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PubMed1987

Interdisciplinary andrology. STDs. AIDS research.

Multidisciplinary andrology deals with clinical application and modern technology for the evaluation and differential diagnosis of male infertility with emphasis on morphological, anatomical, biochemical, immunological, hereditary, and microbiological parameters. Little is known about the effects of diet, disease, stress, environmental, and drugs on male-related unexplained infertility of couples. Regional, national, and international centers of multidisciplinary andrology should provide (1) extensive and unique clinical services; (2) a computerized "patient referral center," (3) self-learning packages (slides/tape programs) for patients; and (4) a computer link to the National Library of Medicine and the Drug Information Center. Specialized laboratories and clinics can be served by expert consultants, visiting professors, bilingual and well-trained clinicians, nurses, laboratory technologists, computer operators, and related allied health personnel. Patient education pamphlets, updated every few years, can be distributed during training workshops when an extensive network of remote teleprinters can be utilized. Qualified client location may install a printer to allow on-site printing of reports in the shortest possible time. Special mailing containers are provided to clients who wish to mail their laboratory specimens. Other clinical services may include the following: 1. Central source of communication and information in andrology; 2. International roster of multidisciplinary andrology centers; 3. Patient referral to centers and consultations for developing countries; 4. Screening of husbands and wives for in vitro fertilization/embryo transfer (IVF/ET); 5. Screening of couples with unexplained infertility for sexually transmitted diseases (STDs) including AIDS; 6. Exchange of research material and methodology; 7. Coordination of multicenter research; 8. Organizing training workshops for clinicians, nurses, and laboratory technicians; 9. Establishing a repository of films, video tapes, slides, catalogs, instrumentation, books, SEM photos, and atlases; 10. Publication and editorial assistance; 11. Consultation for the appropriate selection, purchase, and quality control of instrumentation (all on one computer system); 12. Evaluation of new diagnostic tools for idiopathic infertility and fertility regulation; 13.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1982

Taxonomic relations between archaebacteria including 6 novel genera examined by cross hybridization of DNAs and 16S rRNAs.

DNAs from 16 species of archaebacteria including 6 novel isolates were hybridized with 16S rRNAs from 7 species representing different orders or groups of the urkingdom of archaebacteria. The yields, normalized for the number of genes per microgram of DNA, and the temperature stabilities of all hybrids were determined and related to each other. A taxonomic tree constructed from such fractional stability data reveals the same major divisions as that derived from comparative cataloging of 16S rRNA sequences. The extreme halophiles appear however as a distinct order besides the three known divisions of methanogens. The methanogens, the halophiles and Thermoplasma form one of two clearly recognizable branches of the archaebacterial urkingdom. The order represented by Sulfolobus and the related novel order Thermoproteales form the other branch. Three novel genera, Thermoproteus, Desulfurococcus and the "stiff filaments" represent three families of this order. The extremely thermophilic methanogen Methanothermus fervidus belongs to the Methanobacteriales. SN1, a methanogen from Italy, appears as another species of the genus Methanococcus. Another novel methanogen, M3, represents a genus or family of the order Methanomicrobiales.

Archaea↗
PubMed2001

High-density single-nucleotide polymorphism (SNP) map of the 150-kb region corresponding to the human ATP-binding cassette transporter A1 (ABCA1) gene.

Highly dense catalogs of human genetic variations, in combination with high-throughput genotyping technologies, are expected to clarify individual genetic differences in pharmacological responsiveness and predispositions to common diseases. Here we report single-nucleotide polymorphisms (SNPs) present among 48 Japanese individuals at the locus for the human ATP-binding cassette transporter A1 (ABCA1) gene. ABCA1 plays a key role in apolipoprotein-mediated cholesterol transport, and mutations in this gene are responsible for Tangier disease and familial high-density lipoprotein deficiency associated with reduced cholesterol efflux. We identified a total of 162 SNPs, 149 of which were novel, within the 150-kb region encompassing the entire ABCA1 gene. Eight of the SNPs lie within coding elements, two in 5' flanking regions, 147 in introns, and five in 3' untranslated regions, but none were found in 5' untranslated or 3' flanking regions. The ratio of transitions to transversions was approximately 2.37 to 1. Our dense SNP map of this region could serve as a powerful resource for studies of complex genetic diseases that may be associated with ABCA1 and of individual responses to drug therapy.

