Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance.

Taxanes act by inhibiting microtubule dynamics; in this study, we have investigated mitochondria as an additional target of taxanes. We incubated isolated mitochondria in the presence of taxanes with or without stimulation of the mitochondrial respiratory state. Results showed that they rapidly induced the loss of deltapsim after stimulation of the respiratory state.

Implicit and explicit measures of memory for perceptual information in young adults, healthy older adults, and patients with Alzheimer's disease.

In this study, we examined how implicit and explicit memory for perceptual information (modality and voice) and lexical information varied across three subject groups: healthy young adults, healthy older adults, and age-matched older adults with dementia of the Alzheimer's type (DAT). These groups exhibited cross-modality (abstract) priming of the same magnitude. However, young adults produced greater modality- and voice-specific priming than the other two groups, whose performance was equivalent, suggesting that aging, but not DAT, reduced form-specific priming.

Second generation taxanes: from the natural framework to the challenge of drug resistance.

Taxanes represent the most important class of antitumor agents introduced in cancer therapy in the last decade. The first member of the family was paclitaxel, firstly isolated from Taxus Brevifolia and found active as antitumor agent at the end of 60's. In the mid of 90's, a semi-synthetic taxane derived from 10-deacetylbaccatin III was introduced and thereafter named as docetaxel.

Characterization of the expression of inducible nitric oxide synthase in rat and human liver during hemorrhagic shock.

It has been previously shown that the inducible nitric oxide (NO) synthase (iNOS; NOS-2) is elevated after hemorrhage, and that iNOS-derived NO participates in the upregulation of inflammation as well as lung and liver injury postresuscitation from shock. The purpose of this study was to elucidate the time course of iNOS mRNA expression, as well as the cellular and subcellular localization of iNOS protein in the liver posthemorrhage in rats subjected to varying durations of hemorrhagic shock (HS; mean arterial blood pressure [MAP] = 40 mmHg) with or without resuscitation. Expression of iNOS mRNA in rat liver by real-time reverse transcriptase (RT)-PCR demonstrated iNOS upregulation in shocked animals as compared with their sham counterparts as early as 60 min after the initiation of hemorrhage.

Processing approaches to cognition: the impetus from the levels-of-processing framework.

Processing approaches to cognition have a long history, from act psychology to the present, but perhaps their greatest boost was given by the success and dominance of the levels-of-processing framework. We review the history of processing approaches, and explore the influence of the levels-of-processing approach, the procedural approach advocated by Paul Kolers, and the transfer-appropriate processing framework. Processing approaches emphasise the procedures of mind and the idea that memory storage can be usefully conceptualised as residing in the same neural units that originally processed information at the time of encoding.

Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice.

We sought to determine whether gut-derived microbial factors influence the hepatic or intestinal inflammatory response to hemorrhagic shock and resuscitation (HS/R). Conventional and gnotobiotic mice contaminated with a defined microbiota without gram-negative bacteria were subjected to either a sham procedure or HS/R. Tissue samples were obtained 4 h later for assessing ileal mucosal permeability to FITC dextran and hepatic and ileal mucosal steady-state IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and TNF mRNA levels.

Dietary soy modulation of biochemical parameters in DMBA-induced mammary tumors.

The aim of this study was to extend our previous observations on the soy modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors, by simultaneously investigating the expression of estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta), progesterone receptor (PR), apoptosis, neu, and markers of cell proliferation, such as proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The percentage of ERalpha positive tumors was 65.8% in masses from control animals, and significantly dropped to 36.

Reduced function of the multidrug resistance P-glycoprotein in CD34+ cells of patients with aplastic anaemia.

Drug exposure is implicated in the aetiology of some cases of acquired aplastic anaemia (AA), but the reason for this susceptibility remains unclear. We previously demonstrated that P-glycoprotein (P-gp) function, a drug efflux pump, is decreased in AA lymphocytes. To further evaluate whether P-gp activity is also abnormal in AA stem cells, we examined bone marrow (BM) CD34+ cells from newly diagnosed AA patients (AA-d, n = 25), after immunosuppression (AA-IST, n = 13) and after BM transplantation (AA-BMT, n = 8).

Role of toll-like receptors in changes in gene expression and NF-kappa B activation in mouse hepatocytes stimulated with lipopolysaccharide.

The liver is an important site of host-microbe interaction. Although hepatocytes have been reported to be responsive to lipopolysaccharide (LPS), the global gene expression changes by LPS and mechanism(s) by which LPS stimulates cultured hepatocytes remain uncertain. Cultures of primary mouse hepatocytes were incubated with LPS to assess its effects on the global gene expression, hepatic transcription factors, and mitogen-activated protein (MAP) kinase activation.

Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock.

Administration of pyruvate, an effective scavenger of reactive oxygen species, has been shown to be salutary in numerous models of redox-mediated tissue or organ injury. Pyruvate, however, is unstable in solution and, hence, is not attractive for development as a therapeutic agent. Herein, ethyl pyruvate, which is thought to be more stable than the parent compound, was formulated in a calcium-containing balanced salt solution [Ringer ethyl pyruvate solution (REPS)] and evaluated in a murine model of hemorrhagic shock and resuscitation (HS/R).

Silybin and its bioavailable phospholipid complex (IdB 1016) potentiate in vitro and in vivo the activity of cisplatin.

In this study we investigated whether the flavonoid silybin and its bioavailable derivative IdB 1016 (silipide) could enhance the antitumour activity of cisplatin (CDDP), the most commonly used drug in the treatment of gynaecological malignancies. Silybin alone up to 10 (M was unable to produce a relevant in vitro growth inhibition of A2780 cells, whereas CDDP was effective, giving an IC50 value of 0.5+/-0.

The power of a musical instrument: Franklin, the Mozarts, Mesmer, and the glass armonica.

In 1761 Benjamin Franklin invented the armonica (often referred to as the glass harmonica), an instrument designed to simplify the playing of the musical glasses. The instrument immediately became popular and inspired compositions by Wolfgang Mozart, who had the opportunity to hear and play one at the house of Franz Anton Mesmer. Armonica music was used by Mesmer in his séances, because he felt it could promote healing by propagating a mystical fluid that he called animal magnetism through the body.

Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy.

This study was designed to assess the potential chemopreventive effect of the administration of a standardized soy extract, SOYSELECT, on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. Three groups, 24 females each, were used. Animals were fed either a phytoestrogen-free diet alone (control) or the same diet supplemented with 0.

Associative false recognition occurs without strategic criterion shifts.

In the DRM (Deese/Roediger and McDermott) false memory paradigm, subjects studied lists of words associated with nonpresented critical words. They were tested in one of four instructional conditions. In a standard condition, subjects were not warned about the DRM Effect.

Factors that determine false recall: a multiple regression analysis.

In the Deese-Roediger-McDermott (DRM) paradigm, subjects study lists of words that are designed to elicit the recall of an associatively related critical item. The 55 lists we have developed provide levels of false recall ranging from .01 to .

Characterization of two new alleles at the goat CSN1S2 locus.

Two novel alleles at the goat CSN1S2 locus have been identified: CSN1S2(F) and CSN1S2(D). Sequence analyses revealed that the CSN1S2(F) allele is characterized by a G --> A transition at the 13th nucleotide in exon 3 changing the seventh amino acid of the mature protein from Val to Ile. The CSN1S2(D) allele, apparently associated with a decreased synthesis of alpha s2-casein, is characterized by a 106-bp deletion, involving the last 11 bp of the exon 11 and the first 95 bp of the following intron.

Modality effects in false recall and false recognition.

R. E. Smith and R.

Effects of hearing words, imaging hearing words, and reading on auditory implicit and explicit memory tests.

In four experiments, we examined the degree to which imaging written words as spoken by a familiar talker differs from direct perception (hearing words spoken by that talker) and reading words (without imagery) on implicit and explicit tests. Subjects first performed a surface encoding task on spoken, imagined as spoken, or visually presented words, and then were given either an implicit test (perceptual identification or stem completion) or an explicit test (recognition or cued recall) involving auditorily presented words. Auditory presentation at study produced larger priming effects than did imaging or reading.

Direct comparison of auditory implicit memory tests.

In this experiment, we examined the degree to which four implicit tests and two explicit tests, all involving auditory presentation, were sensitive to the perceptual characteristics of the stimuli presented during study. Presenting stimuli visually decreased priming in all the implicit memory tests, relative to auditory presentation. However, changing voice between study and test decreased priming only in the implicit memory tests requiring identification of words degraded by noise or by low-pass filtering, but not in those tests requiring generation from word portions (stems and fragments).

Healers & dealers.

While some physicians aggressively seek opportunities to build lucrative business ventures, others resist the intrusion of business issues and risks into their practices. A key to success is ensuring a good fit between an organization's business model and its physician's professional values and business dispositions. This article describes how to assess physicians' readiness for business risk, and it provides a framework for evaluating different business models in light of the professional values and business risk profiles of the organization's physicians.