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Advancements in cutting-edge molecular profiling techniques, such as next-generation sequencing and bioinformatic analytic tools, have allowed researchers to examine tumour biology in detail and stratify patients based on factors linked with clinical outcome and response to therapy. This manuscript highlights the most relevant prognostic and predictive biomarkers in kidney, bladder, prostate and testicular cancers with recognised impact in clinical practice. In bladder and prostate cancer, new genetic acquisitions concerning the biology of tumours have modified the therapeutic scenario and led to the approval of target directed therapies, increasing the quality of patient care. Thus, it has become of paramount importance to choose adequate molecular tests, i.e., FGFRscreening for urothelial cancer and BRCA1-2alterations for prostate cancer, to guide the treatment plan for patients. While no tissue or blood-based biomarkers are currently used in routine clinical practice for renal cell carcinoma and testicular cancers, the field is quickly expanding. In kidney tumours, gene expression signatures might be the key to identify patients who will respond better to immunotherapy or anti-angiogenic drugs. In testicular germ cell tumours, the use of microRNA has outperformed conventional serum biomarkers in the diagnosis of primary tumours, prediction of chemoresistance, follow-up monitoring, and relapse prediction.

Aims: The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE. Background: The correlation between asbestiform fibers, lung cancer, pleural mesothelioma, and other lung diseases is already well established as the pathophisiological pathophysiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing the release of growth factors, cytokines, and reactive oxygen and nitrite species, with DNA damage that causes chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivoas it results upregulated in senescent cells determining a permanent growth-arrest. Objective: Evaluate the possible role of the histone variant in the organism in response to deep insight understanding the mechanisms of toxicity and the cellular response to FE. Methods: Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical immunohistochemical evaluations. Densitometric, morphometric, and statistical analysis analyses were conducted. Results: Tissue sections of FE exposed sheep demonstrated overexpression of MacroH2A.1 vsunexposed samples. The data suggest an involvement of these this molecule in the cellular response triggered by FE directed exposure. Conclusion: In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.

•Identified carcinogenic effects of asbestiform fibers, including chrysotile and amphibole, on MPM development.•Analyzed NOA impact, focusing on Fluoro-edenite in Biancavilla, Italy, and its correlation with MPM cases.•Explored epigenetic changes from NOA exposure, particularly mesothelin methylation, as an MPM marker.•Studied inflammation and methylation differences in 125 exposed and 125 non-exposed construction workers.•Used Pearson correlation to reveal intricate biomarker relationships and potential health impacts of FE.

AbstractObjectiveToll-like receptor 4 (TLR-4) is a transmembrane protein involved in the innate immune system and has been implicated in the pathogenesis of temporomandibular joint dysfunction (TMD). The purpose of this study was to histologically examine the level of expression of TLR-4 relative to severity of TMD.MethodsThirty-one human TMJ disc samples were immunostained for TLR-4 and evaluated for intensity of stain. Among the samples, 8 were control samples, 16 were from patients with anterior disc displacement with reduction (ADDwR), and 7 were from patients with anterior disc displacement without reduction (ADDwoR).ResultsThere was no statistically significant difference in intensity of stain between groupings (p = 0.673).ConclusionsThe results indicate a negative correlation between TMD and the expression of TLR-4.

Healthcare workers (HCWs) are exposed to biological hazards on a daily basis. The aim of the present study was to evaluate the risks of infection after occupational exposure to blood or body fluids among HCWs operating in the period 2013–2014, in a university hospital of Southern Italy. The frequency of accidents during the 2-year period was always lower than 5%. In 2013, 103 cases occurred; in 2014, the number of injuries had significantly decreased (n = 60). In 2013, an anti-hepatitis B surface antigen protective titer was only found in 70% of cases; in 2014, the subjects with a positive titer rose to 82%. No HCWs showed seroconversion to the main blood-borne pathogens. The implementation of strict prevention measures after the accidents reported in 2013 allowed the significant reduction of the number of injuries in 2014.

