tbuckley/cabot-search huggingface dataset:
Direct Transcriptional Activation of Promyelocytic Leukemia Protein by IFN Regulatory Factor 3 Induces the p53-Dependent Growth Inhibition of Cancer Cells
Authors: Tae-Kyung Kim, Joong-Seob Lee, Se-Yeong Oh, Xun Jin, Yun-Jaie Choi, Tae-Hoon Lee, Eun ho Lee, Young-Ki Choi, Seungkwon You, Yong Gu Chung, Jang-Bo Lee, Ronald A. DePinho, Lynda Chin, Hyunggee Kim
Journal: Cancer Research (2007)

Abstract IFN regulatory factor 3 (IRF3) is a transcriptional factor that plays a crucial role in activation of innate immunity and inflammation in response to viral infection, and is also involved in p53-dependent inhibition of cell growth. Although functional activation of IRF3 by viral infection is relatively well documented, the biological role and regulatory mechanism underlying cell growth inhibition by IRF3 are poorly understood. Here, we show a novel regulatory pathway connecting IRF3-promyelocytic leukemia protein (PML)-p53 in primary and cancer cell lines. Overexpression of IRF3 induces p53-dependent cell growth inhibition in cancer cell lines with normal p53 activity. In addition, doxycycline-induced expression of IRF3 in U87MG cells inhibits tumor growth in nude mice in vivo. IRF3 is found to increase expression of PML by a direct transcriptional activation as determined by PML-promoter-luciferase and chromatin immunoprecipitation assays. When PML is depleted by RNA interference–mediated knockdown, IRF3 fails to increase p53 acetylation and its transcriptional activity. Taken together, the results of the present study indicate that direct transcriptional activation of PML by IRF3 results in the p53-dependent growth inhibition of normal and cancer cells in vitro and in vivo, which is suggestive of a novel regulatory network between the innate immune response and tumor suppression. [Cancer Res 2007;67(23):11133–40]
Cytophilic immunoglobulin G binding on neutrophils from a child with malignant osteopetrosis who developed fatal acute respiratory distress mimicking transfusion-related acute lung injury
Authors: Prema R. Madyastha, Elaine K. Jeter, L. Lyndon Key
Journal: American Journal of Hematology (1996)

A 16-month-old boy, diagnosed at age 3 months with osteopetrosis, was treated since age 6 months with rhIFN-gamma in combination with rhM-CSF. The child developed acute respiratory distress within 1 hr of a paternal platelet transfusion. Both the child and the father were blood group type O, and platelets were collected the previous day from the father. Chest X-ray revealed right pulmonary consolidation and a complete "whiteout" on the left. By 24 hr, the lungs had the appearance of adult respiratory distress syndrome (ARDS). Over the course of the next 11 days, the child remained intubated and hypotensive, and died of respiratory insufficiency 11 days later. ARDS was confirmed at autopsy. Pre- and posttransfusion patient's sera, as well as paternal serum, were tested by granulocyte agglutination and flow cytometry against granulocytes (PMN) from the patient, father, mother, and routine cell-panel donors and lymphocytes for the presence of neutrophil-specific and lymphocyte (HLA) antibodies, to rule out classical transfusion-related acute lung injury (TRALI). Both the patient's and the paternal sera were devoid of antibodies, but the patient's neutrophils demonstrated strong binding of cytophilic IgG accompanied by extremely low serum IgG and IgG1 levels. Since rhIFN-gamma is known to upregulate Fc gamma receptor type I (Fc(gamma)RI) with high affinity for IgG1, the binding of cytophilic IgG suggests that the patient's neutrophils may have been activated in vivo. The case report of another child with osteopetrosis has also been described. Although the blood specimen was not available for serological studies, this 4 1/2-year-old child treated with rhIFN-gamma and rhM-CSF also died of adult respiratory distress syndrome, with similar clinical presentations.
DESCRIPTIVE PICTURE OF BERIBERI
Authors: NAGIB T. ABDOU
Journal: JAMA (1918)

