tbuckley/cabot-search huggingface dataset:
Thyroid Hormone Receptors Suppress Pituitary Tumor Transforming Gene 1 Activity in Hepatoma
Authors: Ruey-Nan Chen, Ya-Hui Huang, Chau-Ting Yeh, Chen-Hsin Liao, Kwang-Huei Lin
Journal: Cancer Research (2008)

Abstract Pituitary tumor transforming gene 1 (PTTG1) is expressed in most tumors. However, whether thyroid hormone (T3) and its receptors (TR) regulate PTTG1 in human hepatocellular carcinomas (HCC) remains unclear. Previous cDNA microarrays revealed PTTG1 is down-regulated by T3/TR. This study investigated the significance of PTTG1 regulation by T3 in HCC cells. The PTTG1 mRNA and protein expression were repressed by T3 in HCC cell lines overexpressing TR. However, after knockdown of TRs expression by RNA interference, PTTG1 repression by T3 was abolished. Similar results were observed in thyroidectomized rats. To localize the regulatory region in the PTTG1 promoter, serial deletions within the PTTG1 promoter region were constructed. The promoter activity of the PTTG1 gene was repressed (25–51%) by T3. Additionally, these findings indicate that PTTG1 may be regulated by Sp1. The critical role of the −594 and −520 Sp1 binding sites was confirmed by electrophoretic mobility shift assay. Transfection with Sp1 expression vector enhanced the activity of the PTTG1 promoter fragment reporter. Also, Sp1 was down-regulated in HCC cells and in thyroidectomized rat after T3 treatment. Additionally, ectopic expression of PTTG1 promotes cell proliferation in Hep3B hepatoma cells. Conversely, knockdown of PTTG1 or Sp1 expression reduced cell proliferation in HepG2 cells. Notably, the expression of PTTG1 and Sp1 was inversely correlated with the expression of TR proteins in HCC. Together, these findings indicate that PTTG1 gene expression is mediated by Sp1 and is indirectly down-regulated by T3. Finally, overexpression of PTTG1 or SP1 in HCCs is TR-dependent and crucial in the development of HCC. [Cancer Res 2008;68(6):1697–1706]
Tumour necrosis factor alpha stimulated rheumatoid synovial microvascular endothelial cells exhibit increased shear rate dependent leucocyte adhesion in vitro
Authors: S E Abbot, W J D Whish, C Jennison, D R Blake, C R Stevens
Journal: Annals of the Rheumatic Diseases (1999)

To investigate endothelial cell adhesion molecule expression and leucocyte adhesion to endothelial cells isolated from the microvasculature of rheumatoid arthritic synovial tissue (SMEC) in comparison with similar cells isolated from healthy subcutaneous adipose tissue (ADMEC) or from umbilical veins (HUVEC).Cultured endothelial cells were treated with tumour necrosis factor alpha (TNFalpha) for 2-24 hours before the assessment of cell surface E-selectin, vascular (VCAM-1) or intercellular cell adhesion molecule-I (ICAM-1) expression. Neutrophil and T lymphocyte adhesion to TNFalpha treated endothelial cells was assessed using static and shear dependent assay systems.VCAM-1 expression by SMEC was significantly less sensitive to TNFalpha stimulation than HUVEC or ADMEC. E-selectin expression by SMEC appeared to be more sensitive to TNFalpha stimulation and maximal expression was about 30% greater in comparison with HUVEC or ADMEC. Sensitivity to TNFalpha induction and maximal ICAM-1 expression was similar in all three endothelial cell types. Static neutrophil adhesion to TNFalpha stimulated SMEC was significantly increased in comparison with HUVEC, however this phenomenon was dependent on the presence of neutralising antibodies to ICAM-1. At shear rates in excess of 2.4 dynes/cm(2) significantly more neutrophils and, predominantly CD45RO+, T lymphocytes adhered to TNFalpha stimulated SMEC than HUVEC.Rheumatoid synovial endothelial cells differentially regulate E-selectin and VCAM-1. The increased ability of TNFalpha stimulated synovial endothelial cells to support leucocyte adhesion may help to explain the leucocyte, in particular CD45RO+ T-lymphocyte, recruitment observed in the rheumatoid synovium.
Acute cyclosporine-induced nephrotoxicity in renal transplant recipients
Authors: C Wissmann, F J Frey, P Ferrari, D E Uehlinger
Journal: Journal of the American Society of Nephrology (1996)

