tbuckley/cabot-search huggingface dataset:
Association of Schizophrenia in 22q11.2 Deletion Syndrome and Gray Matter Volumetric Deficits in the Superior Temporal Gyrus
Authors: Eva W.C. Chow, Andrew Ho, Corie Wei, Eduard H.J. Voormolen, Adrian P. Crawley, Anne S. Bassett
Journal: American Journal of Psychiatry (2011)

Individuals with 22q11.2 deletion syndrome are known to be at high risk of developing schizophrenia. Previous imaging studies have provided limited data on the relation of schizophrenia expression in 22q11.2 deletion syndrome to specific regional brain volumetric changes. The authors hypothesized that the main structural brain finding associated with schizophrenia expression in 22q11.2 deletion syndrome, as for schizophrenia in the general population, would be gray matter volumetric deficits, especially in the temporal lobes.MR brain images from 29 patients with 22q11.2 deletion syndrome and schizophrenia and 34 comparison subjects with 22q11.2 deletion syndrome and no history of psychosis were analyzed using a voxel-based morphometry method that also yielded volumes for related region-of-interest analyses. The authors compared data from the two groups using an analysis of covariance model correcting for total intracranial volume, age, sex, IQ, and history of congenital cardiac defects. The false discovery rate threshold was set at 0.05 to account for multiple comparisons.Voxel-based morphometry analyses identified significant gray matter reductions in the left superior temporal gyrus (Brodmann's area 22) in the schizophrenia group. There were no significant between-group differences in white matter or CSF volumes. Region-of-interest analyses showed significant bilateral gray matter volume reductions in the temporal lobes and superior temporal gyri in the schizophrenia group.The structural brain expression of schizophrenia associated with the highly penetrant 22q11.2 deletion involves lower gray matter volumes in temporal lobe regions. These structural MRI findings in a 22q11.2 deletion syndrome form of schizophrenia are consistent with those from studies involving schizophrenia samples from the general population. The results provide further support for 22q11.2 deletion syndrome as a genetic subtype and as a useful neurodevelopmental model of schizophrenia.
A concealed cause of recurrent renal failure in a patient with juvenile chronic arthritis
Authors: J Hamilton, P Balint, M Field, R D Sturrock
Journal: Annals of the Rheumatic Diseases (1999)

Case reportA 20 year old man with a 17 year history of systemic onset juvenile chronic arthritis (JCA) was admitted with a fever of 38.2°C with increasing joint pain especially at the right hip.Numerous disease modifying agents including corticosteroids had been tried previously, but despite this his disease remained sub-optimally controlled and at age 14 he was diagnosed as having renal amyloid on the basis of proteinuria and an iodine-123-serum amyloid P ( 123 I-SAP) scan and started on treatment with chlorambucil.Bilateral hip replacements were performed but revision surgery was required to the right hip one year later complicated by low grade sepsis with staphylococcus epidermidis.Although mobility remained significantly impaired becuse of the consequences of his hip disease, by the age of 17 sequential 123 I-SAP scanning demonstrated that the amyloid load was small.At that stage he had little in the way of active joint disease.The chlorambucil dose was tapered and stopped.He subsequently defaulted from medical follow up.On admission drug treatment consisted of metoprolol only.His blood pressure (BP) was 130/80 mm Hg.Full blood count (FBC) including lymphocyte count was normal.Clinical examination showed mechanical impairment of the joints but no active synovitis.Flucloxacillin 1 g, four times daily and gentamicin 2.5 mg/kg/day amounting to 50 mg twice daily for a body weight of 42 kg was started to cover the possibility of recurrent hip sepsis.Two days later he became hypotensive (BP 90/60 mm Hg) and anuric with deteriorating renal function-urea 14.5 mmol/l (normal range 2.5-8 mmol/l) and creatinine 320 µmol/l (normal range 40-130 µmol/l) compared with a urea of 9.2 mmol/l and creatinine100 µmol/l at the time of admission.Gentamycin trough level after the third gentamicin dose was 7.9 mg/l (therapeutic range <2 mg/l).The diVerential diagnosis was between gentamicin nephrotoxicity, sepsis and hypoadrenalism secondary to amyloidosis.Gentamicin and metoprolol were stopped.He responded to treatment with intravenous fluids, inotropes and intravenous antibiotics (initially flucloxacillin but later changed to erythromycin and ceftriaxone when what was assumed to be an antibiotic related rash and signs of pneumonia developed.)No fluid was detected on ultrasound examination of the hip performed within
Genotype alone does not predict the clinical course of<i>SFTPC</i>deficiency in paediatric patients
Authors: Carolin Kröner, Simone Reu, Veronika Teusch, Andrea Schams, Ann-Christin Grimmelt, Michael Barker, Joerg Brand, Monika Gappa, Richard Kitz, Boris W. Kramer, Lars Lange, Susanne Lau, Claus Pfannenstiel, Marijke Proesmans, Jürgen Seidenberg, Tugba Sismanlar, Ayse Tana Aslan, Claudius Werner, Stefan Zielen, Ralf Zarbock, Frank Brasch, Peter Lohse, Matthias Griese
Journal: European Respiratory Journal (2015)

