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Biomedical subjects

R Rubenstein

Publications and source records attributed to R Rubenstein.

At least 73 records · Page 4Linked to original sources
PubMed1986

Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains.

Scrapie-associated fibrils (SAFs) are abnormal filamentous structures that are uniquely associated with unconventional slow virus diseases. The antigenic relationships of SAFs from animals infected with four biologically distinct scrapie strains were investigated by using antisera raised to purified SAF proteins. Rabbit antisera were raised to SAFs isolated from mice infected with the ME7 scrapie strain and to SAFs isolated from hamsters infected with the 263K scrapie strain. A strong antigenic relationship was shown among SAF proteins (PrPs) isolated from all scrapie-infected animals (ME7, 139A, and 87V in mice and 263K in hamsters), and this relationship was demonstrable regardless of which antiserum was used. SAF proteins were antigenically distinct from those of paired helical filaments or amyloid isolated from patients with Alzheimer disease. Distinct Western blot profiles were demonstrated for SAFs isolated from animals infected with each scrapie strain. Differences seen among SAFs were independent, at least in part, of host species or genotype, implying that certain specific structural and molecular properties of SAFs are mediated by the strain of scrapie agent.

Alzheimer Disease↗
PubMed1985

Alteration of tyrosine hydroxylase activity in PC12 cells infected with herpes simplex virus type 1.

During infection with herpes simplex virus type 1 (HSV-1) the activity of tyrosine hydroxylase (TH) in PC12 pheochromocytoma cells was initially depressed reaching a nadir at 6 hours post-inoculation, but recovered rapidly with a return to baseline activity by 8 to 9 hours post-inoculation. Subsequently, TH activity again fell with a second more variable rise in activity occurring at 24 hours post-inoculation. Studies with metabolic inhibitors and 2 temperature-sensitive viral mutants indicated that these alterations of TH activity were dissociated from morphological cytopathology and likely required expression of "late" viral gene products. Immunotitration using anti-TH antibody suggested that early depression of TH activity resulted principally from loss of enzyme protein rather than simple enzyme inactivation, and that reconstitution of activity at 9 hours was related to augmented enzyme synthesis. These observations illustrate the complexity of perturbed cellular metabolism during HSV-1 infection and suggest involvement of two unexpected processes: alteration of a specialized cell function as a result of viral genes expressed late in the replicative cycle, and augmented synthesis of a cell-coded gene product during the course of infection.

Cells, Cultured↗
PubMed1985

Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents.

Scrapie-associated fibrils (SAF) were isolated and purified from animals infected with three different scrapie agents: ME7 and 139A in mice, and 263K in hamsters. Mouse ME7 and 139A SAF differed from hamster 263K SAF in morphology, sedimentation rate and protein composition. SAF from the three scrapie agents were distinguishable from each other by their sensitivity to proteinase K digestion. SAF copurified with infectivity in both the hamster and mouse systems. SAF appear to be a unique class of structures which are related but specific for each individual scrapie agent. These properties may correlate with the biological and pathological differences seen among these agents.

Animals↗
PubMed1985

Liposuction for lipomas.

Six cases of giant lipomas were treated by liposuction surgical removal. The method involves only a 1-cm incision and insertion of a liposuction cannula. The fibrous stroma of the lipoma may be more difficult to remove. Liposuction is a safe and easy method of removing giant lipomas.

Abdomen↗
PubMed1984

Psychosocial characteristics of candidates for the prospective evaluation of radial keratotomy (PERK) study.

The National Eye Institute Prospective Evaluation of Radial Keratotomy (PERK) Study is a multicenter clinical trial for the evaluation of radial keratotomy. This article describes the questionnaire data collected on PERK patients and compares them with a similar group of myopic persons studied during the Rand Health Insurance Experiment (heretofore referred to as the Rand study). The PERK patients are young, white myopes who dislike being dependent on corrective lenses but perceive themselves to be more visually impaired than do comparable Rand study myopes. Most female subjects and a plurality of the male subjects have tried contact lenses and quit wearing them mainly because use of the lenses was inconvenient or bothersome. There is no evidence that patients are psychologically or socially deviant. Both male and female subjects expressed a fear of being without vision and cited impatience with the lenses as their major motivation for wanting surgery.

Adolescent↗
PubMed1984

Diagnostic imaging of herpes simplex virus encephalitis using a radiolabeled antiviral drug: autoradiographic assessment in an animal model.

