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Biomedical subjects

C J Pearce

Publications and source records attributed to C J Pearce.

At least 19 recordsLinked to original sources

Calcium antagonists and the kidney.

Calcium antagonists have evolved as an important class of cardiovascular therapeutic agents. Usefulness in treating hypertension, angina pectoris, and cardiac arrhythmias has been established. Investigations show that calcium antagonists have a role in altering renal functions. They are natriuretic and may benefit salt-sensitive hypertensives. They have been shown to block vasoconstriction of the afferent arteriole in the presence of constrictors such as endothelin, thromboxane, norepinephrine, and angiotensin II. These vasoconstrictors may be mediators of nephrotoxins such as radiocontrast agents, and cyclosporine A. Actions of calcium antagonists which are being investigated for potential benefit in ameliorating chronic renal disease include: preventing glomerular hypertrophy, blocking angiotensin II-mediated macromolecule entry into mesangial cells and cytokine release, free-radical scavenger activity, and decreasing calcium deposition within the kidney. Slowing the progression of renal disease with the calcium antagonists has been demonstrated in both short- and long-term trials. Further studies are currently underway.

Animals↗

Paraprotein interference causing pseudohyperphosphataemia: evaluation of an improved methodology.

The measurement of serum inorganic phosphorus by direct acid/molybdate assay is known to be subject to interference by some serum paraproteins. Serum samples from 45 paraproteinaemic patients were used for the measurement of inorganic phosphorus using a manufacturer's kit reagent and a detergent-modified reagent from the same manufacturer. In addition, the same samples were analysed with both reagents following precipitation of serum protein with trichloroacetic acid. Using the original reagent pseudohyperphosphataemia was found in 27% (12/45) of the samples. The modified reagent was free from interference with no significant difference between results from serum and protein-free supernatants.

Blood Proteins↗

Isolation, characterization and structure of a new allenic polyine antibiotic produced by fungus LL-07F275.

Antibiotic 07F275 (1), produced by submerged fermentations of fungal culture LL-07F275, was isolated and characterized despite its inherent instability. Its UV spectrum was identical with that of nemotin, a member of the allenic polyacetylene family, but a molecular weight of 218 daltons indicated a new compound. Structure 1 was determined on the basis of spectroscopic evidence, particularly NMR. Since 1 is a thirteen carbon-containing allenic diyne, it is closely related to mycomycin.

Alkynes↗

Martinomycin, a new polyether antibiotic produced by Streptomyces salvialis. I. Taxonomy, fermentation and biological activity.

Actinomycete culture LL-D37187 has been found to produce the new polyether antibiotic martinomycin. Taxonomic studies, including morphological, physiological, and cell wall chemistry analyses, revealed that culture LL-D37187 is a novel streptomycete species, and the proposed name is Streptomyces salvialis. Martinomycin exhibits activity against the Southern Army Worm (Spodoptera eridania) and Gram-positive bacteria.

Animals↗

Glycothiohexides, novel antibiotics produced by "Sebekia" sp. LL-14E605. I. Taxonomy, fermentation and biological evaluation.

The new glycothiohexide antibiotics, which are related to nosiheptide, were identified in fermentations of an actinomycete belonging to the genus "Sebekia". Strain LL-14E605 was classified as a "Sebekia" based on the presence of both mesodiaminopimelic acid and madurose in the cell wall and the presence of pseudosporangia encasing the spores. Culture LL-14E605 was successfully fermented in 10 to 3,000 liters of a complex medium. Antibiotic activity closely followed cell mass accumulation and usually peaked after 4 to 5 days of incubation. Glycothiohexide alpha demonstrated excellent in vitro activity against Gram-positive bacteria with MICs of 0.03 to 0.06 microgram/ml against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. However, glycothiohexide alpha failed to protect mice against a lethal challenge with Staphylococcus aureus Smith unless it was administered prior to challenge.

Actinomycetales↗

Renal failure and hyperkalemia associated with ketorolac tromethamine.

Three patients who were treated with ketorolac tromethamine (Toradol), an injectable nonsteroidal anti-inflammatory drug for pain management, developed acute renal failure or hyperkalemia or both. These complications were reversible in two cases after discontinuing the drug. Clinical conditions preexisted in each patient that rendered them susceptible to the renal complications of nonsteroidal anti-inflammatory use. It is well known that caution should be observed while using nonsteroidal anti-inflammatory drugs in patients whose renal function may be preserved through prostaglandin-mediated vasodilatory effects. The same cautions apply to ketorolac. Since its major marketed use is as an analgesic and its potent effect on prostaglandin synthesis may not be well recognized, those cautions must be emphasized.

Acute Kidney Injury↗

Hypercalcaemia due to calcium binding by a polymeric IgA kappa-paraprotein.

