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Hypertrophic cardiomyopathy: a systematic review.

CONTEXT: Throughout the past 40 years, a vast and sometimes contradictory literature has accumulated regarding hypertrophic cardiomyopathy (HCM), a genetic cardiac disease caused by a variety of mutations in genes encoding sarcomeric proteins and characterized by a broad and expanding clinical spectrum. OBJECTIVES: To clarify and summarize the relevant clinical issues and to profile rapidly evolving concepts regarding HCM. DATA SOURCES: Systematic analysis of the relevant HCM literature, accessed through MEDLINE (1966-2000), bibliographies, and interactions with investigators. STUDY SELECTION AND DATA EXTRACTION: Diverse information was assimilated into a rigorous and objective contemporary description of HCM, affording greatest weight to prospective, controlled, and evidence-based studies. DATA SYNTHESIS: Hypertrophic cardiomyopathy is a relatively common genetic cardiac disease (1:500 in the general population) that is heterogeneous with respect to disease-causing mutations, presentation, prognosis, and treatment strategies. Visibility attached to HCM relates largely to its recognition as the most common cause of sudden death in the young (including competitive athletes). Clinical diagnosis is by 2-dimensional echocardiographic identification of otherwise unexplained left ventricular wall thickening in the presence of a nondilated cavity. Overall, HCM confers an annual mortality rate of about 1% and in most patients is compatible with little or no disability and normal life expectancy. Subsets with higher mortality or morbidity are linked to the complications of sudden death, progressive heart failure, and atrial fibrillation with embolic stroke. Treatment strategies depend on appropriate patient selection, including drug treatment for exertional dyspnea (beta-blockers, verapamil, disopyramide) and the septal myotomy-myectomy operation, which is the standard of care for severe refractory symptoms associated with marked outflow obstruction; alcohol septal ablation and pacing are alternatives to surgery for selected patients. High-risk patients may be treated effectively for sudden death prevention with the implantable cardioverter-defibrillator. CONCLUSIONS: Substantial understanding has evolved regarding the epidemiology and clinical course of HCM, as well as novel treatment strategies that may alter its natural history. An appreciation that HCM, although an important cause of death and disability at all ages, does not invariably convey ominous prognosis and is compatible with normal longevity should dictate a large measure of reassurance for many patients.

Cardiomyopathy, Hypertrophic↗

Interventions for preventing lower limb soft-tissue injuries in runners.

BACKGROUND: Overuse musculoskeletal injuries occur frequently in runners. Suggestions for prevention have focused on stretching exercises, modifying training schedules and the use of protective devices such as braces and insoles. To date, no systematic analysis of the literature on the effectiveness of these strategies in the prevention of overuse injuries has been published. OBJECTIVES: The objective of the review was to evaluate the evidence from randomised controlled trials on the prevention of lower limb soft-tissue running injuries. SEARCH STRATEGY: An electronic database search included The Cochrane Musculoskeletal Injuries Group specialised register (date of last search October 2000), The Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 1999), MEDLINE (from 1966), EMBASE (from 1980), SPORT Discus (1975-2000), HERACLES (1975-2000), ATLANTES (1980-1996), BIOSIS, CINAHL, SCISEARCH, Current Contents, Index To Theses and Dissertation Abstracts. Date of last search for these databses: May 2000. SELECTION CRITERIA: Any randomised or quasi-randomised trials evaluating interventions to prevent lower limb soft-tissue running injuries. DATA COLLECTION AND ANALYSIS: All trials fulfilling the selection criteria were assessed by two reviewers independently. Data were also extracted independently by the two reviewers using a pre-derived data extraction form. Exploratory analyses, including pooling of results from groups of trials of similar designs were undertaken, using a fixed effects model. Results were reported as relative risks (RR) with 95 per cent confidence intervals (95% CI). MAIN RESULTS: Twelve trials with 8,806 participants were included. In one trial, a single control group was matched to three different included intervention groups. The effectiveness of stretching exercises (5 trials, 1944 participants in the intervention groups, 3159 controls), and of insoles and footwear modification (5 trials, 903 participants in the intervention groups, 3006 controls) in the prevention of lower extremity soft tissue injuries associated with running is unknown. Reducing the distance, frequency and duration of running may be effective in the prevention of lower extremity soft tissue injuries associated with running (3 trials, 514 participants in intervention groups, 1663 controls). Wearing a knee brace with a patellar support ring may be effective in the prevention of running-associated anterior knee pain (1 trial, 27 participants in the intervention group, 33 controls). REVIEWER'S CONCLUSIONS: This review provides some evidence for the effectiveness of the modification of training schedules, but there is insufficient evidence to determine the effectiveness of stretching exercises for major lower limb muscle groups in reducing lower limb soft-tissue running injuries. More studies are required to confirm that knee braces may prevent knee pain, to clarify the role of stretching, and to quantify optimal training loads. Generalisability of the results may be limited by the intensive nature of military training (the context for most of the studies) and the inclusion of only small numbers of women.

