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PubMedDate not supplied

Clinical breast examination: practical recommendations for optimizing performance and reporting.

Clinical breast examination (CBE) seeks to detect breast abnormalities or evaluate patient reports of symptoms to find palpable breast cancers at an earlier stage of progression. Treatment options for earlier-stage cancers are generally more numerous, include less toxic alternatives, and are usually more effective than treatments for later-stage cancers. For average-risk women aged 40 and younger, earlier detection of palpable tumors identified by CBE can lead to earlier therapy. After age 40, when mammography is recommended, CBE is regarded as an adjunct to mammography. Recent debate, however, has questioned the contributions of CBE to the detection of breast cancer in asymptomatic women and particularly to improved survival and reduced mortality rates. Clinicians remain widely divided about the level of evidence supporting CBE and their confidence in the examination. Yet, CBE is practiced extensively in the United States and continues to be recommended by many leading health organizations. It is in this context that this report provides a brief review of evidence for CBE's role in the earlier detection of breast cancer, highlights current practice issues, and presents recommendations that, when implemented, could contribute to greater standardization of the practice and reporting of CBE. These recommendations may also lead to improved evidence of the nature and extent of CBE's contribution to the earlier detection of breast cancer.

Breast Diseases↗
PubMed1984

Differential extraction of tumor-specific transplantation antigen and embryonic antigen from simian virus 40- and adenovirus 7-induced sarcoma cells of hamsters with 1-butanol and 3 M potassium chloride.

Simian virus 40 (SV40)-induced sarcomas and adenovirus 7-induced sarcomas (Adv-7) exhibit both specific tumor-specific transplantation antigens (TSTA) and cross-protective embryonic antigens at the cell surface in the LAK:LVG(SYR) strain of Syrian golden hamsters. Specific SV40 TSTA could be released from the surfaces of living hamster sarcoma cells in a 2.5% crude 1-butanol extract (CBE) and served as immunogen to protect syngeneic recipients against subsequent homologous but not heterologous tumor cell challenge. The CBE-extracted SV40-induced TSTA (tumor-specific) was observed to be free of detectable, cross-protective embryonic antigens (EA) by tumor transplantation assays. The induction of cytotoxic lymphocyte-mediated immunity with the CBE-released TSTA was dependent on the administration of a single sensitizing injection of 12-20 micrograms antigen protein. Higher concentrations (50-1,000 micrograms) of the CBE tumor cell extract, given in a single injection, enhanced tumor growth as did two injections of 12.5 micrograms CBE-extracted SV40-induced TSTA at 1-week intervals. A cross-protective antigen(s), not detected in the CBE tumor extracts, was retained in the intact, 1-butanol-extracted SV40 and Adv-7-induced tumor cell lines after completion of the CBE extraction procedure and in similarly extracted 10-day hamster fetal cells. Some alterations in the normal immunogenicity of EA extracted with CBE followed by KCI from SV40-induced sarcoma cells could be detected in the transplantation assays and lymphocyte transformation assays, whereas EA extracted from CBE-KCI-treated Adv-7 cells or 10-day hamster fetal cells retained normal immunogenicity in vivo and in vitro. These procedures provide a means for successful separation of immunogenic SV40- and Adv-7-induced TSTA from detectable, biologically active, cross-protective EA from the surfaces of these sarcoma cells.

1-Butanol↗
PubMed2004

Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination.

