Putative role of brain acetaldehyde in ethanol addiction.

The putative contribution of brain acetaldehyde (AcH) to ethanol (EtOH) tolerance and dependence (addiction) is reviewed. Although the role of AcH in EtOH addiction has been controversial, there are data showing a relationship. AcH can be formed in the brain tissues through the peroxidatic activity of catalase and by oxidation via other oxidizing enzymes such as cytochrome P-4502E1.

Ethanol metabolism and effects: nitric oxide and its interaction.

Ethanol (EtOH) in alcoholic beverages is consumed by a large number of individuals and its elimination is primarily by oxidation. The role of nitric oxide (NO) in EtOH's effects is important since NO is one of the most prominent biological factors in mammals. NO is constantly formed endogenously from L-arginine.

Estrogen regulated gene expression in response to neoadjuvant endocrine therapy of breast cancers: tamoxifen agonist effects dominate in the presence of an aromatase inhibitor.

Estrogens (E) and estrogen receptors (ER) are implicated in breast cancer growth and are targets of hormonal therapies. Such therapies commonly use aromatase inhibitors (AI) to block E production, or antiestrogens like tamoxifen (TAM), which targets ER. Here we compare genes in pre-and post-treatment tumor pairs of patients with ER+ tumors, that were treated preoperatively with the AI exemestane alone, or with exemestane plus TAM.

Nitric oxide evokes an adaptive response to oxidative stress by arresting respiration.

Aerobic metabolism generates biologically challenging reactive oxygen species (ROS) by the endogenous autooxidation of components of the electron transport chain (ETC). Basal levels of oxidative stress can dramatically rise upon activation of the NADPH oxidase-dependent respiratory burst. To minimize ROS toxicity, prokaryotic and eukaryotic organisms express a battery of low-molecular-weight thiol scavengers, a legion of detoxifying catalases, peroxidases, and superoxide dismutases, as well as a variety of repair systems.

Endometrial cancer cell survival and apoptosis is regulated by protein kinase C alpha and delta.

Endometrial cancer is the most common invasive gynecologic malignancy but the molecular mechanisms underlying its onset and progression are poorly understood. Paradoxically, endometrial tumors exhibit increased apoptosis, correlating with disease progression and poor patient prognosis. Endometrial tumors also show altered activity and expression of protein kinase C (PKC) isoforms, implicated in the regulation of programmed cell death; however, PKC modulation of apoptosis in endometrial cancer cells has not been investigated.

Secretion and fluid transport mechanisms in the mammary gland: comparisons with the exocrine pancreas and the salivary gland.

Milk is a complex fluid composed of proteins, sugars, lipids and minerals, in addition to a wide variety of bioactive molecules including vitamins, trace elements and growth factors. The composition of these components reflects the integrated activities of distinct synthetic, secretion and transport processes found in mammary epithelial cells, and mirrors the differing nutritional and developmental requirements of mammalian neonates. Five general pathways have been described for secretion of milk components.

Fasting decreases free fatty acid turnover in mice overexpressing skeletal muscle lipoprotein lipase.

Skeletal muscle lipoprotein lipase (LPL) overexpression in mice results in whole-body insulin resistance and increased intramuscular triglyceride stores, but decreased plasma triglyceride concentration and unchanged plasma free fatty acid (FFA) concentration. The effects of skeletal muscle LPL overexpression and fasting duration on FFA kinetics are unknown. Transgenic mice with muscle-specific LPL overexpression (MCKhLPL) and control mice (Con) were studied at rest during a 50-minute constant infusion of [9,10- 3H]palmitate to determine FFA kinetics after both 4 and 16 hours of fasting.

MDM2 is required for suppression of apoptosis by activated Akt1 in salivary acinar cells.

Chronic damage to the salivary glands is a common side effect following head and neck irradiation. It is hypothesized that irreversible damage to the salivary glands occurs immediately after radiation; however, previous studies with rat models have not shown a causal role for apoptosis in radiation-induced injury. We report that etoposide and gamma irradiation induce apoptosis of salivary acinar cells from FVB control mice in vitro and in vivo; however, apoptosis is reduced in transgenic mice expressing a constitutively activated mutant of Akt1 (myr-Akt1).

Harm resulting from inappropriate telephone triage in primary care.

Purpose: Our objective was to assess and categorize harm occurring to patients who called their physicians' office after-hours but did not have their call forwarded to the physician because they stated that their call was not an emergency.