Cumulative Trauma Disorders↗

Traditional chinese medicine for the treatment of chronic prostatitis in China: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the effectiveness of Chinese herbal medicine for treating chronic prostatitis (CPT) in China. DESIGN: Electronic medical database from China National Knowledge Infrastructure (CNKI) was searched, language is Chinese; date is from January 1, 1994 to December 31, 2003. A total of 108 trials were found, and all studies with words like "randomization" or "quasi-randomization" in their abstracts were included, whether they used blinding or not. Nineteen theses that met the entry criteria were downloaded and fully printed. Four groups were divided: Chinese herbs orally treated group (based on syndrome differentiation), Chinese herbs externally treated group, Chinese herbs orally and externally treated group, and integrated Western with Chinese herbs treated group. RESULTS: All 19 articles that met the entry criteria were clinical trial studies with low quality (Jadad Score <3). The results showed that Traditional Chinese Medicine (TCM) may benefit the patients who had CPT. However, from the results of the funnel plots analysis of all four groups of clinical trials that met the inclusion criteria in this systematic review are distant asymmetrical and irregular plots, which indicate that a positive publication bias may exist. There was no obvious evidence indicating that the efficacy of the therapy in the treated groups using TCM was superior to that of the control group (Western medicine treatment group). CONCLUSIONS: All of the four groups in the clinical trials have not provided evidence of evidence-based medicine (EBM) A class (including 1a, 1b, 1c level), failed to prove that the TCM may have beneficial effects for patients with CPT, because of low quality in all the trials and a positive publication bias. Therefore, in light of some positive outcomes, a good design of multicentered, randomized, parallel-controlled and blinding trials is needed in order to make further studies, and deserve further examination for the treatment of CPT with TCM.

China↗

Traditional Chinese medicine for the treatment of dermatologic disorders.

Traditional Chinese medicine (TCM) is an alternative method of therapy that can be administered in oral, topical, or injectable forms. It emphasizes the importance of using many herbs that are combined in different formulations for each individual patient. Among some segments of the patient population, it has become increasingly popular as a mode for treating dermatologic diseases. As a result, it is now worthwhile for dermatologists throughout the West to gain some familiarity with this method. Yet, dermatologists are largely unfamiliar with TCM and may possess some misconceptions. We attempt to give a general overview of TCM through the discussion of different clinical studies involving various TCMs. Some proposed mechanisms of action of TCM are also presented. A discussion of adverse effects, including hepatotoxic effects and the need for close monitoring is discussed. A warning regarding the possible contamination of TCMs is also included. Since it is not possible to discuss the application of TCM for every skin disorder, psoriasis and atopic dermatitis are used as the prototype in illustrating the use of TCM. In the future, perhaps a better understanding of TCM will be gained through more systematic analysis and controlled studies with a placebo arm. It is our hope that this article will provide an overview of the efficacy, mechanism of action, as well as adverse effects of TCM.

Drugs, Chinese Herbal↗

Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis.

OBJECTIVE: To appraise the data on systemic adverse effects of inhaled corticosteroids. METHODS: A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies. RESULTS: Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression. CONCLUSIONS: All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.

Administration, Inhalation↗

Efficacy and safety of opioid agonists in the treatment of neuropathic pain of nonmalignant origin: systematic review and meta-analysis of randomized controlled trials.

