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Biomedical subjects

K Zeller

Publications and source records attributed to K Zeller.

At least 19 recordsLinked to original sources
PubMed2006

Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study.

OBJECTIVE: The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen's Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo. METHODS: Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs. RESULTS: From almost identical baseline values of 21.9 +/- 1.2 points (hypericum extract), 21.8 +/- 1.2 points (citalopram) and 22.0 +/- 1.2 points (placebo), the HAMD score was reduced to 10.3 +/- 6.4 (hypericum extract), 10.3 +/- 6.4 (citalopram) and 13.0 +/- 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with "certain", "probable" or "possible" relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as "good" or "very good". CONCLUSION: The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.

Adult↗
PubMed2005

Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline.

OBJECTIVE: The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression. METHODS: A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period. RESULTS: After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as "good" or "very good." CONCLUSIONS: The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.

Adolescent↗
PubMed2005

Analysis of properdin (BF) genotypes associated with litter size in a commercial pig cross population.

Properdin (BF) was investigated as a candidate gene influencing litter size in a commercial pig cross population. The BF gene was chosen because of its integral role in influencing uterine epithelium growth and because several quantitative trait loci (QTL) with impact on reproductive traits have been detected near the centromere of porcine chromosome 7. A total of 123 F2 (Large White x Landrace) x Leicoma sows were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The sows were divided into two extreme performance groups, one with a high litter size (n = 61, > or = 14.3 piglets per litter) and the other with a low litter size (n = 62, < or = 11.3 piglets per litter). Although genotype and allele frequencies were uneven with 2.4% (AA), 16.3% (AB), 81.3% (BB) and 0.11 (A): 0.89 (B), the allele A was the unfavourable one, leading to less offspring. With regard to the level of significance at p < 0.05, the total number of born (TNB) and number of born alive (NBA) piglets were associated with BF genotypes. The genotype AA led to 10.55 TNB and 10.00 NBA, whereas the genotype BB led to 13.19 TNB and 12.11 NBA. The genotype AB was intermediate. In future, a systematic mating test is necessary in order to obtain more balanced genotype frequencies. Furthermore, it should be taken into consideration that the investigated polymorphism is located in an intronic region and the causative mutation is not clear yet.

Animals↗
PubMed2005

Knowledge of sex partner treatment for past bacterial STI and risk of current STI.

OBJECTIVES: Effective partner management is critical in reducing the spread of bacterial sexually transmitted infections (STIs). The purpose of this study was to determine the relation between knowledge of partner treatment for a past STI and current infection in the index patient. METHODS: In a cross sectional analysis, 97 adolescent females sampled from community based health clinics reported that they had a past diagnosis of chlamydia or gonorrhoea in structured, face to face interviews. At the time of the interview, adolescents were also tested for chlamydia and gonorrhoea using urine based ligase chain reaction testing. RESULTS: 66% of the adolescents reported knowing that their partner was treated for the past infection. Those who knew their partner was treated were less likely to have a current infection, compared to those who did not know (11% v 30%, adjusted odds ratio and 95% confidence interval 4.46 (1.41 to 14.29), p<0.05). Correlates of not knowing the sex partner was treated included younger age and being in new sex partnership. CONCLUSIONS: Efforts to encourage young women to follow up directly with their partners regarding treatment may help to reduce repeat infections and further spread. Furthermore, alternative strategies such as patient delivered therapy may help with partner treatment in this vulnerable population.

Adolescent↗
PubMed2005

Acceptability and feasibility of continuous diaphragm use among sex workers in Madagascar.

OBJECTIVES: The diaphragm, a woman controlled, reusable contraceptive device, might prevent some sexually transmitted infections (STIs). We assessed the acceptability and feasibility of use of silicone Wide-Seal Arcing Diaphragms (Milex Products, Chicago, IL, USA) by sex workers in Madagascar. METHODS: Over 8 weeks, we evaluated method acceptability by examining patterns of and problems with women's diaphragm use. We also evaluated several measures of study feasibility, including recruitment and follow up methods. RESULTS: 91 women from three cities (Antananarivo, Tamatave, and Mahajanga) participated, and 87 (96%) completed follow up. At enrolment, participants reported a median of six sex acts with five clients in the previous week. During the follow up period, participants reported a median of three sex acts with three clients during the previous 2 days, and self reported continuous diaphragm use during the previous day increased from 87% to 93%. Seven women became pregnant (incidence 53 pregnancies per 100 woman years). Self reported use of male condoms and diaphragms was fairly constant over the study period: women reported condom use in 61% to 70% of acts and diaphragms in 95% to 97% of acts. The number of participants reporting diaphragm problems decreased from 15 (16%) at the first visit to six (7%) at the final visit. 20 women (22%) needed replacement devices during follow up because their original diaphragms were lost, were the wrong size, or became seriously damaged. CONCLUSIONS: Given the high use and steady decrease in reported problems during the study, we believe diaphragms are acceptable and feasible in this resource poor, low education sex worker population.

