Search PubMed⌕ Search

Biomedical subjects

M B Rosenberg

Publications and source records attributed to M B Rosenberg.

At least 19 recordsLinked to original sources
PubMed1995

Resuscitation of the pediatric patient.

Fortunately, the incidence of pediatric cardiopulmonary arrest is extremely low in the outpatient dental office setting. Because most cardiopulmonary arrests in children result from a progressive deterioration in respiratory function, outcome critically depends on rapid diagnosis and evaluation of the adequacy of ventilation and the pediatric airway. This holds true for any pediatric medical emergency. Our goal must be instituting simple resuscitative measures before full cardiopulmonary arrest develops. Whatever the nature of the medical emergency, caring for a child under these circumstances is challenging. Pediatric Advanced Life Support (PALS) and continual review of the American Heart Association guidelines should be considered by those specializing in the treatment of infants and children. This training will not only bolster practitioner confidence, but enable prompt, effective response for any pediatric medical emergency.

Ambulatory Care↗
PubMed1992

Effects of choline and quiescence on Drosophila choline acetyltransferase expression and acetylcholine production by transduced rat fibroblasts.

Rat-1 fibroblasts were transduced to express Drosophila choline acetyltransferase. The presence of an active enzyme in these cells (Rat-1/dChAT) was confirmed using various methods. Rat-1/dChAT fibroblasts released acetylcholine (ACh) into the culture medium. Moreover, intra- and extracellular levels of ACh could be increased by adding exogenous choline chloride. In addition, serum starvation or confluence-induced quiescence caused an 80% decrease in recombinant choline acetyltransferase activity (compared with actively growing cells). ACh release was also repressed in quiescent fibroblast cultures. Exogenous choline could mitigate the decrease in ACh release. These results indicate that Rat-1 fibroblasts can be genetically modified to produce ACh and that ACh release can be controlled by introducing choline into the culture medium. Furthermore, these data demonstrate that the expression of the retroviral promoter used in this study decreases with the onset of quiescence; however, exogenous choline can increase the amount of ACh released by quiescent fibroblasts.

Acetylcarnitine↗
PubMed1992

Somatic gene transfer of nerve growth factor promotes the survival of axotomized septal neurons and the regeneration of their axons in adult rats.

Intracerebral grafts consisting of primary fibroblasts genetically engineered to express NGF were used to assess the regenerative capacity of cholinergic neurons of the adult rat septum. Our data reveal that NGF-producing grafts sustain a significantly higher proportion of NGF receptor-immunoreactive septal neurons following axotomy (approximately 65-75%) than do grafts of noninfected fibroblasts. In addition, NGF promotes the regeneration of septal axons. Following the ablation of cholinergic septal projections to the hippocampus, NGF-producing grafts placed within the lesion cavity contain large numbers of AChE-positive axons; control grafts, on the other hand, lack such cholinergic axons. Ultrastructural examination reveals that unmyelinated axons within NGF-producing grafts use many different substrates for growth, including astrocytes and components of the extracellular matrix. Grafts of control fibroblasts possess the same cellular and matrix substrates but contain only a small population of axons, probably of peripheral origin. AChE-positive axons growing through NGF-producing grafts provide a new topographically organized input to the deafferented hippocampal dentate gyrus. Furthermore, regenerating septal axons terminate predominantly on the dendritic processes of granular neurons. The dentate gyrus ipsilateral to grafts of noninfected fibroblasts, on the other hand, remains devoid of AChE-positive fibers. From these results, we conclude that the availability of NGF is a necessary requirement to sustain axotomized cholinergic septal neurons and to promote axon regeneration and cholinergic reinnervation of dentate granular neurons by these lesioned neurons. The presence of many permissive substrates (e.g., astrocytes, basal lamina, and collagen) alone, however, is not sufficient to induce axon regrowth from adult septal neurons.

Acetylcholinesterase↗
PubMed1992

Supplemental oxygen after outpatient oral and maxillofacial surgery.

Arterial oxygen saturation (SpO2) was monitored postoperatively with pulse oximetry in 72 dental patients. Intravenous general anesthesia was employed in 57 patients. All of these patients received supplemental oxygen intraoperatively, and of these, 29 received supplemental oxygen postoperatively. Fifteen patients received only local anesthesia without supplemental oxygen and served as the control group. Continuous pulse oximetry revealed 43 episodes of arterial oxygen desaturation (SpO2 decreases greater than 3% from baseline) in patients who did not receive postanesthesia supplemental oxygen and eight episodes of desaturation in patients who did receive postanesthesia oxygen. Patients with a smoking history had more episodes of desaturation than did nonsmokers in the group that received general anesthesia and breathed room air postoperatively. The total amount of methohexital administered had no significant effect on the number of patients with desaturation episodes. These observations emphasize the need for postoperative oxygen for patients who undergo general anesthesia for outpatient oral and maxillofacial surgery.

