tbuckley/cabot-search huggingface dataset:
Abstract 513: Breast cancers are notched up with a proton pump at their leading edge.
Authors: Sahithi Pamarthy, Alice Gilman-Sachs, Kenneth Beaman
Journal: Cancer Research (2013)

Abstract The H+ vacuolar ATPase is a multimeric complex, which acidifies intracellular vesicles and extracellular space. Notch signaling is a key signaling pathway regulating cell proliferation and differentiation during development and cancer. The expression of both V-ATPases and Notch signaling is aberrant in most cancers and hence, are potential targets for therapeutics. It is speculated that the vacuolar ATPases regulate Notch signaling directly by endosomal acidification and indirectly by endocytosis. Here, we studied the role of the a2 isoform of vacuolar ATPase (a2V) in regulating Notch Signaling in Breast cancer. Using confocal microscopy, we traced the location of a2V in MCF7, SKBR3 and MDA-MB231 breast cancer cell lines. We found that a2V is present on the plasma membrane and not on the early endosomes. The amount of a2V correlated with the invasiveness of the cancer. Most importantly, the expression of a2V was restricted to one side of the cells marking their leading edge. Also, no a2V expression was found when cells contacted each other on the inside. Next, we evaluated the effect of a2V knockdown in MDA-MB231 cells. Using siRNA, a2V was knocked down. We found that decrease of a2V enhances the expression of Notch2 and Notch 4 significantly (&amp;gt;1.75 fold). Notch ligands (DLL family) and Notch targets also increased, supporting the finding. When we looked at Wnt pathway genes, we found a significant increase in Wnt4 (&amp;gt;2 fold) and c-Myc(∼3 fold) expression although levels of β-catenin were unchanged. Since c-Myc is known to mediate apoptosis, we looked at apoptotic genes Bax and Bcl2 to after siRNA knockdown of a2V. Although Bax increased, there was no significant change in apoptosis, as seen in PI-annexin assay. Taken together, our data suggests that a2V is important for tumor growth and its presence on leading edge marks aggressiveness of tumors. Interestingly, a2V depletion results in the activation of Notch and several proliferative markers in breast cancer. We postulate that this is due to indirect effects of a2V in endocytosis or in regulating pH dependent enzymes responsible for Notch and Wnt signal transduction. Citation Format: Sahithi Pamarthy, Alice Gilman-Sachs, Kenneth Beaman. Breast cancers are notched up with a proton pump at their leading edge. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 513. doi:10.1158/1538-7445.AM2013-513
The Effect of 6-Mercaptopurine on Immune Response in Man
Authors: Robert H. Levin, Maurice Landy, Emil Frei
Journal: New England Journal of Medicine (1964)

The immunosuppressive effects of certain antitumor agents have been known for more than a decade, and much more information has accumulated.2 3 4 5 Among more recent developments have been a number of investigations emphasizing the fact that the degree and nature of immunosuppression can vary greatly, depending on the antitumor agent and the animal species investigated.6 7 8 9 The immunologic effects of these compounds has provided a rationale for their use in the treatment of a variety of diseases assumed to have an immunologic pathogenesis. Encouraging results have been obtained in various autoimmune and collagen diseases.10 11 12 13 14 15 16 In addition, the suppression of kidney and hematopoietic . . .
Raging Hormones: Do They Rule Our Lives?
Authors: Lila A. Wallis
Journal: JAMA (1995)

In<i>Raging Hormones</i>Gail Vines, a science journalist living in Cambridge, England, presents with lively polemical zeal the issue of whether hormones are in charge of our lives. She lashes out at the medical "establishment" for an imputed belief in biological determinism, which she sees as ascribing to sex hormones the major (or the only) role in dictating human behavior. It is always easy to disparage an opponent (in this case, the medical profession/establishment/investigators/ endocrinologists) by attacking the extremist views of one faction. On the question of hormones, however, medicine does not speak with one voice. And biological determinism has not been in fashion in medicine ever since the epidemiologists and other investigators began to consider the multifactoriality of human health, illness, and behavior. With rare exceptions, few physicians believe that estrogens, androgens, and other chemical messengers predetermine our lives. Genetic and prenatal influences, subsequent experiences and the psychosocial environment,
Assay of Plasma Insulin Activity by the Rat-diaphragm Method
Authors: P. J. Randle
Journal: BMJ (1954)

