tbuckley/cabot-search huggingface dataset:
Endometriotic disease: the role of peritoneal fluid
Authors: P R Koninckx, S H Kennedy, D H Barlow
Journal: Human Reproduction Update (1998)

Peritoneal fluid and the intraovarian milieu are a specific microenvironment. Peritoneal fluid originates mainly as an ovarian exudation product caused by increased vascular permeability, with cyclic variation in volume and steroid hormones which are always higher than in plasma. It contains large amounts of macrophages and their secretion products, and has a large exchange area with plasma through the peritoneum, which is highly permeable for small molecules. Diffusion becomes virtually zero for molecules with a molecular weight of >100000 Da. In women with the luteinized unruptured follicle (LUF) syndrome, concentrations of oestrogens and progesterone are much lower in the luteal phase. Endometriosis is associated with sterile low-grade inflammation, increased concentrations of activated macrophages and many of their secretions, such as cytokines, growth factors and angiogenic factors. Concentrations of CA-125 and of glycodelins are also increased, secreted locally by the endometrial cells. Natural killer (NK) cell function declines, possibly mediated by glycodelins or local intercellular adhesion molecule (ICAM) -1 shedding. The ovary is also a specific microenvironment, with steroid hormone concentrations 1000-fold higher in follicles than in plasma. Endometrial and superficially implanted cells are influenced by peritoneal fluid concentrations so that local environment, rather than inherent cellular differences could explain differences between superficial endometriosis and eutopic endometrium. Differences between superficial implants and endometriotic disease, deep infiltrating or cystic ovarian endometriosis, may thus arise via different endocrine environments. Superficial endometrial implants are regulated by peritoneal fluid factors, whereas deep endometriosis and cystic ovarian endometriosis are influenced by blood or ovarian factors. The endometriotic disease theory considers superficial endometriotic implants and their remodelling as a physiological process in most women, and concentrates on the causes of severe endometriosis such as differences in the eutopic endometrium from women with and without endometriosis (which may indicate hereditary differences), the invasiveness of some endometriotic cells in vitro, focal 'shielding' of endometriotic foci by adhesions, and inhibition of NK activity by ICAM-1 and glycodelins. Endometriotic disease is thus seen as a benign tumour. The type of cellular lesion, hereditary and immunological environments and local hormone concentrations in the ovary and in peritoneal fluid, will decide expression as cystic ovarian endometriosis, deep endometriosis or adenomyosis externa, and whether the latter is associated with adhesions.
Department of Health has failed to prioritise diabetes and allowed postcode lottery standards to prevail, claim MPs
Authors: A. O'Dowd
Journal: BMJ (2012)

The government’s efforts to deal with the growing problem of diabetes have failed so far to address variation in the standard of care across England, MPs have claimed.

The Department of Health, however, has defended its record and said it was dealing with a problem that was growing all the time and real improvements had been made.

During a fiery evidence session of the parliamentary public accounts committee inquiry into management of adult diabetes on 12 June, MPs on the committee accused witnesses from the department of failing to tackle diabetes sufficiently.

The inquiry was prompted by the National Audit Office report The management of adult diabetes services in the NHS 1 published on 23 May, which said that despite …
Duodenal bacterial overgrowth during treatment in outpatients with omeprazole.
Authors: M Fried, H Siegrist, R Frei, F Froehlich, P Duroux, J Thorens, A Blum, J Bille, J J Gonvers, K Gyr
Journal: Gut (1994)

