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J A Chapman

Publications and source records attributed to J A Chapman.

At least 19 recordsLinked to original sources
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↗
PubMed1993

The standardization of estrogen receptors.

Tumour estrogen receptor (ER) status may determine the medical treatment of a patient with breast cancer; yet inter-laboratory results can vary markedly, particularly when absolute cut-offs in fmol/mg cytosol protein are used. The use of standardized log units is proposed to permit greater inter-laboratory comparability. We have assessed the biochemical ER values using the dextran-coated charcoal method with three data sets, two quality control (QC) sets for Ontario laboratories and a data set with values for 184 primary breast cancer patients seen at Women's College Hospital (WCH) between 1985 and 1986. The distributions for all the raw data were skewed toward the lower end of the range; a log transformation improved the symmetry of the distributions. There was marked inter-laboratory variation in the QC data, and standardized log units greatly reduced this variability. The WCH data had similar differentiation by tumour size and nodal status with both the raw data and standardized log units. However, standardized log units provided more consistent evidence of an association between ER and immunohistochemical ERICA. The standardized log units provide quantitative receptor values suitable for multi-centre research, for future work with clinical outcomes, and for the daily management of patients.

Breast Neoplasms↗
PubMed1992

Growing tips of type I collagen fibrils formed in vitro are near-paraboloidal in shape, implying a reciprocal relationship between accretion and diameter.

Collagen fibrils generated in vitro at 37 degrees C by enzymic removal of C-terminal propeptides from type I pC-collagen (an intermediate in the normal processing of type I procollagen to collagen containing the C-terminal propeptides but not the N-terminal propeptides) display shape polarity, with one tip fine tapered and the other coarse tapered. Mass measurements by scanning transmission electron microscopy show that the mass per unit length along both kinds of tip increases roughly linearly over distances of approximately 100 D periods from the fibril end [D (axial periodicity) = 67 nm]. The fine tips of fibrils of widely differing lengths exhibit near-identical mass distributions, the mass in all cases increasing at the rate of approximately 17 molecules per D period, irrespective of fibril length. Coarse tips display less regular behavior. These results show that (i) the shape of a fine tip is not conical but resembles more closely a paraboloid of revolution, and (ii) for this shape to be maintained throughout growth, accretion (rate of mass uptake per unit area) cannot everywhere be the same on the surface of the tip but must decrease as the diameter increases. To a first approximation, accretion alpha (diameter)-1.

Collagen↗
PubMed1992

A comparison of all-subset Cox and accelerated failure time models with Cox step-wise regression for node-positive breast cancer.

Clinical studies usually employ Cox step-wise regression for multivariate investigations of prognostic factors. However, commercial packages now allow the consideration of accelerated failure time models (exponential, Weibull, log logistic, and log normal), if the underlying Cox assumption of proportional hazards is inappropriate. All-subset regressions are feasible for all these models. We studied a group of 378 node positive primary breast cancer patients accrued at the Henrietta Banting Breast Centre of Women's College Hospital, University of Toronto, between January 1, 1977, and December 31, 1986. 85% of these patients had complete prognostic factor data for multivariate analysis, and 96% of the patients were followed to 1990. There was evidence of marked departures from the proportional hazards assumption with two prognostic factors, number of positive nodes and adjuvant systemic therapy. The data strongly supported the log normal model. The all-subset regressions indicated that three models were similarly good. The variables 1) number of positive nodes, 2) tumour size, and 3) adjuvant systemic therapy were included in all three models along with one of three biochemical receptor variables 1) ER, 2) combined receptor (ER- PgR-; ER+PgR-; ER- PgR+; ER+PgR+; or 3) PgR. Better multivariate modeling was achieved by using quantitative prognostic factors, a check for appropriate underlying model-type, and all-subset variable selection. All-subset regressions should be considered for routine use with the many new prognostic factors currently under evaluation; it is very possible that there may not be a single model that is substantially better than others with the same number of variables.

Adult↗
PubMed1992

Surgical treatment of unexpected invasive cervical cancer found at total hysterectomy.

