Neurofibrillary tangles in Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is an autosomal recessive disease, belonging to a clinically heterogeneous group of lipid storage diseases, distinguished by a unique error in cellular trafficking of exogenous cholesterol, associated with lysosomal accumulation of unesterified cholesterol. Unlike Niemann-Pick disease types A and B, there is no primary genetic defect in sphingomyelinase in NPC. During the routine neuropathological study of NPC patients, we found neurofibrillary tangles (NFT) in a series of cases with a slowly progressive chronic course.

Neuropathology of mice with targeted disruption of Hexa gene, a model of Tay-Sachs disease.

A murine model of Tay-Sachs disease, the prototype of the GM2 gangliosidoses, was produced through the targeted disruption of the Hexa gene encoding the subunit of alpha-hexosaminidase A. The mice were completely devoid of beta-hexosaminidase A activity and accumulated GM2 ganglioside in the CNS in an age-dependent manner. Neurons with membranous cytoplasmic bodies (MCBs), identical to those described in Tay-Sachs disease, were identified in the brain of these mice.

Novel electrophoretic protocol for collection of mutations in the lambda light chain immunoglobulin gene in a human B-lymphoblastoid cell strain.

Spontaneous and chemically induced mutation was examined in the lambda light chain immunoglobulin gene in a human B-lymphoblastoid cell strain (T5-1). The hemizygous lambda gene is a unique mutational target gene which codes for a protein that is both expressed on the cell membrane and secreted. Mutations in the lambda gene were detected by analysis of western blots of isoelectric focusing gel electrophoresis of T5-1 cell conditioned culture medium.

Peripheral nerve pathology in Niemann-Pick type C mouse.

The sciatic nerve of the mouse mutant with Niemann-Pick type C disease (NPC mouse) was investigated using light and electron microscopy, and teased-fiber preparations. As early as postnatal day 20, when clinical symptoms were not yet apparent, focal paranodal swellings with an accumulation of small myelin figures in the Schwann cell cytoplasm were noted. These paranodal changes were more pronounced in the distal segment and became progressively conspicuous with increasing age.

Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption.

With the aim of establishing whether a genetically reduced capability of producing apolipoprotein E (apo E) can affect atherogenesis, we have compared the consequences of dietary stress on normal mice and on mice heterozygous or homozygous for a disrupted apo E gene. A dramatically accelerated development of lesions occurred in the vasculature of the homozygous mutants as a result of feeding an atherogenic diet for 12 wk, and extensive deposition of lipid-filled macrophages was found outside the cardiovascular system. In nine heterozygotes fed the atherogenic diet for 12 wk, the amount of apo E in their total plasma lipoproteins increased to a level comparable to normal, but all nine developed much larger foam cell lesions in their proximal aorta than those found in 3 of 9 normal mice fed the same diet.

Parallel evolutionary events in the haptoglobin gene clusters of rhesus monkey and human.

Parallel occurrences of evolutionary events in the haptoglobin gene clusters of rhesus monkeys and humans were studied. We found six different haplotypes among 11 individuals from two rhesus monkey families. The six haplotypes include two types of haptoglobin gene clusters: one type with a single gene and the other with two genes.

Human alveolar macrophage-56 and carcinoembryonic antigen monoclonal antibodies in the differential diagnosis between primary ovarian and metastatic gastrointestinal carcinomas.

The immunohistochemical expression and localization of monoclonal antibodies to carcinoembryonic antigen (CEA) and human alveolar macrophage (HAM-56) were evaluated in primary ovarian and metastatic gastrointestinal (GI) carcinomas. Immunohistochemistry was performed using an avidin-biotin-peroxidase complex method with capillary gap technology on formalin-fixed, paraffin-embedded tissues from 41 primary ovarian epithelial neoplasms, 17 metastatic gastrointestinal malignancies, and 10 tumors of uncertain primary origin. Overall, immunostaining for HAM-56 was positive in 35 (85%) ovarian epithelial neoplasms compared with only two (12%) gastrointestinal cancers.

DNA contents and chromosomes of clonal lines of transformed rat liver epithelial cells and of cells from their derived tumors.

Clonal lines of transformed rat liver epithelial cells, derived from a single population of cloned diploid rat liver epithelial (stem-like) cell line (WB-F344) by exposure in vitro to N-methyl-N'-nitro-N- nitrosoguanidine (MNNG), produce hepatocellular carcinomas, hepatoblastomas and adenocarcinomas in syngeneic rats (Tsao and Grisham, Am. J. Pathol.

Mutagenicity of butadiene and its epoxide metabolites: II. Mutational spectra of butadiene, 1,2-epoxybutene and diepoxybutane at the hprt locus in splenic T cells from exposed B6C3F1 mice.

The mutagenic potential and mutational spectra of butadiene (BD), 1,2-epoxybutene (EB), and diepoxybutane (DEB) were determined in splenic T cells from exposed B6C3F1 mice. Mice exposed by inhalation to 625 p.p.

Mutagenicity of butadiene and its epoxide metabolites: I. Mutagenic potential of 1,2-epoxybutene, 1,2,3,4-diepoxybutane and 3,4-epoxy-1,2-butanediol in cultured human lymphoblasts.

The mutagenic potential of the epoxide metabolites of butadiene (BD) was measured at the tk and hprt loci in TK6 human lymphoblastoid cells. TK6 cells were exposed for 24 h to 0-400 microM 1,2-epoxybutene (EB), 0-800 microM 3,4-epoxy-1,2-butanediol (EBD), or 0-6 microM 1,2,3,4-diepoxybutane (DEB). Treated cells were allowed to grow for several days and then seeded in medium containing either 6-thioguanine or trifluorothymidine to select for hprt- or tk-/- mutants, respectively.

Progressive dysfunction of twitcher Schwann cells is evaluated better in vitro than in vivo.

The twitcher mutant (twi/twi) is an authentic murine model of globoid cell leukodystrophy, a genetic demyelinating disorder, where normally formed myelin degenerates due to a metabolic perturbation of myelin forming cells. We investigated the rate of Schwann cell proliferation in vivo and in vitro using thymidine autoradiography to evaluate cellular function of homozygous twitcher (twi/twi), and heterozygous (+/twi) and normal littermate (+/+) mice. At day 10 prior to onset of demyelination in twi/twi, the thymidine uptake by Schwann cells from sciatic nerves was similar regardless of genotype.

Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression.

Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age.

In vitro interactions of endometrial stromal and epithelial cells in Matrigel: reorganization of the extracellular matrix.

Fragments of human endometrial glands and dispersed endometrial stromal cells were cultured together in a thick layer of reconstituted basement membrane (Matrigel). Epithelial cells kept their glandular morphology whereas stromal cells grew into round clusters of mainly fusiform cells. Transmission electron micrographs showed collagen fibers between stromal cells as well as in surrounding extracellular matrix after 2.

Spacio-temporal progression of demyelination in twitcher mouse: with clinico-pathological correlation.

The twitcher (twi/twi) is an authentic murine model of human globoid cell leukodystrophy (GLD), caused by a deficiency of galactosylceramidase. Similar to human GLD, the twitcher shows progressive deterioration of neurological function and its neuropathology is characterized by a collection of periodic acid-Schift stain (PAS)-positive macrophages in the areas of demyelination. However, there are some differences in the clinico-pathological aspects between human and murine GLD.