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At least 1,369 records · Page 76Linked to original sources
PubMed1990

Urinary vanillylmandelic acid and homovanillic acid levels in randomly-sampled urine for the mass screening of neuroblastoma.

Employing 421 urine samples taken randomly from normal infants and 294 samples from infants with neuroblastoma, we investigated the application of values of vanillylmandelic acid (VMA), homovanillic acid (HVA) and square root of VMA2 + HVA2 to discriminate between patients and normal infants. The establishment of an HVA cut-off level is virtually impossible because of its low sensitivity. In contrast, VMA sensitivity is high, and that of square root of VMA2 + HVA2 is very similar to that of VMA although it includes HVA. Although VMA appears to be able to discriminate well, discrimination employing VMA alone would be dangerous because cases with normal VMA and abnormal HVA would be missed, especially in the first screening for which a mechanical discrimination is performed. Overlooking such cases can be avoided by the adoption of the function square root of VMA2 + HVA2. The present study suggests that the combined use of variables can be more effective than using them separately.

Homovanillic Acid↗
PubMed2001

Single-molecule immunoassay and DNA diagnosis.

Many assays relevant to disease diagnosis are based on electrophoresis, where the migration velocity is used for distinguishing molecules of different size or charge. However, standard gel electrophoresis is not only slow but also insensitive. We describe a single-molecule imaging procedure to measure the electrophoretic mobilities of up to 100000 distinct molecules every second. The results correlate well with capillary electrophoresis (CE) experiments and afford confident discrimination between normal (16.5 kbp) and abnormal (6.1 kbp) mitochondrial DNA fragments, or beta-phycoerythrin-labeled digoxigenin (BP-D) and its immunocomplex (anti-D-BP-D). This demonstrates that virtually all electrophoresis diagnostic protocols from slab gels to CE should be adaptable to single-molecule detection. This opens up the prossibility of screening single copies of DNA or proteins within single biological cells for disease markers without performing polymerase chain reaction (PCR) or other biological amplification.

Antigen-Antibody Complex↗
PubMed1996

Pavlovian conditioning to a diazepam cue with yohimbine as the unconditional stimulus.

On multiple occasions, rats were administered diazepam (2.0 mg/kg, ip) followed 30 min thereafter by yohimbine hydrochloride (2.5 or 5. 0 mg/kg) or isotonic saline (forward conditioning groups). Three additional groups (backward conditioning controls) were given equivalent injections, but in reverse order. After eight such pairings, the effects of a single injection of diazepam on motor performance (balancing on a rotating drum) was assessed. Rats that had received either dose of yohimbine during forward conditioning trials maintained their balance longer than the saline controls. After four additional conditioning trials, the animals' activity patterns in a plus-maze screening test for anxiolytics were examined. Placed into the maze after a single test injection of isotonic saline, the behavior of all groups was virtually identical: less than 16% of total entries into or time spent in the four arms of the maze was spent in the two "open" arms (unprotected by surrounding walls). When tested in the maze again, but 35 min after a single injection of diazepam, the groups that had received diazepam but not yohimbine during the conditioning phase exhibited the expected increase in open-arm activity, and equivalent increases were found in backward conditioning groups. However, the group previously conditioned with 2.5 mg/kg of yohimbine following diazepam also showed an increased open-arm activity when tested with diazepam alone, but it was significantly greater than that seen in the control group. In contrast, the group conditioned with 5.0 mg/kg yohimbine following diazepam exhibited no effect of diazepam upon their plus maze activity; consequently, these animals spent less time in the open arms than either of the other groups. Yohimbine alone normally decreases open-arm activity (a putative "anxiogenic" effect) in a linear dose-dependent fashion. The fact that it had a bidirectional conditional effect on the diazepam cue drug demonstrates that a conditional response in drug --> drug conditioning cannot always be predicted on the basis of the behavioral response to the signaled drug. Consideration is given to possible reasons for these effects of diazepam --> yohimbine pairings in terms of the known neuropharmacological properties of yohimbine.

Animals↗
PubMed2000

Prostate cancer: where we have been, where we are, where we are going.

Prostate cancer has generated more debate over the last decade than perhaps any other malignancy. This stems from many factors, not the least of which is the fact that the histologic incidence far exceeds clinically manifested disease. Despite this fact, prostate cancer remains the most common male malignancy and the second most common cause of cancer-related mortality in most Western societies. Significant advances have occurred in virtually all domains surrounding prostate cancer, including increased understanding of the molecular and genetic basis of the disease, improved methods of early detection and screening, refinement of biopsy techniques, and advances in staging and therapeutic approaches. Even with these advances, the sobering mortality statistics clearly underscore the need for further insight and progress.

