Biomedical subjects
Publications and source records attributed to D L Hughes.
We report the first racemic and stereoselective synthesis of cis- and trans-N-alkylaziridines viaN-chloroamines; using this methodology an N-3,4,5-trimethoxybenzylaziridine was synthesised and efficiently cleaved, affording the corresponding NH aziridine in high yield.
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The reaction of ethoxycarbonylpyrrole-2-thiocarboxamide with sodium hydroxide affords the known title compound, C(5)H(6)N(2)S, whose structure shows a three-dimensional hydrogen-bonded lattice.
[reaction: see text]. A highly regioselective Friedländer reaction is described. By introduction of a phosphonate group at one of the alpha-carbons of a ketone, regioselectivity can be perfectly controlled.
Crystalline alpha-D-galacturonic acid monohydrate has been studied by 13C CPMAS NMR and X-ray crystallography. The molecular dynamics were investigated by evaluating 13C spin-lattice relaxation in the rotating frame (T1rho) and chemical-shift-anisotropy properties of each carbon. Only limited molecular motions can be detected in the low frequency (< 10(4) Hz) range by 13C relaxation time measurements (T1rho) and changes of chemical shift anisotropy properties as a function of temperature. X-ray analysis (at both ambient temperature and 150 K) shows that the acid has the usual chair-shaped, pyranose ring conformation, and that the acid and water molecules are linked, through all their O-H groups, in an extensively hydrogen-bonded lattice.
Addition of the amino acids threonine, serine, proline, and arginine to fermentations of the fungus Glarea lozoyensis influenced both the pneumocandin titer and the spectrum of analogues produced. Addition of threonine or serine altered the levels of the "serine analogues" of pneumocandins B(0) and B(5) and allowed for their isolation and identification. Proline supplementation resulted in a dose-dependent increase in the levels of pneumocandins B(0) and E(0), whereas pneumocandins C(0) and D(0) decreased as a function of proline level. Moreover, proline supplementation resulted in an overall increase in the synthesis of both trans-3- and trans-4-hydroxyproline while maintaining a low trans-4-hydroxyproline to trans-3-hydroxyproline ratio compared to the unsupplemented culture. Pneumocandin production and the synthesis of hydroxyprolines was also affected by addition of the proline-related amino acid arginine but not by the addition of glutamine or ornithine. Zinc, cobalt, copper, and nickel, trace elements that are known to inhibit alpha-ketoglutarate-dependent dioxygenases, affected the pneumocandin B(0) titer and altered the levels of pneumocandins B(1), B(2), B(5), B(6), and E(0), analogues that possess altered proline, ornithine, and tyrosine hydroxylation patterns.
Method development and validation studies have been completed on an assay that will allow the determination of 2,4-dichlorophenoxyacetic acid (2,4-D) in human urine. The accurate determination of 2,4-D in urine is an important factor in monitoring worker and population exposure. These studies successfully validated a method for the detection of 2,4-D in urine at a limit of quantitation (LOQ) of 5.00 ppb (parts per billion) using gas chromatography with mass selective detection (GC/MSD). The first study involved the determination of 2,4-D in control human urine and urine samples fortified with 2,4-D. Due to chromatographic interference, a second study was conducted using 14C-2,4-D to verify the recoverability of 2,4-D from human urine at low levels using the GC/MSD method. The second study supports the results of the original data. The 2,4-D was extracted from human urine using a procedure involving hydrolysis using potassium hydroxide, followed by a liquid-liquid extraction into methylene chloride. The extracted samples were derivatized with diazomethane. The methylated fraction was analyzed by GC/MSD. Quantitation was made by comparison to methylated reference standards of 2,4-D. Aliquots fortified at 5-, 50-, and 500-ppb levels were analyzed. The overall mean recovery for all fortified samples was 90.3% with a relative standard deviation of 14.31%.
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[formula: see text] A short synthesis of carbapenem 1 is described. They key step involves the cross-coupling of an enol triflate with an amino-substituted sp3 carbon. This cross-couping, which allows the introduction of the complete side chain in one step, utilizes a stannatrane as the heteroalkyl transfer reagent.
