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E Brand

Publications and source records attributed to E Brand.

At least 37 records · Page 2Linked to original sources
PubMed1999

The 825C/T polymorphism of the G-protein subunit beta3 is not related to hypertension.

A polymorphism at position 825 (C-->T) of the cDNA that encodes the beta3 subunit (GNB3) of the pertussis toxin-sensitive G protein was recently shown to be associated with human hypertension. To verify this finding and to investigate whether this polymorphism could also be associated with coronary heart disease, we analyzed the GNB3 variant in subjects from 2 previously described studies: Projet d'Etude des Gènes de l'hypertension Artérielle Sévère à modérée Essentielle (PEGASE), a case-control study of moderate to severe hypertension (681 cases and 308 controls), and Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM), a case-control study of myocardial infarction (MI) (564 cases and 633 controls). Genotyping was performed with allele-specific oligonucleotides. Genotype and allele frequencies were in Hardy-Weinberg equilibrium in all groups. Allele and genotype frequencies did not differ significantly between case patients with essential hypertension or MI and control subjects. In the ECTIM study, the 825T allele frequencies in cases and controls from Belfast, Northern Ireland, were 0.31 and 0.30 (P=0.79), respectively; the corresponding frequencies in cases and controls from France were 0.33 and 0.31 (P=0.30), respectively. In the PEGASE study, the 825T allele frequency was 0.35 in female and male cases and 0.31 in male normotensive controls (P=0.12). The odds ratios for hypertension (PEGASE) and MI (ECTIM) associated with T-allele carrying were 1.23 (95% confidence interval, 0.94 to 1.62; P=0.13) and 1.11 (95% confidence interval, 0.88 to 1.39; P=0.37), respectively. There was no association of the GNB3 polymorphism with early onset of hypertension, familial history of hypertension, or blood pressure level. We conclude that the 825C/T polymorphism of the GNB3 gene did not contribute in any important way to the risk of essential hypertension or MI in these studies.

Adult↗
PubMed1999

Glucagon receptor gene mutation (Gly40Ser) in human essential hypertension: the PEGASE study.

A missense mutation (Gly40Ser) in exon 2 of the glucagon receptor gene (GCG-R) was shown to reduce ligand affinity and impair cAMP response. We conducted a case-control study with a sample of 741 French hypertensive patients with moderate to severe hypertension and 412 normotensive control subjects, who were genotyped for this biallelic variant by use of hybridization with allele-specific oligonucleotides. The Gly40Ser polymorphism was not significantly associated with hypertension in the whole study population, although the frequency of 40Ser carriers in hypertensive subjects was double that in normotensive subjects (3.1% in hypertensives versus 1.5%; P=0.087). However, the separate analysis of both genders revealed that 40Ser allele carriers were significantly more frequent (P=0. 035) among male patients (17/429; 4.0%) than among normotensive male controls (2/242; 0.8%), whereas no significant difference was observed in female subjects (6/312 in hypertensives and 4/170 in normotensives). Further studies are required to interpret the significance of this association.

Adult↗
PubMed1999

Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population.

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

Adult↗
PubMed1998

Mutations in cell division proteins FtsZ and FtsA inhibit phiX174 protein-E-mediated lysis of Escherichia coli.

Electron microscopic studies emphasized that the protein-E-specific transmembrane tunnel structure, which permeabilizes Escherichia coli, is not randomly distributed over the cell envelope but is restricted to areas of potential division sites. These sites were located predominantly in the middle of the cell, but approximately one-third of these structures are found at the polar sites. Therefore, E. coli mutant strains with defects in cell division components were tested for their sensitivity to protein-E-mediated lysis. The ftsZ84 and the ftsA12 cell division mutant strains of E. coli were tolerant to protein-E-mediated lysis, whereas the ftsA3 mutant strain was lysed by protein E under conditions nonpermissive for division. The protein-E-tolerant phenotype of ftsZ84 and ftsA12 and the lysis-sensitive phenotype of other components of the septosome (e.g., ftsA3, ftsQ, and ftsI) suggest that initiation of cell division - rather than specific functions of cell division - plays an essential role in protein-E-mediated lysis. SulA-overproducing cells had a lysis-positive phenotype, the ring structure - but not the GTPase function - of FtsZ was impaired.

Animals↗
PubMed1998

Structural analysis and evaluation of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene in human essential hypertension.

