Morphologic analysis of false negative SurePath® slides using Focalpoint™ GS computer-assisted cervical screening technology: An Australian experience.

Background: The trial results of BD FocalPoint™ GS computer assisted screening(FP) of BD SurePath(®) liquid based cervical cytology slides (SP) were published in Diagnostic Cytopathology in 2012.(1) METHOD: The FP-reviewed SP slides were compared to conventional cervical Pap smears (CON) in a split sample of 2198 routine specimens. In all 47 confirmed high grade (HG) cases, FP either selected fields of view (FOV) containing cells suspicious or diagnostic of HG (46/47), or prompted full screening of the slide (1/47) leading to detection of the HG lesion.

Results of an Australian trial using SurePath liquid-based cervical cytology with FocalPoint computer-assisted screening technology.

BD FocalPoint GS™ computer-assisted screening of BD SurePath® liquid-based cervical cytology slides (SP + FP) was compared with screening an accompanying conventional cervical Papanicolaou (Pap) smear (CON) in a split sample trial of 2,198 routine specimens. The rate of unsatisfactory specimens in the SP + FP arm was 0.2% compared with 4.

Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma.

Background: The effect on Paco2 of high concentration oxygen therapy when administered to patients with severe exacerbations of asthma is uncertain.

Methods: 106 patients with severe exacerbations of asthma presenting to the Emergency Department were randomised to high concentration oxygen (8 l/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93% and 95%) for 60 min. Patients with chronic obstructive pulmonary disease or disorders associated with hypercapnic respiratory failure were excluded.

Assuring the quality of quality assurance: seeding abnormal slides into the negative Papanicolaou smears that will be rapid rescreened.

Background: Rapid rescreening (RR) of negative Papanicolaou smears (PS) is used in many countries as a quality-assurance measure. Seeding of abnormal slides has been suggested as a way to increase the sensitivity of this procedure. Since 2004, the authors have carried out RR with seeding before issuing reports.

A three-armed trial of the ThinPrep Imaging System.

We compared the performance of the ThinPrep (TP) Imaging System (TIS) with manual reading of TP slides (TPM) and with manual reading of the paired conventional Pap smear (PS) in terms of sensitivity for and positive predictive value (PPV) of high-grade disease and productivity. The study consisted of 11,416 routine PS and paired TP slides as well as 103 confirmed abnormal TP slides. In terms of sensitivity for the detection of biopsy-confirmed high-grade disease, overall there was no statistically significant difference between TIS-screened TP (TPI) and TPM (81.

Follow-up of cytologic predictions of endocervical glandular abnormalities: histologic outcomes in 123 cases.

Objectives: To determine histologic positive predictive values (PPVs) for three categories of cytologic reports of endocervical glandular abnormalities.

Materials And Methods: We obtained histologic follow-up for 100% of 67 cytologic predictions of adenocarcinoma in situ (AIS) and 82% of 39 predictions of possible AIS (?AIS) made over a 4-year period (1999-2002) and for 25% of 105 atypical endocervical cells (AEC) predictions over a 12-month period (2000). For each category of cytologic report, we determined the histologic yields of high-grade lesions overall and of high-grade glandular lesions.

ADAM-Integrin Interactions: potential integrin regulated ectodomain shedding activity.

ADAMs (a disintegrin and metalloprotease) are a family of cell surface proteins related to the Class III snake venom metalloproteases (SVMP). ADAMs are members of the Metazincin family which includes the matrix matalloproteases and the ADAMTS proteins. Unlike their snake venom relatives, ADAMs are expressed as transmembrane cell surface proteins.

ADAM disintegrin-like domain recognition by the lymphocyte integrins alpha4beta1 and alpha4beta7.

The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin alpha4beta1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins alpha4beta1, alpha4beta7 and alpha9beta1.

Matrix-dependent plasticity of the malignant phenotype of bladder cancer cells.

The purpose of this study was to investigate the effect of cancer- and normal basement membrane-derived extracellular matrix to modulate the phenotype of bladder cancer cell lines. Five lines, varying in malignancy from papilloma to highly undifferentiated and invasive and immortalized human urothelial cells, were grown on two extracellular matrix preparations, Matrigel and SISgel. Matrigel represents matrix remodeled by malignancy while SISgel, obtained from small intestine submucosa (SIS), represents the normal matrix supporting differentiated cell growth.

Integrin alpha4beta1-dependent adhesion to ADAM 28 (MDC-L) requires an extended surface of the disintegrin domain.

ADAMs (a disintegrin and metalloprotease) are a family of proteins that possess functional adhesive and proteolytic domains. ADAM 28 (MDC-L) is expressed by human lymphocytes and contains a disintegrin-like domain that serves as a ligand for the leukocyte integrin, alpha4beta1. To elucidate which residues comprise the alpha4beta1 binding site in the ADAM 28 disintegrin domain, a charge-to-alanine mutagenesis strategy was utilized.

In vitro selection of fibronectin gain-of-function mutations.

Directed protein evolution, which employs a combination of random mutagenesis, phage display, and in vitro selection, was used to identify second-site suppressors of the fibronectin (Fn) cell binding domain mutation Asp1495Ala (RGA). The mutations in the Fn 9th (3fn9) and 10th (3fn10) type III repeats obtained after selection on purified integrins alphaIIbbeta3(D119Y) and alpha5beta1 are reported. The 3fn9-10(D1495A) phage with substitution mutations at Asp1418, which is located within the linker region between 3fn9 and 3fn10, enhanced binding to the integrins alphaIIbbeta3 and alpha5beta1, but not alphavbeta3.