Adolescent↗
PubMed2004

[Highly dosed St. John's wort extract improves quality of life].

AIM: Aim of the post-marketing surveillance was to investigate if the single-dose-administration of highlydosed St. John's Wort extract improves quality of life of patients with depressive symptoms. METHOD: During a twelve week treatment 4337 patients with depression were observed. Mental and physical state of health were documented using the SF-12-sumscore as a measure for quality of life. Further efficacy and tolerability was rated by physician and patient. Adverse drug reactions were documented as well. RESULTS: During therapy the mental and the physical SF-12-sumscore had improved significantly. At the end ofthe observation the values rise up to the norm. About 80 percent of the physicians and patients marked the drug's efficacy as good or very good. Tolerability was assessed as good or very good in more than 95%. CONCLUSION: A post-marketing surveillance including 4337 depressive patients shows that a single-dose therapy with highly dosed St. John's Wort extract causes to improve significantly the quality of life. The patients suffered from mild to moderate depression.

Adult↗
PubMed2002

Preliminary background ozone concentrations in the mountain and coastal areas of Bulgaria.

Urban and non-urban rural ozone (O3) concentrations are high in Bulgaria and often exceed the European AOT40 ecosystem as well as the AOT60 human health standards. This paper presents preliminary estimates to establish background, non-urban O3 concentrations for the southern region of Bulgaria. Ozone concentrations from three distinctly different sites are presented: a mountain site influenced by mountain-valley wind flow; a coastal site influenced by sea-breeze wind flow; and a 1700-m mountain peak site without 'local' wind flow characteristics. The latter offers the best estimate of 46-50 ppb for a background O3 level. The highest non-urban hourly value, 118 ppb, was measured at the mountain-valley site.

Air Movements↗
PubMed2001

A strategy to identify differentially expressed genes using representational difference analysis and cDNA arrays.

Representational difference analysis (RDA) combined with cDNA arrays is an effective approach to identify differentially expressed genes. To identify differentially expressed genes in c-Myc transgenic mouse liver, we compared the virtues of probing commercially available cDNA arrays with either radiolabeled cDNA pools or radiolabeled difference products (DP2) derived from RDA using c-Myc transgenic and normal mouse liver. Probing commercial and custom arrays with DP2 products led to the identification of transcripts of low abundance that were missed when the arrays were initially probed with PCR-amplified cDNA pools. Although DP2 probes also detected abundant transcripts that are highly differentially expressed, they failed to identify abundant transcripts with low differential expression that were detected with cDNA pools. The combined use of radiolabeled cDNA and DP2 products to probe arrays allows a more comprehensive identification of differentially expressed transcripts that are abundant or rare. Our method has the additional benefit of eliminating false-positive transcripts that lack true differential expression and frequently contaminate DP2 pools. Using this method we identified 16 differentially expressed genes in c-Myc transgenic liver, one of which is novel.

Animals↗
PubMed2001

A novel TC deletion resulting in Pro(260)-->Stop in the human LCAT gene is associated with a dominant effect on HDL-cholesterol.

