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Biomedical subjects

C Bellamy

Publications and source records attributed to C Bellamy.

At least 19 recordsLinked to original sources

Minimal evidence of transdifferentiation from recipient bone marrow to parenchymal cells in regenerating and long-surviving human allografts.

Liver, small intestine, and heart allografts in residence for 4 days to 16 years were analyzed by simultaneous XY fluorescent in situ hybridization to search for evidence of the recently described process of transdifferentiation of recipient bone marrow stem cells to allograft parenchymal cells. These studies were carried out in an effort to find conditions associated with maximal levels of engraftment or expansion of the recipient parenchymal cells. Despite prolonged survival up to 16 years, regeneration after severe preservation injury or use of split livers, only rare, isolated and tentatively identified recipient hepatocytes were detected in liver allografts. In intestinal allografts, despite survival of up to 8 years and extensive mucosal regeneration because of severe damage from acute rejection, there was no crypt replacement by recipient epithelial cells. In cardiac allografts, no recipient myocytes were detected despite recipient survival for 2-3 days and 3-4 weeks after myocardial infarcts at 5 and 8 years after transplantation. Parenchymal cell transdifferentiation from recipient bone marrow stem cells was rare to nonexistent in severely injured, regenerating, and long-surviving allografts. The rare isolated recipient parenchymal cells tentatively identified did not appear to behave as stem cells: they did not form clusters and did not increase with time after transplantation. Because of the extremely low frequency, interpretation was difficult. Regardless of these results, a more vigorous search for conditions that promote transdifferentiation is warranted.

Adolescent↗

Changes in non-structural carbohydrate composition during bulbing in sweet and high-solid onions in field experiments.

The composition of non-structural carbohydrate (NSC) content of predominantly long-day onion germplasm has been assessed over several years and in a bi-location trial. It was observed that genetic rather than environmental factors determined the NSC composition of onion bulbs. Glucose was the NSC component which was most closely correlated with genotype. Fructose was the only NSC component that was significantly affected by environment. Sucrose and 1-kestose (DP3 fructans) were not correlated to a large extent to the other NSC components, indicating their transient role in the fructan metabolism. Strong negative correlations were observed between reducing sugars (i.e. fructose and glucose) and dry matter content (DM). Furthermore, it was shown that accessions differed significantly in their fructan accumulation pattern; high DM accessions showed accumulation of fructans over the whole bulbing period, whereas, low DM accessions quickly reached a plateau. Implications for the breeding of high quality onions are discussed.

Journal Article↗

Observed maternal strategies and children's health locus of control in low-income Mexican American families.

This study examined the relationship among mothers' health locus of control (HLOC) beliefs, their socialization strategies, and their children's HLOC beliefs in 80 low-income Mexican American families. Maternal socialization strategies were assessed from videotaped interactions of mothers and children engaged in a structured task. Factor analysis of the coded strategies yielded 4 factors: Tell Answer, Teaching, Clarify, and Reinforce. Findings indicated that maternal-health-internally scores negatively predicted mothers' use of the Tell Answer strategies and positively predicted their use of Teaching strategies. Mothers who believed that Powerful Others (e.g., health professionals) controlled their health were more likely to use the Tell Answer strategy. In contrast, mothers who believed that health was due to chance were less likely to use Teaching. Maternal use of Teaching strategies predicted children's internal HLOC, whereas maternal Tell Answer strategies predicted children's external HLOC. Findings suggest that mothers' HLOC beliefs influence the socialization strategies they use and that these strategies are associated with children's HLOC beliefs.

Attitude to Health↗

Contact sensitization pretransplantation predicts acute hepatic allograft rejection.

The loss of hepatic allografts to the rejection processes is now relatively rare, and the reduction of adverse effects related to immunosuppressive therapy is becoming more important as patients survive longer after transplantation. We therefore investigated the response to a contact neoantigen before liver transplantation as a predictor of acute rejection after transplantation. Forty-one patients with chronic liver disease were sensitized with 0.1% diphenylcyclopropenone while on the waiting list for orthotopic liver transplantation. Fourteen days later an elicitation reaction was performed with 5 different concentrations of diphenylcyclopropenone. Nineteen responded to diphenylcyclopropenone (score range, 1-9). Twenty-two patients had no response. Three patients died before transplantation (all nonresponders). Twelve (63%) of 19 responders had treatment for acute rejection compared with 1 of 19 nonresponders (P < .0001). In addition univariate analysis revealed recipient age, donor age, Child-Pugh class, and immunosuppressive agent to be associated with acute rejection. On multivariate analysis only skin test response was a significant predictor of acute rejection (P = .02). All nonresponders had no or only mild rejection on biopsy, but 12 of 19 responders had moderate or severe acute rejection on biopsy. All patients requiring additional therapy to a single course of corticosteroids for acute rejection had skin test scores greater than 1. We concluded that patients who do not respond to diphenylcyclopropenone sensitization before transplantation develop at most mild acute rejection and that skin test scores identify patients with troublesome rejection. Evaluation of skin test responses to a contact neoantigen may facilitate tailoring of immunosuppressive therapy.

