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J A Chapman

Publications and source records attributed to J A Chapman.

At least 19 recordsLinked to original sources
PubMed1998

Growth of sea cucumber collagen fibrils occurs at the tips and centers in a coordinated manner.

Collagen fibrils are the principle source of mechanical strength in the mutable dermis of the sea cucumber Cucumaria frondosa. To obtain information about the mechanism by which collagen molecules self-assemble into fibrils, we have isolated single intact fibrils with lengths in the range 14-444 microm. These fibrils have been studied by scanning transmission electron microscopy, yielding data that show how cross-sectional mass, and hence the number of molecules in the cross-section, depend on axial location. In an individual fibril, the two ends always display similar mass distributions. The two tips of each fibril must therefore maintain identity in shape and size throughout growth. The linear relationship between cross-sectional mass and distance from the adjacent end shows that a growing tip is (like the tip of a vertebrate collagen fibril) paraboloidal in shape. Comparison of data from many different fibrils, over a wide range of lengths, however, revealed that the paraboloidal tip becomes blunter as the fibril grows in length. In contrast to vertebrate fibrils, those from C. frondosa do not have a central shaft region of constant cross-sectional mass. Rather, the cross-sectional mass increases to a maximum in the center of each fibril. The maximum cross-sectional mass of the fibrils increases exponentially with increasing fibril length. The centrosymmetry, the paraboloidal shape of the tips, and the hyperbolic increase in maximum cross-sectional mass with fibril length, is evidence for a co-ordinated regulation of length and diameter, which differs from the kind of regulation that gives rise to collagen fibrils in vertebrates (chickens and mice).

Animals↗
PubMed1998

Assessing genetic markers of tumour progression in the context of intratumour heterogeneity.

This is a report from the Kananaskis working group on quantitative methods in tumour heterogeneity. Tumour progression is currently believed to result from genetic instability and consequent acquisition of new genetic properties in some of the tumour cells. Cross-sectional assessment of genetic markers for human tumours requires quantifiable measures of intratumour heterogeneity for each parameter or characteristic observed; the relevance of heterogeneity to tumour progression can best be ascertained by repeated assessment along a tumour progressional time line. This paper outlines experimental and analytic considerations that, with repeated use, should lead to a better understanding of tumour heterogeneity, and hence, to improvements in patient diagnosis and therapy. Four general principles were agreed upon at the Symposium: (1) the concept of heterogeneity requires a quantifiable definition so that it can be assessed repeatably; (2) the quantification of heterogeneity is necessary so that testable hypotheses may be formulated and checked to determine the degree of support from observed data; (3) it is necessary to consider (a) what is being measured, (b) what is currently measurable, and (c) what should be measured; and (4) the proposal of working models is a useful step that will assist our understanding of the origins and significance of heterogeneity in tumours. The properties of these models should then be studied so that hypotheses may be refined and validated.

Disease Progression↗
PubMed1998

Assessment of treatment for patients with primary ductal carcinoma in situ in the breast.

