Epistatic interaction between haplotypes of the ghrelin ligand and receptor genes influence susceptibility to myocardial infarction and coronary artery disease.

Data from both experimental models and humans provide evidence that ghrelin and its receptor, the growth hormone secretagogue receptor (ghrelin receptor, GHSR), possess a variety of cardiovascular effects. Thus, we hypothesized that genetic variants within the ghrelin system (ligand ghrelin and its receptor GHSR) are associated with susceptibility to myocardial infarction (MI) and coronary artery disease (CAD). Seven single nucleotide polymorphisms (SNPs) covering the GHSR region as well as eight SNPs across the ghrelin gene (GHRL) region were genotyped in index MI patients (864 Caucasians, 'index MI cases') from the German MI family study and in matched controls without evidence of CAD (864 Caucasians, 'controls', MONICA Augsburg).

Intima-media thickness in the origin of right subclavian artery as an early marker of cardiovascular risk.

Objective: Common carotid artery intima-media thickness (IMT) is considered a factor of cardiovascular risk and an early marker of coronary artery disease. This study aimed to investigate the existence of a correlation between IMT in the carotid arteries and at the origin of the right subclavian artery, as well as to evaluate IMT in the subclavian artery as an earlier marker of cardiovascular risk.

Methods: One hundred and six consecutive patients, 52 males and 54 females, average age 51 years, underwent color Doppler ultrasonography to evaluate carotid and right subclavian arteries.

In vivo assessment of human skin aging by multiphoton laser scanning tomography.

Changes of dermal collagen and elastin content are characteristic for skin aging as well as for pathological skin conditions. To evaluate these changes, we used in vivo multiphoton laser tomography to measure two-photon excited autofluorescence (AF) and second harmonic generation (SHG). We tested 18 patients of all ages and calculated the SHG-to-AF aging index of dermis (SAAID).

Association of the Ghrelin receptor gene region with left ventricular hypertrophy in the general population: results of the MONICA/KORA Augsburg Echocardiographic Substudy.

Growth hormone (GH) can influence left ventricular myocardial growth, structure, and function. The GH secretagogue receptor (GHSR, ghrelin receptor) is known to be involved in GH release and is expressed in the myocardium. We hypothesized that genetic variants within the GHSR are associated with parameters of left ventricular mass (LVM) and geometry.

Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer.

Purpose: To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer.

Methods: In this phase II multicenter trial, the primary objective was assessment of the tumor response rate with gefitinib; secondary objectives included analysis of the pharmacodynamic and biologic profiles in healthy and tumor tissue.

Results: while phosphorylation of mitogen-activated protein kinase was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in Ki67 in skin but not in tumors.

Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study.

Background: The objective of this study was to examine the Minimum Data Set (MDS) and Geriatric Depression Scale (GDS) as measures of depression among nursing home residents.

Methods: The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version.

Induction of remission in a patient with metastatic breast cancer refractory to trastuzumab and chemotherapy following treatment with gefitinib ('Iressa', ZD1839).

Despite new therapies and several treatment options, metastatic breast cancer (MBC) remains incurable. One reason for the low median survival rate may be intense cross-talk between growth factor receptors such as the epidermal growth factor receptor (EGFR/HER1) and the HER2 growth factor receptor. This report describes the case history of a patient with MBC whose disease had progressed despite surgery, radiotherapy and four different chemotherapy regimens, including trastuzumab (a monoclonal antibody that specifically blocks HER2) combined with docetaxel.

Multicolor spectral karyotyping of rat chromosomes.

Rat and mouse have become important animal models to study various human diseases such as cancer. Cytogenetic analysis of the respective karyotypes is frequently required to investigate the causative genetic defects and especially neoplastic cells often show complex chromosome aberrations and many different marker chromosomes. However, structural homogeneity of the chromosomes in these species as well as less pronounced differences in banding patterns make it difficult to assign genetic abnormalities to certain chromosomes by conventional banding techniques.

Alum treatment of poultry litter: decomposition and nitrogen dynamics.

While the poultry industry is a major economic benefit to several areas in the USA, land application of poultry litter to recycle nutrients can lead to impaired surface and ground water quality. Amending poultry litter with alum [Al3(SO4)2 x 14H2O] has received considerable attention as a method of economically reducing ammonia volatilization in the poultry house and soluble phosphorus in runoff waters. The objective of this study was to characterize the effect of alum on broiler litter decomposition and N dynamics under laboratory conditions.

Phase I trial of the antifolate ZD9331 in combination with cisplatin in patients with refractory solid malignancies.

Purpose: To determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of ZD9331 in combination with cisplatin in patients with refractory solid tumors and to describe any preliminary antitumor activity associated with this regimen.

