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L Larue

Publications and source records attributed to L Larue.

At least 37 records · Page 2Linked to original sources

Expression of catenins during mouse embryonic development and in adult tissues.

Classical cadherins are cell-surface glycoproteins that mediate calcium-dependent cell adhesion. The cytoplasmic domain of these glycoproteins is linked to the cytoskeleton through the catenins (alpha, beta and gamma). The catenins are intracellular polypeptides that are part of a complex sub-membranous network modulating the adhesive ability of the cells. One approach to elucidate the role of these molecules in the cell is to investigate their distribution during mouse development and in adult tissues. This study reports that catenins are widely expressed but in varying amounts in embryos and adult tissues. The expression of all three catenins is most prominent in the adult heart muscle and in epithelia of all developmental stages. In other embryonic and adult tissues, lower expression of catenins was detected, e.g., in smooth muscle or connective tissue. Catenins are coexpressed with various cadherins in different tissues. Gastrulation is the first time during embryogenesis when a discrepancy occurs between the expression of catenins and E-cadherin. E-cadherin expression is suppressed in mesodermal cells but not the expression of catenins. This discrepancy suggests that another cadherin may interact with catenins. Similarly, E-cadherin is generally expressed in adult liver but not in the regions surrounding the central veins. In contrast, catenins are uniformly expressed in the liver, suggesting that they are associated with other cadherins in E-cadherin negative cells. Finally, the three catenins are not always concurrently expressed. For example, in peripheral nerves, only beta-catenin is observable, and in smooth muscle plakoglobin is not detectable.

Animals↗

E-cadherin null mutant embryos fail to form a trophectoderm epithelium.

The cell adhesion molecule E-cadherin mediates the compaction process of mouse preimplantation embryos and is important for the maintenance and function of epithelial cell layers. To determine precisely the role of E-cadherin in epithelial biogenesis we monitored the developmental potential of embryos homozygously negative for E-cadherin that were derived from E-cadherin heterozygous transgenic mice. The homozygous negative embryos died around the time of implantation, although they did undergo compaction like their littermate controls, largely due to the presence of residual maternal E-cadherin. At the blastocyst stage, E-cadherin-negative embryos failed to form a trophectodermal epithelium or a blastocyst cavity. These results demonstrate the pivotal role of E-cadherin in one of the most basic morphogenetic events in the development of multicellular organisms, the biogenesis of an epithelium.

Animals↗

Therapeutic abortion during the 2nd and 3rd trimesters of pregnancy using a synthetic derivative of prostaglandin E2, sulprostone, administrated intravenously. Based upon 182 cases.

OBJECTIVE: The purpose of the study is to assess the efficacy of and adverse events linked to the use of intravenous sulprostone during the 2nd or 3rd trimesters of pregnancy for therapeutic abortion. STUDY DESIGN: One hundred eighty-two patients (70 nulliparous, 112 multiparous) were hospitalized for therapeutic abortion. The route of administration was invariably intravenous and one single dose of sulprostone was used: 1000 micrograms of sulprostone diluted in 1 l of isotonic saline solution given as a 10-h infusion. RESULT: Expulsion within the first 24 h was obtained in 70% of cases with a mean induction-expulsion interval of 14 h. In three cases, laparotomy was required for hemorrhagic syndromes. CONCLUSION: Intravenous sulprostone enable evacuation of uterine contents with minimal adverse reaction. Attention should nevertheless be drawn to the existence of hemorrhagic syndromes.

Abortifacient Agents, Nonsteroidal↗

Intravenous sulprostone and uterine scarring based upon 22 cases of therapeutic abortion during 2nd and 3rd trimesters of pregnancy.

A preliminary study in 22 patients with uterine scarring was undertaken using sulprostone by intravenous infusion when therapeutic abortion was deemed necessary during the 2nd and 3rd trimesters of pregnancy. The dosage used was 500 micrograms by slow infusion lasting 10 h. There were no cases of ruptured uterus. Adverse reactions were absent. Results were satisfactory. Mean induction-expulsion duration: 11 h. Expulsion rate in 24 h: 63%. With strict monitoring and in a specialized center, this technique may be suggested when a late therapeutic abortion with a scarred uterus is indicated.

