tbuckley/cabot-search huggingface dataset:
The Role of DOC-2/DAB2 in Modulating Androgen Receptor–Mediated Cell Growth via the Nongenomic c-Src–Mediated Pathway in Normal Prostatic Epithelium and Cancer
Authors: Jian Zhoul, Gina Hernandez, Szu-Wei Tu, Chien-Ling Huang, Ching-Ping Tseng, Jer-Tsong Hsieh
Journal: Cancer Research (2005)

Abstract Prostate cancer is initially responsive to androgen ablation, but prostate cancer tumors invariably progress to an androgen-independent state that is ultimately lethal. The onset of the androgen-independent prostate cancer is often associated with up-regulation of the androgen receptor that can cause antagonists to exhibit agonistic activity, which could lead to the failure of androgen ablation therapy. We describe a unique protein—DOC-2/DAB2 (differentially expressed in ovarian cancer-2/disabled 2)—that antagonizes androgen receptor–mediated cell growth in prostate cancer cells via interaction with c-Src protein. This interaction causes inactivation of Erk and Akt proteins critical for proliferation and survival of prostate cancer cells. However, DOC-2/DAB2 does not change the capacity of androgen receptor to regulate the transcription of androgen-responsive reporter genes, indicating that DOC-2/DAB2 selectively inhibits androgen receptor–mediated cell growth in androgen-independent prostate cancer by disrupting the androgen receptor/c-Src complex. In normal prostatic epithelia, DOC-2/DAB2 protein levels are more abundant than androgen receptor protein levels and reduced endogenous DOC-2/DAB2 protein levels in these cells by DOC-2/DAB2 RNA interference result in enhancing androgen receptor–mediated cell growth. We conclude that DOC-2/DAB2 can modulate androgen receptor–mediated cell growth in both normal and malignant prostatic epithelial cells and the outcome of this study could evolve into a new therapeutic strategy of prostate cancer.
Parasympathetic Control of Cardiac Sympathetic Activity
Authors: Eduardo R. Azevedo, John D. Parker
Journal: Circulation (1999)

Muscarinic receptors on adrenergic nerve terminals attenuate norepinephrine release. The role of these receptors in the modulation of cardiac norepinephrine release in humans remains uncertain.Twelve patients with normal left ventricular (LV) function and 18 with congestive heart failure (CHF) were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) in response to intracoronary acetylcholine (ACh, 5x10(-5) Mol), and in response to intracoronary atropine (12 micrograms/min). ACh did not affect CANESP in the group of subjects with normal LV function, but it caused a significant reduction in those with CHF [197 (150 to 302) versus 168 (87 to 288) pmol/min, P<0.05]. Atropine caused a significant increase in CANESP in those with normal LV function [47 (27 to 51) versus 64 (38 to 139) pmol/min, P<0.05], but no change was observed in the CHF group.Therefore, in the setting of heart failure and sympathetic activation, muscarinic receptor stimulation decreases CANESP, an effect not observed in patients with preserved LV function. Blockade of muscarinic receptors with atropine increased CANESP in patients with normal LV function, suggesting that cardiac parasympathetic tone has inhibitory effects on cardiac sympathetic activity. This basal inhibition was not observed in CHF patients in response to atropine. The lack of basal parasympathetic inhibition of cardiac sympathetic activity may play a role in the pathogenesis of cardiac sympathetic activation in heart failure.
Hard Cases and Hard Law
Authors: Allen E. Smith
Journal: JAMA (1974)

To the Editor.—  The medical profession is under attack—hard cases—and unless it cleans its own house, the public will do so for it—bad law. I want to clarify, if possible, the scrambling of the use of the aphorism, in which  cases means hard because of judicial sympathy for one of the parties, and in which   means a precedent that, if applied, would produce difficulty for people other than the parties in the first instance. As used in an editorial (226:562, 1973), a hard case is one in which there is a serious accusation, and bad law is a harsh remedy applied to the person accused.  My main point, put briefly, is this: The medical profession is, indeed, under heavy attack these days. There is no doubt that the continuing nature of the attack has engendered some paranoia-like attitudes throughout the profession and in the medical establishment. These
Mechanisms and immediate and long-term results of adjunct directional coronary atherectomy after rotational atherectomy
Authors: Gaston R. Dussaillant, Gary S. Mintz, Augusto D. Pichard, Kenneth M. Kent, Lowell F. Satler, Jeffrey J. Popma, Theresa A. Bucher, Jennifer Griffin, Martin B. Leon
Journal: Journal of the American College of Cardiology (1996)
Thyroid Nodule Mimicking Cervical Adenopathy on FDG Positron Emission Tomographic Imaging
Authors: EUGENE C. LIN
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology, University of Colorado Health Sciences Center, Denver, Colorado Received for publication October 22, 2001. Revision accepted February 7, 2002. Reprint requests: Eugene C. Lin, Virginia Mason Medical Center, Mailstop C5-XR, 1100 Nineth Avenue, P.O. Box 900, Seattle, Washington 98111. E-mail: [email protected]
The Etiology of Diabetes Mellitus
Authors: Allan L. Drash
Journal: New England Journal of Medicine (1979)

