tbuckley/cabot-search huggingface dataset:
The Lysine 831 of Vascular Endothelial Growth Factor Receptor 1 Is a Novel Target of Methylation by SMYD3
Authors: Masaki Kunizaki, Ryuji Hamamoto, Fabio Pittella Silva, Kiyoshi Yamaguchi, Takeshi Nagayasu, Masabumi Shibuya, Yusuke Nakamura, Yoichi Furukawa
Journal: Cancer Research (2007)

Abstract We previously identified SMYD3 as a histone methyltransferase and showed that its expression was elevated in colorectal, hepatocellular, and breast carcinomas. In the investigation of methyltransferase activity of SMYD3, we have found that vascular endothelial growth factor receptor 1 (VEGFR1) was also methylated by SMYD3. We further identified the methylated residue at VEGFR1 lysine 831, which is located in the kinase domain and is conserved among VEGFR1 orthologues. We also found that the lysine is followed by serine, which is conserved among some of the methylation targets of histone methyltransferases. Furthermore, methylation of VEGFR1 enhanced its kinase activity in cells. These data should be helpful for the profound understanding of the biological role of SMYD3 and regulatory mechanisms of VEGFR1. Additionally our finding may facilitate the development of strategies that may inhibit the progression of cancer cells. [Cancer Res 2007;67(22):10759–65]
Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens
Authors: Katherine I. Lin, Constantine S. Tam, Michael J. Keating, William G. Wierda, Susan O'Brien, Susan Lerner, Kevin R. Coombes, Ellen Schlette, Alessandra Ferrajoli, Lynn L. Barron, Thomas J. Kipps, Laura Rassenti, Stefan Faderl, Hagop Kantarjian, Lynne V. Abruzzo
Journal: Blood (2008)

Abstract Although immunoglobulin VH mutation status (IgVH MS) is prognostic in patients with chronic lymphocytic leukemia (CLL) who are treated with alkylating agents or single-agent fludarabine, its significance in the era of chemoimmunotherapy is not known. We determined the IgVH somatic mutation status (MS) in 177 patients enrolled in a phase 2 study of fludarabine, cyclophosphamide, and rituximab (FCR) and in 127 patients treated with subsequent chemoimmunotherapy protocols. IgVH MS did not impact significantly on the complete remission (CR) rate of patients receiving FCR or related regimens. However, CR duration was significantly shorter in patients with CLL that used unmutated IgVH than those whose CLL used mutated IgVH (TTP 47% vs 82% at 6 years, P &lt; .001). In a multivariate model considering all baseline characteristics, IgVH MS emerged as the only determinant of remission duration (hazard ratio 3.8, P &lt; .001). Our results suggest that postremission interventions should be targeted toward patients with unmutated IgVH status.
AKT Activation in Human Glioblastomas Enhances Proliferation via TSC2 and S6 Kinase Signaling
Authors: Markus J. Riemenschneider, Rebecca A. Betensky, Saskia M. Pasedag, David N. Louis
Journal: Cancer Research (2006)

Abstract Aberrant AKT (protein kinase B) signaling is common in many cancers, including glioblastoma. Current models suggest that AKT acts directly, or indirectly via the TSC complex, to activate the mammalian target of rapamycin (mTOR) as the main downstream mediator of AKT signaling. mTOR activation results in subsequent activation of S6K and STAT3, as well as suppression (i.e., phosphorylation) of 4E-BP1, leading to cell cycle progression and inhibition of apoptosis. Most studies of this pathway have used in vitro systems or tumor lysate–based approaches. We aimed to delineate these pathways in a primarily in situ manner using immunohistochemistry in a panel of 29 glioblastomas, emphasizing the histologic distribution of molecular changes. Within individual tumors, increased expression levels of p-TSC2, p-mTOR, p-4E-BP1, p-S6K, p-S6, and p-STAT3 were found in regions defined by elevated AKT activation. However, only TSC2, S6K, and S6 activation levels correlated significantly with AKT activation and clustered together in multidimensional scaling analyses. Ki-67 proliferation indices were significantly elevated in p-AKT-overexpressing regions, whereas expression of the apoptosis marker cleaved caspase 3 was generally low and not significantly different between the regions. These findings provide the first in vivo evidence for a close correlation between AKT and TSC2 phosphorylation levels in glioblastoma. Moreover, they suggest that downstream p-AKT effects are primarily mediated by S6 kinase signaling, thus enhancing proliferation rather than inhibiting apoptosis. (Cancer Res 2006; 66(11): 5618-23)
COMPARATIVE DIABETOGENIC ACTION OF THE HYPOPHYSIS FROM VARIOUS ANIMALS
Authors: B. A. Houssay, F. S. Smyth, V. G. Foglia, A. B. Houssay
Journal: The Journal of Experimental Medicine (1942)