The extent of duodenal bacterial overgrowth during the pronounced inhibition of acid secretion that occurs with omeprazole treatment is unknown. The bacterial content of duodenal juice of patients treated with omeprazole was therefore examined in a controlled prospective study. Duodenal juice was obtained under sterile conditions during diagnostic upper endoscopy. Aspirates were plated quantitatively for anaerobic and aerobic organisms. Twenty five outpatients with peptic ulcer disease were investigated after a 5.7 (0.5) weeks (mean (SEM)) treatment course with 20 mg (nine patients) or 40 mg (16 patients). The control group consisted of 15 outpatients referred for diagnostic endoscopy without prior antisecretory treatment. No patient in the control group had duodenal bacterial overgrowth. In the omeprazole group bacterial overgrowth (&gt; or = 10(5) cfu/ml) was found in 14 (56%) patients (p = 0.0003). The number of bacteria (log10) in duodenal juice in patients treated with omeprazole was distinctly higher (median 5.7; range &lt; 2-8.7) when compared with the control group (median &lt; 2; range &lt; 2-5.0; p = 0.0004). As well as orally derived bacteria, faecal type bacteria were found in seven of 14 and anaerobic bacteria in three of 14 patients. Bacterial overgrowth was similar with the two doses of omeprazole. These results indicate that duodenal bacterial overgrowth of both oral and faecal type bacteria occurs often in ambulatory patients treated with omeprazole. Further studies are needed to determine the clinical significance of these findings, particularly in high risk groups during long term treatment with omeprazole.
Psychiatric Morbidity From Long-term Medications
Authors: J. Raymond DePaulo
Journal: JAMA (1982)

The report in this issue ofThe Journalby Escobar and Karno (p 1859) of a chronic hallucinosis associated with long-term use of nasal drops alerts us to the psychiatric morbidity from sympathomimetic medications. The authors express surprise at the small number of previous reports of similar symptoms associated with these preparations because of their ready availability and their tendency to be used on a long-term basis. There are several possible reasons for this. The occurrence of a toxic hallucinatory state may be truly rare. The patient presented here is more psychologically vulnerable (ie, having borderline intelligence and "a lifelong diagnosis of anxiety disorder") than the usual user of nasal drops. His self-regulated dosage of the preparation was clearly excessive. On the other hand, the problem of recognizing chronic drug side effects, particularly when they require the recognition of psychiatric disorders in medical settings, might contribute to the small number
Role of platelet-derived growth factor in glomerular disease.
Authors: R J Johnson, J Floege, W G Couser, C E Alpers
Journal: Journal of the American Society of Nephrology (1993)

An approach for establishing a role for a growth factor in glomerular disease is presented. Using platelet-derived growth factor (PDGF) as an example, there is strong evidence to support the hypothesis that PDGF is a mediator of mesangial cell proliferation in glomerulonephritis. This includes evidence that (1) PDGF is a mitogen for mesangial cells in culture; (2) PDGF is expressed in both experimental and human glomerulonephritis in which mesangial cell proliferation occurs; (3) infusion of PDGF into rats induces mesangial cell proliferation and a hypercellular lesion; and (4) inhibition of PDGF in a model of experimental nephritis significantly reduces the mesangial cell proliferation. However, these data do not answer the question of whether or not the inhibition of PDGF in human diseases would be beneficial in the long term, because some cell proliferation is likely required for normal healing and repair. Further studies will be necessary to resolve this issue.
Role of group-specific component (vitamin D binding protein) in clearance of actin from the circulation in the rabbit.
Authors: P J Goldschmidt-Clermont, H Van Baelen, R Bouillon, T E Shook, M H Williams, A E Nel, R M Galbraith
Journal: Journal of Clinical Investigation (1988)

The possible role of group specific component (Gc) (vitamin D-binding protein) in the clearance of cellular actin entering the circulation was examined with 125I-labeled Gc and actin injected into a rabbit model. Although filamentous F-actin is depolymerized primarily by plasma gelsolin, greater than or equal to 90% 125I-actin injected in either monomeric G- or F-form became complexed eventually with Gc (1:1 molar ratio). Clearance of Gc complexes was much faster (greater than 90% within 5 h) than that of native Gc (t1/2 = 17.2 h). Nephrectomy did not significantly alter the clearance of either Gc or actin. Since Gc complexes are dramatically increased in situations of tissue necrosis such as in fulminant hepatic failure, the current results suggest a crucial role for Gc in sequestration and clearance of released cellular actin.
Endothelial Cells Secrete Triglyceride Lipase and Phospholipase Activities in Response to Cytokines as a Result of Endothelial Lipase
Authors: Weijun Jin, Gwo-Shing Sun, Dawn Marchadier, Edelyn Octtaviani, Jane M. Glick, Daniel J. Rader
Journal: Circulation Research (2003)