Adolescent↗
PubMed1991

Gene transfer into rat airway epithelial cells using retroviral vectors.

Primary cultures of epithelial cells from adult rat tracheas were maintained in vitro on collagen matrices and were exposed to a murine retrovirus vector expressing the E. coli beta-galactosidase gene. Infection was carried out on cells grown as monolayers under medium and on cells grown on raised platforms. Cells maintained at an air-medium interface were highly susceptible to infection with the vector, showing an efficiency of infection of 20-25%, compared with an efficiency of less than 1% for cells grown under medium. Infected beta-galactosidase-expressing cells were seeded into denuded tracheas and were capable of partially repopulating the denuded tracheas grafted subcutaneously into host rats. The susceptibility of these cells to retroviral infection suggests an approach to the treatment of some pulmonary genetic disorders such as cystic fibrosis.

Aerosols↗
PubMed1991

Guidelines for intraoperative monitoring of dental patients undergoing conscious sedation, deep sedation, and general anesthesia.

The promulgation and adoption of intraoperative monitoring standards in medicine for anesthesia has resulted in early detection of untoward events during sedation and anesthesia, lowering of malpractice premiums, and an improvement in the quality of care. The American Dental Society of Anesthesiology has devised specific, detailed monitoring standards with universal applicability in the dental setting.

Anesthesia, Dental↗
PubMed1991

Learning style analysis among oral and maxillofacial surgeons.

Learning style analysis provides a conceptual framework to aid both teachers and students in determining their optimal learning millieu. The four stages of the learning cycle apply to every learning situation, including the training and continuing education of oral and maxillofacial surgeons. Determination of learning style type may correlate with individual success in a particular program or specialty and aid in staff/student interaction and professional growth.

Education, Dental↗
PubMed1990

Gene therapy in the CNS: intracerebral grafting of genetically modified cells.

Grafting cells to the CNS has been suggested and applied as a potential approach to CNS therapy through the selective replacement of cells lost as a result of disease or damage. Independently, studies aimed at direct genetic therapy in model systems have recently begun to suggest conceptually new approaches to the treatment of several kinds of human genetic disease, especially those caused by single gene enzyme deficiencies. We suggest that a combination of these two approaches, namely the graftment into the CNS of genetically modified cells, may provide a new approach toward the restoration of some functions in the damaged or diseased CNS. We present evidence for the feasibility of this approach, including a description of some current techniques for mammalian cell gene transfer and CNS grafting, and several possible approaches to clinical applications. Specifically, we report that fibroblasts, genetically modified to secrete NGF by infection with a retroviral vector and implanted into the brains of rats with a surgical lesion of the fimbria-fornix, prevented the degeneration of cholinergic neurons that would die without treatment.

Animals↗
PubMed1990

Autocrine differentiation of PC12 cells mediated by retroviral vectors.

Rat pheochromocytoma PC12 cells have been modified genetically by the use of replication-defective retroviral vectors containing either the bacterial gene for beta-galactosidase (lac Z) or cDNAs for mouse beta-nerve growth factor (NGF) and the bacterial gene for neomycin resistance. Using the lac Z vector, clonal lines of PC12 cells were obtained in which almost 100% of cells stably expressed this histochemical marker. Infection of PC12 cells or the derived subclone PC12-BAG, which expresses beta-galactosidase, with the NGF vectors resulted in autocrine differentiation as assessed by extensive neurite formation, which occurred within hours after infection and was maintained for weeks in culture. Neurite formation could be partially blocked by antibodies to NGF. The percentage of cells expressing neurite outgrowth was greater than that of PC12 cells treated with exogenous NGF. PC12 cells infected with the NGF vectors were shown to release this trophic factor into the medium using a two-site enzyme immunoassay and a bioassay on 'naive' PC12 cells. PC12 cells genetically modified using these vectors provide a means to: follow the fate of the cells after transplantation into animals; test for delivery in vivo of NGF and catecholamines by grafted, autocrine-differentiated PC12 cells; and study the long-term actions of NGF on responsive cells without adding exogenous NGF.

Animals↗
PubMed1989

Grafting genetically modified cells into the rat brain: characteristics of E. coli beta-galactosidase as a reporter gene.

The utility of grafting genetically modified cells to the mammalian brain was examined using the E. coli beta-galactosidase gene (lacZ) as a reporter gene in retroviral infection. Following implantation of the infected cells to the brain, lacZ continued to be expressed in vivo and could be detected easily with enzyme histochemistry. However, beta-galactosidase-positive cells were also observed in control grafts which had not been infected with the virus. This false-positive staining was found to be endogenous lysosomal activity associated with macrophage infiltration presumably induced by the damage associated with grafting. The E. coli gene product was distinguished from cellular lysosomal beta-galactosidase by using immunohistochemical staining with an antibody specific for E. coli beta-galactosidase. With this antibody, retrovirus-infected cells could be distinguished in the brain, and no false positives were observed in non-infected cells. We conclude that E. coli beta-galactosidase is a useful reporter gene for determining the fate of implanted cells to the brain if appropriate caution is taken to distinguish it from cellular beta-galactosidase by immunocytochemical procedures.