Biomarkers↗
PubMed1994

Cardiac L-type Ca2+ channel triggers transmitter release in PC12 cells.

Among the various voltage-sensitive Ca2+ channels present in PC12 cells are the dihydropyridine (DHP)-sensitive L-channel, the omega-conotoxin (omega-CgTx)-sensitive N-channel, and an atypical omega-CgTx/DHP-insensitive Ca2+ channel. Depolarization-evoked Ca2+ entry and [3H]dopamine release is mediated by L-type Ca2+ channels determined by the use of Ca2+ channel antagonists, and a single protein of 250 kDa is recognized by L-type-specific antibodies. Screening of a PC12 cDNA library revealed two types of Ca2+ channels which were identified by partial sequencing. A pc12-L clone displayed virtually identical sequence homology to the cardiac L-type channel. The identical sequence homology of the single alternative splicing region confirmed clone pc12-L as the rbC-I transcript, a cardiac-neuronal alpha 1 subunit expressed in rat brain. Clone pc12-N displayed identical sequence homology to rbB-I, a neuronal alpha 1 subunit of the N-type Ca2+ channel expressed in rat brain; Northern blot analysis identified RNA of a size similar to that previously described for rat brain.

Animals↗
PubMed2026

Efficient scarless gene editing in Pichia pastoris via survival stress-based intramolecular homologous recombination.

To overcome low efficiency and/or genomic instability induced by DNA cleavage in current genome-editing approaches, a novel pop-in/pop-out-based editing system was developed for Pichia pastoris. An ingenious arrangement of components leads to a more efficient screening by permitting the only type of DNA recombination under defined pressure conditions, in terms of the overall efficiency of gene editing, the system virtually depends on the integration efficiency mediated by single-crossover recombination. It does not rely on exogenous recombinases or programmable nucleases such as Cas9, thereby avoiding nuclease induced double strand breaks and associated off target mutations or chromatin fatigue. This strategy preserves high editing efficiency with no modification to the host's inherent genetic properties. Relative to site-specific recombination methods, its dual MazF counterselection enables seamless editing, avoiding scar sequence-induced genomic instability. In this study, nearly 100% knockout efficiency and over 86.67% integration efficiency were achieved in the described experimental cases with this system, which provides a new gene-editing tool for synthetic biology in Pichia pastoris.

Efficient scarless editing↗
PubMed1997

Duplex ultrasonography in evaluation of splanchnic artery stenosis.

Duplex ultrasonography accurately identifies high-grade stenoses in the SMA. Analysis of velocity data reveals few false positives and virtually no false negatives in the determination of high-grade SMA stenosis by duplex scanning. We therefore utilize duplex scanning to perform early screening studies of patients with symptoms suggestive of chronic visceral ischemia. If the duplex findings are negative, we recommend evaluating for other sources of abdominal pain. If the findings are positive, prompt angiography is indicated. It is important to remember that although duplex scanning can identify mesenteric artery stenosis, it cannot diagnose intestinal ischemia. By establishing duplex scanning as a useful and accessible noninvasive screening tool, it is hoped that the time between onset of visceral ischemic symptoms and diagnosis of chronic visceral ischemia will be shortened significantly, potentially reducing the morbidity and mortality of the disease.

Blood Vessel Prosthesis↗
PubMed2001

The impact of informatics and computational chemistry on synthesis and screening.

High-throughput synthesis and screening technologies have enhanced the impact of computational chemistry on the drug discovery process. From the design of targeted, drug-like libraries to 'virtual' optimization of potency, selectivity and ADME/Tox properties, computational chemists are able to efficiently manage costly resources and dramatically shorten drug discovery cycle times. This review will describe some of the successful strategies and applications of state-of-the-art algorithms to enhance drug discovery, as well as key points in the drug discovery process where computational methods can have, and have had, greatest impact.

Journal Article↗
PubMed2005

Expanding the ChemGPS chemical space with natural products.

Recently various attempts have been made to increase the efficacy and precision of chemical libraries used in high-throughput screening (HTS) drug discovery approaches. One such approach is ChemGPS, which provides a defined chemical space for prescreening evaluation of chemical compound properties or virtual dereplication. In the present study, ChemGPS has been applied to a set of natural products shown to exhibit cyclooxygenase-1 and/or -2 (COX-1/2) inhibition. With the purpose of defining chemical properties and linking these to the observed mode of enzyme inhibition, this resulted in two lines of reasoning. On one hand several specific features of these compounds have been identified and discussed. Overall COX inhibition was frequently correlated with the presence of at least one ring in the structure, fragments exhibiting structural rigidity, and a relatively large molecular size. The concept "size" includes several parameters, e.g., molecular volume, weight, and number of bonds. On the other hand, and possibly even more important, was the unexpected finding that the natural products studied to a large extent fell outside the defined ChemGPS chemical space. Therefore, we also propose an expanded space for natural products: ChemGPS-NP.

