tbuckley/cabot-search huggingface dataset:
Stiff-Man Syndrome in Childhood
Authors: V Markandeyulu, T P Joseph, Thilak Solomon, Joe Jacob, Sudhir Kumar, C Gnanamuthu
Journal: Journal of the Royal Society of Medicine (2001)

Stiff-man syndrome is a disease of sporadic occurrence. An autoimmune pathogenesis is thought to involve the spinal interneuronal circuits, resulting in isolation of the motor neurons from their inhibitory influence1. Most of the reported cases have been in adults.
PMO-086 How useful is feeding jejunostomy in upper gastro intestinal cancer surgery—a retrospective review
Authors: V Daya Shetty
Journal: Gut (2012)

<h3>Introduction</h3> A retrospective review of outcome of 100 consectutive open feeding jejunostomies performed as part upper GI cancer surgery in our Centre in the last 3 years. <h3>Methods</h3> 100 consecutive patients undergoing open insertion of Freka feeding jejunostomy as a part of Upper GI cancer surgery in the last 3 years are included. All feeding tubes were inserted approximately 30cms distal to the duodenojejunal flexure. The average procedure time for jejunostomy placement was 20 min. The feeding jejunostomy was flushed with water on the night of surgery and a standardised feeding regime initiated used from fthe first postoperative day. The standard regime was water at 20 mls/h on day 1 followed by feed (Jevity/Osmolyte) at 30 mls/h on day 2. The rate of feed was increased on daily increment of 10 mls/h/day to achieve target rate based on patient9s nutritional requirements. All patients were discharged with feeding jejunostomy in situ. It was removed at first follow-up clinic appointment 2 weeks after discharge if patient was nutritionally stable. <h3>Results</h3> A total of 100 patients (male: female=66:34) who had feeding jejunostomy tubes inserted are included. The indications were cardio-oesophagectomy (77%); total gastrectomy (19%); inoperable tumour at laparotomy (3%) and in one patient prior to neoadjuvant chemotherapy. There were no intra operative procedure related complications. The median duration the feeding jejunostomy was in situ was 28 days (range 3–238 days). Postoperative feeding tube related complications were seen in 14% (n=14). These include tube fallout (n=5); minimal leak (n=2) and skin puncture site cellulitis (n=7). Enteral feed related complications were seen in 15% (n=15). These complications were minor and they included diarrhoea (n=9), abdominal cramps and bloating (n=4). Major complication was seen in only 6.8% (n=2) both due to feed (Jevity) forming a solid bezoar which caused small bowel obstruction. Laparotomy was necessary in one patient, with full recovery. The other the patient died following small bowel infarction. The availability of enteral route was particularly beneficial in 30 of our patients, to provide additional nutritional support for longer than anticipated, due to post operative difficulties including poor oral intake, anastamotic leak, and respiratory complications. In our series in only 5% (n=5) additional parenteral nutrition was necessary. This includes chyle leak—(n=3) and dislodged feeding tube (n=2). <h3>Conclusion</h3> Feeding jejunostomy aids early establishment of enteral nutrition in patients undergoing upper GI cancer surgery. It is useful in providing continued nutritional support in patients who develop perioperative complications where oral route for nutrition is otherwise unavailable or inadequate, although jejunostomy tube placement and usage can also be a source of morbidity. <h3>Competing interests</h3> None declared.
The Role of the Calcium-Sensing Receptor in the Development and Progression of Cancer
Authors: Zuzana Saidak, Romuald Mentaverri, Edward M. Brown
Journal: Endocrine Reviews (2009)