It has long been known that insulin-deficiency diabetes mellitus (IDDM) results from an inflammatory process of the islet tissue of the pancreas (insulitis), leading to essentially complete destruction of the insulin-producing beta cells. The factors responsible for this destructive process have been the focus of intense research by many investigators. Although the investigative roots go back at least 80 years,1 there has been a considerable advance of knowledge about the cause of diabetes over the past five years.Three interlocking mechanisms have been clearly identified: genetics, viral infections and autoimmunity.2 That genetic influences have a role in the development of . . .
Myopic picosecond laser keratomileusis with the neodymium—yttrium lithium fluoride laser in the cat cornea
Authors: Omar E. Hanuch, Vinay B. Agrawal, Sharon Bassage, Manuel del Cerro, James V. Aquavella
Journal: Ophthalmology (1998)

Objective: The study aimed to evaluate the effects of myopic picosecond laser keratomileusis (PLK) in the feline model with follow-up of up to 6 months.Design: The study design was a case-controlled, feline animal model. Participants:The procedure was completed in 1 eye each of 12 cats divided into 3 groups (group 1, sham operation; group 2, 100-#m lenticle thickness; and group 3, 150-/~m lenticle thickness).The second eye of each cat was used as a control.Intervention: Picosecond laser keratomileusis, a new intrastromal laser technique with the neodymium-yttrium lithium fluoride picosecond laser, was presented.The procedure, analogous to laser keratomileusis in situ, consists of two lamellar ring cuts and one vertical ring-shape cut that define a 4-mm-diameter intrastromal lenticle.Main Outcome Measures: Corneal pachymetry, topography, tonometry, and biomicroscopic examination were performed before and after surgery at scheduled intervals for 6 months.• Results: The mean (_+standard deviation) diopter change for group 2 was 5.4 _+ 3.2 diopters at 1 month and remained stable during the 6-month period.For group 3, the change was 8.1 _+ 0.22 diopters at 1 month and 6.8 +__ 1.5 diopters at 6 months.Group 1 (sham operation) did not show significant diopter change compared with that of control eyes at any timepoint.Pachymetry results for group 1 showed no significant difference in the thickness of the cornea at any timepoint (P >0.05).For groups 2 and 3, the corneal thickness was reduced significantly by 1 month (P <0.05), but it regressed to nearly preoperative values at 3 months.At 6 months, the corneas were clear with no grossly visible scar.With the slit-lamp examination, a faint, thin line of haziness barely was visible in the periphery of the flap.The histologic examination results showed no significant collagen disruption, inflammation, or endothelial irregularities comparing the control with the postoperative corneas.Conclusion: Myopic intrastromal PLK produces a refractive effect on the cornea that depends on the thickness of the lenticle removed and persists after 6 months with minimal stromal haze and no surgical complications.The authors' results, although encouraging, indicate the need for further studies to confirm the efficacy of PLK as a valid refractive procedure.
Challenges in the Enumeration and Phenotyping of CTC
Authors: Frank A.W. Coumans, Sjoerd T. Ligthart, Jonathan W. Uhr, Leon W.M.M. Terstappen
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Presence of circulating tumor cells (CTC) in metastatic carcinoma is associated with poor survival. Phenotyping and genotyping of CTC may permit “real-time” treatment decisions, provided CTCs are available for examination. Here, we investigate what is needed to detect CTC in all patients. Experimental Design: CTCs enumerated in 7.5 mL of blood together with survival from 836 patients with metastatic breast, colorectal, and prostate cancer were used to predict the CTC concentration in the 42% of these patients in whom no CTCs were found and to establish the relation of concentration of CTCs with survival. Influence of different CTC definitions were investigated by automated cell recognition and a flow cytometric assay without an enrichment or permeabilization step. Results: A log-logistic regression of the log of CTC yielded a good fit to the CTC frequency distribution. Extrapolation of the blood volume to 5 L predicted that 99% of patients had at least one CTC before therapy initiation. Survival of patients with EpCAM+, cytokeratin+, CD45− nucleated CTCs is reduced by 6.6 months for each 10-fold CTC increase. Using flow cytometry, the potential three-fold recovery improvement is not sufficient to detect CTC in all patients in 7.5 mL of blood. Conclusions: EpCAM+, cytokeratin+, CD45− nucleated CTCs are present in all patients with metastatic breast, prostate, and colorectal cancer and their frequency is proportional to survival. To serve as a liquid biopsy for the majority of patients, a substantial improvement of CTC yield is needed, which can only be achieved by a dramatic increase in sample volume. Clin Cancer Res; 18(20); 5711–8. ©2012 AACR.
The Cascade Effect in the Clinical Care of Patients
Authors: James W. Mold, Howard F. Stein
Journal: New England Journal of Medicine (1986)

