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R D Rudelli

Publications and source records attributed to R D Rudelli.

15 recordsLinked to original sources
PubMed1992

Nearly ubiquitous tissue distribution of the scrapie agent precursor protein.

The "modified host protein" model of scrapie proposes that the transmissible agent is composed of the degradation-resistant protein, Sp33-37, and that clinical and pathologic signs result from neurotoxic accumulations of this protein. Sp33-37 is an abnormal, amyloidogenic isoform of the normally occurring cellular protein Cp33-37. This study investigated the tissue distribution of Cp33-37 in hamster. In brain, Cp33-37 was most concentrated in the hippocampal formation. Immunohistochemical studies localized Cp33-37 to neurons and surrounding neuropil in hippocampus; septal, caudate, and thalamic nuclei; dorsal root ganglia cells; and large-diameter dorsal root axons. In non-neuronal hamster tissues, Cp33-37 was detected in circulating leukocytes, heart, skeletal muscle, lung, intestinal tract, spleen, testis, ovary, and some other organs. The presence of Cp33-37 in extracerebral tissues indicates that its function is not unique to brain. These results indicate that the molecular substrate for the production of Sp33-37, the scrapie agent, and scrapie amyloid is present in a variety of cerebral and extracerebral sites.

Animals↗
PubMed1991

Analysis of neocortex in three males with the fragile X syndrome.

Fragile X [fraX] syndrome is a common hereditary disorder associated with a fragile site marker at Xq27.3 which clinically presents as a form of mental retardation (MR). Postmortem investigation of 3 fraX positive males with mild to moderate MR did not document any gross neuropathological changes. Golgi analysis of neocortical dendritic spine morphology extended our previous observations of immature, long, tortuous spines in one adult case of fraX (Rudelli, et al., Acta Neuropathologica 67:289-295, 1985) to 2 new cases. Evidence for similar dendritic spine abnormalities was found, although Golgi analysis was less than optimal because of incomplete dendritic stain impregnation. Neocortical intra-layer cell density was also investigated in all 3 cases. Cresyl violet stained neurons were counted in 10 randomly selected fields in neocortical layers II-VI of cingulate and temporal association areas (Brodmann's areas 23 and 38). Neuron counts in fraX and control neocortex showed no significant differences. Thus, abnormal dendritic spine morphology with preservation of neuronal density appears to characterize the neocortex in individuals with this common form of mental retardation.

Adolescent↗
PubMed1991

Alterations in the immune system in cats fed diets with excess cystine.

As part of an ongoing biochemical study in nutrition we examined blood profiles, serum chemistry, lymphocyte transformation and lymphoid pathology in cats fed a diet containing 5% cystine with and without taurine. Automated blood counts of whole blood samples showed a decrease in red blood cell counts accompanied by a significant decrease in hemoglobin and hematocrit in cats fed 5% cystine in the absence of taurine compared to cats fed 0.05% taurine (control). A significant increase was noted in serum cholesterol in cats fed cystine and cystine/taurine compared to cats fed control diets. There were no significant differences in lymphocyte transformation using leukocytes isolated from the spleen and blood with the mitogens, phytohemagglutinin and pokeweed. However, lymphocyte transformation of both spleen and blood without mitogen from the excess cystine group were significantly higher than leukocytes from the 0.05% taurine group (control). Pathological examination of regional lymph nodes, livers, and spleens showed histological abnormalities in cats fed the excess cystine diet. These results indicate that there are alterations in the immune system of cats fed a diet containing 5% cystine with and without dietary taurine.

Animals↗
PubMed1991

Copurification of Sp33-37 and scrapie agent from hamster brain prior to detectable histopathology and clinical disease.

