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Biomedical subjects

R N Rosenberg

Publications and source records attributed to R N Rosenberg.

At least 19 recordsLinked to original sources

Morphological differentiation and proteoglycan synthesis regulate Alzheimer amyloid precursor protein processing in PC-12 and human astrocyte cultures.

A morphologically differentiated strain of rat pheochromocytoma (PC-12H) metabolically labeled with [35S]methionine and incubated with a phorbol ester displayed reduced 140-kDa and increased 15 kDa bands relative to cells incubated without phorbol ester after immunoprecipitation with antisera elicited by the C-terminal peptide of the Alzheimer amyloid precursor protein (APP). These bands correspond to glycosylated full length APP and a C-terminal fragment previously reported by Anderson et al. (Neurosci. Lett. 120:126-128, 1991) to result from a cleavage within the amyloidotic A4 region of APP, which releases a 120 kDa extracellular fragment. The 15 kDa fragment, not immunoprecipitated with an antisera elicited by the N-terminal portion of A4 amyloid, is nonamyloidogenic. Incubation of these cells with p-nitrophenylxyloside, known to inhibit proteoglycan formation, also increased this nonamyloidogenic cleavage of APP. In contrast to these results, an undifferentiated low passage PC-12-L strain constitutively displayed rapid nonamyloidogenic APP cleavage. Incubation of PC-12-L with phorbol ester did not affect the relative abundance of 140 or 15 kDa bands. Growth of PC-12-L with 7 S NGF or dibutyryl cAMP resulted in increased morphological differentiation and decreased APP cleavage which was now phorbol-inducible. Similar analyses of dividing and senescent human astrocytes and normal and F-AD fibroblasts indicate 5-fold lower rates of mid-A4 APP cleavage. Phorbol esters decreased the 140 kDa APP band without affecting the intensity of the 15 kDa band in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid beta-Protein Precursor

Phosphorus 31 NMR of neuroblastoma clonal lines. Effect of cell confluency state and dibutyryl cyclic AMP.

Phosphorus nuclear magnetic resonance is used to study changes in the levels of the major phosphate-containing intermediary metabolites concomitant with induced cellular differentiation in the N-18 and C-46 neuroblastoma clonal lines. The study reveals differences between the 31P-NMR profiles of the two clonal lines and also striking differences attendant to dibutyryl cAMP-mediated morphological differentiation in the N-18 clone. Phosphorus-31 NMR would appear to provide a new technique with which to study genetic differentiation.

Animals

Inverse relationship of the velocities of perceived time and information processing events in the brain: a potential bioassay for neural functions: a hypothesis.

The velocity of elapsing time is not a constant but a relativistic component in the space-time continuum as postulated by Albert Einstein in his general and special relativity theories. The hypothesis presented here is that there is a biological corollary to relativity theory. It is postulated that biological time perception is also not a constant but is related by an inverse relationship between the velocities of neural processing events and perceived elapsing time. A careful analysis of this relationship may potentially offer a sensitive bioassay to determine the integrity of regional brain function under normal conditions and in the presence of specific disease processes. The mechanism for the biological basis of this theorem depends on the presence of a neural circuit developed through evolution which monitors overall brain efficiency and is coordinately linked to neural time perceiving circuits. Several test approaches are presented to validate the hypothesis of biologic time relativity compared to the rate of neural processing.

Adult

Joseph disease: protein patterns in fibroblasts and brain.

The separation of brain and fibroblast proteins was analyzed on two-dimensional acrylamide gels. Proteins were examined from skin fibroblast cultures and brain homogenates from the frontal cerebral cortex, putamen, and cerebellum. Protein species from skin fibroblast cultures of controls and patients with Joseph disease or Huntington disease were not significantly different. The proteins from homogenates of the cerebral cortex, putamen, and cerebellum from controls differed from those of one Joseph disease patient. Two major classes of proteins were increased in the patient's putamen and cerebellum. Proteins of 40,000 and 50,000 daltons--including the glial filamentous acidic protein complex (molecular weight 50,000), and two proteins which migrated near actin--were increased in the cerebellum. The glial filamentous acidic protein complex increased 3.7-fold in the putamen of the patient. These protein changes probably represent gliosis, but may also be an expression of the primary genetic mutation.

Brain Diseases

Induction of cyclic AMP-binding proteins by dibutyryl cyclic AMP in mouse neuroblastoma cells.

