tbuckley/cabot-search huggingface dataset:
Abstract 1499: MT1-MMP two-step activation in tumorigenesis
Authors: Vladislav Golubkov, Piotr Cieplak, Boris Ratnikov, Alexander Aleshin, Wenhong Zhu, Khatereh Motamedchaboki, Alex Strongin
Journal: Cancer Research (2011)

Abstract Elevated activity of membrane type-1 matrix metalloproteinase (MT1-MMP) promotes cancer cell migration, invasion, and metastasis. MT1-MMP is synthesized as a zymogen, the latency of which is maintained by its prodomain. Excision by furin was considered sufficient for the prodomain release and MT1-MMP activation. We determined, however, that the full-length intact prodomain released by furin alone is a potent autoinhibitor of MT1-MMP. Additional MMP cleavages within the prodomain sequence are required to release the MT1-MMP enzyme activity. Using mutagenesis of the prodomain sequence and mass spectrometry analysis of the prodomain fragments, we demonstrated that the intracellular intradomain cleavage of the PGD-L50 site initiates the MT1-MMP activation (first step), whereas the 108RRKR111-Y112 cleavage by furin completes the removal and the degradation of the autoinhibitory prodomain and the liberation of the functional activity of the emerging enzyme of MT1-MMP (second step). Here we used the prodomain-based fluorescent biosensors to demonstrate that the proteolytic steps in MT1-MMP activation are differentially regulated in cancer cells versus normal cells. We determined that the intracellular cleavage of the PGD-L50 site represents an “on” and “off” mechanism that discriminates cancer cells from normal cells. To evaluate the significance of the PGD-L50 site cleavage in tumorigenic potential of MT1-MMP, the MCF7 cells transfected with the wild type MT1-MMP (MCF7-MT1) and the uncleavable L50D mutant (MCF7-L50D) were inoculated in the breast fat pads of nude mice. In 4 weeks palpable tumors were evident in all of the mice that received MCF7-MT1 and MCF7-L50D cells. The MCF7-L50D cells formed small tumors that reached ∼50 mm3 volume and remained unchanged from week 4 till week 10. On the contrary, the MCF7-MT1 tumors grew rapidly and reached ∼700 mm3 volume in 10 weeks. These data suggest that the intracellular cleavage of PGD-L50 site is critical for MT1-MMP two-step activation and tumorigenic activity. This intracellular cleavage does not occur in normal cells and the enzyme remained inhibited by it's non-covalently associated prodomain. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1499. doi:10.1158/1538-7445.AM2011-1499
Findings That Hospital Factors Are Surrogate for Disparities Are Misleading
Authors: Quyen D. Chu, Jonathan Glass
Journal: Journal of Clinical Oncology (2009)

Disparities in Mortality after Surgery for Breast and Colon Cancer," by Breslin et al 1 with great interest.We would like to first congratulate them for their important contribution in the field of cancer disparities.While these efforts are admirable, we would like to strike a note of caution and provide our own institutional experience.Louisiana State University Health Sciences Center-Shreveport (LSUHSC-S) is one of 10 state-run hospitals that serve as a safety net for more than 700,000 uninsured citizens of Louisiana. 2As a tertiary care entity in this so-called charity system, the Feist-Weiller Cancer Center (FWCC) provides high-quality cancer care to all residents of Louisiana, irrespective of their ability to pay for services.We recently published our institutional experience treating 786 patients with stages 0 to III breast cancer.This cohort represents a largely impoverished population: almost 70% of all patients were classified as having either free care or Medicaid, and the median annual income was lower than $17,000 for both African American and white women.In addition, 60% of patients were African Americans, making it one of the largest studies comparing breast cancer outcomes between African American and white women. 3 Despite such a predominance of African Americans in our study, we did not note any disparities in outcomes.In fact, our breast cancer outcomes rivaled those reported in the literature.The 5-year overall survival (OS) for African American and white patients was 81% and 84%, respectively (P ϭ .23).When comparing our results with the National Cancer Data Base (NCDB), for all stages our outcomes were better.For stage 0, 1, 2, and 3, our 5-year OS were 100%, 94%, 84%, and 62%, respectively, versus 93%, 88%, 80%, and 55%, respectively for NCDB.Obviously, these results stand in stark contrast with those reported by Breslin et al.
Inducible nitric oxide synthase and vascular injury
Authors: M Kibbe
Journal: Cardiovascular Research (1999)

