Lectins (hemagglutinins) are a type of proteins that could recognize different sugar structures and specifically initiate reversible binding with them. Though they have been universally found in a variety of organisms, they are exceptionally abundant in legumes. From the initial finding of agglutinating red blood cells to the discovery of recognizing carbohydrates on cell membranes, multiple functions of lectins have been gradually unveiled by numerous researchers across a century. Based on its carbohydrate-binding property, lectins have found great value in the study of glycomics. Many lectin-based biological tools, like lectin affinity chromatography, lectin blotting, lectin histochemistry, lectin microarray and lectin-based biosensor have been developed and applied to the study of glycoproteins. Besides, lectins are also reported to be potential agents for anti-insect, anti-fungi, anti-HIV, anti-bacterial and anti-tumor applications. / The present study focuses on the isolation of a new hemagglutinin from an edible legume, exploration of its anti-colorectal cancer effect and mechanisms, its cytokine inducing function and anti-HIV activities. The protein was purified by liquid chromatography techniques which entailed affinity chromatography on Affi-Gel Blue Gel, ion exchange chromatography on Mono Q and gel filtration on Superdex 75 with an FPLC system. The hemagglutinating activity of this hemagglutinin was demonstrated to be ion-dependent and stable over a wide range of temperatures (20-60℃) and pH (2-11) values. Like most of the lectins or hemagglutinins, this novel hemagglutinin could also attenuate the activity of HIV-1 reverse transcriptase. / This hemagglutinin could potently suppress the proliferation of colorectal carcinoma HCT116 cells and colorectal adenocarcinoma HT29 cells. It induced cell cycle arrest in G0/G1 phase, downregulated the expression of Cyclin D1 and upregulated P21expression. The protein initially bound on the cell membranes most probably through glycoproteins and subsequently entered the cytoplasm, which was achieved as early as 3h post treatment. The hemagglutinin was found to be preferentially localized in Golgi apparatus and initiated aggregation of the Golgi apparatus, which may possibly attenuate its protein processing capacity by reducing total superficial area or even partially blocking the transportation of proteins from the endoplasmic reticulum (ER). The impaired protein reception ability of Golgi apparatus may lead to the protein accumulation in the ER and induce cell apoptosis. Accordingly, two ER stress sensors (IRE1α and ATF6) and one late product of ER stress (CHOP) were found to up-regulated. Apoptosis-inducing effect of this hemagglutinin on HT29 and HCT116 cells were further confirmed using methods based on different principles. Cells treated with the hemagglutinin were observed to undergo