In the latter part of April, 1918, a four masted schooner arrived in New York harbor from a port in British West Africa. The cargo consisted of logs, rubber and cocoa. Of the original crew of ten men, eight of whom were from Finland, the skipper and the cook being German-Americans, eight remained, and all except the skipper were suffering from beriberi. The trip consumed eighty-five days, during which hardships of all sorts were experienced. The remaining seven of the schooner's crew, victims of the original Oriental disease, were detected at quarantine by the boarding officer and brought to the Hoffman Island State Hospital for isolation and treatment. These patients landed in a somewhat prostrated condition, and one of them died the following day of acute dilatation and hypertrophy of the right ventricle, his case being an acute pernicious dry form of beriberi. In addition to the heart, the liver
CHOLANGIOHEPATITIS OR RECURRENT PYOGENIC CHOLANGITIS WITH INTRAHEPATIC AND EXTRAHEPATIC BILE-PIGMENT STONES
Authors: Waltman Walters
Journal: JAMA (1961)

While visiting surgical clinics in Japan and Hong Kong 2 years ago (1959) and again in 1960, I was impressed by the marked differences in the clinical and pathologic features of diseases of the biliary tract among the Japanese and among the Hong Kong Chinese from those of diseases of the same structures among patients of the United States. Although in some cases of recurrent pyogenic cholangitis (cholangiohepatitis) with and without bile-pigment ductal stones the symptoms are somewhat similar to those seen in Western people with chronic recurring cholecystitis, in other cases the difference is marked. In such cases there are crisis-like attacks of such severity that shock-like reactions develop quickly, and unless surgical decompression of the biliary tract is done immediately, the patient not infrequently dies. The clinical picture and the laboratory findings in these cases are so typical, according to McFadzean, that the diagnoses can be made readily
Delay in the diagnosis of pulmonary tuberculosis, London, 1998-2000: analysis of surveillance data
Authors: A. Rodger
Journal: BMJ (2003)

Noted cases of tuberculosis each year have doubled in London since 1987.In 2000, 12.9 cases per 100 000 population in England and Wales were recorded compared with 40.3 cases in London. 1 A delay in the diagnosis of tuberculosis increases the risk of poor clinical outcome-including death and transmission of tuberculosis. 2 3Understanding which factors influence this delay is crucial for controlling tuberculosis.Only one small study has previously investigated delays in the diagnosis of pulmonary tuberculosis in the United Kingdom. 4 Using surveillance data from London, we estimated the delays in diagnosis of tuberculosis and investigated the factors independently associated with delays.
Designing a deprivation payment for general practitioners: the UPA(8) wonderland.
Authors: R A Carr-Hill, T Sheldon
Journal: BMJ (1991)

To analyse critically the deprived area payment introduced in the new general practitioner contract. The payment formula is based on the Jarman underprivileged area index (UPA(8)) and aims at compensating general practitioners for increases in workload.Evaluation of the deprived area payment against the stated policy objective with a set of criteria for developing resource allocation formulas.The degree to which the components of the Jarman index predict the workload of general practitioners; whether construction of the index is sensible and comprehensible; and how the formula incorporates the index and is likely to work in practice.The fact that the index relies on census data and the way the weighting was derived means that the formula will not accurately reflect the workload. The use of statistical transformations obscures the original policy intent. There has been no validation to support the application of the index as part of a national policy. The payments are not linked to the quality of service provided and may have the perverse effect of increasing list size.The formula used as the basis of the deprived area payments is poorly suited to the policy objective of compensating general practitioners for increases in workload. More research is urgently needed to enable the effect of the payment to be monitored and a more empirically sound set of incentives to be developed.
Will the Cost Curve Bend, Even without Reform?
Authors: David M. Cutler
Journal: New England Journal of Medicine (2009)

If there is one certainty about the health care sector, it is that its costs increase over time. U.S. health care spending has more than doubled as a share of national income over the past half-century, and most forecasters believe that the steep growth will continue. The Congressional Budget Office, for example, projects that health care spending will account for one third of the U.S. gross domestic product (GDP) by the middle of this century, up from 17% today. In their latest report, the Medicare trustees have forecast similar growth rates for Medicare costs.But what if this conventional wisdom . . .
Mycoplasma in leukaemia.
Authors: A. J. Beale, G. J. Christofinis
Journal: BMJ (1968)

sera from some leukaemic patients do neutralize growth of mycoplasma first isolated by Negroni, though the inhibitor has not been shown to be antibody, and these results do not solve the problem of the role of this mycoplasma in aetiology of leukaemia, but they make it more likely that it, or an antigenically related organism, does infect man.Our thanks are due to Dr. R. J. C. Harris, who aranged for the tests and coded the samples.-We are, etc.,
Skeletal lead release during bone resorption: effect of bisphosphonate treatment in a pilot study.
Authors: Brian Gulson, Karen Mizon, Howard Smith, John Eisman, Jacqueline Palmer, Michael Korsch, John Donnelly, Kay Waite
Journal: Environmental Health Perspectives (2002)

