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A Roberts

Publications and source records attributed to A Roberts.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mass spectrometry screening of combinatorial mixtures, correlation of measured and predicted electrospray ionization spectra.

Methodology was developed to afford rapid characterization of multicomponent mixtures of small organic molecules prepared by split-and-mix combinatorial synthesis. This methodology involved the use of liquid chromatography mass spectrometry (LC/MS) combined with correlation analysis of measured versus predicted electrospray ionization mass spectra. Low-resolution mass spectra of complex mixtures revealed predictable patterns that confirm library products, assisted in identifying chemical synthesis errors, and assessed overall library integrity. In general, equal signal intensities were observed for most combinatorial mixture components, indicating that differences in electrospray ionization efficiency was not a major limitation to this approach. High-throughput data processing programs and informatics tools were used to speed data analysis and to simplify the presentation of the library characterization results. This approach has been used to characterize combinatorial libraries that were synthesized for a variety of drug-discovery programs. Examples are shown for library formats of 1, 40, 66, 280, and 400 component(s)/well. The applicability of this approach to large combinatorial mixtures should allow direct characterization of massive combinatorial libraries.

Journal Article↗
PubMed2001

Ribosome display and affinity maturation: from antibodies to single V-domains and steps towards cancer therapeutics.

Protein affinity maturation using molecular evolution techniques to produce high-affinity binding proteins is an important step in the generation of reagents for cancer diagnosis and treatment. Currently, the most commonly used molecular evolution processes involve mutation of a single gene into complex gene repertoires followed by selection from a display library. Fd-bacteriophage are the most popular display vectors, but are limited in their capacity for library presentation, speed of processing and mutation frequency. Recently, the potential of ribosome display for directed molecular evolution was recognised and developed into a rapid and simple affinity selection strategy using ribosome complexes to display antibody fragments (scFv). Ribosome display and selection has the potential to generate and display large libraries more representative of the theoretical optima for naïve repertoires (10(14)). Even more important is the application of ribosome display for the affinity maturation of individual proteins by rapid mutation and selection cycles. These display strategies can apply to other members of the immunoglobulin superfamily; for example single V-domains which have an important application in providing specific targeting to either novel or refractory cancer markers. We discuss the application of ribosome display and selection in conjunction with variable domain (CTLA-4) libraries as the first step towards this objective and review affinity maturation strategies for in vitro ribosome display systems.

Amino Acid Sequence↗
PubMed2001

Multicenter evaluation of strategies for serodiagnosis of primary infection with Toxoplasma gondii.

The diagnostic performance of single-serum assays for toxoplasma-specific immunoglobulin (Ig)M. IgA. IgG, and IgE antibodies and of different combinations of such antibody assays in 20 European reference centers was assessed. A panel of 276 sera, of which 73 came from patients who seroconverted within 3 months (acute infection), 49 from patients who had seroconverted 3-12 months earlier (convalescence), and 154 from subjects who had two IgG-positive samples obtained 12 months apart (past infection), was tested with 20 toxoplasma-antibody assays and 195 combinations. In general, every assay with high diagnostic sensitivity showed low diagnostic specificity, i.e. no assay performed alone could reliably distinguish acute from past infection. Furthermore, no single assay (or combination) could separate convalescence from the other stages of toxoplasma infection. However, excellent diagnostic performances were reached by sequential use of highly sensitive IgM assays and methods examining IgG avidity or stage specificity. IgA or IgM assays were less suitable for confirmation of toxoplasma-IgM positivity. This study documents the strength of test combinations in assessing the stage of toxoplasma infection.

Acute Disease↗
PubMed2001

Optimization of cottontail rabbit papilloma virus challenge technique.

Disease induced by Cottontail Rabbit Papilloma Virus (CRPV) scarification in domestic rabbits shares many attributes with disease induced by human papilloma virus (HPV). CRPV induces squamous papillomas in domestic rabbits, of which approximately 70% transform into invasive carcinomas. In advanced tumors, virus is often undetectable, and occasionally, some rabbits undergo spontaneous regression of papillomas. Techniques utilized to scarify rabbit skin are diverse, often labor intensive and time consuming with the possibility for significant variability. Using four unique infection techniques, resultant papilloma incidence, time to onset, and total papilloma volumes were compared to determine an optimal challenge method. Five rabbits were each infected with CRPV via a tattoo gun with and without ink, an intradermal injection, manual use of a tattoo needle, or a sterile blade followed by manual use of a tattoo needle. Papilloma formation was monitored weekly after inoculation for 6 weeks. CRPV papillomas began as pinpoint foci at 3 weeks post challenge and grew exponentially throughout the course of measurement. Individual foci coalesced rapidly to form larger papilloma aggregates. Although intradermal injection was well tolerated and easily performed, it was the worst method of papilloma production (2.2 mm(3) at 6 weeks). The best method, a sterile blade followed by manual use of a tattoo needle, produced significantly larger papillomas over all time periods (>1100 mm(3) at 6 weeks, P<0.01). Inoculation of CRPV using this method produces highly repeatable papillomas beginning 3 weeks post-infection.

Animals↗
PubMed2001

Functional projection distances of spinal interneurons mediating reciprocal inhibition during swimming in Xenopus tadpoles.