OBJECTIVE: To determine the proper management of patients found to have invasive cancer of the cervix on pathologic examination of a uterus removed for benign indications. METHODS: We report 18 patients undergoing hysterectomy who were found to have cervical cancer with invasion deeper than 3 mm and/or lymph-vascular space involvement. None had gross residual tumor following simple hysterectomy. All patients underwent a second operation. Seventeen women underwent a radical parametrectomy, upper vaginectomy, and pelvic lymphadenectomy; one had pelvic and periaortic lymphadenectomy alone because of bilateral grossly positive obturator nodes. RESULTS: Median follow-up was 72 months. One of the 15 women without residual disease or nodal involvement at second operation had pelvic recurrence 66 months after therapy. Three patients with disease identified at radical surgery underwent tailored postoperative pelvic radiation, and two of these had pelvic recurrence. The overall actuarial 5-year survival for the 18 patients was 89%. Operative morbidity was comparable to that of patients undergoing primary radical hysterectomy. CONCLUSION: This study confirms that patients with unexpected invasive cervical cancer found at total hysterectomy can undergo radical re-operation with low morbidity and excellent cure rates.

Actuarial Analysis↗
PubMed1992

The correlation of Ki67 growth factor and ERICA in breast cancer.

Estrogen receptor (ER) status is an accepted prognostic indicator for breast cancer when measured by either the biochemical or immunohistochemical (ERICA) methods. Moreover, ERICA was found to be a better predictor of survival in human breast cancer than the biochemical assay for ER. The antibody to Ki67 recognizes the growth fraction of proliferating cells. We examined 100 primary breast cancers to investigate the relationship between ER status as measured by ERICA and Ki67 reactivity. Of the 56 ERICA positive cases, 47 (84%) were Ki67 negative whereas 30 of the 44 ERICA negative tumors were Ki67 positive (68%). There was evidence of a significant inverse relationship between ERICA and the growth fraction (77% of cases, p less than 0.001). In addition, a cluster of ERICA-positive Ki67-positive tumors that were larger and occurred in older patients was identified as a subset that might require aggressive therapy. Our results suggest that Ki67 may be an important additional criterion for predicting the biological behaviour of breast cancers.

Biomarkers, Tumor↗
PubMed1991

Morphology of sheet-like assemblies of pN-collagen, pC-collagen and procollagen studied by scanning transmission electron microscopy mass measurements.

At high concentrations, type I pN-collagen, pC-collagen and procollagen (the first 2 generated from procollagen by enzymic cleavage of C-propeptides and N-propeptides, respectively) can all be made to assemble in vitro into thin D-periodic sheets or tapes. Scanning transmission electron microscopy mass measurements show that the pN-collagen sheets and procollagen tapes have a mass per unit area corresponding to that of approximately 6.8 monolayers of close-packed molecules. pN-collagen sheets are extensive and remarkably uniform in mass thickness (fractional S.D. 0.035); procollagen tapes are neither as extensive nor as uniform in thickness. The mean thickness of pC-collagen tapes is less and the variability is greater. In pN-collagen sheets, the overlap: gap mass contrast in a D-period is increased from 5:4 (the ratio in a native collagen fibril) to 6:4, showing that the N-propeptides do not project into the gap but are folded back over the overlap zone. Assuming all N-propeptides to be constrained to the two surfaces of a sheet, their surface density can be found from the mass thickness of the sheet. In a lateral direction (i.e. normal to the axial direction where the spacing is D-periodic), the N-propeptide domains are calculated to be spaced, centre to centre, by 2.23 (+/- 0.1) nm on both surfaces. This value (approx. 1.5 x the triple-helix diameter) implies close-packing laterally with adjacent domains in contact. Sheet formation and the "surface-seeking" behaviour of propeptides can be understood in terms of the dual character of the molecules, evident from solubility data, with propeptides possessing interaction properties very different from those displayed by the rest of the molecule. The form and stability of sheets (and of first-formed fibrils assembling in vivo) could, it is suggested, depend on the partially fluid-like nature of lateral contacts between collagen molecules.

Animals↗
PubMed1991

Macromolecular organization of chicken type X collagen in vitro.

