tbuckley/cabot-search huggingface dataset:
Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells
Authors: Fabio Marra, Roberto G. Romanelli, Carlo Giannini, Paola Failli, Sabrina Pastacaldi, Maria Cristina Arrighi, Massimo Pinzani, Giacomo Laffi, Paolo Montalto, Paolo Gentilini
Journal: Hepatology (1999)

Following liver injury, hepatic stellate cells (HSC) undergo proliferation and migrate into damaged areas in response to chemotactic factors. HSC have been shown to regulate leukocyte trafficking by secreting monocyte chemotactic protein–1 (MCP–1), a chemokine that recruits monocytes and lymphocytes. In this study, we explored whether MCP–1 exerts biological actions on HSC. HSC were isolated from normal human livers, cultured on plastic, and studied in their myofibroblast–like phenotype, and three different cells lines were used. Chemotaxis was measured in modified Boyden chambers. Phosphatidylinositol 3–kinase (PI 3–K) was assayed on phosphotyrosine immunoprecipitates. Exposure of HSC to MCP–1 stimulated migration of HSC in a dose–dependent fashion. Maximal stimulation was obtained with 250 ng/mL MCP–1, which resulted in a 3– to 4–fold stimulation of cell migration. Checkerboard analysis showed that the increase in cell migration was almost completely a result of chemotaxis rather than chemokinesis. In contrast, in quiescent HSC, MCP–1 did not exert any effect on cell migration. In leukocytes, MCP–1 activates the pertussis toxin–sensitive CCR2 receptor. However, transcripts for CCR2 could not be shown in HSC, and pertussis toxin only modestly inhibited MCP–1–induced migration. Exposure of HSC to MCP–1 was associated with an increase in cytosolic calcium concentration, PI 3–K activity, protein tyrosine phosphorylation. Blocking calcium influx or pretreatment of HSC with the PI 3–K inhibitor wortmannin markedly reduced cell migration. This study shows, for the first time, a potential direct profibrogenic action of MCP–1 via HSC chemotaxis. MCP–1-dependent signals in these cells are not transduced by CCR2 and may be mediated by alternative chemokine receptors.
Serum inhibitors for human mast cell growth: possible role of retinol
Authors: S. Ishida, T. Kinoshita, N. Sugawara, T. Yamashita, K. Koike
Journal: Allergy (2003)

Background: In vitro culture systems have been used to study the physiological and pathological characteristics of human mast cells. However, there are some differences in proliferation and maturation of mast cells between fetal bovine serum (FBS)‐containing and serum‐deprived cultures. Accordingly, we attempted to identify circulating factor(s) affecting the development of human mast cells. Methods: We measured the serum levels of retinol and several cytokines. To elucidate the antiproliferative effects of the serum, a retinoic acid receptor (RAR α ) antagonist and neutralizing antibodies against cytokines were used. Results: Similar to FBS, human serum dose‐dependently suppressed the growth of tryptase + cells from CD34 + cord blood cells or 20‐week cultured mast cells under stimulation with stem cell factor (SCF). The serum‐mediated inhibition might be based on a decline in proliferation rate. Among inhibitors for mast cell growth, retinol and transforming growth factor (TGF)‐ β 1 were present at high levels in human serum. In contrast with anti‐TGF‐ β 1 antibody, an RAR α antagonist counteracted the serum‐induced suppression of human mast cell proliferation. Conclusions: Our results suggest that retinol and its derivatives act as a circulating regulator for human mast cell growth. The RAR α antagonist may be a useful tool to obtain higher numbers of mast cells in FBS‐containing cultures.
P13.07 * HYPO-FRACTIONATED IMRT FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME
Authors: P. Ciammella, A. Podgornii, M. Galeandro, A. Pisanello, C. Iotti
Journal: Neuro-Oncology (2014)

