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Background: Many digital microscopy images suffer from poor illumination at the peripheries (vignetting), often attributable to factors related to the light path between the camera and the microscope. A commonly [...]

In this study, we aimed to investigate the effect of metabolic syndrome on spermatozoon morphology and histological, histochemical, histomorphometric changes in the testes. Twenty-four male Sprague Dawley rats (60 day-olds) were used for this purpose. The rats in the control group were fed only water and rat food, while the rats in the experimental group were fed with water containing 20% D-fructose and rats food for 16 weeks with ad libitum. At the end of the experimental period, the testes and epididymis of the rats were removed. The testes were embedded in paraffin by performing the necessary histological procedure. In the rat testes with metabolic syndrome, subbasal vacuolization, epithelial vacuolization, desquamation of germinal cells in the epithelium, the presence of germ cells across to tubular lumen for increased. Seminiferous tubule diameter was increased but the epithelial height of the tubules was decreased in the experimental group significantly. It was noted that the basement membrane surrounding the tubules and the capillary wall was thickened in rats with metabolic syndrome. In addition to these findings, apoptotic cells were increased in the experimental group compared to the the control group. It was observed that the rate of abnormal and dead spermatozoa increased. In this study, we determined the negative effects on the testes of the incidence is increasing day by day with metabolic syndrome. Due to its connection with male infertility, it is thought that more comprehensive studies will contribute to the development of scientific data. [ABSTRACT FROM AUTHOR]

AIM: To ascertain the extent of retinoblastoma protein (pRB) expression in comparison to p53 protein and human papilloma viruses (HPV) 16/18 status in cervical carcinomas. METHODS: Fifty cases of invasive cervical carcinoma were HPV typed for genotypes 16 and 18 using consensus primers by polymerase chain reaction (PCR). Immunohistochemistry for pRB and p53 was done on formalin fixed tissue using microwave antigen retrieval and commercially available antibodies. RESULTS: Forty five cases were squamous carcinomas, three were adenocarcinomas, and two were adenosquamous carcinomas. Thirty one cases were HPV 16 positive and one was HPV 18. Sixteen cases showed +4 pRB expression and a further 11 were +3 positive. Seven cases were negative. Only five cases (10%) showed +4 p53 immunostaining, while seven were negative and 15 were +1. Of the 16 pRB +4 positive cases, one was negative for p53 and a further seven were +1 positive. This inverse pattern of staining between pRB and p53 had a p value of < 0.001. No correlation was observed between HPV 16/18 status and p53 and/or pRB staining. CONCLUSIONS: pRB is expressed in the majority of cases of cervical cancer (86%), with more than 75% (+4) of the tumour cell population being positive in 16 cases (32%). There appears to be a general inverse pattern of staining between pRB (high) and p53 (low) in cervical cancer. The expression of both pRB and p53 proteins is independent of the HPV 16/18 status of the tumour. [ABSTRACT FROM PUBLISHER]

AIM: To assess the diagnostic performance of human papillomavirus (HPV) analysis in predicting cervical intraepithelial neoplasia (CIN) grades 2 and 3 in patients with persistent low grade cervical cytological abnormalities. METHODS: Cervical smears from 167 women referred for colposcopy with persistent borderline, wart virus or mildly dyskaryotic changes on cervical screening were analysed by Papanicolaou staining, non-isotopic in situ hybridisation and generic and type specific polymerase chain reaction (PCR) amplification of HPV sequences. Follow up was by cytological and, where appropriate, histological analysis. RESULTS: CIN grade 2 or 3 was identified in 46 patients after a median follow up of 27 months. HPV positivity by both techniques was associated with high grade CIN and with age less than 30 years (median age 33 years). Non-isotopic in situ hybridisation was more predictive but less sensitive than either generic or type specific PCR, but prediction was greater using either molecular technique in women over 30 years of age. CONCLUSIONS: Although the degree of prediction found is of only limited clinical value, the strong association of HPV positivity with both high grade CIN and patient age suggests that further studies of HPV testing in this patient group are warranted. [ABSTRACT FROM PUBLISHER]