The macromolecular structure of type X collagen in the matrices of primary cultures of chick hypertrophic chondrocytes was initially investigated using immunoelectron microscopy. Type X collagen was observed to assemble into a matlike structure with-in the matrix elaborated by hypertrophic chondrocytes. The process of self assembly was investigated at the molecular level using purified chick type X collagen and rotary-shadowing EM. It was shown that under neutral conditions at 34 degrees C, individual type X collagen molecules associate rapidly into multimeric clusters via their carboxy-terminal globular domains forming structures with a central nodule of carboxy-terminal domains and the triple helices radiating outwards. Prolonged incubation resulted in the formation of a regular hexagonal lattice by lateral association of the juxtaposed triple-helical domains from adjacent multimeric clusters. This extended lattice may play an important role in modifying the cartilage matrix for subsequent events occurring in endochondral bone formation.

Animals↗
PubMed1991

Heterogeneity in responses to cancer. Part I: Psychiatric symptoms.

Heterogeneity in psychiatric responses to disease specific diagnosis is demonstrated for two groups of cancer patients who are comparable in prognosis and treatment intensity. Implications of this heterogeneity are drawn for etiological study and for planning psychiatric interventions.

Adaptation, Psychological↗
PubMed1991

Heterogeneity in responses to cancer. Part II: Sexual responses.

Heterogeneity in psychosexual responses to disease-specific diagnosis is demonstrated for two groups of cancer patients with testis cancer and Hodgkin's disease who are comparable in prognosis and treatment intensity. The two groups of patients and their partners are shown to differ in their ability to recover from psychiatric problems associated with the diagnosis and/or treatment of cancer.

Adaptation, Psychological↗
PubMed1990

D-periodic assemblies of type I procollagen.

The solubility limit of purified chick type I procollagen, incubated at 37 degrees C in phosphate-buffered saline, was found to be in the range 1 to 1.5 mg/ml. At higher concentrations large aggregates formed. These comprised: (1) D-periodic assemblies; (2) narrow filaments with no apparent periodicity; and (3) segment-long-spacing-like aggregates. The D-periodic assemblies, which predominated at high concentrations, were separated from the other types of aggregate and found to be ribbon-like. Ribbons were uniform in thickness (approximately 8 nm) and up to 1 micron wide. Staining patterns showed features similar to those in native-type collagen fibrils. Immunolabelling indicated that the carboxyl-terminal propeptide domains were close to the carboxyl-terminal gap-overlap junction, and that the amino-terminal propeptide domains were folded over into the amino-terminal side of the overlap zone. Both propeptide domains appeared to be located on the surface of the assemblies. These observations show that intact propeptide domains hinder, but do not prevent, the formation of D-periodic assemblies. The presence of the propeptide domains on the surface of a growing assembly could restrict its lateral growth and limit its final thickness.

Animals↗
PubMed1990

The collagen fibril--a model system for studying the staining and fixation of a protein.

A collagen fibril is made up of long rod-like molecules regularly D-staggered with respect to one another. This means that (i) its axially projected fine structure, resolvable to approximately 2 nm in electron micrographs, repeats D-periodically (D = 67 nm), and (ii) the amino acid residues contributing to each element of the fine structure can be inferred from sequence data. Electron-optical data from a fibril D-period can can therefore be correlated directly with chemical data. Such correlations confirm the electrostatic nature of the staining reaction when a fibril is positively stained. After negative staining, the principal factor determining the small-scale distribution of stain is local exclusion by 'bulky' amino acid side-chains. ('Bulkiness' is the average cross-sectional area, or 'plumpness', of a side-chain.) A small superimposed positive staining contribution can also be detected. Fixation of collagen by aldehydes and diimidoesters occurs via an initial reaction with lysyl (and hydroxylsyl) side-chains and alpha-amino groups, followed by secondary cross-linking reactions that differ from fixative to fixative. These secondary reactions determine the nature and abundance of the cross-links and the extent to which they influence subsequent staining behaviour.

Amino Acid Sequence↗
PubMed1989

Pleomorphism in type I collagen fibrils produced by persistence of the procollagen N-propeptide.

The assembly of type I collagen and type I pN-collagen was studied in vitro using a system for generating these molecules enzymatically from their immediate biosynthetic precursors. Collagen generated by C-proteinase digestion of pC-collagen formed D-periodically banded fibrils that were essentially cylindrical (i.e. circular in cross-section). In contrast, pN-collagen generated by C-proteinase digestion of procollagen formed thin, sheet-like structures that were axially D-periodic in longitudinal section, of varying lateral widths (up to several microns) and uniform in thickness (approximately 8 nm). Mixtures of collagen and pN-collagen assembled to form a variety of pleomorphic fibrils. With increasing pN-collagen content, fibril cross-sections were progressively distorted from circular to lobulated to thin and branched structures. Some of these structures were similar to fibrils observed in certain heritable disorders of connective tissue where N-terminal procollagen processing is defective. The observations are considered in terms of the hypothesis that the N-propeptides are preferentially located on the surface of a growing assembly. The implications for normal diameter control of collagen fibrils in vivo are discussed.

