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Biomedical subjects

B D Cohen

Publications and source records attributed to B D Cohen.

At least 19 recordsLinked to original sources
PubMed1997

The DAN1 gene of S. cerevisiae is regulated in parallel with the hypoxic genes, but by a different mechanism.

The DAN1 gene is expressed under anaerobic conditions in yeast and completely repressed during aerobic growth. The function of the gene is unknown, and genetic disruption had no effect on fitness which could be detected, even upon prolonged anaerobic growth. Expression of DAN1 was constitutive in a heme-deficient strain, indicating that heme participates in repression. Expression was blocked by heme in anaerobic medium, suggesting that heme acts as a negative co-effector rather than through its metabolic functions, i.e., in the production of a co-effector. Expression of DAN1 was regulated in parallel with the hypoxic gene ANB1, showing identical kinetics of induction and dose response to heme. However, unlike ANB1, DAN1 is not regulated by the repressor of the hypoxic regulon, ROX1, as shown by observation of normal aerobic repression of DAN1 in a strain carrying a deletion of ROX1. These results indicate the existence of a parallel regulatory system which produces an identical response to oxygen by a different mechanism than that controlling the hypoxic regulon.

Anaerobiosis↗
PubMed1996

The relationship between human epidermal growth-like factor receptor expression and cellular transformation in NIH3T3 cells.

A collection of cell lines expressing each human epidermal growth factor receptor (HER) family member alone or in all pairwise combinations in a clone of NIH3T3 cells (3T3-7d) devoid of detectable epidermal growth factor receptor family members has been generated. Transformation, as measured by growth in soft agar, occurred only in the presence of appropriate ligand and only in cells expressing two different HER family members. Transfection of oncogenic neu (Tneu), conferred ligand-independent transformation only in cells which co-expressed HER1, HER3, or HER4, but not when expressed alone or with HER2. Cell lines were also tested for their ability to form tumors in animals. None of the cell lines expressing single HER family members was able to form tumors in animals with the exception of HER1, which was weakly tumorigenic. Although unable to form tumors when expressed alone, HER2 was tumorigenic when expressed with HER1 or HER3, but not HER4. Of all complexes analyzed, cells expressing HER1 + HER2 were the most aggressive. The relationship between HER1 activation, intracellular calcium fluxes, and phospholipase Cgamma1 activation is well established. We found that activation of HER1 was required for the induction of a calcium flux and the phosphorylation of phospholipase Cgamma1. These activities were independent of, and unaffected by, the co-expression of any other family member. Further, heregulin stimulation of all cell lines including those containing HER1 did not demonstrate any effect on intracellular calcium levels or phospholipase Cgamma1 phosphorylation. This demonstrates that heregulin induced cellular transformation by activating HER3- and HER4-containing complexes does not require the activation of either phospholipase Cgamma1 or the mobilization of intracellular calcium.

3T3 Cells↗
PubMed1996

HER4-mediated biological and biochemical properties in NIH 3T3 cells. Evidence for HER1-HER4 heterodimers.

The EGF receptor family of tyrosine kinase growth factor receptors is expressed in a variety of cell types and has been implicated in the progression of certain human adenocarcinomas. The most recent addition to this family of receptors, HER4, was expressed in NIH 3T3 cells to determine its biological and biochemical characteristics. Cells expressing HER4 were responsive to heregulin beta2 as demonstrated by an increase in HER4 tyrosine phosphorylation and ability to form foci on a cell monolayer. HER4 exhibited in vitro kinase activity and was able to phosphorylate the regulatory subunit of phosphatidylinositol 3-kinase and SHC. Peptide competition studies identified tyrosine 1056 of HER4 as the phosphatidylinositol 3-kinase binding site and tyrosines 1188 and 1242 as two potential SHC binding sites. Interestingly, transfection of HER4 into NIH 3T3 cells conferred responsiveness to EGF with respect to colony formation in soft agar. It was also found that in response to heregulin beta2, endogenous murine HER1 or transfected human HER1 became phosphorylated when HER4 was present. This demonstrates that HER1 and HER4 can exist in a heterodimer complex and likely activate each other by transphosphorylation.

