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Biomedical subjects

L Franco

Publications and source records attributed to L Franco.

At least 127 records · Page 7Linked to original sources

C1 proteins: a class of high-mobility-group non-histone chromosomal proteins from the fruit fly Ceratitis capitata.

1. CM-cellulose chromatography of a fraction soluble in 5% perchloric acid from Ceratitis capitata chromatin yields three proteins, C1a1, C1a2 and C1b, which have been purified to electrophoretical homogeneity. 2. C1a1, C1a2 and C1b analyse like high mobility group (HMG) non-histone chromosomal proteins, although they do not exactly correspond with those from vertebrates. It is proposed that C1 proteins, as well as Drosophila D1 [Rodríguez Alfageme et al. (1980) Chromosoma, 78, 1-31] are representative of a class of insect-specific HMG proteins. Tryptic fingerprints show that C1a1 and C1a2 are very similar, but C1b is a somewhat distinct protein. Circular dichroism studies have shown that these preparations do not appreciably fold on increasing ionic strength. 3. The interactions between DNA and C1 proteins have been studied. These proteins precipitate DNA in 0.15 M NaCl, 0.015 M sodium citrate and the precipitation curves are cooperative. Soluble complexes between C1 proteins and DNA could be prepared in low ionic strength media and their thermal denaturation profiles obtained. C1 proteins do not destabilize DNA under the conditions used to prepare the complexes but the three proteins stabilize DNA to a different degree. From these studies it has been concluded that the association constant of C1b to DNA is smaller than that of C1a1 and C1a2.

Animals↗

Estrogen receptors and responsiveness of advanced breast cancer to chemotherapy.

We reviewed 89 patients with disseminated breast cancer who had at least one valid estrogen receptor (ER) assay and who underwent one or several trials of chemotherapy. The responses were assessed by two independent extramural reviewers. Of the 89 patients, 81 were evaluable; 28 of 36 (77.8) ER-positive (ER+) and 28 of 45 (60.7%) ER-negative (ER-) tumors reached at least one remission. Of patients who had received Adriamycin-containing therapy, 13/20 (65%) ER+ and 12/34 (35.3%) ER-tumors experienced a remission . ER+ breast cancer tends to respond better to Adriamycin-containing combinations than ER-negative tumors. This study does not support the thesis that lack of estrogen receptor in breast cancer predicts favorable for response to chemotherapy.

Adult↗

Structural studies on histones H1. Circular dichroism and difference spectroscopy of the histones H1 and their trypsin-resistant cores from calf thymus and from the fruit fly Ceratitis capitata.

A peptide containing the globular region of the histone H1 from the fruit fly Ceratitis capitata has been isolated after limited tryptic digestion of insect H1. The composition of this trypsin-resistant core resembles that of the homologous peptide from calf thymus H1, although the insect H1 core possesses one cysteine, two tyrosines, one histidine, and more isoleucine and less glycine and leucine than the calf thymus H1 core. Circular dichroism measurements indicate that all the fragments that possess an ordered secondary structure (approximately 11% in both calf thymus H1 and Ceratitis H1) are present in the trypsin-resistant cores. Both calf thymus and Ceratitis H1 and their trypsin-resistant cores fold cooperatively on titration with NaOH, though the folding of the cores is less cooperative than that for the parentmolecules. On the other hand, salt-induced folding of both cores and intact molecules is noncooperative. The environment of the tyrosyl residues in both calf thymus and Ceratitis H1 has been studied by circular dichroism in the region 250-300 nm and by difference spectroscopy; their pKa' values have also been determined. The results suggest that one of the tyrosyl residues of Ceratitis H1 is buried in the hydrophobic core, in an environment similar to that of calf thymus tyrosine-72, while the second tyrosyl residue of the insect H1 molecule, which titrates with a lower pKa' value (approximately 9.30 in the absence of salt and approximately 9.80 in the presence of 0.3 M KF), is on the surface of the trypsin-resistant core. Due to the limited number of aromatic residues in the histone molecules, the above-mentioned techniques proved to be useful tools to study conformational transitions.

Amino Acids↗

The acute inflammatory process in copper-deprived rats.

Copper is clearly involved in experimental and human inflammation, as suggested by a large body of data, some of which obtained in our own laboratories. With the purpose to further investigate the role of copper in the inflammatory process, we have studied the development of carrageenan foot oedema and carrageenan pleurisy in rats treated with a copper-deficient diet according to the following schedule: (1) foot oedema in rats maintained on a 0.4 p.p.m. copper-deficient diet for 1 and 3 months; (2) foot oedema and pleurisy in rats maintained on a 0.2 p.p.m. copper-deficient diet for 1 month; (3) foot oedema and pleurisy in rats maintained on a 0.6-0.8 p.p.m. copper-deficient diet for 5 months. With these experiments we have shown an enhancement of the inflammatory reaction which, apparently, is both time and copper content dependent. The possibility that endogenous copper could play a key role in modulating the acute inflammatory process is discussed.

Acute Disease↗

Concerning the role of endogenous copper in the acute inflammatory process.

The development of two models of acute inflammation (carrageenan-induced foot oedema and pleurisy) was studied in rats after 1 month of a 0.2 p.p.m. copper-deficient diet and after 5 months of a 0.6-0.8 p.p.m. copper-deficient diet. A 'pro-inflammatory' effect of copper deficiency was observed with the 0.2 p.p.m. diet, whilst no effect was evident following the 0.6-0.8 p.p.m. copper deficient diet. These results are briefly commented upon.

Acute Disease↗

Large-scale isolation of a native deoxyribonucleohistone complex from baker's yeast.

A method for large scale isolation of a native deoxyribonucleohistone complex from yeast is described. Crude chromatin, obtained after disrupting yeast cells at low ionic strength, contains a large amount of lipids, partially due to contaminating membranes. Most of them are removed by a Triton X-100 treatment, followed by step-gradient centrifugation. About 90% of the pellet may be solubilized by mild procedures, the composition of the soluble material being: histone/DNA = 1.0;nonhistone proteins/DNA = 0.55; RNA/DNA = 0.18. Histones can be obtained with high purity. Micrococcal nuclease digests DNA to yield a series of oligomeric fragments, with an average repeat length of about 160 base pairs. Circular dichroism spectra show that (theta) 270 is reduced by about 30% when compared to pure DNA and that chromosomal proteins are not denatured. These results indicate that the components of the complex conserve the native state.

Chromatin↗

Effect of calcitonin on different inflammatory models.

The effect of synthetic salmon calcitonin was studied on adjuvant arthritis, pertussis vaccine edema, tuberculin skin reaction, passive direct Arthus reaction and nystatin edema. The results show that calcitonin inhibits these inflammatory processes.

Animals↗