tbuckley/cabot-search huggingface dataset:
Improved Grading of Breast Adenocarcinomas Based on Genomic Instability
Authors: Ulrike Kronenwett, Sören Huwendiek, Carin Östring, Neil Portwood, Uwe J. Roblick, Yudi Pawitan, Ayodele Alaiya, Roland Sennerstam, Anders Zetterberg, Gert Auer
Journal: Cancer Research (2004)

Abstract Numerous investigations have shown that in primary breast adenocarcinomas DNA aneuploidy in contrast to DNA diploidy indicates high malignancy potential. On the basis of the study of 104 breast carcinomas, we describe a subtype of aneuploidy, which demonstrates a low degree of malignancy. In image cytometric DNA histograms, this subtype possessed a low percentage (≤8.8%) of nonmodal DNA values as measured by the stemline scatter index (SSI), which is defined as sum of the percentage of cells in the S-phase region, the G2 exceeding rate and the coefficient of variation of the tumor stemline. The cut point of SSI = 8.8% (P = 0.03) enabled us to also subdivide diploid and tetraploid tumors into clinically low and high malignant variants. One possible reason for aneuploidy is impaired distribution of chromosomes at mitosis caused by numerical or structural centrosome aberrations. Cyclins A and E seem to be involved in centrosome duplication. Real-time quantitative PCR measurements of cyclin A and E transcript levels and immunohistochemical determination of cyclin A protein expression showed statistically significantly increased values in the tumors with a high SSI (&amp;gt;8.8%), compared with those with a low SSI. A pilot study demonstrated centrosomal aberrations in an average of 9.6% of the measured cells in four aneuploid carcinomas with high SSI values and in an average of 2.5% of the cells in three aneuploid and three diploid tumors with low SSI. Our data indicate that the SSI, most likely reflecting the degree of genomic instability, allows additional classifying of the known aneuploid, diploid, and tetraploid categories of primary breast adenocarcinomas into low and high malignant subtypes.
A pathogenic role of visceral fat beta 3-adrenoceptors in obesity.
Authors: F Lönnqvist, A Thöme, K Nilsell, J Hoffstedt, P Arner
Journal: Journal of Clinical Investigation (1995)

Increased release of free fatty acids (FFA) from visceral fat cells to the portal venous system may cause several meta- bolic disturbances in obesity.However, this hypothesis and the underlying mechanism remain to be demonstrated.In this study catecholamine-induced lipid mobilization through lipolysis in omental adipose tissue was investigated in vitro in 25 markedly obese subjects (body mass index range 35- 56 kg/M2) undergoing weight reduction surgery and in 19 nonobese subjects (body mass index range 20-28 kg/m2) undergoing cholecystectomy.Release of FFA and glycerol, induced by norepinephrine or adrenergic receptor subtype- specific agonists, were determined in isolated omental fat cells.The obese subjects had higher fat cell volume, blood pressure, plasma insulin levels, blood glucose, plasma tri- glycerides, and plasma cholesterol than the controls.There was evidence of upper-body fat distribution in the obese group.The rate of FFA and glycerol response to norepinephrine was increased twofold in the cells of obese subjects; no significant reutilization of FFA during catecholamine- induced lipolysis was observed in any of the groups (glyc- erol/FFA ratio near 1:3).There were no differences in the lipolytic sensitivity to 183-or 182-adrenoceptor specific ago- nists between the two groups.However, .83-adrenoceptorsensitivity was 50 times enhanced (P = 0.0001), and the coupling efficiency of these receptors was increased from 37 to 56% (P = 0.01) in obesity.Furthermore, the obese sub- jects demonstrated a sixfold lower alpha2-adrenoceptor sen- sitivity (P = 0.04)..83-Adrenoceptorsensitivity, but not alpha2-, ,BI-, or 182-adrenoceptor sensitivity, correlated with norepinephrine-induced lipolysis (r = -0.67,P = 0.0001) and fat cell volume (r = -0.71,P = 0.0001).In conclusion, catecholamine-induced rate of FFA mobi- lization from omental fat cells is accelerated due to elevated rate of lipolysis in obesity, mainly because of an increased /33-adrenoceptor function, but partly also because of a de- creased alpha2-adrenoceptor function.This promotes an in- creased release of FFA to the portal system, which may contribute to the parallel metabolic disturbances observed
Genetic and clinical characterisation of familial adenomatous polyposis: a population based study
Authors: A-L Moisio
Journal: Gut (2002)

