Aromatase Inhibitors in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer: Profiles of Psychological Symptoms and Quality of Life in Different Patient Clusters.

BACKGROUND: Aromatase inhibitors (AIs) as adjuvant therapy after breast cancer (BC) surgery have demonstrated to reduce the risk of disease recurrence, to lower the risk of contralateral BC, and to improve survival when compared to tamoxifen in patients with limited-stage hormone receptor-positive (HR+) BC. However, AIs are associated with adverse events that can have a significant impact on patient quality of life (QoL). AIM: This study aimed to identify profiles of psychological symptoms and QoL in HR+ BC patients undergoing AI therapy. METHOD: Data were collected with questionnaires administered at three time points: AI initiation (t0); 3 months after AI initiation (t1); and 6 months after AI initiation (t2). The FACT-G, FACT-B, and FACT-ES questionnaires were used to assess QoL; psychological symptoms were assessed using the SCL-90-R. RESULTS: 43 women were enrolled in the study (t0), and 37 completed the t1 evaluation and 29 the t2 evaluation. We found (1) a progressive decrease over time in FACT-G and FACT-ES scores, in particular in the Physical, Emotional, and Endocrine subscales, and an increase in the SOM (somatization) subscale of the SCL-90-R; (2) the presence of 4 clusters related to different psychological symptoms and QoL evolution over time; (3) that patients belonging to the cluster characterized by worsening symptoms and QoL during time differed from the others in the Emotional subscale of the FACT-B and in the GSI (Global Score), OCD (obsessive-compulsive), DEP (depression), ANX (anxiety), and SLP (sleep disorders) dimensions of the SCL-90-R and had significantly higher BMI levels; and (4) that 3 items from the SCL-90-R and 2 items from FACT Emotional Well-Being subscale were predictive of the "worst" cluster. CONCLUSIONS: Although larger studies are needed to confirm these results, our data open up new ways of investigation into the effects of AIs on QoL in HR+ BC patients.

[Implementation of the ICD-ICF model in rehabilitation medicine: report of a clinical case in rehabilitative cardiology]. / Implementazione del modello ICD-ICF in medicina riabilitativa: presentazione di un caso clinico in cardiologia riabilitativa.

SUMMARY: This patient entered a Cardiac Rehabilitation Program after coronary artery bypass graft. Concomitant diseases and the degree of disability have been coded according to International Classification of Functioning (ICF). Rehabilitation multidisciplinary program has been started (physician, nurses, physiotherapist and nutritionist); atrial fibrillation, anaemia, pleural effusion, surgical wounds inflammation were treated. Educational program allowed a better knowledge of the diseases the patient is bearing; low functional capability diagnosed at admittance improved thanks to the coordinated intervention of professionals involved. Coding diseases and disabilities at admission ensured a detailed identification of patient's issues and allowed the identification and the proposal for a targeted rehabilitation program. The improvement of medical ICF codes b280, b810 and b820, of physiotherapeutic codes b235, d450, d4551 and d455 and of nursing codes b280, b810 and b820 depends on the marked reduction of disability level.

Phytochemical analysis and effects on ingestive behaviour of a Caralluma fimbriata extract.

Caralluma fimbriata Wall. is currently used as a "natural slimming" food supplement, likely due to its content in pregnane glycosides. In the present study, a commercially available Caralluma fimbriata extract (Slimaluma®; CFE, 100 mg/kg) has been evaluated for its ability to affect the ingestive behaviour in female rats, also with reference to the modulation of the brain neuropeptides NPY and ORX.The interference of CFE with α-amylase and lipase enzymes has been investigated in vitro, as possible peripheral mechanism of action. Also, the chemical composition of CFE has been assessed by NMR and spectrophotometric analysis. Results from in vivo study showed that CFE induced effects neither on blood parameters, nor on liver and gut histomorphology. Interestingly, a reduction in body weight gain with an increase in water intake and hypothalamic levels of NPY and ORX peptides were found. Phytochemical analysis, showed CFE contained about 12% of pregnane glycosides and 1.3% of polyphenols. Present results suggest possible effects of C. fimbriata on ingestive behaviour, likely mediated by central and peripheral mechanisms.

