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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
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1986

Serum iodothyronine concentrations during introduction of thyroxine replacement therapy in hypothyroidism.

Serum concentrations of total and free T4 (TT4 and FT4), total and free T3 (TT3 and FT3), rT3, T4 binding globulin (TBG), T3 uptake (T3U) and TSH were measured in 12 patients with severe hypothyroidism before and during the introduction of replacement therapy with oral T4. The dose of T4 was increased by increments of 50 micrograms at intervals of 4 weeks to a total of 200 micrograms daily. There was a linear correlation between the concentrations of FT3 and FT4 (FT3 = 1.35 + 0.23FT4, r = 0.916, P less than 0.001). The correlation between TT3 and TT4 was more complex: the data were best fitted by the expression TT3 = 0.195 square root TT4, (r = 0.936, P less than 0.001). The relatively greater rise in TT3 initially may reflect a greater binding of T3 by TBG when the concentration of T4 is low. TBG concentration fell after 50 and 100 micrograms of T4 but did not change at the higher doses. There was a simple linear relation between TT4 and rT3 (rT3 = -0.022 + 0.0027TT4, r = 0.921, P less than 0.001). The expected inverse relation between TSH concentration and the thyroid hormones was seen, the three closest correlations being between the logarithm of the TSH concentration and FT3, the ratio T4/TBG and FT4 (r = 0.927, -0.917 and -0.900 respectively). These correlations were significantly better (P less than 0.05) than the correlations with untransformed TSH values. Suppression of TSH occurred while FT3 tended to remain within normal limits, but FT4 was often raised.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The effect of amiodarone on thyroxine kinetics.

Amiodarone was given by daily intraperitoneal injection (10 mg/kg body weight) to a group of 11 New Zealand white rabbits. Over 6 weeks there were significant increases (P less than 0.01) in plasma total T4 concentration (43 +/- 8 to 60 +/- 13 nmol/l; mean +/- 1 SD) and rT3 concentration (0.12 +/- 0.06 to 0.31 +/- 0.16 nmol/l) and a significant fall in total plasma T3 (2.3 +/- 0.3 to 1.7 +/- 0.2 nmol/l). The plasma clearance of T4 in rabbits treated with amiodarone for 6 weeks was significantly reduced relative to controls (64 +/- 25 vs 109 +/- 19 ml/kg per day, P less than 0.01) but the production rate was unchanged (3.8 +/- 1.8 vs 3.7 +/- 1.4 nmol/kg per day). In the amiodarone treated animals the increased plasma T4 concentration was entirely accounted for by the reduced clearance. It is inferred that the normal output of T4 by the thyroid is pituitary dependent and that TSH secretion is sustained in the presence of hyperthyroxinaemia because of amiodarone induced partial inhibition of T4 utilization by the thyrotroph.

Amiodarone↗
PubMed1985

Iodothyronine kinetics in the rabbit: an experimental model.

Turnover studies of thyroxine (T4), 3,5,3'-tri-iodothyronine (T3) and 3,3',5'-tri-iodothyronine (rT3) have been performed in the rabbit. A novel modification of a conventional radioimmunoassay has been used to measure specific 125I-labelled iodothyronines in small volumes of plasma in the presence of other 125I-labelled metabolites. Kinetic analysis of plasma disappearance of tracer was performed by a new theoretical approach. For T4 the mean (+/- S.D.) plasma concentration, clearance and production rates were 34 +/- 12 nmol/l, 109 +/- 19 ml/kg per day and 3.7 +/- 1.4 nmol/kg per day respectively (n = 9). For T3 the corresponding values were 2.04 +/- 0.42 nmol/l, 1.52 +/- 0.29 litres/kg per day and 3.07 +/- 0.76 nmol/kg per day (n = 8), and for rT3 0.12 +/- 0.04 nmol/l, 5.7 +/- 1.7 litres/kg per day and 0.69 +/- 0.23 nmol/kg per day (n = 8). The combination of these two new methodologies affords a simple and convenient means of studying iodothyronine metabolism under normal and abnormal conditions. The techniques employed may be generally applied to turnover studies of other compounds of physiological interest which can be measured by radioimmunoassay.

Animals↗
PubMed1978

Sub-unit assembly in the biosynthesis of neomycin. The synthesis of 5-O-beta-D-ribofuranosyl and 4-O-beta-D-ribofuranosyl-2,6-dideoxystreptamines.

The preparation of the deoxy- analogues of two pseudodisaccharide fragments of neomycin, 5-O-beta-D-ribofuranosyl-2,6-dideoxy-streptamine and 6-deoxyneamine is described. When added to the growth medium of a deoxystreptamine-idiotroph of Streptomyces rimosus forma paromomycinus only the latter was incorporated into antibiotic, suggesting an obligatory order for the assembly of sub-units. 4-O-beta-D-Ribofuranosyl-2,6-dideoxystreptamine was also prepared. When added to the growth medium of a deoxystreptamine-idiotroph of Streptomyces fradiae it was converted into the 6-deoxyneomycins, apparently after hydrolysis to 2,6-dideoxystreptamine. The structure of the protected derivatives of the ribofuranosyl 2,6-dideoxystreptamines, potentially useful intermediates for the synthesis of novel antibiotics, was shown by using 15C NMR spectroscopy.

Hexosamines↗
PubMed1976

The role of the pseudo-disaccharide neamine as an intermediate in the biosynthesis of neomycin.

By using wild-type and deoxystreptamine-negative mutants of Streptomyces fradiae grown in media containing [6(-3)H]glucose or [U-14C]glucose, and by subsequent hydrolysis of the labelled neomycin produced, neamines labelled with 3H in both rings I and II, but with 14C in ring I only, were prepared. A mixture of these two forms of neamine was converted by deoxystreptamine-negative Streptomyces rimosus forma paromomycinus into neomycin (not paromomycin) with a 30% yield. The3H: 14C ratio in this neomycin was the same as the measured in neamine produced by hydrolysis of the neomycin, and in unused neamine reisolated from the incubation medium. The 3H:14C ratio in the neomycin was not affected by the presence of unlabelled deoxystreptamine during the incubation. The radioactivity in the neomycin was associated with rings I and II only. It is concluded that the added neamine is incorporated into antibiotic intact, without initial hydrolysis, and that the probable first step in the subunit assembly of neomycin is the formation of neamine.

Disaccharides↗