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Biomedical subjects

C F Williams

Publications and source records attributed to C F Williams.

15 recordsLinked to original sources

Floral dimorphism, pollination, and self-fertilization in gynodioecious GERANIUM RICHARDSONII (Geraniaceae).

The selective maintenance of gynodioecy depends on the relative fitness of the male-sterile (female) and hermaphroditic morphs. Females may compensate for their loss of male fitness by reallocating resources from male function (pollen production and pollinator attraction) to female function (seeds and fruits), thus increasing seed production. Females may also benefit from their inability to self-fertilize if selfing and inbreeding depression reduce seed quality in hermaphrodites. We investigated how differences in floral resource allocation (flower size) between female and hermaphroditic plants affect two measures of female reproductive success, pollinator visitation and pollen receipt, in gynodioecious populations of Geranium richardsonii in Colorado. Using emasculation treatments in natural populations, we further examined whether selfing by autogamy and geitonogamy comprises a significant proportion of pollen receipt by hermaphrodites. Flowers of female plants are significantly smaller than those of hermaphrodites. The reduction in allocation to pollinator-attracting structures (petals) is correlated with a significant reduction in pollinator visitation to female flowers in artificial arrays. The reduction in attractiveness is further manifested in significantly less pollen being deposited on the stigmas of female flowers in natural populations. Autogamy is rare in these protandrous flowers, and geitonogamy accounts for most of the difference in pollen receipt between hermaphrodites and females. Female success at receiving pollen was negatively frequency dependent on the relative frequency of females in populations. Thus, two of the prerequisites for the maintenance of females in gynodioecious populations, differences in resource allocation between floral morphs and high selfing rates in hermaphrodites, occur in G. richardsonii.

Journal Article↗

Distinctive gene expression patterns in human mammary epithelial cells and breast cancers.

cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tumors. Clusters of coexpressed genes identified through manipulations of mammary epithelial cells in vitro also showed consistent patterns of variation in expression among breast tumor samples. By using immunohistochemistry with antibodies against proteins encoded by a particular gene in a cluster, the identity of the cell type within the tumor specimen that contributed the observed gene expression pattern could be determined. Clusters of genes with coherent expression patterns in cultured cells and in the breast tumors samples could be related to specific features of biological variation among the samples. Two such clusters were found to have patterns that correlated with variation in cell proliferation rates and with activation of the IFN-regulated signal transduction pathway, respectively. Clusters of genes expressed by stromal cells and lymphocytes in the breast tumors also were identified in this analysis. These results support the feasibility and usefulness of this systematic approach to studying variation in gene expression patterns in human cancers as a means to dissect and classify solid tumors.

Algorithms↗

Sources of artifact and systematic error in quantitative snapshot of FLASH imaging and methods for their elimination.

Snapshot FLASH preceded by a preparation sequence is used to measure NMR parameters. Some preparation information is lost during snapshot FLASH acquisition as the magnetization evolves towards the steady state. This problem is often addressed by assuming that image intensity is proportional to the central k-space line, which may be sampled immediately after preparation using a centric-reordered scheme. Although some limitations of this assumption have been discussed, they are often ignored in parameter measurement. In this study, magnetization evolution effects in snapshot FLASH were investigated by computer simulation and phantom experiments in the context of T2 measurement. It was found that the standard analysis may lead to significant error in parameter measurement. Some improvement may be obtained using a more sophisticated analysis to take account of magnetization evolution. However, at the expense of a 50% reduction in signal intensity, accurate values may be obtained by a novel method that uses crusher gradients to eliminate evolved magnetization.

Artifacts↗

A novel fast split-echo multi-shot diffusion-weighted MRI method using navigator echoes.