AbstractObjectiveTemporomandibular joint dysfunction (TMD) may affect a patient’s quality of life, and one of the etiologies can be anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDWoR). Interleukin 1 Receptor 1 (IL-1R1) is a membrane receptor that plays an important role on initiating immune and inflammatory response by binding the agonists ligands of IL-1 alpha and IL-1 beta. Therefore, the aim of this study was to evaluate, through immunohistochemical analysis, the association of IL-1R1 with TMD.MethodsThirty-nine human disc samples were collected and composed three different groups: ADDwR (n = 19), ADDwoR (n = 12), and control group (n = 8). The samples were immunostained with IL-1R1 antibody and evaluated on both quantity and intensity of staining.ResultsThere was a statistically significant difference (p < 0.05) between the control and test groups for both quantity and intensity of staining.ConclusionIL1-R1 was associated with ADDwR and ADDwoR in TMD discs of humans.

ABSTRACTULK1 (unc-51 like autophagy activating kinase 1) is a core component at multiple steps of canonical macroautophagy/autophagy. The activity of ULK1 is tightly regulated by several post-translational modifications, including ubiquitination, yet the deubiquitinase (DUB) responsible for its reversible deubiquitination has not been described. Here, we identified USP1 (ubiquitin specific peptidase 1) as a key player in the modulation of ULK1 K63-linked deubiquitination. Moreover, both USP1 depletion and its chemical inhibition by pimozide are coupled to a reduction of ULK1 in Triton X-100 soluble cellular lysates, and its compartmentalization to a fraction that can be solubilized in 5 M urea. In USP1-depleted cells this fraction is also enriched in SQSTM1 (sequestosome 1), the aggresome marker HDAC6 (histone deacetylase 6), and the prototype of USP1 targets FANCD2 (FA complementation group D2). Consistently, in USP1-depleted and pimozide-treated cells, ULK1 forms protein aggregates enriched in SQSTM1, as detected by both immummunofluorescence and co-immunoprecipitation studies. Notably, depletion of USP1 inhibits canonical autophagic flux and promotes an alternative route leading to lysosomal-mediated degradation of SQSTM1. Our findings reveal a novel function of the USP1-ULK1 axis as a modulator of the switch between canonical and unconventional autophagy. Further, we provide the first evidence supporting the existence of a subset of breast tumors co-expressing ULK1 and MAP1LC3B (microtubule associated protein 1 light chain 3 beta) proteins. Because the USP1 inhibitor pimozide affects breast cancer cell growth, targeting USP1 in those tumors relying on autophagy for growth might prove to be a convenient therapeutic strategy.Abbreviations: ATG13: autophagy related 13; BECN1: beclin 1; BZ: bortezomib; CAPN1: calpain 1; DUB: deubiquitinase; FANCI: FA complementation group I; FANCD2: FA complementation group D2; FZR1: fizzy and cell division cycle 20 related 1; HDAC6: histone deacetylase 6; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; PMZ: pimozide; SH3GLB1: SH3 domain containing GRB2 like, endophilin B1; SQSTM1: sequestosome 1; TRAF6: TNF receptor associated factor 6; ULK1: unc-51 like autophagy activating kinase 1; USP1: ubiquitin specific peptidase 1; WDR48: WD repeat domain 48

Age is an important prognostic factor in melanoma; notably, elderly patients tend to present with advanced stage skin melanoma (SM) and worse outcome. Moreover, SM is an immunogenic cancer, and its interaction with the aging immune system could have an effect on biologic behaviour of this disease. Tumour-infiltrating lymphocytes (TILs) could represent the host response in SM; it has been shown that higher grade of TILs is associated with better survival. Moreover, programmed death ligand 1 (PD-L1) and cyclooxygenase-2 (COX-2) are potential markers of host immune response and inflammation. We retrospectively reviewed 113 consecutive cases of early-stage SM that occurred in patients aged greater than or equal to 65 years at the time of diagnosis, followed between January 2010 and March 2014 at the University and General Hospital of Udine, Italy. The aim of this study was to evaluate TILs grade, PD-L1 expression on TILs and tumour expression of PD-L1 and COX-2 and their prognostic value in elderly patients with early SM. A better disease-free survival as well as melanoma-specific survival (MSS) was significantly associated with TILs [hazard ratios (HR): 0.41, 95% confidence interval (CI): 0.20–0.84, P=0.02 and HR: 0.37, 95% CI: 0.17–0.82, P=0.01, respectively]. PD-L1 positivity on TILs was associated with a better MSS (HR: 0.41, 95% CI: 0.17–0.97, P=0.04). Moreover, among patients with TILs, those showing COX-2 positivity on tumour cells and no PD-L1 expression on TILs had a worse disease-free survival and MSS (HR: 5.18, 95% CI: 1.33–20.23, P=0.018; HR: 6.21, 95% CI: 1.20–32.24, P=0.03; respectively). Immune and inflammatory markers deserve further investigation in aging patients with melanoma.

