Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice.

Salvia divinorum is a natural occurring hallucinogen that is traditionally used by the Mazatec Indians of central Mexico. The diterpene salvinorin A was identified as an active component of S. divinorum over 20 years ago, but only recently has biochemical screening indicated that a molecular target of salvinorin A in vitro is the kappa-opioid receptor.

Patient outcomes after axillary lymph node dissection for breast cancer: use of postoperative continuous local anesthesia infusion.

Background: Although considered a safe surgical procedure, axillary lymph node dissection (ALND) is associated with postoperative numbness, paresthesias, pain, and muscle weakness. Despite meticulous surgical technique and the absence of long thoracic or thoracodorsal nerve injury, the risk of these complications are reported as great as 35% to 50%, with a subset of patients developing chronic pain syndromes.

Methods: Female patients (n = 27) undergoing Level I-II ALND for breast cancer were recruited.

Tissue angiotensin-converting enzyme inhibitors: are they more effective than serum angiotensin-converting enzyme inhibitors?

Since their discovery in the 1980s, angiotensin-converting enzyme (ACE) inhibitors have been shown to decrease angiotensin formation, prevent breakdown of bradykinin, and may also act on peptides of the renin-angiotensin system. They are effective in reducing the risk of heart failure, myocardial infarction, and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure, and have been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure. They may preserve endothelial function and counteract initiation and progression of atherosclerosis.

Unusual forms of immature sporulating Coccidioides immitis diagnosed by fine-needle aspiration biopsy.

Coccidioidomycosis is an endemic infection acquired by inhalation of the spores (arthroconidia) of the thermally dimorphic fungus, Coccidioides immitis. The arthroconidia transform into spherical cells called mature spherules in the lung. Immature spherules and other atypical forms of immature C immitis have rarely been found in vivo.

Do all patients with coronary artery disease benefit from angiotensin converting enzyme inhibitors?

Cumulative evidence supports the use of angiotensin-converting enzyme (ACE) inhibitors for stable coronary artery disease in patients with and without heart failure. The dose and unique properties of ACE inhibitors, trial data, differences in trial design and demographics, may all contribute to variable responses in clinical outcomes. Pending direct comparator clinical trials between a tissue ACE inhibitor vs a plasma ACE inhibitor, evidence indicates that both ramipril and perindopril can be recommended for secondary risk prevention.

Structural model of the Plasmodium CDK, Pfmrk, a novel target for malaria therapeutics.

Malaria, with 300-500 million clinical cases resulting in 1-3 million fatalities a year, is one of the most deadly tropical diseases. As current antimalarial therapeutics become increasingly ineffective due to parasitic resistance, there exists an urgent need to develop and pursue new therapeutic strategies. Recent genome sequencing and molecular cloning projects have identified several enzymes from Plasmodium (P.

3D-QSAR comparative molecular field analysis on delta opioid receptor agonist SNC80 and its analogs.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) for a series of delta opioid receptor agonists: SNC80 analogs. Quantum chemical calculations on SNC80 show that protonation is preferred at the basic N4 atom over the alternative N1 atom, accordingly N4 protonation may contribute significantly to ligand-receptor interactions under physiologically relevant conditions. Statistically significant and predictive CoMFA models were achieved by pooling biological data from independent published sources, including compounds with both alphaR and alphaS benzylic configurations.

Three dimensional nanofibrillar surfaces induce activation of Rac.

Studies to define the mechanisms by which the extracellular matrix (ECM) activates Rho GTPases within the cell have generally focused on the chemistry of the macromolecules comprising the ECM. Considerably less information is available to assess the role of the physical structure of the ECM, particularly its three dimensional (3D) geometry. In this report, we examined the effect of 3D surfaces on the activation states of Rho GTPases within NIH 3T3 fibroblasts and normal rat kidney cells.

An update on enhanced external counterpulsation.

The development of advanced revascularization techniques has resulted in the growth of a subset of patients with coronary artery disease who are nonrevascularizable and are considered to have refractory angina. Enhanced external counterpulsation (EECP) has been developed for the management of these patients with chronic, refractory disease. Evidence has shown that through improvement of vascular endothelial function and recruitment of collateral vessels, EECP provides many clinical benefits.

3D-QSAR comparative molecular field analysis on opioid receptor antagonists: pooling data from different studies.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were constructed using comparative molecular field analysis (CoMFA) on a series of opioid receptor antagonists. To obtain statistically significant and robust CoMFA models, a sizable data set of naltrindole and naltrexone analogues was assembled by pooling biological and structural data from independent studies. A process of "leave one data set out", similar to the traditional "leave one out" cross-validation procedure employed in partial least squares (PLS) analysis, was utilized to study the feasibility of pooling data in the present case.

Proteoglycan-collagen XV in human tissues is seen linking banded collagen fibers subjacent to the basement membrane.

Type XV is a large collagen-proteoglycan found in all human tissues examined. By light microscopy it was localized to most epithelial and all nerve, muscle, fat and endothelial basement membrane zones except for the glomerular capillaries or hepatic/splenic sinusoids. This widespread distribution suggested that type XV may be a discrete structural component that acts to adhere basement membrane to the underlying connective tissue.

Epothilone induced cytotoxicity is dependent on p53 status in prostate cells.

Background: Epothilones are a promising class of drugs in clinical trials of prostate cancer that target the microtubules, similar to taxanes, and induce apoptosis in taxane resistant tumors. The tumor suppressor p53 is one important molecular mechanism of chemotherapy resistance that in some studies predicted tumor sensitivity to paclitaxel. We hypothesized that epothilone induced cytotoxicity would be influenced by the status of p53 in prostate cells.