Pitfalls in oncology: a unique case of thoracic splenosis mimicking malignancy in a patient with resected breast cancer.

Thoracic splenosis (TS) is a condition of autotransplantation of splenic tissue into the pleural cavity after thoraco-abdominal trauma, with diaphragmatic and spleen injury. It is usually asymptomatic and discovered as an incidental finding at imaging performed for other reasons. Its differential diagnosis regards different benign and malignant conditions and should be discerned avoiding invasive procedures. We report a case of thoracic mass associated with pleural nodules mimicking malignancy in a patient with resected breast cancer for whom a diagnosis of TS was made early by using non-invasive methods. Briefly, we review the literature data on TS, comment concisely the possible implications of using invasive procedures and describe the current non-invasive techniques available. Furthermore, we highlight the importance of an accurate medical history collection, the role of the multidisciplinary board and their impact on treatment decision making. Finally, we conclude that clinical information and imaging would be the discriminating factors to avoid unnecessary invasive procedures.

Bevacizumab Prevents Brain Metastases Formation in Lung Adenocarcinoma.

Patients with nonsquamous non-small cell lung cancer (nsNSCLC; largely lung adenocarcinoma) are at high risk of developing brain metastases. Preclinical data suggested that anti-VEGF-A therapy may prevent the formation of nsNSCLC brain metastases. Whether non-brain metastases are also prevented, and whether bevacizumab shows a brain metastases-preventive activity in cancer patients is unknown. Data of one nsNSCLC (stage IIIB/IV, AVAiL) and two breast cancer bevacizumab trials (HER2 negative, AVADO; HER2 positive, AVEREL) were retrospectively analyzed regarding the frequency of the brain versus other organs being the site of first relapse. For animal studies, the outgrowth of PC14-PE6 lung adenocarcinoma cells to brain macrometastases in mice was measured by intravital imaging: under control IgG (25 mg/kg) treatment, or varying doses of bevacizumab (25 mg/kg, 2.5 mg/kg, 0.25 mg/kg). Brain metastases as site of first relapse were significantly less frequent in the bevacizumab arm of the AVAiL trial (HR = 0.36, P < 0.001). In AVADO and AVEREL, no significant difference was seen. In mice, bevacizumab treatment led to secondary regressions of non-brain macrometastases, but did not reduce their total incidence, and did not improve survival. In a brain-seeking nsNSCLC metastasis model, treatment with bevacizumab inhibited brain metastases formation, which resulted in improved overall survival. In summary, bevacizumab has the potential to prevent brain metastases in nsNSCLC, but no preventive activity could be detected outside the brain. These data indicate that anti-VEGF-A agents might be particularly relevant for those stage III nsNSCLC patients who are at high risk to develop future brain metastases. Mol Cancer Ther; 15(4); 702-10. ©2016 AACR.

Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence.

The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features.

Trans-thoracic biopsy of lung lesions: FNAB or CNB? Our experience and review of the literature.

PURPOSE: This study was performed to determine the type and incidence of complications of fine-needle aspiration biopsy (FNAB) and core biopsy (CNB) performed under computed tomography (CT) guidance to characterise lung lesions, and assess the diagnostic accuracy of the two techniques. MATERIALS AND METHODS: In 2009-2011, we performed 124 lung biopsies (66 CNB and 56 FNAB) on 121 patients with a mean age of 72.4 years. Exclusion criteria were pulmonary resection, pleural lesions and/or effusions, and inadequate blood-coagulation profile. All examinations were acquired after contrast-agent administration in a craniocaudal direction from the lung apex to base during a single inspiratory breath-hold, with standardised parameters. Each lesion was scanned with 13-15 slices that could be repeated whenever necessary to document the needle track and for lesion centring, by positioning a metallic marker perpendicular to the centring light to indicate the point of needle access. Unless otherwise clinically indicated, 4 h after the procedure chest radiography was performed. RESULTS: Age was found to be a factor influencing the complications: pneumothorax in young subjects (31 %) and parenchymal haemorrhage in the elderly (30 %), with CNB but not with FNAB. We had more complications with the right lung: 50 % of pneumothorax cases in the upper lobe with CNB and 40 % of cases of haemorrhage in the lower lobe with FNAB. The anterior approach gave rise to more complications with CNB, while the posterior approach with FNAB. CNB had more complications than FNAB for lesions ≤ 3.5 cm (31 vs. 18 % pneumothorax), and >3.5 cm (34 vs. 9 % haemorrhage). There was no significant correlation with lesion histology, needle calibre or number of passes (probably due to the small number of procedures done with needles other than 18 G in CNB or 22 G in FNAB or involving more than one needle pass). The diagnostic accuracy of FNAB, done with a pathologist's extemporaneous assessment of sample adequacy, was 94.83 % against 81.82. % of CNB. CONCLUSIONS: FNAB under CT guidance is subject to a lower rate of complications and, if performed in the presence of the pathologist, has a greater diagnostic accuracy compared to CNB.

