Pinning energy and anisotropy properties of a Fe(Se, Te) iron based superconductor.

The measurements of DC magnetization M as a function of magnetic field (H) and time (t) have been performed in order to study the superconducting and pinning properties of a Fe(Se, Te) iron based superconductor fabricated by means of the Bridgman technique. By performing the superconducting hysteresis loops M(H) at different temperatures in the case of perpendicular and parallel field, the critical current density Jc (H) has been extracted in the framework of the Bean critical state model for both configurations. The Jc (H) curves have shown the presence of the second magnetization peak effect that causes an anomalous increase in the field dependence of the critical current density. In order to obtain the Jc anisotropy of the sample, we have performed the ratio between perpendicular and parallel critical current density values [Formula: see text] and compared its values with the literature ones. The information regarding the pinning energy U have been extracted by means of the relaxation of the irreversible magnetization M(t) in the case H∣∣c. In particular, performing relaxation measurements at different temperatures and magnetic fields, the temperature dependence of the pinning energy U(T) at different magnetic fields has been obtained showing an anomalous temperature scaling of the curves. The presence of a maximum in the U(T) curves suggests a pinning crossover at a given field and temperature H cr(T). The H cr(T) values have been fitted with the equation H cr(T) = H cr(0) (1 - T/T*) n whose results confirm the correlation between the elastic/plastic crossover and the end of the peak effect phenomenon.

Modified transverse coloplasty pouch: new reconstruction techniques after total mesorectal excision. Our experience.

AIM: The incidence of rectal cancer continues to rise. The functional results after complete Total Mesorectal Excision (TME) depend on the segment of colon used for reconstruction of colonic continuity and the form, the volume and the functional proprieties of the "neorectum". The aim of our study is evaluate the efficacy of our Modified Transverse Coloplasty Pouch (MTCP) after the treatment of low rectal cancer in terms of functional outcomes and quality of life. PATIENTS AND METHODS: The study included 136 patients, underwent TME from January 2007 to December 2016 with diagnosis of extraperitoneal carcinoma of the rectum. The average distance of the tumor from the dentate line was 5.6 cm. Our follow-up protocol included functional outcome evaluation at 7th post-operative day (POD), 2nd month, and 6th month after the surgery. RESULTS: All patients (M/F 84/52) underwent anterior rectal resection (TME) with MTCP. Frequency of bowel movements per 24 hours in the studied patients compared at 7th POD, 2 months, and 6 months. Since the first post-operative weeks there is an encouraging reduction of the frequency of bowel movements. CONCLUSION: Modified Transverse Coloplasty Pouch (MTCP) had better functional results and quality of life compared to patients with a Colonic J Pouch (CJP) and traditional Transverse Coloplasty Pouch (TCP).

Pilonidal disease mimicking anterior anal fistula and associated with posterior anal fistula: a two-step surgery. Case report.

AIM: Anal fistula is a common disease originated from abscess according the cryptoglandular theory. A rare etiology is the pilonidal disease. In our case we observed a pilonidal disease mimicking an anterior perianal fistula, associated with another posterior anal fistula. CASE PRESENTATION: A 36-year old man was referred to our department with an anal fistula with an anterior opening. Despite the clinical examination and the endoanal ultrasound, only during the surgery we discovered the origin of the anterior fistula from a misdiagnosed pilonidal sinus. There was also a posterior anal fistula in communication with the same abscess of the anterior one. We performed a two-step surgery with a first fistulectomy of the anterior tract, a drainage of abscess and the positioning of a seton for the posterior fistula. After about one month and the fall of the seton we evaluate the good healing of posterior anal fistula and excised the residual pilonidal sinus. CONCLUSION: This misdiagnosed pilonidal disease created in our clinical report a true challenge. Our goal was to eliminate as much disease as possible, but also to avoid major complications or recurrences. We refused an aggressive approach and chose a two-step surgery, with in the first approach not only a demolitive time but also a reconstruction to facilitate healing, and in the second time the complete eradication of the pathology.

Systemic and compartmentalised immune responses in a Leishmania braziliensis-macaque model of self-healing cutaneous leishmaniasis.

