tbuckley/cabot-search huggingface dataset:
<i>N-cadherin</i> Gene Expression in Prostate Carcinoma Is Modulated by Integrin-Dependent Nuclear Translocation of Twist1
Authors: Nelson R. Alexander, Nhan L. Tran, Harish Rekapally, Carol E. Summers, Carlotta Glackin, Ronald L. Heimark
Journal: Cancer Research (2006)

Abstract The gain of N-cadherin expression in carcinomas has been shown to be important in the regulation of cell migration, invasion, and survival. Here, we show that N-cadherin mRNA expression in PC-3 prostate carcinoma cells is dependent on β1 integrin–mediated cell adhesion to fibronectin and the basic helix-loop-helix transcription factor Twist1. Depletion of Twist1 mRNA by small interfering RNA resulted in decreased expression of both Twist1 and N-cadherin and the inhibition of cell migration. Whereas Twist1 gene expression was independent of β1 integrin–mediated adhesion, Twist1 protein failed to accumulate in the nuclei of cells cultured in anchorage-independent conditions. The increased nuclear accumulation of Twist1 following cell attachment was suppressed by treatment with an inhibitor of Rho kinase or a β1 integrin neutralizing antibody. The effect of Twist1 on induction of N-cadherin mRNA required an E-box cis-element located within the first intron (+2,627) of the N-cadherin gene. These data raise the possibility that integrin-mediated adhesion to interstitial matrix proteins during metastasis differentially regulates the nuclear/cytoplasmic translocation and DNA binding of Twist1, activating N-cadherin transcription. (Cancer Res 2006; 66(7): 3365-9)
Cognitive Behavior Approach to Loss of Clinical Effect During Long-Term Antidepressant Treatment: A Pilot Study
Authors: Giovanni A Fava, Chiara Ruini, Chiara Rafanelli, Silvana Grandi
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The aims of this investigation were to explore the feasibility of a cognitive behavior approach to loss of clinical effect during long-term antidepressant therapy and to compare it with dose increase. METHOD: Ten patients with recurrent depression who relapsed while taking antidepressant drugs were randomly assigned to dose increase and clinical management or to cognitive behavior therapy and maintenance of the antidepressant drug at the same dose. RESULTS: Four of five patients responded to a larger dose, but all had relapsed again on that dose by the 1-year follow-up. Four of five patients responded to cognitive behavior therapy, and only one relapsed during follow-up. CONCLUSIONS: The data suggest that application of a cognitive behavior therapy approach is feasible when there is a loss of clinical effects during long-term antidepressant treatment and may carry long-term benefits. The results need to be confirmed with large-scale controlled studies.
Polyps and colorectal cancer in South African Blacks.
Authors: I Segal, S A Cooke, D G Hamilton, L Ou Tim
Journal: Gut (1981)

This study reflects the fact that cancer of the large bowel is uncommon in South African Blacks, and that colorectal polyps do not appear to constitute a precursor to most colorectal cancers. Furthermore, it is shown that dietary factors associated with this cancer in Western populations are not evident in the Black population. In the South African White population, however, the disease behaves in a similar way to that observed in Western countries. Other definitive differences found were the absence of multiple synchronous cancers and diverticular disease in the Blacks with colorectal cancer. It is thus postulated that dietary factors are absent, or have not been present for a sufficient length of time to influence the development of polyps or polyp--cancer sequence in this population. It is also possible that the adenoma--carcinoma progression observed in Western countries may not be relevant to the development of all colorectal carcinomas in communities such as those reported here.
Racial variation in the association between gestational age and perinatal mortality: prospective study
Authors: Imelda Balchin, John C Whittaker, Roshni R Patel, Ronald F Lamont, Philip J Steer
Journal: BMJ (2007)

