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BackgroundSeveral studies indicate that age-related macular degeneration (AMD) and atherosclerosis may share common pathogenetic pathways. The aim of this study was to determine the role of systemic matrix metalloproteinases (MMPs) in AMD, given that MMPs are implicated in the pathogenesis of atherosclerosis.MethodsThis study determined the plasma matrix metalloproteinases (MMP-2 and MMP-9) levels in three groups of subjects: group 1 included subjects with age-related maculopathy (ARM), group 2 included subjects with choroidal neovascularization (CNV) owing to AMD and group 3 consisted of age-matched controls.ResultsThe mean plasma levels of MMP-2 were not significantly different in the three groups. In contrast, the mean plasma MMP-9 levels were significantly higher in ARM and CNV groups compared to that of the control group. However, there was no significant difference in MMP-9 levels between ARM and CNV groups.ConclusionThis is the first study that reveals a link between raised plasma MMP-9 levels with AMD. Further studies are required to identify the factors that contribute to this association.Eye (2008) 22, 855–859; doi:10.1038/sj.eye.6702722; published online 16 February 2007 [ABSTRACT FROM AUTHOR]

To identify factors affecting current smokers' intention to quit smoking and factors associated with successful quitting among ex-smokers in Hong Kong. A cross-sectional survey of Chinese patients attending medical and surgical Specialist Outpatient Clinics (SOPCs) of public hospitals in Hong Kong, using a structured questionnaire. Results of the 642 respondents, 21% were current smokers, 9% were ex-smokers and 69% were non-smokers. 74% of the smokers reportedly received quitting advice from doctors. Among the current smokers, past quitting attempts, receiving information from sources other than doctors, believing that doctor's advice was useful, believing that all smokers should quit smoking and a positive attitude towards quitting were associated with intention to quit. Among those who had attempted to quit, being older (aged 50 or above), being retired/unemployed and consuming more than 10 cigarettes per day were associated with successful quitting. We found that advice from doctors on quitting smoking did not have any impact on Chinese smokers quitting or future intention to quit and reflect the inadequacy of advice given by Hong Kong doctors. The predictors of intention to quit and successful quitting identified in the study could be used to design future smoking cessation services.

Unlabelled: If rectal cancer does not penetrate the fascia propria of the rectum and the rectum is removed with the fascial envelope intact (extrafascial excision), then local recurrence of the cancer will be minimal. Modern imaging techniques have identified a fascial plane surrounding the rectum and mesorectum, and it has been suggested that this is the fascia propria. The aim of this study was to identify whether this plane is the rectal fascia propria and whether tumor invasion through this fascia can be identified preoperatively., Methods: Two separate experiments were performed: 1) pelvic magnetic resonance imaging was performed before and after dissection and marking of the plane of extrafascial dissection of the rectum of a cadaver; and 2) magnetic resonance imaging was performed in 43 rectal cancer patients preoperatively. Two radiologists independently reported the depth of tumor invasion in relation to the fascia propria. The tumors were resected by extrafascial excision, and a pathologist independently reported the relation of the tumor to the fascia propria., Results: The marker inserted in the extrafascial plane showed that the plane visualized on pelvic magnetic resonance imaging was the fascia propria dissected in extrafascial excision of the rectum. The magnetic resonance imaging detected tumor penetration through the fascia propria with a sensitivity of 67 percent, a specificity of 100 percent, and an accuracy of 95 percent., Conclusion: The surgical fascia propria can be identified on preoperative magnetic resonance imaging in patients with rectal cancer. Tumor invasion through this fascia can be detected on magnetic resonance imaging. This method of assessment offers a new way to select those patients who require preoperative radiotherapy.