Mouse neuroblastoma cells grown in the presence of 1 mM N6,O2'-dibutyryl-cyclic AMP showed a 3-fold increase in cyclic AMP-binding proteins. The role of dibutyryl cyclic AMP in the introduction of cyclic AMP-binding proteins in these cells has been studied. Induced cyclic AMP-binding proteins were observed in the cytoplasm 15 h after dibutyryl cyclic AMP treatment. The increase in cyclic AMP-binding proteins required RNA and protein synthesis. It is suggested that the 15-h lag occurs at the post-transcriptional and/or translational level. Cyclic AMP-binding proteins are found in both soluble and particulate cell fractions. Dibutyryl cyclic AMP increased binding proteins in both fractions. The control and dibutyryl cyclic AMP-induced binding proteins showed similar affinity for cyclic AMP. The data indicate that dibutyryl cyclic AMP caused the following sequential events: a 12-fold increase in cyclic AMP levels; a 40% increase in phosphodiesterase activity; and a 300% (3-fold) increase in cyclic AMP-binding proteins. It is suggested that the differentiation of mouse neuroblastoma cells involves increased levels of cyclic AMP and cyclic AMP-binding proteins.

3',5'-Cyclic-AMP Phosphodiesterases

Thermolability in Wernicke's encephalopathy.

A patient with signs of Wernicke's disease had low body temperature and showed thermolability when challenged with cold and heat. This man expressed no feelings of thermal discomfort about his persistently low core temperature or about induced changes in his core temperature. He also showed abnormalities in his febrile response to pyrogen and in his circadian temperature rhythm. Treatment with thiamine hydrochloride resulted in substantial improvement in these thermoregulatory deficits.

Alcoholism

Creatine kinase BB isoenzyme levels by radioimmunoassay in patients with neurological disease.

Creatine kinase BB (CK-BB) isoenzyme was measured by radioimmunoassay in serum and in cerebrospinal fluid from 61 patients with various neurological disorders. Statistically significant elevations of CK-BB isoenzyme in the serum were observed in patients with acute cerebrovascular accidents and in those with seizures and a prolonged alteration in level of consciousness. Statistically significant elevations of CK-BB isoenzyme in the cerebrospinal fluid were also found in patients who had suffered acute cerebrovascular accidents. Some patients with central nervous system infections, acute demyelinating disease, certain drug overdoses, head trauma, and complex migraine also had elevations of serum and CSF CK-BB isoenzyme. In 2 patients with elevations of CK-BB isoenzyme, the elevations in serum occurred later than those detected in the cerebrospinal fluid. If CK-BB elevations determined by radioimmunoassay can be demonstrated to be quantitatively related to the extent of brain damage, then these determinations in conjunction with experimental animal models and newer radiological techniques should allow evaluation, in an objective and precise manner, of measures designed to decrease that damage.

Brain Damage, Chronic

Effect of dopamine agonist (Lergotrile mesylate) therapy on twenty-four hour secretion of prolactin in treated Parkinson's disease.

Plasma PRL was measured at 20-min intervals in six patients with Parkinson's disease under various treatment protocols. In addition, 24-h mean GH levels were measured. The results of these studies showed that two untreated patients with Parkinson's disease had normal 24-h mean PRL levels with the normal increase during sleep. During chronic treatment with L-dopa-carbidopa (Sinemet), the 24-h PRL level was 12.8 +/- 4.9 ng/ml (mean +/- SD) and there was persistence of augmented PRL secretion during sleep. The 24-h mean GH level ranged from 1.5-4.4 ng/ml, with a mean of 2.5 ng/ml. The addition of a dopamine agonist (Lergotrile mesylate) resulted in a significant (P less than 0.01) suppression of the 24-h mean PRL levels and abolition of the normal sleep augmentation after 2 weeks of therapy. This suppression was maintained in one patient who was restudied 4 months after the addition of dopamine agonist therapy to L-dopa-carbidopa. The 24-h mean GH levels did not change significantly after the addition of the dopamine agonist when compared to L-dopa-carbidopa alone. These results suggest a dichotomy between the PRL and GH responses to combined L-dopa-carbidopa and dopamine agonist therapy. In addition, the preservation of normal PRL regulation in the two untreated patients with Parkinson's disease suggests that dopaminergic neurons are not universally affected in this disorder.

Adult

Serum antibodies to cytomegalovirus in myasthenia gravis: effects of thymectomy and steroids.

The etiology of the immunologic abnormalities in myasthenia gravis (MG) remains unknown. Evidence for persistent viral infection was sought by determining serum antibody titers to several enveloped RNA and DNA viruses. Compared to healthy controls matched for age, sex, geography and socioeconomic status, patients with MG were more likely to have elevated titers of complement-fixing antibody to cytomegalovirus (CMV). Patients with MG not treated with thymectomy or steroids had elevated CMV titers, whereas thymectomized or steroid-treated patients did not; the differences were statistically significant (p less than 0.01). These results are consistent with the hypothesis that there is persistent viral antigenic stimulation in the myasthenic thymus, arising from viral protein incorporation into epithelioid-myoid cell surface membranes and subsequent induction of an antibody to these acetylcholine receptor (AChR)-bearing thymic cells. This antibody then cross-reacts with AChR at the neuromuscular junction.

Adult