ATP Binding Cassette Transporter 1↗
PubMed2004

IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells.

Recognition of microbial products through TLRs triggers the expression of several cytokines that regulate innate and adaptive immunity. Signaling by various TLRs is not equivalent and leads to differential gene induction. This study analyzed the responses of human dendritic cells (DCs) and PBMCs stimulated with agonists of TLR2, TLR3, TLR4, TLR5, and TLR7, first individually and then in combination. Several cytokines were equally induced by all TLR agonists, but four genes, IFN-beta, IFN-gamma-inducible protein 10 (IP-10), IL-12p35, and IL-15, showed a very restricted pattern of induction. Thus, each TLR appears to possess a distinctive ability to activate DCs or PBMCs, suggesting that TLR-mediated responses cannot be simply cataloged as resembling either TLR2 (MyD88 dependent) or TLR4 (MyD88 independent) and that other signaling modalities may exist. The analysis of DC and PBMC activation by combinations of TLR agonists revealed that TLR2 agonists are able to block the induction of IP-10, IL-12p35, and IFN-gamma, but not IL-15 and IFN-beta, by TLR3 and TLR4. TLR2 stimulation led to rapid release of IL-10 that is responsible for inhibition of IP-10 and IL-12p35 induction. Cross-talk between different TLRs may modify the primary responses of TLR to their agonist, adding a further level of complexity to the regulation of innate immunity.

Autocrine Communication↗
PubMed2004

Collaborative study for establishment of a global standard for the potency assay of human anti-D immunoglobulin.

An international collaborative study aimed at establishing a global standard for the potency assay of anti-D immunoglobulin was started in 2002. 25 laboratories participated in this study run under the common aegis of the World Health Organization, the United States Food and Drug Administration (US-FDA) and the European Directorate for the Quality of Medicines (EDQM). The potencies of three candidate materials and the US-FDA standard (lot 3) included for comparison were evaluated using AutoAnalyzer, competitive enzyme-linked immunoassay (competitive EIA), flow cytometric methods or own "in-house" methods. Critical reagent, standardised procedures and standardised assay design were provided for either method, where appropriate. Central statistical evaluation of the potency data submitted by the participants was performed using a parallel line model. Agreement between laboratories and assay methods for all samples was observed. Intra-laboratory variability was lowest for laboratories performing flow cytometry and highest for laboratories that performed their in-house methods. Inter-laboratory variability was acceptable for all samples when assayed by AutoAnalyzer, competitive (EIA) and flow cytometric methods. It was concluded that sample A is most suitable to serve as a global standard and that sample C could serve as a reserve European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) batch provided that suitable stability is demonstrated. Sample A was adopted by the Ph. Eur. Commission at its 115th session (March 2003) as the first Ph. Eur. BRP (available from the EDQM: catalog number Y0000219) with the assigned potency of 285 IU/ampoule.

Chromatography, High Pressure Liquid↗
PubMed1997

Cigarette promotional items in public schools.