AIM: Mutations of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive form of hypertension. We therefore investigated the question of whether variants of the 11beta-HSD2 gene can contribute to genetic susceptibility to essential hypertension. SUBJECTS AND METHODS: We performed a linkage study in 162 French hypertensive sibships using the affected sib-pair method on 347 sibling pairs and a polymorphic microsatellite marker that we identified in a 30 kb cosmid clone containing the 11beta-HSD2 gene. The coding sequence, introns 2-4 and 350 bp of the 5'-flanking region of the 11beta-HSD2 gene were screened for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism, and a single polymorphism, Glu178/Glu (G534A), was identified in exon 3, which did not change the encoded amino acid sequence. A case-control study was conducted on 370 hypertensive subjects with a positive family history of hypertension and 783 French subjects with hypertension with or without a family history of hypertension, compared with 313 normotensive control subjects, all of whom were analyzed for the newly identified bi-allelic polymorphism. RESULTS: Statistical analyses using the affected sib-pair method did not show significant linkage between the 11beta-HSD2 microsatellite marker and hypertension. Furthermore, no positive association with hypertension was found with the Glu178/Glu (G534A) polymorphism. CONCLUSION: Our data do not suggest that variants of the 11beta-HSD2 gene contribute substantially to essential hypertension in Caucasians.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Evaluation of the angiotensinogen locus in human essential hypertension: a European study.

Different family and case-control studies support genetic linkage and association at the human angiotensinogen (AGT) locus with essential hypertension. To extend these previous observations, a European collaborative study of nine centers was set up to create a large resource of affected sibling pairs. The AGT locus was studied using a highly polymorphic dinucleotide repeat in the 3'-flanking region of the gene in 350 European families, comprising 630 affected sibling pairs. Statistical analyses using two different methods did not show any evidence for linkage either in the whole panel or in family subsets selected for severity or early onset of disease. Although several arguments from association studies suggest a role of the AGT gene in essential hypertension, this large family study did not replicate the initial linkage reported in smaller studies. Our results highlight the difficulty of identifying susceptibility genes by linkage analysis in complex diseases.

Adult↗
PubMed1998

Structural analysis and evaluation of the aldosterone synthase gene in hypertension.

Anomalies in either of the tightly linked genes encoding the enzymes CYP11B1 (11beta-hydroxylase) or CYP11B2 (aldosterone synthase) can lead to important changes in arterial pressure and are responsible for several monogenically inherited forms of hypertension. Mutations in these genes or their regulatory regions could thus contribute to genetic variation in susceptibility to essential hypertension. To test this hypothesis, we performed 2 complementary studies of the CYP11B1/CYP11B2 locus in essential hypertension. After characterizing a DNA contig containing the CYP11B1 gene and mapping the gene in the Centre d'Etudes du Polymorphisme Humain reference panel of families, we performed a linkage study with 292 hypertensive sibling pairs and a highly informative microsatellite marker near CYP11B1. We also analyzed the association of 2 frequent biallelic polymorphisms of the CYP11B2 gene, 1 in the promoter at position -344 (-344C/T) and the other, a common gene conversion in intron 2, with hypertension in 380 hypertensive patients and 293 normotensive individuals. Statistical analyses did not show significant linkage of the CYP11B1 microsatellite marker to hypertension. No positive association with hypertension was found with the gene conversion in intron 2, but a positive association with hypertension was found with the -344T allele. The hypertensive and normotensive samples differed significantly in both genotype (P=0.023) and allele frequencies (P=0.010). Our data suggest a modest contribution of the CYP11B2 gene to essential hypertension.

Adult↗
PubMed1997

In vitro expression of the diphtheria toxin A-chain gene under the control of human chorionic gonadotropin gene promoters as a means of directing toxicity to ovarian cancer cell lines.

