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Biomedical subjects

M Weller

Publications and source records attributed to M Weller.

At least 379 records · Page 21Linked to original sources
PubMed1973

Protein kinase activity in membrane preparations from ox brain. Stimulation of intrinsic activity by adenosine 3':5'-cyclic monophosphate.

1. Properties of the stimulation by cyclic AMP of the intrinsic protein kinase activity of membrane fragments from ox brain were studied. 2. Stimulation of activity declined from about 100% at 1min to less than 20% at 10min. The time-course was explained by the observation that cyclic AMP did not stimulate turnover of protein-bound serine phosphate once the membrane protein was fully phosphorylated. 3. Cyclic AMP accelerated the activity of a component of the basal activity rather than activating a different kinase. 4. The pH optimum for both the stimulated and basal activities was 7.2-7.4. NaCl (100mm) and KCl (10-100mm) inhibited the stimulated activity but did not affect the basal activity. 5. Strychnine and theophylline inhibited both activites equally, but the stimulated activity was more sensitive to inhibition by adenosine, bicuculline, vinblastin, veratrine, N-ethylmaleimide and cysteine. 6. No firm evidence for a role for endogenous cyclic AMP in the basal activity was found, but the possibility was not excluded. 7. Some 90% of both the stimulated and basal activities remained in an insoluble form after treatment of the membrane fragments with Triton X-100 (0.5%).

Adenosine↗
PubMed1973

The state of phosphorylation in vivo of membrane-bound phosphoproteins in rat brain.

The alkali-labile P content of membrane protein prepared from rapidly frozen rat brain was measured, CuSO(4) being used to inhibit protein phosphatase activity during subcellular fractionation. The P content of the membrane fraction was significantly increased (+12%) over the control value by incubation of homogenates with ATP before fractionation. This suggests that the membrane protein in rat brain is normally only partially phosphorylated.

Animals↗
PubMed1972

Determination of adenosine 3':5'-cyclic monophosphate in cerebral tissues by saturation analysis. Assessment of a method using a binding protein from ox muscle.

1. The Gilman (1970) procedure for determining cyclic AMP (adenosine 3':5'-cyclic monophosphate) by saturation analysis gave erroneous results when applied to the analysis of extracts of whole brain or preparations of membrane fragments from brain. 2. The extracts contained a non-diffusible factor, which enhanced the binding of cyclic AMP by the muscle protein fraction. 3. Extracts also contained material which inhibited binding, but net inhibition of binding was only observed when relatively concentrated extracts were analysed. 4. The error introduced by the factors modifying binding could be eliminated by incorporation of unlabelled internal standards in the unknowns. The design adopted enables a statistical estimate to be made of the standard error of a single assay. 5. The modified assay was used to determine bound cyclic AMP and adenylate cyclase activity in cerebral membrane fragments. Five preparations of synaptic membrane fragments contained less than 3.5pmol of cyclic AMP/mg of protein; a microsomal fraction from rat contained 65pmol of cyclic AMP/mg of protein.

Adenosine Triphosphate↗
PubMed1971

Turnover of protein-bound phosphorylserine in membrane preparations from ox brain catalysed by intrinsic kinase and phosphatase activity.

1. The turnover of protein-bound phosphorylserine in preparations of membrane fragments from ox brain cortex was studied. 2. Turnover was considered to arise from the action of intrinsic protein kinases and phosphatases on a membrane protein or proteins. 3. Properties of the kinase system were studied by measuring the rate of incorporation of (32)P from gamma-labelled ATP into protein-bound phosphorylserine isolated from partial acid hydrolysates of membrane proteins. 4. Properties of the phosphatase system were studied by observing the rate of loss of (32)P from membrane preparations pre-labelled with [(32)P]ATP. 5. Net phosphorylation and dephosphorylation of membrane protein was observed during incubation of membrane preparations with and without ATP. 6. The rate of turnover was about 4nmol of P/h per mg of protein at 20 degrees C; dephosphorylation was considered to be the rate-limiting step.

Adenosine Triphosphate↗
PubMed1970

Ageing.

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Aging↗
PubMedDate not supplied

Psychosis and destitution at Christmas 1985-88.

Surveys of the destitute were conducted over four successive Christmas periods in Central London, UK. Functional psychosis with hallucinations and/or delusions, either current (19%) or in the past (22%), were associated with extreme social isolation and imprisonment.

Bias↗
PubMedDate not supplied

New aspects of immunotherapy of leptomeningeal metastasis.

Immunotherapeutic approaches to leptomeningeal metastasis (LM) include the intrathecal application of cytokines such as interleukin-2 (IL-2) and interferon-alpha (IFN-alpha), and lymphokine-activated killer cells (LAK cells). Results in a rodent model of leptomeningeal gliomatosis with intrathecal IL-2 application are discouraging, but some clinical improvement and clearance of neoplastic cells from CSF have been seen in patients with LM from melanoma treated with intrathecal IL-2 alone, and in patients with LM from primary brain tumors and squamous cell carcinoma of the tongue treated with intrathecal LAK cells and IL-2. The neurotoxicity of this therapy, mainly increased intracranial pressure, has been considerable but generally manageable. However, IFN-alpha caused severe neurotoxicity in form of an only partly reversible progressive vegetative state in the majority of patients. Considering the small number of patients treated with IL-2 and LAK cells, its value for the treatment of LM could only be stated by further investigation. In future, the application of recently discovered cytokines such as Fas-ligand, the continuous paracrine cytokine release by genetically modified cells, or vaccination strategies using genetically modified tumor cells might offer new immunotherapeutic approaches in LM.

Animals↗