tbuckley/cabot-search huggingface dataset:
Lymphaticosclerosis: a new way of thinking about lymphatic vessel obstruction
Authors: A. Trujillo, J.W. Breslin
Journal: British Journal of Dermatology (2015)

ORIGINAL ARTICLE, p 1286 Lymphoedema is a progressive condition that often manifests following cancer surgeries that involve removal or irradiation of lymph nodes. The symptoms may range from mild to severe and debilitating, and in the latter case can significantly increase susceptibility to infection and restrict quality of life.1 2 It is clear that removal of lymph nodes or severing of lymphatic vessels can cause an immediate interruption of the normal flow of lymph from the upstream vessel network into the downstream collecting vessels.3 However, the pathological mechanisms that progressively lead to severe secondary (acquired) lymphoedema are unclear, as are the reasons why different individuals receiving the same procedure may exhibit wide‐ranging severities of lymphatic dysfunction. In this issue of the BJD, Ogata et al.4 have investigated the change in phenotype of lymphatic smooth muscle cells during lymphoedema. The authors studied lymphatic vessels from 29 randomly chosen patients who had developed secondary leg lymphoedema after surgical removal of tumours, were refractory to congenital conservative therapy and received a lymphaticovenous anastomosis procedure. Typically, the collecting lymphatics that are responsible for pumping of lymph in the limbs have a thin layer of circular smooth muscle cells, which intrinsically contracts. The phasic contractions of these cells, in concert with intraluminal one‐way valves composed of endothelial cells and connective tissue, allow forward propulsion of lymph through the system.5 Ogata et al.4 observed a striking change in the collecting lymphatic wall in patients with chronic lymphoedema, with a markedly thickened smooth muscle layer, increased collagen deposition and apparent invasion of smooth muscle cells into the intimal layer. In cases of more severe lymphoedema, stenosis or ‘lymphaticosclerosis’ of the lymphatic lumen due to overgrowth of lymphatic smooth muscle cells was apparent. In addition, labelling of the myosin heavy chain isoforms SM1 and SM2 was reduced in lymphatic smooth muscle, and transmission electron microscopy revealed an increase in synthetic organelles, such as sarcoplasmic reticulum and Golgi complex, while contractile myofilaments were reduced.4 Collectively, these findings suggest that the progression of surgery‐induced lymphatic injury into lymphoedema involves re‐entry of lymphatic smooth muscle cells into a proliferative stage to respond to the injury, followed by their failure to mature and remodel appropriately. This change in the phenotype of lymphatic smooth muscle is akin to a common problem with angioplasty: restenosis of the lumen after plaque removal due to the synthetic vascular smooth muscle phenotype.6
Leiomyomas of the lower respiratory tract.
Authors: S H White, N B Ibrahim, C P Forrester-Wood, K Jeyasingham
Journal: Thorax (1985)

Leiomyomas account for about 2% of benign tumours of the lower respiratory tract. From the relatively few cases reported in the literature, it appears that these tumours most commonly occur in the fourth decade, although one third of patients are under the age of 20 years. The distribution of leiomyomas favours the distal part of the tracheobronchial tree and the most common site for tracheal lesions is the membranous portion of the lower third. Over 90% of pulmonary parenchymal leiomyomas, which themselves are more common in women, are incidental findings on chest radiographs whereas bronchial lesions are important causes of irreversible lung damage. Tracheal lesions may present as bronchial asthma. Accurate early diagnosis rests on a high index of clinical suspicion and histological examination of bronchoscopic biopsy specimens or frozen section material obtained at exploratory thoracotomy. Treatment could be conservative surgery, but 65% of reported cases have been managed by lobectomy or pneumonectomy as a result of advanced irreversible lung disease or unawareness of the benign nature of the lesion.
Insulin Restriction and Associated Morbidity and Mortality in Women with Type 1 Diabetes
Authors: Ann E. Goebel-Fabbri, Janna Fikkan, Debra L. Franko, Kimberly Pearson, Barbara J. Anderson, Katie Weinger
Journal: Diabetes Care (2008)