AIMS: To determine the relative diagnostic performance of non-isotopic in situ hybridisation (NISH) and a dot-blot assay for detecting human papillomavirus (HPV) on exfoliated cervical cells; and to correlate the results with cytopathological assessment. METHODS: Cervical smears and cytological samples were obtained from 122 patients during the same clinical examination and the presence of HPV sequences determined by NISH and dot-blot analysis, respectively. RESULTS: Dot-blot analysis gave an autoradiographic signal in 15 of 121 (12.4%) cases, while NISH detected viral genomes in 38 of 114 (33.3%) cases. Even in the presence of koilocytosis, where vegetative replication of the virus occurs, NISH was positive in over twice as many cases as dot-blot analysis (NISH 90%, dot-blot 40%), while in smears within normal cytological limits, where the viral copy number is likely to be considerably lower, the differences were more striking (NISH 31%, dot-blot 5%). CONCLUSIONS: These data show that NISH on cytological smears is more sensitive than a standardised dot-blot hybridisation assay for detecting HPV infection in cytological material and is therefore a more appropriate screening tool. [ABSTRACT FROM PUBLISHER]

AIM: To develop a methodology for direct detection of high risk human papillomavirus (HPV) infection in routine cervical smears by non-isotopic in situ hybridisation (NISH) which can be compared with cytopathological assessment of the same cells. METHODS: The methodology was established using cultured cells and routine cervical smears hybridised with digoxigenin labelled probes for HPV, 16, 18, 31, and 33. The technique was applied to the analysis of 53 patients from a sexually transmitted disease clinic. RESULTS: The optimal sensitivity achieved for single HPV detection in cultured cells was 1-2 copies of HPV 16 per cell and that for detection of a cocktail of HPV types in routine cervical smears was 2.5-12 copies per cell. Of parallel smears taken from patients with a normal Papinacolau-stained smear 33.3% (24) contained a HPV 16, 18, 31, and 33 signal indicating an occult HPV infection. The prevalence of these HPV types was similar in women in whom a cytopathological diagnosis of wart virus infection was made (64.7%, 17) and in patients with mild dyskaryosis (75%, 12). CONCLUSIONS: The methodology evolved localises HPV sequences directly to epithelial cell nuclei, which can be morphologically assessed by haematoxylin counterstaining. Sample contamination with exogenous viral sequences can be distinguished from true infection. In this study, a HPV signal was not found in morphologically normal epithelial cells. The methods described will permit the detection of HPV sequences in routinely collected cervical smears and the evaluation of the natural history and potential clinical relevance of HPV infection without changes in clinical practice. [ABSTRACT FROM PUBLISHER]

AIMS: To determine the relative diagnostic sensitivity of non-isotopic in situ hybridisation (NISH) for the diagnosis of human papillomavirus (HPV) on matched smears and biopsy specimens; to compare the NISH signal type in the two samples; and to correlate the NISH data with the morphological diagnosis. METHODS: HPV samples were assayed individually by NISH with digoxigenin labelled probes (HPV6, 11, 16, 18, and 33) on routinely collected paraffin wax embedded cervical biopsy specimens and for high risk HPVs with a cocktail of similarly labelled probes (HPV16, 18, 33) on matched smears. These were taken at the same colposcopic examination from 32 patients investigated for an abnormal cervical Papanicolaou (PAP) stained smear. RESULTS: An HPV signal was present in 18 (56%) biopsy specimens and in 14 (44%) smears. There was higher concordance of sets of data in the presence of cytopathic wart virus changes. The superiority of biopsy over smear in detecting HPV was mainly the result of examining the entire cervical biopsy specimen rather than cells scraped from the cervical surface. The NISH signal type in both biopsy specimen and smear was similar; it has been shown that NISH type 1 signal correlates with episomal viral replication and type 2 and 3 signals with viral integration. CONCLUSIONS: These data show that NISH on cervical smears is a worthwhile primary screen for HPV infection. The NISH signal types in cervical smears are similar to those previously described in cervical biopsy specimens. [ABSTRACT FROM PUBLISHER]

