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Gestational diabetes. Incidence, maternal characteristics, and perinatal outcome.

Accurate estimates of the incidence of abnormal glucose tolerance during pregnancy are virtually nonexistent. Screening select populations of women with risk factors for the condition and the nonrandom, non-population-based nature of most studies have given rise to wide variances in reported incidence. We analyzed data from the states of Mississippi and Washington and from the National Natality and Fetal Mortality Surveys conducted in 1980 in an attempt to provide more accurate population-based estimates of the incidence of gestational diabetes mellitus (GDM). In the national surveys GDM was noted (screening and diagnostic criteria were unavailable) as a complication in 0.38% of all sampled pregnancies; overt (type I and type II) diabetes was noted in 0.78%. Mean maternal age for the GDM group was 28.4 yr; 85% were white (81% controls) and 15% non-white (19% controls). Prepregnancy weights were higher in the GDM group by an average of 20 lb. However, mean weight gain was less in this group than in controls (23 versus 29 lb). Perinatal mortality was noted in approximately 2.8% (1.3% in controls) of the offspring in GDM-complicated pregnancies and congenital malformations in 6.4% (7.9% in controls). Methodologic problems were encountered and included lack of screening and diagnostic criteria, underreporting, and underrecording.

Birth Weight↗

Knowledge of the adenomatous polyposis coli gene and its clinical application.

Familial adenomatous polyposis (FAP) is one of the most clearly defined and well understood of the inherited colorectal cancer syndromes. It is an autosomal dominant condition with high (> 90%) penetrance. Clinically, it is characterized by multiple (> 100) adenomatous polyps in the colon and rectum; variant features in addition to the colonic polyps may include polyps in the upper gastrointestinal tract and other extracolonic manifestations. Since the risk of colorectal cancer in untreated FAP is virtually 100%, screening and intervention for at-risk persons has consisted of annual colon examinations by endoscopy beginning around puberty. The objective of this regimen is early detection of colonic polyps in those who have FAP, followed by preventive colectomy. Because of recent findings that most cases of FAP are due to mutations of the adenomatous polyposis coli gene at chromosome 5q21, genetic testing will probably be incorporated as the first step in the management of individuals at risk for this condition, and screening regimens can be modified. Genetic counselling about the consequences of presymptomatic gene testing is an important component of this process.

Adenomatous Polyposis Coli↗

Putative dynamics of vasopressin in its V1a receptor binding site.

The molecular architecture of the GPCRs, including the dynamic set of interactions between the receptor and the ligand, is one of the key structural questions of biophysical approaches. In the present study, molecular dynamics (MD) simulations were performed on the well-validated molecular model of the vasopressin V1a receptor applying different parameters (i.e., force fields, time variation, use of constraints) in order to sample the conformational space of the endogenous ligand arginine vasopressin (AVP), to explore different putative binding modes, and to analyze the simulation results with respect to experimental data. Noteworthy, it is to mention that for the first time a model of the vasopressin receptor remained stable in a 500 ps MD simulation run under vacuo boundary conditions using the Kollman all-atom FF even though no constraints were imposed. Conclusively, we determined an optimized experimental procedure for studying the dynamics and structure-functionship of this highly important family of GPCRs: the use of MD simulations with the Kollman all-atom force-field parameters on a constrained receptor. Our simplified model may be used as a basis for structure based design of new GPCR ligands and for in silico screening of virtual combinatorial chemistry libraries.

Arginine↗

[Construction and analysis of SSH library of Gossypium barbadense upon infection with Verticillium dahliae].

Roots were collected from the seedlings inoculated with pathogen Verticillium dahliae after 2, 4, 8, 12, 24, 48, 72 and 96 hours for total RNA extraction. The cDNAs from the inoculated seedlings were used as the tester and those from the control seedlings as the driver. SSH method was employed to find the differently expressed cDNAs responding to the pathogen. T/A clone library was constructed containing 534 clones. The cDNA inserts were amplified from the bacterial clones directly with M13 primers by PCR. The size of the products ranged 0.2 - 1.2 kb with an average size of 0.5 kb. The SSH products were dotted on nylon filters, and the positive clones were screened by virtual Northern blotting with probes of the two kinds of initiative cDNAs. Totally 78 clones which were up-regulated and putatively involved in the defense response of G. barbadense were identified and sequenced. Sequence similarity searches were performed with the Blastn and Blastx. Most of them showed high or partial homology to genes or ESTs induced by different stresses in Arabidopsis thaliana and other species,such as the pathogenesis-related 10 family of G. hirsumtum and disease resistance-responsive family protein in Arabidopsis thaliana. The results would be helpful to understand the molecular mechanisms of disease response in cotton.