Difficulties in obtaining diffusion-weighted images of acceptable quality using conventional hardware and in a reasonable time have hindered the clinical application of diffusion-weighted magnetic resonance imaging (DWI). Diffusion-weighted fast spin-echo (FSE) sequences offer the possibility of fast DWI on standard hardware without the susceptibility problems associated with echoplanar imaging. However, motion in the presence of diffusion-sensitizing gradients can prevent fulfilment of the Meiboom Gill phase condition, leading to destructive interference between echo components and consequent signal losses. A recently proposed single-shot FSE sequence employed split-echo acquisition to address this problem. However, in a segmented FSE sequence, phase errors differ between successive echo trains, causing "ghosting" in the diffusion-weighted images that are not eliminated by split-echo acquistion alone. A DWI technique is presented that combines split-echo acquisition with navigator echo phase correction in a segmented FSE sequence. It is shown to be suitable for diffusion measurements in vivo using standard hardware.

Brain↗

Genome-wide analysis of DNA copy-number changes using cDNA microarrays.

Gene amplifications and deletions frequently contribute to tumorigenesis. Characterization of these DNA copy-number changes is important for both the basic understanding of cancer and its diagnosis. Comparative genomic hybridization (CGH) was developed to survey DNA copy-number variations across a whole genome. With CGH, differentially labelled test and reference genomic DNAs are co-hybridized to normal metaphase chromosomes, and fluorescence ratios along the length of chromosomes provide a cytogenetic representation of DNA copy-number variation. CGH, however, has a limited ( approximately 20 Mb) mapping resolution, and higher-resolution techniques, such as fluorescence in situ hybridization (FISH), are prohibitively labour-intensive on a genomic scale. Array-based CGH, in which fluorescence ratios at arrayed DNA elements provide a locus-by-locus measure of DNA copy-number variation, represents another means of achieving increased mapping resolution. Published array CGH methods have relied on large genomic clone (for example BAC) array targets and have covered only a small fraction of the human genome. cDNAs representing over 30,000 radiation-hybrid (RH)-mapped human genes provide an alternative and readily available genomic resource for mapping DNA copy-number changes. Although cDNA microarrays have been used extensively to characterize variation in human gene expression, human genomic DNA is a far more complex mixture than the mRNA representation of human cells. Therefore, analysis of DNA copy-number variation using cDNA microarrays would require a sensitivity of detection an order of magnitude greater than has been routinely reported. We describe here a cDNA microarray-based CGH method, and its application to DNA copy-number variation analysis in breast cancer cell lines and tumours. Using this assay, we were able to identify gene amplifications and deletions genome-wide and with high resolution, and compare alterations in DNA copy number and gene expression.

Chromosomes, Human, Pair 17↗

The complete sequence of four major structural proteins of African horse sickness virus serotype 6: evolutionary relationships within and between the orbiviruses.

The amino acid sequences of four major capsid proteins of African horse sickness virus (serotype 6, AHSV-6) have been determined from analyses of cDNA clones representing the L2, L3, M6 and S7 RNA segments. The AHSV-6 L3 RNA segment has an open reading frame of 2715 base pairs and encodes the inner capsid protein VP3 which comprises 905 amino acids. The VP3 layer forms the subcore of the virion and is surrounded by the VP7 protein which is encoded by the S7 gene. The AHSV-6 S7 gene was found to be 1047 nucleotides in length with a coding capacity for the VP7 protein of 349 amino acids. These core proteins are encapsulated by the outer capsid proteins VP5 and VP2 which are encoded by the M6 and L2 genes respectively. The M6 gene of AHSV-6 was determined to be 1564 nucleotides in length and encoded a protein product of 504 amino acids while the L2 gene comprised 3203 nucleotides which encoded a predicted protein product of 1051 amino acids. Comparison of these four sequences with the core protein sequences of other serotypes of African horse sickness virus, Bluetongue virus which infects sheep, and Epizootic haemorrhagic disease virus of deer, demonstrated that despite the pathobiological properties and host range of these distinct orbiviruses, extreme conservation is evident within the capsid genes. Sequence analyses also suggested that the similarity levels between serogroups depict the structure and function of the individual capsid proteins. The data indicated that the evolution of the capsid genes of gnat transmitted orbiviruses is strongly influenced by functional and structural constraints.