To determine if the risks of perinatal mortality and antepartum stillbirth associated with post term birth increase earlier during pregnancy in South Asian and black women than in white women, and to investigate differences in the factors associated with antepartum stillbirth between the racial groups.Prospective study using logistic regression analysis.15 maternity units in northwest London from 1988 to 2000.197 061 nulliparous women self reported as white, South Asian, or black, who delivered a single baby weighing at least 500 g at 24-43 completed weeks' gestation.Gestation specific perinatal mortality, antepartum stillbirth rates, and independent factors for antepartum stillbirth by racial groups. Results The crude gestation specific perinatal mortality patterns for the three racial groups differed (P<0.001). The perinatal mortality rate among black women was lower than among white women before 32 weeks but was higher thereafter. Perinatal mortality was highest among South Asian women at all gestational ages and increased the fastest at term. After adjusting for the confounders of antepartum stillbirth (placental abruption, congenital abnormality, low birth weight, birth weight <10th centile, meconium passage, fever, maternal body mass index > or =30, and maternal age > or =30), the excess mortality among black women after 32 weeks was not significant. After adjusting for confounding, South Asian women still had a significantly higher risk of antepartum stillbirth (odds ratio 1.8, 95% confidence interval 1.2 to 2.7). Conclusions The risk of perinatal mortality increased earlier in gestation among South Asian women than among white women. The most important factor associated with antepartum stillbirth among white women was placental abruption, but among South Asian and black women it was birth weight below 2000 g.
E-3810 Is a Potent Dual Inhibitor of VEGFR and FGFR that Exerts Antitumor Activity in Multiple Preclinical Models
Authors: Ezia Bello, Gennaro Colella, Valentina Scarlato, Paolo Oliva, Alexander Berndt, Giovanni Valbusa, Sonia Colombo Serra, Maurizio D'Incalci, Ennio Cavalletti, Raffaella Giavazzi, Giovanna Damia, Gabriella Camboni
Journal: Cancer Research (2011)

Tumor angiogenesis is a degenerate process regulated by a complex network of proangiogenic factors. Existing antiangiogenic drugs used in clinic are characterized by selectivity for specific factors. Antiangiogenic properties might be improved in drugs that target multiple factors and thereby address the inherent mechanistic degeneracy in angiogenesis. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family members and their cognate receptors are key players in promoting tumor angiogenesis. Here we report the pharmacologic profile of E-3810, a novel dual inhibitor of the VEGF and FGF receptors. E-3810 potently and selectively inhibited VEGF receptor (VEGFR)-1, -2, and -3 and FGF receptor (FGFR)-1 and -2 kinases in the nanomolar range. Ligand-dependent phosphorylation of VEGFR-2 and FGFR-1 was suppressed along with human vascular endothelial cell growth at nanomolar concentrations. In contrast, E-3810 lacked cytotoxic effects on cancer cell lines under millimolar concentrations. In a variety of tumor xenograft models, including early- or late-stage subcutaneous and orthotopic models, E-3810 exhibited striking antitumor properties at well-tolerated oral doses administered daily. We found that E-3810 remained active in tumors rendered nonresponsive to the general kinase inhibitor sunitinib resulting from a previous cycle of sunitinib treatment. In Matrigel plug assays performed in nude mice, E-3810 inhibited basic FGF-induced angiogenesis and reduced blood vessel density as assessed by histologic analysis. Dynamic contrast-enhanced magnetic resonance imaging analysis confirmed that E-3810 reduced the distribution of angiogenesis-sensitive contrast agents after only 5 days of treatment. Taken together, our findings identify E-3810 as a potent antiangiogenic small molecule with a favorable pharmacokinetic profile and broad spectrum antitumor activity, providing a strong rationale for its clinical evaluation.
Time course of lung function changes in atypical pneumonia.
Authors: L N Benusiglio, H Stalder, A F Junod
Journal: Thorax (1980)

We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae.
Mode of Fixation of the Scapula, Suggested by a Study of the Movements of that Bone in Extreme Flexion of the Shoulder-Joint: its Bearing upon Fracture of the Coracoid Process
Authors: W. A. Lane
Journal: BMJ (1888)