CONTEXT: In the United States, an estimated 2 million persons have neuropathic pain that is often resistant to therapy. The use of opioids for neuropathic pain remains controversial, in part because studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment. OBJECTIVE: To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain based on published randomized controlled trials (RCTs). DATA SOURCES: We searched MEDLINE (1966 to December 2004) and the Cochrane Central Register of Controlled Trials (fourth quarter, 2004) for articles in any language, along with reference lists of reviews and retrieved articles, using a combination of 9 search terms for RCTs with 32 terms for opioids and 15 terms for neuropathic pain. STUDY SELECTION: Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded. DATA EXTRACTION: Data were extracted by 2 independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects. DATA SYNTHESIS: Twenty-two articles met inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = 8-56 days; n = 8) trials. The short-term trials had contradictory results. In contrast, all 8 intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. A fixed-effects model meta-analysis of 6 intermediate-term studies showed mean posttreatment visual analog scale scores of pain intensity after opioids to be 14 units lower on a scale from 0 to 100 than after placebo (95% confidence interval [CI], -18 to -10; P<.001). According to number needed to harm (NNH), the most common adverse event was nausea (NNH, 3.6; 95% CI, 2.9-4.8), followed by constipation (NNH, 4.6; 95% CI, 3.4-7.1), drowsiness (NNH, 5.3; 95% CI, 3.7-8.3), vomiting (NNH, 6.2; 95% CI, 4.6-11.1), and dizziness (NNH, 6.7; 95% CI, 4.8-10.0). CONCLUSIONS: Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain. Intermediate-term studies demonstrate significant efficacy of opioids over placebo for neuropathic pain, which is likely to be clinically important. Reported adverse events of opioids are common but not life-threatening. Further RCTs are needed to establish their long-term efficacy, safety (including addiction potential), and effects on quality of life.

Analgesics, Opioid↗

Mental health problems, use of mental health services, and attrition from military service after returning from deployment to Iraq or Afghanistan.

CONTEXT: The US military has conducted population-level screening for mental health problems among all service members returning from deployment to Afghanistan, Iraq, and other locations. To date, no systematic analysis of this program has been conducted, and studies have not assessed the impact of these deployments on mental health care utilization after deployment. OBJECTIVES: To determine the relationship between combat deployment and mental health care use during the first year after return and to assess the lessons learned from the postdeployment mental health screening effort, particularly the correlation between the screening results, actual use of mental health services, and attrition from military service. DESIGN, SETTING, AND PARTICIPANTS: Population-based descriptive study of all Army soldiers and Marines who completed the routine postdeployment health assessment between May 1, 2003, and April 30, 2004, on return from deployment to Operation Enduring Freedom in Afghanistan (n = 16,318), Operation Iraqi Freedom (n = 222,620), and other locations (n = 64,967). Health care utilization and occupational outcomes were measured for 1 year after deployment or until leaving the service if this occurred sooner. MAIN OUTCOME MEASURES: Screening positive for posttraumatic stress disorder, major depression, or other mental health problems; referral for a mental health reason; use of mental health care services after returning from deployment; and attrition from military service. RESULTS: The prevalence of reporting a mental health problem was 19.1% among service members returning from Iraq compared with 11.3% after returning from Afghanistan and 8.5% after returning from other locations (P<.001). Mental health problems reported on the postdeployment assessment were significantly associated with combat experiences, mental health care referral and utilization, and attrition from military service. Thirty-five percent of Iraq war veterans accessed mental health services in the year after returning home; 12% per year were diagnosed with a mental health problem. More than 50% of those referred for a mental health reason were documented to receive follow-up care although less than 10% of all service members who received mental health treatment were referred through the screening program. CONCLUSIONS: Combat duty in Iraq was associated with high utilization of mental health services and attrition from military service after deployment. The deployment mental health screening program provided another indicator of the mental health impact of deployment on a population level but had limited utility in predicting the level of mental health services that were needed after deployment. The high rate of using mental health services among Operation Iraqi Freedom veterans after deployment highlights challenges in ensuring that there are adequate resources to meet the mental health needs of returning veterans.

Adult↗

Slight instability of a FMR-1 allele over three generations in a family from the general population.

