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M Browning

Publications and source records attributed to M Browning.

48 records · Page 3Linked to original sources
PubMed1980

Trifluoperazine inhibits hippocampal long-term potentiation and the phosphorylation of a 40,000 dalton protein.

Brief high frequency stimulation induces long-term potentiation (LTP) and changes in the endogenous phosphorylation of a 40,000 dalton protein in the hippocampus in a calcium-dependent manner. In the present paper we report that 40 microM trifluoperazine (TFP), a phenothiazine that binds calmodulin and blocks its activity, inhibits LTP in the hippocampal slice. In addition, calmodulin stimulates and TFP inhibits the phosphorylation of the 40,000 dalton protein (as well as that of several other proteins) in a dose-dependent fashion.

Animals↗
PubMed1979

Synaptic phosphoproteins: specific changes after repetitive stimulation of the hippocampal slice.

Repetitive stimulation (100 pulses per second for 1 second) of the Schafer collateral-commissural system of the rat hippocampus induces long-term potentiation of synaptic strength and produces significant changes in the subsequent endogenous phosphorylation of a 40,000-dalton protein from synaptic plasma membranes. This effect is not observed after stimulation in calcium-deficient media or after simulation at the rate of one pulse per second for 100 seconds. These findings provide evidence that repetitive synaptic activation can alter the phosphorylation machinery of the synaptic region and suggest a biochemical process which may be involved in the production of neuronal plasticity.

Animals↗
PubMed1979

Biochemical and physiological studies of long-term synaptic plasticity.

High frequency stimulation of fiber systems in the mammalian hippocampus produces a semipermanent increase in synaptic efficacy. This effect, long-term potentiation (LTP), has been of considerable interest as a potential substrate of memory due to its rapid onset and extreme persistence. Experiments are described that indicate that the locus of LTP is confined to the synaptic complex of the fibers stimulated; further, Ca2+ is shown to be essential for the initiation of LTP and may play a role in triggering this increase in synaptic efficiency. Data from biochemical analyses of LTP indicate that a 40,000 dalton synaptic membrane protein shows a highly reliable change in its endogenous phosphorylation following high frequency hippocampal stimulation. Phosphorylase kinase, a Ca2+ sensitive enzyme, is shown to specifically catalyse the phosphorylation of this 40,000 dalton protein. The data are discussed in terms of a working model in which the Ca2+ dependent phosphorylation of the 40,000 dalton protein produced by high frequency stimulation is a biochemical intermediate in the production of LTP.

Animals↗
PubMed1972

Changes in human drug metabolism after long-term exposure to hypnotics.

The influence of the newer, non-barbiturate hypnotics Mandrax (diphenhydramine-methaqualone) and nitrazepam on drug-metabolizing capacity was assessed and compared with the effect of amylobarbitone, a known inducer of drug-metabolizing enzymes. Plasma antipyrine and phenylbutazone half-lives and urinary output of 6beta-hydroxycortisol were used as indices. Volunteer subjects were exposed to therapeutic amounts of these agents and, in the case of Mandrax and barbiturates, further studies were carried out in dependent patients.Mandrax but not nitrazepam increased the rate of drug metabolism, presumably by enzyme induction. The degree of induction was comparable with that produced by hypnotic doses of amylobarbitone. The Mandrax-dependent and barbiturate-dependent patients were the fastest metabolizers studied. It is concluded that drug interactions resulting from interference with drug metabolism are as likely to occur with Mandrax as with barbiturates. On the other hand, it is unlikely that such drug interactions would occur with nitrazepam.

Adolescent↗
PubMed1972

Drug-metabolizing capacity in states of drug dependence and withdrawal.