WTm -RDMAZLOUkLVA 1047gical trt t of disease; for Mr. Hill assts that he.had rot only extirpated eghty-eight genuine cancers, all of which except four had ulIcerated, with only two deaths; but that of seventy- seven such cases, sixty-six continued free of cancer as long as they lived, so that " the different patients lived as long after extir- pation of the cancer as, according to the bills of mortality, they would have done had they never had any cancer, or undergone any operation."Sir Charles in this way disposes, to his own satisfac- tion, of his friend the " late justly esteemed" Dr. A. Munro.I have no desire to follow his example, and attempt to strengthen my opinion regarding carcinomas of the breast which should be oper- ated on by refemng to figures, for " everyone knows how eaBy it is to twist statistics to auit any nioral which the manipulator is anxious to enforce."Excluding cases of cancer which have advanced beyond hope of relief and those whose health is seriously compromised by some other disease, Sir B. Brodie avoided operating on rapidly-growing carcinomas, as well as on those very slowly-growing tumours above referred to.He was also disposed to hesitate in operating
Salvage treatment with paclitaxel and gemcitabine for patients with non-small-cell lung cancer after cisplatin- or docetaxel-based chemotherapy: A multicenter phase II study
Authors: N. Androulakis, C. Kouroussis, S. Kakolyris, S. Tzannes, E. Papadakis, C. Papadimitriou, A. Geroyianni, T. Georgopoulou, I. Dimopoulou, J. Souglakos, A. Kotsakis, N. Vardakis, D. Hatzidaki, V. Georgoulias
Journal: Annals of Oncology (1998)
Role of the thyroid gland in the development and maintenance of spontaneous hypertension in rats.
Authors: F Rioux, B A Berkowitz
Journal: Circulation Research (1977)

We studied the vascular mechanisms involved in the prevention of the development of hypertension following thyroidectomy. Ablation of the thyroid gland of 4-week-old spontaneously hypertensive (SH) rats inhibited the development of hypertension and reduced the sensitivity of aortic strips to the vasoconstrictors phenylephrine, norepinephrine, and potassium chloride and the vasodilator isoproterenol. Daily injections of a replacement dose of L-thyroxine caused a complete recurrence of hypertension in these rats. This was accompanied by complete recovery of the aortic sensitivity to the vasconstrictors and isoproterenol. In 10-week-old SH rats thyroidectomy prevented a further increase of blood pressure but did not reverse the hypertention. Here, the aortic sensitivity to vasoactive substances also was reduced but to a lesser extent than in the SH rats thyroidectomized at 4 weeks of age. Hypertension was not obviously associated with hyperfunction of the thyroid gland. Furthermore, we found that at 4 weeks of age, during the prehypertensive period, SH rats have a significantly lower (42%) serum thyroxine level than age-matched normotensive Kyoto Wistar, American Wistar, and Sprague-Dawley rats. However, at 6 and 9 weeks, the serum thyroxine levels of SH rats are similar to those of the normotensive rats. In conclusion, we propose that the reduced sensitivity to endogenous vasoconstrictors in arteries of SH rats following juvenile ablation of the thyroid gland may prevent the development of hypertension in these rats. Moreover, the low serum thyroxine level in SH rats during the prehypertensive period may explain why young SH rats do not develop hypertension before 6 weeks of age.
Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current
Authors: Thomas Desplantez, Megan L. McCain, Philippe Beauchamp, Ghislaine Rigoli, Barbara Rothen-Rutishauser, Kevin Kit Parker, Andre G. Kleber
Journal: Cardiovascular Research (2012)

