tbuckley/cabot-search huggingface dataset:
All-trans- and 9-cis-retinoic acid: potent direct inhibitors of primitive murine hematopoietic progenitors in vitro.
Authors: S E Jacobsen, C Fahlman, H K Blomhoff, C Okkenhaug, L S Rusten, E B Smeland
Journal: The Journal of Experimental Medicine (1994)

Retinoic acid (RA) stimulates the clonal proliferation of mature bone marrow progenitor cells and inhibits the growth of leukemic progenitors, whereas its effects on normal primitive hematopoietic progenitors have not yet been investigated. This study investigated the ability of all-trans- and 9-cis-RA to modulate the proliferation and differentiation of murine Lin-Sca-1+ bone marrow progenitor cells. Both RA isoforms inhibited in a reversible and dose-dependent fashion, the proliferation of multi- but not single-factor responsive Lin-Sca-1+ progenitor cells. The 50% effective dose was 10 nM for both all-trans- and 9-cis-RA. Maximum inhibition was observed at 100-1,000 nM RA, resulting in a 50-75% reduction in the number of proliferative clones. Lin-Sca-1+ cells with high proliferative potential were preferentially inhibited by RA, resulting in a 80-100% inhibition depending on the hematopoietic growth factors stimulating their growth. The inhibitory effects of RA were directly mediated on the target cell, since the effects were observed at the single cell level. Furthermore, autocrine transforming growth factor beta (TGF-beta) production can probably not account for the observed inhibitory effects of RA, since a TGF-beta neutralizing antibody did not block RA-induced inhibition. Whereas RA, in general, is a differentiation-inducing agent, treatment of Lin-Sca-1+ progenitors resulted in the accumulation of an increased fraction of blasts and immature myeloid cells. Thus, RA inhibits the proliferation as well as differentiation of normal primitive hematopoietic progenitor cells.
Role of Acetylcholine in the Renal Vasoconstrictor Response to Sympathetic Nerve Stimulation in the Dog
Authors: JOHN C. MCGIFF, ROBERT B. P. BURNS, MARVIN R. BLUMENTHAL
Journal: Circulation Research (1967)

The renal blood vessels were studied for a cholinergic determinant of their response to renal nerve stimulation. In dogs anesthetized with morphine and chloralose, control values were: mean aortic blood pressure 147 ± 4 mm Hg, renal blood flow 257 ± 12 ml/min. Acetylcholine (ACh) in 1-, 10- and 100-µg doses (all drugs given into the renal artery) increased renal blood flow, whereas 1000 µg of ACh reduced renal blood flow by 35%. After atropine and physostigmine, 1 µg of ACh did not alter renal blood flow, while 10, 100 and 1000 µg of ACh reduced renal blood flow by 6, 40 and 72%, respectively. After reserpine pretreatment, ACh in all doses increased renal blood flow (range of the means from 20 to 30%). The vasoconstrictor action of ACh was also blocked by phentolamine, guanethidine and hexamethonium. The renal vasoconstrictor response to renal nerve stimulation was blocked by guanethidine, but not by hexamethonium. These observations suggest that hexamethonium opposes ACh by barring its entry into the nerve terminals, whereas guanethidine blocks the intraneuronal release of norepinephrine by ACh. The vasoconstrictor response to nerve stimulation was reduced by atropine and augmented by physostigmine. Hemicholinium, which blocks the synthesis of ACh, attenuated the renal vasoconstriction produced by nerve stimulation. The results suggest that ACh may function in the canine kidney to liberate norepinephrine during activity of the sympathetic nerves.
Diagnosis of Fetal Maturity as Requisite for Elective Obstetrical Delivery
Authors: Howard G. McQuarrie
Journal: JAMA (1977)

