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Biomedical subjects

Robert L White

Publications and source records attributed to Robert L White.

11 recordsLinked to original sources
PubMed2006

The influence of structural features on facile McLafferty-type, even-electron rearrangements in tandem mass spectra of carboxylate anions.

In contrast to the well-described McLafferty rearrangement in odd-electron cations, relatively little has been reported on comparable rearrangements in even-electron ions, especially negative ions. This work reports a systematic study using tandem mass spectrometry (MS/MS) fragment ion spectra of carboxylate anions having a suitably acidic proton in the gamma position. The rearrangement process was studied in both ion trap and triple quadrupole mass spectrometers; characteristic enolate anions and stable neutral products were formed at low collision energies. The process has diagnostic and analytical potential in, for example, the analysis of peptides having C-terminal serine residues and of 3-hydroxy- or 3-aminocarboxylic acids in complex mixtures.

Acrylates↗
PubMed2006

Ketoprofen gel as an adjunct to physical therapist management of a child with Sever disease.

BACKGROUND AND PURPOSE: Sever disease is the most common cause of heel pain in athletic children. The purpose of this case report is to describe the addition of ketoprofen gel to the physical therapy intervention of a child with Sever disease. CASE DESCRIPTION: The patient was an 8-year-old girl diagnosed with Sever disease. Physical therapy intervention consisted of 6 visits over a 3-week period with traditional interventions (including rest, discontinuation of activities that aggravate the condition, hot and cold packs, heel lifts, calf stretching, and strengthening) and the addition of ketoprofen gel to reduce local inflammation and relieve pain. OUTCOMES: The patient demonstrated improvement in all outcome measures: pain rating, the Lower Extremity Functional Scale, strength, and range of motion. DISCUSSION: The child had relief of pain and returned to activities after 18 days of intervention, which was 30 days less than reports of intervention in the literature that did not include the use of ketoprofen gel.

Administration, Topical↗
PubMed2005

Delay-period activity in visual, visuomovement, and movement neurons in the frontal eye field.

In the present study, we examined the role of frontal eye field neurons in the maintenance of spatial information in a delayed-saccade paradigm. We found that visual, visuomovement, and movement neurons conveyed roughly equal amounts of spatial information during the delay period. Although there was significant delay-period activity in individual movement neurons, there was no significant delay-period activity in the averaged population of movement neurons. These contradictory results were reconciled by the finding that the population of movement neurons with memory activity consisted of two subclasses of neurons, the combination of which resulted in the cancellation of delay-period activity in the population of movement neurons. One subclass consisted of neurons with significantly greater delay activity in the preferred than in the null direction ("canonical"), whereas the other subclass consisted of neurons with significantly greater delay activity in the null direction than in the preferred direction ("paradoxical"). Preferred direction was defined by the saccade direction that evoked the greatest movement-related activity. Interestingly, the peak saccade-related activity of canonical neurons occurred before the onset of the saccade, whereas the peak saccade-related activity of paradoxical neurons occurred after the onset of the saccade. This suggests that the former, but not the latter, are directly involved in triggering saccades. We speculate that paradoxical neurons provide a mechanism by which spatial information can be maintained in a saccade-generating circuit without prematurely triggering a saccade.

Animals↗
PubMed2005

A novel method for STR-based DNA profiling using microarrays.

We describe a novel method for rapidly identifying and distinguishing between different DNA sequences using short tandem repeat (STR) analysis and DNA microarrays. The method can be used to deduce identity, length, and number of STRs of the target molecule. We refer to this technique as the "variable-length probe array" method for STR profiling (VLPA). The method involves hybridization of the unknown STR target sequence to a DNA microarray displaying complementary probes that vary in length to cover the range of possible STRs. A post-hybridization enzymatic digestion of the DNA hybrids is then used to selectively remove labeled single-stranded regions of DNA from the microarray surface. The number of repeats in the unknown target is then deduced based on the pattern of target DNA that remains hybridized to the array. This DNA profiling technique is useful for performing forensic analysis to uniquely identify individual humans or other species.

