A One Year Audit of Fine Needle Aspiration Cytology For the Pre-Operative Diagnosis of Breast Disease

In 1988, 985 patients presenting with breast disease, most with a palpable abnormality, were investigated by the triple approach (clinical examination, imaging and fine needle aspiration cytology [FNAC]). Using FNAC, 28% of patients were diagnosed as having carcinoma, 45% benign disease, 4% had suspicious cytology and 3% equivocal cytology. The remaining 20% had inadequate aspirates. Two false positive diagnoses of carcinoma were made (a false positive rate of 0.7%); one was a case of high grade non-Hodgkin's lymphoma and the other a papillary lesion with epithelial atypia. The false negative rate was 6.4%. Of these 49 patients, six had carcinoma-in-situ and 19 had low grade tumours. The absolute and complete sensitivities for the diagnosis of carcinoma in this series were 84.7% and 91.9% respectively and the absolute and complete specificities 99.7% and 98.3%, respectively. These figures compare favourably with those from other centres and confirm the efficacy of FNAC as part of the triple approach to the diagnosis of breast disease. The use of FNAC has resulted in a reduction in the number of Trucut and frozen section biopsies performed. Eighty three per cent of the patients with benign disease diagnosed by the triple approach have avoided excision biopsy, none of whom have subsequently been found to have carcinoma. Eighty patients with advanced breast carcinoma were spared operative intervention.     

Focus: A Multifaceted Battle Against Cancer: Extracting Knowledge from Chemical Imaging Data Using Computational Algorithms for Digital Cancer Diagnosis

Fourier transform infrared (FTIR) spectroscopic imaging is an emerging microscopy modality for clinical histopathologic diagnoses as well as for biomedical research. Spectral data recorded in this modality are indicative of the underlying, spatially resolved biochemical composition but need computerized algorithms to digitally recognize and transform this information to a diagnostic tool to identify cancer or other physiologic conditions. Statistical pattern recognition forms the backbone of these recognition protocols and can be used for highly accurate results. Aided by biochemical correlations with normal and diseased states and the power of modern computer-aided pattern recognition, this approach is capable of combating many standing questions of traditional histology-based diagnosis models. For example, a simple diagnostic test can be developed to determine cell types in tissue. As a more advanced application, IR spectral data can be integrated with patient information to predict risk of cancer, providing a potential road to precision medicine and personalized care in cancer treatment. The IR imaging approach can be implemented to complement conventional diagnoses, as the samples remain unperturbed and are not destroyed. Despite high potential and utility of this approach, clinical implementation has not yet been achieved due to practical hurdles like speed of data acquisition and lack of optimized computational procedures for extracting clinically actionable information rapidly. The latter problem has been addressed by developing highly efficient ways to process IR imaging data but remains one that has considerable scope for progress. Here, we summarize the major issues and provide practical considerations in implementing a modified Bayesian classification protocol for digital molecular pathology. We hope to familiarize readers with analysis methods in IR imaging data and enable researchers to develop methods that can lead to the use of this promising technique for digital diagnosis of cancer.     

The Cytological Recognition of African Siderosis On Bone Smears

Eight cases of African siderosis primarily recognized on cytological smears are presented and discussed. All the smears were obtained from Jamshidi needle biopsies of vertebral bodies. Six cases showed siderosis only, while a seventh showed two pathological processes on one slide, namely metastatic keratinizing squamous carcinoma and siderosis. The remaining case showed cytological evidence of tuberculosis and siderosis. All cases were histologically confirmed, an additional feature in two cases being osseous tuberculosis which was not evident on the cytological smears. A search of the literature failed to reveal any report on the cytological recognition of this disease, or its association with tuberculosis.     

Focal contacts of spreading platelets with the substratum

Contacts with glass substratum formed by the spreading rabbit platelets were examined by an antibody-exclusion method; monoclonal antibodies against 80 kD bovine serum protein were used. It was found that platelets form focal contacts in the course of spreading. The size of the largest focal contacts formed by platelets is smaller than that of the contacts formed by fibroblasts. The antibody-exclusion method revealed focal contacts of platelets much more clearly than interference reflection microscopy (IRM). The similarity of reactions involved in spreading platelets and of large nucleus-containing tissue cells is discussed.     