<b>Background:</b> Familial adenomatous polyposis (FAP) is a rare autosomal dominantly inherited disease predisposing to colon cancer and caused by germline mutations in the APC (adenomatous polyposis coli) gene. <b>Aims:</b> We conducted a population based study to evaluate the prevalence and clinical implications of APC mutations among Finnish FAP kindreds. A possible founder effect in parallel with previous observations in hereditary non-polyposis colon cancer (HNPCC) was addressed. <b>Patients:</b> Affected individuals from 65 kindreds were included. <b>Methods:</b> The APC gene was screened for mutations using the protein truncation test and heteroduplex analysis. Haplotype analysis was performed with four flanking microsatellite markers. Families that failed to show any mutations were scrutinised with Southern blot hybridisation and allelic expression analysis. <b>Results:</b> Thirty eight different germline mutations in APC were identified in 47 kindreds (72%). The majority of these mutations were novel and unique to each family. Although sharing the classical polyposis phenotype, families without detectable APC mutations differed from mutation positive families in the following respects: firstly, mean age at polyposis diagnosis was higher (38.6 years (48 individuals) <i>v</i> 30.0 years (140 individuals); p=0.001); and secondly, the proportion of kindreds lacking extracolonic disease was higher (6/18 <i>v</i> 5/47; p=0.04). <b>Conclusions:</b> Our results may pave the way for predictive testing in mutation positive families and should stimulate further molecular studies in mutation negative families. No founder effect was observed, which is in contrast with HNPCC in the same population.
In situ characterization of CD4+ T cell behavior in mucosal and systemic lymphoid tissues during the induction of oral priming and tolerance
Authors: Bernd H. Zinselmeyer, John Dempster, Alison M. Gurney, David Wokosin, Mark Miller, Hsiang Ho, Owain R. Millington, Karen M. Smith, Catherine M. Rush, Ian Parker, Michael Cahalan, James M. Brewer, Paul Garside
Journal: The Journal of Experimental Medicine (2005)

The behavior of antigen-specific CD4+ T lymphocytes during initial exposure to antigen probably influences their decision to become primed or tolerized, but this has not been examined directly in vivo. We have therefore tracked such cells in real time, in situ during the induction of oral priming versus oral tolerance. There were marked contrasts with respect to rate and type of movement and clustering between naive T cells and those exposed to antigen in immunogenic or tolerogenic forms. However, the major difference when comparing tolerized and primed T cells was that the latter formed larger and longer-lived clusters within mucosal and peripheral lymph nodes. This is the first comparison of the behavior of antigen-specific CD4+ T cells in situ in mucosal and systemic lymphoid tissues during the induction of priming versus tolerance in a physiologically relevant model in vivo.
Arthritis in acute febrile neutrophilic dermatosis (Sweet's syndrome)
Authors: J M Nolla, X Juanola, J Valverde, D Roig-Escofet, X Pagerols, O Servitge
Journal: Annals of the Rheumatic Diseases (1990)

Letters to the editor showed signs of lung inflammatory activity.The electromyographic examination showed involvement of the left trigeminal nerve.Typical sclerodermal abnormalities were found by capillaroscopy and in the oesophageal examinations with barium swallow and mano- metric recordings.The diagnosis of systemic sclerosis was established according to the American Rheumatism Association criteria.Because of the lung abnormalities he received 1 mg/kg a day of prednisone with stepwise dose reduction in the ensuing six months.There was a favourable clinical evolution with normalisation of the lung 67Ga scan and defmite improvement of the spirometric recordings.Six months later he complained of impotence with a preserved libido and normal ejaculation.Examination of the external genitalia showed a uniform induration of the corpora cavernosa without involvement of the overlying skin.A pelvic radiography and an ultrasound examination of the penis showed no abnormalities.This patient is the third reported case with the association of two fibrotic disorders such as systemic sclerosis and Peyronie's disease.Our patient presented in addition bilateral Dupuytren's contractures, which suggests a common pathogenetic mechanism.In our series of 70 patients (63 women, seven men) this was the only case observed.In contrast with the other two reported male cases, our patient had a more extensive involvement of the penis.Probably the incidence of this complication is greater than one would infer from the few reported cases.On the one hand, patients may be reluctant to discuss their symptoms and, on the other, there are no prospective studies aimed at establishing the true incidence of Peyronie's disease in systemic sclerosis.This complication may cause impotence, although as noticed by other authors the more common cause of impotence in patients with scleroderma is the vascular involvement that limits the blood flow of the arteries of the penis.6Treatment of Peyronie's disease seems diffi- cult.Several approaches, such as steroids, vitamin E, or p-aminobenzoic acid, have been tried without success.Surgical approaches, such as the removal of the fibrotic plaques and placement of a skin graft, have also been tried with variable success.In a few cases spon- taneous regression of the plaques has occurred.Treatment seems indicated in the initial stages of the disease, when signs of an acute inflam- matory process are present.In this patient we considered the possibility of placing a prosthetic device, a procedure that so far the patient is not willing to undergo.Further studies are needed to clarify the relation between these two disorders.
Clinical features of Old World cutaneous leishmaniasis in elderly patients
Authors: M.J. Yazdanpanah, M. Banihashemi, S.M. Mohammadi, Z. Hatami, F. Livani, H. Esmaili, V. Mashayekhi-Goyonlo
Journal: British Journal of Dermatology (2014)