We report on a family segregating a FMR-1 allele within the "grey zone" of triplet repeat length (n = 51). The allele showed a 1-unit increment when transmitted through a female meiosis and a 1-unit increment when transmitted through a male of the next generation. At the following generation, a pregnant woman had amniocentesis performed. The latter showed she transmitted the allele unchanged (n = 53) to her male fetus. This family was not ascertained through an affected subject, and there was no family history of mental retardation. Thus our observation reflects the natural history of an unstable allele in the general population. Systematic analysis of such alleles may help refine our understanding of the grey zone of triplet repeat length.

Alleles↗

Prostate cancer and smoking: a review of case-control and cohort studies.

BACKGROUND: The purpose of this study was to undertake a systematic analysis of the relation between smoking and prostate cancer. METHODS: All published case-control and cohort studies including relevant data on this topic were collected. The magnitude of potential sources of divergent results among case-control studies was estimated comparing current, former, and ever to never smokers, stratified by type of controls (hospital vs. population) and by race. Cohort studies were discussed individually. RESULTS: Neither a clinically nor a statistically significant association between smoking and prostate cancer seems likely, but it cannot be ruled out entirely. The association between other purported risk factors and prostate cancer is not likely to be confounded by the incomplete measurement and control for smoking habits because smoking and prostate cancer are not related. CONCLUSIONS: For a valid assessment of other risk factors in prostate cancer patients the collection of complete smoking information is therefore less critical than in patients with other diseases. For a definitive assessment of the effect of smoking on prostate cancer incidence and mortality however, future studies need to focus on the collection of information on lifetime smoking habits, including tar exposure.

Case-Control Studies↗

Developmental expression of perlecan during murine embryogenesis.

Perlecan is a modular heparan sulfate proteoglycan that is an intrinsic constituent of all basement membranes and extracellular matrices. Because of its strategic position and unique structure, perlecan has been implicated in modulating the activity of various growth factors required for normal development and tissue homeostasis. To gain insights into the potential function of perlecan in vivo, we examined the spatiotemporal distribution of its mRNA and protein core during murine embryogenesis. We utilized a new affinity-purified antibody that recognizes specifically the protein core of perlecan together with an in situ RT-PCR approach to perform a systematic analysis of perlecan expression and deposition during murine ontogeny. Perlecan appeared early (E10.5) in tissues of vasculogenesis including heart, pericardium, and major blood vessels. Its early expression coincided with the development of the cardiovascular system. Subsequently (E11-13), the greatest deposition of perlecan occurred within the developing cartilage, especially the cartilage undergoing endochondral ossification, where it remained elevated throughout all the developmental stages, and up to adulthood. Interestingly, the mRNA levels of perlecan were always higher in all the vascularized tissues, principally within endothelial cells, while chondrocytes displayed relatively low mRNA levels. This suggests a higher biosynthesis and turnover rates in the blood vessels vis-à-vis those of cartilaginous and other mesenchymal tissues. During later stages of development (E13-17.5) perlecan mRNA levels progressively increased and its expression correlated with the onset of tissue differentiation of various parenchymal organs including the developing kidneys, lungs, liver, spleen, and gastrointestinal tract. The central nervous system showed no perlecan expression with the exception of the calvaria and choroid plexus. Collectively, the results indicate that perlecan may play crucial roles not only in vasculogenesis but also in the maturation and maintenance of differentiated tissues, including cartilage.

Animals↗

Prenatal development of cranial base in normal Korean fetuses.

BACKGROUND: The cranial base is not only an end result of complex segmental growth of rostral end of axial skeleton but also has a tremendous impact on the development of the brain and facial structure. However, little is known about the method for the systematic analysis of the shape of the cranial base in the developing human fetus. We used roentgenograms of the cranial base and eviscerated bones for the assessment of the development of the cranial bony complex. METHODS: The cranial base was removed from 64 normal human fetuses after 18-40 weeks of gestation. Roentgenograms were taken perpendicular to the cranial base. Major anatomical landmarks are defined as follows: the center of pituitary fossa of sphenoid bone (point S), the growth center of zygomatic bone, the anterior point of nasal septum, otic cartilage, and anterior and posterior growth centers of maxilla. The anterior cranial base angle, the middle cranial base angle, the posterior cranial base angle, the maxillary trapezoid area, the horizontal middle face area, and the occipital cranial base triangle area are defined from the landmarks, and the growth of each parameter was analyzed by gestational age. RESULTS: The proportional growth of the anterior, middle, and posterior cranial fossae could be assessed by the angles around the center of the pituitary fossa (point S) and by the anterior, middle, and posterior cranial base angles. The anterior cranial base angle was relatively constant during the fetal period at 107.4-112.5 degrees, whereas the middle cranial base angle gradually increased, and the posterior cranial base angle decreased. With increasing gestational age, the horizontal middle face area increased rapidly, in contrast to those of the maxillary trapezoid area, occipital cranial base triangle area, or foramen magnum area. CONCLUSIONS: The important keys in the structural development of the normal human cranial base are anterior, middle, and posterior cranial base angles. We could define the developmental pattern of human cranial base, which in turn provides a model of a standard growth pattern applicable to the study of the different malformations in the craniofacial structure.