The calcium-sensing receptor (CaR) is responsive to changes in the extracellular Ca2+ (Ca2+o) concentration. It is a member of the largest family of cell surface receptors, the G protein-coupled receptors, and it has been shown to be involved in Ca2+o homeostasis. Apart from its primary role in Ca2+o homeostasis, the CaR may be involved in phenomena that allow for the development of many types of benign or malignant tumors, from parathyroid adenomas to breast, prostate, and colon cancers. For example, whereas the CaR is expressed in both normal and malignant breast tissue, increased CaR levels have been reported in highly metastatic primary breast cancer cells and breast cancer cell lines, possibly contributing to their malignancy and associated alterations in their biological properties. In these settings the CaR exhibits oncogenic properties. Enhanced CaR expression and altered proliferation of prostate cancer cells in response to increased Ca2+o have also been described. In contrast, colon and parathyroid cancers often present with reduced or absent CaR expression, and activation of this receptor decreases cell proliferation, suggesting a role for the CaR as a tumor suppressor gene. Thus, the CaR may play an important role in the development of many types of neoplasia. Herein, we review the role of the CaR in various benign and malignant tumors in further detail, describing its contribution to parathyroid tumors, breast, prostate, and colon cancers, and we evaluate how pharmacological manipulations of this receptor may be of interest for the treatment of certain cancers in the future.
Inducible nitric oxide synthase in T cells regulates T cell death and immune memory
Authors: Monika Vig, Smita Srivastava, Usha Kandpal, Hadassah Sade, Virginia Lewis, Apurva Sarin, Anna George, Vineeta Bal, Jeannine M. Durdik, Satyajit Rath
Journal: Journal of Clinical Investigation (2004)

The progeny of T lymphocytes responding to immunization mostly die rapidly, leaving a few long-lived survivors functioning as immune memory. Thus, control of this choice of death versus survival is critical for immune memory. There are indications that reactive radicals may be involved in this death pathway. We now show that, in mice lacking inducible nitric oxide synthase (iNOS), higher frequencies of both CD4 and CD8 memory T cells persist in response to immunization, even when iNOS+/+ APCs are used for immunization. Postactivation T cell death by neglect is reduced in iNOS–/– T cells, and levels of the antiapoptotic proteins Bcl-2 and Bcl-xL are increased. Inhibitors of the iNOS-peroxynitrite pathway also enhance memory responses and block postactivation death by neglect in both mouse and human T cells. However, early primary immune responses are not enhanced, which suggests that altered survival, rather than enhanced activation, is responsible for the persistent immunity observed. Thus, in primary immune responses, iNOS in activated T cells autocrinely controls their susceptibility to death by neglect to determine the level of persisting CD4 and CD8 T cell memory, and modulation of this pathway can enhance the persistence of immune memory in response to vaccination.
MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment
Authors: Monica Spinola, Felicia S. Falvella, Francesca Colombo, James P. Sullivan, David S. Shames, Luc Girard, Paola Spessotto, John D. Minna, Tommaso A. Dragani
Journal: Molecular Cancer (2010)

Abstract Background MFSD2A (major facilitator superfamily domain containing 2) gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer. Results Here we show that MFSD2A expression is strongly downregulated in non-small cell lung cancer cell lines of different histotypes and in primary lung adenocarcinomas. Experimental modulation of MFSD2A in lung cancer cells is associated with alteration of mRNA levels of genes involved in cell cycle control and interaction with the extracellular matrix. Exogenous expression of MFSD2A in lung cancer cells induced a G1 block, impaired adhesion and migration in vitro , and significantly reduced tumor colony number in vitro (4- to 27-fold, P &lt; 0.0001) and tumor volume in vivo (~3-fold, P &lt; 0.0001). siRNA knockdown studies in normal human bronchial epithelial cells confirmed the role of MFSD2A in G1 regulation. Conclusion Together these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.
Focal and Segmental Glomerulosclerosis in Mice with Podocyte-Specific Expression of Mutant α-Actinin-4
Authors: Jean-Louis Michaud, Lyne I. Lemieux, Manon Dubé, Barbara C. Vanderhyden, Susan J. Robertson, Chris R.J. Kennedy
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Mutations in the gene encoding α-actinin-4 (ACTN4), an actin crosslinking protein, are associated with a form of autosomal dominant focal segmental glomerulosclerosis (FSGS). To better study its progression, a transgenic mouse model was developed by expressing murine α-actinin-4 containing a mutation analogous to that affecting a human FSGS family in a podocyte-specific manner using the murine nephrin promoter. Consistent with human ACTN4-associated FSGS, which shows incomplete penetrance, a proportion of the transgenic mice exhibited significant albuminuria (8 of 18), while the overall average systolic BP was elevated in both proteinuric and non-proteinuric ACTN4-mutant mice. Immunofluorescence confirmed podocyte-specific expression of mutant α-actinin-4, and real-time RT-PCR revealed that HA-ACTN4 mRNA levels were higher in proteinuric versus non-proteinuric ACTN4-mutant mice. Only proteinuric mice exhibited histologic features consistent with human ACTN4-associated FSGS, including segmental sclerosis and tuft adhesion of some glomeruli, tubular dilatation, mesangial matrix expansion, as well as regions of podocyte vacuolization and foot process fusion. Consistent with such podocyte damage, proteinuric ACTN4-mutant kidneys exhibited significantly reduced mRNA and protein levels of the slit diaphragm component, nephrin. This newly developed mouse model of human ACTN4-associated FSGS suggests a cause-and-effect relationship between actin cytoskeleton dysregulation by mutant α-actinin-4 and the deterioration of the nephrin-supported slit diaphragm complex. E-mail: [email protected]
Criteria to indicate testosterone administration.
Authors: A T Kicman, R V Brooks, S C Collyer, D A Cowan, M N Nanjee, G J Southan, M J Wheeler
Journal: British Journal of Sports Medicine (1990)

