Search PubMed⌕ Search

Biomedical subjects

D J Mann

Publications and source records attributed to D J Mann.

22 records · Page 2Linked to original sources

Skeletal buffer function and symptomatic magnesium deficiency.

A major factor relating to the oversight of neurological dysfunction and seizures caused by magnesium (Mg++) depletion, involves the buffer functions of the skeletal system orchestrated primarily by the parathyroid. A Mg++ depleted subject may appear relatively asymptomatic until a short period after homeostatic responses go into effect. The results can be devastating if not recognized promptly and treated appropriately. This series of events can best be demonstrated in veterinary medicine but we propose that analogous syndromes occur in clinical medicine. Evidence is presented to support the hypothesis that in subjects with parathyroid hyperactivity and Mg++ deficiency, the stimulus of a rise in serum ionic calcium (Ca++), and the resultant inhibition of parathyroid hormone (PTH) secretion, trigger the transfer of Ca++, Mg++ and other ions from the extracellular space into the exchangeable bone compartment. More importantly, there is a transfer of Mg++ ions from the cerebrospinal fluid into the blood and ultimately into the bone compartment. If the gradient is large and the stimulus adequate, neurological signs and symptoms may be induced. The degree of Ca++ and Mg++ depletion of the peripheral bone and the amount and duration of Ca++ ion increase largely determine the duration and severity of symptoms. The symptom complex is facilitated by sympathetic stimulation. An analogous situation may exist with sodium (Na+).

Animals↗

Protein serine/threonine phosphatases; an expanding family.

Five protein serine/threonine phosphatases (PP) have been identified by cloning cDNA from mammalian and Drosophila libraries. These novel enzymes, which have not yet been detected by the techniques of protein chemistry and enzymology, are termed PPV, PP2Bw, PPX, PPY and PPZ. The complete amino acid sequences of PPX, PPY and PPZ and an almost complete sequence of PPV are presented. In the catalytic domain PPV and PPX are more similar to PP2A (57-69% identity) than PP1 (45-49% identity), while PPY and PPZ are more similar to PP1 (66-68% identity) than PP2A (44% identity). The cDNA for PP2Bw encodes a novel Ca2+/calmodulin-dependent protein phosphatase only 62% identical to PP2B in the catalytic domain. Approaches for determining the cellular functions of these protein phosphatases are discussed.

Amino Acid Sequence↗

Modification of WR-2721 toxicity and radioprotection by an inhibitor of alkaline phosphatase.

We used levamisole, an inhibitor of alkaline phosphatase, to study the role of that enzyme in mediating the metabolic activation, toxicity, and radioprotection of WR-2721 in intact mice. We found the toxicity of WR-2721 was slightly decreased by prior subcutaneous (SQ) injection of 40 mg/kg of levamisole. In studying the effect of levamisole on WR-2721 radioprotection, we found that intraperitoneal (i.p.) injection of levamisole had little or no effect on radioprotection of the gastrointestinal and the hematopoietic systems. Even this small reduction of protection was due in part to the toxicity of levamisole as demonstrated when levamisole was injected following, rather than before, WR-2721-radiation treatment. To determine whether levamisole inhibited the activation (i.e., dephosphorylation) of WR-2721 to WR-1065, we assayed WR-1065 in the jejunum using an HPLC electrochemical assay. SQ injection of 75 mg/kg levamisole 10 min prior to WR-2721 reduced the WR-1065 observed 10 min after WR-2721 administration by 37%. In conclusion, levamisole appears to be too toxic and non-specific to be useful in studying and regulating the metabolism, toxicity and radioprotection of WR-2721.

Alkaline Phosphatase↗

Presence of neuromedin B-like immunoreactivity in the brain and gut of rat and guinea-pig.

A recently developed specific radioimmunoassay for neuromedin B, originally isolated from porcine spinal cord, was used to investigate its distribution in rat and guinea-pig brain and gut. In both species, neuromedin B-like immunoreactivity was present in several regions of brain, and high concentrations occurred in the pituitary. The immunoreactivity was widely distributed throughout the entire length of gastrointestinal tract and pancreas, and relatively high concentrations were found in the oesophagus and rectum. Immunocytochemistry localised neuromedin B-like immunoreactivity to nerve fibers in the rat brain and gut. Immunoreactive fibres were visualized in the medial thalamus and were found very frequently in the circular muscle of the gut. Gel permeation chromatography of pituitary and intestinal extracts from both species revealed presence of two peaks of neuromedin B-like immunoreactivity, the later of which co-eluted with the synthetic porcine neuromedin B standard. Reverse phase high pressure liquid chromatography showed that material corresponding to the later peak was eluted in the exact position of synthetic porcine neuromedin B, whereas the larger molecular size material from the earlier peak was more hydrophobic in nature.

Amino Acid Sequence↗