Methods: We collected data on 4949 calls handled by our answering service for 1 year in a family medicine residency office in Denver, CO. Of the 2835 after-hours clinical calls, we reviewed all 288 clinical calls that were not forwarded to the "on-call" physician.

Diversity in the olfactory epithelium of bony fishes: development, lamellar arrangement, sensory neuron cell types and transduction components.

In this study we use a taxon-based approach to examine previous, as well as new findings on several topics pertaining to the peripheral olfactory components in teleost fishes. These topics comprise (1) the gross anatomy of the peripheral olfactory organ, including olfactory sensory neuron subtypes and their functional parameters, (2) the ultrastructure of the olfactory epithelium, and (3) recent findings regarding the development of the nasal cavity and the olfactory epithelium. The teleosts are living ray-finned fish, and include descendants of early-diverging orders (e.

Stress urinary incontinence in women: diagnosis and medical management.

Stress urinary incontinence (SUI) is the most common form of urinary incontinence in women and is associated with high financial, social, and emotional costs. The history and physical examination can identify most patients with a significant stress incontinence component without the need for urodynamic testing. A variety of pharmacologic agents have been used off-label, but an evidence-based pharmacologic treatment has not been readily available.

The role of Rat1 in coupling mRNA 3'-end processing to transcription termination: implications for a unified allosteric-torpedo model.

The torpedo model of transcription termination by RNA polymerase II proposes that a 5'-3' RNA exonuclease enters at the poly(A) cleavage site, degrades the nascent RNA, and eventually displaces polymerase from the DNA. Cotranscriptional degradation of nascent RNA has not been directly demonstrated, however. Here we report that two exonucleases, Rat1 and Xrn1, both contribute to cotranscriptional degradation of nascent RNA, but this degradation is not sufficient to cause polymerase release.

The transcription factor ZEB1 is aberrantly expressed in aggressive uterine cancers.

The transcription factor ZEB1 (deltaEF1 in mice) has been implicated in cellular processes during development and tumor progression including epithelial to mesenchymal transition. deltaEF1 null mice die at birth, but heterozygotes expressing a LacZ reporter inserted into the deltaEF1 gene live and reproduce. Using these mice, we observed ZEB1 promoter activity in the virgin myometrium, and stroma and myometrium of the pregnant uterus.

Differential regulation of cell growth and gene expression by FGF-2 and FGF-4 in pituitary lactotroph GH4 cells.

Fibroblast growth factors, FGF-2 and FGF-4, are reported to play divergent roles in pituitary differentiation and tumor formation, stimulating cell differentiation or proliferation, respectively. However, mitogenic responses to FGFs have not been extensively characterized and little is known about the molecular mechanisms by which specific FGF isoforms may mediate distinct biological responses. Here we show that FGF-4 but not FGF-2 stimulated DNA synthesis and cell proliferation in GH4 cells.

Dissection of the bacteriophage Mu strong gyrase site (SGS): significance of the SGS right arm in Mu biology and DNA gyrase mechanism.

The bacteriophage Mu strong gyrase site (SGS), required for efficient phage DNA replication, differs from other gyrase sites in the efficiency of gyrase binding coupled with a highly processive supercoiling activity. Genetic studies have implicated the right arm of the SGS as a key structural feature for promoting rapid Mu replication. Here, we show that deletion of the distal portion of the right arm abolishes efficient binding, cleavage, and supercoiling by DNA gyrase in vitro.

Estradiol regulates different genes in human breast tumor xenografts compared with the identical cells in culture.

In breast cancers, estrogen receptor (ER) levels are highly correlated with response to endocrine therapies. We sought to define mechanisms of estrogen (E) signaling in a solid breast tumor model using gene expression profiling. ER(+) T47D-Y human breast cancer cells were grown as xenografts in ovariectomized nude mice under four conditions: 1) 17beta-estradiol for 8 wk (E); 2) without E for 8 wk (control); 3) E for 7 wk followed by 1 wk of E withdrawal (Ewd); or 4) E for 8 wk plus tamoxifen for the last week.

ASF1 binds to a heterodimer of histones H3 and H4: a two-step mechanism for the assembly of the H3-H4 heterotetramer on DNA.

The first step in the formation of the nucleosome is commonly assumed to be the deposition of a histone H3-H4 heterotetramer onto DNA. Antisilencing function 1 (ASF1) is a major histone H3-H4 chaperone that deposits histones H3 and H4 onto DNA. With a goal of understanding the mechanism of deposition of histones H3 and H4 onto DNA, we have determined the stoichiometry of the Asf1-H3-H4 complex.

