Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth

Pleiotrophin (PTN) is an important developmental cytokine that is highly expressed during embryogenesis but shows very limited expression in adult tissues, where it is largely restricted to the brain. High PTN serum levels are associated with a variety of solid tumors. We recently showed that patients with multiple myeloma (MM) also have elevated serum levels of this protein and the amount of PTN correlated with the patients' disease status and response to treatment. In this study, we demonstrate that MM cell lines and the malignant cells from MM patients' bone marrow produced PTN and secreted PTN protein into the supernatants during short-term culture. Moreover, Ptn gene expression correlated with the patients' disease status. Inhibition of PTN with a polyclonal anti-PTN antibody reduced growth and enhanced apoptosis of MM cell lines and freshly isolated bone marrow tumor cells from MM patients in vitro. Importantly, this antibody also markedly suppressed the growth of MM in vivo using a severe combined immunodeficiency (SCID)-hu murine model. This represents the first study showing the importance of PTN in the growth of any hematological disorder. Because the expression of this protein is very limited in normal adult tissues, PTN may represent a new target for the treatment of MM.     

Less smoke and minimal tissue carbonization using a thulium laser for laparoscopic partial nephrectomy without hilar clamping in a porcine model

PURPOSE: We evaluated the utility of a thulium laser and a novel implementation of its use for laparoscopic partial nephrectomy to achieve precise, smokeless, and hemostatic dissection without hilar clamping and with minimal charring in a porcine model. MATERIALS AND METHODS: Laparoscopic transperitoneal lower-pole partial nephrectomy was performed in five Yorkshire farm pigs without clamping of the renal hilum. All animals were kept alive for 1 week. Using a 365-mum laser fiber, a 30 W thulium laser was used to produce full-thickness cortical excisions of the lower-pole renal cortex. The laser fiber was delivered through the working channel of a 16F flexible cystoscope inserted through a 10-mm laparoscopic port. The laser incision was directed by manual deflection of the cystoscope along with low-pressure saline irrigation through the cystoscope. RESULTS: Laparoscopic partial nephrectomy was completed in all cases without perioperative complications and with an estimated blood loss of <50 mL. The thulium laser was able to cut tissue and simultaneously to coagulate vessels as large as 1.6 mm. The flexible cystoscope with concurrent saline irrigation permitted precise laser control for dissection with minimal tissue charring and no smoke to obscure visibility. At 1 week, the cut edge of the tissue showed minimal necrosis with preservation of histologic architecture. CONCLUSIONS: Laparoscopic partial nephrectomy with the thulium laser provides precise dissection and hemostasis without hilar clamping. Minimal tissue charring and no smoke generation improve visibility.     

Complete Nucleotide Sequence of IT-227/82, An Avian Paramyxovirus Type-1 Strain of Pigeons (Columba Livia)

This paper describes the complete genome sequence of IT-227/82, a strain of avian paramyxovirus type-1 of pigeon (PPMV-1). IT-227/82 is an antigenic variant of Newcastle disease virus (NDV) of chickens. The genome is 15,192 nucleotides (nt) long, similarly to the previously published NDV strain ZJ1. It is, however, six nt longer than the genomes of NDV strains LaSota/46 and Beaudette C. The six-nt insertion was located in the 5′ non-coding region of the nucleoprotein (NP) gene. The presence of this six-nt insertion showed no correlation with the virulence or the reservoir of the NDV strains sequenced so far. The genome length of 15,186 or 15,192 nt can be connected however, to “old” (I, II, III and IV) and “new” (V, VI, VII and VIII) NDV genotypes, respectively. Comparison of open reading frames indicated that the PPMV-1 strain IT-227/82 encodes the longest W protein, (227 amino acids). The length of the W protein showed remarkable differences even within genotypes and cannot be regarded, therefore, as a phylogenetic feature. The haemagglutinin-neuraminidase protein of strain IT-227/82 consists of 571 amino acids, similarly to genotypes IV, V and VII NDV strains, while genotype I and II strains have longer HN proteins, 616 and 577 amino acids, respectively. The length of the haemagglutinin-neuraminidase protein possesses phylogenetic importance.     

Traumatic dental injuries in an urban adolescent population in Tirana,Albania

Abstract – Aim: The aim of this study was to gather information about traumatic dental injuries (TDI) in an urban adolescent Albanian population. Material & methods: A cross‐sectional survey was carried out to acquire epidemiological data about TDI in the permanent incisors of Albanian adolescents. Participants (n = 2789) were adolescents of both genders, aged 16–18 years, attending public high schools in Tirana. Results: The occurrence of TDI in the incisors ranged from 8.9% of 16‐year‐olds to 10.5% of 18‐year‐olds. A greater proportion of boys (12.4%) had TDI compared with girls (7.7). The most commonly reported causes were collisions (27.5%) followed by physical leisure activities and sports (mainly cycling and swimming/diving) (14.1%) and falls (13.4%). Of the adolescents affected by TDI, 32% had unmet treatment need because of no or inadequate treatment. Adolescents living in districts with low socio‐economic level had significantly more TDI with unmet treatment need than those living in districts with high socio‐economic level. Conclusion: The occurrence of TDI among Albanian adolescents was moderate. Adolescents who came from low socio‐economic districts had a greater probability of having TDI with unmet treatment need.     

