tbuckley/cabot-search huggingface dataset:
Work Capacity and Efficiency of the Autotransplanted Heart
Authors: WILLARD M. DAGGETT, VALLEE L. WILLMAN, THEODORE COOPER, C. ROLLINS HANLON
Journal: Circulation (1967)

Total extrinsic denervation of the heart was accomplished in six animals by cardiac autotransplantation. The work capacity and efficiency were studied in the postoperative period, when there was depletion of catecholamine stores. The left ventricular oxygen consumption (VO 2 ) of these six cardiac autotransplants (average body weight, 13.6±0.6 kg) and six normal dogs (average body weight, 14.0±0.4 kg) were compared with a right-heart bypass at similar heart rates, mean arterial blood pressures, and systemic flows. The two groups of animals achieved comparable levels of stroke work (17.3 g-m) over the same range of filling pressures. Average maximum rates of left ventricular pressure development were also similar (autotransplants 2455±278 mm Hg/sec, versus 2267±209 mm Hg/sec for normal dogs). At VO 2 /100 g left ventricle, autotransplants averaged 9.54±0.97 cc/min and normal dogs 9.62±0.76 cc/min. However, left ventricular weights in the autotransplant group were significantly greater (110.9±6.2 g) than in the normal dogs (96.7±3.4 g), and represented a significantly greater percentage of body weight (8.2±0.5% versus sus 6.6±0.3%). Total left ventricular VO 2 was greater in autotransplants during performance of comparable levels of external work and at comparable degrees of contractility. No systematic difference in handling of glucose, lactate, or pyruvate was noted between the groups. Respiratory quotients were 1.0 or greater. The normal dogs showed no net change in circulating catecholamines across the coronary bed, whereas autotransplants always showed a net uptake of catecholamines. Myocardial mitochondria were enlarged in electron micrographs of the ventricular myocardium of the autotransplants. The totally extrinsically denervated cardiac autotransplant can achieve a level of performance similar to that of a normal heart, but is less efficient in doing so. Alterations in utilization of circulating catecholamines may aid the hemodynamic adaptation to the cardiac denervation.
Thioredoxin-binding protein-2 (TBP-2/VDUP1/TXNIP) regulates T-cell sensitivity to glucocorticoid during HTLV-I-induced transformation
Authors: Z Chen, D A Lopez-Ramos, E Yoshihara, Y Maeda, H Masutani, K Sugie, M Maeda, J Yodoi
Journal: Leukemia (2010)

Although glucocorticoid (GC) is widely used for treating hematopoietic malignancies including adult T-cell leukemia (ATL), the mechanism by which leukemic cells become resistant to GC in the clinical course remains unclear. Using a series of T-cell lines infected with human T lymphotropic virus type-I (HTLV-I), the causative virus of ATL, we have dissected the transformation from interleukin (IL)-2-dependent to -independent growth stage. The transformation associates the loss of thioredoxin-binding protein-2 (TBP-2), a tumor suppressor and regulator of lipid metabolism. Here we show that TBP-2 is responsible for GC-induced apoptosis in ATL cells. In the IL-2-dependent stage, dexamethasone induced TBP-2 expression and apoptosis, both of which were blocked by GC receptor (GR) antagonist RU486. Knockdown of TBP-2 consistently reduced the amount of GC-induced apoptosis. In IL-2-independent stage, however, expression of GR and TBP-2 was suppressed and GC failed to induce apoptosis. Forced expression of GR led the cells to mild sensitivity to GC, which was also accomplished by treatment with suberoylanilide hydroxamic acid, a TBP-2 inducer. A transfection experiment showed that TBP-2 expression induced apoptosis in IL-2-independent ATL cells. Thus, TBP-2 is likely to be one of the key molecules for GC-induced apoptosis and a potential target for treating the advanced stage of ATL.
Early Signs of Atherosclerosis in Diabetic Children on Intensive Insulin Treatment
Authors: Hanna Dis Margeirsdottir, Knut Haakon Stensaeth, Jakob Roald Larsen, Cathrine Brunborg, Knut Dahl-Jørgensen
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate early stages of atherosclerosis and predisposing factors in type 1 diabetic children and adolescents compared with age- and sex-matched healthy control subjects. RESEARCH DESIGN AND METHODS All children and adolescents with type 1 diabetes, aged 8–18 years in Health Region South-East in Norway were invited to participate in the study (n = 800). A total of 40% (n = 314) agreed to participate and were compared with 118 age-matched healthy control subjects. Carotid artery intima-media thickness (cIMT) and elasticity were measured using standardized methods. RESULTS Mean age of the diabetic patients was 13.7 years, mean diabetes duration was 5.5 years, and mean A1C was 8.4%; 97% were using intensive insulin treatment, and 60% were using insulin pumps. Diabetic patients had more frequently elevated cIMT than healthy control subjects: 19.5% were above the 90th centile of healthy control subjects, and 13.1% were above the 95th centile (P &amp;lt; 0.001). Mean cIMT was higher in diabetic boys than in healthy control subjects (0.46 ± 0.06 vs. 0.44 ± 0.05 mm, P = 0.04) but not significantly so in girls. There was no significant difference between the groups regarding carotid distensibility, compliance, or wall stress. None of the subjects had atherosclerotic plaque formation. Although within the normal range, the mean values of systolic blood pressure, total cholesterol, LDL cholesterol, and apolipoprotein B were significantly higher in the diabetic patients than in the healthy control subjects. CONCLUSIONS Despite short disease duration, intensive insulin treatment, fair glycemic control, and no signs of microvascular complications, children and adolescents with type 1 diabetes had slightly increased cIMT compared with healthy control subjects, and the differences were more prominent in boys.
Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice.
Authors: A W Mould, K I Matthaei, I G Young, P S Foster
Journal: Journal of Clinical Investigation (1997)