In South Africa asymptomatic wart virus infection diagnosed by morphological criteria occurs in 16-20% of all ethnic groups; the incidence in black women is 66%. To identify human papillomavirus (HPV) types the prevalence of HPV in cervical intraepithelial neoplasia (CIN) in South African women (n = 72) with age matched British women (n = 73) was compared by non-isotopic in situ hybridisation (NISH) using digoxigenin labelled probes for HPV 6, 11, 16, 18, 31, 33 and 35 on archival biopsy specimens. A higher proportion of British biopsy specimens (68%) contained HPV than those from South Africa (50%) in CIN 2 and 3; this difference was due to HPV 16. Thirty six per cent of the positive biopsy specimens from South African women also contained HPV 33/35 compared with 16% in the United Kingdom. There was no difference in HPV detection with age in either group. These data indicate that HPV types vary geographically, with "minor" HPV types being more common in South Africa. Three qualitatively distinct NISH signals were observed; a diffuse (type 1) signal in superficial cells, mainly koilocytes; a punctate signal (type 2) in basal/"undifferentiated" cells in CIN 3; and combined type 1 and 2 signals in CIN with wart virus infection (type 3). The punctate signal may represent HPV integration. [ABSTRACT FROM PUBLISHER]

When first reported, EBM/11 reacted with mononuclear phagocyte system cells only in fresh frozen sections, but it has been shown to have similar cellular specificity in routine formalin fixed, paraffin wax embedded tissue. This was achieved by limited proteolysis with protease XIV before immunocytochemical staining. In archival biopsy specimens EBM/11 produced granular cytoplasmic staining of alveolar macrophages, Kupffer cells, tingible body macrophages and sinus histiocytes, cells of splenic cords, cortical and medullary macrophages of thymus; blood monocytes, peritoneal and mesothelial macrophages; bone marrow mononuclear cells, megakaryocytes and osteoclasts; lamina propria macrophages in the gastrointestinal tract, and connective tissue cells (presumptive macrophages) of thyroid, gall bladder, skin, pancreas, ovary, myometrium, endometrium, cervix, kidney, prostate, placenta, myocardium and breast. Unlike other anti-macrophage antibodies, EBM/11 did not react with granulocytes, lymphocytes, plasma cells, platelets, endothelial and epithelial cells in paraffin wax sections. It did not label skin Langerhans' cells, microglial cells, and interdigitating reticulum cells (as in frozen sections). This study opens a new area for the specific identification by EBM/11 of mononuclear phagocyte system cells in archival biopsy specimens. It also raises the possibility that some monoclonal antibodies, believed to be reactive only in frozen sections, may react in archival tissue after limited proteolysis with an appropriate enzyme. [ABSTRACT FROM PUBLISHER]

A simple reproducible protocol for detecting multiple copy human genes and viral DNA in routine formalin fixed paraffin embedded tonsil and brain, by in situ hybridisation with biotinylated probes, is described. The protocol consists of digestion of formalin fixed paraffin sections, with 0.4% pepsin in 0.01 M hydrochloric acid for one hour at 37 degrees C, followed by hybridisation with biotinylated probes. The biotinylated probes used for establishing the conditions for in situ localisation of DNA were total placental DNA (TG1), pHY 2.1 (a Y chromosome probe), and herpes simplex virus I and II. In human male tonsil TG1 labelled all nuclei and pHY 2.1 reacted only with nuclear Y bodies. In herpes encephalitis the virus was detected in some glial cells and neurones. [ABSTRACT FROM PUBLISHER]

Alcohol induces a variety of changes in the liver: fatty change, hepatitis, fibrosis, and cirrhosis. The histopathological appearances of these conditions are discussed, with special attention to differential diagnosis. Many forms of alcoholic liver disease are associated with Mallory body formation and fibrosis. Mallory bodies are formed, at least in part, from intermediate filaments. Associated changes in intermediate filament organisation in alcoholic liver disease also occur. Their significance in the pathogenesis of hepatocyte death may be related to abnormalities in messenger RNA function. The mechanisms underlying hepatic fibrogenesis are also discussed. [ABSTRACT FROM PUBLISHER]