Studies were conducted to determine whether accumulation of the scrapie agent protein Sp33-37 in brain correlated with the appearance of the scrapie agent or with pathology. The concentrations of the scrapie agent and Sp33-37 were measured in purified fraction P5 isolated from hamster brains at weekly intervals after inoculation. The scrapie agent concentration in fraction P5 was approximately 10(-1) LD50/g brain 1 day post-inoculation and increased to 10(9.4) LD50/g at day 77. Sp33-37 was first detected in P5 at day 21, when the agent titre was 10(3.9) LD50/g. Sp33-37 concentration increased in concert with the scrapie agent concentration, although the apparent rate of increase was somewhat lower for the protein than for the agent. The histopathological evidence of disease, consisting of mild vacuolation and gliosis, was first seen at 35 days, but was not conspicuous until 49 to 56 days post-inoculation. Vacuolation and gliosis increased until termination of the experiment at day 77. Amyloid plaques were first detected at 56 days and were widespread at day 77. Clinical disease was first seen in these animals at day 66, with an average onset at day 71. Control animals inoculated with buffer alone showed some mild gliosis, but were otherwise normal. The fact that Sp33-37 purified with the scrapie agent isolated from brain 14 days prior to detectable (light microscopic) pathology supports the theory that Sp33-37 is the major structural component of the scrapie agent and not solely a product of the pathology.

Animals↗
PubMed1990

The mRNA encoding the scrapie agent protein is present in a variety of non-neuronal cells.

PrP 27-30, a unique protease-resistant protein associated with scrapie infectivity, derives from the proteolytic cleavage of a larger precursor encoded by a host gene. To identify sites of PrP biosynthesis, in situ hybridization was done using cloned PrP cDNA as a probe. In rodent brain, PrP mRNA was expressed in neurons, ependymal cells, choroid plexus epithelium, astrocytes, pericytes, endothelial cells and meninges of both scrapie-infected and uninfected animals. PrP mRNA was also detected in vitro in isolated brain microglia cells. Pulmonary cells and heart muscle cells contained high levels of this mRNA. Hybridization was not detected in spleen, confirming earlier RNA blot experiments indicating extremely low levels of PrP mRNA in this tissue. Results indicate that PrP mRNA is a normal component in a variety of non-neuronal tissues and may explain the origin of the amyloid plaques present in the subependymal region of scrapie-infected brain.

Animals↗
PubMed1989

Postmortem detection of measles virus in non-neural tissues in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis, a rare, progressive, fatal central nervous system disease of children, is caused by measles virus. Clinical signs occur months to several years after recovery from acute measles infection. It is not known where the virus persists while the disease is inapparent. Involvement of organs outside the central nervous system has rarely been documented. To search for possible peripheral reservoirs of measles virus we used in situ hybridization to probe for measles virus RNA and immunocytochemical studies to localize measles virus antigens ina variety of organs taken at autopsy from confirmed cases of subacute sclerosing panencephalitis. Seven of 9 cadavers were found to contain measles virus RNA or antigens, or both, in at least one location outside the central nervous system. These sites included lymphoid organs such as thymus, spleen, lymph nodes, and tonsil, suggesting a role for lymphocytes in disease pathogenesis. Virus was also detected in kidney, lung, and glandular tissues such as pancreas, adrenal, and pituitary. These reservoirs may provide the antigenic stimulus leading to the elevated response characteristic for subacute sclerosing panencephalitis.

Adolescent↗
PubMed1989

Chromosomal abnormalities in amniotic fluid cell cultures: a comparison of apparent pseudomosaicism in Chang and RPMI-1640 media.

The finding of chromosome mosaicism is one of the most difficult problems in fetal chromosome analysis. Whether the finding indicates true mosaicism or pseudomosaicism must be investigated. Studies detailing the incidence of true mosaicism and pseudomosaicism have been reported (Hsu & Perlis 1984, Bui et al. 1984, Worton & Stern 1984) but do not correlate pseudomosaicism with any particular type of culture media. Benn & Hsu (1985) compared cell growth and chromosome abnormalities in amniotic fluid cell cultures grown in Chang medium and RPMI-1640 medium and found no statistically significant difference in the rate of abnormalities in the two media. We have previously shown that Chang medium exhibited more abnormalities which were not verified in second and third cultures (Masia et al. 1986). In the current study we examined 212 cases grown in both Chang and RPMI-1640 media, and compared apparent single and multiple cell pseudomosaic abnormalities to medium type. The number of observed abnormalities was 22, occurring in 19 of the cases studied. Apparent pseudomosaic chromosome anomalies were observed in 18 Chang cultures and in 4 RPMI-1640 cultures. Statistical analysis found significant correlation between medium type and the degree of observed pseudomosaic cells. We conclude that the rate at which pseudomosaic cells are observed is partly a function of medium type, and in our laboratory Chang medium caused apparent pseudomosaicism at a greater level than RPMI-1640 medium.

