tbuckley/cabot-search huggingface dataset:
Phase I Study of (6R)-5, 10-Dideazatetrahydrofolate: a Folate Antimetabolite Inhibitory to De Novo Purine Synthesis
Authors: M. S. Ray, F. M. Muggia, C. G. Leichman, S. M. Grunberg, R. L. Nelson, R. W. Dyke, R. G. Moran
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : Cancer chemotherapy with folate antimetabolites has been traditionally targeted at the enzyme dihydrofolate reductase and is based on the requirement of dividing tumor cells for a supply of thymidylate and purines. However, a new compound, 5, 10-dideazatetrahydrofolate (DDATHF, whose 6 R diastereomer is also known as Lometrexol), has become available that prevents tumor cell growth by inhibiting the first of the folatedependent enzymes involved in de novo purine synthesis, glycinamide ribonucleotide formyltransferase. Purpose : We investigated the toxicity and therapeutic activity of DDATHF in a phase I clinical trial. Methods : DDATHF was given at one of the following dose levels to 33 patients (16 females and 17 males) with malignant solid tumors: 3.0 mg/m per week (level A) to 10 patients, 4.5 mg/m per week (level B) to 13 patients, or 6.0 mg/m per week (level C) to 10 patients. Each drug cycle consisted of three weekly injections of DDATHF followed by a 2-week rest prior to redosing in the next cycle. Results : Of 33 patients, 27 received at least one full cycle of DDATHF. Thrombocytopenia was the major doselimiting toxicity, and it was severe in one of 10 patients during the first cycle and in two of four patients during the second cycle. Because of cumulative toxicity at 6.0 mg/m, second or later cycles were abbreviated to two weekly doses. Stomatitis was generally mild, but it was doselimiting in one patient. Neutropenia was infrequent and mild, and normocytic anemia requiring blood transfusion was common with repeat dosing. Leucovorin was given for grade 2 or greater thrombocytopenia and resulted in hematologic recovery within 1 week in all eight patients so treated. Without leucovorin, the thrombocytopenia lasted from 7 to 49 days in three patients. A partial response was noted in one patient with non-small-cell lung cancer and a minor response in one patient with breast cancer. Three patients with colorectal cancer achieved stable disease for greater than 3 months with improvement in carcinoembryonic antigen levels in one patient. Conclusions : DDATHF has an unusual pattern of toxicity with repetitive dosing, and humans with advanced cancer are considerably more sensitive than would be predicted from previous animal studies. Although doses of 6.0 mg/m per week on our schedule have been determined to be safe, repeated cycles require careful monitoring because of cumulative toxic effects. Implications : Additional phase I studies of DDATHF that relate toxicity to folate intake and tissue folate pools appear warranted. [J Natl Cancer Inst 85:1154–1159, 1993]
Novel Neurotrophic Factors, Receptors, and Oncogenes
Authors: P A Walicke
Journal: Annual Review of Neuroscience (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Tisbury Union Infirmary
Authors: J. L. Green
Journal: BMJ (1859)

LJAN. 1, 185g. in the groin.In the kidney, uriniferous tubules with dege.nerated epithelium were easily traced out.REIMARKS.There are a few points in this case worthy of a remark.Few cases are on record of such a disease attacking a child so young.The tumour seems to have been excited first of all by a blow, and to have slowly increased ; but without pain or inconveni6nce to the child until, four months
Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance: Implications for type 2 diabetes
Authors: Yumie Takeshita, Toshinari Takamura, Yuki Kita, Hitoshi Ando, Teruyuki Ueda, Kenichiro Kato, Hirofumi Misu, Hajime Sunagozaka, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
Journal: Metabolism (2012)
Overexpression of Vascular Endothelial Growth Factor in the Germinal Matrix Induces Neurovascular Proteases and Intraventricular Hemorrhage
Authors: Dianer Yang, Jessica M. Baumann, Yu-Yo Sun, Mianzhi Tang, Richard Scott Dunn, Ann L. Akeson, Steven G. Kernie, Suhas Kallapur, Diana M. Lindquist, Eric J. Huang, Stanley Steven Potter, Hung-Chi Liang, Chia-Yi Kuan
Journal: Science Translational Medicine (2013)