There has been renewed interest in impacts on physiologic systems in the middle and older age groups, especially from fractures and hypertension. Increased blood lead (BPb) levels in postmenopausal females, which are thought to arise from bone demineralization, may also relate to other health effects including hypertension. Taking advantage of natural differences in lead isotope signature between Australian sources of lead and those from other countries, a 2-year pilot study was performed in premenopausal and postmenopausal females and male partners in which the subjects were administered a bisphosphonate, alendronate, for 6 months. The aim of the study was to determine how lead isotopes and lead concentrations changed in relation to bone remodeling processes. Premenopausal subjects were a woman (and male partner) from Bosnia and two women from Colombia. The postmenopausal subject was a woman from Russia. Her male partner and one man from Sri Lanka were included. Multigenerational Australian subjects were 2 perimenopausal women and 1 postmenopausal woman. Each subject had blood and urine samples collected for markers of bone turnover and for lead isotope studies monthly for 7-9 months before, for 3 months during, and for up to 6 months after treatment with alendronate to inhibit bone resorption. Each subject thus acted as his or her own control. As predicted, there were significant decreases in the lead isotope ratio, (206)Pb/(204)Pb, for the migrant subjects during treatment compared with the pretreatment period (p < 0.01). After cessation of treatment, an increasing isotope ratio for the postmenopausal subject (and older male partner) occurred later than for premenopausal subjects, indicative of prolonged efficacy of the alendronate for the older subjects. The average BPb concentrations in migrant subjects decreased by about 20% during the treatment compared with the pretreatment period (p < 0.01). To our knowledge, these are the first BPb concentrations reported over monthly to quarterly intervals for environmentally exposed adults over an extended period. The changes in lead isotopic composition and lead concentration are consistent with a decrease in bone resorption and associated mobilization of lead during alendronate therapy. Older subjects at risk of fractures may benefit from treatment with antiresorptive therapy, such as the potent bisphosphonates, with the added bonus of lower release of lead from bones and thus less risk of the potential adverse health effects of increased BPb levels.
Neutrophil marrow cellularity in neutropenia
Authors: John T. Dancey, Leonard H. Brubaker
Journal: American Journal of Hematology (1982)

Abstract In order to identify individuals in whom marrow abnormalities might be contributing to or responsible for neutropenia, we quantitatively examined the number and distribution of cells comprising neutrophil marrow in patients with blood neutrophils less than 2,000/μl. Neutrophil marrow cellularity was determined from ferrokinetic estimation of normoblast numbers and neutrophil‐normoblast ratios obtained from marrow biopsy sections. Only two of 30 patients exhibited the change in cellularity expected of a normal marrow responding to removal of circulating neutrophils: reduced numbers of segmented cells, an expanded mitotic pool, and a normal ratio of metamyelocytes and band forms to promyelocytes and myelocytes. Twenty‐three patients had basal mitotic pool size or increased numbers of segmented marrow cells despite neutropenia, a hypoplastic mitotic pool, or a reduction in the number of metas and bands relative to promyelocytes and myelocytes. The results in individual patients were consistent with hypoplasia, subnormal proliferative or release responses, loss of cells during ontogeny, or combinations thereof. In five cases the results could not be so classified. Clinical observations seldom predicted marrow cellularity. Diverse disorders of marrow function appear to be common among neutropenic patients. Neutropenia constitutes a rich field for study of neutrophil marrow physiology.
Environmental Exposures in Cytogenetically Defined Subsets of Acute Nonlymphocytic Leukemia
Authors: Martin M. Crane
Journal: JAMA (1989)