OBJECTIVE—To determine whether insulin restriction increases morbidity and mortality in women with type 1 diabetes. RESEARCH DESIGN AND METHODS—This is an 11-year follow-up study of women with type 1 diabetes. A total of 234 women (60% of the original cohort) participated in the follow-up. Mean age was 45 years and mean diabetes duration was 28 years at follow-up. Mean BMI was 25 kg/m2 and mean A1C was 7.9%. Measures of diabetes self-care behaviors, diabetes-specific distress, fear of hypoglycemia, psychological distress, and eating disorder symptoms were administered at baseline. At follow-up, mortality data were collected through state and national databases. Follow-up data regarding diabetes complications were gathered by self-report. RESULTS—Seventy-one women (30%) reported insulin restriction at baseline. Twenty-six women died during follow-up. Based on multivariate Cox regression analysis, insulin restriction conveyed a threefold increased risk of mortality after controlling for baseline age, BMI, and A1C. Mean age of death was younger for insulin restrictors (45 vs. 58 years, P &amp;lt; 0.01). Insulin restrictors reported higher rates of nephropathy and foot problems at follow-up. Deceased women had reported more frequent insulin restriction (P &amp;lt; 0.05) and reported more eating disorder symptoms (P &amp;lt; 0.05) at baseline than their living counterparts. CONCLUSIONS—Our data demonstrate that insulin restriction is associated with increased rates of diabetes complications and increased mortality risk. Mortality associated with insulin restriction appeared to occur in the context of eating disorder symptoms, rather than other psychological distress. We propose a screening question appropriate for routine diabetes care to improve detection of this problem.
Long-Term Outcomes Among Localized Prostate Cancer Survivors: Health-Related Quality-of-Life Changes After Radical Prostatectomy, External Radiation, and Brachytherapy
Authors: David C. Miller, Martin G. Sanda, Rodney L. Dunn, James E. Montie, Hector Pimentel, Howard M. Sandler, William P. McLaughlin, John T. Wei
Journal: Journal of Clinical Oncology (2005)

Purpose We sought to elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a well-characterized cohort of prostate cancer (PC) survivors 4 to 8 years after primary treatment. Patients and Methods Patients who had been evaluated previously at a median of 2.6 years after radical prostatectomy (RP), external radiation (three-dimensional conformal radiation therapy [3-D CRT]), or brachytherapy (BT) were recontacted at a median of 6.2 years after treatment. The clinical relevance of long-term HRQOL impairment among survivors was established by comparison with controls of similar age. Factors associated with HRQOL changes during this interval were evaluated. Results Of the 964 eligible men, 709 (73.5%) completed measurable questionnaires. In four domains (urinary irritative-obstructive, urinary incontinence, bowel, and sexual), significant HRQOL differences were detected for at least one of the therapy groups, compared with controls (all P &lt; .05). During the 4-year interval, significant improvement was observed for the urinary irritative-obstructive (P &lt; .0001) and bowel (P &lt; .0001) domains among BT patients, whereas urinary incontinence HRQOL worsened for both the BT (P = .0017) and 3-D CRT (P = .0008) treatment groups. Overall sexual HRQOL deteriorated for the 3-D CRT cohort (P = .0017), as well as for controls (P = .0136). Among RP patients, significant HRQOL changes were not observed. Conclusion During a 4-year interval from earlier to longer-term phases of PC treatment survivorship, sexual, urinary, and bowel dysfunction remain significant concerns among early-stage PC treatment survivors, compared with control men. Although postprostatectomy HRQOL remains relatively stable during this interval, disease-specific HRQOL continues to evolve among men treated with BT and 3-D CRT.
Thiocyanate as a marker of saliva in gastric juice?
Authors: P B Boulos, P F Whitfield, M Dave, R G Faber, M Hobsley
Journal: Gut (1980)

One source of error in gastric secretion studies is swallowed saliva. The possibility that salivary thiocyanate might be used to measure this contamination has been investigated. Thiocyanate concentration was measured in saliva and gastric juice collected simultaneously in 22 duodenal ulcer patients undergoing routine insulin and histamine secretion studies. On stimulation, despite the increase in the rate of gastric secretion this was not matched by an appropriate fall in the concentration of thiocyanate in gastric juice. Moreover, in one-third of the gastric juice specimens, the thiocyanate concentration was greater than in the simultaneous samples of saliva. Thus, contrary to what has been claimed, thiocyanate is present not only in saliva but also in gastric juice. Therefore it cannot be used as a marker of salivary contamination. An adequate marker of this source of error has not yet been found.
Cryptic Sex in the Smallest Eukaryotic Marine Green Alga
Authors: N. Grimsley, B. Pequin, C. Bachy, H. Moreau, G. Piganeau
Journal: Molecular Biology and Evolution (2009)

