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Biomedical subjects

R F Marsh

Publications and source records attributed to R F Marsh.

At least 55 records · Page 3Linked to original sources
PubMed1983

Neural pathogenesis of experimental scrapie after intraocular inoculation of hamsters.

Hamsters were inoculated intravitreally with the scrapie agent. All animals developed scrapie and retinal degeneration typical of scrapie. The retinal degeneration was greater in the inoculated eyes than in the uninoculated eyes. Replication of the scrapie agent was rapid in the inoculated eye. Infectivity then spread slowly down the ipsilateral optic nerve to the brain. The replication in the brain paralleled that in the retina of the uninoculated eye. The results support a neural spread of scrapie.

Animals↗
PubMed1982

Retinal degeneration during clinical scrapie encephalopathy in hamsters.

Weanling hamsters were inoculated intracerebrally with brain suspensions from normal or scrapie-infected hamsters. A third group of uninoculated animal was fed cuprizone. Histologic and electron microscopic examination of the neural retinas and retinal pigment epithelium was done. At 50 days postinoculation, when scrapie-infected animals began to show clinical signs of encephalopathy, there was a variable degree of photoreceptor degeneration. By the time animals were moribund, at 74 days postinoculation, photoreceptor degeneration was severe, as demonstrated by loss of most outer and inner segments and cell bodies. The outer plexiform, inner nuclear, and inner plexiform layers were reduced in thickness. Some retinal pigment epithelial cells contained lipoidal inclusions. The neural retinas and retinal pigment epithelium of noninfected and cuprizone-treated animals were normal. We have previously shown that the scrapie agent accumulates in the retina; that together with our present work, we conclude that the scrapie agent is the cause of photoreceptor degeneration in experimentally inoculated hamsters.

Animals↗
PubMed1982

Photoreceptor degeneration preceding clinical scrapie encephalopathy in hamsters.

Hamsters experimentally inoculated with scrapie had histologic and ultrastructural changes in their retinas before clinical signs of central nervous system disease became evident at 50 days postinoculation. The retinal changes were limited to the photoreceptors and began with degenerative changes in the inner segments as early as 8 days postinoculation. As the inner segment lesions became more prominent, associated degenerative changes within outer segments were seen (38 days postinoculation). An influx of macrophages was associated with increasing degenerative changes; these cells engulfed cellular debris did not appear to contribute directly to the degenerative process. Retinas having the greatest damage to the inner segment area also had moderate reduction in outer nuclear layer density and outer segment length, and in numbers of outer segments. All of the retinal changes described occurred almost exclusively in the central to mid-region of retina with relative sparing of peripheral retina.

Animals↗
PubMed1981

Tyrosine aminotransferase deficiency in mink (Mustela vision): a model for human tyrosinemia II.

Mink pseudodistemper, a recessive disease associated with high blood tyrosine levels, is an animal analogue of the human inborn error of metabolism, tyrosinemia II. Affected mink and man have eye and skin lesions. Affected mink have no hepatic tyrosine aminotransferase (TAT) activity, as measured immunologically and biochemically. Hepatic mitochondrial aspartate aminotransferase is increased to 188% of control. This new genetic animal model of TAT deficiency should allow new studies of tyrosine metabolism.

Amino Acid Metabolism, Inborn Errors↗
PubMed1980

Replication of the scrapie agent in ocular neural tissues.

Optic nerves and retinas removed from hamsters experimentally inoculated with the scrapie agent contain a high titer of infectivity. Ophthalmoscopic examination of these animals revealed gross lesions of retinopathy as early as 3 weeks before the onset of clinical signs of brain degeneration. These results suggest that the scrapie agent may spread centrifugally in nerve fibers after intracerebral inoculation and that the scrapie-associated retinopathy seen in hamsters is directly induced by the agent rather than the result of retrograde degeneration from central neural damage.

Animals↗
PubMed1978

Membrane-free scrapie activity.

Determinations of scrapie activity in subcellular fractions from infected hamster brains through the asymptomatic and symptomatic course of infection revealed the presence of substantial amounts of scrapie infectivity in the 100,000 X g supernatant fractions, indicating that association with physically discernible membrane structures is not necessary for the transmission of the scrapie agent. An increase of scrapie infectivity in the 100,000 X g supernatant fractions after vigorous homogenization of infected membrane-rich fractions suggests that the agent is identical in membrane-rich and 100,000 X g supernatant fractions.

Animals↗
PubMed1977

Ocular effects of scrapie agent in hamsters: preliminary observations.

Scrapie is caused by one of a group of so-called slow viruses responsible for the subacute spongiform encephalopathies. In the present study, young hamsters were inoculated intracerebrally with hamster-adapted scrapie agent. At termination, all inoculated animals showed signs and central nervous system pathology compatible with scrapie infection. The eyes appeared well developed grossly, but histologically the retina and optic nerve were abnormal. There were varying degrees of thinning of the retina, with the photoreceptor layer being most severely affected. Although the ganglion cell layer was not much different from the controls, the optic nerve appeared more cellular than that of the controls.

