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Biomedical subjects
Publications and source records attributed to R Jones.
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Indicine N-oxide, a pyrrolizidine alkaloid, was given to a five-year-old boy with refractory acute myelocytic leukemia. Three days after receiving the drug the patient developed signs and symptoms of acute hepatic failure. The patient died nine days after receiving the drug and an autopsy showed massive hepatic necrosis. The acute hepatic failure observed in this patient may have been secondary to indicine N-oxide toxicity.
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We have used monoclonal antibodies to study the mobility and distribution of three different antigens on the cell surface of rat spermatozoa. We classified two of the antigens (designated 2B1 and 2D6) as 'mobile', since when detected by indirect immunofluorescence they were situated over the entire sperm flagellum and were susceptible to antibody-induced patching. Patching was critically dependent upon antibody concentrations and was much reduced at 4 degrees C. Patching of the 2B1 antigen was not induced by the 2B1 monoclonal antibody alone. Thus, 2B1 antibody labelled directly with fluorescein bound with a uniform distribution over the sperm flagellum, but this uniform fluorescence was made patchy on subsequent incubation in an unlabelled second antibody layer of anti-mouse IgG anti-serum. By 'Western blotting', the 2B1 antigen was found to be located to a 40 kD molecular weight polypeptide. The remaining 'fixed' antigen (designated 1B6) was not susceptible to antibody-induced patching, and was restricted to a discrete domain on the post-acrosomal region of the sperm surface. We discuss the relationship between mobility of sperm surface antigens and their segregation to discrete domains on the plasma membrane.
The physiological, pharmacological and morphological characteristics of guinea-pig vas deferens supplied by hypogastric nerves rendered inactive by decentralisation were compared with those of vas deferens in which the nerve supply had been chronically stimulated for 3-9 days using implanted electrodes. No change was seen in decentralised preparations prior to 7 days, but from 8-15 days, increased sensitivity to application of noradrenaline in vitro was observed, which was shown to be related to reduced transmitter uptake by nerve terminals as well as to an increase in postjunctional sensitivity; there was also increased fatigability 7-14 days following decentralisation. Continuous stimulation of hypogastric nerves at 2 Hz for 4-8 h daily for 4-8 days resulted in enhanced transmitter uptake and reduced responses to noradrenaline; this was associated with a slight increase in noradrenaline content and a faster adrenergic neuromuscular response with a shorter latency. No appreciable changes in nerve or muscle structure studied by electron microscopy were observed following decentralisation, but there was an increase of between 12.5 and 29.6% in the number of close (less than 100 nm) neuromuscular junctions following chronic stimulation for 8 days.
Previous studies have shown that minced regenerating smooth muscle of the guinea-pig vas deferens becomes reinnervated by nerves growing in from the surrounding intact vas deferens. Using electron microscopy, we have examined the effect of altering activity in the preganglionic nerves, either by decentralisation, or by chronic stimulation of the hypogastric nerve, in vivo, on the reinnervation of regenerating smooth muscle cells. Chronic stimulation induced earlier reinnervation than that seen in unstimulated (sham-operated) or decentralised preparations; the number of nerve profiles present in four preparations stimulated for up to 7 days was approximately 10-20 times that seen in unstimulated or decentralised preparations. However, electron micrographs revealed that "empty" nerve terminals were a feature following stimulation for longer periods. Decentralised preparations showed little change of reinnervation, at least up to 7 weeks. Compensatory changes in the density of innervation were found in the unstimulated contralateral vas deferens.
Although ventricular dysfunction is suspected to underlie congestive heart failure in sickle cell anemia (SCA), ejection indexes of left ventricular (LV) pump performance have been found to be normal. The increased preload and decreased afterload of SCA increases the ejection phase indexes and might obscure true LV dysfunction. Therefore, the preload and afterload independent end-systolic stress-volume index was compared in 11 patients with SCA and in 11 normal volunteers. End-systolic pressure and echocardiographic LV dimensions were determined during rest, leg raise, hand-grip and amyl nitrite inhalation. Systemic vascular resistance (afterload) was decreased to 1,033 +/- 314 dynes s cm-5 (mean +/- standard deviation) in SCA from 1,701 +/- 314 dynes s cm-5 in normal subjects. End-diastolic volume index (preload) was increased to 102 +/- 24 ml/m2 in SCA from 66 +/- 10 ml/m2 in normal subjects. Cardiac index was increased to 4.7 +/- 1.1 liters/min/m2 in SCA from 2.8 +/- 0.8 liters/min/m2 in normal subjects. Ejection fractions were similar: 0.59 +/- 0.09 in SCA versus 0.62 +/- 0.07 in normal subjects. However, in patients with SCA, the ratio of resting end-systolic stress-volume index was decreased (1.5 +/- 0.5 in SCA versus 2.8 +/- 0.6 in normal subjects) and the slope of the end-systolic stress versus end-systolic volume index relation was decreased (2.7 +/- 1.3 in SCA versus 4.4 +/- 1.8 in normal subjects), suggesting LV dysfunction in those patients. Thus, LV muscle contractile performance is depressed in SCA. Increased preload and decreased afterload compensate for the LV dysfunction and maintain a normal ejection fraction and high cardiac output.
