host cell to repair in vitro irradiated plasmid DNA.

Apoptosis↗
PubMed1998

A match made in heaven? A pilot study of patient-therapist match.

The authors report on a study of patient-therapist match in 50 psychodynamic psychotherapy dyads. Sixty-six percent of patients and therapists agreed about the quality of the match, with 58% of patients and 56% of therapists reporting that the match was positive. Positive match correlated with positive patient and therapist assessments about the progress and process of therapy, but not with perceived similarity of personal characteristics. Patients' and therapists' perceptions about their similarities and differences from one another did not correlate. This study suggests it is both possible and important to gather data from both patient and therapist when studying match.

Adult↗
PubMed1996

Hepatoma-derived integrated HBV DNA causes multi-stage transformation in vitro.

The hepatoma-derived hepatitis B virus (HBV) DNA insert HU-a has recently been shown to contain two viral transactivator genes, X and preS2 /S. We report here that HU-a induces malignant transformation after stable transfection of the fetal mouse hepatocyte line FMH202, as indicated by soft agar growth and nude mouse tumorigenicity. Transfections with HU-a subclones, containing the X gene of the preS2 /S gene alone or sequences without transactivator gene, respectively, suggested that the X gene is essential for transformation. Sequential stages of transformation and tumor progression were analysed by injection of the stably transfected FMH202 lines into nude mice, explanation of the resulting tumors and re-establishment of cell lines from the tumors. Comparison of two HU-a-transformed cell lines by HBV mRNA hybridization, Southern analysis and chromosomal in situ hybridization revealed that integrated HBV DNAs were involved in major chromosomal rearrangements in both cases. Interestingly, recombination of the HBV Dna insert during the nude mouse passage had completely abolished HBV-specific transcription in one case, indicating that expression of integrated HBV genes, while presumably involved in early transformation, is dispensable at later stages of tumor progression. The sequential transformation observed in this experimental system suggests that expression of the X gene by integrated viral DNA and subsequent hepatocyte genome mutations might both contribute to HBV-associated liver carcinogenesis.

Animals↗
PubMed1996

The effects of electroconvulsive therapy on quantitative electroencephalograms. Relationship to clinical outcome.

BACKGROUND: The efficacy of electroconvulsive therapy (ECT) is determined by stimulus electrical intensity and electrode placement. Three theories offer different accounts for why increasing the stimulus dosage of right unilateral ECT enhances antidepressant effects. This study examined the effects of ECT on interictal quantitative electroencephalograms (EEGs), contrasting these theories in their predictions regarding global, lateralized, and topographic changes in ECT-induced slow-wave activity. The time course of EEG changes and associations with efficacy were also determined. METHODS: Sixty-two inpatients with major depressive disorder were randomized to ECT conditions that differed in stimulus intensity (low vs high dosage) and electrode placement (right unilateral vs bilateral). Resting, eyes closed, 19-lead EEG recordings were obtained at pretreatment, following a single treatment, following an average of 7 treatments, during the week following the ECT course, and after a 2-month follow-up period. RESULTS: Electroconvulsive therapy produced a marked short-term increase in delta and theta power. At a 2-month follow-up, there were no significant alterations in any frequency band. The ECT treatment conditions differed markedly in efficacy. Global and lateralized EEG effects did not distinguish effective and ineffective forms of treatment. Effective forms of ECT resulted in increased delta power in prefrontal regions, and this change was associated with the magnitude of symptomatic improvement. CONCLUSION: The induction of slow-wave activity in prefrontal cortex is linked to the efficacy of ECT.

Delta Rhythm↗
PubMed1996

The fate of training cases.

The authors regard the treatment of analytic patients as a crucial, formative and ultimately integrative experience in a candidate's development that has received remarkably little direct attention as an aspect of analytic education. From 1983 to 1992 a questionnaire was sent to all graduates of the Columbia University Psychoanalytic Center for Training and Research asking for information on training cases, both those terminated before graduation and those still ongoing at the time of graduation. The authors report data on pre-graduation candidate case experience, treatment duration of training cases, the impact of graduation on the course of analysis and on a global assessment of the outcome. 70 per cent of the 71 who graduated between 1983 and 1992 returned the questionnaire. The survey showed that before graduation the average candidate had a cumulative nine-year experience of treating training cases. 35 per cent of cases terminated before graduation and were invariably considered to have an unsuccessful outcome. Thus the 'failed case' was a common event and should be anticipated as part of a candidate's education. There was no evidence of precipitous termination of cases after graduation; in fact the data suggest that graduation has no discernible effect on the timing of termination. The vast majority of candidates at Columbia continue to be supervised after graduation, which suggests that graduation is only a marker in the training of an analyst, rather than the point of completion. With respect to outcome, 23 per cent of the 151 terminated cases were rated successful. Though this finding is consistent with previous reports, the methodological limitations of this study limit the confidence in this result. One of the important issues raised by these results is the impact of training requirements on the candidate's education and the Fate of Training Cases.

