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Biomedical subjects

M Barber

Publications and source records attributed to M Barber.

At least 19 recordsLinked to original sources

Formation of [b(n) + 17 + Ag]+ product ions from Ag+ cationized native and acetylated peptides.

We compared the tandem mass spectra of a range of native and acetylated Ag(+) cationized peptides to determine the influence of the derivatization step on the abundance of the [b(n) + 17 + Ag](+) product ions. Using tripeptides, the smallest for which the mechanisms to generate [b(2) - 1 + Ag](+) and [b(2) + 17 + Ag](+) products are both operative, we found that in most cases acetylation causes an increase in the abundance of the C-terminal rearrangement ion, [b(2) + 17 + Ag](+), relative to the rival N-terminal rearrangement ion, [b(2) - 1 + Ag](+). The presence of a free amino group to bind to the metal ion significantly influences the relative abundances of the product ions. We propose a mechanism for the formation of the [b(n) + 17 + Ag](+) that is based on the formation of a five-membered oxazolidin-5-one and tetrahedral carbon intermediate that may collapse to a peptide upon release of CO and an imine, aided by the fact that the ring formed during C-terminal rearrangement is both a hemiacylal and hemiaminal. We also identified an influence of amino acid sequence on the relative abundances of the [b(n) + 17 + Ag](+) and [b(n) - 1 + Ag](+) product ions, whereby bulky substituents located on the alpha-carbon of the amino acid to the C-terminal side of the cleavage site apparently promote the formation of the [b(n) + 17 + Ag](+) product over [b(n) - 1 + Ag](+) when the amino acid to the N-terminal side of the cleavage site is glycine. The latter ion is the favored product, however, when the bulky group is positioned on the alpha-carbon of the amino acid to the N-terminal side of the cleavage site.

Journal Article↗

The incidence of severe physical child abuse in Wales.

OBJECTIVES: The purposes of this study were: (1) to ascertain the incidence and nature of severe physical child abuse in Wales; (2) to ascertain the incidence of all physical abuse in babies under 1 year of age; and (3) to determine whether child protection registers (CPR) accurately reflect the numbers of children who are physically abused. METHODS: This is a population-based incidence study based in Wales, UK, for 2 years from April 1996 through March 1998. Children studied were under the age of 14 with severe physical abuse consistent with the criminal law level of Grievous Bodily Harm. This included seven categories of injury (death; head injury including subdural hemorrhage; internal abdominal injury; physical injury in Munchausen Syndrome by Proxy including suffocation; fracture; burn or scald; adult bite). Cases were ascertained by a pediatrician surveillance reporting system (WPSU). A criterion for inclusion was multidisciplinary agreement that physical abuse had occurred (at case conference, strategy meeting, or Part 8 Review). The incidence of all babies under 1 year of age with physical abuse was also studied. Ascertainment of babies under the age of 1 year was undertaken from CPR as well as the WPSU. RESULTS: Severe abuse is six times more common in babies [54/100,000/year (95% CI +/- 17.2)] than in children from 1 year to 4 years of age [9.2/100,000 (95% CI +/- 3.6)]. It is 120 times more common than in 5- to 13-year-olds [0.47/100,000 (95% CI +/- 0.47)]. This is mainly because two types of serious abuse (brain injury including subdural hemorrhage and fractures) are more common in babies under the age of 1 year than older children. Using data from two sources (the WPSU and CPRs), the incidence of physical abuse in babies is 114/100,000 (CI 114 +/- 11.8) per year. This equates to 1 baby in 880 being abused in the first year of life. The largely rural Health Authority area in Wales had incidence figures for abuse in babies that were 50% of the three other predominantly urban Health Authority areas. Boys throughout the series were more at risk of being severely abused than girls (p < .025). Only 29% of the babies under 1 year of age on the CPR had actually been injured. Thirty percent of abused babies under the age of 1 year and 73% of severely abused children over the age of 1 year had caused previous concern to health professionals regarding abuse or neglect. CONCLUSIONS: Physical abuse is a significant problem in babies under the age of 1 year. Very young babies (under 6 months old) have the highest risk of suffering damage or death as a result of physical abuse. Severe abuse, in particular subdural hematoma and fracture, is much more common in babies than in older children. There is evidence of failure of secondary prevention of child abuse by health professionals, with a greater need to act on concerns regarding abuse and neglect. Interagency child protection work in partnership with parents should focus more on protecting babies under age 1 year from further abuse than on maintenance of the infant within an abusive home. The CPR is not intended as an accurate measure of children suffering abuse. It is a record of children requiring a child protection plan and must not be used as a measure of numbers of abused children.

