Increased levels of 5-HT1A receptor binding in ventral visual pathways in Parkinson's disease.

Visual hallucinations are common in advanced Parkinson's disease (PD). The pathophysiology of visual hallucinations may involve enhanced serotonergic neurotransmission. The atypical antipsychotics clozapine and quetiapine, which have affinity for 5-HT(2A) and 5-HT(1A) receptors, are effective against visual hallucinations in PD.

Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations.

Well-formed visual hallucinations (VH) are common in patients with Parkinson's disease (PD). The pathophysiology of VH in PD is unknown but may involve structures mediating visual processing such as the inferior temporal cortex. Serotonergic type 2A (5-HT(2A)) receptors have been linked to many psychiatric disorders, including psychosis.

Cell partitioning during the directional solidification of trehalose solutions.

Previous studies have demonstrated that ice/cell interaction influences post thaw viability and specific cryoprotective agents can affect those interactions. Trehalose, a disaccharide, has been shown to have a protective benefit during conventional slow freezing. Existing theories have been put forth to explain the protective benefit of trehalose during desiccation and vitrification, but these theories do not explain the protective benefit observed during conventional freezing protocols.

Postthaw viability of precultured hepatocytes.

Hepatocytes are being studied for a wide variety of applications, including drug metabolism studies, gene therapy, and use in liver-assist devices for temporary liver support. The ability to cryopreserve isolated hepatocytes would permit the pooling of cells to reach the required therapeutic coordination of the cell supply with patient care regimes and the completion of safety and quality-control testing. The objective of this investigation was to develop a method of cryopreserving isolated hepatocytes that will retain high levels of function and facilitate the use of the cells in different applications.

Influence of preculture on the prefreeze and postthaw characteristics of hepatocytes.

Recent studies performed in our laboratory have shown that a brief period of preculture prior to cryopreservation improves the postthaw viability of hepatocytes. The purpose of this investigation is to characterize specific metabolic and biochemical characteristics of the hepatocytes (both frozen and nonfrozen) to help elucidate the role of preculture on the postthaw viability. Fresh and thawed hepatocytes were cultured in a bioartificial liver (BAL) to determine albumin secretion as a function of time in culture.

Freezing characteristics of genetically modified lymphocytes for the treatment of MPS II.

The freezing characteristics of genetically modified lymphocytes obtained from a donor with mucopolysaccharidosis type II (MPS II) were determined using cryomicroscopy and controlled rate freezing studies to determine postthaw viability. The cells from a donor with MPS II used in this investigation were cultured and transduced with a retroviral vector for the iduronate-2-sulfatase (IDS) enzyme for clinical studies for human gene therapy. The water transport and intracellular ice formation (IIF) characteristics of the cells were determined after completion of the culture and transduction protocol.

Subzero osmotic characteristics of intact and disaggregated hepatocyte spheroids.

This study has been conducted to examine basic transport characteristics of pig hepatocytes cultured as spheroids for use in a bioartificial liver. Static osmotic experiments were conducted by subjecting hepatocyte spheroids in solutions of increasing sucrose concentrations. A Boyle-van't Hoff plot was used to extrapolate an osmotically inactive volume, V(b), of 0.

Cryobiophysical characteristics of genetically modified hematopoietic progenitor cells.

The freezing responses of hematopoietic progenitor cells isolated from normal donors and from donors with mucopolysaccharidosis type I (MPS I) were determined using cryomicroscopy and analyzed using theoretical models for water transport and intracellular ice formation. The cells from donors with MPS I used in this investigation were cultured and transduced with a retroviral vector for the alpha-l-iduronidase (IDUA) enzyme in preclinical studies for human gene therapy. The water transport and intracellular ice formation (IIF) characteristics were determined at different time points in the culture and transduction process for hematopoietic progenitor cells expressing CD34 antigen from donors with MPS I and from normal donors.

Freezing characteristics of isolated pig and human hepatocytes.

The cellular response of isolated hepatocytes from pigs, humans, and human hepatoblastoma cells to freezing was characterized using cryomicroscopy and analyzed using a thermodynamic model for water transport and Intracellular Ice Formation (IIF). The value for the reference permeability, Lpg, was found to be 5.8(10)-13, 1.