CONTEXT: Current recommendations for women who have a BRCA1 or BRCA2 mutation are to undergo breast surveillance from age 25 years onward with mammography annually and clinical breast examination (CBE) every 6 months; however, many tumors are detected at a relatively advanced stage. Magnetic resonance imaging (MRI) and ultrasound may improve the ability to detect breast cancer at an early stage. OBJECTIVE: To compare the sensitivity and specificity of 4 methods of breast cancer surveillance (mammography, ultrasound, MRI, and CBE) in women with hereditary susceptibility to breast cancer due to a BRCA1 or BRCA2 mutation. DESIGN, SETTING, AND PARTICIPANTS: A surveillance study of 236 Canadian women aged 25 to 65 years with BRCA1 or BRCA2 mutations who underwent 1 to 3 annual screening examinations, consisting of MRI, mammography, and ultrasound at a single tertiary care teaching hospital between November 3, 1997, and March 31, 2003. On the day of imaging and at 6-month intervals, CBE was performed. MAIN OUTCOME MEASURES: Sensitivity and specificity of each of the 4 surveillance modalities, and sensitivity of all 4 screening modalities vs mammography and CBE. RESULTS: Each imaging modality was read independently by a radiologist and scored on a 5-point Breast Imaging Reporting and Data System scale. All lesions with a score of 4 or 5 (suspicious or highly suspicious for malignancy) were biopsied. There were 22 cancers detected (16 invasive and 6 ductal carcinoma in situ). Of these, 17 (77%) were detected by MRI vs 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE. The sensitivity and specificity (based on biopsy rates) were 77% and 95.4% for MRI, 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE, respectively. There was 1 interval cancer. All 4 screening modalities combined had a sensitivity of 95% vs 45% for mammography and CBE combined. CONCLUSIONS: In BRCA1 and BRCA2 mutation carriers, MRI is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone. Whether surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women requires further investigation.

Adult↗
PubMed1989

Effects of tannins from different sources on airway epithelial and platelet function.

The uniqueness of tannin isolated from aqueous extracts of cotton bracts (CBE) on the electrophysiological and ion transport properties of the canine tracheal epithelium and on 5-hydroxytryptamine (5-HT) release from platelets was investigated. The effect of CBE from Deltapine 41 cotton picked before (green, containing high-concentration, high-molecular-weight tannin) and after (brown, containing low-concentration, low-molecular-weight tannin) senescence and Darjeeling tea extracts and tannin isolated from Darjeeling tea were compared to the effects of Acala SJ-2 CBE and Acala SJ-2 tannin. Green Deltapine 41 CBE was similar to Acala SJ-2 CBE in decreasing short-circuit current (Isc) and net chloride secretion and in producing a dose-response release of 5-HT from platelets. Both Green and Brown Deltapine 41 CBE altered the paracellular pathway, but were less potent than Acala SJ-2 CBE. Brown Deltapine 41 CBE stimulated chloride transport in the airway epithelium and did not produce 5-HT release from human platelets. Darjeeling tea and tea tannin increased Isc and net chloride secretion and caused 5-HT release from platelets only at high concentrations. These studies demonstrate that all tannins are not alike; they suggest that molecular weight and concentration may be important for tannin activity and that the tannin in cotton bracts extract may be unique to cotton in its effect on the airway epithelium and on platelets.

Airway Resistance↗
PubMed2004

Role of B-esterases in assessing toxicity of organophosphorus (chlorpyrifos, malathion) and carbamate (carbofuran) pesticides to Daphnia magna.

In this study, the cladoceran Daphnia magna was exposed to two model organophosphorous and one carbamate pesticides including malathion, chlorpyrifos and carbofuran to assess acetylcholinesterase (AChE) and carboxylesterase (CbE) inhibition and recovery patterns and relate those responses with individual level effects. Our results revealed differences in enzyme inhibition and recovery patterns among the studied esterase enzymes and pesticides. CbE was more sensitive to organophosphorous than AChE, whereas both CbE and AChE showed equivalent sensitivities to the carbamate carbofuran. Recovery patterns of AChE and CbE activities following exposure to the studied pesticides were similar with 80-100% recoveries taking place 12 and 96 h after exposure to organophosphorous and carbamates pesticides, respectively. The physiological role of AChE and CbE inhibition patterns in Daphnia was examined by using organophosphorous and carbamate compounds alone and with specific inhibitors of CbE. Under exposure to organophosphorous pesticides, survival of Daphnia juveniles was impaired at AChE inhibition levels higher than 50% whereas under exposure to the carbamate carbofuran low levels of AChE inhibition affected mortality. Inhibition of CbE by 80-90% increased toxicity to organophosphorous and carbamate pesticides by up to two- and four-fold, respectively. Our results suggest that both AChE and CbE enzymes are involved in determining toxicity of Daphnia to the studied chemicals and that AChE inhibition levels higher than 50% can be considered of environmental concern to Daphnia species.

