Biomedical subjects
Publications and source records attributed to F Lefevre.
Using as a probe pig genomic DNA, including the complete interferon alpha gene, we have mapped the leukocyte interferon gene on pig chromosome 1 by in situ hybridization. A total of 196 silver grains were noted on the 106 metaphases scored: 31% of the grains were observed on chromosome 1, and 67% of these were localized in the region 1q2.2----q2.7.
The mode of action of rat interferon (IFN) on growth of the R3230AC mammary adenocarcinoma was studied in vivo in Fischer female rats. A dose of 1 X 10(4) units of rat IFN given thrice weekly inhibited the growth of the transplanted mammary tumors. Of the five eicosanoids measured in the tumor, the content of four arachidonate products, prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane (TX) B2, was higher in mammary tumors from IFN-treated rats than the control rats. PGE2 was the major eicosanoid. In vitro PG synthesis (PGE1, PGE2, and PGF2 alpha) was lower in tumor microsomes prepared from IFN-treated tumors. These data suggest that the tumor content of four arachidonate products in the IFN-treated tumors was related to the in vivo effects of rat IFN. Indomethacin, a cyclooxygenase inhibitor, also inhibited tumor growth. Furthermore, when indomethacin was administered daily in combination with rat IFN, the tumor-inhibiting effect of rat IFN was reduced. These observations suggest that the effects of eicosanoids appear to be biphasic in this tumor model. Inhibition of arachidonic acid metabolism resulted in tumor growth inhibition, a finding consistent with the view that eicosanoid production is required for tumor enhancement. Conversely, in the experiments with rat IFN, retardation of tumor growth is associated with a greater amount of arachidonic acid metabolism, and indomethacin prevents this effect. Eicosanoids appear to be required for tumor-inhibiting effects of rat IFN, and yet inhibition in vivo of eicosanoid synthesis also resulted in retardation of tumor growth. Although the precise mechanism of action in each situation is unclear, these apparently contradicting results are consistent with the biphasic actions of eicosanoids reported in some normal tissues and transformed tumor cell lines.
The genes of the RF strain of bovine rotavirus have been cloned into pBR 322 following the synthesis and hybridization of cDNA transcribed from both strands of in vitro polyadenylated genomic RNA. Cloned rotavirus DNAs were assigned to most of the 11 genomic RNA segments by Northern blot hybridization. The complete sequence of gene 6 that codes for the major inner capsid protein has been determined. The gene is 1356 nucleotides long and possesses an unique long open reading frame that could encode a protein (397 amino acids) of similar size to the known gene 6 product. Comparison of the RF bovine rotavirus gene 6 sequence with the sequence of the simian rotavirus gene 6, showed these genes to be very similar in nucleotide sequence (87% homology). Most of the base changes are silent and the predicted amino acid sequences are almost identical (97% homology).
Tissue prostaglandin (PG) content and production by human breast cancers were measured in 24 human mammary carcinoma specimens. The 5 compounds studied were PGE1, PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TXB2. The tissue content of all 5 compounds was higher in neoplastic tissue in comparison with the paired noncancerous breast tissue. However, microsomal PG synthetase activity in vitro in noncancerous and neoplastic breast tissue was comparable. Increased thromboxane formation was associated with three clinical variables--tumour size, axillary lymph node metastases and distant metastasis. A lesion negative for either oestrogen or progesterone receptor content tended to produce more TXB2 but lower PGE2 and 6-keto-PGF1 alpha. Results obtained in this pilot study may provide clues as to what direction future larger studies could take in the search for reliable prognostic indicators for breast cancer.
