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Biomedical subjects

M A Walker

Publications and source records attributed to M A Walker.

At least 19 recordsLinked to original sources

Synthesis of a novel C-10 spiro-epoxide of paclitaxel.

New analogues of paclitaxel (1a, active constituent of Taxol) were synthesized containing an epoxide at the C-10 position. The introduction of the epoxide was carried out by selective removal of the C10-acetate followed by protection of the C2'- and C7-hydroxyl groups. After oxidation to yield a ketone at the C10-position, this intermediate was reacted with dimethylsulfonium ylide. Deprotection and further manipulations provide the C10-spiro epoxide of paclitaxel (1b) and the corresponding C7-MOM ether (1c).

Antineoplastic Agents, Phytogenic↗

Simple sequence repeat analysis of a clonally propagated species: a tool for managing a grape germplasm collection.

The USDA germplasm repositories help to preserve the genetic variability of important crop species by collecting and maintaining representative cultivars and related germplasm. Simple sequence repeat markers with high allelic diversity were used to type 41 grapevines from 40 accessions. All vines were either seedless table grape cultivars or cultivars with names similar to table grape cultivars. The proportion of shared alleles was selected as the most appropriate statistical measure of genetic distance for this population. In conjunction with morphological traits, known synonyms were confirmed and a previously unknown synonym was discovered. An alleged synonym in the literature was disproved by the DNA data. The data were consistent with known parentage, where such data were available. Two mislabeled vines in the USDA collection were identified. UPGMA grouped the cultivars loosely into three groups: a group of nine mostly Middle Eastern cultivars, a group of 22 accessions mostly from Russia and Afghanistan that were morphologically similar to 'Thompson Seedless', and a third very loose group of 11 accessions consisting mostly of eastern European wine grape cultivars. The limitations and usefulness of this type of analysis are discussed.

Alleles↗

Biology and management of grape phylloxera.

Grape phylloxera, Daktulosphaira vitifoliae (Homoptera: Phylloxeridae), is a worldwide pest of grapevines. Its life cycle has sexual and asexual portions with forms that feed from leaf and root galls. Not all forms occur throughout the insect's range. Root forms predominate on Vitis vinifera cultivars; leaf forms predominate on other Vitis species characteristic of the American native range. Other conditions influence expression of the life cycle. Hosts and conditions similarly affect life table performance. Damage to grapevines is by secondary soilborne pathogens attacking the feeding site and by physiological interaction of the insect with the grapevine, though the latter has not been well studied. Resistant rootstocks derived from native American Vitis are the primary control tool. The insect varies genetically and relative to performance on hosts. Use of insecticides is limited in effect, and other control methods are not proven. More research on the biology, ecology, and management of phylloxera is needed.

Animals↗

Schizophrenia and the frontal lobes: post-mortem stereological study of tissue volume.

BACKGROUND: It has been suggested that there is frontal lobe involvement in schizophrenia, and that it may be lateralised and gender-specific. AIMS: To clarify the structure of the frontal lobes in schizophrenia in a post-mortem series. METHOD: The volume of white matter and cortical components of the frontal lobes was measured in brains of controls and patients with schizophrenia using planimetry and the Cavalieri principle. The components measured were: superior frontal gyrus, middle frontal gyrus, a composite of inferior frontal gyrus and orbito-frontal cortex, as well as total frontal lobe cortex and white matter. In addition, the anterior cingulate gyrus was measured. RESULTS: No diagnosis, gender, diagnosis x side, diagnosis x gender or diagnosis x gender x side interactions were observed in the volume of any of the components, the grey matter as a whole or the white matter. No evidence for volumetric inter-group differences was found for the anterior cingulate gyrus. CONCLUSIONS: Such structural abnormalities as are present in the frontal lobes are more subtle than straightforward alterations in tissue volume; they may include changes in shape and the pattern of gyral folding.

Adult↗

Seasonal capacity of attached and detached vineyard roots to support grape phylloxera (Homoptera: Phylloxeridae).