We have recently introduced a macaque (Macaca mulatta) model of Leishmania braziliensis-induced chronic granulomatous cutaneous lesions affecting the nasal mucosa. Using an L. braziliensis strain that produces self-healing dermal lesions in macaques, here we characterises the systemic and local cell-mediated immune responses that led to controlled growth of granulomas in the infected host. As detected using flow cytometry, more cytokine-producing T-cell subsets were observed in granuloma-derived leukocytes that were analysed directly ex vivo than in the in vitro-restimulated cells from the peripheral blood and skin-draining lymph nodes (dLNs). We demonstrate that antigen-specific interferon-gamma (IFN-gamma)- or tumour necrosis factor alpha (TNF-alpha)-producing CD4(+) and CD8(+) cells are likely important for the immunological effectiveness of granulomas. However, their resolution can be ascribed to the concomitant recruitment of interleukin (IL)-10-producing CD4(+)CD25(+) regulatory T (Treg) cells that suppress the effector T-cell-mediated inflammatory response. The findings confirm that the macaque model can be used to fully elucidate the regulatory mechanisms that may render granulomas inadequate for fighting intracellular pathogens, which will need to be considered in the development of any therapeutic strategy designed to prevent immune pathology.

The microvascular network of the pituitary gland: a model for the application of fractal geometry to the analysis of angioarchitecture and angiogenesis of brain tumors.

In geometrical terms, tumor vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic, together with the highly variable vessel shapes and surfaces, leads to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological features have now been well established, quantitative analyses of neovascularity in two-dimensional histological sections still fail to view tumor architecture in non-Euclidean terms, and this leads to errors in visually interpreting the same tumor, and discordant results from different laboratories. A review of the literature concerning the application of microvessel density (MVD) estimates, an Euclidean-based approach used to quantify vascularity in normal and neoplastic pituitary tissues, revealed some disagreements in the results and led us to discuss the limitations of the Euclidean quantification of vascularity. Consequently, we introduced fractal geometry as a better means of quantifying the microvasculature of normal pituitary glands and pituitary adenomas, and found that the use of the surface fractal dimension is more appropriate than MVD for analysing the vascular network of both. We propose extending the application of this model to the analysis of the angiogenesis and angioarchitecture of brain tumors.

Dynamics of immune granuloma formation in a Leishmania braziliensis-induced self-limiting cutaneous infection in the primate Macaca mulatta.

In order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better understand how Leishmania are able to survive for years within immunologically active granulomas. In the present study, we used a macaque (Macaca mulatta) model of infection with Leishmania braziliensis as a means of assessing the usefulness of this primate system. This model more closely mirrors human protective immunity to Leishmania than the murine model; therefore, we used it to study the host inflammatory granulomatous response involved in the control of cutaneous leishmaniasis. Infected primates developed localized long-term skin ulcerations, but complete spontaneous clinical healing occurred in all infected animals. The infection induced the recruitment and activation of inflammatory mast cells, granulocytes, mononuclear phagocytes, and lymphocytes at the site of infection. During the acute reaction, polymorphonuclear leukocytes were more prominent than other cell types and apparently destroyed many parasites; macrophages then rapidly engulfed dying neutrophils together with their parasitic cargo. In the chronic phase, persisting parasites induced a typical T helper (Th) cytokine, type 1-mediated, immunity-induced granulomatous reaction. By this time, more or less differentiated macrophage accumulations were found, and these evolved to become mature tissue granulomas consisting of all the specific cell types found within human granulomas. In the healing stage, fibroblasts proliferated at the periphery and finally invaded the granulomas with fibrotic substitution. These findings point to the feasibility of using this model to elucidate the potentially disabling Th1-cell mechanisms that may eventually render the host granulomatous response inadequate for fighting L. braziliensis infections.

Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival.

Proper attachment to the extracellular matrix (ECM) is essential for cell survival. The loss of integrin-mediated cell-ECM contact results in an apoptotic process termed anoikis. However, mechanisms involved in regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we demonstrate that reactive oxygen species (ROS) produced through the involvement of the small GTPase Rac-1 upon integrin engagement exert a mandatory role in transducing a pro-survival signal that ensures that cells escape from anoikis. In particular, we show that ROS are responsible for the redox-mediated activation of Src that trans-phosphorylates epidermal growth factor receptor (EGFR) in a ligand-independent manner. The redox-dependent phosphorylation of EGFR activates both extracellular signal-regulated protein kinase and Akt downstream signalling pathways, culminating in degradation of the pro-apoptotic protein Bim. Hence, our results shed new light on the mechanism granting the adhesion-dependent antiapoptotic effect, highlighting a fundamental role of ROS-mediated Src regulation in ensuring anoikis protection.

Leishmania infantum-induced primary and challenge infections in rhesus monkeys (Macaca mulatta): a primate model for visceral leishmaniasis.