Is a dexamethasone-sparing strategy capable of preventing acute and delayed emesis caused by combined doxorubicin and paclitaxel for breast cancer? Analysis of a phase II trial.

OBJECTIVE: The effectiveness of palonosetron without delayed dexamethasone dosing against emesis was investigated in patients scheduled to receive the corticosteroid-containing combination of doxorubicin and paclitaxel (AT) for 3 cycles. METHODS: Chemo-naïve women with breast cancer receiving doxorubicin (60 mg/m(2)) and paclitaxel (200 mg/m(2)) were eligible. Patients received palonosetron 0.25 mg intravenously before chemotherapy, however, all patients also received a premedication consisting of prednisone (25 mg orally the evening before therapy) and hydrocortisone (250 mg intravenously just before paclitaxel). The primary end point was complete control (CC; no vomiting, no rescue anti-emetics, and no more than mild nausea) during the overall phase (days 1-5) following cycle 1. RESULTS: Seventy-six patients were enrolled and evaluable (median age 50 years). Fifty-six patients (74%; 95% CI 62-83%) achieved overall CC. Acute (day 1) and delayed (days 2-5) CC rates were 78 and 74%, respectively. No vomiting rates for the acute, delayed and overall phases were 85, 85 and 83%, respectively. An exploratory analysis showed only a small decrease in the probability of achieving CC between cycle 1 (74%) and cycle 3 (66%). CONCLUSION: The dexamethasone-sparing strategy prevented emesis in more than 70% of breast cancer patients receiving their initial cycle of AT chemotherapy.

AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer.

PURPOSE The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) -positive locally recurrent/metastatic breast cancer (LR/MBC). PATIENTS AND METHODS Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior adjuvant trastuzumab, prior (neo)adjuvant taxane, hormone receptor status, and measurable disease and were randomly assigned to receive docetaxel 100 mg/m(2) plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. The primary end point was progression-free survival (PFS). Additional end points included overall survival, response rate (RR), safety, quality of life, and translational research. Results Baseline characteristics of the 424 patients were balanced between treatment arms. Most patients had visceral metastases, 43% had a disease-free interval less than 12 months, and 85% had measurable disease. Median follow-up was 26 months. The hazard ratio for investigator-assessed PFS was 0.82 (95% CI, 0.65 to 1.02; P = .0775; median PFS, 13.7 v 16.5 months in the non-bevacizumab and bevacizumab arms, respectively; PFS events in 72%). The Independent Review Committee-assessed PFS hazard ratio was 0.72 (95% CI, 0.54 to 0.94; P = .0162; median PFS, 13.9 v 16.8 months, respectively; PFS events in 53%). The RR was 70% versus 74%, respectively (P = .3492). Grade ≥ 3 febrile neutropenia and hypertension were more common with bevacizumab-containing therapy. High baseline plasma vascular endothelial growth factor A (VEGF-A) concentrations were associated with greater bevacizumab benefit (not statistically significant). CONCLUSION Combining bevacizumab with docetaxel and trastuzumab did not significantly improve investigator-assessed PFS. The potential predictive value of plasma VEGF-A is consistent with findings in HER2-negative LR/MBC, warranting prospective evaluation.

