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Biomedical subjects

D J Crawford

Publications and source records attributed to D J Crawford.

At least 19 recordsLinked to original sources
PubMed2003

Effect of cavity margin shavings to ensure completeness of excision on local recurrence rates following breast conserving surgery.

AIMS: The presence of residual disease at the excision margin after breast conserving surgery is the most important risk factor for local recurrence. One method for assessing tumour margin involvement is to take shavings from the wall of the resulting cavity following wide excision of the lesion. METHODS: We have reviewed our experience of shaving the margin of the cavity as our method to ensure completeness of excision. RESULTS: Of 351 patients treated with breast conservation 61 patients had residual disease in the cavity margin biopsies. Younger age, axillary lymph node status, multi-focal tumours and high grade tumours were significantly correlated with margin involvement. In patients who had clear margins eight patients (2.8%) had developed a local recurrence at follow-up of 55 months (25-89 months). CONCLUSIONS: In our hands the use of cavity margin shavings allows us to achieve an acceptable rate of local control.

Breast Neoplasms↗
PubMed2002

The role of lymph node sampling and radiotherapy in the management of the axilla in early breast cancer.

Management of the axilla in early breast cancer is an issue of ongoing debate. We reviewed our experience in 312 patients who underwent axillary lymph node sampling between 1994 and 1998, of whom 81 patients (24%) had axillary lymph node metastasis. There have been two axillary recurrences, one associated with local recurrence to the breast and one presenting with distant metastasis. There were no patients with isolated axillary disease as their only site of recurrence and no axillary failures in the node-positive group treated with axillary sampling and radiotherapy. Axillary lymph node sampling effectively stages the axilla. This can safely be followed by radiotherapy to the axilla in case of lymph node metastasis. Axillary lymph node sampling forms a sound basis to develop new techniques, such as sentinel lymph node biopsy currently investigated by ongoing trials.

Journal Article↗
PubMed2001

Breeding System and pollination of selected plants endemic to Juan Fernandez Islands.

We conducted field studies on the Juan Fernández Islands flora on the breeding system of 25 endemic species from 17 families. We recorded data on flower features, pollen and ovule number, pollen/ovule ratio, pollen size, self-compatibility, floral visitors, and pollination. Flowers are mostly hermaphrodite, inconspicuous, small, and green. Six species are dioecious. Over 80% of the cosexual species are self compatible. However, many species are dichogamous (mostly protandrous); thus, even the self-compatible species may require pollen transfer. Selfing through geitonogamy seems to be the most common system, and several species express mixed breeding systems. Floral visitors are uncommon to rare, except for two hummingbird species (one native and one endemic) that visit five species we studied. In more than 300 h of observation of flowers over three field seasons, we detected only 23 native insect visits representing ten species (Diptera, Lepidoptera, and Coleoptera). One species each of an introduced ant and an introduced bee were also observed on some flowers, all near the single human settlement of San Juan Bautista. Wind directly moving pollen, or indirectly via shaking the flowers, is the most important pollen distribution mechanism. The majority of the wind-pollinated species bear some typical anemophilous features, but also others not characteristic of wind pollination, that presumably represent the condition of their biotically pollinated ancestors. Floral features often reflect ancestral reproductive systems, so floral biology studies of oceanic islands in particular must be done with cognizance of presumed ancestral forms, because the observed characters can be misleading.

Journal Article↗
PubMed2000

Timing the eastern Asian-eastern North American floristic disjunction: molecular clock corroborates paleontological estimates.

Sequence data of the chloroplast gene rbcL were used to estimate the time of the well-known eastern Asian-eastern North American floristic disjunction. Sequence divergence of rbcL was examined for 22 species of 11 genera (Campsis, Caulophyllum, Cornus, Decumaria, Liriodendron, Menispermum, Mitchella, Pachysandra, Penthorum, Podophyllum, and Phryma) representing a diverse array of flowering plants occurring disjunctly in eastern Asia and eastern North America. Divergence times of putative disjunct species pairs were estimated from synonymous substitutions, using rbcL molecular clocks calibrated for Cornus. Relative rate tests were performed to assess rate constancy of rbcL evolution among lineages. Corrections of estimates of divergence times for each species pair were made based on rate differences of rbcL between Cornus and other species pairs. Results of these analyses indicate that the time of divergence of species pairs examined ranges from 12.56 +/- 4.30 million years to recent (<0.31 million years), with most within the last 10 million years (in the late Miocene and Pliocene). These results suggest that the isolation of most morphologically similar disjunct species in eastern Asia and eastern North America occurred during the global climatic cooling period that took place throughout the late Tertiary and Quaternary. This estimate is closely correlated with paleontological evidence and in agreement with the hypothesis that considers the eastern Asian-eastern North American floristic disjunction to be the result of the range restriction of a once more or less continuously distributed mixed mesophytic forest of the Northern Hemisphere that occurred during the late Tertiary and Quaternary. This implies that in most taxa the disjunction may have resulted from vicariance events. However, long-distance dispersal may explain the disjunct distribution of taxa with low divergence, such as Menispermum.

