A semi-empirical method for prediction of antigenic determinants on protein antigens

AbstractAnalysis of data from experimentally determined antigenic sites on proteins has revealed that the hydrophobic residues Cys, Leu and Val, if they occur on the surface of a protein, are more likely to be a part of antigenic sites. A semi-empirical method which makes use of physicochemical properties of amino acid residues and their frequencies of occurrence in experimentally known segmental epitopes was developed to predict antigenic determinants on proteins. Application of this method to a large number of proteins has shown that our method can predict antigenic determinants with about 75% accuracy which is better than most of the known methods. This method is based on a single parameter and thus very simple to use

Benign mixed epithelial stromal tumor of the renal pelvis with exophytic growth: case report

BACKGROUND: Mixed epithelial and stromal tumor (MEST) is a distinctive benign composite neoplasm of the kidney predominantly seen in females mostly in the perimenopausal period. Although these tumors are known to arise from renal pelvis, our case was distinct in that it had no intrapelvic component growing in exophytic fashion. CASE REPORT: A 35 year old female patient presented to us with vague abdominal pain. She had undergone excision of bilateral ovarian cystic masses for cystic teratoma twelve years earlier. A computed tomography scan of abdomen and pelvis showed a 9 × 7 cm uniformly solid mass with poor contrast enhancement situated in the inferomedial aspect of the left kidney. On exploration, the mass was arising from the inferior and anterior aspect of left renal pelvis, and was attached to it with a narrow pedicle. There was no adherence or attachment to the renal parenchyma. The mass was excised preserving the kidney. Microscopically, the tumor was composed of large collagenized areas containing bundles of spindle cells and several 'microcysts' lined by cuboidal epithelium suggestive of a benign mixed epithelial stromal tumor. DISCUSSION: Mixed epithelial tumors usually present in perimenopausal women as a partially cystic mass. Tumors are composed of irregular mixtures of cystic and solid areas, glands with variable complexity and distribution and the stromal component is characterized by a spindle cell proliferation. Commonly, it arises from the renal parenchyma and pelvis and nephrectomy is advocated to manage these tumors. CONCLUSION: MEST is a distinctive benign tumor of the kidney that should be distinguished from other renal neoplasms. MEST arising from the renal pelvis and growing exophytically is a rare entity. The overall prognosis is favorable

Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix

BACKGROUND: Malignant mixed mullerian tumors (MMMT) are rare biphasic malignant neoplasm. The commonest site of their occurrence in female genital tract is body of the uterus. MMMT of the cervix is extremely rare. CASE PRESENTATION: We report the clinical, pathological and immunohistochemical profile and diagnostic difficulties in a case of giant MMMT of the cervix in a postmenopausal woman who presented with a large cervical mass. On microscopic examination, initially tumor appeared to be endometrial stromal sarcoma, however, immunohistochemical examination revealed the biphasic nature of the tumor. The malignant epithelial component was basaloid squamous carcinoma with homologous sarcomatous component. The patient was treated with surgery. However, she experienced vaginal vault recurrence four months after the initial treatment, which was successfully treated with pelvic radiotherapy. CONCLUSION: Accurate diagnosis of cervical MMMT is important for appropriate treatment of the patient

High Fidelity Processing and Activation of the Human α-Defensin HNP1 Precursor by Neutrophil Elastase and Proteinase 3

The azurophilic granules of human neutrophils contain four α-defensins called human neutrophil peptides (HNPs 1–4). HNPs are tridisulfide-linked antimicrobial peptides involved in the intracellular killing of organisms phagocytosed by neutrophils. The peptides are produced as inactive precursors (proHNPs) which are processed to active microbicides by as yet unidentified convertases. ProHNP1 was expressed in E. coli and the affinity-purified propeptide isolated as two species, one containing mature HNP1 sequence with native disulfide linkages (“folded proHNP1”) and the other containing non-native disulfide linked proHNP1 conformers (misfolded proHNP1). Native HNP1, liberated by CNBr treatment of folded proHNP1, was microbicidal against Staphylococcus aureus, but the peptide derived from misfolded proHNP1 was inactive. We hypothesized that neutrophil elastase (NE), proteinase 3 (PR3) or cathepsin G (CG), serine proteases that co-localize with HNPs in azurophil granules, are proHNP1 activating convertases. Folded proHNP1 was converted to mature HNP1 by both NE and PR3, but CG generated an HNP1 variant with an N-terminal dipeptide extension. NE and PR3 cleaved folded proHNP1 to produce a peptide indistinguishable from native HNP1 purified from neutrophils, and the microbicidal activities of in vitro derived and natural HNP1 peptides were equivalent. In contrast, misfolded proHNP1 conformers were degraded extensively under the same conditions. Thus, NE and PR3 possess proHNP1 convertase activity that requires the presence of the native HNP1 disulfide motif for high fidelity activation of the precursor in vitro