The neonatal intensive care unit, an integral part of regional planning in maternal and child care, has enhanced the lowering of perinatal mortality to 14.9 per 1,000 live births in 1977. Associated with regional planning is the outcome assessment by audit of risks and benefits of medical care. Maisels et al (p 2036) have audited and identified  delivery of the fetus as an obstetrical hazard when fetal maturity is not established and verified before delivery.  The use of elective delivery by patient request or for hospital service and physician's convenience requires reexamination for its merit. Newer audit outcome not previously identified by widely diversified centers with low local incidence of complication, when combined and examined by regional data, seems unacceptable when iatrogenically caused asphyxia, respiratory distress syndrome, pneumothorax, pneumomediastinum, and large financial costs are reported.  In addition, parenting disorders, failure of normal growth and development, subsequent unexplained death syndromes,
Comparison of n-acetyl-β-d-glucosaminidase and alanine aminopeptidase activities for evaluation of microangiopathy in diabetes mellitus
Authors: Nobuo Shimojo, Shigeru Kitahashi, Keiichi Naka, Atsuo Fujii, Kiyoshi Okuda, Shiro Tanaka, Satoru Fujii
Journal: Metabolism (1987)
NHS improving—but could still do better, admits health secretary
Authors: Tiago Villanueva
Journal: BMJ (2004)

The overall performance of the NHS has improved substantially, says the NHS chief executive, Nigel Crisp.

But the health secretary, John Reid, accepts there is still room for improvement: “Progress is being made fast and visibly, but we have still a long way to go,” he said.

Mr Crisp's annual report, published last week, covers the period from March 2003 to March 2004. The chief executive said that the number of people waiting more than six months for inpatient treatment had fallen by just under 60%, from 189 054 to …
New procedures affecting the conduct of clinical trials in the United Kingdom.
Authors: J P Griffin, J R Long
Journal: BMJ (1981)

Changes have recently been introduced to facilitate the conduct of clinical trials of new drugs in the United Kingdom. These changes became necessary because early developmental work on new drugs was going abroad to the detriment of British industry and with a loss of skill in our departments of clinical pharmacology. The scheme also gives formal recognition to the part played by ethics committees in considering approval of the ethical aspects of clinical trials of new drugs.
Micropuncture measurement of lung microvascular pressure profile during hypoxia in cats.
Authors: Y Nagasaka, J Bhattacharya, S Nanjo, M A Gropper, N C Staub
Journal: Circulation Research (1984)

To determine the lung microvascular pressure profile during hypoxia, we micropunctured the subpleural microcirculation of isolated perfused cat lungs. Our procedures involved exsanguinating a cat, then cannulating its pulmonary artery, left atrium, and trachea. Using the cat's own blood, we perfused the lungs at pulmonary artery and left atrial pressures of 18 and 9 cm water, respectively, to obtain lung blood flow of 81 +/- 29 ml/(kg body weight x min), which we held constant throughout the experiment. We stabilized the lung surface with a vacuum ring and micropunctured 30- to 50-micrometers arterioles and venules to measure microvascular pressure by the servo-null method. During micropuncture, we held the lungs at constant inflation using airway pressure of 8 cm water. We varied the oxygen concentration of the inflation gas from 30% during baseline to 2% during hypoxia. We studied groups with high (more than 7.5) or normal pH. During normoxia, 27, 44, and 29% of the pressure drop occurred in the arterial, capillary and venous segments, respectively. During hypoxia, the increase in pulmonary vascular resistance, which was marked in both groups, was significantly greater in the normal pH group. All segmental pressure drops increased significantly during hypoxia. However, the predominant increase occurred in the arteries where segmental pressure drop increased by 148% and 210%, respectively, in the high and normal pH groups. We conclude that the major site of hypoxic vasoconstriction is in the pulmonary arteries.
Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor
Authors: Bastian Hoechst, Torsten Voigtlaender, Lars Ormandy, Jaba Gamrekelashvili, Fei Zhao, Heiner Wedemeyer, Frank Lehner, Michael P. Manns, Tim F. Greten, Firouzeh Korangy
Journal: Hepatology (2009)

Abstract Several immune suppressive mechanisms that evade the host immune response have been described in patients with hepatocellular carcinoma (HCC); one of these mechanisms is expansion of myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to inhibit T cell responses in tumor-bearing mice, but little is known about these cells in humans. Here, we have analyzed and characterized the effect of MDSCs on the innate immune system, in particular, their interaction with natural killer (NK) cells in patients with HCC. MDSCs from patients with HCC inhibited autologous NK cell cytotoxicity and cytokine secretion when cultured together in vitro. This suppression was dependent on cell contact, but did not rely on the arginase activity of MDSCs, which is a hallmark function of these cells. However, MDSC-mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells. Conclusion: Our study suggests a new role for MDSCs in patients with HCC in disarming the innate immune system and further contributing to the immune suppressor network in these patients. These findings have important implications when designing immunotherapy protocols. (Hepatology 2009.)
Lifetime and Twelve-Month Prevalence Rates of Major Depressive Episodes and Dysthymia Among Chinese Americans in Los Angeles
Authors: David T. Takeuchi, Rita Chi-Ying Chung, Keh-Ming Lin, Haikang Shen, Karen Kurasaki, Chi-Ah Chun, Stanley Sue
Journal: American Journal of Psychiatry (1998)