1. Drug-metabolizing capacity was assessed in 8 barbiturate-dependent and in 3 Mandrax-dependent patients using, as indices, plasma antipyrine half-life and in some cases urinary output of 6beta-hydroxycortisol. For comparison, antipyrine half-life was also measured in volunteers before and after a period of taking hypnotic doses of these agents.2. Both indices indicated a very high drug-metabolizing capacity in the dependent subjects on admission, the antipyrine half-life value in the barbiturate patients being the shortest reported to date for any drug-exposed group. The urinary output of 6beta-hydroxycortisol was approximately three times that in a control population.3. This induction of drug-metabolizing capacity presumably contributed to the marked drug tolerance observed in the dependent patients.4. It appeared that drug-metabolizing capacity eventually returned to normal levels after withdrawal of the barbiturate.5. It is concluded that the abnormal drug-metabolizing capacity of dependent patients must be taken into account in assessing dose requirements for other drugs.

Adult↗
PubMedDate not supplied

Synapsin I in intraocular hippocampal transplants during maturation and aging: effects of brainstem cografts.

The role of target innervation for maintenance of synaptic proteins in the hippocampal formation during aging was investigated. Fetal CA1 tissue and brainstem tissue containing the nucleus locus coeruleus was dissected from albino rats and grafted sequentially into the anterior chamber of the eye of adult rat recipients. Synapsin protein distribution and levels were evaluated by immunohistochemistry and quantitative immunolabeling in single hippocampal grafts or brainstem-hippocampal double grafts at 6, 12, or 24 mo postgrafting. The synapsin levels in 6-mo-old single hippocampal transplants were significantly lower than those in situ, and remained at these lower levels at 12 and 24 mo. On the contrary, synapsin levels were close to normal in the hippocampal portion of double grafts in the 6- and the 12-mo-group. However, in the 24-mo-old double transplants the levels had declined significantly, approaching levels seen in single hippocampal grafts. The immunoblot results were supported by morphological observations with synapsin antibodies and immunohistochemistry. The present data demonstrate that hippocampal tissue maintained near normal synapsin levels when grafted together with brainstem tissue, as compared to the lower levels seen in single hippocampal grafts. This normalization of synapsin levels was, however, not seen in the aged hippocampal-brainstem double grafts.

Aging↗
PubMedDate not supplied

Sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients: a 48-week retrospective multicenter study.

BACKGROUND: Nevirapine, a nonnucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the durable suppression of HIV with nevirapine when used along with other nucleosides in HIV-infected patients who are treated in clinical practice needs further evaluation. PURPOSE: To evaluate the sustained efficacy of nevirapine in combination with two nucleoside analogues in the treatment of HIV-infected patients in routine clinical practice. DESIGN: A multicenter study from January 1997 to December 2000, with follow-up through 48 weeks, was conducted at four different genitourinary medicine clinics in the United Kingdom. Forty-four HIV-infected patients received nevirapine and two nucleoside analogues. Information from case notes regarding age, sex, side effects, viral load, and CD4 lymphocyte counts at baseline, 24 weeks, and 48 weeks was collected and analyzed. Virologic suppression, defined as HIV RNA concentration of less than 400 copies/mL at Weeks 24 and 48, was considered as the main outcome measure. RESULTS: Out of 44 patients, 41 were men with a mean age of 39.3 years (95% CI 36.7-41.8). The baseline viral load was 2.11 x 10(2) to 9.74 x 10(5) copies/mL (median 7.7 x 10(4) and CD4 counts 6 to 605 cells/dL (M = 247; 95% CI 198-295). Of 39 patients who completed 48 weeks of treatment, viral load suppression was attained in 31 patients (79.4%; 95% CI 66.8-92.0) at 24 weeks and in 27 patients (69.2%; 95% CI 54-83) at 48 weeks. The CD4 lymphocyte count increased in 32 (82%) patients (mean 106 cells/dL, 95% CI 73-139, p =.0001, Wilcoxon signed rank test) after 24 weeks and in 33 (84.6%) patients (mean 160 cells/dL, 95% CI 115-204, p =.0001, Wilcoxon signed rank test) after 48 weeks of treatment. Of 20 patients whose baseline viral load was <100000, 16 had viral load suppressed at 24 weeks and 15 at 48 weeks (p =.6, chi-square test). CONCLUSION: A regime of nevirapine with two nucleoside analogues provided durable suppression of plasma viral load in HIV infected patients, with significant improvement in the CD4 cell count.

Adult↗