AbstractObjective: Temporomandibular disorders (TMD) are a group of conditions affecting the temporomandibular joint (TMJ), leading to jaw dysfunction, joint and muscle pain, and a decrease in quality of life. A communication network of pro- and anti-inflammatory mediators called cytokines maintains the homeostasis of the TMJ. This review will focus on the Interleukin (IL) family of cytokines, which have been quantified in TMJ synovial fluids in a variety of studies. IL-1α and IL-1β have pro-inflammatory effects, while the endogenous receptor antagonist (IL-1RA) inhibits the pro-inflammatory effects of IL-1.Methods: A literature search (2006–2016) to identify eligible studies was completed using the PubMed database. Studies identified used saline irrigation to quantify cytokine profiles in synovial fluid of healthy and/or dysfunctional joints.Results: The initial search yielded 111 articles, 5 of which met the inclusion criteria after inter-reviewer discussion.Conclusions: Articles that compared IL-1 concentrations in TMD vs. control groups found significant differences.

Purpose: Interleukin-1 beta (IL-1β) is a cytokine that participates in the regulation of immune responses and inflammatory reactions. It is hypothesized that IL-1 levels may be elevated in patients suffering from temporomandibular joint dysfunction. The purpose of this study was to determine the association of IL-1β expression with TMD using an immunohistochemical approach to evaluate the joint disc.Materials and methods: A total of 39 human temporomandibular joint disc samples were collected, with 31 samples in the test group. Nineteen of the test group samples were from discs of patients with anterior disc displacement with reduction, and 12 of the samples were from patients with anterior disc displacement without reduction. Eight control samples were used in the control group. The samples were immunostained and evaluated on both quantity and intensity of staining.Results: There was a statistically significant difference (p < 0.05) between the control and test groups for both quantity and intensity of staining.Conclusion: IL-1β plays a role in the inflammatory process and degradation of TMJ discs in patients with TMJ dysfunctions.

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Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The aryl hydrocarbon receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs. In response to AhR activation, MCs produce IL-17 and reactive oxygen species, highlighting the potential impact of AhR ligands on inflammation via MCs. Here, we investigated the possibility that endometrial MCs promote an inflammatory microenvironment by sensing AhR ligands, thus sustaining endometriosis development. Using human endometriotic tissue (ET) samples, we performed the following experiments: (i) examined the cytokine expression profile; (ii) counted AhR-expressing MCs; (iii) verified the phenotype of AhR-expressing MCs to establish whether MCs have a tolerogenic (IL-10-positive) or inflammatory (IL-17-positive) phenotype; (iv) measured the presence of AhR ligands (tryptophan-derived kynurenine) and tryptophan-metabolizing enzymes (indoleamine 2,3-dioxygenase 1 (IDO1)); (v) treated ET organ cultures with an AhR antagonist in vitroto measure changes in the cytokine milieu; and (vi) measured the growth of endometrial stromal cells cultured with AhR-activated MC-conditioned medium. We found that ET tissue was conducive to cytokine production, orchestrating chronic inflammation and a population of AhR-expressing MCs that are both IL-17 and IL-10-positive. ET was rich in IDO1 and the AhR-ligand kynurenine compared with control tissue, possibly promoting MC activation through AhR. ET was susceptible to treatment with an AhR antagonist, and endometrial stromal cell growth was improved in the presence of soluble factors released by MCs on AhR activation. These results suggest a new mechanistic role of MCs in the pathogenesis of endometriosis.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue outside the uterus. A diffuse infiltration of mast cells (MCs) is observed throughout endometriotic lesions, but little is known about how these cells contribute to the network of molecules that modulate the growth of ectopic endometrial implants and promote endometriosis-associated inflammation. The aryl hydrocarbon receptor (AhR), a transcription factor known to respond to environmental toxins and endogenous compounds, is present in MCs. In response to AhR activation, MCs produce IL-17 and reactive oxygen species, highlighting the potential impact of AhR ligands on inflammation via MCs. Here, we investigated the possibility that endometrial MCs promote an inflammatory microenvironment by sensing AhR ligands, thus sustaining endometriosis development. Using human endometriotic tissue (ET) samples, we performed the following experiments: (i) examined the cytokine expression profile; (ii) counted AhR-expressing MCs; (iii) verified the phenotype of AhR-expressing MCs to establish whether MCs have a tolerogenic (IL-10-positive) or inflammatory (IL-17-positive) phenotype; (iv) measured the presence of AhR ligands (tryptophan-derived kynurenine) and tryptophan-metabolizing enzymes (indoleamine 2,3-dioxygenase 1 (IDO1)); (v) treated ET organ cultures with an AhR antagonist in vitro to measure changes in the cytokine milieu; and (vi) measured the growth of endometrial stromal cells cultured with AhR-activated MC-conditioned medium. We found that ET tissue was conducive to cytokine production, orchestrating chronic inflammation and a population of AhR-expressing MCs that are both IL-17 and IL-10-positive. ET was rich in IDO1 and the AhR-ligand kynurenine compared with control tissue, possibly promoting MC activation through AhR. ET was susceptible to treatment with an AhR antagonist, and endometrial stromal cell growth was improved in the presence of soluble factors released by MCs on AhR activation. These results suggest a new mechanistic role of MCs in the pathogenesis of endometriosis.