OBJECTIVES: To assess the prevalence of ownership of cigarette promotional items (CPIs) by rural northern New England students and to examine the association between CPI ownership and smoking behavior. DESIGN AND SETTING: Voluntary, self-administered survey of 1265 sixth- through 12th-grade students representing 79% to 95% of all students attending 5 rural New Hampshire and Vermont public schools in October 1996. We examined the association between ownership of a CPI and smoking behavior through regression models and conducted a sensitivity analysis on the findings. MAIN OUTCOME MEASURES: Adjusted odds of being a smoker (lifetime use of > or = 100 cigarettes) and, among never smokers and experimental smokers, adjusted cumulative odds of having higher levels of smoking uptake given CPI ownership. RESULTS: One third of students owned a CPI. Prevalence of ownership did not vary by grade or sex, but was higher among poor-to-average school performers (45.0% vs 21.0% for excellent school performers, P < .001) and children whose friends and family members smoked (43.4% vs 13.8% for students with no family members or friends smoking, P < .001). Cigarette promotional items included articles of clothing (T-shirts, hats, backpacks, and jackets), smoking paraphernalia (lighters and ashtrays), camping gear, and electronics. More than half of CPIs (58.2%) bore the Marlboro logo, and almost one third (31.7%) bore the Camel logo. These items were obtained directly from catalogs or vendors 22.4% of the time. Whereas only 4.5% of students reported bringing a CPI to school with them the day of the survey, 44.5% reported seeing such an item at school the day of the survey. After controlling for confounding factors, such as having friends who smoke, students who owned CPIs were 4.1 times more likely to be smokers than those who did not own CPIs (95% confidence interval [CI], 3.1-5.5). Never and experimental smokers (n = 1008) who owned CPIs were more likely to be in a higher category on the smoking uptake index in grades 6 (cumulative odds ratio [OR = 5.7, 95% CI, 1.9-16.8), 7 (OR = 1.8, 95% CI, 0.9-3.7), 8 (OR = 2.3, 95% CI, 1.1-4.8), and 9 (OR = 2.1, 95% CI, 1.1-3.9), periods when children are most vulnerable to initiating cigarette use. A sensitivity analysis indicated that an unmeasured confounder of CPI ownership and smoking was unlikely to alter our conclusions. CONCLUSIONS: Cigarette promotional items are owned by one third of students in these rural northern New England schools. These items are highly visible in the public school setting, and their ownership is strongly associated with initiation and maintenance of smoking behavior. These data lend support to a ban on CPIs to be included in US Food and Drug Administration regulations to prevent tobacco use among US youth.

Adolescent↗
PubMed1994

Recursive deconvolution of combinatorial chemical libraries.

A recursive strategy that solves for the active members of a chemical library is presented. A pentapeptide library with an alphabet of Gly, Leu, Phe, and Tyr (1024 members) was constructed on a solid support by the method of split synthesis. One member of this library (NH2-Tyr-Gly-Gly-Phe-Leu) is a native binder to a beta-endorphin antibody. A variation of the split synthesis approach is used to build the combinatorial library. In four vials, a member of the library's alphabet is coupled to a solid support. After each coupling, a portion of the resin from each of the four reaction vials was set aside and catalogued. The solid support from each vial is then combined, mixed, and redivided. The steps of (i) coupling, (ii) saving and cataloging, and (iii) randomizing were repeated until a pentapeptide library was obtained. The four pentapeptide libraries where the N-terminal amino acid is defined were screened against the beta-endorphin antibody and quantitated via an ELISA. The amino acid of the four pools that demonstrated the most binding was then coupled to the four tetrapeptide partial libraries that had been set aside and catalogued during the split synthesis. This recursive deconvolution was repeated until the best binders were deduced. Besides the anticipated native binder, two other members of the library displayed significant binding. This recursive method of deconvolution does not use a molecular tag, requires only one split synthesis, and can be applied to the deconvolution of nonlinear small-molecule combinatorial libraries and linear oligomeric combinatorial libraries, since it is based only on the procedure of the synthesis.

Amino Acid Sequence↗
PubMed2007

Reporting adverse events in randomized controlled trials.

PURPOSE: How randomized controlled trial results are reported may minimize concerns and detection of adverse side effects. We aimed to describe the methods of reporting adverse events in these published trials. METHODS: Five frequently cited journals were investigated: Annals of Internal Medicine, British Medical Journal, JAMA, The Lancet, and the New England Journal of Medicine. For each journal, all randomized controlled trials conducted on the use of a medication were selected from January 2000 through June 2003. All issues of each journal were reviewed manually. Information retrieved included any mention of adverse events in the abstract, methods, results, or discussion section of the article; or inclusion of adverse events data in tables or figures. We also cataloged whether there was a separate subheading in the results section for reporting adverse events. Reports of trials that referred to methods described in a previous report were excluded. RESULTS: There were 521 eligible articles. Explicit mention of adverse events was in 328 (63%) of abstracts (range 47-66%), 380 (73%) of methods (range 51-81%), 464 (89%) of results (range 80-95%), and 250 (48%) of tables (range 31-49%). There was a separate subheading for adverse events in 240 (46%) (range 22-64%) of the eligible articles. CONCLUSION: There is variation among authors and journals as to the location of reporting adverse events and the means by which it is done. Authors and editors should include specific information on adverse events when reporting the results of randomized controlled trials. It would be ideal if there was more consistency among authors and journals as to how these adverse events are described.

