tbuckley/cabot-search huggingface dataset:
The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle
Authors: Francisco Ferrezuelo, Neus Colomina, Bruce Futcher, Martí Aldea
Journal: Genome biology (2010)

The G1-to-S transition of the cell cycle in the yeast Saccharomyces cerevisiae involves an extensive transcriptional program driven by transcription factors SBF (Swi4-Swi6) and MBF (Mbp1-Swi6). Activation of these factors ultimately depends on the G1 cyclin Cln3.To determine the transcriptional targets of Cln3 and their dependence on SBF or MBF, we first have used DNA microarrays to interrogate gene expression upon Cln3 overexpression in synchronized cultures of strains lacking components of SBF and/or MBF. Secondly, we have integrated this expression dataset together with other heterogeneous data sources into a single probabilistic model based on Bayesian statistics. Our analysis has produced more than 200 transcription factor-target assignments, validated by ChIP assays and by functional enrichment. Our predictions show higher internal coherence and predictive power than previous classifications. Our results support a model whereby SBF and MBF may be differentially activated by Cln3.Integration of heterogeneous genome-wide datasets is key to building accurate transcriptional networks. By such integration, we provide here a reliable transcriptional network at the G1-to-S transition in the budding yeast cell cycle. Our results suggest that to improve the reliability of predictions we need to feed our models with more informative experimental data.
Filing Systems for Medical Literature
Authors: Malvin Cole
Journal: JAMA (1979)

To the Editor.—  Karl Singer, MD, reported inThe Journala system of journal data retrieval. With one or two small modifications, I have known this as the Jeghers' system and have used this excellent retrieval system since 1954. The system was taught to me by Harold Jeghers, MD, while I was a medical student at Georgetown University. I highly recommend it.
Randomized trial of fluconazole versus low‐dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation
Authors: L.P. Koh, A. Kurup, Y.T. Goh, S.M.C. Fook‐Chong, P.H.C. Tan
Journal: American Journal of Hematology (2002)

Abstract Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low‐dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug‐associated toxicity was suspected, or systemic fungal infection was suspected or proven. High‐dose amphotericin B (0.5–1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad‐spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P &gt; 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P &gt; 0.05). We conclude that fluconazole is as effective as low‐dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation. Am. J. Hematol. 71:260–267, 2002. © 2002 Wiley‐Liss, Inc.
PTU-050 Efficacy of Endoscopically Applied 5% Intra-Rectal Formalin to Treat Radiation-Induced Rectal Bleeding
Authors: H Jolly, A C Muls, H J Andreyev
Journal: Gut (2013)

<h3>Introduction</h3> Up to 50% of patients develop rectal bleeding after pelvic radiotherapy. Radiation-induced bleeding may be trivial and after appropriate endoscopic assessment, patients can be reassured and do not need treatment. Others develop troublesome bleeding affecting quality of life. 1–5% become transfusion dependent. The optimal treatment of radiation-induced bleeding and safety of available treatment modalities is controversial. <h3>Methods</h3> A service evaluation was performed to assess outcomes of patients treated with intra-rectal formalin for radiation-induced rectal bleeding. Patients were offered formalin treatment if bleeding affected quality of life, they had no evidence of rectal ulceration and bowel function had been otherwise optimised. 5% formalin was delivered to the rectum using a gastroscope after full bowel preparation with the unsedated patient lying prone. Wet gauze was firmly applied to the perineum to prevent formalin leakage. 30–35mls formalin, sufficient to cover the telangiectasia, was instilled. The gastroscope was not removed. After 3 minutes, the formalin was washed out with water. If required, treatments were repeated 6–8 weeks later. Patients completed a questionnaire before each treatment and at follow-up. They were also asked to indicate on a 10cm visual analogue scale (VAS) the degree of nuisance currently caused by bleeding. <h3>Results</h3> 27 men, median age 73 (range 56–81) were treated between 2008 and 2012. All received radiotherapy for prostate cancer in the previous 4 years. 41% (n = 11) had required ≥1 blood transfusions, 48% (n = 13) iron supplementation. 52% (n = 14) regularly soiled their clothes with blood. 22% (n = 6) had not responded to previous argon plasma coagulation. Median follow-up was 28 months (range 2–48). 67% (n = 18) reported improvement; reduction in frequency (52%, n = 14), and/or amount (44%, n = 12) of bleeding. Patients required 1–4 treatments (median 2) to achieve adequate improvement. Median baseline VAS score was 6.7cm (range 4.3–9.9). After one treatment, VAS scores improved by a median of 2.5cm (range 0.6–5.0), after 2 treatments by 3cm from baseline (range 0.7–6.1cm) and at follow up by 3.8cm (range 0–8.7). Two patients experienced serious complications. One who had chronic lymphocytic leukaemia developed septicaemia and pneumonia the following day. The organism responsible was not a bowel organism. The other developed an anterior rectal wall fistula in an area of intense radiation change requiring surgery 18 months later. Neither complication was considered to be caused by the formalin. <h3>Conclusion</h3> 67% patients with radiation-induced rectal bleeding experience a satisfactory reduction in bleeding following treatment with intra-rectal formalin. Further studies comparing with other treatment modalities are required. <h3>Disclosure of Interest</h3> None Declared
International differences in patients, care, and outcomes associated with acute myocardial infarction: the hero-2 trial
Authors: John Simes, Harvey D. White, Ian C. Marschner, Sergei Varshavsky, Rafael Diaz, Robert G. Wilcox, Paul W. Armstrong, Chris B. Granger, John K. French, Frans Van de Werf, Philip E. Aylward
Journal: Journal of the American College of Cardiology (2002)
Phase II trial of high-dose dexamethasone for previously treated immunoglobulin light-chain amyloidosis
Authors: Morie A. Gertz, Martha Q. Lacy, John A. Lust, Philip R. Greipp, Thomas E. Witzig, Robert A. Kyle
Journal: American Journal of Hematology (1999)