Objective:The authors' goal was to estimate the lifetime and 12-month rates of major depressive episodes and dysthymia for Chinese Americans who reside in Los Angeles. This effort, the Chinese American Psychiatric Epidemiological Study, is the first large-scale community psychiatric epidemiological study on an Asian American ethnic group that used DSM-III-R criteria for major depressive episodes and dysthymia.Method:A multi-stage sampling design was used to select respondents for participation in the survey. The sample included 1,747 adults, 18–65 years of age, who resided in Los Angeles County and who spoke English, Mandarin, or Cantonese.Results:Approximately 6.9% of the respondents had experienced an episode of major depression and 5.2% had had dysthymia in their lifetime. The 12-month rates of depressive episode and dysthymia were 3.4% and 0.9%, respectively. The most consistent correlate of lifetime and 12-month depressive episode and dysthymia was social stress, measured by past traumatic events and recent negative life events. Conclusions:The Chinese American Psychiatric Epidemiological Study provides a rare opportunity to investigate the heterogeneity within a single Asian American ethnic group, Chinese Americans, and to identify the subgroups among Chinese Americans who may be most at risk for mental health problems. Am J Psychiatry 1998; 155: 1407-1414
Notes on the Climate and Diseases of Central Uruguay
Authors: H. J. Walker
Journal: BMJ (1901)

THIS paper Irefers to the rural inhabitants of the zone of the Uruguay Republic which lies in lat. 320 43' S., long. 560 8' W., about i6o miles north of Montevideo, and about the same distance from the sea, the River Uruguay, and the Brazilian frontier.The mean annual temperature of the district is 6o0 F. Spring and autumn averages running from 720 max. to 490 min., summer from 84.70 to 58.40, and winter from 60.50 to 41.30.The highest shade temperature recorded is 1060, and the lowest I90.The average annual rainfall is 46 inches, falling on 94 days, and with a duration of 329 hours per annum.April and September are the rainiest months, February being the driest.It is not at all infrequent to find an inch of rain falling in an hour.On individual days the dryness of the air is frequently very great, and on the other hand, but with much less frequency, the humidity is so excessive that even inside the houses everything becomes permeated with a most penetrating damp.The rapid alternations from the one to the other of these extreme states of the atmosphere forms a marked feature of the climate of the interior of Uruguay.The average number of thunderstorms in the year is 48, and there is no doubt that they are inti- mately associated with the rainfall and with the great and sudden changes that occur from time to time in the direction of the wind, and in the temperatureL_and humidity of the atmosphere.The general physical character of Central Uruguay is undu- lating, showing low hill ranges, some rather stony, some with no surface stone, of no great elevation, in few instances rising more than ioo feet over the nearest running water.The soil is of a very varied character, in some parts a stiff black elay, difficult to work but very rich; in others, light black loam in-
Abstract 2250: Role of single strand binding protein 1 in TERT recruitment to telomeres and in maintaining telomere G-overhangs
Authors: Tej K. Pandita, Raj Pandita
Journal: Cancer Research (2014)