To develop a new approach to the diagnosis of herpes simplex encephalitis, we used a radiolabeled antiviral drug, 2'-fluoro-5-methyl-1-beta-D-arabinosyluracil labeled with carbon 14 ([14C]FMAU), as a probe for selectively imaging brain infection in a rat model by quantitative autoradiography. A high correlation was found between focal infection, as defined by immunoperoxidase viral antigen staining, and increased regional [14C]FMAU uptake in brain sections. Two potential sources of false-positive imaging were defined: high concentrations of drug in the choroid plexus because of its higher permeability compared with brain, and drug sequestration by proliferating uninfected cell populations. Our results support the soundness of the proposed strategy of using a labeled antiviral drug that is selectively phosphorylated by herpes simplex virus type 1 thymidine kinase in conjunction with scanning methods for human diagnosis, and also define some of the factors that must be taken into account when planning clinical application.

Animals↗
PubMed1984

In vitro replication of scrapie agent in a neuronal model: infection of PC12 cells.

A rat phaeochromocytoma cell line, termed PC12, was used to study scrapie replication. These cells, in response to the addition of nerve growth factor (NGF), exhibit a number of neuronal properties including morphological differentiation, electrophysiological responsiveness, and neurotransmitter synthesis. Cultures were exposed to scrapie brain homogenate (strain 139A), harvested every week for up to 6 weeks, and assayed for scrapie infectivity. Scrapie replication in vitro was monitored by injecting scrapie agent-exposed NGF-treated PC12 cells into mice and measuring time intervals from injection to onset of clinical symptoms. Mouse incubation periods vary inversely with the amount of scrapie infectivity present. Cells harvested at 7 and 14 days after exposure to scrapie agent showed a decrease in the level of infectivity followed by an increase at subsequent time points. The increase in scrapie infectivity from early to late time intervals after agent exposure clearly indicated replication in vitro. A fusion agent was not necessary to establish infection, and the addition of mouse peritoneal macrophages caused a reduction in the yield of infectivity per culture. Examination of cells by phase-contrast microscopy failed to reveal any cytopathology.

Animals↗
PubMed1984

Early inhibition of acetylcholinesterase and choline acetyltransferase activity in herpes simplex virus type 1 infection of PC12 cells.

Early in the course of productive Herpes simplex virus type 1 (HSV-1) infection of PC12 cells, activities of both acetylcholinesterase (AChE) and choline acetyltransferase (CAT) fell. Studies using metabolic inhibitors and a temperature-sensitive mutant of the virus suggested that the decline in activities of both enzymes was associated with events occurring early in the replicative cycle related to expression of the immediate-early (alpha) group of viral polypeptides. HSV-1 gene products thus may alter specialized cell functions well before the production of viral progeny and initiation of cell lysis. The early clinical manifestations of nervous system viral infection may reflect focal metabolic disturbance rather than, or in addition to, simple cell death.

Acetylcholinesterase↗
PubMed1984

Mild clinical course in two South African cases of sickle-cell anaemia.

Clinical, haematological and gene mapping data are presented on two South African cases of sickle-cell anaemia. Both individuals, who are siblings, have experienced a very mild clinical course. Restriction endonuclease analysis showed that 1 sibling was homozygous for alpha+-thalassaemia (genotype alpha-/alpha-), whereas the other had a full complement of alpha-globin genes. Both showed markedly elevated levels of Hb F. The maintenance of high levels of Hb F is the most probable explanation for the moderate clinical expression of the disorder in these patients.

Adult↗
PubMed1983

Replication of thymidine kinase deficient herpes simplex virus type 1 in neuronal cell culture: infection of the PC 12 cell.

Replication of a thymidine kinase deficient (TK-) mutant of herpes simplex virus type 1 (HSV-1) was compared to replication of its parental TK+ strain in the PC 12 cell. This is a cell which ceases cell division and undergoes neuron-like morphological and physiological differentiation in the presence of nerve growth factor (NGF). No difference between mutant and parental strain replication was detected either when these cells were infected in the proliferative state or while maintained under the influence of NGF. Neither viral TK nor enhanced cellular TK activity was detected during TK- HSV-1 replication, which proceeded in the presence of selective antiviral drugs that inhibited TK+ HSV-1 viral replication. Moreover, thymidylate synthetase was inhibited early in TK- infection, and reutilization of thymine nucleotides derived from degraded cellular DNA was not detected. Under the conditions of these in vitro studies, increased production of dTTP as a result of enhanced TK activity did not appear to be rate-limiting, despite the non-dividing "differentiated" state of the PC 12 cell.

Animals↗
PubMed1983

Lactic acidosis in severe asthma.

Twelve patients with severe asthma in whom lactic acidosis developed are presented. All had an arterial blood pH level lower than that expected for the measured partial pressure of arterial carbon dioxide, all had an abnormally large anion gap, and the blood lactate level exceeded 2.8 mmol/liter. Respiratory acidosis subsequently developed in eight patients, and six required intubation. Lactic acidosis can develop in patients with severe asthma. Such patients are in danger of the development of respiratory failure and must be treated vigorously and observed closely.