Ostreococcus spp. are common worldwide oceanic picoeukaryotic pelagic algae. The complete genomes of three strains from different ecological niches revealed them to represent biologically distinct species despite their identical cellular morphologies (cryptic species). Their tiny genomes (13 Mb), with approximately 20 chromosomes, are colinear and densely packed with coding sequences, but no sexual life cycle has been described. Seventeen new strains of one of these species, Ostreococcus tauri, were isolated from 98 seawater samplings from the NW Mediterranean by filtering, culturing, cloning, and plating for single colonies and identification by sequencing their ribosomal 18S gene. In order to find the genetic markers for detection of polymorphisms and sexual recombination, we used an in silico approach to screen available genomic data. Intergenic regions of DNA likely to evolve neutrally were analyzed following polymerase chain reaction amplification of sequences using flanking primers from adjacent conserved coding sequences that were present as syntenic pairs in two different species of Ostreococcus. Analyses of such DNA regions from eight marker loci on two chromosomes from each strain revealed that the isolated O. tauri clones were haploid and that the overall level of polymorphism was approximately 0.01. Four different genetic tests for recombination showed that sexual exchanges must be inferred to account for the between-locus and between-chromosome marker combinations observed. However, our data suggest that sexual encounters are infrequent because we estimate the frequency of meioses/mitoses among the sampled strains to be 10(-6). Ostreococcus tauri and related species encode and express core genes for mitosis and meiosis, but their mechanisms of cell division and recombination, nevertheless, remain enigmatic because a classical eukaryotic spindle with 40 canonical microtubules would be much too large for the available approximately 0.9-microm(3) cellular volume.
Phase I Study of Topotecan, Ifosfamide, and Etoposide (TIME) with Autologous Stem Cell Transplant in Refractory Cancer: Pharmacokinetic and Pharmacodynamic Correlates
Authors: Janelle B. Perkins, Steven C. Goldstein, Jana L. Dawson, Jongphil Kim, Teresa L. Field, James S. Partyka, Karen K. Fields, Beth L. Maddox, Christine E. Simonelli, Anthony M. Neuger, Richard M. Lush, Daniel M. Sullivan
Journal: Clinical Cancer Research (2011)

To determine the maximum tolerated dose (MTD) of topotecan in combination with ifosfamide, mesna, and etoposide (TIME), followed by autologous hematopoietic cell transplant (HCT), in patients with chemotherapy-refractory malignancies.Patients were treated with (in mg/m(2)/d) ifosfamide 3,333, mesna 3,333, and topotecan 3.3 to 28.3 during days -8 through -6 and etoposide 500 (days -5 through -3) followed by HCT on day 0. Once MTD was defined, we expanded this dosing cohort to include patients with high-risk lymphoma due to activity seen during dose escalation. Topotecan pharmacokinetic analyses were carried out, and topoisomerase I levels and activity were measured.The topotecan MTD in this regimen was 64 mg/m(2) (21.3 mg/m(2)/d). Mucositis was dose limiting and correlated with topotecan dose level and area under the curve (AUC). Dose level was also correlated with length of hospitalization, number of days of parenteral nutrition, and neutrophil and platelet engraftment. Topotecan AUC was significantly correlated with time to platelet recovery. The baseline peripheral blood mononuclear cell topoisomerase I level was found to be a significant positive predictor for overall and progression-free survival. Topotecan AUC was positively correlated with dose level, with a trend toward decreasing clearance with increasing dose.Topotecan can be a useful drug in the high-dose setting given its activity in some malignancies when given in standard dose. Pharmacokinetic monitoring may be a valuable tool for optimizing the use of topotecan and to avoid toxicity seen with high-systemic exposures. Baseline topoisomerase I levels may have an important role in predicting topotecan efficacy.
Efficacy of high loading doses of liposomal amphotericin B in the treatment of experimental invasive pulmonary aspergillosis
Authors: J. Gavaldá, T. Martín, P. López, X. Gomis, J.L. Ramírez, D. Rodríguez, Ó. Len, Y. Puigfel, I. Ruiz, A. Pahissa
Journal: Clinical Microbiology and Infection (2005)
A Pleiotrophin C-terminus peptide induces anti-cancer effects through RPTPβ/ζ
Authors: Zoi Diamantopoulou, Oya Bermek, Apostolos Polykratis, Yamina Hamma-Kourbali, Jean Delbé, José Courty, Panagiotis Katsoris
Journal: Molecular Cancer (2010)