A detection method for testosterone administration was developed using radioimmunoassay to measure the urinary ratios of testosterone (T) to epitestosterone (E) and to luteinizing hormone (LH). A comparative study of the effect on these ratios of a single intramuscular injection of testosterone heptanoate followed by stimulation with human chorionic gonadotrophin (HCG) in three normal men was undertaken. To allow immediate investigation, a commercially supplied epitestosterone antiserum was used. This study showed that both T/E and T/LH ratios could be used to detect testosterone administration, the latter also being an indicator of HCG use due to cross-reactivity with the LH antiserum. Subsequently, an epitestosterone antiserum of superior specificity was raised and used in a study to demonstrate the insignificant effect of exercise on these ratios. Finally, an intramuscular injection of a combined preparation of testosterone/epitestosterone heptanoates resulted in raised ratios of T/LH but not of T/E. This demonstrated the importance of the T/LH ratio in circumstances where the T/E ratio can be easily circumvented.
Microglia Induce Motor Neuron Death via the Classical NF-κB Pathway in Amyotrophic Lateral Sclerosis
Authors: Ashley E. Frakes, Laura Ferraiuolo, Amanda M. Haidet-Phillips, Leah Schmelzer, Lyndsey Braun, Carlos J. Miranda, Katherine J. Ladner, Adam K. Bevan, Kevin D. Foust, Jonathan P. Godbout, Phillip G. Popovich, Denis C. Guttridge, Brian K. Kaspar
Journal: Neuron (2014)
GENETIC REGULATION OF GLUTAMATE RECEPTOR ION CHANNELS
Authors: Scott J. Myers, Raymond Dingledine, Karin Borges
Journal: The Annual Review of Pharmacology and Toxicology (1999)

Transcriptional and translational regulation of glutamate receptor expression determines one of the key phenotypic features of neurons in the brain--the properties of their excitatory synaptic receptors. Up- and down-regulation of various glutamate receptor subunits occur throughout development, following ischemia, seizures, repetitive activation of afferents, or chronic administration of a variety of drugs. The promoters of the genes that encode the NR1, NR2B, NR2C, GluR1, GluR2, and KA2 subunits share several characteristics that include multiple transcriptional start sites within a CpG island, lack of TATA and CAAT boxes, and neuronal-selective expression. In most cases, the promoter regions include overlapping Sp1 and GSG motifs near the major initiation sites, and a silencer element, to guide expression in neurons. Manipulating the levels of glutamate receptors in vivo by generating transgenic and knockout mice has enhanced understanding of the role of specific glutamate receptor subunits in long-term potentiation and depression, learning, seizures, neural pattern formation, and survival. Neuron-specific glutamate receptor promoter fragments may be employed in the design of novel gene-targeting constructs to deliver future experimental transgene and therapeutic agents to selected neurons in the brain.
A phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor support in patients with solid tumours
Authors: P.L.R. Mitchell, R. Basser, M. Chipman, A. Grigg, J. Cebon, I.D. Davis, J. Zalcberg, S. Ng, F. Appia, M. Green
Journal: Annals of Oncology (2003)
Treatment of the elderly colorectal cancer patient: SIOG expert recommendations
Authors: D. Papamichael, R. Audisio, J.-C. Horiot, B. Glimelius, J. Sastre, E. Mitry, E. Van Cutsem, M. Gosney, C.-H. Köhne, M. Aapro
Journal: Annals of Oncology (2008)
Inhibition of Tumor Growth and Elimination of Multiple Metastases in Human Prostate and Breast Xenografts by Systemic Inoculation of a Host Defense–Like Lytic Peptide
Authors: Niv Papo, Dalia Seger, Arik Makovitzki, Vyacheslav Kalchenko, Zelig Eshhar, Hadassa Degani, Yechiel Shai
Journal: Cancer Research (2006)