Animals↗
PubMed2002

Effect of clinical breast examination training on practitioner's perceived competence.

Effective clinical breast exam (CBE) training should not only improve screening technique but also reduce barriers to performing CBE by increasing perceived competence and self-efficacy. Using the vertical strip technique with silicone breast models and live patients, 4-day CBE training sessions were provided to 34 nurse-practitioners. Trainees perceived a significant decrease in the size of breast lesion they could detect after training (P < 0.0001). The size of the detectable lesion reported prior to training was correlated with the years of CBE experience (P < 0.05); however, the size of the detectable lesion after training was not significantly related to previous CBE experience. Trainees with less CBE experience prior to training reported greater improvement in the ability to detect smaller lesions (P < 0.05). Results indicate a significant CBE training effect on perceived competence, and suggest that nurse practitioners from all levels of experience can benefit significantly from CBE training. O 2002 International Society for Preventive Oncology.

Adult↗
PubMed1986

Interactions of a water extract of cotton bract with dog isolated airway smooth muscle.

The inhalation of cotton dust by cotton-mill workers causes byssinosis, a disease characterized by chest tightness and other symptoms indicative of bronchoconstriction. In the present study the dog isolated trachealis smooth muscle preparation was employed to examine the ability of a crude, water extract of cotton bracts (CBE) to (1) cause contractile responses mediated by receptors, (2) modify responses of the tissue to a number of excitatory and inhibitory agents, and (3) alter responsiveness of the preparations to electrical field stimulation mediated by intrinsic cholinergic, excitatory nerves and adrenergic, inhibitory nerves. CBE evoked contraction of the tissues by an action that did not involve muscarinic, histamine, or 5-hydroxytryptamine receptors. The maximum tissue responses to exogenous histamine, 5-hydroxytryptamine, and isoproterenol were enhanced significantly in the presence of CBE, while those to KCl and methacholine were unaffected. The sensitivities (EC50 values) of the tissues to these agents were not, however, altered by CBE. Contractions induced by cholinergic nerve stimulation were increased in the presence of CBE, via a mechanism that appears, at present, to result from a prejunctional facilitation of acetycholine release. Relaxations to adrenergic nerve stimulation were not affected by CBE. Results suggest that, in addition to its direct, contractile activity, CBE can alter indirectly the responsiveness of the tissue to a number of endogenous mediator substances. Intrinsic, cholinergic excitatory nerves may be a target for the acute action of CBE as well.

Animals↗
PubMed2001

CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the interleukin-3 survival signal.

The Ces-2/E2A-HLF binding element (CBE) is recognized by Caenorhabditis elegans death specification gene product Ces-2 and human acute lymphocytic leukemia oncoprotein E2A-HLF. In an attempt to identify a cellular CBE-binding protein(s) that may be involved in apoptosis regulation in mammals, multiple nuclear binding complexes of CBE were identified in various mammalian cell lines and tissues by electrophoretic mobility shift assay. Cyclic AMP (cAMP)-responsive element (CRE)-binding protein (CREB) was present in one major CBE complex of Ba/F3 and TF-1 cells, and both in vitro-translated and Escherichia coli-synthesized CREB bound to CBE. Activation of CREB by cAMP-elevating chemicals or the catalytic subunit of protein kinase A (PKAc) resulted in induction of the CBE-driven reporter gene. Stimulation of Ba/F3 cells with interleukin-3 (IL-3) promptly induced phosphorylation of CREB at serine(133) partially via a PKA-dependent pathway. Consistently, Ba/F3 cell survival in the absence of IL-3 was prolonged by activation of PKA. Conversely, treatment of cells with a PKA inhibitor or expression of the dominant negative forms of the regulatory subunit type I of PKA and CREB overrode the survival activity of IL-3. Last, the bcl-2 gene was demonstrated to be one candidate cellular target of the CREB-containing CBE complex, as mutations in the CRE and CBE sites significantly reduced the IL-3 inducibility of the bcl-2 promoter. Together, our results suggest that CREB is one cellular counterpart of Ces-2/E2A-HLF and is part of IL-3 dependent apoptosis regulation in hematopoietic cells.