Field experiments were conducted to evaluate population densities and survival, developmental rate, and fecundity of grape phylloxera, Daktulosphaira vitifoliae (Fitch), as influenced by root attachment or detachment from mature, field-grown, Vitis vinifera L. grapevines through the growing season. Experiments were performed using artificial infestations of California biotype A grape phylloxera. Thirty-day bioassays on attached- and detached-roots were repeated monthly from May to September in 1997 (cultivar 'Carignane') and April to September in 1998 (cultivar 'Thompson Seedless'). The bioassays showed that attached roots had lower population densities than detached roots in all months of both years. Densities varied by month, tending to be higher in spring than in summer. Of the population parameters studied, survival was most influenced by attachment condition, being higher on detached than on attached roots by up to 25-fold. These results imply the importance of vine-related mortality factors to grape phylloxera population density. Influence of root attachment condition on developmental rate and fecundity was not uniform across bioassay months for either year; however, in the four out of 21 assays where there was a significant difference it favored detached roots by twofold. Fruit harvest resulted in higher survival in the July assay but not for assays in August and September; however, neither developmental rate nor fecundity was affected by harvest in any ofthe assays. We conclude that mortality rather than nutritional factors are most limiting for field populations on susceptible vines. This work suggests that detachment of roots as occurs with root girdling by root pathogens may increase grape phylloxera populations on infested, susceptible vines. These results imply that excised root bioassays over-estimate grape phylloxera virulence and underestimate rootstock resistance.

Animals↗

A two-component pericyclic reaction for synthesis of substituted benzofurans and aryl-quaternary carbon bonds.

The reaction shown is presumed to be a new [3,3]-sigmatropic rearrangement involving an O-arylsulfoxonium species or related sulfurane. It allows a sulfoxide and a phenol to be joined and rearranged in one operation at or below room temperature, coupling an aromatic to a quaternary carbon and creating benzofurans or articulated dihydrobenzofurans in a number of examples.

Journal Article↗

A null mutation in HLA-G is not associated with preeclampsia or intrauterine growth retardation.

Modulation of the expression of genes of the major histocompatibility complex (MHC) in tissues at the maternal-fetal interface almost certainly plays a role in successful development of the semi-allogeneic fetus. While expression of the classical class I genes (HLA-A, B, C) is low to non-existent at this site, the non-classical molecule, HLA-G, is expressed uniquely in fetal cells at the maternal-fetal interface. The recent demonstration that homozygotes for a deletion mutation in exon 3 (1597DeltaC) of HLA-G do not express the full-length HLA-G1 isoforms indicates a potential reduction in expression of this isoform in heterozygotes. If the full-length isoform of HLA-G (i.e. HLA-G1) contributes to proper invasion of maternal spiral arteries by extravillous cytotrophoblast, then 1597DeltaC heterozygotes could be at increased risk for disorders of trophoblast invasion. Two populations, infants with intrauterine growth retardation (IUGR) and infants of preeclamptic (PE) mothers, were genotyped for the 1597DeltaC polymorphism. The frequency of 1597DeltaC in these samples was not significantly different from healthy controls, suggesting that heterozygotes for this deletion mutation are not at significantly increased risk for PE or IUGR (P = 0.727 and 0.803, respectively).

Adolescent↗

The cost effectiveness of larval therapy in venous ulcers.

The treatment of necrotic ulcers involves considerable nursing time and expense. The current standard treatment involves repeated application of hydrogels. Larval debridement therapy (LDT) has been shown anecdotally to clear ulcers of necrotic slough but has never been compared directly with 'modern' therapies. The aim of this study has been to compare LDT with hydrogel dressings in the treatment of necrotic venous ulcers. 12 patients with sloughy venous ulcers were randomised to receive either LDT or the control therapy--a hydrogel. Effective debridement occurred with a maximum of one larval application in 6/6 patients. 4/6 patients [corrected] in the hydrogel group still required dressings at one month. The median cost of treatment of the larval group was 78.64 Pounds compared with 136.23 Pounds for the control treatment group (p < 0.05). The study confirms both the clinical efficacy and cost effectiveness of larval therapy in the debridement of sloughy venous ulcers.

Adult↗

Anomalous asymmetry of fusiform and parahippocampal gyrus gray matter in schizophrenia: A postmortem study.

OBJECTIVE: Anomalies of structure and asymmetry of the parahippocampal gyrus (origin of the perforant path input to the hippocampal formation in the medial temporal lobe) have been shown in some postmortem studies of schizophrenia, but previous studies have not included the fusiform gyrus (which may have a role in facial recognition and naming), adjacent to the parahippocampal gyrus on the ventral occipitotemporal surface. METHOD: The volumes of gray matter in the left and right parahippocampal and fusiform gyri were assessed with a stereological point-counting technique in the temporal lobes from formalin-fixed brains of 27 comparison subjects and 31 patients with schizophrenia. Age was a covariate and gender was a factor in the analysis. RESULTS: In relation to the comparison subjects, the schizophrenic patients (both sexes) had lower volumes of both the parahippocampal and fusiform gyri on the left side. For both structures a left-greater-than-right volume asymmetry was present in the comparison subjects, but this asymmetry was reversed in the parahippocampal and fusiform gyri of the schizophrenic patients. A sex difference was present with respect to age at onset-degree of anomaly of asymmetry for both gyri increased with age at onset in men but not in women. CONCLUSIONS: The findings add substance to the view that the sex-related dimension of symmetry/asymmetry is integral to the disease process in schizophrenia and draw attention to the fusiform gyrus as a structure of particular interest in relation to disturbances of identification and naming in psychosis.

