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Biomedical subjects

R A Brumback

Publications and source records attributed to R A Brumback.

171 records · Page 10Linked to original sources
PubMedDate not supplied

Alzheimer disease fibroblasts are hypersensitive to the lethal effects of a DNA-damaging chemical.

A group of fibroblast lines from three patients with the sporadic form of Alzheimer disease (AD) showed a small but statistically significant hypersensitivity to the lethal effects of the DNA-damaging chemical N-methyl-N'-nitro-nitrosoguanidine (MNNG) when compared with lines from eight normal control subjects. A fibroblast line from a patient with a dominantly inherited form of familial AD had a hypersensitivity similar to that of the three sporadic AD lines. However, fibroblast lines from a group of five patients with spinal muscular atrophy (SMA) were not hypersensitive to the chemical, demonstrating that not every primary neuronal degeneration manifests hypersensitivity to this chemical. These findings are consistent with the possibility that a defect in DNA-repair mechanisms may be the cause of the in vitro hypersensitivity, as well as the premature death of neurons in vivo, in both the sporadic and familial forms of AD.

Alzheimer Disease↗
PubMedDate not supplied

Comparative effects of long-term ethanol consumption and forebrain lesions on maze learning and active avoidance behavior in rats.

Male rats consumed a liquid diet containing 10.7% ethanol as their only source of food and fluid for 6.5 months, beginning at 2 months of age. During withdrawal, there were no differences between the alcohol group and their pair-fed or free-fed controls on EEG, body temperature, irritability and tremor measures. In behavioral tests begun 4-5 weeks after withdrawal, the rats that had consumed alcohol acquired accurate spatial behavior in a cross maze task more slowly than controls, but were unimpaired in shuttle-avoidance learning. In concurrent studies with groups of rats that had sustained lesions of the dorsal hippocampus, the mamillary bodies (MMB), or the mediodorsal thalamus, the pattern of behavioral deficits after MMB lesions was found to be qualitatively similar to that observed after the cessation of long-term alcohol consumption. These findings provide renewed hope that a useful rodent model for studying the neuropsychology of cognitive deficits associated with human alcoholism can be developed.

Alcoholism↗
PubMedDate not supplied

Life-long overexpression of S100beta in Down's syndrome: implications for Alzheimer pathogenesis.

Chronic overexpression of the neurite growth-promoting factor S100beta has been implicated in the pathogenesis of neuritic plaques in Alzheimer's disease. Such plaques are virtually universal in middle-aged Down's syndrome, making Down's a natural model of Alzheimer's disease. We determined numbers of astrocytes overexpressing S100beta, and of neurons overexpressing beta-amyloid precursor protein (beta-APP), and assayed for neurofibrillary tangles in neocortex of 20 Down's syndrome patients (17 weeks gestation to 68 years). Compared to controls, there were twice as many S100beta-immunoreactive (S100beta+) astrocytes in Down's patients at all ages: fetal, young, and adult (p = 0.01, or better, in each age group). These were activated (i.e., enlarged), and intensely immunoreactive, even in the fetal group. There were no neurofibrillary changes in fetal or young Down's patients. The numbers of S100beta+ astrocytes in young and adult Down's patients correlated with the numbers of neurons overexpressing beta-APP (p < 0.05). Our findings are consistent with the idea that conditions--including Down's syndrome--that promote chronic overexpression of S100beta may confer increased risk for later development of Alzheimer's disease.

Adult↗
PubMedDate not supplied

Cerebral degenerations producing dementia: importance of neuropathologic confirmation of clinical diagnoses.

Dementia is a major public health concern with our increasing elderly population and currently affects more than three million Americans at an annual cost of $50 billion. The marked overlap in symptomatology between Alzheimer's disease and other primary parenchymal degenerations makes antemortem diagnosis based on clinical assessment tentative at best, with error rates of 25% commonly reported. Accurate diagnosis is of vital importance in order to improve our understanding of these illnesses, evaluate potential therapies, and provide appropriate genetic counseling to family members. Direct neuropathologic examination at autopsy is currently the only reliable method for assuring accurate diagnosis, and should be undertaken in all demented patients. To illustrate the importance of these principles, we present three patients who were clinically diagnosed with Alzheimer's disease, and subsequently found to have other dementing illnesses by careful postmortem neuropathologic examination.

Adult↗
PubMedDate not supplied

Adult-onset xeroderma pigmentosum neurological disease--observations in an autopsy case.

Xeroderma pigmentosum (XP) is an inherited disease with defective DNA repair. Patients develop skin cancer because of unrepaired DNA damage produced by the ultraviolet radiation (UV) in sunlight. Many XP children also develop XP neurological disease (ND), consisting of sensorineural hearing loss (SNHL) and a primary neuronal degeneration of the central and peripheral nervous systems. Since the harmful UV in sunlight cannot reach the nervous system, the cause of the death of XP neurons has been hypothesized to result from the inability to repair their DNA that has been damaged by endogenous metabolites. Progressive XP ND originating in an adult has been identified in only a single case. Although clinically asymptomatic at the age of 47 years, the patient had audiometric evidence of a developing mild SNHL together with elicited signs and electrophysiologic evidence of a peripheral neuropathy. She died of metastatic endocervical adenocarcinoma at 49 years of age. We describe here the neuropathological findings in this patient, including examination of the inner ear. Despite clinical evidence of SNHL, there were no anatomic abnormalities of the inner ear. However, the dorsal root ganglia (DRG) showed ongoing neuronal loss. Our findings indicate that XP ND originating in this adult is, like XP ND in children, a primary neuronal degeneration that manifests first in the peripheral nervous system.

Age of Onset↗
PubMedDate not supplied

Perineurial cell ensheathement of muscle fibers: a new syndrome of fatigable muscle weakness mimicking myasthenia gravis.

Many newly discovered pathological and physiological variants of neuromuscular junction function have been identified. We report a case of a myasthenia gravis-like syndrome with onset of ptosis at age six years and eventual evaluation for peripheral weakness twenty years later. Subsequent muscle biopsy showed a previously unreported finding of perineurial cell ensheathement of the muscle fibers. We suggest that the ensheathement of the muscle cells by perineurial cells may alter the microenvironment interfering with neuromuscular transmission.

Adult↗
PubMedDate not supplied

Agenesis of cerebellum associated with arrhinencephaly.

Complete cerebellar agenesis or aplasia is an extremely rare condition with few previously reported cases. We identified a 38-week gestation infant with microcephaly who had complete cerebellar agenesis associated with arrhinecephaly. There was complete lack of the efferent and afferent limbs of the cerebellum, including the nuclei of the basis pontis, the inferior olivary nuclei, ascending spinal and medullary afferents, deep cerebellar nuclei and their afferents, and the red nucleus. Although complete cerebellar agenesis is rare, cerebellar hypoplasia is more common and can be sporadic, asymmetric, or represent clinically, genetically, and pathologically diverse examples of primary cerebellar or vermian hypoplasia.

Cerebellum↗