DNA↗
PubMed2004

Biosynthesis of the dichloroacetyl component of chloramphenicol in Streptomyces venezuelae ISP5230: genes required for halogenation.

Five ORFs were detected in a fragment from the Streptomyces venezuelae ISP5230 genomic DNA library by hybridization with a PCR product amplified from primers representing a consensus of known halogenase sequences. Sequencing and functional analyses demonstrated that ORFs 11 and 12 (but not ORFs 13-15) extended the partially characterized gene cluster for chloramphenicol (Cm) biosynthesis in the chromosome. Disruption of ORF11 (cmlK) or ORF12 (cmlS) and conjugal transfer of the insertionally inactivated genes to S. venezuelae gave mutant strains VS1111 and VS1112, each producing a similar series of Cm analogues in which unhalogenated acyl groups replaced the dichloroacetyl substituent of Cm. 1H-NMR established that the principal metabolite in the disrupted strains was the alpha-N-propionyl analogue. The sequence of CmlK implicated the protein in adenylation, and involvement in halogenation was inferred from biosynthesis of analogues by the cmlK-disrupted mutant. A role in generating the dichloroacetyl substituent was supported by partial restoration of Cm biosynthesis when a cloned copy of cmlK was introduced in trans into VS1111. Complementation of the mutant also indicated that inactivation of cmlK rather than a polar effect of the disruption on cmlS expression had interfered with dichloroacetyl biosynthesis. The deduced CmlS sequence resembled sequences of FADH2-dependent halogenases. Conjugal transfer of cmlK or cmlS into S. venezuelae cml-2, a chlorination-deficient strain with a mutation mapped genetically to the Cm biosynthesis gene cluster, did not complement the cml-2 lesion, suggesting that one or more genes in addition to cmlK and cmlS is needed to assemble the dichloroacetyl substituent. Insertional inactivation of ORF13 did not affect Cm production, and the products of ORF14 and ORF15 matched Streptomyces coelicolor A3(2) proteins lacking plausible functions in Cm biosynthesis. Thus cmlS appears to mark the downstream end of the gene cluster.

Amino Acid Sequence↗
PubMed2003

A neural network model of flexible spatial updating.

Neurons in many cortical areas involved in visuospatial processing represent remembered spatial information in retinotopic coordinates. During a gaze shift, the retinotopic representation of a target location that is fixed in the world (world-fixed reference frame) must be updated, whereas the representation of a target fixed relative to the center of gaze (gaze-fixed) must remain constant. To investigate how such computations might be performed, we trained a 3-layer recurrent neural network to store and update a spatial location based on a gaze perturbation signal, and to do so flexibly based on a contextual cue. The network produced an accurate readout of target position when cued to either reference frame, but was less precise when updating was performed. This output mimics the pattern of behavior seen in animals performing a similar task. We tested whether updating would preferentially use gaze position or gaze velocity signals, and found that the network strongly preferred velocity for updating world-fixed targets. Furthermore, we found that gaze position gain fields were not present when velocity signals were available for updating. These results have implications for how updating is performed in the brain.

Animals↗
PubMed2003

Phase III quality-of-life study results: impact on patients' quality of life to reducing xerostomia after radiotherapy for head-and-neck cancer--RTOG 97-09.

