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Biomedical subjects

N Cole

Publications and source records attributed to N Cole.

27 records · Page 2Linked to original sources

Potassium intake and cardiovascular reactivity in children with risk factors for essential hypertension.

OBJECTIVES: Our study objectives were as follows: (1) to determine whether urinary excretion of potassium is lower in black than in white children, (2) to determine whether cardiovascular reactivity (CVR) varies inversely with dietary intake of potassium, and (3) to confirm that CVR is greater in black than in white children, and in children with a family history of hypertension than in those without such a history. STUDY DESIGN: Baseline measurements included 24-hour urinary sodium, potassium, and creatinine levels and food intake (by questionnaire). Resting and stress blood pressure were measured during blood sampling, cold water foot immersion, and a video game before and after 1 week each of supplementation with potassium citrate, 1.5 mmol/kg per day, and placebo administered in random order. RESULTS: Thirty-nine children aged 7 to 15 years were studied. White subjects had higher baseline excretion of potassium than black subjects (p < 0.001) and higher vegetable intake (p < 0.01), which were positively correlated (r = 0.53, p < 0.001). At baseline, the 24-hour urinary potassium/creatinine ratio varied inversely with diastolic CVR to the video game stressor in white children (r = -0.55, p = 0.02). Cardiovascular reactivity was not attenuated measurably by potassium supplementation compared with placebo. The CVR was greater in children with a family history of hypertension than in those without, but was not greater in black children than in white children. CONCLUSIONS: The urinary potassium/creatinine ratio is higher in white than black children because their intake of vegetables is greater; dietary potassium intake may modulate CVR, particularly in white children with a family history of hypertension, but may need to be supplemented for more than 1 week to demonstrate attenuation of CVR; and a family history of hypertension may be a stronger predictor of enhanced CVR than is race.

Adolescent↗

High-dose cytosine arabinoside in the treatment of acute myeloid leukaemia.

Cytosine arabinoside (Ara-C) has earned its recognition as the most important antileukaemic drug currently available for the treatment of acute myeloid leukaemia. Approximately 60-80% of patients less than 60 years of age can be expected to enter complete remission if treated with standard-dose Ara-C (100-200 mg/m2) in combination with an anthracycline. The efficacy of Ara-C appears clinically to be dose and schedule dependent. A 15-30 fold dose escalation in Ara-C can elicit a therapeutic response in patients who have previously failed treatment with standard-dose Ara-C or other anti-leukaemic drugs. The use of high-dose cytosine arabinoside (HDAC 3 gm/m2) appears rational based on cytosine pharmacology. Drug-scheduling is used to exploit drug synergy when HDAC is given in combination with asparaginase or fludarabine (+/- G-CSF) in a schedule-dependent fashion. Toxicity following Ara-C is also dose- and schedule-dependent. Central nervous system toxicity--particularly cerebellar dysfunction--although rare, is particularly serious because it may preclude further use of the drug. Older patients are particularly susceptible. This article will describe the rationale for and the value of HDAC alone or in combination with other cytotoxics in the treatment of acute myeloid leukaemia.

Acute Disease↗

Temperature and developmental plasticity of muscle phenotype in herring larvae

Myogenesis, the expression of myofibrillar protein isoforms and the development of muscle innervation were investigated in Clyde herring (Clupea harengus L.) in two successive spawning seasons at temperatures ranging from 5 &deg;C to 15 &deg;C. Myotube formation occurred in a rostral to caudal progression at similar somite stages at all temperatures. Superficial mononuclear muscle pioneer fibres were present at the horizontal septum. Myofibrillogenesis was retarded with respect to somite stage at low temperatures; for example, by the 50-somite stage, myofibrils were observed in the muscle pioneers of the first 31 somites at 12 &deg;C, but only the first 20 somites at 5 &deg;C. In the electron microscope, the earliest stages of myofibril assembly were observed in the muscle pioneer cells and in a proportion of the multinucleated myotubes within the same somite. By the end of somitogenesis, the density of myofibrils in the rostral myotomes was much higher at 15 &deg;C than at 5 &deg;C. Embryonic isoforms of myosin light chain 2 (LC2), troponin I and troponin T were identified in the presumptive white muscle using two-dimensional gel electrophoresis. Expression of the embryonic isoforms was gradually switched off during the larval stages. The size range over which embryonic isoforms were present was inversely related to rearing temperature. For example, the adult pattern of myosin LC2 expression was established at 11 mm total length (TL) at 15 &deg;C, but not until 15 mm TL at 5 &deg;C. Acetylcholinesterase staining was apparent at the myosepta in 31-somite stage embryos at 15 &deg;C, but not until approximately the 40-somite stage at 5 &deg;C. The red muscle fibres of larvae were initially innervated only at their myoseptal ends. The temperature at which the red muscle fibres became multiply innervated was inversely related to body size, occurring at 12&shy;14 mm at 12 &deg;C, but not until 16&shy;19 mm at 5 &deg;C. We conclude that the temperature during early development determines the relative timing and degree of expression of the myogenic programme, resulting in significant phenotypic variation in the swimming muscles of the larval stages. Our results highlight a potential mechanism whereby early thermal experience could influence survival and hence the strength of particular year classes of fish.

