Pericentromeric organization at the fusion point of mouse Robertsonian translocation chromosomes

In mammals, Robertsonian (Rb) translocation (the joining of two telo/acrocentric chromosomes at their centromere to form a metacentric) is the most effective process in chromosomal evolution leading to speciation; its occurrence also affects human health (through the induction of trisomies) and the fertility of farm animals. To understand the mechanism of Rb translocation, we used the house mouse as a model system and studied the organization of pericentromeric satellite DNAs (satDNA) of telocentrics and Rb chromosomes, both minor and major satDNA. The chromosome-orientation fluorescence in situ hybridization (CO-FISH) technique was used to analyze the major satDNA. To detect the very small amount of minor satDNA, a procedure was developed that combines CO-FISH with primed in situ labeling and conventional FISH and is five times more sensitive than the CO-FISH procedure alone. It was found that both the major and the minor satDNA tandem repeats are oriented head-to-tail in telocentric and Rb chromosomes, and their polarity is always the same relative to the centromere. We suggest that all tandemly repetitive satDNAs in a species probably are locked into such a symmetry constraint as a universal consequence of chromosomal evolution. Rb translocation breakpoints were found localized within the minor satDNA of telocentrics, and these sequences contributed symmetrically to the formation of the centromeric region of the Rb chromosomes. These results are important for an understanding of the geometry of Rb translocations and suggest the study of DNA orientation as a new tool for investigating these rearrangements

Evolutive pattern of Calomys hummelincki (Husson, 1960; Rodentia, Sigmodontinae) inferred from cytogenetic and allozymic data.

The main purpose of this research was to understand the evolutive history of the sigmodontine rodent Calomys hummelincki (Husson 1960), tribe Phyllotini from chromosomal and allozymic data, and evaluate the hypotheses that explains the colonization and evolution of sigmodontine rodents in South America. C. hummelincki is restricted to the Northern South American region, which comprises Venezuela, Aruba and Curaçao islands where specimen sampling was done. The cytogenetic analysis showed that all populations studied have the same diploid number (2n=60) and fundamental number (FN=64). Constitutive heterochromatin was observed on pericentromeric positions in almost all chromosomes. NOR regions were observed on four pairs of acrocentric chromosomes. G-banding allowed us to identify almost all pair positions in the C. hummelincki chromosome complement. The G-banding also permitted a comparison of the C. hummelincki pattern with those published for C. callidus, C. venustus and C. laucha species. G-banded information indicates that hummelincki is not directly derived from laucha. The results are constrained with published allozymic and molecular data obtained in previous studies. The overall analysis seems to support Reig´s hypothesis of a south to north colonization of genus Calomys in South America

Proximal Humerus Reconstruction after Tumor Resection: An Overview of Surgical Management

Proximal humerus is one of the anatomical sites that are most frequently involved by bone and soft tissue malignant tumors. Alone or in association with adjuvant treatments, surgery represents the main therapeutic option to treat and eradicate these diseases. Once the first-line option, in the last decades, amputation lost its role as treatment of choice for the large majority of cases in favor of the modern limb sparing surgery that promises to preserve anatomy and - as much as possible - upper limb functionality. Currently, the main approaches used to replace proximal humerus after a wide resection in oncologic surgery can be summarized in biological reconstructions (allograftsand autografts), prosthetic reconstructions (anatomic endoprostheses, total reverse shoulder prostheses), and graft-prosthetic composite reconstructions. The purpose of this overview is to present nowadays surgical options for proximal humerus reconstruction in oncological patients, with their respective advantages and disadvantages

The use of a non-biological, bridging, antiprotrusio cage in complex revision hip arthroplasty and periacetabular reconstructive oncologic surgery. Is still today a valid option?: A mid/long-term survival and complications’ analysis

