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Biomedical subjects

S Allard

Publications and source records attributed to S Allard.

At least 19 recordsLinked to original sources

TOM1p, a yeast hect-domain protein which mediates transcriptional regulation through the ADA/SAGA coactivator complexes.

The hect-domain has been characterized as a conserved feature of a group of E3 ubiquitin ligases. Here we show that the yeast hect-domain protein TOM1p regulates transcriptional activation through effects on the ADA transcriptional coactivator proteins. Null mutations of tom1 result in similar defects in transcription from ADH2 and HIS3 promoters, and enhanced transcription from the GAL10 promoter as do null mutations in ngg1/ada3. Strains with disruptions of both ngg1 and tom1 have the same phenotype as strains with a disruption of only ngg1 implying that these genes are acting through the same pathway. In the absence of TOM1p, the normal associations of the ADA proteins with SPT3p and the TATA-binding protein are reduced. The action of TOM1p is most likely mediated through ubiquitination since mutation of Cys3235 to Ala, corresponding residues of which are required for thioester bond formation with ubiquitin in other hect-domain proteins, results in similar changes in transcription as the null mutation. A direct role for TOM1p in regulation of ADA-associated proteins is further supported by the finding that SPT7p is ubiquitinated in a TOM1p-dependent fashion and that TOM1p coimmunoprecipitates with the ADA proteins.

Acetyltransferases

Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone.

This open-label, randomized, three-way crossover study of 28 healthy premenopausal women was conducted to compare the impact of concomitant rifabutin and rifampicin on the safety, pharmacokinetics, and pharmacodynamics of the oral contraceptives ethinylestradiol and norethindrone (Ortho-Novum 1/35; Ortho Pharmaceutical, Raritan, NJ). Each participant received oral contraceptives daily for 21 days for the first control cycle, then was randomized to one of two sequences to receive oral contraceptives with concomitant rifampicin and rifabutin at equal doses of 300 mg/day for 10 days. Ethinylestradiol, norethindrone, follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone, rifampicin, and rifabutin (and metabolite) were measured in plasma over the same time frames in all three cycles. Safety was assessed from before the beginning to the end of each cycle. Twenty-two subjects completed all three cycles. Compared with the control cycle, rifabutin and rifampicin significantly altered the disposition of the oral contraceptive. Area under the concentration-time curve from 0 to 24 hours (AUC0-24) and maximum plasma concentration (Cmax) of ethinylestradiol decreased by 64% and 42%, respectively, after coadministration with rifampicin and by 35% and 20%, respectively, after coadministration with rifabutin. The AUC0-24 of norethindrone decreased by 60% and 20% after coadministration with rifampicin and rifabutin, respectively. Unlike progesterone levels, FSH and LH levels increased during coadministration with rifampicin and rifabutin. The incidence of spotting was significantly higher after coadministration with rifampicin (36.4%) and rifabutin (21.7%) than during the control cycle (3.7%). Although both rifampicin and rifabutin affected the pharmacokinetics of ethinylestradiol and norethindrone, the magnitude of this effect was more pronounced with rifampicin. Likewise, the fact that the highest incidence of spotting occurred with rifampicin was consistent with higher metabolic induction by rifampicin. Despite the fact that there was no change in progesterone levels, it is recommended that patients be advised to use additional contraceptive methods while receiving rifabutin or rifampicin with oral contraceptives to prevent inadvertent pregnancy.

Adolescent

Sense of coherence--a protective factor for depression in rheumatoid arthritis.

OBJECTIVE: A stress-vulnerability model of depression was investigated in patients with rheumatoid arthritis (RA). Antonovsky's Sense of Coherence (SOC) was examined as a factor protecting against depression. METHOD: Relationships between sociodemographic factors, disease activity, functional impairment, pain, depression, and SOC were assessed using multivariate methods in a cross sectional sample of 89 consecutive outpatients with RA. RESULTS: Increased prevalence of depression was associated with low SOC and high self-rated pain levels, but not with other factors assessed. By multiple regression analysis, independent contributions to depression were observed for SOC (23% of variance) and for pain (24% of variance), but not functional impairment or disease activity. CONCLUSION: Comprehensive models of adjustment in RA need to include protective factors such as SOC, in addition to pain and other pathological variables. SOC may be helpful in identifying individuals with RA who are particularly vulnerable to depression, who may be helped by focused psychological interventions such as cognitive therapy.