Total serum calcium concentration was raised in a 63-year-old lady with multiple myeloma and markedly elevated serum IgA kappa-paraprotein concentration. Symptoms of hypercalcaemia were absent, and serum ionized calcium was normal, suggesting calcium binding by the abnormal protein. This was demonstrated directly after isolation of the paraprotein and characterization of the calcium/protein interaction. After reduction of the paraprotein with mercaptoethanol, sodium dodecyl sulphate polyacrylamide gradient gel electrophoresis revealed two bands corresponding to light and heavy chains, but under non-reducing conditions the isolated paraprotein migrated in a series of bands, possibly representing polymeric forms of the basic immunoglobulin moiety.

Aged↗

The effect of methylation inhibitors on citreamicin biosynthesis in Micromonospora citrea.

When the citreamicin-producing organism Micromonospora citrea NRRL 189351 was incubated in the presence of the methylation inhibitors sinefungin or aminopterin, biosynthesis of the zeta component was stimulated approximately 20 to 200-fold above the level normally produced. Inhibition of a second methylation reaction, which is superficially very similar to the first, was not detected. Other known methylation inhibitors failed to yield any change in the natural pattern of citreamicins produced. This approach is an excellent route for preparing citreamicin zeta, which can be used as a substrate for semi-synthesis or for further biosynthetic studies.

Adenosine↗

The effects of mercuric chloride on calmodulin-mediated Ca2+ transport in rat brain.

We have shown previously that mercuric chloride (HgCl2) inhibits in vitro vasopressin release from the isolated rat neurohypophysis with maximum inhibition occurring with 0.5 mM HgCl2. Associated with the inhibition of hormone release is an increase in 45Ca+2 uptake, an increase in cytosolic 45Ca+2, and a reduction of 45Ca+2 accumulation by mitochondria in the intact gland. In the present series of studies, the effect of HgCl2 on calmodulin (CM) function in neural tissue preparations is reported. Mercuric chloride (0.5 mM) reduced 45Ca+2 binding to CM purified from bovine neurohypophyses by 20% and inhibited endogenous CM-stimulated Ca,Mg-ATPase activity from rat brain mitochondria in a dose-dependent fashion. Ca,Mg-ATPase activity was inhibited by 50 and 80% with 0.5 and 5.0 mM HgCl2, respectively. CM-stimulation of Ca,Mg-ATPase activity was inhibited by calmidazolium (CMZ) with maximal inhibition seen with 0.1 mM CMZ. Reversibility of the HgCl2 interaction with CM was demonstrated using CM-stimulated phosphodiesterase (PDEase) activity from rat brain. HgCl2 inhibited both basal and CM-stimulated PDEase activity in a dose-dependent manner with maximum inhibition occurring with 1.0 mM HgCl2. Preexposure of CM to an inhibitory concentration (1.0 mM) of HgCl2 resulted in no loss of stimulatory PDEase enzyme activity. From these results, we conclude that HgCl2 reversibly interferes with 45Ca+2 binding to CM and also inhibits CM-regulated Ca+2 pumping enzyme systems in the neurohypophysis. The inhibition of vasopressin release from the intact gland in the presence of HgCl2 thus, may be associated with a disruption of calcium in the neurohypophysis.

Animals↗

Ehrlichiosis: a cause of bone marrow hypoplasia in humans.

Infection with Ehrlichia canis should be suspected in patients with fever, headache, malaise, leukopenia, thrombocytopenia, and a history of recent exposure to ticks. The cytopenia is caused by bone marrow hypoplasia which may be severe. The disease may be confused with spotless Rocky Mountain spotted fever but can be differentiated from this infection serologically with acute and convalescent sea. In humans, recovery has occurred with and without antibiotic therapy. However, prompt antibiotic therapy is advised prior to serologic studies, especially in immunocompromised individuals, splenectomized persons, and patients with AIDS-who may develop a more overwhelming rickettsial infection.

Bone Marrow↗

Mercuric chloride inhibition of vasopressin release from the isolated neurointermediate lobe of the rat pituitary.

The effects of HgCl2 and ouabain on vasopressin release and Ca2+ uptake and distribution was examined in the neurointermediate lobe of the rat pituitary. HgCl2 (0.5 mM) inhibited vasopressin release by approx. 90% in both basal and potassium depolarized states. With 0.1 mM HgCl2 vasopressin release was inhibited by 50% in the depolarized state, but release was not effected in basal state. On the other hand, ouabain (0.5 mM) caused a 3-fold stimulation of vasopressin release in the depolarized state. Both HgCl2 (0.5 mM) and ouabain (0.5 mM) increased net 45Ca+2 uptake by about 80% in groups of neurointermediate lobes. Following 45Ca+2 uptake, HgCl2 (0.5 mM), which is absorbed by the neurointermediate lobe, produced an increase in cytosolic 45Ca+2 content and a decrease in mitochondrial 45Ca+2 content compared to control. In comparison, ouabain (0.5 mM), which does not penetrate the neurointermediate lobe, gave no change in cytosolic 45Ca+2, but an increase in mitochondrial 45Ca+2. These results suggest that HgCl2 inhibits vasopressin release from the neurointermediate lobe of the rat pituitary at a point distal to Ca+2 uptake by the gland.

Animals↗