The endothelium interacts extensively with lipids and lipoproteins, but there are very few data regarding the ability of endothelial cells to secrete lipases. In this study, we investigated the ability of endothelial cells to secrete the triglyceride lipase and phospholipase activities characteristic of endothelial lipase (EL), a recently described member of the triglyceride lipase gene family. No lipase activities were detected under basal conditions, but treatment with cytokines significantly stimulated the expression of both activities. Using antibodies to EL, we determined that both activities were primarily a result of this enzyme. In addition to the increase in lipolytic activity, cytokine treatment was demonstrated to substantially upregulate EL protein and EL mRNA in a dose-dependent manner. Cytokines did not change EL mRNA stability. Both new protein synthesis and activation of NF-kappaB influenced the induction of EL by cytokines, suggesting that multiple pathways contribute to this process. The upregulation of EL by cytokines is in sharp contrast to the downregulation by cytokines of the other two major members of this gene family, lipoprotein lipase and hepatic lipase, and has implications for the physiological role of EL in inflammatory conditions and its potential role in the modulation of lipoprotein metabolism during inflammatory conditions, including atherosclerosis.
Thrombokinetics in man
Authors: Laurence A. Harker, Clement A. Finch
Journal: Journal of Clinical Investigation (1969)

Platelet production, distribution, and destruction have been quantitated in normal man and in selected patients with platelet disorders. In most instances, total production as calculated from the megakaryocyte mass agreed with production estimated from platelet turnover. In patients with megaloblastosis, a discrepancy between these two measurements indicated the presence of ineffective thrombopoiesis. Thrombopoiesis was regulated by (a) alterations in megakaryocyte number, and (b) changes in megakaryocyte volume (produced by changes in endomitosis). The volume-endomitosis changes were closely related to the peripheral platelet count and were a useful indicator of thrombopoietic stimulus. Thrombocytopenic disorders have been classified on the basis of the disturbed physiology into disorders of (a) production (hypoproliferative or ineffective), (b) distribution (splenic pooling), or (c) destruction (immune or consumptive). Less than a twofold increase in platelet production in the presence of significant thrombocytopenia was taken to represent impaired proliferation. Thrombocytosis was classified as reactive or autonomous. Reactive thrombocytosis was consistently associated with a mean megakaryocyte volume and endomitosis less than normal but appropriate for the elevated circulating platelet count. In contrast, the average megakaryocyte volume and nuclear number were always greater than normal in thrombocythemia findings indicating autonomy.
Colonoscopic study of 50 patients with colonic tuberculosis.
Authors: S Shah, V Thomas, M Mathan, A Chacko, G Chandy, B S Ramakrishna, D D Rolston
Journal: Gut (1992)

Fifty patients with colonic tuberculosis are reported in whom a colonoscopic diagnosis confirmed by histological examination was possible in 40. Bacteriological studies did not increase the diagnostic yield. Abdominal pain was the most common symptom (90%) and an abdominal mass the most common abnormal physical finding (58%). A nodular mucosa with areas of ulceration was the usual colonoscopic finding. Ileocaecal disease was found in 16, ileocaecal and contiguous ascending colon disease in 14, segmental colonic tuberculosis in 13, ileocaecal disease and non-confluent involvement of another part of the colon in five, and pancolitis in two patients. This report emphasises that colonoscopy is a useful procedure for diagnosing colonic tuberculosis and that segmental colonic tuberculosis is not uncommon.
Cell Cycle-Related Kinase: A Novel Candidate Oncogene in Human Glioblastoma
Authors: S. S. M. Ng, Y.-T. Cheung, X.-M. An, Y. C. Chen, M. Li, G. Hoi-Yee Li, W. Cheung, J. Sze, L. Lai, Y. Peng, H. H. X. Xia, B. C. Y. Wong, S.-Y. Leung, D. Xie, M.-L. He, H.-F. Kung, M. C. Lin
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundMedian survival for patients with glioblastoma multiforme, the most aggressive glioma, is only 12–15 months, despite multimodal treatment that includes surgery, chemotherapy, and radiotherapy. Thus, identification of genes that control the progression of glioblastoma multiforme is crucial for devising new therapies. We investigated the involvement of cell cycle–related kinase (CCRK), a novel protein kinase that is homologous to cyclin-dependent kinase 7, in glioblastoma multiforme carcinogenesis.
Hypoxia-Adenosinergic Immunosuppression: Tumor Protection by T Regulatory Cells and Cancerous Tissue Hypoxia
Authors: Michail V. Sitkovsky, Jorgen Kjaergaard, Dmitriy Lukashev, Akio Ohta
Journal: Clinical Cancer Research (2008)