Abstract We report on a short host defense–like peptide that targets and arrests the growth of aggressive and hormone-resistant primary human prostate and breast tumors and prevents their experimental and spontaneous metastases, respectively, when systemically inoculated to immuodeficient mice. These effects are correlated with increased necrosis of the tumor cells and a significant decrease in the overall tumor microvessel density, as well as newly formed capillary tubes and prostate-specific antigen secretion (in prostate tumors). Growth inhibition of orthotopic tumors derived from stably transfected highly fluorescent human breast cancer cells and prevention of their naturally occurring metastases were visualized in real time by using noninvasive whole-body optical imaging. The exclusive selectivity of the peptide towards cancer derives from its specific binding to surface phosphatidylserine and the killing of the cancer cells via cytoplasmic membrane depolarization. These data indicate that membrane disruption can provide a therapeutic means of inhibiting tumor growth and preventing metastases of various cancers. (Cancer Res 2006; 66(10): 5371-8)
Successful treatment of combined proliferative and membranous lupus nephritis using a full corticosteroid-free regimen
Authors: Bruno Tedeschi, Laurent Arnaud, Miguel Hie, Alexis Mathian, Zahir Amoura
Journal: Annals of the Rheumatic Diseases (2013)

Dear Sir,

Thirty to seventy per cent of patients with systemic lupus erythematosus (SLE) eventually develop lupus nephritis (LN), with increased risk for renal failure and cardiovascular events, conferring reduced survival. Current recommendations for first-line treatment of proliferative LN involve an induction therapy using a combination of high-dose intravenous steroids followed by oral steroids and either cyclophosphamide (CYC) or mycophenolate mofetil (MMF), then a maintenance phase with oral corticosteroids and either MMF or azathioprine.1 LN mandates long-term treatment and therefore exposes patients to corticosteroids adverse events. Recently, an observational study using no oral steroids has shown promising preliminary results.2 Therefore, the use of an alternative full steroid-free treatment regimen would be a major advance in LN.

In 2001, a 37-year-old man was diagnosed with SLE based on the presence of arthritis, leucopenia, antinuclear antibodies (1:320) with positive search for anti-dsDNA and anti-Sm antibodies. He had a past medical history of gout and was treated with allopurinol. In 2003, treatment with hydroxychloroquine and intermittent oral prednisone (no more than 10 mg/day) was started for polyarthritis. In 2008, without any sign of active lupus, he …
IMMUNODEVIATION BY PASSIVE ANTIBODY, AN EXPRESSION OF SELECTIVE IMMUNODEPRESSION
Authors: Philippe Vuagnat, Thérèse Neveu, Guy André Voisin
Journal: The Journal of Experimental Medicine (1973)

The effect of passively administered IgG1 and IgG2 anticarrier antibodies on the IgG1 and IgG2 antihapten response has been studied. Guinea pigs were immunized with dinitrophenylated bovine gamma globulin mixed with purified IgG1 or IgG2 antihuman gamma globulin antibodies, i.e., antibodies directed against a limited range of the carrier determinants. Humoral IgG1 and IgG2 anti-DNP antibody contents were assayed at weekly intervals and 4 to 10 days after a booster injection of antigen in saline given on the 12th wk. The main finding was the sustained suppressive effect of passive IgG1 anti-carrier antibodies on the active IgG1 antihapten response. This result is compared with the enhancing effect of passive IgG1 antihapten antibodies and is discussed in the light of T cell-B cell and hapten-carrier relationships, leading to the proposal of a regulatory function of the Fc portion of the IgG1 anticarrier antibody, combined with the antigen, on the T cell.
Genomic transcriptional response to loss of chromosomal supercoiling in Escherichia coli
Authors: Brian J Peter, Javier Arsuaga, Adam M Breier, Arkady B Khodursky, Patrick O Brown, Nicholas R Cozzarelli
Journal: Genome biology (2004)

