Parafrenias: nosografía y presentación clínica.

La parafrenia ha sido una de las últimasgrandes invenciones de la psiquiatría clásica. Tantola escuela francesa como la escuela alemana han discutidofuertemente y descrito esta entidad clínica quees una forma intermediaria entre la paranoia y la esquizofrenia.Originariamente evocada por Kahlbaumy luego descrita por Kraepelin hace ya más de cienaños, el término caerá en el olvido con la aparicióndel manual diagnóstico DSM III, donde será retomadadentro de conceptos tan variados como la esquizofreniao el trastorno delirante crónico.Nos preguntamos si en la hora actual de los manualesde psiquiatría estandarizados, es todavía posibleobservar este concepto clínico rico en matices. Exponiendoun caso de parafrenia, también discutimossu presentación clínica, su proceso evolutivo y losdiagnósticos diferenciales posibles

Wheat germ cell-free expression system as a pathway to improve protein yield and solubility for the SSGCID pipeline

A set of 44 protein targets was used to test expression in the wheat germ cell-free system, the vast majority of which were expressed and soluble in this system; further increases in solubility were achieved by addition of the NVoy polymer

Phenomenological contribution to understanding of vocally disruptive behaviour: A clinical case study in a patient with dementia.

Behavioural and psychological symptoms of dementia (BPSD) cause great suffering in patients and their families. Phenomenology can help clarify the diagnosis and propose some new therapeutic responses using Daseinsanalyse. Separation issues understood using the phenomenological description of the melancholic type (MT) by Tellenbach may further shed light on our understanding of depression in dementia. In a 90-year-old woman presenting with advanced (Clinical Dementia Rating 3) mixed dementia and BPSD in the form of vocally disruptive behaviour (VDB), we discuss separation anxiety as the aetiopathogenic hypothesis. Depression and BPSD were assessed using the Neuropsychiatric Inventory, Cornell scale, and Montgomery-Åsberg Depression Rating Scale to confirm our second phenomenological diagnostic hypothesis, ie, melancholy. The Big Five Inventory scale filled in by a proxy was also used to evaluate the patient's premorbid personality. We then propose an explanatory frame of VDB and depression through the standard phenomenological assessment of its relation to time, space, self, and other. Confirming MT, we found an inhibited temperament and low openness to experience in the patient, as well as a symbiotic relationship with a close relative (the other). Separation anxiety may well explain the patient's MT expressed by VDB. Melancholic type and her symbiotic relationship led to a situation unbearable to the patient and her close relative unable to delegate care to a specialized team. Phenomenology in vocally disruptive behaviour in dementia. We have found new explanations in similar clinical cases in dementia as follows. A patient presenting with vocally disruptive behaviour has a melancholic type, a behavioural-inhibited temperament, and marital violence in the past. Phenomenology may help explain this profile with neurobiological disorders. The life trajectory, from childhood into older age, must be taken into account to understand behavioural and psychological symptoms of dementia

The development of the albino rat, Mus norvegicus albinus. I. From the pronuclear stage to the stage of mesoderm anlage; end of the first to the end of the ninth day

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50236/1/1050260205_ftp.pd

Messina: A Novel Analysis Tool to Identify Biologically Relevant Molecules in Disease

BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package

Prediction of specificity-determining residues for small-molecule kinase inhibitors

<p>Abstract</p> <p>Background</p> <p>Designing small-molecule kinase inhibitors with desirable selectivity profiles is a major challenge in drug discovery. A high-throughput screen for inhibitors of a given kinase will typically yield many compounds that inhibit more than one kinase. A series of chemical modifications are usually required before a compound exhibits an acceptable selectivity profile. Rationalizing the selectivity profile for a small-molecule inhibitor in terms of the specificity-determining kinase residues for that molecule can be an important step toward the goal of developing selective kinase inhibitors.</p> <p>Results</p> <p>Here we describe S-Filter, a method that combines sequence and structural information to predict specificity-determining residues for a small molecule and its kinase selectivity profile. Analysis was performed on seven selective kinase inhibitors where a structural basis for selectivity is known. S-Filter correctly predicts specificity determinants that were described by independent groups. S-Filter also predicts a number of novel specificity determinants that can often be justified by further structural comparison.</p> <p>Conclusion</p> <p>S-Filter is a valuable tool for analyzing kinase selectivity profiles. The method identifies potential specificity determinants that are not readily apparent, and provokes further investigation at the structural level.</p

17-allyamino-17-demethoxygeldanamycin treatment results in a magnetic resonance spectroscopy-detectable elevation in choline-containing metabolites associated with increased expression of choline transporter SLC44A1 and phospholipase A2

Abstract Introduction 17-allyamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is currently in clinical trials in breast cancer. However, 17-AAG treatment often results in inhibition of tumor growth rather than shrinkage, making detection of response a challenge. Magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) are noninvasive imaging methods than can be used to monitor metabolic biomarkers of drug-target modulation. This study set out to examine the MRS-detectable metabolic consequences of Hsp90 inhibition in a breast cancer model. Methods MCF-7 breast cancer cells were investigated, and MRS studies were performed both on live cells and on cell extracts. 31P and 1H MRS were used to determine total cellular metabolite concentrations and 13C MRS was used to probe the metabolism of [1,2-13C]-choline. To explain the MRS metabolic findings, microarray and RT-PCR were used to analyze gene expression, and in vitro activity assays were performed to determine changes in enzymatic activity following 17-AAG treatment. Results Treatment of MCF-7 cells with 17-AAG for 48 hours caused a significant increase in intracellular levels of choline (to 266 ± 18% of control, P = 0.05) and phosphocholine (PC; to 181 ± 10% of control, P = 0.001) associated with an increase in expression of choline transporter SLC44A1 and an elevation in the de novo synthesis of PC. We also detected an increase in intracellular levels of glycerophosphocholine (GPC; to 176 ± 38% of control, P = 0.03) associated with an increase in PLA2 expression and activity. Conclusions This study determined that in the MCF-7 breast cancer model inhibition of Hsp90 by 17-AAG results in a significant MRS-detectable increase in choline, PC and GPC, which is likely due to an increase in choline transport into the cell and phospholipase activation. 1H MRSI can be used in the clinical setting to detect levels of total choline-containing metabolite (t-Cho, composed of intracellular choline, PC and GPC). As Hsp90 inhibitors enter routine clinical use, t-Cho could thus provide an easily detectable, noninvasive metabolic biomarker of Hsp90 inhibition in breast cancer patients