Animals↗
PubMed2006

Neoplastic transformation of ciliary body epithelium is associated with loss of opticin expression.

BACKGROUND: Opticin is a recently discovered glycoprotein present predominantly in the vitreous humour. It is synthesised and secreted by the ciliary body epithelium (CBE) from the initiation of CBE development in the embryo, and production continues throughout life. AIM: To determine whether a variety of ciliary body tumours synthesise opticin to characterise further its role in ciliary body health and disease. METHODS: Immunohistochemistry was used to determine the distribution of opticin in normal human CBE, and in hyperplastic and neoplastic CBE lesions. RESULTS: Opticin was immunolocalised to the basal cell surface and basement membrane material of the non-pigmented CBE in nine donor eyes as well as four hyperplastic lesions of the CBE (Fuchs's adenoma). By contrast, none of eight neoplastic lesions (two adenoma and six adenocarcinoma) of CBE stained for opticin. CONCLUSION: The present series supports the theory that opticin is produced by the non-pigmented CBE throughout adult life. Loss of opticin expression by this tissue is associated with and could contribute towards neoplastic transformation.

Adenocarcinoma↗
PubMed2006

Is active glucose transport present in bovine ciliary body epithelium?

Hyperglycemia is a major risk factor for diabetic cataract formation. Effective regulation of glucose transport by the ciliary body epithelium (CBE) is pivotal to normal glycemic control in the anterior eye, which in turn affects the glucose level of the crystalline lens. The present study aimed to characterize the glucose transport mechanisms across the bovine blood-aqueous barrier (BAB) represented by the CBE. With an Ussing-type chamber, the glucose transport kinetics were measured and characterized in the presence and absence of various glucose transporter inhibitors. The saturation characteristics of the CBE to glucose were estimated from an Eadie-Hofstee plot. The mRNA expression of glucose transporters in specific regions of the bovine CBE was assessed using RT-PCR. The trans-CBE glucose flux was found to be sensitive to the glucose transporter inhibitors cytochalasin B, phloretin, and phlorizin. The transport system had a kinetic constant of 5.3 mM and a maximum velocity of 349.5 nmol.h(-1).cm(-2). Gene expression for GLUT1, GLUT3, GLUT4, GLUT5, and SGLT2 was observed in both the pars plana and pars plicata regions of the bovine CBE. This study demonstrates that glucose transport across the bovine CBE is primarily passive in nature. However, the novel findings of 1) the presence of a phlorizin-sensitive glucose flux and 2) gene expression for SGLT2 mean that a potential role for active glucose transport cannot be ruled out. The elucidation of the exact function of SGLT2 in the bovine CBE may shed important light on the glucose transport and physiology of the BAB and inform future studies of glycemic control in relation to diabetic cataract formation.

Animals↗
PubMed1988

Bronchoalveolar cell activation after inhalation of a bronchoconstricting agent.