Asia↗
PubMed2000

RAPD marker diversity within and divergence among species of Dendroseris (Asteraceae: Lactuceae).

Random Amplified Polymorphic DNA (RAPD) markers were used to measure genetic diversity within and divergence among species of Dendroseris (Asteraceae: Lactuceae), a genus endemic to the Juan Fernandez Islands, Chile. Results were compared to previous studies employing allozymes. For five of the species, RAPD banding patterns distinguished all individuals examined, and different mutilocus genotypes were found even in species exhibiting no allozyme diversity. RAPD band diversities ranged from 0.003 to 0.022 within species; >90% of total diversity was among species and <10% within them. Relative levels of allozyme and RAPD diversity were similar for some species, particularly those with highest and lowest diversities, but overall there was no significant correlation. Relationships inferred from a neighbor-joining tree generated from RAPD bands were similar to results obtained from morphology, chloroplast DNA (cpDNA) restriction site mutations, and sequences from the internal transcribed spacer regions of nuclear ribosomal DNA (ITS), but somewhat better resolution was achieved. Relationships shown by allozymes differed from trees based on other data; this ostensibly is a result of the sharing of ancestral alleles and the absence of alleles generated subsequent to speciation. Dendroseris represents an example where RAPD markers, because of their greater variability, provide a useful alternative to allozymes for assessing diversity in rare species endemic to oceanic islands and for resolving relationships among the species.

Journal Article↗
PubMed2000

Plant genetic diversity in the Canary Islands: a conservation perspective.

The Canary Islands are an Atlantic volcanic archipelago with a rich flora of ∼570 endemic species. The endemics represent ∼40% of the native flora of the islands, and ∼20% of the endemics are in the E (endangered) category of the International Union for Conservation of Nature. A review of allozyme variation in 69 endemic species belonging to 18 genera and eight families is presented. The average species-level genetic diversity (H(T)) at allozyme loci is 0.186, which is twice as high as the mean reported for endemics of Pacific archipelagos. Possible factors contributing to this higher diversity are discussed, but the reasons remain obscure. An average of 28% of the allozyme diversity within species resides among populations, indicating a high level of interpopulational differentiation. Studies of reproductive biology indicate that many of the endemic species are outcrossers. The high total diversity within species, the relatively high differentiation among populations, and the outcrossing breeding systems have implications for species conservation. Decreased population sizes in outcrossing species would promote biparental inbreeding and increase inbreeding depression. The relatively high proportion of allozyme diversity among populations indicates that the most effective strategy for preserving genetic variation in species is to conserve as many populations as possible. The genetic diversity in many Canary Island endemics is endangered by: (1) overgrazing by introduced animals, such as barbary sheep, goats, mouflons, rabbits, and sheep; (2) interspecific hybridization following habitat disturbance or planting of endemics along roadsides or in public gardens; (3) competition with alien plant species; and (4) decline of population size because of urban development and farming.

Journal Article↗
PubMed1999

Indirect regulation of translational termination efficiency at highly expressed genes and recoding sites by the factor recycling function of Escherichia coli release factor RF3.

Prokaryotic release factor RF3 is a stimulatory protein that increases the rate of translational termination by the decoding release factors RF1 and RF2. The favoured model for RF3 function is the recycling of RF1 and RF2 after polypeptide release by displacing the factors from the ribosome. In this study, we have demonstrated that RF3 also plays an indirect role in the decoding of stop signals of highly expressed genes and recoding sites by accentuating the influence of the base following the stop codon (+4 base) on termination signal strength. The efficiency of decoding strong stop signals (e.g. UAAU and UAAG) in vivo is markedly improved with increased RF3 activity, while weak signals (UGAC and UAGC) are only modestly affected. However, RF3 is not responsible for the +4 base influence on termination signal strength, since prfC- strains lacking the protein still exhibit the same qualitative effect. The differential effect of RF3 at stop signals can be mimicked by modest overexpression of decoding RF. These findings can be interpreted according to current views of RF3 as a recycling factor, which functions to maintain the concentration of free decoding RF at stop signals, some of which are highly responsive to changes in RF levels.

Base Sequence↗
PubMed1999

Reproductive biology of Lactoris fernandeziana (Lactoridaceae).