Visceral leishmaniasis (VL) was experimentally induced in rhesus macaques (Macaca mulatta) by intravenously inoculating 2 x 10(7)amastigotes/kg of body weight of Leishmania infantum. The macaques developed a systemic disease showing characteristic features of human VL such as fever, diarrhoea, body weight loss, anaemia, hypergammaglobulinaemia and transient lymphocytosis, as well as lymph node, liver and/or spleen enlargement. Nine weeks after infection, one primate showed pronounced weight loss, became moribund and was euthanized. The necropsy findings included granulomas composed of parasite-containing macrophages, lymphocytes and plasma cells in the liver, spleen and lymph nodes. The remaining macaques had a sustained course of infection but developed a mild-to-moderate illness that subsequently showed evidence of self-cure. Of note, pathological findings included a typical cell-mediated immunity-induced granulomatous reaction that had an effect on the control of parasite replication. All infected monkeys responded with increased production of anti-Leishmania-specific IgG antibodies. Despite the fact that clinical resistance to L. infantum was not consistently associated with a parasite-specific cell-mediated immune response, drug-cured macaques from the primary infection acquired immunity to homologous re-infection. These findings point to the feasibility of using the L. infantum macaque model for pre-clinical evaluation of novel chemotherapeutics or vaccine candidates for human VL.

Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa', ZD1839) in non-small-cell lung cancer.

Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated antitumour activity and favourable tolerability in Phase II studies. We investigated whether EGFR expression levels could predict for response to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC), who received gefitinib (250 mg day(-1)) as part of a worldwide compassionate-use programme. Tissue samples were analysed by immunohistochemistry to assess membrane EGFR immunoreactivity. Of 147 patients enrolled in our institution, 50 patients were evaluable for assessment of both clinical response and EGFR expression. The objective tumour response rate was 10% and disease control was achieved in 50% of patients. Although high EGFR expression was more common in squamous-cell carcinomas than adenocarcinomas, all objective responses were observed in patients with adenocarcinoma. Response and disease control with gefitinib were not associated with high EGFR expression. Overall, median survival was 4 months, and the 1-year survival rate was 18%. Strong EGFR staining correlated with shorter survival time for all patients. Gefitinib demonstrated promising clinical activity in this group of patients with NSCLC. These results have also shown that EGFR expression is not a significant predictive factor for response to gefitinib.

Leishmania (Viannia) braziliensis-induced chronic granulomatous cutaneous lesions affecting the nasal mucosa in the rhesus monkey (Macaca mulatta) model.

The present studies on infections with Leishmania (Viannia) braziliensis in rhesus macaques were made to characterize the evolution of different parasite strains and the immune responses they elicited in this experimental host. A standardized inoculum of promastigotes was injected intradermally either above the eyelid or on the forearm of each monkey. Sixteen infected monkeys developed longstanding infections which lasted until the end of the observation period (33 months). The time required for lesion development was very variable, not only for the isolates showing molecular differences but also for individual animals in groups infected with the same parasite strain. The inocula produced lesions of variable severity, ranging from localized cutaneous leishmaniasis (CL) with a tendency to spontaneous healing to non-healing disease. One infected animal developed persistent metastatic skin and mucosal lesions. Anti-Leishmania antibodies and parasite-specific T-cell responses were induced by the experimental infections. As the granulomatous inflammatory response found at the lesions in L. (V.) braziliensis-infected M. mulatta was similar to that in patients with CL, this primate model could be useful for studying the pathophysiology and immunoregulatory events associated with disease evolution, as well as for the evaluation of new drugs or candidate vaccines.

Simultaneous staining of cytoplasmic iron and collagen matrix in human liver biopsy specimens.

One of the major liver fibrogenic activators is the cellular iron overload that can severely damage parenchymal and non-parenchymal cells. The aim of this study was to investigate a histochemical staining technique that allows the simultaneous detection of the irregular deposition of matrix collagen and both the amount and distribution of iron in liver cells on the same histological section. The method was evaluated using 3-microm histological sections obtained from ten standard liver biopsy specimens taken from patients with hepatitis C virus-related diseases and simultaneous liver cell iron overload. The results indicate that the double-staining technique is simple, sensitive and rapid, and can be routinely applied to liver biopsy specimens for diagnostic purposes. Furthermore, it may also facilitate the study of the complex relationship between hepatic fibrosis and iron overload during common genetic or secondary liver metabolic disorders.

Fractal geometry: a useful tool for quantifying irregular lesions in human liver biopsy specimens.

