tbuckley/cabot-search huggingface dataset:
Immunohistochemical study of collagen types in human foetal lung and fibrotic lung disease.
Authors: E D Bateman, M Turner-Warwick, B C Adelmann-Grill
Journal: Thorax (1981)

Highly purified type-specific anti-collagen antibodies (prepared in animals to types I, II, III, and IV bovine collagen) were used in an indirect immunofluorescence method for the study of human lung collagen. The tissue localisation of each collagen type, and the apparent type I:III collagen ratio was assessed in normal foetal and adult lung and in fibrotic lung lesions. In the latter, the relationship of the findings to the natural history of the lesion was considered. This method was compared with routine connective tissue stains. The following observations were made. (1) Foetal lung in the canalicular phase of development proved a useful substrate for validating and standardizing the procedure. (2) Collagen fluorescence was more sensitive than connective tissue stains in detecting collagen in foetal tissues and sites of early fibrosis. (3) On the basis of collagen-type fluorescence, two distinctive patterns of fibrosis were recognised. Areas of mature collagen surrounding vessels and bronchi and in established scar tissue, for example in asbestotic pleural plaques, were virtually exclusively type I collagen. By contrast, areas of early active fibrosis like sarcoid nodules and organising pneumonia, which usually contained variable numbers of fibroblasts and chronic inflammatory cells, were characterised by an increased proportion of type III collagen and a greater intensity of both types I and III collagen fluorescence. The possible significance of this change in type III:I collagen ratio is discussed. Determination of the stage of fibrotic lesions by this method might have applications in the prediction of disease progression, and influence management of some conditions.
The End of the Line for Hookworm? An Update on Vaccine Development
Authors: Eileen Devaney
Journal: PLoS Medicine (2005)

Human hookworms are parasitic nematodes infecting about 700 million individuals, largely in tropical regions of the world [1]. In endemic areas, most infected people carry a mixed worm burden, including Ascaris lumbricoides (roundworms), Trichuris trichuria (whipworms), and Ancylostoma duodenale and/or Necator americanus (both hookworms). Of these soil-transmitted helminths, hookworms are the most pathogenic because of their propensity to feed on blood, resulting in anaemia, particularly in those with low iron reserves such as children and women of reproductive age.
Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma
Authors: RJ Hancox, MR Sears, DR Taylor
Journal: European Respiratory Journal (1998)

Polymorphisms affecting amino acids 16 and 27 of the beta2-adrenoceptor alter receptor regulation in vitro. Whether these polymorphisms alter the response to beta2-agonist therapy in asthma is unknown. In a previous study of 64 asthmatics, most experienced a deterioration in asthma control during regular inhaled beta2-agonist (fenoterol) treatment, while a minority improved. We have determined the beta2-adrenoceptor genotypes in these subjects, to establish whether changes in asthma control during the earlier study were influenced by beta2-adrenoceptor polymorphism. The genotypes coding for amino acids 16 and 27 were identified in 60 subjects using allele-specific polymerase chain reaction. The effects of regular beta2-agonist treatment on asthma control were compared between genotypes. There was no association between genotype and change in overall asthma control during regular beta2-agonist treatment. Only two of 10 markers of asthma control showed changes that were significantly associated with genotype: subjects homozygous for glycine at position 16 had no increase in bronchial responsiveness to methacholine during regular treatment; subjects homozygous for glutamic acid at position 27 had no increase in evening peak expiratory flow rates during regular treatment. These differences are the opposite of those that would have been predicted by the results of in vitro studies. In these subjects, the deleterious response to regular inhaled beta2-agonist treatment was not related to beta2-receptor polymorphism.
Oral Immunotherapy of Children with Rhinoconjunctivitis due to Birch Pollen Allergy A Double Blind Study
Authors: C. Möller, S. Dreborg, Å. Lanner, B. Björkstén
Journal: Allergy (1986)