Airway inflammation is thought to be an important determinant of bronchoconstriction and bronchial hyperreactivity. We have recently demonstrated that bronchoconstriction induced by an aqueous extract of cotton bracts (CBE) is associated with bronchoalveolar complement activation, release of polymorphonuclear neutrophil (PMN) chemoattractants by pulmonary cells, and increased numbers of bronchoalveolar lavage PMN's. In the present study we performed bronchoalveolar lavage (BAL) on subjects after CBE or control (saline) challenge and examined whether BAL cells were activated in vitro to produce other inflammatory agonists. After CBE administration, cultured BAL cells released increased amounts of the reactive O2 species, superoxide (O2-.), and the cyclooxygenase products prostaglandin E2 and thromboxane B2. Although none of these in vitro parameters of BAL cell activation appeared to correlate with the degree of bronchoconstriction induced by CBE, BAL fluid levels of thromboxane B2 were also increased after CBE administration and in vivo amounts of this eicasanoid did correlate with the degree of bronchoconstriction induced by CBE (r = 0.50, P less than 0.04). Finally, although cell culture supernatants were highly chemotactic for PMN's, concentrations of leukotriene B4 were not increased, suggesting other chemotaxins were released by BAL cells in this setting. We conclude that CBE administration activates bronchoalveolar cells to release reactive O2 species and cyclooxygenase products that may be important in the bronchoconstricting response to CBE.

Adult↗
PubMed1997

A catalytic amino acid and primary structure of active site in Aspergillus niger alpha-glucosidase.

The catalytic amino acid residue of Aspergillus niger alpha-glucosidase (ANGase) was identified by modification with conduritol B epoxide (CBE), a mechanism-based irreversible inactivator. The inactivation by CBE followed pseudo-first order kinetics. The interaction of CBE and ANGase conformed to a model with a reversible enzyme-inhibitor complex formed before covalent inactivation. A competitive inhibitor, Tris, decreased the inactivation rate. The incorporation of one mole of CBE per mole of ANGase was completely abolished the enzyme activity. A dissociated carboxyl group (-COO-) in the active site was suggested to attack the C-1 of CBE. ANGase was composed of two subunits (P1 and P2), of which P2 was modified by CBE. The labelled residue was included in a peptide (LY3) that was obtained from Lys-C protease digestion of CBE-bound P2. The sequence analysis of CBE-labelled LY3 showed that an Asp was the modified residue, that is, one of the catalytic amino acid residues of ANGase. The primary structure of LY3 was determined by analyzing the sequence of peptide fragments prepared by several proteases.

Amino Acid Sequence↗
PubMed1983

Extraction of immunogenic and suppressogenic antigens from variants of B16 melanoma exhibiting low or high metastatic potentials.

This investigation examined the effect of soluble antigen prophylaxis on s.c. and metastatic growth of B16 variants which demonstrated either a low or high propensity to colonize the lungs (B16-F1 and B16-F10, respectively) of syngeneic C57BL/6J mice. The two variants share a tumor-associated antigen, since immunization with crude butanol extracts (CBEs) of B16-F1 cells protected hosts against s.c. challenge with either B16-F1 or B16-F10 cells. CBE from B16-F10 (CBE-F10) were unable to engender a measurable immune response against s.c. challenge with either tumor variant. Pretreatment with 100 to 300 micrograms CBE from F1 cells was also effective in reducing the outgrowth of experimentally induced B16-F1 or B16-F10 pulmonary foci. However, mice immunized with 100 micrograms CBE-F10 bore significantly more pulmonary tumors than did phosphate-buffered saline-treated controls. The enhancing and protective activities were specific for the B16 tumor and could be adoptively transferred 24 hr prior to tumor challenge by i.p. injection of 5 X 10(7) spleen cells from CBE-immunized mice. The enhancing activity in the CBE-F10 immune spleen cell population was abolished by depletion of adherent cells onto plastic. Adoptive transfer of the CBE-F10-immune adherent cell population did not affect metastatic growth, suggesting that, in this experimental system, the adherent population was not an efferent suppressor and could not recruit host elements to effect suppression. Indeed, spleen cell-mixing experiments demonstrated that only immune adherent cells combined with immune nonadherent cells could partially reconstitute the tumor growth-enhancing potential of the unfractionated CBE-F10-immune spleen cell population.

Animals↗
PubMed2004

Mammography benefit in the Canadian National Breast Screening Study-2: a model evaluation.