Abortifacient Agents, Nonsteroidal↗

[Myomectomy using laparoscopy. 23 cases].

The authors report their experience with laparoscopy for myomectomy and analyze their results (mean size of myomas: 7.5 cm, route of extraction: vaginal 56%). This is a recent, promising technique which requires further evaluation.

Adult↗

Melanocyte culture lines from Tyr-SV40E transgenic mice: models for the molecular genetic evolution of malignant melanoma.

Transgenic Tyr-SV40E mice previously produced on the C57BL/6 inbred-strain background, with SV40 oncogenic sequences specifically expressed in pigment cells, are predisposed to melanoma [Bradl, M., Klein-Szanto, A., Porter, S. & Mintz, B. (1991). Proc. Natl. Acad. Sci. USA, 88, 164-168]. Separate lines of these animals differ genetically only in the number of copies and chromosomal site of integration of the transgene. Skin melanocytes from young mice with no apparent skin lesions were established in continuous culture from hemizygous donors with low, medium and high numbers of transgene copies, and from a homozygous offspring of the low-copy mouse line. The standard culture conditions enable C57BL/6 wild-type melanocytes to become stably immortalized without transformation. The transgenic cell lines all changed over time in an orderly progression. However, with greater numbers of transgene copies, the cells more rapidly displayed shorter doubling times, increased anchorage independence, reduced serum and growth factor requirements, decreased tyrosinase expression and melanin content, increased oncogene expression, and capacity to form malignant melanomas when tested by grafting. Melanocytes with the lowest number of transgene copies were of special interest. They grew more rapidly than the wild-type cells from the outset, but did not become tumorigenic until an apparently small number of still-unknown genetic changes had spontaneously occurred, or until the number of transgene copies was increased slightly by homozygosity. In contrast to the hemizygous low-copy cells, the homozygous counterparts underwent striking and rapid transformational changes and early conversion to malignancy. Thus such low-copy transgenic melanocyte lines afford an exceptional opportunity for molecular analysis of somatic genetic evolution toward malignant melanoma.

Animals↗

Genetic predisposition of transgenic mouse melanocytes to melanoma results in malignant melanoma after exposure to a low ultraviolet B intensity nontumorigenic for normal melanocytes.

Tyr-SV40E transgenic mice are susceptible to melanoma due to simian virus 40 oncogenic sequences specifically expressed in pigment cells. Skin melanomas form relatively late. Therefore, melanocyte cell lines have been established from very young transgenic animals, when they showed no skin lesions, so that the spontaneous and gradual progress of the cells toward tumorigenesis could be characterized under culture conditions in which wild-type cells of the same inbred strain remain untransformed. Melanocytes of an in vitro transgenic line were irradiated with very low intensities of ultraviolet B (UVB) (280- to 320-nm wavelength) light at culture passages when the cells had not achieved anchorage independence. After a single exposure to 0.7 mJ/cm2 of UVB radiation, the cells became anchorage independent and formed foci at confluence; however, cells propagated from the foci were not tumorigenic. After one exposure to 1.75 mJ/cm2, more numerous and larger foci resulted, and the cells grown from them yielded malignant melanomas in graft hosts. Wild-type melanocytes were not transformed at these UVB doses. At least two genetic changes contributing to malignant conversion--in addition to the initiating effect of the transgene--are likely to have occurred, one change leading to anchorage independence and another to further progress toward malignancy. Cells at these stages provide an opportunity to isolate the relevant genes and identify any molecular defects attributable to UVB. Tumorigenesis after a very low UVB dose in cells where an initiating stimulus is already present suggests that some other stimulus, such as a gene or a carcinogen, might lead to melanoma in conjunction with exposure to relatively little UVB.

Animals↗

Hysteroscopic diagnosis of ectopic pregnancy.