Abstract Background Pleiotrophin, also known as HARP (Heparin Affin Regulatory Peptide) is a growth factor expressed in various tissues and cell lines. Pleiotrophin participates in multiple biological actions including the induction of cellular proliferation, migration and angiogenesis, and is involved in carcinogenesis. Recently, we identified and characterized several pleiotrophin proteolytic fragments with biological activities similar or opposite to that of pleiotrophin. Here, we investigated the biological actions of P(122-131), a synthetic peptide corresponding to the carboxy terminal region of this growth factor. Results Our results show that P(122-131) inhibits in vitro adhesion, anchorage-independent proliferation, and migration of DU145 and LNCaP cells, which express pleiotrophin and its receptor RPTPβ/ζ. In addition, P(122-131) inhibits angiogenesis in vivo , as determined by the chicken embryo CAM assay. Investigation of the transduction mechanisms revealed that P(122-131) reduces the phosphorylation levels of Src, Pten, Fak, and Erk 1 / 2 . Finally, P(122-131) not only interacts with RPTPβ/ζ, but also interferes with other pleiotrophin receptors, as demonstrated by selective knockdown of pleiotrophin or RPTPβ/ζ expression with the RNAi technology. Conclusions In conclusion, our results demonstrate that P(122-131) inhibits biological activities that are related to the induction of a transformed phenotype in PCa cells, by interacing with RPTPβ/ζ and interfering with other pleiotrophin receptors. Cumulatively, these results indicate that P(122-131) may be a potential anticancer agent, and they warrant further study of this peptide.
Protection of Normal Proliferating Cells Against Chemotherapy by Staurosporine-Mediated, Selective, and Reversible G1 Arrest
Authors: Xiaomei Chen, Michael Lowe, Thaddeus Herliczek, Michael J. Hall, Christopher Danes, David A. Lawrence, Khandan Keyomarsi
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: A major limiting factor in human cancer chemotherapy is toxicity in normal tissues. Our goal was to determine whether normal proliferating cells could be protected from chemotherapeutic agents by taking advantage of the differential drug sensitivity of cell cycle G1 checkpoint in normal and cancer cells. Methods: Normal mammary epithelial cells and mammary cancer cells were initially treated with staurosporine at a cytostatic (i.e., nonlethal) concentration, which preferentially arrests normal cells in the G0/G1 phase of the cell cycle without affecting the proliferation of tumor cells. After the selective arrest of normal cells in G0/G1, both normal and tumor cells were treated with doxorubicin or camptothecin, two cytotoxic (i.e., lethal) chemotherapeutic agents. Cells were then allowed to recover in drug-free medium for 12 days. Results: After pretreatment of both normal and tumor cells with staurosporine followed by treatment with doxorubicin or camptothecin, tumor cells were selectively killed by chemotherapeutic agents, whereas normal cells resumed proliferation after the drugs were removed. Pretreatment with staurosporine also protected normal circulating lymphocytes that had been induced to proliferate in vitro with phytohemagglutinin from chemotherapeutic agents. Staurosporine-induced arrest of normal cells in G0/G1 phase was reversible, and arrested cells tolerated doses of camptothecin that were more than 100-fold higher than necessary to eradicate all tumor cells in culture. Staurosporine-mediated G0/G1 arrest targets the retinoblastoma protein (pRb) pathway and was accompanied by a rapid decrease in cyclin-dependent kinase (CDK) 4 protein levels, increased binding of CDK inhibitors p21 and p27 to CDK2, and inhibition of CDK2 activity in normal cells. Conclusions: Breast cancer cells with defective checkpoints regulated by the pRb pathway can be targeted specifically with chemotherapeutic agents, following staurosporine-mediated, selective and reversible G0/G1 arrest in normal cells.
Nω-Nitro-L-arginine Administration Corrects Peripheral Vasodilation and Systemic Capillary Hypotension and Ameliorates Plasma Volume Expansion and Sodium Retention in Portal Hypertensive Rats
Authors: Fa-Yauh Lee, Luis A. Colombato, Agustin Albillos, Roberto J. Groszmann
Journal: Hepatology (1993)