Abdominal Injuries↗

Ecological forecasts: an emerging imperative.

Planning and decision-making can be improved by access to reliable forecasts of ecosystem state, ecosystem services, and natural capital. Availability of new data sets, together with progress in computation and statistics, will increase our ability to forecast ecosystem change. An agenda that would lead toward a capacity to produce, evaluate, and communicate forecasts of critical ecosystem services requires a process that engages scientists and decision-makers. Interdisciplinary linkages are necessary because of the climate and societal controls on ecosystems, the feedbacks involving social change, and the decision-making relevance of forecasts.

Agriculture↗

Incidence and inheritance of resistance to METI-acaricides in European strains of the two-spotted spider mite (Tetranychus urticae) (Acari: Tetranychidae).

A strain of Tetranychus urticae (Koch; Acari: Tetranychidae), collected from hops (Humulus humuli L; Cannabaceae) in England with a short history of tebufenpyrad use, exhibited resistance to four METI (mitochondrial electron transport inhibitor)-acaricides; tebufenpyrad, pyridaben, fenazaquin and fenpyroximate. Resistance factors for these compounds in a microimmersion assay were 46, 346, 168 and 77 respectively, and corresponded to those exhibited by a Japanese METI-acaricide-resistant reference strain. Levels of resistance remained stable without further selection, and selection with tebufenpyrad did not increase them. The UK strain was also resistant (c 6-fold) to bifenthrin. Crosses of homozygous, diploid females with hemizygous, haploid males showed that, in the UK strain, METI-acaricide resistance was paternally and maternally inherited, and was an incompletely dominant trait. Another tebufenpyrad-resistant strain from the UK, originating from a chrysanthemum nursery (Chrysanthemum foeniculaceum Giseke; Asteraceae) was collected eight months later at a site c 210 km distant from the first. These are the first published incidences of METI-acaricide resistance in Europe and implications for the future use of these compounds are discussed.

Animals↗

Mass-directed fractionation and isolation of pharmaceutical compounds by packed-column supercritical fluid chromatography/mass spectrometry.

An automated packed-column semi-preparative supercritical fluid chromatography/mass spectrometry (SFC/MS) system incorporating mass-directed fraction collection has been designed and implemented as an alternative to preparative HPLC and preparative HPLC/MS (PrepLC/MS) for the purification of pharmaceutical compounds. The system incorporates a single quadrupole mass spectrometer and a supercritical fluid chromatograph. Separations were achieved using a binary solvent system consisting of carbon dioxide and methanol. Purification of SFC-separated compounds was achieved incorporating mass-directed fraction collection, enabling selective isolation of the target molecular weight compound and eliminating the collection of undesired compounds (e.g., by-products, excess starting materials, etc.). Cross contamination between fractions and recoveries of the system were investigated. Mass spectrometer ionization with basic mobile additives is discussed, and examples of preparative SFC/MS chiral separations are presented. Early experiences suggest SFC will be a powerful and complementary technique to HPLC for the purification of pharmaceutical compounds.

Carbon Dioxide↗

Systematic reviews.

Explore the source record for details and available documents.

Databases, Factual↗

Development of cloned embryos from adult rabbit fibroblasts: effect of activation treatment and donor cell preparation.

This research was to study the in vitro and in vivo development of cloned embryos derived from adult rabbit fibroblasts following various activation protocols. Effects of serum starvation and passage number of donor cells on the efficiency of cloning were also examined. In experiment I, oocytes were activated either by electric pulses or by electric pulses followed by culture with 6-dimethylaminopurin (DMAP). For experiment II, the best activation protocol from experiment I was employed for cloning using adult rabbit fibroblasts that were cultured for 0-15 passages. In experiment III, the effect of serum starvation of the donor cells on cloning was examined. Finally, in experiment IV, embryo transfers were conducted. These experiments showed that combined electrical pulse and DMAP treatment resulted in superior parthenogenetic blastocyst development (up to 29%), and that activation of the cytoplast before versus after fusion was not different in supporting the in vitro development of nuclear transferred embryos (16%-18% blastocysts). Adult fibroblasts derived from nonpassaged cells were less capable of developing into blastocysts than passaged cells (6% vs. 17%). Serum starvation of donor cells improved cleavage (up to 71%) but did not improve blastocyst development (13%), and no progeny was obtained, irrespective of the treatment. Cell-cycle analysis of adult rabbit fibroblast cells showed that passage 6 and 12 cells were more likely to be in G(0)/G(1) than passage 0 cells, which agrees with the improved embryo development in the passaged-cell groups.