Animals↗
PubMed1989

NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum.

Adult cholinergic interneurons of the neostriatum are not immunoreactive for monoclonal antibody to NGF receptor, whereas the developing neostriatum is immunoreactive for this same antibody. Chronic NGF infusion into the adult neostriatum resulted in reexpression of the NGF receptor such that many cholinergic interneurons became immunoreactive for NGF receptor. NGF infusion dramatically increased the size and choline acetyltransferase immunoreactivity of these same cholinergic neurons. Additionally, in situ hybridization demonstrated an increase in the number of cells expressing NGF receptor mRNA in the NGF-infused striatum. These findings indicate that central cholinergic neurons which lose their NGF receptors during postnatal development will resume their NGF responsiveness when the tissue is damaged. Such a damage-induced mechanism may act to enhance the action of trophic factors, including NGF, released at the site of injury and enhance the responsiveness of damaged CNS neurons to exogenously administered trophic factors.

Aging↗
PubMed1989

Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease.

Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2]. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell culture medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease.

Animals↗
PubMed1988

Grafting genetically modified cells to the damaged brain: restorative effects of NGF expression.

Fibroblasts were genetically modified to secrete nerve growth factor (NGF) by infection with a retroviral vector and then implanted into the brains of rats that had surgical lesions of the fimbria-fornix. The grafted cells survived and produced sufficient NGF to prevent the degeneration of cholinergic neurons that would die without treatment. In addition, the protected cholinergic cells sprouted axons that projected in the direction of the cellular source of NGF. These results indicate that a combination of gene transfer and intracerebral grafting may provide an effective treatment for some disorders of the central nervous system.

Acetylcholinesterase↗
PubMed1987

Grafting genetically modified cells to the brain: possibilities for the future.

Diagnostic and therapeutic approaches to disorders of the central nervous system (CNS) are particularly difficult to develop because of the relative inaccessibility of the mammalian brain to study and chemical treatment, the complexity and interconnectedness of CNS subsystems, and the profound and continued lack of fundamental understanding of the relationship between structure and function in the CNS. Neural grafting in the CNS has recently suggested a potential approach to CNS therapy through the selective replacement of cells lost as a result of disease or damage. Independently, studies aimed at direct genetic therapy in model systems have recently begun to suggest conceptually new approaches to the treatment of several kinds of human genetic disease, especially those caused by single-gene enzyme deficiencies. We suggest that a combination of these two approaches, namely the grafting into the CNS of genetically modified cells, may provide a new approach toward the restoration of some functions in the damaged or diseased CNS. We present evidence for the feasibility of this approach, including a description of some current techniques for mammalian cell gene transfer and CNS grafting, and several possible approaches to clinical applications.

Brain↗
PubMed1987

Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated nerve growth factor.

We have used biologically active derivatives of beta-nerve growth factor (NGF), modified by biotinylation via carboxyl groups, to target the specific binding of liposomes to cultured rat and human tumor cells bearing NGF receptors. Liposomes, to be used for targeting, were prepared by conjugating streptavidin to phospholipid amino groups on liposomes prepared by reverse-phase evaporation. Approximately 2,000 streptavidin molecules were incorporated per liposome. Addition of biotinylated NGF, but not of unmodified NGF, could mediate the subsequent binding of radiolabeled streptavidin-liposomes to rat pheochromocytoma PC12 cells in suspension at 4 degrees C. In contrast, incubation with biotinylated NGF did not mediate the binding of hemoglobin-conjugated liposomes. Under optimal incubation conditions, approximately 570 streptavidin-liposomes were specifically bound per cell. Biotinylated NGF was also used to obtain specific binding of streptavidin-liposomes containing encapsulated fluorescein isothiocyanate-labeled dextran to PC12 cells or human melanoma HS294 cells. When HS294 cells were incubated at 37 degrees C following targeted liposome binding at 4 degrees C, the cell-associated fluorescence appeared to become internalized, displaying a perinuclear pattern of fluorescence similar to that observed when lysosomes were stained with acridine orange. Trypsin treatment abolished cell-associated fluorescence when cells were held at 4 degrees C but did not alter the fluorescence pattern in cells following incubation at 37 degrees C. When liposomes containing carboxyfluorescein, a dye capable of diffusing out of acidic compartments, were targeted to HS294 cells, subsequent incubation at 37 degrees C resulted in diffuse cytoplasmic fluorescence, suggesting that internalized liposomes encounter lysosomal or prelysosomal organelles.

Adrenal Gland Neoplasms↗