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Biomedical subjects

J Renaud

Publications and source records attributed to J Renaud.

At least 19 recordsLinked to original sources

Nodal order parameter in electron-doped Pr(2-x)CexCuO(4-delta) superconducting films.

The London penetration depth, lambda(ab)(T), is reported for thin films of the electron-doped superconductor Pr(2-x)Ce(x)CuO(4-delta) with varying Ce concentration, x=0.13, 0.15, and 0.17. Measurements down to 0.35 K were carried out using a tunnel-diode oscillator with excitation fields applied both perpendicular and parallel to the conducting planes. Films at all three doping levels exhibited power law behavior indicative of d-wave pairing with impurity scattering. These results are fully consistent with previous measurements on single crystals.

Journal Article↗

Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during muscle fatigue.

The effects of 10 microM glibenclamide, an ATP-sensitive K(+) (K(ATP)) channel blocker, and 100 microM pinacidil, a channel opener, were studied to determine how the K(ATP) channel affects mouse extensor digitorum longus (EDL) and soleus muscle during fatigue. Fatigue was elicited with 200-ms-long tetanic contractions every second. Glibenclamide did not affect rate and extent of fatigue, force recovery, or (86)Rb(+) fractional loss. The only effects of glibenclamide during fatigue were: an increase in resting tension (EDL and soleus), a depolarization of the cell membrane, a prolongation of the repolarization phase of action potential, and a greater ATP depletion in soleus. Pinacidil, on the other hand, increased the rate but not the extent of fatigue, abolished the normal increase in resting tension during fatigue, enhanced force recovery, and increased (86)Rb(+) fractional loss in both the EDL and soleus. During fatigue, the decreases in ATP and phosphocreatine of soleus muscle were less in the presence of pinacidil. The glibenclamide effects suggest that fatigue, elicited with intermittent contractions, activates few K(ATP) channels that affect resting tension and membrane potentials but not tetanic force, whereas opening the channel with pinacidil causes a faster decrease in tetanic force, improves force recovery, and helps in preserving energy.

Action Potentials↗

Use of selective serotonin reuptake inhibitors for the treatment of childhood panic disorder: a pilot study.

This preliminary study examines the effectiveness and safety of selective serotonin reuptake inhibitors (SSRIs) for the treatment of panic disorder in children and adolescents. In a prospective open label study, 12 children and adolescents with panic disorder were treated with SSRIs, and if necessary, with benzodiazepines, for a period of 6-8 weeks and were followed for approximately 6 months. During the trial, clinician-based and self-report rating scales for anxiety and depression, functioning, and side effects, were administered. Using the Clinical Global Impression Scale (CGIS) 75% of patients showed much to very much improvement with SSRIs without experiencing significant side effects. After controlling for changes in depressive symptoms, self-report and clinician-based anxiety scales also showed significant improvement. At the end of the trial, 67% of patients no longer fulfilled criteria for panic disorder and 4 patients remained with significant residual symptoms. In conclusion, SSRIs appear to be a safe and promising for the treatment of children and adolescents with panic disorder, however, randomized controlled trials evaluating the effects of SSRIs and other interventions (e.g., cognitive therapy) for treating panic disorder in children and adolescents are warranted. It appears that until the SSRIs begin to exert their effects, a benzodiazepine adjunct treatment might be helpful for patients with severe panic disorder.

Adolescent↗

Suicide in adolescents with disruptive disorders.

OBJECTIVE: To determine the psychiatric risk factors for suicide in adolescents with disruptive disorders. METHOD: Fifty-nine adolescent suicide completers and 18 community controls, both having a probable or definite current DSM-III diagnosis of disruptive disorders, were compared. RESULTS: Adolescents with disruptive disorders who committed suicide had higher rates of current substance abuse, past suicide attempt, family history of substance abuse, and family history of mood disorder than disruptive community controls. CONCLUSIONS: Disruptive adolescents appear to be at risk for completed suicide when comorbid substance abuse and past history of suicide attempt are present. The risk increases if the adolescents have a past history of physical abuse and if they have parents with substance abuse and mood disorders. Clinicians should be aware of these risk factors and implement active interventions to prevent suicide. Treatment should focus on treating not only the adolescents, but also their family members. The findings of this study also highlight the need for future research in the prevention of suicide in adolescents with disruptive disorders and comorbid substance abuse.