Human lecithin:cholesterol acyltransferase (LCAT) plays a key role in the biogenesis of circulating high-density lipoprotein-cholesterol (HDL-C) and reverse cholesterol efflux. We investigated the molecular defect in the LCAT gene in a family with low levels of HDL-C. The proband, a 53-year-old woman from Oklahoma City, had a HDL-C level of 0.21 mmol/l. The LCAT activity in the proband was 5 nmol/ml/h and cholesterol esterification rate was 54.2 nmol/ml/h, consistent with LCAT deficiency. Analysis of polymerase chain reaction (PCR) amplified subgenomic fragments of LCAT DNA on polyacrylamide gels revealed heteroduplex bands in the proband and three other affected individuals in exon 6. DNA sequence analyses of the proband's LCAT gene identified a 2 base pair deletion (TC) (base pairs 4544-4545, corresponding to amino acid 255) in the heteroduplex allele, thereby converting Pro(260) to a premature stop codon and a predicted truncated protein of 260 amino acids. This is approximately 60% of the length of the normal translated protein. The heterozygous individuals also revealed significant reduction in apolipoprotein A-1 levels compared with the unaffected family members (n=4). The marked reduction in HDL-C in the proband and sibling suggests a dominant effect of this mutation on HDL-C levels. Furthermore, because the deletion results in a heterozygous allele that can be detected by a simple PCR reaction and polyacrylamide gel-size fractionation, it may be possible to rapidly screen susceptible individuals for the presence of this mutation.

Base Sequence↗
PubMed2000

HOXA5 regulates expression of the progesterone receptor.

The majority of breast carcinomas show reduced or no expression of the transcription factor, HOXA5. Recently, we have shown that HOXA5 is a potent transactivator of p53 in breast cells and thus may affect the response of breast cancer cells to DNA damage. To determine whether HOXA5 played a role in growth and homeostasis in breast cells, we studied its interaction with the progesterone receptor. The progesterone receptor (PR) belongs to the superfamily of nuclear receptors whose members co-ordinate morphogenesis of the mammary gland in response to binding to their cognate ligands. An increased expression of the endogenous PR gene was seen in MCF-7 cells following induced expression of an exogenously transfected HOXA5 gene. HOXA5, but not HOXB4, -B5, or -B7 activated the PR promoter in two breast cancer cell lines, MCF-7 and Hs578T. Deletion and mutation analysis of the promoter identified a single HOXA5-binding site required for transactivation of the PR gene by HOXA5. HOXA5 binds directly to this site in the PR promoter. Thus, HOXA5 may behave as a transcriptional regulator of multiple target genes, two among which are p53 and the progesterone receptor.

Base Sequence↗
PubMed1999

Function of the c-Myc oncogenic transcription factor.

The c-myc gene and the expression of the c-Myc protein are frequently altered in human cancers. The c-myc gene encodes the transcription factor c-Myc, which heterodimerizes with a partner protein, termed Max, to regulate gene expression. Max also heterodimerizes with the Mad family of proteins to repress transcription, antagonize c-Myc, and promote cellular differentiation. The constitutive activation of c-myc expression is key to the genesis of many cancers, and hence the understanding of c-Myc function depends on our understanding of its target genes. In this review, we attempt to place the putative target genes of c-Myc in the context of c-Myc-mediated phenotypes. From this perspective, c-Myc emerges as an oncogenic transcription factor that integrates the cell cycle machinery with cell adhesion, cellular metabolism, and the apoptotic pathways.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1999

Molecular standardization of mating type terminology in the Gibberella fujikuroi species complex.

Mating type in the Gibberella fujikuroi species complex is controlled by a single locus with two alleles and is usually identified following sexual crosses with standard, female-fertile tester isolates. The mating type alleles have been arbitrarily designated "+" and "-" within each biological species, and the nomenclature is tied to the standard tester strains. We developed a pair of PCR primers that can be used to amplify a unique fragment of one of the mating type alleles (MAT-2) from at least seven of the biological species in this species complex. Based on the amplification pattern, we propose a replacement for the existing, arbitrary +/- terminology that is presently in use. The new terminology is based on DNA sequence similarities between the mating type allele fragments from the biological species of the G. fujikuroi species complex and the corresponding fragments from other filamentous ascomycetes.

Crosses, Genetic↗
PubMed1998

Apolipoprotein A-I(Zavalla) (Leu159-->Pro): HDL cholesterol deficiency in a kindred associated with premature coronary artery disease.

We investigated the molecular defect causing high density lipoprotein cholesterol (HDL-C) deficiency in a male proband and his family members. Amplification and sequencing of genomic DNA disclosed a novel base-pair substitution at residue 159 in the apolipoprotein (apo) A-I gene. This substitution resulted in the loss of an AviII restriction site and a predicted substitution of leucine with proline at residue 159. Restriction enzyme analysis demonstrated absence of the AviII site in 19 of 40 biological family members. Compared with familial controls, subjects with the apoA-I(Zavalla) variant had reduced HDL-C (1.16 versus 0.27 mmol/L, P<0.0001), apoA-I (38.7 versus 124.4 mg/dL, P<0.0001), and apoA-II (14.3 versus 19.0 mg/dL, P<0.0001) levels. Two subjects who have developed coronary artery disease to date possess additional cardiovascular risk factors. Other heterozygotes for apoA-I(Zavalla) are presently without symptomatic coronary artery disease. This study identifies a monogenic cause of hypoalphalipoproteinemia, with the single base-pair substitution having a dominant effect on the low HDL-C phenotype. In addition, it extends recent observations that HDL-C deficiency states may be more prone to the development of premature coronary artery disease when accompanied by additional cardiovascular risk factors.