OBJECTIVES: Glioblastoma (GBM) is the most common malignant primary brain tumour in adults. Surgery and radiotherapy constitute the cornerstones for the therapeutic management of GBM. The standard treatment today is maximal surgical resection followed by concomitant chemo-radiation therapy followed by adjuvant TMZ according to Stupp protocol. Despite the progress in neurosurgery, radiotherapy and oncology, the prognosis still results poor. In order to reduce the long time of standard treatment, maintaining or improving the clinical results, in our institute we have investigated the effects of hypo-fractionated radiation therapy for patients with GBM. PATIENTS AND METHODS: Sixty-seven patients affected by GBM who had previously undergone surgical resection (total, subtotal or biopsy) were enrolled between October 2005 and December 2011 in a single institutional study of hypo-fractionated intensity modulated radiation therapy (IMRT) followed or not by adjuvant chemotherapy with TMZ (6-12 cycles). The most important eligibility criteria were: biopsy-proven GBM, KPS ≥60, age ≥18 years, no previous brain irradiation, informed consensus. Hypo-fractionated IMRT was delivered to a total dose of 25 Gy in 5 fractions prescribed to 70% isodose. Response to treatment, OS, PFS, toxicity and patterns of recurrence were evaluated, and sex, age, type of surgery, Karnofsky performance status, Recursive Partitioning Analysis (RPA) classification, time between surgery and initiation of radiotherapy were evaluated as potential prognostic factors for survival. RESULTS: All patients have completed the treatment protocol. Median age was 64,5 years (range 41-82 yrs) with 31 females (46%) and 36 males (54%). Median KPS at time of treatment was 80. The surgery was gross total in 38 patients and subtotal in 14 patients; 15 patients underwent only biopsy. No grade 3-4 acute or late neurotoxicity was observed. With median follow-up of 14.9 months, the median OS and PFS were 13.4 and 7.9 months, respectively. CONCLUSIONS: The hypo-fractionated radiation therapy can be used for patients with GBM, resulting in favourable overall survival, low rates of toxicity and satisfying QoL. Future investigations are needed to determine the optimal fractionation for GBM.
Testosterone deficiency induces markedly decreased serum triglycerides, increased small dense LDL, and hepatic steatosis mediated by dysregulation of lipid assembly and secretion in mice fed a high-fat diet
Authors: Takafumi Senmaru, Michiaki Fukui, Hiroshi Okada, Yusuke Mineoka, Masahiro Yamazaki, Muneo Tsujikawa, Goji Hasegawa, Jo Kitawaki, Hiroshi Obayashi, Naoto Nakamura
Journal: Metabolism (2013)
Failure to achieve a major cytogenetic response by 12 months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia
Authors: Constantine S. Tam, Hagop Kantarjian, Guillermo Garcia-Manero, Gautam Borthakur, Susan O'Brien, Farhad Ravandi, Jenny Shan, Jorge Cortes
Journal: Blood (2008)
Upregulated synthesis of both apolipoprotei A-I and apolipoprotein B in familial hyperalphalipoproteinemia and hyperbetalipoproteinemia
Authors: Hartmut H.-J. Schmidt, Richard E. Gregg, Uwe J.F. Tietge, Ulrike Beisiegel, Loren A. Zech, H.Bryan Brewer, Michael P. Manns, Dubo Bojanovski
Journal: Metabolism (1998)
Surgeon found liable for injuries because did not inform patient of risks
Authors: C. Dyer
Journal: BMJ (2002)

An English court of appeal has ruled that a neurosurgeon who performed a microdiscectomy without warning the patient of the risks involved, was responsible for the patient's injuries even though the surgery was not negligently performed.

Giving the judgment of the court, Sir Denis Henry said: “The appeal raises important and difficult issues, not so far considered at appellate level in this country, of when a doctor should be held to have caused the injury the risk of which he failed to give proper warning to his patient.”

Sir Denis, Lady Justice Hale, and Sir …
The human superior colliculus: Neither necessary, nor sufficient for consciousness?
Authors: Susanne Watkins, Geraint Rees
Journal: Behavioral and Brain Sciences (2007)

Non-invasive neuroimaging in humans permits direct investigation of the potential role for mesodiencephalic structures in consciousness. Activity in the superior colliculus can be correlated with the contents of consciousness, but it can be also identified for stimuli of which the subject is unaware; and consciousness of some types of visual stimuli may not require the superior colliculus.
A role for advocacy in general medicine
Authors: S M Hopkins
Journal: BMJ (1999)

My 93 year old mother announced her forthcoming death with equanimity and surprising accuracy, as she told a friend, “Don't bother coming next week, dear; I won't be here.”