Quercetin-induced yeast apoptosis through mitochondrial dysfunction under the accumulation of magnesium in Candida albicans

Latterly, the upsurge in use of antifungal drugs has brought about the emergence of several drug-resistance strains, making it skeptical to continue relying on current therapeutic regime. In the necessity of resistance-free antifungal agent, flavonoids presented possibilities of replacing existing drugs, displaying antifungal activity against pathogenic fungi. Among them, quercetin, one of the most representative flavonoids, exhibited antifungal activity against Candida albicans. To inspect the further understanding regarding quercetin, the antifungal mode of action of quercetin was investigated. In the initial step, the apoptosis was monitored after quercetin treatment. Moreover, intracellular levels of Mg²⁺ was assessed and was determined that Mg²⁺ increase occurred under the influence of quercetin. In addition, several features of mitochondrial dysfunction were monitored. Mitochondrial dysfunction triggers decrease in mitochondrial redox levels and leads to disruption in mitochondrial antioxidant system. Increased intracellular ROS and decreased intracellular redox levels were also displayed, indicating the occurrence of overall disruption in antioxidant systems. Sequentially, DNA fragmentation was observed and this DNA damage in turn induces apoptosis. In analyses, hexaamminecobalt(III) chloride (Cohex) was applied to inhibit Mg²⁺ transport between cytosol and mitochondria. Cohex attenuated the effects induced by quercetin, which demonstrates that the presence of Mg²⁺ is essential in quercetin-induced apoptosis.     

Biosynthesis of bacterial glycogen: purification and characterization of ADPglucose pyrophosphorylase with modified regulatory properties from Escherichia coli B mutant CL1136-504

The l-thyroxine binding site in human serum thyroxine-binding globulin was investigated by affinity labeling with N-bromoacetyl-l-thyroxine (BrAcT₄). Competitive binding studies showed that, in the presence of 100 molar excess of BrAcT₄, binding of thyroxine to thyroxine-binding globulin was nearly totally abolished. The reaction of BrAcT₄ to form covalent binding was inhibited in the presence of thyroxine and the affinity-labeled thyroxinebinding globulin lost its ability to bind thyroxine. These results indicate BrAcT₄ and thyroxine competed for the same binding site. Affinity labeling with 2 mol of BrAcT₄/mol of thyroxine-binding globulin resulted in the covalent attachment of 0.7 mol of ligand. By amino acid analysis and high voltage paper electrophoresis, methionine was identified as the major residue labeled (75%). Lysine, tyrosine, and histidine were also found to be labeled to the extent of 8, 8, and 5%, respectively.     

Early conception factor lateral flow assays for pregnancy in the mare

The ECF™ lateral flow assay test is marketed to detect non-pregnancy in mares. The objectives of the present study were to determine the accuracy of the ECF test, the accuracy of the electronic reader accompanying the ECF test, and agreement between two human readers and the electronic reader. Serum samples were collected from anestrus, cycling but not inseminated, and inseminated mares, and were evaluated with the ECF™ test (EDP Biotech Company, Knoxville, TN, USA) at The Ohio State University and at the EDP Biotech Laboratory. Specificity ranged from 0.07 to 0.16, the negative predictive value ranged from 0.15 to 0.33, and accuracy ranged from 0.43 to 0.52. The electronic reader did not add improve the accuracy or predictive values of the test. Based on the electronic reader, 80.0% of the serum samples collected from the anestrus mares were false positives; Readers 1 and 2 had 60.0 and 33.3% false positives, respectively. For samples collected during the estrous cycle, 83.9% were false positives by the electronic reader, whereas Readers 1 and 2 had 43.7 and 26.4% false positives. We concluded that, regardless of whether the test strips were evaluated by a human or electronic reader, this assay was not accurate for determination of the non-pregnant mare.     