Adolescent↗

A risk-benefit assessment of pharmacotherapies for clinical depression in children and adolescents.

Child and adolescent major depressive disorders are common and recurrent disorders. The prevalence of major depressive disorders is estimated to be approximately 2% in children and 4 to 8% in adolescents. Major depressive disorders in children are frequently accompanied by other psychiatric disorders, poor psychosocial outcome and a high risk of suicide and substance abuse, indicating the need for effective treatment and prevention. The use of antidepressant medications as the first line of treatment for children and adolescents with mild to moderate major depressive disorders has been questioned. However, some subgroups of patients may benefit from initial treatment with antidepressants. These subgroups may include patients who are unwilling or unable to undergo psychotherapy, have not responded to at least 8 to 12 sessions of psychotherapy, have bipolar, atypical or severe depression or have recurrent depression. Currently, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors are the first medication choice because of their efficacy, benign adverse effect profile, ease of use and low risk of death following an overdose. Further research in continuation and maintenance treatments, treatment of comorbid conditions, subtypes of depression, e.g. bipolar, atypical, seasonal, and combinations of pharmacotherapy and psychotherapy are needed. In addition, studies of the pharmacokinetics, pharmacodynamics and long term adverse effects of antidepressant medications in children and adolescents are warranted.

Adolescent↗

Pharmacologic treatment for children and adolescents with anxiety disorders.

Pediatric anxiety disorders are common illnesses that, if left untreated, may induce academic, family, and interpersonal problems. Cognitive-behavioral techniques and other psychotherapeutic interventions may be adequate for the treatment of most anxiety disorders. For patients with severe symptoms or for whom psychotherapeutic approaches are not adequate, medications are indicated. Among the available medications, the SSRIs are currently the first choice; however, other medications, such as the benzodiazepines and the TCAs, may be used alone or sometimes in combination with the SSRIs. Caution with respect to medication interactions and side effects is indicated. In particular, long-term side effects in these medications have not been well studied.

Adolescent↗

Rapid response to psychosocial treatment for adolescent depression: a two-year follow-up.

OBJECTIVE: To examine the differential course and treatment outcome of patients who participated in a randomized clinical trial, comparing cognitive, family, and supportive psychotherapies for adolescent major depressive disorder. METHOD: In a sample of 100 depressed adolescents, remission, clinical recovery, recurrence, and functional improvement were examined at the end of acute treatment and at 1- and 2-year follow-up, according to their type of response to treatment. Rapid response was defined as a decline of > or = 50% in the Beck Depression Inventory (BDI) score from pretreatment until the beginning of the second session of psychotherapy, intermediate as a decline of < 50% but > 0%, and initial nonresponse as a BDI score that stayed the same or increased. RESULTS: Rapid responders showed a better outcome at acute treatment, 1-year, and in some measures, 2-year follow-up. For those who had recurrences over time, rapid responders showed a longer period before recurrence. Subjects were most likely to respond rapidly, or not at all, in the supportive cell. CONCLUSIONS: These findings suggest that milder forms of depression may benefit from initial supportive therapy or short trials of more specialized types of psychotherapy. The use of a placebo run-in period might help to "wash out" nonspecific responders.

Adolescent↗

Total synthesis of taxol.

Taxol, a substance originally isolated from the Pacific yew tree (Taxus brevifolia) more than two decades ago, has recently been approved for the clinical treatment of cancer patients. Hailed as having provided one of the most significant advances in cancer therapy, this molecule exerts its anticancer activity by inhibiting mitosis through enhancement of the polymerization of tubulin and consequent stabilization of microtubules. The scarcity of taxol and the ecological impact of harvesting it have prompted extension searches for alternative sources including semisynthesis, cellular culture production and chemical synthesis. The latter has been attempted for almost two decades, but these attempts have been thwarted by the magnitude of the synthetic challenge. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids.