This study aimed to analyze β-defensin-3 and β-defensin-4 in human TMJ synovial fluid obtained from patients affected by osteoarthritis (OA), in order to better understand the pathogenic mechanism that underlies this joint damage.

Primary adenocarcinomas of the gastrointestinal tract showing a diffuse thyroid transcription factor-1 (TTF-1)-positive immunostaining are extremely uncommon and this finding in the biopsy specimen could yield to misleading diagnosis of a metastatic lung tumor. We report the clinical and pathological features of 2 cases, occurring in a 62-year-old woman and in a 66-year-old man. The first one is a gastric adenocarcinoma with liver metastasis; the other one is a gallbladder adenocarcinoma discovered during the screening for the colorectal cancer. Both the neoplasms showed a diffuse TTF-1 positivity and both the patients did not have any evidence of lung cancer. Neither a gastric adenocrcinoma with diffuse TTF-1 expression nor a TTF-1-positive gallbladder adenocarcinoma has been described before.

Leiomyosarcoma of the inferior vena cava is a rare tumor that is usually fatal. The tumor may grow very slowly or occasionally very rapidly, shows extensive local invasion, and metastasizes more frequently than previously believed. Complete surgical resection remains the only potential curative therapeutic option. The aim of this study was to report the clinical experience in the management of a patient with leiomyosarcoma. A 65-year-old woman with a history of vague abdominal pain and leg swelling underwent computed tomography which demonstrated an occlusion of the inferior vena cava. The patient received a complete excision of the tumor without reconstruction and histological analysis confirmed the diagnosis of leiomyosarcoma type 1. At 3 years, the patient is still doing well with minimal leg edema and a contrast-enhanced CT demonstrates no evidence of recurrence locally or in distant sites. Leiomyosarcoma is a rare and aggressive tumor that presents with non-specific symptoms. Computerized tomography with 3-D reconstruction is a useful tool to define the presence and entity of the collateral circulation and therefore to decide on the surgical strategy. Resection probably offers the best opportunity for long-term survival.

A platform composed of a microwave (MW)-assisted tissue-processing system and an automated embedding system has been recently introduced in pathology laboratories. Needle core biopsy (NCB) is an established, highly accurate method for diagnosing breast lesions and for providing important pathologic, predictive, and prognostic information such as biomarker expression in case of breast carcinoma. The aim of this study was to evaluate whether breast NCBs processed with the MW-assisted tissue-processing system and automatically embedded show good-quality histology preparations and whether they are suitable for the assessment of estrogen receptor (ER), progesterone receptor (PR), Ki-67, and HER2 in breast carcinoma. A series of 233 consecutive breast NCBs processed by both conventional and MW-assisted tissue-processing systems was included in this study. The histomorphologic and immunohistochemical quality, as well as the results of the evaluation of the biomarkers, were compared—the conventional processing method being the gold standard for comparison. The quality of hematoxylin-eosin and immunohistochemical tissue sections provided by the new system is comparable to that obtained after the conventional processing method. Moreover, in breast carcinomas, a perfect agreement between the paired tissues when evaluating ER and PR status (Cohen =1) and a very good agreement when evaluating Ki-67 (=0.91) and HER2 (=0.93) have been found. In conclusion, applying strict criteria in tissue-handling steps, breast NCB can be processed and automatically embedded with these platforms. The diagnosability and the evaluation of the main prognostic and predictive biomarkers have been proved to be reliable.