The CNBSS-2 among women aged 50-59 did not show any significant difference in breast cancer mortality between a control arm screened annually by CBE and a study arm screened by CBE and mammography. Because of this design, the benefit of screening compared to no screening could not be evaluated. We therefore conducted a modeling effort to estimate the benefit of mammography or CBE compared to no screening. We incorporated demographic, epidemiologic and screening characteristics of the CNBSS-2 in MISCAN. Stage-specific sensitivities of CBE, with and without mammography, and breast cancer incidence rate in the trial were estimated by comparing observed trial data with model predictions. We predicted the number of breast cancer deaths for both study arms of the CNBSS-2 and in the absence of screening, assuming improvement in prognosis by early detection. We estimated a 24-29% higher breast cancer incidence rate in the CNBSS-2 than the average Canadian rate. Estimated sensitivity of CBE (control arm) varied from 0.29 to 0.48 for stage T1c and from 0.6 to 0.65 for stage T2+. Estimated sensitivity of CBE supplemented with mammography (study arm) varied from 0.5 to 0.79 for stage T1c and was 0.95 for stage T2+. Expected breast cancer mortality reduction by annual CBE screening is 20.5% compared to no screening. Estimated breast cancer mortality reduction by mammography screening compared to no screening for the CNBSS-2 fell within the range 13.6-34.1%. Enrolled women had above average risk. Screening sensitivity in both arms was high. A benefit of mammography screening is supported by our modeling of the CNBSS-2 results.

Breast Neoplasms↗
PubMed1988

Active site directed inhibition of a cytosolic beta-glucosidase from calf liver by bromoconduritol B epoxide and bromoconduritol F.

Hydrolysis of p-nitrophenyl-beta-D-glucoside by cytosolic beta-glucosidase proceeds with retention of the anomeric configuration. Whereas inactivation of the enzyme by the glucosidase inhibitor conduritol B epoxide (CBE) was extremely slow (ki(max)/Ki 0.57 M-1 min-1) it reacted 130 times more rapidly with 6-bromo-6-deoxy-CBE (Br-CBE). The beta-glucosidase could be labeled with [3H]Br-CBE; incorporation of 1 mol inhibitor/mol enzyme resulted in complete loss of activity. Most of the bound inhibitor was released after denaturation and treatment with ammonia as (1,3,4/2,5,6)-6-bromocyclohexanepentol, thus demonstrating the formation of an ester bond with an active site carboxylate by trans-diaxial opening of the epoxide ring. It was concluded from the Ki values for the epoxide inhibitors and for coduritol B with the cytosolic enzyme and corresponding data for the lysosomal beta-glucosidase that the unusually low reactivity with CBE and Br-CBE is probably due to the inability of the cytosolic enzyme to effectively donate a proton to the epoxide oxygen. An extremely rapid inactivation of the cytosolic beta-glucosidase was caused by bromoconduritol F ((1,2,4/3)-1-bromo-2,3,4-trihydroxycyclohex-5-ene) with ki(max)/Ki 10(5) M-1 min-1. In contrast with the Br-CBE-inhibited enzyme the beta-glucosidase inhibited by bromoconduritol F was subject to spontaneous reactivation with t1/2 approximately 20 min.

Animals↗
PubMed1983

Bioassays of smooth muscle contracting agents in cotton mill dust and bract extracts: arachidonic acid metabolites as possible mediators of the acute byssinotic reaction.