Patients with interstitial lung disease due to surfactant protein C ( SFTPC ) mutations are rare and not well characterised. We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations. 17 patients (seven male) were followed over a median of 3 years (range 0.3–19). All patients were heterozygous carriers of autosomal dominant SFTPC mutations. Three mutations (p.L101P, p.E191 K and p.E191*) have not been described before in the context of surfactant protein C deficiency. Patients with alterations in the BRICHOS domain of the protein (amino acids 94–197) presented earlier. At follow-up, one patient was healthy (2 years), six patients were “sick-better” (2.8 years, range 0.8–19), seven patients were “sick-same” (6.5 years, 1.3–15.8) and three patients were “sick-worse” (0.3 years, 0.3–16.9). Radiological findings changed from ground-glass to increasing signs of fibrosis and cyst formation with increasing age. Empiric treatments had variable effects, also in patients with the same genotype. Prospective studies with randomised interventions are urgently needed and can best be performed in the framework of international registers.
Remodeling and Airway Hyperresponsiveness but Not Cellular Inflammation Persist after Allergen Challenge in Asthma
Authors: Harsha H. Kariyawasam, Maxine Aizen, Julia Barkans, Douglas S. Robinson, A. Barry Kay
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Airway hyperresponsiveness (AHR) increases up to 2 weeks after allergen inhalational challenge of subjects with asthma who show a late-phase asthmatic reaction (dual responders). Cellular inflammation and airway remodeling are increased 24 hours after allergen challenge.To determine whether persistence of increased AHR is associated with persistent activation of remodeling and enhanced inflammation.Fiberoptic bronchoscopy was performed at baseline and at 24 hours and 7 days after allergen inhalational challenge of dual responders with mild-moderate asthma. At each time point, AHR, spirometry, and expression of tenascin (extracellular matrix protein), procollagen I, procollagen III, and heat shock protein (HSP)-47 (markers of collagen synthesis), and alpha-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of airway remodeling, together with numbers of mucosal major basic protein-positive eosinophils, CD68(+) macrophages, CD3(+), CD4(+), CD8(+) T cells, elastase-positive neutrophils, and tryptase-positive mast cells.AHR was increased from baseline at 24 hours and 7 days after allergen challenge. Reticular basement membrane tenascin expression was elevated at 24 hours and returned to baseline levels at 7 days. Reticular basement membrane procollagen III expression was significantly elevated at 7 days. Expression of procollagen I, HSP-47, and alpha-smooth muscle actin were all higher at 7 days compared with 24 hours. At 24 hours, eosinophil, macrophage, neutrophil, and CD3(+) T cells were increased but had returned to baseline by 7 days.In dual responders with asthma, the 24-hour increase in airway wall cellular inflammation after allergen challenge resolves by 7 days, whereas the increases in AHR and markers of remodeling persist.
Patients with early arthritis who fulfil the 1987 ACR classification criteria for rheumatoid arthritis but not the 2010 ACR/EULAR criteria
Authors: Se Jin Jung, Sang-Won Lee, You Jung Ha, Kwang-Hoon Lee, Yoon Kang, Min-Chan Park, Soo-Kon Lee, Yong-Beom Park
Journal: Annals of the Rheumatic Diseases (2012)