The role nitric oxide (NO) plays in the cardiovascular system is complex and diverse. Even more controversial is the role that the inducible NO synthase enzyme (iNOS) serves in mediating different aspects of cardiovascular pathophysiology. Following arterial injury, NO has been shown to serve many vasoprotective roles, including inhibition of platelet aggregation and adherence to the site of injury, inhibition of leukocyte adherence, inhibition of vascular smooth muscle cell (VSMC) proliferation and migration, and stimulation of endothelial cell (EC) growth. These properties function together to preserve a normal vascular environment following injury. In this review, we discuss what is known about the involvement of iNOS in the vascular injury response. Additionally, we discuss the beneficial role of iNOS gene transfer to the vasculature in preventing the development of neointimal thickening. Lastly, the pathophysiology of transplant vasculopathy is discussed as well as the role of iNOS in this setting.
Remission of Tumor-Stage Mycosis Fungoides Following Intravenously Administered Acyclovir
Authors: Lionel Resnick
Journal: JAMA (1984)

MYCOSIS fungoides is a T-cell lymphoma that begins in the skin, frequently involves internal organs, and is usually fatal. Chronic dermatitis may be the initial manifestation of the disease, with plaques, tumors, and ulcerations developing later. Altered immunity is common in the late stages of the disease, and death is frequently caused by infection. After the formation of cutaneous tumors, the median survival time is less than three years despite various forms of treatment.<sup>1</sup>The cause of mycosis fungoides is not known, but chronic stimulation of the immune system by viral antigens has been postulated to be important in the pathogenesis of lymphomas, including mycosis fungoides.<sup>2</sup> We report a case of complete clearing of extensive ulcerated tumors in a patient with mycosis fungoides following therapy with intravenously (IV) administered acyclovir. <h3>REPORT OF A CASE</h3> A 58-year-old woman with a seven-year history of scaly papules and plaques on the
NICE at 10
Authors: F. Godlee
Journal: BMJ (2009)

NICE (the National Institute for Health and Clinical Excellence) is 10 years old. Controversial from its inception and constantly in the public eye, NICE’s survival alone is surely something to celebrate. A search on bmj.com for the past 10 years finds the institute mentioned in three articles a week on average. Looking back over this coverage, my sense is that the BMJ has shown support for NICE by being a critical friend. This week we continue that tradition with a cluster of articles challenging NICE on several fronts, as well as a podcast interview …
In vivo time-lapse imaging shows diverse niche engagement by quiescent and naturally activated hematopoietic stem cells
Authors: Narges M. Rashidi, Mark K. Scott, Nico Scherf, Axel Krinner, Jens S. Kalchschmidt, Kleoniki Gounaris, Murray E. Selkirk, Ingo Roeder, Cristina Lo Celso
Journal: Blood (2014)
Recipe for Implementation of a Program for Hospitalizing the Mentally Ill
Authors: Victor M. Victoroff
Journal: JAMA (1963)

IN OHIO, the laws which defined commitment procedures affecting the mentally ill were antique and ponderous and reflected long-extinct medical and social doctrine. Pressure and demand for change had been vociferous from psychiatrists, but leadership from them and from physicians generally had been virtually nonexistent. Lay mental health associations, the Probate Judges Association, bar associations, and the State Division of Mental Hygiene, in an insular manner, had perceived iniquity in the laws and in a desultory, uncoordinated manner, often conflicting with each other and with the medical profession, proposed remedies for obvious defects.  In October, 1961, after a year of hard work and serendipity, a new hospitalization law was passed by the legislature of Ohio. This new statute incorporates many enlightened principles filling the requirement for caring for the mentally ill and protecting their civil rights.  Provisions of the Law
BCG and Cancer
Authors: Robert C. Bast, Berton Zbar, Tibor Borsos, Herbert J. Rapp
Journal: New England Journal of Medicine (1974)