Adult↗

Comparison of nuclear scintigraphy and acetaminophen absorption as a means of studying gastric emptying in horses.

OBJECTIVE: To evaluate the correlation between halftime of liquid-phase gastric emptying (T50), determined with nuclear scintigraphy using technetium Tc 99m pentetate, and absorption variables of orally administered acetaminophen. ANIMALS: 6 mature horses. PROCEDURE: Technetium Tc 99m pentetate (10 mCi) and acetaminophen (20 mg/kg of body weight) were administered simultaneously in 200 ml of water. Serial left and right lateral images of the stomach region were obtained with a gamma camera, and T50 determined separately for counts obtained from the left side, the right side and the geometric mean. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness of fit of the data. Serial serum samples were taken, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 240 minutes and the absorption constant (Ka) were determined, using a parameter estimation program. Correlations were calculated, using the Spearman rank correlation coefficient. RESULTS: Correlations between T50 and Tmax and between T50 and Ka were significant. CONCLUSIONS AND CLINICAL RELEVANCE: Tmax and Ka are valuable variables in the assessment of liquid-phase gastric emptying using acetaminophen absorption. Acetaminophen absorption may be a valuable alternative to nuclear scintigraphy in the determination of gastric emptying rates in equine patients with normally functioning small intestine.

Acetaminophen↗

Fire-based EMS.

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Ambulances↗

Genetic structure of an introduced pest, grape phylloxera (Daktulosphaira vitifoliae Fitch), in Europe.

A model for the genetic structure of grape phylloxera populations in Europe was developed using hierarchical sampling techniques and AFLP-PCR (amplified fragment length polymorphism--polymerase chain reaction) methodology. One-hundred three European and 6 North American phylloxera populations were studied. An additional European sampling set comprising 60 samples was analyzed to study regional subdivision. The populations grouped into two clusters loosely correlated with collection site location. Phylloxera populations collected from northern (above lat 43 degrees) geographic regions were significantly different from southern (below 43 degrees) populations. The northern cluster was more heterogeneous than the southern cluster, possibly reflecting holocyclic versus anholocyclic reproduction. Microgeographic scales of phylloxera genetic structure displayed as much variation within as among host plants. The host plant did not affect the genetic structure of European phylloxera as revealed in two independent experiments.

Animals↗

Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial.

BACKGROUND: Couples with unexplained recurrent miscarriage may have an alloimmune abnormality that prevents the mother from developing immune responses essential for the survival of the genetically foreign conceptus. Immunisation with paternal mononuclear cells is used as a treatment for such alloimmune-mediated pregnancy losses. However, the published results on this treatment are conflicting. In this study (the Recurrent Miscarriage [REMIS] Study), we investigated whether paternal mononuclear cell immunisation improves the rate of successful pregnancies. METHODS: Women who had had three or more spontaneous abortions of unknown cause were enrolled in a double-blind, multicentre, randomised clinical trial. 91 were assigned immunisation with paternal mononuclear cells (treatment) and 92 immunisation with sterile saline (control). The primary outcomes were the inability to achieve pregnancy within 12 months of randomisation, or a pregnancy which terminated before 28 weeks of gestation (failure); and pregnancy of 28 or more weeks of gestation (success). Two analyses were done: one included all women (intention to treat), and the other included only those who became pregnant. FINDINGS: Two women in each group received no treatment, and eight (three treatment, five control) were censored after an interim analysis. In the analysis of all randomised women who completed the trial, the success rate was 31/86 (36%) in the treatment group and 41/85 (48%) in the control group (odds ratio 0.60 [95% CI 0.33-1.12], p=0.108). In the analysis of pregnant women only, the corresponding success rates were 31/68 (46%) and 41/63 (65%; odds ratio 0.45 [0.22-0.91], p=0.026). The results were unchanged after adjustment for maternal age, number of previous miscarriages, and whether or not the couple had had a previous viable pregnancy. Similar results were obtained in a subgroup analysis of 133 couples with no previous livebirth. INTERPRETATION: Immunisation with paternal mononuclear cells does not improve pregnancy outcome in women with unexplained recurrent miscarriage. This therapy should not be offered as a treatment for pregnancy loss.