Acidosis↗
PubMed1983

Preservation of catecholamine uptake and release in herpes simplex virus type 1-infected PC12 cells.

The PC12 cell line, which is derived from a rat pheochromocytoma and possesses a number of 'differentiated' neuronal properties, was used to characterize the effect of herpes simplex virus type 1 (HSV-1) infection on the uptake and release of catecholamines. Both the uptake of [3H]norepinephrine and the content and K+-induced release of endogenous catecholamines were remarkably preserved during the course of productive infection. HSV-1 infection is thus selective in its effects on the host cell and certain specialized functional properties may be retained in the face of otherwise profound metabolic alterations.

Animals↗
PubMed1983

Flashbacks among soldiers discharged as unfit who abused more than one drug.

Of 280 soldiers discharged from military service in 1971 as unfit, 207 reported the heavy use of at least one drug (most of these abused more than one drug) and 146 (52%) reported having flashbacks. Most flashbacks were of a simple visual nature, but repeat "trips," complex subjective experiences, and persistent difficulties in concentration were often reported. The prevalence and severity of flashbacks increased with drug use, particularly with hallucinogens and marijuana. Because psychological, social, and physiological factors may all contribute to flashback phenomena, other populations need to be studied to determine the extent to which these findings can be generalized.

Adolescent↗
PubMed1982

Herpes simplex virus infection of isolated autonomic neurons in culture: viral replication and spread in a neuronal network.

Cultures of isolated neurons, derived from the superior cervical ganglion (SCG) of the newborn rat and maintained in the absence of nonneuronal cells, were infected with herpes simplex virus (HSV) type 1. By phase-contrast microscopy, including time-lapse cinematography, cytopathologic changes appeared first in neuronal cell bodies and only approximately 24 hours later were axonal abnormalities detectable. Despite low yields of viral progeny, infection spread readily within the two-dimensional network of neurons and their processes. Immunoperoxidase staining for viral antigens confirmed the replication and spread of virus and revealed that antigen extended along axons during infection. Antiviral antibody added to the overlay medium slowed but did not prevent the spread of infection, indicating that virus passed from neuron to neuron over axonal pathways. Despite alteration of neuronal macromolecular synthesis early in infection, axonal transport is apparently preserved long enough to allow propagation of virus over interconnecting neural pathways.

Animals↗
PubMed1982

Teaching the mental status examination: comparison of three methods.

The authors compared videotape and lecture methods of teaching the mental status examination to a second-year medical school class. The results of each teaching method were evaluated by a multiple-choice examination and a feedback questionnaire and were compared with the results from teaching the mental status examination using simulated patients in a previous year's class. There was no clear difference in examination results for students exposed to different instructional methods. On the feedback questionnaire, students appeared to prefer instruction in whatever form it was given. The authors discuss the significance of these findings.

Clinical Competence↗
PubMed1981

Tyrosine hydroxylase activity in the superior cervical ganglion during herpes simplex virus infection: correlation with viral titers and viral antigen.

The activity of tyrosine hydroxylase (TH) was measured in the superior cervical ganglion (SCG) of the mouse during herpes simplex virus (HSV) infection. TH activity remained at control levels or actually increased during acute infection at a time when viral titers of SCG homogenates were at their peak and viral antigen was detected in from one-third to one-half of ganglionic neurons. A rapid decline in TH activity followed and coincided with falling viral titers, disappearance of viral antigen and replacement of neurons by inflammatory cells. Immunization partially prevented this reduction of TH activity. In addition, when mice were immunosuppressed by cyclophosphamide, TH activity was relatively preserved early in the course of infection despite high viral titers in the ganglion and the presence of viral antigen and histopathological alterations in nearly 100% of neurons. These results suggest that a cellular 'luxury function', in this case TH activity, can be preserved and perhaps even augmented during neuronal HSV infection. Indeed, activity of this enzyme may persist until late into the acute phase of infection, perhaps up to the point of cell death induced either by immune-mediated or direct virus-induced cell lysis.

Animals↗
PubMed1980

Effects of cortisone on decrease of serum albumin secondary to experimental infections.

The observation that severe clinical bacterial infections are associated with decreases in total serum albumin levels was confirmed in experiments involving dogs and rats. In rodents, the injection of methylprednisolone sodium succinate after the onst of the infection significantly reduced the decrease in the serum albumin values. However, this protective or corrective effect did not occur if the steroid was given prior to the infection. The effect of cortisone may be due to its capacity to stimulate albumin synthesis by the parenchyma of the liver.

Animals↗