3T3 Cells↗
PubMed1995

HER4 expression correlates with cytotoxicity directed by a heregulin-toxin fusion protein.

We have constructed, expressed, and purified a fusion protein, HAR-TX beta 2, consisting of heregulin-beta 2 fused to a binding-defective form of Pseudomonas exotoxin A, PE40. The fusion protein was found to induce receptor tyrosine phosphorylation in CEM cells transfected with HER4 alone or in combination with HER2 but not in cells transfected with HER2 or HER1 alone. The phosphorylation of receptor tyrosines was both dose-dependent and saturable in amounts similar to those shown to be active for native heregulin. HAR-TX beta 2 was specifically cytotoxic toward a variety of carcinoma cell lines in the ng/ml range. However, some tumor cell lines were found to be insensitive to the cytotoxic action of the fusion protein even at > 2 micrograms/ml. Relative amounts of HER4, HER3, and HER2 were determined on seven cell lines sensitive and four cell lines insensitive to HAR-TX beta 2. All lines that express HER4 were killed by HAR-TX beta 2, while none lacking HER4 were affected. HAR-TX beta 2 was able to bind to and signal via tyrosine phosphorylation in cell lines that co-express HER2 and HER3 in the absence of HER4 without inducing cytotoxicity. Thus HAR-TX beta 2 may prove to be a useful reagent for the targeting and elimination of HER4-positive tumor cells.

ADP Ribose Transferases↗
PubMed1995

The use of orthodontics before fixed prosthodontics in restorative dentistry.

For a variety of reasons, orthodontic intervention is often overlooked as a viable modality to correct occlusal, axial, rotational, and space discrepancies before undertaking fixed prosthetic rehabilitation. However, patient treatment is being enhanced as never before by such intervention. This valuable treatment option facilitates tooth preparation, path of insertion, optimum oral hygiene, and a better pontic and abutment design, while occlusal forces can be directed against the long axes of the teeth for a more predictable prognosis. Moreover, this interdisciplinary approach can be cost-effective to patients and their treating dentists from the standpoint of producing more stable, durable, and esthetic restorations.

Adult↗
PubMed1994

Development of new adhesive pulp capping materials.

The pulp capping materials currently available do not adhere to dentine but cover it and therefore extensive removal of tooth tissue is necessary to expose sufficient dentine for the adhesives used to secure the restoration (the adhesives do not adhere to the capping material). The authors describe how two new pulp capping materials have been developed, which combine the properties required for pulp capping with an ability to adhere to dentine.

Acrylic Resins↗
PubMed1994

Pulp response to a novel adhesive calcium hydroxide based cement.

This study compares pulp responses to 3 formulations of calcium hydroxide, namely: a) An experimental adhesive calcium hydroxide cement containing polyacrylic acid, b) Dycal (L.D> Caulk Co, Milford, Delaware) Batch Nos 176970/176990, c) "Analar" calcium hydroxide mixed with sterile distilled water. After 28 days dentine bridges were present in 77% of teeth capped with the test material, 64% of teeth treated with Dycal and in 62% of teeth capped with calcium hydroxide and water. Inflammatory infiltrates were observed in a number of teeth remote from the bridges. Bacteria were detected in these specimens. Exposed rat molar pulp responses to an experimental adhesive calcium hydroxide cement were similar to to those observed with 2 other calcium hydroxide formulations.

Animals↗
PubMed1993

Perception of self and other in major depression.

Previous research on the nature of person perception in depression has been inconclusive. This investigation differs from earlier studies in that extensive free-response descriptions of other people and self were collected from patients with major depression and from nonpsychiatric control Ss. In comparison with control Ss, depressed patients described fewer positive aspects not only of self but also of parents and significant others and reported more negative aspects of these people. Cluster analysis (HICLAS) also showed that more cognitive differentiation of negative self-perceptions (negative self-complexity) was characteristic of clinical depression. In both control Ss and patients, a positive (or negative) view of self was highly correlated (.85 or more) with a positive (or negative) view of parents and significant others. These correlations were significantly stronger than those between self and less important others.