The mechanism of cooperation between IL-5 and eotaxin for the selective accumulation of eosinophils at sites of allergic inflammation is unknown. In this investigation we have used IL-5 deficient mice to define the relationship between this cytokine and eotaxin in the regulation of blood eosinophilia and eosinophil homing and tissue accumulation. Both IL-5 and eotaxin could independently induce a rapid and pronounced blood eosinophilia in wild type mice when administered systemically. In contrast, only eotaxin induced a pronounced blood eosinophilia in IL-5 deficient mice. The eosinophilic response induced by intravenous eotaxin in wild type mice did not correlate with a significant reduction in the level of bone marrow eosinophils, whereas intravenous IL-5 resulted in depletion of this store. These results suggest the existence of two mechanisms by which eosinophils can be rapidly mobilized in response to intravenous eosinophil chemoattractants; first, mobilization of an IL-5 dependent bone marrow pool, and second, an eotaxin-induced sequestration of eosinophils from tissues into the blood. Subcutaneous injection of eotaxin induced a local tissue eosinophilia in wild type mice but not in IL-5 deficient mice. Furthermore, tissue eosinophilia in wild type mice, but not in IL-5 deficient mice, was enhanced by adoptive transfer of eosinophils or the administration of intravenous IL-5. However, pretreatment of IL-5 deficient mice with intraperitoneal IL-5 for 72 h restored eosinophil homing and tissue accumulation in response to subcutaneous eotaxin. We propose that eotaxin secreted from inflamed tissue may play an important role in initiating both blood and tissue eosinophilia in the early phases of allergic inflammation. Furthermore, IL-5 is not only essential for mobilizing eosinophils from the bone marrow during allergic inflammation, but also plays a critical role in regulating eosinophil homing and migration into tissues in response to eotaxin and possibly other specific chemotactic stimuli.
D7-04: Carbon ion radiotherapy for peripheral stage I non small-cell lung cancer
Authors: Masayuki Baba, Toshio Sugane, Mio Nakajima, Tadaaki Miyamoto, Reiko Imai, Hidefumi Ezawa, Susumu Kandatsu, Tadashi Kamada, Junetsu Mizoe, Hirohiko Tsujii
Journal: Journal of Thoracic Oncology (2007)
Detection of venom by enzyme linked immunosorbent assay (ELISA) in patients bitten by snakes in Thailand.
Authors: K Silamut, M Ho, S Looareesuwan, C Viravan, V Wuthiekanun, D A Warrell
Journal: BMJ (1987)