A transgenic mouse model implicates specific neurovascular proteases in the pathogenesis of intracranial hemorrhage in preterm infants.
HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses
Authors: Cristina Scielzo, Paolo Ghia, Antonio Conti, Angela Bachi, Giuseppe Guida, Massimo Geuna, Massimo Alessio, Federico Caligaris-Cappio
Journal: Journal of Clinical Investigation (2005)

We used a proteomic approach for identifying molecules involved in the pathogenesis of chronic lymphocytic leukemia (CLL). We investigated 14 patients who were completely concordant for IgV(H) mutational status (unmutated vs. mutated), CD38 expression (positive vs. negative), and clinical behavior (progressive vs. stable); these patients were characterized as having either poor or good prognoses. The 2 patient subsets differed in the expression of hematopoietic lineage cell-specific protein 1 (HS1). In patients with poor prognoses, most HS1 protein was constitutively phosphorylated, whereas only a fraction was phosphorylated in patients with good prognoses. This difference was investigated in a larger cohort of 26 unselected patients. The survival curve of all 40 patients analyzed revealed that patients with predominately phosphorylated HS1 experience a significantly shorter median survival time. As HS1 is a protein pivotal in the signal cascade triggered by B cell receptor (BCR) stimulation, we studied its pattern of expression following BCR engagement. Normal mature B cells stimulated by anti-IgM shifted the non- or less-phosphorylated form of HS1 toward the more phosphorylated form. Naive B cells showed both HS1 forms while memory B cells expressed mainly the phosphorylated fraction. These data indicate a central role for antigen stimulation in CLL and suggest a new therapeutic target for patients with aggressive disease.
Dynamic soft tissue mobilisation increases hamstring flexibility in healthy male subjects
Authors: D Hopper, S Deacon, S Das, A Jain, D Riddell, T Hall, K Briffa
Journal: British Journal of Sports Medicine (2005)

Objectives: The purpose of this study was to investigate the effect of dynamic soft tissue mobilisation (STM) on hamstring flexibility in healthy male subjects. Methods: Forty five males volunteered to participate in a randomised, controlled single blind design study. Volunteers were randomised to either control, classic STM, or dynamic STM intervention. The control group was positioned prone for 5 min. The classic STM group received standard STM techniques performed in a neutral prone position for 5 min. The dynamic STM group received all elements of classic STM followed by distal to proximal longitudinal strokes performed during passive, active, and eccentric loading of the hamstring. Only specific areas of tissue tightness were treated during the dynamic phase. Hamstring flexibility was quantified as hip flexion angle (HFA) which was the difference between the total range of straight leg raise and the range of pelvic rotation. Pre- and post-testing was conducted for the subjects in each group. A one-way ANCOVA followed by pairwise post-hoc comparisons was used to determine whether change in HFA differed between groups. The α level was set at 0.05. Results: Increase in hamstring flexibility was significantly greater in the dynamic STM group than either the control or classic STM groups with mean (standard deviation) increase in degrees in the HFA measures of 4.7 (4.8), −0.04 (4.8), and 1.3 (3.8), respectively. Conclusions: Dynamic soft tissue mobilisation (STM) significantly increased hamstring flexibility in healthy male subjects.
Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer
Authors: Charles L. Vogel, Melody A. Cobleigh, Debu Tripathy, John C. Gutheil, Lyndsay N. Harris, Louis Fehrenbacher, Dennis J. Slamon, Maureen Murphy, William F. Novotny, Michael Burchmore, Steven Shak, Stanford J. Stewart, Michael Press
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. RESULTS: The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. CONCLUSION: Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.
Deficits in Physical Function Among Young Childhood Cancer Survivors
Authors: Megan C. Hoffman, Daniel A. Mulrooney, Julia Steinberger, Jill Lee, K. Scott Baker, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2013)