Bornstein (1950) described a method for the assay of insulin in human plasma which was based on the fall of blood sugar of alloxan-diabetic hypophysectomized adrenalectomized rats (A.D.H.A. rats).Subsequently Bornstein and his colleagues determined the insulin content of plasma from various types of diabetic by this method (Bornstein and Trewhella, 1951 ; Bornstein and Lawrence, 1951a, 1951b).The published results of these workers were of such interest as to merit further study.A.D.H.A. rats prepared in this laboratory have proved to be too delicate and to possess too unstable a blood sugar to permit their use for accurate insulin assay.Groen et al. (1952) described a method for the detec- tion and assay of insulin in human plasma which was based on the glucose uptake of the isolated normal rat diaphragm survivirig in vitro; as was first shown by Gemmill (1940), this uptake is raised by the in vitro addition of insulin to the fluid in which the isolated diaphragm is suspended.This method has been criti- cally investigated as a quantitative procedure for the assay of insulin and a modified procedure applied to the determination of the insulin activity of normal huLman plasma. MethodsAnimnals.-Thehemidiaphragms of normal male albino Wistar rats of 100-150 g. were used in these experiments.The animals were starved for 18 to 24 hours before use.For the preparation of alloxan-diabetic hypophysecto- mized rats (A.D.H. rats) male albino Wistar rats of 170-220 g. were used.They were first of all hypophysecto- mized, and then, one week later, made diabetic by the intravenous administration of alloxan.Insulin.-A single sample of crystalline insulin (Boots) of potency 23.2 units per mg.was used as standard in these experiments.Solutions of this were freshly pre- pared for each assay.Human Subjects.-Thedifferent samples of plasma collected from human subjects are designated as ran-
CHANGES IN THE ELECTROCARDIOGRAMS ACCOMPANYING EXPERIMENTAL CHANGES IN RABBITS' HEARTS
Authors: Francis R. Fraser
Journal: The Journal of Experimental Medicine (1915)

1. In rabbits transient and also permanent enlargements of the heart occur as the result of the intravenous injection of adrenalin, spartein and adrenalin, diphtheria toxin, and streptococci. 2. Transient and permanent enlargements of the heart to the left are associated with decrease in the size of the upwardly directed waves of the Q, R, S group in Lead II of the electrocardiograms and increase in the downwardly directed. Transient enlargement to the right is associated with changes in the opposite direction. 3. The stages in the process of enlargement have been observed and are associated with gradual changes in the size of these waves. 4. A diminution in the size of all the waves of the Q, R, S group was observed in degenerative conditions of the heart muscle. 5. Extreme degeneration of the structures of the heart was associated with slowing of the heart's action, lengthening of conduction time (P-Q), and lengthening of the time occupied by the individual waves of the electrocardiogram. 6. Ectopic ventricular contractions were seen in rabbits injected intravenously with suspensions of living streptococci.
Bertram John Bickford Thurstan Brewin Neil Geddes Clarkson Hendry Barclay Renfrew Hillis Margaret Brown Keeble (nee Morton) James Corson Lees Shibtosh Roy Anna Violet Seager (nee Thompson) Kenneth Southgate Derek Wilson
Authors: C. Herbert, G. Rees, A. Adam, J. Bath, M. Keeble, J G Begg, Q. Quamruzzaman, J. Seager, D. Bailey, D. Henderson
Journal: BMJ (2001)
CARRIER FUNCTION IN ANTI-HAPTEN IMMUNE RESPONSES
Authors: David H. Katz, William E. Paul, Edmond A. Goidl, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1970)