Lactoris fernandeziana, monotypic in its family, is endemic to the cloud forests of Robinson Crusoe Island. Although there has been considerable study of the relationships of Lactoris, as a rare species and as a putative primitive paleoherb, little is known of its reproductive biology. Knowledge of the latter is essential for effective conservation programs. The species is gynomonoecious. The overall proportion of flowers is ∼1 female:1 hermaphrodite. The inconspicuous semipendulous green flowers, usually in mixed-gender inflorescences, do not produce rewards. Hermaphrodite flowers are herkogamous and protogynous. Pollen grains are shed from the extrorse anthers in permanent dry tetrads. There is a mean of 12879 tetrads per hermaphrodite flower. Both flower types bear an average of ∼18 ovules. The P/O (pollen/ovule) ratios imply facultative or obligate xenogamy, but hand pollinations show that Lactoris is self-compatible. No floral visitors were ever observed, but stigmata of open-pollinated flowers bore tetrads, and 64% of such styles had pollen tubes. Flowers enclosed in large mesh (1 mm) bags bore similar numbers of tetrads and pollen tubes. Thus, we conclude that Lactoris is anemophilous, a syndrome perhaps reflected by the P/O ratio. Low genetic diversity (isozymes and DNA) supports selfing and implies limited distance wind pollen dispersal. The small size of the island, the ± 1000 extant Lactoris plants, coupled with anemophily, self-compatibility, and pendant flower position, have yielded a geitonogamous system with high seed set and low genetic diversity. If inbreeding depression is expressed, it is in seed germination and seedling vigor, for Lactoris is very difficult to cultivate. For this species, effective conservation practices need to focus on habitat preservation and promotion of outcrossing.

Journal Article↗
PubMed1996

A common origin for woody Sonchus and five related genera in the Macaronesian islands: molecular evidence for extensive radiation.

Woody Sonchus and five related genera (Babcockia, Taeckholmia, Sventenia, Lactucosonchus, and Prenanthes) of the Macaronesian islands have been regarded as an outstanding example of adaptive radiation in angiosperms. Internal transcribed spacer region of the nuclear rDNA (ITS) sequences were used to demonstrate that, despite the extensive morphological and ecological diversity of the plants, the entire alliance in insular Macaronesia has a common origin. The sequence data place Lactucosonchus as sister group to the remainder of the alliance and also indicate that four related genera are in turn sister groups to subg. Dendrosonchus and Taeckholmia. This implies that the woody members of Sonchus were derived from an ancestor similar to allied genera now present on the Canary Islands. It is also evident that the alliance probably occurred in the Canary Islands during the late Miocene or early Pliocene. A rapid radiation of major lineages in the alliance is consistent with an unresolved polytomy near the base and low ITS sequence divergence. Increase of woodiness is concordant with other insular endemics and refutes the relictural nature of woody Sonchus in the Macaronesian islands.

Atlantic Islands↗
PubMed1996

Rational design of novel immunosuppressive drugs: analogues of azathioprine lacking the 6-mercaptopurine substituent retain or have enhanced immunosuppressive effects.

Clinical use of the immunosuppressive drug azathioprine is limited by potentially serious toxic effects related to depression of bone marrow function. The immunosuppressive and toxic properties of azathioprine are regarded as being properties of the cytotoxicity of its metabolite, 6-mercaptopurine (6-MP). However, azathioprine has an immunosuppressive effect additional to that attributable to 6-MP alone, and we propose that this is associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic immunosuppressants by replacing the 6-MP component of azathioprine with nontoxic thiols. We have synthesized and tested in vitro 24 such analogues, with two being further tested in vivo. In the human mixed lymphocyte reaction, virtually all compounds showed some degree of activity, 10 compounds being more active than azathioprine. In vivo, two compounds were more effective than azathioprine at prolonging graft survival in mice. In an oral toxicity study in male CD1 mice at doses equivalent to those at which azathioprine caused severe bone marrow depression both analogues had no toxic effects. Our results show that the immunosuppressive effects and bone marrow toxicity of azathioprine are not a consequence of release of 6-MP alone, and with appropriate modification can be separated, an approach which may lead to less toxic immunosuppressive drugs.

Animals↗
PubMed1996

The translational stop signal: codon with a context, or extended factor recognition element?

Wide ranging studies of the readthrough of translational stop codons within the last 25 years have suggested that the stop codon might be only part of the molecular signature for recognition of the termination signal. Such studies do not distinguish between effects on suppression and effects on termination, and so we have used a number of different approaches to deduce whether the stop signal is a codon with a context or an extended factor recognition element. A data base of natural termination sites from a wide range of organisms (148 organisms, approximately 40,000 sequences) shows a very marked bias in the bases surrounding the stop codon in the genes for all organisms examined, with the most dramatic bias in the base following the codon (+4). The nature of this base determines the efficiency of the stop signal in vivo, and in Escherichia coli this is reinforced by overexpressing the stimulatory factor, release factor 3. Strong signals, defined by their high relative rates of selecting the decoding release factors, are enhanced whereas weak signals respond relatively poorly. Site-directed cross-linking from the +1, and bases up to +6 but not beyond make close contact with the bacterial release factor-2. The translational stop signal is deduced to be an extended factor recognition sequence with a core element, rather than simply a factor recognition triplet codon influenced by context.