obvious chromatin condensation, mitochondrial membrane depolarization and phosphatidylserine exposure. An apoptosis initiator (Apaf-1) and one important indicator (cleaved PARP) of cell apoptosis were accordingly detected. Besides, intraperitoneal administration of this hemagglutinin to colorectal tumor bearing nude mice could slow down the growth of tumors. / At last, this hemagglutinin exerted an immunomodulatory function on splenocytes by stimulating the mRNA expression level of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), interferon- gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α). Secretion of IL-1β and IL-2 from splenocytes also increased with the concentration of this hemagglutinin. / In a short conclusion, we have isolated a new hemagglutinin with anti-HIV RT, anti-colorectal cancer and immunomodulatory activities. / 凝集素（血凝素）是一类能够识别不同糖结构并能和它们发生可逆性结合的蛋白。虽然他们在许多生物体内均有发现，但这类蛋白在豆科植物中的含量尤其丰富。经过一个多世纪来众多研究者的努力，从最初认识到其具有红血细胞凝集功能到糖类识别作用，凝集素的诸多功能已被逐步挖掘。基于其独特的糖结构识别特性，凝集素在糖组学的研究中具有重大意义。许多基于凝集素的生物方法，如凝集素亲和层析法，凝集素印迹法，凝集素组织化学，凝集素生物芯片以及基于凝集素的生物传感器已被研究出来, 并用于研究糖蛋白。除此之外，研究表明，凝集素还具有抗虫，抗真菌，抗HIV，抗细菌和抗癌等活性。 / 该凝集素可以极大抑制结肠直肠癌HCT116细胞和结直肠腺癌HT29细胞增殖，引发细胞周期停滞，分别下调和上调Cyclin D1和P21的表达。该蛋白极有可能首先通过和细胞表面的糖蛋白结合而附在细胞膜上，然后进入细胞内。该过程可在往细胞培养液内加入该蛋白后的3小时内完成。该凝集素优先与细胞内的高尔基体结合，随后引发高尔基体聚集。该聚集作用可能会通过减少高尔基体总表面积甚至阻塞内质网和高尔基体间的蛋白运输，进而减弱高尔基体处理蛋白质的能力。当高尔基体接受蛋白的能力降低时，蛋白可能会堆积在内质网上并进一步引发细胞程序性死亡。相应地，两个内质网应激感受蛋白IRE1α和 ATF6以及内质网应激后期产物CHOP均被发现上调。该凝集素对HT29细胞和HCT116细胞的凋亡诱导作用采用不同的方法进行了进一步的确认，这些方法都是基于不同检测原理进行的。结果表明，该凝集素可导致细胞产生明显的染色质凝缩，线粒体膜电位去极化和磷脂酰丝氨酸外翻。与此相应地，凋亡启动蛋白Apaf-1和凋亡后期蛋白(被剪切的PARP)可在处理后的细胞中检测到。通过腹腔注射的方法给接种大肠癌细胞的裸鼠给药可降低肿瘤的生长速度。 / 本研究的工作包括：从一种可食用豆类中提取一种新的凝集素；检测其抗大肠癌的作用和机制；研究其细胞素诱导作用以及抗HIV活性。该蛋白采用液相色谱法分离提纯，其中包括亲和层析柱Affi-Gel Blue Gel, 离子交换层析柱Mono Q 和凝胶层析柱Superdex 75，后两种层析法在FPLC系统上操作。该蛋白的红血细胞凝集作用具有金属阳离子依赖性，并在20-60℃和pH2-11范围内保持活性稳定。像许多其它的凝集素一样，该蛋白也可以削弱HIV逆转录酶活性。 / 最后，该蛋白还具有免疫调节作用，它可促进白细胞介素-2，白细胞介素-6，白细胞介素-1β，干扰素-γ和肿瘤坏死因数-α在mRNA水平上的表达并刺激白细胞介素-2和细胞介素-1β的分泌。 / 综上所诉，本研究分离提纯了一种新凝集素，它具有抗HIV，抗大肠癌和免疫调节作用。 / Dan, Xiuli. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 153-170). / Abstracts also in Chinese. / Title from PDF title page (viewed on 05, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Includes bibliographical references. / xiii, 260 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examins Fecal Occult Blood Test (FOBT) screening as a possible means of reducing mortality from colorectal cancer in Australia. Consists of an evaluation of a FOBT screening program in South Australia (in terms of numbers of cancers detected, accuracy of the test used, costs of the program and characteristics of participants) and surveys of the general population and of South Australian general practitioners, providing information on knowledge, attitudes and practices in relation to colorectal cancer and its prevention. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine, 1995?