Increased interleukin-10 mRNA stability in melanoma cells is associated with decreased levels of A + U-rich element binding factor AUF1.

Abnormal production of interleukin-10 (IL-10) is observed in some pathologic conditions. For example, compared with normal melanocytes, IL-10 expression is elevated in melanoma cells. IL-10 overexpression could inhibit both immune surveillance and tumor rejection.

A dance between interferon-alpha/beta and p53 demonstrates collaborations in tumor suppression and antiviral activities.

In the recent paper by Takaoka et al. (2003), the authors demonstrate that interferons-alpha and -beta stimulate p53 expression but not p53 activation. The increase in p53 expression translates into significant enhancement of apoptosis and reduction of chemotherapeutic dosages in vitro to destroy tumor cells.

Pentamidine-induced alteration in restriction endonuclease cleavage of plasmid DNA.

We have used restriction enzymes and DNaseI as probes to determine the specificity of pentamidine binding to plasmid DNA. Cleavage of plasmid pAZ130 by EcoRI, EcoRV and ApaI is inhibited by pentamidine, cleavage by XbaI, NotI and AvaI is unaffected, while cleavage by XhoI, which recognizes the same sequence as AvaI, is stimulated. DNaseI footprinting of DNA containing these restriction sites revealed that pentamidine protection is not strictly limited to AT-rich regions.

Loss of types XV and XIX collagen precedes basement membrane invasion in ductal carcinoma of the female breast.

Ductal and lobular carcinomas comprise most malignancies of the female breast and the morbidity and mortality associated with breast cancer. During the progression from in situ to invasive stages, tumour cells penetrate the epithelial and vascular basement membranes (BM) to realize full metastatic potential. While the definition of these structures has primarily resulted from analysis of laminin and type IV collagen, characterization of newly discovered BM/BM zone (BMZ) proteins will further elucidate the interactions between tumour cells and the host stroma.

Prevalence and age of onset for drug use in seven international sites: results from the international consortium of psychiatric epidemiology.

This study compares lifetime prevalence and age of first use (onset) for alcohol, cannabis, and other drugs in six international sites. Data from seven epidemiologic field surveys that used compatible instruments and study designs were compiled for cross-site analyses by the International Consortium of Psychiatric Epidemiology (ICPE). The world health organization's composite international diagnostic instrument (WHO-CIDI) and additional items were used to ascertain drug use in each site.

Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain.

This clinical protocol describes virus-based gene transfer for Canavan disease, a childhood leukodystrophy. Canavan disease, also known as Van Bogaert-Bertrand disease, is a monogeneic, autosomal recessive disease in which the gene coding for the enzyme aspartoacylase (ASPA) is defective. The lack of functional enzyme leads to an increase in the central nervous system of the substrate molecule, N-acetyl-aspartate (NAA), which impairs normal myelination and results in spongiform degeneration of the brain.

Components of disparity vergence eye movements: application of independent component analysis.

The "dual mode" theory for the control of disparity vergence eye movements states that two control components, a preprogrammed "transient" component and a feedback-controlled "sustained" component, mediate the motor response. Although prior experimental work has isolated and studied the transient component, little is known of the sustained component's contribution to the dynamic vergence response. The timing between the two components and their relative magnitudes are of interest as they relate to the strategies used by the brain to coordinate and control the two components.

Adaptive modification of disparity vergence components: an independent component analysis study.

Purpose: Although a disparity vergence stimulus produces a smooth exponential-like response, considerable experimental evidence indicates that it is the product of at least two motor components: a pulselike transient component and a steplike sustained component. Recently, a new application of independent component analysis (ICA) has been used to decompose the vergence step response into these underlying components. Other recent experiments have shown that the vergence system is capable of rapidly modifying its dynamic characteristics (short-term adaptation) when exposed to specially designed "adapting" stimuli.

Inactivation of olfactory sensilla of a single morphological type differentially affects the response of Drosophila to odors.

The olfactory organs on the head of Drosophila, antennae and maxillary palps, contain several hundred olfactory hairs, each with one or more olfactory receptor neurons. Olfactory hairs belong to one of three main morphological types, trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial distribution patterns on the surface of the antenna and maxillary palps. Here we show that targeting expression of the cell-death gene reaper to basiconic sensilla (BS) causes the specific inactivation of most olfactory sensilla of this type with no detectable effect on other types of olfactory sensilla or the structure of the antennal lobe.

Novel genes expressed in subsets of chemosensory sensilla on the front legs of male Drosophila melanogaster.

Detection of courtship-activating female pheromones by contact chemoreceptors on the front legs of male Drosophila melanogaster is thought to play an important role in triggering courtship behavior. However, the chemosensory organs, cells, and molecules responsible are not known. We have isolated two genes, CheA29a and CheB42a, expressed in nonneuronal auxiliary cells within two nested subsets of chemosensory sensilla on the front legs of sexually mature, adult males.

Ubiquitin-associated (UBA) domains in Rad23 bind ubiquitin and promote inhibition of multi-ubiquitin chain assembly.

Rad23 is a DNA repair protein that promotes the assembly of the nucleotide excision repair complex. Rad23 can interact with the 26S proteasome through an N-terminal ubiquitin-like domain, and inhibits the assembly of substrate-linked multi-ubiquitin (multi-Ub) chains in vitro and in vivo. Significantly, Rad23 can bind a proteolytic substrate that is conjugated to a few ubiquitin (Ub) moieties.