[Eulogy of Guy Laroche (1884-1984)].
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Biomedical subjects
Publications and source records attributed to J Roche.
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Rat liver chromatin is stripped of H1 histone by exposure to 0.5 M NaCl and reassociated with individual purified subfractions of H1 by salt-step dialysis. The effectiveness of proteins H1-1 and H1 in the condensation of DNA is monitored by transient electric birefringence and circular dichroism. Steady-state birefringence and relaxation time measurements show that reconstitutions are not perfect although some features of native chromatin are restored when a ratio of 2 moles of H1 per nucleosome is used. The amplitude of the positive birefringence is better recovered with H1-1 than with H1 but the values of relaxation times and molar ellipticities indicate that reconstituted samples exhibit a more compact and rigid structure compared to that of native chromatin.
Eighteen cases are reported in which the myelographic appearances of adhesive arachnoiditis were found. These patients have had intrathecal steroid injections as either the only procedure or the most likely procedure that could have induced such changes. Adhesive arachnoiditis has not been found at this hospital in the absence of some type of intervention. Other possible iatrogenic causes of arachnoiditis have been excluded in this group. The literature on the aetiology and symptomatology of steroid-induced arachnoiditis is reviewed.
A randomized four-way crossover study was carried out in 12 healthy volunteers to investigate the pharmacokinetics of a new oral combination of frusemide (40 mg) and amiloride (5 mg), formulated as a single tablet. The experimental design of this bioequivalence study used commercially-available 40 mg frusemide tablets and 5 mg amiloride tablets as reference drugs, administered either separately or concomitantly. From a statistical analysis of plasma levels of frusemide and amiloride, no significant differences between the reference drugs alone and the combination tablet were seen in peak plasma levels, mean times to peak or mean areas under the plasma concentration-time curves (AUCs). The ratio of AUCs of the combination tablet to the reference drugs approached a limiting value many hours prior to complete elimination of the drug and hence reliable bioavailability comparisons were possible with blood sampling up to 24 hours post-dose.
An outbreak of epidemic keratoconjunctivitis (EKC) in a rural area is described. It was characterised by its explosive outbreak, relatively short duration and high infectivity. The aetiology is discussed.
The standard radiological reports of 50 carotid angiograms were reviewed with regard to the presence of ulceration at the carotid bifurcation. The angiograms were then specifically re-examined retrospectively by a radiologist and the presence or absence of ulceration commented on. The macroscopic features of the carotid endarterectomy specimens of the same patients undergoing carotid endarterectomy were then examined by an independent observer. The results of these three examinations were then compared. There were 28 ulcers in 23 of the 50 specimens with 12 large ulcers (greater than three mm diameter) and 16 small ulcers (less than three mm). In the diagnosis of ulcers, the initial radiological report showed a sensitivity of 32% and a specificity of 97.2%, with an accuracy of 79%, whilst on the retrospective search for ulcers the sensitivity rose to 67.8% whilst the specificity fell to 55.5%, with an accuracy of 59%. The factors affecting the accuracy of the detection of carotid ulcers by angiography are discussed. Angiography in its present form has limitations in diagnosing carotid ulceration.
Thyroglobulin biosynthesis was studied in thyroid glands of rats treated during 30 days with a daily dose of propranolol, a non-selective beta-adrenergic blocking drug. Studies were carried out by extraction of soluble proteins from homogenates after incubation of the glands in presence of [3H]-4,5-L-leucine and [3H]-D-1-galactose. Thyroglobulin 19S, 12S and 4-8S soluble proteins were separated and identified by ultracentrifugation in a saccharose gradient. The glands of rats treated with propranolol showed a decreased amount of soluble proteins as well as a decreased incorporation of [3H] labeled markers. 19S thyroglobulin is poorly represented, but very large amounts of the 12S monomer are present; this suggests an impairment in the dimerization of the 12S subunit, absent in normal controls. This impairment could be due to a structure modification. Propranolol reduces the biosynthesis of thyroglobulin in thyroid gland as well as the formation of T3 from T4 in peripheral tissues; its therapeutical use against thyrotoxicosis is thus justified. The study of its action on the dimerisation of the 12S subunit could be of interest to clear the mechanism of thyroglobulin biosynthesis.
Groups of rats have been treated for one month with a daily dose of 50 mg/kg of body weight/day of isoniazide a product used therapeutically in man against tuberculosis. The animals submitted to this experiment showed an increase of thyroid weight (39%) and a decrease of its content in water soluble proteins, including thyroglobulin and precursors. These proteins have been labeled in vitro by [3H]-4,5-L-leucine and by [3H]-galactose, by incubation of isolated glands during 4 h in a medium containing this labeled marker. The decrease of thyroglobulin-like proteins was of 20-37% for [3H]-D-1-galactose, labeled fraction and of 46-53% for the [3H]-leucine labeled fraction. Two thirds of the radioactive protein sedimented by ultracentrifugation in a sucrose gradient were present in a 12S monomer of thyroglobulin. This suggests an impairment of biosynthesis of 19S thyroglobulin, in which two of the subunit are associated. Under experimental conditions adopted this 19S protein was labeled by [3H]-leucine, but not by [3H]-galactose. Two other antituberculous agents studied, ethambutol and rifamizine, exerted not the same effects on thyroid gland in rats. Therefore a control of thyroid function appear to be necessarily only in man treated by isoniazine.
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Computed tomography detected intra-abdominal abscess with 97% accuracy in 111 patients who underwent 135 separate scans. A true negative ratio of 0.98, and a true positive ratio of 0.96 was obtained. Further important findings, unrelated to the presence of abscesses, were detected in 41 of the 135 scans. The information given by computed tomography significantly modified clinical management in over 55% of studies performed.
Carbohydrate chains formation into thyroglobulin (Tg) is a prerequisite for thyroid hormones formation and completeness of carbohydrates chains is necessary for secretion of Tg into the follicles. Tg biosynthesis has been investigated by in vitro experiments, incubating rat thyroid glands with labeled amino-acid and carbohydrate in the presence of tunicamycin, a specific inhibitor of protein glycosylation. Tunicamycin inhibit Tg biosynthesis which is impaired in carbohydrate chains addition but slightly in the polypeptide synthesis, as shown by inhibition of 3H-glucosamine incorporation. Thus tunicamycin inhibits carbohydrate incorporation into Tg without affecting the polypeptide chain growth and decreases its secretion into the follicles.
Thyroid biosynthesis in glassed eels (Anguilla anguilla L.) was studied to establish whether salinity changes could affect it, when they live in sea water or in fresh water containing 125I. Aqueous extrait of homogenized cephalic heads of glassed eels contains an iodinated protein 17-19 S having thyroglobulin-like properties and including iodotyrosins (MIT and DIT) and thyroid hormones (3 and T4). Biosynthesis of this proteins is roughly twice more important in fresh water than in sea water at 19-21 degrees C and its specific radioactivity (125I) is practically double in fresh water.
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Central nervous system disorders are not uncommon in patients with hyperparathyroidism and hypercalcaemia. Usually these consist of neuropsychiatric disturbances but acute encephalopathies and seizures may occur. A rare manifestation is cerebral infarction. A patient is presented with neuroradiological evidence of infarction caused by cerebral arterial spasm which appears related to hypercalcaemia due to hypervitaminosis D. Arterial spasm is suggested as a possible aetiological factor in focal neurological lesions associated with hypercalcaemia.