Thirty children with rhinoconjunctivitis due to birch pollinosis were treated in a double blind manner for 10 months with enteric‐coated capsules containing either a birch pollen preparation ( n = 14) with doses up to 1.4 × 10 6 biologic units per day or placebo ( n = 16). Compared with the placebo group the actively treated children had less symptoms during the birch pollen season after 3 months of therapy (P = 0.035). Skin prick reactions decreased significantly more in the active group than in the placebo group after 10 months (P = 0.01). Conjunctival sensitivity was lower in the active group than in the placebo group after 3 months of treatment (P = 0.01) but not after 10 months. Compared with the placebo group treated children more often increased their levels of IgG ( P = 0.007) and pre‐seasonal IgE ( P = 0.001) against birch. There was a seasonal increase of IgE antibody level against birch in the placebo but not in the treatment group ( P &lt; 0.001). None of the treated children developed asthma, compared with five of the untreated children. No general reactions occurred and few side effects were seen during the treatment period. We conclude that in children with birch pollinosis oral immunotherapy with high doses of a biologically potent preparation in enteric‐coated capsules is effective, easy to perform, economic and safe.
Postprandial Mineral Metabolism and Secondary Hyperparathyroidism in Early CKD
Authors: Tamara Isakova, Orlando Gutierrez, Anand Shah, Lorraine Castaldo, Julie Holmes, Hang Lee, Myles Wolf
Journal: Journal of the American Society of Nephrology (2008)

Normophosphatemia and normocalcemia are maintained in chronic kidney disease (CKD) by increased levels of fibroblast growth factor-23 (FGF-23) and parathyroid hormone (PTH), but the stimuli for secretion of these hormones in early CKD are incompletely understood. Most human physiologic studies have focused on random or fasting measurements of phosphorus, calcium, FGF-23, and PTH, but in this study, the hypothesis was that measurements in the postprandial state may reveal intermittent stimuli that lead to increased FGF-23 and PTH levels. The 4-h postprandial response in 13 patients with CKD and fasting normophosphatemia and normocalcemia (mean GFR 41 +/- 8 ml/min per m(2)) was compared with 21 healthy volunteers. Compared with healthy subjects, fasting patients with CKD had significantly higher levels of FGF-23 and fractional excretion of phosphorus; lower fractional excretion of calcium; and no difference in serum calcium, phosphorus, and PTH levels. After standardized meals, urinary phosphorus excretion in both groups increased despite unchanged serum phosphorus and FGF-23 levels. Postprandial urinary calcium excretion also increased in both groups, and this was accompanied by significantly reduced serum calcium and increased PTH levels in patients with CKD only; therefore, FGF-23 does not seem to be an acute postprandial regulator of phosphaturia in CKD or in health, but inappropriate postprandial calciuria with episodic, relative hypocalcemia may represent a previously unreported mechanism of secondary hyperparathyroidism in CKD.
Peripheral Arterial Disease and Renal Transplantation
Authors: Jon J. Snyder, Bertram L. Kasiske, Ross Maclean
Journal: Journal of the American Society of Nephrology (2006)

It was hypothesized that peripheral arterial disease (PAD) is less frequent after kidney transplantation than among comparable patients who are on the deceased-donor waiting list. The cumulative incidences and risk factors for PAD were compared among 43,427 adult transplant recipients and 53,309 adults who were placed on the renal transplant waiting list between 1995 and 2003. All patients had Medicare primary insurance coverage, and Medicare claims were used to identify PAD. For patients with diabetes, the 3-yr cumulative incidence of de novo PAD was 24% on the waiting list versus 20% after transplantation. For patients without diabetes, the 3-yr cumulative incidence was 9% on the waiting list versus 5% after transplantation. The adjusted relative risk (RR) for PAD among patients without diabetes was 0.73 (95% confidence interval [CI] 0.66 to 0.80; P < 0.0001) in the transplant population versus the waiting list population, whereas among patients with diabetes, it was 0.88 (95% CI 0.82 to 0.96; P = 0.0024). A diagnosis of PAD on the waiting list was associated with an almost three-fold increase in the RR for death for patients without diabetes (2.98; 95% CI 2.71 to 3.27; P < 0.0001) and with diabetes (2.92; 95% CI 2.71 to 3.15; P < 0.0001). After transplantation, de novo PAD increased the RR for death almost two-fold in patients without diabetes (1.92; 95% CI 1.63 to 2.26; P < 0.0001) and with diabetes (1.83; 95% CI 1.58 to 2.12; P < 0.0001). The incidence of PAD is higher on the waiting list than after transplantation and is associated with an increased risk for death among patients with and without diabetes.
Proximal Reflux as a Cause of Adult-Onset Asthma
Authors: Yoshihiro Komatsu, Toshitaka Hoppo, Blair A. Jobe
Journal: JAMA Surgery (2013)