Two days later she had a severe stroke which robbed her of speech and most movement, but not her intellect. Despite her clearly indicated wish to remain in the rest home and the home's willingness to care for her, the locum insisted that she be admitted to the geriatric ward of the general hospital. For the next two weeks she suffered all that modern medicine could throw at her in the face of a clearly terminal prognosis and her admittedly incoherent protests. It was her worst nightmare come true. When I visited, tears trickled down her cheeks, she grasped my hand with her one good hand, and clearly conveyed her desperate wish for the drips and tablets to stop, and for the daily lifting out of bed to sit slumped in a …
Significance of Myocytes With Positive DNA In Situ Nick End-Labeling (TUNEL) in Hearts With Dilated Cardiomyopathy
Authors: Motoo Kanoh, Genzou Takemura, Jun Misao, Yukihiro Hayakawa, Takuma Aoyama, Kazuhiko Nishigaki, Toshiyuki Noda, Takako Fujiwara, Kazunori Fukuda, Shinya Minatoguchi, Hisayoshi Fujiwara
Journal: Circulation (1999)

Background —The presence of apoptotic myocytes has been reported in human hearts with dilated cardiomyopathy (DCM) on the basis of a positive finding of DNA in situ nick end-labeling (TUNEL). However, ultrastructural evidence of myocyte apoptosis has not been obtained. Methods and Results —A total of 80 endomyocardial biopsies were obtained from right and left ventricles of 20 patients with DCM and 20 normal control subjects. TUNEL-positive myocytes were found by light microscope in 15% of DCM specimens (controls, 0%, P &lt;0.05), and the percentage of TUNEL-positive myocytes per section in DCM was 1.0±2.7% (mean±SD). According to TUNEL at the electron microscopic level (EM-TUNEL), immunogold particles, which label DNA breaks with 3′-OH terminals, were markedly accumulated in the bizarre-shaped nuclei, with widespread clumping of chromatin (so-called “hypertrophied nuclei”) of the myocytes obtained from DCM. Their ultrastructure was neither apoptotic nor necrotic but rather that of living cells. Taq polymerase–based DNA in situ ligation assay, which detects double-stranded DNA fragments more specifically than TUNEL, did not detect a positive reaction in any case. In mirror sections, all of the TUNEL-positive myocytes in DCM simultaneously expressed proliferating cell nuclear antigen, which is required for both DNA replication and repair, but Ki-67, a replication-associated antigen, was completely negative in all cases, which appeared to rule out cell proliferation activity. Conclusions —Most of the TUNEL-positive myocytes in hearts with DCM are not apoptotic but rather living cells with increasing activity of DNA repair.
PENILE CHANCRE WITH RINGWORM: REPORT OF CASE
Authors: F. J. Eichenlaub
Journal: JAMA (1922)

This case seems worthy of record as a warning to those who might make the same error in a similar case. A man, aged 28, married, was referred to me for diagnosis of a penile lesion. Examination revealed an elevated, circular, well indurated, scaly lesion. There was no real ulceration. The patient admitted extramarital exposure, with the use of a condom. The duration of the lesion was two weeks, and there was no palpable inguinal adenopathy and no sign of generalized syphilis. Dark-field examination by Dr. LeComte had been negative. In spite of the location, I made a clinical diagnosis of epidermophytosis. Dr. Hazen saw the patient and diagnosed chancre, clinically. He was convinced of his apparent error when I was able to demonstrate the ringworm fungus to him, and found typical ringworm lesions on the feet. The patient disappeared for two months, during which time the lesion rapidly healed
Doctors and drops.
Authors: G Gallagher, I Mackay
Journal: BMJ (1991)

to a serotoninergic antidepressant such as fluvoxamine than do depressive patients without an underlying compulsive personality.This is important as the personality ofa depressive patient can easily be assessed for orientation with a selective type of compound.In the past many studies have tried to predict treatment response to selective antidepressants by using biological markers such as the concentration of neurotransmitter metabolites in urine or cerebrospinal fluid, with controversial results.)Moreover, these methods entail elaborate techniques for collecting body fluids and for assay.Finally, our finding that depressive patients with a compulsive personality respond better to a sero- toninergic antidepressant suggests some biochemical similarity in central serotonin disturbance between this subtype of depression and obsessive-compulsive disorder.1 Jenike MA.Drug treatment of obsessive-compulsive disorder.
Double blind placebo controlled trial of pulse treatment with methylprednisolone combined with disease modifying drugs in rheumatoid arthritis.
Authors: T M Hansen, P Kryger, H Elling, D Haar, M Kreutzfeldt, M W Ingeman-Nielsen, A T Olsson, C Pedersen, A Rahbek, N Tvede
Journal: BMJ (1990)