Preimmunization of either guinea pigs or rabbits to bovine gamma globulin (BGG) prepares the animals for markedly enhanced antibody responses to 2,4-dinitrophenyl-BGG (DNP-BGG). This phenomenon is observed both in the primary anti-DNP antibody response to DNP-BGG and in the secondary anti-DNP antibody response to DNP-BGG in animals primed with DNP-ovalbumin (DNP-OVA). The BGG preimmunization is most effective if the antigen is administered as a complete Freund's adjuvant emulsion; in rabbits, a dose of 1 µg of BGG is more effective than a dose of 50 µg, whereas the reverse is true in guinea pigs. Transfusion of homologous anti-BGG sera fails to replace active immunization with BGG in the preparation of animals for these enhanced anti-DNP antibody responses. Both the immunoglobulin class and the average association constant for ϵ-DNP-L-lysine of the anti-DNP antibody produced in these enhanced responses is determined by the mode and time of immunization with haptenic conjugates and is not appreciably influenced by the nature of the carrier preimmunization. These studies indicate that the carrier specificity of hapten-specific anamnestic antibody responses is largely due to the interaction of two independent cell associated recognition units, one specialized for carrier and the other specific for haptenic determinants.
Mental health of unemployed men in different parts of England and Wales.
Authors: P R Jackson, P Warr
Journal: BMJ (1987)

In a study of mental health among unemployed men two contrasting hypotheses about the importance of the local unemployment rate were examined--namely, that very high local unemployment might be associated with either impoverishment or resilience of the community, which would affect health in opposite ways. The mental health of 954 unemployed men registered at 41 unemployment benefit offices in England and Wales was assessed by the general health questionnaire, men in areas of particularly high unemployment being compared with men in areas of moderate and relatively low unemployment. Scores for ill health were significantly lower in areas of particularly high unemployment, even when personal factors known to affect mental health during unemployment were controlled for. These results support the hypothesis that communities with high rates of unemployment develop resilience that is beneficial for the mental health of the unemployed.
Influence of an Early-Onset Age of Type 1 Diabetes on Cerebral Structure and Cognitive Function
Authors: Stewart C. Ferguson, Annette Blane, Joanna Wardlaw, Brian M. Frier, Petros Perros, Rory J. McCrimmon, Ian J. Deary
Journal: Diabetes Care (2005)

OBJECTIVE—Children who develop type 1 diabetes before age 7 years (early-onset diabetes; EOD) have comparatively poorer cognitive abilities. Whether this relates to psychosocial consequences of chronic illness or organic factors related to diabetes and its complications remains unresolved. We hypothesized that if differences in neuroradiological structure and cognitive ability coexisted in those who had EOD, then an organic component to their etiology was likely. RESEARCH DESIGN AND METHODS—A cohort of 71 young adults with long-duration type 1 diabetes diagnosed during childhood or adolescence participated in a cross-sectional evaluation of cognitive ability (neuropsychological test battery) and brain structure (magnetic resonance imaging). Diabetes onset age, preceding severe hypoglycemia exposure, retinopathy status, and diabetes duration were examined as potential correlates of cognitive and neuroradiological differences. No participants had previous neuropsychological pathology. RESULTS—In EOD participants (n = 26), current intellectual ability (Wechsler Adult Intelligence Scale−Revised performance IQ; P = 0.03) and information processing ability (Choice Reaction Time; P = 0.006) were comparatively poorer than was observed in those with later- onset diabetes (n = 45). Furthermore, lateral ventricular volumes were 37% greater (P = 0.002) and ventricular atrophy was more prevalent (61 vs. 20%; P = 0.01) in the EOD group than in those who had later-onset type 1 diabetes. CONCLUSIONS—An early childhood onset of type 1 diabetes was associated with mild central brain atrophy and significant differences in intellectual performance in adulthood, implying that neurodevelopment may be adversely affected by EOD. The differences observed in brain structure support an organic contribution to their etiology but do not exclude a coexistent contribution of psychosocial factors.
Predisposing factors for anterior cruciate ligament injury
Authors: Antonis Papoutsidakis
Journal: British Journal of Sports Medicine (2011)