Animals↗
PubMed1976

Properties of the scrapie agent-endomembrane complex from hamster brain.

Subcellular fractionation of scrapie-infected hamster brain indicated the association of the scrapie agent with a component of the endomembrane system. Characterization by equilibrium density gradient centrifugation, electron microscopy, and marker enzymes suggested a primary association with rough and smooth endoplasmic reticulum and a possible incorporation into the plasma membrane. DNA polymerase activity demonstrated a direct correlation with regions of scrapie activity from the gradient fractions. A scrapie-related product was detected after (3H)TMP incorporation and analysis on 2.2% polyacrylamide gels. Analysis of nucleic acid species extracted from subcellular fractions resulted in a greater quantity from healthy brain; however, no qualitative distinctions were detected.

Adenosine Triphosphatases↗
PubMed1976

Transmissible mink encephalopathy. Reduced spongiform degeneration in aged mink of the Chediak-Higashi genotype.

Mink which are 18 months or older and are dying of transmissible mink encephalopathy (TME) have been found to have a marked reduction in spongiform degeneration of the brain if they are homozygous for the Aleutian gene and thus exhibit the autosomal recessive disorder known as the Chediak Higashi (CH) syndrome. CH mink younger than 1 year, and young or old non-CH mink have a typical lesion profile with widespread microvacuolation of the neuropile. Whereas aged CH mink have reduced spongiform degeneration at both the light and electron microscopic level, there is no other apparent alteration in the TME disease process. The length of incubation, clinical signs, astrocytic response, and brain concentration of the TME agent are comparable to those seen in non-CH mink. We conclude that spongiform degeneration is a secondary change in TME and speculate that vacuolation may be the result of lysosomal enzymes causing an increase in ganglioside catabolism.

Age Factors↗
PubMed1975

Transmissible mink encephalopathy: infectivity of corneal epithelium.

Corneal epithelium from hamsters dying of transmissible mink encephalopathy contained a virus titer of 10-4.8 times the 50 percent lethal dose (10-4.8 LD50) per 0.05 milliliter when assayed as a cell suspension derived directly from the infected animal. After one passage in tissue culture, an equivalent concentration of cells contained only 10-0.8 LD50 per 0.05 milliliter.. It is concluded that corneal tissues are infectious; the infectivity may be mainly associated with free nerve endings. However, the most important immediate inference is that corneas from human beings affected with Creuzfeldt-Jakob disease are likely to be lethal if transplanted to healthy recipients.

Animals↗
PubMed1975

Comparison of scrapie and transmissible mink encephalopathy in hamsters. II. Clinical signs, pathology, and pathogenesis.

Scrapie and transmissible mink encephalopathy were studied in hamsters; clinical signs, pathology, and the replication of the agents of each disease in brain and spleen were compared. The most noticeable clinical sign in scrapie-affected hamsters was a distinct cerebellar ataxia beginning 16 weeks after inoculation. Ataxia was not prominent in animals affected with transmissible mink encephalopathy; these animals gradually became more and more lethargic. The pathology in the central nervous system in both diseases consisted of astrocytic hypertrophy, microvacuolation of the neuropil, and neuronal degeneration. The scrapie agent appeared to have a greater effect on nuclear masses, especially those present in brain stem and the central white matter of the cerebellum. The earliest lesions in both diseases were detected near pia arachnoid surfaces and adjacent to the ventricular system. These initial sites of involvement suggest that the cerebrospinal fluid may be an important route by which inocula are disseminated to susceptible cells after intracerebral inoculation. Both agents multiplied rapidly in brain, reaching titers greater than 10-8 ld-50/0.05 ml before the onset of clinical signs. Titers in spleen were 4-6 logs lower than titers in brain at every point measured during the asymptomatic or clinical course of disease.

Animals↗
PubMed1975

Comparison of scrapie and transmissible mink encephalopathy in hamsters. I. Biochemical studies of brain during development of disease.

A series of 15 different biochemical measurements were made on brains taken at stages throughout the development of scrapie and of transmissible mink encephalopathy in hamsters. With both diseases biochemical abnormalities were found only after the development of early histologic lesions, when animals showed clinical signs of disease. Changes were recorded in body weight, in the activities of six glycosidases, and the rates of incorporation of DNA and of glycoprotein precursors. The profiles of changes in hamster brain were almost indistinguishable,qualitatively and quantitatively, in the two diseases, an observation suggesting a close similarity in the way both disease-producing agents interact with this particular host species, . However, there were some major differences between the profile of changes in hamster scrapie and that previously observed in mouse scrapie. Thus it would appear that many of the well-characterized abnormalities of mouse scrapie are not fundamentally involved in the development of disease but represent mainly secondary changes.

Animals↗