Clinical StudiesPrevention of Acute Leukemia by Neonatal Vaccination with BCGReports that BCG inhibits the development of experimental neoplasms, including spontaneous murine leukemia, have prompted several groups to consider the possibility of lowering the incidence of leukemia in a human population by means of BCG vaccination. By comparing records of leukemia deaths with records of children receiving BCG vaccination at less than 15 years of age in the Province of Quebec, Davignon et al.131 132 133 found that death from leukemia was approximately half as common among children who had been vaccinated against BCG as among those who had not. The . . .
ACVBP versus CHOP plus Radiotherapy for Localized Aggressive Lymphoma
Authors: Félix Reyes, Eric Lepage, Gérard Ganem, Thierry J. Molina, Pauline Brice, Bertrand Coiffier, Pierre Morel, Christophe Ferme, Andre Bosly, Pierre Lederlin, Guy Laurent, Hervé Tilly
Journal: New England Journal of Medicine (2005)

Chemoradiotherapy is standard treatment for localized aggressive lymphoma. To determine the optimal therapy for nonelderly persons with low-risk localized lymphoma, we conducted a randomized trial comparing chemoradiotherapy with chemotherapy alone.Previously untreated patients less than 61 years old with localized stage I or II aggressive lymphoma and no adverse prognostic factors according to the International Prognostic Index were randomly assigned to three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus involved-field radiotherapy (329 patients) or chemotherapy alone with dose-intensified doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) plus sequential consolidation (318 patients).With a median follow-up of 7.7 years, event-free and overall survival rates were significantly higher in the group given chemotherapy alone than in the group given CHOP plus radiotherapy (P<0.001 and P=0.001, respectively). The five-year estimates of event-free survival were 82 percent (95 percent confidence interval, 78 to 87 percent) for patients receiving chemotherapy alone and 74 percent (95 percent confidence interval, 69 to 78 percent) for those receiving chemoradiotherapy. The respective five-year estimates of overall survival were 90 percent (95 percent confidence interval, 87 to 93 percent) and 81 percent (95 percent confidence interval, 77 to 86 percent). In a multivariate analysis, event-free and overall survival rates were affected by treatment group, independently of tumor stage and the presence or absence of bulky disease.In patients under 61 years of age, chemotherapy with three cycles of ACVBP followed by sequential consolidation is superior to three cycles of CHOP plus radiotherapy for the treatment of low-risk localized lymphoma.
Lack of control of liver gluconeogenesis in cholestatic rats with reduced portal blood flow
Authors: José Eduardo de Salles Roselino, Orlando de Castro-e-silva, Reginaldo Ceneviva
Journal: Hepatology (1992)

ABSTRACT Previous studies indicated a role for ischemia in the metabolic changes induced by cholestasis. Liver pyruvate kinase is a key enzyme for the concurrent control of glycolysis and gluconeogenesis. In this experiment the control of pyruvate kinase activity was investigated in cholestatic rats. Pyruvate kinase kinetics changed from a sigmoidal type in sham–operated rats to a hyperbolic type in obstructed rats. The change in the enzymatic kinetics paralleled the reduction in the portal blood flow, which reached 50% of the control value 7 days after obstruction. Dibutyryl cyclic AMP (5 μmol/kg body wt) plus theophylline 0.1 mmol/L failed to inactivate the enzyme when injected into the portal veins of rats whose livers were obstructed 7 days before. Both the kinetics changes and the lack of phosphorylation control are compatible with ischemia. (HEPATOLOGY 1992;16:1055-1060.)
Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV+ subjects.
Authors: P De Paoli, S Zanussi, C Simonelli, M T Bortolin, M D'Andrea, C Crepaldi, R Talamini, M Comar, M Giacca, U Tirelli
Journal: Journal of Clinical Investigation (1997)

HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients. 10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated. These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIV+ patients by improving their immune response to microorganisms or vaccines.
Noninvasive Quantification of Myocardial Blood Flow in Humans
Authors: Egbert U. Nitzsche, Yong Choi, Johannes Czernin, Carl K. Hoh, Sung-Cheng Huang, Heinrich R. Schelbert
Journal: Circulation (1996)