IN biology, the term "cascade" refers to a process that, once started, proceeds stepwise to its full, seemingly inevitable, conclusion. Common examples are the clotting cascade and the complement cascade. Processes that occur in molecular systems often have correlates in larger systems. It is our contention that cascade effects are frequently operative in the clinical care of patients, and that recognition of this fact gives us a better understanding of the clinical decision-making process.The cascade effect that we will describe generally consists of an initiating factor or factors, followed by a series of events that seem to be a . . .
Not good enough
Authors: C. Brown
Journal: BMJ (2009)

We had just arrived in France for a week’s skiing. I checked my email in the hotel lobby, and there it was—the outcome of my specialty trainee level 3 (ST3) interview. “You were well below the standard we expect of registrars in this deanery. You will not proceed to ST3 but instead will go onto an ST2-3 transition post.” Suddenly, my guaranteed run-through training had suffered a year long hiccup. 

Although I’m not one of those people who always knew they …
Why neutrality on assisted dying is not an option for doctors' professional organisations
Authors: J. Saunders
Journal: BMJ (2012)

Both the public and politicians reasonably expect medical professional bodies to offer an overall judgment on the desirability of legislation if it affects medical practice or if doctors have special experience of the issue in question. There is nothing different in principle between one issue of public policy and another: NHS reform, smoking, or assisted death.

When a policy is strongly divisive, responsible organisations will consult and publish their …
Serum levels of C-reactive protein predict acute complications and restenosis after PTCA in unstable angina
Authors: Antonino Buffon, Giovanna Liuzzo, Luigi M. Biasucci, Gaelano Quaranta, Giuseppina Caligiuri, Francesco Summaria, Rita L. Grillo, Antonio G. Rebuzzi, Filippo Crea, Attilio Maseri
Journal: Journal of the American College of Cardiology (1996)
Assessing systemic 11[beta ]-hydroxysteroid dehydrogenase with serum cortisone/cortisol ratios in healthy subjects and patients with diabetes mellitus and chronic renal failure
Authors: Masato Homma, Akihisa Tanaka, Kumiko Hino, Hiroe Takamura, Toshihiko Hirano, Kitaro Oka, Masao Kanazawa, Takashi Miwa, Yoko Notoya, Tomoyuki Niitsuma, Tohru Hayashi
Journal: Metabolism (2001)
Treatment of Hyperlipidemia
Authors: Robert I. Levy, Joel Morganroth, Basil M. Rifkind
Journal: New England Journal of Medicine (1974)

