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M Benedict

Publications and source records attributed to M Benedict.

29 records · Page 2Linked to original sources
PubMed1995

Bcl-x and Bcl-2 inhibit TNF and Fas-induced apoptosis and activation of phospholipase A2 in breast carcinoma cells.

Tumor necrosis factor (TNF) induces cel death in several tumor cell lines by undefined mechanisms. Using a cDNA expression cloning strategy we identified two cDNAs that completely inhibit the TNF-induced death pathway in MCF7 breast carcinoma cells. These cDNAs encoded for Bcl-2 and Bcl-x. To compare the cytotoxic signal transduction pathway induced by the TNF receptor versus that induced by Fas, we transfected MCF7 cells with a Fas expression construct. The resulting cell line, MCF-Fas, was highly sensitive to cytotoxicity induced by TNF or anti-Fas. Expression of either bcl-2 or bcl-x in these cells rendered them completely resistant to lysis induced by either TNF or Fas. Interestingly, exposure of MCF-Fas cells to anti-Fas or TNF induced activation of phospholipase A2 (PLA2), while only TNF activated NF-kappa B. Activation of PLA2 was completely blocked whereas activation of NF-kappa B was unaffected by overexpression of either bcl-x or bcl-2. Moreover, PLA2-inhibitors, quinacrine and dexamethasone, partially inhibited cytotoxicity induced by either TNF or anti-Fas. These data suggest an involvement of PLA2 in both TNF- and Fas-mediated cytotoxicity and a novel mechanism of action for bcl-2 and bcl-x, i.e. inhibition of arachidonic acid metabolism, by which they may, in addition of apoptosis, modulate inflammation.

Antigens, Surface↗
PubMed1994

Persistence of disturbed adipocyte metabolism in streptozocin-induced diabetic rats despite near-euglycemia with phlorizin.

It is widely accepted that hyperglycemia per se incites and perpetuates the diabetic state by adverse effects on beta cell insulin secretion and peripheral insulin action. Examination of the latter locus has revealed glucose-related abnormalities in facilitated glucose transport. Beyond the plasma membrane, however, there is scant data examining whether hyperglycemia influences important intracellular metabolic events. We recently described a sizable reduction in post-transport, in situ metabolism in permeabilized fat cells from streptozocin-induced diabetic rats. Of importance, the diabetes-related deficit was entirely ameliorated by insulin therapy. In this study we examined whether hyperglycemia per se contributes to this altered intracellular metabolic effect. By infusing phlorizin, near euglycemia was achieved for at least four days in streptozocin-induced diabetic rats. The phlorizin-treated diabetic rats had improved (intact cell) rates of insulin-stimulated 2-deoxyglucose uptake. Despite this, permeabilized fat cell studies revealed no improvement or deterioration in diabetic intracellular metabolism as measured by both the oxidation of [6-14C]glucose-6-phosphate via the citric acid cycle or its incorporation into triglyceride. We conclude that hypoinsulinemia, and not hyperglycemia, mediates the disturbance in porous diabetic adipocyte cellular metabolism.

Adipocytes↗
PubMed1993

Nm23 and breast cancer metastasis.

The majority of breast cancer patients succumb to metastatic disease. We summarize published and recent research concerning the nm23 gene in breast cancer metastasis. In a murine developmental study, nm23 expression increased with the functional differentiation of the mammary gland in nulliparous and pregnant animals. In human breast cancer, five studies have now demonstrated a significant association between reduced nm23 expression, at the RNA or protein levels, and aggressive tumor behavior. Nm23-negative tumor cells have been observed in comedo ductal carcinoma in situ lesions in two independent studies, indicating that decreases in nm23 expression begin prior to actual histologically identifiable invasion. Transfection studies, in which human nm23-H1 cDNA was expressed in the metastatic human MDA-MB-435 breast carcinoma cell line, indicate that nm23-H1 suppresses in vivo metastatic potential by 50-90%. Finally, our data in melanoma and breast carcinoma transfection systems suggest that the biochemical mechanism of nm23 suppressive activity is likely not due to its nucleoside diphosphate kinase activity, association with GAP proteins, or secretion from cells.

Animals↗
PubMed1993

Child maltreatment in family foster care.

Predictors of maltreatment of children living in family foster care were sought in characteristics of foster homes. Four characteristics that presented increased risk were identified: homes that had younger foster mothers, homes in which children shared bedrooms with other family members, homes about which case-workers had reservations, and homes that were restricted for placement of certain children. Kinship-care homes were found to present decreased risk.