AimsRemodelling and regional gradients in expression of connexins (Cx) are thought to contribute to atrial electrical dysfunction and atrial fibrillation. We assessed the effect of interaction between Cx43, Cx40, and Cx45 on atrial cell-to-cell coupling and inward Na current (INa) in engineered pairs of atrial myocytes derived from wild-type mice (Cx43+/+) and mice with genetic ablation of Cx43 (Cx43−/−).
Diagnostic Testing Following Screening Mammography in the Elderly
Authors: H. Gilbert Welch, Elliott S. Fisher
Journal: JNCI Journal of the National Cancer Institute (1998)

To provide some sense of the general frequency and timing of diagnostic testing following screening mammography in the United States, we investigated the experience of women screened in the Medicare population.By use of Medicare's National Claims History System, we identified a cohort (n=23172) of women 65 years old or older screened during the period from January 1, 1995, through April 30, 1995, and tracked each woman over the subsequent 8 months for the performance of additional breast imaging and biopsy procedures. Using two claims-based definitions for newly detected breast cancer, we also estimated the positive predictive value of screening mammography.For every 1000 women aged 65-69 years who underwent screening, 85 (95% confidence interval [CI]=79-91) had follow-up testing in the subsequent 8 months; 76 (95% CI=71-82) had additional breast imaging, and 23 (95% CI=20-26) had biopsy procedures. Corresponding numbers for women aged 70 years or more were similar. Some women underwent repeated examinations; 13% of those receiving diagnostic mammograms had more than one; 11% of those undergoing biopsy procedures had more than one. About half of the women who underwent a biopsy had the procedure more than 3 weeks after the imaging test upon which the decision to perform a biopsy was presumably made. The estimated positive predictive value of an abnormal screening mammogram (defined as a mammogram that engendered additional testing) was 0.08 (95% CI=0.06-0.10) for women aged 65-69 years and 0.14 (95% CI=0.12-0.16) for women aged 70 years or more.Additional testing is a frequent consequence of screening mammography and may require a considerable period of time to come to closure. The need for additional testing, however, is weakly predictive of cancer.
LEVEL OF ADRENO-CORTICAL SUBSTANCE IN THE BLOOD DURING HYPOGLYCEMIC TREATMENTS FOR SCHIZOPHRENIA
Authors: ESTHER BOGEN TIETZ, SANFORD M. BIRNBAUM
Journal: American Journal of Psychiatry (1942)

1. Chemical studies on the levels of adrenalin-cortical material in the blood show marked differences in the cases who recover from insulin shock therapy as compared with those who fail to recover. 2. The curves of recovered cases are characterized by a rising residual A-C level and a stability in the amounts present even under the stress of hypoglycemic coma and electric shock. 3. Failures are characterized by a persistently low A-C value with great susceptibility to change when shocks are applied. 4. The significance of these findings for an understanding of schizophrenia is discussed.
The constitutive mobilization of bone marrow-repopulating cells into the peripheral blood in idiopathic myelofibrosis
Authors: Mingjiang Xu, Edward Bruno, Joseph Chao, Hongyu Ni, Valerie Lindgren, Rafael Nunez, Nadim Mahmud, Guido Finazzi, Steven M. Fruchtman, Uday Popat, Enli Liu, Josef T. Prchal, Damiano Rondelli, Giovanni Barosi, Ronald Hoffman
Journal: Blood (2004)
Cytotoxic effect of 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: implication for targeted therapy
Authors: Tapas K Sengupta, Gilles M Leclerc, Ting Ting Hsieh-Kinser, Guy J Leclerc, Inderjit Singh, Julio C Barredo
Journal: Molecular Cancer (2007)