Cephalometry↗

Cancer spread in the larynx: a pathologic basis for conservation surgery.

BACKGROUND: Previous pathologic studies of the spread of laryngeal carcinoma have drawn inferences about the site of origin of tumors, their mechanisms of growth, or the role of structures as potential barriers to tumor spread. Most of the information is based on the study of advanced or recurrent tumors and is difficult to apply to conservation surgical technique. We carried out a systematic analysis of a wide range of laryngeal tumors with the aim of providing a basis for conservation surgery. METHODS: We analyzed tumor invasion of the laryngeal spaces and the laryngeal framework in relation to the mucosal tumor extent by axial sectioning of 80 sequential partial and total laryngectomy specimens. RESULTS: Invasion of a particular laryngeal space could be accurately predicted by mucosal tumor extent and vocal cord mobility. Invasion of the laryngeal framework was associated with tumor extension to the ventricle, subglottis, or pyriform fossa. The thyroid cartilage and the cricothyroid space and ligament were the most frequent sites of invasion. CONCLUSIONS: The mucosal distribution of a tumor and observation of vocal cord mobility can be used to determine accurately the extent of tumor invasion of the laryngeal spaces and framework and therefore the extent of resection necessary.

Biopsy, Needle↗

Value of sphincter electromyography in the diagnosis of multiple system atrophy.

It is clinically important, to distinguish between idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA) not only because of the implications for prognosis but also because urinary incontinence is often an early troublesome feature of MSA and by making the correct neurological diagnosis inappropriate urological surgery may be avoided. Onuf's nucleus in the sacral cord is the location of the anterior horn cells innervating the sphincters, and it is among central nervous system sites affected by neuronal cell loss in MSA but not in IPD. A systematic analysis of motor units recorded from the sphincter looking for changes of chronic reinnervation has therefore been used to distinguish between these conditions. Sphincter electromyography (EMG) was carried out in 126 patients with suspected MSA with review of their case notes up to 2 years later. Of those in whom a diagnosis of MSA was made, 82% had had an abnormal sphincter EMG.

Adult↗

Mutation characterization of CFTR gene in 206 Northern Irish CF families: thirty mutations, including two novel, account for approximately 94% of CF chromosomes.

A variety of mutation detection techniques, including restriction endonuclease digestion, allele specific oligonucleotides, and automated fluorescent sequencing, were used in the identification of 15 CFTR mutations representing 86.7% of CF chromosomes in 206 Northern Irish cystic fibrosis (CF) families. A systematic analysis of the 27 exons and intron/exon boundaries of the CFTR gene was performed using denaturing gradient gel electrophoresis (DGGE) in an attempt to characterise the 55 unknown CF mutations in 51 patients. Twenty different mutations were detected by DGGE on 30 chromosomes accounting for a further 7.3% of CF alleles. Fifteen of these mutations had not previously been found in Northern Ireland, and two are novel, M1I(G > T) and V562L. In total, 30 CFTR mutations account for 93.9% of the 412 Northern Irish CF chromosomes tested. The three major CF mutations in Northern Ireland are delta F508, G551D, and R117H with respective frequencies of 68.0%, 5.1%, and 4.1%. The efficacy of the DGGE technique was proven by the detection of 77 out of 77 control variants from all the CFTR exons. DGGE is a highly efficient and sensitive method for mutation screening especially in large genes where the mutation spectrum is known to be heterogeneous.

Alleles↗

Pediatric large volume peripheral blood progenitor cell collections from patients under 25 kg: a primer.