Source: Masters Abstracts International, Volume: 47-06, page: 3551. Advisers: Florence J. Dallo; Raul Caetano. Includes bibliographical references.

Increasing number of people is diagnosed with colorectal neoplasms (CRN) in the form of polyps or cancers. Colorectal cancer (CRC) is one of the most common causes of cancer deaths among Chinese in Hong Kong. Advances in diagnosis and treatments have increased the survival rate of CRN patients, resulting in a large group of cancer survivors. Preserving and maintaining health-related quality of life (HRQOL) has become an important direction in research and clinical care of patients with CRN. This research aimed to evaluate the HRQOL and its association with socio-demographics and disease-related characteristics among patients with CRN, and illustrate how HRQOL data could be converted to preference for the estimation of quality adjustment of life years in health economic evaluations. This research comprised of three parts. First was the establishment of the validity and reliability of the traditional Chinese version of Functional Assessment of Cancer Therapy-Colorectal (FACT-C) as a HRQOL measure for Chinese patients by a cross-sectional sample of 536 adult patients with CRN. Psychometric testing and concurrent validation of the FACT-C with European Organization for Research and Treatment of Cancer Core Questionnaire plus Colorectal-specific Module Questionnaire and the Short-Form 12-item Health Survey_Version2 (SF-12V2) were carried out. Second was a longitudinal study on the HRQOL of 554 CRN patients at baseline, six (n=479) and twelve (n=414) months of recruitment. The associations of HRQOL with socio-demographics and disease-related factors, and change of HRQOL over time were explored. Comparisons of HRQOL between CRN patients and the general population and among different CRN groups were made. Cross-sectional data were used to develop mapping functions to estimate SF-6D preference scores from FACT-C subscale scores. Third was the application of the health preference scores by CRN stages collected at baseline of the longitudinal study, in combination with survival data extracted from the literature in a Markov model on the cost-effectiveness of different CRC screening strategies (colonoscopy, guaiac and immunochemical fecal occult blood tests) in comparison to no screening in terms of quality-adjusted life-years gained. This research comprised of three parts. First was the establishment of the validity and reliability of the traditional Chinese version of Functional Assessment of Cancer Therapy-Colorectal (FACT-C) as a HRQOL measure for Chinese patients by a cross-sectional sample of 536 adult patients with CRN. Psychometric testing and concurrent validation of the FACT-C with European Organization for Research and Treatment of Cancer Core Questionnaire plus Colorectal-specific Module Questionnaire and the Short-Form 12-item Health Survey_Version2 (SF-12V2) were carried out. Second was a longitudinal study on the HRQOL of 554 CRN patients at baseline, six (n=479) and twelve (n=414) months of recruitment. The associations of HRQOL with socio-demographics and disease-related factors, and change of HRQOL over time were explored. Comparisons of HRQOL between CRN patients and the general population and among different CRN groups were made. Cross-sectional data were used to develop mapping functions to estimate SF-6D preference scores from FACT-C subscale scores. Third was the application of the health preference scores by CRN stages collected at baseline of the longitudinal study, in combination with survival data extracted from the literature in a Markov model on the cost-effectiveness of different CRC screening strategies (colonoscopy, guaiac and immunochemical fecal occult blood tests) in comparison to no screening in terms of quality-adjusted life-years gained. Psychometric analysis confirmed that FACT-C had satisfactory reliability, construct validity and responsiveness in Chinese patients Patients with CRN reported worse physical HRQOL but better mental HRQOL and similar health preference score compared to the general population. Disease severity indicated by tumor stage at initial diagnosis was the most significant determinant of HRQOL of CRN patients. Rectal cancer also significantly associated with a decrease in physical HRQOL and health preference scores. Markov modelling showed that immunochemical fecal occult blood (I-FOBT) yearly was the most effective and two-yearly was the most cost-effective screening strategy compared to no screening. / published_or_final_version / Family Medicine and Primary Care / Doctoral / Doctor of Philosophy