Adaptation, Psychological

Minimal interaction between fluoxetine and multiple-dose zolpidem in healthy women.

The objective was to evaluate possible pharmacokinetic and pharmacodynamic interactions for repeated nightly zolpidem dosing with fluoxetine. Twenty-nine healthy female volunteers (mean age, 25. 6 years) received zolpidem (10 mg) and fluoxetine (20 mg) in the following open design: zolpidem on night 1 followed by 1 washout day, a daily morning dose of fluoxetine on days 3 through 27, and a morning dose of fluoxetine plus an evening dose of zolpidem on days 28 through 32. Plasma levels of zolpidem, fluoxetine, and norfluoxetine were determined at the transitions from one regimen to the next. Morning psychomotor tests were performed on days 1, 2, 28, 29, and 33. Steady-state plasma concentrations of fluoxetine/norfluoxetine were reached by day 24 of fluoxetine dosing. No significant differences in any pharmacokinetic parameters for fluoxetine and norfluoxetine were observed between day 27 and day 32. There were no significant differences in AUC, maximal plasma concentration, or time to maximal concentration parameters for zolpidem plasma concentrations among nights 1, 28, and 32. There was a statistically significantly increased t1/2 for zolpidem on night 32, compared with night 28 (3.64 and 3.29 hr, respectively). There were no significant differences in the next-morning Digit Symbol Substitution Test performance at any time in the study. Both zolpidem and fluoxetine were well tolerated alone or during coadministration. These findings indicate the absence of clinically significant pharmacokinetic or pharmacodynamic interactions between fluoxetine and zolpidem (five consecutive doses) when the drugs are coadministered to healthy women. Therefore, based on these observations, short-term cotherapy with fluoxetine (20 mg) and zolpidem (10 mg) appears safe.

Adult

Life-threatening fish allergy successfully treated with immunotherapy.

Manifestations of fish allergy can include near-fatal anaphylactic reaction. In very sensitive patients, fish odors and cooking vapors may have some allergenic activity. We reported a case of life-threatening fish allergy in a girl of 39 months referred for three episodes of Quincke edema with wheezing, cyanosis and severe urticaria after fish consumption or inhalation. Reagins were found against codfish and direct skin prick test with fresh food (codfish) showed important local reaction. Strict avoidance of fish in the diet is usually the only recommended procedure. However, in this particular case, the life-threatening nature of the allergic reaction was the major consideration to perform a desensitization. The child was treated by RUSH immunotherapy using codfish extracts from BENCARD company, following the schedule for insect venom allergy described by Pharmacia. Immunotherapy was performed immediately after determination of the threshold of sensitivity by specific skin prick tests and intra-dermal injections. Desensitization was initiated with a 1/10 dilution of the cut-off solution and 5 subcutaneous injections were administered daily. When important local reactions were observed, additional doses were necessary to obtain tolerance. After the RUSH therapy, the child was submitted to uncooked codfish odors without any reaction. No reaction has been observed even when the child has accidentally eaten a little piece of codfish.

Animals

Molecular characterization of two Brassica napus pollen-expressed genes encoding putative arabinogalactan proteins.

Two highly homologous cDNA clones, Sta 39-3 and Sta 39-4, corresponding to mRNAs highly expressed in Brassica napus cv Westar stamens were isolated by differential screening and characterized. Northern blot and in situ analyses demonstrated that Sta 39-3 and Sta 39-4 transcripts accumulate in pollen following the first pollen mitosis and are abundant at pollen maturity, thus identifying them as "late" pollen genes. Sta 39-3 and Sta 39-4 belong to a small gene family. Their predicted proteins share similarities with those deduced from recently isolated cDNAs encoding arabinogalactan proteins, which include a similar molecular mass (approximately 13 kD); high levels of alanine, proline, serine, and threonine, which are interspersed throughout the protein with no obvious repetitive motif; low levels of cysteine, histidine, tryptophan, and tyrosine; and hydrophobic N- and C-terminal ends. The Sta 39-3 and Sta 39-4 proteins may play a role in pollen germination and tube growth.

Amino Acid Sequence

The effect of co-administration of zolpidem with fluoxetine: pharmacokinetics and pharmacodynamics.