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy affecting children. Despite significant progress and success in the treatment of ALL, a significant number of children continue to relapse and for them, outcome remains poor. Therefore, the search for novel therapeutic approaches is warranted. The aim of this study was to investigate the AMP activated protein kinase (AMPK) as a potential target in childhood acute lymphoblastic leukemia (ALL) subtypes characterized by non-random translocation signature profiles. We evaluated the effects of the AMPK activator AICAR on cell growth, cell cycle regulators and apoptosis of various childhood ALL cells. Results We found that treatment with AICAR inhibited cell proliferation, induced cell cycle arrest in G1-phase, and apoptosis in CCRF-CEM (T-ALL), NALM6 (Bp-ALL), REH (Bp-ALL, TEL/AML1) and SupB15 (Bp-ALL, BCR/ABL) cells. These effects were abolished by treatment with the adenosine kinase inhibitor 5'-iodotubericidin prior to addition of AICAR indicating that AICAR's cytotoxicity is mediated through AMPK activation. Moreover, we determined that growth inhibition exerted by AICAR was associated with activation of p38-MAPK and increased expression of the cell cycle regulators p27 and p53. We also demonstrated that AICAR mediated apoptosis through the mitochondrial pathway as revealed by the release of cytochrome C and cleavage of caspase 9. Additionally, AICAR treatment resulted in phosphorylation of Akt suggesting that activation of the PI3K/Akt pathway may represent a compensatory survival mechanism in response to apoptosis and/or cell cycle arrest. Combined treatment with AICAR and the mTOR inhibitor rapamycin resulted in additive anti-proliferative activity ALL cells. Conclusion AICAR-mediated AMPK activation was found to be a proficient cytotoxic agent in ALL cells and the mechanism of its anti-proliferative and apoptotic effect appear to be mediated via activation of p38-MAPK pathway, increased expression of cell cycle inhibitory proteins p27 and p53, and downstream effects on the mTOR pathway, hence exhibiting therapeutic potential as a molecular target for the treatment of childhood ALL. Therefore, activation of AMPK by AICAR represents a novel approach to targeted therapy, and suggests a role for AICAR in combination therapy with inhibitors of the PI3K/Akt/mTOR pathways for the treatment of childhood in ALL.
Doctors should check datasheets
Authors: J M. Dixon
Journal: BMJ (1996)

EDITOR,—I found Adrian Parkinson's short article on the importance of taking a drug history extremely interesting.1 Last summer, a few days after we had returned from the Dominican Republic, my 6 year old son had a grand mal seizure on waking from sleep. He had been completely well previously. During the few hours that he was in hospital he was seen by three doctors; …
Post-myocardial infarct p27 fusion protein intravenous delivery averts adverse remodelling and improves heart function and survival in rodents
Authors: Filip Konecny, Jian Zou, Mansoor Husain, Rüdiger von Harsdorf
Journal: Cardiovascular Research (2012)

AimsP27Kip1 (p27) blocks cell proliferation through the inhibition of cyclin-dependent kinase 2 (cdk-2). Despite robust expression in the heart, little is known about the regulation and function of p27 in this terminally differentiated tissue. Previously, we demonstrated that p27 exerts anti-apoptotic and growth-inhibitory effects through interaction with casein kinase 2 (ck2) in neonatal rat cardiomyocytes. Here, we test the hypothesis that delivery of a transactivator of transcription (TAT)-p27 fusion protein (TAT.p27) will improve cardiac function and survival in a rat model of myocardial infarction (MI).
Gut hormone release after intestinal resection.
Authors: H S Besterman, T E Adrian, C N Mallinson, N D Christofides, D L Sarson, A Pera, L Lombardo, R Modigliani, S R Bloom
Journal: Gut (1982)

To investigate the possible role of gut and pancreatic hormones in the adaptive responses to gut resection, plasma concentrations of the circulating hormones were measured, in response to a test breakfast, in patients with either small or large intestinal resection and in healthy control subjects. In 18 patients with partial ileal resection a significant threefold rise was found in basal and postprandial levels of pancreatic polypeptide, a fourfold increase in motilin, and more than a twofold increase in gastrin and enteroglucagon levels compared with healthy controls. In contrast, nine patients with colonic resection had a threefold rise in levels of pancreatic polypeptide only. One or more of these peptides may have a role in stimulating the adaptive changes found after gut resection.