Blotting, Northern↗

Solution-phase library screening for the identification of rare clones: isolation of an alpha 1D-adrenergic receptor cDNA.

alpha 1-Adrenergic receptor (alpha 1-AR) subtypes (alpha 1A and alpha 1B) play a critical role in vascular smooth muscle contraction and circulatory homeostasis. Transcripts for these guanine nucleotide-binding protein-coupled receptors are extremely low in abundance, however, and isolation of their cDNAs is difficult. We have developed a novel technique for identifying rare clones in a cDNA library, which has been used successfully to isolate a cDNA clone encoding an alpha 1D-AR. A 564-bp polymerase chain reaction product encoding a region between the third and sixth transmembrane domains of the alpha 1D-AR was first generated using rat brain mRNA as template and highly degenerate primers. The primers corresponded to those domains but contained mismatches to the alpha 1B-AR sequences. A 3-kb transcript was identified with this polymerase chain reaction probe, by Northern analysis of rat hippocampus. However, traditional plaque hybridization failed to identify a cDNA in a rat hippocampus lambda gt10 library. By solution-phase screening of virtually the entire library, a cDNA containing a 3-kb insert was identified, amplified, and purified. This insert encodes a 560-amino acid protein corresponding to the topology of guanine nucleotide-binding protein-coupled receptors. This receptor has approximately 71% amino acid identity, in the transmembrane regions, to the hamster and rat alpha 1B-ARs. Characterization of the receptor expressed in COS-7 cells, by ligand binding and photoaffinity labeling, revealed some of the characteristics of an alpha 1A-AR. However, unlike alpha 1A-ARs characterized previously in membrane preparations or in solubilized partially purified preparations, the expressed receptor could be extensively inactivated by chlorethylclonidine. In addition, it displays ligand-binding properties that are not consistent with an alpha 1A-AR. This indicates that the cDNA clone that we have isolated encodes a novel alpha 1-AR subtype, which we classify as the alpha 1D-AR.

Animals↗

Rapid detection of ras oncogenes in human tumors: applications to colon, esophageal, and gastric cancer.

We have developed a rapid, nonradioactive large scale method for the detection of ras oncogenes in human tumors. DNA is amplified by the polymerase chain reaction (PCR), and then digested with specific restriction enzymes to detect either endogenous or primer-mediated Restriction Fragment Length Polymorphisms (RFLPs). We report here that three of 15 colon tumors tested contain K-ras codon 12 aspartic acid mutations and one, along with the HCT 116 colon carcinoma cell line, contains a K-ras codon 13 aspartic acid mutation. On the other hand, we did not detect H- or K-ras codon 12 mutations or the K-ras codon 13 aspartic acid mutation in 25 esophageal and 27 gastric cardia tumors isolated from patients in Lin-xing County, China. By incorporating nucleotide substitutions in PCR primers, this method can be applied towards the rapid, non-radioactive screening of virtually any genetic disease caused by known point mutations.

Codon↗

[Progestogen tests after the menopause].

There is virtually no screening for endometrial cancer after the menopause. The methods so-far available (cervico-vaginal smear or endouterine specimens) are either unreliable or else difficult to perform. The progestogen tests are, in contrast, easy for any doctor to carry out, acceptable to patients, fairly reliable and low cost, which should make their widespread use possible. The administration of a progestogen to a post-menopausal woman should not produce bleeding unless the endometrium is hyperplasic or proliferative. 1 366 tests of this type were carried out and resulted, amongst other discoveries, in the detection of 5 cases of asymptomatic cancers of the endometrium and 2 cases of ovarian cancer.

Endometrial Hyperplasia↗

Rapid and large-scale method to detect K-ras gene mutations in tumor samples.

We have developed a rapid and large-scale method for the detection of K-ras gene mutations in tumors. First, DNA is amplified by an asymmetric PCR; second, the single-strand dinitrophenyl (DNP)-labeled amplified DNA is hybridized specifically to oligonucleotide probes affixed on a tube. Finally, perfectly matched duplexes are easily detected by a monoclonal anti-DNP antibody bearing 125I. The usefulness of this technique is illustrated by analyzing K-ras codon 12 mutations in human colorectal samples. This reliable assay procedure can be applied to the rapid screening of virtually any genetic disease caused by previously described point mutations.

Aged↗

[Rationalizing the organization and structure of a trauma surgery clinic based on rationing of personal and financial resources--analysis, simulation and conversion using modern data processing techniques].

With a system of modeling, simulation, animation of information, communication in medicine (mosaic-m) the structures of organisation and information in a level 1 trauma center were analysed and animated as a virtual environment on screen in a first step. One result: in existing paper orientated documentation 50% of documentation was redundant. In a second step the requirements of the future information system were described systematically, user- and organisation-oriented. All components (hard- and software) were simulated an screen that the user could work virtually in the future working place. With mosaic-m the user is fully integrated in analysing and developing a new information system in the clinic.