Lecture 5 In sports, especially in football, one of the most common knee injuries is the anterior cruciate ligament (ACL) tear, which usually (70%) occurs through non-contact mechanisms that include; sudden deceleration, landing and pivoting manoeuvres which are repeatedly performed. Studies have shown that the incidence of ACL tear in female athletes is two to eight times higher than in men athletes. The research effort to determine the risk factors for sustaining non-contact ACL injuries is increasing as concerns grow about the larger number of incidents, the greater treatment costs and the serious consequences of those injuries. Mechanically, ACL injury occurs when an excessive tension force is applied on the ACL. A non-contact ACL injury occurs when a person generates great forces or moments at the knee that apply excessive loading on the ACL. There are number of studies that show that the anterior shear force at the proximal end of the tibia is a major contributor to ACL loading, while there are valgus, varus and internal rotation moments at the knee. According to these ACL loading mechanisms, a small knee flexion angle, a strong quadriceps muscle contraction or a great posterior ground reaction force can increase ACL loading. The literature also shows that individuals at high risk have a smaller knee flexion angle during athletic tasks than individuals at low risk. Recent biomechanical studies demonstrated that female recreational athletes exhibited small knee flexion angles in running, jumping and cutting tasks. The results of other studies showed that the peak ACL strain occurred at the impact peak vertical ground reaction force shortly after initial contact between the foot and the ground. The risk factors for non-contact ACL injuries fall into four distinct categories: environmental, anatomic, hormonal and biomechanical. Recently, a high level of friction between shoes and the playing surface has been identified as a major risk factor for a non-contact ACL injury in the sport of the team handball. In football, there are studies that show that more non-contact ACL injuries occur when the surface is dry. Higher levels of friction between the shoe and the surface are generally associated with better performance but a higher injury risk. That's why we see an increase of ACL tears in areas with artificial grass in football grounds. There is a need to continue to define specific, neuromuscular, proprioceptive and motor control factors associated with injury. However, until specific predictive and protective factors are identified, training and prevention programmes should continue to be implemented, assessed and improved. There is a pressing need to improve public and participant awareness of the risk of ACL injury and the possibilities for prevention.
Does Insulin Therapy Promote, Reduce, or Have a Neutral Effect on Cancers?
Authors: Hertzel C. Gerstein
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Indian surgeon challenges banon xenotransplantation
Authors: G. Mudur
Journal: BMJ (1999)

An Indian doctor who was arrested two years ago after transplanting pig organs into a man with end stage heart disease has said that he will continue xenotransplantation trials later this year. Dr Dhani Ram Baruah, a cardiac surgeon from India's northeastern Assam state, has also sought damages from the government for what he …
Keratin variants are overrepresented in primary biliary cirrhosis and associate with disease severity†
Authors: Bihui Zhong, Pavel Strnad, Carlo Selmi, Pietro Invernizzi, Guo‐Zhong Tao, Angela Caleffi, Minhu Chen, Ilaria Bianchi, Mauro Podda, Antonello Pietrangelo, M. Eric Gershwin, M. Bishr Omary
Journal: Hepatology (2009)