Introduction: Burch–Schneider-like antiprotrusio cages (B-SlAC) still remain helpful implants to bridge severe periacetabular bone losses. The purpose of this study was to evaluate outcomes and estimate both cages’ failures and complication risks in a series of B-SlAC implanted in revision of failed total hip arthroplasties (THA) or after resection of periacetabular primary or secondary bone malignancies. Risk factors enhancing the chance of dislocations and infections were checked. Materials and methods: We evaluated 73 patients who received a B-SlAC from January 2008 to January 2018. Group A, 40 oncological cases (22 primary tumors; 18 metastases); Group B, 33 failed THAs. We compared both Kaplan–Meier estimates of risk of failure and complication with the cumulative incidence function, taking account the competing risk of death. Cox proportional hazards model was utilized to identify possible predictors of instability and infection. Harris hip score HHS was used to record clinical outcomes. Results: Medium follow-up was 80 months (24–137). Average final HHS was 61 (28–92), with no differences within the two groups (p > 0.05). The probabilities of failure and complications were 57% and 26%, respectively, lower in the oncologic group than in the rTHA group (p =0.176; risk 0.43) (p = 0.52; risk 0.74). Extended ileo-femoral approach and proximal femur replacement (p =0.02, risk ratio = 3.2; p = 0.04, rr = 2.1) were two significant independent predictors for dislocations, while belonging to group B (p = 0.04, rr = 2.6) was predictable for infections. Conclusion: Burch–Schneider-like antiprotrusio cages are a classical non-biological acetabular reconstruction method that surgeons should bear in mind when facing gross periacetabular bone losses, independently of their cause. However, dislocation and infection rates are high. Whenever possible, we suggest preserving the proximal femur in revision THA, and to use a less-invasive postero-lateral approach to reduce dislocation rates in non-oncologic cases

Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma

The current improvements in therapy against osteosarcoma (OS) have prolonged the lives of cancer patients, but the survival rate of five years remains poor when metastasis has occurred. The Cancer Stem Cell (CSC) theory holds that there is a subset of tumor cells within the tumor that have stem-like characteristics, including the capacity to maintain the tumor and to resist multidrug chemotherapy. Therefore, a better understanding of OS biology and pathogenesis is needed in order to advance the development of targeted therapies to eradicate this particular subset and to reduce morbidity and mortality among patients. Isolating CSCs, establishing cell cultures of CSCs, and studying their biology are important steps to improving our understanding of OS biology and pathogenesis. The establishment of human-derived OS-CSCs from biopsies of OS has been made possible using several methods, including the capacity to create 3-dimensional stem cell cultures under nonadherent conditions. Under these conditions, CSCs are able to create spherical floating colonies formed by daughter stem cells; these colonies are termed "cellular spheres". Here, we describe a method to establish CSC cultures from primary cell cultures of conventional OS obtained from OS biopsies. We clearly describe the several passages required to isolate and characterize CSCs

The role of the Bcl-2 family of proteins in the pathogenesis of B-cell chronic lymphocytic leukaemia