Abstract Telomeres cap the ends of all eukaryotic chromosomes from degradation or end-to-end fusions. Mammalian telomeres are maintained by telomerase which is a ribonucleoprotein complex that includes a reverse transcriptase catalytic unit called TERT and a functional telomerase RNA (TR or TERC), which acts as a template to maintain telomere length. Telomerase maintains telomere length, by overcoming incomplete lagging strand synthesis known as the “end replication problem” during DNA replication. Mammalian stem and cancer cells utilize telomerase to extend telomeric G-overhangs to partially (stem cells) or completely (tumor cells) maintain telomere ends. Cells expressing telomerase also have higher levels of single strand binding 1 (SSB1) protein, which has a known critical role in the DNA damage responses and double strand break repair specifically by homologous recombination. We have established that SSB1 binds specifically to G-strand telomeric DNA in vitro, and associates in vivo with telomeres both in human and mouse cell lines. Interestingly, SSB1 interacts with the TERT protein, and determines the amount of TERT interaction with telomeres. Deletion/depletion of SSB1 reduces TERT interaction with telomeres and leads to G-overhang loss, but has no effect on in vitro telomerase activity. We will discuss, how SSB1 is required for telomerase recruitment to telomeres to facilitate G-strand DNA extension and to maintain telomeres. Citation Format: Tej K. Pandita, Raj Pandita. Role of single strand binding protein 1 in TERT recruitment to telomeres and in maintaining telomere G-overhangs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2250. doi:10.1158/1538-7445.AM2014-2250
An Outbreak of Gastroenteritis and Fever Due to<i>Listeria monocytogenes</i>in Milk
Authors: Craig B. Dalton, Constance C. Austin, Jeremy Sobel, Peggy S. Hayes, William F. Bibb, Lewis M. Graves, Bala Swaminathan, Mary E. Proctor, Patricia M. Griffin
Journal: New England Journal of Medicine (1997)

After an outbreak of gastroenteritis and fever among persons who attended a picnic in Illinois, chocolate milk served at the picnic was found to be contaminated with Listeria monocytogenes.In investigating this outbreak, we interviewed the people who attended the picnic about what they ate and their symptoms. Surveillance for invasive listeriosis was initiated in the states that receive milk from the implicated dairy. Stool and milk samples were cultured for L. monocytogenes. Serum samples were tested for IgG antibody to listeriolysin O.Forty-five persons had symptoms that met the case definition for illness due to L. monocytogenes, and cultures of stool from 11 persons yielded the organism. Illness in the week after the picnic was associated with the consumption of chocolate milk. The most common symptoms were diarrhea (present in 79 percent of the cases) and fever (72 percent). Four persons were hospitalized. The median incubation period for infection was 20 hours (range, 9 to 32), and persons who became ill had elevated levels of antibody to listeriolysin O. Isolates from stool specimens from patients who became ill after the picnic, from sterile sites in three additional patients identified by surveillance, from the implicated chocolate milk, and from a tank drain at the dairy were all serotype 1/2b and were indistinguishable on multilocus enzyme electrophoresis, ribotyping, and DNA macrorestriction analysis.L. monocytogenes is a cause of gastroenteritis with fever, and sporadic cases of invasive listeriosis may be due to unrecognized outbreaks caused by contaminated food.
The Response of the Flicker Fusion Threshold to Nitroglycerin and Its Potential Value in the Diagnosis, Prognosis, and Therapy of Subclinical and Clinical Cardiovascular Disease
Authors: L. R. KRASNO, A. C. IVY
Journal: Circulation (1950)

Flicker fusion threshold (F.F.T.) means the frequency with which successive flashes of light must occur to just appear to the eye free from flicker. A simple portable machine is described which will deliver flashes of light at any required interval. Patients with hypertension or anemia have a lower than normal F.F.T.; furthermore, administration of nitroglycerin, 0.4 mg. sublingually, or papaverine, intravenously, raises the threshold in patients with hypertension and coronary disease and lowers it in normal individuals. It is suggested that this test may be of use in the diagnosis of equivocal cases and for the evaluation of therapeutic measures.
Intimations of Mortality
Authors: CHARLES D. ARING
Journal: Annals of Internal Medicine (1968)

Students of medicine receive little (if any) specific instruction in the care of the dying. This likely reflects the conflicted feelings of physicians (and society) about it. Studies reveal that physicians are afraid of death in greater proportion than patients. The physician's role in caring for the dying has been defined by Feder: "I don't have any idea how to help a person to die, but I am sure we can do much to help a person to live until the time of death." This living, as any life, should entail dignity, respect, and humanity. The immediate threat of dying is isolation, a condition that a hospital, as an agent of society, does much to impose. To be graceful among the dying requires the physician to become aware of his feelings about death. With energies neurotically encumbered, graceful use of the self is not likely. Death can be natural if we will make it so; it is not a taboo surrounded by disapproval or shame.
THE ESSENTIALS OF SUCCESS IN VAGINAL HYSTERECTOMY.Read in the Section of Obstetrics and Diseases of Women, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: HENRY T. BYFORD
Journal: JAMA (1893)