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The effects on growth, body composition, and metabolism of a protein-restricted diet supplemented with essential aminoacids, the calcium-ketoacids of valine, leucine, isoleucine, and phenylalanine, and the calcium-hydroxyacid of methionine, were investigated in seven growth-retarded children with chronic renal failure. During 0.4 to 1.0 years of treatment there were significant increases in growth velocity and upper arm circumference SD scores, body cell mass (intracellular water calculated as tritium space minus corrected sodium bromide space) and serum transferrin. Blood urea and urea:creatinine ratio fell in all children. Renal function assessed from plasma creatinine and 51Cr EDTA clearance did not change significantly. During treatment there was an increase in plasma calcium, high levels necessitating brief interruption of therapy in two children, and a decrease in plasma phosphate. Levels of serum parathormone fell in all children, and were correlated inversely with plasma calcium and positively with plasma phosphate. Abnormalities compared to control children in blood aminoacid and branched-chain ketoacid levels were unaffected by treatment. These results suggest that a protein-restricted diet supplemented with essential aminoacids and calcium-keto and hydroxyacids may be useful to improve linear growth and nutritional status in children with chronic renal failure, and that a reduction in hyperparathyroidism may be partly responsible for some of the beneficial effects observed.
Glycoproteins on the plasma membrane of testicular and cauda epididymidal spermatozoa have been labeled with galactose oxidase/NaB [3H]4 and sodium metaperiodate/NaB[3H]4, followed by analysis on SDS polyacrylamide gels. The major glycoprotein labeling on testicular spermatozoa has a molecular weight 110,000 whereas on cauda epididymidal spermatozoa greater than 90% of the radio-label is incorporated into proteins of molecular weight 32,000. These 32,000-mol wt X proteins are homologous with proteins of similar molecular weight purified from the epididymal secretion and which have been shown previously to be synthesized in the caput epididymidis under hormonal control. Immunofluorescence revealed that the 32,000-mol wt proteins are present on the flagellum of mature but not immature spermatozoa and that they have a patchy distribution suggesting that they are mobile within the plane of the membrane. The membrane-bound 32,000-mol wt proteins possess hydrophobic domains as revealed by charge-shift electrophoresis and they also label with a lipophilic photoaffinity probe suggesting that they are in contact with the lipid bilayer. The evidence indicates that there is a considerable reorganization of the molecular structure of the plasma membrane of spermatozoa during maturation in the epididymis and that some of the changes are brought about by a direct interaction with epididymal secretory proteins.
Using a laser cytopherometer, the electrophoretic mobility of glutaraldehyde-fixed erythrocytes from patients with multiple sclerosis (MS) has been compared with that of cells from control subjects. The effect of incubating cells with different concentrations of linoleic acid (LA) has been tested. At a concentration of 20 micrograms LA per 2 x 10(7) cells, slower mobilities were observed, on average, than those of control subjects, but there was overlap between control and patient groups. At a higher concentration of LA (160 micrograms per 2 x 10(7) cells), many of the MS samples showed a slower mobility than the control samples, although overlap was still evident. The value of the application of laser cytopherometry compared with conventional cytopherometry to this type of test is discussed.
Thirty-four patients with advanced adenocarcinoma of the gastrointestinal tract have been treated with high-dose 5-fluorouracil modulated by concomitant allopurinol therapy, in combination with either razoxane or adriamycin. These regimens offer no advance over current treatment.
Gene coding assignments for growth restriction, neutralization and subgroup specificities were determined for two human rotavirus strains, DS-1 and W, which represent two distinct serotypes. The 4th gene segment of both viruses was associated with restriction of growth in cell culture. The 9th gene segment of W virus and 8th segment of DS-1 were associated with serotype specificity, while the 6th gene segment of W virus was associated with subgroup specificity.
Two newborn infants had isolated radial nerve lesion documented on electromygraphy. Fibrillation potentials present in one child at age 6 days suggest the possibility of an in utero onset. Skin necrosis present above the triceps muscle and radial nerve favors an entrapment mechanism, possibly from the umbilical cord. Because both patients had complete resolution in 4 months, it is important to differentiate this lesion form the more common but more serious medial brachial plexus lesion.
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Spermatozoa from the testis and cauda epididymidis were solubilized by detergent treatment and electrophoresis on SDS polyacrylamide gels revealed that the relative amounts of 13 detergent-extractable proteins decreased during passage of spermatozoa through the epididymis, 6 increased, whilst the remainder showed little or no change. Lactoperoxidase-catalysed iodination of plasma membrane proteins showed that the components carrying most of the label in testicular spermatozoa had Mr values of 110 000, 94 000, 84 000, 55 000 and 42 000 whereas on cauda epididymal spermatozoa the Mr values were 47 000, 24 000, 17 000, 14 500 and 13 500. Substantial differences were also noted in the protein composition of rete testis fluid and cauda epididymal plasma. The results support the concept that there is a considerable reorganization of the molecular architecture of the plasma membrane of spermatozoa during maturation in the epididymis.