Assessment of MDA efficiency for genotyping using cloned embryo biopsies.

The possibility to genotype embryos prior to implantation would have advantages for increasing the speed of selection of cattle. Reliable genotyping requires more DNA than can be obtained from biopsies of embryos, if they are to remain viable. Multiple displacement amplification (MDA) is a whole genome amplification technique used to increase the amount of DNA from biopsies for analysis. Reduced genome coverage resulting in Allele Drop Out (ADO) at heterozygous loci or missing genotypes are drawbacks of MDA. The present article describes the correlation between the input DNA quantity or embryo biopsy size and MDA success. Missing genotypes and ADO drastically increased when fewer than 30-40 cells or the genomic equivalents were used. However, embryo viability was found to be reduced if biopsied with more than 10 cells. Therefore, in vitro cell culture was investigated as a means to increase the number of cells available and the genotyping reliability.

Comparative study on carotid revascularization (endarterectomy vs stenting) using markers of cellular brain injury, neuropsychometric tests, and diffusion-weighted magnetic resonance imaging.

OBJECTIVE: Subclinical alterations of cerebral function can occur during or after carotid revascularization and can be detected by a variety of standard tests. This comparative study assessed the relationship among serum levels for two biochemical markers of cerebral injury, postoperative diffusion-weighted magnetic resonance imaging (DW-MRI), and neuropsychometric testing in patients undergoing carotid endarterectomy (CEA) or carotid artery stenting (CAS) for high-grade asymptomatic carotid stenosis. METHODS: Forty-three consecutive asymptomatic patients underwent carotid revascularization by endarterectomy (CEA, 20) or stenting (CAS, 23). They were evaluated with DW-MRI and the Mini-Mental State Examination (MMSE) test preoperatively and 5 points (P = .001). Analysis of S100beta and NSE levels showed a significant increase at 24 hours in CAS patients compared with CEA patients (P = .02). The MMSE score at 6 months showed a nonsignificant increase vs the postoperative score in both groups. CONCLUSIONS: Biochemical markers measurements of brain damage combined with neuropsychometric tests and DW-MRI can be used to evaluate silent injuries after CAS. The mechanisms of rise in S100beta and NSE levels at 24 hours after CAS may be due to increased perioperative microembolization rather than to hypoperfusion. Further studies are required to assess the clinical significance of those tests in carotid revascularization.

Chelidonium majus is not hepatotoxic in Wistar rats, in a 4 weeks feeding experiment.

AIM OF THE STUDY: Aerial parts of Chelidonium majus L. (Papaveraceae family) are traditionally used in the treatment of gallstones and dyspepsia, however several cases of hepatotoxicity are reported. In this work we evaluated the effects on liver function of a C. majus extract, obtained from the herbal material responsible for one case of hepatotoxicity. MATERIALS AND METHODS: Experiments were performed in Wistar rats, after oral administration of doses corresponding to 1.5 and 3g/(kg day) of herbal drug, for 2 or 4 weeks. Blood samples were collected to perform biochemical analysis, whereas liver samples were used for histomorphological and immunohistochemical examination along with the determination of oxidative stress parameters. RESULTS: No significant modification in animal body weight, food consumption, enzyme activities, hepatic histomorphology and MDA formation, at either time or dosage level. Conversely, C. majus induced a slight but significant decrease of GSH levels and SOD activity, especially at the high dose. CONCLUSIONS: Our study suggests that C. majus, at doses about 50 and 100 times higher than those generally used in humans, does not alter hepatic function. However, the reduction in GSH levels and SOD activity suggests particular attention in use of C. majus or its preparations in situations (pharmacological treatments, physio-pathological conditions, etc.) that can compromise liver function.

Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12.