Computer Simulation↗

Computed tomographic virtual colonoscopy computer-aided polyp detection in a screening population.

BACKGROUND & AIMS: The sensitivity of computed tomographic (CT) virtual colonoscopy (CT colonography) for detecting polyps varies widely in recently reported large clinical trials. Our objective was to determine whether a computer program is as sensitive as optical colonoscopy for the detection of adenomatous colonic polyps on CT virtual colonoscopy. METHODS: The data set was a cohort of 1186 screening patients at 3 medical centers. All patients underwent same-day virtual and optical colonoscopy. Our enhanced gold standard combined segmental unblinded optical colonoscopy and retrospective identification of precise polyp locations. The data were randomized into separate training (n = 394) and test (n = 792) sets for analysis by a computer-aided polyp detection (CAD) program. RESULTS: For the test set, per-polyp and per-patient sensitivities for CAD were both 89.3% (25/28; 95% confidence interval, 71.8%-97.7%) for detecting retrospectively identifiable adenomatous polyps at least 1 cm in size. The false-positive rate was 2.1 (95% confidence interval, 2.0-2.2) false polyps per patient. Both carcinomas were detected by CAD at a false-positive rate of 0.7 per patient; only 1 of 2 was detected by optical colonoscopy before segmental unblinding. At both 8-mm and 10-mm adenoma size thresholds, the per-patient sensitivities of CAD were not significantly different from those of optical colonoscopy before segmental unblinding. CONCLUSIONS: The per-patient sensitivity of CT virtual colonoscopy CAD in an asymptomatic screening population is comparable to that of optical colonoscopy for adenomas > or = 8 mm and is generalizable to new CT virtual colonoscopy data.

Adenomatous Polyps↗

Tissue-plastinated vs. celloidin-embedded large serial sections in video, analog and digital photographic on-screen reproduction: a preliminary step to exact virtual 3D modelling, exemplified in the normal midface and cleft-lip and palate.

This study analyses tissue-plastinated vs. celloidin-embedded large serial sections, their inherent artefacts and aptitude with common video, analog or digital photographic on-screen reproduction. Subsequent virtual 3D microanatomical reconstruction will increase our knowledge of normal and pathological microanatomy for cleft-lip-palate (clp) reconstructive surgery. Of 18 fetal (six clp, 12 control) specimens, six randomized specimens (two clp) were BiodurE12-plastinated, sawn, burnished 90 microm thick transversely (five) or frontally (one), stained with azureII/methylene blue, and counterstained with basic-fuchsin (TP-AMF). Twelve remaining specimens (four clp) were celloidin-embedded, microtome-sectioned 75 microm thick transversely (ten) or frontally (two), and stained with haematoxylin-eosin (CE-HE). Computed-planimetry gauged artefacts, structure differentiation was compared with light microscopy on video, analog and digital photography. Total artefact was 0.9% (TP-AMF) and 2.1% (CE-HE); TP-AMF showed higher colour contrast, gamut and luminance, and CE-HE more red contrast, saturation and hue (P < 0.4). All (100%) structures of interest were light microscopically discerned, 83% on video, 76% on analog photography and 98% in digital photography. Computed image analysis assessed the greatest colour contrast, gamut, luminance and saturation on video; the most detailed, colour-balanced and sharpest images were obtained with digital photography (P < 0.02). TP-AMF retained spatial oversight, covered the entire area of interest and should be combined in different specimens with CE-HE which enables more refined muscle fibre reproduction. Digital photography is preferred for on-screen analysis.

Artifacts↗

Strategies and techniques for identification of novel bioactive compounds--CHI's second annual conference. 7-9 October 1998, Zurich, Switzerland.

This conference on recent developments in the discovery of novel therapeutic candidates was organized by Amy Dasch (Cambridge Healthtech Institute, Newton Upper Falls, MA, USA; http://www.xensei.com/conferences). The conference provided an overview of all relevant aspects of the rapidly changing paradigms in drug research. Gene technology creates a vast number of new biological targets. The progress in combinatorial chemistry and high-throughput screening (HTS) is accompanied by the development of virtual libraries, large screening programs, and the generation of enormous sets of data. Correspondingly, the lectures covered such different topics as target identification and assay development, HTS technology, combinatorial library design and synthesis, chemoinformatics, and the integration of these components into the discovery of novel pharmaceutical compounds, the development of agricultural chemicals, and other applications. A most valuable addition was reports on case histories in drug development from pharmaceutical companies utilizing these technologies. About 100 scientists, many of them from European countries, attended the meeting. In total, 25 lectures were presented in four sessions: molecular diversity and library design; combinatorial synthesis; HTS; computational methodologies and chemoinformatics. Like other commercially organized conferences, this meeting was well-planned. The balance of speakers from small venture capital companies, large pharmaceutical and agricultural firms gave a broad overview of recent progress in the rational design, combinatorial synthesis, and HTS of new bioactive compounds, as well as on different approaches to handling large data sets and deriving structure-activity relationships from such data.