Although vaginal ultrasonography combined with plasma beta-hCG determination can provide a reliable diagnosis and location of ectopic pregnancy, the results can be difficult to interpret in the early stages when hCG levels are low. Hysteroscopy can be used in such cases to differentiate between ectopic pregnancy and non-viable uterine pregnancy when viable uterine pregnancy has been ruled out. General anaesthesia and laparoscopy are avoided. We performed 60 hysteroscopic procedures between January 1989 and December 1990 in patients with suspected ectopic pregnancies. The pregnancy had been located by means of vaginal ultrasonography in every case in which the hCG was above 1500 IU/ml and in 36% of cases in which the beta-hCG was below this level. Hysteroscopy was hindered by metrorrhagia in three cases and was inconclusive in one, necessitating laparoscopy. Diagnosis was possible in all the remaining cases, as follows: ectopic pregnancy in 41 cases, with an empty uterus and occasional bleeding from an ostium; non-viable uterine pregnancy in 18 cases, with the presence of material within the cavity. Hysteroscopy therefore confirmed the diagnosis in 55% of the cases and was itself diagnostic in a further 43% of cases. Its sensitivity for the diagnosis of ectopic pregnancy was 100% and its specificity 95%. We propose a diagnostic decision tree.

Chorionic Gonadotropin↗

Spontaneous malignant transformation of melanocytes explanted from Wf/Wf mice with a Kit kinase-domain mutation.

The W/Kit mouse locus, affecting proliferation and survival of pigment cells, blood cells, and germ cells, is known to encode a tyrosine kinase growth factor receptor and is considered a protooncogene; yet it has not heretofore been causally implicated in any malignancies of those cells. The Wf/Wf mutant mouse coat comprises viable and inviable melanoblast clones, seen ultimately as pigmented and white transverse stripes--the latter more prominent. Judging from the pattern, all clones initially expand, and the inviable ones then undergo programmed cell death prenatally. To observe skin melanocytes of the viable clones during extended proliferation, the cells were explanted from individual young mice. An unusually large number of primary explants failed to survive--a result consistent with a growth handicap. In 3 of the 10 surviving cell lines, many cells spontaneously underwent a series of striking changes with the classic features of transformation. The two transformed lines that have been tested by grafting to immunosuppressed hosts formed undifferentiated invasive tumors compatible with malignant amelanotic melanoma. None of our 52 other melanocyte lines of the coisogenic wild-type strain and 13 other natural genotypes have become transformed under the same culture conditions. Molecular analysis of the Wf gene revealed a single change from wild-type: a point mutation affecting the catalytic region in the kinase domain of the Kit protein. The apparent growth disadvantage due to the mutation may allow selection for melanocytes mobilizing more efficient pathways, thus leading to neoplasia. Production of both viable and inviable melanoblast clones is unlikely to be due only to the kinase mutation; possibly the degree, duration, and consistency of expression of this locus may be controlled by cis elements outside the coding region.

Animals↗

In utero early suspicion of superfetation by ultrasound examination: a case report.

We report the case of a dichorionic and diamniotic pregnancy with the unique feature of an early ultrasound diagnosis of a 4-week size difference, which persisted throughout pregnancy. At birth, the twins had a 1-month difference in physical and neurological maturity. We believe that only the phenomenon of a superfetation can explain this difference. We report the cases found in the literature.

Journal Article↗

[Major sickle cell anemia and pregnancy. Systematic prophylactic transfusions. 13 case reports].

The seriousness of sickle cell disease together with pregnancy has led doctors to look for therapies which have yet scarcely shown their worth. Systematic blood transfusions in pregnancy did seem to improve the prognosis for both mother and fetus. Prophylactic transfusion has made it possible for us to carry thirteen pregnancies to term. There was no mortality either of fetus or mother while the morbidity either of fetus or mother while the morbidity was significantly cut down to new pathologies which were easily treated. The absence of any side effects from the transfusions encourages us to contribute this treatment working together with a highly competent blood transfusion bank.

Adult↗

[Ovarian hyperstimulation syndrome during in vitro fertilization stimulations. Comparison between the experience of the Center for Medically Assisted Procreation of the Saint Antoine maternity department and a review of the literature].

The authors present their experience with the severe ovarian hyperstimulation syndrome when they were using stimulation for IVF and ET and they compare it with the literature. Over a period of 23 months. 154 stimulations were carried out using a long protocol associated with a CnRH agonist and hMG. 142 vaginal aspirations were carried out. The clinical pregnancy rate was 19% per aspiration and 21.9% per transfer. Of the 142 patients who were aspirated five had severe ovarian hyperstimulation with a favourable outcome. The authors suggest a physiopathological comparison for ovarian hyperstimulation and the management to be carried out when this complication occurs. They emphasise how potentially serious this complication is and that there has been no physiopathological explanation for its recrudescence since GnRH agonist have started to be used.