The high mobility group I, Y, and I-C proteins are low-molecular-weight, nonhistone chromosomal proteins that play a general role modulating gene expression during development and the immune response. Consistent with their role in early development, all three proteins are expressed at high levels during embryogenesis, and their expression is markedly diminished in differentiated cells. Exceptions to the general repression of these genes in adult tissues involve (1) A burst of synthesis of the HMG I protein during the immune response (during lymphocyte activation and preceding cytokine/adhesion molecule gene expression), (2) A constitutive expression of the HMG I and Y proteins in photoreceptor cells, and (3) Derepression of HMG I, Y, and often I-C expression in neoplastic cells. Work from several laboratories has now uncovered how these proteins participate in gene activation: (1) By altering the chromatin structure around an inducible gene-and thus influencing accessibility of the locus to regulatory proteins-(2) By facilitating the loading of transcription factors onto the promoters, and (3) By bridging adjacent transcription factors on a promoter via protein/protein interactions. Despite the similar structures and biochemical properties of the three proteins, the work has also provided clues to a division of labor between these proteins. HMG I and Y have demonstrable roles in enhanceosome formation, whereas HMG I-C has a specific role in adipogenesis. C-terminal truncations of HMG I-C and wild-type HMG Y appear to function in a manner analogous to oncogenes, as assessed by cellular transforation assays and transgenic mice. Future work should clearly define the similarities and differences in the biological roles of the three proteins, and should evolve to include attempts at pharmaceutical intervention in disease, based upon structural information concerning HMG I interactions with DNA and with regulatory proteins.

The paired-like homeodomain transcription factor CRX (cone-rod homeobox) is involved in regulating photoreceptor gene expression and rod outer segment development. Mutations in CRX have been associated with several retinal degenerative diseases. These conditions range from Leber congenital amaurosis (a severe cone and rod degeneration of childhood onset) to adult onset cone-rod dystrophy and retinitis pigmentosa (an adult onset condition that primarily affects rods). The goal of this study is to better understand the molecular basis of CRX function and to provide insight into how mutations in CRX cause such a variety of clinical phenotypes. We performed deletion analysis in conjunction with DNA binding and transient transfection-based transactivation studies to identify the functional domains within CRX. DNA binding requires a complete homeodomain. Furthermore, truncated proteins that did not contain an intact homeodomain failed to demonstrate detectable expression in tissue culture upon transfection. Transactivation analysis indicated that both the OTX tail and the WSP domain are important for controlling positive regulatory activity of CRX. Interestingly, the mapped CRX transactivation domains were also critical when coexpressed with NRL. Specifically, the synergy between CRX and NRL was constant regardless of which CRX variant was used.

The nonhistone chromosomal proteins high mobility group I(Y) [HMG I(Y)] have been shown to function as architectural transcription factors facilitating enhanceosome formation on a variety of mammalian promoters. Specifically, they have been shown to act as a "molecular glue" mediating protein-protein and protein-DNA contacts within the enhanceosome complex. HMG I(Y) proteins are expressed at high levels in embryonic and transformed cells and have been implicated in transcriptional regulation in these cells. Terminally differentiated cells, however, have been reported to express only minimal, if any, HMG I(Y). In contrast to these observations, we show here that adult mouse retinal photoreceptors, which are terminally differentiated cells, express high levels of these proteins. Using retinoblastoma cells as an approximate model, we further demonstrate in transiently transfected cells that inhibition of HMG I(Y) expression and mutation of HMG I(Y) binding sites significantly reduce rhodopsin promoter activity. DNase I footprint analysis indicates that HMG I protein interacts with a discrete site within the rhodopsin proximal promoter. This site overlaps with the binding site for Crx, a paired-like homeodomain transcription factor that is essential for photoreceptor functioning and that when mutated causes several forms of human photoreceptor degeneration. Both biochemical and functional experiments demonstrate that HMG I(Y) physically associate with Crx and that their interaction with DNA is required for high-level transcription of the rhodopsin gene. These data provide the first demonstration that HMG I(Y) can be important for gene activation in terminally differentiated cells.