The ability of an enzyme linked immunosorbent assay (ELISA) to detect venom was evaluated in 251 patients bitten by four of the commonest poisonous snakes in Thailand. Serum was tested only from patients who brought the snakes that had bitten them. About one third of all bitten patients had detectable venom antigenaemia, though a smaller proportion were symptomatic. Serum venom concentrations on admission correlated with the severity of clinical manifestations. The test was sensitive and specific even for specimens that had been collected and stored under suboptimal conditions. The technique is suitable for forensic use in cases of suspected snakebite. The combination of snake identification and venom antigen detection should be a more reliable means of studying the epidemiology of snakebite than the measurement of venom antibodies in a population.
Implications of advanced biomedical research and technology
Authors: M. K. DuVal
Journal: JAMA (1972)

Extraordinary advances in the biological and medical sciences in this century have raised serious ethical, social, and legal problems. Some of these problems are associated with: control of birth rates, "genetic engineering," organ transplantation, prolongation of dying, selective life saving, and behavior modification through drugs. The US Department of Health, Education, and Welfare has engaged in a continuing examination and discussion of the questions posed by clinical investigation in research conducted or funded by the National Institutes of Health. Several groups in the private sector have considered the legal, social, and ethical implications of advances in the health sciences. All this represents development of responsible decision points within our society for addressing and treating the issues and implications associated with advanced biomedical research.
GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal–induced apoptosis
Authors: Marie-Liesse Asselin-Labat, Muriel David, Armelle Biola-Vidamment, Damiana Lecoeuche, Maria-Christina Zennaro, Jacques Bertoglio, Marc Pallardy
Journal: Blood (2004)
Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside
Authors: Stephen F. Vatner, Charles B. Higgins, Thomas Patrick, Dean Franklin, Eugene Braunwald
Journal: Journal of Clinical Investigation (1971)

The effects of ouabain (G-strophanthin) 20 mug/kg, on left ventricular (LV) pressure (P), diameter (D), velocity of contraction (dD/dt), and dP/dt were studied in conscious dogs instrumented with ultrasonic diameter gauges and miniature pressure gauges. The effects of ouabain were compared on separate occasions in the same dogs after cardiac depression with propranolol, 3.0 mg/kg, and also after general anesthesia with Na pentobarbital, 30 mg/kg. Maximal pressor effects were observed in the first 10 min, but maximal effects on the contractile state occurred at 30 min after ouabain. At this time, in conscious dogs, ouabain had increased LV isolength systolic pressure by 5%, LV isolength velocity by only 9%, and LV (dP/dt)/P by 21%, while end systolic diameter (ESD) decreased slightly and end diastolic diameter (EDD) and heart rate (HR) were unchanged. After anesthesia, ouabain increased LV systolic pressure by 8%, velocity 32%, (dP/dt)/P by 47%, and ESD decreased by 1.2 mm while EDD rose slightly and HR fell by 26 beats/min. Returning HR to control with atrial pacing decreased EDD 0.9 mm below control. After cardiac depression with propranolol, ouabain caused responses similar to those observed in the anesthetized dogs. Thus, the cardiac glycoside was found to exert only minor inotropic effects on the nonfailing heart of conscious dogs but far more striking inotropic responses in the anesthetized state.
VIP blockade leads to microcephaly in mice via disruption of Mcph1-Chk1 signaling
Authors: Sandrine Passemard, Vincent El Ghouzzi, Hala Nasser, Catherine Verney, Guilan Vodjdani, Adrien Lacaud, Sophie Lebon, Marc Laburthe, Patrick Robberecht, Jeannette Nardelli, Shyamala Mani, Alain Verloes, Pierre Gressens, Vincent Lelièvre
Journal: Journal of Clinical Investigation (2011)