Adult↗

[A uterus with two scars: can we allow vaginal delivery?].

This study gives the results of a year in which the active conduct of a trial of labour was carried out on uteruses that had scars in them. This approach allowed 22% of women to deliver vaginally out of a total of 41 patients. Of 17 patients (41.4%) that were put down for a tentative trial delivery, 9 (53%) did deliver vaginally. This approach seems to have been reasonable and beneficial so long as proper precautions were taken. The prognosis is better if there has been a previous vaginal delivery.

Cesarean Section↗

Clonal coat color variation due to a transforming gene expressed in melanocytes of transgenic mice.

Transgenic mice of an inbred black strain were previously produced with the Tyr-SV40E transgene, comprising simian virus 40 transforming sequences driven by the tyrosinase promoter, in order to obtain melanomas; the animals were found to be lighter than normal in coat color, to various degrees. As described here, hypopigmentation resulted from diminished differentiation of melanized pigment granules in the melanocytes of the hair bulbs in vivo and occurred autonomously in cultured melanocytes. Whereas some of the mice had single-color coats, most (7/13) had coats of two or three colors; in addition, one single-color founder produced a two-color descendant. These eight mice had patterns seen in natural genotypes; the most striking were transversely striped to various extents, with regions of left-right asymmetry on either side of the dorsal midline. The patterns visualized the same clonal developmental territories of coat melanocytes displayed in allophenic mice that are formed from conjoined early embryo cells of different color genotypes. Some of the Tyr-SV40E transgenics were also cellular genotypic mosaics, probably arising by late integration of the transgene. However, one transgenic founder with a completely striped coat proved to be true-breeding, with autosomal inheritance of the pattern. The inherited striped pattern thus exemplifies the formation of phenotypically different but genetically identical developmental clones, or phenoclones, among cells of the same type. This line of transgenic mice provides exceptional material for experimental analysis of the molecular basis for clonal variation in gene expression and of the fate of oncogenic phenoclones of melanocytes occurring in the same individual.

Animals↗

Mosaicism of tyrosinase-locus transcription and chromatin structure in dark vs. light melanocyte clones of homozygous chinchilla-mottled mice.

The chinchilla-mottled (cm) mutation at the mouse tyrosinase-encoding locus leads to a transversely striped pattern of dark- and light-grey coat colors in homozygotes. The same basic pattern occurs in various other genotypes and has previously been found to represent the clonal developmental history of melanocytes. In a homozygote such as cm/cm, cis-acting mechanisms would be expected to account for the color differences. To search for these mechanisms, the genomic structure of the mutation was examined and compared with the wild-type, and its function was compared in cultured melanocyte clones of the respective colors. Evidence from restriction mapping indicated that the coding region of the mutant gene resembles that of the fully and uniformly pigmented wild-type. However, the upstream sequences are rearranged in the mutation. The rearrangement begins 5 kb 5' of the transcription initiation site and is estimated to encompass at least 30 kb of distal upstream sequence. At least two stable functional states of the cm gene were detectable: Light-cell clones have low levels of tyrosinase-specific transcription, reduced DNAase I sensitivity of tyrosinase chromatin, and no detectable hypersensitive sites near the gene; dark-cell clones have higher (but subnormal) levels of transcription, greater sensitivity of chromatin to DNAase I, and a hypersensitive site in the promoter region. The changed relation between the structural gene and its upstream region may separate it from cis-acting control elements, resulting in reduced and variable ability to achieve the appropriate chromatin configuration near the time of melanocyte determination; differences in expression among clonal initiator cells are then mitotically perpetuated.

Alleles↗

[Primary biliary cirrhosis and pregnancy. Apropos of a clinical case. Review of the literature].

The appearance of pruritus and abnormal liver function tests (cellular damage) during pregnancy should of course suggest the diagnosis of intrahepatic cholestasis of pregnancy. However, these signs must also be recognized as signs of other hepatic diseases, especially primary biliary cirrhosis. The diagnosis is based on the search for antimitochondrial antibodies. This mode of presentation must not be overlooked because of major therapeutic consequences. The disease course often stabilizes with ursodeoxycholic acid, if administrated early.

Adult↗