Keratins (K) 8 and 18 variants predispose carriers to the development of end-stage liver disease and patients with chronic hepatitis C to disease progression. Hepatocytes express K8/K18, whereas biliary epithelia express K8/K18/K19. K8-null mice, which are predisposed to liver injury, spontaneously develop anti-mitochondrial antibodies (AMA) and have altered hepatocyte mitochondrial size and function. There is no known association of K19 with human disease and no known association of K8/K18/K19 with human autoimmune liver disease. We tested the hypothesis that K8/K18/K19 variants associate with primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterized by the presence of serum AMA. In doing so, we analyzed the entire exonic regions of K8/K18/K19 in 201 Italian patients and 200 control blood bank donors. Five disease-associated keratin heterozygous variants were identified in patients versus controls (K8 G62C/R341H/V380I, K18 R411H, and K19 G17S). Four variants were novel and included K19 G17S/V229M/N184N and K18 R411H. Overall, heterozygous disease-associated keratin variants were found in 17 of 201 (8.5%) PBC patients and 4 of 200 (2%) blood bank donors (P < 0.004, odds ratio = 4.53, 95% confidence interval = 1.5-13.7). Of the K19 variants, K19 G17S was found in three patients but not in controls and all K8 R341H (eight patients and three controls) associated with concurrent presence of the previously described intronic K8 IVS7+10delC deletion. Notably, keratin variants associated with disease severity (12.4% variants in Ludwig stage III/IV versus 4.2% in stages I/II; P < 0.04, odds ratio = 3.25, 95% confidence interval = 1.02-10.40), but not with the presence of AMA.K8/K18/K19 variants are overrepresented in Italian PBC patients and associate with liver disease progression. Therefore, we hypothesize that K8/K18/K19 variants may serve as genetic modifiers in PBC.
Radiographic abnormalities and exposure to asbestos-contaminated vermiculite in the community of Libby, Montana, USA.
Authors: Lucy A Peipins, Michael Lewin, Sharon Campolucci, Jeffrey A Lybarger, Aubrey Miller, Dan Middleton, Christopher Weis, Michael Spence, Brad Black, Vikas Kapil
Journal: Environmental Health Perspectives (2003)

Mining, handling, processing, and personal or commercial use of asbestos-contaminated vermiculite have led to widespread contamination of the Libby, Montana, area. We initiated a medical testing program in response to reports of respiratory illness in the community. The purpose of this analysis was to identify and quantify asbestos-related radiographic abnormalities among persons exposed to vermiculite in Libby and to examine associations between these outcomes and participants' self-reported exposures. A cross-sectional interview and medical testing were conducted in Libby from July through November 2000 and from July through September 2001. A total of 7,307 persons who had lived, worked, or played in Libby for at least 6 months before 31 December 1990 completed the interview. Of those, 6,668 participants > or = 18 years of age received chest radiographs to assess the prevalence of pleural and interstitial abnormalities. We observed pleural abnormalities in 17.8% of participants and interstitial abnormalities in < 1% of participants undergoing chest radiography. We examined 29 occupational, recreational, household, and other exposure pathways in the analysis. The prevalence of pleural abnormalities increased with increasing number of exposure pathways, ranging from 6.7% for those who reported no apparent exposures to 34.6% for those who reported > or = 12 pathways. The factors most strongly associated with pleural abnormalities were being a former W.R. Grace worker, being older, having been a household contact of a W.R. Grace worker, and being a male. In addition to being a former W.R. Grace worker, environmental exposures and other nonoccupational risk factors were also important predictors of asbestos-related radiographic abnormalities.
People with asthma are most at risk of complications from swine flu, study shows
Authors: O. Ellis
Journal: BMJ (2009)

The government has released further information on the underlying conditions that can cause swine flu to become more dangerous, showing that asthma is the most common comorbidity found in those who are admitted to hospital.

The figures come from a study conducted by the Flu Clinical Information Network (FLU-CIN) and funded by the Department of Health, which looked at a sample of 192 patients in England who had been hospitalised with the H1N1 virus. It found that lung disease was the most common underlying condition, with more than 25% of those admitted having …
Nonsurgical Treatment of Gallstones
Authors: Gerald Salen, G.S. Tint
Journal: New England Journal of Medicine (1989)

During the past 18 years, three approaches have been introduced as alternatives to surgical treatment of gallbladder stones,1 2 3 4 a condition known since antiquity. All have as their objective the dissolution of the stones, leaving the gallbladder intact and stone-free. Elimination of the stones should be accompanied by relief of symptoms and should prevent the development of more serious complications — e.g., cholecystitis, pancreatitis, cholangitis, or obstructive jaundice.In contrast to cholecystectomy, for which prior knowledge of the composition of the stones is unnecessary, dissolution therapy is effective only for cholesterol stones. Gallstones composed predominantly of pigment (bilirubin polymers) or calcium . . .