Cyclosporine A causes an acute reduction in GFR. The interindividual variable reduction in GFR is most likely the result of arteriolar vasoconstriction. Vasoconstriction is attributable either to a local effect of cyclosporine on renal blood vessels (intrinsic mechanism) or to a systemic effect of cyclosporine on circulating and/or neuronal factors (extrinsic mechanism). The aim of the investigation presented here was to establish whether intrinsic or extrinsic mechanisms account for the interindividual differences in the susceptibility to acute cyclosporine-induced nephrotoxicity. For that purpose, this study took advantage of the clinical transplant situation in which two (intrinsically identical) kidneys from a cadaveric donor are transplanted into two (extrinsically) different subjects. The preexisting regular daily cyclosporine doses were raised by 25% for 2 wk and by 50% for another 2 wk in 16 patients with stable renal graft function, representing eight pairs of patients, each of whom had received kidneys from the same donor. In these patients, a mean (+/- SD) maximum cyclosporine-induced increase in serum creatinine concentration of 13 +/- 11% (P < 0.001) and in serum BUN of 27 +/- 33% (P < 0.01), together with a decline in the fractional uric acid excretion of 51 +/- 89% (P < 0.02) were observed. The percentage change in serum creatinine concentrations after increased dosing of cyclosporine paralleled within the subjects receiving their kidneys from the same donor, i.e., when one recipient experienced a large percentage of change after increases of cyclosporine dosing, the corresponding recipient of a kidney from the same donor had a change of the same magnitude. Seven of eight pairs showed a consistent response with respect to a clinically significant increase in serum creatinine concentration of > 15%, with a consistent response purely by chance being < 5%. Thus, the transplanted kidney itself rather than the recipient determines the susceptibility to acute cyclosporine-induced nephrotoxicity.
Treatment of Bacillary Dysentery (Flexner) with Sulphapyridine
Authors: W. G. Masefield
Journal: BMJ (1941)

MEDICAL MEMORANDAEDICAL URNAL199days after a dose of diphtheria toxin-antitoxin.Vaughan and Pipes (1936) described a case very similar to the present one in which a severe reaction was caused by 0.1 c.cm. of anti-tetanic serum given intradermally.An interesting feature of our case was the rapidly spreading inflammation of lymphatic vessels and glands draining ;he site of injection.It is obvious that such a reaction must be due to the presence of some substance flowing along the lymphatic which causes dilatation of the surrounding capillaries as it travels.Whether this substance is the actual serum injected or some tissue product is unknown, but it is interesting to realize that 0.02 c.cm. of serum intra- dermally can produce such an intense and prolonged lymphangitis as was observed. SummaryA case of allergic shock after the intradermal injection of horse serum is described in a youth aged 18, who was also sensitive to poison ivy, pollen, and salmon protein.A severe systemic reaction was induced by as little as 0.02 c.cm. of serum given intradermally.The case emphasizes the importance of skin-testing before the therapeutic use of serum, particularly in patients with a family or personal history of allergic disease.
Functional hyposplenism in alcoholic liver disease: a toxic effect of alcohol?
Authors: A F Muller, P J Toghill
Journal: Gut (1994)