Of all the anterior hypophyses tested, those of the human produced the most marked diabetogenic action in the dog with its pancreatic tissue reduced to 4 gm., and in the hypophysectomized and pancreatectomized toad. The human hypophysis also produced diabetogenic action in the normal dog on daily doses of 1.26 mg. per kilo per day for 2 days. The hypophysectomized dog with its pancreas reduced to 4 gm. is very sensitive to the anterior hypophyseal diabetogenic action and is the best test animal for demonstrating such action in mammals. The anterior hypophysis of man, toad, rat, and chicken produces in such animals a diabetogenic action with doses of from 10 to 15 mg. per kilo per day. The bovine anterior hypophysis has identical action in 20 mg. doses. That of canine origin was much less active in a few though inconclusive experiments. It was impossible to demonstrate a diabetogenic action with either guinea pig hypophysis or with that of fish probably because insufficient doses were injected. The diabetogenic action was not obtained by the injection of other organ extracts of toads, dogs and oxen, of corticosterone (30, 40, and 60 mg. in 4 days) or of desoxycorticosterone (80 mg. and 200 mg. in 4 days). The toad (Bufo arenarum Hensel), deprived of its hypophysis and pancreas is the most sensitive biological reactor for testing the diabetogenic action. In this animal the diabetogenic action of anterior hypophyses from varied sources decreased in the following order: man, dog, toad (Bufo arenarum Hensel), white rat, guinea pig, chicken (whole hypophysis), ox, serpent (Constrictor constrictor (L.)), the fish "corvina" Micropogon opercularis (Quoy and Gaimard, 1824), and "merluza" Merlucius hubbsi (Marini, 1933).
Behavioral consequences of bone marrow transplantation in the treatment of murine mucopolysaccharidosis type VII.
Authors: L Bastedo, M S Sands, D T Lambert, M A Pisa, E Birkenmeier, P L Chang
Journal: Journal of Clinical Investigation (1994)

The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII caused by deficient beta-glucuronidase activity. Bone marrow transplantation has been shown to correct some of their biochemical and pathological abnormalities but its efficacy in correcting their neurological functional deficits is unknown. We transplanted the neonatal gusmps/gusmps mice and their normal controls and evaluated their central nervous system function with two behavioral tests: the grooming test, a developmentally regulated and genetically based activity, and a Morris water maze test which assessed spatial learning abilities. The two transplanted groups groomed less than the normals, were unable to remember the location of an invisible platform from day to day, and were severely impaired at developing strategies to locate the platform in unfamiliar locations. The performance of both normal and mutant transplanted groups was clearly inferior to the untreated normals and, in some instances, close to or worse than the untreated mutants, even though the enzyme abnormalities of the mutants have been partially corrected. Hence, the behavioral deficits in the mutant mice were not restored to normal while similarly treated normal mice showed significant functional deterioration, indicating the detrimental consequence of this therapy in the neonatal period.
Chronic hyperkalemia impairs ammonium transport and accumulation in the inner medulla of the rat.
Authors: T D DuBose, D W Good
Journal: Journal of Clinical Investigation (1992)