Base Sequence↗
PubMed1995

Documentation of reticulate evolution in peonies (Paeonia) using internal transcribed spacer sequences of nuclear ribosomal DNA: implications for biogeography and concerted evolution.

The internal transcribed spacers (ITS) of nuclear ribosomal DNA of 33 species of genus Paeonia (Paeoniaceae) were sequenced. In section Paeonia, different patterns of nucleotide additivity were detected in 14 diploid and tetraploid species at sites that are variable in the other 12 species of the section, suggesting that reticulate evolution has occurred. Phylogenetic relationships of species that do not show additivity, and thus ostensibly were not derived through hybridization, were reconstructed by parsimony analysis. The taxa presumably derived through reticulate evolution were then added to the phylogenetic tree according to additivity from putative parents. The study provides an example of successfully using ITS sequences to reconstruct reticulate evolution in plants and further demonstrates that the sequence data could be highly informative and accurate for detecting hybridization. Maintenance of parental sequences in the species of hybrid origin is likely due to slowing of concerted evolution caused by the long generation time of peonies. The partial and uneven homogenization of parental sequences displayed in nine species of putative hybrid origin may have resulted from gradients of gene conversion. The documented hybridizations may have occurred since the Pleistocene glaciations. The species of hybrid origin and their putative parents are now distantly allopatric. Reconstruction of reticulate evolution with sequence data, therefore, provides gene records for distributional histories of some of the parental species.

Asia↗
PubMed1994

Cyclic sequential endocrine therapy for advanced breast cancer using a combination of tamoxifen and megestrol acetate.

A cyclical, sequential combination of tamoxifen and megestrol acetate (group B) was compared with conventional therapy (tamoxifen alone, group A) in 261 breast cancer patients. There was no statistically significant difference between groups for overall response rate (complete+partial response: group A, 35.8%, group B, 40.8%; p = 0.505) or for median response duration in responders (group A, 128 weeks, group B, 136 weeks; p = 0.488). Median survival from randomization was longer in those patients receiving sequential therapy (group A, 90 weeks, group B, 134 weeks) with a significantly lower relative death rate (group B/group A = 0.67; p = 0.011). This survival benefit appears to be due to a delay in progression among nonresponders in the sequential therapy group.

Adult↗
PubMed1991

Does exercise stress alter susceptibility to bacterial infections?

Swimming was used for evaluating alterations in performance capacity and as a means for studying the influence of exercise stress on susceptibility to Streptococcus pneumoniae and Francisella tularensis infections in two strains of rats, i.e. Fisher-Dunning (FD) and Sprague-Dawley (SD). The performance capacity was reduced by both diseases and was correlated to the dose of the given micro-organism. FD rats, however, were more susceptible to the infection and showed a greater deterioration than SD rats. The effects of exercise stress on disease lethality varied with the time that it was performed. Strenuous exercise immediately before infection drastically reduced susceptibility to either of the bacteria, while a similar bout of exercise performed after infection increased disease-related mortality in both diseases.

Animals↗
PubMed1991

Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats.

The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection.

Animals↗
PubMed1991

Effects of training on metabolic responses and performance capacity in Streptococcus pneumoniae infected rats.

These experiments were designed to study whether endurance training prior to Streptococcus pneumoniae infection in rats (N = 15 in each group) alters lethality, performance capacity, and related energy metabolism. A 5-d.wk-1, 4-wk-long pre-infection training program with gradually increasing swim time caused no protection from lethality (48% at 72 h post-inoculation), but performance capacity increased by 68% (P less than 0.01). The catabolic responses as evidenced by changes in insulin and glucagon levels were less pronounced. Mobilization of free fatty acids increased twofold (P less than 0.01), and improved ketonemic adaptation (47%, P less than 0.01) occurred with concomitant saved carcass, liver, and skeletal muscle glycogen contents (P less than 0.01). This shift from carbohydrate toward fat metabolism during exercise as a result of training was also reflected by 21% lower (P less than 0.01) blood lactate levels. It was concluded that the improved metabolic status, characterizing the trained as compared with the untrained host, is partly preserved during ongoing acute gram-positive bacterial infection.

Animals↗
PubMed1988

Haemorrhage from an adhesion-related mesenteric varix in a patient with portal hypertension.

We report a case of profuse gastrointestinal haemorrhage from an ileal varix, in a segment of bowel adherent to the site of a previous incisional hernia repair, in a patient with portal hypertension. This is a rare but recognised complication of portal hypertension. Localisation of the bleeding point was achieved by radionuclide scanning and the segment of abnormal bowel was successfully resected.

Female↗