In a preliminary paper [Thérapie 34, 397 (1979), we showed that cysteine enhances bismuth digestive absorption in rats. In this paper, we have studied in rats the effects of various thiol compounds (mercaptopropionic acid, penicillamine, cysteine, homocysteine, 2-mercaptoethylamine, mercaptoethane) and nonthiol compounds (methionine, serine, alanine) orally administered on the absorption and elimination of bismuth also given orally. Bismuth was measured in blood and urine by electrothermal atomic absorption spectrophotometry. All of the thiol substances, and particularly cysteine, homocysteine, and mercaptopropionic acid, have considerably enhanced bismuth absorption and elimination; whereas, nonthiol substances have had no effect. Moreover, the acute toxicity of bismuth was enhanced when bismuth was given as a complex with cysteine (LD50 = 156 +/- 20 mg/kg). Studies by nmr spectroscopy of interactions between bismuth and these organic compounds have shown that bismuth induces an important chemical shift of the protons of the alpha carbon of the sulfhydrile group. Mainly, studies of C and N have confirmed this fact. The selectivity of such a complexation, in our pH conditions, may be tentatively explained on the ground of hard and soft acid and base (HSAB) theory. We have suggested that an increase in the concentration of thiol compounds in the gastrointestinal tract arising from food, or more probably from microorganism synthesis, could be an explanation for human encephalopathies.
In pentobarbital (35.0 mg/kg) anaesthetised dogs, bolus injections of prazosin into the femoral artery (3.0--300.0 microgram) provoked a dose-related fall in the vascular resistance of the innervated hind limb. In contrast to papaverine, prazosin failed to produce the same effect in dogs under spinal anaesthesia even when the intrinsic femoral vascular tone was increased with vasopressin. However, vasodilator effects of prazosin were again observed when the tone of the limb was elevated by either stimulating the sympathetic lumbar chain or by infusing alpha-adrenoceptor agonists. A significant reduction of both aortic blood pressure and pressor response to bilateral carotid artery occlusion was noted in a group of normotensive dogs anaesthetised 12 h after the last dose of prazosin given twice daily at 0.5 mg/kg, p.o., for 3 day period. This short-term treatment modified neither the resting heart rate nor the positive chronotropic effect induced by either intravenous noradrenaline or electrical stimulation of pre- and post-ganglionic nerve fibres of the right stellate ganglion. However, it prevented the larger increase in heart rate in response to bilateral carotid occlusion in placebo-treated dogs after section of the vagi. A decrease in baseline sympathetic tone of the perfused hind limb as well as vasoconstrictor effects produced by i.a. injections of several alpha-adrenoceptor agonists and electrical stimulation of the lumbar sympathetic chain was observed in prazosin-treated animals. The dose--pressor response profiles to these alpha-adrenoceptor stimulants after prazosin were not parallel to those obtained in the control group. The vasoconstrictor response to angiotensin II was not changed by prazosin. In rabbit aortic strips, prazosin (0.1--3.0 micrometer) produced competitive antagonism of the contractile responses induced by cirazoline, noradrenaline and phenylephrine. In contrast to papaverine, prazosin in concentrations up to 100.0 micrometer neither relaxed the aortic strips contracted by potassium ions nor modified the concentration-response curve to calcium ions. These studies indicate that blood pressure lowering effects of prazosin given acutely or for three days can be accounted for by a clear-cut functional impairment of vascular postsynaptic alpha-adrenoceptors. No evidence for a direct myorelaxant property of prazosin could be obtained in these studies.
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We evaluated a new liquid homogeneous assay for the direct measurement of high density lipoprotein cholesterol (HDL-C Plus) in seven laboratories. The assay includes two reagents which can be readily used in most available clinical chemistry analyzers. The total CVs of the new method were below 4.6% and the bias in relation to the designated comparison method was below 3.9%. The total error ranged between 4 to 7%. HDL-C values determined by this method were in good agreement with those obtained by the old homogeneous assay using lyophilized reagents, and other homogeneous and precipitation assays (0.944 < r < 0.996). The assay was linear up to at least 3.89 mmol/l HDL-C. Hemoglobin did not interfere, whereas in icteric samples slight deviations were observed. Lipemia up to 11.3 to 22.6 mmol/l triglycerides did not interfere with this homogeneous HDL-C assay. In samples of patients with paraproteinemia, discrepant results were seen. This liquid homogeneous HDL-C assay was easy to handle and produced similar results in all laboratories participating in this study. This method will enable clinical laboratories to reliably measure HDL-C for risk assessment of coronary heart disease.
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