Biomedical subjects
Publications and source records attributed to M Newman.
Lithium at a therapeutically effective concentration of 1 mM caused significant inhibition of the rise in cyclic AMP induced by noradrenaline in fresh surgically-obtained slices of human brain.
Lithium is a unique drug in its clinical profile in psychiatry. Lithium has numerous biochemical effects, but none has yet been proven to be its mode of therapeutic action. Inhibition of noradrenaline-sensitive adenylate cyclase is reviewed as the only biochemical effect of lithium shown to occur in both animals and man at therapeutic lithium concentrations. A tetracycline antibiotic, demeclocycline, also blocks noradrenaline-sensitive adenylate cyclase. A clinical trial of demeclocycline in mania would provide a test of the adenylate cyclase theory of lithium action.
Normal values for the amplitudes of digital sensory nerve action potentials were obtained from 190 control subjects, using an orthodromic surface-recording technique. Lower limits were calculated, taking into account laterality, age and sex; the ratios of amplitudes between different digits were also estimated. The results in control subjects were compared with those of 20 cases of trauma involving root avulsion or extraspinal injury, 38 patients with intraspinal disease, 6 patients with extraspinal disorder and 9 cases of neuralgic amyotrophy. The variability of the dermatomes is discussed and it is concluded that digital sensory potential amplitudes offer a useful method of determining the site of a nerve lesion, provided certain limitations are recognized.
DNA at the end point of the gene deletion associated with one form of hereditary persistence of fetal hemoglobin (HPFH) was cloned and used as a probe in gene mapping experiments to analyze the extent and approximate 3' end points of various deletions associated with HPFH and delta beta-thalassemia. The deletions in the two known forms of deletion-type HPFH were shown to be considerably more extensive than in the two cases of delta beta-thalassemia studied. The overall extents of the deletions in the two types of HPFH were quite similar in both cases and the 3' end points were located at a minimum distance of approximately equal to 52 and 57 kilobases from the 3' extremity of the beta-globin gene. In contrast, the 3' end points of the deletions in the two forms of delta beta-thalassemia were located approximately equal to 5 and 10 kilobases to the 3' side of the beta-globin gene. The extent of these deletions and the nature of the DNA brought into the vicinity of the gamma-globin genes by the deletions may therefore be a more important influence on the phenotype of the deletions than the specific nature of the DNA sequences that are deleted within the non-alpha-globin gene cluster as a result of the mutations.
Explore the source record for details and available documents.
High affinity binding sites for [3H]adenosine in rat brain and in turkey erythrocytes can be identified by binding experiments. Displacement experiments using a number of adenosine analogs indicate that these high affinity sites do not represent the R-type adenosine receptors which mediate activation of adenylate cyclase, although the binding is theophylline sensitive. Similarly, the binding of [3H]adenosine is not to the P-site, which mediates inhibition of adenylate cyclase, since the high affinity binding persists in the presence of 2',5'-dideoxyadenosine. Furthermore, these results remain qualitatively similar also in the presence of dipyridamole which blocks adenosine transport sites. We conclude that theophylline sensitivity does not indicate that [3H]adenosine binding sites correspond to adenosine receptors coupled to adenylate cyclase.
1. Noradrenaline and histamine, when added to superfused guinea-pig cerebral-cortical tissues, increased both cyclic AMP-dependent and -independent histone kinase activities of some, but not of all, subsequently isolated subcellular fractions, and decreased their cyclic [(3)H]AMP-binding capacity, which was concluded to be due to an increase in endogenously bound cyclic AMP. 2. Adenosine and 2-chloroadenosine also diminished the cyclic [(3)H]AMP-binding capacities, but did not affect the histone kinase activities. 3. DEAE-cellulose chromatography and stability to KCl additions showed that the greater part of the histone kinase of the present preparations corresponded to the type II enzyme [of Corbin, Keely & Park (1975) J. Biol. Chem.250, 218-225], with a lesser amount of type I activity. Different sites of cyclic AMP accumulation in relation to these or other kinases are considered in interpreting the differential tissue responses to the neurohumoural agents examined.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
1. The subcellular distribution of cyclic AMP in guinea-pig cerebral-cortical tissue was determined before and after electrical stimulation, and after a period of continued incubation after electrical stimulation, with and without the presence of histamine. 2. Electrical stimulation and histamine increased the cyclic AMP content of all fractions, the greatest increase occurring in the supernatant fraction. 3. Continued incubation after cessation of electrical stimulation diminished the cyclic AMP of the total homogenate and supernatant fractions, but increased that of the synaptosomal fraction. 4. Further fractionation of the synaptosomal fractions from stimulated tissues suggested that most of their soluble cyclic AMP was in a higher-molecular-weight form than was that of the tissue supernatant. 5. It is suggested that protein binding and cytoplasmic transport of cyclic AMP are involved in the changes observed.
Explore the source record for details and available documents.
1. Adenosine was determined in rapidly frozen rat and guinea-pig brain and in guinea-pig cerebral tissues after incubation in vitro. Adenosine concentrations were approx. 2nmol/g wet wt. in frozen tissue, diminished at room temperature, and returned to 2nmol/g on incubation in oxygenated glucose/salines. 2. Superfusion with noradrenaline then increased the tissue's adenosine concentration 2.5-fold, and hypoxia caused an 8-fold increase. 3. Electrical stimulation alone or in the presence of noradrenaline or histamine increased the tissue's adenosine and cyclic AMP, but adenosine concentrations reached their peak later and were maintained for longer than those of cyclic AMP. 4. Superfusion with l-glutamate with and without electrical excitation raised adenosine concentrations to 15-34nmol/g. The increases in cyclic AMP on electrical stimulation, superfusion with glutamate or a combination of these treatments were diminished by addition of adenosine deaminase or theophylline. 5. It is concluded that adenosine can be produced endogenously in cerebral systems, in sufficient concentrations to accelerate an adenosine-activated adenylate cyclase, and by this route can contribute to the cerebral actions of electrical stimulation and of the neurohumoral agents. In certain instances cyclic AMP as substrate contributes to an increase in adenosine.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A group of 238 patients with cerebral palsy were identified of whom 108 could be studied through their charts. Only 20 of these patients had strabismus. Of this group, 10 received no surgical therapy. In these patients followed up to a period of four years, no evidence of significant change in the strabismic deviation was found. Patients who were treated by medical and optical means alone did not show evidence of improvement. Surgical therapy was effective in providing a cosmetically acceptable result. Surgery was performed between two and one-half and 13 years of age in eight patients, with an average age of surgery of 6.5 years. The results which we obtained are comparable to those obtained by others at an earlier age. It does not appear that the age of surgery affects the ultimate cosmetic nor functional outcome in children with cerebral palsy.
Explore the source record for details and available documents.