BACKGROUND: Mesenchymal stem cells (MSCs) have been recently investigated for their potential use in regenerative medicine. MSCs, in particular, have great potential, as in various reports they have shown pluripotency for differentiating into many different cell types. However, the ability of MSCs to differentiate into tendon cells in vitro has not been fully investigated. RESULTS: In this study, we show that equine bone marrow mesenchymal stem cells (BM-MSCs), defined by their expression of markers such as Oct4, Sox-2 and Nanog, have the capability to differentiate in tenocytes. These differentiated cells express tendon-related markers including tenomodulin and decorin. Moreover we show that the same BM-MSCs can differentiate in osteocytes, as confirmed by alkaline phosphatase and von Kossa staining. CONCLUSION: As MSCs represent an attractive tool for tendon tissue repair strategies, our data suggest that bone marrow should be considered the preferred MSC source for therapeutic approaches.

Early elevation of interleukin-1beta and interleukin-6 levels after bare or drug-eluting stent implantation in patients with stable angina.

INTRODUCTION: Drug-eluting stent (DES) implantation represents an important innovation in the treatment of coronary artery disease. However, inflammatory-related complications, including subacute thrombosis and in-stent restenosis, are still important limitations to percutaneous coronary intervention (PCI). The aim of this study was to compare early local release of interleukin 1beta (IL-1beta) and IL-6 proinflammatory cytokines after elective placement of either bare metal stents or DES. MATERIALS AND METHODS: IL-1beta and IL-6 levels were assayed in plasma obtained from the coronary sinus both before and 20 min after stent implantation in 59 patients with stable angina, who were randomly assigned to receive bare, paclitaxel-, or sirolimus-eluting stents during elective PCI. RESULTS: We found that IL-1beta and IL-6 levels were significantly increased in the coronary sinus of patients receiving either bare, paclitaxel- or sirolimus-eluting stents 20 min after stent implantation as compared with basal concentrations. The variation in the level of both cytokines was comparable among the three study groups. CONCLUSIONS: A local release of proinflammatory cytokines occurs shortly after coronary stent placement, including DES, which is possibly related to plaque rupture and/or endothelium traumatism following the stenting procedure. This suggests that precocious anti-inflammatory treatment could be of benefit to further improve the PCI clinical outcome.

Expression and localization of calreticulin in tobacco anthers and pollen tubes.

The developmental expression pattern and localization of calreticulin were studied in Nicotiana tabacum L. anthers, pollen and pollen tubes. High transcript and protein levels were detected throughout anther development. Immunolocalization of calreticulin in the anthers showed particular dense label in tapetum and pollen at developmental stage 2, when the tapetum is highly active and the pollen tetrads are formed. Much lower transcript and protein levels were detected in dry and hydrated pollen and in pollen tubes. Immunofluorescence labeling of both chemically fixed and cryo-fixed and freeze-substituted pollen tubes showed the presence of calreticulin in Golgi apparatus and endoplasmic reticulum (ER). Calreticulin was seen throughout the stacks in the Golgi apparatus and in the areas with coated-Golgi vesicles but much less so in the ER. Calreticulin was not found in the secretory vesicles. A relatively intense label was occasionally seen adjacent to the wall of the tube. No significant label was observed in mitochondria, vacuoles, generative cells, cell wall or callose plugs. The present results are consistent with a role of calreticulin in Ca2+-dependent folding of secreted glycoproteins in tapetum, pollen and pollen tubes.

A comprehensive radiation hybrid map of the bovine genome comprising 5593 loci.

A bovine whole genome 7000-rad radiation hybrid (RH) panel, SUNbRH(7000-rad), was constructed to build a high-resolution RH map. The Shirakawa-USDA linkage map served as a scaffold to construct a framework map of 3216 microsatellites on which 2377 ESTs were ordered. The resulting RH map provided essentially complete coverage across the genome, with 1 cR7000 corresponding to 114 kb, and a cattle-human comparative map of 1716 bovine genes and sequences annotated in the human genome, which covered 79 and 72% of the bovine and human genomes, respectively. We then integrated the bovine RH and comparative maps with BAC fingerprint information in to construct a detailed, BAC-based physical map covering a reported 40-cM quantitative trait locus region for intramuscular fat or "marbling" on BTA 4. In summary, the new, high-resolution SUNbRH7000-rad, comparative, Shirakawa-USDA linkage, and BAC fingerprint maps provide a set of genomic tools for fine mapping regions of interest in cattle.