Irregularity and complexity are the main features of every biological system, including human tissues, cells and sub-cellular components. These two properties of the organized biological matter cannot be quantified by means of the classical Euclidean geometry, which is able to measure regular object, practically unknown in Nature. The aims of our paper were a) to underline the importance of the shape of a biological structure, b) to investigate the fractal geometry for quantifying the liver histo-pathological structures, and c) to explain the significance of several terms used in the fractal analysis of complex biological systems.

Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma.

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91% of informative cases (10/11) with al least 1 marker compared to 58% of cases (7/12) in PZ group and 70% of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43% of loci in PIN, 37% in TZ tumors and 31% in PZ tumors. At chromosome 11, LOH was detected in 26% of loci in the TZ group, in 7% of loci in the PZ group and in 13% of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22% and 21% of loci, respectively, compared to 10% detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73% of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8% and 10% in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.

Leishmania (Leishmania) major-infected rhesus macaques (Macaca mulatta) develop varying levels of resistance against homologous re-infections.

Seven rhesus macaques were infected intradermally with 10(7) promastigotes of Leishmania (Leishmania) major. All monkeys developed a localized, ulcerative, self-healing nodular skin lesion at the site of inoculation of the parasite. Non-specific chronic inflammation and/or tuberculoid-type granulomatous reaction were the main histopathological manifestations of the disease. Serum Leishmania-specific antibodies (IgG and IgG1) were detected by ELISA in all infected animals; immunoblot analyses indicated that numerous antigens were recognized. A very high degree of variability was observed in the parasite-specific cell-mediated immune responses [as detected by measuring delayed-type hypersensitivity (DTH) reaction, in vitro lymphocyte proliferation, and gamma interferon (IFN-gamma) production] for individuals over time post challenge. From all the recovered monkeys (which showed resolution of the lesions after 11 weeks of infection), 57.2% (4/7) and 28.6% (2/7) animals remained susceptible to secondary and tertiary infections, respectively, but the disease severity was altered (i.e. lesion size was smaller and healed faster than in the primary infection). The remaining monkeys exhibited complete resistance (i.e. no lesion) to each rechallenge. Despite the inability to consistently detect correlates of cell-mediated immunity to Leishmania or correlation between resistance to challenge and DTH, lymphocyte transformation or IFN-gamma production, partial or complete acquired resistance was conferred by experimental infection. This primate model should be useful for measuring vaccine effectiveness against the human disease.

Protection against cutaneous leishmaniasis induced by recombinant antigens in murine and nonhuman primate models of the human disease.

Leishmaniasis affects approximately 2 million people each year throughout the world. This high incidence is due in part to the lack of an efficacious vaccine. We present evidence that the recombinant leishmanial antigens LmSTI1 and TSA, which we identified and characterized previously, induce excellent protection in both murine and nonhuman primate (rhesus monkey) models of human cutaneous leishmaniasis. The remarkable protection induced by LmSTI1 and TSA in an animal model that is evolutionarily close to humans qualifies this antigen combination as a promising candidate subunit vaccine against human leishmaniasis.

Primary genitourinary melanoma.

OBJECTIVES: To describe the presentation, management, and clinical outcome of patients with genitourinary melanoma. METHODS: We identified 14 patients with genitourinary melanoma treated at Memorial Sloan-Kettering Cancer Center, New York and Tripler Army Medical Center, Honolulu, Hawaii. The presentation, surgical treatment, disease progression, and outcome of these patients were reviewed. Survival was analyzed, using the Kaplan-Meier product limit method. RESULTS: The presentation and management of patients with genitourinary melanoma were varied. Overall, the prognosis was poor, with a median survival of 43 months, and only 3 patients were alive, without disease, at last follow-up. Our findings confirm a poor prognosis in patients with this rare disease. CONCLUSIONS: Genitourinary melanoma is a rare form of the disease with an unfavorable clinical outcome. Less than one third of patients survive long term, although patients with scrotal melanomas may have a better prognosis.

Assignment to chromosome 12q24.33, gene organization and splicing of the human KRAB/FPB containing zinc finger gene ZNF84.

FISH analysis was used to assign the human ZNF84 gene to chromosome 12q24.33, a region associated with recurrent breakpoints and allelic loss in several human cancers. In this report we show that the ZNF84 coding region is organized in four exons; two are dedicated to encoding the KRAB/FPB-A and KRAB/FPB-B modules, the remaining exons encode the N-terminal amino acids and C-terminal array of zinc finger units, respectively.