Osteoclasts (OCs) and other cells of the mononuclear phagocyte system possess receptors for adhesive proteins present in the extracellular matrix. The antigenic phenotype of OCs and foreign body giant cells (FBGCs) was investigated for the presence of several integrin molecules and other largely platelet-associated antigens involved in cell adhesion reactions. Both OCs and FBGCs expressed the α-chains of the vitronectin receptor (CD51) and of the VLA-2 (CDw49b) and VLA-4 (CDw49d) molecules as well as their respective β-chains, gpIIIa (CD61) and CD29. OCs and FBGCs also expressed CD9 and CD55 (DAF-Decay Accelerating Factor) and strongly reacted with antibodies directed against fibrinogen, fibronectin and vitronectin; the latter are ligands for several of the above matrix protein receptors. The data suggest that cell-cell and cell-matrix interactions involving adhesive proteins may be important in OC and FBGC function. [ABSTRACT FROM AUTHOR]

Primary angiosarcomas of the kidney are very rare but highly aggressive tumors showing poor prognosis. We present a case of primary renal angiosarcoma occurring in a 60-year-old man with left flank pain. CT images depicted a huge exophytic mass (14 cm in diameter) in the left kidney, exhibiting central extensive hemorrhage or necrosis without contrast enhancement. The mass showed centripetal peripheral nodular enhancement on dynamic contrast-enhanced CT images. We suggest its inclusion in the differential diagnosis of cases of hemorrhagic renal tumors with prominent vasculature. [ABSTRACT FROM AUTHOR]

Augmentation of digital images is almost always a necessity in order to obtain a reproduction that matches the appearance of the original. However, that augmentation can mislead if it is done incorrectly and not within reasonable limits. When procedures are in place for ensuring that originals are archived and image manipulation steps reported, scientists not only follow good laboratory practices but avoid ethical issues associated with post-processing and protect their labs from any future allegations of scientific misconduct. Also, when procedures are in place for the correct acquisition of images, the extent of post-processing is minimized or eliminated. These procedures include color balancing (for brightfield images), keeping tonal values within the dynamic range of the detector, frame averaging to eliminate noise (typically in fluorescence imaging), use of the highest bit depth when a choice is available, flatfield correction, and archiving of the image in a non-lossy format (not JPEG).When post-processing is necessary, the commonly used applications for correction include Photoshop and ImageJ, but a free program (GIMP) can also be used. Corrections to images include scaling the bit depth to higher and lower ranges, removing color casts from brightfield images, setting brightness and contrast, reducing color noise, reducing "grainy" noise, conversion of pure colors to grayscale, conversion of grayscale to colors typically used in fluorescence imaging, correction of uneven illumination and flatfield correction, blending color images (fluorescence), and extending the depth of focus. These corrections are explained in step-by-step procedures in the chapter that follows., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

AIMS: To determine which type of human papillomavirus (HPV) is associated with cervical adenocarcinoma and whether the virus was integrated or episomal in two continents. METHODS: Biopsy specimens from the UK (n = 16) and South Africa (n = 22) were analysed by non-isotopic in situ hybridisation (NISH) for HPV types 6, 11, 16, 18, 31, 33, and 35 on archival biopsy specimens using digoxigenin labelled probes. RESULTS: A total of 20 adenocarcinomas (53%) from both groups contained HPV DNA. In the UK group, seven and four cases contained HPV 18 (44%) and 16 (25%) respectively. In the South African group, nine cases contained HPV 18 (41%) while HPV DNA was not detectable in the other 13 cases. Hence HPV 18 was present in 80% of HPV positive adenocarcinomas. CONCLUSIONS: The HPV 16 or 18 genome was integrated in all viral positive cases. In two cases HPV 18 was also present in an episomal form. These data indicate that HPV integration is common to cervical adenocarcinoma in two continents by the same methodology. The lower prevalence of HPV 18 detection in the South African group may have been due to the presence of other or unsequenced HPV types. [ABSTRACT FROM PUBLISHER]