Management of renal cell carcinoma with solitary metastasis

BACKGROUND: Distant metastasis are common in Renal cell carcinoma (RCC) nearly one forth of the patients have metastasis at presentation while another 50% develop metastasis during the follow-up. A small percentage of these are solitary metastasis. We describe survival after surgical excision or radiotherapy of solitary metastatic lesion from renal cell carcinoma PATIENTS AND METHODS: Between 1988–2001, 43 patients with solitary metastasis to different sites from renal cell carcinoma underwent either surgical excision or radiotherapy were analyzed. The solitary nature of the lesions was confirmed by investigations. All patients have had radical nephrectomy for the primary lesion. Survival analysis was carried out by Kaplan Meier Method. RESULTS: All solitary metastatic lesions were treated with intent of cure either by excision or radiotherapy. Of these, 13 patients had solitary metastasis at the time of presentation in whom 3-year overall median survival was 26 months. The survival of those who developed solitary metastases during follow-up after nephrectomy for primary was 45 months. The patients with long interval between diagnosis and development of metastasis, early stage and low grade of the primary tumor had better prognosis. CONCLUSION: Complete resection of either synchronous or metachronous solitary metastases from renal cell carcinoma is justified and can contribute to a long-term survival in this select group of patients

Accuracy of intraoperative frozen section in the diagnosis of ovarian neoplasms: Experience at a tertiary oncology center

BACKGROUND: Epithelial ovarian neoplasms are an important cause of morbidity and mortality in women. The surgical management of ovarian neoplasms depends on their correct categorization as benign, borderline or malignant. This study was undertaken to evaluate the accuracy of intra-operative frozen section in the diagnosis of various categories of ovarian neoplasms. METHODS: Intraoperative frozen section diagnosis was retrospectively evaluated in 217 patients with suspected ovarian neoplasms who underwent surgery as primary line of therapy at our institution. This was compared with the final histopathologic diagnosis on paraffin sections. RESULTS: In 7 patients (3.2%) no opinion on frozen section was possible. In the remaining 210 patients frozen section report had a sensitivity of 100%, 93.5% and 45.5% for benign, malignant and borderline tumors. The corresponding specificities were 93.2%, 98.3% and 98.5% respectively. The overall accuracy of frozen section diagnosis was 91.2%. The majority of cases of disagreement were in the mucinous and borderline tumors. CONCLUSION: Intraoperative frozen section has high accuracy in the diagnosis of suspected ovarian neoplasms. It is a valuable tool to guide the surgical management of these patients and should be routinely used in all major oncology centers

Detecting malicious activities with user-agent-based profiles

Hypertext transfer protocol (HTTP) has become the main protocol to carry out malicious activities. Attackers typically use HTTP for communication with command-and-control servers, click fraud, phishing and other malicious activities, as they can easily hide among the large amount of benign HTTP traffic. The user-agent (UA) field in the HTTP header carries information on the application, operating system (OS), device, and so on, and adversaries fake UA strings as a way to evade detection. Motivated by this, we propose a novel grammar-guided UA string classification method in HTTP flows. We leverage the fact that a number of ‘standard’ applications, such as web browsers and iOS mobile apps, have well-defined syntaxes that can be specified using context-free grammars, and we extract OS, device and other relevant information from them. We develop association heuristics to classify UA strings that are generated by ‘non-standard’ applications that do not contain OS or device information. We provide a proof-of-concept system that demonstrates how our approach can be used to identify malicious applications that generate fake UA strings to engage in fraudulent activities

Unsupervised methodology to unveil content delivery network structures

A method for analyzing a content delivery network. The method includes obtaining network traffic flows corresponding to user nodes accessing contents from a set of servers of the content delivery network, extracting a timing attribute from each network traffic flow associated with a server, where the timing attribute is aggregated into a timing attribute dataset of the server based on all network traffic flows associated with the server, generating a statistical measure of the timing attribute dataset as a portion of a feature vector representing the server, where the feature vector is aggregated into a set of feature vectors representing the set of servers, analyzing the set of feature vectors based on a clustering algorithm to generate a set of clusters, and generating, based on the set of clusters, a representation of server groups in the content delivery network

Bilateral testicular metastasis from prostatic adenocarcinoma mimicking an intertubular pattern of seminoma and expressing Rhamm

Adenocarcinoma of prostate metastasizing to testis is a rare occurrence and is incidentally detected in orchiectomy specimens. The pattern of metastasis may mimic a primary neoplasm of testis like a seminoma or lymphoma and pose a diagnostic difficulty for the pathologist. A rare case of bilateral testicular metastasis of prostatic adenocarcinoma is presented wherein the metastatic cells expressed CD168, a receptor for hyaluronan mediated motility (Rhamm), implicated in the development of androgen independence in prostate cancer