Modulation of tachykinin and cytokine release in patients with coronary disease undergoing percutaneous revascularization.

Plasma levels of substance P (SP) and neurokinin A (NKA) tachykinin and of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) cytokines were assayed in plasma obtained from peripheral blood of 19 patients presenting with stable chronic coronary stenosis and 12 patients with acute coronary syndrome (ACS). Plasma samples were obtained before, during, and after percutaneous coronary intervention (PCI) consisting of implantation of a metallic stent. Fourteen healthy subjects without any evident risk factors for coronary artery disease (CAD) were also included for comparison at basal time. We found that plasma levels of both IFN-gamma and TNF-alpha were significantly higher in patients with chronic or acute CAD than those in control subjects at the time of presentation. NKA and IFN-gamma levels were also significantly increased in ACS patients compared with those in patients with stable disease. The analysis performed during and after PCI revealed that IFN-gamma levels increased 15 min after stent implantation in both chronic and ACS patients and that TNF-alpha levels increased in chronic patients only compared to basal values. In addition, a significant decrease of both NKA and SPA levels 48 h after the end of the revascularization procedure was observed in ACS patients. These data suggest that modulation of tachykinin and/or cytokine release with proinflammatory activity in chronic or acute cardiac ischemia and during following coronary stenting might play an important role in heart tissue damage and in long-term inflammatory complications of PCI.

Endoplasmic reticulum stress-induced programmed cell death in soybean cells.

In animal cells, the endoplasmic reticulum may participate in programmed cell death by sensing and transducing apoptotic signals. In an attempt to analyze the role of the endoplasmic reticulum in plant programmed cell death we investigated the effect of cyclopiazonic acid, a specific blocker of plant endoplasmic reticulum-type IIA Ca2+-pumps, in soybean cells. Cyclopiazonic acid treatment elicited endoplasmic reticulum stress and a biphasic increase in cytosolic Ca2+ concentration, followed by the induction of a cell death program. Cyclopiazonic acid-induced programmed cell death occurred with accumulation of H2O2, cytochrome c release from mitochondria, caspase 9- and caspase 3-like protease activation, cytoplasmic shrinkage and chromatin condensation. Chelation of cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethil ester) failed to inhibit cyclopiazonic acid-induced cell death. Taken together, our results provide evidence for a role of the endoplasmic reticulum and mitochondria in regulating cyclopiazonic acid-induced programmed cell death in soybean cells, probably via a cross-talk between the two organelles.

A radiation hybrid map for the bovine Y Chromosome.

Screening a bovine Y Chromosome-specific DNA library resulted in 34 new microsatellites, six of which mapped to the pseudoautosomal region (PAR), and 28 localized to the Y-specific region. These microsatellites, together with 23 markers previously mapped to the bovine Y Chr, were scored on a 7000-rad cattle-hamster radiation hybrid (RH) panel. Retention frequency of individual markers ranged from 18.5% to 76.5% with an average of 48.4%. Markers with high retention frequency (>55%) were found to exist in multiple copies on the Y Chr. Thirteen markers were placed on the PAR RH map with the AmelY gene proximal to the pseudoautosomal boundary and 46 markers, including Sry and Tspy gene, on the Y-specific region of the RH map. The microsatellites developed and mapped in this work will be useful for comparative mapping of cattle, sheep, and goat, studying the origin, evolution, and migration of bovidae species and provide an initial platform to develop a high-resolution map of the Y Chr and positional cloning of Y-specific genes.

Diltiazem impairs maturation and functions of human dendritic cells.

The aim of this study was to define the effects of diltiazem, a calcium antagonist drug used in cardiology and in clinical transplantation, on the differentiation and maturation of human dendritic cells (DC). Herein, we demonstrate that diltiazem, in association with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to differentiate into cells with many of the characteristic of DC. However, diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4-induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12 and reveal a reduced ability to stimulate alloreactive T-cell responses as well as in inducing interferon-gamma producing Th1 cells. These effects may contribute to a decreased DC-dependent T-cell activation and may help to explain the immunoregulatory function of diltiazem and its effectiveness in preventing transplant rejection.