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Biomedical subjects

F Michel

Publications and source records attributed to F Michel.

At least 253 records · Page 14Linked to original sources

Inhibition of prostaglandin synthetase by di- and triphenylethylene derivatives: a structure-activity study.

The syntheses of new di- and triphenylethylene derivatives are described along with their X-ray analysis and NMR study, which have helped to establish their conformation. Screening of over 50 derivatives for inhibition of prostaglandin synthetase (PGS) activity in bovine seminal vesicle microsomes has revealed that many of the triphenylethylene derivatives are potent inhibitors of PGS. Several even show marked activity at the extremely low concentration (IC50) of about 4 X 10(-8) M, which is two orders of magnitude lower than the active concentration of the majority of known nonsteroidal antiinflammatory agents (IC50 approximately equal to 10(-6) M). Unlike the latter, these compounds are not carboxylic acids. Furthermore, in contrast to biphenyl, diphenylmethane, or unsymmetrical, alpha, alpha'-diphenylethylene PGS inhibitors, the presence of a beta-phenyl ring was an essential requirement for high potency. The best inhibitors possessed a cyanide group (acids, amides, and amines were poor inhibitors), methoxy in preference to hydroxy groups on the alpha-phenyl rings, and a halogen (F or Cl) in a para position on the beta-phenyl ring. These data provide additional insight into the nature of the PGS binding site.

Animals↗

Spontaneous diabetes mellitus syndrome in the rat. II. T lymphopenia and its association with clinical disease and pancreatic lymphocytic infiltration.

We have studied the occurrence of two phenotypic components (pancreatic lymphocytic infiltration [PLI] of the pancreas and T lymphocytopenia) of the spontaneous insulin-dependent diabetic syndrome (IDDM) in the progeny of hybrids obtained by crossing BB diabetic rats with rats of inbred strains differing from the BB rat at the major histocompatibility complex, RT1. Both PLI and T lymphopenia were seen in animals with all three possible genotypes in both (BUF x BB) and (LEW x BB) lines. PLI was seen in all IDDM animals. T lymphopenia was strongly associated with overt IDDM in both lines (chi 2 = 22.28, p = 0.00002 and chi 2 = 19.28, p less than 0.00001). In addition, T lymphopenia was associated with PLI with and without IDDM in both lines (chi 2 = 8.32, p = 0.0039 an chi 2 = 3.95, p = 0.0467). Not all animals exhibiting PLI without overt IDDM had depressed T cells. Not all animals with T lymphopenia had PLI with or without IDDM. In both lines, the overt IDDM occurred only in animals with at least one RT1 u haplotype derived from the BB rat, confirming our previously reported association of IDDM and RT1. We interpret this evidence to suggest that the overt IDDM syndrome requires one MHC-linked gene and at least two non-MHC-linked genes, which determine susceptibility to PLI and to circulating T lymphocyte depression.

Animals↗

[Factor analysis of the structure-activity relationship of di- and triphenylethylenes in 2 biochemical tests].

This paper deals with the study of biochemical activity, by means of correspondence analysis, of about fifty original molecules of di- and triphenylethylene structures. The pharmacological experiments were made on glutamate deshydrogenase and prostaglandine synthetase. A typology of several molecular groups is established and the effects of various substituents are specified.

Animals↗

Comparison of fungal mitochondrial introns reveals extensive homologies in RNA secondary structure.

The complete sequences of nine Saccharomyces cerevisiae mitochondrial introns, six of which carry long open reading frames, have already been published. We have recently determined the sequence of an intron in the large ribosomal mitochondrial RNA of Kluyveromyces thermotolerans (Jacquier et al., in preparation), which we found to be closely related to its S. cerevisiae counterpart. This latter result prompted us to undertake a systematic search for possible homologous elements in the other, available sequences with the help of an original computer program. A previously unsuspected wealth of evolutionarily conserved sequences and secondary structures was thus uncovered. Seven at least of the available sequences may be folded up into elaborate secondary structure models, the cores of which are nearly identical. These models result in bringing together the exon-intron junctions into relatively close spatial proximity and looping out either all or most of the sequences in open reading frame, when present. These results and their possible implications with respect to the mechanism of splicing are discussed in the light of available genetic and biochemical data.

Base Sequence↗

The hierarchical approach to the DNA stability problem. I. Patterns in non-equilibrium denaturation and renaturation.

As proposed by Azbel (Phys. Rev. Letters, 1973, 31, 589-592), DNA sequences may be uniquely divided into embedded segments with different lengths and stabilities, each of them a potential denaturation unit. This "hierarchical" approach to the DNA stability problem was originally devised for the analysis of equilibria situations. We have extended it to deal quantitatively with various locally irreversible denaturation/renaturation processes that play a leading part in most actual experiments. Special emphasis is placed on (1) describing and delimiting major experimental domains with respect to reversibility/irreversibility, and (2) the quantitative treatment of bidirectional denaturation processes which are shown to lend themselves to an original, hierarchical analysis.

Base Composition↗

The hierarchical approach to the DNA stability problem. II. Some applications and speculations with yeast mitochondrial DNA as an example.