Funding sources: The research council of the Mashhad University of Medical Sciences, Mashhad, Iran financially supported this study, grant number 6572. Conflicts of interest: none declared. Dear Editor, Leishmaniasis encompasses a group of chronic infections caused by over 20 species of the Leishmania genus. It is transmitted by sandflies between animal and human hosts and accounts for a complicated health problem in endemic areas, often of developing countries.1 The elderly population has specific health characteristics: alterations in the immune system,2 hormonal changes,3 altered attention to illness and treatment, irregular and multiple drug consumption, comorbidities and different disease presentations.4 5 Müller et al.2 have shown that in older rats the severity of leishmaniasis lesions and the number of parasites were less than in younger rats. Davies et al.6 have reviewed the epidemiology of leishmaniasis in five countries in South America; they reported a lower number of lesions in older people. However, Guessous‐Idrissi et al.7 indicated more severe and larger lesions in older patients in an epidemiological study in north Morocco. A shortage of studies about leishmaniasis in the elderly population and their contradictory results encouraged us to conduct a descriptive prospective study between April 2010 and March 2011 on confirmed cases of cutaneous leishmaniasis in Mashhad, Iran, to evaluate the clinical features of cutaneous leishmaniasis in two age groups: a younger group (age ≤ 20 years) and an older group (age ≥ 60 years). Demographic data, the past medical history of the patients, and the site, number, size and duration of the lesions were recorded. The clinical manifestation and the pattern of lesions were categorized as stated in Table 1. The area of lesions was calculated as a circle, the diameter of which was the mean of the largest and smallest diameter of each lesion.
Clinical and Laboratory Features of Murine Typhus in South Texas, 1980 Through 1987
Authors: J. Stephen Dumler
Journal: JAMA (1991)

--The clinical and laboratory features of patients with murine typhus have not been extensively reviewed since 1946. We have updated these findings in patients from south Texas who were examined by modern clinical and laboratory methods from 1980 through 1987.--Patients were identified by serological methods in this case series, and clinical, epidemiologic, laboratory, and therapeutic data were compiled and analyzed.--The majority of patients (77 of 80) were identified in a primary care community hospital setting; the remainder (3 of 80) were ambulatory hospital outpatients.--From 1980 through 1987, a total of 345 patients were diagnosed with murine typhus; 90 of these patients were seen at four hospitals in south Texas; of these, 80 had clinical and laboratory data available for review.--The frequency of common clinical manifestations (eg, headache, fever, and rash) and laboratory findings (eg, leukocyte and platelet counts and serum chemistry abnormalities) of patients with infectious diseases was tabulated. Clinical severity was semiquantitatively assessed and was correlated with clinical, laboratory, and therapeutic results.--Most cases (69%) occurred from April through August. Rash occurred in 54%; the triad of fever, headache, and rash was observed in only 12.5% of patients when first examined by a physician; respiratory and gastrointestinal symptoms were also frequent. Multiple organ involvement was documented by frequent abnormal laboratory findings of the hematologic, respiratory, hepatic, and renal systems. Disease severity was related to older patient age, the presence of renal dysfunction, leukocytosis, and hypoalbuminemia, and previous therapy with sulfa antibiotics.--Infection by Rickettsia typhi causes a systemic illness with clinical and laboratory abnormalities not previously recognized or described. Early clinical diagnosis and treatment are needed to avoid undue morbidity and mortality.
Can Psychiatry Cross the Quality Chasm? Improving the Quality of Health Care For Mental and Substance Use Conditions
Authors: Harold Alan Pincus, Ann E.K. Page, Benjamin Druss, Paul S. Appelbaum, Gary Gottlieb, Mary Jane England
Journal: American Journal of Psychiatry (2007)

