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Biomedical subjects

F Clément

Publications and source records attributed to F Clément.

At least 19 recordsLinked to original sources

Follicular growth and ovarian dynamics in mammals.

General characteristics of female reproductive activity, such as seasonality, cyclicity and triggering of ovulation differ widely among mammals, but common mechanisms underlie ovarian function. In all mammals, follicles begin to grow from a pool of primordial follicles constituted early in life, continuously throughout the life of the female. Follicular development involves two phases. In a first phase (basal follicular growth), follicles grow slowly and follicular growth rate is tightly related to proliferation of granulosa cells. Basal follicular growth is mainly under the control of growth factors of paracrine origin. In these follicles, FSH may exert an indirect mitogenic effect on granulosa cells by enhancing expression of growth factors or growth factor receptors. In a second phase (terminal follicular growth), follicular growth is rapid and occurs by enlargement of the antrum. In addition, it is accompanied by important changes in differentiation of follicular cells. Terminal follicular development is strictly dependent on gonadotrophins. FSH plays determinant roles in enhancing granulosa cell differentiation and survival. These actions are mediated or modulated in an important way by paracrine factors, particularly steroids and growth factors. LH stimulates steroidogenesis in theca cells and sustains terminal maturation of granulosa cells in preovulatory follicles. Follicular growth, atresia and ovulation are accompanied by important tissue remodelling processes, which are under the fine control of proteinases and inhibitors of proteinases. In particular matrix metalloproteinases and their inhibitors are probably involved in the control of rapid terminal follicular growth and regression of atretic follicles as well as in follicular rupture at ovulation.

Animals

Tetrasomy 8 in a patient with acute nonlymphocytic leukemia: a metaphase and interphase study with fluorescence in situ hybridization.

Tetrasomy 8 constitutes a relatively rare recurring chromosome defect in myeloid disorders. The patient reported here, a 71-year-old man, presented with tetrasomy 8 as the sole chromosome abnormality associated with an acute nonlymphocytic leukemia of the M2 type. He failed to respond to chemotherapy and died one year after diagnosis. Following conventional cytogenetics and fluorescence in situ hybridization (FISH) with a centromeric probe specific for chromosome 8, tetrasomy 8 was detected in 61% of the metaphases analyzed and trisomy 8 in 39%. FISH analysis of interphase nuclei confirmed the existence of tetrasomic (35%) and trisomic cells (56%) and revealed a number of cells with two chromosomes 8 (8%). This normal population may represent lymphocytes or myeloid cells that escaped conventional analysis due to their inability to divide or to the small number of metaphases available. The relatively higher proportion of tetrasomic cells in metaphase compared with interphase may be attributed to a proliferative advantage of tetrasomic cells in vitro or to the longer duration of their cell cycle. The simultaneous presence of trisomic and tetrasomic cells confirms the hypothesis of a clonal relationship between trisomy 8 and tetrasomy 8. Our case brings further evidence to the specificity of tetrasomy 8 to myeloid disorders and to the association of this chromosome abnormality with a relatively poor prognosis. However, new patients must be studied to further delineate this cytogenetic entity.

Aged

[Heart rate fluctuations in the horse at rest: (1) Investigation of heart rate changes by spectrum analysis].

The heart rate fluctuations at rest were studied in order to explore the emotionality of the horses by isolating the influence of the autonomic control. This paper presents a method of spectral analysis which was used to analyse the heart rate variability in the frequency domain. The heartbeat intervals were recorded during 1 h and a series of 1,024 heartbeats was extracted to compute a power spectrum of density. This was obtained by calculating the Fourier transform of the autocorrelation function of the series. This spectral analysis was applied to heart rate recordings in order to illustrate its sensitivity. The normal heart rate fluctuations at rest were compared with those obtained after atropine and atropine+adrenaline injections. The normal power spectrum revealed several low frequency components (< 0.1 cycle/beat). The atropine injection reduced heart rate variability while the atropine+adrenaline injection increased the power of low frequency fluctuations.

Animals

[Heart rate fluctuations in the horse at rest: (2) Biological variation factors related to behavioural profile].

Variability of heart rate was analysed within a sample of 30 horses in order to determine the influence of factors (animal, age, sex and breed) associated with different behavioural patterns. The heart rate fluctuations were analysed by computing the power spectral density of a series of heartbeat intervals. A generalized linear model was used to compare the spectra and to reveal the effect of each factor: animal age, sex and breed. The scale and shape of spectral densities were significantly different between animals. This individual variability was partly explained by the sex and age effects while the breed effect had only a weak influence. Young horses and mares exhibited a greater heart rate fluctuation which may be related to their higher emotionality.