Abortion, Habitual↗

The size and fiber composition of the anterior commissure with respect to gender and schizophrenia.

BACKGROUND: In light of evidence for deviations in asymmetry and alterations in the anatomy of the corpus callosum in schizophrenia, this study examined the anterior commissure in post mortem brains (n = 14 female control patients, 15 male control patients, 11 female schizophrenic patients, 15 male schizophrenic patients). METHODS: Measures were made of the cross-sectional area of the anterior commissure in the midsagittal plane. In addition, the fiber density and fiber number were measured in a subset of cases (n = 10 female control subjects, 10 male control subjects, 8 female schizophrenic patients, 9 male schizophrenic patients), using the Palmgren silver stain and stereological methods. RESULTS: In control subjects, fiber numbers were greater (p = .024) in women than men. In schizophrenia, the cross-sectional area was unaffected, but for fiber density there was a significant gender x diagnosis interaction (p = .026), corresponding to a reduction in female, but not male patients with schizophrenia. CONCLUSIONS: The reduction in density of fibers in the anterior commissure is consistent with an alteration of interhemispheric connectivity in schizophrenia, but the restriction of the finding to women emphasizes the relevance of gender to understanding the nature of the hemispheric interaction.

Age Distribution↗

Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs.

This review is a survey of various approaches to targeting cytotoxic anticancer drugs to tumors primarily through biomolecules expressed by cancer cells or associated vasculature and stroma. These include monoclonal antibody immunoconjugates; enzyme prodrug therapies, such as antibody-directed enzyme prodrug therapy, gene-directed enzyme prodrug therapy, and bacterial-directed enzyme prodrug therapy; and metabolism-based therapies that seek to exploit increased tumor expression of, e.g., proteases, low-density lipoprotein receptors, hormones, and adhesion molecules. Following a discussion of factors that positively and negatively affect drug delivery to solid tumors, we concentrate on a mechanistic understanding of selective drug release or generation at the tumor site.

Antibodies, Monoclonal↗

Schizophrenia and temporal lobe asymmetry. A post-mortem stereological study of tissue volume.

BACKGROUND: A previous report by Crow of a left-sided increase in temporal horn volume in schizophrenia implies a left-sided loss of tissue. AIMS: To elucidate the structural nature of schizophrenia. METHOD: The volume of grey matter in the temporal pole and inferior, middle and superior temporal gyri was measured, in addition to the total volume of grey and white matter, in the temporal lobes of the brains of 29 patients with schizophrenia and 27 controls. RESULTS: We found a significant left-sided reduction in the superior temporal gyrus in both males and females with schizophrenia, which was related to increasing age of onset in the males. The total volume of temporal lobe grey and white matter was also significantly reduced. Although being more marked on the left than the right, the lateralisation for these total grey and white measures (by contrast with the superior temporal gyrus alone) did not attain formal statistical significance. CONCLUSIONS: Confirmation of a lateralised reduction in the superior temporal gyrus, which is differentially related to age of onset according to gender, adds to evidence that the changes in schizophrenia are in systems that are lateralised. The findings implicate language as the relevant function.

Adult↗

Partial tracheal obstruction due to chondromas in ball pythons (Python regius).

Over a 9-mo period, three adult ball pythons (Python regius) (one male, two females) were evaluated for severe dyspnea. Partial obstructions of the tracheal lumen were identified radiographically and/or visualized with a 3.0-mm rigid laparoscope inserted into the tracheal lumen in all three snakes. Administration of systemic antibiotics and nebulization resulted in partial improvement of the dyspnea. In two snakes, the tracheal lesions were removed with a rigid laparoscope and a flexible biopsy instrument inserted into the tracheal lumen. The other snake died and was necropsied. Histologically, the lesions from two snakes were determined to be benign chondromas. The chondromas were composed of a variably disorganized chondroid matrix populated by quiescent, normal-appearing chondrocytes within lacunae, although the chondrocytes were increased in density compared with normal hyaline cartilage and contained rare mitotic figures. The tracheal masses in one snake grew by expansion, not invasion, and were focally continuous with a mineralized cartilage tracheal ring, suggesting a benign nature. This is the second report of tracheal chondroma in ball pythons. Tracheal chondromas are exceedingly rare in humans and domesticated animals, suggesting a possible predisposition of ball pythons for this neoplasm.

Animals↗