In 2001, a seminal Institute of Medicine report, Crossing the Quality Chasm: A New Health System for the 21st Century , put forth a comprehensive strategy for improving the quality of U.S. health care. This strategy attained considerable traction within the overall U.S. health care system and subsequent attention in the mental health community as well. A new Institute of Medicine report, Improving the Quality of Health Care for Mental and Substance Use Conditions , examines the quality chasm strategy in light of the distinctive features of mental and substance use health care, including concerns about patient decision-making abilities and coercion into care, a less developed quality measurement and improvement infrastructure, lagging use of information technology and participation in the development of the National Health Information Infrastructure, greater separations in care delivery accompanied by more restrictions on sharing clinical information, a larger number of provider types licensed to diagnose and treat, more solo practice, and a differently structured marketplace. This article summarizes the Institute of Medicine's analysis of these issues and recommendations for improving mental and substance use health care and discusses the implications for psychiatric practice and related advocacy efforts of psychiatrists, psychiatric organizations, and other leaders in mental and substance use health care.
Characterization of a Topoisomerase II Gene Rearrangement in a Human Small-Cell Lung Cancer Cell Line
Authors: M. Binaschi, G. Giaccone, A. F. Gazdar, P. De Isabella, G. C. B. A. Ricotti, G. Capranico, F. Zunino
Journal: JNCI Journal of the National Cancer Institute (1992)

Small-cell lung cancer (SCLC) is a highly chemosensitive tumor, but the recurrent disease that is common after initial response is often unresponsive to further chemotherapy. Although the mechanisms of drug resistance in SCLC have not been established, studies suggest that alterations of the nuclear enzyme DNA topoisomerase II may reduce the sensitivity of the cell to drug action. This enzyme is recognized as a primary target for cytotoxic activity of important antitumor agents. In this study, we attempted to determine if altered forms of DNA topoisomerase II are responsible for reduced drug sensitivity. We characterized a rearrangement of the topoisomerase II p170 gene (also known as TOP2) in a relatively chemoresistant SCLC cell line, NCI-H69, and compared topoisomerase II expression and activity in this line with those in the chemosensitive NCI-H187 cell line. Fragments of complementary DNA from the topoisomerase II gene were generated by polymerase chain reaction. Immunodetec-tion was accomplished by using the monoclonal antibody 7E6 against the human topoisomerase II pl70 isoform. Using DNA probes corresponding to different complementary DNA regions, we showed that the rearrangement was localized at the 3′ terminus of one allele of the topoisomerase II gene. In addition to the normal 6.2-kilobase (kb) topoisomerase II messenger RNA (mRNA), the NCI-H69 line expressed a 7.4-kb topoisomerase II transcript, presumably encoded by the rearranged allele. Moreover, this transcript, although longer than the normal mRNA, lacked a substantial portion of the 3′-terminal pl70 gene coding sequence. Topoisomerase II activity in nuclear extracts, as determined by the P4 phage DNA-unknotting assay, was more easily detected and measured at lower NaCl concentrations in NCI-H69 than in NCI-H187 cells. These results are consistent with the hypothesis that the chemoresistant NCI-H69 cell line may express, in addition to the normal enzyme, an altered topoisomerase II enzyme possibly encoded by the 7.4-kb mRNA, which in turn may be transcribed from the rearranged gene allele. These observations emphasize the role of topoisomerase II in determining drug sensitivity and suggest that such gene rearrangements may contribute to resistance of SCLC cells to topoisomerase II inhibitors. [J Natl Cancer Inst 84:1710–1716, 1992]
Is histology required for the diagnosis of alcoholic hepatitis? a review of published randomised controlled trials
Authors: R. Hamid, E. H. Forrest
Journal: Gut (2011)