Age Factors

[Cerebral protection by retrograde perfusion in the treatment of acute aortic dissection].

Four consecutive patients underwent resection and graft replacement of ascending aorta or aortic arch for acute dissection. Retrograde cerebral perfusion (RCP) was used during circulatory arrest. RCP at 15 degrees C was administered through the superior vena cava. Duration of cerebral ischaemia and cardiopulmonary bypass averaged 33 and 156 minutes respectively. Retrograde perfusion flow was regulated from 100 to 800 ml/minute to maintain an internal jugular vein pressure of about 25 cm H2O. All patients survived. Three patients awoke neurologically intact. Minor neurological disturbance was found in 1 patient, he was discharged from hospital at day 11 without any detectable neurological deficit. This technique was attractive because it provided a dry operative field unencumbered by perfusion cannulas or clamps, facilitated construction of a more secure distal anastomosis, and avoided the risk of further injury resulting from the aortic cross clamp. It seems that RCP allows longer circulatory arrest time.

Acute Disease

Two-dimensional polyacrylamide gel electrophoresis analysis of cryoglobulins and identification of an IgM-associated peptide.

The clonality of immunoglobulins (Igs) in cryoprecipitates (n = 41) was studied by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Our series included 24 cryoglobulins characterized by immunofixation electrophoresis (IF), 12 'trace amount' cryoglobulins, defined by a protein content in the precipitate of less than 0.05 mg/ml of serum, and five cryoglobulins of undetermined protein composition by IF. 2-D PAGE analysis showed polyclonal IgG associated either with monoclonal Igs (type II cryoglobulins; n = 14) or with polyclonal IgM (type III cryoglobulins; n = 14). In ten cryoprecipitates (two 'trace amount' cryoglobulins as well as seven of 19 type II and as one of five type III cryoglobulins by IF) polyclonal IgG were associated with a mixture of polyclonal and monoclonal IgM. These cryoglobulins were tentatively named type II-III cryoglobulins. A monoclonal IgM was observed in one cryoprecipitate (type I cryoglobulins). Two cryoglobulins presented unexpected 2-D patterns, characterized by the presence of oligoclonal IgM, with trace amounts of Igs of different isotypes (tentatively named type II-III(variant) cryoglobulins). A peptide of 44 kDa with a pI of 5.45 was observed in all cryoglobulins containing IgM (n = 40). This peptide was also present in purified monoclonal or polyclonal IgM fractions. N-terminal microsequencing (12 amino acid residues) revealed that this IgM-associated peptide was an unknown protein. Our results highlight the role of 2-D PAGE as an aid in the analysis of cryoglobulins.

Amino Acid Sequence

Isolation of specific DNA fragments of Mycobacterium avium and their possible use in diagnosis.

We cloned and sequenced two DNA fragments (DT1 and DT6) from Mycobacterium avium serotype 2 for use in the identification of members of the M. avium-M. intracellulare complex (MAC). Reference strains of MAC belonging to serovars 1 to 28 were examined by using these DNA fragments as probes. The study revealed that the DT6 probe hybridized with DNAs from M. avium strains (serovars 1 to 6, 8 to 11, and 21), while the DT1 probe hybridized with DNAs from serovars 2, 3, 7, 12 to 20, and 23 to 25. DT1- and DT6-derived oligonucleotides were selected for use as primers in a polymerase chain reaction test. Amplification of the DT1 and DT6 sequences may provide the basis for a rapid and reliable assay for the detection of mycobacteria belonging to MAC.

Animals

Pulsed field gel electrophoresis of representatives of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains.

Using field inversion gel electrophoresis (FIGE), different Mycobacterium tuberculosis strains, such as phage prototypes, exhibit different DNA restriction patterns which are easy to compare. Virulent and avirulent variants of M. tuberculosis H37, as well as daughter strains of M. bovis BCG, display characteristic DNA profiles. BCG strains isolated from suppurative adenitis following vaccination of French patients showed patterns identical to the BCG Pasteur strain used for vaccination. These results demonstrate that FIGE of DNA restriction fragments generated by DraI represents a suitable technique for the analysis of mycobacteria at a genomic level. The DraI profiles allow the differentiation and precise identification of the BCG Pasteur, Glaxo, Russian and Japanese strains.

DNA, Bacterial

Clonality of cold agglutinins in patients with hemolytic anemia: an analysis by high-resolution two-dimensional gel electrophoresis.