Acute Disease↗

Effective tamoxifen therapy of breast cancer involves both antiproliferative and pro-apoptotic changes.

Despite knowledge of oestrogen receptor status, it is not always possible to predict which breast cancers will respond to tamoxifen. We have previously reported that decreased expression of Bcl-2 and/or Ki-S1 were associated with tumour response to neo-adjuvant tamoxifen in 50 elderly women with oestrogen receptor (ER)-positive breast cancer. In this study, we confirm that the expression of Bcl-2 and Ki-S1 are surrogates for the frequency of apoptosis and mitosis respectively, within these untreated breast cancers, with an inverse relationship between Bcl-2 expression and the apoptotic index (P<0.05), and a positive relationship between Ki-S1 expression and the mitotic index (P<0.01). However, after 3 months' tamoxifen treatment these relationships were no longer apparent. Moreover, amongst the 27 tumours in which Bcl-2 expression was reduced during the 3 months' therapy, there was a significant correlation between the response to therapy and the increase in apoptosis (P<0.05), whereas in those tumours in which Bcl-2 did not fall with therapy, there was a significant correlation between response and the decrease in mitosis (P<0.05). These data suggest there are at least two mechanisms for effective tamoxifen therapy: increased apoptosis as a consequence of reduced Bcl-2 expression, and decreased proliferation.

Aged↗

The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: a randomized, double-blind, single-center study.

Anastrozole, an orally active, nonsteroidal aromatase inhibitor, was evaluated in a randomized, double-blind, single-center study to determine its efficacy as neoadjuvant therapy in postmenopausal women with newly diagnosed, estrogen receptor-rich, locally advanced or large (>3 cm), operable breast cancers. Twenty-four eligible patients were recruited into the study and received either 1 mg (n = 12) or 10 mg (n = 12) of anastrozole daily over a 3-month period. Tumor volumes were estimated clinically, by using caliper measurements and ultrasound (at baseline and after 1, 2, and 3 months' treatment) and by mammography (at baseline and after 3 months). Tumor volume was also measured in surgical specimens. Twenty-one patients were classified as T2, two patients as T3, and one patient as T4B at baseline. Three patients had clinical evidence of lymph node involvement. When considering the difference between the volume as measured by each assessment and the actual pathological volume, the interquartile range and the difference between the maximum and minimum values were smaller for ultrasound when compared with those measured with calipers and mammography. Therefore, of the three clinical assessments of tumor volume used in this study, the data suggest that ultrasound may be the most accurate. The median reductions in tumor volumes as measured by ultrasound for those patients with a measurable 12-week assessment were 80.5 and 69.6% for anastrozole (1 and 10 mg, respectively) after 12 weeks of treatment and 75.5% when both doses were grouped together. Moreover, of these patients, 11 of 12 given 1 mg and 7 of 11 given 10 mg of anastrozole were found on ultrasound to have a >50% reduction in tumor volume after 12 weeks of treatment. Of the 17 patients who would have required a mastectomy at initiation of treatment, 15 were suitable for breast conservation after anastrozole treatment. These results suggest that anastrozole is highly effective as neoadjuvant therapy in postmenopausal women with estrogen receptor-rich, large, operable breast cancer. Future studies comparing anastrozole with tamoxifen as a neoadjuvant treatment should be considered.

Aged↗

Lessons from the use of aromatase inhibitors in the neoadjuvant setting.