Collection of peripheral blood progenitor cells from small pediatric patients provides many social and technical challenges not faced when collecting from adult patients. This paper provides a single institutions experience with 85 collections from 14 patients less than 25 kg of weight over a 2 year period. Specific challenges include obtaining venous access, anticoagulation, volume shifts, and obtaining patient cooperation. A systematic analysis of options for access, alternative modes of anticoagulation, and the effect of large ratios of extra-corporeal volume to patient's blood volume are discussed. Access uniformly required central venous catheters (CVC) ranging from 7-10 Fr. Anticoagulation included systemic heparinization titrating dose by activated clotting time in all cases and combined with citrate at a ratio of 1:25-1:30 in most cases. Collections were performed on a COBE Spectra, after priming with leukoreduced irradiated red cells and omitting both the initial 120cc diversion and rinse back of red cells at the end. Social challenges include issues of assent and ability to distract patients for the duration of a prolonged collection. Progenitor yields from collections from 14 patients were quantitated by CD34+ assay in all cases and CFU-GM in ten of 14 patients. A median of 4.5 x 10(6)/kg CD34+ cells were obtained for each collection. Complications, including those related to catheter access, are enumerated. In summary, large volume peripheral blood progenitor collection can be safely and efficaciously performed in small pediatric patients.

Body Weight↗

Two-hybrid systematic screening of the yeast proteome.

The yeast two-hybrid system is a genetic method that detects protein-protein interactions. One application is the detection by library screening of new interactors of a protein of known function. In the August issue of Nature Genetics, Fromont-Racine et al. showed for the first time that the construction of the protein interaction map of a complex pathway, such as that of the mRNA splicing machinery, is now possible, because of the combination of recent technical improvements elaborated in several laboratories. With a yeast cell mating procedure that increases screen efficiency, they used their complex yeast genomic library of 5 x 10(6) clones to test 700 x 10(6) interactions against 15 proteins. They identified and classified 170 potential interactors, including approximately 70 proteins of previously unknown function. More than 25% of the interactors are probably biologically relevant. The achievements of Fromont-Racine et al. have opened the way to the systematic analysis of the protein interaction networks of the 6,000 open reading frames-yeast proteome. This task requires, however, automation of the library screens and creation of a two-hybrid library database.

Fungal Proteins↗

Mining protein data from two-dimensional gels: tools for systematic post-planned analyses.

There is a considerable need to develop comprehensive, systematic mechanisms to analyze the vast number of proteins that orchestrate various cellular functions and to identify proteins associated with disease or that are affected by pharmacological agents. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) continues to be relied upon to analyze protein constituents of cells and tissues. We have developed a Laboratory Information Processing System (LIPS) as a computer-based tool for capturing quantitative and qualitative changes in thousands of proteins detected in 2-D gels of various types. Protein databases have been developed to serve as a repository for data processing of the basic and derived data and of findings derived from different studies. There have been remarkable advances both in database technology as well as in the computer hardware that have benefited our effort at mining protein data from 2-D gels. We here review our current efforts aimed at improving the performance and features of our 2-D related protein databases, with particular emphasis on the tools we utilize for database mining via a systematic analysis of information known as post-planned analysis.

Acrylic Resins↗

Two-dimensional polyacrylamide gel electrophoresis map of bovine ovarian fluid proteins.

Molecular mechanisms underlying the cystic degeneration of ovarian follicles in the dairy cow have not been clarified yet. A useful approach for complementing endocrinological and clinical studies could be represented by the systematic analysis of the protein patterns in follicular and cystic fluid. With this aim, a two-dimensional polyacrylamide gel electrophoresis map of proteins contained in fluid from bovine ovarian follicles at different stages of development and from bovine ovarian cyst has been obtained. About 200 spots were detected after silver staining. Polypeptides from nine spots or series of spots have been identified by N-terminal sequencing, and further analysis of the map has been performed by gel comparison. Alpha-1-antitrypsin, albumin, serotransferrin and apolipoprotein A-I and A-IV were located on the map. Comparison between protein patterns revealed the differential expression of some spots among follicles of smaller diameter, follicles of larger diameter, and cysts. This could represent the first step toward the identification of proteins differentially expressed and associated with ovarian cyst development.

Amino Acid Sequence↗