Background [ 13 N]Ammonia has been validated in dog studies as a myocardial blood flow tracer. Estimates of myocardial blood flow by [ 13 N]ammonia were highly linearly correlated to those by the microsphere and blood sample techniques. However, estimates of myocardial blood flow with [ 13 N]ammonia in humans have not yet been compared with those by an independent technique. This study therefore tested the hypothesis that the [ 13 N]ammonia positron emission tomographic technique in humans gives estimates of myocardial blood flow comparable to those obtained with the [ 15 O]water technique. Methods and Results A total of 30 pairs of positron emission tomographic flow measurements were performed in 30 healthy volunteers; 15 volunteers were studied at rest and 15 during adenosine-induced hyperemia. Estimates of average and of regional myocardial blood flow by the [ 13 N]ammonia and the [ 15 O]water approaches correlated well ( y =0.02+1.02 x , r =.99, P &lt;.001, SEE=0.023 for average and y =0.06+1.00 x , r =.97, P &lt;.001, SEE=0.025 for regional values) over a flow range of 0.45 to 4.74 mL·min −1 ·g −1 . At rest, mean myocardial blood flow was 0.64±0.09 mL·min −1 ·g −1 for [ 13 N]ammonia and 0.66±0.12 mL·min −1 ·g −1 for [ 15 O]water ( P =NS). For adenosine-induced hyperemia, mean myocardial blood flow was 2.63±0.75 mL·min −1 ·g −1 for [ 13 N]ammonia and 2.73±0.77 mL·min −1 ·g −1 for [ 15 O]water ( P =NS). The coefficient of variation as an index of the observed heterogeneity of myocardial blood flow averaged, for [ 13 N]ammonia, 9±4% at rest and 12±7% during stress and, for [ 15 O]water, 14±11% at rest and 16±9% during stress. The coefficients of variation for [ 15 O]water were significantly higher than those for [ 13 N]ammonia ( P =.004 at rest and P =.03 during stress). Conclusions The two approaches yield comparable estimates of myocardial blood flow in humans, which supports the validity of the [ 13 N]ammonia method in human myocardium previously shown only in animals. However, the [ 15 O]water approach reveals a greater heterogeneity (presumably method-related), which might limit the accuracy of sectorial myocardial blood flow estimates in humans.
Drug Antisubstitution Laws
Authors: E. William Kean
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Russell E. Johnson, Jr.'s letter (221:715, 1972) points out that he and many of his fellow pharmacists are opposed to changing or amending the present antisubstitution laws. This statement may be valid for the pharmacists of Des Moines, Iowa. However, it is not true here in New Jersey, the most densely populated state. A poll recorded in the secretary's minutes of the Sept 23, 1971, general meeting of the Cumberland-Salem Pharmaceutical Association shows that an overwhelming number (two thirds) of the members are in favor of changing the antisubstitution laws. I believe that if the poll were to be taken today, even a greater number of pharmacists would be in favor of the change. Since last September many "me too" products have been marketed—and it appears that many of the "new drugs" that are shipped automatically to many pharmacies are actually "me too's" or duplications. To most
Letter: Trasylol for pancreatitis.
Authors: G L Haberland
Journal: BMJ (1974)

packed with British graduates as ours are with those of the underdeveloped and under- doctored countries?Dr. Baber regrets that Ivan Illich (and I) cannot offer a "practical solution."I would find one highly suspect, ibut of set purpose the piece I wrote began "La condition humane," the title of a 1920s novel by Andre Malraux about Chinese revolutionary activity, a novel that ended on a note of disillusionment.But look, I was trying to imply, at China today: it is the most hopeful country in the world.Dr. Millar asks "CAn Adam now replace the fruit and tiptoe through the unnown grass again with Eve, ignorant even of their nakedness?"Facetious- ness aside, I suspect-and so, I find, do many young people-that something as
GENERAL PUERPERAL SEPTICEMIA TREATED BY INTRA-ABDOMINAL IRRIGATION WITH NORMAL SALINE SOLUTION; RECOVERY.
Authors: JAMES HAWLEY BURTENSHAW
Journal: JAMA (1903)