Abstract Cancerous tissue protection from tumor-recognizing CD8+ and CD4+ T cells (antitumor T cells) limits the therapeutic potential of immunotherapies. We propose that tumor protection is to a large extent due to (a) inhibition of antitumor T cells by hypoxia-driven accumulation of extracellular adenosine in local tumor microenvironment and due to (b) T regulatory cell-produced extracellular adenosine. The adenosine triggers the immunosuppressive signaling via intracellular cyclic AMP–elevating A2A adenosine receptors (A2AR) on antitumor T cells. In addition, the activated antitumor T cells in hypoxic tumor microenvironment could be inhibited by elevated levels of immunosuppressive hypoxia-inducible factor-1α. Complete rejection or tumor growth retardation was observed when A2AR has been genetically eliminated or antagonized with synthetic drug or with natural A2AR antagonist 1,3,7-trimethylxanthine (caffeine). The promising strategy may be in combining the anti-hypoxia-adenosinergic treatment that prevents inhibition of antitumor T cells by tumor-produced and T regulatory cell-produced adenosine with targeting of other negative regulators, such as CTL antigen-4 blockade. Observations of tumor rejection in mice and massive prospective epidemiologic studies support the feasibility of anti-hypoxia-adenosinergic combined immunotherapy.
Marine n-3 PUFAs modulate IKs gating, channel expression, and location in membrane microdomains
Authors: Cristina Moreno, Alicia de la Cruz, Anna Oliveras, Sanjay R. Kharche, Miriam Guizy, Nùria Comes, Tomáš Starý, Carlotta Ronchi, Marcella Rocchetti, Isabelle Baró, Gildas Loussouarn, Antonio Zaza, Stefano Severi, Antonio Felipe, Carmen Valenzuela
Journal: Cardiovascular Research (2014)

Polyunsaturated fatty n-3 acids (PUFAs) have been reported to exhibit antiarrhythmic properties. However, the mechanisms of action remain unclear. We studied the electrophysiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on IKs, and on the expression and location of Kv7.1 and KCNE1. Experiments were performed using patch-clamp, western blot, and sucrose gradient techniques in COS7 cells transfected with Kv7.1/KCNE1 channels. Acute perfusion with both PUFAs increased Kv7.1/KCNE1 current, this effect being greater for DHA than for EPA. Similar results were found in guinea pig cardiomyocytes. Acute perfusion of either PUFA slowed the activation kinetics and EPA shifted the activation curve to the left. Conversely, chronic EPA did not modify Kv7.1/KCNE1 current magnitude and shifted the activation curve to the right. Chronic PUFAs decreased the expression of Kv7.1, but not of KCNE1, and induced spatial redistribution of Kv7.1 over the cell membrane. Cholesterol depletion with methyl-β-cyclodextrin increased Kv7.1/KCNE1 current magnitude. Under these conditions, acute EPA produced similar effects than those induced in non-cholesterol-depleted cells. A ventricular action potential computational model suggested antiarrhythmic efficacy of acute PUFA application under IKr block. We provide evidence that acute application of PUFAs increases Kv7.1/KCNE1 through a probably direct effect, and shows antiarrhythmic efficacy under IKr block. Conversely, chronic EPA application modifies the channel activity through a change in the Kv7.1/KCNE1 voltage-dependence, correlated with a redistribution of Kv7.1 over the cell membrane. This loss of function may be pro-arrhythmic. This shed light on the controversial effects of PUFAs regarding arrhythmias.
Ultrastructural study of extramammary Paget's disease—histologically showing transition from bowenoid pattern to Paget's disease pattern
Authors: T. YAMAMURA, T. HONDA, Y. MATSUI, K. YOSHIKAWA, K. AOZASA
Journal: British Journal of Dermatology (1993)