Objective: To study retrospectively the identification, characteristics, and localization of myospherulosis in different types of renal cell carcinomas., Design: Twenty-seven consecutive renal cell carcinomas treated by radical nephrectomy in 1 year were studied. All the tumor and nontumor slides were examined for myospherulosis. The demographic data, histological type of renal cell carcinoma, Robson stage, and Fuhrman grades were recorded., Results: Myospherules were found in 10 cases. They were associated with the clear cell type and a higher nuclear grade. The cell type remained the only significant factor when these 2 factors were tested together with the tumor stage by logistic regression. Myospherulosis tended to be found in younger patients but was not associated with the sex or the side of the tumor. They were scattered within tumor cystic spaces or among sheets of tumor cells. Some of the myospherules might arise from histiocytes or even tumor cells. Compared with previous reports of myospherulosis associated with exogenous or endogenous lipid, the myospherules associated with renal cell carcinoma were smaller and more uniform in size. There is no associated fibrosis or foreign body giant cell reaction., Conclusion: As far as we know, this is the first report of myospherulosis occurring in malignant tumors in human, and their associated features are different from those previously described for myospherulosis related to exogenous or endogenous lipid.

Purpose: It is now agreed that it is of vital importance to maintain the fascia propria as an intact envelope around the mesorectum to prevent tumor spillage while performing rectal excision for cancer. There are several surgical techniques described to achieve an intact fascial envelope, each arising from differing descriptions of the fascia propria of the rectum. The aim of this study was to describe the detailed surgical anatomy of the fascia propria., Methods: Thirteen rectal specimens surgically removed by the technique of extrafascial excision were subjected to gross inspection, dissection, and histologic and electron microscopic examination. The attachments, thickness, and composition of the fascia propria were determined., Results: The fascia propria is a continuous fascial sleeve surrounding the rectum and mesorectum that can be dissected as a complete "sock" off a fresh extrafascial specimen. It is 154 (+/- 1 standard deviation = 61-391) microm thick, is thinner anteriorly than posteriorly (P < 0.05), and is composed predominantly of collagen. It can be identified surgically at the pelvic brim as a shiny membrane and lies inside the hypogastric nerves and the pelvic plexuses., Conclusion: The fascia propria forms a sleeve around the mesorectum, offering a surface against which to dissect, enabling safe removal of the rectum with its intact mesorectum while preserving the autonomic nerves of the pelvis. The term "extrafascial excision" highlights the importance of the fascia propria in this operation.

Conjunctival melanotic lesions in Chinese were studied and compared with those of Caucasians. These lesions were diagnosed in Chinese patients over a two-year period. They were excised under the clinical diagnoses of nevi, primary acquired melanosis (PAM) and malignant melanoma. For the cases included, the histology slides and clinical information were reviewed. Eighteen cases of nevi and nine non-nevoid lesions were identified. Among the non-nevoid lesions, there were eight cases of basal cell hyperpigmentation (one congenital, five acquired, two unknown) and one malignant melanoma. Benign or atypical melanocytic hyperplasias (MH) were not seen. This pattern is very different from that of Caucasian series. Acquired hyperpigmentation is almost only seen in Chinese and seldom in Caucasians. On the other hand, atypical MH is only seen in Caucasians, and not in Chinese. We conclude that conjunctival hyperpigmentation is associated with ethnicity and does not progress to MH, whether benign or atypical. It should be recognised as a distinct entity of no malignant potential that is part of the PAM clinical spectrum.

The high mobility group (HMG) 1 protein is a highly conserved and ubiquitous chromosomal protein found enriched in active chromatin. In this study, we have investigated the effect of estrogen on the expression of the human high mobility group protein HMG1 gene and found that the HMG1 mRNA level in MCF-7 cells was sharply increased 2.5-fold after 30 min of estrogen treatment. Under continuous estrogen treatment, the HMG1 mRNA level decreased to a 1.5 times that of the basal level at 90 min and remained at this elevated level under estrogen treatment for up to 24 h. These results support the recent finding by Verrier et al. (C.S. Verrier, 1997, Mol. Endocrinol. 11, 1009-1019) that HMG1 promotes the binding of the estrogen receptor to the estrogen response element and further reinforce our believe that HMG1 plays a significant role in estrogen-induced gene expression.