Journal Article↗

Quantitative assessment of the association of the alpha-I fragment of spectrin with oligomers of intact spectrin.

The alpha-I fragment of human spectrin that carries the binding site on the alpha-chain of spectrin for the beta-chain has been purified from limited trypsin digests of spectrin by means of FPLC. The self-association of spectrin and the binding of the alpha-I fragment to spectrin heterodimers and to tetramers have been quantified through the use of gel electrophoresis, staining with Coomassie Blue, and quantification of the bound dye following elution with pyridine. The parameters of self-association were found to be consistent with those estimated from sedimentation equilibrium analysis. The data were consistent with a model in which both self-association and the binding of the alpha-I fragment are considered to occur through an intermediate in which the alpha-beta interface is initially dissociated. The alpha-beta interface in the heterodimer was found to be less stable than that of higher oligomers by approx. 3 kJ/mol.

Binding Sites↗

Enhancement of self-association of human spectrin by polyethylene glycol.

1. In the presence of polyethylene glycol, the self-association of human spectrin is enhanced in a manner that depends approx. exponentially on the mass concentration of polyethylene glycol. 2. For a given mass concentration, the enhancement is independent of the molecular weight of the polyethylene glycol. 3. These data are consistent with the operation of excluded volume effects, and support the contention that the association of spectrin is likely to be increased in the presence of the high concentration of hemoglobin within the erythrocyte in vivo.

Binding Sites↗

The self-association of ovine erythrocyte spectrin.

1. Spectrin extracted from ovine erythrocyte membranes at low temperature shows association behaviour similar to that reported for human and bovine erythrocytes. 2. The spectrin tetramer is the predominant oligomer, the dimer is well represented, and smaller amounts of hexamer and higher oligomers are present. 3. The estimates of parameters describing the self-association of purified ovine spectrin studied by sedimentation equilibrium analysis were found to be indistinguishable from those obtained for human spectrin under the same conditions, within the precision of the measurements. 4. The data suggest that the cooperative isodesmic model may be general for spectrin, and not a peculiarity of the human.

Animals↗

The effects of ionic strength on the self-association of human spectrin.

The self-association of human spectrin has been studied by means of sedimentation equilibrium in the analytical ultracentrifuge at pH 7.5 and over a range of ionic strength from 0.009 to 1.0 M. Increasing ionic strength above 0.1 M reduces the equilibrium constants for all of the measurable steps in the self-association reaction. These results support the concept of charge-charge interactions stabilizing the tetramer and higher oligomers with respect to the heterodimer. In addition, increasing ionic strength brought about a dissociation of the heterodimer to component polypeptide chains. Dissociation to the heterodimers is also enhanced with a decrease in ionic strength below 0.05 M. This low ionic strength-dependent dissociation is consistent with generalised electrostatic repulsion; however, this effect also correlates with some loss of alpha-helical content as revealed by circular dichroism. The secondary, tertiary and quaternary structures may all be partially disrupted by electrostatic free energy at low ionic strength.

Erythrocyte Membrane↗

Replication of human cytomegalovirus at supra-optimal temperatures is dependent on the virus strain, multiplicity of infection and phase of virus replication.

The kinetics of replication of five strains of human cytomegalovirus (CMV) were studied to determine the influence of (i) temperature, (ii) virus strain, (iii) m.o.i. and (iv) cell type. Relative to growth at 37 degrees C (m.o.i. = 3 to 9) eclipse periods were extended from 24 to 48 h at 33 degrees C and to 72 h at 40.5 degrees C. Yields were reduced at 33 degrees C and almost eliminated at 40.5 degrees C. No replication occurred in most instances at 40.5 degrees C and with 0.05 p.f.u./cell. Temperature shift studies (40.5 to 37 degrees C) indicated that the block to replication at 40.5 degrees occurred about 12 to 16 h p.i. resulting in little synthesis of CMV DNA or late antigens. The degree of inhibition of late functions at 40.5 degrees C is virus strain and m.o.i. dependent, but is not dependent on the type of fibroblastic cell used. These data suggest that persistent CMV infections are favoured at 40.5 degrees C.

Antigens, Viral↗