OVER the past decade considerable insight into the mechanisms involved in normal and abnormal lipid transport as well as the mode of action of hypolipidemic drugs has been achieved.1 This progress has made the approach to the hyperlipidemic patient increasingly more precise and effective.It is now realized that hyperlipidemia is the sign of a heterogeneous group of disorders differing in clinical features, prognosis and, most important, responsiveness to therapy. No one diet is effective in all the lipid transport disorders. Similarly, none of the currently available hypolipidemic drugs are effective in all the hyperlipidemias, some having a very limited . . .
Long-Term Paraprosthetic-Enteric Fistula Only Diagnosed After Upper Gastrointestinal Endoscopy
Authors: V. O. Maestro, M. Gómez-Rubio, G. P. Vigara, E. M. Barbero, E. J. de la Morena Madrigal, J. G. Alvarez
Journal: Endoscopy (1996)
P2-294: Activity of TS-1 in advanced non-small cell lung cancer patients who received at least two prior chemotherapy including platinum and docetaxel, and/or EGFR-TKIs
Authors: Akira Ono, Nobuyuki Yamamoto, Satoshi Igawa, Yukiko Nakamura, Asuka Tsuya, Haruyasu Murakami, Masahiro Endo, Toshiaki Takahashi
Journal: Journal of Thoracic Oncology (2007)
Intrinsic mechanism of the enhanced rate-dependent QT shortening in the R1623Q mutant of the LQT3 syndrome
Authors: Y OGINOSAWA, T NAGATOMO, H ABE, N MAKITA, J MAKIELSKI, Y NAKASHIMA
Journal: Cardiovascular Research (2004)

In the type 3 long QT syndrome (LQT3), arrhythmia events tend to occur at rest or during sleep. One of the mutations, R1623Q, is located in the voltage sensor of the cardiac sodium channel (hH1), and patients with R1623Q mutation have been also reported to show bradycardia-dependent cardiac events. Although the mutant channel has been characterized by inactivation gating defects, the intrinsic mechanism(s) that might explain why arrhythmia attack is most prevalent at slower heart rates has not been investigated.cDNA encoding either the wild-type or the R1623Q mutant of hH1 was stably transfected into HEK293 cells. I(Na) was recorded using a whole-cell patch-clamp technique at 23 degrees C.A train of 50 depolarizing pulses from holding potentials (-120 and -80 mV) to -20 mV or a train of 50 action potential waveforms was applied at different frequencies. When using a rectangular waveform voltage clamp protocol, rate-dependent reduction of I(Na) was holding voltage-dependent but was not different between peak I(Na) and late I(Na). However, using the action potential clamp, preferential rate-dependent reduction of the phase 3 I(Na) was obvious as compared with peak I(Na). The discrepancy in the rate-dependent reduction between protocols was attributed to accelerated recovery from inactivation under non-equilibrium condition.The rate dependency of phase 3 I(Na) under non-equilibrium gating is a novel mechanism to explain the enhanced rate-dependent QT-shortening in LQT3 patients. Our findings are important for genotype-phenotype correlations in LQT3 mutants as well as for understanding the function of S4 segment of domain IV region in the cardiac Na(+) channel.
Tobacco Smoking and Bladder Cancer
Authors: David Dowdy
Journal: JAMA (2011)

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
878-5 Provisional versus systematic T stenting: Insights from a large prospective single-center database
Authors: André Kokis, Gunasekaran Sengottuvel, Thierry Lefèvre, Samer Mansour, Yves Louvard, Pierre Dumas, Christophe Loubeyre, Marie-Claude Morice
Journal: Journal of the American College of Cardiology (2004)
THE PROGRESSION OF PERI-STENT CONTRAST STAINING IS ASSOCIATED WITH VERY LATE STENT THROMBOSIS IN PATIENTS AFTER SIROLIMUS ELUTING STENT IMPLANTATION
Authors: Takeshi Tada, Kazushige Kadota, Mitsuru Yoshino, Koshi Miyake, Haruki Eguchi, Noriyuki Ohashi, Yuki Hayakawa, Naoki Saito, Suguru Ohtsuru, Daiji Hasegawa, Yoshikazu Shigemoto, Seiji Habara, Hiroyuki Tanaka, Shingo Hosogi, Yasushi Fuku, Naoki Oka, Harumi Kato, Hiroyuki Yamamoto, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2011)
Sudden death after exertion in apparently healthy boy.
Authors: R C Connor
Journal: BMJ (1969)

Medical Memorandain other organs in man, it provides some evidence of liver function.Other liver-dependent coagulation factors, as measured by the prothrombin time (one-stage and two-stage), were well maintained.There was also evidence of the development of a hypercoagulable phase as suggested by the slow fall in fibrinogen, increasing factor VIII levels, and thrombocyto- penia.Antilymphocyte globulin, however, was also being administered and fibrin degradation products were not measured.Although the histological appearances are difficult to evaluate in tenns of function, it was-considered that in the absence of arterial thrombosis the liver would have been expected to survive.There was only moderate evidence of rejection as indicated by mononuclear cell infiltration.In conclusion, satisfactory function has been demonstrated in a human liver allograft after prolonged ischaemia, protected by the simple method of core-cooling in situ and infusion of a preservative solution.Whereas expermental evaluation of this technique in the dog provided only three and a half hours of safe ischaemia (Schalm, 1968), this interval may apparently be extended in man.We wish to thank Mr. N. C. Keddie, under whose care the patient was first admitted, for referring the case for transplantation.
Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro.
Authors: T Suda, F Tozawa, M Yamada, T Ushiyama, N Tomori, T Sumitomo, Y Nakagami, H Demura, K Shizume
Journal: Journal of Clinical Investigation (1988)

