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Tih-Shih W Lee

Publications and source records attributed to Tih-Shih W Lee.

5 recordsLinked to original sources
PubMed2006

Increased expression of phosphate-activated glutaminase in hippocampal neurons in human mesial temporal lobe epilepsy.

Patients with mesial temporal lobe epilepsy (MTLE) have increased basal concentrations of extracellular glutamate in the epileptogenic versus the non-epileptogenic hippocampus. Such elevated glutamate levels have been proposed to underlie the initiation and maintenance of recurrent seizures, and a key question is what causes the elevation of glutamate in MTLE. Here, we explore the possibility that neurons in the hippocampal formation contain higher levels of the glutamate synthesizing enzyme phosphate-activated glutaminase (PAG) in patients with MTLE versus patients with other forms of temporal lobe epilepsy (non-MTLE). Increased PAG immunoreactivity was recorded in subpopulations of surviving neurons in the MTLE hippocampal formation, particularly in CA1 and CA3 and in the polymorphic layer of the dentate gyrus. Immunogold analysis revealed that PAG was concentrated in mitochondria. Double-labeling experiments indicated a positive correlation between the mitochondrial contents of PAG protein and glutamate, as well as between PAG enzyme activity and PAG protein as determined by Western blots. These data suggest that the antibodies recognize an enzymatically active pool of PAG. Western blots and enzyme activity assays of hippocampal homogenates revealed no change in PAG between MTLE and non-MTLE, despite a greatly (>50%) reduced number of neurons in the MTLE hippocampal formation compared to non-MTLE. Thus, the MTLE hippocampal formation contains an increased concentration and activity of PAG per neuron compared to non-MTLE. This increase suggests an enhanced capacity for glutamate synthesis-a finding that might contribute to the disrupted glutamate homeostasis in MTLE.

Adolescent↗
PubMed2005

Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus.

An abnormal accumulation of extracellular K+ in the brain has been implicated in the generation of seizures in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis. Experimental studies have shown that clearance of extracellular K+ is compromised by removal of the perivascular pool of the water channel aquaporin 4 (AQP4), suggesting that an efficient clearance of K+ depends on a concomitant water flux through astrocyte membranes. Therefore, we hypothesized that loss of perivascular AQP4 might be involved in the pathogenesis of MTLE. Whereas Western blot analysis showed an overall increase in AQP4 levels in MTLE compared with non-MTLE hippocampi, quantitative ImmunoGold electron microscopy revealed that the density of AQP4 along the perivascular membrane domain of astrocytes was reduced by 44% in area CA1 of MTLE vs. non-MTLE hippocampi. There was no difference in the density of AQP4 on the astrocyte membrane facing the neuropil. Because anchoring of AQP4 to the perivascular astrocyte endfoot membrane depends on the dystrophin complex, the localization of the 71-kDa brain-specific isoform of dystrophin was assessed by immunohistochemistry. In non-MTLE hippocampus, dystrophin was preferentially localized near blood vessels. However, in the MTLE hippocampus, the perivascular dystrophin was absent in sclerotic areas, suggesting that the loss of perivascular AQP4 is secondary to a disruption of the dystrophin complex. We postulate that the loss of perivascular AQP4 in MTLE is likely to result in a perturbed flux of water through astrocytes leading to an impaired buffering of extracellular K+ and an increased propensity for seizures.

Adolescent↗
PubMed2005

Psychodynamic perspectives of collaborative treatment.

In contemporary psychiatric practice, collaborative treatment between a psychiatrist and psychotherapist is very common. Much attention has been devoted to the fiscal, ethical, and legal issues relevant to this treatment modality. However, such collaboration had been proposed long before the advent of managed care, which has accelerated the trend to separate the dynamic and the biologic. While fiscal considerations have been highlighted of late, the underlying tension between the dynamic and biologic remains and with it the complexity and potential pitfalls that directly and indirectly affect patient care. These issues are often neglected or kept in the realm of the unconscious. The key issues of transference, countertransference, and dynamic issues related to medication are discussed from the perspectives of the psychiatrist, the therapist, and the patient. In this article, the authors review the literature in order to revisit and reframe psychodynamic issues, as a timely reminder for clinicians to look at patients in different frameworks, and as a means of enhancing the effectiveness of collaborative treatment.

Countertransference↗