The basis for longitudinal coordination among spinal neurons during locomotion is still poorly understood. We have now examined the functional projection distances for the longitudinal axons of reciprocal inhibitory 'commissural interneurons' in the spinal cord of young Xenopus tadpoles. In quiescent animals, glycinergic inhibitory postsynaptic potentials (IPSPs) were evoked in ventral spinal neurons by stimulating small rostral and caudal groups of commissural interneuron somata at different distances on the opposite side of the hindbrain and spinal cord. Unitary IPSPs, produced by single synaptic contacts, could be distinguished from background noise. Local cord stimulation at different distances revealed maximum functional projection distances up to approximately 0.5 mm for both descending and ascending axons, but with the probability of recording connections falling steeply over this distance. These maximum longitudinal projection distances are smaller than predicted by axonal anatomy (approximately 1.2 mm). We then measured functional projection distances during swimming by examining the synaptic output of a surgically isolated group of rostral commissural interneurons, mapping the occurrence of the mid-cycle, reciprocal IPSPs they produced in more caudal neurons. IPSPs occurred with high probability up to 0.9 mm away, nearly twice the projection distance found in quiescent tadpoles. These results show that synaptic contacts from commissural interneurons could influence longitudinal coupling during swimming at distances of up to 0.9 mm (approximately 4-5 myotome segments or approximately 25% of the spinal cord). They provide direct evidence for functional projection distances of a characterized class of interneurons belonging to a spinal locomotor pattern generator.

Animals↗
PubMed2001

Perinatal morbidity and mortality rates in severe twin-twin transfusion syndrome: results of the International Amnioreduction Registry.

OBJECTIVE: Serial aggressive amnioreduction is the most widely used therapy for pregnancies that are complicated by twin-twin transfusion syndrome. Survival rates reported with this therapy are 33% to 83%, the wide range attributable to the small number of patients in these case series. Similarly, data on morbidity in survivors are imprecise. We instituted the international twin-twin transfusion syndrome registry to determine the perinatal survival and morbidity rates and the factors that influence perinatal outcome in patients with twin-twin transfusion syndrome who were treated with serial aggressive amnioreduction from 1990 to 1998. STUDY DESIGN: A total of 223 sets of twins who were diagnosed with twin-twin transfusion syndrome before 28 weeks' gestation from 20 fetal medicine referral centers were analyzed, with follow-up data until 4 weeks after birth. RESULTS: Three hundred forty-six twins (78%; 182 recipients and 164 donors) were born alive. Two hundred sixty-six twins (60%; 144 recipients and 122 donors) were alive 4 weeks after birth. Both fetuses survived to 4 weeks in 108 pregnancies (48.4%), whereas, at least 1 fetus survived in 158 pregnancies (70.8%). The interval between the last amnioreduction and delivery ranged from zero to 138 days (median, 17.5 days). In the infants who survived to 4 weeks after birth, abnormalities on neonatal cranial scan were diagnosed in 24% of recipients and in 25% of donors. Logistic regression analysis indicated that the survival rate was significantly related to gestational age at diagnosis, presence of end-diastolic blood flow in the umbilical artery velocity waveforms, presence of hydrops, mean volume of amniotic fluid removed per week, larger birth weight, and gestational age at delivery. The hemoglobin level difference at birth was the only significant parameter to predict abnormal cranial ultrasonography in newborns. CONCLUSION: These data document perinatal survival and neonatal morbidity rates in severe twin-twin transfusion syndrome that were treated by serial aggressive amnioreduction. Outcome was influenced by several perinatal risk factors, which may be used to counsel patients before and during therapy.

Amnion↗
PubMed2001

Complicated monochorionic twin pregnancies: experience with bipolar cord coagulation.

OBJECTIVE: The purpose of the study was to evaluate our experience with ultrasound-guided bipolar diathermy forceps for cord occlusion in complicated monochorionic twin pregnancies. STUDY DESIGN: Seventeen consecutive cases were included: 9 cases were twin-to-twin transfusion syndrome; 2 cases were twin reversed arterial perfusion syndrome, and 6 cases were discordant for fetal abnormality. Bipolar diathermy was performed under local anesthetic with the use of 3-mm forceps with ultrasound guidance. RESULTS: Cord occlusion was successfully accomplished in all cases between 18 and 27 weeks' gestation. There were 2 deaths of the co-twin within 12 hours; 1 death was due to cord hemorrhage, and 1 death was unexplained. One neonatal death occurred after delivery at 27 weeks, and 1 woman with twin-to-twin transfusion syndrome elected termination of pregnancy when hydrocephaly was diagnosed 7 days after the procedure (probably related to the underlying pathologic condition). All other co-twins are alive and well, although 2 pregnancies were complicated by preterm delivery and premature rupture of membranes before 30 weeks' gestation. CONCLUSION: Bipolar diathermy is an effective procedure for cord occlusion, although it still has significant morbidity and mortality rates.

Diseases in Twins↗
PubMed2001

Infectious diseases of refugees and immigrants: dengue fever.

PURPOSE: To describe the assessment and management of chronic wounds and detail current recommendations for optimal wound care practices. DATA SOURCES: Selected scientific literature, clinical practice guidelines, and the authors' clinical experience. CONCLUSION: Multiple factors play a role in the problems associated with chronic wounds. Wound care is costly in regards to medical care, as well as costly in terms of the hardship placed on the patient, family and staff. Too often, wound care practices are based on rituals than research. IMPLICATIONS FOR PRACTICE: The assessment and management of chronic wounds needs to be individualized according to a thorough assessment of the wound, the patients' lifestyle, and the caregiver's knowledge and skill for managing th wound. It is also important to know what wound care products are available and the types of wounds appropriate for their use.

Bed Rest↗
PubMed2001

Ascariasis.

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Adult↗