To assess whether monthly treatment with intravenous methylprednisolone enhances or accelerates the effect of disease modifying drugs in patients with rheumatoid arthritis.A 12 month double blind, placebo controlled, multicentre trial in which patients with active rheumatoid arthritis were randomly allocated to receive pulses of either methylprednisolone or saline every four weeks for six months. At the start of the pulse treatment all patients were started on penicillamine or azathioprine.Four rheumatology departments in Denmark.97 Patients (71 women, 26 men) aged 23-84 (mean 60) who had active rheumatoid arthritis of at least four weeks' duration despite treatment with non-steroidal anti-inflammatory drugs.Monthly clinical recording of morning stiffness, number of tender and swollen joints, blinded observers' evaluation of therapeutic effect, and patients' self assessed condition. Concomitant laboratory measurements of erythrocyte sedimentation rate and concentrations of C reactive protein and haemoglobin. Radiography to determine the number of erosions at the start of treatment and after 12 months.57 Patients completed the trial, taking the same disease modifying drug throughout. Evaluation four weeks after each pulse treatment and at 12 month follow up showed no significant differences between the methylprednisolone and placebo groups in any of the clinical or laboratory variables. Radiography showed the same degree of progression of erosions in both groups. Evaluation of the total data on 97 patients and on the 57 who completed the trial showed the same lack of significance between the treatment groups.Intravenous pulse treatment with steroids can be recommended only for rapid temporary relief of flares of disease in patients with rheumatoid arthritis. The response is short lived. Repeated pulses of methylprednisolone at four week intervals do not improve the results of treatment with drugs that induce remission such as penicillamine and azathioprine.
Genomic fluidity is a necessary event preceding the acquisition of tumorigenicity during spontaneous neoplastic transformation of WB-F344 rat liver epithelial cells
Authors: Michelle J. Hooth, Jack L. Vincent, William B. Coleman, Sharon C. Presnell, Joe W. Grisham, Gary J. Smith
Journal: Hepatology (1998)

The genomic evolution of a cohort of WB-F344 rat liver epithelial cell lineages undergoing spontaneous neoplastic transformation was followed to define the mechanistic relationship between genomic instability and progression to the neoplastic phenotype. Eighteen independent populations of WB-F344 cells (initiated from a single diploid-founding population) were subjected to 12 cycles of selective growth at confluent cell density, and cellular DNA contents were measured after each selection cycle. Flow cytometry demonstrated significant gains in the amount of G 1 DNA after selection cycles 3, 6, and 7 in 44% (8 of 18), 89% (16 of 18), and 39% (7 of 18) of the cell populations, respectively. All populations subsequently lost DNA and returned to a diploid or pseudo-diploid DNA content within 1 to 2 selection cycles after the appearance of an increased DNA content. Additionally, appearance and subsequent disappearance of aneuploid or tetraploid subpopulations was observed in 11% (2 of 18) and 83% (15 of 18) of the experimental lineages, respectively. Although perturbations of G 1 DNA content were apparent as early as selection cycle 3, at least 8 cycles of selective growth were required for the acquisition of tumorigenicity. While the independent lineages demonstrated significant fluctuations in G 1 DNA content between selection cycles 3 and 8, the majority (11 of 13) of the populations contained a diploid or pseudo-diploid DNA content at the time tumorigenicity was expressed. Genomic instability preceded the acquisition of tumorigenic potential in rat liver epithelial cells subjected to selective growth conditions of maintenance at confluence, and may be required for its expression.
Reducing the risk of nosocomial HIV infection in British health workers working overseas: role of post-exposure prophylaxis
Authors: C. F Gilks, D. Wilkinson
Journal: BMJ (1998)