Previously we demonstrated in rats that chronic hyperkalemia had no effect on ammonium secretion by the proximal tubule in vivo but that high K+ concentrations inhibited ammonium absorption by the medullary thick ascending limb in vitro. These observations suggested that chronic hyperkalemia may reduce urinary ammonium excretion through effects on medullary transport events. To examine directly the effects of chronic hyperkalemia on medullary ammonium accumulation and collecting duct ammonium secretion, micropuncture experiments were performed in the inner medulla of Munich-Wistar rats pair fed a control or high-K+ diet for 7-13 d. In situ pH and total ammonia concentrations were measured to calculate NH3 concentrations for base and tip collecting duct and vasa recta. Chronic K+ loading was associated with significant systemic metabolic acidosis and a 40% decrease in urinary ammonium excretion. In control rats, 15% of excreted ammonium was secreted between base and tip collecting duct sites. In contrast, no net transport of ammonium was detected along the collecting duct in high-K+ rats. The decrease in collecting duct ammonium secretion in hyperkalemia was associated with a decrease in the NH3 concentration difference between vasa recta and collecting duct. The fall in the NH3 concentration difference across the collecting duct in high-K+ rats was due entirely to a decrease in [NH3] in the medullary interstitial fluid, with no change in [NH3] in the collecting duct. These results indicate that impaired accumulation of ammonium in the medullary interstitium, secondary to inhibition of ammonium absorption in the medullary thick ascending limb, may play an important role in reducing collecting duct ammonium secretion and urinary ammonium excretion during chronic hyperkalemia.
ON A SPECIAL FORM OF DILATATION AND DISPLACEMENT OF THE STOMACH
Authors: T. S. Short
Journal: BMJ (1908)

given, whether by mouth or rectum, were probably produced by the acld, and not by the base of the salt, as no similar aooidents have occurred when'the carbonate has'be'en given, and the symptoms were quite unlike those generally pro- duced by acuse poisoning with heavy metals.The reporters of these cases suggest that some nitrite was formed by intes- tinal fermentation from the subnitrate, as the symptoms (nausea, cyanosis, prostration, full bounding and rapid pulse, fast repDiration) were similar to those of nitrite polsoning.Mr. Finnemore, Pharmacist to Gu)'d Hbspital, has 'kindly Investigated the question for me from the chemical stand- point.He writes: "Two grams of bismuth subnitrate were added to 50 a.om. of 0.25 per cent.HOl (to represent the gastric juice) at a temperature of 380 C. In eight minutes a portion was filtered off, and only a trace of H01 w3s found in the filtrate; in fifteen minute3 no HCI was present.On testing the filtrate, however, it was found that HNO3 was present, and on titration it was proved to be nearly of the same strength as the HCl originally employed.The reaction which occurs is Bi ON03 + HOI = BI 001 + HNO3."If insufficlent HCl is present in the stomach to act on all of the very large doses of bismuth nitrate given, the residue of the salt would be converted by the alkalire juioes in the intes- tines into the oxycarbonate with simultaueous formation of sodium nitrate.The nitric acid would be rapidly absorbed and would circulate as sodium nitrate, and all the sodium nitrate formed in the intestines would a-lso ba absorbed.From four ounces of the subnttrate of bismuthb one ounce of sodium nitrate would be formed.It has been proved that when large doses of nitrates are taken, a small proportion is excreted as nittite.Hence it is quite conceivable that when half an ounce, or an ounee, of sodium nitrate is absorbed into the circulatioD, sufficient nitrite would be formed from it to give rise to serious symptoms of polioning.In vriew of the fact tbat two oundes of bfsmuth carbonate produce no constipation in normal individuals, It beoomes a matter wortby of further investigation how the ten grairs (one ninety-slxth part of the dose !), so often given with apparent success in cases of diarrhoea, can act.
Physician Bias in Cesarean Section-Reply
Authors: Robin N. Phillips
Journal: JAMA (1983)

<h3>In Reply.—</h3> We are pleased to respond to the interesting comments made by Drs Goodlin and Poma. The Table is a short summary of an analysis performed on the same patient populations as described in our original communication. The data represent only preliminary results and will be followed by a more detailed report elsewhere. We analyzed primary cesarean section patterns according to time separately for our ward population, primarily treated by the house staff, and our private patient population, primarily treated by their private individual obstetrician. As may be seen from the Table, only a rather minute difference in cesarean section distribution could be noticed between these two groups. What was noteworthy, however, was the timing of the individual peak incidence. While the cesarean section incidence for ward patients usually peaked in the early afternoon hours, private patients generally peaked in the early morning hours. Even though these peak time
1033-117 Ventilatory response to early phase of exercise: An useful index for comprehensive clinical assessment of patients with heart failure and novel predictor of prognosis
Authors: Tomasz Witkowski, Ewa Jankowska, Robert Zymlinski, Agnieszka Kus-Klinowska, Waldemar Banasiak, Piotr Ponikowski
Journal: Journal of the American College of Cardiology (2004)
The Challenge of the Acquired Immunodeficiency Syndrome
Authors: MARGARET M. HECKLER
Journal: Annals of Internal Medicine (1985)

