Biomedical subjects

R H Takahashi

Publications and source records attributed to R H Takahashi.

6 recordsLinked to original sources

PubMed2002

Alzheimer beta-amyloid peptides: normal and abnormal localization.

Alzheimer's disease (AD) neuropathology is characterized by accumulation of "senile" plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are principally composed of aggregates of up to 42/43 amino acid beta-amyloid (A beta) peptides. The discovery of familial AD (FAD) mutations in the genes for the amyloid precursor protein (APP) and presenilins (PSs), all of which increase A beta42 production, support the view that A beta is centrally involved in the pathogenesis of AD. A beta42 aggregates readily, and is thought to seed the formation of fibrils, which then act as templates for plaque formation. A beta is generated by the sequential intracellular cleavage of APP by beta-secretase to generate the N-terminal end of A beta, and intramembranous cleavage by gamma-secretase to generate the C-terminal end. Cell biological studies have demonstrated that A beta is generated in the ER, Golgi, and endosomal/lysosomal system. A central question involving the role of A beta in AD concerns how A beta causes disease and whether it is extracellular A beta deposition and/or intracellular A beta accumulation that initiates the disease process. The most prevalent view is that SPs are composed of extracellular deposits of secreted A beta and that A beta causes toxicity to surrounding neurons as extracellular SP. The recent emphasis on the intracellular biology of APP and A beta has led some investigators to consider the possibility that intraneuronal A beta may directly cause toxicity. In this review we will outline current knowledge of the localization of both intracellular and extracellular A beta.

Alzheimer Disease↗

PubMed2001

Recent advances in the MOBJ algorithm for training artificial neural networks.

This paper presents a new scheme for training MLPs which employs a relaxation method for multi-objective optimization. The algorithm works by obtaining a reduced set of solutions, from which the one with the best generalization is selected. This approach allows balancing between the training error and norm of network weight vectors, which are the two objective functions of the multi-objective optimization problem. The method is applied to classification and regression problems and compared with Weight Decay (WD), Support Vector Machines (SVMs) and standard Backpropagation (BP). It is shown that the systematic procedure for training proposed results on good generalization neural models, and outperforms traditional methods.

Algorithms↗

PubMed2000

Monoclonal antibodies against topoisomerase I suppressed DNA relaxation and HIV-1 cDNA synthesis.

Human immunodeficiency virus type 1 (HIV-1) virion is known to carry a number of cellular components including cellular topoisomerase I. Previously, we have demonstrated that topoisomerase I enhances HIV-1 cDNA synthesis in reverse transcription (RT) assays in vitro. In the present study, we have produced six monoclonal antibodies (MAbs) against human topoisomerase I. The MAbs suppressed nicking/closing of supercoiled DNA and cDNA synthesis in an endogenous reverse transcription (ERT) assay using a detergent-disrupted HIV-1 virion. Thus, the results suggest that topoisomerase I plays an important role in RNA-directed DNA polymerization.

Animals↗

PubMed1999

Analysis of human lymphotropic T-cell virus type II-like particle production by recombinant baculovirus-infected insect cells.

The molecular processes involved in retrovirus assembly and budding formation remain poorly understood. The gag-pro-pol genes of human lymphotropic T-cell virus type II (HTLV-II) are translated into Gag, Gag-Pro, or Gag-Pro-Pol by frameshift events. In the present study, we investigated the roles of the gag, pro, and pol regions of HTLV-II in viral particle formation using recombinant baculoviruses. In this study we could successfully produce mature HTLV-II viral particles containing core structures using a construct expressing the entire gag-pro-pol region. We also investigated the role of the pol region in particle formation. Deletion of the pol region affects viral particle assembly or release very little, indicating that the gag-pro region is sufficient for viral particle formation and maturation. Expression of the Gag proteins alone or Gag proteins with inactivated viral proteases (Pro) resulted in the formation of viral particles; however, these particles did not contain core structures. These results suggest the intracellular expression of Gag with Pro of HTLV-II is essential for the production of mature virus particles, whereas that of Pol is not.

Animals↗

PubMed1999

Increased levels of epsilon and gamma isoforms of 14-3-3 proteins in cerebrospinal fluid in patients with Creutzfeldt-Jakob disease.

We established four hybridoma cell lines producing monoclonal antibodies (MAbs) against 14-3-3 proteins. Immunoblot analysis revealed that epsilon and gamma isoforms were specifically increased in premortem cerebrospinal fluid samples from patients with sporadic Creutzfeldt-Jakob disease. Furthermore, dot immunoblot analysis showed that MAbs were more specific for native antigen than polyclonal antibodies were.

14-3-3 Proteins↗

PubMed1999

Characterization of antibodies raised against bovine-PrP-peptides.

To analyze the antigenicity of peptides derived from bovine prion protein (PrP) cDNA, we immunized rabbits with four synthetic peptides and compared the immunoreactivity of antibodies to PrPs from various species by immunoblotting and immunohistochemistry. Two of the antibodies reacted strongly with all PrPs. The other antibodies, raised against overlapping peptides close to two glycosylation sites, did not recognize PrPSc-mouse but did recognize PrPSc-sheep which contains two sugar residues and PrPCJD with or without a sugar residue. Our results suggest that these antibodies may have species-specificity for both glycosylation status and amino acid sequences of the protein. In conclusion, we identified two regions in bovine-PrP which appear suitable for raising antibodies that detect various kinds of PrPs, and one region (Ab103-121) which appears suitable for raising antibodies that detect several species of PrPs. These antibodies may be useful for diagnosing prion diseases and for researching their pathogenesis.

Amino Acid Sequence↗