Amniotic Fluid↗
PubMed1985

Adult fragile X syndrome. Clinico-neuropathologic findings.

Fragile X syndrome [fra (X)] is currently accepted as the second most frequent chromosomal disorder associated with developmental disability. Although next to Down syndrome in frequency, no postmortem studies of confirmed adult cases had been reported. The autopsy examination of a 62-year-old, moderately retarded man with the fra (X) syndrome confirmed the preferential involvement of cerebral and testicular structures in this disorder. Dendritic spine abnormalities of the type observed in trisomic chromosomal disorders were associated with synaptic immaturity. Severe testicular hypogonadism accompanied bilateral macro-orchidism, normal penis, and unilateral hydrocele. Valvular, articular, and testicular interstitial compartments showed normal histochemical staining characteristics for glycoproteins and lipids.

Brain↗
PubMedDate not supplied

Fragile X syndrome: neuropathology center.

There is an acute need for additional neuropathological information in the fra(X) or Martin-Bell syndrome. We propose a centralized fra(X) neuropathological research center to promote research and understanding of the underlying neuropathologic changes. Brain specimens can be sent to our center for neuropathological analysis. Reports will be sent to the contributing health professionals. Clinicians and relatives are encouraged to request autopsies and to contact the Center regarding brain donations for purposes of research and understanding.

Academies and Institutes↗
PubMedDate not supplied

The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities.

We have evaluated 62 fragile X syndrome [fra(X)] individuals (55 males and 7 females) with different degrees of developmental disabilities that were clinically non-progressive and non-focal in character. The mean age for the 55 males was 23.1 years +/- 14.3 SD with a range of 2-70: for the 7 females, the mean age was 15.7 years +/- 3.5 SD with a range of 10-20 years. Mental retardation (MR) was found in 53 males (8/53 [15.1%] mild, 26/53 [49.1%] moderate, 14/53 [26.4%] severe, and 5/53 [9.4%] profound). Learning disabilities were found in 2/55 (3.6%) of males. One of the 7 females had mild and one had moderate MR: the other 5 were learning disabled. Autistic stigmata were present in 10/62 (16%) of the patients. Only 14/62 (23%) had a history of seizures, all of which were controlled with anticonvulsants. In 36/62 cases, an electroencephalogram (EEG) was performed. We compared these data with that of others. Brain stem auditory evoked response (BAER) was performed in 12 cases. Abnormalities were found in only 5/12. Neuroimaging and computerized cranial transaxial tomography (CT scan) were performed on 21/62 (34%) of the patients. Only 8 of these 21 (38%) studies were abnormal. One patient died; neuropathological studies showed mild brain atrophy, with light microscopic and ultrastructural abnormalities. Rapid Golgi dendritic spine patterns showed that the proximal apical segments were abnormally developed. Very thin, long tortuous spines with prominent terminal heads and irregular dilatations were present. Marked reductions in the length of the synapses, as determined on EPTA-postfixed tissue where noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Brain morphology in the Galloway syndrome.

The Galloway syndrome is a rare autosomal recessive disease consisting of congenital microencephaly associated with congenital nephrotic syndrome, and in some cases with hiatus hernia [Galloway and Mowatt, 1968]. The case presented is that of a microencephalic infant with the nephrotic syndrome who died at 11 3/4 months after a course characterized by convulsions, developmental delay, hypotonia and hyperreflexia. Brain weight was 270 g. The frontal, parietal, and rostral temporal cortex was pachygyric. Microscopically there was lack of cortical stratification, immature cortical neurons, improper orientation of cortical neurons (seen in the Golgi stained sections), and glioneuronal ectopias in the leptomeninges. There was hypomyelination in the brain stem and spinal cord, and no myelin in the hemispheres. There was also complete absence of the internal granular layer of the cerebellum. The dentate gyrus within the hippocampal formation was absent and the inferior olivary nuclei were hypoplastic. The mechanism of neuronal migration abnormalities and the significance of associated nephrosis is discussed.

Brain↗