The effects of corticotropin-releasing hormone (CRH) and dexamethasone on proopiomelanocortin (POMC) mRNA levels in cultured pituitary adenoma cells were studied in 10 patients with Cushing's disease. As a control, POMC mRNA levels in cells from nonadenomatous tissues were examined in four patients. Human POMC mRNA in the cells was analyzed by Northern blot hybridization. Human POMC DNA probe hybridized with only a single size class of RNA (approximately 1,200 nucleotides) from the adenoma and nonadenoma cells of each patient. The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone. CRH increased POMC mRNA levels in these cells in a dose- and time-dependent manner. The minimum concentration of CRH required to elevate POMC mRNA levels in these cells exposed for 15 h was 0.1 nM. The minimum duration of 1 nM CRH treatment required to increase these levels was 3 h under our conditions. Inhibitory effects of 1 and 10 micrograms/dl dexamethasone on ACTH release and POMC mRNA levels in nonadenoma cells were greater than those in adenoma cells. These results suggest the following: (a) that the mRNA in cultured pituitary adenoma cells is qualitatively the same as that in vivo; (b) that responses of mRNA levels to CRH are time- and dose-dependent; and (c) that adenoma cells resist the inhibitory effect of dexamethasone on POMC mRNA levels and ACTH release.
Pancreatic necrosis in progressive systemic sclerosis.
Authors: A A Abraham, A Joos
Journal: Annals of the Rheumatic Diseases (1980)

Fatal pancreatic necrosis, secondary to extensive acute arteritic changes, is reported in a case of progressive systemic sclerosis. The patient presented first with hypertension and renal involvement, with active vascular lesions demonstrated by biopsy. The renal lesion at necropsy was inactive, showing the characteristic concentric fibrosis only, while the pancreatic vascular lesions were both chronic proliferative and acute in type.
Effectiveness and hazards of case finding for a high cholesterol concentration.
Authors: S Kinlay, R F Heller
Journal: BMJ (1990)

OBJECTIVE--To see whether adults with high blood cholesterol concentrations (greater than 6.5 mmol/l) detected by case finding return to their doctor, receive appropriate advice, and report changes in their diet and whether adults found not to have high cholesterol concentrations on case finding are discouraged from changing their diet. DESIGN--Follow up study. SETTING--Seven general practices in the lower Hunter region of Australia. PARTICIPANTS--600 Men and women aged 25-65 who had their blood cholesterol concentrations measured three to four months earlier while attending their general practitioner. Analysis conducted on 552 (92%) who returned follow up postal questionnaires. MEASUREMENTS AND MAIN RESULTS--Of the 125 subjects found to have blood cholesterol concentrations greater than 6.5 mmol/l, 102 (82%) returned to their doctor and 83 of these recalled receiving dietary advice. 93 (75%) Subjects with high concentrations reported changing their diet compared with 72 (46%) subjects with concentrations of greater than 5.5-6.5 mmol/l and 44 (17%) subjects with lower concentrations. Overall 333 (61%) of all respondents who answered reported not changing their diet, the most common reason (nearly half the sample; n = 266) being that their cholesterol concentration was "all right." Adults without high cholesterol concentrations who returned to their doctor were also significantly more likely to recall their doctor saying that they did not need to lower their concentrations (less than or equal to 5.5 mmol/l = 61%; greater than 5.5-6.5 mmol/l = 12%; greater than 6.5 mmol/l = 5%) and significantly less likely to recall receiving dietary advice (less than or equal to 5.5 mmol/l = 13%; greater than 5.5-6.5 mmol/l = 60%; greater than 6.5 mmol/l = 82%). CONCLUSIONS--High risk strategies which require everyone to be tested for high cholesterol concentrations may interfere with population strategies designed to reduce everyone9s dietary intake of fat.