Clinical staging of prostate cancer: a computer-simulated study of transperineal prostate biopsy.

Objective: To identify the precise location of prostate cancer within the gland and thus possibly permit more aggressive therapy of the lesion, while potentially sparing the noncancerous gland from ablative therapy.

Materials And Methods: Three-dimensional "solid" computer models were reconstructed for 86 autopsy specimens and 20 stage T1c radical prostatectomy specimens. Transperineal biopsies were simulated for grid sizes of 5-mm (method A) and 10-mm (method B) with an 18 G, 23-mm long biopsy needle.

The yeast histone chaperone chromatin assembly factor 1 protects against double-strand DNA-damaging agents.

The removal of histones from DNA and their subsequent replacement is likely to be necessary for all processes that require access to the DNA sequence in eukaryotic cells. The histone chaperone chromatin assembly factor 1 (CAF-1) mediates histone H3-H4 assembly during DNA replication and nucleotide excision repair in vitro. We have found that budding yeast deleted for the genes encoding CAF-1 are highly sensitive to double-strand DNA-damaging agents.

Effect of anionic ion-pairing reagent hydrophobicity on selectivity of peptide separations by reversed-phase liquid chromatography.

Despite the continuing dominance of trifluoroacetic acid (TFA) as the anionic ion-pairing reagent of choice for peptide separations by reversed-phase high-performance liquid chromatography (RP-HPLC), we believe that a step-by-step approach to re-examining the relative efficacy of TFA compared to other ion-pairing reagents is worthwhile, particularly for the design of separation protocols for complex peptide mixtures, e.g., in proteomics applications.

Effect of anionic ion-pairing reagent concentration (1-60 mM) on reversed-phase liquid chromatography elution behaviour of peptides.

The homologous series of volatile perfluorinated acids-trifluoroacetic acid (TFA), pentafluoropropionic acid (PFPA) and heptafluorobutyric acid (HFBA)--continue to be excellent anionic ion-pairing reagents for reversed-phase high-performance liquid chromatography (RP-HPLC) after more than two decades since their introduction to this field. It was felt that a thorough, step-by-step re-examination of the effects of anionic ion-pairing reagents over a wide concentration range on RP-HPLC peptide elution behaviour is now due, particularly considering the continuing dominance of such reagents for peptide applications. Thus, RP-HPLC was applied over a range of 1-60 mM phosphoric acid, TFA, PFPA and HFBA to two mixtures of 18-residue synthetic peptides containing either the same net positive charge (+4) or varying positive charge (+1, +2, +3, +4).

The perchlorate anion is more effective than the trifluoroacetate anion as an ion-pairing reagent for reversed-phase chromatography of peptides.

The addition of salts, specifically sodium perchlorate (NaClO4), to mobile phases at acidic pH as ion-pairing reagents for reversed-phase high-performance liquid chromatography (RP-HPLC) has been generally overlooked. To demonstrate the potential of NaClO4 as an effective anionic ion-pairing reagent, we applied RP-HPLC in the presence of 0-100 mM sodium chloride (NaCl), sodium trifluoroacetate (NaTFA) or NaClO4 to two mixtures of synthetic 18-residue peptides: a mixture of peptides with the same net positive charge (+4) and a mixture of four peptides of +1, +2, +3 and +4 net charge. Interestingly, the effect of increasing NaClO4 concentration on increasing peptide retention times and selectivity changes was more dramatic than that of either NaCl or NaTFA, with the order of increasing anion effectiveness being Cl- << TFA- < C104-.

Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair.

Many recent studies have demonstrated recruitment of chromatin-modifying enzymes to double-strand breaks. Instead, we wanted to examine chromatin modifications during the repair of these double-strand breaks. We show that homologous recombination triggers the acetylation of N-terminal lysines on histones H3 and H4 flanking a double-strand break, followed by deacetylation of H3 and H4.

Formation of ethyl nitrite in vivo after ethanol administration.

The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitro from the reaction of ethanol with peroxynitrite, as well as after administration of ethanol to mice. Ethyl nitrite analyte was determined by using gas chromatography--mass spectrometry with headspace analysis with the use of a solid-phase microextraction device. Peroxynitrite was allowed to react with ethanol under a variety of conditions in vitro.