Models, Molecular↗

Transcription of the histone H5 gene is regulated by three differentiation-specific enhancers.

Histone H5, an early marker of the avian erythroid lineage, is expressed at low levels in early erythroid precursors and at higher levels in more mature cells. We show that the increase in H5 expression is due to transcriptional activation of the H5 gene following differentiation of precursor CFU(E). We have found and characterized two upstream enhancers, E1 (between -2233 and -1878 from the site of transcription initiation, +1) and E3 (between -1321 and -1163), and confirmed the presence of a downstream enhancer (C. D. Trainor, S. J. Stamler, and J. D. Engel, Nature [London] 328:827-830, 1987) E7 (between +846 and +1181) which are responsible for the increase in H5 gene transcription. The enhancers had a weak effect in nondifferentiated CFU(E) but a strong effect when the cells were induced to differentiate. Cooperation among the three enhancers, however, was not required for H5 gene activity in the differentiated cells. The enhancers contain binding sites for several ubiquitous and erythroid cell-specific nuclear proteins, including GATA-1, as demonstrated with GATA-1-specific antibodies. Although the GATA sites were required for enhancer function, the concentration of GATA-1, GATA-2, and GATA-3 decreased during cell differentiation, and overexpression of these factors had little effect on H5 transcription. Hence, the differentiation-specific effect of the enhancers is not mediated by changes in relative levels of the GATA factors. Functional analysis of the H5 promoter indicated that the requirement of several elements, including a GC box necessary for transcription enhancement, did not change during the early stages of CFU(E) differentiation. However, the UPE, a positive element in proliferating CFU(E) recognized by the transcription factor H4TF2, was dispensable in the differentiated cells. These results suggest that as the cells enter the final stages of differentiation, there is a reprogramming of the regulatory factors that control H5 transcription and that the enhancers rescue and increase the activity of the promoter.

Amino Acid Sequence↗

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↗

[Focal infection? Did you say focal infection ... focal infection and uveitis].

A chronic seat of infection more often than not situated in the E.N.T. area is responsible for remote pathological symptoms commonly called focal infection. The eye may be a target organ, where focal infection appears in the form of a uveitis. Four clinical observations are reported as demonstration. The transmission mechanism operates through an immune phenomenon from bacterial antigens which engender reactions of hypersensitivity. The E.N.T. specialist must be aware of these symptoms and seek a pharyngeal, sinusal or latent buccodental infection.

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↗

Recognition of (dG)n.(dC)n sequences by endonuclease G. Characterization of the calf thymus nuclease.

We report the purification of endonuclease G (Ruiz-Carrillo, A., and Renaud, J. (1987) EMBO J. 6, 401-407) from calf thymus nuclei and whole tissue. The enzyme has been enriched 29,000-fold, and the activity was unambiguously identified with a 26-kDa protein after renaturation following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native nuclease behaves as a 50-kDa species by gel filtration, suggesting that it is composed of two subunits, presumably identical. In terms of absolute amounts, endonuclease G (endo G) is a nuclear enzyme although it was also detected in purified mitochondria. Endo G is highly specific for (dG)n.(dC)n tracts in DNA, nicking either strand of relaxed substrates with similar kinetics. The sensitivity of the homopolymer tracts is proportional to their length (from n = 8 to 29), insofar as the flanking sequences are constant. However, the overall rate of cleavage is influenced by the composition of the flanking DNA. Minor cleavage sites contain shorter (dG)n.(dC)n clusters (n = 3-7). Endo G efficiently cleaves (dC)n but not (dG)n runs in single-stranded DNA, suggesting that it may recognize an asymmetric strand conformation of the homopolymer tracts. Endo G does not recognize other homo(co)-polymer sequences or cruciform structures in DNA.

Animals↗