Clinical Competence↗
PubMed1994

Physical properties and quantification of the ECT stimulus: I. Basic principles.

The physical properties of the electroconvulsive therapy (ECT) stimulus markedly affect both efficacy and side effects. We review basic principles in characterizing these physical properties and in quantifying the ECT stimulus. The topics discussed include the application of Ohm's law, alternative composite units of ECT dosage (energy and charge), the use of constant-current, constant-voltage, and constant-energy principles in ECT devices, the nature of current shunting in ECT and the determinants of impedance, the relations between impedance and seizure threshold, the seizure-eliciting efficiency of alternative stimulus waveforms and of stimulus parameter configurations, and the role of reactive components (capacitance and inductance) in the ECT circuit. New findings are also presented regarding several of these issues.

Electric Impedance↗
PubMed1993

EEG manifestations during ECT: effects of electrode placement and stimulus intensity.

This study examined the ictal electroencephalographic (EEG) characteristics of four forms of electroconvulsive therapy (ECT) known to differ in efficacy. Previously, we demonstrated that titrated, low-dose right unilateral ECT reliably produces generalized seizures of adequate duration, but is remarkably weak in antidepressant effects. Using a new rating scale, we found that specific features of the ictal and immediate postictal EEG varied significantly with ECT stimulus intensity and electrode placement. The low-dose right unilateral condition differed from more effective forms of ECT in having the longest polyspike phase duration, averaging twice that of the other conditions; it was also the condition least likely to manifest bioelectric suppression immediately following seizure termination. In contrast, high-dose bilateral ECT--a treatment with particularly rapid antidepressant effects--resulted in the greatest peak slow-wave amplitude in both hemispheres. Total seizure duration did not differ among the four treatment conditions. These findings indicate that seizure duration is not a useful marker of therapeutic efficacy, and instead provide preliminary evidence that other features of the EEG may be more useful markers of treatment adequacy.

Adult↗
PubMed1993

Hepatitis B virus transactivator HBx uses a tumour promoter signalling pathway.

The hepatitis B virus (HBV) transactivator protein HBx is enigmatic in that it stimulates a striking variety of promoters which do not share a common cis-regulatory element. As it does not bind to DNA, it has been speculated that HBx acts indirectly through cellular pathways. Under certain conditions HBx can have an oncogenic potential, which may be relevant for HBV-associated liver carcinogenesis, but until now the mechanism for transactivation and cell transformation by HBx was unclear. We report here that HBx uses a complex signal transduction pathway for transactivation. An increase in the endogenous protein kinase C (PKC) activator sn-1,2-diacylglycerol and the subsequent activation of PKC give rise to activation of the transcription factor AP-1 (Jun-Fos). As a result, HBx transactivates through binding sites for AP-1 and other PKC-dependent transcription factors (AP-2, NF-kappa B), thereby explaining the as-yet incomprehensible variety of HBx-inducible genes. As the PKC signal cascade also mediates cell transformation by tumour-promoting agents, the mechanism presented here might account for the oncogenic potential of HBx.

Animals↗
PubMed1991

Multiple simian virus 40 enhancer elements mediate the trans-activating function of the X protein of hepatitis B virus.

Transient transfections of tissue culture cells with plasmids encoding the X protein of hepatitis B virus result in a transcriptional trans-activation of certain target genes. Our experiments reveal that several individual simian virus 40 enhancer elements and a control element present in the mouse major histocompatibility class I gene H-2Kb are able to mediate the trans-activating function of the X protein. The data suggest that known cellular transcription factors that bind specifically to the multiple enhancer elements participate in trans-activation.

Base Sequence↗
PubMedDate not supplied

The hepatitis B virus transactivator HBx causes elevation of diacylglycerol and activation of protein kinase C.

Chronic infection with hepatitis B virus (HBV) is accompanied by an increasing risk of developing hepatocellular carcinoma. There are indications that the HBx protein of HBV is involved in the process of tumour formation. HBx also transactivates several transcription factor binding sites. Recently, we reported that HBx can use a tumour promotor pathway for transactivation. In particular, we found that transactivation of the binding motif for transcription factor AP-1 (JUN/FOS) by HBx is dependent on functional protein kinase C (PKC), as indicated by abolition of the transcriptional stimulation following downregulation or inhibition of the enzyme. Moreover, HBx activates PKC, probably via increasing the endogenous PKC activator sn-1,2-diacylglycerol (DAG). Here we extend these data and report on the time course of PKC activation. We found that activation of PKC by HBx is transient and differs from activation of PKC by the ras oncogene product or phorbol ester in that it does not lead to rapid downregulation of the enzyme subsequent to the activation. Moreover, we provide evidence that an increase in cellular DAG is observable not only as an early event in response to HBx but also in cell lines transformed after transfection with HBV DNA and stably expressing HBx. Besides its important role in the regulation of cellular genes, PKC is also the intracellular receptor for tumour-promoting agents and an activator of proto-oncogenes, suggesting that our observations might provide an explanation for the oncogenic properties of HBx.

3T3 Cells↗