Adenine↗

Six cloned calves produced from adult fibroblast cells after long-term culture.

Cloning whole animals with somatic cells as parents offers the possibility of targeted genetic manipulations in vitro such as "gene knock-out" by homologous recombination. However, such manipulation requires prolonged culture of nuclear donor cells. Previous successes in cloning have been limited to the use of cells collected either fresh or after short-term culture. Therefore, demonstration of genetic totipotency of cells after prolonged culture is pivotal to combining site-specific genetic manipulations and cloning. Here we report birth of six clones of an aged (17-year-old) Japanese Black Beef bull using ear skin fibroblast cells as nuclear donor cells after up to 3 months of in vitro culture (10-15 passages). We observed higher developmental rates for embryos derived from later passages (10 and 15) as compared with those embryos from an early passage (passage 5). The four surviving clones are now 10-12 months of age and appear normal, similar to their naturally reproduced peers. These data show that fibroblasts of aged animals remain competent for cloning, and prolonged culture does not affect the cloning competence of adult somatic donor cells.

Animals↗

Abnormalities of flavin monooxygenase as an etiology for sideroblastic anemia.

We postulated that a deficiency of flavin monooxygenase (FMO)-a ferrireductase component of cells-could produce sideroblastic anemia. FMO is an intracellular ferrireductase which may be responsible for the obligatory reduction of ferric to ferrous iron so that reduced iron can be incorporated into heme by ferrochelatase. Abnormalities of this mechanism could result in accumulation of excess ferric iron in mitochondria of erythroid cells to produce ringed sideroblasts and impair hemoglobin synthesis. To investigate this hypothesis we obtained blood from patients with sideroblastic anemia and normal subjects. Extracts of peripheral blood lymphocytes were used to measure ferrireduction by utilization of NADPH. Lymphoid precursors are reported to accumulate iron in mitochondria similarly to erythroid precursors. Utilization of lymphoid precursors avoided the need for bone marrow aspirations. We studied three patients with sideroblastic anemia. One patient and his asymptomatic daughter had a significant decrease in ferrireductase activity. They also had markedly diminished concentrations of FMO in lymphocyte protein extracts on Western blots. This was accompanied by increased concentration of mobilferrin in the extracts. These results suggest that abnormalities of FMO and mobilferrin may cause sideroblastic anemia and erythropoietic hemochromatosis in some patients.

Aged↗

Human cholecystokinin-A receptor is not an oncofetal protein.

The CCK-A (cholecystokinin-A) receptor is selectively expressed by human pancreatic adenocarcinomas, suggesting a possible role in pancreatic tumorigenesis. In animals, pancreatic CCK receptor expression varies during ontogeny and neoplastic transformation. This study examined the temporal expression of CCK receptors in human fetal, postnatal, and adult pancreas to determine whether the appearance of CCK-A receptors in pancreatic adenocarcinomas reflected oncofetal antigen or pancreatic neoantigen expression. Messenger ribonucleic acid (mRNA) was isolated from six paraffin-embedded normal pancreatic autopsy specimens ranging in age from 17 weeks postfertilization through 26 days following full-term delivery, and samples of adult human tissues, including pancreas and pancreatic adenocarcinoma. Using reverse transcription-polymerase chain reactions, CCK-B receptor mRNA was expressed in all specimens of normal fetal and postnatal human pancreas, adult pancreas, and pancreatic adenocarcinomas. CCK-A receptor mRNA was selectively expressed only in pancreatic adenocarcinomas. These data suggest that selective CCK-A receptor expression in pancreatic adenocarcinomas reflects neoantigen expression in humans.

Adenocarcinoma↗

Double crystals.

The lowest-energy way to enclose and separate two planar regions of prescribed areas is found, where the energy is given by the l1 norm ('Manhattan metric'), in which horizontal and vertical directions use less energy than other directions, as in some crystals. With the assumption that interfaces carry a fraction lambda of the energy of exterior faces, it is proved that there are three possible types of energy-minimizing double crystals. The dependence of these three types of lambda as well as the ratio of the areas of the two regions is discussed, and some paths for further study are suggested.