Childhood cancer survivors (CCSs) are at risk for physical disability. The aim of this investigation was to characterize and compare physical performance among CCSs and a group of siblings age < 18 years and determine if diagnosis, treatment, and physical activity levels were associated with lower performance scores.CCSs ≥ 5 years from diagnosis and a sibling comparison group were recruited and evaluated for strength, mobility, and fitness. Physical performance measures were compared in regression models between survivors and siblings by diagnosis and among survivors by treatment exposures and physical activity levels.CCSs (n = 183; mean age ± standard deviation [SD], 13.5 ± 2.5 years; 53% male) scored lower than siblings (n = 147; mean age ± SD, 13.4 ± 2.4 years; 50% male) on lower-extremity strength testing, the timed up-and-go (TUG) test, and the 6-minute walk (6MW) test, despite reporting similar levels and types of habitual physical activity. The lowest scores were prevalent among survivors of CNS tumors and bone and soft tissue sarcomas on strength testing (score ± SD: CNS tumors, 76.5 ± 4.7; sarcoma 67.1 ± 7.2 v siblings, 87.3 ± 2.4 Newton-meters quadricep strength at 90° per second; P = .04 and .01, respectively) and among CNS tumor survivors on the TUG (score ± SD: 5.1 ± 0.1 v siblings, 4.4 ± 0.1 seconds; P < .001) and 6MW tests (score ± SD: 533.3 ± 15.6 v siblings, 594.1 ± 8.3 m; P < .001).CCSs may have underlying physiologic deficits that interfere with function that cannot be completely overcome by participation in regular physical activity. These survivors may need referral for specialized exercise interventions in addition to usual counseling to remain physically active.
Racial group, socioeconomic status, and the development of persistent proteinuria in systemic lupus erythematosus
Authors: N D Hopkinson
Journal: Annals of the Rheumatic Diseases (2000)

Systemic lupus erythematosus (SLE) patients of Afro-Caribbean and Asian origin living in the United Kingdom have a more severe spectrum of disease compared with the white population but whether this is attributable to genetic host factors or environmental factors is unclear. This study examines time from first symptom to onset of persistent proteinuria, as a marker of renal disease, to assess which factors are important.The 189 patients studied were ascertained using multiple methods and included 161 white, 22 Afro-Caribbean and six Asian patients. Time of first observation of persistent proteinuria (>/=0.5 g/day) was taken as onset of renal SLE. Initial univariate analysis to determine which factors are associated with onset of renal disease was followed by using a Cox's proportional hazards regression model enabling analysis of several prognostic factors at the same time. Variables included three measures of socioeconomic status, ethnic group and the presence or absence of different autoantibodies.There was no effect from any socioeconomic variable. Using forwards stepwise selection, the following had independent effects (p<0.05) on the development of renal SLE: Afro-Caribbean race (hazard rate ratio 4.4 (1.9-10.2), compared with white population); and the presence of IgG anti-cardiolipin antibodies (hazard rate ratio 2.6 (1.2-5.7)).Differing socioeconomic factors do not explain the increased frequency of lupus nephritis in Afro-Caribbean patients with SLE, but rather there are important genetic or other host differences. The independent effect of IgG anti-cardiolipin antibodies warrants further investigation.
Recent advances in molecular biological techniques and their relevance to pulmonary research
Authors: B W S Robinson
Journal: Thorax (2000)

There have been a number of major advances in molecular biology in the past few years and the aim of this review is to describe some of these advances, focusing on their benefits and limitations when applied to investigating pulmonary disorders.It is written with the practising pulmonary researcher in mind, not as an introduction for the uninitiated.Useful web addresses and a list of references are included to enable interested readers to examine each technique in detail.New technologies either improve existing techniques or develop new approaches to old questions in order to generate information more quickly, easily, accurately or in a more easily repeatable fashion then existing methods. 1 Some of the most powerful new technologies include polymerase chain reaction (PCR) advances, "diVerence analysis" (that is, the discovery of diVerent gene expression patterns between diVerent cells), transgenic/gene knockout technology, and gene delivery to tissues/gene therapy.
Release of Pressor Substances from Renal Grafts Originating from Rats with Renal Hypertension
Authors: TERUO OMAE, GEORGE M. C. MASSON, IRVINE H. PAGE
Journal: Circulation Research (1961)