OBJECTIVE: Our goal was to determine whether toxicity of the diphtheria toxin A-chain gene regulated by the human chorionic gonadotropin promoter can be directed to malignant ovarian cell lines. STUDY DESIGN: Plasmids containing diphtheria toxin A-chain gene linked to the regulatory elements of the metalloergothioneine and human chorionic gonadotropin promoters were transfected into the cell lines. Expression of diphtheria toxin A-chain gene was determined by the inhibition of a cotransfected luciferase reporter gene. RESULTS: Cytotoxicity of the diphtheria toxin A-chain gene is shown in a dose-responsive manner. Transfection of a plasmid expressing the diphtheria toxin A-chain gene controlled by a constitutive promoter readily inhibits protein synthesis. Specific inhibition of luciferase protein synthesis occurs in ovarian cancer cells transfected with the diphtheria toxin A-chain gene under the control of the human chorionic gonadotropin promoters when compared with normal ovarian epithelial cells or fibroblasts. CONCLUSIONS: These data demonstrate the preferential expression of the diphtheria toxin A-chain gene, regulated by the human chorionic gonadotropin promoter, to ovarian cancer cell lines. This provides an avenue for targeting such cells for suicide, toxin, or cytokine genes.

Carcinoma↗
PubMed1997

Diagnosis and assessment of depression and suicidality using the NIMH Diagnostic Interview Schedule for Children (DISC-2.3).

The diagnostic Interview Schedule for Children (DISC-2.3) was studied in a sample of 265 adolescent inpatients to determine type and concurrent validity of depressive symptoms and depressive disorder diagnoses for different DISC-2.3 informants (parent, adolescent, both). The Children's Depression Rating Scale--Revised, Reynolds Adolescent Depression Scale (RADS), Suicide Ideation Questionnaire--Junior, Spectrum of Suicide Behavior Scale, and clinical consensus diagnoses were used to assess concurrent validity. Results indicated that (1) parents, compared to adolescents, reported a higher prevalence of all depressive symptoms with the exception of weight change; (2) DISC-2.3 depressive and suicidality symptoms were related positively to independent validating criteria for all informant conditions, suggesting good concurrent validity; (3) the DISC-2.3 both informant condition correctly identified the most depressive disorders; and (4) the parent, but not the adolescent, DISC-2.3 Informant condition contributed to the prediction of clinical consensus diagnoses of depression after taking into account RADS scores.

Adolescent↗
PubMed1997

Suicidal adolescents after hospitalization: parent and family impacts on treatment follow-through.

OBJECTIVE: To help determine optimal strategies for treating suicidal adolescents, the authors studied family predictors of compliance with recommended psychotropic medication monitoring, individual therapy, and parent guidance/family therapy sessions. METHOD: Sixty-six hospitalized, suicidal adolescents participated in a comprehensive diagnostic evaluation and depression/suicidality assessment. Family/parental assessment measures were the Family Assessment Device, Social Adjustment Inventory for Children and Adolescents (parent-adolescent subscales), Symptom Checklist-90-Revised, and Social Adjustment Scale-Self Report. Follow-up evaluation, 6 months posthospitalization, consisted of structured telephone interviews assessing treatment follow-through. RESULTS: Compliance with recommended medication follow-up (66.7%) and individual therapy (50.8%) was better than compliance with parent guidance/family therapy (33.3%) sessions. The most dysfunctional families and those with the least involved/affectionate father-adolescent relationships had the poorest follow-through with parent guidance/family therapy. Mothers' depressive and paranoid symptoms were linked with less adolescent individual therapy and family therapy follow-through. Mothers' hostility was associated with less medication follow-up. CONCLUSIONS: Follow-through was best for medication and individual therapy. Multiple family/parental predictors of poor follow-through suggest the need for alternative or supplemental treatment strategies.

Adolescent↗
PubMed1997

Prediction of positive outcomes for adolescent psychiatric inpatients.

OBJECTIVE: To identify individual, parent/family, and treatment follow-through predictors of outcome for adolescent psychiatric inpatients 6 months after hospital discharge. METHOD: Eighty-nine adolescents participated in a comprehensive baseline evaluation during psychiatric hospitalization. Baseline measures included the Diagnostic Interview Schedule for Children, Social Adjustment Inventory for Children and Adolescents, Reynolds Adolescent Depression Scale (RADS), and Suicidal Ideation Questionnaire-Junior (SIQ-Jr). Structured telephone follow-up interviews assessed treatment follow-through, suicidal behaviors, rehospitalizations, living changes, and social adaptive functioning. The RADS and SIQ-Jr were also readministered. RESULTS: Baseline indices of adolescent functioning emerged as the strongest predictors of outcomes. Hierarchical multiple regression analyses indicated that baseline depression severity, a cluster of parent/family indices, and medication follow-through were significant predictors of outcome depression severity. Baseline social adaptive functioning, presence/absence of conduct disorder, and medication follow-through were significant predictors of outcome social adaptive functioning. CONCLUSIONS: The nature and course of adolescent psychopathology was difficult to disrupt, with baseline characteristics as the strongest predictors of outcome. Nevertheless, the significance of medication follow-through as a predictor suggests that treatment-related gains are possible.