The aim of the present study is to evaluate the clinical and biological factors (including markers of angiogenesis) as potential predictors of prognosis and benefit from metronomic therapy in patients with advanced breast cancer (ABC). Recent data suggest antiangiogenic activity of metronomic therapy. The study population included 62 patients with pretreated ABC who received cyclophosphamide and methotrexate orally. Tumour samples were analysed by immunohistochemistry for HER2, Ki-67, thymidine phosphorylase (TP), vascular endothelial growth factor and vascular endothelial growth factor receptor. The results from immunohistochemical analysis and clinico-pathological variables were studied to test their potential association with benefit from metronomic therapy. The median overall survival, progression-free survival and survival postprogression were 7.1 (range 0.2–38.3), 2.6 (range 0.2–28.9) and 3 (range 0–34.2) months, respectively. Among the clinical variables, age, performance status and previous therapy with taxanes were significantly associated with outcomes. Among the molecular markers, TP was found to be associated with progression-free survival. Metronomic therapy is an effective choice for ABC. Young women with a more indolent disease had the greatest benefit from this treatment. TP tumour expression might aid decision making but these findings must be confirmed in larger prospective, properly designed studies.

Numerous, but not all, anatomical variants of the hepatic artery are known presently. New or extremely rare anatomical variations of the hepatic arteries can however be encountered in the current practice. The first case report was documented using computed tomography and refers to a rare variation: retroportal proper hepatic artery anastomosed with the superior mesenteric artery by an arc of Bühler. The second case report presents the results of a dissection study, where a middle hepatic artery (MHA) was found arising in a common gastrohepatic trunk with the right gastric artery, from the stem of the proper hepatic artery; that MHA coursed over the left hepatic artery, hiding it. Moreover, in case report 2, an accessory right hepatic artery was found arising from the superior mesenteric artery. In the third case reported in this article, an arterial loop was found joining the common hepatic artery and gastroduodenal artery and further sending an ascending branch, diagnosed as MHA, and a descending one, considered as a duplicate gastroduodenal artery. We could not find in any previous reports variants such as those found in case reports 2 and 3, thus we consider these to be extremely rare. However, surgeons and radiologists must be aware of such rare morphological possibilities of the hepatic artery.

Aquaporins (AQP) are family of water channels found in several epithelial and endothelial cells, whose recent identification has provided insights into water transport in several tissues, including the central nervous system (CNS). Since brain edema continues to be the main cause of death from several CNS diseases, such as stroke, much of the interest in AQPs and their functional contribution to the water balance is due to their possible role in clearing edema water from the brain and in managing hydrocephalus and benign intracranial hypertension, suggesting that they could be targets for future treatments of various brain conditions, particularly vascular diseases. AQPs also seem to be involved in cell migration, and a mechanism of AQP-facilitated cell migration has been proposed where local osmotic gradients created at the tip of the lamellipodium drive water influx, facilitating lamellipodial extension and cell migration. AQP-facilitated cell migration was also detected in tumour cells, suggesting that it may have an important role in tumour angiogenesis and spread, and accounting for AQP expression in many tumour cell types and for correlations found between AQP expression and tumour stage in some tumours.

This study describes, microscopically, the pathologic findings correlated to malpositioning of the human temporomandibular joint disc. The specimens studied consisted of 21 discs removed from patients affected by temporomandibular joint arthropathy. The specimens were cut longitudinally and were fixed overnight in 10% neutral-buffered formalin. They were embedded in paraffin with anatomic orientation preserved. Three- to 4-μm thick sections were cut according to routine procedures and mounted on slides. Then they were stained with Goldner-modified-Mallory staining used for morphologic study at light microscopy. Abnormal collagen fiber arrangements, fragmentation of collagen fibrils, new vessel formation, meniscal tears, mucoid degeneration of the disc matrix, chondrocyte-like cells proliferation, sometimes with clonal aggregation, and hyalinization were detected in temporomandibular joint disc specimens with internal derangement, although with a different extent. From our observations, it seems that in most cases, the temporomandibular joint disc responded to internal derangement without reduction with a fragmentation of collagen fibers because hyalinization of disc matrix occurred very rarely. Moreover, disc derangement without reduction is characterized also by a change in cell population phenotype.