Origin of bombesin-like peptides in human fetal lung

Four different forms of bombesin-like immunoreactive peaks were detected in extracts of human fetal lung by the use of reversed-phase high performance liquid chromatography (HPLC). Peaks I, II, III and IV, (increasing retention time), were eluted using a 14-38% of acetonitrile gradient containing 0.1% trifluoroacetic acid (TFA). Peak II was the major material found in the extract of human fetal lung obtained at 16-20 weeks gestation. None of the four compounds contained in the eluted peaks had the same retention time as amphibian bombesin or porcine gastrin releasing peptide (GRP). On reversed-phase HPLC using two different solvent systems TFA or heptafluorobutyric acid (HFBA) as a hydrophobic counter ion, and in gel filtration chromatography, the chromatographic behavior of the main peak (peak II) was the same as that of the carboxyl terminal fragments of GRP, GRP18-27 or GRP19-27. This suggested that the peptide(s) in peak II resembled in composition the carboxy terminal 9 or 10 amino acids of porcine GRP. Following tryptic digestion the material in peak IV was converted to the more polar compound present in peak II. Two other peptide peaks were eluted close to peak II and these were presumed to be a modification of this main peak. One of the possible biosynthetic steps in the formation of bombesin-like peptides in human fetal lung could be a tryptic conversion of a less polar peptide to a more polar form (peak IV to II).     

Different requirements for Ia-bearing accessory cells in mitogen versus antigen induction of human B-cell responses

The accessory cell requirements for the induction of proliferative and specific antibody responses of human lymphocytes stimulated with either antigen or mitogen were examined. An Ia-negative human myeloid tumor cell line, K562, could substitute for monocytes in the proliferation of monocyte-depleted lymphocytes in response to pokeweed mitogen (PWM) stimulation. K562 cells could also act as accessory cells in the PWM-induced anti-keyhole limpet hemocyanin (KLH) antibody synthesis of cells from a KLH-immunized donor. In contrast, only monocytes and not K562 cells could function as accessory cells in antigen-induced lymphocyte proliferation as well as in antigen-induced, antigen-specific antibody production. However, K562 cells, like monocytes, were able to positively and negatively regulate polyclonal immunoglobulin responses. Thus, Ia-bearing accessory cells can function in antigen-induced proliferation and antibody responses while non-Ia-bearing cells can function in mitogen-induced, but not anti-geninduced responses. These studies indicate a dichotomy in the nature of required accessory cells in antigen-induced versus mitogen-induced human lymphocyte responses and strongly suggest an obligatory role of Ia or an Ia-related molecule on accessory cells in antigen-induced responses of human lymphocytes.     

Studies on the rat glomerular basement membrane: Age-related changes in composition

To examine the effect of age on the glomerular basement membrane, compositional analyses were performed on membranes isolated in highly purified form from rats at different stages of their growth (35 to 200 days old). Substantial age-related changes were observed in the amino acid composition of the basement membranes. A significant correlation with age (P < 0.01) was evident in the contents of 3- and 4-hydroxyproline, threonine, serine, alanine, valine, half-cystine, hydroxylysine, and lysine. Of these amino acids, hydroxylysine and both isomers of hydroxyproline demonstrated a progressive increase with age, while the others were found to decline. The direct relationship of hydroxylysine content with age (P < 0.001) was associated with an inverse correlation of lysine with age (P < 0.001) so that the ratio of hydroxylysine to lysine increased in a highly significant manner from 0.92 at 35 days to 1.33 at 200 days. This elevation in the hydroxylysine content was accompanied by an augmentation in the number of saccharide units linked to it so that the percentage glycosylation of this amino acid was not significantly affected by age. The relative differences in the hydroxylysine and lysine levels between young and older rats were maintained in sodium dodecyl sulfateextracted membranes. These results suggest that the compositional changes observed during the aging process reflect an alteration in the subunit makeup of the basement membrane, possibly due to an increased synthesis or decreased degradation of the more collagen-like polypeptide components.