Adverse Drug Reaction Reporting Systems↗
PubMed1998

Chronic fatigue syndrome and seasonal affective disorder: comorbidity, diagnostic overlap, and implications for treatment.

This study aimed to determine symptom patterns in patients with chronic fatigue syndrome (CFS), in summer and winter. Comparison data for patients with seasonal affective disorder (SAD) were used to evaluate seasonal variation in mood and behavior, atypical neurovegetative symptoms characteristic of SAD, and somatic symptoms characteristic of CFS. Rating scale questionnaires were mailed to patients previously diagnosed with CFS. Instruments included the Personal Inventory for Depression and SAD (PIDS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE), which catalogs the current severity of a wide range of somatic, behavioral, and affective symptoms. Data sets from 110 CFS patients matched across seasons were entered into the analysis. Symptoms that conform with the Centers for Disease Control and Prevention (CDC) case definition of CFS were rated as moderate to very severe during the winter months by varying proportions of patients (from 43% for lymph node pain or enlargement, to 79% for muscle, joint, or bone pain). Fatigue was reported by 92%. Prominent affective symptoms included irritability (55%), depressed mood (52%), and anxiety (51%). Retrospective monthly ratings of mood, social activity, energy, sleep duration, amount eaten, and weight change showed a coherent pattern of winter worsening. Of patients with consistent summer and winter ratings (n = 73), 37% showed high global seasonality scores (GSS) > or = 10. About half this group reported symptoms indicative of major depressive disorder, which was strongly associated with high seasonality. Hierarchical cluster analysis of wintertime symptoms revealed 2 distinct clinical profiles among CFS patients: (a) those with high seasonality, for whom depressed mood clustered with atypical neurovegetative symptoms of hypersomnia and hyperphagia, as is seen in SAD; and (b) those with low seasonality, who showed a primary clustering of classic CFS symptoms (fatigue, aches, cognitive disturbance), with depressed mood most closely associated with irritability, insomnia, and anxiety. It appears that a subgroup of patients with CFS shows seasonal variation in symptoms resembling those of SAD, with winter exacerbation. Light therapy may provide patients with CFS an effective treatment alternative or adjunct to antidepressant drugs.

Adult↗
PubMedDate not supplied

ZINC--a free database of commercially available compounds for virtual screening.

A critical barrier to entry into structure-based virtual screening is the lack of a suitable, easy to access database of purchasable compounds. We have therefore prepared a library of 727,842 molecules, each with 3D structure, using catalogs of compounds from vendors (the size of this library continues to grow). The molecules have been assigned biologically relevant protonation states and are annotated with properties such as molecular weight, calculated LogP, and number of rotatable bonds. Each molecule in the library contains vendor and purchasing information and is ready for docking using a number of popular docking programs. Within certain limits, the molecules are prepared in multiple protonation states and multiple tautomeric forms. In one format, multiple conformations are available for the molecules. This database is available for free download (http://zinc.docking.org) in several common file formats including SMILES, mol2, 3D SDF, and DOCK flexibase format. A Web-based query tool incorporating a molecular drawing interface enables the database to be searched and browsed and subsets to be created. Users can process their own molecules by uploading them to a server. Our hope is that this database will bring virtual screening libraries to a wide community of structural biologists and medicinal chemists.

Databases, Factual↗
PubMed2004

Assessing internal tobacco industry knowledge of the neurobiology of tobacco dependence.

The recent availability of internal tobacco industry documents provides a significant resource for evaluating industry understanding of the pharmacological, psychosocial, and behavioral mechanisms underlying tobacco dependence. In this study, we catalog the range of efforts undertaken by tobacco manufacturers seeking knowledge of these mechanisms. Some areas of industry research, such as cellular and molecular studies of nicotine and its effects, are widely available in the open literature. Of greater interest are internal research projects that have demonstrated direct influence on product development. These include studies of smoker psychology and behavior, evoked-response studies of tobacco-delivered nicotine, the effects of sensory perception, dose-related effects, and the development of nicotine analogs and synergists. Our findings suggest extensive industry knowledge of mechanisms that determine smoker perception and behavior, and application of this knowledge in product development, including control of sensory response, uptake of nicotine, and product effects. Independent research recently has begun to consider the contributions of tobacco product ingredients and design factors to the determination of risk, severity, and prevalence of addiction. However, the application of these findings to cessation and treatment efforts is still quite limited. We conclude that clinical research would greatly benefit from further examination of the decades of knowledge accumulated by tobacco manufacturers.