Biological Products↗
PubMed1999

A method for identifying differentially expressed genes in rare populations of primary human hematopoietic cells.

Differential display (DD) is widely employed for identifying uniquely expressed genes within two different cell populations. While potentially powerful, DD is problematic because apparent positive clones require time-consuming verification which may be made even more difficult if only small amounts of starting material are available. We have devised a screening approach to address these issues in primary human hematopoietic cells. Candidate clones are identified in a slot-blot format and verified by 'Virtual Northern' blot analyses using globally amplified cDNA as the verification probe. This method is fast, and since it requires only approximately 0.2 microg of total RNA, it is particularly useful when only limited amounts of study tissue are available.

Blotting, Northern↗
PubMed2006

A treadmill and motion coupled virtual reality system for gait training post-stroke.

A virtual reality (VR)-based locomotor training system has been developed for gait rehabilitation post-stroke. The system consists of a self-paced treadmill mounted onto a 6-degrees-of-freedom motion platform. Virtual environments (VEs) that are synchronized with the speed of the treadmill and the motions of the platform are rear-projected onto a screen in front of the walking subject. A feasibility study was conducted to test the capability of two stroke patients and one healthy control to be trained with the system. Three VE scenarios (corridor walking, street crossing, and park stroll) were woven into a gait-training program that provided three levels of complexity (walking speed, slopes, collision avoidances), progression criteria (number of successful trials) and knowledge of results. Results show that, with practice, patients can effectively increase their gait speed as demanded by the task and adapt their gait with respect to the change in physical terrain. However, successful completion of tasks requiring adaptation to increasing demands related to speed and physical terrains does not necessarily predict the patient's ability to anticipate and avoid collision with obstacles during walking. This feasibility study demonstrates that persons with stroke are able to adapt to this novel VR system and be immersed in the VEs for gait training.

Computer Simulation↗
PubMed2006

The physician's role in selecting a factor replacement therapy.

Over the past 20 years, transmissions of human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus have been virtually eliminated from plasma-derived or recombinant therapy in the USA, a record that can be largely attributed to the use of effective screening and inactivation technologies for known pathogens. The next significant threat will likely come from the emergence of a new, blood-borne infectious disease, perhaps one transmitted by a non-lipid-enveloped virus or prion, for which current inactivation methods are ineffective. Following the HIV crisis of the 1980s, government, patient advocacy groups, medical and scientific communities and the manufacturers of clotting therapies can learn from the past and approach potential threats from emerging pathogens in a proactive and productive manner. For clinicians, this includes actively engaging patients in a dialogue about all the factors that may influence their choice of clotting factor therapies, including emerging pathogens, patient convenience, consistency and reliability of supply, relative cost/benefit ratios, reimbursement issues (where applicable), patient preference and brand loyalty. It is our obligation as healthcare providers to understand potential risks and help make proactive decisions with our patients, decisions that often must be made in an environment of scientific uncertainty. Threats from infectious agents that were once deemed theoretical can, and often do, ultimately become real, with serious implications for morbidity and mortality.

Blood Component Transfusion↗
PubMed1989

Nucleotide sequence of cDNA coding for saporin-6, a type-1 ribosome-inactivating protein from Saponaria officinalis.

We have isolated and sequenced partial cDNA clones that encode SO-6, a ribosome-inactivating protein from Saponaria officinalis. A cDNA library was constructed from the leaves of this plant and screened with synthetic oligonucleotide probes representing various portions of the protein. The deduced amino acid sequence shows the signal peptide and a coding region virtually accounting for the entire amino acid sequence of SO-6. The sequence reveals regions of similarity to other ribosome-inactivating proteins, especially in a region of the molecule where critical amino acid residues might participate in the active site.

Amino Acid Sequence↗
PubMed2004

Design of highly specific ligands of fibrin for therapeutic applications.