Journal Article↗

Virtual trackballs revisited.

Rotation of three-dimensional objects by a two-dimensional mouse is a typical task in computer-aided design, operation simulations, and desktop virtual reality. The most commonly used rotation technique is a virtual trackball surrounding the object and operated by the mouse pointer. This article reviews and provides a mathematical foundation for virtual trackballs. The first, but still popular, virtual trackball was described by Chen et al. We show that the virtual trackball by Chen et al. does not rotate the object along the intended great circular arc on the virtual trackball and we give a correction. Another popular virtual trackball is Shoemake's quaternion implementation, which we show to be a special case of the virtual trackball by Chen et al.. Shoemake extends the scope of the virtual trackball to the full screen. Unfortunately, Shoemake's virtual trackball is inhomogeneous and discontinuous with consequences for usability. Finally, we review Bell's virtual trackball and discuss studies of the usability of virtual trackballs.

Algorithms↗

Depth on a flat screen.

The hypothesis was tested that the coupling of parallax shifts between objects depicted on a monitor screen around a fixation point with the head movements of an observer viewing this screen monocularly around a point coinciding with the fixation point is sufficient to create a convincing depth impression and to enable the observer to make reliable estimations of depth. The estimates were based on monocular vision and involved the aligning of wedges. The investigation consisted of two analogous experiments carried out simultaneously, one on depth estimations virtually in the screen and one on depth estimations virtually in front of the screen. In each experiment three conditions were compared: an active condition in which the coupling of parallax shifts and observer's head movements operated, a passive condition in which it did not, and a real-life set-up to measure the maximum reliability in depth estimation. The hypothesis is confirmed: in the active condition the variances in the alignments are significantly smaller than in the passive condition and approach those in the real-life set-up. This holds not only for estimates in the screen but also for estimates in front of the screen, that is, we can make a thing apparently leap out of the screen towards the observer. Results are interpreted against the background of the debate between the direct and the indirect theories of perception.

Cues↗

Virtual endoscopy: a promising new technology.

Growing evidence shows that early detection of cancer can substantially reduce mortality, necessitating screening programs that encourage patient compliance. Radiology is already established as a screening tool, as in mammography for breast cancer and ultrasonography for congenital anomalies. Advanced processing of helical computed tomographic data sets permits three-dimensional and virtual endoscopic models. Such models are noninvasive and require minimal patient preparation, making them ideal for screening. Virtual endoscopy has been used to evaluate the colon, bronchi, stomach, blood vessels, bladder, kidney, larynx, and paranasal sinuses. The most promising role for virtual endoscopy is in screening patients for colorectal cancer. The technique has also been used to evaluate the tracheobronchial tree for bronchogenic carcinoma. Three-dimensional and virtual endoscopy can screen, diagnose, evaluate and assist determination of surgical approach, and provide surveillance of certain malignancies.

Bronchoscopy↗

Follow-up and evaluation of skin cancer screening in British Columbia.

BACKGROUND: Skin cancer screening is thought to be a useful public health tool for the early detection of skin cancers. However, few studies have reported on follow-up and outcome of subjects who have a positive screen. OBJECTIVE: The aims of this study were to evaluate attendance at skin cancer screening clinics in British Columbia for the period 1994 and 1995 and to assess follow-up outcome among participants who were identified to have a potentially serious skin lesion that warranted further medical review. METHODS: A self-administered questionnaire was sent to participants screening positive for skin cancer and to their attending physicians. RESULTS: Five hundred twenty people were screened. Of these, 105 were referred for evaluation of a potential malignancy or precursor lesion. One melanoma, 3 basal cell carcinomas, 4 atypical nevi, and 1 actinic keratosis were histologically confirmed in 76 referred participants for whom follow-up information was available. The positive predictive values ranged from 17% to 89% depending on the screening diagnosis. Several false-positive results and one false-negative result were observed. Reasons for not seeking recommended follow-up were addressed. CONCLUSIONS: Our yield and positive predictive values for different screening diagnoses were virtually identical to those previously reported in larger US studies. Improved communication between screening physicians and screening participants may improve follow-up rates in those people who would benefit from further medical care.

Adult↗