Byssinosis is an occupational respiratory disease contracted by cotton mill workers who inhale cotton mill dust. The acute byssinotic reaction is characterized by a drop in the 1-sec forced expiratory volume (FEV1.0) on Monday following a weekend's absence from work. This physiological reaction is the result of the contraction of bronchial smooth muscle, which causes narrowing of small airways. An isolated tissue bath technique was used to assay smooth muscle contractions induced by cotton dust extract (CDE) and cotton bract extract (CBE). CBE-induced contractions of rat stomach smooth muscle were blocked (82%) by 100 ng/ml methysergide (blocks 5-hydroxytryptamine (5HT) 100%); CDE was not significantly blocked by methysergide (13%). CDE-induced contractions were blocked (100%) by 25 micrograms/ml indomethacin and 100 micrograms/ml salicylic acid (blocks prostaglandin F2 alpha (PGF2 alpha) 100%). The portion of CBE contracting ability not blocked by methysergide was blocked totally by indomethacin. Blocking agents ineffective against CDE or CBE include atropine (acetylcholine blocker), pyrilamine maleate and diphenhydramine (histamine blockers), imidazole and 7-(1-imidazolyl)heptanoic acid (7IHA) (thromboxane blockers), and carboxypeptidase B2 (kinin blocker). The data suggest that cotton bract contains 5HT, which is responsible for a majority of the CBE-induced contraction and a minority of the CDE-induced contraction. The data also suggest that cotton dust and bract contain a substance which causes the release of PGF2 alpha which in turn causes the contraction of smooth muscle. This substance is responsible for a majority of the CDE-induced and a minority of the CBE-induced contractions. Radioimmunoassay (RIA) confirmed PGF2 alpha release from rat fundal smooth muscle when exposed to CDE and CBE. Increased synthesis and release of arachidonic acid metabolites might be a major mechanism in the bronchoconstriction observed in the acute byssinotic reaction.

Acute Disease↗
PubMed1987

Glucocerebrosidase deficiency and lysosomal storage of glucocerebroside induced in cultured macrophages.

A cell culture model stimulating the genetic deficiency of glucocerebrosidase has been developed, utilizing macrophages and conduritol B epoxide (CBE), the specific irreversible inhibitor of the enzyme. Rat peritoneal macrophage glucocerebrosidase was completely inhibited when cells were treated with 10 microM CBE for 16 h or 100 microM CBE for 2 h. The t1/2 of inactivation was 30 min at 10 microM concentration. When cells were washed free of CBE, the enzyme activity reappeared linearly with time, reaching 50% of control activity 48 h after removal of the inhibitor. CBE-treated macrophages have normal phagocytic activity toward [3H]glycine-coupled latex beads and a normal number of mannose receptors. CBE was found to have no effect on other lysosomal enzymes. When [14C]glucocerebroside, encapsulated in multilamellar liposomes with alpha-D-mannopyranoside covalently coupled to the surface, was fed to glucocerebrosidase-depleted macrophages, the radiolabelled glycolipid accumulated and was undegraded. Subcellular fractionation on a Percoll density gradient demonstrated that the stored glucocerebroside in the CBE-treated macrophages was localized in lysosomes.

Animals↗
PubMed1998

An assessment of the influence of clinical breast examination reports on the interpretation of mammograms in a breast screening program. Ontario Breast Screening Program Radiologists Research Group.

The population-based Ontario Breast Screening Program (OBSP) provides two-yearly screening by both nurse examiner clinical breast examination (CBE) and two-view mammography to women aged 50 to 69. CBE alone accounts for about 5% of cancer detection. The purpose of this study was to determine whether CBE information affects radiologists' interpretation of mammography. Interpretation was defined by 1) radiologists' referral rates for diagnostic evaluation and 2) radiologists' accuracy in distinguishing cancer from non-cancer on mammograms. Mammograms were obtained from women randomly selected from those screened in the OBSP between 1990 and 1992. Selection was stratified by whether or not the nurse examiner had independently referred for diagnostic evaluation. Additional women diagnosed with breast cancer were selected to increase the precision of the receiver-operating characteristic (ROC) curve. Each participating OBSP radiologist read a set of mammograms twice, approximately three weeks apart. The first reading was based on mammograms alone. At the second reading, the CBE report was included on the reporting form. Among 620 women referred by the nurse, radiologist referral rate increased from 37.7% to 40.8% (p = 0.079) when CBE information was available. Among the 637 not referred by the nurse, radiologist referral rate decreased from 29.8% to 25.6% (p = 0.005). There was little effect on the sensitivity and specificity of radiologist referral and the areas under the two ROC curves (with and without CBE information) were not significantly different (p = 0.571). Although there was some effect of CBE information on radiologists' pattern of referral, there was no effect on accuracy of cancer detection.

Breast Neoplasms↗