The experience of gynecologists is gradually establishing the fact that the removal of the uterus through the vagina is not in itself a very dangerous operation. Of course there is a mortality connected with all operations involving any considerable amount of cutting, but there is nothing about the one under consideration involving any special, unavoidable danger. What there is comes not so much from the' danger of the operation as from certain avoidable circumstances which may be considered under three heads, viz: 1. Unsuitable cases for operations; 2. Imperfection in the technique; 3. Mistakes in the after-treatment. It would be absurd to maintain that unfavorable circumstances can always be avoided in practice, yet there is much to be accomplished in that direction, and a great majority of the deaths due to the operation ought not to occur. 1.<i>Unsuitable Cases for Operation</i>.—Unfortunately, the great majority of cases are unsuitable ones—
PROPENSITY-MATCHED PATIENT LEVEL COMPARISON OF THE TAXUS LIBERTÉ AND TAXUS ELEMENT (ION) PACLITAXEL-ELUTING STENTS: DOES STENT PLATFORM MAKE A DIFFERENCE?
Authors: Dean J. Kereiakes, Louis A. Cannon, John A. Ormiston, Mark A. Turco, Hong Wang, Paul Underwood, Keith D. Dawkins
Journal: Journal of the American College of Cardiology (2011)
Oxidative stress in fatty livers of obese Zucker rats: Rapid amelioration and improved tolerance to warm ischemia with tocopherol
Authors: Kyle Soltys, George Dikdan, Baburao Koneru
Journal: Hepatology (2001)

Fatty livers in humans and rats are less tolerant of ischemia, endotoxin, and alcohol. We hypothesized that fatty livers of obese (Ob) Zucker rats are oxidatively stressed and oxidative stress could be relieved by antioxidant treatment, leading to improved tolerance to ischemia. Total glutathione (GSH), tocopherol (TOC), ascorbic acid (AA), catalase (CAT), superoxide dismutase (SOD), and selenium-glutathione peroxidase (Se-GPx) were measured in the livers of Ob and lean (Ln) Zucker rats before and after treatment with high-dose TOC and ascorbate. Also, survival in treated Ob rats following a lethal 90 minutes of partial in vivo warm ischemia was examined. Fatty livers of Ob rats contained significantly less GSH, TOC, and CAT, in comparison with livers of Ln rats. Immunoblotting showed significantly decreased CAT protein without changes in mRNA in fatty livers. There were no significant differences in AA, SOD, and Se-GPx between the 2 groups. Pretreatment with TOC and ascorbate over 48 hours completely corrected the decreases in GSH, TOC, and CAT. Most importantly, TOC with or without ascorbate pretreatment significantly improved survival in Ob rats following ischemia in a dose-dependent manner. In conclusion, TOC administration corrected the oxidative stress in fatty livers of Ob Zucker rats and improved survival following lethal ischemia. Additional studies are needed to determine the efficacy of TOC-a relatively inexpensive agent-in treating patients with fatty livers in a variety of clinical conditions, possibly including liver transplantation.
Monkeypox without Exanthem
Authors: Matthew W. Lewis, Mary Beth Graham, Erika Hammarlund, Jon Hanifin, Mark K. Slifka
Journal: New England Journal of Medicine (2007)

To the Editor: We report on two unvaccinated adult patients from the same household who had strikingly divergent clinical presentations after monkeypox infection. Although readily identifiable disease symptoms developed in both patients, one of them presented with a disseminated skin eruption that included more than 100 pocks, whereas the other had no evident eruption suggestive of monkeypox. Analysis of the findings in the latter patient revealed a rare, specific description of monkeypox without exanthem1 and illustrates the difficulty of relying on clinical algorithms alone for the diagnosis of atypical or vaccine-modified orthopoxvirus infections. Patient 1 (whom Reed et al. refer . . .
JAK2 V617F impairs hematopoietic stem cell function in a conditional knock-in mouse model of JAK2 V617F–positive essential thrombocythemia
Authors: Juan Li, Dominik Spensberger, Jong Sook Ahn, Shubha Anand, Philip A. Beer, Cedric Ghevaert, Edwin Chen, Ariel Forrai, Linda M. Scott, Rita Ferreira, Peter J. Campbell, Steve P. Watson, Pentao Liu, Wendy N. Erber, Brian J. P. Huntly, Katrin Ottersbach, Anthony R. Green
Journal: Blood (2010)