Immunoglobulin light-chain amyloidosis (AL) is a rare disorder characterized by production of a monoclonal light chain. This insoluble light chain, or a fragment thereof, deposits in tissues as amyloid and results in disruption of organ function and, ultimately, in death. Although melphalan and prednisone are beneficial in approximately 30% of patients with the disease, many patients fail to respond, and the median survival with this disease remains < 2 years. There is a need for new agents for those patients who fail to respond to melphalan-based chemotherapy. A study was undertaken of high-dose dexamethasone in the treatment of 19 patients with AL because of reports of its benefits in previously untreated patients with amyloidosis and its known activity in the management of multiple myeloma, which has many characteristics in common with AL. In this cohort, 3 of 19 patients showed an objective organ response of the disease. The median survival of the entire group was 11.2 months. We conclude that high-dose dexamethasone therapy is of occasional benefit in patients previously treated for amyloidosis. Combining dexamethasone with other therapies may increase the response rate.
Effect of ethanol on polyamine synthesis during liver regeneration in rats.
Authors: A M Diehl, M Wells, N D Brown, S S Thorgeirsson, C J Steer
Journal: Journal of Clinical Investigation (1990)

Ethanol consumption retards the hepatic regenerative response to injury. This may contribute to the pathogenesis of liver injury in alcoholic individuals. The mechanisms responsible for ethanol-associated inhibition of liver regeneration are poorly understood. To determine if the antiregenerative effects of ethanol involve modulation of polyamine metabolism, parameters of polyamine synthesis were compared before and during surgically induced liver regeneration in ethanol-fed rats and isocalorically maintained controls. After partial hepatectomy, induction of the activity of ornithine decarboxylase (ODC), the rate limiting enzyme for polyamine synthesis, was delayed in rats that had been fed ethanol. This was correlated with reduced levels of putrescine, ODC's immediate product. Increases in hepatic spermidine and spermine were also inhibited. Differences in ODC activity between ethanol-fed and control rats could not be explained by differences in the expression of ODC mRNA or by differences in ODC apoenzyme concentrations, suggesting that chronic ethanol intake inactivates ODC posttranslationally. Supplemental putrescine, administered at partial hepatectomy and 4 and 8 h thereafter, increased hepatic putrescine concentrations and markedly improved DNA synthesis and liver regeneration in ethanol-fed rats. These data suggest that altered polyamine metabolism may contribute to the inhibition of liver regeneration that occurs after chronic exposure to ethanol.
Alternate-Day Amphotericin B Therapy in the Treatment of Rhinocerebral Phycomycosis (Mucormycosis)
Authors: DENNIS J. BATTOCK
Journal: Annals of Internal Medicine (1968)