A method is described for grafting kidneys on bilaterally nephrectomized rats without interrupting renal blood flow. Under these conditions, normal kidneys caused a pressor response characterized by a gradual rise in pressure suggesting a continuous endocrine secretion. Kidneys from rats made hypertensive by unilateral clipping of the renal artery, renal encapsulation, or partial infarction were tested during the acute and chronic stages of the experimental disease. Wrapped and infarcted kidneys, as well as the untouched contralateral organs, released little or no pressor substances. On the other hand, clipped kidneys released normal or slightly greater amounts of pressor substances; the eontralateral untouched kidney did not elicit any pressor effect. Morphological examination showed a relationship between presence of nephroselerotic lesions and absence of, or decrease of, reninlike pressor substance released. Both changes are believed to be due to high renal vascular pressure against which the partly clipped kidney is protected. These observations suggest that, if renin is a primary factor in the pathogenesis of renal hypertension, hypertension due to renal artery constriction has a mechanism different from that caused by renal manipulation or infarction.
International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)
Authors: S Giralt, E A Stadtmauer, J L Harousseau, A Palumbo, W Bensinger, R L Comenzo, S Kumar, N C Munshi, A Dispenzieri, R Kyle, G Merlini, J San Miguel, H Ludwig, R Hajek, S Jagannath, J Blade, S Lonial, M A Dimopoulos, H Einsele, B Barlogie, K C Anderson, M Gertz, M Attal, P Tosi, P Sonneveld, M Boccadoro, G Morgan, O Sezer, M V Mateos, M Cavo, D Joshua, I Turesson, W Chen, K Shimizu, R Powles, P G Richardson, R Niesvizky, S V Rajkumar, B G M Durie
Journal: Leukemia (2009)
Alcoholic liver disease: dose and threshold—new thoughts on an old topic
Authors: C P DAY
Journal: Gut (1997)

<h3>Abstract</h3> <h3>Objective</h3> To show that limiting dual antiplatelet therapy (DAPT) to six months in patients with event-free ST-elevation myocardial infarction (STEMI) results in a non-inferior clinical outcome versus DAPT for 12 months. <h3>Design</h3> Prospective, randomised, multicentre, non-inferiority trial. <h3>Setting</h3> Patients with STEMI treated with primary percutaneous coronary intervention (PCI) and second generation zotarolimus-eluting stent. <h3>Participants</h3> Patients with STEMI aged 18 to 85 that underwent a primary PCI with the implantation of second generation drug-eluting stents were enrolled in the trial. Patients that were event-free at six months after primary PCI were randomised at this time point. <h3>Interventions</h3> Patients that were taking DAPT and were event-free at six months were randomised 1:1 to single antiplatelet therapy (SAPT) (ie, aspirin only) or to DAPT for an additional six months. All patients that were randomised were then followed for another 18 months (ie, 24 months after the primary PCI). <h3>Main outcome measures</h3> The primary endpoint was a composite of all cause mortality, any myocardial infarction, any revascularisation, stroke, and thrombolysis in myocardial infarction major bleeding at 18 months after randomisation. <h3>Results</h3> A total of 1100 patients were enrolled in the trial between 19 December 2011 and 30 June 2015. 870 were randomised: 432 to SAPT versus 438 to DAPT. The primary endpoint occurred in 4.8% of patients receiving SAPT versus 6.6% of patients receiving DAPT (hazard ratio 0.73, 95% confidence interval 0.41 to 1.27, P=0.26). Non-inferiority was met (P=0.004 for non-inferiority), as the upper 95% confidence interval of 1.27 was smaller than the prespecified non-inferiority margin of 1.66. <h3>Conclusions</h3> DAPT to six months was non-inferior to DAPT for 12 months in patients with event-free STEMI at six months after primary PCI with second generation drug-eluting stents. <h3>Trial registration</h3> Clinicaltrials.gov NCT01459627.
A mouse gene on chromosome 5 that restricts infectivity of mink cell focus-forming recombinant murine leukemia viruses.
Authors: J W Hartley, R A Yetter, H C Morse
Journal: The Journal of Experimental Medicine (1983)