Desmoplastic ameloblastoma is a rare tumour, and we know of only 43 previously reported cases. We report seven Chinese patients (five men and two women) with the desmoplastic variant of ameloblastoma, which makes up 9% of all ameloblastomas diagnosed during the years 1981-1995. The age ranged from 18 to 68 years (mean 43). Five of the tumours were in the maxilla and two were in the mandible. Five of them were situated anteriorly, the remaining two cases involving both anterior and posterior maxilla. The features of the 42 cases previously reported were reviewed and were compared with those in the present study. Our results differ in that we found a male predominance, wider age range and more tumours in the maxilla. Histologically, this variant of ameloblastoma is characterized by abundant collagenous stroma. Because the epithelial clusters may show prominent squamous metaplasia or may be compressed into thin strands in most areas, the appearance may mimic a squamous odontogenic tumour or odontogenic fibroma. The behaviour of this variant of ameloblastoma is likely to be the same as that of the classic ameloblastoma.

The clinicopathological data of adult Chinese patients identified to have 'significant pulmonary thromboembolism (PTE)' at autopsy in Queen Mary Hospital (QMH) Hong Kong, from 1990 to 1994 inclusive, were analysed retrospectively. The prevalence of PTE was documented and data were compared with published series of Caucasian patients. The parameters studied included sex-age distribution, associated diseases, symptomatology, site of venous thrombosis, duration of admission and intervals between surgery and death. The rate of PTE was 4.7% (4.5% in males and 5.2% in females). The mean age of PTE patients was significantly higher than that of non-PTE patients (p < 0.001). Two clinicopathological features worthy of note are: (1) as in Caucasian patients, most Chinese patients with 'significant PTE' do not present with leg symptoms although many of them are found to have deep vein thrombosis (DVT) at postmortem; and (2) DVT in these patients is found in the calf veins rather than in the more proximal deep veins. The recently identified racial differences in hemostasis that may contribute to the differences between Chinese and Caucasian people are discussed.

Objective: To find out whether massive bleeding or free perforation of advanced gastric carcinoma affect long term survival after gastrectomy., Design: Retrospective analysis of prospectively collected data., Setting: Teaching hospital, Hong Kong., Interventions: Gastrectomy., Main Outcome Measures: Long term survival., Results: Data of 50 patients with gastric carcinoma that had penetrated the serosa (pT3) and who were operated on between 1985 and 1990 were analysed. A total of 17 patients with tumour free perforation and 10 with massive bleeding underwent emergency gastrectomy, and 23 patients with comparable uncomplicated tumours had elective gastrectomy. Twelve variables that could have influenced survival including malignant perforation, bleeding, or the absence of complications were analysed using the Cox's proportional hazards model. Survival was influenced only by proliferative cell nuclear antigen (PCNA) index and not by perforation, bleeding, or the uncomplicated nature of the tumour., Conclusions: These findings suggest that perforation or bleeding from advanced gastric carcinomas do not significantly affect long term survival after gastrectomy.

The gene on chromosome 12 coding for the human protein HMGI-C has been cloned and partially sequenced. It consists of five exons, the first and last of which include long untranslated regions. The 5' UTR includes a (CA/T)n tract and a polymorphic (CT)n tract. Exons II, III and IV (87, 51 and 33 bp) are dispersed over > 30 kb. Exons I-III separately encode the three basic DNA binding domains ('A-T hooks'), exon IV encodes an 11 amino acid sequence characteristic of HMGI-C and absent from the human HMGI(Y) gene [Friedmann, M., Holth, L. T., Zoghbi, H. Y. and Reeves, R. (1993) Nucleic Acids Res., 21, 4259-4267], whilst exon V encodes the acidic C-terminal domain, which is subject to multiple phosphorylation. The HMGI-C gene is thus a striking example of the separation of functional protein elements into different coding exons.

The HMGI family contains three members: I, Y and I-C. HMGI and HMGY are alternative splicings of the same gene and are essential transcription factors at several genetic loci. HMGI-C is transcribed from a different gene and is observed only in highly transformed cells. This work shows that human I-C is present in a more restricted range of cell types than I/Y and is absent from hemopoietic cells, as noted for mouse I-C. However, high expression in a human hepatoma line allowed the cloning of the cDNA and 812 bp of 5'-untranslated, 330 bp of coding and 58 bp of 3'-untranslated DNA were sequenced. The open reading frame showed 4 amino acid substitutions and one additional amino acid when compared to mouse I-C, none of them in the basic DNA binding motifs.