Postmenopausal patients with oestrogen receptor-positive locally advanced T4b, N0-1, M0 and large operable breast cancers T2>3 cm, T3, T4, N0-1 and M0 have been treated with 2.5 mg letrozole (12 patients), 10 mg letrozole (12 patients), 1 or 10 mg anastrozole (24 patients) and 20 mg tamoxifen (65 patients). There was no apparent difference in response rate between 2.5 and 10 mg letrozole. Only 17 patients with anastrozole have so far completed the 3-month treatment period. Median clinical, mammographic and ultrasound reductions in tumour volumes for patients treated with letrozole were 81% (95% confidence interval (CI) 66-88), 77% (95% CI 64-82) and 81% (95% CI 69-86) respectively and for anastrozole, values were 87% (95% CI 59-97), 73% (95% CI 58-82) and 64% (95% CI 52-76) respectively. This compares with a median reduction in tumour volume for tamoxifen-treated patients as assessed by ultrasound of 48% (95% CI 27-48). There were seven complete clinical responses (CR), sixteen patients who achieved 50% or greater reduction in tumour volume (PR) and one no change (NC) for letrozole and four CRs, twelve PRs and one progressive disease for anastrozole. Best radiological responses were one CR, twenty PRs and three NCs for letrozole and one CR, fifteen PRs and one NC for anastrozole. This study has shown that the new aromatase inhibitors, letrozole and anastrozole, are highly effective agents in the neoadjuvant setting and they should now be compared with tamoxifen as first-line treatment in a randomised study.

Aged↗

Biodiversity assessment and conservation strategies

The efficient representation of all species in conservation planning is problematic. Often, species distribution is assessed by dividing the land into a grid; complementary sets of grids, in which each taxon is represented at least once, are then sought. To determine if this approach provides useful surrogate information, species and higher taxon data for South African plants and animals were analyzed. Complementary species sets did not coincide and overlapped little with higher taxon sets. Survey extent and taxonomic knowledge did not affect this overlap. Thus, the assumptions of surrogacy, on which so much conservation planning is based, are not supported.

Journal Article↗

The expression of Ki-S1 and BCL-2 and the response to primary tamoxifen therapy in elderly patients with breast cancer.

Ki-S1, a marker of proliferation, and bcl-2, the gene product of which is an antagonist of apoptosis, have been measured in 51 ER-positive primary breast cancers before and during tamoxifen treatment and then related to clinical response. Both markers were detected in the majority of tumours before treatment and, quantitatively, initial expression of Bcl-2 protein, but not Ki-S1, was significantly related to the percentage reduction in tumour volume as assessed by ultrasound. Staining for both markers was lower in post treatment samples than in those taken prior to treatments, but concordant decreases in staining indices were seen in only 11 of the 51 tumours. The results demonstrate, using clinical material, that the response to tamoxifen may involve changes in proliferation and/or susceptibility to cell-death.

Aged↗

Cultural, molecular, and immunological characterization of the etiologic agent for atypical canine ehrlichiosis.

More than 100 cases of canine ehrlichiosis, with three fatalities, were serologically negative by the indirect immunofluorescent antibody (IFA) test with Ehrlichia canis or E. sennetsu antigen but were reactive at titers of 10 to 640 with E. risticii. Ehrlichia-like agents were isolated from three such cases. The agents isolated from those cases were morphologically indistinguishable from each other and from a prototype, E. risticii, the etiologic agent of equine monocytic ehrlichiosis, in terms of growth characteristics and by light or electron microscopy. The patterns of and products from PCR were identical to those of E. risticii. The 16S rRNA sequences were distinct from those of E. canis and E. ewingii but were identical to those of E. risticii. A PCR product corresponding to the 5' half of the 16S rRNA gene was obtained from amplification of DNA from E. risticii and both sources of the atypical canine ehrlichiosis agent but was not obtained from uninfected host cells. The entire sequence of 719 nucleotides was identical for all three sources. The percentages of relatedness of the partial 16S rRNA gene of the atypical canine ehrlichiosis agent to E. risticii, E. sennetsu, E. platys, E. equi, E. phagocytophila, E. canis, E. chaffeensis, and E. ewingii were 100.0, 98.9, 83.7, 83.0, 83.0, 82.2, 81.8, and 81.5, respectively. These data are consistent with the identity of these isolates as E. risticii. The caninotropic characteristics of naturally acquired infections due to E. risticii are herein described for the first time, and the epizootiological implications are discussed in relation to the host range of E. risticii, which may include dogs as reservoirs.

Animals↗

On a donor run.

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Heart Transplantation↗

Sexual transmission of human papillomaviruses in heterosexual and male homosexual couples, studied by DNA hybridisation.

The prevalence of human papillomavirus (HPV) 6, 11, 16, and 18 in 36 heterosexual couples and seven male homosexual couples with genital warts was investigated for evidence of sexual transmission of genital HPV. The prevalence of virus type and number of copies of viral genome equivalents/cell in the lesions were assessed, and the factors influencing transmission analysed. Our results show that HPV 6 and, to a lesser extent, HPV 11 were the types most readily transmitted, and that transmission appears to depend on the copy number and the duration and frequency of exposure.

DNA, Viral↗