Epithelia‐ and leukocyte‐associated antimicrobial peptides provide immediate protection against microbial infections by rapidly inactivating potential pathogens. Bac5 is a member of the cathelicidin family of antimicrobial peptides and is stored in the cytoplasmic granules of bovine neutrophils. We investigated the expression of this gene in airway and intestine, and although the gene was not found to be locally expressed in these tissues, a strong Bac5 induction signal was detected by in situ hybridization in neutrophils infiltrating infected lung, consistent with expression of this gene in activated neutrophils. The Bac5 gene was also induced in bovine peripheral neutrophils stimulated with Escherichia colior purified lipopolysaccharide (LPS) but not in other blood cells and in resting neutrophils. The levels of Bac5 mRNA increased at 12–24 h post‐stimulation, and a dose‐dependent increase in Bac5 expression was determined in the presence of increasing amounts of LPS. A metabolically labeled product with a molecular weight compatible with that of proBac5 was immunoprecipitated from cell‐free media of stimulated neutrophils, suggesting that the newly synthesized polypeptide is released extracellularly. Collectively, these results provide the first evidence that fully differentiated neutrophils are capable of de novo synthesis and secretion of a granule‐associated antimicrobial peptide.

Heat shock proteins (HSPs) are believed to represent a cellular stress response mechanism that protects intracellular proteins from damaging events. Some studies have demonstrated an enhanced expression of large-molecular-weight HSPs in diseased systematic joints.

Mutations of mitochondrial DNA (mtDNA) are associated with different human diseases, including cancer and aging. Reactive oxygen species produced during oxidative phosphorylation are a major source of mtDNA damage. It is not clear, however, whether DNA repair mechanisms, able to abolish effects due to oxidative damage, are present in mitochondria. APE/Ref-1 is a nuclear protein possessing both redox activity (by which activates, “in vitro”, the DNA-binding functions of several transcription factors) and DNA repair activity over apurinic/apyrimidinic sites. Immunohistochemical evidences indicate that in follicular thyroid cells, APE/Ref-1 is located in both nucleus and cytoplasm. Electronmicroscopy immunocytochemistry performed in the rat thyroid FRTL-5 cell line, indicates that part of the cytoplasmatic APE/Ref-1 is located in mitochondria. The presence of APE/Ref-1 inside mitochondria is further demonstrated by western blot analysis after cell fractionation. In the Kimol cell line (which is derived from FRTL-5, transformed by the Ki-ras oncogene) the amount of mitochondrial APE/Ref-1 is reduced by three to fourfold with respect to the normal FRTL-5 cells. These results suggest that: (i) a machinery capable of repairing DNA damaged by oxidative stress is present in mitochondria and (ii) mtDNA repair mechanisms may be impaired during cell transformation.

The aim of this study was to evaluate the diagnostic accuracy of large core breast biopsy with the use of the perforated compression grid (PCG) in a series of 106 consecutive mammographically detected breast lesions. The PCG consists in a fenestrated paddle that replaces the usual mammographic compressor. Each hole in the grid is marked by letters and numbers in order to obtain the coordinates of the area to biopsy. By analysing the two orthogonal projections, the depth of the lesion in the breast is calculated. With the breast positioned in the PCG, a skin incision is made. After calculations about the depth of needle insertion, the tip of the needle is inserted proximally to the target area. In such a way, taking into consideration the total running of the needle (23 mm), a correct sampling is assured, and multiple needle passes are performed. Sensitivity was of 90.62 and 90.90%, specificity was of 100 and 95.45% and positive predictive value was of 100 and 90.90% by excluding and including suspicious diagnoses, respectively, for each computation. In conclusion, the study indicated that image-guided core biopsy performed by the approach of PCG is a cost-effective, simple and accurate technique for the diagnosis of breast lesions, and it could be proposed as a low-cost alternative where the stereotactic equipment is not available.