Functional hyposplenism, seen in some patients with alcoholic liver disease, may contribute to the increased susceptibility to infections. As hyposplenism does not complicate non-alcohol related chronic liver disease, it is probably secondary to a toxic effect of alcohol. Over a two year period the case notes of 82 patients with alcoholic liver disease, whose splenic function had been assessed by the counting of pitted erythrocytes using differential interference microscopy, were reviewed to monitor mortality and the effects of hyposplenism. Thirteen patients (seven with hyposplenism) had serial measurements of pitted erythrocyte count made to assess the effect of abstinence from alcohol on splenic function. Thirty one of the 82 alcoholic patients had pitted erythrocyte counts greater than 2%. Eighteen of 82 (16%) patients died over the two years and 11 of these had been unable to stop drinking. Only one patient died of sepsis. Five patients (6%) had pitted erythrocyte counts comparable with those in splenectomised patients. In 12 of 13 patients who had abstained from alcohol for two months, the pitted erythrocyte count fell from a median of 3 to 1.3% (mean: 8.1 to 2.6%. p = 0.01). The pitted red cell count in two patients increased. One had abstained, the other had continued to drink heavily. Short term mortality in alcoholics is high, particularly if they continue to drink heavily. Only a few of these deaths are secondary to infection. Splenic function, as assessed by these methods, improves in most patients with abstinence, suggesting that the functional hyposplenism may be a result of a direct toxic effect of alcohol on the spleen.
Tumorigenicity of Indian muntjac diploid cells by the proviral integration of sarcoma gene of a mouse retrovirus.
Authors: M Hatanaka, R Klein
Journal: The Journal of Experimental Medicine (1979)

The transformed clonal isolates of Indian muntjac diploid cells by a mouse sarcoma virus, 43-2XV, were tested for tumorigenicity in athymic nude mice. In spite of the indistinguishable transformed morphology, the tumorigenicity exhibited four different patterns: (a) no tumor formation; (b) slowly growing regressive tumor formation; (c) rapidly growing regressive tumor formation; and (d) rapidly growing progressive tumor formation. This demonstrates that the same diploid host cells transformed by the same virus reveal variable patterns of tumorigenic expression and some transformed host cells lack the tumorigenicity entirely. The findings that there are at least two chromosomes and four recombinant sites assigned for the proviral integrations of the sarcoma gene into the Indian muntjac gene (M. Hatanaka, R. Klein, R. Kominami, T. Oikawa, H. Okabe, N. Tsuchida, E. C. Connors, and A. Carrano. Transformation of Indian muntjac diploid cells by the proviral integration of sarcoma gene of a mouse retrovirus. Manuscript in preparation.) lead us to propose a hypothesis that variable expressions of tumorigenicity under the neutral background of immune responses, may arise from variable integrations of the sarcoma gene into the host chromosome.
The Effects of Clozapine and Risperidone on Spatial Working Memory in Schizophrenia
Authors: Susan R. McGurk, Cameron Carter, Robert Goldman, Michael F. Green, Stephen R. Marder, Haiyi Xie, Nina R. Schooler, John M. Kane
Journal: American Journal of Psychiatry (2005)

The purpose of this investigation was to evaluate the effects of clozapine and risperidone on spatial working memory in patients with schizophrenia.Spatial working memory performance was evaluated at baseline and after 17 and 29 weeks in 97 patients with schizophrenia participating in a multisite trial.Compared with baseline performance while receiving conventional antipsychotic medication, risperidone improved, and clozapine worsened, spatial working memory performance.The differential effects of these medications on spatial working memory may be due to the anticholinergic effects of clozapine and prefrontal dopamine-enhancing effects of risperidone.
Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers.
Authors: M J Taussig, A J Munro, R Campbell, C S David, N A Staines
Journal: The Journal of Experimental Medicine (1975)

Further mapping of the mouse T-cell factor specific for poly(Try,Glu)-polyD-LAla--polyLys is reported. It is shown to be a product of the I-A subregion of the H-2 complex by the use of antisera either raised specifically against or made specific, by absorption, for different regions of the H-2 complex. The factor cooperates across allogeneic barriers, e.g., when factor produced by one strian is combined with bone marrow cells of other H-2 incompatible strains.
THE COMMUNITY MENTAL HEALTH CENTRE
Authors: F. E. McNAIR
Journal: American Journal of Psychiatry (1965)

There has been an increased demand for psychiatric service since the advent of the regional clinic, and a wider service has been given than was previously possible. Utilization of service has been the greatest nearer the clinic. There has been a reduction in mental hospital admissions by one-half in two of the three health units served. The incidence of suicide has not been altered. The service depends greatly on other professional resources. The only limitation on the admission of cases to the psychiatric unit in the general hospital has been on the basis of their willingness to remain voluntarily, though this term is very broadly interpreted. Hospital care has not always been needed even for the acute psychotic or relapsing psychotic cases. Service has been the key to both professional and community acceptance of regional development. The initial population served has been 150,000 people, and this is far too many for one regional development. At the end of the year other provision was made for Kamloops and the South Central Health Unit. The greatest problem presented has been for the psychiatrist to get away from calls for additional demands for service in his free time. This service, to be effective, requires the development of new resources, such as more foster homes, group living homes, residential treatment centres for children, sheltered workshops and more hospital beds. The mental health clinic belongs thoroughly to the region it serves. The direction and pace of further development can be determined by the citizens of the region. There is much greater reliance on human resources than upon bricks and mortar.
Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age
Authors: G. de Meer, N. A. H. Janssen, B. Brunekreef
Journal: Allergy (2005)