As discussed in the preceding article [1] hierarchical analysis of DNA sequences should make it possible to treat complex unfolding (and refolding) processes involving both equilibrium and non-equilibrium subtransitions. Hence a variety of actual experimental situations may be analyzed. This is demonstrated with the help of a 1950 bp yeast mitochondrial DNA sequence encompassing part of the 21S ribosomal RNA gene: excellent fit of complex denaturation and renaturation profiles is achieved with only two adjustable parameters. The advantage of dealing with objectively defined stability units is also apparent when stability profiles are compared to known functional maps: striking correlations may be brought out and their possible significance is briefly discussed.

Base Composition↗

Growth and sexual maturation in ewes: the role of photoperiod, diet and temperature on growth rate and the control of prolactin, thyroxine and luteinizing hormone secretion.

The relationship of photoperiod, temperature and diet on growth rate and serum concentrations of thyroxine (T4), prolactin (PRL) and luteinizing hormone (LH) were studied in ewe lambs from 9 to 32 wk of age. Lambs reared on a diet supplying 1.78 Kcal/g net energy had higher (P less than .025) serum T4 concentrations and greater average daily gain (ADG) than lambs fed a lower energy ration (1.5 Kcal/g). Long artificial photoperiod of 16 h of light neither improved ADG nor altered T4 concentrations compared with ambient (natural light) or a short artificial photoperiod of 8 h light. Serum PRL concentrations were correlated (r = .83 to .74; P less than .01) to ambient temperature during the seasonal transition from summer to fall and temperature also determined the magnitude of photoperiodic stimulation of PRL levels in winter. Temperature had no effect on basal LH concentrations for lambs kept in warm (15 to 20 C) vs cold (0 to 15 C) environments for 6 wk, but the LH surge induced by estradiol was delayed (P less than .05) by the warm environment. The correlation (r = .015) between serum PRL levels and ADG was not significant, although serum PRL concentrations were dependent upon dietary energy levels. These observations do not support a positive relationship of PRL or photoperiod to ADG in the ewe lamb.

Animals↗

[Thymic seminomas (author's transl)].

The authors report on three cases of thymic seminoma treated between 1971 and 1981. These tumours, first described by Friedman in 1981. These tumours, first described by Friedman in 1951, belong to the group of extra-gonadal germinal tumours. They constitute about 2.5% of all thymic masses. The most probable pathogenic theory is abnormal migration of germinal cells from the vitelline sac to the embryonic thymus. Thymic seminomas are usually found in young men and are asymptomatic in 30% of the cases. Macroscopically, they present as solid tumours capable of invading the surrounding structures. Histologically, they resemble gonadal seminomas but are sometimes difficult to identify, which is unfortunate since treatment is dependent upon an accurate histological diagnosis. The authors suggest that the tumour should be biopsied under mediastinal fluoroscopy, so that an accurate histological diagnosis can be made. Treatment consists of surgical excision, which should be restricted and on no account should destroy important structures, completed by mediastinal radiotherapy. The mean survival time is 6.3 years; the 5-year survival rate is 75%.

Adult↗

BSP clearance as the most reliable criterion of hepatic dysfunction after jejunoileal bypass in the rat: arguments in favor of the existence of a pathogenetic mechanism involving a transient malnutrition state.

In rats subjected to 90% jejunoileal by-pass or in sham-operated controls, liver function was compared to plasma nutritional state and adaptation of the intestine in continuity over a period of 3 months. While the plasma levels of GOT, GPT, and esterases A and C as cholinesterase C did not differ in either group, the percentage of retention of BSP increased until 8 weeks, then returned progressively to control values 12 weeks after small-bowel bypass. In contrast, plasma nonesterified fatty acid levels decreased significantly until 6 weeks, then recovered control values over the following periods. Plasma total protein and albumin levels also diminished after jejunoileal bypass, the most marked decrease being at the 4th postoperative week. The increase in villus size following the intestinal bypass was considered pronounced for the ileum between the 8th and the 12th week. These results suggest that BSP clearance is the most reliable criterion for hepatic dysfunction in the rat subjected to a jejunoileal bypass. In addition, the parallelism between the variations of BSP clearance, intestinal adaptation, and plasma nutritional state argue for the "nutritional" theory as the most probable explanation for the formation of hepatic lesions.

Animals↗

[Vasoactive intestinal peptide (VIP) in the Verner-Morrison syndrome (author's transl)].

An early diagnosis of the Verner-Morrison syndrome will greatly enhance the chances of curative resection. There is a striking need for a simple diagnostic test. A number of suggestions have been made for the presumed hormone mediator of this syndrome. Numerous reports have led to a wide acceptance that vasoactive intestinal peptide (VIP) is the responsible mediator for the pharmacologic actions of this peptide are similar to the physiological characteristics noted in the watery diarrhea syndrome. A raised plasma VIP concentration, on the other hand, would suggest the presence of a tumour. These observations argue for the radioimmunoassay measurement of plasma VIP in a patient with the watery diarrhea syndrome.

Adenoma, Islet Cell↗

[Islet cell transplantation and diabetes (author's transl)].

It is now apparent that transplantation of islet cells is biologically feasible in experimental animals utilizing adult neonatal or fetal islet cells and employing many different sites for implantation of the islet cells. It is reasonable to expect that with successful acquisition of new basic information in immunology, endocrinology, metabolism and developmental biology islet cell transplantation should be used as a therapeutic approach to human diabetes.

Animals↗