Adolescent↗
PubMed1997

Bacterial ghosts as multifunctional vaccine particles.

Expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts have been produced from a variety of bacteria including Escherichia coli. Salmonella typhimurium, Salmonella enteritidis, Vibrio cholerae, Klebsiella pneumoniae, Actinobacillus pleuropneumoniae, Haemophilus influenzae, Pasteurella haemolytica, Pasteurella multocida, and Helicobacter pylori. Such ghosts are used as non-living candidate vaccines and represent an alternative to heat or chemically inactivated bacteria. In recombinant ghosts, foreign proteins can be inserted into the inner membrane prior to E-mediated lysis via specific N-, or C-, or N- and C-terminal anchor sequences. The export of proteins into the periplasmic space or the expression of recombinant S-layer proteins vastly extents the capacity of ghosts or recombinant ghosts as carriers of foreign epitopes or proteins. Oral, aerogenic or parenteral applications of (recombinant) ghosts in experimental animals induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of ghosts and recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in the production of ghosts used as vaccines or as carriers of relevant antigens. The inserted target antigens into the inner membrane or into S-layer proteins are not limited in size.

Adjuvants, Immunologic↗
PubMed1996

Predictors of comorbid alcohol and substance abuse in depressed adolescents.

OBJECTIVE: To identify clinical profiles discriminating depressed adolescents on the basis of comorbid alcohol/substance use disorders and to determine whether or not profiles with high predictive power are gender-specific. METHOD: One hundred three adolescent inpatients with major depression (65 girls, 38 boys) participated in a comprehensive diagnostic evaluation. Independent assessments of depression, suicidality, and psychosocial adjustment were conducted using well-validated instruments. RESULTS: Gender-specific clinical profiles were identified that predicted alcohol/substance abuse in depressed adolescents with high levels of sensitivity (90%). The significant discriminant function for depressed girls included the following predictors: longer depressive episodes, more conduct problems and psychosocial impairment, and more active involvement in relationships with boys. The significant discriminant function for depressed boys included conduct disorder, older age, and schoolwork problems. These profiles correctly identified most depressed adolescents with comorbid alcohol/substance abuse. CONCLUSIONS: Given that alcohol abuse and depression are associated with highly impaired social functioning and increased risk of self-harm, sensitivity in case identification is critical. Clinicians should conduct comprehensive assessments of alcohol/substance abuse in depressed adolescents with the identified clinical profiles.

Adolescent↗
PubMed1993

Fellow's vein.

Explore the source record for details and available documents.

Humans↗
PubMed1993

The decline of CA 125 level after surgery reflects the size of residual ovarian cancer.

OBJECTIVE: To determine whether the decline in CA 125 level after surgery can predict the extent of residual disease. METHODS: In a prospective, nonrandomized clinical trial, 27 women with advanced ovarian cancer (stage III or IV) underwent primary or secondary cytoreductive surgery. CA 125 levels were measured before surgery and 3-14 days postoperatively. The mean postoperative decline was compared by size of residual disease. RESULTS: In women with all visible cancer resected, the mean (+/- standard error of the mean) decline in CA 125 was 91 +/- 4% (1032 +/- 473 U/mL preoperatively to 90 +/- 31 U/mL postoperatively). With less than 2.0 cm residual, there was an 85 +/- 2% decline in CA 125 after surgery (3061 +/- 835 U/mL preoperatively to 456 +/- 146 U/mL postoperatively). In patients with residual disease larger than 2.0 cm, the levels dropped 36 +/- 10% (2958 +/- 1587 to 1904 +/- 708 U/mL). If CA 125 declined less than 60% from the preoperative level, the sensitivity, specificity, and positive and negative predictive values for residual disease larger than 2.0 cm were all 100%. CONCLUSION: By using the ratio of CA 125 levels before and after cytoreductive surgery, one can predict the likelihood that the patient was left with less than 2.0 cm residual disease.

Adenocarcinoma↗