Materials And Methods: Patients received combination therapy with ZD9331 as a 30-min infusion on days 1 and 8 of a 21-day cycle at doses of 100 or 130 mg/m(2), followed by cisplatin at 50 or 75 mg/m(2) as a 30- to 60-min infusion on day 1 only.

Results: A total of 16 patients received 59 cycles of ZD9331 and cisplatin.

A new synthetic approach to the C ring of known as well as novel bryostatin analogues.

[reaction: see text] A new approach to the synthesis of the C ring subunit of known and potential bryostatin analogues is described. The convergent approach, illustrated above, requires fewer steps and offers greater flexibility in rapidly accessing diverse C ring analogues.

Cytogenetic evolution of human ovarian cell lines associated with chemoresistance and loss of tumorigenicity.

In order to identify genomic changes associated with a resistant phenotype acquisition, we used comparative genomic hybridization (CGH) to compare a human ovarian cell line, Igrov1, and four derived subcell lines, resistant to vincristine and presenting a reversion of malignant properties. Multicolor FISH (Multiplex-FISH and Spectral Karyotype) and conventional FISH are also used to elucidate the karyotype of parental cell line. The drug-resistant subcell lines displayed many chromosomal abnormalities suggesting the implication of different pathways leading to a multidrug resistance phenotype.

Phosphate ester serum albumin affinity tags greatly improve peptide half-life in vivo.

A series of phosphate ester based small molecules designed to bind tightly to serum albumin were applied to the amino terminus of an anticoagulant peptide in an effort to increase its protein binding in vivo. The tagged peptides exhibited high affinity for both rabbit and human serum albumin when passed through liquid chromatographic columns with serum albumins incorporated into the stationary phase. The peptides were then administered intravenously to rabbits and found to have a greater than 50-fold increase in plasma half life.

Origins of PDZ domain ligand specificity. Structure determination and mutagenesis of the Erbin PDZ domain.

The LAP (leucine-rich repeat and PDZ-containing) family of proteins play a role in maintaining epithelial and neuronal cell size, and mutation of these proteins can have oncogenic consequences. The LAP protein Erbin has been implicated previously in a number of cellular activities by virtue of its PDZ domain-dependent association with the C termini of both ERB-B2 and the p120-catenins. The present work describes the NMR structure of Erbin PDZ in complex with a high affinity peptide ligand and includes a comprehensive energetic analysis of both the ligand and PDZ domain side chains responsible for binding.

Diminished antibody response to hepatitis B immunization in children with sickle cell disease.

Hepatitis B surface antibody titers were routinely measured in 150 children with sickle cell disease (SCD) after immunization, and the seroconversion rate was found to be lower than that in the general population (89% vs. 97%, P = 0.002).

Albumin affinity tags increase peptide half-life in vivo.

Small organic molecules that bind tightly to serum albumin were applied to the amino terminus of an anticoagulant peptide in an effort to increase its protein binding in vivo. The tagged peptides were evaluated for their ability to be retained on liquid chromatographic columns with serum albumins incorporated into the stationary phase. Those which demonstrated significant affinity were administered intravenously to rabbits and found to have significantly increased plasma half-lives.

The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF.

Erbin is a recently described member of the LAP (leucine-rich repeat and PDZ domain) protein family. We used a C-terminally displayed phage peptide library to identify optimal ligands for the Erbin PDZ domain. Phage-selected peptides were type 1 PDZ ligands that bound with high affinity and specificity to the Erbin PDZ domain in vitro.

[Treatment of brain metastases].

The treatment of metastastic disease to the brain requires integration of neurosurgical, radiotherapeutic and oncological principles. Surgical resection is mandatory if a brain tumor manifests as an apparently unifocal lesion of a newly discovered neoplastic disorder. Furthermore, surgery is to be selected to alleviate signs and symptoms of increased intracranial pressure which can be caused by a mass effect and/or by obstruction of the CSF pathways.

Highly comprehensive karyotype analysis by a combination of spectral karyotyping (SKY), microdissection, and reverse painting (SKY-MD).

A technique disclosing most information about chromosome modifications is the technique of choice for the analysis of chromosome alterations. The newly developed method for microdissection of fluorescence-labeled chromosomes (FISH-MD) can improve upon this expectation in combination with 24-color spectral karyotyping (SKY). The highly efficient way to detect chromosome modifications by SKY and the detailed specification of aberrant chromosomes by FISH-MD prompted us to use both techniques in a combined approach called SKY-MD.

Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination.

Sex-determination mechanisms in birds and mammals evolved independently for more than 300 million years. Unlike mammals, sex determination in birds operates through a ZZ/ZW sex chromosome system, in which the female is the heterogametic sex. However, the molecular mechanism remains to be elucidated.