<h3>Introduction</h3> The need for liver biopsy to diagnose alcoholic hepatitis (AH) in the clinical setting remains controversial. Coagulopathy and/or ascites may preclude percutaneous biopsy and facilities for transjugular biopsy are not universally available. Despite this, some experts still advocate that biopsy confirmation of AH is a prerequisite for determining diagnosis, prognosis and treatment strategy for this condition. <h3>Aim</h3> The authors aimed to review the already published literature in the form of randomised controlled trials (RCTs) of therapy for AH. This was primarily to determine if these data could determine the need for histology in the selection of patients for study. <h3>Methods</h3> Studies published from 1970 to 2010 were identified through a MEDLINE computer search and manual search of the bibliographies of identified articles. Inclusion and exclusion criteria for each study were determined. The number of biopsies performed and the patients excluded as a consequence of incompatible histology were recorded. <h3>Results</h3> The authors identified 43 published RCTs trials, with adequate data available in 39. 11 of the trials required 'biopsy proven' AH prior to randomisation of patients, however the histological criteria for the diagnosis of AH varied widely between studies. Where figures were provided, it appears 1668 liver biopsies were undertaken in these trials with 1409 showing evidence of AH (84.5%). However if studies defined a minimum value of bilirubin (usually &gt;80–85 μmol/l) as an entry criterion, or the minimum value of bilirubin described was &gt;80 μmol/l, 96% of biopsies confirmed AH (405 of 422 biopsies: p&lt;0.0001 (95% CI 12.2% to 18.2% compared with studies without such stipulations). Where co-existent cirrhosis was mentioned, 839 of 1187 (70.7%) of biopsies had evidence of this. There was no correlation between the proportion of patients with cirrhosis and the mortality in the placebo treated patients (p=0.81; 95% CI −0.54 to 0.44). <h3>Conclusion</h3> Overall the diagnosis of AH is confirmed in over 80% of cases, but this clinical diagnostic accuracy increases to over 95% with a minimum value of bilirubin. Co-existent cirrhosis does not influence short-term prognosis. These data indicate that in most cases histology is not necessary for the diagnosis and management of AH.
Glomerular Endothelial Cells Form Diaphragms during Development and Pathologic Conditions
Authors: Koichiro Ichimura, Radu V. Stan, Hidetake Kurihara, Tatsuo Sakai
Journal: Journal of the American Society of Nephrology (2008)

Unlike most fenestrated capillary endothelial cells, adult glomerular endothelial cells (GEnC) are generally thought to lack diaphragms at their fenestrae, but this remains controversial. In this study, morphologic and immunocytochemical analyses demonstrated that, except for a small fraction, GEnC of adult rats lacked diaphragmed fenestrae, which contain the transmembrane glycoprotein PV-1. In contrast, the GEnC in embryonic rats exhibited diaphragmed fenestrae and expressed PV-1 protein. The luminal surface of the fenestral diaphragm possesses a high density of anionic sites, thereby compensating for the functional immaturity of the embryonic glomerular filtration barrier. In addition, GEnC with diaphragmed fenestrae and PV-1 expression were significantly increased in adult rats with Thy-1.1 nephritis, presumably reflecting a process of restorative remodeling of the glomerular capillary tuft after injury; therefore, the reappearance of PV-1 expression and diaphragmed fenestrae may serve as a marker of glomerular capillary remodeling.
Heparin‐induced thrombocytopenia: Association with a platelet aggregating factor and arterial thromboses
Authors: Philip L. Cimo, Joel L. Moake, Ronald S. Weinger, Yoram Ben‐Menachem, Kamal G. Khalil
Journal: American Journal of Hematology (1979)

Abstract Eleven patients with heparin‐induced thrombocytopenia were studied. Thrombocytopenia appeared 3–16 days following the initiation of prophylactic or therapeutic doses of heparin. The mean lowest platelet count recorded was 48,000/mm 3 . When heparin was stopped, recovery from thrombocytopenia began within 24 hours and was complete by ten days. Two patients developed fatal thromboses, and two others had myocardial infarctions while thrombocytopenic. In the serum of seven patients, including three of the four with arterial thrombosis, a heparin‐dependent platelet aggregating factor was present. The factor caused release of platelet 14 C serotonin but did not lyse platelets. It was present in the globulin fraction of all positive sera, and in one serum studied it was isolated in the IgG/IgA immunoglobulin fraction. The factor was not present in 16 normal sera or in the sera of 15 nonthrombocytopenic patients receiving heparin. Our observations suggest that heparin‐induced thrombocytopenia is common and that, in some patients it may be accompanied by severe arterial thrombosis. In vivo platelet aggregation is a possible explanation for the thrombocytopenia and the thrombosis in this disorder.