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T McMahon

Publications and source records attributed to T McMahon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Protein kinase A regulates regulates inhibition of N- and P/Q-type calcium channels by ethanol in PC12 cells.

Ethanol inhibits L-type Ca++ channels, but little is known about its effect on other voltage-gated Ca++ channels. To examine non-L-type channels we used nerve growth factor-differentiated PC12 cells treated with the L channel blocker nifedipine. Using selective Ca++ channel antagonists, we found that N-type and P/Q-type channels mediate most of the remaining depolarization-evoked Ca++ rise. Ethanol (10-150 mM) inhibited depolarization-induced rises in intracellular Ca++ with maximal inhibition of 46% achieved using 50 mM ethanol. Inhibition was time dependent, requiring at least 8 min to develop fully. Ethanol did not alter Ca++ mobilization, sequestration, extrusion or capacitative entry. Sp-adenosine cyclic 3',5'-phosphorothioate, a specific activator of protein kinase A (PKA), blocked inhibition by ethanol, whereas the protein kinase C activator phorbol 12-myristate, 13-acetate did not. Okadaic acid, an inhibitor of protein phosphatases type-1 and type-2A, also blocked inhibition by ethanol with an IC50 of 3 nM. This was prevented by inhibiting PKA, indicating that the action of okadaic acid was due to increased PKA-mediated phosphorylation. These results indicate that ethanol can inhibit N-type and P/Q-type channels and this is antagonized by activating PKA. The findings suggest the sensitivity of these channels to ethanol is regulated by a phosphoprotein that is a substrate for PKA and protein phosphatase type-2A.

Animals↗
PubMed1995

Overexpression of epsilon-protein kinase C enhances nerve growth factor-induced phosphorylation of mitogen-activated protein kinases and neurite outgrowth.

Protein kinase C (PKC) activation enhances neurite outgrowth in several cell lines and primary neurons. The PKC isozymes that mediate this response are unknown. One clue to their identity has come from studies using PC12 cells treated with ethanol. In these cells, ethanol increases levels of delta-PKC and epsilon-PKC and markedly enhances nerve growth factor (NGF)-induced neurite outgrowth and activation of mitogen-activated protein (MAP) kinases by a PKC-dependent mechanism. Since these findings suggest that delta-PKC or epsilon-PKC can promote neural differentiation, we studied neurite outgrowth in stably transfected PC12 cell lines that overexpress these isozymes. Overexpression of epsilon-PKC markedly increased NGF-induced neurite outgrowth. This effect was blocked by down-regulating PKC or by treating cells with the PKC inhibitor GF 109203X. In addition, overexpression of epsilon-PKC enhanced NGF-induced phosphorylation of MAP kinases. In contrast, overexpression of delta-PKC did not alter responses to NGF. These results demonstrate that epsilon-PKC promotes NGF-induced neurite outgrowth by enhancing NGF signal transduction. These findings suggest a role for epsilon-PKC in neural differentiation and plasticity.

Amino Acid Sequence↗
PubMed1995

Construction of murine coronavirus mutants containing interspecies chimeric nucleocapsid proteins.

Targeted RNA recombination was used to construct mouse hepatitis virus (MHV) mutants containing chimeric nucleocapsid (N) protein genes in which segments of the bovine coronavirus N gene were substituted in place of their corresponding MHV sequences. This defined portions of the two N proteins that, despite evolutionary divergence, have remained functionally equivalent. These regions included most of the centrally located RNA-binding domain and two putative spacers that link the three domains of the N protein. By contrast, the amino terminus of N, the acidic carboxy-terminal domain, and a serine- and arginine-rich segment of the central domain could not be transferred from bovine coronavirus to MHV, presumably because these parts of the molecule participate in protein-protein interactions that are specific for each virus (or, possibly, each host). Our results demonstrate that targeted recombination can be used to make extensive substitutions in the coronavirus genome and can generate recombinants that could not otherwise be made between two viruses separated by a species barrier. The implications of these findings for N protein structure and function as well as for coronavirus RNA recombination are discussed.

Amino Acid Sequence↗
PubMed1995

Depolarization-induced neurite outgrowth in PC12 cells requires permissive, low level NGF receptor stimulation and activation of calcium/calmodulin-dependent protein kinase.

Neuronal activity is required for normal neural development. Excessive activity can cause abnormal growth of neural processes and may contribute to formation of epileptic foci. Using PC12 cells, we investigated mechanisms by which depolarization regulates neurite growth. Depolarization with 45 mM KCl induced neurite outgrowth only if NGF receptors were partly activated by overexpression of p140trkA or by treatment with a low concentration of NGF that alone was insufficient to stimulate neurite formation. Depolarization-induced neurite growth was reduced by inhibitors of L-type Ca2+ channels, Ca2+/calmodulin-dependent protein (CaM) kinases II and IV, and transcription. These results identify a novel mechanism by which depolarizing stimuli synergize with subthreshold activation of NGF receptors to induce neurite growth through a Ca2+ and CaM kinase-dependent signal transduction pathway.

Animals↗
PubMed1993

Protein kinase C isozymes that mediate enhancement of neurite outgrowth by ethanol and phorbol esters in PC12 cells.