Since early treatment of depression with Selective Serotonin Reuptake Inhibitor (SSRI) can be associated with insomnia, daytime antidepressive therapy with SSRI is often combined with nighttime administration of a hypnotic. This study attempted to evaluate the pharmacokinetic and pharmacodynamic interactions between zolpidem 10 mg, a short-acting hypnotic, and fluoxetine 20 mg, an SSRI. Twenty-seven healthy male volunteers (mean age 23.5 years, range 20 - 29) received zolpidem and fluoxetine in the following open design: zolpidem on night 1, a morning dose of fluoxetine daily from day 2 through day 18 and zolpidem on night 18. Using HPLC, plasma levels of zolpidem, fluoxetine, and norfluoxetine were determined throughout night 1 for zolpidem, night 18 for zolpidem, fluoxetine, and norfluoxetine on days 16 and 17 for fluoxetine and norfluoxetine. Morning psychomotor tests were performed on days 1, 2, 18, and 19. Statistical analysis of data consisted of repeated measures of ANOVA. There was no significant difference in AUC, C(max), and T1/2 of zolpidem plasma concentrations between night 1 (zolpidem) and night 18 (zolpidem and fluoxetine). There was a significantly higher zolpidem plasma level at 0.5 hours after dosing together with a significantly shorter T(max) on night 18 compared to night 1. There was no significant difference in C(min) of plasma fluoxetine and norfluoxetine levels between day 16 and 17 of fluoxetine dosing, and there was no difference in T(max) between day 17 (fluoxetine) and day 18 (fluoxetine and zolpidem). There was a 3 - 4% increase in AUC and C(max) of fluoxetine and norfluoxetine plasma concentrations in the presence of zolpidem. There was no difference in the next morning performance tests after nighttime treatment of zolpidem alone after 17 consecutive days of fluoxetine treatment, or after zolpidem in the presence of steady-state plasma concentrations of fluoxetine. Both zolpidem and fluoxetine were well tolerated alone or in combination. It is concluded that the onset of action of zolpidem may possibly be shortened in the presence of fluoxetine, but no other significant pharmacokinetic or pharmacodynamic interactions occurred between zolpidem and fluoxetine.

Adult

Recombination of endogenous D2 dopamine receptor gene with a metallothionein promoter in GH4C1 cells confers functional and inducible D2 response.

We have previously shown that expression of a functional endogenous D2 short dopamine receptor is obtained in GH4C1 cells following transfection with a plasmid that confers resistance to neomycin (pRSVNeo) (Allard et al. (1993) Biochem. Biophys. Res. Commun. 193, 801-807). In order to better understand the mechanisms responsible for such a phenomenon, we cloned and sequenced the 5' region of the D2 gene present in native GH4C1 cells as well as the cDNA of transfected cells. No homology with the published sequence of the rat D2 dopamine receptor promoter was found; however, this region has perfect homology with the mouse metallothionein promoter. In cells expressing D2 receptor, the promoter is fully functional and can regulate dopaminergic D2 receptor mRNA levels and receptor expression in a dose-dependent manner in the presence of Zn2+ or Cd2+. The receptor level is raised from 500 to 3000 fmol/mg of protein in the presence of 100 microM of Zn2+. These results suggest that in GH4C1 cells, a recombination between the mouse metallothionein promoter and the D2 dopamine receptor took place. This system provides us with a cell line expressing an endogenous dopamine D2 receptor in which the level of expression can be easily modulated.

Animals

Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses.

The pharmacokinetics and suction-induced blister fluid penetration of cefdinir following single oral administrations of 200, 300, 400, and 600 mg were studied in 16 healthy young male volunteers according to a Latin square design. Plasma, blister, and urine samples were assayed by high-pressure liquid chromatography. We observed a nonlinear relationship (P = 0.02) between the dose and the maximum concentration in plasma as well as between the dose and the area under the concentration-time curve (AUC) in plasma (P < 0.001), which may be indicative of a limited absorption process. This resulted in a lower AUC value than expected as well as a smaller fraction of cefdinir excreted unchanged at a dose of 600 mg. Renal clearance decreased with increasing doses (P < 0.006; analysis of variance with the Latin square design and Games-Howell procedure). Maximal cefdinir concentrations in blister fluid were delayed compared with concentrations in plasma. Blister fluid penetration measured by the ratio of the AUC in blister fluid to the AUC in plasma was extensive (92.4 to 108.4%). Cefdinir concentrations in blister fluid remained equal to or higher than the concentrations in plasma from 6 to 12 h following cefdinir administration. On the basis of the concentrations in blister fluid and the in vitro MIC data, we estimated that cefdinir at 200 to 400 mg administered twice daily would be adequate to treat uncomplicated skin infections caused by Streptococcus pyogenes. Seven volunteers experienced episodes of light-to-moderate diarrhea. These adverse events occurred irrespective of dose.