Adult↗
PubMed1993

Transformation-specific interaction of the bovine papillomavirus E5 oncoprotein with the platelet-derived growth factor receptor transmembrane domain and the epidermal growth factor receptor cytoplasmic domain.

The bovine papillomavirus E5 transforming protein appears to activate both the epidermal growth factor receptor (EGF-R) and the platelet-derived growth factor receptor (PDGF-R) by a ligand-independent mechanism. To further investigate the ability of E5 to activate receptors of different classes and to determine whether this stimulation occurs through the extracellular domain required for ligand activation, we constructed chimeric genes encoding PDGF-R and EGF-R by interchanging the extracellular, membrane, and cytoplasmic coding domains. Chimeras were transfected into NIH 3T3 and CHO(LR73) cells. All chimeras expressed stable protein which, upon addition of the appropriate ligand, could be activated as assayed by tyrosine autophosphorylation and biological transformation. Cotransfection of E5 with the wild-type and chimeric receptors resulted in the ligand-independent activation of receptors, provided that a receptor contained either the transmembrane domain of the PDGF-R or the cytoplasmic domain of the EGF-R. Chimeric receptors that contained both of these domains exhibited the highest level of E5-induced biochemical and biological stimulation. These results imply that E5 activates the PDGF-R and EGR-R by two distinct mechanisms, neither of which specifically involves the extracellular domain of the receptor. Consistent with the biochemical and biological activation data, coimmunoprecipitation studies demonstrated that E5 formed a complex with any chimera that contained a PDGF-R transmembrane domain or an EGF-R cytoplasmic domain, with those chimeras containing both domains demonstrating the greatest efficiency of complex formation. These results suggest that although different domains of the PDGF-R and EGF-R are required for E5 activation, both receptors are activated directly by formation of an E5-containing complex.

3T3 Cells↗
PubMed1993

The conserved C-terminal domain of the bovine papillomavirus E5 oncoprotein can associate with an alpha-adaptin-like molecule: a possible link between growth factor receptors and viral transformation.

The bovine papillomavirus E5 gene encodes an oncoprotein that can independently transform rodent fibroblasts. This small 44-amino-acid protein is thought to function through the activation of growth factor receptors. E5 activation of the epidermal growth factor receptor results in an increase in the number of activated receptors at the cell surface. This finding suggests that E5 may act by inhibiting the normal down regulation of activated epidermal growth factor receptor via coated pit-mediated endocytosis. We have constructed a fusion protein consisting of glutathione S-transferase and the conserved C-terminal domain of E5 (GST-E5) in order to identify E5-associated cellular proteins that may be involved in its transforming activity. We have identified a 125-kDa cellular protein with a strong associated serine kinase activity that specifically associated with GST-E5 in the reduced form but not with GST-E5 fusions that contained changes in several conserved amino acids. Microsequence and biochemical analyses suggest that p125 is a novel member of the alpha-adaptin family. Since alpha-adaptins have previously been shown to be involved in coated pit-mediated cell surface receptor endocytosis and down regulation, these results suggest that p125 may be an alpha-adaptin-like molecule involved in growth factor receptor down regulation and that E5 may act by inhibiting its activity.

3T3 Cells↗
PubMed1992

Self-structure in borderline personality disorder.

Self-structural theory is applied to the interpersonal aspects of borderline personality disorder. The notion of interpersonal contrasting, a cognitive maneuver, is introduced to account for the sharp changes between divergent self-states characteristic of the disorder. The theory and three prototypical self-states are illustrated with data from a borderline patient by means of a procedure derived from the theory.

Borderline Personality Disorder↗
PubMed1992

Effect of thermal placement techniques on some physical properties of gutta-percha.

