Acute myocardial infarction. Recommendations for medical management and primary angioplasty.

Deaths from acute myocardial infarction have declined in recent years, thanks to the introduction of thrombolytic drugs and therapy with other types of medication that are beneficial when appropriately used. In this article, the authors review the mechanism of action of these agents and focus on recent clinical trials, indications and contraindications, and proper administration. They also discuss the place of primary angioplasty as an alternative to thrombolytic therapy.

A comparison of two methods to teach smoking-cessation techniques to medical students.

Purpose: To evaluate two smoking-cessation practice exercises, one using standardized patients (SPs), the other using role playing by medical students.

Method: In the spring of 1994 all 120 first-year University of California, San Francisco, School of Medicine Students were given lectures on the health effects of smoking and how physicians can help patients quit. Afterward some of the students were randomly assigned to two groups in which to practice counseling patients: Group 1 (n = 35) used SPs, Group 2 (n = 37) used role playing.

Configurational analysis for case formulation.

Diagnosis by DSM-IV is seldom sufficient to the task of planning and conducting treatment by psychotherapy. Formulation is vital for the task. I have developed a formulation approach called configurational analysis, and usually employ this tool in my work with individual adult cases.

Three-dimensional structures and contexts associated with recurrent amino acid sequence patterns.

We have used cluster analysis to identify recurring sequence patterns that transcend protein family boundaries. A subset of these patterns occur predominantly in a single type of local structure in proteins. Here we characterize the three-dimensional structures and contexts in which these sequence patterns occur, with particular attention to the interactions responsible for their structural selectivity.

Molecular mechanisms of hepatic fibrosis and principles of therapy.

Tremendous insights into the understanding of hepatic fibrosis have taken place over the past ten years. Foremost among these is the recognition that hepatic stellate cells (formerly known as lipocytes, Ito cells, or fat-storing cells) play a central role based on their ability to undergo activation following liver injury of any cause. Stellate cell activation is a broad phenotypic response, characterized by distinct functional changes in proliferation, contractility, fibrogenesis, cytokine secretion, and matrix degradation.

Mossy fiber reorganization in the epileptic hippocampus.

Reorganization of dentate granule cell axons (mossy fibers) is a prominent aspect of the pathological changes observed in human temporal lobe epilepsy. Although recent work has begun to address the significance of mossy fiber reorganization, the specific and overall functional consequences of these network changes remain poorly understood. New studies are beginning to provide insight into molecular mechanisms underlying this process.

1,2-Benzisothiazolin-3-one (Proxel): irritant or allergen? A clinical study and literature review.

The isothiazolinone, 1,2-benzisothiazolin-3-one (Proxel), is a popular preservative, as well as a skin sensitizer and irritant. Patch test studies have been performed with different concentrations and vehicles. The current suggested patch test concentration is 0.

Purification and characterization of defensins from cystic fibrosis sputum.

Objective And Design: Cystic fibrosis (CF) sputum contains large numbers of neutrophils whose most abundant granule proteins are defensins. Within phagolysosomes, defensins kill microbes; however, extracellular defensins can be toxic to human cells. To begin to explore the possibility that defensins damage CF airways, this study examines the concentration and properties of defensins in CF sputum.

Indirect T-cell allorecognition: perspectives for peptide-based therapy in transplantation.

Indirect allorecognition is an important component of allotransplant rejection. Although the initial indirect alloresponse is limited to a few dominant determinants on donor major histocompatibility complex (MHC) molecules, subsequent spreading to additional determinants on recipient and donor antigens is common. Gilles Benichou and colleagues discuss the mechanisms by which immunodominance is acquired or disrupted in indirect alloresponses, and examine the implications for the design of peptide-based selective immunotherapy in transplantation.

Vagal branches involved in inhibition of bradykinin-induced synovial plasma extravasation by intrathecal nicotine and noxious stimulation in the rat.

1. Stimulation of cutaneous and spinal visceral nociceptive afferents and intrathecal nicotine reduces bradykinin-induced plasma extravasation (BK-induced PE) in the knee joint of the rat. This depression is mediated by the hypothalamo-pituitary-adrenal (HPA) axis and is potentiated by subdiaphragmatic vagotomy.

Regulation of neuronal nitric oxide synthase through alternative transcripts.