Three previous investigations have reported a relationship between clonal chromosome abnormalities in marrow of patients with acute nonlymphocytic leukemia and employment in occupations involving mutagenic chemicals, but the effects of other exposures were not described. Environmental exposure profiles, gathered by questionnaire, were therefore compared using a case-control study design in 235 newly diagnosed patients with acute nonlymphocytic leukemia: 126 with abnormal and 109 with normal karyotypes. The univariate odds ratio for occupation at diagnosis was 4.6, which, when adjusted for demographic and other exposures by logistic regression, was reduced to 2.5 (95% confidence interval, 0.5 to 12.8). Adjusted point estimates for other exposures were 4.3 (1.4 to 13.3) for prior cytotoxic therapy, 1.7 (0.9 to 3.1) for cigarette smoking, and 1.9 (1.0 to 3.4) for alcohol use. Dose-response relationships were present for both tobacco and alcohol consumption. Associations between specific abnormalities (+8, -7I-7q, [corrected] inv16, t[8;21]) and certain exposures were also present. These results suggest that life-style exposures may be associated with cytogenetic lesions in persons with acute nonlymphocytic leukemia.
Consensus on general medical contraindications to organ donation?
Authors: S. M. Gore, W. J. Armitage, J. D. Briggs, A. Crombie, D. L. Easty, C. J. Hinds, N. V. Jamieson, P. Johnston, S. Large, E. Major
Journal: BMJ (1992)

During 1989 and 1990 in England and Wales 453 bias between raters.In only four cases, including a MRC Biostatistics Unit, confirmed brain stem dead patients in intensive care neonate and a haemophilic patient, was there serious Cambridge CB2 2SRwere reported to a confidential audit' as having a disagreement (contraindicated versus transplantable).Sheila M Gore, senior general medical contraindication to organ donation.In The two raters had commented as follows: KI (1)-"I statistician 437 cases the contraindication was briefly specified.seldom used code 3 because in most cases the contra- Because the incidence of general medical contraindicaindication given could have been genuine.I have United Kingdom tions to organ donation varied very significantly by therefore used code 2 a fair number of times and it Transplant Support region in England-from 9% in Oxford and Wessex would be most interesting to know more about these Service, Bristol BS10OSND (24 out of 266 confirmed brain stem deaths) to 27% in patients as I suspect there are a significant number W John Armitage, senior the North East Thames region and East Anglia (65 out where a transplant surgeon would have felt the contrascientist of 237 confirmed brain stem deaths)'-we speculated indication was not genuine"; KI (2)-"When there wasRenal Unit, Western that there might be a lack of consensus among insufficient information I used code 2. It was perfectly Infirmary, Glasgow specialties on the medical contraindications to organ possible that given all the information I might have GIl 6NTdonation and disagreements also within specialties.We then regarded transplantation to be contraindicated, J Douglas Briggs, consultant investigated these possibilities and report here our but maybe the bottom line is that it is a relatively easy renal physician results.thing to discuss the doubtful cases with the transplant team and let it be a shared decision as to whether St Mary's Hospital, patients are offered for transplantation or not."London W2 iNY Methods
Competition between sympathetic vasoconstriction and metabolic vasodilation in the canine coronary circulation.
Authors: D E Mohrman, E O Feigl
Journal: Circulation Research (1978)

The role of a-receptor constriction of coronary vessels in response to cardiac sympathetic activation was evaluated in closed-chest, chloralose-anesthetized dogs.Cardiac sympathetic activation was produced (1) directly by intracoronary norepinephrine infusion at several different rates and (2) reflexly by carotid sinus hypotension.The resulting changes in coronary blood flow and myocardial oxygen consumption were recorded before and after a-receptor blockade with dibozane (3.0 mg/kg, iv) or phenoxybenzamine (0.5 mg/kg, intracoronary).The changes in coronary blood flow were normalized to changes in myocardial metabolism by division of the oxygen delivery (coronary flow times arterial oxygen content) by the change in myocardial oxygen consumption per 100 g of myocardium.Before a-receptor blockade, either intracoronary norepinephrine infusion or reflex sympathetic activation from the carotid sinus resulted in an increase of only 0.85 ml/100 g mirr' in oxygen delivery for each increase of 1 ml/100 g min" 1 in cardiac oxygen consumption.Under these circumstances, myocardial oxygen extraction increased and coronary venous oxygen content fell.After a-receptor blockade, either intracoronary norepinephrine infusion or a carotid sinus reflex resulted in an increase of 1.23 ml/100 g min ' in oxygen delivery for each increase of 1 ml/100 g min' 1 in cardiac oxygen consumption.Myocardial oxygen extraction and coronary venous oxygen content changed only slightly after a-receptor blockade.The greater coronary vasodilation and lesser change in cardiac oxygen extraction after a-receptor blockade were significantly different (P < 0.001) from the values before blockade.It is concluded that the coronary a-receptor constrictor mechanism competes with metabolic vasodilation during sympathetic activation even when there are large increases in myocardial metabolism.The net effect of the a-receptor constrictor influence is to restrict the metabolically related flow increase by about 30%, thus increasing oxygen extraction and decreasing coronary venous oxygen content.IT HAS LONG been known that stimulation of the sympathetic innervation of the heart results in tachycardia and augmented contractility, accompanied by increased myocardial oxygen consumption, increased coronary blood flow, and decreased coronary sinus oxygen content. 1 " 8 Coronary sinus oxygen content decreases because
Prognostic significance of cardiac cinefluoroscopy for coronary calcific deposits in asymptomatic high risk subjects
Authors: Robert C. Detrano, Nathan D. Wong, Weiyi Tang, William J. French, Demetrios Georgiou, Eddy Young, Oleh S. Brezden, Terence M. Doherty, Kenneth A. Narahara, Bruce H. Brundage
Journal: Journal of the American College of Cardiology (1994)
DEFIBRILLATION THRESHOLD TESTING DURING IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR IMPLANTATION IMPAIRS CARDIAC SYSTOLIC AND DIASTOLIC FUNCTION AND PROLONGS BLOOD PRESSURE RECOVERY IN PATIENTS WITH HEART FAILURE
Authors: Norihisa Toh, Nobuhiro Nishii, Kazufumi Nakamura, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito
Journal: Journal of the American College of Cardiology (2011)
What is the place of laser lithotripsy in the treatment of common bile duct stones?
Authors: T. Saurebruch
Journal: Hepatology (1989)