Some clinical techniques for the placement of gutta-percha root fillings involve the application of heat. This study was undertaken to assess the effects of intracanal heating techniques on the following properties of gutta-percha: coefficient of thermal expansion, softening temperature, phase transition temperature and organic content. Samples from each of four products were prepared by three different methods. The materials were studied by thermomechanical analysis, simultaneous thermogravimetry and differential thermal analysis, and by measurement of weight loss on ashing. It was shown that the techniques of gutta-percha placement involving heating in the root canal caused reversible physical changes in the materials without any apparent change in chemical composition. The average coefficient of thermal expansion was 137 x 10(-6)/degrees C, the softening temperature was 55.5 degrees C, there were two characteristic phase changes, and the organic content was 25%.

Differential Thermal Analysis↗
PubMed1992

Orthodontic adjunctive treatment in fixed prosthodontics.

The purpose of this article has been to increase the restorative dentist's appreciation for the rationale justifying preprosthodontic orthodontic treatment. It has not been intended to identify all the specific indications for the use of orthodontic treatment to enhance prosthodontic treatment nor has it been intended as a reference to assist the restorative dentist in placing and using orthodontic appliances. Figure 12 illustrates a typical case in which the combination of orthodontic and prosthodontic treatment resulted in a more favorable outcome than prosthodontic treatment alone. When planning prosthodontic treatment, the dentist should embrace a dynamic view of tooth position and determine whether restorative treatment can be enhanced by tooth movement. Improved tooth position can eliminate potentially pathologic occlusion and create a healthier periodontal environment that is easier to maintain. In addition, it permits the dentist to place restorations that often require less natural tooth reduction during preparation, and that are more esthetic, functional, stable, and durable. Orthodontic treatment that accomplishes these benefits may be limited to a partial fixed appliance localized to one segment of an arch or require a more extensive fixed appliance. Much of this treatment can be accomplished by the interested restorative dentist. Addressing more comprehensive orthodontic problems in patients requiring prosthodontic care is best managed through a restorative dentist and orthodontist team approach to treatment.

Dental Stress Analysis↗
PubMed1991

Identification and characterization of the neurofibromatosis type 1 protein product.

The neurofibromatosis type 1 (NF1) gene responsible for von Recklinghausen neurofibromatosis is related to regulators of ras proteins, and a portion of NF1 that is homologous to the ras GTPase-activating protein (GAP) encodes a similar GTPase-stimulating activity. We have raised rabbit antisera to a bacterially synthesized 48-kDa peptide corresponding to the GAP-related domain of NF1 (NF1-GRD). These antisera immunoprecipitated the NF1-GRD peptide, and one of them specifically inhibited the GTPase-stimulating activity of NF1-GRD. The sera specifically detected a 280-kDa protein in lysates of mouse NIH 3T3 and human HeLa cells. This protein corresponds to the NF1 gene product, as shown by several criteria, including partial proteolysis. Subcellular fractionation revealed that while GAP is predominantly cytoplasmic, all of the NF1 was recovered in a pellet (100,000 x g) fraction. NF1 was present in a large molecular mass complex in fibroblast and Schwannoma cell lines and appears to associate with a very large (400-500 kDa) protein in both cell types. The relevance of these findings to cellular regulation of p21ras is discussed.

3T3 Cells↗
PubMed1991

Castable glass ceramic crowns and their reaction to endodontic therapy.

The purpose of this investigation was to determine how castable glass (Dicor) crowns would react to both cold testing and endodontic access intervention. Full crown preparations were made on six extracted maxillary teeth. The teeth were then forwarded to Dentsply International, York, Pa. Six castable glass crowns were fabricated to fit these teeth and returned to us. Subsequently the teeth were dried and the crowns were cemented. Scanning electron micrographs of the cemented crowns were made, and endodontic access openings were drilled. The teeth were also cold tested with standard methods. The teeth were then again subjected to scanning electron microscopy to determine any changes the crowns might have undergone. One crown cracked around the gingival collar as scanning electron microscopy was performed. The other crowns did not exhibit any problems such as cracking or crazing from either the access openings or the cold testing.

Ceramics↗