Journal Article↗

The superposition of a temporally incoherent magnetic field inhibits 60 Hz-induced changes in the ODC activity of developing chick embryos.

Previously, we have shown that the application of a weak (4 microT) 60 Hz magnetic field (MF) can alter the magnitudes of the ornithine decarboxylase (ODC) activity peaks which occur during gastrulation and neurulation of chick embryos. We report here the ODC activity of chick embryos which were exposed to the superposition of a weak noise MF over a 60 Hz MF of equal (rms strength). In contrast to the results we obtain with a 60 Hz field alone, the activity of ODC in embryos exposed to the superposition of the incoherent and 60 Hz fields was indistinguishable from the control activity during both gastrulation and neurulation. This result adds to the body of experimental evidence which demonstrates that the superposition of an incoherent field inhibits the response of biological systems to a coherent MF. The observation that a noise field inhibits ODC activity changes is consistent with our speculation that MF-induced ODC activity changes during early development may be related to MF-induced neural tube defects at slightly later stages (which are also inhibited by the superposition of a noise field).

Animals↗

Use of guanylyl cyclase C for detecting micrometastases in lymph nodes of patients with colon cancer.

INTRODUCTION: Guanylyl cyclase C appears to be expressed only in colorectal cancer cells in extraintestinal tissues. Thus, guanylyl cyclase C may be useful as a marker to detect colorectal cancer micrometastases not detectable by histopathology in lymph nodes of patients. METHODS: Twelve patients with colon adenocarcinoma, Dukes Stages A through C2, and one patient with a tubulovillous adenoma were included in this study. Forty-two lymph nodes were collected from fresh surgical specimens, and each was examined by histopathology and reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers. Histopathology identified colon cancer cells in 6 of 16 lymph nodes from five Dukes Stage C patients but not in lymph nodes from the patient with a tubulovillous adenoma, the Dukes Stage A patient, or six Dukes Stage B patients. Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers was performed on all 42 lymph nodes. RESULTS: Guanylyl cyclase C messenger RNA was not detected by reverse transcription followed by polymerase chain reaction in lymph nodes from the patient with the tubulovillous adenoma or the patient with Dukes Stage A colon carcinoma. Seven lymph nodes from Dukes Stage C patients revealed guanylyl cyclase C messenger RNA including six lymph nodes containing histopathologically confirmed metastases. Of significance, guanylyl cyclase C messenger RNA was detected in 6 of 21 lymph nodes from Dukes Stage B patients. Indeed, clinical staging of two patients could be upgraded from B to C using reverse transcription followed by polymerase chain reaction and guanylyl cyclase C-specific primers. CONCLUSION: Reverse transcription followed by polymerase chain reaction using guanylyl cyclase C-specific primers might be useful to more accurately assess micrometastases in lymph nodes of colorectal cancer patients undergoing disease staging.

Adenocarcinoma↗

Resistance training frequency: strength and myosin heavy chain responses to two and three bouts per week.

Seventeen subjects performed resistance training of the leg extensor and flexor muscle groups two (2/wk) or three (3/wk) times per week. Changes in the relative myosin heavy chain (MHC) isoform contents (I, IIa and IIx) of the vastus lateralis and isometric, isokinetic and squat-lift one-repetition maximum (1 RM) strength were compared between conditions after both a common training period (6 weeks) and number of training sessions (18). After 6 weeks and 18 sessions (9 weeks for the 2/wk group), increments in 1RM strength for the 3/wk and 2/wk groups were similar [effect size (ES) differences approximately 0.3, 3/wk > 2/wk], whereas the 2/wk group presented greater isokinetic (ES differences = 0.3-1.2) and isometric (ES differences approximately 0.7) strength increases than the 3/wk condition. A significant (P < 0.05) increase in MHC IIa percentage was evident for the 2/wk group after 18 sessions. Both training groups exhibited a trend towards a reduction in the relative MHC IIx and an increase in MHC IIa contents (ES range = 0.5-1.24). However, correlations between changes in the strength and MHC profiles were weak (r2: 0.0-0.5). Thus, isometric and isokinetic strength responses to variations in training frequency differed from 1RM strength responses, and changes in strength were not strongly related to alterations in relative MHC content.

Adolescent↗