Using PC12 cells to study ethanol's effects on growth of neural processes, we found that ethanol enhances NGF- and basic FGF-induced neurite outgrowth. Chronic ethanol exposure selectively up-regulates delta and epsilon protein kinase C (PKC) and increases PKC-mediated phosphorylation in PC12 cells. Since PKC regulates differentiation, we investigated the role of PKC in enhancement of neurite outgrowth by ethanol. Like ethanol, 0.3-10 nM phorbol 12-myristate, 13-acetate (PMA) increased NGF-induced neurite outgrowth. However, higher concentrations did not, and immunoblot analysis demonstrated that 100 nM PMA markedly depleted cells of beta, delta and epsilon PKC. PMA (100 nM) also down-regulated beta, delta and epsilon PKC in ethanol-treated cells and completely prevented enhancement of neurite outgrowth by ethanol. In contrast, the cAMP analogue 8-bromoadenosine cAMP did not completely mimic the effects of ethanol on neurite outgrowth, and ethanol was able to enhance neurite formation in mutant PC12 cells deficient in protein kinase A (PKA). These findings implicate beta, delta or epsilon PKC, but not PKA, in the neurite-promoting effects of ethanol and PMA. Since chronic ethanol exposure up-regulates delta and epsilon, but not beta PKC, these findings suggest that delta or epsilon PKC regulate neurite outgrowth.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Simultaneous caries induction and calculus formation in rats.

Weanling specific pathogen-free Osborne-Mendel rats were fed a high-calcium, high-phosphorus diet with various levels of sucrose and inoculated with Streptococcus sobrinus strain 6715-13WT and Actinomyces viscosus strain OMZ-105 in order to determine whether calculus and caries could develop simultaneously. Rats consumed diets designated RC-16-5, RC-16-25, or RC-16-50 which partially replaced the corn starch component with progressively higher levels of sucrose, thus, to 5, 25, or 50% sucrose. In general, bacterial recoveries of A. viscosus declined with higher sucrose content of the diet, but a pattern of recovery for S. sobrinus was less clear with respect to dietary sucrose. S. sobrinus, however, was recovered at higher percentages from the tooth surface flora at the later two of three sampling dates. Most calculus--identified by the brittle quality, staining characteristics, and apatitic x-ray diffraction patterns of tooth surface deposits--was formed on the maxillary molars, and most carious lesions occurred on mandibular molars. While there was minimal association of the calculus score with the amount of sucrose in the diet, calculus scores increased greatly from 23 to 43 days after infectious challenge. Caries scores, of both fissure and smooth surfaces, by contrast, increased in a dose-response fashion with increasing dietary sucrose and with time. It is thus possible to induce calculus formation and caries simultaneously in specific pathogen-free Osborne-Mendel rats consuming a high-calcium and -phosphorus diet conducive to calculus formation and containing sucrose.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinomyces viscosus↗
PubMed1991

Young suicide attempters compared with a control group: psychological, affective, and attitudinal variables.

Suicide attempters admitted to a general hospital psychiatric ward completed questionnaires to elicit information following their suicide attempt. Compared to normal controls who had never attempted suicide, suicide attempters were significantly more hopeless, depressed, and hostile. The suicide attempts seemed to occur in response to stress. A crisis intervention model was suggested as the most appropriate way of managing these patients.

Adaptation, Psychological↗
PubMed1988

Bicarbonate-based dental powder, fluoride, and saccharin inhibition of dental caries associated with Streptococcus mutans infection of rats.

The effects of NaHCO3-based dental powder containing NaF and sodium saccharin on dental caries and Streptococcus mutans recoveries in rats were studied. Weanling specific-pathogen-free Osborne-Mendel (SPFOM) rats were inoculated with S. mutans NCTC-10449S. Four infected groups were topically treated with either demineralized water (DW), a dental powder suspended such that there was 1 part solid per 2 parts DW, 0.073% NaF, or a combination of 0.073% NaF and 0.5% Na-saccharin (Nas). NaF-supplemented DW (at 10 ppm F-) was provided to a 5th group of infected rats as a positive treatment control, but this group was otherwise untreated. A sixth but uninfected group was topically treated with DW. All topical treatments were given once for 1 min daily per rat, for 5 days per week. Animals' teeth were swabbed for recovery of 10449S and total recoverable flora. Recoveries of 10449S were lower from powder-treated rats than from DW-treated rats. This difference approached but did not reach statistical significance. Total caries scores were 51% lower for the dental powder, 36% lower for the topical NaF, 34% lower for the combined NaF-Nas, and 54% lower for the NaF-supplemented drinking water group, all p less than 0.001. While all of the treatments inhibited smooth-surface caries, the dental powder effects, like those for the combined NaF-Nas, and NaF drinking water, were evident in fissure tooth surfaces as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Who provides patients with drug information?

One hundred and fifty four patients were interviewed to determine the type and source of information that they had received about drugs that had been prescribed for them. Most had been told how often to take the drugs (145 (94%)) and how much to take each time (143 (93%)), but few had been informed about side effects (49 (32%)) and fewer had received written information (22 (14%)). Pharmacists most commonly supplied information about how often to take the drugs (105 (68%)), how much to take each time (99 (64%)), and the best way to take it (109 (71%)). Doctors most often gave information about duration of treatment (116 (75)) and possible side effects (126 (82%)). Few patients requested specific information on their own initiative. More research is needed to determine how best to communicate drug information to patients.

Drug Information Services↗
PubMed1986

Radiation damage to the brain: neuropsychiatric aspects.

Although radiation necrosis of the brain is a recognized complication of irradiation of the central nervous system, the psychiatric aspects of this phenomenon are less well defined. Two cases of radiation necrosis in which psychiatric symptoms were a prominent part of the clinical picture are presented. Factors that determine the evolution and clinical presentation of radiation necrosis are reviewed. In particular, the role of the consultation psychiatrist in the diagnosis and management of such patients is discussed.

Adenoma↗