DBA/1, DBA/2, CBA/N, and CBA/Ca mice carry a gene which specifically restricts infectivity of mink cell focus-forming (MCF) murine leukemia viruses. The gene, designated Rmcfr, is dominant or semidominant and maps to chromosome 5; it is closely linked to the morphologic marker gene Hm. The Rmcf gene may be of much use as a means of determining the role of MCF viruses in various forms of leukemogenesis.
The Vascular Disrupting Agent, DMXAA, Directly Activates Dendritic Cells through a MyD88-Independent Mechanism and Generates Antitumor Cytotoxic T Lymphocytes
Authors: Africa Wallace, David F. LaRosa, Veena Kapoor, Jing Sun, Guanjun Cheng, Arminder Jassar, Aaron Blouin, Lai-Ming Ching, Steven M. Albelda
Journal: Cancer Research (2007)

Abstract 5,6-Di-methylxanthenone-4-acetic acid (DMXAA) is a small molecule in the flavanoid class that has antitumor activity. Although classified as a “vascular disrupting agent,” we have recently conducted studies showing that DMXAA has remarkable efficacy in a range of tumors, working primarily as an immune modulator that activates tumor-associated macrophages and induces a subsequent CD8+ T-cell–mediated response. To more completely analyze the effect of DMXAA on CD8+ T-cell generation, we treated mice bearing tumors derived from EG7 thymoma cells that express the well-characterized chicken ovalbumin neotumor antigen. Treatment with DMXAA led to cytokine release, tumor cell necrosis, and ultimately reduction in tumor size that was lymphocyte dependent. Within 24 h of administration, we observed dendritic cell activation in tumor-draining lymph nodes (TDLN). This was followed by a rapid and marked increase in the number of tetramer-specific CD8+ T cells in the spleens of treated animals. In contrast, the vascular disrupting agent combretastatin A4-phosphate, which caused a similar amount of immediate tumor necrosis, did not activate dendritic cells, nor induce an effective antitumor response. Using in vitro systems, we made the observation that DMXAA has the ability to directly activate mouse dendritic cells, as measured by increased expression of costimulatory molecules and proinflammatory cytokine release via a pathway that does not require the Toll-like receptor adaptor molecule MyD88. DMXAA thus has the ability to activate tumor-specific CD8+ T cells through multiple pathways that include induction of tumor cell death, release of stimulatory cytokines, and direct activation of dendritic cells. [Cancer Res 2007;67(14):7011–9]
South West of England and Wales Dermatological Society.
Authors: R.P. Warin
Journal: British Journal of Dermatology (1976)

Journal Article South West of England and Wales Dermatological Society: 8 February 1975, Bristol Royal Infirmary Get access R.P. Warin R.P. Warin Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue 2, 1 February 1976, Pages 227–228, https://doi.org/10.1111/j.1365-2133.1976.tb04376.x Published: 01 February 1976
Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study
Authors: Michael D. Radmacher, Guido Marcucci, Amy S. Ruppert, Krzysztof Mrózek, Susan P. Whitman, James W. Vardiman, Peter Paschka, Tamara Vukosavljevic, Claudia D. Baldus, Jonathan E. Kolitz, Michael A. Caligiuri, Richard A. Larson, Clara D. Bloomfield
Journal: Blood (2006)
Distribution of somatostatin-immunoreactive nerve fibres in Peyer's patches.
Authors: E Feher, M Fodor, G Burnstock
Journal: Gut (1992)

The distribution of somatostatin-immunoreactive nerve fibres in Peyer's patches of the cat was demonstrated by immunocytochemical techniques. A large number of immunoreactive nerve fibres was observed in the tela submucosa very close to the Peyer's patches. Some immunoreactive nerve cell bodies were also found in this layer. The immunoreactive nerve terminals ran around the margin of the follicles and only a few nerve fibres were observed in the centre of follicles. Electron-microscopic investigation showed that these immunoreactive nerve terminals were in very close contact with lymphocytes and plasma cells, where no Schwann cell sheath was interposed. The gap between the nerve processes and the lymphocytes and plasma cells was about 20-200 nm, and occasionally less. These results provide morphological evidence consistent with the view that somatostatin has a neuroimmunomodulatory action.