To determine the patterns and proximity of reflux events in patients with adult-onset asthma (AOA) using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess outcomes of antireflux surgery (ARS) in patients with AOA. DESIGN Retrospective review of prospectively collected data.University hospital. PATIENTS, INTERVENTIONS, AND OUTCOMES: All patients with AOA referred to our testing center underwent HMII, and those with abnormal proximal exposure, defined as laryngopharyngeal reflux at least once a day and/or high esophageal reflux at least 5 times a day, subsequently underwent ARS.From October 1, 2009, through June 30, 2011, a total of 31 patients with AOA (4 men and 27 women; mean age, 53 years) underwent HMII. Of 27 patients with available information, 11 (41%) had objective evidence of reflux disease. Nineteen patients (70%) had concomitant typical reflux symptoms. Despite a frequently negative DeMeester score, abnormal proximal exposure, which occurred in the upright position, was observed in 19 patients (70%). Of 20 patients who subsequently underwent ARS, asthma symptoms improved in 18 (90%), and 6 of them discontinued or reduced pulmonary medications at a mean (range) follow-up of 4.6 (0.6-15.2) months. Pulmonary function test results before and after ARS revealed that of 5 patients, 4 (80%) had improvement of the forced expiratory volume in the first second of expiration and/or the peak expiratory flow rate, which correlated with symptomatic improvement.Adult-onset asthma is associated with abnormal proximal exposure of the aerodigestive tract to refluxate; these patients respond to ARS despite negative pH test results. Patients with AOA should undergo testing with HMII because they would not be detected with conventional pH testing.
Steroid-Resistant Kidney Transplant Rejection
Authors: H. ANDREAS BOCK
Journal: Journal of the American Society of Nephrology (2001)

Decreases in transplant function may be attributable to a variety of conditions, including prerenal and postrenal failure, cyclosporin A (CsA) toxicity, polyoma nephritis, recurrent glomerulonephritis, and rejection. The diagnosis of rejection should therefore be made on the basis of a transplant biopsy of adequate size, before the initiation of any therapy. Pulse steroid treatment (three to five 0.25- to 1.0-g pulses of methylprednisolone, administered intravenously) is the usual first-line therapy and has a 60 to 70% success rate, although orally administered prednisone (0.25 g) may be just as efficacious. Even if reverted, any rejection should trigger an at least temporary increase in basal immunosuppression, consisting of an increase in CsA or tacrolimus target levels, the addition of steroids or an increase in their dosage, the addition of mycophenolate mofetil, or a switch from CsA to tacrolimus. The addition of rapamycin or its RAD derivative may fulfill the same purpose. Steroid resistance should not be assumed before the fifth day of pulse steroid treatment, although histologic features of vascular rejection may indicate the need for more aggressive treatment earlier. Steroid-resistant rejection is traditionally treated with poly- or monoclonal antilymphocytic antibodies, with success rates of 60 to 70%. Their potential benefit must be carefully balanced against the risks of infection and lymphoma. More recently, mycophenolate mofetil has been successfully used to treat steroid-resistant rejection, but only of the interstitial (cellular) type. Switching from CsA to tacrolimus for treating recurrent or antibody-resistant rejection is successful in approximately 60% of cases. Plasmapheresis and intravenously administered Ig have been used in some desperate cases, with surprising success. Because none of the available drugs has a significantly better profile of therapeutic versus adverse effects, the possible benefits of continued rejection therapy must be continuously balanced with the potential for serious, sometimes fatal, side effects.
Altered endothelin-1 binding following balloon angioplasty of pig coronary arteries: effect of the ETA receptor antagonist, LU 135252
Authors: M Dashwood
Journal: Cardiovascular Research (1999)

