Showing papers by "John Q. Trojanowski published in 1992"

Modified avidin-biotin technique

Abstract: A method for preparing an antigen specific probe is provided by incubating a primary antigen specific monoclonal antibody with a biotinylated secondary antibody to produce a complex of the primary and secondary antibodies. The staining pattern produced by these probes reflects the specificity of the monoclonal antibody in the complex and the labeling of irrelevant, endogenous immunoglobulins is reduced substantially. This novel, indirect immunohistochemical method can be used to study normal and diseased tissues using a variety of monoclonal antibodies.

Medulloblastomas and related primitive neuroectodermal brain tumors of childhood recapitulate molecular milestones in the maturation of neuroblasts.

Abstract: We review here recent data that have brought into sharper focus a number of important biological properties of the neoplastic cells in childhood primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS). Studies of this group of tumors, as exemplified by posterior fossa medulloblastomas (MBs), suggest that neoplastic cells in PNETs partially recapitulate stages in the maturation of normal human neuroblasts. These findings may contribute to the elucidation of the mechanisms involved in tumor initiation and progression because oncogenes and antioncogenes appear to exert their effects in a cell type-specific manner that also depends on the maturational state of a given cell. Currently, a large body of data suggests that populations of cells in PNETs (e.g., MBs) exhibit one or more molecular stem cells or partially committed neuron-like precursors from the cell cycle, followed by their terminal differentiation into neurons. This, together with the orchestrated interactions of as yet unidentified oncogenes and antioncogenes in these PNET cells, may represent a cluster of molecular abnormalities that underly the emergence of the highly malignant phenotype that characterizes childhood PNETs.

Phosphorylated high molecular weight neurofilament protein in the peripheral motor, sensory and sympathetic neuronal perikarya: system-dependent normal variations and changes in amyotrophic lateral sclerosis and multiple system atrophy.

Abstract: Using monoclonal antibody (Ta-51) that specifically binds phosphorylated high molecular weight neurofilament (pNFH) proteins, we investigated the occurrence of perikaryal pNFH in the spinal ventral horn motoneurons, intermediolateral column (ILC) neurons, sympathetic ganglion neurons and dorsal root ganglion (DRG) neurons obtained from patients with amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) and from control cases. In the controls, a system-dependent variation in perikaryal Ta-51 immunoreactivity was observed. Very few ventral horn cells and ILC neurons were stained with Ta-51, while large population of DRG neurons and sympathetic neurons were Ta-51 positive. The incidence of perikaryal immunoreactivity in the ventral horn cells was significantly increased in ALS and MSA. Some ILC neurons in ALS were Ta-51 positive and their incidence was significantly higher than that of the controls. These data suggest that both ILC neurons and ventral horn cells are affected with respect to pNFH metabolism in ALS and MSA. No significant difference was, however, detected in the Ta-51 immunoreactivity of both DRG and sympathetic ganglion neurons in ALS and MSA as compared with the controls.

Epitope analysis of senile plaque components in the hippocampus of patients with Parkinson's disease.

Abstract: We conducted an epitope analysis of senile plaque (SP) proteins on hippocampal SPs in patients with Parkinson9s disease (PD), using a library of antibodies to proteins implicated in the genesis of hippocampal SPs in Alzheimer9s disease (AD). The library included antibodies to the β-amyloid protein (β-AP), domains outside the β-AP in β-amyloid precursor proteins (β-APPs), ubiquitin, diverse neuronal cytoskeletal proteins, and polypeptides located mainly in axon terminals. We obtained samples of hippocampus at autopsy from 14 PD patients, 10 of whom were demented. As in the AD hippocampus, the SPs detected by conventional stains in five of the 10 demented subjects contained the β-AP and flanking domains in β-APPs as well as epitopes in T, neurofilament proteins, and synaptophysin. Further, with the exception of the β-AP, epitopes in the other proteins were confined to the coronas of SPs, while clathrin light chain, microtubule-associated protein 5, and neural cell adhesion molecules were almost undetectable or absent in the neuropil occupied by SPs. The same group of antibodies rarely labeled SPs in the other five demented PD subjects or in the four nondemented PD subjects, and conventional stains for amyloid and neurofibrillary pathology revealed rare SPs in these cases. Hence, when conventional stains reveal lesions diagnostic of AD in PD patients, the molecular features of the hippocampal SPs in these patients are the same as those in SPs of the AD hippocampus.

A novel modification of the avidin-biotin complex method for immunohistochemical studies of transgenic mice with murine monoclonal antibodies.

Abstract: When mouse tissues are probed with murine monoclonal antibodies (MAb) by indirect immunohistochemistry, the secondary antibody detects tissue-bound MAb and irrelevant, endogenous mouse immunoglobulins. The latter are a source of confounding background, especially in diseased tissues. To circumvent this problem, we generated complexes of primary MAb and biotinylated secondary antibodies in vitro for use as antigen-specific probes. After blocking free binding sites in the complexed secondary antibodies with normal mouse serum, the complexes were applied to mouse tissue sections and tissue-bound complexes were visualized with an avidin-biotin detection system. Complexes formed with 12 different rat or mouse MAb were used to probe sections of normal mice, tumor-bearing transgenic mice, and mice with tumor xenografts. The staining patterns produced by these probes reflected the specificity of the MAb in the complexes, and the labeling of irrelevant, endogenous mouse immunoglobulins was reduced substantially. This novel, indirect immunohistochemical method can be exploited to study normal and diseased mouse tissues using a variety of murine MAb.

Autopsy: cutting away the myths.

Abstract: Autopsy serves to monitor quality of care, determines means of death in puzzling medical situations and medicolegal cases, documents true disease rates and provides other essential data for registries and research. This article discusses the current status of autopsy, reasons for the declining rate, and myths commonly held by patients and their families. The neuroscience nurse can clarify misperceptions, provide accurate and timely information in a sensitive and articulate manner, and support patients and their families in their decisions about autopsy.