A number of cases have been reported in which the abdominal cavity has been subjected to irrigation for puerperal sepsis, with indifferent results; but the accompanying report is unique, so far as I am able to determine, on account of the length of time the irrigation was practiced, the effect of the irrigation on the kidneys and peritoneum, and the ultimate recovery of the patient without the ordinary sequels of septic peritonitis. The patient was a French woman, aged 24, unmarried, secretary to a woman of considerable wealth. She became pregnant during the latter part of August, 1902. During October and November she made frequent attempts to produce abortion by means of various drugs, hot-water vaginal douches and the like, but unsuccessfully. Early in December a meddle-some woman friend initiated her into the mysteries of instrumental procedure, and during the evening of December 9 she inserted an ordinary wooden penholder
The Effect of Glucose Variability on the Risk of Microvascular Complications in Type 1 Diabetes
Authors: Eric S. Kilpatrick, Alan S. Rigby, Stephen L. Atkin
Journal: Diabetes Care (2006)

Our analysis (1) of the Diabetes Control and Complications Trial (DCCT) dataset showed no relationship between pre- and postprandial glucose variability (SD) and the risk of microvascular complications. Wilson, on behalf of the Diabetes Research in Children Network (DirecNet) Study Group (2), makes the point that continuous glucose monitoring can detect larger postprandial glucose excursions than the single-point measurements taken in the DCCT. We agree that it would seem appropriate that future studies should employ this technique.

As part of their analysis of glucose measurement in the DCCT, the article by Service and O’Brien (3) did indeed contain an analysis that found glucose variability to have the same lack of influence on retinopathy risk as ourselves, and for that they deserve credit. By specifically investigating the question of glucose variability, our article …
Risks and Benefits of Estrogen Use
Authors: Noel S. Weiss
Journal: New England Journal of Medicine (1975)

Existing data indicate that high levels of endogenous estrogens, in particular estrone, predispose to endometrial cancer. Estrogen preparations came into use in the 1930s, and evidence has been accumulating to incriminate them also in cases of endometrial cancer. A recent rise in the incidence of endometrial cancer has followed wider use of these hormones. The risk among postmenopausal estrogen users has been estimated to be 4-8 times the 1/1000/year of postmenopausal nonusers. If estrogens are prescribed to menopausal and postmenopausal patients, such patients should be monitored for the development of endometrial carcinoma. Whether they should be given estrogens at all is still controversial.
The Cost and Impact of Scaling Up Pre-exposure Prophylaxis for HIV Prevention: A Systematic Review of Cost-Effectiveness Modelling Studies
Authors: Gabriela B. Gomez, Annick Borquez, Kelsey K. Case, Ana Wheelock, Anna Vassall, Catherine Hankins
Journal: PLoS Medicine (2013)

Gabriela Gomez and colleagues systematically review cost-effectiveness modeling studies of pre-exposure prophylaxis (PrEP) for preventing HIV transmission and identify the main considerations to address when considering the introduction of PrEP to HIV prevention programs.
Use of Esophagectomy to Treat Recurrent Hyperplastic Tissue Obstruction Caused by Multiple Metallic Stent Insertion for Corrosive Stricture
Authors: J.-S. Chen, S.-P. Luh, F. Lee, C.-I. Tsai, J.-M. Lee, Y.-C. Lee
Journal: Endoscopy (2000)

We report a case of a 75-year-old woman who received repeated metallic stent insertion for corrosive esophageal injury. She underwent esophagectomy and gastric tube reconstruction about 3 years after injury because both stents were occluded in turn by overgrowth of granulation tissue. The gross and microscopic changes of the esophagus secondary to prolonged stent insertion are described. In the literature, no reports of similar cases have been recorded. Our limited experience revealed that using metallic stents to treat benign esophageal stricture should be handled very cautiously because of the complications which can commonly occur and are difficult to manage. Repeated stent insertion, although effective for temporarily relieving dysphagia, is ineffective in the long run and can create complications. We suggest that the feasibility of esophagectomy should be evaluated after the improvement of the general condition of the patient.