High-resolution two-dimensional gel electrophoresis (2-DGE) was used to analyse plasma samples and partially purified cold agglutinins (CA) obtained from two selected patients. Both presented an acute hemolytic anemia with CA of high thermal amplitude, normal immunoglobulin levels, no detectable paraproteinemia, and no clinical evidence of a malignant B-cell disorder. The electrophoretograms of their plasma showed evident alternations of the "normal" protein profile, which were directly related to hemolysis (absence of the spots of haptoglobin and in one case of those of hemopexin), but no monoclonal gammopathy. The electrophoretograms of their purified CA revealed two clearly different spot patterns respectively corresponding to a monoclonal IgM and to polyclonal IgM. These results show that the clonality of CA associated with hemolytic anemia can be easily determined by 2-DGE. This technique may be very useful to discriminate chronic cold agglutinin disease in the early phase from "parainfectious" CA.

Adult

[The treatment of acute lymphatic leukemia in adults: pilot project with intensive early therapy without a maintenance phase].

Acute lymphoblastic leukemia (ALL) is conventionally treated in three phases: remission induction, consolidation and maintenance. In adults initial remission rates of nearly 80% can be achieved. The 3 to 5 year leukemia free survival is 20 to 40%. Most relapses occur during maintenance, despite continuous therapy for 2 to 3 years. The value of maintenance therapy following intensive induction in adults is not documented. In this pilot study we treated 34 patients with ALL in five Swiss centers between 1986 and 1989 with intensive induction/consolidation therapy alone. Three induction/consolidation courses were applied: course I, 43 days, consisting of daunomycin, vincristine, prednisone, methotrexate, L-asparaginase and intrathecal CNS prophylaxis; course II, 6 days, consisting of high dose cytosine arabinoside and VP-16; course III, three non randomized arms, either allogeneic or autologous bone marrow transplantation (BMT) or high dose cyclophosphamide and repeated intrathecal therapy alone. 32 patients (94%) reached complete remission (CR): 24 after course I (71%), 7 after course II (cumulative 91%) and one after course III only (cumulative 94%). 3 patients had early, relapses before course III, 3 died of infection, and 2 of graft-versus-host disease. One patient had refractory leukemia in all three courses. 26 patients (76%) were in CR after completion of therapy. 16 relapsed within 1 to 17 months (median 5). 10 patients are free of disease after 10 to 44 months (median 24): 5 had had allogeneic BMT, 3 autologous BMT and 2 cyclophosphamide in course III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Genotypic and phenotypic evidence of T-cell leukemia in a patient successfully treated by interferon-alpha for typical hairy cell leukemia.

A 53-year-old man was diagnosed to have typical hairy cell leukemia. Immunophenotyping of frozen splenic tissue showed clonality of hairy cells for mu lambda, confirmed by the corresponding immunoglobulin gene rearrangements. The patient was successfully treated with interferon-alpha (IF-alpha). In the fifth year of treatment with IF-alpha the morphology of peripheral blood mononuclear cells (PBMC) and of bone marrow infiltration changed with the appearance of numerous small to intermediate shaped lymphocytes of a T-helper phenotype. Frank leukemia, resistant to IF-alpha treatment and ultimately aggressive chemotherapy, developed. Emergence of this second clonal disease was confirmed by rearrangement studies performed on PBMC; rearrangements of both alleles of the TCR beta were identified, whereas the JH and lambda IVS genes were in germline configuration. The outgrowth of a second, malignant T-cell clone paralleled by the disappearance (down-regulation?) of the initial B-cell clone while under cytokine treatment is consistent with the possibility that IF-alpha favoured the emergence of this second clone.

Bone Marrow

[Achondrogenesis. Ultrasonic diagnosis and clinical and anatomopathologic comparison].

The authors report two cases of achondrogenesis, the first of which was diagnosed in utero. Ultrasonographic abnormalities suggested the diagnosis, which was confirmed radiographically. The diagnosis of achondrogenesis in utero made it possible to avoid a Cesarian. It is always difficult to extract the malformed fetus. The histopathology findings make it possible to codify this rare type of congenital and lethal chondrodysplasia. Achondrogenesis is probably inherited in a recessive and autosomic fashion.

Achondroplasia

[Monoclonal gammopathies of undetermined significance called "MGUS"].

While the discovery of a monoclonal gammopathy in the blood of a patient sometimes leads to the diagnosis of multiple myeloma, immunocytoma or other B-cell lymphoproliferative syndromes, "secondary" monoclonal dysproteinemia is seldom considered. In most cases "monoclonal gammopathy of undetermined significance" (MGUS) is diagnosed. After ten years about 25% of these cases evolve to true multiple myeloma or Waldenström's disease. Other MGUS usually remain asymptomatic, though sometimes a complication such as amyloidosis or cryoglobulinemia may occur as a result of the "perverse" effect of the monoclonal protein. Some cases are described.

Aged