Adolescent↗
PubMed1997

Alternative splicing in lecithin:cholesterol acyltransferase mRNA: an evolutionary paradigm in humans and great apes.

Lecithin:cholesterol acyltransferase (LCAT), an important enzyme affecting reverse cholesterol transport, is expressed in liver and cultured fibroblasts. Sequencing of LCAT cDNA clones demonstrated the coexistence of two mRNA products. In addition to the normal transcript, we identified an alternate message with a splice-mediated insertion of a 95 bp Alu cassette at the junction of exons 5 and 6. In humans, the alternate transcript represents 5-20% of the complete LCAT message in cultured fibroblasts and liver. It is present in humans and the great apes but not in lesser apes (gibbon, siamang) or lower-order primates (e.g., old or new world monkeys). Sequencing of intron 5 of the LCAT locus in several primates revealed a G-->A transition at the splice donor recognition site in the Alu repeat of the gibbon and a G-->A substitution in the last position of the 95 bp Alu sequence of the rhesus monkey, an old world monkey. Both substitutions have been associated with exon skipping in other genes. These results demonstrate that alternative splicing of LCAT mRNA is variant among primates and suggest a potential role of Alu elements in the evolutionary diversity of proteins.

Alternative Splicing↗
PubMed1997

Distribution of Glut1 glucose transporters in different brain structures compared to glucose utilization and capillary density of adult rat brains.

Glut1 is a specific transporter system that mediates glucose transfer across the blood-brain barrier (BBB). Although the main location of Glut1 is in the capillary endothelium of the brain, its local distribution in different brain regions is not as well defined. In the present investigation, the local pattern of Glut1 distribution was determined in 13 brain structures using an immunoautoradiographic method developed for this purpose. A polyclonal antibody directed against the C-terminal amino acid sequence of Glut1 was applied to cryosections of rat brains. A secondary antibody was added that had been coupled to [35S]. Results show a heterogeneous distribution of Glut1 in the brain with activities of [35S] ranging from 65% below to 15% above the mean. White matter activity was lower than gray matter activity. For comparison, capillary sections were counted in corresponding cryosections by indirect immunofluorescence using fibronectin antibodies. In addition, local cerebral glucose utilization (LCGU) was analyzed in identical brain structures of conscious rats by the quantitative autoradiographic 2-deoxyglucose method. Significant correlations were found between Glut1 density and either LCGU or capillary density. Results indicate a tight coupling of Glut1 transporter density and capillary density to the LCGU of different BBB structures in adult rats.

Animals↗
PubMed1996

Postnatal distribution of Glut1 glucose transporter and relative capillary density in blood-brain barrier structures and circumventricular organs during development.

In the adult brain, Glut1 is associated with capillaries that form a tight barrier whereas Glut1 is lacking in capillaries with non-barrier properties, i.e. the circumventricular organs. In the present study the postnatal developmental changes of brain capillaries and Glut1 were compared in different tight and non-barrier structures. Rats were investigated at birth, 5th postnatal day (P5), P10, P15, P20, P30 and at the age of one year. Antibody stains of brain capillaries (fibronectin) and of Glut1 were visualized by fluorescent microscopy in identical brain cryosections. All brain capillaries of structures that have a tight barrier in adult animals showed the existence of Glut1 during postnatal development. Most non-barrier structures lacked Glut1 in their capillary endothelium after birth although Glut1 was found in the area postrema and subfornical organ at P0 and disappeared thereafter. The relative capillary density in tight barrier structures of the gray matter was more than doubled from birth to P20 with minor changes later. In contrast white matter structures missed any significant increase during development. It is concluded that Glut1, as an indicator of barrier properties, is existing in all blood-brain barrier structures at birth already. The capillary densities observed in different brain structures at birth are not related to the values found in adult animals.

Age Factors↗