Endoscopic retrograde laser lithotripsy of common bile duct stones is a new technique which can be carried out through the endoscope without anaesthesia using ordinary endoscopic equipment. In the method described here a flashlamp pulsed Neodymium YAG laser (wave length 1064mm) was used. Light energy was transmitted along a highly flexible quartz fibre with a diameter of 0.2mm. This new technique was used in nine patients with concrements in the common bile duct, which could not be removed with the established endoscopic techniques. In eight of the nine the concrements (maximum diameter 4.7 × 3.1 cm) could be fragmented and in six the fragments could be extracted from the common bile duct. The total energy required was 80-300J; complications were not observed.
Diabetes in Urban African-Americans. I. Cessation of Insulin Therapy Is the Major Precipitating Cause of Diabetic Ketoacidosis
Authors: Victoria C Musey, Jenny K Lee, Rochanda Crawford, Morel Ann Klatka, Debra McAdams, Lawrence S Phillips
Journal: Diabetes Care (1995)

OBJECTIVE To identify the causes of diabetic ketoacidosis (DKA) in a large urban hospital. RESEARCH DESIGN AND METHODS Consecutive patients admitted during a 3-month period with a primary diagnosis of DKA and who had moderate-to-severe illness as shown by serum glucose &amp;gt;13.9 mmol/l (&amp;gt;250 mg/dl), bicarbonate &amp;lt;15 mmol/l, and pH &amp;lt;7.35 were studied. Diabetes nurse educators interviewed patients and reviewed their medical records for the following: precipitating causes of DKA; content of previous diabetes education; frequency of blood glucose monitoring; recognition of symptoms of metabolic decompensation; and types of medical assistance obtained once patients were ill. RESULTS There were 56 episodes of DKA, and 75% of the episodes were in patients with known diabetes. In the known diabetic patients, the most common cause of DKA was stopping insulin therapy, which occurred in 67% of episodes. Half of the patients (50%) stopped insulin because of reported lack of money to buy insulin from an outside pharmacy or get transportation to the hospital; 21% stopped insulin because of lack of appetite; 14% stopped insulin because of behavioral or psychological reasons; and 14% did so because they did not know how to manage diabetes on sick days. Of the known diabetic patients, &amp;gt;80% recalled having been instructed as to blood glucose testing and acute and chronic complications, but fewer patients recalled having been instructed as to insulin dose adjustment (28%) or sick day management (35%). Symptoms of decompensated diabetes were recognized in 55% of the 42 episodes of DKA in patients with known diabetes. However, only 5% of patients contacted the Diabetes Unit when they became ill; the majority (95%) went directly to the emergency room. CONCLUSIONS DKA occurred most often in patients with known diabetes who stopped insulin therapy because of reported lack of money for purchasing insulin or for transportation to the hospital and limited self-care skills in diabetes management. In urban African-American populations, up to two-thirds of the episodes of DKA may be preventable by improving patient education and access to care.