Autosomal recessive primary microcephaly (MCPH) is a genetic disorder that causes a reduction of cortical outgrowth without severe interference with cortical patterning. It is associated with mutations in a number of genes encoding protein involved in mitotic spindle formation and centrosomal activities or cell cycle control. We have shown previously that blocking vasoactive intestinal peptide (VIP) during gestation in mice by using a VIP antagonist (VA) results in microcephaly. Here, we have shown that the cortical abnormalities caused by prenatal VA administration mimic the phenotype described in MCPH patients and that VIP blockade during neurogenesis specifically disrupts Mcph1 signaling. VA administration reduced neuroepithelial progenitor proliferation by increasing cell cycle length and promoting cell cycle exit and premature neuronal differentiation. Quantitative RT-PCR and Western blot showed that VA downregulated Mcph1. Inhibition of Mcph1 expression led to downregulation of Chk1 and reduction of Chk1 kinase activity. The inhibition of Mcph1 and Chk1 affected the expression of a specific subset of cell cycle–controlling genes and turned off neural stem cell proliferation in neurospheres. Furthermore, in vitro silencing of either Mcph1 or Chk1 in neurospheres mimicked VA-induced inhibition of cell proliferation. These results demonstrate that VIP blockade induces microcephaly through Mcph1 signaling and suggest that VIP/Mcph1/Chk1 signaling is key for normal cortical development.
Mosquito Gene Map
Authors: Tracy Hampton
Journal: JAMA (2007)

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Patients we don't like
Authors: D. K. Sokol
Journal: BMJ (2013)

Doctors should not let their moral evaluations of patients affect their treatment



A few months ago I represented a man who had been involved in a road crash. Shortly before the trial we discussed—in private—what had happened on that day.

During the trial, it became evident that under cross examination my client was lying. There was video footage to confirm it. He had also breached my trust and lied to me repeatedly. Not a white lie, or a slight inaccuracy, but whopping great untruths. With each passing minute, as his credibility floundered, my resolve to win the case weakened. I grew emotionally more distant from my client. By the end of the cross examination I was filled with a profound dislike for him. It was an unsettling experience.

The trial was not over. In my closing submissions I still had to persuade the judge that my client was not negligent.

Similar situations arise in medicine. …
The New Tuberculosis
Authors: Dixie E. Snider, William L. Roper
Journal: New England Journal of Medicine (1992)

Events during the past decade have dramatically changed the nature and magnitude of the problem of tuberculosis. Much of what many physicians learned in training about this disease is no longer true. In many respects, tuberculosis has become a new entity.The strategy used to control tuberculosis in the United States has been based on a two-pronged approach: identifying and treating persons with active disease (to cure them and prevent further transmission) and identifying and treating those with subclinical infection (to prevent the development of the disease). Until recently, this strategy generally was successful. The incidence of tuberculosis declined steadily, . . .
State Medical Boards Discipline More, Want Role in Health System Reform
Authors: Charles Marwick
Journal: JAMA (1994)

MORE PROBLEM physicians were disciplined last year by state medical licensing boards than in the previous 3 years. In 1993, a total of 3711 cases were recorded; there were 3370 in 1992. These figures on disciplinary actions taken by medical boards were released last month by the Federation of State Medical Boards. Hormoz Rassekh, MD, the federation's president and a psychiatrist in Council Bluffs, Iowa, notes that a total of 3081 prejudicial actions were taken against problem physicians. Actions involved punitive measures ranging from loss of license to limitation or restriction of license to probation to formal reprimand. The numbers represent nearly a 15% increase over the last 4 years, while the 1993 prejudicial actions taken by medical boards represent an increase of 3.6% over those in 1992. "This indicates the readiness of state medical boards to deal with the issues confronting medicine and delivery of medical care," said Rassekh,
International Review of Connective Tissue Research
Authors: H. R. Catchpole
Journal: JAMA (1964)

This handsomely produced volume, the first in a series, covers aspects of fibroblast, collagen, hormone effects, elastase, calcification, diabetes, and atherosclerosis. Even admitting the bounds of eclecticism permitted by the field, it is a vaguely unsatisfactory package. Duplication of subject matter was noted editorially. Atherosclerosis, for example, permeates three chapters in addition to its own. More serious is the problem of over-reviewing. While the topic of collagen is probably unavoidable in an introductory volume, some of its phases are quite well known, and we may question whether really enough is happening in the realms of collagen molecular structure or in fibrillogenesis to justify their review almost annually. Critical appraisal and controversy, though encouraged editorially, is evidently for the future. All this is not to deny that individual chapters are excellent. Yet, perusal of the chapter on hormonal control of connective tissue would lead to the curious conclusion that everybody is
Maintained Reduction of Intraocular Pressure by Prostaglandin F2α-1-Isopropyl Ester Applied in Multiple Doses in Ocular Hypertensive and Glaucoma Patients
Authors: Carl B. Camras, Earlene C. Siebold, Jacqueline S. Lustgarten, Janet B. Serle, Sandford C. Frisch, Steven M. Podos, Laszlo Z. Bito
Journal: Ophthalmology (1989)
Abstract 5315: PET imaging with the proliferation tracer 18F-FLT as early, non-invasive predictor of everolimus effect on tumor growth: Studies in human neuroendocrine tumor xenografts in mice
Authors: Camilla Bardram Johnbeck, Mette Munk Jensen, Anne Mette Fisker Hag, Jacob Madsen, Ulrich Knigge, Andreas Kjaer
Journal: Cancer Research (2011)