African Horse Sickness Virus↗

The influence of stimulated echoes on contrast in fast spin-echo imaging.

Tissue contrast obtained using fast spin-echo (FSE) and conventional spin-echo (SE) sequences is not identical and a number of mechanisms are thought to contribute to these contrast differences. The effect of stimulated echoes has previously been apparently ruled out as a contributing mechanism. Signal-to-noise ratios of single-slice matched FSE and conventional SE sequences were compared in aqueous solutions of CuSO4, Cr2(SO4)3 and MnSO4 with various T1 and T2 values. Enhancement of the FSE signal was observed in short T2 solutions and the effect was greater in samples where the T1 to T2 ratio was high. Reducing the refocusing pulse flip angle to increase the contribution from stimulated echoes also resulted in slightly increased enhancement. Experimental results were verified by computer simulations. Our results show that stimulated echoes do contribute to the contrast differences between FSE and conventional SE images and may be significant in the imaging of brain hemorrhage.

Computer Simulation↗

Essentiality of the lateral cervical spine radiograph.

Proper interpretation of the lateral cervical spine (C-spine) film is a prime emergency medicine responsibility. Patients with potential neck injury must be identified rapidly and handled carefully; their C-spine films must be interpreted quickly and accurately. We stress the urgency in obtaining a good, readable lateral C-spine film and present a systemic "ABCs" approach to reading this film. This approach includes specific, sequential attention to Alignment, Bony integrity, Cartilaginous structures, and the surrounding Soft-tissue spaces. In the cases of 50 consecutive patients with C-spine injuries (49 adults, one child) seen recently in our emergency medicine program, we have correlated traumatic mechanisms with specific injury patterns. These analyses have been meshed with data from the patients' medical records and radiographs. In a significant number of instances (greater than 25% in this series), objective, careful radiographic interpretation is more important to the patient's objective, careful radiographic interpretation is more important to the patient's welfare than is any other diagnostic modality -- including history and physical examination.

Adult↗

Effects of irradiation on mixed müllerian tumors of the uterus.

A retrospective study of 54 patients with histologically proven malignant mixed müllerian tumors of the uterus was undertaken with main emphasis on the evaluation of the effects of irradiation on pelvic tumor control. The tumors were staged according to the FIGO classification for endometrial carcinoma and 24 were classified as Stage I, 10 as Stage II, 13 as Stage III and seven as Stage IV. Patients with Stage I and II were treated with surgery alone (9 patients, three surviving) or preoperative intracavitary irradiation (13 patients, eight surviving) or preoperative combination of intracavitary and external irradiation (12 patients, six surviving). Five patients with Stage III and IV were treated with surgery alone, two were treated with a combination of irradiation and surgery and 11 with radiation alone. None of these patients survived. In seven patients showing no residual tumor in the uterine specimen after irradiation, no pelvic failures were noted, whereas seven of 17 (41.2%) with residual tumor developed pelvic recurrences. In patients with Stage I treated with surgery alone, three out of six recurred in the pelvis whereas only three of 17 (17%) receiving preoperative irradiation developed pelvic recurrences. However, in Stage II six of eight patients treated with preoperative irradiation failed in the pelvis. Correlation with the doses of irradiation given to the uterus or the pelvic lymph nodes indicate that with doses below 5000 rads a significantly higher number of pelvic recurrences take place, whereas these are uncommon with doses over 6000 rads. The difference in pelvic recurrences between dosage levels is not, however, statistically significant. It is suggested that patients with Stage I and II malignant mixed müllerian tumors of the uterus should be treated with preoperative radiation and total hysterectomy with bilateral salpingo-oophorectomy. Patients with more advanced disease have extremely poor prognosis and should be treated with radiation therapy alone. This tumor has a high propensity to spread through lymphatics and hematogenous metastases are seen in approximately 75% of the patients. Because of this dissemination, significant improvements in survival rate will not be seen until effective cytotoxic agents are available.

Female↗

Pelvic exenterations.

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Activities of Daily Living↗