Objective: Since raised levels of endothelin-1 (ET-1) have been detected in the human coronary sinus following percutaneous transluminal angioplasty (PTCA) we investigated the role of ET-1 in the etiology of vascular restenosis. Methods: Balloon angioplasty of coronary arteries was performed in pigs and the animals were treated with placebo or the endothelin (ETA) receptor antagonist LU 135252 (30 mg/kg/day). After 4 weeks vascular stenosis and the distribution of endothelin and its receptors was evaluated. Results: The pronounced neointima formation in the control group (neointima:media ratio=0.87±0.36) was significantly reduced by LU 135252 (0.43±0.30, P<0.001). Angioplasty caused a significant increase in medial ETA (approximately 275%, P<0.026) and ETB (approximately 250%, P<0.001) binding to injured, compared with non-injured segments, an effect that was also reduced by LU 135252 (ETA=11.5% increase; ETB=14% increase). The neointima of control animals exhibited ET-1 like immunoreactivity as well as ETA and ETB binding sites. Conclusion: These data indicate that endothelin is locally-released from endothelial and vascular smooth muscle cells following angioplasty which binds to ETA and ETB receptor sites in the neointima and media. Since administration of the ETA antagonist LU 135252 markedly reduces neointima formation and medial ET binding, we conclude that vascular smooth muscle cell proliferation and subsequent neointima formation is mediated predominantly via ETA receptors. These data underscore the therapeutic potential of ETA antagonists in reducing the degree of restenosis following vascular injury.
Mutations in Multiple PKD Genes May Explain Early and Severe Polycystic Kidney Disease
Authors: Carsten Bergmann, Jennifer von Bothmer, Nadina Ortiz Brüchle, Andreas Venghaus, Valeska Frank, Henry Fehrenbach, Tobias Hampel, Lars Pape, Annegret Buske, Jon Jonsson, Nanette Sarioglu, Antónia Santos, Jose Carlos Ferreira, Jan U. Becker, Reinhold Cremer, Julia Hoefele, Marcus R. Benz, Lutz T. Weber, Reinhard Buettner, Klaus Zerres
Journal: Journal of the American Society of Nephrology (2011)

Autosomal dominant polycystic kidney disease (ADPKD) is typically a late-onset disease caused by mutations in PKD1 or PKD2, but about 2% of patients with ADPKD show an early and severe phenotype that can be clinically indistinguishable from autosomal recessive polycystic kidney disease (ARPKD). The high recurrence risk in pedigrees with early and severe PKD strongly suggests a common familial modifying background, but the mechanisms underlying the extensive phenotypic variability observed among affected family members remain unknown. Here, we describe severely affected patients with PKD who carry, in addition to their expected familial germ-line defect, additional mutations in PKD genes, including HNF-1β, which likely aggravate the phenotype. Our findings are consistent with a common pathogenesis and dosage theory for PKD and may propose a general concept for the modification of disease expression in other so-called monogenic disorders.
Foundation trusts still have to prove their worth, say MPs
Authors: A. O'Dowd
Journal: BMJ (2008)

NHS foundation trusts should be independently evaluated to judge their real performance to date, says a report by a cross party group of MPs.

The report, by the parliamentary health select committee, which looked at foundation trusts and their regulator, Monitor, also calls for the trusts to work more closely with other NHS organisations.

Foundation trusts, of which there are now 107, were introduced in England in 2004 as a new type of NHS organisation with a greater degree of financial and management freedom from central government.

For their short inquiry MPs took oral and written evidence from a number of witnesses, including Monitor, academic commentators, and representatives of trusts and other NHS …
A Phase II Study of Induction Therapy with Carboplatin and Gemcitabine among Patients with Locally Advanced Non-small Cell Lung Cancer
Authors: J G.J.V. Aerts, V Surmont, R.J. van Klaveren, K.Y. Tan, S Senan, G van Wijhe, R Vernhout, G.T. Verhoeven, H.C. Hoogsteden, J.P. van Meerbeeck
Journal: Journal of Thoracic Oncology (2006)
A Modification of the Operation of Inguinal Colotomy
Authors: R. C. Bailey
Journal: BMJ (1900)

INGUINAL COLOTOMY.[IMTL-n c LTm 44X infantile hernia.Demmeaux has suggested that whether the sac first present in the scrotum be congenital or acquired, the press of intestine on a weak and loosely supported neck may cause a diverticulum slowly to develop.Such pouch may be in front or behind, to the inner or outer side.If rupture of the neck of a femoral sac occurs the bowel miiay pass into the subperitoneal tissue.Callisen recorded in 1777 a case where, owing to rupture of the sac below the neck, the bowel had escaped and made for itself a lodgment between the pectineus and psoas muscles.rThese conditions may be represented in tabular form thus:True.False.I. Reduction into a pro-peritoneal I. Rupture of the sac at the neck sac; rarely an iaterstitial sac.or elsewhere, with escape of fluid 2. Reduction of the whole sac, only.The hernial swelling becomes with contents, within the abdomen, considerably smaller, but the bowel outside the peritoneum, the mutual rema-ins strangled.Xzelations of sac and contents being 2. Reduction of part of the hernial undisturbed.contents.A small portion remain- 3. Rupture of the neck of the sac ing in the canal, paralysed and stiff .irits division during operation and with iDflammatory products, under- extravasation of the hernial con-goes a " secondary" strangulation.lpnts into the subperitoneal tissue.
Preliminary report of an intensified, short duration chemotherapy protocol for the treatment of pediatric non-Hodgkin's lymphoma in India
Authors: S. Advani, S. Pai, M. Adde, S. Vaidya, T. Vats, K. Naresh, P.A. Kurkure, C.N. Nair, D. Venzon, I. Margrath
Journal: Annals of Oncology (1997)
Inhibition of Adhesion, Invasion, and Metastasis by Antibodies Targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen)
Authors: Rosalyn D. Blumenthal, Hans J. Hansen, David M. Goldenberg
Journal: Cancer Research (2005)