BACKGROUND: Current mammographic technology has resulted in increased detection of ductal carcinoma in situ (DCIS). It is necessary to assess which patients presenting with DCIS are good candidates for breast conservation and which of these patients should receive adjuvant radiation. METHODS: We accrued clinical data for 124 patients with a primary diagnosis of DCIS from 1979 through 1994. Primary therapy was a mastectomy for 18 patients, and a lumpectomy for 106 patients. Only 18 of the latter group of patients received adjuvant radiotherapy. For the 88 lumpectomy-alone patients (median follow-up, 5.2 years), we evaluated the effects of clinical (age and initial presentation) and pathologic (nuclear grade, architecture, parenchymal involvement, calcifications, and measured margins) factors on recurrence of DCIS or the development of invasive breast cancer. RESULTS: Patients who underwent lumpectomy with or without adjuvant radiotherapy (median follow-up, 5.0 years) were significantly more likely to have recurrence of DCIS (P=.05) than those who underwent mastectomy (median follow-up, 6.7 years): 18% (19/106) versus 0% (0/18), respectively; lumpectomy-alone patients experienced a 19% (17/88) rate of DCIS recurrence. All recurrent DCIS was ipsilateral. For lumpectomy-alone patients, the factors associated with ipsilateral recurrence of DCIS were extent of involvement of the parenchyma (P=.01, for univariate; P=.07, for multivariate) and initial presentation (P=.05, for univariate; P=.07, for multivariate). Eleven lumpectomy-alone patients developed invasive breast cancer (6 ipsilateral, 5 contralateral); none of the 18 lumpectomy patients who received adjuvant radiation developed invasive disease. None of the factors investigated, including primary surgery and adjuvant radiotherapy, were associated with a significant effect on the development of invasive disease. CONCLUSIONS: Longer follow-up is required to determine if the benefits of either mastectomy or radiotherapy following lumpectomy persist. There is a suggestion that patients under 40 years of age or women who present with nipple discharge might be considered for either adjuvant radiotherapy following lumpectomy or a simple mastectomy.

Adult↗
PubMed1998

Competing causes of death for primary breast cancer.

BACKGROUND: A patient's likelihood of dying from breast cancer or another cause can be assessed with competing risks analyses. METHODS: Data for a cohort of 678 patients with primary invasive breast cancer accrued from 1971 to 1990, updated to 1995, included cause of death (e.g., breast cancer vs. other cause). We investigated the effects of age, tumor size, nodal status, ER, PgR, and adjuvant therapy (hormones, chemotherapy, radiotherapy) on type of death and time to death for patients of all ages and for those over the age of 65 years. RESULTS: Although there were no significant univariate differences in breast cancer death rates by age group (P=0.94), more patients over the age of 65 years died from other causes (41/207 [20%] of those older than 65 years vs. 16/471 [3%] of those younger than 65 years; P <.001). In competing risks analyses, older age was associated with non-breast cancer death, whereas larger tumor size was associated with breast cancer death. PgR was positively, and nodal status negatively, associated with survival, regardless of type. In the older patient group, the competing risks analyses identified similar effects for age and tumor size; in addition, higher ER assay values were less likely to be associated with breast cancer death. CONCLUSIONS: With increased lifespan, there will be more breast cancer cases in women older than 65 years; we have shown that women in this group have more non-breast cancer deaths. It becomes important, then, to delineate differential effects of prognostic factors on competing causes of death.

Adult↗
PubMed1998

Vascular injuries in total knee arthroplasty. A review of the problem with special reference to the possible effects of the tourniquet.

Considering the proximity of the major vascular structures to the back of the knee, vascular complications of total knee arthroplasty are relatively rare. A patient who developed acute vascular insufficiency immediately following a total knee arthroplasty is reported. This stimulated a survey of arterial complications encountered by members of the British Association for the Surgery of the Knee. The majority of surgeons still use a tourniquet but will modify their practice if there is anxiety about vascular status. The mechanism of injury to the vascular system is either direct trauma or thrombosis. The outcome following treatment after direct injury is extremely good. The outcome after thrombosis is extremely poor. There is no recorded case of thrombosis occurring when a tourniquet was not used. Whether all knee arthroplasties should be done without a tourniquet is discussed. Early intervention is vital if a vascular injury is suspected.

Aged↗
PubMed1997

The effect of non-polar liquids and non-ionic detergents on the ultrastructure and assembly of rat tail tendon collagen fibrils in vitro.

Non-ionic detergents or emulsions of non-polar liquids when added to solutions of rat tail tendon collagen (RTTC) or to the dispersed fibrils produced similar conspicuous ultrastructural modifications in the form of a D-periodic lesion between bands c2 and d in the 'gap region' of the fibril close to the start of the overlap region. The size and extent of the lesion in some fibrils indicates that at least some of the collagen molecules rupture. In an attempt to detect peptide fragments produced in this way we ran SDS-PAGE gels of collagen fibrils treated with the non-ionic detergent Triton X-100. These contained two peptides (44 and 32 kDa) not seen in controls. The lesions are thought to result from interactions between the hydrophobic part of non-polar liquids or detergents with an anomalous part of the fibril's D-period. The anomalous region has a high concentration of hydrophobic and alanyl residues but exceptionally few charged and hydroxyproline ones. We suggest that the anomalous region may play a part in storing and dissipating strain energy and permitting cross-link formation. Similar collagen-lipid interactions may occur under pathological conditions.