ExcerptThis is a conference of quantity (more than 2000 scientists and guests from around the world) matched by the quality of its participants. The purpose of the conference is to discuss, probe, and plan a unified attack on a disease that leaves few survivors in its wake. Acquired immunodeficiency syndrome (AIDS) kills. The danger of the syndrome's deadly thrust is compounded because, like the iceberg's mammoth underwater size, the long gestation period of AIDS gives no initial warning of the omnipresent danger. This danger is why, in the first months of my tenure as Secretary of Health and Human Services,...
Diseasing of America: Addiction Treatment Out of Control
Authors: Barbara G. Orrok
Journal: JAMA (1990)

There is no question that "the drug problem" has taken center stage in the American consciousness in recent years. Use of illegal drugs has gone from the questionably halcyon days of counterculture mind expansion to the current situation of mainstream drug use accompanied by the acquired immunodeficiency syndrome, violent crime, and other societal maladies, directly and indirectly touching all Americans. Government policies to combat the manufacture and distribution of drugs are increasingly prominent in domestic and foreign policy, and programs to recognize and treat substance abuse and dependence are being promoted by employers, educators, and even health insurers. Treatment of addiction seems to have become big business. In these times of attempts to cut back health care costs, a treatment modality that is growing is of some interest. Dr Peele opens his provocative book with some incisive observations and questions. He disagrees with the idea that an addiction is a
Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect
Authors: M. B. Bowie, K. D. McKnight, D. G. Kent, L. McCaffrey, P. A. Hoodless, C. J. Eaves
Journal: Journal of Clinical Investigation (2006)

The regulation of HSC proliferation and engraftment of the BM is an important but poorly understood process, particularly during ontogeny. Here we show that in mice, all HSCs are cycling until 3 weeks after birth. Then, within 1 week, most became quiescent. Prior to 4 weeks of age, the proliferating HSCs with long-term multilineage repopulating activity displayed an engraftment defect when transiting S/G2/M. During these cell cycle phases, their expression of CXC chemokine ligand 12 (CXCL12; also referred to as stromal cell–derived factor 1 [SDF-1]) transiently increased. The defective engrafting activity of HSCs in S/G2/M was reversed when cells were allowed to progress into G1 prior to injection or when the hosts (but not the cells) were pretreated with a CXCL12 antagonist. Interestingly, the enhancing effect of CXCL12 antagonist pretreatment was exclusive to transplants of long-term multilineage repopulating HSCs in S/G2/M. These results demonstrate what we believe to be a new HSC regulatory checkpoint during development. They also suggest an ability of HSCs to express CXCL12 in a fashion that changes with cell cycle progression and is associated with a defective engraftment that can be overcome by in vivo administration of a CXCL12 antagonist.
Socioeconomic status and lung function among primary school children in Canada.
Authors: K Demissie, P Ernst, J A Hanley, U Locher, D Menzies, M R Becklake
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We examined the relationship of lung function level to socioeconomic status (SES) using a cross-sectional design among 989 primary school children selected from 18 Montreal schools and studied between April 1990 and November 1992. Information on each child's health, demographics, home exposure to tobacco smoke, pets, and cooking and heating fuel used in the child's home was collected by questionnaire. Spirometry was performed at school. Parental occupation was used to establish SES. After adjusting for personal, familial, and environmental factors, in boys but not in girls, FEV1 and FVC were progressively larger in higher categories of SES (p < 0.001 for linear trend). After taking into account the effect of multiple comparisons and adjusting for personal, familial, and environmental factors, boys from families in the lowest category of SES were found to have an FEV1 lower by 8.2% (95% CI, -13.8 to -2.1) and an FVC lower by 8.1% (95% CI, -13.4 to -2.6) when compared with the most advantaged. These results provide evidence that socioeconomic status, independent of common indoor exposures, is a risk factor for lower FEV1 and FVC among boys.
Gagging public health doctors
Authors: S. Sheard
Journal: BMJ (1994)

On 1 April 1996 the last vestiges of public health advocacy in Britain will be abolished when the eight regional health authorities are replaced by eight analogous NHS Executive regional offices.1 The regional directors of public health and their staff will become civil servants and hence constrained in speaking out on matters of public health. One consequence will be that the directors, the leaders of public health medicine, will not be allowed to become office holders in the Faculty of Public Health Medicine.