Nitric oxide (NO) participates in diverse physiological processes ranging from neurotransmission to muscle relaxation. Neuronal-derived NO can be either beneficial or detrimental depending on the cellular context. Neuronal NO synthase (nNOS) must therefore be tightly regulated.

Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat.

1. In this study, we examined the mechanism(s) by which s.c.

Postextrasystolic U wave augmentation, a new marker of increased arrhythmic risk in patients without the long QT syndrome.

Objectives: We attempted to determine the correlation between the presence of postextrasystolic changes in the STU segment and a history of sustained ventricular arrhythmias.

Background: Postextrasystolic U wave augmentation (a marked increment in U wave amplitude after premature ventricular complexes [PVCs]) is an adverse prognostic sign in the "pause-dependent long QT syndrome." However, the prevalence of postextrasystolic changes in patients without the long QT syndrome is unknown.

Retinal development: on the crest of an exciting wave.

Propagated waves of excitation in developing neural tissues may be a critical feature of maturation. Recent findings shed new light on the mechanisms underlying these waves.

Parkinson's disease. Diagnosis and treatment.

Although Parkinson's disease is primarily a neurologic disorder, primary care physicians should be knowledgeable about the disease and its treatment because most patients will see their primary care physician first for their symptoms. Furthermore, in today's setting of managed care, primary care physicians will likely be called on even more to assume primary responsibility for the treatment of patients afflicted with Parkinson's disease; neurologists will likely play the role of consultants who see a patient only periodically and offer recommendations and advice for the primary care physicians to implement.

Resistant hypertension. Suggestions for dealing with the problem.

With appropriate evaluation of both patient- and physician-related factors, many cases of resistant hypertension can be resolved. Patients often do not understand the implications of their disease and need specific information regarding the importance of compliance with medication schedules and dietary restrictions. Physicians should also consider the possibility of drug resistance or the presence of an identifiable secondary cause, such as renal artery stenosis, chronic renal parenchymal disease, or pheochromocytoma.

Hypertension in women and the elderly. Some puzzling and some expected findings of treatment studies.

Almost 65% of the US population over age 60 has hypertension (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg), which is strongly related to increased rates of coronary artery disease (CAD), stroke, and death. The need for treatment seems obvious. However, in young and middle-aged women, treatment is not straightforward, and trials have not specifically targeted this group.

Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy.

Becker muscular dystrophy is an X-linked disease due to mutations of the dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), an identified enzyme in the dystrophin complex, is uniquely absent from skeletal muscle plasma membrane in many human Becker patients and in mouse models of dystrophinopathy. An NH2-terminal domain of nNOS directly interacts with alpha 1-syntrophin but not with other proteins in the dystrophin complex analyzed.

Chemical chaperones correct the mutant phenotype of the delta F508 cystic fibrosis transmembrane conductance regulator protein.

Mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) often result in a failure of the protein to be properly processed at the level of the endoplasmic reticulum (ER) and subsequently transported to the plasma membrane. The folding defect associated with the most common CFTR mutation (delta F508) has been shown to be temperature sensitive. Incubation of cells expressing delta F508 CFTR at lower growth temperatures results in the proper processing of a portion of the mutant CFTR protein.

Influence of molecular and chemical chaperones on protein folding.

Protein folding inside the cell involves the participation of accessory components known as molecular chaperones. In addition to their active participation in the folding process, molecular chaperones serve as a type of 'quality control system', recognizing, retaining and targeting misfolded proteins for their eventual degradation. It is now known that a number of human diseases arise as a consequence of specific point mutations or deletions within genes encoding essential proteins.

Localization and developmental expression of surfactant proteins D and A in the respiratory tract of the mouse.

Surfactant protein D (SP-D) is synthesized and secreted by pulmonary epithelial cells. Like surfactant protein A (SP-A), SP-D is a collagen-like glycoprotein belonging to the "collectin" class of C-type lectins that may play an important role in pulmonary host defense. To begin studies on SP-D gene regulation and function using the mouse as an animal model, we identified the cellular sites of SP-D gene expression in adult mouse lung and trachea and characterized the developmental expression of SP-D mRNA in murine fetal and newborn lungs.

Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle.

Nitric oxide (NO) functions as a molecular mediator in numerous processes in cellular development and physiology. Differential expression and regulation of a family of three NO synthase (NOS) gene products help achieve this diversity of action. Previous studies identify post-translational modification and interaction of NOS with specific protein targets as tissue-specific modes of regulation.