The lymphocyte metalloprotease MDC-L (ADAM 28) is a ligand for the integrin alpha4beta1.

The interaction of lymphocytes with other cells is critical for normal immune surveillance and response. MDC-L (ADAM 28), a member of the ADAM (a disintegrin and metalloprotease) protein family, is expressed on the surface of human lymphocytes. ADAMs possess a disintegrin-like domain similar in sequence to small non-enzymatic snake venom peptides that act as integrin antagonists.

Recognition of fibronectin by the platelet integrin alpha IIb beta 3 involves an extended interface with multiple electrostatic interactions.

Normal platelet function is dependent on the ability of integrin alpha IIb beta 3 (glycoprotein IIb/IIIa) to interact with components of the subendothelial matrix, such as fibronectin (Fn), exposed at sites of vascular injury. Studies using synthetic peptides derived from human Fn sequences Asp(1373)--Thr(1383) and Arg(1493)--Asp(1495) have suggested a role for both the 9th (3fn9) and 10th (3fn10) type III repeats of this ligand in binding to alpha IIb beta 3. In this study, we have taken a charge-to-alanine mutagenesis approach to evaluate the importance of these sites, and other charged residues, within the context of recombinant 3fn9--10 modules for binding to alpha IIb beta 3.

Clonal restriction of platelet-associated anti-GPIIb/IIIa autoantibodies in patients with chronic ITP.

Chronic immune thrombocytopenic purpura is due to platelet destruction induced by autoantibodies against platelet surface antigens. Prior studies show that some serum autoantibodies are light-chain restricted, suggesting a clonal origin. Since plasma and platelet-associated antibody from the same patient may bind to different epitopes.

Subdividing atypical glandular cells of undetermined significance according to the Australian modified Bethesda, system: analysis of outcomes.

Background: The Australian modification of the Bethesda system (TBS) for reporting endocervical cellular abnormalities differs from TBS in having a "high grade" category for prediction of adenocarcinoma in situ (AIS), an "inconclusive" category requiring that AIS be excluded (AISEX), and a "low grade" category (Enatyp) for when only minor changes are seen in endocervical cells.

Methods: From subsequent follow-up, the authors evaluated the proportion of histologically confirmed high grade lesions (squamous, glandular, or endometrial) in each cytologic reporting category, for cases in which no concurrent squamous abnormality was also predicted.

Results: From information was available for 95.

MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes.

The metalloprotease disintegrin cysteine-rich (MDC) proteins are a recently identified family of transmembrane proteins that function in proteolytic processing of cell surface molecules and in cell adhesion. Since lymphocytes must interact with a constantly changing environment, we hypothesized that lymphocytes would express unique MDC proteins. To identify MDC proteins expressed in human lymph node, a polymerase chain reaction-based strategy combined with degenerate oligonucleotide primers was employed.

Comparison of ThinPrep and Pap smear in relation to prediction of adenocarcinoma in situ.

Objective: To compare the accuracy of reporting split-sample ThinPrep (SSTP) and the Pap smear (PS) in cases of histologically confirmed adenocarcinoma in situ (AIS) and to ascertain the reasons for any discrepancies.

Study Design: Comparison of prospective PS and ThinPrep (TP) predictions with unblinded review of TP slides.

Results: In 30 paired cytologic samples, AIS was originally accurately predicted by PS in 20 (67%) and SSTP in 14 (47%).

Evaluation of the ThinPrep Pap test as an adjunct to the conventional Pap smear.

Objective: To evaluate the ThinPrep Pap test as an adjunct to the conventional Pap smear.

Design And Setting: Prospectively collected cervical samples were split for independent screening at a large specialised private gynaecological pathology practice in Sydney.

Main Outcome Measures: Detection of additional significant abnormalities (cervical intraepithelial neoplasia 1, or more severe); changed management recommendations from "repeat smear in 12 months" or ".

Evaluation of the CytoRich slide preparation process.

Objective: To compare the quality and sensitivity of CytoRich slides with conventional cytologic smears and to evaluate the benefits of using this technology as an add-on procedure.

Study Design: The study design consisted of non-randomized, paired cervical samples. The subjects were 2,125 Sydney women who were routine patients of 13 gynecologists and 8 general practitioners and had cytologic smears taken between January and June 1995.

Characterization of autoantigenic epitopes on platelet glycoprotein IIb/IIIa using random peptide libraries.

Most patients with chronic immune thrombocytopenic purpura (ITP) have autoantibodies directed against the glycoprotein (GP) IIb/IIIa complex. We have used a filamentous phage library that displays random linear hexapeptides to identify peptide sequences recognized by these autoantibodies. Plasma antibody eluates from two patients were used to select for phage displaying autoantibody-reactive peptides.

A non-thrombocytopenic bleeding disorder due to an IgG4-kappa anti-GPIIb/IIIa autoantibody.

Autoantibodies in chronic immune thrombocytopenic purpura occasionally interfere with platelet function. We describe a patient with a normal platelet count who had clinically significant mucosal bleeding, a prolonged bleeding time and abnormal platelet aggregation. The patient had high titres of an IgG4 kappa autoantibody, directed to a cation-dependent epitope on platelet glycoprotein IIb/IIIa, which blocked the binding of fibrinogen and fibronectin to this complex.