Animals↗
PubMed1997

Promotion of breast cancer screening in communities: a research agenda.

This paper used the National Cancer Institute of Canada (NCIC) cancer control framework to review research on participation in breast cancer screening programs and identify areas for further study. Cancer Lit, MEDLINE, CINAHL, Sociofile, Health and the Public Affairs Information Service databases were searched for literature published from 1990 to 1995. Information was also obtained from provincial breast cancer screening programs and Health Canada. Interventions designed to promote participation in screening programs have not been effective. Involvement of the target community, however, increased success and sustainability. Barriers to initial participation within screening programs include alternative sources of screening and the lack of funds to screen all eligible women. Studies show that participation decreases with successive screening rounds. The priorities for study are development of: a theoretical framework for recruitment strategies, a method to capture all Canadian screening results including those performed through provincial health insurance plans and a mechanism to deliver screening to all eligible Canadian women.

Academies and Institutes↗
PubMed1996

Enzymic control of collagen fibril shape.

The shape of collagen fibrils growing in vitro in a cell-free enzyme/substrate system is shown to be dependent on the enzyme/substrate (E/S) ratio. Long fibrils with tapered ends were generated by exposing pCcollagen (procollagen from which the N-propeptides had been removed) to procollagen C-proteinase (which acts by cleaving the C-propeptides from the pCcollagen, converting it to insoluble fibril-forming collagen). Tip shape profiles, established quantitatively by scanning transmission electron microscopy, depended critically on the C-proteinase/pCcollagen ratio. The finest tips occurred at low ratios, the coarsest at high ratios. All fibrils had molecules oriented with amino termini closest to the pointed ends, i.e. N,N-bipolar fibrils in which molecules change orientation abruptly at one location along the fibril. Fibrils had maximal diameter at this molecular switch region. Shape asymmetric fibrils occurred at low E/S ratios, near-shape symmetric fibrils occurred at high ratios. Fibrils generated at low E/S ratios bore the closest resemblance to those formed in vivo except that the central shaft regions of fibrils formed in vitro showed no tendency to be limited to a uniform diameter.

Bone Morphogenetic Protein 1↗
PubMed1996

Collagen fibril formation.

Collagen is most abundant in animal tissues as very long fibrils with a characteristic axial periodic structure. The fibrils provide the major biomechanical scaffold for cell attachment and anchorage of macromolecules, allowing the shape and form of tissues to be defined and maintained. How the fibrils are formed from their monomeric precursors is the primary concern of this review. Collagen fibril formation is basically a self-assembly process (i.e. one which is to a large extent determined by the intrinsic properties of the collagen molecules themselves) but it is also sensitive to cell-mediated regulation, particularly in young or healing tissues. Recent attention has been focused on "early fibrils' or "fibril segments' of approximately 10 microns in length which appear to be intermediates in the formation of mature fibrils that can grow to be hundreds of micrometers in length. Data from several laboratories indicate that these early fibrils can be unipolar (with all molecules pointing in the same direction) or bipolar (in which the orientation of collagen molecules reverses at a single location along the fibril). The occurrence of such early fibrils has major implications for tissue morphogenesis and repair. In this article we review the current understanding of the origin of unipolar and bipolar fibrils, and how mature fibrils are assembled from early fibrils. We include preliminary evidence from invertebrates which suggests that the principles for bipolar fibril assembly were established at least 500 million years ago.

Animals↗
PubMed1996

Factors associated with local breast cancer recurrence after lumpectomy alone.