The work presented here is aimed at designing high-affinity ligands for the fibrin gamma (312-324) epitope. This epitope is specific for fibrin recognition, as it is exposed only on the fibrin surface, while in fibrinogen it is buried in the protein bulk. This property makes it very useful for therapeutic applications. In fact, it may be exploited in driving systems for targeted delivery of thrombolytic drugs toward the specific compartment where they are needed. It will then allow avoidance of serious unwanted side effects produced by a conventional systemic administration. The approach chosen for designing putative ligands is based on the known three-dimensional (3D) structure of the epitope. A wide virtual library made up of oligo-peptides and analogues designed by a combinatorial approach, on the basis of chemical complementarity criteria, has been screened by means of a docking/scoring approach (DOCK program). The peculiarity of the problem under study required a considerable effort in finding a method enabling the experimental validation of the design work results. In fact the selected biological target is absolutely new, so that neither a endogenous, nor a synthetic high-affinity ligand is known up to now. It does not allow for the validation of computational results by means of classical binding tests based on the use of known labeled high-affinity ligands. Preliminary binding essayes were so carried out by means of the Plasmon Surface Resonance (PSR) technique. The experimental results suggested that most of the molecules predicted to be good ligands by means of the selected computational tools, could carry the wanted affinity toward the selected target.

Amino Acid Sequence↗
PubMed2001

Effects of audiovisual distraction during dental prophylaxis.

BACKGROUND: Fear and anxiety often inhibit patients from seeking dental care. Audiovisual, or A/V, distraction techniques have been shown to reduce patient anxiety and pain during dental procedures. The authors investigated the effects of a virtual image A/V eyeglass system on patients' anxiety and pain. METHODS: Twenty-seven routine dental prophylaxis patients participated and completed the Dental Fear Survey and the Fear of Pain Questionnaire-III before treatment. In random order, the clinician scaled and polished two quadrants in subjects while they watched and listened to a standard video using the A/V eyeglasses and two quadrants while they did not. A posttreatment questionnaire was administered to both the patient and the clinician. RESULTS: Subjects reported less anxiety and discomfort when using the A/V eyeglass system than when they did not. Most subjects preferred to use the A/V equipment rather than receive traditional treatment. The clinician experienced no significant technical interference during the use of the A/V device. The use of the A/V eyeglasses led to decreased treatment time in the first one-half of the procedure. The system appeared to lead to some decreases in the physiological parameters over the course of treatment, with the highest systolic blood pressure occurring after the condition with no use of A/V eyeglasses. CONCLUSIONS: A virtual image A/V system is beneficial in the reduction of fear, pain and procedure time for most dental prophylaxis patients. CLINICAL IMPLICATIONS: Use of screening questionnaires may be helpful for identifying anxious patients. An A/V device may be beneficial to the clinician and the mildly or moderately anxious patient.

Adult↗
PubMed2005

"In silico" design of potential anti-HIV actives using fragment descriptors.

Substructural Molecular Fragments (SMF) method was applied for computer-aided design of new compounds potentially possessing high anti-HIV activities: tetrahydroimidazobenzodiazepinone (TIBO) derivatives and 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. Using available experimental data, the SMF method was first applied to build QSAR models based on fragment descriptors (atom/bond sequences and "augmented atoms"). The focused virtual combinatorial libraries containing 891 TIBO derivatives and 2640 HEPT derivatives were then generated systematically attaching selected substituents to corresponding Markush structures. Finally, a screening of those libraries using developed QSAR models led to several hits potentially possessing high anti-HIV activity.

Anti-HIV Agents↗
PubMed1994

Review of serologic testing for hepatitis C virus infection and risk of posttransfusion hepatitis C.

Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis and cirrhosis worldwide. Screening volunteer donors for antibody to HCV (anti-HCV) has reduced the risk of posttransfusion hepatitis C to less than 1.0% per recipient. Virtually all persons with acute HCV infection seem to become chronically infected, and an average of 67% acquire chronic liver disease with persistently elevated liver enzyme values. Among anti-HCV-positive blood donors, 70% to 90% are HCV RNA positive, but less than half have biochemical evidence of liver disease. The extraordinarily high rate of persistent infection observed in humans and the lack of protection against rechallenge with homologous HCV strains demonstrated in experimental studies in chimpanzees suggest that HCV fails to induce an effective neutralizing antibody response. This raises major concerns for the development of effective passive or active immunoprophylaxis against hepatitis C.

Blood Donors↗
PubMed1993

APC gene mutations in Italian familial polyposis coli patients.

Adenomatous polyposis coli is an autosomal dominant disease characterized by the development of hundreds of colorectal adenomas in young adults. If prophylactic colectomy is not performed, colorectal cancer develops in virtually all affected individuals by the fifth decade of life. All at-risk relatives older than 10 years of age need to be screened regularly by endoscopy. Recently, the gene responsible for the disease, the APC gene, was cloned. The finding of inactivating mutations of the APC gene in Italian APC patients allowed us to offer DNA-based diagnostic tests to these families.

Adenomatous Polyposis Coli↗