Function and Regulation of Cytochrome P450 4V2 and the Implications in Bietti’s Crystalline Dystrophy

Thesis (Ph.D.)--University of Washington, 2016-06

Histological analysis of gallbladder diseases in relation to opisthorchiasis in endemic areas of Thailand

Chronic gallbladder disease frequently accompanies infection with the liver fluke, Opisthorchis viverrini, in Northeast Thailand. However, the pathology and pathogenesis of the gallbladder disease have not been described. Accordingly, gallbladder specimens from 187 consecutive patients who had undergone cholecystectomy at a referral hospital in an endemic area in Thailand were histologically characterized in relation to O. viverrini infection. The infection was assessed by the presence of parasite eggs in the bile and/or antibody response to the liver fluke. The average level of parasite-specific IgG was significantly higher in patients with Opisthorchis eggs in the bile than those without (P < 0.001). The main histopathologic features of the gallbladder included inflammation, mucosal atrophy/or hyperplasia, goblet cell metaplasia, mucous gland hyperplasia, Rokitansky-Aschoff sinus formation, dysplasia and fibrosis. The fibrosis was strongly associated with elevated levels of Opisthorchis-specific antibody (P < 0.001) but not with the presence of parasite eggs. Other pathologic features did not vary in frequency or severity with parasitological status. Our results show that severe fibrosis of the gallbladder is a more common histologic feature of cholecystitis among those with O. viverrini infection compared to those without infection. The close relationship between parasite-specific IgG and severe fibrosis suggests that specific immune response to the parasite play an important role in the pathogenesis of the fibrotic change. (C) 2003 Elsevier B.V. All rights reserved.

Soft tissue sarcomas in dogs: A study assessing surgical margin, tumour grade and clinical outcome

The purpose of this prospective clinical study was to quantify the surgical margin necessary to maximise local disease control for canine soft tissue sarcoma of various grades. This was achieved via gross and histopathologic studies. Fourteen dogs underwent surgical treatment for 15 localised, measurable, subcutaneous sarcomas. Surgery and histopathologic evaluation were performed to standardised protocols. Regular examinations for local recurrence and distant metastases were performed for at least 12 months postoperatively. One hundred percent local disease control was achieved with deep margins >10mm and 93% one year disease-free survival with wide margins (i.e. >10mm laterally and one fascial plane or >10mm in depth). There was one case of recurrence. Fascial planes appear to act as biological barriers to local tumour invasion but this protective effect may be overcome with high-grade lesions.

The association between continuous naming speed and word reading skill in fourth- to sixth-grade children

A correlational study was designed to examine the general processing speed and orthographic processing speed accounts of the association between continuous naming speed and word reading skill in children from fourth to sixth grade. Children were given two tests of each of the following constructs: word reading skill, alphanumeric symbol naming speed, nonsymbol naming speed, alphanumeric processing speed, and nonsymbol processing speed. Results were not completely consistent with either the general processing speed or the orthographic processing speed accounts. Although an alphanumeric symbol processing efficiency component is clearly involved, it is argued that the particularly strong association between naming speed and word reading also reflects the efficiency of phonological processing in children of this age.

Typical medullary breast carcinomas have a basal/myoepithelial phenotype

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-fine mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided. The aim of this study was therefore to improve diagnosis by establishing an MBC protein expression profile using immunohistochemistry (IHC) on tissue-microarrays (TMA). Using a series of 779 breast carcinomas ('EC' set), diagnosed initially as MBC, a double-reading session was carried out by several pathologists on all of the histological material to establish the diagnosis as firmly as possible using a 'medullary score'. Only MBCs with high scores, i.e. typical MBC (TMBC) (n = 44) and non-TMBC grade III with no or low scores (n = 160), were included in the IHC study. To validate the results obtained on this first set, a control series of TMBC (n = 17) and non-MBC grade III cases (n = 140) ('IPC' set) was studied. The expression of 18 proteins was studied in the 61 TMBCs and 300 grade III cases from the two sets. The global intra-observer concordance of the first reading for the diagnosis of TMBC was 94%, with almost perfect kappa (kappa) of 0.815. TMBC was characterized by a high degree of basal/myoepithelial differentiation. In multivariate analysis with logistic regression, TMBC was defined by the association of P-cadherin (R = 2.29), MIB1 > 50 (R = 3.80), ERBB2 negativity (R = 2.24) and p53 positivity (RR = 1.45). Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Histological structure of the cancellous bone layer in Bothriolepis canadensis (Antiarchi, Placodermi)

The Placodermi are extinct basal gnathostomes which had extensive dermal and perichondral bone, but which lacked the endochondral bone which characterizes the more derived bony fishes. Thin sections of bone from a specimen of the antiarch placoderm Bothriolepis canadensis, from the Escuminac Formation ( Frasnian, Upper Devonian), Quebec, Canada, reveal that part of the cancellous layer in its dermal and endoskeletal bone formed from perichondral bone trabeculae growing around cartilage spheres. The resultant structure mimics that of osteichthyan endochondral bone. The layout and dimensions of this polygonal mosaic patterning of the bone trabeculae and flattened cartilage spheres resemble those of the prismatic layers of calcified cartilage in chondrichthyans. If the lack of endoskeletal bone in chondrichthyans is a derived character, then the structure identified in B. canadensis could represent a 'template' for the formation of prismatic calcified cartilage in the absence of bone.

Assigning dates to thin gneissic veins in high-grade metamorphic terranes: A cautionary tale from Akilia, southwest Greenland

A granodiorite from Akilia, southwest Greenland, previously suggested to date putative life-bearing rocks to greater than or equal to3.84 Ga, is re-investigated using whole-rock major and trace-element geochemistry, and detailed cathodoluminescence image-guided secondary ion mass spectrometer analyses of zircon U-Th-Pb and rare earth elements. Complex zircon internal structure reveals three episodes of zircon growth and/or recrystallization dated to c. 3.84 Ga, 3.62 Ga and 2.71 Ga. Rare earth element abundances imply a significant role for garnet in zircon generation at 3.62 Ga and 2.71 Ga. The 3.62 Ga event is interpreted as partial melting of a c. 3.84 Ga grey gneiss precursor at granulite facies with residual garnet. Migration of this 3.62 Ga magma (or melt-crystal mush) away from the melt source places a maximum age limit on any intrusive relationship. These early Archaean relationships have been complicated further by isotopic reworking in the 2.71 Ga event, which could have included a further episode of partial melting. This study highlights a general problem associated with dating thin gneissic veins in polyphase metamorphic terranes, where field relationships may be ambiguous and zircon inheritance can be expected.

Basal-like breast carcinomas: clinical outcome and response to chemotherapy

Background: Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival. Material and methods: A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups. Results: It was more likely for patients with BLBCs to be found negative for ER (p < 0.0001), PgR (p < 0.0001) and HER2 (p < 0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p < 0.05) and were associated with significantly shorter disease-free and overall survival (both p, 0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p < 0.05). Conclusions: BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated.

Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16-associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus-like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA-positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16-associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16-associated CIN 3 in patient population studied.

SIFA: A tool for evaluation of high-grade security devices

We describe a tool for analysing information flow in security hardware. It identifies both sub-circuits critical to the preservation of security as well as the potential for information flow due to hardware failure. The tool allows for the composition of both logical and physical views of circuit designs. An example based on a cryptographic device is provided.