Successful treatment of rhinocerebral phycomycosis is limited because of late diagnosis, resistance of the etiological agents to antifungal drugs, inaccessibility of the lesions, and the fulminant nature of the disease, especially in the patient with diabetic acidosis. Two diabetic patients with rhinocerebral phycomycosis and acidosis were successfully treated by [1] alternate-day amphotericin B administered intravenously at 1.2 mg/kg body weight, [2] control of the diabetic acidosis, [3] local surgical excision of involved sinus tissues, and [4] irrigation of paranasal sinuses with amphotericin B. Mean 48-hr serum levels of amphotericin B were 0.34 µg/ml and 0.45 µg/ml in the two patients. The minimal inhibitory concentration of amphotericin B for Rhizopus oryzae in one patient was 1,000 µg/ml. Although the high blood level of amphotericin B needed to inhibit growth of the organism is unattainable using ordinary doses, the drug is known to be effective in vivo in phycomycete-infected animals and should be part of the therapeutic regimen in human phycomycosis. Creatinine clearance was found to be a more sensitive parameter of renal function than blood urea nitrogen or serum creatinine and was decreased in both patients during treatment with amphotericin B. Ater the drug was discontinued, creatinine clearance returned to normal levels in one patient and to near-pretreatment levels in the second patient. Alternate-day therapy with intravenously administered amphotericin B produced serum levels of the drug 48 hr after infusion that are considered to be adequate for most of the systemic mycotic agents. This regimen was tolerated better by the patients and may have offered less hazard of renal damage during treatment than daily therapy.
Acute Mononitrobenzene Poisoning
Authors: J. D. N. Nabarro
Journal: BMJ (1948)

SunmaryAn example of acute porphyria occurring in a young man is described.Abdominal and mental symptoms and neurological signs were present.Pigmentation and photosensitivity were conspicuous features.There was some evidence of a familial distribution of the disease.I am indebted to Dr. G. H. Jennings for his encouragement and permission to publish this report; to Prof. C.
Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis.
Authors: W A Franklin, A F Gazdar, J Haney, I I Wistuba, F G La Rosa, T Kennedy, D M Ritchey, Y E Miller
Journal: Journal of Clinical Investigation (1997)

Individuals with one aerodigestive tract malignancy have a high incidence of second primary aerodigestive tumors. The mechanism for this field effect has not been determined. We studied an individual with widespread dysplastic changes in the respiratory epithelium but no overt carcinoma. The entire tracheobronchial tree obtained at autopsy was embedded in paraffin, and bronchial epithelial cells were isolated by microdissection. DNA extracted from the microdissected cells was analyzed for point mutations in the p53 tumor suppressor gene. A single, identical point mutation consisting of a G:C to T:A transversion in codon 245 was identified in bronchial epithelium from 7 of 10 sites in both lungs. Epithelium at sites containing the p53 mutation was morphologically abnormal, exhibiting squamous metaplasia and mild to moderate atypia. No invasive tumor was found in the tracheobronchial tree or any other location. Cells from peripheral blood, kidney, liver, and lymph node exhibited no abnormality in the p53 gene. The widespread presence of a single somatic p53 point mutation in the bronchi of a smoker suggests that a single progenitor bronchial epithelial clone may expand to populate broad areas of the bronchial mucosa-a novel mechanism for field carcinogenesis in the respiratory epithelium that may be of importance in assessing individuals for risk of a second primary tumor as well as in devising effective strategies for chemoprevention of lung cancer.
Echinococcus Disease of the Left Ventricle
Authors: EDUARDO JOAQUÍN CANABAL, CÉSAR V. AGUIRRE, JORGE DIGHIERO, JOAQUÍN PURCALLAS, JOSÉ M. BALDOMIR, CARLOS V. SUZACQ
Journal: Circulation (1955)

The subject of echinococcus disease of the left ventricle is discussed from the clinical, radiologic, and electrocardiographic point of view. Up to the present very few cases of this condition have been reported in the world literature. In most instances the diagnosis has been made by postmortem examination. The diagnostic criteria presented in this paper may be helpful in the recognition of this disease which, if treated by surgery, may be another form of "reversible" heart disease.
New Convertible Stethoscope
Authors: J. W. Cousins
Journal: BMJ (1882)

THE BRTA7SH MEDICAL 7OUAAAL._ 45wooded ravines, which impart a picturesque beauty to the scene.The highest point in the district is nearly 1300 feet above the sea-level ; and here, in a hamlet close by, I have found cases of goitre.The villages are met with in three situations: (i) on the mountainous moorland ;(2) in the wooded valleys; and (3) on the fertile plain-in all, goitre is to be found.The district may be said, geologically, to stand on the middle and upper oolitic formations.The plain consists of alluvium, upon Kimmeridge clay, in which iron pyrites is found.The hills are mostly tabular, and consist of Kellaways rock, Oxford clay, and calc grit.In one valley alone, at the extreme western boundary of my district, is the Has formation met with.The remaining geological de- tails (for which I am indebted to Mr. C. Fox Strangways, F.G.S.
SLAM/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte-derived dendritic cells
Authors: Bence Réthi, Péter Gogolák, Istvan Szatmari, Ágota Veres, Erika Erdôs, Laszlo Nagy, Éva Rajnavölgyi, Cox Terhorst, Árpád Lányi
Journal: Blood (2005)
Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel
Authors: Jong-Ho Kim, Yoo-Shin Kim, Sungwon Kim, Jae Hyung Park, Kwangmeyung Kim, Kuiwon Choi, Hesson Chung, Seo Young Jeong, Rang-Woon Park, In-San Kim, Ick Chan Kwon
Journal: Journal of Controlled Release (2006)
THE REACTION MECHANISM OF HUMAN C5 IN IMMUNE HEMOLYSIS
Authors: Neil R. Cooper, Hans J. Müller-Eberhard
Journal: The Journal of Experimental Medicine (1970)