Nosocomial HIV transmission is a particular worry for many doctors, medical students, and nurses who seek work experience in low income countries. Firstly, the prevalence of HIV infection among the patients they care for in poor countries is high. Secondly, these health workers are often relatively inexperienced—their technical skills may not be well practised and hence they are likely to be exposed to blood and other body fluids. Thirdly, many developing countries with a high prevalence of HIV lack the resources to implement universal precautions adequately. Finally, poor or inadequate equipment and facilities are more often encountered overseas and can increase the risks of exposure. These occupational risks are clearly additional to the risks from unprotected sex, for which separate preventive measures apply.
<i>LRRK2</i>G2019S as a Cause of Parkinson's Disease in Ashkenazi Jews
Authors: Laurie J. Ozelius, Geetha Senthil, Rachel Saunders-Pullman, Erin Ohmann, Amanda Deligtisch, Michele Tagliati, Ann L. Hunt, Christine Klein, Brian Henick, Susan M. Hailpern, Richard B. Lipton, Jeannie Soto-Valencia, Neil Risch, Susan B. Bressman
Journal: New England Journal of Medicine (2006)

To the Editor: Most cases of Parkinson's disease are considered sporadic and idiopathic, although there is evidence of familial aggregation, and several monogenic forms have been identified.1 Recen...
Molecular genetic analysis of Drosophila rDNA arrays
Authors: Scott M. Williams, Leonard G. Robbins
Journal: Trends in Genetics (1992)

Large repeated DNA arrays are a major component of the eukaryotic genome, but we know little about their internal organization. Understanding their architecture, however, is critical for describing genome structure and for inferring the mechanisms that shape it. One repeated family that is yielding a picture of how structure, function and recombination mechanisms come together is the ribosomal DNA (rDNA) of Drosophila melanogaster.
Prevention and violence.
Authors: K Beswick
Journal: BMJ (1979)

a remission of her psychosis, which reappeared when the drug was stopped.From this followed a trial in 13 cases of acute psychoses of varying aetiology, from which he and his team concluded that the symptoms of psychoses are attributable to hyperactivity of the beta- adrenergic system in the brain.There have been attempts at treatment with beta-blockers by other research teams, which have produced spectacular results in some hands2 and dubiety so far as schizophrenic illness is concerned in others.'Here one cannot rule out, in using such high doses, the possibility of a membrane- stabilising effect; but the doses used by Steinhert and Pugh4 were much lower.
Malnutrition-Related Diabetes Mellitus (MRDM), Not Diabetes-Related Malnutrition: A report on genuine MRDM
Authors: Partha Sarathi Chattopadhyay, Sanjib Kumar Gupta, Rita Chattopadhyay, Prabir Kumar Kundu, Rabindranath Chakraborti
Journal: Diabetes Care (1995)
RASSF1A Mediates p21Cip1/Waf1-Dependent Cell Cycle Arrest and Senescence through Modulation of the Raf-MEK-ERK Pathway and Inhibition of Akt
Authors: Sonja Thaler, Patricia S. Hähnel, Arno Schad, Reinhard Dammann, Martin Schuler
Journal: Cancer Research (2009)

Promoter hypermethylation preventing expression of the RAS association domain family 1 isoform A (RASSF1A) gene product is among the most abundant epigenetic deregulations in human cancer. Restoration of RASSF1A inhibits tumor cell growth in vitro and in murine xenograft models. Rassf1a-deficient mice feature increased spontaneous and carcinogen-induced tumor formation. Mechanistically, RASSF1A affects several cellular functions, such as microtubule dynamics, migration, proliferation, and apoptosis; however, its tumor-suppressive mechanism is incompletely understood. To study the functional consequences of RASSF1A expression in human cancer cells, we made use of a doxycycline-inducible expression system and a RASSF1A-deficient lung cancer cell line. We observed that RASSF1A induces cell cycle arrest in G(1) phase and senescence in vitro and in tumors established in immunodeficient mice. RASSF1A-mediated growth inhibition was accompanied by the up-regulation of the cyclin-dependent kinase inhibitor p21(Cip1/Waf1) and proceeded independently of p53, p14(Arf), and p16(Ink4a). Loss of p21(Cip1/Waf1) or coexpression of the human papilloma virus 16 oncoprotein E7 was found to override RASSF1A-induced cell cycle arrest and senescence. Conditional RASSF1A affected mitogen-activated protein kinase and protein kinase B/Akt signaling to up-regulate p21(Cip1/Waf1) and to facilitate its nuclear localization. In summary, RASSF1A can mediate cell cycle arrest and senescence in human cancer cells by p53-independent regulation of p21(Cip1/Waf1).