Collagen↗
PubMed1989

The regulation of size and form in the assembly of collagen fibrils in vivo.

A possible mechanism for regulating the lateral growth of collagen fibrils in vivo is considered. A growth inhibitor associated with a particular part of the long semiflexible collagen molecule restricts that part of the molecule to the surface of the growing assembly. Lateral accretion ceases when these inhibitors form a complete circumferential layer around the fibril surface. Cell-mediated removal of the inhibitors allows lateral growth to proceed to a second limiting layer, and so on to subsequent limiting layers. In this way, cycles of inhibitor removal and limited lateral accretion permit growth to be synchronized over large populations of fibrils. Observed diameter distributions in bundles of embryonic and neonatal fibrils are those expected from a mechanism of this kind. The mechanism depends on the existence of axial order (D-periodicity) in fibrils, but not on any specific lateral packing of molecules. Rather, contacts between newly assembled molecules are presumed to be partly fluid-like in lateral directions (except where covalent cross-links have formed). Some initial fluidity in lateral packing prior to cross-linking does not preclude the subsequent emergence of quasi-crystalline packing as cross-links form. The cylindrical shape of fibrils in vivo may also be attributable in part to fluidity of intermolecular contacts at the growing surface.

Collagen↗
PubMed1989

GENCOV: a Fortran program that generates randomly censored survival data with covariates.

We present a Fortran program for simulating censored survival data with covariates under the assumption of random censoring. The program generates times distributed according to the uniform distribution, the generalized Gamma distribution, the log-normal distribution and Pettitt's generalized logistic distribution with Box-Cox transformation of the time variable. Covariates can be introduced in the definition of the survival time, resulting in the generalized log-gamma, log-normal and Pettitt's regression models. Thereby the program provides the means for generating censored survival data according to parametric versions of three common regression models for censored survival data: the Accelerated Failure Time, the Proportional Hazards and the Proportional Odds models.

Computer Simulation↗
PubMed1988

Stimulation of protein phosphorylation in mixed glial cell primary cultures and subcultures by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.

Glial cell primary cultures consisting of protoplasmic and fibrous astrocytes, oligodendrocytes and progenitor glial cells incubated in medium containing 0.5% foetal calf serum and treated with 25 nM 12-o-tetradecanoylphorbol-13-acetate (TPA) for periods between 15 and 60 min showed a stimulation of protein phosphorylation which was most prominent in a polypeptide with a molecular weight of about 80,000 Da. Glial subcultures consisting mainly of Type 2 astrocytes, oligodendrocytes and progenitor glia showed a similar TPA stimulation of 80,000 Da protein phosphorylation detectable within 1 min of phorbol ester addition. TPA treatment of primary glial cultures led to an enhancement of phospholipid turnover but exposure of primary glial cultures to concentrations of TPA up to 250 nM caused no morphological change in protoplasmic astrocytes. 4-Phorbol (4-PH) or dimethylsulfoxide (DMSO) was without effect on protein phosphorylation or lipid turnover in glial cultures.

Animals↗
PubMed1988

Protein kinase C activity in soluble fractions from glial cells in primary culture and subcultures.

Protein kinase C (calcium + phospholipid-dependent kinase) activity has been measured in soluble 100,000 g fractions from mixed glial cells in primary culture; in 12 day cultures the specific activity (mean +/- S.D.) was 184 +/- 10 pmol 32P incorporated/10 min/mg protein. In glial cell subcultures lacking protoplasmic astrocytes protein kinase C specific activity was lower. An inhibitor of protein kinase C in 100,000 g supernatants was removed by chromatography through DE-52 anion exchange resin increasing the specific activity of the calcium + phospholipid-dependent kinase about 20 times. Protein kinase C was also associated with membrane fractions from glial cells; the membrane-associated enzyme had a higher specific activity than in the cytoplasm.

Animals↗