Electrochemical oxidation of the hydrosulfide cluster [Fe4S4(SH)4]2- on gold, platinum or vitreous carbon in a methyl cyanide electrolyte leads to the growth of a conducting film. Spectroscopic and other evidence suggests that the film has cubane centres, predominately in the [4Fe4S]3+ oxidation state, which are linked by disulfide ligands to give an anionic array of [Fe4S4(S approximately)4]n- units. X-ray data suggests some long-range order in the electrode material. The polyferredoxin binds redox active cations consistent with an anionic array.
Crystalline 1beta-methyl-2-formyl carbapenem pNB esters were prepared by osmium-mediated oxidative cleavage of the corresponding 2-vinyl derivatives. Reduction of the 2-formyl compounds gave the corresponding 2-hydroxymethyl derivatives, which are key intermediates for the anti-MRS carbapenem candidate (1).
BACKGROUND: The HPA-1 system is carried on the beta3 integrin. HPA-1a (Zw(a), Pl(A1)) is immunogenic in an HPA-1b homozygote (HPA-1b1b). In pregnancy, 1 of 365 women forms anti-HPA-1a, which causes severe thrombocytopenia in 1 in 1100 neonates. Identification of women at risk of forming anti-HPA-1a and the screening of donors to obtain HPA-1a-negative platelets for therapy need reliable, low-cost, automated assays. STUDY DESIGN AND METHODS: A diabody with dual specificity for HPA-1a x D and an IgG1 anti-HPA-1a have been constructed by the use of the genes encoding the first anti-HPA-1a fragment. With these reagents, two complementary HPA-1a phenotyping assays have been developed. RESULTS: This diabody was used in a simple hemagglutination technique to perform HPA-1a phenotyping on soluble glycoprotein IIb/IIIa from EDTA plasma samples. Over 1000 unselected donors have been correctly HPA-1a-phenotyped by use of the diabody. The human recombinant IgG1 anti-HPA-1a was produced in a rat myeloma cell line and was fluorescein labeled for use in a whole-blood flow cytometric HPA-1a phenotyping assay. This IgG1 anti-HPA-1a shows a clear differential between HPA-1a-positive and HPA-1a-negative platelets at nM antibody concentrations. CONCLUSIONS: The two recombinant reagents described are highly suitable for screening and confirmatory HPA-1a phenotyping. They permit rapid determination of the HPA-1a phenotype and are amenable to automation.
The aim of this investigation was to compare in a prospective randomized study the outcome of painful, traumatic knee injuries when treated with either the modified Robert Jones (MRJB) or elastic support bandage (ESB). Patients with moderate or severe unilateral knee injury presenting to our department within 24 h were randomized into two treatment groups receiving either the MRJB or an ESB. The main outcome parameters of the study were the amount of pain relief required, the speed of recovery, mobility and patient preference. The results of our study of 40 patients indicate that the two treatments were equally effective in treating knee sprains, and patients preferred the ESB in the early post-injury period. Therefore, we see no reason to continue using the MRJB for the treatment of sprained knees in the accident and emergency (A&E) setting when a more patient acceptable, time and cost-effective treatment is available.