Cell populations in lesions of cutaneous leishmaniasis of Leishmania (L. ) amazonensis- infected rhesus macaques, Macaca mulatta

The cellular nature of the infiltrate in cutaneous lesion of rhesus monkeys experimentally infected with Leishmania (L.) amazonensis was characterized by immunohistochemistry. Skin biopsies from infected animals with active or healing lesions were compared to non-infected controls (three of each type) to quantitate inflammatory cell types. Inflammatory cells (composed of a mixture of T lymphocyte subpopulations, macrophages and a small number of natural killer cells and granulocytes) were more numerous in active lesions than in healing ones. T-cells accounted for 44.7 +/- 13.1 of the infiltrate in active lesions (versus CD2+ = 40.3 +/- 5.7 in healing lesions) and T-cell ratios favor CD8+ cells in both lesion types. The percentage of cells expressing class II antigen (HLA-DR+) in active lesions (95 +/- 7.1) was significantly higher (P < 0.005) from the healing lesions (42.7 +/- 12.7). Moreover, the expression of the activation molecules CD25 (@ 16), the receptor for interleukin-2, suggests that many T cells are primed and proliferating in active lesions. Distinct histopathological patterns were observed in lesions at biopsy, but healing lesions contained more organized epithelioid granulomas and activated macrophages, followed by fibrotic substitution. The progression and resolution of skin lesions appears to be very similar to that observed in humans, confirming the potential for this to be used as a viable model to study the immune response in human cutaneous leishmaniasis.

Cell populations in lesions of cutaneous leishmaniasis of Leishmania (L.) amazonensis- infected rhesus macaques, Macaca mulatta.

The cellular nature of the infiltrate in cutaneous lesion of rhesus monkeys experimentally infected with Leishmania (L.) amazonensis was characterized by immunohistochemistry. Skin biopsies from infected animals with active or healing lesions were compared to non-infected controls (three of each type) to quantitate inflammatory cell types. Inflammatory cells (composed of a mixture of T lymphocyte subpopulations, macrophages and a small number of natural killer cells and granulocytes) were more numerous in active lesions than in healing ones. T-cells accounted for 44.7 +/- 13.1% of the infiltrate in active lesions (versus CD2+ = 40.3 +/- 5.7% in healing lesions) and T-cell ratios favor CD8+ cells in both lesion types. The percentage of cells expressing class II antigen (HLA-DR+) in active lesions (95 +/- 7.1%) was significantly higher (P < 0.005) from the healing lesions (42.7 +/- 12.7%). Moreover, the expression of the activation molecules CD25 (@ 16%), the receptor for interleukin-2, suggests that many T cells are primed and proliferating in active lesions. Distinct histopathological patterns were observed in lesions at biopsy, but healing lesions contained more organized epithelioid granulomas and activated macrophages, followed by fibrotic substitution. The progression and resolution of skin lesions appears to be very similar to that observed in humans, confirming the potential for this to be used as a viable model to study the immune response in human cutaneous leishmaniasis.

Fractional allelic loss in non-end-stage cirrhosis: correlations with hepatocellular carcinoma development during follow-up.

Hepatocellular carcinoma (HCC) is usually preceded by cirrhosis whose genetic background is still poorly understood. The aim of this study was to evaluate, in non-end-stage cirrhosis, the fractional allelic loss (FAL) at loci mostly reported to be altered in HCC and the microsatellite instability (MSI). Twenty cases of cirrhosis were retrospectively selected. Eleven had developed an HCC during the follow-up (HCC-prone group), while 9 remained HCC-free (HCC-free group). Microdissected hepatocellular cirrhotic nodules from basal liver biopsies, were studied at 20 loci (on the chromosomal arms 1p and 1q, 3p, 4q, 6q, 7q, 8p, 13q, and 18q) and with the mononucleotide repeats BAT26 and TGFbIIR. Genetic changes were detected in both groups. Overall, the FAL index was statistically increased in the HCC-prone group (0.213) as compared to the HCC-free group (0.094; P =.044). Allelic loss at chromosomal arms 1p, 4q, 13q, 18q, and concurrent losses at more than 3 loci were confined to the HCC-prone group. In both groups, MSI was never ascertained using BAT26 and TGFbIIR. In conclusion, an increased FAL index and the lack of MSI characterize the non-end-stage cirrhosis of patients undergoing HCC during follow-up. These data emphasize the role of early clonal changes in chronic liver disease, and their potential predictive significance for clinical use.