Adult

Molecular analysis of two Brassica napus genes expressed in the stigma.

A partial cDNA clone, Pis 63, corresponding to a mRNA highly expressed in Brassica napus pistils, was isolated by differential screening. PCR was used to complete the Pis 63 sequence (Pis 63-1) and to obtain the sequence of another related cDNA (Pis 63-2). Northern blot and in situ analyses demonstrated that these transcripts are expressed in the stigma throughout flower development. Pis 63-1 and Pis 63-2 display similarity to a cotton fibre cDNA clone.

Amino Acid Sequence

Sequence and expression of endogenous S-locus glycoprotein genes in self-compatible Brassica napus.

Brassica napus is an amphidiploid plant which is self-compatible even though it is derived from hybridisation of the self-incompatible species B. oleracea and B. campestris. Experiments were undertaken to establish if S-locus glycoprotein (SLG) genes exist in B. napus and whether these are expressed as in self-incompatible Brassica species. Two different stigma-specific cDNA sequences homologous to SLG genes were obtained from the B. napus cultivar Westar. One of these sequences, SLGWS1, displayed highest homology to class I SLG alleles, whereas the other, SLGWS2, showed greatest homology to class II SLG genes. Both were expressed at high levels in Westar stigmas following a developmental pattern typical of SLG genes in the self-incompatible diploids. We infer that they represent the endogenous SLG genes at the two homologous S-loci. The occurrence of normally expressed SLG genes and its relevance to the self-compatible phenotype of B. napus is discussed.

Alleles

Molecular characterization of two Brassica napus genes related to oleosins which are highly expressed in the tapetum.

Two highly homologous Brassica napus flower cDNA clones, Sta 41-2 and Sta 41-9, were isolated and characterized. These clones were shown to correspond to genes expressed in the tapetum from the early uninucleate microspore stage to the dinucleate stage. The predicted Sta 41-2 and Sta 41-9 proteins possessed characteristics similar to oleosins such as a polar N-terminal domain, a large relatively conserved hydrophobic domain and a long C-terminal domain which consisted of four different groups of repeats. In addition, like oleosins, the Sta 41-2 and Sta 41-9 proteins have a basic pI, lack a signal peptide and are found in a tissue which accumulates lipids in small lipid bodies.

Amino Acid Sequence

Cimetidine-induced myelosuppression after bone marrow transplantation.

A strong temporal correlation was observed between cessation of cimetidine and a sustained increase in blood counts in two marrow transplant recipients. Both were receiving cimetidine from the day of transplantation for prophylaxis of stress ulceration and gastritis. The blood counts of both patients were not increasing satisfactorily 5-6 weeks after marrow transplantation without any obvious cause of marrow suppression. A similar observation has been made with the use of ranitidine after marrow transplantation suggesting that histamine H2-receptor antagonists should be used very cautiously, if at all, in the setting of bone marrow transplantation.

Adolescent

Endoscopic treatment of an oral cephalocele. Case report.

This report describes an unusual cephalocele originating in the temporobasal region and protruding through the sphenopetral area into the oral cavity. A rapid and nonaggressive endoscopic procedure was performed. The relationship between this type of cephalocele, spontaneous anteroinferior temporal encephaloceles, and nasopharyngeal brain heterotopia is discussed.

Cranial Sutures

Specific induction of a functional endogenous D2 short dopamine receptor in GH4C1 cells.

In contrast to lactotrophs, tumoral pituitary cells like GH3 and GH4C1 lack expression of dopamine D2short and D2long receptors. In GH4C1 cells, we observed that the expression of only the short isoform of D2 receptor can be induced after transfection with a plasmid which confers resistance to neomycin (pRSVNeo). High levels of fully functional D2short receptor were obtained in GH4C1 following transfection (528fmol/mg protein). Sequence, pharmacology and coupling of the induced-D2 receptor do not show any difference with the cloned rat D2 short receptor.

Animals