The authors report their experience on the use of a biopsy gun for histological sampling in the field of breast lesions. The use of cytological sampling by (FNAB) fine needle aspiration biopsy has been preferred so far, because it has been thoutht to be simpler, less risky and reliable. Nevertheless, the cytological sampling shows a number of drawbacks such as the need for passes to get sufficient cellular material, frequent problems in diagnosing benign lesions and the decisive influence of the operator's skill. By using a biopsy gun for histological sampling these disadvantages are eliminated. In this case, in fact, the validity of the sample is not influenced by the operator's skill; fewer passes are necessary and their validity does not depend on the nature of the lesion. The personal series of cases involves 91 patients subjected to histological sampling for suspected lesions. Two different kinds of needles were used with one an 18 G diameter and a 23-mm extension of the sytlet, as well as a sampling window 17 mm; the other with the same diameter and extension of the stylet, as as a sampling window 8 mm. The first needle was used in all 91 patients, and the second only in 30. The results were not influenced by the employ of the different kinds of needles. A total of 268 samples were made and 110 lesions were discovered, 79 of which were malignant and 31 benign (fibroadenoma, fibrocystic change and epitheliosis). Three carcinomas were not found (3 false-negative) and one specimen was inadequate. The values of sensibility, specificity and diagnostic accuracy of the method were, respectively, 96.2%, 100% and 97.2%, with 3.8% false-negative due to three cases where the lesion was not centred for guidance mistake.

Cardiac transplantation is characterized by rejection, myocyte loss, interstitial and replacement fibrosis, and loading abnormalities. These modifications contribute to enhance mural and muscle cell stress, activating reactive growth processes in myocytes and interstitial cells. However, it is unknown whether cell cycle related gene product, such as PCNA, and DNA synthesis are stimulated under these conditions. Therefore, 62 endomyocardial biopsies obtained from 17 patients who underwent cardiac transplantation were examined for the immunocytochemical detection of PCNA protein in myocyte and non-myocyte nuclei. In addition, tissue samples were labeledin vitrowith bromodeoxyuridine (BrdU) to document ongoing DNA synthesis. The presence of mitotic images in myocytes and non myocytes were also examined. Biopsies were collected from 1–768 days after surgery. Histologic examination of tissue sections documented that PCNA labeling involved nearly 30% of myocyte nuclei in all patients. Similar percentages of PCNA labeling were detected in interstitial cells, lymphocytes and mononuclear infiltrates. DNA synthesis in myocytes and connective tissue cells was observed in nine and 14 subjects, respectively. BrdU positive lymphocytes and mononuclear infiltrates in 13 cases. Three mitotic figures in myocyte nuclei were identified. PCNA, BrdU labeling and mitosis were not detected in eight myocardial samples obtained from control hearts. These results suggest that the evolution of the transplanted heart involves the expression of a gene which is implicated in DNA replication. The presence of ongoing DNA synthesis and mitosis support the notion that proliferation of myocytes and non muscle cells may be a component of ventricular remodeling after cardiac transplantation.

Twenty-seven cervical condylomata were studied by morphological and immunohistochemical methods (peroxidase-antiperoxidase technique according to Sternberger, with some modifications). The antiserum was obtained from rabbits immunized by human papillomavirus virions; 37% of condylomata stained positively and the koilocytotic cells showed a dark brown nuclear stain. This technique, not particularly useful for diagnostic purposes, could be employed to obtain better understanding of the natural history of these cervical neoplasias.

We have investigated the distribution of TGFβ using antibodies specific for its intracellular and extracellular forms in full-thickness biopsies of patients with SSc, primary Raynaud's phenomenon (PRP), systemic lupus erythematosus (SLE), and from normal subjects. Nine of 11 SSc biopsies demonstrated intracellular TGFβ in endothelial cells while only 6 exhibited extracellular TGFβ. Endothelial cells in skin biopsies of all PRP patients displayed both intracellular and extracellular TGFβ. All other control biopsies were negative. In patients with PRP, some positively staining fibroblasts were found scattered throughout the dermis. Lastly, extracellular TGFβ was localized in the papillary dermis of PRP and SSc biopsies and in all the dermal layers of SLE patients. No significant staining of TGFβ was observed in the endothelial cells, fibroblasts, or in the extracellular matrix of the majority of biopsies from normal subjects. These data suggest that TGFβ may be one of the cytokines involved in the early stages of pathogenesis of SSc, and that endothelial cells in SSc and PRP may be a source and/or a target of TGFβ. Copyright 1993, 1999 Academic Press

Ischemic type biliary lesions (ITBLs), a particular subset of non-anastomotic biliary strictures (NAS), are characterized by intra and extrahepatic strictures that occur in the absence of either hepatic artery thrombosis or stenosis. When they occur within the first year after liver transplantation their development is mostly related to ischemia–reperfusion injury (IRI). The indocyanine green plasma disappearance rate (ICG-PDR) might be able to predict the probability of IRI-induced graft damage after liver transplantation.