This thesis describes a three year study which explored perceptions and experiences of being involved in self care and perceptions of control and self-efficacy over time amongst patients receiving a six month course of chemotherapy treatment for colorectal cancer. The study was underpinned by Leventhal’s Self Regulation Model and aimed to explore how patients undergoing chemotherapy for colorectal cancer perceived the meaning of self care, what they did as part of their self care in managing the effects of their treatment and whether this changed between the beginning and end of their six month course of chemotherapy. The study also set out to explore the relationship between patients’ perceptions of control and self efficacy and their involvement in self care. The study adopted a patient focussed, mixed method, longitudinal approach for complementarity and expansion purposes in which the qualitative findings formed the focus of the investigation, supplemented by the quantitative findings. This was important to provide a greater breadth and range to the study and to obtain a realistic understanding of patients’ perceptions and experiences of being involved in self care during their six month course of chemotherapy treatment and the influence of their perceptions of control and self efficacy on their involvement in self care. Thirty one patients participated in the study and data were collected using qualitative semi structured interviews (with a subsample of patients who participated in the study) and quantitative questionnaires (Illness Perception Questionnaire-revised and the Strategies Used by People to Promote Health) and prospective self care diaries with the full study sample. Data were collected at several time points over the course of patients’ chemotherapy treatment (beginning, middle and end of treatment) and were analysed and integrated in accordance with Tashakkori and Teddlie (1998)’s guidance for integrating qualitative and quantitative findings in a mixed methods study. The study findings revealed that the use of a mixed method, longitudinal study design was a valuable approach for understanding patients’ involvement in self care during chemotherapy for colorectal cancer and the influence of factors, such as their perceptions of control, on their subsequent involvement in their self care. In particular, the principal findings suggested that self care held a range of meanings to the patients in this study. Principally, patients’ self care consisted of two components; physical self care, carried out to manage the physical impact of undergoing treatment, and emotional self care, carried out to manage their emotional response to being diagnosed with, and undergoing treatment for, cancer. The findings suggested that there was no association between patients’ perceptions of control and the degree of self care that they carried out identified in the quantitative analysis. However, in the qualitative analysis, it was revealed that patients’ perceptions of control were likely to influence their attitudes towards their active involvement in self care and the importance with which they viewed this role. In particular, patients who considered themselves to have a high degree of control during their treatment were more likely to believe that they could limit the impact of the treatment through their own actions, that being actively involved in their self care was important and were interested in taking on this role, and that they would use a greater range of self care strategies in helping to manage the impact of their treatment. Conversely patients who considered themselves to have a lower degree of control during their treatment were less likely to believe that they could limit the impact of the treatment through their own actions, that their active involvement in self care was important and were less likely to expect to take on an active role, preferring to leave the management of treatment-related effects to health professionals, whom they regarded as being the “experts”. The findings from this study have implications for nursing practice because they reinforce the importance of the listening to the patient’s experience and how this approach can contribute to a fuller and more accurate understanding of how patients become involved in their self care and the factors that influence this. This is important so that nurses can provide holistic care, tailored to meet their patients’ self care needs and preferences, and to encourage partnership working between patients, nurses, allied health professionals and other agencies in promoting involvement in self care. The findings also have implications for theories relating to self care in emphasising the importance of patient centred models of care and for Leventhal’s Self Regulation Model in adding further support for the components of the model yet also offering a greater understanding of how the model fits with patients’ emotional responses to the effects of illness and its’ treatments. Finally, the study findings have implications for future research, calling for further research to focus on the meaning of constructs such as self care and control from the patients’ perspective and to further explore the use of the mixed methodology in researching and understanding patients’ involvement in self care and the factors that influence this.

published_or_final_version / abstract / toc / Medicine / Master / Master of Philosophy

Folate deficiency, a prevalent vitamin deficiency in America, can stem from environmental and/or genetic causes. The most common inborn error of folate metabolism is deficiency of methylenetetrahydrofolate reductase (MTHFR), which catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Severe MTHFR deficiency results in hyperhomocysteinemia and homocystinuria; patients present with developmental delay, and various neurological and vascular disorders. This thesis describes three mutations identified in the MTHFR locus in patients with severe deficiency: 1025T→C (M→T), 1027T→G (W→G), and 1768G→A (E→K). Genotype-phenotype correlations are described, along with biochemical characterization of three mutations (983A→G (N→S), 1025T→C, 1027T→G). All three mutations exert their effect by decreasing Vmax without changing the enzyme's affinity for its substrate, 5-methyltetrahydrofolate. The 983A→G variant also conferred decreased affinity for FAD, a cofactor. / The more common and mild deficiency observed in the general healthy population is probably due in part to insufficient dietary intake of folate. Folate deficiency has been associated with increased risk for colon cancer. In a pilot study presented here, the impact of altered folate intake on tumor multiplicity in the Min mouse, a model for multiple intestinal neoplasia, was assessed. Folate deficient diets did not produce a consistent change in tumor numbers. However, a linear correlation between S-adenosylmethionine and S-adenosylhomocysteine content of preneoplastic tissue and tumor multiplicity was identified. / This thesis contributes to our understanding of the impact of genetic- and/or dietary-induced folate deficiency on cellular and organismal functions.

Thesis (Dr. P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / "May 2007." Includes bibliographical references (leaves 111-120).

Thesis (M.S.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / Source: Masters Abstracts International, Volume: 46-01, page: 0238. Adviser: Marsha Frazier. Includes bibliographical references.

Source: Dissertation Abstracts International, Volume: 70-07, Section: B, page: 4061. Advisers: Sally W. Vernon; Xianglin L. Du. Includes bibliographical references.