There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions.Examine independent effects on atopic sensitization and symptoms of day care attendance, older siblings, pet ownership, and early infancy's airway disease.A cross-sectional survey among 8-13-year-old school children with complete data for 1555 children.After adjustment for confounders, atopic sensitization occurred less frequently in children that had attended a day care centre (OR: 0.73, 95% CI: 0.55-0.98) or had a cat or dog before 2 years of age (OR: 0.78, 95% CI: 0.61-0.99). Having older siblings yielded a nonsignificant trend towards protection (OR: 0.88, 95% CI: 0.70-1.11). For symptoms, there was no relation with having older sibs, day care attendance and pet ownership, although there was a trend towards protection for the combination of atopy and symptoms. In contrast, children with doctors' treated airway disease before age 2, more frequently reported recent symptoms of wheeze, asthma, rhinitis, or dermatitis (all P < 0.05).Early life environmental exposure to day care, or pets may protect against atopic sensitization. Protection against symptoms only occurred if atopic sensitization was present as well.
Improved Outcome When B-Cell Lymphoma Is Treated with Combinations of Immunoliposomal Anticancer Drugs Targeted to Both the CD19 and CD20 Epitopes
Authors: Puja Sapra, Theresa M. Allen
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We have reported previously that successful immunoliposomal drug therapy with liposomal doxorubicin (DXR) against xenograft B-lymphoma models required targeting against an internalizing B-cell antigen, CD19 (P. Sapra and T. M. Allen. Cancer Res 2002;62:7190–4.). Here we compare targeting of immunoliposomal formulations of DXR with vincristine (VCR) targeted against CD19 versus a noninternalizing (CD20) epitope. We also examine the effect of targeting immunoliposomes with antibody combinations in an attempt to increase the total number of binding sites (apparent antigen density) at the target cell surface. Experimental Design: Cell association of immunoliposomes (CD19-targeted, CD20-targeted, or combinations of the two) with human B-cell lymphoma (Namalwa) cells were studied using radiolabeled liposomes. Therapeutic efficacy of the same formulations was determined in a severe combined immunodeficient murine model. Results: Therapeutic results in severe combined immunodeficient mice bearing Namalwa cells administered anti-CD20-targeted liposomal DXR were barely improved over those found for nontargeted liposomal DXR or free DXR but, surprisingly, administration of anti-CD20-targeted liposomal VCR resulted in a significantly improved therapeutic outcome compared with nontargeted liposomal VCR, free VCR, or anti-CD20-targeted liposomal DXR. Treatment of murine B lymphoma with single injections of combinations of anti-CD19- and anti-CD20-targeted liposomal VCR led to cures in 70% of mice. However, mice injected with similar combinations of liposomal DXR did not have improved survival rates over anti-CD19-targeted liposomal DXR by itself. Conclusions: The success of immunoliposomal therapy in combination regimens varies with the type of encapsulated drug and the nature of the target epitopes.
No-Reflow Phenomenon and Lesion Morphology in Patients With Acute Myocardial Infarction
Authors: Atsushi Tanaka, Takahiko Kawarabayashi, Yoshiharu Nishibori, Toshihiko Sano, Yukio Nishida, Daiju Fukuda, Kenei Shimada, Junichi Yoshikawa
Journal: Circulation (2002)