Brain↗
PubMed2006

A guest molecule-host cavity fitting algorithm to mine PDB for small molecule targets.

Inhaled anesthetic molecule occupancy of a protein internal cavity depends in part on the volumes of the guest molecule and the host site. Current algorithms to determine volume and surface area of cavities in proteins whose structures have been determined and cataloged make no allowance for shape or small degrees of shape adjustment to accommodate a guest. We developed an algorithm to determine spheroid dimensions matching cavity volume and surface area and applied it to screen the cavities of 6,658 nonredundant structures stored in the Protein Data Bank (PDB) for potential targets of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane). Our algorithm determined sizes of prolate and oblate spheroids matching dimensions of each cavity found. If those spheroids could accommodate halothane (radius 2.91 A) as a guest, we determined the packing coefficient. 394,766 total cavities were identified. Of 58,681 cavities satisfying the fit criteria for halothane, 11,902 cavities had packing coefficients in the range of 0.46-0.64. This represents 20.3% of cavities large enough to hold halothane, 3.0% of all cavities processed, and found in 2,432 protein structures. Our algorithm incorporates shape dependence to screen guest-host relationships for potential small molecule occupancy of protein cavities. Proteins with large numbers of such cavities are more likely to be functionally altered by halothane.

Algorithms↗
PubMedDate not supplied

Defibrillator/monitor/pacemakers.

Combined defibrillator/monitors enable the operator to assess and monitor the ECG and rapidly deliver a defibrillating countershock to patients suffering from ventricular fibrillation during a cardiac arrest. In addition, these units provide synchronized cardioversion for treating other arrhythmias, such as ventricular tachycardia, and most now offer external noninvasive pacemaker capability for treating patients with ventricular bradycardia or asystole. Defibrillator/monitors are critical resuscitation instruments and must perform effectively to avoid the otherwise preventable death of a cardiac arrest patient. However, both ECRI and the Food and Drug Administration (FDA) continue to receive a large number of problem reports on these devices each year. Device failures can occur for such reasons as operator error, depleted or defective batteries, or component failures. We evaluated eight units--three intended for crash-cart use and four intended for portable use, all with noninvasive pacemaker capability either standard or as an option, as well as one portable physiologic patient monitor to which a defibrillator (with or without a pacing option) can be attached--from six manufacturers.* We also evaluated one stand-alone noninvasive pacemaker. Although we did not include automated external defibrillators (AEDs) in our study, two of the evaluated units have options that allow them to function as AEDs. We rated the seven crash-cart and portable defibrillator/monitor/pacemakers according to three primary applications: (1) general crash-cart use, (2) prehospital (emergency medical service [EMS]) use, and (3) in-hospital transport. They are rated either Acceptable or Acceptable--Not Recommended for these applications, based primarily on technical performance (including battery operation, which is especially important in portable units), characteristics (such as line-powered operation and portability), features (such as automatic documentation), and human factors design (especially ease of use); some are inappropriate for specific uses because of their respective limitations in these applications. The portable physiologic patient monitor is not rated, but is discussed.** All of the pacemakers available as components of the evaluated units are acceptable for use; however, in most cases, purchasing decisions should be made according to defibrillator/monitor needs. The stand-alone pacemaker is rated Unacceptable because of its numerous performance, safety, and human factors disadvantages and because, other than its being a stand-alone unit, it offers no advantages over the other evaluated pacemakers; see "The Zoll NTP-1000 Stand-alone Noninvasive Pacemaker." Readers are cautioned not to base purchasing decisions on our ratings and rankings alone, but on a thorough understanding of the issues surrounding defibrillator/monitors and noninvasive pacemakers, which can be gained only by reading this study in its entirety.(ABSTRACT TRUNCATED AT 400 WORDS)

Catalogs, Commercial as Topic↗