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Biomedical subjects

S Rousseau

Publications and source records attributed to S Rousseau.

17 recordsLinked to original sources

Repression of the H5 histone gene by a factor from erythrocytes that binds to the region of transcription initiation.

Expression of histone H5, like that of other erythrocyte specific proteins, declines during the latter stages of erythroid maturation because of a decrease in the rate of gene transcription. Here, we report the isolation of cIBR (chicken initiation binding repressor), a 75 kDa DNA binding glycoprotein from mature chicken erythrocytes that recognizes sequences spanning the transcription start sites of the H5 gene. cIBR was found to repress transcription from the H5 promoter in vitro and this effect could be relieved by mutations that lowered the affinity of the factor for its cognate sequence. cIBR inhibited transcription by interfering with assembly of the initiation complex, but it did not affect transcription from pre-assembled complexes. Consistent with this, binding of bacterially expressed human TFIID to the TATA element prevented subsequent binding of cIBR, although the opposite was not true. This, and the fact that cIBR had no effect when bound in a location upstream from the promoter, suggests that binding of cIBR to the start site region causes repression by direct interference with general transcription factors other than TFIID, possibly TFIIB. cIBR was found in mature and relatively late erythrocytes but not in early erythroid cells which actively transcribe the H5 gene; the transcriptionally active cells contain instead cIBF (chicken initiation binding factor). Purified cIBF is a non-glycosylated 68-70 kDa DNA binding protein(s) which also recognizes the region of transcription initiation of the H5 gene.

Animals

Respiratory mechanics in mechanically ventilated newborns: a comparison between passive inflation and occlusion methods.

A passive inflation method was described for measuring total respiratory elastance and resistance during mechanical ventilation in adult patients (Rossi et al., J Appl Physiol 58:1849, 1985). We applied this method to preterm and full-term mechanically ventilated newborn infants and we compared the results with those obtained by the occlusion method. We performed 37 tests in 16 newborn infants (B.W. 880-4,500 g; G.A. 28-42 weeks), between 1 and 45 days of postnatal age, ventilated with a Servo Ventilator 900C, set in controlled-volume mode. Flow was measured through a pneumotachograph inserted between the endotracheal tube (ETT) and the breathing circuit, tidal volume by integration of flow and airway pressure directly at the airway opening. Flow, volume, and pressure were recorded on an X/Y plotter to obtain pressure-volume (P/V), flow-volume (V/V) loops, and pressure-time curves. Occlusion was performed by using the end-inspiratory and the end-expiratory pause buttons of the ventilator. Analysis of P/V and V/V loops provided respiratory system compliance (Crs, infl.), resistance (Rrs, infl.), and "intrinsic positive end-expiratory pressure" (PEEPi, infl.). These values were compared with Crs, occl., Rrs, occl., and PEEPi, occl. measured by the occlusion method. The measurements were well correlated (Crs, infl./Crs, occl.: r = 0.90; Rrs, infl./Rrs, occl.: r = 0.91; PEEPi, infl./PEEPi, occl.: r = 0.91). Rrs, infl./Rrs, occl. and PEEPi, infl./PEEPi, occl. did not differ significantly. However, Crs, occl. was 15% higher than Crs, infl. (P less than 0.01). The passive inflation method is simple to use and well tolerated in preterm and full-term ventilated newborn infants, it provides accurate results, and can be a good alternative to occlusion methods. It requires, however, a constant inflation flow and adaptation to the ventilator.

Airway Resistance

Induction of severe vascular leakage by low doses of Escherichia coli hemolysin in perfused rabbit lungs.

S. aureus alpha-toxin and E. coli hemolysin (Hly) represent two prototypes of pore-forming cytolysins. Both are established virulence factors and have been implicated in the development of septic lung failure. Low doses of these agents cause thromboxane-mediated vasoconstriction and edema formation in isolated perfused rabbit lungs. In a preceding investigation, we observed that alpha-toxin causes overt endothelial cell damage in these lungs, as demonstrable by electron microscopy (Seeger W, Birkemeyer RG, Ermert L, Suttorp N, Bhakdi S, Duncker HR: Lab Invest 63:341, 1990). Here, we present results of a parallel study conducted with E. coli hemolysin. Thromboxane-dependent pulmonary hypertension was suppressed by the addition of acetylsalicylic acid to the perfusion fluid in all cases. Administration of 0.2 hemolytic units (HU; i.e., 20 ng/ml protein) resulted in progressive weight gain after a lag period of 10 to 15 minutes, and 30 minutes after toxin application the gravimetrically determined capillary filtration coefficients (Kfc) were increased greater than 10-fold. Perfusion was terminated when the total lung weight gain surpassed 20 gm. 0.12 HU/ml E. coli hemolysin caused 2- to 3-fold increased capillary filtration coefficients values within 110 minutes, concomitant with intermediate quantities of edema formation (9.7 +/- 2.7 gm). Potassium liberation in the absence of lactate dehydrogenase release occurred in all toxin treated lungs. Electron microscopic examination after perfusion fixation revealed interstitial edema formation in areas remote from the blood-gas exchange barrier. Increased numbers of endothelial plasmalemmal vesicles were visualized at the very onset of edema formation in lungs exposed to 0.2 HU/ml, and after a 110-minute exposure to 0.12 HU/ml of the toxin, but not in lungs exhibiting severe edema (greater than 20 gm weight gain). In contrast to our previous results with alpha-toxin, endothelial cells displayed normal electron density here and were not detached from the fused basal lamina. Hence, although both pore formers provoke severe vascular leakage in our experimental model, the underlying pathways probably divert fundamentally from each other.