Adolescent↗
PubMed1992

High level expression on a chimeric anti-ganglioside GD2 antibody: genomic kappa sequences improve expression in COS and CHO cells.

We report a flexible strategy for the high level expression of a recombinant human monoclonal antibody (mAb) in Chinese hamster ovary (CHO) cells, initially using COS monkey kidney cell transfections to evaluate rapidly modifications to immunoglobulin (Ig) DNA constructs. Using sequential transfections with two amplifiable markers, we generated CHO cell lines and clones that secrete 80-110 micrograms/10(6) cells/24 hours of a mouse-human chimeric IgG1 kappa mAb. This cellular productivity is considerably greater than most murine hybridomas and transfected myelomas. Our data also demonstrate that genomic kappa sequences can improve mAb expression in COS and CHO cells. As a paradigm, we focused our expression studies on a human chimeric form of 3F8, a murine mAb that binds to ganglioside GD2 on neuroblastoma and melanoma tumor cells.

Animals↗
PubMed1992

[Long-term manifestations of laryngeal sarcoidosis].

We report the medical history of a 19 year old female patient with isolated laryngeal sarcoidosis, who was followed for 12 years. It illustrates the typical course of the disease with remissions and relapses until the inflammation is "burnt out." Although the laryngoscopic findings of pale-red swollen supraglottic structures are pathognomonic, diagnosis is rarely assumed at first sight. Long-term administration of cortisone in low dosage is the treatment of choice. Acute exacerbations with increasing airway obstruction may occur at any time, although in general a tracheotomy can be avoided because high-dose cortisone is highly effective. Over the years, the granulomatous character of the inflammation turns into a chronic non-specific one, while the laryngoscopic aspect hardly changed. Once the sarcoidosis is burnt out, the danger of an acute exacerbation diminishes.

Adult↗
PubMed1991

[Spontaneous cerebrospinal rhinorrhea. Etiology--differential diagnosis--therapy].

CSF rhinorrhea is called spontaneous if it is due neither to a trauma, nor an intracranial tumour or a congenital malformation. Spontaneous CSF rhinorrhea is extremely rare: the fistula is usually found in the roof of the ethmoid sinus, less often in the walls of the sphenoid sinus. There is a striking prevalence of female patients. We describe a female patient who showed spontaneous CSF rhinorrhea from a leak in the anterior roof of the sphenoid sinus. The possible aetiology, diagnostic measures and therapy are discussed. Areas of reduced resistance in the anterior skull base may be congenital, or may be acquired due to later focal atrophy. The diagnosis of CSF rhinorrhea can be established by the glucose test, isotope scanning, immunoelectrophoresis and fluorescence endoscopy. The most reliable methods of distinguishing between a traumatic or neoplastic lesion and a spontaneous CSF rhinorrhea are high-resolution computed tomography (CT) and magnetic resonance tomography. High-resolution CT is also the best method for localization of the bony defect. Elevated intracranial pressure must be ruled out carefully. The treatment of choice is closure of the fistula, preferably by the nasal surgeon, using either the endonasal-transseptal, the endonasal-transethmoidal or the paranasal-transethmoidal approach in order to preserve olfaction and to avoid the risk of a frontal lobe lesion which is a complication of the neurosurgical approach. Interposition of a fascial or dural graft is considered to be an important technical detail for achieving a secure closure of the fistula; packing can be avoided by additional sealing of the patch with fibrinogen glue.

Adult↗
PubMed1989

CGP 31358 binds to a site on the NMDA receptor that is coupled to both the transmitter recognition site and the channel domain.

CGP 31358, a novel triazole, inhibited the binding of L-[3H]glutamate and [3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor complex in rat brain synaptic membrane fractions, and showed anticonvulsant activity in mice. It had no effect on the strychnine-insensitive binding of [3H]glycine. Saturation and Hill analyses indicated that CGP 31358 binds to a site on the NMDA receptor which is separate from, but coupled to, both the transmitter recognition site and the channel domain. Available data indicate that this site is distinct from those with which tricyclic antidepressants and ifenprodil interact. CGP 31358 is a new chemical entity with a novel mechanism of action at the NMDA receptor, and as such may form a tool for understanding the molecular pharmacology of this receptor-channel complex.

Animals↗