BACKGROUND: The purpose was to determine the rate of local breast relapse in patients with breast cancer uniformly treated with partial mastectomy but without postoperative radiotherapy and without systemic adjuvant therapy. We also systematically examined the factors associated with local recurrence to determine whether a low-risk subgroup existed. METHODS: A retrospective review of a prospectively followed (median, 8 years) cohort of 293 patients was performed. The end-point was ipsilateral local breast cancer recurrence. The patient's age, tumor size, nodal status, estrogen and progesterone receptor status, histology, and tumor and nuclear grade were studied, as were the presence and amount of carcinoma in situ and the presence of tumor emboli using univariate Kaplan-Meier and Cox step-wise multivariate analyses. RESULTS: The overall local relapse rate was 26% (77 recurrences). Univariate factors significantly associated with decreased local relapse included older age, negative nodes, small tumor size, positive estrogen receptor status, and absence of tumor emboli. Significant multivariate variables were age, nodal status, estrogen receptor status, absence of comedo carcinoma in situ, and tumor emboli. A low-risk subgroup of 66 patients was defined with a 6% 10-year local recurrence rate. CONCLUSION: Important patient and tumor variables associated with local breast cancer relapse after breast-conserving surgery can define a low-risk subgroup.

Adult↗
PubMed1996

Clinical behavior of untreated axillary nodes after local treatment for primary breast cancer.

BACKGROUND: The purpose of this study was to examine the rate of axillary failure in patients with primary breast cancer treated without axillary dissection or radiation and to determine what factors may be associated with axillary failure. METHODS: We studied 112 patients with invasive breast cancer treated for primary disease with breast-conserving surgery without axillary dissection or radiation to the breast or axilla, accrued between 1977 and 1986. Data for these patients were prospectively gathered for a research database and reviewed retrospectively to determine axillary failure. The effects of age, tumor size, estrogen receptor (ER) status, progesterone receptor (PgR) status, histologic grade, nuclear grade, and tumor emboli on time to axillary failure were examined. RESULTS: The median follow-up was 9.6 years. There were 26 axillary recurrences, resulting in a 10-year actuarial nodal control rate of 72%. Patients with nodal failure proceeded to axillary dissection with minimal morbidity. In both univariate and multivariate analyses, only tumor size was significantly associated with axillary failure (p = 0.04 and p = 0.06, respectively). CONCLUSIONS: This study demonstrates a significant effect of tumor size on axillary failure and a reasonable rate of local control in small tumors. Further research should examine the utility of axillary dissection in women with small breast cancers.

Actuarial Analysis↗
PubMed1996

Estrogen replacement in surgical stage I and II endometrial cancer survivors.

OBJECTIVE: Our purpose was to evaluate our experience with estrogen replacement in women with a history of early-stage endometrial cancer and to determine whether it increased the risk for recurrence or death. STUDY DESIGN: A retrospective review was performed of 123 women with surgical stage I and II endometrial adenocarcinoma treated between 1984 and 1994; 62 had received estrogen replacement therapy after cancer therapy. Sixty-one women received no estrogen. Variables analyzed included age parity, surgical stage, grade, depth of myometrial invasion, presence of intercurrent illnesses, duration of follow-up, and duration of estrogen replacement, if applicable. Outcome variables assessed included recurrence rate, time to recurrence, and disease-free interval. RESULTS: The estrogen replacement therapy group had earlier stage disease (p = 0.04) and less severe depth of invasion (p = 0.003); however, the total number of deaths in each group was not significantly different. The disease-free survival in the estrogen replacement therapy group did not differ significantly compared with those not receiving estrogen replacement therapy. The data are suggestive of improved disease-free survival in the estrogen replacement therapy group, which may be related to differences in age, stage, grade, and depth of invasion. The overall recurrence rate was 6.5%, with an overall death rate of 1.6%. CONCLUSIONS: There is no evidence to suggest that estrogen decreased the disease-free interval or increased the risk for recurrence in early-stage disease.