Recently, a joint working group of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) was formed to develop new classification criteria for rheumatoid arthritis (RA),1 2 and announced the 2010 ACR/EULAR classification criteria for identifying patients with early RA.3 The present study was performed in order to determine whether the newly developed 2010 ACR/EULAR criteria would include patients who were previously diagnosed with early RA according to the 1987 ACR criteria.4

We studied 170 patients with early RA patients, who had been classified as having RA according to the 1987 ACR criteria. Early RA was defined by less than 12 months of symptoms. The 2010 ACR/EULAR criteria were applied to patients at the exact time point when they were identified as fulfilling the 1987 ACR criteria. The clinical characteristics and laboratory findings …
Chemical Analyses of Sera Influencing Neoplastic Transformation In Vitro
Authors: Katherine K. Sanford, James F. Burris, Sandra R. Handleman
Journal: JNCI Journal of the National Cancer Institute (1972)

Several types of serum that influence “spenteneous” neoplastic transformation of mouse cells in vitro were analyzed for certain constituents. Because the low molecular-weight fraction of gelding horse serum appears to accelerate neoplastic conversion, gelding horse serum was tested for possible contamination with low molecular-weight chlorinated hydrocarbon insecticides, lead, and mercury. Contamination was negligible. Fetal bovine serum, which appears to inhibit neoplastic transformation, was compared with horse and calf serum with respect to certain hormones, 2 enzymes, and 16 elements. Fetal bovine serum differed from the other sera particularly in having high hexosaminidase and galactosidase activities, increased levels of zinc, iron, potassium, phosphorus, and magnesium, and a decreased amount of copper. Mare serum like fetal bovine serum may inhibit transformation as compared with the 2 male sera, gelding and stallion. A comparison of individual pooled samples of mare and stallion with gelding horse sera with respect to 14 elements revealed no distinctive differences except in iron content. Heating fetal bovine and gelding sera to 56° C. for 30 minutes did not destroy the factors influencing neoplastic transformation.
Recombinant birch pollen allergens (rBet v 1 and rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel, and oak pollen: A quantitative IgE inhibition study with sera from different populations☆☆☆★★★
Authors: V NIEDERBERGER, G PAULI, H GRONLUNDC, R FROSCHLA, H RUMPOLD, D KRAFT, R VALENTA, S SPITZAUER
Journal: Journal of Allergy and Clinical Immunology (1998)
Improving Selection Criteria for Lung Cancer Screening. The Potential Role of Emphysema
Authors: Pablo Sanchez-Salcedo, David O. Wilson, Juan P. de-Torres, Joel L. Weissfeld, Juan Berto, Arantzazu Campo, Ana B. Alcaide, Jesús Pueyo, Gorka Bastarrika, Luis M. Seijo, Maria J. Pajares, Ruben Pio, Luis M. Montuenga, Javier J. Zulueta
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55–74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity.Objectives: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion.Methods: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects who met NLST criteria alone, those with computed tomography–detected emphysema, and those who met NLST criteria and/or had emphysema.Measurements and Main Results: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss as many as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%.Conclusions: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed.
Hepatitis C virus and porphyria cutanea tarda: Evidence of a strong association
Authors: Silvia Fargion, Alberto Piperno, Maria Domenica Cappellini, Maurizio Sampietro, Anna Ludovica Fracanzani, Riccardo Romano, Rita Caldarelli, Rosaria Marcelli, Luisa Vecchi, Gemino Fiorelli
Journal: Hepatology (1992)