Abstract Background and aim: Everolimus (RAD001), an oral mTOR inhibitor has shown promising results in the treatment of several types of cancer including neuroendocrine tumors. With the expanding numbers of clinical treatment protocols there is a need for early, non-invasive predictors of treatment response. We hypothesized that PET imaging with the proliferation tracer 3′-Deoxy-3′-[(18)F]fluorothymidine (FLT) could serve as such a predictor. Therefore, we studied in human neuroendocrine tumor xenografts in mice whether PET imaging with FLT could predict, at an early time-point, the effect of everolimus on tumor growth. Methods: In vivo uptake of FLT in human neuroendocrine xenografts (H727) in mice was studied at baseline when tumors were on average 140 mm3. The mice were randomized into two groups. One group of mice (n=10 tumors) were treated with daily i.p. injections of everolimus (5 mg/kg) for 10 days while another group of mice (n=10 tumors) served as control and was given the same volume of vehicle i.p. The mice were FLT scanned at day 0, 1, 3, 7 and 10. Each PET scan was acquired over 15 min 1 h after injection in a tail vein of 10 MBq FLT. In addition, a CT-scan was performed for calculation of tumor volume. The tumors were defined on PET/CT images and FLT uptake was calculated as mean standardized uptake values (SUV). Results: Everolimus treated mice showed a clear reduction in tumor growth compared to the vehicle group at day 7 and 10 (P&amp;lt;0.0001). At day 7 the relative tumor volumes (day 7/day 0) were 1.78±0.10 in the everolimus group and 2.77±0.11 (407 mm3) in the control group. At day 10 the relative tumor volumes (day 10/day 0) were 2.17±0.15 (304 mm3) in the everolimus group and 3.50±0.13 (518 mm3) in the vehicle group. The relative FLT SUV value on day 10 showed significantly reduced uptake (P=0.003) in the everolimus group (0.91±0.06) compared to the control group (1.16±0.04). In the everolimus group FLT uptake at day 3 predicted relative tumor size both at day 7 (R2=0.53; P=0.017) and day 10 (R2=0.60; P=0.024). FLT uptake at day 1 also predicted tumor growth, although only borderline significant, at day 3 (R2=0.38; P=0.060), 7 (R2=0.39; P=0.055) and 10 (R2=0.45; P=0.069). Conclusion: FLT-PET imaging as early as 1 or 3 days after treatment initiation with everolimus predicts neuroendocrine tumor growth over the first 10 days of treatment. We suggest that FLT-PET is a promising tool for early prediction of effect of everolimus in patients with neuroendocrine tumors and may be used for tailoring therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5315. doi:10.1158/1538-7445.AM2011-5315
Death of the Guilds: Professions, States, and the Advance of Capitalism, 1930 to the Present
Authors: George Ross Fisher
Journal: JAMA (1996)

Elliott Krause has certainly produced an illuminating book, particularly for physicians bewildered by the hostility of social forces currently besieging them. This might even be an important classic, depending on how many of the ideas are new with Professor Krause and how many are already circulating in his field. Your reviewer is too unfamiliar with sociology literature to be sure.  The author seemingly changed emphasis while writing the book. The underlying design is to test four professions in five different countries, with 20 vignettes, against a thesis that professions are shaped by the style of theirnational government, particularly the relative dominance of corporate business. Such cultural entertainment does enable physicians to chat knowledgeably with engineers, lawyers, and university professors at a party, or a tourist to understand more about the countries he visits than just the restaurants and museums that happen to be open.  But the emerging central subject of