Aged↗
PubMed1996

Combined fine-needle aspiration, physical examination and mammography in the diagnosis of palpable breast masses: their relation to outcome for women with primary breast cancer.

OBJECTIVE: To examine the combined and individual predictive values of fine-needle aspiration (FNA), physical examination (PE) of the breast and mammography (the "triple test") in diagnosing breast cancer in relation to the results of open surgical biopsy. DESIGN: A study of the records of patients who received both FNA and open surgical biopsy for the same palpable breast lump. The results of diagnostic assessment and open surgical biopsy were categorized as positive or negative. Concordance (percentage of tests found to be correct at biopsy), sensitivity, specificity (percentage of patients without breast cancer for whom the diagnostic test was negative) and positive predictive value (percentage of patients with a positive test found to have breast cancer) were determined for the triple test for each diagnostic modality. In addition, prognostic variables (tumour size, node positivity, estrogen and progesterone receptor status) and outcomes were assessed in patients with a diagnosis of breast cancer. SETTING: A university-affiliated general hospital with a special focus on women's health. PATIENTS: Of 290 patients who had both FNA and open surgical biopsy, 191 underwent all three diagnostic procedures. MAIN OUTCOME MEASURES: The diagnostic accuracy of FNA, PE and mammography to permit preoperative definitive therapy or to allow observation without mandating open surgical biopsy. RESULTS: In 81 patients all three diagnostic modalities were in agreement for a diagnosis of either benign or malignant disease; the concordance for the triple test was 98.8% specificity was 100% and sensitivity was 95.5%. Nodal status, tumour size and outcome were similar whether or not the triple test was positive, but, interestingly, when the triple-test results were positive, estrogen (p < 0.05) and progesterone (p < 0.03) receptor values were more likely to be negative. CONCLUSIONS: When all three diagnostic modalities were in agreement for a diagnosis of malignant disease, the combination of FNA, PE and mammography had excellent concordance with the results of open surgical biopsy, and in this situation definitive treatment may be carried out. If all three modalities are in agreement for a diagnosis of benign disease, a period of close observation with repetition of FNA may be safely entertained. Lack of concordance of the three diagnostic modalities mandates biopsy. Triple-test positively does not predict a worse outcome.

Adult↗
PubMed1995

The Henrietta Banting Breast Centre database: a model for clinical research utilizing a hospital-based inception cohort.

The cohort study design has been used successfully in clinical cancer research. Cohorts, however, are valuable only if they produce results which are valid and generalizable. Some hospital-based inception cohorts satisfy both these requirements and may thus be useful research tools. The development of one such hospital-based cohort, the Henrietta Banting Breast Centre database, is described. This cohort is composed of 1097 women diagnosed with primary breast cancer at Women's College Hospital, Toronto, from January 1977 through December 1986. Details of diagnostic procedures, pathology, treatment, dates and sites of recurrence, and date of death are available on 96% of women. By comparison with published series and with the Ontario Cancer Registry, we have demonstrated validity and generalizability. A major advantage is the ready availability of paraffin tissue blocks on virtually all cases, facilitating analyses of the prognostic importance of specific biologic variables and immunocytochemical hormone assays. Other completed studies and future uses of the cohort are described.

Breast Neoplasms↗
PubMed1994

Vertebrate (chick) collagen fibrils formed in vivo can exhibit a reversal in molecular polarity.

A reversal in molecular polarity can occur in vertebrate collagen fibrils. This has been demonstrated using a method for isolating, from chick embryo tendon, entire collagen fibrils 2 to 14 microns in length and suitable for electron-optical examination. A polarity reversal is present in some, but not all, of these fibrils. Such fibrils have two N-ends. The transition region, occupying several D-periods in which the reversal occurs, is not restricted to a central location in a fibril. Analysis of the fibril banding pattern through the transition region shows that the relative axial alignment of antiparallel molecules brings oppositely-directed C-telopeptides into axial register. This could allow antiparallel molecules to be covalently linked via polymeric cross-links involving these C-telopeptides.

Animals↗