From its inception, public health has held a unique place in the British medical establishment. Public health doctors must often speak out against governmental and public opinion in the interest of the public health. As our expectations for quality of life and health care have increased, so has the scope for intervention in all aspects of public and private life. Thus advocacy and the right of free speech have long been intrinsic components of the public health movement, and they have been regularly attacked.

In 1847, after the appointment of William Henry Duncan …
Endothelium and Regulation of Coagulation
Authors: David M Stern, Ciro Esposito, Herwig Gerlach, Marlene Gerlach, Jane Ryan, Dean Handley, Peter Nawroth
Journal: Diabetes Care (1991)

Endothelial cells form the luminal vascular surface and thus have a central role in the regulation of coagulation. One important way in which endothelial cells control the clotting system is by regulating the expression of binding sites for anticoagulant and procoagulant factors on the cell surface. In the quiescent state, endothelial cells maintain blood fluidity by promoting the activity of numerous anticoagulant pathways, including the protein C/protein S pathway. After activation, as can be brought about by cytokines, the balance of endothelial properties can be tipped to favor clot formation through coordinated induction of procoagulant and suppression of anticoagulant mechanisms. Tumor necrosis factor suppresses the endothelial anticoagulant cofactor thrombomodulin and induces expression of the procoagulant cofactor tissue factor. Working in concert, these changes can allow fibrin formation to proceed in an inflamed focus but maintain blood fluidity in the surrounding area of normal vasculature. Recent studies suggest that similar changes in endothelial coagulant properties can be induced by advanced glycosylation end products, proteins modified by glucose that accumulate in the vasculature at a rapid rate in diabetic subjects, indicating the potential relevance of these mechanisms in diabetic vascular disease.
Diagnosis of Ankle Injuries
Authors: Allan W. March
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Edeiken and Cotler (240:1182, 1978) recently emphasized the importance of stress roentgenograms in diagnosing ligamentous tears in moderate to severe softtissue injuries of the ankle. The authors clearly described those types of ankle fractures that are associated with ligamentous tears and that therefore do not require stress roentgenograms. However, nonroentgenographic techniques of defining complete ligamentous tears were not considered. Since severe ligamentous tears can often be defined on the basis of physical examination alone,<sub>1</sub>attention should be given to both physical examination and simple roentgenograms before selecting patients for stress views of the ankle. To define complete tears of the tibiofibular ligament in severe eversion injuries of the ankle, one may examine the anterior surface of the leg between the midportion of the tibia and fibula. Acute swelling and tenderness in this region suggest a complete tear of the tibiofibular ligament. After tearing of the tibiofibular
Variation of intravenous infusion rates.
Authors: B M Wright
Journal: BMJ (1975)

picture.It seems more likely to have been related to a minimal change glomerulonephritis caused by practolol.This has not pre- viously been described.The long-standing vitiligo may have been a predisposing factor.No election microscopic studies were made and the patient was not skin tested or rechallenged with practolol.
Letter: Shake test on amniotic fluid and the respiratory distress syndrome.
Authors: S G Bhagwanani
Journal: BMJ (1973)

reference care of worried and "difficult" patients and the handling of particular problems such as the social and psychological management of terminal cases, we need the services of trained social workers whose jdb is primarily personal contact with the patient.We should value the essential and excellent help that they can give in overall patient care when encouraged in this func- tion by members of the medical profession who do not find their presence threatening.-We are, etc.,
Assessment of v 3 integrin expression after myocardial infarction by positron emission tomography
Authors: T. Higuchi, F. M. Bengel, S. Seidl, P. Watzlowik, H. Kessler, R. Hegenloh, S. Reder, S. G. Nekolla, H. J. Wester, M. Schwaiger
Journal: Cardiovascular Research (2008)

AimsThe purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an 18F-labelled αvβ3 integrin antagonist (18F-Galacto-RGD) to monitor the integrin expression after myocardial infarction.