Mirror movements in patients with Parkinson's disease

Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = ?0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization. © 2007 Movement Disorder Society     

Lagophthalmy of VII nerve palsy--therapeutical approaches

Facial nerve palsy is impairing orbicular muscle function leading to lagophthalmos. This disease impairs patients' quality of life by exposure keratopathy which is accompanied by ocular pain and deteriorate visual acuity at a variable degree. The paper's aim is to show up the place of lagophthalmos in anterior ocular segment pathology and to evidence the results obtained by us with a new therapeutical method applied in several cases. All cases with lagophthalmos have ocular complications like exposure kerato-conjunctivitis. The treatment was both conservative and surgical which consisted in majority of cases in blepharoraphy with its inconveniencies, aesthetical and functional. We have applied a new surgical method--gold weight superior lid implantation--in 4 cases and the results are promising.     

Alpha1-antitrypsin inhibits angiogenesis and tumor growth

Disturbances of the ratio between angiogenic inducers and inhibitors in tumor microenvironment are the driving force behind angiogenic switch critical for tumor progression. Angiogenic inhibitors may vary depending on organismal age and the tissue of origin. We showed that alpha(1)-antitrypsin (AAT), a serine protease inhibitor (serpin) is an inhibitor of angiogenesis, which induced apoptosis and inhibited chemotaxis of endothelial cells. S- and Z-type mutations that cause abnormal folding and defective serpin activity abrogated AAT antiangiogenic activity. Removal of the C-terminal reactive site loop had no effect on its angiostatic activity. Both native AAT and AAT truncated on C-terminus (AATDelta) inhibited neovascularization in the rat cornea and delayed the growth of subcutaneous tumors in mice. Treatment with native AAT and truncated AATDelta, but not control vehicle reduced tumor microvessel density, while increasing apoptosis within tumor endothelium. Comparative analysis of the human tumors and normal tissues of origin showed correlation between reduced local alpha(1)-antitrypsin expression and more aggressive tumor growth.     

Different familial transmission patterns in bipolar I disorder with onset before and after age 25

Gene identification in common disorders such as Alzheimer disease and breast cancer has greatly profited from the use of age of onset as criterion to delineate subgroups of disease characterized by different inheritance patterns. In bipolar affective disorder, where the majority of linkage studies have produced conflicting results, studies reporting clinical characteristics and familial occurrence of disease have suggested that age of onset might serve as an indicator for identifying more homogeneous subgroups of disease. Our study was the first to examine this hypothesis by the means of segregation analysis. We investigated a sample of 177 bipolar I probands recruited from consecutive admissions and their first‐ and second‐degree relatives (2,407 subjects). Probands were subdivided into an early‐onset (n = 107) and a late‐onset group (n = 70) using an age of onset of 25 as a cut‐off point. This age was chosen because the observed age of onset distribution was bimodal with a cut‐off of 25 years. Morbid risks for affective disorder were found significantly higher (P = 0.01) in relatives of probands with an early onset than in probands with late onset of disease. The segregation analysis showed that the disease is transmitted differently in early‐ and late‐onset groups. In the early‐onset group, a non‐Mendelian major gene with a polygenic component was favored while the data in the late‐onset group were compatible with a multifactorial model. This result may have important implications for future molecular studies aiming at the identification of disease‐associated genes. © 2001 Wiley‐Liss, Inc.     

Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2.

PURPOSE: To determine whether altering the dietary content of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E(2) (PGE(2)) levels. EXPERIMENTAL DESIGN: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection. RESULTS: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase-mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE(2) levels, and decreased vascular endothelial growth factor expression. CONCLUSION: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE(2) and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.     

Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells.

PURPOSE: HDAC inhibitors (HDACIs) have been shown to inhibit cancer cell proliferation, stimulate apoptosis, and induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of the HDACIs [suberoyl anilide bishydroxamine, valproic acid (VPA), trichostatin A, and sodium butyrate] against six endometrial cancer cell lines. EXPERIMENTAL DESIGN: Endometrial cancer cells were treated with a variety of HDACIs, and the effect on cell growth, cell cycle, and apoptosis was measured. The ability of VPA to inhibit the growth of endometrial tumors growing in immunodeficient mice was also assessed. RESULTS: Clonogenic assays showed that all cancer cell lines were sensitive to the growth inhibitory effect of HDACIs. Cell cycle analysis indicated that treatment with HDACIs decreased the proportion of cells in S phase and increased the proportion of cells in the G(0)-G(1) and/or G(2)-M phases of the cell cycle. Terminal deoxynucleotidyl transferase-mediated nick end labeling assays showed that HDACIs induced apoptosis. This was concomitant with altered expression of genes related to malignant phenotype, including an increase in p21(Waf1), p27(Kip7), and E-cadherin and a decrease in Bcl-2 and cyclin-D1 and -D2. Chromatin immunoprecipitation analysis revealed a remarkable increase in levels of acetylated histones associated with the p21 promoter after suberoyl anilide bishydroxamine treatment. In nude mice experiments, VPA inhibited significantly human uterine tumor growth without toxic side effects. CONCLUSIONS: These results suggest that HDACIs are effective in inhibiting growth of endometrial cancer cells in vitro and in nude mice, without toxic side effects. The findings raise the possibility that HDACIs may prove particularly effective in treatment of endometrial cancers.