Porphyria cutanea tarda in human beings is believed to be due to reduced hepatic uroporphyrinogen decarboxylase activity. However, extrinsic factors such as alcohol abuse and drug intake are required for clinical manifestation of the disease. In addition to typical cutaneous lesions, patients with porphyria cutanea tarda usually have chronic liver disease and moderate iron overload. Of 74 Italian patients with porphyria cutanea tarda, hepatitis C virus antibodies were detected in 76% by enzyme-linked immunoassay and in 82% by recombinant immunoblot assay. Viral genome, studied with nested polymerase chain reaction, was found in the sera of 49 subjects--47 positive and 2 indeterminate on recombinant immunoblot assay. Five percent of the patients were HBsAg-positive, and about 40% had had past hepatitis B contacts. Alcohol abuse was present in 38%. Liver biopsies performed in 42 patients showed chronic persistent hepatitis in 7 patients, chronic active hepatitis in 22 patients, fibrosis in three patients and cirrhosis in 10 patients. Hepatitis C virus antibody was detected in 100% of patients with chronic active hepatitis and in about 80% of all other groups. Alcohol abuse was more frequent in patients with cirrhosis (80%) than in the other groups. In Italian patients with porphyria cutanea tarda, the prevalence of hepatitis C virus infection was very high, comparable to that in non-A, non-B hepatitis and high-risk patient groups. Hepatitis C virus is probably the main pathogenetic factor of the liver disease of patients with porphyria cutanea tarda.
Adenoviral Delivery of Osteoprotegerin Ameliorates Bone Resorption in a Mouse Ovariectomy Model of Osteoporosis
Authors: Brad Bolon, Christopher Carter, Mark Daris, Sean Morony, Casey Capparelli, Angela Hsieh, Mingfu Mao, Paul Kostenuik, Colin R. Dunstan, David L. Lacey, Jackie Z. Sheng
Journal: Molecular Therapy (2001)

Osteoprotegerin (OPG) regulates bone resorption by inhibiting osteoclast formation, function, and survival. The current studies employed a mouse ovariectomy (OVX) model of estrogen deficiency to investigate gene therapy with OPG as a means of preventing osteoporosis. Young adult females injected with a recombinant adenoviral (Ad) vector carrying cDNA of either full-length OPG or a fusion protein combining the hOPG ligand-binding domain with the human immunoglobulin constant domain (Ad-hOPG-Fc) developed serum OPG concentrations exceeding the threshold needed for efficacy. However, elevated circulating OPG levels were sustained for up to 18 months only in mice given Ad-hOPG-Fc. Administration of Ad-hOPG-Fc titers between 10(7) and 10(9) pfu yielded dose-dependent increases in serum OPG. Mice subjected to OVX or sham surgery followed by immediate treatment with Ad-hOPG-Fc had significantly more bone volume with reduced osteoclast numbers in axial and appendicular bones after 4 weeks. In contrast, animals given OVX and either a control vector or vehicle had significantly less bone than did comparably treated sham-operated mice. This study demonstrates that a single adenoviral gene transfer can produce persistent high-level OPG expression and shows that gene therapy to provide sustained delivery of OPG may prove useful in treating osteoporosis.
Hepatic sinusoidal vasodilators improve transplanted cell engraftment and ameliorate microcirculatory perturbations in the liver
Authors: Sanjeev Slehria, Pankaj Rajvanshi, Yoshiya Ito, Rana P. Sokhi, Kuldeep K. Bhargava, Christopher J. Palestro, Robert S. McCuskey, Sanjeev Gupta
Journal: Hepatology (2002)