Abstract CEACAM5 and CEACAM6 are overexpressed in many cancers and are associated with adhesion and invasion. The effects of three monoclonal antibodies targeting different epitopes on these antigens (NH2-terminal [MN-3] and A1B1 domains [MN-15] shared by CEACAM5 and CEACAM6 and the A3B3 domain [MN-14] restricted to CEACAM5) were evaluated in migration, invasion, and adhesion assays in vitro using a panel of human pancreatic, breast, and colonic cancer cell lines, and in the GW-39 human colonic micrometastasis model in vivo. MN-3 Fab′ and MN-15 Fab′ were both effective at inhibiting cell migration. MN-15 Fab′ treatment inhibited invasion, reducing cell penetration through an extracellular matrix (ECM). MN-3 Fab′ also decreased invasion but was less effective than MN-15 Fab′ in four of five cell lines. All three monoclonal antibody (mAb) Fabs decreased adhesion of tumor cells to endothelial cells by 49% to 58%. MN-15 Fab′ but not MN-3 or MN-14 Fabs induced a decrease in adhesion of three of six cell lines to the ECM protein, fibronectin, but adhesion to vitronectin, laminin, collagen-I, and collagen-IV was not affected. In vivo studies showed that treatment with MN-3 Fab′ or MN-15 Fab′ of mice implanted with GW-39 human colonic cancer cells increased their survival (P &amp;lt; 0.025 and P &amp;lt; 0.01, respectively). These studies show that antibody Fabs that target either CEACAM5 or CEACAM6 affect cell migration, cell invasion, and cell adhesion in vitro, and that MN-15 and MN-3 Fabs have antimetastatic effects in vivo, resulting in improved survival of mice with metastases. Thus, blocking the N and A1B1 domains of CEACAM5/CEACAM6 can impede the metastatic process.
Apoptotic cell instillation after bleomycin attenuates lung injury through hepatocyte growth factor induction
Authors: Ye-Ji Lee, Changsuk Moon, Seung Hae Lee, Hyun-Jeong Park, Ju-Young Seoh, Min-Sun Cho, Jihee Lee Kang
Journal: European Respiratory Journal (2012)

Apoptotic cell clearance by macrophages and neighbouring tissue cells induces hepatocyte growth factor (HGF) secretion. HGF plays a key role in alveolar epithelial regeneration and reconstruction after lung injury. Direct in vivo exposure to apoptotic cells enhances HGF production, resulting in attenuation of pulmonary injury. We investigated the direct effect of in vivo exposure to apoptotic cells in bleomycin-stimulated lungs (2 days old) on HGF induction. Furthermore, sequential changes of bleomycin-induced HGF production following apoptotic cell instillation related to the changes in inflammatory and fibrotic responses were assessed. At 2 h after apoptotic cell instillation into bleomycin-stimulated lungs, the levels of HGF mRNA and protein production, and apoptotic cell clearance by alveolar macrophages were enhanced. Furthermore, HGF induction persistently increased following apoptotic cell instillation up to 21 days after bleomycin treatment. Apoptotic cell instillation attenuated bleomycin-induced pro-inflammatory mediator production, inflammatory cell recruitment and total protein levels. Apoptotic cell instillation also induced antiapoptotic and antifibrotic effects. These anti-inflammatory and antiapoptotic effects could be reversed by co-administration of HGF-neutralising antibody. These findings indicate that in vivo exposure to apoptotic cells enhances transcriptional HGF production in bleomycin-stimulated lungs, resulting in attenuation of lung injury and fibrosis.