Abstract Background The chromosome of Escherichia coli is maintained in a negatively supercoiled state, and supercoiling levels are affected by growth phase and a variety of environmental stimuli. In turn, supercoiling influences local DNA structure and can affect gene expression. We used microarrays representing nearly the entire genome of Escherichia coli MG1655 to examine the dynamics of chromosome structure. Results We measured the transcriptional response to a loss of supercoiling caused either by genetic impairment of a topoisomerase or addition of specific topoisomerase inhibitors during log-phase growth and identified genes whose changes are statistically significant. Transcription of 7% of the genome (306 genes) was rapidly and reproducibly affected by changes in the level of supercoiling; the expression of 106 genes increased upon chromosome relaxation and the expression of 200 decreased. These changes are most likely to be direct effects, as the kinetics of their induction or repression closely follow the kinetics of DNA relaxation in the cells. Unexpectedly, the genes induced by relaxation have a significantly enriched AT content in both upstream and coding regions. Conclusions The 306 supercoiling-sensitive genes are functionally diverse and widely dispersed throughout the chromosome. We propose that supercoiling acts as a second messenger that transmits information about the environment to many regulatory networks in the cell.
Renal Vasodilatory Action of Dopamine in Patients With Heart Failure
Authors: Uri Elkayam, Tien M.H. Ng, Parta Hatamizadeh, Munir Janmohamed, Anilkumar Mehra
Journal: Circulation (2008)

BACKGROUND: A "renal dose" of dopamine is often used to increase renal blood flow; however, data on the magnitude of effect and site of action in patients with heart failure are scarce. METHODS AND RESULTS: Renal effects of intravenous dopamine (1, 2, 3, 5, and 10 mug . kg(-1) . min(-1)) were evaluated in 13 patients with chronic heart failure. Renal blood flow was calculated from renal artery cross-sectional area measured with intravascular ultrasound and renal blood flow velocity-time integral measured by the intravascular Doppler technique. Cross-sectional area increased and was significantly higher than baseline (0.30+/-0.04 cm(2)) at 5 mug . kg(-1) . min(-1) (0.36+/-0.05 cm(2)) and 10 mug . kg(-1) . min(-1) (0.38+/-0.06 cm(2)). The velocity-time integral was significantly higher than baseline (22+/-3 cm) at doses of 3 and 5 mug . kg(-1) . min(-1) (both 31+/-4 cm). Renal blood flow increased, whereas renal vascular resistance decreased, reaching statistical significance at 2 mug . kg(-1) . min(-1) through 10 mug . kg(-1) . min(-1). Cardiac output gradually increased, reaching statistical significance at doses of 5 and 10 mug . kg(-1) . min(-1) (5.5+/-0.5 and 6.1+/-0.7 versus 4.5+/-5.2 L/min at baseline), but the increase in renal blood flow appeared proportionately larger than corresponding increases in cardiac output. CONCLUSIONS: Dopamine is associated with an increase in renal blood flow in patients with heart failure. This effect is due to dilation of both the large conductance and small resistance renal blood vessels. Further evaluation of the efficacy and safety of dopamine for improvement of renal function in hospitalized patients with heart failure is warranted.
MECHANISM OF GRAFT-<i>VERSUS</i>-HOST-INDUCED LYMPHADENOPATHY IN MICE
Authors: Eugene E. Emeson, Donald R. Thursh
Journal: The Journal of Experimental Medicine (1973)

Graft-vs.-host (GVH)-induced lymphadenopathy of the popliteal lymph node has been produced in C57BL/6 x A/J F1 (BAF1) mice by injecting A/J spleen cells into the rear footpads. By giving 51Cr-labeled BAF1 lymphoid cells intravenously to the hosts, 24 h before sacrifice, we have demonstrated that a large portion of the GVH-induced lymphadenopathy is due to the trapping of circuating lymphocytes in the challenged lymph nodes. Most of the remaining enlargement can be attributed to proliferation of host cells within the reacting lymph nodes. Conditions have been defined under which the weights and [14C]thymidine incorporation of the popliteal nodes can be plotted against the dose of injected A/J spleen cells on a double-log scale to give a linear dose-response. The popliteal lymph node GVH assay is a simple and effective means of quantitating immune reactivity to histocompatibility antigens in mice.