Animals

The role of laparoscopy in acute pelvic infections.

54 patients presented by history, physical examination and laboratory tests with suspected pelvic inflammatory disease (PID). The use of laparoscopy as a diagnostic tool proved in 13 cases (24%) that the presumptive diagnosis was incorrect. Bacteriological studies revealed chlamydial infection in 21 of 41 cases, in 6 cases only at laparoscopy in the pelvic cavity, gonococcal in 9 of 41 cases; mycoplasmas were identified in 15 cases, being the only pathogen in 7. In 9 cases, no recognized pathogens were isolated. Polymicrobism was frequent. Follow-up studies identified 5 cases of treatment failure; 2 of Gonococcus and 3 of Chlamydia, and detected 3 cases of Chlamydia which had not been identified initially. We discuss the use of laparoscopy in the diagnosis and for follow-up and treatment of PIDs.

Acute Disease

Hyperprolactinemia and temporal lobe epilepsy in a woman: concomitant and persistent prolactin suppression and temporal lobe epilepsy relief.

It has been reported that hyperprolactinemia may be associated with increased temporal lobe activity. Coexisting hyperprolactinemia (97.5 +/- 3.2 ng/ml) related to a pituitary tumefaction (8 mm) and Temporal Lobe Epilepsy (TLE), were observed in a 37-year-old woman. Carbamazepin (CBZ) therapy induced a marked improvement in TLE symptoms and EEG recordings, but did not influence hyperprolactinemia and related symptoms. Long-lasting (27 months) normoprolactinemia (19.4 +/- 0.6 ng/ml) and TLE relief were achieved on a dopamine (DA) agonist medication, e.g. pergolide mesylate, 25-50 micrograms/day given over 8 months, and persisted as long as 27 months after drug withdrawal. Posttreatment CT scans showed progressive shrinkage of the pituitary tumor (2 mm) associated with an empty-sella. It is proposed that, whenever TLE and hyperprolactinemia coexist, therapy with a DA agonist such as pergolide mesylate, resulting in normoprolactinemia, may be beneficial in TLE control.

Adult

Basal expression of the histone H5 gene is controlled by positive and negative cis-acting sequences.

Sequences from -3500 to +1365 of the chicken histone H5 gene have been analyzed for the presence of cis-acting elements in H5 expressing (transformed CFU-E) and non-expressing cells (fibroblasts). The region from -3500 to -115 had little effect on transcription. Proximal upstream sequences contain a negative element (UNE, -115 to -95), capable to also repress the activity of the heterologous HSV tk promoter, and two positive elements, a consensus GC-box (-83 to -74) and a proximal element (UPE, -54 to -38). The sequence of the UPE is highly related to the histone H4 subtype-specific element and it has been conserved in the duck H5 and the human and mouse H1(0) genes at equivalent positions. Although the effect of the UNE, GC-box and UPE was not tissue-specific, sequences from -38 to +77 appear to confer a degree of tissue specificity to the promoter. An activating erythroid-specific element (DE) was found downstream of the H5 gene (+1042 to +1185). The activity of the DE was modest but independent of position and orientation and required the presence of the promoter proximal elements. The DE harbors the sequence AGATAA that is recognized by a protein factor, presumably the same that binds to other erythrocyte-specific enhancers. The low activity of DE in the CFU-E may be related to the low concentration of the AGATAA-binding factor in the differentiation-blocked cells.

Animals

Pilot phase I study using zidovudine in association with a 10-day course of anti-CD4 monoclonal antibody in seven AIDS patients.

Experimental evidence has demonstrated that monoclonal antibody (MAb) 13B8.2, a workshop-qualified anti-CD4 MAb, (1) inhibits in vitro syncytium formation as well as in vitro HIV infection of CD4+ T cells; (2) delivers negative signals to T cells, thus preventing T-cell activation and viral replication; (3) contributes to CD4+ T-cell clearance by its Fc portion, and (4) induces an immune response by the patient, contributing potentially to an anti-idiotypic response of interest for the control of the immune parameters of the disease. On this basis a phase I study combining zidovudine treatment and a 10-day course of anti-CD4 MAb was performed in seven AIDS patients (Centers for Disease Control group IV). The treatment was well tolerated. MAb dosage and schedule were adjusted on the basis of circulating CD4+ cells and MAb pharmacokinetics; immunological and virological parameters were also monitored. One patient presented a transient increment in CD4+ T cells associated with augmented T-cell function, the suppression of p24 in the serum and a negative RT assay. A second patient had a steady increment of CD4+ T cells after completion of the treatment, with a transient decrease of serum p24 5 days after completion of the anti-CD4 protocol.

Acquired Immunodeficiency Syndrome

[Chlamydia trachomatis cervicitis].

Cervicitis due to Chlamydia trachomatis is common in certain groups of women examined by the authors. It is clinically discrete, having no special characteristics and often not even showing clinical manifestations. However, it is the stage of infection of the genital apparatus which it is desirable to detect in order to prevent the serious tubal complications to which a too large number of young women is subject. Clinical medicine permits diagnosis and prescribes treatment for patients and, if possible, their partners. The principal difficulty is to know when to invoke them.

Adolescent

[Criteria of the diagnosis and treatment of carotid atheromatosis].

This retrospective study concerning 102 patients was undertaken to study the therapeutic decisions in these patients when they presented with symptoms of cerebral vascular insufficiency, mostly from the territory of the carotid artery, either transient or accompanied by a deficit. The current literature on the subject is also mentioned. The clinical outcome with regard to the quality of life, seems to have been better in patients who were subjected to carotid endarterectomies than in those who received medical treatment.

Aged