The data presented here indicate that the C5 reaction step may proceed via the specific attachment of C5 to EAC1,4,2,3 and the formation of a hemolytically active C5 intermediate complex. During this process only a minor proportion (less than 4%) of C5 offered to EAC1,4,2,3 becomes bound, although the remaining C5 also participates in the reaction as evidenced by its inactivation in the fluid phase. Once bound, C5 is exceptionally efficient in producing hemolysis, requiring less than seven specifically bound molecules per cell for the production of a hemolytic lesion. The extent of formation of the C5 intermediate complex is primarily dependent on the number of molecules of C4, 2 and C3 present on the cells employed for its generation. In these respects, the mode of action of C5 is completely analogous to that of the other components of complement thus far investigated. The C5 step differs, however, in other aspects. The binding of C5 is influenced by C6 and C7, components which are thought to act subsequent to it in the complement sequence. In addition, the hemolytic activity of the isolated C5 intermediate complex is exceedingly labile, having an average half-life at 30 degrees C of only 9 min. This characteristic distinguishes the C5 step, along with the C2 step, as potentially rate-limiting in the complement reaction. However, unlike C2, C5 remains firmly cell-bound during the decay process and apparently undergoes an alteration in situ which renders it hemolytically unreactive. Finally, C5 is unique in that it readily adsorbs in native form to unsensitized erythrocytes. This nonspecifically bound C5 remains firmly attached, although it may be specifically utilized as a source of C5 by an ongoing complement reaction. The significance of the marked affinity of native C5 for cell-surface receptors remains to be determined.
Compliance, cost, and common sense limit cancer control in colitis.
Authors: J E Lennard-Jones
Journal: Gut (1986)

Leading articleCompliance, cost, and common sense limit cancer control in colitis In this issue a Swedish group' describe the results of a cancer surveillance programme over eight years in 71 patients with long standing extensive or substantial colitis.Their well presented study adds support to the development of such programmes which have also been reported from a number of other centres.In an elegant application of decision theory, Gage2 has shown that a patient's five year survival is likely to be better with surveillance, despite its limitations, than with operation advised solely on the basis of extent of disease and a long history.His analysis is, however, limited to a decision late in the course of the illness and misses the point that preventive surgery to be most successful should be undertaken during the lag phase before the cancer risk begins to rise.His analysis is concerned with the early treatment of carcinoma, using dysplasia as a marker, rather than regarding colectomy for dysplasia without carcinoma as the optimal result.The ideal of colectomy at the stage of dysplasia in all patients has not so far been achieved and carcinoma tends to develop in association with dysplasia, or less commonly without, as in the Swedish series.The advantages of a surveillance programme thus have to be assessed as presumed prevention of cancer by removing a dysplastic colon in some patients and early treatment of carcinoma by colectomy in others.The carcinoma risk in colitis is best assessed by life table analysis, though such calculations can be misunderstood and give the impression that the actual cancer risk is higher than it is.The classic actuarial analysis gives the probability of survival when every death is included as in the Registrar General's life expectancy tables.It is then possible to calculate the cumulative mortality of the original cohort in successive age periods.In calculations of cancer risk in colitis, however, many patients are withdrawn from the analysis during successive years because they have a procto- colectomy or die from various causes, particularly in older age groups.The calculation gives the risk of carcinoma among those who remain under follow up which is the clinically relevant figure because they are the patients we have to advise.To say that this risk applies to the original cohort, however, expresses the belief that those patients who had surgery or died would have been subject to a similar risk if they had lived or kept their colon.The actual risk among the original cohort is overestimated because some of the members never have the opportunity to develop carcinoma.The term life table has a connotation of mortality and it may be thought that the development of a carcinoma in colitis is invariably fatal.In fact, survival is at least 30% in the next five years in all cases,3 and greater if the tumour is treated before distant spread has occurred.45 Advice to patients is based on the duration of their disease, its extent, 1403