Background — The no-reflow phenomenon is associated with poor functional and clinical outcomes for patients with acute myocardial infarction (AMI). In the era of primary intervention, accurately identifying lesions at high risk of no reflow is of crucial importance. At present, no study into the relationship between lesion morphology and no reflow has been performed. The aim of this study was to investigate the relationship between preintervention intravascular ultrasound (IVUS) lesion morphology and the no-reflow phenomenon. Methods and Results — This study comprised 100 consecutive patients with AMI who underwent preintervention IVUS and were successfully recanalized with primary balloon angioplasty or stenting. IVUS was again performed to identify and exclude any mechanical vessel obstruction in cases of thrombolysis in myocardial infarction flow grade 0, 1, or 2 after intervention in the absence of angiographic stenosis. Angiographic no reflow was seen in 13 patients (13%). Univariate analysis indicated that hypercholesterolemia, fissure and dissection, lipid pool–like image, lesion, and reference external elastic membrane cross-sectional area correlate with the no-reflow phenomenon. Multivariate logistic regression analysis showed that lipid pool–like image ( P &lt;0.05; odds ratio 118; 95% CI, 1.28 to 11 008) and lesion elastic membrane cross-sectional area ( P &lt;0.05; odds ratio 1.55; 95% CI 1.01 to 2.38) are independent predictive factors of no-reflow phenomenon after reperfusion for AMI. Conclusions — Large vessels with lipid pool–like image are at high risk for no reflow after primary intervention for AMI. Also, plaque content may play a role in damage to the microcirculation after primary intervention for AMI.
Inhibition of leucocyte adhesion molecule upregulation by tumor necrosis factor alpha: a novel mechanism of action of sulphasalazine.
Authors: S M Greenfield, A S Hamblin, Z S Shakoor, J P Teare, N A Punchard, R P Thompson
Journal: Gut (1993)

The effects of the cytokine tumour necrosis factor alpha and the calcium ionophore A23187 upon CD11a, CD11b, CD11c and CD18 leucocyte membrane expression was analysed in whole blood using monoclonal antibodies and flow cytometry. Both agents significantly increased the density of CD11b/CD18 membrane expression on monocytes and granulocytes, but had no effects on adhesion molecule expression on lymphocytes. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA) and sulphapyridine upon adhesion molecule upregulation were then examined; 10(-3) and 10(-4) M sulphasalazine and 5-ASA significantly reduced tumour necrosis factor alpha induced CD11b/CD18 upregulation on monocytes and granulocytes but had no effects upon A23187 mediated upregulation. Sulphapyridine was inactive. These results suggest that sulphasalazine and 5-ASA may interfere with mechanisms of leucocyte recruitment in inflammatory bowel disease.
Exercise training is beneficial in patients with non-cystic fibrosis bronchiectasis - A multi-centre, randomised controlled trial
Authors: Annemarie Lee, Catherine Hill, Nola Cecins, Sue Jenkins, Christine McDonald, Angela Burge, Linda Rautela, Robert Stirling, Philip Thompson, Anne Holland
Journal: European Respiratory Journal (2012)

Background:  Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic cough and sputum production, exercise limitation and reduced quality of life (QOL), but the role of exercise training in this patient group is unclear. The aim of this study was to determine the effects of exercise training on cough-related symptoms, QOL and exercise capacity.   Methods:  Participants with non-CF bronchiectasis with a modified Medical Research Council dyspnoea score ≥1 were randomised to receive eight weeks of twice-weekly supervised exercise training or twice-weekly telephone support. The incremental shuttle walk distance (ISWD), 6-minute walk distance (6MWD), the Chronic Respiratory Disease Questionnaire, Leicester Cough Questionnaire and Hospital Anxiety and Depression Scale were measured by a blinded assessor at baseline and following intervention.   Results:  Eighty-five participants, aged (mean [SD]) 64 (13) years, FEV 1  74 (22)% predicted and median modified Medical Research Council score of 1(IQR 3) were included. Of those in the exercise training group (n=42), 35 (83%) completed the program. There was a greater magnitude of change in the ISWD (mean difference 62m, 95% CI 24 to 101m) and the 6MWD (mean difference 41m, 95% CI 19 to 63m) in the exercise training group compared to the control group. Exercise training significantly reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but there was no difference in cough-related QOL or mood between groups.   Conclusions:  Exercise training in non-CF bronchiectasis improves exercise capacity and symptoms of dyspnoea and fatigue. Ongoing follow up will assess changes in these effects over time.