Recently, sensitive non-isotopic in situ hybridisation (NISH) methodology for the detection of human DNA and human papilloma virus (HPV) DNA in archival paraffin blocks of cervix was described. An amended protocol, now used in this laboratory for detection of these genes by NISH is presented. The amendments include the following: protease digestion at 37 degrees C; tissue dehydration in air rather than ethanol; stringency washing in formamide solution; blocking non-specific binding of avidin alkaline phosphatase with a modified buffer; and increasing the concentration of avidin alkaline phosphatase for detecting low abundance DNA. These changes simplify and increase the sensitivity of the protocol such that "Y" chromosome repeats are visualised in almost all female cells. [ABSTRACT FROM PUBLISHER]

It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals and virus infections. The functions of NK cells in the gut are much more complex. Gut NK cells are not precisely organized in lymphoid aggregates but rather scattered in the epithelium or in the stroma, where they come in contact with a multitude of antigens derived from commensal or pathogenic microorganisms in addition to components of microbiota. Furthermore, NK cells in the bowel interact with several cell types, including epithelial cells, fibroblasts, macrophages, dendritic cells, and T lymphocytes, and contribute to the maintenance of immune homeostasis and development of efficient immune responses. NK cells have a key role in the response to intestinal bacterial infections, primarily through production of IFNγ, which can stimulate recruitment of additional NK cells from peripheral blood leading to amplification of the anti-bacterial immune response. Additionally, NK cells can have a role in the pathogenesis of gut autoimmune inflammatory bowel diseases (IBDs), such as Crohn's Disease and Ulcerative Colitis. These diseases are considered relevant to the generation of gastrointestinal malignancies. Indeed, the role of gut-associated NK cells in the immune response to bowel cancers is known. Thus, in the gut immune system, NK cells play a dual role, participating in both physiological and pathogenic processes. In this review, we will analyze the known functions of NK cells in the gut mucosa both in health and disease, focusing on the cross-talk among bowel microenvironment, epithelial barrier integrity, microbiota, and NK cells. [ABSTRACT FROM AUTHOR]

This review mainly summarizes disease, immune-pathology and the clinical usefulness, advances, potential applications and limitations of new, cutting-edge technology (MG/MP-PCR and/or ARMS-MG/MP-PCR) in the detection of female genital tuberculosis (FGTB) disease and gene polymorphism among infertile patients. The investigation was set in the Department of Zoology, Osmania University and National Institute of Nutrition, Hyderabad, India. Desired articles were critically reviewed and analysed. Keywords and NET searches were conducted in all electronic databases starting from September, 2006. Full-text English-language reviews and research articles describing FGTB, infertility, gene polymorphism, conventional polymerase chain reaction (PCR) and multigene (MG)/multiprimer (MP)-PCR were included. The current review provides a comprehensive overview on the PCR and types (multiplex, nested, RT etc.) including the reagents, cycling conditions and pitfalls in the detection of FGTB disease and gene polymorphism among infertile patients. It provides limited information on MG/MP-PCR. At present, conventional PCR, MG/MP-PCR and/or amplification refractory mutation system (ARMS)-MG/MP-PCR have emerged as scientific innovations and perform significant function in medical research, mutational analysis and clinical investigations. This review admits that MG/MP-PCR and/or ARMS-MG/MP-PCR has the capacity to diagnose disease rapidly and to genotype a large number of samples. MG/MP-PCR and/or ARMS-MG/MP-PCR are considered as simple, reliable, non-isotopic, low-cost, fast, accurate and relatively easy-to-perform procedure. This review suggests that this method needs to be critically evaluated using huge number of clinical samples occurring across the world and then can be accredited for clinical utilization. [ABSTRACT FROM AUTHOR]