OBJECTIVE: Professional skepticism and concerns regarding diagnostic reliability hinder research in dissociative disorders and multiple personality disorder. The reported frequency of multiple personality disorder in different psychiatric settings ranges from 2.4% to 35%. The authors conducted a replication study of multiple personality disorder ascertainment in women admitted to a state hospital over a 5.5-month period. METHOD: Responses to the Dissociative Experiences Scale and to the Dissociative Disorders Interview Schedule were obtained, along with data on length of stay, county of admission referral, admission commitment status, and discharge diagnoses, for 176 female inpatients in a state hospital. Of 421 women representing 483 consecutive admissions, 121 were discharged before they could be assessed for study, 64 were excluded, 60 declined to participate, 176 enrolled in the study, and 175 completed the research procedures. RESULTS: Twenty-one women (12%) met criteria for multiple personality disorder based on the Dissociative Disorders Interview Schedule; these women were significantly younger than the women without multiple personality disorder. Scores on the Dissociative Experiences Scale of the women with multiple personality disorder (mean = 59.5, SD = 19.6) were significantly higher than the scores of women without multiple personality disorder (mean = 22.5, SD = 20.1), but considerable overlap occurred. There was no significant difference between groups in length of stay or admission status. CONCLUSIONS: The authors conclude that 1) the wide variability in multiple personality disorder detection is partially due to site-specific ascertainment biases and 2) despite its apparent usefulness for screening purposes, the Dissociative Experiences Scale requires more comprehensive evaluation before it can be applied broadly.
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Eukaryotic protein synthesis initiation factor (eIF)-4C was purified from wheat germ and the molecular weight was calculated to be approximately 19,000 by SDS-polyacrylamide gel electrophoresis. A similar molecular weight was determined by gel filtration chromatography indicating that wheat germ eIF-4C is functional as a single polypeptide chain. An efficient in vitro translation system dependent upon the addition of eIF-4C was developed. This system was used to determine the concentrations of eIF-4C required for the half-maximal rate of translation of satellite tobacco necrosis virus RNA, alfalfa mosaic virus RNA 4, and barley alpha-amylase mRNA. No significant differences in the concentrations of eIF-4C required for the translation of these mRNAs were observed, although differences were noted for eIF-4A and eIF-4F. This finding suggests that eIF-4C is not involved in the binding of mRNA to 40 S ribosomal subunits. In heterologous assays, rabbit reticulocyte eIF-4C was as active as wheat germ eIF-4C in the wheat germ eIF-4C-dependent system. In addition, wheat germ eIF-4C substituted for rabbit reticulocyte eIF-4C in in vitro assay systems from rabbit reticulocytes. These results indicate that eIF-4C from wheat and rabbit contain conserved functional domains.
In this report, it is shown that eIF-4B exhibits ATP hydrolysis activity in a ribosome-dependent fashion. This activity is significantly enhanced by the addition of eIF-4A and eIF-4F, although neither of these factors, alone or together, display a significant ribosome-dependent ATPase activity. Sepharose-6B gel filtration experiments with combinations of nonlabeled and 14C reductively methylated initiation factors (eIF-4A, eIF-4B, eIF-4F, and eIF-3) provide evidence that both eIF-4B and eIF-4F, but not eIF-4A, interact with ribosomes in the presence of specific factors and ATP. It is not known with which ribosomal subunit(s) these factors interact. In ultraviolet radiation-induced crosslinking studies, an eIF-4A and/or eIF-4F and ATP-dependent crosslinking of eIF-4B to radiolabeled oligo(A)12-18 was observed. Past studies with oxidized-cap mRNA achieved cross-linking of all three of these factors, driven by the specific interaction of eIF-4F p24 with the m7GTP cap structure; this is the first reported instance of only eIF-4B cross-linking to RNA.
Social phobia was studied in a North Carolina community, using DSM-III criteria. Two kinds of comparison were made: social phobia v. non-social phobia, and comorbid social phobia v. non-comorbid social phobia. Six-month and lifetime prevalence rates were 2.7 and 3.8% respectively. Social phobia had an early onset, lasted a long time and rarely recovered. Predictors of good outcome recovery in a logistic regression analysis were onset of phobia after age 11, absence of psychiatric comorbidity and greater education. The disorder was often missed in medical consultation. Increased rates of psychiatric comorbidity existed, especially for other anxiety disorders and for schizophrenia/schizophreniform disorder. There was increased risk of neurological disorder. Social phobia was also associated with an increased rate of suicide attempts, antisocial behaviour and impaired school performance during adolescence, impaired medical health, increased health-seeking behaviour, poor employment performance, reduced social interaction and impaired social support. Comorbidity accounted for some, but not all observed differences.