B-cell chronic lymphocytic leukaemia (B-CLL) is an acquired neoplastic disease characterised by a clonal accumulation of long-lived, functionally immature and CD5+ B-lymphocytes, which particularly accumulate in the lymphatic system, peripheral blood, bone marrow, spleen and liver. Symptoms include lymphocytosis, immune system dysfunction and autoimmune disease, but transformation to more aggressive forms of neoplastic disease occur and development of a second malignancy is not uncommon. The disease is one of later years being unusual before 50 years of age, the rates of incidence vary on a racial basis, and it has a highly variable prognosis. Some patients die within months of diagnosis despite intensive treatment, whilst others survive for 30-plus years without any form of medical intervention and die of unrelated causes. The principal causes of death in patients whose deaths are directly related to the disease are opportunistic infection due to the impairment of immune system function and bleeding disorders. No treatment has been shown to cure the disease or consistently extend life expectancy. It has been recognised for more than 30 years that the accumulation of malignant cells in B-CLL is at least as important in the pathogenesis of the disease as their neoplastic proliferation. With the discoveries that Bcl-2 extended the life of follicular lymphoma cells by conferring resistance to apoptosis and was commonly expressed in B-CLL cells, it was extrapolated that Bcl-2 might play a similar role in the development of the disease by extending the life span of B-CLL cells. Bcl-2 has frequently been shown to be over expressed in B-CLL cells and genetic translocations and/or malfunction of Bcl-2 family regulating molecular entities may play a part in this. However, since its discovery, Bcl-2 has been shown to be part of a large family of genes which is highly and evolutionarily conserved. Members of the bcl-2 family are defined by sequence homology in four Bcl-2 homology (BH) regions and a hydrophobic membrane-spanning domain, with the possession of specific BH domains determining whether individual proteins have pro- or anti-apoptotic activity. Family members such as Bcl-2 and Bcl-XL extend the life span of cells, whilst others such as Bax and Bak shorten it. Oltvai, Milliman and Korsmeyer have proposed a general model of apoptosis, in which the cell's apoptotic fate is determined by the cellular balance between pro- and anti-apoptotic bcl-2 family members. The effect of unregulated expression of Bcl-2 family members in B-CLL cells conforms to this paradigm and resistance to apoptosis appears to be conferred through a cellular imbalance of power between pro- and anti-apoptotic bcl-2 family members, particularly Bcl-2 and Bax, which is tilted in favour of cell survival. However, the apoptotic fate of B-CLL cells, and hence the neoplasm, may be influenced by other family members, with Mcl-1, Bcl-XL, Bak, with the non-family but Bcl-2-associated protein, Bag-1, also found expressed in B-CLL cells. Similarities between the structure of the more conserved family members and other pore-forming proteins, along with the ability of Bcl-2, Bcl-XL, and Bax to form pores in synthetic membranes, suggest that they may exert their influence through pore-forming activities in intracellular membranes, particularly mitochondrial membranes. Bcl-2 family members may regulate apoptosis by changing the permeability of membranes to ions and apoptosis-inducing molecules, and physical interactions between Bcl-2 family proteins mediated by the BH domains may be important in both pore-forming and pore-inhibiting activities. Research findings suggest that the levels of Bcl-2 family members in B-CLL cells may be modulated by a wide range of largely extracellular influences, including the cytokines interleukin-4 (IL-4), IL-8, IL-10, interferon-a (IFN-?), IFN-?, and basic fibroblast growth factor (bPGF). Levels of Bcl-2 family members may also be modulated by contact between B-CLL cells and bone marrow (BM) stromal cells, activation of lgM, CD95, CD40 or CD6, the p53 gene product, and co-cultivation with CDw32-transfected murine fibroblasts. Such modulation may offer some insight into the pathogenesis of the disease, an explanation for the higher level expression of Bcl-2 family members in B-CLL, and an explanation for the highly variable prognosis. Additionally, if Bcl-2 family members can be shown unequivocally to be controlled by any of these molecular entities, the existence of these influences may offer the opportunity to reduce the neoplastic cells' apoptotic threshold by manipulating the relative levels of pro- and anti-apoptotic Bcl-2 family members as a treatment regime, or prior to more conventional treatment regimes

Diagnosis of vulvar lesions by non-invasive optical analysis: a pilot study

A procedure that could allow an early in vivo and non-invasive detection of vulvar lesions would be extremely useful. We tested an innovative optical method (Optiprobe), which uses a harmless, visible light source for the in vivo, on-line detection of minimal alterations in the structure of vulvar epithelium. A group of 3 female volunteers without gynecological symptoms were first screened to evaluate optical properties of normal vulvar tissue. Next, a group of 16 patients undergoing gynecological examination for vulvar lesions was evaluated by the Optiprobe at suspected sites before these sites were biopsied for histological analysis. Adjacent, non-involved sites were also measured to provide internal controls. Histological analysis of the biopsies identified one case that did not show obvious alterations, 4 cases of high-grade vulvar intraepithelial neoplasia (VIN), 5 cases of vulvitis, and 6 cases of lichen sclerosis (LS)

Large aneurysmal bone cyst of iliac bone in a female child: a case report

<p>Abstract</p> <p>Background</p> <p>Symptomatic aneurysmal bone cysts in pediatric age group with an expansile lesion in ilium is a rare occurrence.</p> <p>Case</p> <p>An 11-year-old female presented with a swelling over her right iliac region and numbness along the medial aspect of thigh. Clinicoradiological diagnosis was aneurysmal bone cyst confirmed on fine needle aspiration cytology. Excision curettage (wide margin excision of the soft tissue tumor and intralesional curettage in the region of acetabulum) of the tumor was performed in view of proximity to acetabular roof and endangered hip stability.</p> <p>Result</p> <p>At follow up of 18 months, the child has full painless range of movements in the hip joint with no recurrence.</p> <p>Conclusions</p> <p>Pelvic aneurysmal bone cysts are distinctly rare in pediatric age. The lesion was associated with an atypical symptom of numbness along the femoral nerve distribution. Hip stability and range of movements were major concern in this patient. Although many treatment options are described, surgical excision still remains the mainstay. In our case, we performed excision curettage, with good outcome.</p

Parthenogenesis In The Tropical Gekkonid Lizard, Nactus Arnouxii (Sauria: Gekkonidae)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137400/1/evo02464.pd