Recent advances in nonlinear multimodal imaging, eg, the combination of coherent anti-Stokes Raman scattering, 2-photon excited autofluorescence, and second-harmonic generation, have shown the great potential of this imaging technique for medical diagnostics. To extract reliable diagnostic information from these multimodal images, a complex image-processing pipeline is necessary. A major part of this image-processing pipeline is the elimination of the mosaicking artifact caused by an uneven illumination within the images. While this problem is well known in image processing of photographic images and methods to solve it were developed, their direct application to multimodal images does not yield satisfactory results. This fact results from the nonlinearity of the measurement modalities and characteristics of the multimodal images itself. In this contribution, different approaches to correct the mosaicking are considered and adapted to multimodal images. In this tutorial article, an investigation and comparative analysis of correction methods were performed, and practical recommendations for the application of different methods are given. The results of this paper can be applied to the development of complete or partial automatic software for medical diagnostics using nonlinear multimodal imaging techniques. [ABSTRACT FROM AUTHOR]

Background: There is no good prognostic indicator for biliary atresia (BA). We reviewed liver biopsies taken during the initial procedure to find a prognostic marker.Methods: Thirty-two BA cases underwent Kasai operation from 1976 to 2009. We compared two groups at 1, 3, and 9 years. Group A required liver transplantation or died. Group B survived with their native liver. Biopsies were analyzed for liver fibrosis, portal-central vein bridging (P-C bridging), ductal plate malformation (DPM) and the number of the bile ducts in portal canal/measured surface area of the portal canal (BDP ratio). Statistical comparisons of the multiple data were evaluated by Mann-Whitney U test, Student's t test and Pearson's Chi-square test. Regression analysis with P < 0.05 was considered significant.Results: BDP ratios (/mm(2)) were 2.4 ± 1.5 in Group A1 (n = 9) vs 4.6 ± 2.4 in Group B1 (n = 23) (P = 0.01); 2.6 ± 1.4 in Group A3 (n = 14) vs 5.1 ± 2.5 in Group B3 (n = 18) (P < 0.01), 3.0 ± 2.2 in Group A9 (n = 15) vs 4.9 ± 2.5 in Group B9 (n = 15) (P < 0.05). There was no significant difference in any other finding.Conclusion: The BDP ratio is a sound prognostic indicator in BA. [ABSTRACT FROM AUTHOR]

Osteoclasts are multinucleated cells derived from mononuclear phagocyte precursors (monocytes, macrophages); in the canonical pathway of osteoclastogenesis, these cells fuse and differentiate to form specialised bone-resorbing osteoclasts in the presence of receptor activator for nuclear factor kappa B ligand (RANKL). Non-canonical pathways of osteoclastogenesis have been described in which several cytokines and growth factors are able to substitute for RANKL. These humoral factors can generally be divided into those which, like RANKL, are tumour necrosis family (TNF) superfamily members and those which are not; the former include TNFα lymphotoxin exhibiting inducible expression and competing with herpes simplex virus glycoprotein D for herpesvirus entry mediator, a receptor expressed by T lymphocytes (LIGHT), a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF); the latter include transforming growth factor beta (TGF-β), interleukin-6 (IL-6), IL-8, IL-11, nerve growth factor (NGF), insulin-like growth factor-I (IGF-I) and IGF-II. This review summarises the evidence for these RANKL substitutes in inducing osteoclast differentiation from tissue-derived and circulating mononuclear phagocytes. It also assesses the role these factors are likely to play in promoting the pathological bone resorption seen in many inflammatory and neoplastic lesions of bone and joint including rheumatoid arthritis, aseptic implant loosening and primary and secondary tumours of bone. [ABSTRACT FROM AUTHOR]