After transplantation, hepatocytes entering liver sinusoids are engrafted, whereas cells entrapped in portal spaces are cleared. We studied whether hepatic sinusoidal dilatation will increase the entry of transplanted cells in the liver lobule, improve cell engraftment, and decrease microcirculatory perturbations. F344 rat hepatocytes were transplanted intrasplenically into syngeneic dipeptidyl peptidase IV (DPPIV)-deficient rats. Animals were treated with adrenergic receptor blockers (phentolamine, labetalol), a calcium channel blocker (nifedipine), and splanchnic vasodilators (nitroglycerine, calcitonin gene-related peptide [CGRP], glucagon). Transplanted cells were localized by histochemistry. The hepatic microcirculation was studied with in vivo videomicroscopy. Changes in cell translocations were analyzed by injection of (99m)Tc-labeled hepatocytes. Pretreatment with phentolamine and nitroglycerine increased transplanted cell entry in liver sinusoids, whereas labetalol, nifedipine, CGRP, and glucagon were ineffective. Increased deposition of transplanted cells in sinusoids resulted in greater cell engraftment. In vivo microscopy showed disruption of sinusoidal blood flow immediately after cell transplantation with circulatory restoration requiring more than 12 to 24 hours after cell transplantation. However, in nitroglycerine-treated animals, sinusoidal blood flow was perturbed less. Nitroglycerine did not meaningfully increase intrapulmonary cell translocations. In conclusion, these findings indicate that hepatic sinusoidal capacitance is regulated by alpha-adrenergic- and nitroglycerine-responsive elements. Sinusoidal vasodilatation benefited intrahepatic distribution of transplanted cells and restored hepatic microcirculation after cell transplantation. This shall facilitate optimization of clinical cell transplantation and offers novel ways to investigate vascular mechanisms regulating hepatic sinusoidal reactivity.
Epigenetic Loss of Mucosa-Associated Lymphoid Tissue 1 Expression in Patients with Oral Carcinomas
Authors: Tadashige Chiba, Genta Maeda, Shuichi Kawashiri, Koroku Kato, Kazushi Imai
Journal: Cancer Research (2009)

Mucosa-associated lymphoid tissue 1 (MALT1), which is located in a genomic region that encodes unknown tumor suppressor gene(s), activates nuclear factor-kappaB in lymphocyte lineages. However, its expression and role in the pathology of malignant tumors of epithelial origin is not known. In the present study, we examined MALT1 expression and its implications for the pathology of oral carcinomas. Immunostaining localized MALT1 in the nucleus of normal oral epithelial cells, but the expression was absent in 45.0% of carcinomas (49 of 109 cases) especially at the invasive front. The loss of expression was correlated with tumor recurrence (P = 0.007) and poor patient survival (P < 0.001), and it was an independent prognostic determinant (P < 0.001). MALT1-negative carcinomas exhibited microsatellite instability at the MALT1 locus and a specific cytosine methylation positioned at -256 from the gene, and the expression was recovered by demethylation treatment. In contrast to lymphocyte lineages, carcinoma cells showed MALT1 located at the nucleus independent of its domain structures, and its loss of expression induced the epithelial-mesenchymal transition. These results show that MALT1 is expressed in the nucleus of oral epithelial cells and that its expression is epigenetically inactivated during tumor progression, suggesting that the detection of MALT1 expression is a useful predictive and prognostic determinant in the clinical management of oral carcinomas.
Distribution of Sympathetic Fibers in the Left Ventricular Epicardial Plexus of the Dog
Authors: WILLIAM P. GEIS, MICHAEL P. KAYE
Journal: Circulation Research (1968)

Myocardial contractile force in five areas of the left ventricle was measured in 14 dogs under chloralose anesthesia prior to and following segmental chemical epicardiectomy. Electrical stimulation of the stellate ganglia was performed before and after each segment of epicardium was destroyed, and records of myocardial contractile response to stimulation were obtained. Epicardiectomy resulted in ablation of contractile response in specific areas of the left ventricle. In a recent publication from our laboratory (Circulation Res. 22: 315, 1968), the predominance of an epicardial distribution of sympathetic fibers was demonstrated. As an extension of that work, this study demonstrates the projection of fibers from both left and right stellate ganglia and the innervation of both anterior and posterior surfaces of the left ventricle. The major projections of sympathetic fibers are oriented along an axis passing from base to apex and can be interrupted by epicardial destruction in the area of the cephalad portion of the anterior descending coronary artery and adjacent to the origin of the left marginal artery.