In portal hypertensive states, peripheral vasodilation leads to sodium retention and plasma volume expansion. N omega-nitro-L-arginine, a specific biosynthesis inhibitor of the vasodilator nitric oxide, has been shown to acutely reverse peripheral vasodilation and the vascular hyporesponsiveness to endogenous and exogenous vasoconstrictors observed in portal hypertensive rats. This study investigated whether N omega-nitro-L-arginine treatment in portal hypertensive rats prevents peripheral vasodilation and therefore ameliorates plasma volume expansion and sodium retention. For 2 days before partial portal vein ligation or sham operation and then continuously for 4 days after the operation, animals received either placebo (0.9% saline) or N omega-nitro-L-arginine (approximately 2 micrograms/kg/min) intravenously through a subcutaneously implanted Alzet osmotic pump (model 2ML1; Alza, Palo Alto, CA). In portal hypertensive rats, N omega-nitro-L-arginine treatment significantly increased mean arterial pressure (placebo vs. N omega-nitro-L-arginine, 123 +/- 4 vs. 150 +/- 2 mm Hg, respectively; p < 0.001) and systemic vascular resistance (3.8 +/- 0.2 vs. 5.6 +/- 0.3 mm Hg/ml/min/100 gm body weight; p < 0.001), associated with a decrease in the cardiac index (33.5 +/- 1.0 vs. 27.0 +/- 1.1 ml/min/100 gm body weight; p < 0.001). N omega-nitro-L-arginine treatment also induced a decrease in plasma volume (4.6 +/- 0.1 vs. 4.1 +/- 0.1 ml/100 gm body weight; p < 0.001) and extracellular sodium space (39.4 +/- 0.7 vs. 37.4 +/- 0.4 ml/100 gm body weight; p < 0.05) without changes in serum sodium.(ABSTRACT TRUNCATED AT 250 WORDS)
Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry
Authors: D Farge
Journal: Annals of the Rheumatic Diseases (2004)

To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases.Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier).Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75).This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.
Survival and function of mouse embryonic stem cell-derived cardiomyocytes in ectopic transplants
Authors: K Johkura
Journal: Cardiovascular Research (2003)

Objective: Embryonic stem cell-derived cardiomyocytes are a useful source for cell transplantation into the heart, as well as for tissue engineering of the extracardiac vascular system. The present study was designed to investigate the survival and contractile function of embryonic stem cell-derived cardiomyocytes around large blood vessels to assess the feasibility of their ectopic use for future engineering of cardiovascular tissues. Methods: The mouse embryonic stem cell-derived cardiomyocytes were transplanted into the retroperitoneum of the adult nude mice, and the myocardial tissues that developed were characterized by electrophysiological and histological techniques. Results: Macroscopic and electrophysiological analyses showed spontaneously contracting transplants in the host retroperitoneum 7 and 30 days after transplantation. Immunohistochemistry detected developing cardiomyocytes in the transplants on Day 7, which formed the myocardial tissues. They were positive for cardiac troponin I, cadherin, connexin 43, and proliferating cell nuclear antigen, but negative for α-smooth muscle actin. Vascular formation was discernible in the transplant tissues. By Day 30, more mature myocardial tissues had been established in the transplants. Electron microscopic study emphasized that the transplant tissues comprised cardiomyocytes, in which myofibrils with organized sarcomeres were observed. Desmosomes, fasciae adherens and gap junctions were evident in the cellular junctions. Conclusions: The cardiomyocytes derived from the mouse ES cells were demonstrated to be viable and function in the ectopic site of the host retroperitoneum up to Day 30, following a process of proliferation and differentiation. Vascularization and host perfusion beneficial for the survival of the cardiomyocytes occurred in the transplants.
Treatment and outcome of Wilms' tumour patients: an analysis of all cases registered in the UKW3 trial
Authors: K. Pritchard-Jones, V. Moroz, G. Vujanić, M. Powis, J. Walker, B. Messahel, R. Hobson, G. Levitt, A. Kelsey, C. Mitchell
Journal: Annals of Oncology (2012)