Histoiogical, immunohistochemical, and ultrastructural studies were performed on two cases of histologically unusual extramammary Paget's disease. Histologically, the central area of the lesions showed a bowenoid pattern, and the peripheral area showed typical extramammary Paget's disease. The transition zone showed an intermediate pattern. All these areas were positive for CHA and EMA, and negative for S‐100 protein. Ultrastructually. in the intermediate pattern, the tumour cells had abundant cytoplasmic glycogen, and the widened intercellular spaces contained numerous glycogen particles, which were probably secreted hy the tumour cells. It is well known that eccrine glands, but not apocrine glands, secrete glycogen particles. Therefore, the present findings suggest that some cases of extramammary Paget's disease are a proliferation of germinative cells with eccrine gland differentiation.
Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease
Authors: N Soler, S Ewig, A Torres, X Filella, J Gonzalez, A Zaubet
Journal: European Respiratory Journal (1999)

The effect of bacterial colonization of the bronchi on the progress of airflow limitation is not well known. Therefore, the pattern of airway inflammation in smokers and patients with stable chronic obstructive pulmonary disease (COPD) and its relation to bronchial microbial colonization was assessed. Eight nonsmoking and 18 smoking controls as well as 52 patients with COPD (28 mild, 11 moderate and 13 severe) were studied. All subjects were investigated by means of flexible bronchoscopy including protected specimen brush and bronchoalveolar lavage (BAL) sampling. Differential cell counts, cytokine (interleukin (IL)-1beta, IL-6, IL-8, IL-10 and tumour necrosis factor-alpha(TNF-alpha) concentrations and microbial patterns were determined in BAL fluid. Forced expiratory volume in one second (FEV1) % of the predicted value was inversely correlated with pack-yrs of cigarette smoking (r=-0.47, p&lt;0.0001), the percentage of neutrophil (p=-0.56, p&lt;0.0001) and IL-6 (p=-0.37, p=0.01) and IL-8 concentration (p=-0.43, p=0.004) in BAL fluid. Accordingly, pk-yrs of cigarette smoking (p=0.39, p=0.01) and IL-8 (p=0.69, p&lt;0.0001) and TNFalpha (p=0.4, p&lt;0.005) were positively correlated with the percentage of neutrophils in BAL fluid. Smoking controls and COPD patients were mainly colonized in the bronchial tree (33%) by community endogenous potentially pathogenic micro-organisms (PPMs). Colonization rates and patterns of PPMs were not affected by severity of airflow obstruction. The presence of PPMs was significantly associated with higher percentages of neutrophils (33.2+/-10.4% versus 10.1+/-3.5%, p=0.02) and TNF-alpha concentration (29.9+/-10.8 versus 6.3+/-2.1 pg x mL(-1), p=0.01) in BAL fluid. In conclusion, bronchial neutrophilia is a key inflammatory pattern in chronic obstructive pulmonary disease patients. Bronchial colonization with potentially pathogenic micro-organisms may represent an independent stimulus for additional airway inflammation.
Asthma deaths in Scotland and in Wales
Authors: I. W B GRANT;
Journal: Thorax (2000)

It is surprising to say the least that, although the two inquiries into asthma deaths published recently in Thorax 1 2 made the point that most asthma deaths occurred outside hospital (the Welsh study commented on the “relative rarity” of deaths in hospital), neither addressed the question as to whether more prompt admission to a hospital with respiratory intensive care facilities could have prevented some, or even many, of the domestic deaths.

The Respiratory Unit at the Northern General Hospital in Edinburgh first addressed that question as long ago as 19683 when it inaugurated a self-admission scheme for patients known by the unit to be subject to life threatening attacks of asthma, whereby the often long delays inherent in conventional admission procedures were bypassed with the …
Dye Dilution in Canine Heart-Lung Preparations
Authors: C. W. SHEPPARD, BILLY L. COUCH, BENNETT L. CROWDER
Journal: Circulation Research (1960)

In a large series of canine heart-lung preparations, system volumes were determined by the T 1824 dye bolus teehnic of Hamilton. Results were compared with volumes independently determined by equilibration of label in a recirculating system. The mean differences of values in the largest group of experiments was 3.9 ml., and was not significantly different from zero. A small but significant mean difference in a second smaller group is discussed relative to the basic postulates of the method.