DNA coating on dental titanium (Ti) implants is attracting attention due to its osteogenic properties. The aim of the present study was to evaluate in vitro and in vivo bioactivities of a multilayered DNA/protamine (D/P) coating on Ti implant by simulated body fluid (SBF) immersion experiments and implantation experiments into extracted sockets of rat molars. Two types of DNA, 300 base pair (bp) and 7000 bp fragments, were used. Protamine was initially immobilized onto Ti implants using a tresyl chloride-activated method and DNA and protamine were then alternatively deposited after the immobilization of protamine by a layer-by-layer technique. A multilayered D/P-coating was confirmed by X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy measurements. The deposition of apatite progressed more on the surfaces of multilayered D/P-coated Ti implants than on those of nontreated Ti implants in SBF immersion experiments. Animal implantation experiments showed that multilayered D/P-coated Ti implants provided a significantly higher bone-to-implant (BIC) contact ratio 3 weeks after implantation. No significant difference was observed in the BIC ratio 9 weeks after implantation. The results of the present study demonstrated that a multilayered D/P-coating promoted new bone formation at the early stages of the bone healing process. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1500-1509, 2016. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 infection and polymorphisms in the HLA-DQB1 (rs6457617) and IL-1β -511 (rs16944) loci with the development of uterine cervical cancer (CaCx). The distribution of HLA-DQB1 G > A and IL-1β −511 C/T polymorphisms was determined in HPV-negative cervical swabs from normal women ( N = 111) and compared with cervical swabs of HPV-cleared normal women (once HPV infected followed by natural clearance of the infection, N = 86), HPV16/18-positive cervical intraepithelial neoplasia (CIN, N = 41) and CaCx biopsies ( N = 107). The A-allele containing genotypes (i.e. G/A and A/A) of HLA-DQB1 was significantly associated with CaCx compared with HPV-negative [OR = 2.56(1.42-4.62), p = 0.001] or HPV-cleared [OR = 2.07(1.12-3.87), p = 0.01] normal women, whereas the T-allele containing genotypes (i.e. C/T and T/T) of IL-1β showed increased risk of CIN [OR = 3.68(0.97-16.35), p = 0.03; OR = 3.59(0.92-16.38), p = 0.03] and CaCx development [OR = 2.03(1.03-5.2), p = 0.02; OR = 2.25(0.96-5.31), p = 0.04] compared with HPV-negative or HPV-cleared normal women. Considering these two loci together, it was evident that the T- and A-alleles rendered significantly increased susceptibility for development of CIN and CaCx compared with HPV-negative and HPV-cleared normal women. Moreover, the T-allele of IL-1β showed increased susceptibility for CIN [OR = 3.62(0.85-17.95), p = 0.04] and CaCx [OR = 2.39(0.91-6.37), p = 0.05] development compared with the HPV-cleared women, even in the presence of the HLA-DQB1 G-allele. Thus, our data suggest that persistent HPV16/18 infection in the cervix due to the presence of the HLA-DQB1 A-allele and chronic inflammation due to the presence of the IL-1β -511 T-allele might predispose women to CaCx development. [ABSTRACT FROM AUTHOR]

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Two types of DNA/protamine complexes were prepared from protamine sulfate and 7000 base pair (bp) DNA or original DNA to investigate the effect of the molecular weight of DNA on zeta potential, cell viability, flowability, soft tissue response, and biodegradation rate. The 7000 bp DNA/protamine complex had a negative charge while the original DNA/protamine complex had a positive charge. The cell viabilities (90.4-106.8%) of these complexes were close to each other. The 7000 bp DNA/protamine complex became a softer dough than that of the original DNA/complex when both were kneaded with water. In vivo, the original DNA/protamine complex showed a milder tissue response. The original DNA/protamine complex almost disappeared 30 days after implantation. The 7000 bp DNA/complex disappeared approximately 2 weeks after implantation and areas where samples were implanted became empty. Thereafter, the empty space was gradually replaced by new soft tissues. The original DNA/protamine complex showed low intercalation and groove binding ratios of daunorubicin hydrochloride. Results indicate that high DNA condensation by cationic protamine protected the penetration of degradation enzymes into these complexes. It was found that a high molecular weight of DNA reduced the biodegradation rate and flowability. This study suggests that DNA/protamine complexes could be candidates for biomaterials that control biodegradation rates and flowability. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013. [ABSTRACT FROM AUTHOR]