PURPOSE: To determine whether prevention of hyposalivation after curative radiotherapy (RT) to the head and neck improves patients' quality of life (QOL). METHODS AND MATERIALS: Patients were to receive at least 50 Gy to 50% of the volume of the major salivary glands, provide unstimulated and stimulated saliva samples, and complete the University of Washington head-and-neck QOL tool before RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5 mg or placebo q.i.d. RESULTS: A total of 249 patients was randomized between March 1998 and January 2000. Of these, 214 were eligible for QOL analysis. Patients were evenly distributed between arms by race, gender, tobacco use, tumor site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status of 90% was more common in the pilocarpine arm. Twenty percent of the patients on the pilocarpine arm and 29% of the patients on the placebo arm were taking nutritional supplements. The placebo arm patients had greater mouth pain and chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and 50%, respectively. Despite statistically significant (p = 0.047 and p = 0.049, respectively) preservation of salivary function in the pilocarpine arm, patients on the pilocarpine arm reported difficulties with swallowing (75%), activity (80%), hyposalivation (64%), and taste (81%). No difference was noted between arms at 3 months in mucositis scores, with both arms demonstrating increased requirement for oral nutrients. CONCLUSION: Objective prevention of hyposalivation did not affect patients' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT.

Female↗
PubMed2003

Metabolites of a blocked chloramphenicol producer.

Addition of p-aminophenylalanine (4), an advanced biosynthetic precursor of the antibiotic chloramphenicol (5), to a Streptomyces venezuelae pabAB mutant (VS629) restored chloramphenicol production and led to formation of the non-chlorinated analogue corynecin II (6) and four acetanilide derivatives: p-(acetylamino)phenylalanine (7), p-(acetylamino)benzyl alcohol (13), p-(acetylamino)benzoic acid (14), and p-(acetylamino)phenol (acetaminophen, 16). Metabolite structures were deduced from NMR and MS-MS data and established by chromatographic and spectroscopic comparisons with authentic samples. Reference compound 13 was synthesized by reducing the acid chloride of 14. Shunt pathways are proposed to account for the formation of the metabolites from p-aminophenylalanine.

4-Aminobenzoic Acid↗
PubMed2002

Biosynthesis of the dideoxysugar component of jadomycin B: genes in the jad cluster of Streptomyces venezuelae ISP5230 for L-digitoxose assembly and transfer to the angucycline aglycone.

Eight additional genes, jadX, O, P, Q, S, T, U and V, in the jad cluster of Streptomyces venezuelae ISP5230, were located immediately downstream of jadN by chromosome walking. Sequence analyses and comparisons implicated them in biosynthesis of the 2,6-dideoxysugar in jadomycin B. The genes were cloned in Escherichia coli, inactivated by inserting an apramycin resistance cassette with a promoter driving transcription of downstream genes, and transferred into Streptomyces venezuelae by intergeneric conjugation. Analysis by HPLC and NMR of intermediates accumulated by cultures of the insertionally inactivated Streptomyces venezuelae mutants indicated that jadO, P, Q, S, T, U and V mediate formation of the dideoxysugar moiety of jadomycin B and its attachment to the aglycone. Based on these results and sequence similarities to genes described in other species producing deoxysugar derivatives, a biosynthetic pathway is proposed in which the jadQ product (glucose-1-phosphate nucleotidyltransferase) activates glucose to its nucleotide diphosphate (NDP) derivative, and the jadT product (a 4,6-dehydratase) converts this to NDP-4-keto-6-deoxy-D-glucose. An NDP-hexose 2,3-dehydratase and an oxidoreductase, encoded by jadO and jadP, respectively, catalyse ensuing reactions that produce an NDP-2,6-dideoxy-D-threo-4-hexulose. The product of jadU (NDP-4-keto-2,6-dideoxy-5-epimerase) converts this intermediate to its L-erythro form and the jadV product (NDP-4-keto-2,6-dideoxyhexose 4-ketoreductase) reduces the keto group of the NDP-4-hexulose to give an activated form of the L-digitoxose moiety in jadomycin B. Finally, a glycosyltransferase encoded by jadS transfers the activated sugar to jadomycin aglycone. The function of jadX is unclear; the gene is not essential for jadomycin B biosynthesis, but its presence ensures complete conversion of the aglycone to the glycoside. The deduced amino acid sequence of a 612 bp ORF (jadR*) downstream of the dideoxysugar biosynthesis genes resembles many TetR-family transcriptional regulator sequences.

Amino Acid Sequence↗